bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel flow cytometry procoagulant assay for diagnosis of vaccine-induced immune thrombotic thrombocytopenia
Authors: Lee Christine S.M. , Liang Hai Po Helena , Connor David E. , Dey Agnibesh , Tohidi-Esfahani Ibrahim , Campbell Heather , Whittaker Shane , Capraro David , Favaloro Emmanuel J. , Donikian Dea , Kondo Mayuko , Hicks Sarah M. , Choi Philip Y.-I. , Gardiner Elizabeth E. , Clarke Lisa Joanne , Tran Huyen , Passam Freda H. , Brighton Timothy Andrew , Chen Vivien M.
Published: June 2022

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria) vaccine. The putative mechanism involves formation of pathological anti–platelet factor 4 (PF4) antibodies that activate platelets via the low-affinity immunoglobulin G receptor FcγRIIa to drive thrombosis and thrombocytopenia. Functional assays are important for VITT diagnosis, as not all detectable anti-PF4 antibodies are pathogenic, and immunoassays have varying sensitivity. Combination of ligand binding of G protein–coupled receptors (protease-activated receptor-1) and immunoreceptor tyrosine–based activation motif–linked receptors (FcγRIIa) synergistically induce procoagulant platelet formation, which supports thrombin generation. Here, we describe a flow cytometry–based procoagulant platelet assay using cell death marker GSAO and P-selectin to diagnose VITT by exposing donor whole blood to patient plasma in the presence of a protease-activated receptor-1 agonist. Consecutive patients triaged for confirmatory functional VITT testing after screening using PF4/heparin ELISA were evaluated. In a development cohort of 47 patients with suspected VITT, plasma from ELISA-positive patients (n = 23), but not healthy donors (n = 32) or individuals exposed to the ChAdOx1 nCov-19 vaccine without VITT (n = 24), significantly increased the procoagulant platelet response. In a validation cohort of 99 VITT patients identified according to clinicopathologic adjudication, procoagulant flow cytometry identified 93% of VITT cases, including ELISA-negative and serotonin release assay–negative patients. The in vitro effect of intravenous immunoglobulin (IVIg) and fondaparinux trended with the clinical response seen in patients. Induction of FcγRIIa-dependent procoagulant response by patient plasma, suppressible by heparin and IVIg, is highly indicative of VITT, resulting in a sensitive and specific assay that has been adopted as part of a national diagnostic algorithm to identify vaccinated patients with platelet-activating antibodies.
Inspiratory hyperoxia suppresses lung cancer metastasis through a MYC/SLC1A5-dependent metabolic pathway
Authors: Liu Xiucheng , Qin Hao , Li Zheng , Lv Yin , Feng Shoujie , Zhuang Wei , Quan Xiaoyu , Guo Chen , Chen Chang , Zhang Hao
Published: June 2022

The lack of knowledge about the effect of inspiratory hyperoxia on the lung-specific tumour microenvironment and progression of lung cancer has attracted considerable attention. This study proposes that inspiratory hyperoxia has special significance for the malignant phenotype of lung cancer cells. The effects of different oxygenation parameters on the proliferation, apoptosis, invasion and migration of lung cancer cells were systematically evaluatedin vitroandin vivo. Our results reveal that inspiratory hyperoxia treatment (60% oxygen, 6 h·day−1) not only has no tumour progression-promoting effects, but also suppresses lung cancer metastasis and promotes long-term survival. In addition, we combined transcriptome, proteome and metabolome analysis and found that hyperoxia treatment induced significant intracellular metabolic changes in lung cancer cells. Overall, we established that MYC/SLC1A5-induced metabolic reprogramming and glutamine addiction is a new mechanism that drives lung cancer metastasis, which can be significantly suppressed by inspiratory hyperoxia treatment. These findings are relevant to the debate on the perils, promises and antitumour effect of inspiratory hyperoxia, especially for patients with lung cancer.
Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer
Authors: Wang Yufei , Fang Tianyi , Wang Yimin , Yin Xin , Zhang Lei , Zhang Xinghai , Zhang Daoxu , Zhang Yao , Wang Xibo , Wang Hao , Xue Yingwei
Published: June 2022

Background

The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model.

Methods

We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC.

Results

Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC.

Conclusion

AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC.
YAP1 is essential for malignant mesothelioma tumor maintenance
Authors: Calvet Loreley , Dos-Santos Odette , Spanakis Emmanuel , Jean-Baptiste Véronique , Le Bail Jean-Christophe , Buzy Armelle , Paul Pascal , Henry Christophe , Valence Sandrine , Dib Colette , Pollard Jack , Sidhu Sukhvinder , Moll Jürgen , Debussche Laurent , Valtingojer Iris
Published: June 2022

Malignant pleural mesothelioma, a tumor arising from the membrane covering the lungs and the inner side of the ribs, is a cancer in which genetic alterations of genes encoding proteins that act on or are part of the Hippo-YAP1 signaling pathway are frequent. Dysfunctional Hippo signaling may result in aberrant activation of the transcriptional coactivator protein YAP1, which binds to and activates transcription factors of the TEAD family. Recent studies have associated elevated YAP1 protein activity with a poor prognosis of malignant mesothelioma and its resistance to current therapies, but its role in tumor maintenance is unclear. In this study, we investigate the dependence of malignant mesothelioma on YAP1 signaling to maintain fully established tumors in vivo. We show that downregulation of YAP1 in a dysfunctional Hippo genetic background results in the inhibition of YAP1/TEAD-dependent gene expression, the induction of apoptosis, and the inhibition of tumor cell growth in vitro. The conditional downregulation of YAP1 in established tumor xenografts leads to the inhibition of YAP1-dependent gene transcription and eventually tumor regression. This effect is only seen in the YAP1-activated MSTO-211H mesothelioma xenograft model, but not in the Hippo-independent HCT116 colon cancer xenograft model. Our data demonstrate that, in the context of a Hippo pathway mutated background, YAP1 activity alone is enough to maintain the growth of established tumors in vivo, thus validating the concept of inhibiting the activated YAP1-TEAD complex for the treatment of malignant pleural mesothelioma patients.
Anterior synechiae after penetrating keratoplasty in infants and children with Peters’ anomaly
Authors: Yang Yujing , Xiang Jun , Xu Jianjiang
Published: June 2022

Background

To evaluate anterior synechiae after penetrating keratoplasty (PK) in patients with Peters’ anomaly using anterior segment optical coherence tomography (OCT).

Methods

A retrospective cross-sectional study was performed. The medical records of patients diagnosed with Peters’ anomaly who underwent PK between 2013 and 2018 were reviewed. In addition to basic ophthalmic examinations, images of anterior segment structures were obtained via spectral-domain OCT at baseline and during the postoperative follow-up period. The profiles of postoperative anterior synechiae and multiple potential risk factors were analyzed.

Results

Seventy-one eyes of 58 patients, aged 5 to 23 months, were included. Various extent of postoperative anterior synechiae was observed in 59 eyes (83.1%). OCT findings revealed graft-host junction synechiae, peripheral anterior synechiae, and a combination of both. Disease severity and malposition of the internal graft-host junction were significantly associated with the formation of postoperative synechiae. Multivariate regression analysis found that preexisting iridocorneal adhesion [odds ratio (OR) = 16.639, 95% confidence interval (CI) 1.494–185.294, p = 0.022] was positively correlated with postoperative anterior synechiae, whereas anterior chamber depth (OR = 0.009, 95% CI 0.000–0.360, p = 0.012) and graft size (OR = 0.016, 95% CI 0.000–0.529, p = 0.020) were negatively correlated with postoperative synechiae. In addition, quadrants of preexisting iridocorneal adhesion and width of the host corneal bed were identified as risk factors for increased postoperative anterior synechiae.

Conclusions

Anterior synechiae following PK is a relatively common occurrence in Peters’ anomaly patients and is found to be associated with preexisting iridocorneal adhesion, a shallow anterior chamber, small graft size, graft-host junction malposition, and graft closer to the corneal limbus. These data indicate the need for careful consideration when performing PK on these patients.
Clinical characteristics of infants with port-wine stain and glaucoma secondary to Sturge–Weber Syndrome
Authors: Yan Honggai , Hu Man , Cui Yanhui , Li Li , Liang Tianwei
Published: June 2022

Background

Sturge–Weber Syndrome (SWS) is a rare disease involving the eye, skin, and brain. Port-wine stain (PWS) and glaucoma are common clinical manifestations. This study analysed the clinical characteristics of infants with PWS and glaucoma secondary to SWS.

Methods

Children with PWS and glaucoma secondary to SWS were enrolled. Data were extracted from ophthalmic and systemic examination findings. Ocular examinations included intraocular pressure, anterior segment and fundus examination, and ocular A-scan and B-scan ultrasonography.

Results

Fifty-seven patients were included, with a mean age of 9.9 ± 11.9 months, and 34 (59.6%) patients were male. In all, 61 eyes were diagnosed with glaucoma. Forty-one patients (71.9%) had unilateral facial PWS and glaucoma occurred on the same side. Eight patients (14.0%) had Mongolian spots and ten patients (17.5%) had epilepsy. Corneal changes included corneal oedema (n = 36 eyes, 59.0%), corneal opacity (n = 15 eyes, 24.6%), and Haab lines (n = 13 eyes, 21.3%). Mean corneal diameter and thickness in the eyes with glaucoma was larger than those in the unaffected eyes (12.2 ± 0.7 mm vs 10.8 ± 0.6 mm, P < 0.001; 681.2 ± 106.4 µm vs 578.2 ± 58.2 µm, P < 0.001). The eyes with glaucoma had higher IOP and larger axial length and C/D ratio (19.3 ± 6.2 mmHg vs 11.6 ± 4.2 mmHg, P < 0.001; 21.23 ± 1.93 mm vs 19.68 ± 1.61 mm, P < 0.001; and 0.57 ± 0.18 vs 0.24 ± 0.15, P < 0.001). Thirty-three (57.9%) and 25 (43.9%) patients showed diffuse choroidal haemangioma (DCH) and conjunctival/episcleral haemangiomas, respectively. Ten patients (17.5%) showed iris anterior insertion or hyperpigmentation in the anterior chamber angles. Six of them had Mongolian spots at the same time.

Conclusions

Monocular glaucoma, DCH, and conjunctival/episcleral haemangiomas are common in SWS patients with PWS and glaucoma. Glaucomatous eyes have larger corneal diameter and axial length and thicker cornea. Patients with Mongolian spots have higher incidence of iris anterior insertion or hyperpigmentation in anterior chamber angle.
Effectiveness of antibiotic treatment in children with Lyme neuroborreliosis - a retrospective study
Authors: Arnason Sigurdur , Skogman Barbro H.
Published: June 2022

Background

Lyme neuroborreliosis (LNB) is a tick-borne infection caused by the spirocheteBorrelia burgdorferisensu lato complex with various neurological manifestations. The recommended treatment for LNB in Swedish children has been intravenous ceftriaxone 50–100 mg/kg × 1 (< 8 years of age) or oral doxycycline 4 mg/kg × 1 (≥ 8 years of age) for 10–14 days. Studies on adult LNB patients have shown equal efficacy for ceftriaxone and doxycycline, but no such studies have been conducted on pediatric LNB patients. The aim of this study is to retrospectively evaluate clinical outcome in children with LNB who have received intravenous ceftriaxone or oral doxycycline.

Results

Clinical and laboratory data from three previously conducted prospective studies on children with LNB (1998–2014) were retrospectively analyzed. A total of 321 children (1–19 years of age), who received antibiotic treatment for definite LNB or possible LNB, were included. Clinical outcome at the 2-month follow-up (recovery/non-recovery) was evaluated using Chi2test and logistic multivariate regression analysis. Out of 321 LNB patients, 194 children (60%) had received ceftriaxone and 127 children (40%) had received doxycycline. When comparing clinical outcome between treatment groups, no difference was found (p = 0,217). Results did not change when incorporating relevant clinical and laboratory data into the logistic multivariate regression analysis.

Conclusion

In this large retrospective study, no difference in clinical outcome was found, independent of age, when comparing children who received ceftriaxone with those who received doxycycline, supporting an equal effectiveness for treatment of LNB pediatric patients. However, future randomized comparative treatment studies are warranted for evaluation of efficacy of antibiotic treatment in pediatric LNB patients.
Patients’ and clinicians’ experiences with stratified exercise therapy in knee osteoarthritis: a qualitative study
Authors: Knoop J. , de Joode J. W. , Brandt H. , Dekker J. , Ostelo R. W. J. G.
Published: June 2022

Background

We have developed a model of stratified exercise therapy that distinguishes three knee osteoarthritis (OA) subgroups (‘high muscle strength subgroup’, ‘low muscle strength subgroup’, ‘obesity subgroup’), which are provided subgroup-specific exercise therapy (supplemented by a dietary intervention for the ‘obesity subgroup’). In a large clinical trial, this intervention was found to be no more effective than usual exercise therapy. The present qualitative study aimed to explore experiences from users of this intervention, in order to identify possible improvements.

Methods

Qualitative research design embedded within a cluster randomized controlled trial in a primary care setting. A random sample from the experimental arm (i.e., 15 patients, 11 physiotherapists and 5 dieticians) was interviewed on their experiences with receiving or applying the intervention. Qualitative data from these semi-structured interviews were thematically analysed.

Results

We identified four themes: one theme regarding the positive experiences with the intervention and three themes regarding perceived barriers. Although users from all 3 perspectives (patients, physiotherapists and dieticians) generally perceived the intervention as having added value, we also identified several barriers, especially for the ‘obesity subgroup’. In this ‘obesity subgroup’, physiotherapists perceived obesity as difficult to address, dieticians reported that more consultations are needed to reach sustainable weight loss and both physiotherapists and dieticians reported a lack of interprofessional collaboration. In the ‘high muscle strength subgroup’, the low number of supervised sessions was perceived as a barrier by some patients and physiotherapists, but as a facilitator by others. A final theme addressed barriers to knee OA treatment in general, with lack of motivation as the most prominent of these.

Conclusion

Our qualitative study revealed a number of barriers to effective application of the stratified exercise therapy, especially for the ‘obesity subgroup’. Based on these barriers, the intervention and its implementation could possibly be improved. Moreover, these barriers are likely to account at least partly for the lack of superiority over usual exercise therapy.

Trial registration

The Netherlands National Trial Register (NTR): NL7463 (date of registration: 8 January 2019).
“Even if I’m undetectable, I just feel like I would die”: a qualitative study to understand the psychological and socioeconomic impacts of the COVID-19 pandemic on women living with HIV (WLWH) in Chicago, IL
Authors: Devlin Samantha A. , Johnson Amy K. , McNulty Moira C. , Joseph Olivier L. , Hall André , Ridgway Jessica P.
Published: June 2022

Background

The COVID-19 pandemic has affected the health and well-being of people worldwide, yet few studies have qualitatively examined its cumulative effects on ciswomen living with HIV (WLWH). We aimed to explore how the pandemic has impacted WLWH, including challenges related to HIV care, employment, finances, and childcare. We also investigated how HIV status and different psychosocial stressors affected their mental health.

Methods

We performed 25 semi-structured qualitative interviews with WLWH regarding the ways in which COVID-19 impacted their social determinants of health and physical well-being during the pandemic. 19 WLWH who received care at the University of Chicago Medicine (UCM) and 6 women who received care at Howard Brown Health, a federally qualified health center (FQHC) in Chicago, were interviewed remotely from June 2020 to April 2021. All interviews were audio recorded and transcribed. Interviews were thematically analyzed for commonalities regarding HIV-specific and general experiences of WLWH during the pandemic.

Results

The majority of participants reported COVID-19 impacted their HIV care, such as appointment cancellations and difficulties adhering to antiretroviral therapy. In addition to HIV care obstacles, almost all participants described perceived heightened vulnerability to or fear of COVID-19. The pandemic also affected the socioeconomic well-being of participants, with reported financial strains and employment disruptions. Some mothers took on additional childcare responsibilities, such as homeschooling. Increased mental health concerns and negative psychological effects from the social isolation associated with the pandemic were also experienced by most participants.

Conclusions

We gained invaluable insight into how WLWH were challenged by and adapted to the COVID-19 pandemic, including its destabilizing effects on their HIV care and mental health. Women described how they undertook additional childcare responsibilities during the pandemic and how their HIV status compounded their concerns (e.g., perceived heightened vulnerability to COVID-19). Strategies to better support WLWH in maintaining their overall health throughout the pandemic include childcare assistance, access to affordable mental health services, support groups, and education from HIV care providers. These findings have significant implications for examining future health crises through the perspective of potential gender inequalities.
Comparison of the BOPPPS model and traditional instructional approaches in thoracic surgery education
Authors: Hu Kang , Ma Rui-Jie , Ma Chao , Zheng Qing-Kang , Sun Zhi-Gang
Published: June 2022

Background

BOPPPS (bridge-in, learning objective, pretest, participatory learning, posttest, and summary) is a student-centered modular teaching model that improves classroom teaching effectiveness. This study’s primary aim was to explore whether the BOPPPS model has advantages over traditional instructional approaches in teaching lung cancer courses to clinical medical interns.

Methods

A total of 88 students majoring in clinical medicine of Shandong First Medical University and Shandong University, who had clinical practice in thoracic surgery from January 2018 to December 2019, were divided into two groups, receiving the same lung cancer teaching content. The experimental group (n = 44) utilized the BOPPPS model, while the control group (n = 44) used the traditional instructional approach. A questionnaire was used to attain the students’ satisfaction and self-evaluation of the course, and a post-study examination was used to assess end-of-course performance.

Results

The experimental group’s theoretical examination scores with the BOPPPS teaching model were significantly higher than those in the control group. Students preferred the BOPPPS model more than the traditional instructional approach in course satisfaction, student–teacher interaction, learning initiative, analytical ability, clinical thinking ability, and self-study ability (p < 0.05).

Conclusions

Compared with the traditional instructional approach. The BOPPPS model can better inspire clinical medical students’ enthusiasm for thoracic surgery and enhance the students' comprehensive ability. In a word, the BOPPPS model has better teaching effectiveness in the clinical teaching practice of thoracic surgery, which is worthy of reference and popularization.
Using an interprofessional competency framework to enhance collaborative pediatric nursing education and practice
Authors: Bally Jill M. G. , Spurr Shelley , Hyslop Shannon , Hodgson-Viden Heather , McNair Erick D.
Published: June 2022

Background

Interprofessional education (IPE) provides healthcare students with the knowledge and skills necessary to provide safe and effective collaborative care in a variety of clinical settings. Inclusion of IPE in nursing curricula is required for program accreditation in Canada; a variety of learning strategies at varied levels are used to meet this requirement. As this formal requirement only occurred over the last decade, development, facilitation, and evaluation of IPE interventions are ongoing.

Purpose

The purpose of this study was to examine if exposure to an introductory IPE activity influenced third-year undergraduate nursing students’ perceived ability to practice competent interprofessional collaboration (IPC).

Methods

The introductory IPE activity included ten-hours of interactive lectures and related case studies, grounded in the National Interprofessional Competency Framework, delivered by various healthcare professionals in a third-year nursing theory and clinical course. Following completion of the courses, quantitative data were collected via the Interprofessional Collaborative Competencies Attainment Survey (ICCAS) which was used to evaluate nursing students’ change in competencies for IPC. Frequencies, percentages, and means were used to analyze the demographic data, the Cronbach’s alpha coefficient was used to evaluate the internal reliability of the ICCAS, and paired t-tests were conducted to measure the difference from pre- to post-participation for all 20 items and 6 subscales of the ICCAS.

Results

Study participants (n = 111) completed the ICCAS at the end of the courses to measure change in six competencies. The survey results indicated improvements in all competencies following the IPE activity.

Conclusions

The significant findings demonstrate that exposure to introductory IPE activities, involving nursing students and other healthcare professionals, hold promise for enhancing IPC in pediatric clinical settings. These findings can be used to inform the development of formal IPE interventions.
Targeted RNA next generation sequencing analysis of cervical smears can predict the presence of hrHPV-induced cervical lesions
Authors: Andralojc Karolina M. , Elmelik Duaa , Rasing Menno , Pater Bernard , Siebers Albert G. , Bekkers Ruud , Huynen Martijn A. , Bulten Johan , Loopik Diede , Melchers Willem J. G. , Leenders William P. J.
Published: June 2022

Background

Because most cervical cancers are caused by high-risk human papillomaviruses (hrHPVs), cervical cancer prevention programs increasingly employ hrHPV testing as a primary test. The high sensitivity of HPV tests is accompanied by low specificity, resulting in high rates of overdiagnosis and overtreatment. Targeted circular probe-based RNA next generation sequencing (ciRNAseq) allows for the quantitative detection of RNAs of interest with high sequencing depth. Here, we examined the potential of ciRNAseq-testing on cervical scrapes to identify hrHPV-positive women at risk of having or developing high-grade cervical intraepithelial neoplasia (CIN).

Methods

We performed ciRNAseq on 610 cervical scrapes from the Dutch cervical cancer screening program to detect gene expression from 15 hrHPV genotypes and from 429 human genes. Differentially expressed hrHPV- and host genes in scrapes from women with outcome “no CIN” or “CIN2+” were identified and a model was built to distinguish these groups.

Results

Apart from increasing percentages of hrHPV oncogene expression from “no CIN” to high-grade cytology/histology, we identified genes involved in cell cycle regulation, tyrosine kinase signaling pathways, immune suppression, and DNA repair being expressed at significantly higher levels in scrapes with high-grade cytology and histology. Machine learning using random forest on all the expression data resulted in a model that detected ‘no CIN’ versus CIN2+ in an independent data set with sensitivity and specificity of respectively 85 ± 8% and 72 ± 13%.

Conclusions

CiRNAseq on exfoliated cells in cervical scrapes measures hrHPV-(onco)gene expression and host gene expression in one single assay and in the process identifies HPV genotype. By combining these data and applying machine learning protocols, the risk of CIN can be calculated. Because ciRNAseq can be performed in high-throughput, making it cost-effective, it can be a promising screening technology to stratify women at risk of CIN2+. Further increasing specificity by model improvement in larger cohorts is warranted.
Evaluation of GeneXpert EV assay for the rapid diagnosis of enteroviral meningitis: a systematic review and meta-analysis
Authors: Lin Min , Li Yun-Ran , Lan Qi-Wen , Long Li-Jun , Liu Jia-Qi , Chen Ying-Wen , Cao Xun-Jie , Wu Ge-Yuan , Li Ya-Ping , Guo Xu-Guang
Published: June 2022

Background

GeneXpert enterovirus Assay is a PCR-based assay for Enterovirus meningitis diagnosis. However, there is currently no research about the performance of GeneXpert enterovirus assay in the diagnosis of enterovirus meningitis. Thus, a systematic review and meta-analysis is significant on the topic.

Methods

Embase, Cochrane Library, Web of Science, and PubMed were systematically reviewed with retrieval types. Some criteria were used to filter the studies. Only studies published in English, that made a comparison between GeneXpert enterovirus assay and RT-PCR, and could be formulated in a 2*2 table, were included. The quality of the included studies was evaluated by QUADAS-2. The effect of the GeneXpert enterovirus assay was assessed by the Sensitivity, Specificity, Positive Likelihood Ratio, Negative Likelihood Ratio, Diagnosis Odds Ratio, and summary receiver operating characteristic (SROC) curve. Publication bias and heterogeneity were evaluated by the Deeks' funnel test and Bivariate Box plot respectively.

Results

7 studies were recruited in the analysis. The Pooled Sensitivity was 0.96 [95% CI (0.94–0.97)], Pooled Specificity was 0.99 [95% CI (0.98–0.99)], Positive Likelihood Ratio was 130.46 [95% CI (35.79–475.58)], Negative Likelihood Ratio was 0.04 [95% CI (0.02–0.10)], and Diagnostic Odds Ratio was 3648.23 (95% CI [963.99–13,806.72)]. In SROC Curve, Area Under Curve (AUC) was 0.9980, and Q*= 0.9849. In Deeks' funnel test, the P-value was 0.807 (P > 0.05), indicating no publication bias. The Bivariate Box plot indicated no evident heterogeneity.

Conclusions

The GeneXpert enterovirus assay demonstrated high diagnostic accuracy in diagnosing enterovirus meningitis.
Identification of different proteins binding to Na, K-ATPase α1 in LPS-induced ARDS cell model by proteomic analysis
Authors: Wen Xu-Peng , Long Guo , Zhang Yue-Zhong , Huang He , Liu Tao-Hua , Wan Qi-Quan
Published: June 2022

Background

Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear.

Methods

Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Data are available via ProteomeXchange with identifier PXD032209. The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot.

Results

Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein–protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1).

Conclusions

In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.

Graphical Abstract
Socio-demographic and psychiatric profile of patients hospitalized due to self-poisoning with suicidal intention
Authors: Lumpe Maja , Schurr Johannes , Rabe Christian , Ott Armin , Zellner Tobias , Rentrop Michael , Eyer Florian , Geith Stefanie
Published: June 2022

Objective

To identify the psychiatric profile of patients hospitalized due to self-intoxication associated with suicide-related behavior (SRB).

Methods

In this retrospective single-center study, records of consecutive patients treated for suicidal poisoning in our Clinical Toxicology unit between 1st January 2012 and 31st December 2016, who received at least one psychiatric exploration during their inpatient stay, were analyzed with regard to epidemiological data, ingested substances, psychiatric and somatic comorbidities, suicidal circumstances and follow-up therapy.

Results

Out of 1289 hospitalized patients, 1090 patients with complete data were analyzed. Mean age was 40.5 ± 17.2 years, 66.7% were female. 32.0% of patients had previously engaged in SRB, in 76.3% intention was suicidal. 64.7% of patients had a pre-existing psychiatric disorder (PD). Patients with a pre-existing PD more often displayed prior SRB than those without PD (40.7% vs 15.3%; p < 0.001; Fisher′s exact test), used long-term/on demand medication (70.2% vs 38.9%; p < 0.001), distanced themselves from the current suicide attempt (65.9% vs 50.8%; p < 0.001) and had no detectable trigger (38.7% vs 18.1%; p < 0.001). Partnership conflict was the most commonly named trigger, and it was documented more often in patients without than in those with PD (41.6% vs 25.6%). After psychiatric reevaluation, most patients were diagnosed with mood disorders (29.7%) and stress disorders (17.0%); 32.8% of patients had a combination of two or more PDs.

Conclusion

Hospitalization due to self-poisoning is associated with pre-existing PD, prior SRB and access to psychiatric medication. Detection of these risk factors could allow timely introduction of effective preventive measures tailored to particularly vulnerable subgroups and appropriate relief. However, lack of a detectable trigger in many cases may hamper the identification of those at risk.
Diffusion weighted imaging and diffusion kurtosis imaging in abdominal oncological setting: why and when
Authors: Granata Vincenza , Fusco Roberta , Belli Andrea , Danti Ginevra , Bicci Eleonora , Cutolo Carmen , Petrillo Antonella , Izzo Francesco
Published: June 2022

This article provides an overview of diffusion kurtosis (DKI) imaging in abdominal oncology. DKI allows for more data on tissue structures than the conventional diffusion model (DWI). However, DKI requires high quality images at b-values greater than 1000 s/mm2 and high signal-to-noise ratio (SNR) that traditionally MRI systems are not able to acquire and therefore there are generally amplified anatomical distortions on the images due to less homogeneity of the field. Advances in both hardware and software on modern MRI scanners have currently enabled ultra-high b-value imaging and offered the ability to apply DKI to multiple extracranial sites. Previous studies have evaluated the ability of DKI to characterize and discriminate tumor grade compared to conventional DWI. Additionally, in several studies the DKI sequences used were based on planar echo (EPI) acquisition, which is susceptible to motion, metal and air artefacts and prone to low SNRs and distortions, leading to low quality images for some small lesions, which may affect the accuracy of the results. Another problem is the optimal b-value of DKI, which remains to be explored and not yet standardized, as well as the manual selection of the ROI, which could affect the accuracy of some parameters.
Retraction Note: Curcumin synergizes with 5-fluorouracil by impairing AMPK/ULK1-dependent autophagy, AKT activity and enhancing apoptosis in colon cancer cells with tumor growth inhibition in xenograft mice
Authors: Zhang Pan , Lai Ze-Lin , Chen Hui-Fen , Zhang Min , Wang An , Jia Tao , Sun Wen-Qin , Zhu Xi-Min , Chen Xiao-Feng , Zhao Zheng , Zhang Jun
Published: June 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-022-02409-y.
Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein
Authors: Zhang Lingbing , Zhang Yandan , Qin Xia , Jiang Xuejun , Zhang Jun , Mao Lejiao , Jiang Ziqi , Jiang Yu , Liu Gang , Qiu Jingfu , Chen Chengzhi , Qiu Feng , Zou Zhen
Published: June 2022

Background

SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin–angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS. Recombinant ACE2 protein (rACE2) has been demonstrated to play protective role against SARS-CoV and avian influenza-induced ALI, and more relevant, rACE2 inhibits SARS-CoV-2 proliferation in vitro. However, whether rACE2 protects against SARS-CoV-2-induced ALI in animal models and the underlying mechanisms have yet to be elucidated.

Methods and Results

Here, we demonstrated that the SARS-CoV-2 spike receptor-binding domain (RBD) protein aggravated lipopolysaccharide (LPS)-induced ALI in mice. SARS-CoV-2 spike RBD protein directly binds and downregulated ACE2, leading to an elevation in angiotensin (Ang) II. AngII further increased the NOX1/2 through AT1R, subsequently causing oxidative stress and uncontrolled inflammation and eventually resulting in ALI/ARDS. Importantly, rACE2 remarkably reversed SARS-CoV-2 spike RBD protein-induced ALI by directly binding SARS-CoV-2 spike RBD protein, cleaving AngI or cleaving AngII.

Conclusion

This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT1R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI.
CONET: copy number event tree model of evolutionary tumor history for single-cell data
Authors: Markowska Magda , Cąkała Tomasz , Miasojedow BłaŻej , Aybey Bogac , Juraeva Dilafruz , Mazur Johanna , Ross Edith , Staub Eike , Szczurek Ewa
Published: June 2022

Copy number alterations constitute important phenomena in tumor evolution. Whole genome single-cell sequencing gives insight into copy number profiles of individual cells, but is highly noisy. Here, we propose CONET, a probabilistic model for joint inference of the evolutionary tree on copy number events and copy number calling. CONET employs an efficient, regularized MCMC procedure to search the space of possible model structures and parameters. We introduce a range of model priors and penalties for efficient regularization. CONET reveals copy number evolution in two breast cancer samples, and outperforms other methods in tree reconstruction, breakpoint identification and copy number calling.
Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial
Authors: Ntinginya Nyanda Elias , te Brake Lindsey , Sabi Issa , Chamba Nyasatu , Kilonzo Kajiru , Laizer Sweetness , Andia-Biraro Irene , Kibirige Davis , Kyazze Andrew Peter , Ninsiima Sandra , Critchley Julia A. , Romeo Renee , van de Maat Josephine , Olomi Willyhelmina , Mrema Lucy , Magombola David , Mwayula Issakwisa Habakkuk , Sharples Katrina , Hill Philip C. , van Crevel Reinout ,   On behalf of the PROTID Consortium
Published: June 2022

Background

Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP).

Methods

The ‘Prevention of tuberculosis in diabetes mellitus’ (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM.

Discussion

PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control.

Trial registration

ClinicalTrials.govNCT04600167. Registered on 23 October 2020
Ventilator-associated pneumonia prevention in the Intensive care unit using Postpyloric tube feeding in China (VIP study): study protocol for a randomized controlled trial
Authors: Hu Linhui , Peng Kaiyi , Huang Xiangwei , Wang Zheng , Wu Quanzhong , Xiao Yumei , Hou Yating , He Yuemei , Zhou Xinjuan , Chen Chunbo
Published: June 2022

Background

Ventilator-associated pneumonia is a challenge in critical care and is associated with high mortality and morbidity. Although some consensuses on preventing ventilator-associated pneumonia are reached, it is still somewhat controversial. Meta-analysis has shown that postpyloric tube feeding may reduce the incidences of ventilator-associated pneumonia, which still desires high-quality evidence. This trial aims to evaluate the efficacy and safety profiles of postpyloric tube feeding versus gastric tube feeding.

Methods/design

In this multicenter, open-label, randomized controlled trial, we will recruit 924 subjects expected to receive mechanical ventilation for no less than 48 h. Subjects on mechanical ventilation will be randomized (1:1) to receive postpyloric or gastric tube feeding and routine preventive measures simultaneously. The primary outcome is the proportion of patients with at least one ventilator-associated pneumonia episode. Adverse events and serious adverse events will be observed closely.

Discussion

The VIP study is a large-sample-sized, multicenter, open-label, randomized, parallel-group, controlled trial of postpyloric tube feeding in China and is well-designed based on previous studies. The results of this trial may help to provide evidence-based recommendations for the prevention of ventilator-associated pneumonia.

Trial registration

Chictr.org.cnChiCTR2100051593. Registered on 28 September 2021
Cardiovascular health and four epigenetic clocks
Authors: Lo Yun-Hsiang , Lin Wan-Yu
Published: June 2022

Background

Cardiovascular health (CVH) was defined by the American Heart Association as an integrative idealness of seven clinical or lifestyle factors. Based on populations of European ancestry, recent studies have shown that ideal CVH is associated with a slower aging rate. The aging rate is measured by levels of epigenetic age acceleration (EAA), usually obtained from the residuals of regressing DNA methylation (DNAm) age on chronological age. However, little has been known about the association of CVH with biological aging in Asian populations.

Methods and results

We here analyzed blood DNAm data and clinical/lifestyle factors of 2474 Taiwan Biobank (TWB) participants, to investigate the association of CVH with EAA. CVH was assessed by seven components: smoking status, physical activity, dietary habits, body mass index, total cholesterol, fasting glucose, and blood pressure levels. Four measures of EAA were applied, among which two were based on the first-generation DNAm clocks (HannumEAA and IEAA) and two were based on the second-generation clocks (PhenoEAA and GrimEAA). After excluding 276 individuals with cardiovascular diseases, we regressed EAA on the CVH score (ranging from 0 to 7, integrating the abovementioned seven components) while adjusting for sex, drinking status, and educational attainment.

Our results showed that a decrease in one point in the CVH score was associated with a 0.350-year PhenoEAA (p = 4.5E−4) and a 0.499-year GrimEAA (p = 4.2E−15). By contrast, HannumEAA and IEAA were not significantly associated with the CVH score. We have obtained consistent results within each generation of epigenetic clocks.

Conclusions

This is one of the first studies to comprehensively investigate the associations of CVH with four epigenetic clocks. Our TWB data showed that ideal CVH is associated with lower levels of EAA calculated according to the second-generation epigenetic clocks (PhenoEAA and GrimEAA). Having an ideal CVH status can lower EAA and reduce the risk of aging-related disorders.
Progressive multifocal leukoencephalopathy in a patient with novel mutation in the RAC2 gene: a case report
Authors: Bahrami Sima , Arshi Saba , Nabavi Mohammad , Bemanian Mohammad Hassan , Fallahpour Morteza , Rezaeifar Afshin , Shokri Sima
Published: June 2022

Background

Progressive multifocal leukoencephalopathy is a rare demyelinating disease that is often secondary to lytic destruction of oligodendrocytes and, to a lesser extent, to astrocytes’ response to human neurotrophic John Cunningham polyomavirus. Any underlying congenital disorder of primary or secondary immunodeficiency may predispose to virus infection and possible invasion of the brain. We present the first reported case of progressive multifocal leukoencephalopathy due to a mutation in the RAC2 gene.

Case presentation

We describe the case of a 34-year-old Iranian man with recurrent infections from the age of 2 years, along with other disorders such as nephritic syndrome, factor XI deficiency, and hypogammaglobulinemia. He was treated regularly with intravenous immunoglobulin from the age of 10 years with a diagnosis of common variable immune deficiency. Genetic testing confirmed a novel homozygous mutation in the RAC2 gene in the patient. Owing to the onset of neurological symptoms a few months ago, the patient was completely avaluated, which confirmed the diagnosis of PML. Despite all efforts, the patient died shortly after progression of neurological symptoms.

Conclusions

According to previous studies, progressive multifocal leukoencephalopathy has been associated with 26 cases of primary immunodeficiency. Our patient presents a new case of primary immunodeficiency with progressive multifocal leukoencephalopathy. Accurate examination of these cases can help us to gain insight into the immune response to John Cunningham virus and better treat this potentially deadly disease.
DECIMER—hand-drawn molecule images dataset
Authors: Brinkhaus Henning Otto , Zielesny Achim , Steinbeck Christoph , Rajan Kohulan
Published: June 2022

The translation of images of chemical structures into machine-readable representations of the depicted molecules is known as optical chemical structure recognition (OCSR). There has been a lot of progress over the last three decades in this field, but the development of systems for the recognition of complex hand-drawn structure depictions is still at the beginning. Currently, there is no data for the systematic evaluation of OCSR methods on hand-drawn structures available. Here we presentDECIMER — Hand-drawn molecule images, a standardised, openly available benchmark dataset of 5088 hand-drawn depictions of diversely picked chemical structures. Every structure depiction in the dataset is mapped to a machine-readable representation of the underlying molecule. The dataset is openly available and published under the CC-BY 4.0 licence which applies very few limitations. We hope that it will contribute to the further development of the field.

Graphical Abstract