bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep learning radiomics of dual-modality ultrasound images for hierarchical diagnosis of unexplained cervical lymphadenopathy
Authors: Zhu Yangyang , Meng Zheling , Fan Xiao , Duan Yin , Jia Yingying , Dong Tiantian , Wang Yanfang , Song Juan , Tian Jie , Wang Kun , Nie Fang
Published: August 2022

Background

Accurate diagnosis of unexplained cervical lymphadenopathy (CLA) using medical images heavily relies on the experience of radiologists, which is even worse for CLA patients in underdeveloped countries and regions, because of lack of expertise and reliable medical history. This study aimed to develop a deep learning (DL) radiomics model based on B-mode and color Doppler ultrasound images for assisting radiologists to improve their diagnoses of the etiology of unexplained CLA.

Methods

Patients with unexplained CLA who received ultrasound examinations from three hospitals located in underdeveloped areas of China were retrospectively enrolled. They were all pathologically confirmed with reactive hyperplasia, tuberculous lymphadenitis, lymphoma, or metastatic carcinoma. By mimicking the diagnosis logic of radiologists, three DL sub-models were developed to achieve the primary diagnosis of benign and malignant, the secondary diagnosis of reactive hyperplasia and tuberculous lymphadenitis in benign candidates, and of lymphoma and metastatic carcinoma in malignant candidates, respectively. Then, a CLA hierarchical diagnostic model (CLA-HDM) integrating all sub-models was proposed to classify the specific etiology of each unexplained CLA. The assistant effectiveness of CLA-HDM was assessed by comparing six radiologists between without and with using the DL-based classification and heatmap guidance.

Results

A total of 763 patients with unexplained CLA were enrolled and were split into the training cohort (n=395), internal testing cohort (n=171), and external testing cohorts 1 (n=105) and 2 (n=92). The CLA-HDM for diagnosing four common etiologies of unexplained CLA achieved AUCs of 0.873 (95% CI: 0.838–0.908), 0.837 (95% CI: 0.789–0.889), and 0.840 (95% CI: 0.789–0.898) in the three testing cohorts, respectively, which was systematically more accurate than all the participating radiologists. With its assistance, the accuracy, sensitivity, and specificity of six radiologists with different levels of experience were generally improved, reducing the false-negative rate of 2.2–10% and the false-positive rate of 0.7–3.1%.

Conclusions

Multi-cohort testing demonstrated our DL model integrating dual-modality ultrasound images achieved accurate diagnosis of unexplained CLA. With its assistance, the gap between radiologists with different levels of experience was narrowed, which is potentially of great significance for benefiting CLA patients in underdeveloped countries and regions worldwide.
Differential enrichment of H3K9me3 in intrahepatic cholangiocarcinoma
Authors: Hu Sheng , Wang Xuejun , Wang Tao , Wang Lianmin , Liu Lixin , Ren Wenjun , Liu Xiaoyong , Zhang Weihan , Liao Weiran , Liao Zhoujun , Zou Renchao , Zhang Xiaowen
Published: August 2022

Background

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor, which poses a serious threat to human health. Histone 3 lysine 9 trimethylation (H3K9me3) is a post-translational modification involved in regulating a broad range of biological processes and has been considered as potential therapeutic target in types of cancer. However, there is limited research on investigating profiles of histone modification H3K9me3 in ICC patients.

Methods

In this study, we applied the ChIP-seq technique to investigate the effect of H3K9me3 on ICC. Anti-H3K9me3 antibody was used for ChIP-seq in ICC (RBE cell lines) and HIBEpic (normal cell lines). MACS2 (peak-calling tools) was then used to identify the peaks recorded in RBE and HIBEpic cell lines. Gene expression, mutation and clinical data were downloaded from TCGA and cBioPortal databases.

Results

H3K9me3 exhibited abnormal methylation and influenced the process of abnormal gene expression in patients suffering from ICC. The Wnt/β-Catenin signaling pathway (also known as simply the WNT signaling pathway) was enriched in H3K9me3-regulated genes.

Conclusions

We are the first to report that H3K9me3 may play an important role in the progression of ICC. It promotes the understanding of epigenetic molecular mechanisms for ICC.
Down-regulated miR-146a expression with increased neutrophil extracellular traps and apoptosis formation in autoimmune-mediated diffuse alveolar hemorrhage
Authors: Hsieh Yu-Tung , Chou Yu-Chi , Kuo Pin-Yu , Tsai Hung-Wen , Yen Yi-Ting , Shiau Ai-Li , Wang Chrong-Reen
Published: August 2022

Background

Increasing evidences have suggested an important role of microRNAs (miRNAs) in regulating cell death processes including NETosis and apoptosis. Dysregulated expression of miRNAs and increased formation of neutrophil extracellular traps (NETs) and apoptosis participate in autoimmune-mediated diffuse alveolar hemorrhage (DAH), mostly associated with pulmonary capillaritis in systemic lupus erythematosus (SLE) patients. In particular, besides the inhibition of apoptosis, miR-146a can control innate and acquired immune responses, and regulate the toll-like receptor pathway through targeting TRAF6 to reduce the expression of pro-inflammatory cytokines/chemokines like IL-8, a NETosis inducer.

Methods

Expression of miR-146a, TRAF6 and NETs were examined in peripheral blood neutrophils (PBNs) and lung tissues from SLE-associated DAH patients, and in neutrophils and pristane-induced DAH lung tissues from C57BL/6 mice. To assess NETs formation, we examined NETosis-related DNAs morphology and crucial mediators including protein arginine deiminase 4 and citrullinated Histone 3. Expression of miR-146a and its endogenous RNA SNHG16 were studied in HL-60 promyelocytic cells and MLE-12 alveolar cells during NETosis and apoptosis processes, respectively. MiR-146a-overexpressed and CRISPR-Cas13d-mediated SNHG16-silenced HL-60 cells were investigated for NETosis. MiR-146a-overexpressed MLE-12 cells were analyzed for apoptosis. Pristane-injected mice received intra-pulmonary miR-146a delivery to evaluate therapeutic efficacy in DAH.

Results

In DAH patients, there were down-regulated miR-146a levels with increased TRAF6 expression and PMA/LPS-induced NETosis in PBNs, and down-regulated miR-146a levels with increased TRAF6, high-mobility group box 1 (HMGB1), IL-8, NETs and apoptosis expression in lung tissues. HMGB1-stimulated mouse neutrophils had down-regulated miR-146a levels with increased TRAF6, IL-8 and NETs expression. PMA-stimulated HL-60 cells had down-regulated miR-146a levels with enhanced NETosis. MiR-146a-overexpressed or SNHG16-silenced HL-60 cells showed reduced NETosis. Apoptotic MLE-12 cells had down-regulated miR-146a expression and increased HMGB1 release, while miR-146a-overexpressed MLE-12 cells showed reduced apoptosis and HMGB1 production. There were down-regulated miR-146a levels with increased TRAF6, HMGB1, IL-8, NETs and apoptosis expression in mouse DAH lung tissues. Intra-pulmonary miR-146a delivery could suppress DAH by reducing TRAF6, IL-8, NETs and apoptosis expression.

Conclusions

Our results demonstrate firstly down-regulated pulmonary miR-146a levels with increased TRAF6 and IL-8 expression and NETs and apoptosis formation in autoimmune-mediated DAH, and implicate a therapeutic potential of intra-pulmonary miR-146a delivery.
Remodeling of tumor microenvironment for enhanced tumor chemodynamic/photothermal/chemo-therapy
Authors: Zhang Ying , Zhu Jingyao , Zhang Zheng , He Dannong , Zhu Jun , Chen Yunsheng , Zhang Yixin
Published: August 2022

The anticancer treatment is largely affected by the microenvironment of the tumors, which not only resists the tumors to the thermo/chemo-therapy, but also promotes their growth and invasion. In this work, the angiogenesis factor is balanced by combining with the breathing hyperoxygen, for regulating the tumor microenvironment and also for relieving hypoxia and high tissue interstitial pressure, which promote drug delivery to tumor tissues by increasing the in vivo perfusion and reversing the immunosuppressive tumor. In addition, the designed multifunctional nanoparticles have a great potential for applications to the tumor dual-mode imaging including magnetic resonance (MR) and photoacoustic (PA) imaging. This work proposes a promising strategy to enhance the thermo/chemo-therapy efficacy by remodeling the tumor microenvironment, which would provide an alternative to prolong the lifetime of tumor patients.

Graphical Abstract
A case study of combined neoadjuvant chemotherapy and neoadjuvant immunotherapy in resectable locally advanced esophageal cancer
Authors: Dai Huiru , Liu Minling , Li Xueying , Li Tingwei , Huang Wensheng , Liao Jiehao , Li Yun , Fang Shuo
Published: August 2022

Background

The prognosis of patients under existing neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy requires improvement. Whereas programmed cell death 1 (PD-1) inhibitors have shown promising response in advanced esophageal cancer, they have not been used in the perioperative treatment of resectable locally advanced esophageal cancer. Whether immunotherapy can be incorporated into neoadjuvant therapy has became a challenging question for researchers.

Case presentation

We present a case of a 65-year-old male who had a history of progressive dysphagia for approximately 1 month. He underwent pertinent studies including computed tomography (CT)，gastroscopy，and pathological biopsy resulting in a diagnosis of medium-low differentiated squamous carcinoma of the thoracic segment of the esophagus (cT2N2M0 stage III). After 4 cycles of neoadjuvant chemotherapy combined with immunotherapy, gastroscopy showed the lesion in the esophagus was no longer present. Subsequently, the patient received thoracoscopic radical resection of esophageal cancer and achieved a pathological complete response (pCR) in postoperative pathological evaluation. During the whole treatment, no adverse effect was recorded and to date no evidence of recurrence has been recorded.

Conclusion

Our report suggest that neoadjuvant chemotherapy combined with immunotherapy not only improve the R0 resection and pCR rate in patients with resectable locally advanced esophageal cancer, but also the adverse effects are within the control range. However, the selection of therapeutic strategy, predictors of response to treatment, and interval time between neoadjuvant treatment and surgery still await more reliable evidence-based studies with large prospective samples.
MiR-1254 suppresses the proliferation and invasion of cervical cancer cells by modulating CD36
Authors: Zhang Jun , Li Xing , Yang Jing , Zhang Yan
Published: August 2022

Background

This study aimed to elucidate the roles of miR-1254 in cervical cancer progression and to explore the underlying mechanisms.

Methods

The expression levels of miR-1254 in normal-cancer cervical tissues and cells were measured using quantitive real-time polymerase chain reaction (qRT-PCR). The invasive and proliferative abilities of cervical cancer cell lines transfected with negative control (NC) mimic or miR-1254 mimic were measured using transwell, CCK-8, and colony formation assays. The binding sites between CD36 and miR-1254 were determined using luciferase reporter assays. The correlation of CD36 and miR-1254 with cervical cancer development was re-confirmed by co-transfection of miR-1254 mimic and CD36 overexpression using CCK-8, colony formation, transwell and western blot assays.

Results

MiR-1254 was expressed at significantly lower levels in the cervical cancer cell lines and tissues than in the controls. The functional assays revealed that upregulation of miR-1254 inhibited the invasion and proliferation of cervical cancer cells. The luciferase reporter assays demonstrated that CD36 messenger RNA and miR-1254 bound to one another. CD36 overexpression reversed the inhibitory effects of upregulated miR-1254 in the cervical cancer cells, suggesting that miR-1254 regulates cervical cancer progression by modulating CD36.

Conclusion

miR-1254 attenuated the invasion and proliferation of cervical cancer cells by modulating the expression levels of CD36.
A rare left ventricular cardiac myxoma mimicking fibroma
Authors: Xia Liang-Yan , Zhu Hong-Ling , Li Rong-Hang , Pan Xiao-Hua , Liu Bo , Xu Jing
Published: August 2022

Background

In most cases, it is not difficult to differentiate common left ventricular (LV) cardiac myxomas from fibromas because they are different disease entities and have different imaging findings. Herein, we present a case of a tumor with histological characteristics of a LV cardiac myxoma even though its imaging and macroscopical views were similar to that of fibroma.

Case presentation

A 65-year-old woman was admitted to the hospital with chest tightness and palpitations which persisted for 2 years. Transthoracic echocardiogram and transesophageal echocardiography revealed a 23 mm × 8 mm, polyp-like-shaped, homogeneous, firm, solitary, mobile and solitary LV mass, which protruded into the left atrium during systole, resulting in mild mitral regurgitation. LV contrast-enhanced echocardiography revealed that there was little contrast agent filling in the LV mass. To further clarify the nature of the mass, non-enhanced and contrast-enhanced coronary computed tomography (CT) angiograms showed a 19 mm × 8 mm relatively homogeneous low density with punctate calcifications mass and no significant enhancement. Thus, we preoperatively diagnosed her condition as a LV fibroma and performed excision of the tumor under cardiopulmonary by-pass by using port-access approach through right mini-thoracotomy. The postoperative pathological diagnosis of the tumor was in fact a LV myxoma.

Conclusions

LV cardiac myxomas mimicking fibroma makes diagnosis difficult, and sonographers should be aware of this imaging changes.
Challenges, facilitators and barriers to the adoption and use of a web-based national IRD registry: lessons learned from the IRD-PT registry
Authors: Marques João Pedro , Vaz-Pereira Sara , Costa José , Marta Ana , Henriques José , Silva Rufino
Published: August 2022

Rare disease registries increase research accessibility for patients, while providing clinicians/investigators with a coherent data ecosystem necessary to boost research and patient care. The IRD-PT registry is a national, web-based, interoperable registry for inherited retinal degenerations (IRDs) designed to generate scientific knowledge and collect high-quality data on the epidemiology, genomic landscape and natural history of IRDs in Portugal. In two years, the number of enrolled patients almost doubled (537 to 1060). Still, the registry has a lower-than-expected adoption rate, with only 4 centers across Portugal actively enrolling patients. This highlights a strong need to understand factors that may be hindering the registry’s nationwide adoption. The purpose of this manuscript is to analyze challenges, facilitators and barriers to the adoption and use of the IRD-PT registry, and to discuss avenues for improvement, focusing on keeping the registry sustainable in the long run. We believe that this exercise may help other rare disease registries to improve user adherence and engagement, ultimately contributing to develop more sustainable and successful registries in the field.
Irradiation induces DJ-1 secretion from esophageal squamous cell carcinoma cells to accelerate metastasis of bystander cells via a TGF-β1 positive feedback loop
Authors: Gu Junjie , Sun Yuanyuan , Song Jiahang , Zhao Ruiling , Di Xiaoke , Zhang Yumeng , Ge Xiaolin , Zhang Shu , Gu Yun , Sun Xinchen
Published: August 2022

Background

Radiation-induced bystander effect (RIBE) can promote tumor metastasis contributing to the failure of radiotherapy for esophageal squamous cell carcinoma (ESCC). Aberrant expression of DJ-1 has been identified in ESCC; however, the relationship between DJ-1 and RIBE in ESCC remains unknown.

Methods

We detected DJ-1 in the serum and cell supernatants by enzyme-linked immunosorbent assay (ELISA) and evaluated tumor metastasis by phenotypic experiments in vivo and in vitro. RNA-seq, mass spectrometry, western blot (WB), immunoprecipitation (IP), and dual-luciferase reporter assays were performed to explore the underlying mechanisms.

Results

DJ-1 was highly expressed in the serum of patients with ESCC receiving radiotherapy and was significantly overexpressed in the medium of ESCC cells receiving irradiation. DJ-1 promoted tumor metastasis via the TGF-β1 pathway. Mechanistic studies revealed that DJ-1 bound to HSC70 to promote Smad3 phosphorylation and nuclear aggregation in a protein-interaction manner, which activated the transcription of Thrombospondin-1 (TSP1). Subsequently, the activation of TGF-β1 by TSP1 re-promoted Smad3 phosphorylation and nuclear aggregation, constituting a positive feedback loop to strengthen the metastasis of ESCC cells, which was effectively blocked by LY2109761 and LSKL. Moreover, higher levels of serum DJ-1 in patients with ESCC were related to a poorer prognosis of radiotherapy.

Conclusions

Irradiation can induce ESCC cells secreting DJ-1. Secreted DJ-1 enters bystander cells to initiate activation of the TGF-β1 pathway via the DJ-1/HSC70/Smad3 signaling axis. The TSP1/TGF-β1/Smad3 positive feedback pathway constitutes the core pathway that promotes ESCC metastasis. DJ-1 is a useful biomarker for predicting the efficacy of radiotherapy and a potential therapeutic target for reversing RIBE in ESCC.

Graphical Abstract

Schematic diagram showing the underlying mechanism
that irradiation-induced secretion of DJ-1 accelerates the metastasis of
bystander ESCC cells.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigen detection in the Emergency Department: data from a pediatric cohort during the fourth COVID-19 wave in Italy
Authors: Pepe Angela , Valitutti Francesco , Veneruso Deborah , Bove Martina , De Anseris Anna Giulia Elena , Nazzaro Lucia , Pisano Pasquale , Melis Daniela , Mandato Claudia
Published: August 2022

Background

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has been challenging health care systems and made it necessary to use rapid and cost-effective testing methods, particularly in Emergency Department (ED) settings. Rapid Antigen Diagnostic Tests (RADTs) are a valid alternative to the gold standard RT-PCR, even in pediatric populations. This retrospective observational study has been conducted on a pediatric cohort afferent to the ED of the San Giovanni di Dio and Ruggi d’Aragona University Hospital in Salerno, tested at Point of Care with RADT Panbio® (Abbott), from September 1st, 2021 to February 28th, 2022, analyzing the positivity rate and clinical features of the cohort, also in reference to the rise of positive cases observed in the aforementioned period, and to the introduction in Italy of SARS-CoV-2 vaccination for children and teens on December 16th, 2021.

Methods

Data regarding access to the pediatric ED were extracted from the hospital’s electronic database system. Parallel to this, we conducted a narrative literature search using PubMed database focusing on the use of RADT in pediatric ED and compared our data with the national pandemic trend.

Results

During the observation period, 1890 patients were tested for the presence of SARS-CoV-2 with RADT and the 2.7% of children resulted positive, with a peak in January 2022. The main symptoms in positive patients were: fever (n = 34; 66.7%), cough (n = 11; 21.5%), headache (n = 4; 7.8%), chest pain (n = 2; 3.9%) and abdominal pain (n = 1; 2%). Patients were divided into three different age groups (A, B, C) basing on the different access timing to vaccination; no statistically significant difference was detected in the distribution of positivity in these three groups (p > 0.05). Number of positive children in group A was greater in the post-vaccine group. Our data are concordant with the national trend of the pandemic showing a fourth wave peak in January 2022.

Conclusion

The use of RADT as a first point-of-care screening may be helpful, time-saving and cost-sparing. Our study shows that, during the observation period, most children admitted to the ED for fever, actually tested positive for SARS-CoV-2 with a statistically greater difference than negative children. Instead, number of patients admitted for cough was statistically higher among negative than positive ones, probably due to the circulation of other respiratory viruses in children.
Early hyperoxia and 28-day mortality in patients on venoarterial ECMO support for refractory cardiogenic shock: a bicenter retrospective propensity score-weighted analysis
Authors: Moussa Mouhamed Djahoum , Beyls Christophe , Lamer Antoine , Roksic Stefan , Juthier Francis , Leroy Guillaume , Petitgand Vincent , Rousse Natacha , Decoene Christophe , Dupré Céline , Caus Thierry , Huette Pierre , Guilbart Mathieu , Guinot Pierre-Grégoire , Besserve Patricia , Mahjoub Yazine , Dupont Hervé , Robin Emmanuel , Meynier Jonathan , Vincentelli André , Abou-Arab Osama
Published: August 2022

Background

The mortality rate for a patient with a refractory cardiogenic shock on venoarterial (VA) extracorporeal membrane oxygenation (ECMO) remains high, and hyperoxia might worsen this prognosis. The objective of the present study was to evaluate the association between hyperoxia and 28-day mortality in this setting.

Methods

We conducted a retrospective bicenter study in two French academic centers. The study population comprised adult patients admitted for refractory cardiogenic shock. The following arterial partial pressure of oxygen (PaO2) variables were recorded for 48 h following admission: the absolute peak PaO2(the single highest value measured during the 48 h), the mean daily peak PaO2(the mean of each day’s peak values), the overall mean PaO2(the mean of all values over 48 h), and the severity of hyperoxia (mild: PaO2 < 200 mmHg, moderate: PaO2 = 200–299 mmHg, severe: PaO2 ≥ 300 mmHg). The main outcome was the 28-day all-cause mortality. Inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in baseline characteristics.

Results

From January 2013 to January 2020, 430 patients were included and assessed. The 28-day mortality rate was 43%. The mean daily peak, absolute peak, and overall mean PaO2values were significantly higher in non-survivors than in survivors. In a multivariate logistic regression analysis, the mean daily peak PaO2, absolute peak PaO2, and overall mean PaO2were independent predictors of 28-day mortality (adjusted odds ratio [95% confidence interval per 10 mmHg increment: 2.65 [1.79–6.07], 2.36 [1.67–4.82], and 2.85 [1.12–7.37], respectively). After IPW, high level of oxygen remained significantly associated with 28-day mortality (OR = 1.41 [1.01–2.08];P = 0.041).

Conclusions

High oxygen levels were associated with 28-day mortality in patients on VA-ECMO support for refractory cardiogenic shock. Our results confirm the need for large randomized controlled trials on this topic.
Evaluation of tumour heterogeneity by 18F-fluoroestradiol PET as a predictive measure in breast cancer patients receiving palbociclib combined with endocrine treatment
Authors: Liu Cheng , Hu Shihui , Xu Xiaoping , Zhang Yongping , Wang Biyun , Song Shaoli , Yang Zhongyi
Published: August 2022

Background

Predictive biomarkers are needed to identify oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer (MBC) patients who would likely benefit from cyclin-dependent kinase 4 and 6 inhibitors combined with endocrine therapy. Therefore, we performed an exploratory study to evaluate the tumour heterogeneity parameters based on 16α-18F-fluoro-17β-oestradiol (18F-FES)-PET imaging as a potential marker to predict progression-free survival (PFS) in MBC patients receiving palbociclib combined with endocrine therapy.

Methods

Fifty-six ER + MBC patients underwent 18F-FES-PET/CT before the initiation of palbociclib. 18F-FES uptake was quantified and expressed as the standardized uptake value (SUV). Interlesional heterogeneity was qualitatively identified according to the presence or absence of 18F-FES-negative lesions. Intralesional heterogeneity was measured by the SUV-based heterogeneity index (HI = SUVmax/SUVmean). Association with survival was evaluated using the Cox proportional hazards model.

Results

A total of 551 metastatic lesions were found in 56 patients: 507 lesions were identified as 18F-FES-positive, 38 lesions were distributed across 10 patients without 18F-FES uptake, and the remaining 6 were liver lesions. Forty-three patients obtained a clinical benefit, and 13 developed progressive disease (PD) within 24 weeks. Nine out of 10 patients with an 18F-FES-negative site developed PD, and the median PFS was only 2.4 months. Among 46 patients with only 18F-FES-positive lesions, only four patients had PD, and the median PFS was 23.6 months. There were statistically significant differences between the two groups (P < 0.001). For the subgroup of patients with only 18F-FES-positive lesions, low FES-HI patients experienced substantially longer PFS times than those with high FES-HI (26.5 months vs. 16.5 months, P = 0.004).

Conclusions

18F-FES-PET may provide a promising method for identifying and selecting candidate ER + /HER2- MBC patients who would most likely benefit from palbociclib combined with endocrine treatment and could serve as a predictive marker for treatment response.

Trial registration NCT04992156, Date of registration: August 5, 2021 (retrospectively registered).
Identifying and correcting repeat-calling errors in nanopore sequencing of telomeres
Authors: Tan Kar-Tong , Slevin Michael K. , Meyerson Matthew , Li Heng
Published: August 2022

Nanopore long-read sequencing is an emerging approach for studying genomes, including long repetitive elements like telomeres. Here, we report extensive basecalling induced errors at telomere repeats across nanopore datasets, sequencing platforms, basecallers, and basecalling models. We find that telomeres in many organisms are frequently miscalled. We demonstrate that tuning of nanopore basecalling models leads to improved recovery and analysis of telomeric regions, with minimal negative impact on other genomic regions. We highlight the importance of verifying nanopore basecalls in long, repetitive, and poorly defined regions, and showcase how artefacts can be resolved by improvements in nanopore basecalling models.
E-Mental-Health aftercare for children and adolescents after partial or full inpatient psychiatric hospitalization: study protocol of the randomized controlled DigiPuR trial
Authors: Finkbeiner Marlene , Kühnhausen Jan , Schmid Johanna , Conzelmann Annette , Dürrwächter Ute , Wahl Lena-Marie , Kelava Augustin , Gawrilow Caterina , Renner Tobias J.
Published: August 2022

Background

During reintegration to daily school life following psychiatric hospitalization, children and adolescents are confronted with various challenges and are at risk for rehospitalization. Tailored post-discharge services could support a successful readjustment and accompany the high-risk transition period after discharge. The study DigiPuR (“Digital gestützte Psychotherapie und Reintegration,” digitally supported psychotherapy and reintegration) aims to establish and to evaluate an innovative digital aftercare program to alleviate challenges during reintegration and improve cross-sectoral care.

Methods

DigiPuR is a randomized controlled trial comparing a digital aftercare service with regular aftercare (TAU) (planned N = 150, 25 children/adolescents, 25 parents, and 25 teachers in each group). In the intervention group, direct communication via secure and regular video calls until 8 weeks after discharge and a secure messenger system between the hospital, family, and school, as well as, if needed, external support systems, are established. A longitudinal pre-post-follow-up assessment at admission, discharge, and 8, 24, and 36 weeks after discharge takes place supplemented by a daily smartphone-based ambulatory assessment from a triadic perspective of patients, parents, and teachers. Primary outcomes include whether participants in the intervention group have fewer readmissions and higher treatment satisfaction and health-related quality of life as well as lower symptom severity than participants in the control group.

Discussion

The present study is essential to address the cross-sectoral challenges associated with reintegration into daily (school) life following child and adolescent psychiatric hospitalization and to determine possible needed adaptations in partial or full inpatient settings. If applicability and efficacy of the aftercare service can be demonstrated, integration into regular care will be sought.

Trial registration

ClinicalTrials.govNCT04986228. Registered on August 2, 2021
Study protocol of brief intervention using gene polymorphism information for excessive drinking among Japanese college students and adults aged 20–30 years: a randomized controlled trial
Authors: Owaki Yukiko , Yoshimoto Hisashi , Saito Go , Goto Takahiro , Kushio Satoshi , Nakamura Akihiro , Togo Yusuke , Mori Kazumasa , Hokazono Hideki
Published: August 2022

Background

The alcohol-metabolizing enzyme aldehyde dehydrogenase 2 (ALDH2) is a carcinogenic acetaldehyde-degrading enzyme, and its low activity is a genetic constitution peculiar to East Asians. People with low alcohol dehydrogenase 1B activity (ADH1B*1/*1 genotype) have a high risk of developing head and neck cancer and alcoholism. The study aims to evaluate the effectiveness of brief interventions for excessive drinking among college students and adults in their 20s, including information on five constitutions that combine the ALDH2 and ADH1B genotypes.

Methods

Participants comprised university students and staff aged 20–30 years who had consumed ≥40 g (males) or ≥20 g (females) of pure alcohol; they were classified into intervention and control groups using a simple randomization method. Participants anonymously filled out questionnaires linked to identification numbers and recorded the drinking days and amounts on the drinking calendar. The intervention group will then be tested for genotype testing using saliva (5 types of combinations of ALDH2 and ADH1B enzyme activities); the result report will arrive approximately 1 month later. We will conduct a 30-min face-to-face or online intervention. The control group will be merely given the conventional materials, and genetic testing will be performed voluntarily after 6 months (end of study). The intervention group will undergo questionnaire surveys 1 month after the intervention and 3 and 6 months after baseline. Questionnaire surveys will be conducted 1, 3, and 6 months after baseline for the control group. The average amount of drinking before and after the intervention, attribute/baseline data between the two groups, and time-series data were compared using various analysis tools. For interventions, we engaged in dialog based on intervention materials that added genotyping content to the existing materials, result reports, baseline data, and drinking calendar records. Participants’ ingenuity is respected to support their drinking behavior and goal setting.

Discussion

Individual information on the genetic makeup of alcohol-metabolizing enzymes provided during the intervention is more personal and objective than general health information, especially in Japan, where the ALDH2 low activity rate is high. This information may be useful for health care and precautionary measures.

Trial registration

R000050379, UMIN000044148, Registered on June 1, 2021.

Scientific Title: Examination of simple intervention using genetic polymorphism information for excessive drinking.
Evaluating a couple communication skills training (CCST) intervention for advanced cancer: study protocol for a randomized controlled trial
Authors: Porter Laura S. , Ramos Katherine , Baucom Donald H. , Steinhauser Karen , Erkanli Alaattin , Strauman Timothy J. , Zafar S. Yousuf , Check Devon K. , Leo Karena , Liu Evan , Keefe Francis J.
Published: August 2022

Background

For patients and their intimate partners, advanced cancer poses significant challenges that can negatively impact both individuals and their relationship. Prior studies have found evidence that couple-based communication skills interventions can to be beneficial for patients and partners. However, these studies have been limited by reliance on in-person treatment delivery and have not targeted couples at high risk for poor outcomes. This study tests the efficacy of a Couples Communication Skills Training (CCST) intervention delivered via videoconference for couples reporting high levels of holding back from discussing cancer-related concerns, a variable associated with poorer psychological and relationship functioning.

Methods

This RCT is designed to evaluate the efficacy of CCST in improving patient and partner relationship functioning (primary outcome). Secondary outcomes include patient and partner psychological functioning and patient symptoms and health care use. We also examine the role of objective and self-reported communication behaviors as mediators of treatment effects. Two hundred thirty patients with advanced lung, gastrointestinal, genitourinary, and breast cancer and their partners will be randomized to CCST or an education control intervention. Participants in both conditions complete self-reported outcome measures at baseline, mid-treatment, post-treatment, and 3 months post-treatment. Objective measures of communication are derived from video-recorded couple conversations collected at baseline and post-treatment. An implementation-related process evaluation (assessing implementation outcomes and potential barriers to/facilitators of implementation) will be conducted to inform future efforts to implement CCST in real-world settings.

Discussion

This trial can yield important new knowledge about effective ways to improve patient and partner adjustment to advanced cancer.

Trial registration

This study trial is registered at clinicaltrials.gov (Trial # NCT04590885); registration date: October 19, 2020.
The efficacy and tolerability of sports drink versus water in bowel preparations: a randomised controlled study
Authors: Zhang Zhixin , Gao Hui , Yuan Xin , Liu Cenqin , Bao Zhenfei , Yu Siyi , Xie Haofen , Wang Weihong , Xie Jiarong , Xu Lei
Published: August 2022

Background

An optimal bowel preparation can result in an improved colonoscopy. This study was to compare the effectiveness and safety of the use of a sports drink (Mizone) plus polyethylene glycol (PEG) solution with a water plus PEG solution in bowel preparations.

Methods

This was a randomised controlled study. All of the included patients were randomly divided into the following two groups: the PEG + Mizone group and the PEG + water group. The palatability of the solution was measured through the use of questionnaires. Additionally, bowel cleanliness was evaluated according to the Ottawa Bowel Preparation Scale (OBPS, 0–14, with higher values indicating worse cleanliness), as well as with the aid of colonoscopy videos.

Results

A total of 270 patients were enrolled. The rate of adequate bowel preparation was 74.8% in the PEG + Mizone group and 68.9% in the PEG + water group, with a risk difference of 5.9% (95% CI: − 4.8–16.6%), which indicated noninferiority (noninferiority margin: − 9.5% <  − 4.8%). However, patients rated the palatability (65.9% vs 44.4%, P < 0.001) and willingness to recommend or repeat (88.9% vs 75.6%, P = 0.004) the administration of the PEG + Mizone preparation as being better than those of the PEG + water preparation. The rates of adverse events during the bowel preparations were not significantly different between the two groups, except for bloating (PEG + Mizone vs PEG + water, 4.4% vs 13.3%, P = 0.010).

Conclusion

The concomitant use of PEG + Mizone was a well tolerated and effective bowel preparation, compared with the PEG + water treatment.

Trial registration

ClinicalTrials.gov NCT04247386. Registered on 30 Jan 2020.
A prediction model for worsening diabetic retinopathy after panretinal photocoagulation
Authors: Li Jinglan , Li Xuanlong , Lei Mingxing , Li Wanyue , Chen Wenqian , Ma Tianju , Gao Yi , Ye Zi , Li Zhaohui
Published: August 2022

Background

As one of the severe complications of diabetes mellitus, diabetic retinopathy (DR) is the leading cause of blindness in the working age worldwide. Although panretinal photocoagulation (PRP) was standard treatment, PRP-treated DR still has a high risk of progression. Hence, this study aimed to assess the risk factors and establish a model for predicting worsening diabetic retinopathy (DR-worsening) within five years after PRP.

Methods

Patients who were diagnosed with severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and treated with PRP were included, and those patients were randomly assigned to either a training or validation cohort. The multivariate logistic regression analysis was used to screen potential risk factors for DR-worsening in the training cohort. Then the model was established after including significant independent risk factors and further validated using discrimination and calibration.

Results

A total of 271 patients were included, and 56.46% of patients had an outcome of DR-worsening. In the training cohort (n = 135), age (odds ratio [OR] = 0.94, 95% confidence interval [CI] 0.90–0.98), baseline best corrected visual acuity (logMAR) (OR = 10.74, 95% CI 1.84–62.52), diabetic nephropathy (OR = 9.32, 95% CI 1.49–58.46), and hyperlipidemia (OR = 3.34, 95% CI 1.05–10.66) were screened out as the independent risk factors, which were incorporated into the predictive model. The area under the receiver operating characteristic curve and calibration slope in the training and validation cohort were 0.79, 0.96 (95% CI 0.60–1.31), and 0.79, 1.00 (95% CI 0.66–1.34), respectively. Two risk groups were developed depending on the best cut-off value of the predicted probability, and the actual probability was 34.90% and 82.79% in the low-risk and high-risk groups, respectively (P < 0.001).

Conclusions

This study developed and internally validated a new model to predict the probability of DR-worsening after PRP treatment within five years. The model can be used as a rapid risk assessment system for clinical prediction of DR-worsening and identify individuals at a high risk of DR-worsening at an early stage and prescribe additional treatment.
The association between advanced glycation end products (AGEs) and ABC (hemoglobin A1C, blood pressure, and low-density lipoprotein cholesterol) control parameters among patients with type 2 diabetes mellitus
Authors: Rezaei Mohaddeseh , Rabizadeh Soghra , Mirahmad Maryam , Hajmiri Minoo Sadat , Nakhjavani Manouchehr , Hemmatabadi Mahboobeh , Shirzad Nooshin
Published: August 2022

Background

Diabetes-induced chronic hyperglycemia results in the formation and aggregation of advanced glycation end-products (AGEs), which are products of non-enzymatic glycosylation of lipids or proteins. The development of diabetic complications can be accelerated by AGEs. In the current study, we aimed to explore the relationship between AGEs levels and ABC goals of diabetes control (A: Hemoglobin A1C < 7.0%, B: Blood pressure < 140/90 mmHg, and C: low-density lipoprotein cholesterol [LDL] < 100 mg/dL).

Methods

In the current cross-sectional study, 293 patients with type 2 diabetes mellitus (T2D), were enrolled. Demographic and clinical characteristics of the individuals were collected. AGEs levels were measured using quantitative fluorescence spectroscopy. Finally, the association of AGEs levels with patients' characteristics and ABC goals was assessed.

Results

Higher serum AGEs concentration was detected in older age, smoking patients and those with higher diastolic blood pressure, lower high-density lipoprotein (HDL) level, lower body mass index (BMI) and retinopathy. Moreover, the T2D patients who achieved higher numbers of ABC goals of diabetes were younger age (P-value = 0.003), with lower hemoglobin A1C (P-value = 0.001), fasting blood sugar (P-value = 0.002) diastolic blood pressure (P-value = 0.001), systolic blood pressure (P-value = 0.001), cholesterol (P-value = 0.001), LDL (P-value = 0.001), and AGEs (P-value = 0.023) levels. Diabetic patients with AGEs levels above 73.9% were about 2.2 times more likely to achieve none of ABC treatment goals (95% CI 1.107–3.616).

Conclusion

Our results revealed the relationship between AGEs and ABC goal achievement, and microvascular diabetic complications, and imply that AGEs measurement may be valuable in the monitoring of diabetic patients' complications and treatment adjustment.
SCIFER: approach for analysis of LINE-1 mRNA expression in single cells at a single locus resolution
Authors: Stow Emily C. , Baddoo Melody , LaRosa Alexis J. , LaCoste Dawn , Deininger Prescott , Belancio Victoria
Published: August 2022

Background

Endogenous expression of L1 mRNA is the first step in an L1-initiated mutagenesis event. However, the contribution of individual cell types to patterns of organ-specific L1 mRNA expression remains poorly understood, especially at single-locus resolution. We introduce a method to quantify expression of mobile elements at the single-locus resolution in scRNA-Seq datasets called Single Cell Implementation to Find Expressed Retrotransposons (SCIFER). SCIFER aligns scRNA-Seq reads uniquely to the genome and extracts alignments from single cells by cell-specific barcodes. In contrast to the alignment performed using default parameters, this alignment strategy increases accuracy of L1 locus identification by retaining only reads that are uniquely mapped to individual L1 loci. L1 loci expressed in single cells are unambiguously identified using a list of L1 loci manually validated to be expressed in bulk RNA-Seq datasets generated from the same cell line or organ.

Results

Validation of SCIFER using MCF7 cells determined technical parameters needed for optimal detection of L1 expression in single cells. We show that unsupervised analysis of L1 expression in single cells exponentially inflates both the levels of L1 expression and the number of expressed L1 loci. Application of SCIFER to analysis of scRNA-Seq datasets generated from mouse and human testes identified that mouse Round Spermatids and human Spermatogonia, Spermatocytes, and Round Spermatids express the highest levels of L1 mRNA. Our analysis also determined that similar to mice, human testes from unrelated individuals share as much as 80% of expressed L1 loci. Additionally, SCIFER determined that individual mouse cells co-express different L1 sub-families and different families of transposable elements, experimentally validating their co-existence in the same cell.

Conclusions

SCIFER detects mRNA expression of individual L1 loci in single cells. It is compatible with scRNA-Seq datasets prepared using traditional sequencing methods. Validated using a human cancer cell line, SCIFER analysis of mouse and human testes identified key cell types supporting L1 expression in these species. This will further our understanding of differences and similarities in endogenous L1 mRNA expression patterns in mice and humans.
An improved target tracking scheme based on MC-MPMC method for mobile wireless sensor networks
Authors: Lv Chunfeng , Zhu Jianping , Tao Zhengsu , Pi Yihai
Published: August 2022

Target tracking is crucial to many applications in wireless sensor networks (WSNs). Existing tracking schemes used in WSNs can basically be classified two categories, clustering and predicting. Considering network clustering consumes much energy for limited-energy WSNs, a predicting target tracking scheme is proposed called MC-MPMC (measurement compensation-based mixture population Monte Carlo) which tracks the target based on predicted locations in this work. Adaptive mixture PMC model for generating proposals varying from each iteration is proposed to guarantee sampling diversity. And also, extra measurements or observations generating method is introduced to compensate missed prediction locations or false estimations, avoiding tracking behavior degradation. Firstly, samples drawn from the proposals of next iteration can be generated by a mixture method to avoid sample degeneracy. Secondly, sample weights are jointly computed based on adaptive fusion of compensation measurement and true measurements. Thirdly, HTC method is combined to MC-MPMC scheme to decrease energy consumption in WSNs. Then, the proposed method is verified through comprehensive experiments about tracking error, delay and consumption predictions. Moreover, performance comparisons of MC-MPMC with other tracking schemes are also proposed.
Validation of a shortened version of the Eating Attitude Test (EAT-7) in the Arabic language
Authors: Fekih-Romdhane Feten , Obeid Sahar , Malaeb Diana , Hallit Rabih , Hallit Souheil
Published: August 2022

Background

Eating disorders are quite common around the world, disabling, and potentially lethal; but they remain so far under-captured and subject to substantial delays in treatment. We propose through this study to develop and validate a shortened version of the Eating Attitude Test (EAT) in the Arabic language among non-clinical Arabic-speaking Lebanese participants from the general population.

Methods

1175 participants enrolled in this cross-sectional study, based on an online survey. The Eating Attitude Test-26 items, Drunkorexia Motives and Behaviors Scales and Lebanese Anxiety Scale were used to answer our objectives.

Results

Our results confirmed validity and reliability of the questionnaire. Exploratory Factor Analyses showed that all items converged over a one-factor solution, with an excellent Cronbach’s alpha (> 0.9). Confirmatory Factor Analyses found that the 7-item-version yielded excellent model fit. The instrument also revealed strong evidence of divergent validity, being highly correlated with measures of anxiety and drunkorexia motives and behaviors.

Discussion

Findings provided evidence supporting that the Arabic seven-item one-factor structure of the scale (EAT-7) is valid, reliable, and can be used in clinical practice, preventive interventions and future eating disorders research in Arab settings.