bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and validation of a prognostic model of RNA binding proteins in clear cell renal carcinoma
Authors: Han Wenkai , Fan Bohao , Huang Yongsheng , Wang Xiongbao , Zhang Zhao , Gu Gangli , Liu Zhao
Published: May 2022

Background

The dysfunction of RNA binding proteins (RBPs) is associated with various inflammation and cancer. The occurrence and progression of tumors are closely related to the abnormal expression of RBPs. There are few studies on RBPs in clear cell renal carcinoma (ccRCC), which allows us to explore the role of RBPs in ccRCC.

Methods

We obtained the gene expression data and clinical data of ccRCC from the Cancer Genome Atlas (TCGA) database and extracted all the information of RBPs. We performed differential expression analysis of RBPs. Risk model were constructed based on the differentially expressed RBPs (DERBPs). The expression levels of model markers were examined by reverse transcription-quantitative PCR (RT-qPCR) and analyzed for model-clinical relevance. Finally, we mapped the model's nomograms to predict the 1, 3 and 5-year survival rates for ccRCC patients.

Results

The results showed that the five-year survival rate for the high-risk group was 40.2% (95% CI = 0.313 ~ 0.518), while the five-year survival rate for the low-risk group was 84.3% (95% CI = 0.767 ~ 0.926). The ROC curves (AUC = 0.748) also showed that our model had stable predictive power. Further RT-qPCR results were in accordance with our analysis (p < 0.05). The results of the independent prognostic analysis showed that the model could be an independent prognostic factor for ccRCC. The results of the correlation analysis also demonstrated the good predictive ability of the model.

Conclusion

In summary, the 4-RBPs (EZH2, RPL22L1, RNASE2, U2AF1L4) risk model could be used as a prognostic indicator of ccRCC. Our study provides a possibility for predicting the survival of ccRCC.
Peritoneal dialysis catheter salvage performed by nephrologists in tunnel exposure management
Authors: Kang Seok Hui , Kim A. Young , Do Jun Young
Published: May 2022

Background

Tunnel exposure, a non-infectious complication, is a rare finding in peritoneal dialysis (PD) patients, which has been described in some case reports. Our study aimed to present catheter salvage therapy using a revision procedure of tunnel exposure by nephrologists.

Methods

Our retrospective study was conducted between July 1998 and October 2021. We identified all PD patients with tunnel exposure from a database of a tertiary medical center. Tunnel exposure was diagnosed following gross inspection by clinicians during outpatient consultations. We attempted revision with partial external cuff shaving and creating a new tunnel without catheter change.

Results

Fourteen cases in 12 patients were diagnosed as tunnel exposure. The median age at presentation of tunnel exposure was 51 years. Eleven patients underwent revision, and the PD catheter was removed in one patient. The patients who underwent revision were followed up for 6 months. The catheter salvage rate was 72.7%.

Conclusions

The present study demonstrated that catheter revision performed by nephrologists could be a valuable alternative for original catheter salvage before considering catheter removal in tunnel exposure management.
Nomogram-based risk prediction of macrosomia: a case-control study
Authors: Du Jing , Zhang Xiaomei , Chai Sanbao , Zhao Xin , Sun Jianbin , Yuan Ning , Yu Xiaofeng , Zhang Qiaoling
Published: May 2022

Background

Macrosomia is closely associated with poor maternal and fetal outcome. But there is short of studies on the risk of macrosomia in early pregnancy. The purpose of this study is to establish a nomogram for predicting macrosomia in the first trimester.

Methods

A case-control study involving 1549 pregnant women was performed. According to the birth weight of newborn, the subjects were divided into macrosomia group and non-macrosomia group. The risk factors for macrosomia in early pregnancy were analyzed by multivariate logistic regression. A nomogram was used to predict the risk of macrosomia.

Results

The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed that prepregnancy overweight (OR: 2.13 95% CI: 1.18–3.83)/obesity (OR: 3.54, 95% CI: 1.56–8.04), multiparity (OR:1.88, 95% CI: 1.16–3.04), the history of macrosomia (OR: 36.97, 95% CI: 19.90–68.67), the history of GDM/DM (OR: 2.29, 95% CI: 1.31–3.98), the high levels of HbA1c (OR: 1.76, 95% CI: 1.00–3.10) and TC (OR: 1.36, 95% CI: 1.00–1.84) in the first trimester were the risk factors of macrosomia. The area under ROC (the receiver operating characteristic) curve of the nomogram model was 0.807 (95% CI: 0.755–0.859). The sensitivity and specificity of the model were 0.716 and 0.777, respectively.

Conclusion

The nomogram model provides an effective mothed for clinicians to predict macrosomia in the first trimester.
Leveraging artificial intelligence to predict ERG gene fusion status in prostate cancer
Authors: Dadhania Vipulkumar , Gonzalez Daniel , Yousif Mustafa , Cheng Jerome , Morgan Todd M. , Spratt Daniel E. , Reichert Zachery R. , Mannan Rahul , Wang Xiaoming , Chinnaiyan Anya , Cao Xuhong , Dhanasekaran Saravana M. , Chinnaiyan Arul M. , Pantanowitz Liron , Mehra Rohit
Published: May 2022

Background

TMPRSS2-ERG gene rearrangement, the most common E26 transformation specific (ETS) gene fusion within prostate cancer, is known to contribute to the pathogenesis of this disease and carries diagnostic annotations for prostate cancer patients clinically. The ERG rearrangement status in prostatic adenocarcinoma currently cannot be reliably identified from histologic features on H&E-stained slides alone and hence requires ancillary studies such as immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or next generation sequencing (NGS) for identification.

Methods

Objective

We accordingly sought to develop a deep learning-based algorithm to identify ERG rearrangement status in prostatic adenocarcinoma based on digitized slides of H&E morphology alone.

Design

Setting, and Participants: Whole slide images from 392 in-house and TCGA cases were employed and annotated using QuPath. Image patches of 224 × 224 pixel were exported at 10 ×, 20 ×, and 40 × for input into a deep learning model based on MobileNetV2 convolutional neural network architecture pre-trained on ImageNet. A separate model was trained for each magnification. Training and test datasets consisted of 261 cases and 131 cases, respectively. The output of the model included a prediction of ERG-positive (ERG rearranged) or ERG-negative (ERG not rearranged) status for each input patch.

Outcome measurements and statistical analysis: Various accuracy measurements including area under the curve (AUC) of the receiver operating characteristic (ROC) curves were used to evaluate the deep learning model.

Results and Limitations

All models showed similar ROC curves with AUC results ranging between 0.82 and 0.85. The sensitivity and specificity of these models were 75.0% and 83.1% (20 × model), respectively.

Conclusions

A deep learning-based model can successfully predict ERG rearrangement status in the majority of prostatic adenocarcinomas utilizing only H&E-stained digital slides. Such an artificial intelligence-based model can eliminate the need for using extra tumor tissue to perform ancillary studies in order to assess for ERG gene rearrangement in prostatic adenocarcinoma.
Neonatal bilateral adrenal hemorrhage and adrenal insufficiency accompanied by Subgaleal hematoma: a case report with brief review of literature
Authors: Esslami Golnaz Ghazizadeh , Moienafshar Atousa
Published: May 2022

Background

Neonatal adrenal hemorrhage (NAH) is an almost infrequent phenomenon (0.2–0.55%). Mechanical compression and alterations of venous pressure during delivery are considered the most probable explanations. Approximately 10% of the cases might have bilateral involvement. Clinical symptoms include abdominal mass, poor feeding, vomiting, prolonged jaundice, and anemia. Subgaleal hemorrhage (SGH) is one of the most clinically remarkable and potentially hazardous postnatal cranial injuries.

Case presentation

An early-term Iranian male neonate who was born through spontaneous vaginal delivery and experienced shoulder dystocia was diagnosed with bilateral NAH leading to adrenal insufficiency requiring glucocorticoid and mineralocorticoid supplementation. The SGH and jaundice were other postnatal complications. Serial monthly abdominal and brain ultrasound revealed complete regression of lesions after 70 days. However, after 16 months, the neonate has been still treated with hydrocortisone and fludrocortisone for the adrenal insufficiency diagnosis. He has a lower limit weight for age; however, developmental milestones have been appropriate for age.

Discussion and conclusion

Adrenal hemorrhage and SGH should be examined and looked for, particularly with proven evidence of difficult delivery and asphyxia in at-risk newborns. Clinical and ultrasound follow-up is mandatory for the assessment of hemorrhage resolution and conservative management. The early detection and treatment of adrenal insufficiency by laboratory examination is strongly recommended in bilateral cases. Furthermore, the early recognition of postnatal SGH to prevent clinical and neurological outcomes seems essential.
Pain and pain management in children and adolescents receiving hospital care: a cross-sectional study from Sweden
Authors: Andersson Viveka , Bergman Stefan , Henoch Ingela , Simonsson Hanna , Ahlberg Karin
Published: May 2022

Background

Pain is a common symptom in children receiving hospital care. Adequate pain management in paediatric patients is of the utmost importance. Few studies have investigated children’s own experiences of pain during hospitalization.

Aim

To describe the prevalence of pain, self-reported pain intensity at rest and during movement, pain management and compliance with pain treatment guidelines in children and adolescents receiving hospital care. Furthermore, to examine self-reported statements about pain relief and how often staff asked about pain.

Methods

A quantitative, cross-sectional study with descriptive statistics as the data analysis method was conducted at a county hospital in western Sweden. Sixty-nine children/adolescents aged 6–18 years who had experienced pain during their hospital stay were included. A structured, verbally administered questionnaire was used to obtain pain reports. The participants were also asked what they considered alleviated pain and how often they told staff about pain. Patient demographics, prescribed analgesics and documentation of pain rating were obtained from medical records.

Results

Fifty children/adolescents (72%) experienced moderate to severe pain in the previous 24 hours. At the time of the interview 36% reported moderate to severe pain at rest and 58% during movement. Seven participants (10%) reported severe pain both at rest and during movement. About one-third were on a regular multimodal analgesic regimen and 28% had used a validated pain rating scale. Thirty children/adolescents (43%) reported that they had experienced procedural pain in addition to their underlying pain condition. Most of the children/adolescents (74%) reported that analgesics provided pain relief. Forty (58%) stated that various non-pharmacological methods were helpful.

Conclusions

Despite evidence-based guidelines, half of the children/adolescents experienced moderate to severe pain, highlighting the need for improvement. Pain levels should be assessed both at rest and during movement. Response to treatment should be evaluated to prevent undertreatment of pain. Compliance with guidelines and professional communication are of the utmost importance for pain management in children/adolescents. Non-pharmacological methods are a valuable part of a pain management strategy. This study shows that it is important to evaluate and improve pain care also outside specialised tertiary clinics.
High levels of depressive symptoms and low quality of life are reported during pregnancy in Cape Coast, Ghana; a longitudinal study
Authors: Pobee Ruth Adisetu , Setorglo Jacob , Kwashie Klevor Moses , Murray-Kolb Laura E.
Published: May 2022

Background

Significant rates of anxiety, depressive symptoms, and low quality of life (QoL) have been found among pregnant women in developed countries. These psychosocial disturbances have not been adequately assessed during pregnancy in many developing countries.

Methods

Women were recruited in their first trimester of pregnancy (< 13 weeks; n = 116) and followed through to their 2nd (n = 71) and 3rd (n = 71) trimesters. Questionnaires were used to collect data on anxiety symptoms (Beck Anxiety Inventory; BAI), depressive symptoms (Center for Epidemiological Studies-Depression Inventory; CES-D), and quality of life (RAND SF-36; QoL). Psychometric analyses were used to determine the reliability of the questionnaires in this context. The proportion of pregnant women with psychosocial disturbances at each trimester was determined. Repeated measures ANOVA were used to examine changes in psychosocial outcomes over time; and generalized estimating equation to determine if gestational age predicted the psychosocial outcomes whilst controlling for sociodemographic variables.

Results

Participants were aged 27.1 ± 5.2 years, on average. Psychometric analyses revealed a 4-factor solution for BAI (18 items), 1-factor solution for CES-D (13 items) and 4-factor solution for RAND SF-36 (26 items). The prevalence estimate of psychosocial disturbances was 34%, 10%, 2% (anxiety), 49%, 31%, 34% (depressive symptoms), and 46%, 37%, 59% (low QoL) for 1st, 2nd and 3rd trimesters, respectively. Gestational age and food insecurity were significant predictors of depressive symptoms, anxiety symptoms and QoL.

Conclusions

In this population of Ghanaian women, the levels of depressive symptoms and low QoL observed across pregnancy should be recognized as major public health problems and efforts to address these should be put in place. Addressing food insecurity may be a major step to solve not only the physical needs of the pregnant woman but also the psychological needs.
Non-adherence to COVID-19 containment behaviours: results from an all-Ireland telephone survey
Authors: Dempster Martin , O’Connell Nicola , Graham Christopher D. , O’Connor Cliodhna , Zgaga Lina , Burke Emma , Mather Luke , Nicolson Gail , Barry Joe , Scally Gabriel , Nolan Ann , Tobin Katy , Crowley Philip , Darker Catherine D.
Published: May 2022

Background

COVID-19 public health measures like handwashing and social distancing can help stem the spread of the virus. Adherence to guidelines varies between individuals. This study aims to identify predictors of non-adherence to social distancing and handwashing guidelines.

Methods

A cross-sectional weekly telephone survey was conducted over eight weeks (11/06/2020–05/08/2020). The sample included adults resident on the island of Ireland (75:25 split between ROI and NI). Data were collected on demographics, threat perceptions, fear of COVID-19, response efficacy and self-efficacy, response cost and social norms, COVID-19 behaviours, mood, loneliness, and self-reported health.

Results

3011 participants were surveyed. Handwashing non-adherers were more likely to be male (OR: 5.2, 95% CI: 2.4 – 11.3), to have higher levels of loneliness (OR: 1.86, 95% CI: 1.1 – 3.1), and higher perceptions of handwashing costs (OR: 3.4, 95% CI: 2.2 – 5.2). Those reporting rarely engaging in social distancing were more likely to be members of lower socioeconomic groups, to be younger (OR: 0.97, 95% CI: 0.96 – 0.98), male (OR: 1.67, 95% CI: 1.1 – 2.5), healthcare workers (OR: 1.98, 95% CI: 1.1 – 3.4), to report lower mood (OR: 1.72, 95% CI: 1.3 – 2.2), were less likely to live in households with people aged under-18 (OR: 0.75, 95% CI: 0.6 – 0.9), and to have lower fear of COVID-19 (OR: 0.79, 95% CI: 0.6 – 0.9).

Conclusions

Non-adherers to handwashing differ to social distancing non-adherers. Public health messages should target specific demographic groups and different messages are necessary to improve adherence to each behaviour.
Biomechanical properties of a suture anchor system from human allogenic mineralized cortical bone matrix for rotator cuff repair
Authors: Schanda Jakob E. , Obermayer-Pietsch Barbara , Sommer Gerhard , Heuberer Philipp R. , Laky Brenda , Muschitz Christian , Pastl Klaus , Pastl Eva , Fialka Christian , Mittermayr Rainer , Grillari Johannes , Foessl Ines
Published: May 2022

Background

Suture anchors (SAs) made of human allogenic mineralized cortical bone matrix are among the newest developments in orthopaedic and trauma surgery. Biomechanical properties of an allogenic mineralized suture anchor (AMSA) are not investigated until now. The primary objective was the biomechanical investigation of AMSA and comparing it to a metallic suture anchor (MSA) and a bioabsorbable suture anchor (BSA) placed at the greater tuberosity of the humeral head of cadaver humeri. Additionally, we assessed the biomechanical properties of the SAs with bone microarchitecture parameters.

Methods

First, bone microarchitecture of 12 fresh frozen human cadaver humeri from six donors was analyzed by high-resolution peripheral quantitative computed tomography. In total, 18 AMSAs, 9 MSAs, and 9 BSAs were implanted at a 60° angle. All three SA systems were systematically implanted alternating in three positions within the greater tuberosity (position 1: anterior, position 2: central, position 3: posterior) with a distance of 15 mm to each other. Biomechanical load to failure was measured in a uniaxial direction at 135°.

Results

Mean age of all specimens was 53.6 ± 9.1 years. For all bone microarchitecture measurements, linear regression slope estimates were negative which implies decreasing values with increasing age of specimens. Positioning of all three SA systems at the greater tuberosity was equally distributed (p = 0.827). Mean load to failure rates were higher for AMSA compared to MSA and BSA without reaching statistical significance between the groups (p = 0.427). Anchor displacement was comparable for all three SA systems, while there were significant differences regarding failure mode between all three SA systems (p < 0.001). Maximum load to failure was reached in all cases for AMSA, in 44.4% for MSA, and in 55.6% for BSA. Suture tear was observed in 55.6% for MSA and in 22.2% for BSA. Anchor breakage was solely seen for BSA (22.2%). No correlations were observed between bone microarchitecture parameters and load to failure rates of all three suture anchor systems.

Conclusions

The AMSA showed promising biomechanical properties for initial fixation strength for RCR. Since reduced BMD is an important issue for patients with chronic rotator cuff lesions, the AMSA is an interesting alternative to MSA and BSA. Also, the AMSA could improve healing of the enthesis.
A novel reliability-based regression model to analyze and forecast the severity of COVID-19 patients
Authors: Bakhtiarvand Negar , Khashei Mehdi , Mahnam Mehdi , Hajiahmadi Somayeh
Published: May 2022

Background

Coronavirus outbreak (SARS-CoV-2) has become a serious threat to human society all around the world. Due to the rapid rate of disease outbreaks and the severe shortages of medical resources, predicting COVID-19 disease severity continues to be a challenge for healthcare systems. Accurate prediction of severe patients plays a vital role in determining treatment priorities, effective management of medical facilities, and reducing the number of deaths. Various methods have been used in the literature to predict the severity prognosis of COVID-19 patients. Despite the different appearance of the methods, they all aim to achieve generalizable results by increasing the accuracy and reducing the errors of predictions. In other words, accuracy is considered the only effective factor in the generalizability of models. In addition to accuracy, reliability and consistency of results are other critical factors that must be considered to yield generalizable medical predictions. Since the role of reliability in medical decisions is significant, upgrading reliable medical data-driven models requires more attention.

Methods

This paper presents a new modeling technique to specify and maximize the reliability of results in predicting the severity prognosis of COVID-19 patients. We use the well-known classic regression as the basic model to implement our proposed procedure on it. To assess the performance of the proposed model, it has been applied to predict the severity prognosis of COVID-19 by using a dataset including clinical information of 46 COVID-19 patients. The dataset consists of two types of patients’ outcomes including mild (discharge) and severe (ICU or death). To measure the efficiency of the proposed model, we compare the accuracy of the proposed model to the classic regression model.

Results

The proposed reliability-based regression model, by achieving 98.6% sensitivity, 88.2% specificity, and 93.10% accuracy, has better performance than classic accuracy-based regression model with 95.7% sensitivity, 85.5% specificity, and 90.3% accuracy. Also, graphical analysis of ROC curve showed AUC 0.93 (95% CI 0.88–0.98) and AUC 0.90 (95% CI 0.85–0.96) for classic regression models, respectively.

Conclusions

Maximizing reliability in the medical forecasting models can lead to more generalizable and accurate results. The competitive results indicate that the proposed reliability-based regression model has higher performance in predicting the deterioration of COVID-19 patients compared to the classic accuracy-based regression model. The proposed framework can be used as a suitable alternative for the traditional regression method to improve the decision-making and triage processes of COVID-19 patients.
Shared genetic links between frontotemporal dementia and psychiatric disorders
Authors: Li Chunyu , Pang Dejiang , Lin Junyu , Yang Tianmi , Shang Huifang
Published: May 2022

Background

Epidemiological and clinical studies have suggested comorbidity between frontotemporal dementia (FTD) and psychiatric disorders. FTD patients carrying specific mutations were at higher risk for some psychiatric disorders, and vice versa, implying potential shared genetic etiology, which is still less explored.

Methods

We examined the genetic correlation using summary statistics from genome-wide association studies and analyzed their genetic enrichment leveraging the conditional false discovery rate method. Furthermore, we explored the causal association between FTD and psychiatric disorders with Mendelian randomization (MR) analysis.

Results

We identified a significant genetic correlation between FTD and schizophrenia at both genetic and transcriptomic levels. Meanwhile, robust genetic enrichment was observed between FTD and schizophrenia and alcohol use disorder. Seven shared genetic loci were identified, which were mainly involved in interleukin-induced signaling, synaptic vesicle, and brain-derived neurotrophic factor signaling pathways. By integrating cis-expression quantitative trait loci analysis, we identified MAPT and CADM2 as shared risk genes. MR analysis showed mutual causation between FTD and schizophrenia with nominal association.

Conclusions

Our findings provide evidence of shared etiology between FTD and schizophrenia and indicate potential common molecular mechanisms contributing to the overlapping pathophysiological and clinical characteristics. Our results also demonstrate the essential role of autoimmunity in these diseases. These findings provide a better understanding of the pleiotropy between FTD and psychiatric disorders and have implications for therapeutic trials.

Graphical abstract
ctDNA-adjusted bTMB as a predictive biomarker for patients with NSCLC treated with PD-(L)1 inhibitors
Authors: Nie Wei , Wang Zhi-Jie , Zhang Kai , Li Bing , Cai Yi-Ran , Wen Feng-Cai , Zhang Ding , Bai Yue-Zong , Zhang Xue-Yan , Wang Shu-Yuan , Cheng Lei , Zhong Hua , Liu Li , Wang Jie , Han Bao-Hui
Published: May 2022

Background

In non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs), higher blood tumor mutational burden (bTMB) was usually associated with better progression-free survival (PFS) and objective response rate (ORR). However, the association between bTMB and overall survival (OS) benefit remains undefined. It has been reported that patients harboring a high level of circulating tumor DNA (ctDNA) had poor survival. We hypothesized that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs.

Methods

Our study was retrospectively performed in three cohorts, including OAK and POPLAR cohort (n = 853), Shanghai and Wuhan (SH&WH) cohort (n = 44), and National Cancer Center (NCC) cohort (n = 47). Durable clinical benefit (DCB) was defined as PFS lasting ≥ 6 months. The cutoff value of ctDNA-adjusted bTMB for DCB prediction was calculated based on a receiver operating characteristic curve. Interaction between treatments and ctDNA-adjusted bTMB was assessed.

Results

The bTMB score was significantly associated with tumor burden, while no association was observed between ctDNA-adjusted bTMB with tumor burden. In the OAK and POPLAR cohort, significantly higher ORR (P = 0.020) and DCB (P< 0.001) were observed in patients with high ctDNA-adjusted bTMB than those with low ctDNA-adjusted bTMB. Importantly, the interactions between ctDNA-adjusted bTMB and treatments were significant for OS (interactionP = 0.019) and PFS (interactionP = 0.002). In the SH&WH cohort, the interactions between ctDNA-adjusted bTMB and treatment were marginally significant for OS (interactionP = 0.081) and PFS (interactionP = 0.062). Similar result was demonstrated in the NCC cohort.

Conclusions

Our study indicated that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs. The potential of ctDNA-adjusted bTMB as a noninvasive predictor for immunotherapy should be confirmed in future studies.
Copy number variation of urine exfoliated cells by low-coverage whole genome sequencing for diagnosis of prostate adenocarcinoma: a prospective cohort study
Authors: Guan Youyan , Wang Xiaobing , Guan Kaopeng , Wang Dong , Bi Xingang , Xiao Zhendong , Xiao Zejun , Shan Xingli , Hu Linjun , Ma Jianhui , Li Changling , Zhang Yong , Shou Jianzhong , Wang Baiyun , Qian Ziliang , Xing Nianzeng
Published: May 2022

Background

Non-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa.

Methods

We enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether.

Results

In patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7–95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83–0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1–99.5%) high grade tumors and 60.0% (95% CI 17.0–92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history.

Conclusions

Urine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors.
EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression
Authors: Yang Meiqin , Hu Haoran , Wu Sufang , Ding Jianyi , Yin Bo , Huang Baoyou , Li Fang , Guo Xiaoqing , Han Lingfei
Published: May 2022

Background

Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear.  

Methods

CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR.

Results

circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions.

Conclusions

As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer.
Examining the effects of femoral anteversion and passive hip rotation on ACL injury and knee biomechanics: a systematic review and meta-analysis
Authors: Hogg Jennifer A. , Waxman Justin P. , Shultz Sandra J.
Published: May 2022

Purpose

Greater femoral internal rotation (via anteversion or passive hip ROM) is associated with knee biomechanics thought to contribute to anterior cruciate ligament (ACL) injury, but it is unknown if femoral internal rotation contributes to actual ACL injury occurrence. The objective of this systematic review and meta-analysis was to quantify the extent to which femoral anteversion and hip range of motion (ROM) influence knee biomechanics consistent with ACL injury and actual ACL injury occurrence.

Methods

Using PRISMA guidelines, PubMed, CINAHL, SportDiscus, and Scopus databases were searched. Inclusion criteria were available passive hip ROM or femoral anteversion measure, ACL injury OR biomechanical analysis of functional task. Two reviewers independently reviewed titles, abstracts, and full texts when warranted. Included studies were submitted to Downs & Black Quality Assessment Tool. Meta-analyses were conducted for comparisons including at least two studies.

Results

Twenty-three studies were included (11 injury outcome, 12 biomechanical outcome). Decreased internal rotation ROM was significantly associated with history of ACL injury (MD -5.02°; 95% CI [-8.77°—-1.27°]; p = 0.01; n = 10). There was no significant effect between passive external rotation and ACL injury (MD -2.62°; 95% CI [-5.66°—- 0.41°]; p = 0.09; n = 9) Participants displaying greater frontal plane knee projection angle had greater passive external rotation (MD 4.77°; 95% CI [1.17° – 8.37°]; p = 0.01; n = 3). There was no significant effect between femoral anteversion and ACL injury (MD -0.46°; 95% CI [-2.23°—1.31°]; p = 0.61; n = 2). No within-sex differences were observed between injured and uninjured males and females (p range = 0.09 – 0.63).

Conclusion

Though individuals with injured ACLs have statistically less passive internal and external rotation, the observed heterogeneity precludes generalizability. There is no evidence that femoral anteversion influences biomechanics or ACL injury. Well-designed studies using reliable methods are needed to investigate biomechanical patterns associated with more extreme ROM values within each sex, and their prospective associations with ACL injury.

Level of evidence: IV.
Comprehensive molecular characterization of hypertension-related genes in cancer
Authors: Jiang Yanan , Shi Chunpeng , Tian Songyu , Zhi Fengnan , Shen Xiuyun , Shang Desi , Tian Jinwei
Published: May 2022

Background

During cancer treatment, patients have a significantly higher risk of developing cardiovascular complications such as hypertension. In this study, we investigated the internal relationships between hypertension and different types of cancer.

Methods

First, we comprehensively characterized the involvement of 10 hypertension-related genes across 33 types of cancer. The somatic copy number alteration (CNA) and single nucleotide variant (SNV) of each gene were identified for each type of cancer. Then, the expression patterns of hypertension-related genes were analyzed across 14 types of cancer. The hypertension-related genes were aberrantly expressed in different types of cancer, and some were associated with the overall survival of patients or the cancer stage. Subsequently, the interactions between hypertension-related genes and clinically actionable genes (CAGs) were identified by analyzing the co-expressions and protein–protein interactions.

Results

We found that certain hypertension-related genes were correlated with CAGs. Next, the pathways associated with hypertension-related genes were identified. The positively correlated pathways included epithelial to mesenchymal transition, hormone androgen receptor, and receptor tyrosine kinase, and the negatively correlated pathways included apoptosis, cell cycle, and DNA damage response. Finally, the correlations between hypertension-related genes and drug sensitivity were evaluated for different drugs and different types of cancer. The hypertension-related genes were all positively or negatively correlated with the resistance of cancer to the majority of anti-cancer drugs. These results highlight the importance of hypertension-related genes in cancer.

Conclusions

This study provides an approach to characterize the relationship between hypertension-related genes and cancers in the post-genomic era.
Internet of Things enabled real time cold chain monitoring in a container port
Authors: Cil Ahmet Yunus , Abdurahman Dini , Cil Ibrahim
Published: May 2022

Purpose

Seaports are regarded as significant actors in global logistics and supply chains since a large part of the cargoes carried over the globe are being processed there. When the cold chain broken down during transport and storage in the ports, the humidity, nutrition, temperature and time conditions to be required for the growth of the bacteria occur, and rapid reproduction occurs and the properties of the products are rapidly deteriorating. It is imperative that especially medicines, some chemical substances and foodstuffs need to be transported without breaking the cold chain in the logistics. The monitoring and control of the temperature and humidity level is important in the time period between the loading of these containers in special areas in ports, the loading of freight in open areas, or the loading of freight on roads and railway carriages. For this reason, precise monitoring and control of the system is vital in the port logistics management.

Method

In this study, an IoT-enabled system is designed for Container Ports by developing software, interface and equipment that will enable remote monitoring of temperature, humidity and other necessary key status parameters.

Findings

The developed IoT-based system provides audible and visual warning, e-mail and SMS communication, similar to a monitoring screen such as a heart graph monitor, when the instant values of the refrigerated container are transmitted to the database, when the defined upper and lower values are approached. All these data and major change information are archived in the database and retrospective situation analysis and data analysis can be performed.

Conclusion

Using technologies such as Wireless Sensor Network (WSN) and RFID, an IoT-enabled Cold Chain Logistics system has been proposed that provides real-time monitoring of products in containers at ports, providing DS services to logistics providers and customers. In this context, it was explained how the ambient parameter values were collected in real time using WSN and IEEE 802.15.4, how the collected data was sent to the server via the GSM gateway. In the port scenario, activation devices such as IEEE 802.15.4 and RFID were modeled using the OPNET simulator. The developed model was carried out in accordance with the principles of EPCglobal Gen 2. With the proposed approach, smart solutions provide a smarter flow of information. The results show that IoT- enabled cold chain systems have a great potential for managing, monitoring, receiving and determining abnormal events related to temperature-sensitive products in real time.
A 3D printed model of the female pelvis for practical education of gynecological pelvic examination
Authors: Kiesel Matthias , Beyers Inga , Kalisz Adam , Joukhadar Ralf , Wöckel Achim , Herbert Saskia-Laureen , Curtaz Carolin , Wulff Christine
Published: May 2022

Background

Pelvic palpation is a core component of every Gynecologic examination. It requires vigorous training, which is difficult due to its intimate nature, leading to a need of simulation. Up until now, there are mainly models available for mere palpation which do not offer adequate visualization of the concerning anatomical structures. In this study we present a 3D printed model of the female pelvis. It can improve both the practical teaching of gynecological pelvic examination for health care professionals and the spatial understanding of the relevant anatomy.

Methods

We developed a virtual, simplified model showing selected parts of the female pelvis. 3D printing was used to create a physical model.

Results

The life-size 3D printed model has the ability of being physically assembled step by step by its users. Consequently, it improves teaching especially when combining it with commercial phantoms, which are built solely for palpation training. This is achieved by correlating haptic and visual sensations with the resulting feedback received.

Conclusion

The presented 3D printed model of the female pelvis can be of aid for visualizing and teaching pelvic anatomy and examination to medical staff. 3D printing provides the possibility of creating, multiplying, adapting and sharing such data worldwide with little investment of resources. Thus, an important contribution to the international medical community can be made for training this challenging examination.
3D probabilistic geology differentiation based on airborne geophysics, mixed Lp norm joint inversion, and physical property measurements
Authors: Wei Xiaolong , Sun Jiajia
Published: May 2022

The physical property models obtained from geophysical inversions can be converted to a 3D quasi-geology model via a process called geology differentiation. Recent works indicate that the geology differentiation can help maximize the value of the information contained in geophysical data. However, it remains largely unexplored as to how to quantify the uncertainties of a 3D quasi-geology model. We approach this problem by using a recently developed mixed [Formula: see text] norm regularization and a priori physical property measurements. We use mixed [Formula: see text] norm joint inversion to construct a large sequence of physical property models based on the Gzz component of the airborne gravity gradient and magnetic measurements. The available physical property measurements are used to determine which physical property models to accept. We then construct a sequence of 3D quasi-geology models by performing the geology differentiation for all of the accepted models, which allows us to compute the probabilities of our geology differentiation results. We apply our approach to a set of field data collected over the Decorah area located in northeast Iowa. We successfully quantify the uncertainties of the spatial extents for the identified geologic units and compute probabilities of geologic units at any location in our study area. The proposed workflow has broad implications for 3D geologic model building based on multiple geophysical and/or rock sample measurements.
Physical Activity and Quality of Life in Malaysian Breast Cancer Survivors: A Longitudinal Study
Authors: Islam Tania , Lin Lee Yi , Danaee Mahmoud , Taib Nur Aishah
Published: May 2022

PURPOSE

Regular physical activity (PA) after a diagnosis of breast cancer(BC) is associated with reduced morbidity and a higher quality of life (QOL). Investigate the association of PA and QOL among Malaysian BC survivors in this prospective cohort study.

METHODS

A total of, 133 BC women were interviewed at baseline, one year, and three-year after diagnosis of BC in a tertiary referral center in Klang Valley. The Global Physical Activity Questionnaire and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire were used to measure PA and QOL of the survivors. A generalized estimating equation was performed to examine the association of PA and QOL longitudinally.

RESULTS

The mean age was 56.89 (± 10.56) years old, and the majority were Chinese (50.4%). At baseline, 48.1% of patients were active and it declined to 39.8% at one year, and 35.3% at third year. Three years after diagnosis (Adjusted Odds Ratio [AOR]: 1.74, P = .021), being underweight (AOR: 3.43, P = .004) and being Malay (AOR: 1.86, P = .042) were found to be significant associating factors with inactivity. Overall, the QOL was observed to decrease over the years. Global health status, physical and cognitive functioning had a significant declining trend from baseline to three years ( P = < 0.001, P = < 0.001 and P = .001 respectively). For symptom scales, patients experienced more fatigue over time too ( P = .006). When analysing the association of PA and QOL, being active significantly improve role functioning ( P = .022). At one year, being active also significantly reduced constipation symptoms ( P = .048).

CONCLUSION

The findings showed that BC survivors in Malaysia had inadequate PA levels at diagnosis and further decreased over time. Their QOL had a declining trend, but PA was found to improve constipation symptoms and role functioning. Thus, it is essential to promote PA throughout their follow-ups with more focus on Malay ethnicity.
A Qualitative Exploration of the Acceptability of an Online Web Application to Promote Breast and Cervical Cancer Screening in Primary Care Settings in Malaysia
Authors: Cheong Ai Theng , Lee Ping Yien , Ghazali Sazlina Shariff , Rashid Aneesa Abdul , Ng Chirk Jenn , Teo Chin Hai , Rajoo Yamuna , Ching Ong Siu , Jaganathan Maheswari , Ho Bee Kiau , Teo Soo-Hwang
Published: May 2022

PURPOSE

In Malaysia, breast and cervical are the most common and third most common cancers respectively. They are associated with high morbidity and mortality in women. With the rapid development of information communication technology and widespread adoption of mobile devices in low to middle-income countries, online web applications (app) could be one of the strategies to engage patients to go for screening programs.

METHODS

Fifteen (15) health care professionals (HCPs) and 25 patients visiting the primary care were interviewed through focus groups and in-depth interviews to determine the acceptability of an online web application to promote screening for these cancers.

RESULTS

Both HCPs and patients expressed that an online web app would be beneficial to the technology-savvy group such as the younger generation. However, the older-aged group could benefit from it with some assistance. The primary consideration identified is the user's information technology (IT) competency. Participants suggested that the use of easy-to-use features (eg, download method), visually easy-to-understand formats (eg, less text and more pictures, videos), and provision of support to navigate the web app may be critical to ensure good uptake of a web app on screening. Contents of the app suggested to be included were: individual risk assessment for the users of the app, benefits of screening, information addressing patients' barriers such as fear, embarrassment, logistic, and cost issues.

CONCLUSION

The findings of our study may be useful as a guide to developing an online web app to promote breast and cervical cancer screening.
ANPEP: A Potential Regulator of Tumor Cell—Immune Metabolic Interactions in Prostate Cancer of Men of African Descent
Authors: Elkenawi Asmaa , Awasthi Shivanshu , Serna Amparo , Dhillon Jasreman , Yamoah Kosj
Published: May 2022

PURPOSE

Prostate cancer (PCa) is the leading cause of male cancer deaths in Africa. In USA, African American men (AA) experience higher mortality rate compared to European American men (EA). While socioeconomics factors contribute toward these disparities, distinct molecular mechanisms in AA remain important drivers. For example, in previous work, we discovered that PCa form AA men harbored a significantly higher expression of Aminopeptidase N (ANPEP) as compared with EA. Aminopeptidase N regulates immune cell function and mediates tumor cell migration but its role in PCa remains uninvestigated.

METHODS

We explored ANPEP expression related to a range of genomic classifiers in multiple datasets. We then prospectively examined the differentially expressed genes in PCa tissues collected from 120 AA and 120 EA patients enrolled on the VANDAAM clinical trial. We further correlated ANPEP expression with various signatures related to immune and metabolic activity. We also experimentally examined the expression of ANPEP in different components of tumor microenvironment.

RESULTS

In the VANDAAM study, ANPEP represents the top differentially expressed gene between AA and EA men. Our data driven approach revealed that ANPEP correlates with signature of cholesterol transport and androgen signaling. Interestingly, these signatures dominate in PCa with high macrophage infiltration. Deconvolution of immune cell content using computational approaches indeed demonstrated that only AA patients with high ANPEP expression significantly accumulated high content of inflammatory macrophages. Further experimental findings showed that ANPEP indeed represents a marker of tumor-associated macrophages, a type of immune cells known to contribute to PCa progression.

CONCLUSION

We have identified ANPEP as a macrophage-related gene with a potential role in cholesterol metabolism and AR signaling in AA. Future work will focus on the functional role of ANPEP activity in the tumor immune microenvironment using Liquid chromatography-high resolution mass spectrometry and explants derived from AA and EA PCa patients.