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A transcriptome-wide association study identified susceptibility genes for hepatocellular carcinoma in East Asia

Gastroenterol Rep (Oxf). 2024 Jun 5;12:goae057. doi: 10.1093/gastro/goae057. eCollection 2024.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is prevalent in East Asia. Although genome-wide association studies (GWASs) of HCC have identified 23 risk regions, the susceptibility genes underlying these associations largely remain unclear. To identify novel candidate genes for HCC, we conducted liver single-tissue and cross-tissue transcriptome-wide association studies (TWASs) in two populations of East Asia.

METHODS: GWAS summary statistics of 2,514 subjects (1,161 HCC cases and 1,353 controls) from the Chinese Qidong cohort and 161,323 subjects (2,122 HCC cases and 159,201 controls) from the BioBank Japan project were used to conduct TWAS analysis. The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC. TWAS identified genes were further annotated by Metascape, UALCAN, GEPIA2, and DepMap.

RESULTS: We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction. Of these, 13 genes were located in novel regions. Besides, we found 83 genes overlapped in the Chinese and Japanese cohorts with P < 0.05, of which, three genes (NUAK2, HLA-DQA1, and ATP6V1G2) were discerned by both single-tissue and cross-tissue TWAS approaches. Among the genes identified through TWAS, a significant proportion of them exhibit a credible role in HCC biology, such as FAM96B, HSPA5, POLRMT, MPHOSPH10, and RABL2A. HLA-DQA1, NUAK2, and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.

CONCLUSIONS: Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.

PMID:38846986 | PMC:PMC11153834 | DOI:10.1093/gastro/goae057

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Impact of metformin on melanoma: a meta-analysis and systematic review

Front Oncol. 2024 May 23;14:1399693. doi: 10.3389/fonc.2024.1399693. eCollection 2024.

ABSTRACT

BACKGROUND: There is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.

METHODS: Selection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using ‘Melanoma’ and ‘Metformin’ as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and I 2 statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.

RESULTS: A total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I2 = 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I2 = 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I2 = 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I2 = 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.

DISCUSSION: The improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.

PMID:38846983 | PMC:PMC11153730 | DOI:10.3389/fonc.2024.1399693

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Optical diagnosis in still images of colorectal polyps: comparison between expert endoscopists and PolyDeep, a Computer-Aided Diagnosis system

Front Oncol. 2024 May 23;14:1393815. doi: 10.3389/fonc.2024.1393815. eCollection 2024.

ABSTRACT

BACKGROUND: PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to predict the histology of colonic lesions.

OBJECTIVE: To compare the diagnostic performance of PolyDeep and expert endoscopists for the optical diagnosis of colorectal polyps on still images.

METHODS: PolyDeep Image Classification (PIC) is an in vitro diagnostic test study. The PIC database contains NBI images of 491 colorectal polyps with histological diagnosis. We evaluated the diagnostic performance of PolyDeep and four expert endoscopists for neoplasia (adenoma, sessile serrated lesion, traditional serrated adenoma) and adenoma characterization and compared them with the McNemar test. Receiver operating characteristic curves were constructed to assess the overall discriminatory ability, comparing the area under the curve of endoscopists and PolyDeep with the chi- square homogeneity areas test.

RESULTS: The diagnostic performance of the endoscopists and PolyDeep in the characterization of neoplasia is similar in terms of sensitivity (PolyDeep: 89.05%; E1: 91.23%, p=0.5; E2: 96.11%, p<0.001; E3: 86.65%, p=0.3; E4: 91.26% p=0.3) and specificity (PolyDeep: 35.53%; E1: 33.80%, p=0.8; E2: 34.72%, p=1; E3: 39.24%, p=0.8; E4: 46.84%, p=0.2). The overall discriminative ability also showed no statistically significant differences (PolyDeep: 0.623; E1: 0.625, p=0.8; E2: 0.654, p=0.2; E3: 0.629, p=0.9; E4: 0.690, p=0.09). In the optical diagnosis of adenomatous polyps, we found that PolyDeep had a significantly higher sensitivity and a significantly lower specificity. The overall discriminative ability of adenomatous lesions by expert endoscopists is significantly higher than PolyDeep (PolyDeep: 0.582; E1: 0.685, p < 0.001; E2: 0.677, p < 0.0001; E3: 0.658, p < 0.01; E4: 0.694, p < 0.0001).

CONCLUSION: PolyDeep and endoscopists have similar diagnostic performance in the optical diagnosis of neoplastic lesions. However, endoscopists have a better global discriminatory ability than PolyDeep in the optical diagnosis of adenomatous polyps.

PMID:38846970 | PMC:PMC11153726 | DOI:10.3389/fonc.2024.1393815

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The long noncoding RNA SUMO1P3 as urinary biomarker for monitoring bladder cancer progression

Front Oncol. 2024 May 23;14:1325157. doi: 10.3389/fonc.2024.1325157. eCollection 2024.

ABSTRACT

INTRODUCTION: Urothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients’ workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression.

METHODS: This study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls.

RESULTS: SUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application.

DISCUSSION: We have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a.

PMID:38846969 | PMC:PMC11153750 | DOI:10.3389/fonc.2024.1325157

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Evaluation of Parameters and Nozzle Tip Damage after Clinical Use of Three Hydrophilic Intraocular Lens Injector Models

J Ophthalmol. 2024 May 30;2024:2360368. doi: 10.1155/2024/2360368. eCollection 2024.

ABSTRACT

PURPOSE: To assess the nozzle tip damage and the parameters of three different hydrophilic intraocular lens (IOL) injector models.

METHODS: After routine cataract surgeries at the University Eye Hospital Heidelberg, all the used IOL injectors were collected from the operating room and sent to our laboratory. Nozzle tip damage was assessed under a microscope and graded as follows: no damage (grade 0), slight scratches (1), deep scratches (2), extensions (3), cracks (4), and bursts (5). Each damage grade was assigned a score from 0 to 5, and the total damage score for each injector system was calculated and compared. Nozzle tip parameters (diameters and areas), plunger tip parameters, and tip angles were also measured in each model.

RESULTS: The damage scores were (median, Q3-Q1): 1 (1-1) for Accuject, 1 (1-1) for Bluemixs, and 1 (1-1) for RayOne. There was no statistically significant difference in the damage scores between the study groups (P > 0.05). The outer cross-sectional vertical and horizontal diameters were 1.69 and 1.69 mm for Accuject, 1.69 and 1.69 mm for Bluemixs, and 1.70 and 1.71 mm for RayOne. Plunger tip areas were 0.78 mm2 for Accjuect, 0.74 mm2 for Bluemixs, and 0.43 mm2 for RayOne. Plunger tip area/inner cross-sectional area of the nozzle tip (%) was 31.2% for RayOne, 66.7% for Accuject, and 63.8% for Bluemixs. The tip angles for three injector models were 56° (Accuject), 56° (Bluemixs), and 44° (RayOne).

CONCLUSIONS: All the injector models showed mild to moderate damage to the nozzle tip after IOL implantation, even with smaller diameter tips. RayOne resulted in the lowest ratio between plunger tip area and inner cross-sectional area of the nozzle tip and a better distribution of damage categories than the other two groups. All three injector models had relatively small tip parameters. If smaller incisions are required in certain patients, smaller tip parameters should be considered.

PMID:38846928 | PMC:PMC11156505 | DOI:10.1155/2024/2360368

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Efficacy of acupuncture treatment for breast cancer-related insomnia: study protocol for a multicenter randomized controlled trial

Front Psychiatry. 2024 May 23;15:1301338. doi: 10.3389/fpsyt.2024.1301338. eCollection 2024.

ABSTRACT

BACKGROUND: Insomnia is one of the most common symptoms among breast cancer patients, which can be present throughout all stages of breast cancer. As a non-pharmacological alternative treatment, acupuncture has been suggested to improve sleep situations in patients with cancer suffering from insomnia. However, there is a lack of well-designed, high-quality clinical evidence regarding the efficacy of acupuncture in the treatment of breast cancer-related insomnia. This study is conducted to evaluate the efficacy and safety of acupuncture treatment for breast cancer-related insomnia.

METHODS: This study was designed as a multicenter, randomized, sham-controlled clinical trial. A total of 264 eligible patients with breast cancer-related insomnia will be randomized into an acupuncture group and a sham acupuncture group in a 1:1 ratio. In the trial, patients in the acupuncture and sham acupuncture groups will receive 12 sessions over a consecutive 4-week period. The primary outcome will be the treatment response rate of Insomnia Severity Index (ISI) at week 4; secondary outcomes include treatment remission rate of ISI, Sleep Efficiency (SE) obtained by the use of Sleep diary, treatment response rate of ISI at 8th and 16th weeks of follow-up, the mean changes of ISI, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Questionnaire – Core 30 (QLQ-C30), sleep parameters recorded in Actigraphy and weekly usage of remedial drugs. Adverse events will be recorded throughout the study. All analyses will be based on the ITT principle and performed with SAS 9.4 statistical software.

DISCUSSION: This trial will evaluate the clinical efficacy and safety of acupuncture for breast cancer-related insomnia. If proven effective, acupuncture will provide an effective option for patients with breast cancer-related insomnia, which will play a positive role in helping patients reduce their use of sleeping medications.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05510700.

PMID:38846918 | PMC:PMC11153751 | DOI:10.3389/fpsyt.2024.1301338

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Hematological parameters to predict post-COVID-19 immune response among vaccinated and nonvaccinated individuals: a retrospective cross-sectional study

Ann Med Surg (Lond). 2024 Apr 16;86(6):3330-3336. doi: 10.1097/MS9.0000000000002064. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: This study finds the changes in the hematological parameters of healthy individuals to predict the immune status against coronavirus disease 2019 (COVID-19) among COVID -19 vaccinated and nonvaccinated individuals.

METHODS: A comparative cross-sectional study among 210 healthy individuals was conducted. All individuals were divided into three groups, that is, IgG positive, IgG negative, and IgG and IgM positive, based on ELISA. Data analysis was done using SPSS version 25 for Windows.

RESULTS: A statistically significant effect was found among the three groups in terms of mean levels of hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), red blood cells (RBC), RDW-CV, lymphocyte, neutrophil, eosinophils, and basophil count. The study also showed that 52.8% (n=74) had neither taken vaccination nor had any history of previous COVID-19 infection but were IgG antibody positive.

CONCLUSION: There was a statistically significant difference among hematological parameters between immune and nonimmune groups, and it can predict the COVID-19 immune status.

PMID:38846900 | PMC:PMC11152799 | DOI:10.1097/MS9.0000000000002064

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Epidemiology of measles in southern Iran: trends, challenges, and vaccination insights

Ann Med Surg (Lond). 2024 Apr 3;86(6):3273-3280. doi: 10.1097/MS9.0000000000002004. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: Measles, a highly contagious and vaccine-preventable disease, continues to present global public health challenges. This retrospective study focused on measles outbreaks in Hormozgan province, southern Iran, spanning from 2014 to 2019.

METHODS: Between 2014 and 2019, patients suspected of having measles, as reported by medical centers in Hormozgan, were subject to a comprehensive evaluation. The diagnosis of measles was conclusively established through the use of real-time polymerase chain reaction (RT-PCR) testing. A detailed collection of pertinent data was undertaken. SPSS software, version 21, was employed for statistical analysis.

RESULTS: In the current study, out of 1291 clinically suspected measles cases, 151 were PCR-confirmed, with an average age of 16.77 years (±10.46), comprising 50.9% males and 49.1% females. The annual distribution showed varied incidence: 8.4% in 2014, peaking at 18.8% in 2015, then fluctuating to 11.4% in 2016, 0.8% in 2017, and 17.9% in 2018, with no cases in 2019. Among confirmed cases, 16.5% were vaccinated, while 68.2% were not, and 15.23% had unknown vaccination status.

CONCLUSION: This retrospective study highlights the ongoing challenge of measles in Hormozgan province, Iran, from 2014 to 2019. Despite measles being preventable by vaccination, a significant number of cases were confirmed among both vaccinated and unvaccinated individuals, indicating gaps in immunization coverage and effectiveness. The fluctuating annual incidence, with a peak in 2015 and no cases in 2019, suggests variable success in disease control efforts. This underscores the need for enhanced surveillance, improved vaccination strategies, and public health interventions to effectively combat measles outbreaks in this region.

PMID:38846899 | PMC:PMC11152772 | DOI:10.1097/MS9.0000000000002004

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Acute coronary syndrome in young (≤45 years) patients: a multi-centre observational study

Ann Med Surg (Lond). 2024 May 6;86(6):3303-3309. doi: 10.1097/MS9.0000000000002125. eCollection 2024 Jun.

ABSTRACT

INTRODUCTION: Acute coronary syndrome (ACS) in young individuals (≤45 years) is increasingly recognized as a significant health concern, yet research in this demographic remains limited, particularly within the Palestinian context. This study aims to bridge this gap by comprehensively investigating the clinical characteristics, age-specific profiles, gender disparities, treatment modalities, and angiographic patterns of ACS in young patients compared to their older counterparts.

MATERIALS AND METHODS: A multi-centre observational study was conducted, enroling 468 participants aged 18-55 diagnosed with ACS and admitted to three prominent Palestinian hospitals. Data were collected from medical records, and statistical analysis was performed to assess demographic characteristics, clinical presentations, risk factors, treatment strategies, and outcomes.

RESULTS: The majority of participants were male (87%), with a higher proportion in the older age group (>45 years). Clinical presentations varied, with non-ST segment elevation myocardial infarction (NSTEMI) being the most common diagnosis (48%). Risk factors such as smoking, hypertension, and diabetes were prevalent, with notable gender and age-specific differences. Percutaneous coronary intervention (PCI) was the predominant treatment strategy (83%), with consistent medication use across age groups.

CONCLUSION: ACS in young patients poses a significant public health challenge in Palestine, necessitating tailored preventive strategies and comprehensive management approaches. Understanding the unique demographic and clinical characteristics of young ACS patients is crucial for informing targeted interventions and policies aimed at reducing the burden of cardiovascular disease in this population. These findings contribute valuable insights to the existing literature and underscore the importance of further research in this area to improve outcomes and mitigate the impact of ACS in young individuals globally.

PMID:38846856 | PMC:PMC11152806 | DOI:10.1097/MS9.0000000000002125

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Effects on ondansetron of postdural puncture headache after cesarean section under spinal anesthesia

Ann Med Surg (Lond). 2024 Apr 22;86(6):3385-3390. doi: 10.1097/MS9.0000000000002081. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: Spinal anesthesia is commonly performed for cesarean section, however, postdural puncture headache (PDPH) is one of its most common adverse effects. Ondansetron is an antiemetic for cancer treatment and analgesia-induced nausea and vomiting. In this study, the authors aim to evaluate the effect of postoperative ondansetron on PDPH.

METHODS: In this randomized controlled clinical trial study, 120 pregnant patients are ASA ll, undergoing elective cesarean section, were randomized into two groups (placebo or study). The patients in the study group, immediately after the birth of a baby and 24 h after the operation, received ondansetron 4 mg IV while the placebo group received a placebo. The severity and incidence of headache, postoperative nausea and vomiting, dizziness, neck and lower back pain, and the use of analgesia was assessed in the two groups.

RESULTS: The significant meaning of the time effect (P<0.001) indicated that regardless of the group, for each unit increase in time, the chance of developing a headache increased by 23%, which was statistically significant. Also, the significant meaning of the group effect indicated that regardless of time, patients who did not take indomethacin had ~4.11 times higher chances of developing a headache compared to those who received the medication, which was statistically significant (P=0.004).

CONCLUSION: The administration of ondansetron significantly reduces the occurrence of postspinal anesthesia headaches and neck pain. There was no significant difference in headache severity between the two study groups.

PMID:38846852 | PMC:PMC11152813 | DOI:10.1097/MS9.0000000000002081