This study provides a high-level discussion, conclusion, and recommendations on the underutilization of human papilloma virus vaccination (HPVV) in Saskatchewan, Canada, drawing on the findings of individual and group interviews conducted as a part of a qualitative mixed-method study. It is structured in the following way. First, it reiterates key findings from the overall study at the system, provider, and patient levels by locating them in the published literature. Second, it identifies and discusses cross-cutting themes (from the themes identified) at three levels (system, provider, and patient). It then provides a concluding section drawing from our qualitative effort to address the overarching goal of addressing inequitable HPVV uptake by advocating “systems thinking” to enhance overall HPVV uptake. It concludes by providing broad recommendations and implications.

In the etiology of a large number of metabolic disorders, free radicals are involved in the first line, in particular in the physiopathology of cancers. This interventional study aimed to evaluate in vitro the DPPH radical scavenging activity of a hydroalcoholic extract of Cymbopogon citratus (HAECC) and its antiproliferative activity in human osteosarcoma.

The antiproliferative activity of HAECC was assessed in vitro in MG-63 human osteosarcoma cells. Normal rabbit fibroblasts were used to evaluate the biocompatibility of a plant extract. Cell viability was assessed by the 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT test). The antiradical activity of HAECC was also evaluated in vitro with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Moreover, total flavonoid content of HAECC was quantified by the aluminum chloride colorimetric method.

At low concentrations, the HAECC had high antiradical activity (p < 0.001), although it was lower than that of the ascorbic acid standard. HAECC (final concentration of 125 and 250 µg/mL) compared with the vehicle (DMSO 1%) did not affect normal fibroblast viability (p > 0.05) but significantly inhibited the proliferation of MG-63 tumor cells (p < 0.5) inducing a delay in tumor growth without complete suppression. HAECC had more pronounced cytotoxic activity on MG-63 cancer cells (p < 0.05) than on normal cells (p > 0.05). The HAECC had a high total flavonoid content of 4.127333 ± 0.205 mg quercetin equivalent/100 mg extract.

The HAECC contained active antiproliferative compounds with synergistic cytotoxic effects on a cancer cell line.

Endoscopic biopsy and histopathological examination remain one of the critical methods for high-risk subjects (HRS) screening for esophageal squamous cell carcinoma (ESCC) in symptom-free subjects (SFS) of high-incidence areas (HIA) for ESCC. Almost 90% of the symptom-free residents show normal esophageal epithelia in HIA of ESCC. Based on that, overexamination by endoscopy was found in the screening of early ESCC. Furthermore, in large-scale screening on SFS in HIA of ESCC, the application of endoscopy is limited because of the complicated protocol, high cost, and shortage of experienced endoscopists. The authors suggest a two-step screening method. The first step involves a non-invasive serological screening by which to determine the blood level of neoplasm-related molecules which indirectly reflects the esophageal epithelial lesions. Endoscopic and histopathological examinations are involved in the second step. The second step will decrease the screening cost and improve the effectiveness of endoscopic examination for large-scale screening in HIA of ESCC. It is crucial to combine the two steps within a cooperative medical system in rural villages and communities in cities for extensive application.

Colorectal cancer (CRC) ranks third in incidence and second in mortality worldwide. In Ecuador, there are 2,481 new CRC cases per year and 2,366 cancer deaths yearly. CRC presents in stages III-IV in more than 50% of patients. The standard treatment for CRC is chemotherapy, with an overall survival (OS) of 29–31 months. The status of biomarkers KRAS, NRAS, BRAF, and MSI provides prognostic and predictive value. This study aimed to determine OS and progression-free survival (PFS) for metastatic CRC based on these molecular markers with a minimum follow-up of one year.

This was an observational longitudinal analytical study at the Hospital de Especialidades Eugenio Espejo (HEEE). We obtained demographic, anatomopathological-molecular, and clinical data from the medical records of patients with metastatic CRC from July 1, 2018 until December 31, 2020.

Data were collected from a total of 177 patients. The median follow-up was 21.6 months. The median PFS was 15 months (11.6–18.3) in those with mutated (MT) markers, 18 months (15.7–20.2) for wild type (WT), and 9 months (4.1–13.8) for not performed markers (NR), with a hazard ratio (HR) for PFS in MT versus WT of 0.76; the 95% confidence interval (CI) (0.4–1.4) with p = 0.4. for OS was 21 months (17.1–24.8) for MT markers, 22 months (17.7–26.2) for WT markers, and 19 months (17.7–20.2) for NR. There were no significant differences in OS for MT vs. WT: HR = 1.38, 95% CI (0.8–2.3) p = 0.6. There was no significant association between OS or PSF and KRAS, NRAS, BRAF, and MSI mutations. KRAS was the most mutated marker, with a frequency of 40.2%.

In the first monocentric study of mutations in metastatic CRC patients from Ecuador, patients with WT molecular markers reached the most prolonged OS and PFS, and KRAS had the highest mutation frequency. However, further studies with larger sample sizes are required to corroborate our findings.

Cancer remains a significant threat to public health globally. Within the Traditional Chinese Medicine (TCM) framework, cancer is perceived not merely as an isolated disease but as a manifestation of a broader imbalance within the human body. Recent advancements in modern medicine have garnered increased attention toward the integrative approach to cancer therapy, combining conventional treatments with TCM practices focusing on achieving a holistic balance. This article aims to delineate the comprehensive perspective of TCM in integrative cancer therapy, emphasizing its foundational principles of personalized treatment grounded in syndrome differentiation and treatment.

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate gene expression by either degrading or inhibiting the translation of mRNAs and have significant roles in the development of various tumors. A polymorphism (rs2682818) in miR-618 has been confirmed to be correlated with susceptibility to various cancers. Nonetheless, its role has not been investigated in neuroblastoma to date. Therefore, we assessed whether the miR-618 rs2682818 C>A polymorphism was correlated with neuroblastoma risk in the Chinese population.

We performed this case-control study with 402 neuroblastoma patients and 473 cancer-free controls from Jiangsu Province, China. The TaqMan method was used to genotype the miR-618 rs2682818 polymorphism. We evaluated the strength of the correlation between this polymorphism and susceptibility to neuroblastoma based on the odds ratios (ORs) and 95% confidence intervals (CIs), which were calculated by logistic regression models.

Overall, no significant correlation was observed between the rs2682818 C>A polymorphism and the risk of neuroblastoma. Nevertheless, we conducted a further stratification analysis and discovered that, compared to the CC genotype of rs2682818, the subjects with CA/AA genotypes had a lower risk to neuroblastoma developing in the adrenal gland (adjusted OR = 0.57, 95% CI: 0.35–0.91, p = 0.018).

We first discovered that the miR-618 rs2682818 C>A polymorphism had an essential role in significantly decreasing susceptibility to neuroblastoma in the adrenal gland.

Renal function is the basic focus of examination before kidney cancer surgery and determines the choice of surgery procedure. The prediction of renal function after surgery may also affect the surgical method, and it will certainly affect the prognosis of the patient. Herein, we provide a review of the relevant literature on partial nephrectomy (PN) and radical nephrectomy (RN) respectively, discuss methods for estimating kidney function, and compare effects. We found that the most reliable way to predict new baseline glomerular filtration rate (GFR) after PN was the quantitative estimation of the Percent of Preserved Parenchymal Mass (PPPM), while the simplest way to predict new-baseline GFR after RN was derivation from contralateral kidney, with ≥45 mL/min/1.73 m2 considered a good cutoff to evaluate the kidney function and survival outcomes. In addition, based on AI, the imaging-guided analysis would provide a feasible, simple, and reliable prediction model.

Host-specific genetics, such as epigenetic profiles and genetic variants, can contribute to the pathogenesis of infectious diseases. Strong associations have been previously identified in infections by human immunodeficiency virus (HIV), Plasmodium falciparum, norovirus, and influenza A virus. Despite the efforts to characterize the role of host genetics in severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2) infection, this comprehension remains incipient. Coronavirus disease 2019 (COVID-19) can evolve with a wide spectrum of manifestations, ranging from asymptomatic and mild cases to severe forms with acute respiratory distress syndrome, multi-organ complications, and even death. Classic clinical risk factors only partially explain this interindividual variability, suggesting that host genetics may contribute to the heterogeneity of courses. Robust evidence has revealed the multiple associations of genes (ABO, PPP1R15A, SLC6A20, IFNAR2, OAS, TYK2, CCR2, CCR5, TLR7, ApoE, TMPRSS2, HLA, ACE2, etc.) with the susceptibility and/or severity of SARS-CoV-2 infection. In addition, the genetics behind the established risk factors have been considered: at least four loci associated with COVID-19 severity (DPP9, FOXP4, SFTPD and MUC5B) have been previously linked to lung fibrosis, interstitial lung disease, lung carcinomas, and/or decreased lung function. In summary, identifying the host-specific genetic factors may improve our knowledge of risk groups for infection and severe outcomes, as well as the biological mechanisms of therapeutic relevance. Therefore, the present literature review aims to understand the genetics underlying the patterns of susceptibility and prognosis of COVID-19.

Mitochondria are one of the most crucial components of the cell. Aging has a critical impact on mitochondria. Various studies have shown that the relationship between aging and mitochondria is multifaceted. In this review, we focused on mitochondrial DNA mutations and their impact on the cardiovascular system during aging and oxidative stress. While mitochondria contain their own DNA, part of their proteome is encoded by nuclear DNA, which further complicates the inheritance of mitochondrial diseases, making almost all methods of transmission of various pathologies possible. We provide a discussion on mitochondrial DNA mutagenesis and the most common problems associated with mitochondrial DNA mutations.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced into cytopathology practice more than 5 years ago. It classifies the salivary gland lesion into 6 diagnostic categories and provides the risk of malignancy (ROM) and clinical management guidelines for each category. More than 100 articles have confirmed the applicability of this reporting system in routine practice and its important role in providing a uniform reporting system for salivary gland fine-needle aspiration. At the same time, new questions and feedback for improvement have emerged, as well as opportunities for clarification. For example, questions related to the non-diagnostic category are multiple-fold. First, although the cytologic criterion of the non-diagnostic category is currently defined as “<60 lesional cells or normal salivary gland tissue within the clinical setting of an evident mass”, this has not been established or validated in the literature. Second, the ROM for the non-diagnostic category is high. Another question surrounds the interesting topic of sub-classifying current MSRSGC categories, as the risk of malignancy could vary in tumors of the same category. The last one concerns the incorporation of the ever-increasing number of molecular markers and antibody detection of gene re-arrangements, so-called next-generation immunohistochemistry (IHC) markers, into routine cytopathology practice. The quick application of next-generation sequencing into pathology practice provides an exciting opportunity for salivary gland cytopathology diagnosis.

Artificial intelligence (AI) with machine learning tools are used to search, store, and analyze medical data to benefit both physicians and the health of patients in various ways. With the advancement in machine learning algorithms and bioinformatics techniques, AI has become an essential part of modern healthcare society. AI algorithms and deep learning applications support clinicians with managing health records, making diagnoses and clinical decisions, prescribing medication, determining mental health, and imaging analysis. Clinicians gain rapid access to information and research relevant to the needs of the patients. As some algorithms compete with and sometimes outperform clinicians, it is necessary to fully integrate this technology into daily medical practices. However, we must recognize the strengths and weaknesses of AI, and obtain the perspectives of experts outside the medical field to enable the inclusion of the ethical, philosophical, sociological, psychological, behavioral, and economical aspects of machine behavior when understanding the evolving interaction of machines with humans, so that it can be used for advantageous purposes. AI technology cannot be considered a replacement for physicians, rather it can act as multiple task-oriented device support to ease the burden on clinicians so that they can provide better care of life to patients at every level.

Hepatitis B virus (HBV) is a widely prevalent liver infection that can cause acute or chronic hepatitis. Although current treatment modalities are highly effective in the suppression of viral levels, they cannot eliminate the virus or achieve definitive cure. This is a consequence of the complex nature of HBV-host interactions. Major challenges to achieving sustained viral suppression include the presence of a high viral burden from the HBV DNA and hepatitis B surface antigen (HBsAg), the presence of reservoirs for HBV replication and antigen production, and the HBV-impaired innate and adaptive immune response of the host. Those therapeutic methods include cell entry inhibitors, HBsAg inhibitors, gene editing approaches, immune-targeting therapies and direct inhibitors of covalently closed circular DNA (cccDNA). Novel approaches that target these key mechanisms are now being studied in preclinical and clinical phases. In this review article, we provide a comprehensive review on mechanisms by which HBV escapes elimination from current treatments, and highlight new agents to achieve a definitive HBV cure.

Traditional Chinese Medicine has been implemented in clinical practice for thousands of years to treat rheumatoid arthritis (RA). Aconitum carmichaelii Debx (Fuzi) and Paeonia lactiflora Pall (Baishao) are a common herb-pair that is used in many herbal prescriptions to treat RA. However, the mechanism of Fuzi and Baishao for treating RA remains unclear. Here, we used a systems pharmacology and molecular docking approach to investigate the mechanism of Fuzi and Baishao in the treatment of RA.

We obtained active compounds and targets through a database search and manual supplementation, followed by network construction and protein-protein interaction construction, which were then verified using molecular docking, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses.

We obtained 56 active compounds (including a duplicate compound), 102 targets, and 54 pathways using our systems approach. The results indicate that both herbs are involved in IL-17 and tumor necrosis factor signaling pathways through albumin, interleukin-6, glyceraldehyde-3-phosphate dehydrogenase, epidermal growth factor receptor, prostaglandin-endoperoxide synthase 2, and other targets in the treatment of RA. After the combination, the number of targets, pathways, and specific targets on pathways increased.

This research provides new insight into this particular herb pair and novel research directions for the treatment of RA with Fuzi and Baishao.

Despite advances in current treatment options, Hepatocellular Carcinoma (HCC) recurrence still presents as a significant clinical challenge. After initial treatment, HCC recurrence occurs in a considerable portion of patients without an available standardized protocol for managing such an incident. Recurrence of advanced liver disease may make surgical treatment options impossible, in which case, locoregional therapy should be considered as an alternative. This review article discusses recurrent HCC after initial treatment and available non-surgical treatment options. Along with systemic therapy, liver-targeted therapies for recurrent HCC including, radiofrequency, microwave ablation, transarterial chemoembolization, and stereotactic body radiation therapy are promising options. Thermal ablation with radiofrequency or microwave ablation is a suitable treatment option for patients who experience smaller tumor recurrences but are not operable because of comorbidities, impaired liver functions, or tumor locality. Transarterial chemoembolization or radioembolization using Yttrium-90 can be used for patients with an incurable disease and have comparatively low adverse effects.

Nonalcoholic fatty liver disease (NAFLD) particularly affects patients with type 2 diabetes and obesity. The incidence of NAFLD has increased significantly over the last decades and is now pandemically across the globe. It is a complex systemic disease comprising hepatic lipid accumulation, inflammation, lipotoxicity, gut dysbiosis, and insulin resistance as main features and with the potential to progress to cirrhosis and hepatocellular carcinoma (HCC). In numerous animal and human studies the gut microbiota plays a key role in the pathogenesis of NAFLD, NAFLD-cirrhosis and NAFLD-associated HCC. Lipotoxicity is the driver of inflammation, insulin resistance, and liver injury. Likewise, western diet, obesity, and metabolic disorders may alter the gut microbiota, which activates innate and adaptive immune responses and fuels hereby hepatic and systemic inflammation. Indigestible carbohydrates are fermented by the gut microbiota to produce important metabolites, such as short-chain fatty acids and succinate. Numerous animal and human studies suggested a pivotal role of these metabolites in the progression of NAFLD and its comorbidities. Though, modification of the gut microbiota and/or the metabolites could even be beneficial in patients with NAFLD, NAFLD-cirrhosis, and NAFLD-associated HCC. In this review we collect the evidence that exogenous and endogenous hits drive liver injury in NAFLD and propel liver fibrosis and the progressing to advanced disease stages. NAFLD can be seen as the product of a complex interplay between gut microbiota, the immune response and metabolism. Thus, the challenge will be to understand its pathogenesis and to develop new therapeutic strategies.

We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid (tauro-THBA) in cholestasis.

Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS). The concentration of tauro-THBA was compared between ABCB4-mutated patients with different prognoses. The areas under the curve (AUCs) of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve (ROC), with another patient cohort for further verification.

The overall hydrophobicity indices of bile acids in ABCB4-mutated patients (12.99±3.25 m) were significantly lower than those of healthy controls (14.02±1.74 m, p<0.000). That was due to markedly increased bile acid modifications including conjugation, sulfation, and ketonization. Differences in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not significant. ROC analysis indicated that levels of tauro-THBA of <60 nM yielded an AUC of 0.900 with a sensitivity of 80% and specificity of 87.5% for ABCB11-mutated patients with different prognoses (p=0.0192). Of the 15 patients with good prognosis, 14 were classified correctly and four of the five patients with a poor prognosis were classified correctly (14:15 vs. 1:5, p=0.005) with tauro-THBA as a classifier.

Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gamma-glutamyl transferase intrahepatic cholestasis patients.

Acinar cell carcinoma (ACC) of the pancreas is a rare malignant neoplasm with a poor prognosis. When in the pancreas, the diagnosis is relatively straightforward, based on characteristic cytomorphologic features and positive staining for acinar enzyme products such as trypsin and BCL10. However, ACC may occur in extra-pancreatic locations, where features overlapping with other entities can make the diagnosis challenging if not considered . Here, we report a case of pancreatic ACC that presented as a large splenic mass with a radiologically and grossly unremarkable pancreas. The patient was subsequently found to have a BRCA2 germline mutation. This case is presented to highlight an unusual presentation of ACC; review the cytopathologic, histologic, and immunohistochemical characteristics of ACC; and add to the literature associating ACC with BRCA2 mutations, which may have therapeutic and familial testing implications.