Genetic screening of liver cancer: State of the art.

Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy.

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies. In this narrative review, we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease, immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following. We focused on the anti-gliadin antibodies, antibodies to different isoforms of tissue transglutaminase (TG) (anti-TG2, 3, and 6 antibodies), anti-glycine receptor antibodies, anti-glutamine acid decarboxylase antibodies, anti-deamidated gliadin peptides antibodies, etc. Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction, presented as different neurological disorders. We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis.

Neurodegenerative diseases (NDDs) affect millions of people worldwide. They develop due to the pathological accumulation and aggregation of various misfolded proteins, axonal and synaptic loss and dysfunction, inflammation, cytoskeletal abnormalities, defects in DNA and RNA, and neuronal death. This leads to the activation of immune responses and the release of the antibodies against them. Recently, it has become clear that autoantibodies (Aabs) can contribute to demyelination, axonal loss, and brain and cognitive dysfunction. This has significantly changed the understanding of the participation of humoral autoimmunity in neurodegenerative disorders. It is crucial to understand how neuroinflammation is involved in neurodegeneration, to aid in improving the diagnostic and therapeutic value of Aabs in the future. This review aims to provide data on the immune system's role in NDDs, the pathogenic role of some specific Aabs against molecules associated with the most common NDDs, and their potential role as biomarkers for monitoring and diagnosing NDDs. It is suggested that the autoimmune aspects of NDDs will facilitate early diagnosis and help to elucidate previously unknown aspects of the pathobiology of these diseases.

Applications of time series analysis in epidemiology: Literature review and our experience during COVID-19 pandemic.

Time series analysis is a valuable tool in epidemiology that complements the classical epidemiological models in two different ways: Prediction and forecast. Prediction is related to explaining past and current data based on various internal and external influences that may or may not have a causative role. Forecasting is an exploration of the possible future values based on the predictive ability of the model and hypothesized future values of the external and/or internal influences. The time series analysis approach has the advantage of being easier to use (in the cases of more straightforward and linear models such as Auto-Regressive Integrated Moving Average). Still, it is limited in forecasting time, unlike the classical models such as Susceptible-Exposed-Infectious-Removed. Its applicability in forecasting comes from its better accuracy for short-term prediction. In its basic form, it does not assume much theoretical knowledge of the mechanisms of spreading and mutating pathogens or the reaction of people and regulatory structures (governments, companies, etc.). Instead, it estimates from the data directly. Its predictive ability allows testing hypotheses for different factors that positively or negatively contribute to the pandemic spread; be it school closures, emerging variants, etc. It can be used in mortality or hospital risk estimation from new cases, seroprevalence studies, assessing properties of emerging variants, and estimating excess mortality and its relationship with a pandemic.

Blood Coagulation and Thrombotic Disorders following SARS-CoV-2 Infection and COVID-19 Vaccination.

Although abundant data confirm the efficacy and safety profile of the developed vaccines against COVID-19, there are still some concerns regarding vaccination in high-risk populations. This is especially valid for patients susceptible to thrombotic or bleeding events and hesitant people due to the fear of thrombotic incidents following vaccination. This narrative review focuses on various inherited and acquired thrombotic and coagulation disorders and the possible pathophysiologic mechanisms interacting with the coagulation system during immunization in view of the currently available safety data regarding COVID-19 vaccines. Inherited blood coagulation disorders and inherited thrombotic disorders in the light of COVID-19, as well as blood coagulation and thrombotic disorders and bleeding complications following COVID-19 vaccines, along with the possible pathogenesis hypotheses, therapeutic interventions, and imaging for diagnosing are discussed in detail. Lastly, the lack of causality between the bleeding and thrombotic events and COVID-19 vaccines is debated, but still emphasizes the importance of vaccination against COVID-19, outweighing the minimal risk of potential rare adverse events associated with coagulation.

Endothelial Dysfunction and Pregnant COVID-19 Patients with Thrombophilia: A Narrative Review.

Pregnancy with SARS-CoV-2 infection can raise the risk of many complications, including severe COVID-19 and maternal-fetal adverse outcomes. Additionally, endothelial damage occurs as a result of direct SARS-CoV-2 infection, as well as immune system, cardiovascular, and thrombo-inflammatory reactions. In this narrative review, we focus on endothelial dysfunction (ED) in pregnancy, associated with obstetric complications, such as preeclampsia, fetal growth retardation, gestational diabetes, etc., and SARS-CoV-2 infection in pregnant women that can cause ED itself and overlap with other pregnancy complications. We also discuss some shared mechanisms of SARS-CoV-2 pathophysiology and ED.

High Concordance of CT Colonography and Colonoscopy Allows for the Distinguishing and Diagnosing of Intestinal Diseases.

(1) Although new imaging methods for examining the GIT with high diagnostic capabilities were introduced, the improvement and implementation of safe, efficient, and cost-effective approaches continue, and GIT diseases are still challenging to diagnose; (2) Methods: We aim to show the possibilities of computed tomography (CT) colonography for early diagnosis of colon diseases using a multidetector 32-channel CT scanner after appropriate preparation; (3) Results: After a colonoscopy was performed earlier, 140 patients were examined with CT colonography. Complete colonoscopy was performed in 80 patients (57.1%) out of 140 who underwent CT colonography. Incomplete colonoscopy was observed in 52 patients (37.2%); in 5 patients (3.6%), it was contraindicated, and in 3 patients (2.1%), it was not performed because of patients' refusal. We determined that in cases of complete FCS in 95% of patients, CT colonography established the same clinical diagnosis as FCS. In cases of incomplete, refused, or contraindicated FCS in 32.7% (17 patients), FCS failed to diagnose correctly. The main reasons for incomplete colonoscopy were: intraluminal obturation of tumor nature-17 patients (33%), extraluminal obturation (compression) from a tumor formation-4 patients (8%), stenotic changes of non-tumor nature-11 patients (21%), congenital diseases with changes in the length of the lumen of the intestinal loops-7 patients (13%), and subjective factors (pain, poor preparation, contraindications) in 13 patients (25%); (4) Conclusions: Our results confirmed that CT colonography is a method of choice in cases of negative FCS results accompanied by clinical data for the neoplastic process and in cases of incomplete and contraindicated FCS. Also, the insufflation system we developed optimizes the method by improving the quality of the obtained images and ensuring good patient tolerance.

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases: State-of-the-art.

Although the coronavirus disease 2019 (COVID-19) pandemic was declared to be no longer "a public health emergency of international concern" with its wide range of clinical manifestations and late complications, severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat, especially to the elderly and patients with comorbidities. Patients with oncologic diseases are vulnerable to severe infection and death. Indeed, patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity. Unfortunately, cancer patients are usually excluded from vaccine trials and investigations of post-vaccinal immune responses and the effectiveness of the vaccines. We aimed to elucidate to what extent patients with cancer are at increased risk of developing severe COVID-19 and what is their overall case fatality rate. We also present the current concept and evidence on the effectiveness and safety of COVID-19 vaccines, including boosters, in oncology patients. In conclusion, despite the considerably higher mortality in the cancer patient group than the general population, countries with high vaccination rates have demonstrated trends toward improved survival of cancer patients early and late in the pandemic.

Long-term effectiveness, outcomes and complications of bariatric surgery.

Dietary imbalance and overeating can lead to an increasingly widespread disease - obesity. Aesthetic considerations aside, obesity is defined as an excess of adipose tissue that can lead to serious health problems and can predispose to a number of pathological changes and clinical diseases, including diabetes; hypertension; atherosclerosis; coronary artery disease and stroke; obstructive sleep apnea; depression; weight-related arthropathies and endometrial and breast cancer. A body weight 20% above ideal for age, gender and height is a severe health risk. Bariatric surgery is a set of surgical methods to treat morbid obesity when other treatments such as diet, increased physical activity, behavioral changes and drugs have failed. The two most common procedures currently used are sleeve gastrectomy and gastric bypass. This procedure has gained popularity recently and is generally considered safe and effective. Although current data show that perioperative mortality is low and better control of comorbidities and short-term complications is achieved, more randomized trials are needed to evaluate the long-term outcomes of bariatric procedures. This review aims to synthesize and summarize the growing evidence on the long-term effectiveness, outcomes and complications of bariatric surgery.

The End or a New Era of Development of SARS-CoV-2 Virus: Genetic Variants Responsible for Severe COVID-19 and Clinical Efficacy of the Most Commonly Used Vaccines in Clinical Practice.

Although the chief of the World Health Organization (WHO) has declared the end of the coronavirus disease 2019 (COVID-19) as a global health emergency, the disease is still a global threat. To be able to manage such pandemics in the future, it is necessary to develop proper strategies and opportunities to protect human life. The data on the SARS-CoV-2 virus must be continuously analyzed, and the possibilities of mutation and the emergence of new, more infectious variants must be anticipated, as well as the options of using different preventive and therapeutic techniques. This is because the fast development of severe acute coronavirus 2 syndrome (SARS-CoV-2) variants of concern have posed a significant problem for COVID-19 pandemic control using the presently available vaccinations. This review summarizes data on the SARS-CoV-2 variants that are responsible for severe COVID-19 and the clinical efficacy of the most commonly used vaccines in clinical practice. The consequences after the disease (long COVID or post-COVID conditions) continue to be the subject of studies and research, and affect social and economic life worldwide.

Islet transplantation-immunological challenges and current perspectives.

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes (T1D) by transplanting pancreatic beta cells. Overall, pancreatic islet transplantation has improved to a great extent, and cellular replacement will likely become the mainstay treatment. We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced. Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h. Approximately 54% of the patients gained insulin independence at the end of the first year, while only 20% remained insulin-free at the end of the second year. Eventually, most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation, which imposed the need to improve immunological factors before transplantation. We also discuss the immunosuppressive regimens, apoptotic donor lymphocytes, anti-TIM-1 antibodies, mixed chimerism-based tolerance induction, induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes, pretransplant infusions of donor apoptotic cells, B cell depletion, preconditioning of isolated islets, inducing local immunotolerance, cell encapsulation and immunoisolation, using of biomaterials, immunomodulatory cells, etc.

In Silico Probiogenomic Characterization of Lactobacillus delbrueckii subsp. lactis A4 Strain Isolated from an Armenian Honeybee Gut.

A Lactobacillus delbrueckii ssp. lactis strain named A4, isolated from the gut of an Armenian honeybee, was subjected to a probiogenomic characterization because of its unusual origin. A whole-genome sequencing was performed, and the bioinformatic analysis of its genome revealed a reduction in the genome size and the number of the genes-a process typical for the adaptation to endosymbiotic conditions. Further analysis of the genome revealed that Lactobacillus delbrueckii ssp. lactis strain named A4 could play the role of a probiotic endosymbiont because of the presence of intact genetic sequences determining antioxidant properties, exopolysaccharides synthesis, adhesion properties, and biofilm formation, as well as an antagonistic activity against some pathogens which is not due to pH or bacteriocins production. Additionally, the genomic analysis revealed significant potential for stress tolerance, such as extreme pH, osmotic stress, and high temperature. To our knowledge, this is the first report of a potentially endosymbiotic Lactobacillus delbrueckii ssp. lactis strain adapted to and playing beneficial roles for its host.

Intravenous Immunoglobulins as Immunomodulators in Autoimmune Diseases and Reproductive Medicine.

Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few diseases, while in most cases, their application is off-label and thus different from their registered therapeutic indications according to the summary of product characteristics. In this review, we present the state-of-the-art use of IVIGs in various autoimmune conditions and immune-mediated disorders associated with reproductive failure, as approved therapy, based on indications or off-label. IVIGs are often an alternative to other treatments, and the administration of IVIGs continues to expand as data accumulate. Additionally, new insights into the pathophysiology of immune-mediated disorders have been gained. Therefore, the need for immunomodulation has increased, where IVIG therapy represents an option for stimulating, inhibiting and regulating various immune processes.

Pandemic control - do's and don'ts from a control theory perspective.

Managing a pandemic is a difficult task. Pandemics are part of the dynamics of nonlinear systems with multiple different interactive features that co-adapt to each other (such as humans, animals, and pathogens). The target of controlling such a nonlinear system is best achieved using the control system theory developed in engineering and applied in systems biology. But is this theory and its principles actually used in controlling the current coronavirus disease-19 pandemic? We review the evidence for applying principles in different aspects of pandemic control related to different goals such as disease eradication, disease containment, and short- or long-term economic loss minimization. Successful policies implement multiple measures in concordance with control theory to achieve a robust response. In contrast, unsuccessful policies have numerous failures in different measures or focus only on a single measure (only testing, vaccines, etc.). Successful approaches rely on predictions instead of reactions to compensate for the costs of time delay, on knowledge-based analysis instead of trial-and-error, to control complex nonlinear systems, and on risk assessment instead of waiting for more evidence. Iran is an example of the effects of delayed response due to waiting for evidence to arrive instead of a proper risk analytical approach. New Zealand, Australia, and China are examples of appropriate application of basic control theoretic principles and focusing on long-term adaptive strategies, updating measures with the evolution of the pandemic.

COVID-19 in patients with gastrointestinal stromal tumors: Recommendations for management and vaccination.

The coronavirus disease 2019 (COVID-19) pandemic profoundly affected the management and treatment of patients with malignancies. Based on the progress reported in the literature, we reviewed the recommendations for treatment and vaccination in patients with gastrointestinal stromal tumor (GIST) during COVID-19. We focus on whether there is a risk and what could be the possible effects of vaccinating patients with GIST/cancer. Since the situation is quickly changing, and the health services have been severely disrupted, the diagnosis, treatment and recommendations for vaccination of these patients against COVID-19 are still not updated. The approval of vaccines in the pandemic gave hope that we would soon be able to return to a more normal life. However, the oncology community needs to adapt and provide the most effective treatment and care models for patients with rare cancer, such as GIST. Collecting data on the impact of vaccination in patients with GIST/cancer also will be beneficial in expanding knowledge about the future planning of treatment strategies and optimizing care in the event of a subsequent pandemic.

Effectiveness and safety of COVID-19 vaccines in patients with diabetes as a factor for vaccine hesitancy.

Diabetes mellitus is one of the most common comorbid conditions encountered in patients with severe acute respiratory syndrome coronavirus 2 infection accompanied by significantly increased mortality, prolonged hospital stay, and requirement of invasive mechanical ventilation. This review aims to present the effectiveness and safety profile of available coronavirus disease 2019 (COVID-19) vaccines in people with diabetes as a potential cause of hesitancy for vaccination. Data from published research proves a robust immune response following immunization for COVID-19 in diabetic patients with substantial production of virus-neutralizing antibodies; however, the observed immune response was unequivocally weaker than that in individuals without diabetes. This observation was further enhanced by the findings that worse glycemic control was associated with more suppressed antibody production. In contrast, individuals with optimal glycemic control performed similarly to healthy controls. In addition to the need for strict glucose monitoring and adequate diabetes treatment, those findings reinforce the concept of diabetes-induced secondary immune deficiency and necessitate the application of booster doses to diabetic patients with priority. Nevertheless, after vaccination, reported adverse events were not different from those in the general population. No increase in severe adverse events was documented. While single case reports detected transient increases in blood glucose post-vaccination, more extensive trials could not replicate such a relationship.

Mucosal COVID-19 vaccines: Risks, benefits and control of the pandemic.

Based on mucosal immunization to promote both mucosal and systemic immune responses, next-generation coronavirus disease 2019 (COVID-19) vaccines would be administered intranasally or orally. The goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is to provide adequate immune protection and avoid severe disease and death. Mucosal vaccine candidates for COVID-19 including vector vaccines, recombinant subunit vaccines and live attenuated vaccines are under development. Furthermore, subunit protein vac-cines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings, resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines. Additional to their ability to trigger stable, protective immune responses at the sites of pathogenic infection, the development of 'specific' mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics. However, their efficacy and safety should be confirmed.

Relationship Between Time of Admission, Help-Seeking Behavior, and Psychiatric Outcomes: "From Dusk Till Dawn".

Introduction: Day and time of admission influence treatment outcomes and prognosis in several medical specialties; this seems related to resources' ability. It is largely unknown whether this also applies to mental health services. We investigate the relationship between time of admission, patients' demographic and clinical profile, and treatment outcomes. Methods: Demographic and clinical profiles of admitted and discharged patients to a general psychiatric ward between January 1st, 2013 and December 31st, 2020, were analyzed. In addition, we used the last year (i.e., 2020) to monitor rehospitalization. Time of admission was defined as weekdays (working day, weekend) and dayshifts (daytime, dusk, and dawn). Results: During the study period, 12,449 patient admissions occurred. The mean age of the sample was 48.05 ± 20.90 years, with 49.32% (n = 6,140) females. Most admissions (n = 10,542, 84%) occurred on working days. Two-fifths of admissions (39.7%, n = 4,950) were compulsory, with a higher rate outside daytime hours. Patients had slight differences in the clinical profile, resulting from evaluating the different items of the Health of Nation Outcome Scale (HoNOS). Patients admitted on night shifts, weekends, and holidays showed a shorter length of stay; patients compulsorily admitted during daytime (disregarding the day of the week) had a longer length of stay. All patient groups achieved a robust clinical improvement (i.e., an HoNOS score reduction of around 50%), with similar readmission rates. Discussion: The main finding of our study is the relationship between "daytime hours" and fewer compulsory admissions, a result of the interplay between demographics, clinical characteristics, and out-of-clinic service availability (such as ambulatory psychiatric- psychological praxis; day-clinic; home-treatment). The differing clinical profile, in turn, determines differences in treatment selection, with patients admitted after office hours experiencing a higher rate of coercive measures. The shorter length of stay for out-of-office admissions might result from the hospitalization as an intervention. These results should encourage the implementation of outpatient crisis-intervention services, available from dusk till dawn.

Impact of language proficiency on mental health service use, treatment and outcomes: "Lost in Translation".

BACKGROUND: Mastery of a language is bound to place of origin; low language proficiency is thus related to migration and cultural differences, all of which influence access to mental health care, treatment and outcomes. Switzerland, being multilingual, allows the disentangling of language proficiency from migration and, to some extent, culture. This study uses propensity score matching to explore how language proficiency relates to help-seeking behaviour, service use, treatment and outcomes in patients with mental health disorders. METHODS: We used the first admission of patients admitted to and discharged from an academic psychiatric hospital in Switzerland between January 1st, 2013 and December 31st, 2019, with an observation period of one-year post-discharge (until December 31st, 2020). We paired 2101 patients with low language proficiency to 2101 language proficient patients, balancing baseline sociodemographic and clinical characteristics using propensity score matching. RESULTS: Patients with low language proficiency had a higher probability of compulsory admission (OR: 1.79, 99%CI: 1.60-2.02); which remained after adjustment for confounders (OR: 1.51; 99%CI: 1.21-1.89). Whilst in treatment, they had higher rates of compulsory medication (OR: 1.73, 99%CI: 1.16-2.59) and seclusion/restraint (OR: 1.87, 99%CI: 1.25-2.79). Furthermore, patients initially admitted voluntarily had a higher probability of being compulsorily retained (OR: 1.74, 99%CI: 1.24-2.46). Both groups showed similar clinical improvement rates and service use parameters. CONCLUSIONS: Our results demonstrate that low language proficiency constitutes a risk factor for coercive measures throughout hospitalisation. The results demonstrate the need for an increase in language sensitivity in psychiatric care.

A Snapshot Picture of the Fungal Composition of Bee Bread in Four Locations in Bulgaria, Differing in Anthropogenic Influence.

Information about the fungal composition of bee bread, and the fermentation processes to which the fungi contribute significantly, is rather scarce or fragmentary. In this study, we performed an NGS-based metagenomics snapshot picture study of the fungal composition of bee bread in four locations in Bulgaria during the most active honeybee foraging period at the end of June 2020. The sampling locations were chosen to differ significantly in climatic conditions, landscape, and anthropogenic pressure, and the Illumina 2 × 250 paired-end reads platform was used for amplicon metagenomics study of the ITS2 region. We found that some of the already reported canonical beneficial core fungal species were present within the studied samples. However, some fungal genera such as Monilinia, Sclerotinia, Golovinomyces, Toxicocladosporium, Pseudopithomyces, Podosphaera and Septoriella were reported for the first time among the dominant genera for a honeybee related product. Anthropogenic pressure negatively influences the fungal composition of the bee bread in two different ways-urban/industrial pressure affects the presence of pathogenic species, while agricultural pressure is reflected in a decrease of the ratio of the beneficial fungi.