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Many important aspects of biological knowledge at the molecular level can be represented by pathways. Through their analysis, we gain mechanistic insights and interpret lists of interesting genes from experiments (usually omics and functional genomic experiments). As a result, pathways play a central role in the development of bioinformatics methods and tools for computing predictions from known molecular-level mechanisms. Qualitative as well as quantitative knowledge about pathways can be effectively represented through biochemical networks linking the biochemical reactions and the compounds (e.g., proteins) occurring in the considered pathways. So, repositories providing biochemical networks for known pathways play a central role in bioinformatics and in systems biology. Here we focus on Reactome, a free, comprehensive, and widely used repository for biochemical networks and pathways. In this paper, we: (1) introduce a tool StARGate-X (STatistical Analysis of the Reactome multi-GrAph Through nEtworkX) to carry out an automated analysis of the connectivity properties of Reactome biochemical reaction network and of its biological hierarchy (i.e., cell compartments, namely, the closed parts within the cytosol, usually surrounded by a membrane); the code is freely available at https://github.com/marinoandrea/stargate-x; (2) show the effectiveness of our tool by providing an analysis of the Reactome network, in terms of centrality measures, with respect to in- and out-degree. As an example of usage of StARGate-X, we provide a detailed automated analysis of the Reactome network, in terms of centrality measures. We focus both on the subgraphs induced by single compartments and on the graph whose nodes are the strongly connected components. To the best of our knowledge, this is the first freely available tool that enables automatic analysis of the large biochemical network within Reactome through easy-to-use APIs (Application Programming Interfaces).

Background: The rise of multi-drug-resistant Gram-negative bacteria necessitates the development of new antimicrobial agents. Cefiderocol shows promising activity by exploiting bacterial iron transport systems to penetrate the outer membranes of resistant pathogens. Objectives: This study evaluates the efficacy of cefiderocol testing methods and trailing effect impact using a ComASP® Cefiderocol panel, disk diffusion (DD), and MIC test strips (MTS) compared to iron-depleted broth microdilution (ID-BMD). Methods: A total of 131 Gram-negative strains from clinical samples was tested by commercial methods and the gold standard. Results were interpreted as per 2024 and 2023 EUCAST guidelines. Results: ID-BMD revealed high cefiderocol susceptibility among Enterobacterales and Pseudomonas aeruginosa, with one Klebsiella pneumoniae isolate being resistant. Acinetobacter baumannii exhibited higher MIC values, particularly considering trailing effects that complicated MIC readings. ComASP® showed 97% categorical agreement (CA) and 66% essential agreement (EA) with ID-BMD for Enterobacterales but failed to detect the resistant K. pneumoniae. DD tests demonstrated variable CA (72% or 93%), and 38% or 34% of strains within the ATU according to EUCAST Breakpoint Tables v13.0 and 14.0, respectively, with major errors only. MTS for P. aeruginosa had 100% CA but 44% EA, and often underestimated MIC values. Conclusions: The study emphasizes the need for standardized criteria to address trailing effects and ATU and highlights the discrepancies between testing methods. While cefiderocol resistance remains rare, accurate susceptibility testing is crucial for its effective clinical use. The findings suggest that current commercial tests have limitations, necessitating careful interpretation and potential supplementary testing to guide appropriate antibiotic therapy. [ABSTRACT FROM AUTHOR]

The intersection of Human Immunodeficiency Virus (HIV) infection and cardiovascular disease (CVD) represents a significant area of concern; advancements in antiretroviral therapy (ART) have notably extended the life expectancy of people living with HIV (PLWH), concurrently elevating the prevalence of chronic conditions such as CVD. This paper explores the multifaceted relationship between HIV infection, ART, and cardiovascular health, focusing on the mechanisms by which HIV and ART contribute to increased cardiovascular risk, including the promotion of endothelial dysfunction, inflammation, immune activation, and metabolic disturbances. We highlight the critical roles of HIV-associated proteins—Tat, Nef, and gp120—in accelerating atherosclerosis through direct and indirect pathways that exacerbate endothelial damage and inflammation. Additionally, we address the persistent challenge of chronic inflammation and immune activation in PLWH, factors that are strongly predictive of non-AIDS-related diseases, including CVD, even in the context of effective viral suppression. The impact of ART on cardiovascular risk is examined, with particular attention to the metabolic implications of specific ART regimens, which can influence lipid profiles and body composition, thereby modifying CVD risk. The therapeutic potential of statins, aspirin, and emerging treatments such as PCSK9 inhibitors in mitigating cardiovascular morbidity and mortality among PLWH is discussed, alongside considerations for their use in conjunction with ART. Our review underscores the necessity for a comprehensive, multidisciplinary approach to cardiovascular care in PLWH, which integrates vigilant cardiovascular risk assessment and management with HIV treatment. As we navigate the evolving landscape of HIV care, the goal remains to optimize treatment outcomes while minimizing cardiovascular risk, ensuring that the gains in longevity afforded by ART translate into improved overall health and quality of life for PLWH. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) remains a prevalent malignancy and a significant global public health concern, primarily driven by persistent human papillomavirus (HPV) infections. The infectious nature of HPV underscores the preventability of CC through vaccination and screening programs. In addition to HPV, factors such as age, parity, smoking, hormonal contraceptives, and HIV co-infection elevate the risk of CC. HIV-associated immunodeficiency exacerbates susceptibility to infections and cancers, making CC a defining condition for acquired immune deficiency syndrome (AIDS) and one of the most commonly diagnosed cancers among women living with HIV (WLWH). These women face higher risks of HPV exposure due to sexual behavior and often encounter economic, social, and psychological barriers to screening. HIV and HPV co-infection can potentially accelerate CC carcinogenesis, with WLWH typically being diagnosed with CC earlier than their HIV-negative counterparts. Antiretroviral therapy (ART), which reduces AIDS-related mortality, also lowers the risk of invasive CC. The interaction between HIV and HPV is intricate and bidirectional. This summary reviews current evidence on HPV infection and CC in WLWH, highlighting the connections across pathogenesis, prevention, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Out of 39.9 million adults living with HIV in 2022, 20 million were women. Despite bearing a significant burden, women remain underrepresented in clinical trials, including those for antiretroviral treatments (ART). This study evaluates the safety and efficacy of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimen in a real-life cohort of 99 women with HIV (females with HIV, FWH) over 48 and 96 weeks. Methods: A retrospective cohort study utilized data from the Sardinian HIV Network and Sicilian HIV Cohort (SHiNe-SHiC) research group. The study included FWH, who started B/F/TAF as a treatment switch. The primary objectives were achieving and maintaining an HIV RNA level of <50 copies/mL at 48 and 96 weeks. Secondary objectives included treatment safety, durability, and reasons for discontinuation. Data on demographics, viro-immunological markers, lipid profiles, and treatment interruptions were extracted for analysis. Results: Among the 99 FWH, the median age was 51.9 years, and the median duration of HIV was 15.1 years. At baseline, 80.8% had undetectable HIV-RNA, which increased to 93.8% at 96 weeks. There was a statistically significant increase in CD4 cells/mL (48w p < 0.001, 96w p < 0.001) and CD4/CD8 ratio (48w p < 0.009, 96w p < 0.048), and reductions in total cholesterol (48w p < 0.003, 96w p < 0.006) and LDL (48w p < 0.004, 96w p < 0.009) levels at 48 and 96 weeks. Nine treatment interruptions were noted, with one due to adverse events. The regimen was well-tolerated overall. Conclusions: B/F/TAF demonstrated high efficacy and safety in this real-world cohort of FWH, highlighting the critical need for gender-focused research in HIV treatment. Ensuring equitable access to effective treatment options for women is imperative for the global health community's efforts to eliminate HIV. [ABSTRACT FROM AUTHOR]

The present study describes the case of a 33-year-old male patient, who was diagnosed with concurrent infections of Rhodococcus hoagii (R. hoagii), Mycobacterium intracellulare (M. intracellulare), human immunodeficiency virus (HIV) and syphilis. This patient, a homeless farm laborer with no prior medical treatments, exhibited symptoms including persistent fever and cough, and was admitted to hospital. Treatment was initiated with a combination of anti-retroviral therapy with emtricitabine/tenofovir alafenamide/dolutegravir, and antibiotics (azithromycin, rifampicin, amikacin and ethambutol) targeted at both R. hoagii and M. intracellulare, alongside adjustments for drug-drug interactions due to rifampicin administration. Despite initial improvements and discharge after 21 days with scheduled outpatient follow-ups, the patient did not return for further treatment monitoring. The case presented herein underscores the challenges in managing complex infections in severely immunocompromised patients and highlights the need for integrated treatment approaches, careful drug management, and robust follow-up systems to ensure adherence and prevent relapse. In addition, the present case report contributes to the limited literature available on R. hoagii infections in HIV-infected individuals and highlights the need for early intervention and comprehensive management in similar clinical scenarios [ABSTRACT FROM AUTHOR]

A dysregulated host response to infection causes organ dysfunction in sepsis and septic shock, two potentially fatal diseases. They continue to be major worldwide health burdens with high rates of morbidity and mortality despite advancements in medical care. The goal of this thorough review was to present a thorough summary of the current body of knowledge about the prevalence of sepsis and septic shock worldwide. Using widely used computerized databases, a comprehensive search of the literature was carried out, and relevant studies were chosen in accordance with predetermined inclusion and exclusion criteria. A narrative technique was used to synthesize the data that were retrieved. The review's conclusions show how widely different locations and nations differ in terms of sepsis and septic shock's incidence, prevalence, and fatality rates. Compared to high-income countries (HICs), low- and middle-income countries (LMICs) are disproportionately burdened more heavily. We talk about risk factors, comorbidities, and difficulties in clinical management and diagnosis in a range of healthcare settings. The review highlights the need for more research, enhanced awareness, and context-specific interventions in order to successfully address the global burden of sepsis and septic shock. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has revealed a diverse spectrum of clinical manifestations in the pediatric population, including the rare but notable presentation of unilateral parotitis. This comprehensive review explores the complexities surrounding SARS-CoV-2-associated unilateral parotitis in children. It addresses the initial clinical presentation, diagnostic challenges, treatment strategies, and the wider epidemiological impacts of this unusual symptom. The review synthesizes the available literature, providing insights into the pathophysiological mechanisms underlying this atypical manifestation and its implications for pediatric healthcare during the pandemic. Through the rigorous analysis of reported cases, this study underscores the need for increased awareness and a broad differential diagnosis among clinicians. It also emphasizes the importance of continued research to delineate the full clinical spectrum of COVID-19 in children. [ABSTRACT FROM AUTHOR]

Despite significant advances in the management of antiretroviral therapy (ART), leading to improved life expectancy for people living with HIV (PLWH), the incidence of non-AIDS-defining cancers, including breast cancer, has emerged as a critical concern. This review synthesizes current evidence on the epidemiology of breast cancer among HIV-infected individuals, highlighting the potential for an altered risk profile, earlier onset, and more advanced disease at diagnosis. It delves into the molecular considerations underpinning the relationship between HIV and breast cancer, including the role of immunosuppression, chronic inflammation, and gene expression alterations. Additionally, it examines the complexities of managing breast cancer in the context of HIV, particularly the challenges posed by ART and anticancer agents' cross-toxicities and drug–drug interactions. The review also addresses survival disparities, underscoring the need for improved cancer care in this population. By identifying gaps in knowledge and areas requiring further research, this review aims to illuminate the complexities of HIV-associated breast cancer, fostering a deeper understanding of its epidemiology, molecular basis, and clinical management challenges, thereby contributing to better outcomes for individuals at the intersection of these two conditions. This narrative review systematically explores the intersection of HIV infection and breast cancer, focusing on the impact of HIV on breast cancer risk, outcomes, and treatment challenges. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has been chiefly linked with substantial respiratory complications. However, emerging studies have brought attention to the occurrence of severe muscle inflammation (myositis) related to COVID-19, potentially leading to multi-organ failure and increased mortality. Myositis is generally characterized by heightened serum creatine kinase (CK) levels. Acute myositis is characterized by an infiltration of viruses into calf muscle fibers, which may cause a subsequent inflammatory response leading to calf muscle pain. Symptomatic and supportive management, along with explanation and reassurance, is all that is required in managing this condition. While the association between myositis and severe outcomes has been recognized in adults, it remains less understood in the pediatric population. The current retrospective study, conducted at Policlinico San Marco University Hospital in Catania, aimed to analyze clinical and laboratory factors associated with myositis in pediatric patients with SARS-CoV-2 infection. Between January 2022 and January 2023, ten pediatric patients diagnosed with myositis and SARS-CoV-2 infection were evaluated. The study highlighted clinical manifestations such as fever, calf muscle pain, and abnormal gait. Lab results showed elevated CK levels among other findings. All patients underwent treatment, with the majority recovering without complications. A notable correlation was observed between CK levels, blood urea nitrogen (BUN), and the urea/creatinine ratio (UCR). The study also discusses potential pathophysiological mechanisms behind SARS-CoV-2's impact on skeletal muscles, emphasizing an indirect inflammatory response. Our findings underscore that while myositis in children with SARS-CoV-2 infection appears to follow a benign and self-limiting trajectory, it is crucial to monitor specific markers for early intervention and management. Further research is warranted to elucidate the underlying mechanisms and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum (P. falciparum) malaria continues to pose a significant threat to public health worldwide, particularly in endemic areas. While the majority of cases can be effectively treated and cured, recurrences of P. falciparum malaria are not uncommon and can occur years following initial exposure. This phenomenon adds a new level of complexity to the management and prevention of the disease. The present study describes the compelling clinical case of a patient who contracted malaria despite not having been in an endemic region for over a decade. The patient had previously been infected and treated for the same disease. With low parasitemia, the patient was successfully treated with anti-malarial drugs; however, certain aspects of his medical history remained unclear. The present study also discusses the possibility that this case represents P. falciparum recrudescence or cryptic malaria, drawing on existing literature to contextualize the findings. The case presented herein highlights the need for continued vigilance in the diagnosis and treatment of P. falciparum malaria, particularly in instances of recurrence. Furthermore, it underscores the ongoing challenges posed by this persistent and insidious disease. [ABSTRACT FROM AUTHOR]