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Abdominal and pelvic pain with an associated pelvic mass is a very common emergency situation. There is always a management dilemma for most emergency physicians regarding these patients. A 46-year-old postmenopausal woman was admitted to our emergency department (ED) with complaints of massive abdominal distention. Abdominal and pelvis magnetic resonance imaging (MRI) was performed, which revealed a huge pelvic abdominal mass. All tumor markers were within normal limits. However, the ovarian cancer antigen (CA 125) level was elevated. As there was a strong suspicion of malignancy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Her final histopathology report was suggestive of uterine leiomyoma. Uterine leiomyomas are the most common benign uterine tumors in women. Surgical treatment is the gold standard, especially for older women with severe symptoms and no desire for future fertility. Although the combination of a pelvic tumor and a high-level of CA 125 arouses suspicion of gynecological malignancy, other benign conditions should always be considered in the differential diagnosis. There is limited evidence to support an association between elevated CA 125 levels and uterine fibroids so far. However, conditions such as the coexistence of adenomyosis and tumor size can affect the level of this marker in uterine fibroids.

Xanthones and benzothiazoles are important classes of heterocyclic compounds with versatile biological activities. Herein, we describe a straightforward and scalable synthesis of 5-chloro-6-oxo-6H-xantheno[4,3-d]thiazole-2-carbonitrile, a thiazole-fused xanthone, via a six-step approach, using Appel’s salt for the synthesis of the thiazole ring. The thiazole-fused xanthone was fully characterized employing 1H and 13C NMR spectra, using direct and long-range heteronuclear correlation experiments (HMBC and HMQC).

Belzutifan was recently approved for the management of Von Hippel–Lindau disease (VHL). Given the morbidity of recurrent treatment, systemic therapy to reduce or eliminate the need for surgery has been long-awaited. Herein, we sought to gain insight about future utilization by surveying VHL experts in the United States. A survey developed by members of the VHL Alliance (VHLA) Clinical Advisory Council was distributed to kidney cancer providers at VHLA and National Comprehensive Cancer Network (NCCN) centers. Surveys were administered on a secure web-based platform. A total of 60 respondents from 29 institutions participated. Urologists (50%) and medical oncologists (43%) represented the majority of participants. The majority (98%) of respondents anticipated that belzutifan’s approval would signifi-cantly change the current treatment landscape. Most reported that therapy should be continuous (76%). There was a difference in willingness to prescribe belzutifan by specialty (38% of urologists vs 91% of medical oncologists (P = 0.02). In individuals with renal tumors

Background: The value of normal C-reactive protein (CRP) in psoriatic arthritis (PsA) is debatable. Objectives: To test the hypothesis that CRP is frequently normal in contemporary real-world PsA patients, despite active disease. Design: In this cross-sectional study, patients were divided into two groups: CRP ⩽ 0.5 mg/dl (normal) and CRP > 0.5 mg/dl (increased). Having as dependent variable the CRP status, these groups were compared for disease-related features, including composite disease activity indices [clinical Disease Activity in PSoriatic Arthritis (cDAPSA) and minimal disease activity (MDA)] and patient-reported outcomes (PROs). Agreement between CRP status and cDAPSA/MDA scores was calculated (Cohen’s kappa). Methods: Data from consecutive PsA patients attending two outpatient rheumatology clinics (January 2019–June 2021) were analysed. Results: From 128 patients enrolled (51.6% females; mean ± standard deviation age: 53.4 ± 11.7 years; 23.4%, 48.4% and 64.1% treated with glucocorticoids, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs, respectively), two-thirds (66.4%, n = 85) had normal CRP values. CRP status was not associated with any of the disease-related parameters and PROs, but only with ESR [odds ratio: 1.04 (95% confidence interval: 1.01–1.06), p = 0.005]. Among patients with normal CRP, 45.9% (39/85) were on non-MDA state, while 21.2% (18/85) had cDAPSA-moderate and 5.9% (5/85) had cDAPSA-high disease activities. Conversely, 54.2% (39/72) of patients on non-MDA state and 52.3% (23/44) of those with cDAPSA-moderate or cDAPSA-high disease activity had normal CRP values. Cohen’s kappa between normal CRP and MDA, cDAPSA-remission, and cDAPSA-remission/low disease activity was –0.26, –0.21 and –0.22, respectively, displaying total disagreement. Conclusion: Normal CRP in PsA should not be used as surrogate marker of remission or low/MDA, therefore needs to be interpreted with caution in clinical decision-making.

In this paper, research on the relationship between forest fires and meteorology is carried out using simple meteorological variables (temperature, wind, and precipitation) from a few well-selected Greek meteorological stations. The 5 years (1998, 2000, 2007, 2012, and 2021) which recorded burnt areas for more than the 25-year average (37,000 ha) had as a common characteristic, on the one hand, a much drier than usual two-month period (July–August) following a winter period with a shortage of rainfall, and on the other hand a number of days with very high temperatures higher than the average of the last 25 years. The latter implies that average temperatures in all three summer months were at least 1 °C above their normal value. In the years following, the burnt areas were below their average regardless of the precipitation and summer temperature patterns. However, when precipitation during the two-month period (July–August) was two or more times more than normal, fire seasons had, at most, one-third of the 25-year average of burned areas, regardless of the precipitation of the winter periods preceding and summer temperatures in those years. This is very important as already in the early days of each fire season it will be possible to make an estimation of its outcome and to prepare more appropriately when the accuracy of the long-term seasonal forecast of temperature and rainfall anomalies is improved.

Ovarian cancer (OC) is characterized by silent progression and late-stage diagnosis. It is critical to detect and accurately diagnose the disease early to improve survival rates. Tumor markers have emerged as valuable tools in the diagnosis and management of OC, offering non-invasive and cost-effective options for screening, monitoring, and prognosis. Purpose: This paper explores the diagnostic importance of various tumor markers including CA-125, CA15-3, CA 19-9, HE4,hCG, inhibin, AFP, and LDH, and their impact on disease monitoring and treatment response assessment. Methods: Article searches were performed on PubMed, Scopus, and Google Scholar. Keywords used for the searching process were “Ovarian cancer”, “Cancer biomarkers”, “Early detection”, “Cancer diagnosis”, “CA-125”,“CA 15-3”,“CA 19-9”, “HE4”,“hCG”, “inhibin”, “AFP”, “LDH”, and others. Results: HE4, when combined with CA-125, shows improved sensitivity and specificity, particularly in early-stage detection. Additionally, hCG holds promise as a prognostic marker, aiding treatment response prediction and outcome assessment. Novel markers like microRNAs, DNA methylation patterns, and circulating tumor cells offer potential for enhanced diagnostic accuracy and personalized management. Integrating these markers into a comprehensive panel may improve sensitivity and specificity in ovarian cancer diagnosis. However, careful interpretation of tumor marker results is necessary, considering factors such as age, menopausal status, and comorbidities. Further research is needed to validate and refine diagnostic algorithms, optimizing the clinical significance of tumor markers in ovarian cancer management. In conclusion, tumor markers such as CA-125, CA15-3, CA 19-9, HE4, and hCG provide valuable insights into ovarian cancer diagnosis, monitoring, and prognosis, with the potential to enhance early detection.

Since December 2019, the COVID-19 pandemic has had a significant impact on healthcare systems worldwide, prompting policymakers to implement measures of isolation and eventually adopt strict national lockdowns, which affected mobility, healthcare-seeking behavior, and services, in an unprecedented manner. This study aimed to analyze the effects of these lockdowns on hip-fracture epidemiology and care services, compared to nonpandemic periods in previous years. We retrospectively collected data from electronic patient records of two major hospitals in Western Greece and included patients who suffered a fragility hip fracture and were admitted during the two 5-week lockdown periods in 2020, compared to time-matched patients from 2017–2019. The results showed a drop in hip-fracture incidence, which varied among hospitals and lockdown periods, and conflicting impacts on time to surgery, time to discharge after surgery, and total hospitalization time. The study also found that differences between the two differently organized units were exaggerated during the COVID-19 lockdown periods, highlighting the impact of compliance with social-distancing measures and the reallocation of resources on the quality of healthcare services. Further research is needed to fully understand the specific variations and patterns of geriatric hip-fracture care during emergency health crises characterized by limited resources and behavioral changes.

Background: HIV DNA mirrors the number of infected cells and the size of the HIV viral reservoir. The aim of this study was to evaluate the effect of pre-cART HIV DNA levels as a predictive marker of immune reconstitution and on the post-cART CD4 counts trends. Methods: HIV DNA was isolated from PBMCs and quantified by real-time PCR. Immune reconstitution was assessed up to four years. Piecewise-linear mixed models were used to describe CD4 count changes. Results: 148 people living with HIV (PLWH) were included. The highest rate of immune reconstitution was observed during the first trimester. There was a trend showing that high HIV RNA level resulted in greater increase in CD4 count, especially during the first trimester of cART (difference above vs. below median 15.1 cells/μL/month; 95% CI −1.4–31.5; p = 0.073). Likewise, higher HIV DNA level would predict greater CD4 increases, especially after the first trimester (difference above vs. below median 1.2 cells/μL/month; 95% CI −0.1–2.6; p = 0.071). Higher DNA and RNA levels combined were significantly associated with greater CD4 increase past the first trimester (difference high/high vs. low/low 2.1 cells/μL/month; 95% CI 0.3–4.0; p = 0.024). In multivariable analysis, lower baseline CD4 counts predicted a greater CD4 rise. Conclusions: In successfully treated PLWH, pre-cART HIV DNA and HIV RNA levels are predictors of immune reconstitution.

ObjectiveChronic HIV-1 infection leads to widespread inflammation and immune dysregulation. The gastrointestinal mucosa, a primary site for HIV-1 replication, is thought to play a significant role in this response. MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression, including immune activation and inflammation. Here we investigate miR expression and function in the colonic mucosa during HIV-1 infection.Design and methodsUsing miR profiling, we examined miR expression in the colonic mucosa of HIV-infected patients. These miRs were further parsed to identify those that most likely function in HIV-related inflammation. Using bioinformatics tools, we identified potential target genes which were confirmed using in-vitro functional testing.ResultsWe identified 12 miRs that were differentially expressed in the colonic mucosa of HIV-infected patients with high versus undetectable plasma viral concentrations. Of these, both miR-26a and miR-29a were downregulated in untreated HIV-1 infection, yet not in the colonic mucosa from inflammatory bowel disease. This downregulation occurs within the first hours after infection. These miRs were further shown to directly target IL-6 and STAT3, respectively, with similar changes confirmed in an ex-vivo explant infection model.ConclusionmiR-26a and miR-29a levels are decreased in the colonic mucosa during chronic HIV-1 infection, and this change may be initiated during acute infection. Both miRs de-repress the IL-6/STAT3 signaling pathway, which could contribute to increased inflammation during infection. These miRs may represent novel therapeutic targets for HIV-1-associated inflammation in the colonic mucosa.

Gene expression, signal transduction, protein/chemical interactions, biomedical literature cooccurrences, and other concepts are often captured in biological network representations where nodes represent a certain bioentity and edges the connections between them. While many tools to manipulate, visualize, and interactively explore such networks already exist, only few of them can scale up and follow today's indisputable information growth. In this review, we shortly list a catalog of available network visualization tools and, from a user-experience point of view, we identify four candidate tools suitable for larger-scale network analysis, visualization, and exploration. We comment on their strengths and their weaknesses and empirically discuss their scalability, user friendliness, and postvisualization capabilities.

Profiling of proteome dynamics is crucial for understanding cellular behavior in response to intrinsic and extrinsic stimuli and maintenance of homeostasis. Over the last 20 years, mass spectrometry (MS) has emerged as the most powerful tool for large-scale identification and characterization of proteins. Bottom-up proteomics, the most common MS-based proteomics approach, has always been challenging in terms of data management, processing, analysis and visualization, with modern instruments capable of producing several gigabytes of data out of a single experiment. Here, we present ProteoSign, a freely available web application, dedicated in allowing users to perform proteomics differential expression/abundance analysis in a user-friendly and self-explanatory way. Although several non-commercial standalone tools have been developed for post-quantification statistical analysis of proteomics data, most of them are not end-user appealing as they often require very stringent installation of programming environments, third-party software packages and sometimes further scripting or computer programming. To avoid this bottleneck, we have developed a user-friendly software platform accessible via a web interface in order to enable proteomics laboratories and core facilities to statistically analyse quantitative proteomics data sets in a resource-efficient manner. ProteoSign is available at http://bioinformatics.med.uoc.gr/ProteoSign and the source code at https://github.com/yorgodillo/ProteoSign.

The timing and causes for erosional events at the Kastrouli (Greece) archeological site – a Late Myceneaen with reuse in later periods – are presented. Two borehole sediment cores (max 6 m depth), collected from the footsteps of the settlement hill plain, were studied. Sedimentary analysis and luminescence dating techniques investigate and identify periods of soil aggradation in this record. Moreover, optically stimulated luminescence (OSL) dating confirmed the concept of an ancient lake during Kastrouli settlement times. Macroscopic overview of the stratigraphic structure for each core, included lithological and textural evaluation of the core sediments, assessments of grain size, and determination of the geochemical and mineralogical composition of the sediments. X-ray powder diffraction (XRPD), X-ray fluorescence (XRF), and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) techniques were applied for the mineralogical and geochemical analysis. OSL ages from seven sediment horizons spanned from the Ottoman period to archaic times. All lithological findings correlate with the results of the electrical tomography survey conducted in same area. Extrapolation of the Logarithmic fitting of the data back in time of prehistoric Late Mycenaean era of Kastrouli verifies a lake deeper than 10 m, with a considerable enhancement in soil aggradation of 1.2 cm/year. Attempts to dry out the area are evidenced by the hydraulic works found in two engineering sinkholes. Sedimentation changes had occurred in the local environment over the last 2500 years, and soil aggradation underwent significant fluctuations in the two studied cores. The Roman period (a wet period) and the Byzantine period experienced high aggradation rates. By contrast, soil aggradation rates in southern Phokis (Kastrouli region) have remained exceedingly low from the Ottoman era (circa 13th century) to the present. In the context of the Phokis case study, it appears that the sedimentation rates, driven by climate, have strengthened anthropogenic activities. [ABSTRACT FROM AUTHOR]

Sea level rise is not a problem for the future alone. It is already affecting many small to medium cities on the East Coast of the USA. These cities are adapting to their problems without sufficient help from the federal or state government. To escape the perils of short-term reactionary ad hoc measures to deal with such problems, there is a need to utilize longer-term visions and frameworks. One such approach, Adaptation Pathway Planning, requires the involvement of locally affected people. This study looks at the perceptions and preferred adaptation solutions of the residents of St. Augustine and the Hyde Park neighborhood in Tampa, FL, two cities that are already experiencing the worsening flooding effects caused by rising seas. The results show that those living in areas at higher risk, and which are already experiencing frequent tidal flooding, had a greater knowledge of this risk and a higher desire for increased action from multiple levels of government. Also, such people were more aware of what their municipalities were already doing to adapt. Finally, when faced with two different scenarios of the possible rise in sea levels by 2050, those presented with the higher scenarios were more likely to choose a wider range of adaptation countermeasures. All this indicates the need to carefully consider the awareness of residents regarding the effects of sea level rise and how long-term adaptation should be discussed with them. [ABSTRACT FROM AUTHOR]

BackgroundCholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo.MethodsA functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors.ResultsThe screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas.ConclusionsTaken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma.