Evolution of Single-Session Therapy: A Bibliometric Analysis.

OBJECTIVE: This bibliometric analysis aimed to explore the publication and citation metrics of the research literature on single-session therapy (SST) to understand its current status, trends, and future prospects. METHODS: Seventy-five keywords were validated by subject matter experts. Publications from 1972 through September 2023 were extracted from the bibliometric website Lens.org. Publication trends, citation patterns, prominent journals, and influential authors were examined as part of the bibliometric analysis. Citation network analysis, bibliographic coupling of authors, and coauthorship network analysis were also performed. RESULTS: A total of 301 SST publications, including 18 books, 85 book chapters, and 176 journal articles, were found, published by 493 authors. The citation- and publication-related metrics suggested a growing level of subject matter expertise over time. Initially, single-author publications held more prominence than collaborative work, but this pattern shifted. From 2011 to 2020, scholarly interest surged, resulting in 144 publications during this period. CONCLUSIONS: This bibliometric analysis, the first systematic exploration of the SST knowledge base, can be used to expand and enrich future SST research.

ST2 and IL-33 polymorphisms and the development of childhood asthma: a prospective birth cohort study in Finnish children.

The ST2/IL-33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of ST2 and IL-33 polymorphisms with serum soluble (s) ST2 and IL-33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single-nucleotide polymorphisms (SNPs) in ST2 and IL-33 were determined, and associations of the SNP variants with serum levels of sST2 and IL-33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with ST2 rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with ST2 rs13408661. No differences were observed between subjects with studied IL-33 SNPs. Children who carried genetic variants of ST2 rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of IL-33 rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant.

Poleward migration of tropical corals inhibited by future trends of seawater temperature and calcium carbonate (CaCO3) saturation.

Poleward range expansion of marine organisms is commonly attributed to anthropogenic ocean warming. However, the extent to which a single species can migrate poleward remains unclear. In this study, we used molecular data to examine the current distribution of the Pocillopora damicornis species complex in Taiwan waters and applied niche modeling to predict its potential range through the end of the 21st Century. The P. damicornis species complex is widespread across shallow, tropical and subtropical waters of the Indo-Pacific regions. Our results revealed that populations from subtropical nonreefal coral communities are P. damicornis, whose native geographical ranges are approximately between 23°N and 35°N. In contrast, those from tropical reefs are P. acuta. Our analysis of 50 environmental data layers demonstrated that the concentrations of CaCO3 polymorphs had the greatest contributions to the distributions of the two species. Future projections under intermediate shared socioeconomic pathways (SSP) 2-4.5 and very high (SSP5-8.5) scenarios of greenhouse gas emissions showed that while sea surface temperature (SST) isotherms would shift northwards, saturation isolines of two CaCO3 polymorphs, calcite (Ωcal) and aragonite (Ωarag), would shift southwards by 2100. Subsequent predictions of future suitable habitats under those conditions indicated that distinct delimitation of geographical ranges for the two species would persist, and neither would extend beyond its native geographical zones, indicating that tropical Taiwan waters are the northern limit for P. acuta. In contrast, subtropical waters are the southern limit for P. damicornis. We concluded that the decline in CaCO3 saturation would make high latitudes less inhabitable, which could be one of the boundary elements that limit poleward range expansion driven by rising SSTs and preserve the latitudinal diversity gradient (LDG) on Earth. Consequently, poleward migration of tropical reef corals to cope with warming oceans should be reevaluated.

IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury.

Radiotherapy for treating breast cancer is associated with cardiac damage. This study aimed to investigate the role of the interleukin (IL)-33/soluble receptor ST2 (sST2) axis in radiation-induced cardiac injury. Expressions of IL-33 and sST2 were detected in breast cancer patients following radiotherapy, radiation-induced cardiac damaged mice model, and cardiomyocytes using quantitative real-time PCR (qRT-PCR) and immunohistochemical assay. Cardiac injury was evaluated through an ultrasound imaging system and hematoxylin & eosin staining. The transcriptional factor was assessed using dual-luciferase reporter assay and chromatin immunoprecipitation. The results indicated that IL-33 and sST2 were highly expressed in breast cancer patients, which further elevated post-6 months but reduced after 12 months of radiotherapy. Radiation induces cardiac dysfunction and elevated IL-33 and sST2 levels in a time-dependent manner. However, silencing of IL-33 decreased sST2 expression to alleviate radiation-induced cardiac dysfunction. The IL-33 could be transcriptional activated by TCF7L2 by binding to IL33 promoter sites, which mutation alleviated cardiomyocyte injury caused by radiation. Additionally, radiation treatment resulted in higher levels of TCF7L2, IL-33, and sST2 in cardiomyocytes, and TCF7L2 knockdown reduced IL-33 and sST2 expression. In conclusion, TCF7L2 transcriptional-activated IL-33 mediated sST2 to regulate radiation-induced cardiac damage, providing novel insights into radiotherapy-induced cardiac damage.

Possibilities of predicting adverse cardiovascular events based on the analysis of clinical and instrumental research methods, as well as sST2 in patients after myocardial infarction.

OBJECTIVE: Aim: To determine the possibility of predicting adverse cardiovascular events based on the analysis of clinical and instrumental research methods, as well as sST2 in patients after myocardial infarction. PATIENTS AND METHODS: Materials and Methods: The study included 64 patients who suffered an acute myocardial infarction and underwent PCI with balloon angioplasty and stenting of the infarct-related vessel in the acute period. The predictors of adverse cardiovascular events were assessed events during 1 year of observation. Indicators of echocardiography and coronary angiography were assessed and concentrations sST2. RESULTS: Results: A worse prognosis was associated with intermediate ejection fraction (EF) (odds ratio (OR)=3.981, p<0.05), left aneurysm ventricle (LV) (OR=29.5, p<0.05), high concentrations of sST2 (OR=1.017, p<0.05) and scores on the Syntax scale (OR=1.001, p<0.05). CONCLUSION: Conclusions: In patients who underwent percutaneous coronary intervention for myocardial infarction, adverse outcome during the next 2 years is associated with coronary and echocardiographic parameters, as well as biochemical indicators of myocardial stress and fibrosis. HF patients with intermediate EF, LV aneurysm, high sST2 concentrations, and high Syntax scores have the worst prognosis.

Dominant contribution of atmospheric nonlinearities to ENSO asymmetry and extreme El Niño events.

Extreme El Niño events have outsized impacts and strongly contribute to the El Niño Southern Oscillation (ENSO) warm/cold phase asymmetries. There is currently no consensus on the respective importance of oceanic and atmospheric nonlinearities for those asymmetries. Here, we use atmospheric and oceanic general circulation models that reproduce ENSO asymmetries well to quantify the atmospheric nonlinearities contribution. The linear and nonlinear components of the wind stress response to Sea Surface Temperature (SST) anomalies are isolated using ensemble atmospheric experiments, and used to force oceanic experiments. The wind stress-SST nonlinearity is dominated by the deep atmospheric convective response to SST. This wind-stress nonlinearity contributes to ~ 40% of the peak amplitude of extreme El Niño events and ~ 55% of the prolonged eastern Pacific warming they generate until the following summer. This large contribution arises because nonlinearities consistently drive equatorial westerly anomalies, while the larger linear component is made less efficient by easterly anomalies in the western Pacific during fall and winter. Overall, wind-stress nonlinearities fully account for the eastern Pacific positive ENSO skewness. Our findings underscore the pivotal role of atmospheric nonlinearities in shaping extreme El Niño events and, more generally, ENSO asymmetry.

Somatostatin-SSTR3-GSK3 modulates human T-cell responses by inhibiting OXPHOS.

Introduction: Somatostatin (SST) is a peptide hormone primarily synthesized in the digestive and nervous systems. While its impact on the endocrine system is well-established, accumulating evidence suggests a crucial role for SST and its analogues in modulating immune responses. Despite this, the precise mechanism through which SST regulates T cells has remained largely unknown. Methods: To elucidate the impact of SST on human T cells, we conducted a series of experiments involving cell culture assays, molecular analyses, and metabolic profiling. Human T cells were treated with SST, and various parameters including proliferation, cytokine production, and metabolic activities were assessed. Additionally, we employed pharmacological inhibitors and genetic manipulations to dissect the signaling pathways mediating SST's effects on T cells. Results: We showed that SST diminishes T-cell proliferation by influencing IL-2 production and T-cell mitochondrial respiration, while having no discernible impact on TCR-induced glycolysis. Our findings also identified that the regulatory influence of SST on T-cell responses and metabolism is contingent on its receptor, SSTR3. Moreover, we demonstrated that SST governs T-cell responses and metabolism by acting through the T-cell metabolic checkpoint GSK3. Discussion: Our study provides novel insights into the immunoregulatory function of SST in human T cells, highlighting the complex interplay between hormonal signaling and immune regulation. Understanding the molecular mechanisms underlying SST's effects on T cells may offer therapeutic opportunities for manipulating immune responses in various pathological conditions.

The State-of-the-Art Mechanisms and Antitumor Effects of Somatostatin in Colorectal Cancer: A Review.

Somatostatin, a somatotropin release inhibiting factor (SST, SRIF), is a widely distributed multifunctional cyclic peptide and acts through a transmembrane G protein-coupled receptor (SST1-SST5). Over the past decades, research has begun to reveal the molecular mechanisms underlying the anticancer activity of this hormonal peptide. Among gastrointestinal tract (GIT) tumors, direct and indirect antitumor effects of SST have been documented best in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and less well in non-endocrine cancers, including sporadic colorectal cancer (CRC). In the latter, the signaling pathways involved in the antitumor function of SST are primarily MAPK/ERK/AKT and Wnt/ß-catenin. Direct (involving the MAPK pathway) and indirect (VEGF production) antiangiogenic effects of SST in CRC have also been described. The anti-inflammatory role of SST in CRC is emphasized, but detailed molecular mechanisms are still being explored. The role of SST in tumor genome/tumor microenvironment (TME)/host's gut microbiome interactions is only partially known. The results of SST analogues (SSAs)' treatment of sporadic CRC in monotherapy in vivo are not spectacular. The current review aims to present the state-of-the-art mechanisms and antitumor activity of endogenous SST and its synthetic analogues in CRC, with particular emphasis on sporadic CRC.

Removal efficiency of antibiotic residues, antibiotic resistant bacteria, and genes across parallel secondary settling tank and membrane bioreactor treatment trains in a water reclamation plant.

Antimicrobial resistance is recognized as a potent threat to human health. Wastewater treatment facilities are viewed as hotspots for the spread of antimicrobial resistance. This study provides comprehensive data on the occurrences of 3 different antibiotic resistant opportunistic pathogens (with resistance to up to 5 antibiotics), 13 antibiotic resistant genes and intI1, and 22 different antimicrobial residues in a large water reclamation plant (176 million gallons per day) that runs a conventional Modified Ludzack-Ettinger (MLE) reactor followed by a secondary settling tank (SST) and membrane bioreactor (MBR) in parallel. All the antibiotic resistant bacteria and most of the antibiotic resistance genes were present in the raw influent, ranging from 2.5 × 102-3.7 × 106 CFU/mL and 1.2× 10-1-6.5 × 1010 GCN/mL, respectively. MBR outperformed the SST system in terms of ARB removal as the ARB targets were largely undetected in MBR effluent, with log removals ranging from 2.7 to 6.8, while SST only had log removals ranging from 0.27 to 4.6. Most of the ARG concentrations were found to have significantly higher in SST effluent than MBR permeate, and MBR had significantly higher removal efficiency for most targets (p < 0.05) except for sul1, sul2, blaOXA48, intI1 and 16S rRNA genes (p > 0.05). As for the antibiotic residues (AR), there was no significant removal from the start to the end of the treatment process, although MBR had higher removal efficiencies for azithromycin, chloramphenicol, erythromycin, erythromycin-H2O, lincomycin, sulfamethoxazole and triclosan, compared to the SST system. In conclusion, MBR outperformed SST in terms of ARB and ARGs removal. However low removal efficiencies of most AR targets were apparent.

Long-term studies on West Antarctic Peninsula phytoplankton blooms suggest range shifts between temperate and polar species.

The Western Antarctic Peninsula (WAP) experiences one of the highest rates of sea surface warming globally, leading to potential changes in biological communities. Long-term phytoplankton monitoring in Potter Cove (PC, King George Island, South Shetlands) from the 1990s to 2009 revealed consistently low biomass values, and sporadic blooms dominated by cold-water microplankton diatoms. However, a significant change occurred between 2010 and 2020, marked by a notable increase in intense phytoplankton blooms in the region. During this period, the presence of a nanoplankton diatom, Shionodiscus gaarderae, was documented for the first time. In some instances, this species even dominated the blooms. S. gaarderae is recognized for producing blooms in temperate waters in both hemispheres. However, its blooming in the northern Southern Ocean may suggest either a recent introduction or a range shift associated with rising temperatures in the WAP, a phenomenon previously observed in experimental studies. The presence of S. gaarderae could be viewed as a warning sign of significant changes already underway in the northern WAP plankton communities. This includes the potential replacement of microplankton diatoms by smaller nanoplankton species. This study, based on observations along the past decade, and compared to the previous 20 years, could have far-reaching implications for the structure of the Antarctic food web.

Long-term prognostic importance of high levels of sST2 in patient with AMI: a meta-analysis.

OBJECTIVE: This meta-study aimed to assess the connection between soluble suppression of tumorigenicity 2 (sST2) and extended clinical outcomes in individuals diagnosed with acute myocardial infarction (AMI). METHODS: We systematically collected pertinent literature from PubMed, Embase and Web of Science. The primary effect measures employed in this research were the hazard ratio and 95% confidence intervals. The quality and publication bias of included studies were evaluated. Subgroup analysis was conducted to explore the diversity in study outcomes. RESULTS: This comprehensive meta-analysis ultimately encompassed thirteen studies, involving a total of 11,571 patients. Elevated levels of sST2 were identified as an adverse prognostic indicator, demonstrating a substantial association not only with overall mortality (combined HR 2.4, 95% CI 1.6-3.5, P < 0.01) but also with major adverse cardiovascular events (MACEs) (HR 2.5, 95% CI 1.5-4.2, P < 0.01). Subgroup analyses revealed that increased sST2 levels were linked to higher rates of all-cause mortality and MACEs in patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and other unselected subcategories of AMI. CONCLUSION: Increased sST2 could predict the long-term prognosis in patients suffering from AMI.

J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking morphine.

There is a large unmet need for novel pain-killers to improve relief of painful diabetic neuropathy (PDN). Herein, we assessed the efficacy of the somatostatin type 4 (SST4) receptor agonist, J-2156, for relief of PDN in rats. Diabetes was induced with streptozotocin (STZ; 70 mg/kg) and bilateral hindpaw hypersensitivity was fully developed by 8-week post-STZ. In the intervals, 8-12-weeks (morphine-sensitive phase; Phase 1) and 16-18-weeks (morphine-hyposensitive phase; Phase 2) post-STZ, rats received a single dose of intraperitoneal (i.p.) J-2156 (10, 20, 30 mg/kg), gabapentin (100 mg/kg i.p.), subcutaneous morphine (1 mg/kg) or vehicle. Hindpaw withdrawal thresholds (PWTs) were assessed using von Frey filaments pre-dose and at regular intervals over 3-h post-dose. In Phase 1, J-2156 at 30 mg/kg evoked significant anti-allodynia in the hindpaws with maximal effect at 1.5 h compared with 1 h for gabapentin and morphine. The durations of action for all three compounds were greater than 3 h. The corresponding mean (±SEM) extent and duration of anti-allodynia (ΔPWT AUC) for gabapentin did not differ significantly from that for J-2156 (30 mg/kg) or morphine. However, in Phase 2, the ΔPWT AUC for morphine was reduced to approximately 25% of that in Phase 1, mirroring our previous work. Similarly, the mean (±SEM) ΔPWT AUC for J-2156 (30 mg/kg) in Phase 2 was approximately 45% of that for Phase 1 whereas for gabapentin the mean (±SEM) ΔPWT AUCs did not differ significantly (p > 0.05) between the two phases. Our findings further describe the preclinical pain relief profile of J-2156 and complement previous work in rat models of inflammatory pain, neuropathic pain and low back pain. SST4 receptor agonists hold promise as novel therapeutics for the relief of PDN, a type of peripheral neuropathic pain that is often intractable to relief with clinically used drug treatment options.

Somatostatin receptor subtype 2A expression and genetics in 184 paragangliomas: a single center retrospective observational study.

PURPOSE: Adrenal and extra-adrenal paragangliomas (PGLs) are a group of neuroendocrine tumors (NETs) with strong heterogeneity, which often express somatostatin receptor subtype 2 A (SSTR2A). However, the association between SSTR2A expression and genetic status of PGLs remains unclear. The purpose of the study was to identify whether various pathogenic variants (PVs) had an impact on SSTR2A expression in PGLs. METHODS: This retrospective study included 184 patients with pathologically confirmed PGLs. The immunohistochemical expression of SSTR2A were studied in 184 tumors and PVs were tested in 159 tumor samples. Clinical and genetic data were compared in SSTR2A positive and negative PGLs. RESULTS: SSTR2A was positive in 63.6% (117/184) of all tumors. PGLs with negative SSTR2A were more likely to be extra-adrenal (37.0% vs 18.0%; P = 0.005) and exhibited a considerably greater proportion of PVs (75.4% vs. 49.0%; P = 0.001) than those with positive SSTR2A. Compared to those without PVs, a higher proportion of PGLs with PVs in cluster 1B (P = 0.004) and cluster 2 (P = 0.004) genes, especially VHL (P = 0.009), FGFR1 (P = 0.010) and HRAS (P = 0.007), were SSTR2A negative. SSTR2A was positive in all tumors (4/4) with SDHx PVs and in 87.5% (7/8) of metastatic PGLs. CONCLUSIONS: SSTR2A negativity was correlated with extra-adrenal tumor location and PVs in cluster 1B and cluster 2 genes such as VHL, FGFR1 and HRAS. Immunohistochemistry of SSTR2A should be taken into consideration in the personalized management of PGLs.

Monitoring Off-Shore Fishing in the Northern Indian Ocean Based on Satellite Automatic Identification System and Remote Sensing Data.

Satellite-derived Sea Surface Temperature (SST) and sea-surface Chlorophyll a concentration (Chl-a), along with Automatic Identification System (AIS) data of fishing vessels, were used in the examination of the correlation between fishing operations and oceanographic factors within the northern Indian Ocean from March 2020 to February 2023. Frequency analysis and the empirical cumulative distribution function (ECDF) were used to calculate the optimum ranges of two oceanographic factors for fishing operations. The results revealed a substantial influence of the northeast and southwest monsoons significantly impacting fishing operations in the northern Indian Ocean, with extensive and active operations during the period from October to March and a notable reduction from April to September. Spatially, fishing vessels were mainly concentrated between 20° N and 6° S, extending from west of 90° E to the eastern coast of Africa. Observable seasonal variations in the distribution of fishing vessels were observed in the central and southeastern Arabian Sea, along with its adjacent high sea of the Indian Ocean. Concerning the marine environment, it was observed that during the northeast monsoon, the suitable SST contributed to high CPUEs in fishing operation areas. Fishing vessels were widely distributed in the areas with both mid-range and low-range Chl-a concentrations, with a small part distributed in high-concentration areas. Moreover, the monthly numbers of fishing vessels showed seasonal fluctuations between March 2020 and February 2023, displaying a periodic pattern with an overall increasing trend. The total number of fishing vessels decreased due to the impact of the COVID-19 pandemic in 2020, but this was followed by a gradual recovery in the subsequent two years. For fishing operations in the northern Indian Ocean, the optimum ranges for SST and Chl-a concentration were 27.96 to 29.47 °C and 0.03 to 1.81 mg/m3, respectively. The preliminary findings of this study revealed the spatial-temporal distribution characteristics of fishing vessels in the northern Indian Ocean and the suitable ranges of SST and Chl-a concentration for fishing operations. These results can serve as theoretical references for the production and resource management of off-shore fishing operations in the northern Indian Ocean.

Disparities in Olfactory Dysfunction in African Americans.

OBJECTIVES: To examine olfactory performance in African Americans (AA) and Whites by comparing individual scent scores on objective olfactory tests to assess potential racial-ethnic differences of scent detection. METHODS: Cross-sectional study of healthy participants, age 18+ years, and without sinonasal inflammatory disease from June 2021 to April 2022. Included participants self-identified as AA or White. Patients were recruited from outpatient clinics at University of Kansas Medical Center, and the local community. Two smelling tests were employed: Affordable Rapid Olfactory Measurement Array (AROMA) and Sniffin' Sticks (SST-12). Sino-Nasal Outcome Test (SNOT-22) was used for self-reported olfactory function . Pearson correlation and chi-square tests were used to detect statistical significance. RESULTS: Our sample included 102 (46 AA and 56 Whites) participants. AROMA and SST-12 scores were significantly correlated in AA (P < .01, Pearson's Rho = .642) and Whites (P < .05, Pearson's Rho = .297). Mean scores on AROMA were significantly lower for AAs: 64.2 and Whites: 75.5 (P < .01). On AROMA, AA less accurately identified the scents of Licorice, Orange, Lavender, Cinnamon, Clove, and Rosemary (P < .05). Similarly, SST-12 mean scores for AAs: 84.2 were also lower than Whites: 89.9 (P < .01). On SST-12, AA less accurately identified the scent of pineapple Based on SST-12 scoring criteria, 60.9% of AA and 30.4% of Whites were classified as hyposmic (P < .05). SNOT-22 Smell scores were equivalent for both groups. CONCLUSION: On both tests of olfaction, AA performed worse than Whites and a greater proportion of AA were considered hyposmic compared to Whites. This is a discrepancy with self-reported olfaction, which showed no difference between Whites and AA. AA performed significantly worse than their White counterparts on several scents, with possible implications regarding cultural appropriateness of scents used in olfactory testing.

HLA-haploidentical T-cell receptor αßT/B-cell-depleted stem cell transplantation for Fanconi anemia.

HLA-haploidentical stem cell transplantation (haplo-SCT) using post-transplant high-dose cyclophosphamide (PT-CY) is an alternative choice when a suitable donors is unavailable. However, PT-CY is difficult in patients with Fanconi anemia (FA) due to their high vulnerability to alkylating agents. For FA, we prefer haplo-SCT by T-cell receptor αßT-cell and B-cell depletion (αßT/B-depleted haplo-SCT), which can reduce the risks of PT-CY-related complications and graft-versus-host disease (GVHD). An 11-year-old boy with diagnosed FA (FANCG mutation) and bone marrow failure was to receive αßT/B-depleted haplo-SCT from his father (HLA 4/8 allele matched) due to absence of an HLA-matched donors. αßT/B-depleted peripheral blood stem cells (CD34 + cell count, 1.17 × 107/kg; αß + T-cell count, 1.3 × 105/kg) were infused following conditioning consisting of fludarabine (150 mg/m2), cyclophosphamide (40 mg/kg), anti-thymocyte globulin (5 mg/kg), rituximab (375 mg/m2), and thoraco-abdominal irradiation (3 Gy). Tacrolimus was used for GVHD prophylaxis until day + 30. Neutrophil engraftment was achieved on day + 9, and complete chimerism was confirmed on days + 28 and + 96. At 12-month post-SCT, the patient was well without GVHD or any other complications. αßT/B-depleted haplo-SCT is a good choice not only for patients unsuitable for PT-CY, but also for all pediatric recipients to reduce SCT-related complications.

Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis.

BACKGROUND & AIMS: With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. METHODS: 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman's correlation and AUROC analyses. RESULTS: Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman's rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65-0.83), and 0.67(95%CI 0.56-0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. CONCLUSIONS: sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4.

Dynamics of land, ocean, and atmospheric parameters associated with Tauktae cyclone.

During the pre- and post-monsoon season, the eastern and western coasts are highly vulnerable to cyclones. The tropical cyclone "Tauktae" formed in the Arabian Sea on 14 May 2021 and moved along the west coast of India, and landfall occurred on 17 May 2021. During the cyclone, the maximum wind speed was 220 km/h with a pressure of 935 mb affecting meteorological, atmospheric parameters, and weather conditions of the northern and central parts of India causing devastating damage. Analysis of satellite, Argo, and ground data show pronounced changes in the oceanic, atmospheric, and meteorological parameters associated during the formation and landfall of the cyclone. During cyclone generation (before landfall), the air temperature (AT) was maximum (30.51 °C), and winds (220 km/h) were strong with negative omega values (0.3). The relative humidity (RH) and rainfall (RF) were observed to be higher at the location of the cyclone formation in the ocean and over the landfall location, with an average value of 81.28% and 21.45 mm/day, respectively. The concentration of total column ozone (TCO), CO volume mixing ratio (COVMR), H2O mass mixing ratio (H2O MMR), aerosol parameters (AOD, AE) and air quality parameter (PM) was increased over land and along the cyclone track, leading to a deterioration in the air quality. The strong wind mixes the air mass from the surroundings to the local anthropogenic emissions, and causing strong mixing of the aerosols. The detailed results show a pronounced change in the ocean, land, meteorological, and atmospheric parameters showing a strong land-ocean-atmosphere coupling associated with the cyclone.

Current role of pasireotide in the treatment of acromegaly.

"First-generation" somatostatin receptor agonists (SSTRAs) octreotide and lanreotide are the most commonly used first-line pharmacological therapy for patients with acromegaly. A subset of patients respond only partially or not at all to the first-generation SSTRA, necessitating the use of additional pharmacological agents or other modes of therapy. Pasireotide is a "second-generation" SSTRA that has multi-receptor activity. Prospective studies have shown promise in the use of pasireotide in patients with poor response to first-generation SSTRA. Here we elucidate the molecular pathways of resistance to first-generation SSTRA, the mechanism of action, pre-clinical and clinical evidence of the use of pasireotide in patients having incomplete / lack of response to first-generation SSTRA. We also discuss the clinical, pathological, and radiological markers predicting response to pasireotide, and the difference in side-effect profiles of pasireotide, compared to first-generation SSTRA.

An Approach to Intersectionally Target Mature Enteroendocrine Cells in the Small Intestine of Mice.

Enteroendocrine cells (EECs) constitute only a small proportion of Villin-1 (Vil1)-expressing intestinal epithelial cells (IECs) of the gastrointestinal tract; yet, in sum, they build the largest endocrine organ of the body, with each of them storing and releasing a distinct set of peptides for the control of feeding behavior, glucose metabolism, and gastrointestinal motility. Like all IEC types, EECs are continuously renewed from intestinal stem cells in the crypt base and terminally differentiate into mature subtypes while moving up the crypt-villus axis. Interestingly, EECs adjust their hormonal secretion according to their migration state as EECs receive altering differentiation signals along the crypt-villus axis and thus undergo functional readaptation. Cell-specific targeting of mature EEC subtypes by specific promoters is challenging because the expression of EEC-derived peptides and their precursors is not limited to EECs but are also found in other organs, such as the brain (e.g., Cck and Sst) as well as in the pancreas (e.g., Sst and Gcg). Here, we describe an intersectional genetic approach that enables cell type-specific targeting of functionally distinct EEC subtypes by combining a newly generated Dre-recombinase expressing mouse line (Vil1-2A-DD-Dre) with multiple existing Cre-recombinase mice and mouse strains with rox and loxP sites flanked stop cassettes for transgene expression. We found that transgene expression in triple-transgenic mice is highly specific in I but not D and L cells in the terminal villi of the small intestine. The targeting of EECs only in terminal villi is due to the integration of a defective 2A separating peptide that, combined with low EEC intrinsic Vil1 expression, restricts our Vil1-2A-DD-Dre mouse line and the intersectional genetic approach described here only applicable for the investigation of mature EEC subpopulations.