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The current study presents data on the structure of populations of an endemic species Phlomis nubilans Zakirov under a drought climate. The rare species P. nubilans belongs to the respective endemic genus of Uzbekistan. We studied the ontogenetic structure of populations, and the current state of P. nubilans populations was estimated based on a set of climate factors.

Lily varieties are a plant that grows in moderate humidity and moderate temperature. Therefore, they are not widely grown in Uzbekistan. As with other ornamental bulbous plants, Lilies have been developed in various ways, and it is important to learn which methods work best in which environment. Lily varieties are propagated by bulbs, bulbs, cuttings, leaves, small buds on the stem (bulbous) and seeds. These methods of reproduction allow selection of varieties suitable for a specific environment by determining the degree of influence of various external environmental factors along with substrates. Empoli, Honeymoon, Purple price cultivars belonging to the OT hybrids group showed higher values of Empoli cultivar than other cultivars when studying the effect of temperature and humidity of the sphagnum substrate on the rooting and length of the pods isolated from onion heads. Optimum humidity and temperature indicators of the substrate with sphagnum were determined for all studied varieties.

Objective: To compare operating time and blood loss in patients undergoing total laparoscopic hysterectomies (TLH) for benign conditions with either the Marseal™ IQ 5 mm (MS) or the Ligasure™ 5 mm (LS) vessel-sealing device.Design and Setting: A randomized controlled clinical trial (RCT) in two German gynecology departments.Patients: 74 patients scheduled to undergo TLH for a symptomatic fibroid uterus, adenomyosis or severe meno-metrorrhagia.Interventions: Patients were randomized to receive a TLH with either the MS or the LS device. 27 variables were prospectively collected to address potential confounding issues.Measurement and Main Results: Operating time, defined as the time period between the first (round ligament dissection) and the last (uterine vessels sealing) use of the device, estimated and calculated intraoperative blood loss. The mean operating time (95% confidence interval, CI) was 22.7 min (95% CI 17.6-27.7) for LS and 26.4 min (95% CI 20-32.8) for the MS device (p = .89). The estimated intraoperative blood loss was 164 ml (95% CI 110-217) for LS and 160 ml (95% CI 116-203) for the MS device (p = .36). The multivariate analyses accounting for BMI, endometriosis, uterine weight and appearance of fibroids did not reveal any significant effect of the type of device used on operating time and estimated blood loss.Conclusion: In this RCT, both devices provided reliable and effective sealing and dissection. The reusable MS showed non-inferiority against the disposable LS device with regard to operating time and estimated intraoperative blood loss. [ABSTRACT FROM AUTHOR]

A canonical variable coefficient nonlinear Schrödinger equation with a four-dimensional symmetry group containing SL(2, ℝ) group as a subgroup is considered. This typical invariance is then used to transform by a symmetry transformation a known solution that can be derived by truncating its Painlevé expansion and study blow-ups of these solutions in theLp-norm forp > 2,L∞-norm and in the sense of distributions. [ABSTRACT FROM AUTHOR]

Variational principles for real eigenvalues of self-adjoint operator pencils in nonseparated root zones are studied. [ABSTRACT FROM AUTHOR]

Metastasis to the brain is a frequent complication of advanced melanoma. Historically, patients with melanoma brain metastasis (MBM) have had dismal outcomes, but outcomes have improved with the development of more effective treatments, including stereotactic radiosurgery and effective immune and targeted therapies. Despite these advances, MBM remains a leading cause of death from this disease, and many therapies show decreased efficacy against these tumors compared with extracranial metastases. This differential efficacy may be because of recently revealed unique molecular and immune features of MBMs-which may also provide rational new therapeutic strategies., Competing Interests: Disclosure M. Hasanov and Y. Acikgoz do not report any conflicts of interest. M.A. Davies is supported by the Dr Miriam and Sheldon G. Adelson Medical Research Foundation, United States, the AIM at Melanoma Foundation, , United States, the NIH, United States/NCI (P50CA221703), the American Cancer Society and the Melanoma Research Alliance, Cancer Fighters of Houston, the Anne and John Mendelsohn Chair for Cancer Research, and philanthropic contributions to the Melanoma Moon Shots Program of MD Anderson. M.A. Davies has been a consultant to Roche/Genentech, Array, Pfizer, Novartis, BMS, GSK, Sanofi-Aventis, Vaccinex, Apexigen, Eisai, Iovance, Merck, and ABM Therapeutics, and has been the PI of research grants to MD Anderson by Roche/Genentech, GSK, Sanofi-Aventis, Merck, Myriad, Oncothyreon, Pfizer, ABM Therapeutics, and LEAD Pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Pancreatic cancer (PC) is the third cause of cancer-related deaths. Early detection and interception of premalignant pancreatic lesions represent a promising strategy to improve outcomes. We evaluated risk factors of focal pancreatic lesions (FPLs) in asymptomatic individuals at hereditary high risk for PC., Methods: This is an observational single-institution cohort study conducted over a period of 5 years. Surveillance was performed through imaging studies (EUS or magnetic resonance imaging/magnetic resonance cholangiopancreatography) and serum biomarkers. We collected demographic characteristics and used univariate and multivariate logistic regression models to evaluate associations between potential risk factors and odd ratios (ORs) for FPL development., Results: A total of 205 patients completed baseline screening. Patients were followed up to 53 months. We detected FPL in 37 patients (18%) at baseline; 2 patients had lesions progression during follow-up period, 1 of them to PC. Furthermore, 13 patients developed new FPLs during the follow-up period. Univariate and multivariate analyses revealed that new-onset diabetes (NOD) is strongly associated with the presence of FPL (OR, 10.94 [95% confidence interval, 3.01-51.79; P < 0.001]; OR, 9.98 [95% confidence interval, 2.15-46.33; P = 0.003]). Follow-up data analysis revealed that NOD is also predictive of lesions progression or development of new lesions during screening (26.7% vs. 2.6%; P = 0.005)., Conclusions: In a PC high-risk cohort, NOD is significantly associated with presence of FPL at baseline and predictive of lesions progression or new lesions during surveillance., Competing Interests: A.M. receives royalties from Cosmos Wisdom Biotechnology and Thrive Earlier Detection, an Exact Sciences Company, and is a consultant for Freenome and Tezcat. F.M. is an SAB Member at Neological Biosciences. Dr Bhutani is Walter H Wriston Distinguished Professor for Pancreatic Cancer Research. Manoop S. Bhutani is a senior associate editor of the journal. This article was subject to the journal's standard procedures, with peer review handled independently of the editor and his research group., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Scholar Media Publishing.)

Background: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients., Methods: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA)., Results: A total of 791 MBM patients (PE, n = 332; CE, n = 459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9-12.4) and improved in the CE vs PE (14.4 vs 10.3 months, P < .001). Elevated serum lactate dehydrogenase (LDH) was the only factor associated with worse OS in both PE and CE patients. Factors associated with survival in CE MBM patients included patient age, primary tumor Breslow thickness, prior immunotherapy, leptomeningeal disease, symptomatic MBMs, and whole brain radiation therapy. Several factors associated with OS in the PE were not significant in the CE. RPA demonstrated that elevated serum LDH and prior immunotherapy treatment are the most important determinants of survival in CE MBM patients., Conclusions: OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489., (© 2022 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Combination immunotherapy with sequential administration may enhance metastatic melanoma (MM) patients with long-term disease control. High Dose Aldesleukin/Recombinant Interleukin-2 (HD rIL-2) and ipilimumab (IPI) offer complementary mechanisms against MM. This phase IV study assessed the sequenced use of HD rIL-2 and IPI in MM patients. Eligible Stage IV MM patients were randomized to treatment with either two courses of HD rIL-2(600,000 IU/kg) followed by four doses of IPI 3 mg/kg or vice-versa. The primary objective was to compare one-year overall survival (OS) with historical control (46%, Hodi et al., NEJM 2010). Secondary objectives were 1-year progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) profile. Evaluable Population (EP) included patients who received at least 50% of planned treatment with each drug. Thirteen and 16 patients were randomized to receive HD rIL-2 first, and IPI first, respectively. One-year OS rate was 75% for intention to treat population. Eighteen patients were included in EP, 8 in HD rIL-2, 10 in IPI first arm. In EP, 1-year OS, PFS and ORR rates were 87%, 68%, and 50%, respectively. The frequency of AEs was similar in both arms with 13 patients experiencing Grade 3 or higher AEs, 3 resulting in the end of study participation. There was one HD rIL-2-related death, from cerebral hemorrhage due to thrombocytopenia. In this study with small sample size, HD rIL-2 and IPI were safe to administer sequentially in MM patients and showed more than additive effects. 1-year OS was superior to that of IPI alone from historical studies., Competing Interests: MH, DRM, RH, BT, LFl, LFe have no conflicts of interest to disclose. WHS reports grants and personal fees from Bristol-Myers Squibb, during the conduct of the study; grants and personal fees from Merck, grants and personal fees from Novartis, personal fees from Regeneron, grants from Genentech, outside the submitted work. LDC’s institution (University of Arizona) received payments from Prometheus Laboratories to support the conduct of this study. LDC receives research funding, paid to the institution (University of Washington), from Eli Lilly, AADi, BluePrint Medicine, Iterion, Gradalis, Philogen, Advenchen Laboratories, and CBA Pharma. LDC has received honoraria or has served on advisory boards for Daaichi Sankyo, BluePrint Medicines, and Regeneron. GAD reports position at the advisory board for Clinigen and institutional research support from Bristol-Myers Squibb and Clinigen. SH reports position at advisory board for Cardinal Health, Bristol-Myers Squibb, Immunomedics, Pfizer, and Speakers bureau at Bristol-Myers Squibb. MM reports other interests from Exicure, Blueprints Medicine, Immunocore, Amgen, Trieza, Array Biopharma, Biontech, and Novartis, outside the submitted work. GD reports fees from Novartis, Merck & Co, and Bristol-Myers Squibb. NG is employed by study sponsor Prometheus Labs, Clinigen, Inc. SPP reports institutional clinical trial support from Bristol Myers Squibb, InxMed, Novartis, Provectus, and Reata; advisory board participation for Cardinal Health and Castle Biosciences; data safety monitoring board activities for Immunocore, and personal fees from Merck outside the submitted work., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Recent studies defined a potentially important role of the microbiome in modulating pancreatic ductal adenocarcinoma (PDAC) and responses to therapies. We hypothesized that antibiotic usage may predict outcomes in patients with PDAC. We retrospectively analyzed clinical data of patients with resectable or metastatic PDAC seen at MD Anderson Cancer from 2003 to 2017. Demographic, chemotherapy regimen and antibiotic use, duration, type, and reason for indication were recorded. A total of 580 patients with PDAC were studied, 342 resected and 238 metastatic patients, selected retrospectively from our database. Antibiotic use, for longer than 48 hrs, was detected in 209 resected patients (61%) and 195 metastatic ones (62%). On resectable patients, we did not find differences in overall survival (OS) or progression-free survival (PFS), based on antibiotic intake. However, in the metastatic cohort, antibiotic consumption was associated with a significantly longer OS (13.3 months vs. 9.0 months, HR 0.48, 95% CI 0.34-0.7, p = 0.0001) and PFS (4.4 months vs. 2 months, HR 0.48, 95% CI 0.34-0.68, p = <0.0001). In multivariate analysis, the impact of ATB remained significant for PFS (HR 0.59, p = 0.005) and borderline statistically significant for OS (HR 0.69, p = 0.06). When we analyzed by chemotherapy regimen, we found that patients who received gemcitabine-based chemotherapy as first-line therapy (n = 118) had significantly prolonged OS (HR 0.4, p 0.0013) and PFS (HR 0.55, p 0.02) if they received antibiotics, while those receiving 5FU-based chemotherapy (n = 98) had only prolonged PFS (HR 0.54, p = 0.03). Antibiotics-associated modulation of the microbiome is associated with better outcomes in patients with metastatic PDAC., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease >100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5-5.6), and the median overall survival was 11.9 months (95% CI 9.0-16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release.

Mycobacterial skin infections are rare, with a wide spectrum of clinical features in immunocompromised individuals. Overall, they represent <2% of all forms of extrapulmonary tuberculosis. Tuberculous cellulitis is considered a skin manifestation of miliary tuberculosis. We present a case of tuberculous cellulitis in an immunocompetent patient.

Introduction: We aimed to determine the prevalence and landscape of germline mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis. Methods: Patients from two cohorts were studied, the high-risk cohort (HRC), which included 584 PDAC patients who received genetic counseling at The University of Texas MD Anderson Cancer Center, and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence and landscape of mutations were determined, and clinical characteristics including survival were analyzed. Results: A total of 409 patients underwent genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher prevalence of germline mutations compared with the GC: 17.3% versus 6.81%. The most common mutations in both cohorts were in BRCA1/2 and mismatch-repair (MMR) genes. Patients younger than 60 years old had significantly higher prevalence of germline mutations in both the HRC [odds ratios (OR), 1.93 ± 1.03-3.70, P = 0.039] and GC (4.78 ± 1.10-32.95, P = 0.036). Furthermore, PDAC patients with germline mutations in the GC had better overall survival than patients without mutations (HR, 0.44; 95% CI of HR, 0.25-0.76, P = 0.030). Discussion: Germline mutations are highly prevalent in patients with PDAC of early onset and can be predictive of better outcomes. Considering emerging screening strategies for relatives carrying susceptibility genes as well as impact on therapy choices, genetic counseling and testing should be encouraged in PDAC patients, particularly those of young onset. Cancer Prev Res; 11(11); 679-86. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Rationale: Tamoxifen has been used in women with hormone receptor-positive breast cancer and has been shown to successfully reduce both recurrence and mortality. On the contrary, long-term use of tamoxifen has hormone-related urogenital side effects which decrease the quality of life of the patients., Patient Concerns: In this case report, we present a breast cancer patient receiving tamoxifen who developed urinary incontinence; we discuss the effects of tamoxifen on urinary incontinence, which decreases quality of life of the patients who were evaluated in our clinic., Diagnoses: Breast cancer, urinary incontinence., Interventions: Temporarily discontinuing tamoxifen., Outcomes: Urinary incontinence resolved., Lessons: Based on the case we reported and literature, estrogen can cause a dose-dependent increase in incontinence, but more preclinical and clinical studies of both estrogen and SERMs are needed to support this notion; given the fact that some small-scale clinical studies have not proven a direct relationship between tamoxifen and urinary incontinence. We suggest that clinicians faced with the issue should temporarily stop usage of the drug once the complaint of urinary incontinence arises.