Network Flow-Based Refinement for Multilevel Hypergraph Partitioning

We present a refinement framework for multilevel hypergraph partitioning that uses max-flow computations on pairs of blocks to improve the solution quality of a k-way partition. The framework generalizes the flow-based improvement algorithm of KaFFPa from graphs to hypergraphs and is integrated into the hypergraph partitioner KaHyPar. By reducing the size of hypergraph flow networks, improving the flow model used in KaFFPa, and developing techniques to improve the running time of our algorithm, we obtain a partitioner that computes the best solutions for a wide range of benchmark hypergraphs from different application areas while still having a running time comparable to that of hMetis

Medication sparing after medical cannabis initiation:A case study of a chronic pain patient in Project Twenty21

Prescribed cannabinoids are legal in the UK and are increasingly being used for a variety of conditions, with one of the most frequent conditions being chronic pain. Within this cohort, there is developing evidence that cannabis-based medicinal products are associated with opioid and other medication sparing. However, at present, the National Institute for Health and Care Excellence (NICE) does not recommend the prescription of cannabis-based medicinal products to treat chronic pain due to the lack of randomised controlled trial evidence for this condition. Here we present a case study of a 61-year-old woman with idiopathic small fibre neuropathy, who was prescribed the gabapentinoid pregabalin, in combination at different times with various other agents including amitriptyline, duloxetine, lamotrigine, meloxicam and topical capsaicin, over a 17-year period for the associated neuropathic pain. Although her pain was relatively well controlled, the patient reported hearing loss, sleepiness, tinnitus, confusion and worsening anxiety possibly as a result of prolonged pregabalin use. Efforts were made to reduce the pregabalin dose but any attempts to reduce below a total daily dose of 350 mg resulted in unacceptable pain for the patient. In 2021, the patient was enrolled in Project Twenty21, the UK's first medical cannabis registry, and prescribed full plant extract delta-9-tetrahydrocannabinol 10 mg: cannabidiol 15 mg/mL of oil, prescribed at a dose range of 0.1–0.5 mL twice daily. As a result, the patient managed to reduce her pregabalin down to 37.5 mg total daily dose. The patient now feels she has ‘been given a second chance at life’ and her husband describes her as ‘a new woman’. This patient feels that she is in a position to finally stop treatment with pregabalin, as a result of medical cannabis controlling her pain. Highlighting the potential benefits of cannabis-based medicinal products to treat chronic pain, our case study indicates the value of including real-world evidence when assessing the benefits and safety of cannabis-based medicinal products

Genetic dissection of apoptosis and cell cycle control in response of colorectal cancer treated with preoperative radiochemotherapy

BACKGROUND: In previous analyses we identified therapy-induced upregulation of the CDK inhibitor p21(CIP/WAF-1 )and consequently decreased tumor cell proliferation or loss of Bax as adverse factors for survival in rectal cancer treated with radiochemotherapy. Here, we address the individual role of p53 and its transcriptional targets, p21(CIP/WAF-1 )and Bax, on apoptosis induced by individual components of multimodal anticancer therapy, i.e. 5-fluorouracil (5-FU), ionising γ-radiation (IR) and heat shock/hyperthermia. METHODS: We analysed tumor samples 66 patients with rectal carcinoma treated by a neoadjuvant approach with radiochemotherapy ± heat shock/hyperthermia for the expression and mutation of p53 and the expression of p21(CIP/WAF-1 )and Bax. These data were correlated with the tumor response. The functional relevance of p53, p21(CIP/WAF-1 )and Bax was investigated in isogeneic HCT116 cell mutants treated with 5-FU, IR and heat shock. RESULTS: Rectal carcinoma patients who received an optimal heat shock treatment showed a response that correlated well with Bax expression (p = 0.018). Local tumor response in the whole cohort was linked to expression of p21(CIP/WAF-1 )(p < 0.05), but not p53 expression or mutation. This dichotomy of p53 pathway components regulating response to therapy was confirmed in vitro. In isogeneic HCT116 cell mutants, loss of Bax but not p53 or p21(CIP/WAF-1 )resulted in resistance against heat shock. In contrast, loss of p21(CIP/WAF-1 )or, to a lesser extent, p53 sensitized predominantly for 5-FU and IR. CONCLUSION: These data establish a different impact of p53 pathway components on treatment responses. While chemotherapy and IR depend primarily on cell cycle control and p21, heat shock depends primarily on Bax. In contrast, p53 status poorly correlates with response. These analyses therefore provide a rational approach for dissecting the mode of action of single treatment modalities that may be employed to circumvent clinically relevant resistance mechanisms in rectal cancer

Practice and Effectiveness of Outpatient Psycho-Oncological Counseling for Cancer Patients

Objective: Because of various types of psychological distress, cancer patients are encouraged to attend outpatient psycho-oncological and psychosocial counseling. The aim of this prospective study was an analysis of the impact and success of existing counseling resources

Identification of early molecular markers for breast cancer

<p>Abstract</p> <p>Background</p> <p>The ductal carcinoma <it>in situ </it>(DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma. Since DCIS is a curable disease, it would be highly desirable to identify molecular markers that allow early detection. Mice transgenic for the WAP-SV40 early genome region were used as a model for DCIS development. Gene expression profiling was carried out on DCIS-bearing mice and control animals. Additionally, a set of human DCIS and invasive mammary tumors were analyzed in a similar fashion. Enhanced expression of these marker genes in human and murine samples was validated by quantitative RT-PCR. Besides, marker gene expression was also validated by immunohistochemistry of human samples. Furthermore <it>in silico </it>analyses using an online microarray database were performed.</p> <p>Results</p> <p>In DCIS-mice seven genes were identified that were significantly up-regulated in DCIS: DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1 and SPP1. A similar up-regulation of homologues of the murine genes was observed in human DCIS samples. Enhanced expression of these genes in DCIS and IDC (invasive ductal carcinoma) was validated by quantitative RT-PCR and immunohistochemistry.</p> <p>Conclusions</p> <p>By comparing murine markers for the ductal carcinoma <it>in situ </it>(DCIS) of the mammary gland with genes up-regulated in human DCIS-samples we were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas in the future. The similarities between gene expression in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS is of utmost relevance for the survival of patients who are at high risk of developing breast carcinomas.</p