Clearance of Driver Mutations after Transplantation for Myelofibrosis.

Background: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for myelofibrosis. Driver mutations are the pathophysiological hallmark of the disease, but the role of mutation clearance after transplantation is unclear.

Methods: We used highly sensitive polymerase-chain-reaction technology to analyze the dynamics of driver mutations in peripheral-blood samples from 324 patients with myelofibrosis (73% with mutations, 23% with mutations, and 4% with mutations) who were undergoing transplantation after reduced-intensity conditioning.

Clinical and Immune Effects of Peri-Transplantation JAK Inhibition for Myelofibrosis.

Despite the introduction of JAK inhibitors, allogeneic hematopoietic cell transplant remains the only potentially curative treatment for patients with myelofibrosis but has considerable treatment-related complications. Whether the incorporation of JAK inhibition into the transplant algorithm leads to improved outcomes is still unclear. Here, we analyzed different transplant platforms in myelofibrosis patients undergoing a first transplant, comparing immune profiles and outcomes of (1) 33 patients continuing JAK inhibition at start of conditioning until stable engraftment (PERI-group), (2) 38 patients receiving JAK inhibition prior to transplant until start of conditioning (PRE-group), and (3) 38 patients that had never received JAK inhibition (NON-group).

Impact of overweight and obesity on radiation dose and outcome in patients undergoing pulmonary vein isolation by cryoballoon and pulsed field ablation.

Background: Pulmonary vein isolation (PVI) using pulsed field ablation (PFA) or cryoballoon ablation (CBA) are commonly used single-shot techniques for the treatment of patients with atrial fibrillation (AF). The number of overweight (BMI 25-30 kg/m) and obese (BMI>30 kg/m) patients undergoing PVI is increasing, but data on this patient population is limited.

Methods: Consecutive AF patients with a BMI ≥25 kg/m undergoing PFA- or CBA-PVI were included in this retrospective analysis.

Efficacy and safety of pulsed field ablation compared to cryoballoon ablation in the treatment of atrial fibrillation: a meta-analysis.

Aims: Pulmonary vein isolation (PVI) represents the gold standard in the treatment of atrial fibrillation (AF) and the use of single-shot techniques, such as cryoballoon ablation (CBA) and pulsed field ablation (PFA) using a pentaspline catheter, has gained prominence. Recent studies hypothesize that PFA might be superior to CBA, although procedural efficacy and safety data are inconsistent. A meta-analysis was conducted to compare both energy sources for the treatment of AF.

Anti-T-lymphocyte globulin (ATLG) compared to post-transplant cyclophosphamide as GvHD prophylaxis in ALL patients undergoing allogeneic stem cell transplantation.

We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n = 74) or PTCy (n = 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p = 0.9 and 0.

Pulsed field ablation and cryoballoon ablation for pulmonary vein isolation: insights on efficacy, safety and cardiac function.

Background: Pulmonary vein isolation (PVI) has become the cornerstone treatment of atrial fibrillation (AF). While in cryoablation cell damage is caused by thermal effects, lately, pulsed field ablation (PFA) has been established as a novel non-thermal tissue-specific ablation modality for PVI. However, data comparing outcomes of patients undergoing either PFA or cryoballoon ablation (CBA) for primary PVI are sparse.

Evaluation of a Virtual Dance Class for Cancer Patients and Their Partners during the Corona Pandemic-A Real-World Observational Study.

Background: During the corona pandemic, all courses on physical activity for cancer patients were canceled. The aim of our study was to evaluate the feasibility of switching dancing classes for patients and their partners to online classes.

Methods: Patients and partners from courses at four different locations who consented to the online course offer were asked to fill in a pseudonymous questionnaire on access to the training, technical challenges, acceptance and well-being (1-item visual analog scale from 1 to 10) before and after the training.

[Exercise and physical activity for patients with prostate cancer].

In the past, it was thought that physical rest was relevant for recovery of patients with prostate cancer; however, more recently there has been a paradigm shift towards physical activity parallel to oncological treatment. Diagnosis and treatment of prostate cancer are associated with limitations at various levels and side effects [9], which in the course of therapy can be a potentially therapy-limiting factor associated with dose reduction, delay or even discontinuation of therapy with negative consequences for outcome and median survival. The current study situation on the topic of physical activity in prostate cancer includes various studies with differentiated physical activity interventions and treatment time points.

Phase III Study of F-PSMA-1007 Versus F-Fluorocholine PET/CT for Localization of Prostate Cancer Biochemical Recurrence: A Prospective, Randomized, Crossover Multicenter Study.

The objective of this study was to compare F-PSMA-1007 PET/CT and F-fluorocholine PET/CT for the localization of prostate cancer (PCa) biochemical recurrence. This prospective, open-label, randomized, crossover multicenter study included PCa patients with prior definitive therapy and suspected PCa recurrence. All men underwent both F-PSMA-1007 PET/CT and F-fluorocholine PET/CT (102 received F-PSMA-1007 PET/CT first and 88 received F-fluorocholine PET/CT first).

A virtual dance sport class for cancer patients: the trainer perspective.

Purpose: Due to the corona, pandemic classes with physical activity for cancer patients were postponed. For an ongoing program with ballroom dancing classes for patients and their partners, the training was switched to a digital format.

Methods: We evaluated the training by structured written interviews of the trainers including an open report part concerning the development and realization of the project, the teaching and training concept and their experiences as trainers.

Efficient Synthesis of Benzothiazinone Analogues with Activity against Intracellular Mycobacterium tuberculosis.

8-Nitrobenzothiazinones (BTZs) are a promising class of antimycobacterial agents currently under investigation in clinical trials. Starting from thiourea derivatives, a new synthetic pathway to BTZs was established. It allows the formation of the thiazinone ring system in one synthetic step and is applicable for preparation of a wide variety of BTZ analogues.

Influence of ballroom dancing on fatigue, body image, self-efficacy, and endurance of cancer patients and their partners.

Physical activity has a high importance for cancer patients. The present study aimed to evaluate the influence of ballroom dancing on fatigue, body image, self-efficacy, and functional exercise capacity for patients with cancer. We collected data among participants of a regular dance training program for cancer patients with a questionnaire including the Body Image Scale (BIS), Brief Fatigue inventory (BFI), Short Scale for Measuring General Self-efficacy Beliefs (ASKU), and the 6-min walking test (6-MWT).

[2-Chloro-3-nitro-5-(tri-fluoro-meth-yl)phen-yl](piperidin-1-yl)methanone: structural characterization of a side product in benzo-thia-zinone synthesis.

1,3-Benzo-thia-zin-4-ones (BTZs) are a promising new class of anti-tuberculosis drug candidates, some of which have reached clinical trials. The title compound, the benzamide derivative [2-chloro-3-nitro-5-(tri-fluoro-meth-yl)phen-yl](piper-id-in-1-yl)methanone, CHClFNO, occurs as a side product as a result of competitive reaction pathways in the nucleophilic attack during the synthesis of the BTZ 8-nitro-2-(piperidin-1-yl)-6-(tri-fluoro-meth-yl)-1,3-benzo-thia-zin-4-one, following the original synthetic route, whereby the corresponding benzoyl iso-thio-cyanate is reacted with piperidine as secondary amine. In the title compound, the nitro group and the nearly planar amide group are significantly twisted out of the plane of the benzene ring.

Induced pluripotent stem cell-based disease modeling identifies ligand-induced decay of megalin as a cause of Donnai-Barrow syndrome.

Donnai-Barrow syndrome (DBS) is an autosomal-recessive disorder characterized by multiple pathologies including malformation of forebrain and eyes, as well as resorption defects of the kidney proximal tubule. The underlying cause of DBS are mutations in LRP2, encoding the multifunctional endocytic receptor megalin. Here, we identified a unique missense mutation R3192Q of LRP2 in an affected family that may provide novel insights into the molecular causes of receptor dysfunction in the kidney proximal tubule and other tissues affected in DBS.

Macrophages protect against loss of adipose tissue during cancer cachexia.

Background: Cancer cachexia represents a central obstacle in medical oncology as it is associated with poor therapy response and reduced overall survival. Systemic inflammation is considered to be a key driver of cancer cachexia; however, clinical studies with anti-inflammatory drugs failed to show distinct cachexia-inhibiting effects. To address this contradiction, we investigated the functional importance of innate immune cells for hepatocellular carcinoma (HCC)-associated cachexia.

Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis.

The hypoxia-inducible transcription factor HIF-1 is appreciated as a promising target for cancer therapy. However, conditional deletion of HIF-1 and HIF-1 target genes in cells of the tumor microenvironment can result in accelerated tumor growth, calling for a detailed characterization of the cellular context to fully comprehend HIF-1's role in tumorigenesis. We dissected cell type-specific functions of HIF-1 for intestinal tumorigenesis by lineage-restricted deletion of the Hif1a locus.

Cancer patients' needs for virtues and physicians' characteristics in physician-patient communication: a survey among patient representatives.

Background: Data on patients' needs with respect to physicians' ethical behavior and virtues are important but not available in most cases.

Patients And Methods: In an iterative process together with patients' representatives, we developed a standardized questionnaire which was distributed to the representatives of the Women's Self-Help after Cancer in Germany. We started with the classical ethical virtues and clustered them to characteristics.

Mutations in Disordered Regions Can Cause Disease by Creating Dileucine Motifs.

Many disease-causing missense mutations affect intrinsically disordered regions (IDRs) of proteins, but the molecular mechanism of their pathogenicity is enigmatic. Here, we employ a peptide-based proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1, ITPR1, and CACNA1H) lead to an increased clathrin binding.

Novel insight into the reaction of nitro, nitroso and hydroxylamino benzothiazinones and of benzoxacinones with Mycobacterium tuberculosis DprE1.

Nitro-substituted 1,3-benzothiazinones (nitro-BTZs) are mechanism-based covalent inhibitors of Mycobacterium tuberculosis decaprenylphosphoryl-β-D-ribose-2'-oxidase (DprE1) with strong antimycobacterial properties. We prepared a number of oxidized and reduced forms of nitro-BTZs to probe the mechanism of inactivation of the enzyme and to identify opportunities for further chemistry. The kinetics of inactivation of DprE1 was examined using an enzymatic assay that monitored reaction progress up to 100 min, permitting compound ranking according to k/K values.

Effect of ballroom dancing on the well-being of cancer patients: Report of a pilot project.

The present study aimed to evaluate the feasibility of ballroom dancing for patients with cancer and their partners, and develop a simple method for assessing its effects on the patients' well-being. A total of 11 pairs (14 patients and 8 healthy partners) participated. Participation was open, and there were no restrictions in terms of the type of cancer, treatment or comorbidities.

A complex of the ubiquitin ligase TRIM32 and the deubiquitinase USP7 balances the level of c-Myc ubiquitination and thereby determines neural stem cell fate specification.

The balance between stem cell maintenance and differentiation has been proposed to depend on antagonizing ubiquitination and deubiquitination reactions of key stem cell transcription factors (SCTFs) mediated by pairs of E3 ubiquitin ligases and deubiquitinating enzymes. Accordingly, increased ubiquitination results in proteasomal degradation of the SCTF, thereby inducing cellular differentiation, whereas increased deubiquitination stabilizes the SCTF, leading to maintenance of the stem cell fate. In neural stem cells, one of the key SCTFs is c-Myc.

Ballroom dancing as physical activity for patients with cancer: a systematic review and report of a pilot project.

Background: Physical activity has positive effects on cancer patients. Dancing addresses diverse bio-psycho-social aspects. Our aim was to assess the evidence on ballroom dancing and to develop the setting for a pilot project.