Self-reported determinants for subjective financial distress: a qualitative interview study with German cancer patients.

Objectives: Patient-reported financial effects of a tumour disease in a universal healthcare setting are a multidimensional phenomenon. Actual and anticipated objective financial burden caused by direct medical and non-medical costs as well as indirect costs such as loss of income can lead to subjective financial distress. To better understand subjective financial distress, the presented study explores self-reported determinants for subjective financial distress in German patients with cancer, aiming to inform a new German-language patient-reported outcome measure for determining the financial effects of a tumour disease.

Antimicrobial Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia Isolates from Europe, Asia, and Latin America (2018-2023).

Background: The occurrence of Stenotrophomonas maltophilia infections, especially pneumonia, has increased consistently in the last years. We evaluated the antimicrobial susceptibility of a large collection of S. maltophilia collected in Europe, Asia, and Latin America.

A novel amino-pyrimidine inhibitor suppresses tumor growth via microtubule destabilization and Bmi-1 down-regulation.

Colorectal cancer (CRC), one of the diseases posing a threat to global health, according to the latest data, is the third most common cancer globally and the second leading cause of cancer-related deaths. The development and refinement of novel structures of small molecular compounds play a crucial role in tumor treatment and overcoming drug resistance. In this study, our objective was to screen and characterize novel compounds for overcoming drug resistance via the B Lymphoma Mo-MLV insertion region 1 (Bmi-1) reporter screen assay.

Screening and Preparation of Nanobodies for SIGLEC-15 Detection.

As an important member of the Siglec family, SIGLEC-15 plays an important role in osteoclast differentiation, bone remodeling, and tumor immune evasion. In the tumor microenvironment, SIGLEC-15 functions independently of the B7-H1/PD-1 pathway. In this study, the SIGLEC-15 fusion protein (SIGLEC-15-Fc) was successfully expressed and purified using a eukaryotic expression system.

Derivatization of ophiobolin A and cytotoxicity toward breast and glioblastoma cancer stem cells: Varying the ketone and unsaturated aldehyde moieties.

To gain further insights into the importance of the unsaturated 1,4-ketoaldehyde moiety of ophiobolin A (OpA) for the potency and selectivity observed toward cancer stem cells, several derivatives were synthesized through controlled reduction and oxidations of the unsaturated aldehyde and ketone moieties. Structure elucidation of these new OpA derivatives was achieved through detailed NMR studies and comparison to OpA and known isolated congeners possessing variations in these regions. The relative stereochemistry of the newly generated stereocenters was determined by coupling constants in conjunction with conformational analyses (DFT) of the synthetic derivatives.

Smart self-transforming nano-systems for overcoming biological barrier and enhancing tumor treatment efficacy.

Nanomedicines need to overcome multiple biological barriers in the body to reach the target area. However, traditional nanomedicines with constant physicochemical properties are not sufficient to meet the diverse and sometimes conflicting requirements during in vivo transport, making it difficult to penetrate various biological barriers, resulting in suboptimal drug delivery efficiency. Smart self-transforming nano-systems (SSTNs), capable of altering their own physicochemical properties (including size, charge, hydrophobicity, stiffness, morphology, etc.

Targeting pancreatic cancer glutamine dependency confers vulnerability to GPX4-dependent ferroptosis.

Pancreatic ductal adenocarcinoma (PDAC) relies heavily on glutamine (Gln) utilization to meet its metabolic and biosynthetic needs. How epigenetic regulators contribute to the metabolic flexibility and PDAC's response and adaptation to Gln scarcity in the tumor milieu remains largely unknown. Here, we elucidate that prolonged Gln restriction or treatment with the Gln antagonist, 6-diazo-5-oxo-L-norleucine (DON), leads to growth inhibition and ferroptosis program activation in PDAC.

Sequence variants in HECTD1 result in a variable neurodevelopmental disorder.

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy.

Is postoperative adjuvant therapy necessary for pT3N0 oral cavity squamous cell carcinoma?

Background: The current NCCN guidelines advocate for the use of adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) in pT3N0 oral cavity squamous cell carcinoma (OCSCC). Here, we sought to evaluate whether postoperative RT/CRT may confer a survival advantage in pT3N0 patients who lack adverse pathological features.

Methods: A dataset of 852 pT3N0 OCSCC patients treated between 2018 and 2021 was analyzed.

Etoposide-loaded lipopolymer nanoparticles promote Smac minetic activity against inhibitor of apoptosis protein for glioblastoma treatment.

Encapsulated BV6 and SM164, two bivalent second mitochondria-derived activator of caspase (Smac) mimetics, in etoposide (ETO)-lipopolymer nanoparticles (NPs) have been developed to deplete inhibitor of apoptosis proteins (IAP), impair DNA, and produce antagonistic effects on glioblastoma multiforme (GBM) in nude mice. The NPs, composed of cocoa butter (CB) and polyvinyl alcohol (PVA), were stabilized by glycerol monostearate and Pluronic F-127, and grafted with transferrin (Tf) and wheat germ agglutinin (WGA) to dock the blood-brain barrier (BBB) and degenerated dopaminergic neurons. The dual-targeting NPs increased the BBB permeability of BV6, SM164 and ETO via recognizing Tf receptor (TfR) and N-acetylglucosamine that are abundantly expressed on brain microvascular endothelial cells.

Rationally manipulating molecular planarity to improve molar absorptivity, NIR-II brightness, and photothermal effect for tumor phototheranostics.

The secondary near-infrared region (NIR-II) fluorescence imaging-guided photothermal therapy (PTT) offers a noninvasive and light-controllable treatment option for deep-seated cancers. However, the development of NIR-II photothermal agents (NIR-II PTAs) that possess the desired properties of high molar absorption coefficient (ε), fluorescence quantum yield (QY), and photothermal conversion efficiency (PCE) remain a challenge due to the contradiction between radiative and nonradiative processes. Herein, we propose a novel side-chain heteroatom substitution engineering strategy to simultaneously enhance ε, QY, and PCE by modifying the molecular planarity.

Ultrasound-assisted enhancement of bioactive compounds in hawthorn vinegar: A functional approach to anticancer and antidiabetic effects.

In this study, the effects of ultrasound treatment on bioactive components and functional properties of hawthorn vinegar (Crataegus tanacetifolia) were investigated. Parameters such as total phenolic compound (TPC), total flavonoid content (TFC), ascorbic acid (AA), DPPH radical scavenging activity and CUPRAC reducing capacity were optimised by surface response method (RSM) and 14 min duration and 61.40 % amplitude were determined as the most suitable treatment conditions.

What happens after menopause? (WHAM): A prospective controlled study of cognition 24 months after premenopausal risk-reducing salpingo-oophorectomy.

Objective: Women with BRCA1/2 pathogenic variants considering risk-reducing bilateral oophorectomy (RRSO) may be concerned about potential effects of surgical menopause on cognition. Whether RRSO affects cognition and whether hormone therapy (HT) modifies this effect remains uncertain. This study aimed to prospectively measure the effect of premenopausal RRSO on cognition and the modifying effects of HT up to 24 months.

Concepts of Suffering at the End of Life Amongst Emergency, Palliative Care and Geriatric Medicine Physicians in Malaysia.

Background: Palliative Care, Geriatrics and Emergency physicians are exposed to death, terminally ill patients and distress of patients and their families. As physicians bear witness to patients' suffering, they are vulnerable to the costs of caring-the emotional distress associated with providing compassionate and empathetic care to patients. If left unattended, this may culminate in burnout and compromise professional identity.

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial.

Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.

Key Strategies to Promote Professional Wellness and Reduce Burnout in Oncology Clinicians.

Burnout in oncologists has been increasing, especially after the COVID-19 pandemic. This is concerning because burnout can have both personal and professional repercussions, as well as a negative impact on patients and organizational financial health. Drawing on information and ideas discussed at an ASCO Town Hall session at the 2023 Annual Meeting developed by the State of Cancer Care in America Editorial Board, this study reviews key organizational strategies for improving professional well-being and argues for the importance of measuring and researching the well-being of the oncology workforce to ensure healthy work environments.

Ten-Year Trends in Clinician Well-Being and Burnout Among Oncology Fellows in Training: An ASCO State of Cancer Care in America Study.

Purpose: To better understand burnout in oncology and clinician well-being along the career continuum starting with training, we sought to characterize the professional well-being of physicians training in medical oncology in 2023 and to identify trends over time comparing to fellows from a decade prior.

Methods: All US medical oncology fellows taking the 2023 ASCO Medical Oncology In-Training Exam (ITE) were invited to complete an optional post-exam survey evaluating fatigue, satisfaction with work-life integration (WLI), emotional exhaustion and depersonalization. 2023 ITE survey responses were compared to the 2013 ASCO post-ITE survey (n=1345).

Hsp90, DnaK, and ClpB collaborate in protein reactivation.

Hsp70, Hsp90, and ClpB/Hsp100 are molecular chaperones that help regulate proteostasis. Bacterial and yeast Hsp70s and their cochaperones function synergistically with Hsp90s to reactivate inactive and aggregated proteins by a mechanism that requires a direct interaction between Hsp90 and Hsp70 both in vitro and in vivo. and yeast Hsp70s also collaborate in bichaperone systems with ClpB and Hsp104, respectively, to disaggregate and reactivate aggregated proteins and amyloids such as prions.

The impact of specialised gastroenterology services for pelvic radiation disease (PRD): Results from the prospective multi-centre EAGLE study.

To undertake a mixed-methodology implementation study to improve the well-being of men with gastrointestinal late effects following radical radiotherapy for prostate cancer. All men completed a validated screening tool for late bowel effects (ALERT-B) and the Gastrointestinal Symptom Rating Score (GSRS); men with a positive score on ALERT-B were offered management following a peer reviewed algorithm for pelvic radiation disease (PRD). Health-related quality of life (HRQoL) at baseline, 6 and 12 months; and healthcare resource usage (HRU) and patient, support-giver, staff experience and acceptability of staff training (qualitative analysis) were assessed.

Favourable Living Donor Kidney Transplantation Outcomes within a National Kidney Exchange Program: A Propensity Score Matching Analysis.

Background: KEPs (kidney exchange programs) facilitate living donor kidney transplantations (LDKT) for patients with incompatible donors, who are typically higher risk than non-KEP patients because of higher sensitization and longer dialysis vintage. We conducted a comparative analysis of graft outcomes and risk factors for both KEP and non-KEP living donor kidney transplants.

Methods: All LDKTs performed in the Netherlands between 2004-2021 were included.

Sensitivity to Environmental Stress and Adversity and Lung Cancer.

Importance: Sensitivity to environmental stress and adversity may influence lung cancer risk, highlighting a critical link between psychosocial factors and cancer etiology.

Objective: To evaluate whether genetically estimated sensitivity to environmental stress and adversity is associated with lung cancer risk.

Design, Setting, And Participants: Data were obtained from a genome-wide association study identifying 37 independent genetic variants strongly associated with sensitivity to environmental stress and adversity and a cross-ancestry genome-wide meta-analysis from the International Lung Cancer Consortium.

Proximity Ligation Assay to Study Oncogene-Derived Transcription-Replication Conflicts.

Both DNA replication and RNA transcription utilize genomic DNA as their template, necessitating spatial and temporal separation of these processes. Conflicts between the replication and transcription machinery, termed transcription-replication conflicts (TRCs), pose a considerable risk to genome stability, a critical factor in cancer development. While several factors regulating these collisions have been identified, pinpointing primary causes remains difficult due to limited tools for direct visualization and clear interpretation.