302 research outputs found
Feasibility of a 12-month-exercise intervention during and after radiation and chemotherapy in cancer patients: impact on quality of life, peak oxygen consumption, and body composition
Background
Accumulating evidence suggests that exercise is effective in treating many of the acute and chronic side effects of anti-cancer therapy. A recent meta-analysis supported the use of exercise to prevent or treat fatigue and lymphoedema and to improve functional status in breast cancer patients.
Patients and methods
This trial was intended as a controlled, prospective feasibility study evaluating the impact of physical exercise (PE) in cancer patients during and after treatment with radio- and chemotherapy. Inclusion criteria were previous or ongoing treatment for cancer, motivation for PE of 0.5-1hour duration at least twice weekly for at least 3 months. Continuation of PE was encouraged thereafter. Every three months the following endpoints were assessed: Peak oxygen consumption as measured by supervised cardiopulmonary exercise test, body composition and quality of life.
Results
A total of 45 patients were included with a median age of 49 years. Forty were female and five male. Cancer types were: Breast cancer (n = 30/67 %), gastrointestinal cancer (n = 5/12 %), other types (n = 10/22 %). Thirty-eight (84 %) of the patients were included during curative treatment of their disease. Seven (16 %) were considered palliative. Adherence to the PE-programme longer than 6 months was noted for 41/45 (91 %) of the patients. Intensity of PE was thrice weekly in 32/45 (71 %), twice weekly in 11/45 (24 %). Two of 45 patients (5 %) had no PE. Mean peak oxygen consumption increased from 18.8 ± 5.6 ml/min/kg to 20.5 ± 3 ml/min/kg and 19.9 ± 4.7 ml/min/kg at 3 months (p = 0.005) and 12 months (p = 0.003), respectively.
Median fat mass decreased from 30.7 ± 15 kg to 28.9 ± 15 kg and 29.5 ± 13 kg at 3 months (p = 0.001) and 12 months (p = 0.017), respectively. Global health status scores increased from a median baseline value of 54.9 ± 16.3 to 66.4 ± 14 % and 68.0 ± 20.3 % at 3 months (p = 0.001) and 12 months (p = 0.002), respectively.
Conclusion
This exercise programme in cancer patients with 2–3 weekly supervised sessions over three months was well feasible and demonstrated measurable improvement of oxygen consumption, body composition and quality of life. In addition, a 90 %-adherence rate to the PE-programme beyond 6 months was encouraging. Further randomized prospective data in a larger patient population will be collected comparing the impact of two versus four months supervision
Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome
Background. Apoptotic rates in peripheral blood lymphocytes can predict radiation induced normal tissue toxicity. We studied whether apoptosis in lymphocytes has a prognostic value for therapy outcome. Methods. Lymphocytes of 87 rectal cancer patients were ex vivo irradiated with 2 Gy, 8 Gy, or a combination of 2 Gy ionizing radiation and Oxaliplatin. Cells were stained with Annexin V and 7-Aminoactinomycin D and apoptotic and necrotic rates were analyzed by multicolor flow cytometry. Results. After treatment, apoptotic and necrotic rates in CD8+ cells are consistently higher than in CD4+ cells, with lower corresponding necrotic rates. Apoptotic and necrotic rates of CD4+ cells and CD8+ cells correlated well within the 2 Gy, 8 Gy, and 2 Gy and Oxaliplatin arrangements (p≤0.009). High apoptotic CD8+ rates after 2 Gy, 8 Gy, and 2 Gy + Oxaliplatin treatment were prognostically favorable for metastasis-free survival (p=0.009, p=0.038, and p=0.009) and disease-free survival (p=0.013, p=0.098, and p=0.013). Conclusions. Ex vivo CD8+ apoptotic rates are able to predict the patient outcome in regard to metastasis-free or disease-free survival. Patients with higher CD8+ apoptotic rates in the peripheral blood have a more favorable prognosis. In addition to the prediction of late-toxicity by utilization of CD4+ apoptotic rates, the therapy outcome can be predicted by CD8+ apoptotic rates
Deep learning for brain metastasis detection and segmentation in longitudinal MRI data
Brain metastases occur frequently in patients with metastatic cancer. Early
and accurate detection of brain metastases is very essential for treatment
planning and prognosis in radiation therapy. To improve brain metastasis
detection performance with deep learning, a custom detection loss called
volume-level sensitivity-specificity (VSS) is proposed, which rates individual
metastasis detection sensitivity and specificity in (sub-)volume levels. As
sensitivity and precision are always a trade-off in a metastasis level, either
a high sensitivity or a high precision can be achieved by adjusting the weights
in the VSS loss without decline in dice score coefficient for segmented
metastases. To reduce metastasis-like structures being detected as false
positive metastases, a temporal prior volume is proposed as an additional input
of DeepMedic. The modified network is called DeepMedic+ for distinction. Our
proposed VSS loss improves the sensitivity of brain metastasis detection for
DeepMedic, increasing the sensitivity from 85.3% to 97.5%. Alternatively, it
improves the precision from 69.1% to 98.7%. Comparing DeepMedic+ with DeepMedic
with the same VSS loss, 44.4% of the false positive metastases are reduced in
the high sensitivity model and the precision reaches 99.6% for the high
specificity model. The mean dice coefficient for all metastases is about 0.81.
With the ensemble of the high sensitivity and high specificity models, on
average only 1.5 false positive metastases per patient needs further check,
while the majority of true positive metastases are confirmed. The ensemble
learning is able to distinguish high confidence true positive metastases from
metastases candidates that require special expert review or further follow-up,
being particularly well-fit to the requirements of expert support in real
clinical practice.Comment: Implementation is available to public at
https://github.com/YixingHuang/DeepMedicPlu
Benchmarking ChatGPT-4 on ACR Radiation Oncology In-Training (TXIT) Exam and Red Journal Gray Zone Cases: Potentials and Challenges for AI-Assisted Medical Education and Decision Making in Radiation Oncology
The potential of large language models in medicine for education and decision
making purposes has been demonstrated as they achieve decent scores on medical
exams such as the United States Medical Licensing Exam (USMLE) and the MedQA
exam. In this work, we evaluate the performance of ChatGPT-4 in the specialized
field of radiation oncology using the 38th American College of Radiology (ACR)
radiation oncology in-training (TXIT) exam and the 2022 Red Journal gray zone
cases. For the TXIT exam, ChatGPT-3.5 and ChatGPT-4 have achieved the scores of
63.65% and 74.57%, respectively, highlighting the advantage of the latest
ChatGPT-4 model. Based on the TXIT exam, ChatGPT-4's strong and weak areas in
radiation oncology are identified to some extent. Specifically, ChatGPT-4
demonstrates good knowledge of statistics, CNS & eye, pediatrics, biology, and
physics but has limitations in bone & soft tissue and gynecology, as per the
ACR knowledge domain. Regarding clinical care paths, ChatGPT-4 performs well in
diagnosis, prognosis, and toxicity but lacks proficiency in topics related to
brachytherapy and dosimetry, as well as in-depth questions from clinical
trials. For the gray zone cases, ChatGPT-4 is able to suggest a personalized
treatment approach to each case with high correctness and comprehensiveness.
Most importantly, it provides novel treatment aspects for many cases, which are
not suggested by any human experts. Both evaluations demonstrate the potential
of ChatGPT-4 in medical education for the general public and cancer patients,
as well as the potential to aid clinical decision-making, while acknowledging
its limitations in certain domains. Because of the risk of hallucination, facts
provided by ChatGPT always need to be verified
Ecological succession of a Jurassic shallow-water ichthyosaur fall.
After the discovery of whale fall communities in modern oceans, it has been hypothesized that during the Mesozoic the carcasses of marine reptiles created similar habitats supporting long-lived and specialized animal communities. Here, we report a fully documented ichthyosaur fall community, from a Late Jurassic shelf setting, and reconstruct the ecological succession of its micro- and macrofauna. The early 'mobile-scavenger' and 'enrichment-opportunist' stages were not succeeded by a 'sulphophilic stage' characterized by chemosynthetic molluscs, but instead the bones were colonized by microbial mats that attracted echinoids and other mat-grazing invertebrates. Abundant cemented suspension feeders indicate a well-developed 'reef stage' with prolonged exposure and colonization of the bones prior to final burial, unlike in modern whale falls where organisms such as the ubiquitous bone-eating worm Osedax rapidly destroy the skeleton. Shallow-water ichthyosaur falls thus fulfilled similar ecological roles to shallow whale falls, and did not support specialized chemosynthetic communities
Non-professional phagocytosis: a general feature of normal tissue cells
Non-professional phagocytosis by cancer cells has been described for decades. Recently, non-professional phagocytosis by normal tissue cells has been reported, which prompted us to take a closer look at this phenomenon. Non-professional phagocytosis was studied by staining cultured cells with live-cell staining dyes or by staining paraffin-embedded tissues by immunohistochemistry. Here, we report that each of 21 normal tissue cell lines from seven different organs was capable of phagocytosis, including ex vivo cell cultures examined before the 3rd passage as well as the primary and virus-transformed cell lines. We extended our analysis to an in vivo setting, and we found the occurrence of non-professional phagocytosis in healthy skin biopsies immediately after resection. Using dystrophin immunohistochemistry for membrane staining, human post-infarction myocardial tissue was assessed. We found prominent signs of non-professional phagocytosis at the transition zone of healthy and infarcted myocardia. Taken together, our findings suggest that non-professional phagocytosis is a general feature of normal tissue cells
A novel UBE3A sequence variant identified in eight related individuals with neurodevelopmental delay, results in a phenotype which does not match the clinical criteria of Angelman syndrome
Background: Loss of functional UBE3A, an E3 protein ubiquitin ligase, causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, epilepsy, movement or balance disorder, and a characteristic behavioral pattern. We identified a novel UBE3A sequence variant in a large family with eight affected individuals, who did not meet the clinical AS criteria. Methods: Detailed clinical examination and genetic analysis was performed to establish the phenotypic diversity and the genetic cause. The function of the mutant UBE3A protein was assessed with respect to its subcellular localization, stability, and E3 ubiquitin ligase activity. Results: All eight affected individuals showed the presence of a novel maternally inherited UBE3A sequence variant (NM_130838.4(UBE3A):c.1018-1020del, p.(Asn340del), which is in line with a genetic AS diagnosis. Although they presented with moderate to severe intellectual disability, the phenotype did not match the clinical criteria for AS. In line with this, functional analysis of the UBE3A p.Asn340del mutant protein revealed no major deficits in UBE3A protein localization, stability, or E3 ubiquitin ligase activity. Conclusion: The p.(Asn340del) mutant protein behaves distinctly different from previously described AS-linked missense mutations in UBE3A, and causes a phenotype that is markedly different from AS. This study further extends the range of phenotypes that are associated with UBE3A loss, duplication, or mutation
Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients
This study shows radiosensitization by BRAF inhibitors in clinical practice and ex vivo by fluorescence in situ hybridization of chromosomal breaks. Nevertheless, radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib in both the patient study and the ex vivo experiment
Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders
Personality is influenced by genetic and environmental factors1
and associated with mental health. However, the underlying
genetic determinants are largely unknown. We identified six
genetic loci, including five novel loci2,3, significantly associated
with personality traits in a meta-analysis of genome-wide
association studies (N = 123,132–260,861). Of these genomewide
significant loci, extraversion was associated with variants
in WSCD2 and near PCDH15, and neuroticism with variants
on chromosome 8p23.1 and in L3MBTL2. We performed a
principal component analysis to extract major dimensions
underlying genetic variations among five personality traits
and six psychiatric disorders (N = 5,422–18,759). The first
genetic dimension separated personality traits and psychiatric
disorders, except that neuroticism and openness to experience
were clustered with the disorders. High genetic correlations
were found between extraversion and attention-deficit–
hyperactivity disorder (ADHD) and between openness and
schizophrenia and bipolar disorder. The second genetic
dimension was closely aligned with extraversion–introversion
and grouped neuroticism with internalizing psychopathology
(e.g., depression or anxiety)
Variation in structure and properties of poly(glycerol adipate) via control of chain branching during enzymatic synthesis
Poly (glycerol adipate) (PGA) can be produced from divinyl adipate and unprotected glycerol by an enzymatic route to generate a polymer with relatively low molar mass (12 kDa). PGA bears a pendant hydroxyl group which imparts a hydrophilic character to this water insoluble polymer. We have examined the effect of synthesis temperature on polymer characteristics through various techniques including FT-IR, 1H and 13C NMR, surface and thermal analysis, both to expand the data already present in the literature about this material and to understand better its properties for potential pharmaceutical applications. The use of a lipase (Novozym 435) as a catalyst suppresses cross-linking at the pendant glyceryl hydroxyl through steric hindrance at the active site, thus producing polymers with low degrees of branching (5–30%), and removes the need for any pre- or post-polymerization protection/deprotection reactions. Careful temperature control during synthesis can give polymers with reproducible molecular weights and reduced amounts of polymer branching compared to synthesis at higher temperatures. Due to the ability of the synthetic route to produce a range of structures, PGA generated by enzymatic routes may emerge as a useful biodegradable polymer platform to engineer solid dispersions or nanoparticles for healthcare applications
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