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Nucleic Acids Research Feb 2023tRNAs are key partners in ribosome-dependent protein synthesis. This process is highly dependent on the fidelity of tRNA aminoacylation by aminoacyl-tRNA synthetases and... (Review)
Review
tRNAs are key partners in ribosome-dependent protein synthesis. This process is highly dependent on the fidelity of tRNA aminoacylation by aminoacyl-tRNA synthetases and relies primarily on sets of identities within tRNA molecules composed of determinants and antideterminants preventing mischarging by non-cognate synthetases. Such identity sets were discovered in the tRNAs of a few model organisms, and their properties were generalized as universal identity rules. Since then, the panel of identity elements governing the accuracy of tRNA aminoacylation has expanded considerably, but the increasing number of reported functional idiosyncrasies has led to some confusion. In parallel, the description of other processes involving tRNAs, often well beyond aminoacylation, has progressed considerably, greatly expanding their interactome and uncovering multiple novel identities on the same tRNA molecule. This review highlights key findings on the mechanistics and evolution of tRNA and tRNA-like identities. In addition, new methods and their results for searching sets of multiple identities on a single tRNA are discussed. Taken together, this knowledge shows that a comprehensive understanding of the functional role of individual and collective nucleotide identity sets in tRNA molecules is needed for medical, biotechnological and other applications.
Topics: Aminoacylation; Transfer RNA Aminoacylation; Amino Acyl-tRNA Synthetases; Biotechnology; RNA, Transfer
PubMed: 36744444
DOI: 10.1093/nar/gkad007 -
Scientific Reports Sep 2023Post-operative urinary retention is a medical condition where patients cannot urinate despite having a full bladder. Ultrasound imaging of the bladder is used to...
Post-operative urinary retention is a medical condition where patients cannot urinate despite having a full bladder. Ultrasound imaging of the bladder is used to estimate urine volume for early diagnosis and management of urine retention. Moreover, the use of bladder ultrasound can reduce the need for an indwelling urinary catheter and the risk of catheter-associated urinary tract infection. Wearable ultrasound devices combined with machine-learning based bladder volume estimation algorithms reduce the burdens of nurses in hospital settings and improve outpatient care. However, existing algorithms are memory and computation intensive, thereby demanding the use of expensive GPUs. In this paper, we develop and validate a low-compute memory-efficient deep learning model for accurate bladder region segmentation and urine volume calculation. B-mode ultrasound bladder images of 360 patients were divided into training and validation sets; another 74 patients were used as the test dataset. Our 1-bit quantized models with 4-bits and 6-bits skip connections achieved an accuracy within [Formula: see text] and [Formula: see text], respectively, of a full precision state-of-the-art neural network (NN) without any floating-point operations and with an [Formula: see text] and [Formula: see text] reduction in memory requirements to fit under 150 kB. The means and standard deviations of the volume estimation errors, relative to estimates from ground-truth clinician annotations, were [Formula: see text] ml and [Formula: see text] ml, respectively. This lightweight NN can be easily integrated on the wearable ultrasound device for automated and continuous monitoring of urine volume. Our approach can potentially be extended to other clinical applications, such as monitoring blood pressure and fetal heart rate.
Topics: Humans; Urinary Bladder; Algorithms; Neural Networks, Computer; Ultrasonography; Urinary Retention
PubMed: 37777523
DOI: 10.1038/s41598-023-42000-9 -
Molecular Cytogenetics Nov 2023Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare...
BACKGROUND
Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare disease is characterised by dismal prognosis. In recent years, there has been a deeper understanding of RT molecular pathogenesis, and disruptions of apoptosis (TP53) and proliferation (CDKN2A, MYC, NOTCH1) has been described as typical aberrations in RT.
RESULTS
A single-institution cohort of 33 RT patients were investigated by karyotyping, fluorescence in situ hybridization and single nucleotide polymorphism/copy number (CN) arrays. Most of RTs were typically manifested by diffuse large B-cell lymphoma, not otherwise specified, among the remaining cases one was classified as high-grade B-cell lymphoma with 11q aberrations. The most frequent alterations (40-60% of cases) were represented by MYC rearrangement/gain, deletions of TP53 and CDKN2A, IGH rearrangement and 13q14 deletion. Several other frequent lesions included losses of 14q24.1-q32.33, 7q31.33-q36.3, and gain of 5q35.2. Analysis of 13 CLL/SLL-RT pairs showed that RT arised from the CLL/SLL by acquiring of 10 ~ 12 cytogenetic or CN lesions/case, but without acquisition of loss of heterozygosity regions. Our result affirmed the higher genetic complexity in RT than CLL/SLL and confirmed the linear features of RT clonal evolution as predominant.
CONCLUSIONS
Cytogenomic profile was concordant with the literature data, however the role of IGH rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution.
PubMed: 37941034
DOI: 10.1186/s13039-023-00662-0 -
Radiologia 2020On March 2, 1896, the local press in Malaga reported the discovery of X-rays, relating various news items about the use of X-rays and literature about Roentgen's...
On March 2, 1896, the local press in Malaga reported the discovery of X-rays, relating various news items about the use of X-rays and literature about Roentgen's discovery by journalists and other authors. Outstanding among these writings was a periodical directed at the administration and general public called Los Rayos X. Progressively, the first X-ray machines were installed in hospitals during this period, and the first installation in a private medical clinic took place in 1900. In Malaga, the assimilation and progression of the diagnostic and therapeutic use of radiology was slow and affected by peculiarities owing to the social, economic, and cultural circumstances of the period. Influential physicians willing to overcome resistance to advances were able to bring medical practice in Malaga to a level similar to that of other cities.
Topics: History, 19th Century; History, 20th Century; Humans; Newspapers as Topic; Radiology; Spain; X-Rays
PubMed: 31776001
DOI: 10.1016/j.rx.2019.10.001 -
Nucleic Acids Research Sep 2023In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the non-structural protein NSP1 inhibits translation of host mRNAs by binding to the mRNA entry channel...
In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the non-structural protein NSP1 inhibits translation of host mRNAs by binding to the mRNA entry channel of the ribosome and, together with the 5'-untranslated region (UTR) of the viral mRNAs, allows the evasion of that inhibition. Here, we show that NSP1 mediates endonucleolytic cleavages of both host and viral mRNAs in the 5'UTR, but with different cleavage patterns. The first pattern is observed in host mRNAs with cleavages interspersed regularly and close to the 5' cap (6-11 nt downstream of the cap). Those cleavage positions depend more on the position relative to the 5' cap than on the sequence itself. The second cleavage pattern occurs at high NSP1 concentrations and only in SARS-CoV-2 RNAs, with the cleavages clustered at positions 45, 46 and 49. Both patterns of cleavage occur with the mRNA and NSP1 bound to the ribosome, with the SL1 hairpin at the 5' end sufficient to protect from NSP1-mediated degradation at low NSP1 concentrations. We show further that the N-terminal domain of NSP1 is necessary and sufficient for efficient cleavage. We suggest that in the ribosome-bound NSP1 protein the catalytic residues of the N-terminal domain are unmasked by the remodelling of the α1- and α2-helices of the C-terminal domain.
Topics: Humans; COVID-19; Protein Biosynthesis; Ribosomes; RNA, Messenger; SARS-CoV-2; Viral Nonstructural Proteins
PubMed: 37503833
DOI: 10.1093/nar/gkad627 -
Rambam Maimonides Medical Journal Oct 2018Today medical imaging is an essential component of the entire health-care continuum, from wellness and screening, to early diagnosis, treatment selection, and follow-up.... (Review)
Review
Today medical imaging is an essential component of the entire health-care continuum, from wellness and screening, to early diagnosis, treatment selection, and follow-up. Patient triage in both acute care and chronic disease, imaging-guided interventions, and optimization of treatment planning are now integrated into routine clinical practice in all subspecialties. This paper provides a brief review of major milestones in medical imaging from its inception to date, with a few considerations regarding future directions in this important field.
PubMed: 30309440
DOI: 10.5041/RMMJ.10355 -
Reports of Practical Oncology and... 2020This paper describes the role of the Polish Secondary Standard Dosimetry Laboratory (SSDL) in quality assurance in radiotherapy by means of providing calibration of... (Review)
Review
This paper describes the role of the Polish Secondary Standard Dosimetry Laboratory (SSDL) in quality assurance in radiotherapy by means of providing calibration of ionisation chambers, TLD postal dosimetry audits and end-to-end audits for radiation therapy. A historical review of the methods and results are presented. The influence of the SSDL in Warsaw on radiation protection of patients in Poland is discussed. The International Atomic Energy Agency together with World Health Organisation (IAEA/WHO), through its network of SSDLs around the world, propagates newly developed methods for calibration and auditing. Suitable high quality equipment was provided by the IAEA, as well as special materials and technical support to the SSDL in Warsaw. The activity of the SSDL and the services provided for Polish radiotherapy centres have resulted in a reduction of discrepancies between planned doses and doses delivered to patients. The newly tested IAEA methods of end-to-end on-site dosimetry audits allow for monitoring and improving the quality of IMRT in Poland. The traceability of standards used for the calibration of therapy level dosimeters from Polish radiotherapy centres is assured by the IAEA dosimetry laboratory. The consistency of methods performed in the Polish SSDL with the ISO:17025 norm is supervised by the Polish Centre for Accreditation - a member of International Laboratory Accreditation Cooperation (ILAC), for calibration and testing. Due to the rapid technological development of radiotherapy, special attention has to be paid to newly developed methods for dosimetry auditing and institutions which provide services for assuring radiation safety of patients.
PubMed: 32982598
DOI: 10.1016/j.rpor.2020.08.003 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745 -
Cancers Jun 2022Uveal melanoma is the most common primary intraocular malignancy in adults, characterized by an insidious onset and poor prognosis strongly associated with tumor size... (Review)
Review
Uveal melanoma is the most common primary intraocular malignancy in adults, characterized by an insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, a biopsy followed by a pathological exam is used only in certain cases. Therefore, an early and noninvasive diagnosis is essential to enhance patients' chances for early treatment. We reviewed imaging modalities currently used in the diagnostics of uveal melanoma, including fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), as well as positron emission tomography/computed tomography (PET/CT) or magnetic resonance imaging (MRI). The principle of imaging techniques is briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities are explained. We describe UM imaging innovations, show their current usage and development, and explain the possibilities of utilizing such modalities to diagnose uveal melanoma in the future.
PubMed: 35804919
DOI: 10.3390/cancers14133147 -
RoFo : Fortschritte Auf Dem Gebiete Der... Aug 2023Breast imaging represents an integral part of radiology and is subject to strict quality controls. Regarding this, precise diagnostics including multimodal assessment by...
PURPOSE
Breast imaging represents an integral part of radiology and is subject to strict quality controls. Regarding this, precise diagnostics including multimodal assessment by mammography, sonography, and MRI, including image-guided biopsy and localization procedures, is often decisive and must be performed by experts with profound knowledge and skills in all of these procedures.However, due to numerous restructurings, breast imaging has been shifted more and more towards large, specialized centers, resulting in less patient exposition and training opportunities for radiologists in smaller sites. The following whitepaper summarizes the current circumstances and discusses opinions of the participating societies.
MATERIALS
Under the leadership of the German Roentgen Society (DRG) and with the participation of the DRG's AG Mammadiagnostik, the CAFRAD (Chefarztforum Radiologie), the KLR (Konferenz der Lehrstuhlinhaber für Radiologie e. V.), the DRG's Forum Junge Radiologie (FJR) and the Berufsverband der Deutschen Radiologen e. V. (BDR), possible solutions were discussed and consented for a structured training in breast radiology in the future.
RESULTS
In addition to the teaching provided at the primary workplace, qualified training should be ensured through flexible, multi-institutional, interdisciplinary, and cross-sectoral collaboration. Furthermore, the integration of online case collections and close cooperation with certified breast cancer centers and mammography screening units is recommended. It is indispensible that online courses and case collections adhere to the standards of the national societies and include a maximum of one third of the required cases.
CONCLUSION
In order to provide training in breast radiology at a high professional level, a paradigm shift with closer cooperation of all participants is necessary. This includes close collaboration of the breast imaging societies with the federal medical associations to establish new teaching concepts like e-learning in the training schedule of radiologists.
KEY POINTS
· Breast diagnostics is an integral part of radiology training.. · Due to recent restructurings, smaller training centers have difficulties in meeting the case numbers demanded by the Specialist Training Regulations (WBO). Improved integration of the new structures and their adaptation to the needs of education are necessary to guarantee standardized high-quality training of young radiologists.. · The integration of certified case collections enables quality-assured training, even across regions in online-based formats. In accordance with the "blended learning principle", up to one-third of the required number of patient studies can be substituted with cases from a certified case collection.. · Legally secured short- and medium-term internships may complement training in radiology..
CITATION FORMAT
· Sauer ST, Bley TA, Wenkel E et al. Whitepaper: Training in Diagnostic and Interventional Breast Radiology. Fortschr Röntgenstr 2023; 195: 699 - 706.
Topics: Humans; Radiology, Interventional; Curriculum; Learning; Mammography; Ultrasonography
PubMed: 37348527
DOI: 10.1055/a-2081-3549