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Nucleic Acids Research Feb 2024tRNA superwobbling, used by certain bacteria and organelles, is an intriguing decoding concept in which a single tRNA isoacceptor is used to decode all synonymous codons...
tRNA superwobbling, used by certain bacteria and organelles, is an intriguing decoding concept in which a single tRNA isoacceptor is used to decode all synonymous codons of a four-fold degenerate codon box. While Escherichia coli relies on three tRNAGly isoacceptors to decode the four glycine codons (GGN), Mycoplasma mycoides requires only a single tRNAGly. Both organisms express tRNAGly with the anticodon UCC, which are remarkably similar in sequence but different in their decoding ability. By systematically introducing mutations and altering the number and type of tRNA modifications using chemically synthesized tRNAs, we elucidated the contribution of individual nucleotides and chemical groups to decoding by the E. coli and M. mycoides tRNAGly. The tRNA sequence was identified as the key factor for superwobbling, revealing the T-arm sequence as a novel pivotal element. In addition, the presence of tRNA modifications, although not essential for providing superwobbling, was shown to delicately fine-tune and balance the decoding of synonymous codons. This emphasizes that the tRNA sequence and its modifications together form an intricate system of high complexity that is indispensable for accurate and efficient decoding.
Topics: Anticodon; Base Sequence; Codon; Escherichia coli; Glycine; RNA, Transfer; RNA, Transfer, Gly; Mycoplasma mycoides; RNA, Bacterial
PubMed: 38050960
DOI: 10.1093/nar/gkad1136 -
Archive For Rational Mechanics and... 2023We study the fine regularity properties of optimal potentials for the dual formulation of the Hellinger-Kantorovich problem (), providing sufficient conditions for the...
We study the fine regularity properties of optimal potentials for the dual formulation of the Hellinger-Kantorovich problem (), providing sufficient conditions for the solvability of the primal Monge formulation. We also establish new regularity properties for the solution of the Hamilton-Jacobi equation arising in the dual dynamic formulation of , which are sufficiently strong to construct a characteristic transport-growth flow driving the geodesic interpolation between two arbitrary positive measures. These results are applied to study relevant geometric properties of geodesics and to derive the convex behaviour of their Lebesgue density along the transport flow. Finally, exact conditions for functionals defined on the space of measures are derived that guarantee the geodesic -convexity with respect to the Hellinger-Kantorovich distance. Examples of geodesically convex functionals are provided.
PubMed: 38046049
DOI: 10.1007/s00205-023-01941-1 -
BMC Cancer Nov 2023An Organised Cervical Cancer Screening Programme (OCCSP) was started in Poland in 2006/2007. Each woman aged 25 to 59 is eligible for a free Pap test every 3 years in...
BACKGROUND
An Organised Cervical Cancer Screening Programme (OCCSP) was started in Poland in 2006/2007. Each woman aged 25 to 59 is eligible for a free Pap test every 3 years in OCCSP. Despite implementation of the OCCSP, the age-standardised cervical cancer (CC) incidence and mortality rates in 2019 were 7.3/100 000 and 3.9/100 000 respectively and were still higher than those in Western European countries with well-organised screening programmes. Apart from low coverage of the OCCSP, suboptimal performance of the screening test (conventional cytology) may be partially responsible for this situation. Several countries have already incorporated high risk Human Papillomavirus (hrHPV) testing in CC screening as a more sensitive tool reducing the risk of missing precancerous lesions and allowing for extension of screening intervals. The European Guidelines for Quality Assurance in Cervical Cancer Screening recommend pilot evaluation of a new screening test in country-specific conditions before its implementation.
METHODS
The HIPPO project (HPV testing In Polish POpulation-based cervical cancer screening program) is a randomised health services study nested in the OCCSP in Poland. The project will randomise 33 000 women aged 30-59 years to cytology or hrHPV testing (ratio: 1:1) with age stratification. In the cytology arm women with repeated Atypical Squamous Cells of Undetermined Significance (ASC-US) or ≥ Low-Grade Squamous Intraepithelial Lesions (LSIL) are referred for colposcopy. In the other arm, hrHPV ( +) women with ≥ ASC-US reflex Liquid-Based Cytology (LBC) are referred for colposcopy. Primary endpoints include detection rates of histologically confirmed high grade intraepithelial lesions or worse (CIN2 +) in each arm.
DISCUSSION
This pilot randomised healthcare study nested in the OCCSP in Poland will assess and compare the performance of hrHPV testing to current standard-cytology in order to make decisions on implementation of HPV-based screening in the country.
TRIAL REGISTRATION
This randomised healthcare service study was prospectively registered at https://clinicaltrials.gov/ (identifier: NCT04111835, protocol ID 28/2019) on 19th of September 2019.
Topics: Female; Humans; Pregnancy; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia; Poland; Early Detection of Cancer; Papillomavirus Infections; Mass Screening; Atypical Squamous Cells of the Cervix; Colposcopy; Health Policy; Papillomaviridae; Vaginal Smears; Randomized Controlled Trials as Topic
PubMed: 37978452
DOI: 10.1186/s12885-023-11597-5 -
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 -
World Journal of Nuclear Medicine Sep 2023Our objective was to study the radiation exposure rate as function of time in the administration of radioiodine iodine-131 (I-131) for the treatment of...
Radiation Safety and External Radiation Exposure Rate of Patients Receiving I-131 Therapy for Hyperthyroidism and Remnant Ablation as Outpatient: An Institutional Experience.
Our objective was to study the radiation exposure rate as function of time in the administration of radioiodine iodine-131 (I-131) for the treatment of thyrotoxicosis or Graves' disease and remnant ablation on an outpatient basis at the Department of Nuclear Medicine, and also, to study the impact of revised discharge criteria for radioiodine therapy enforced by the Atomic Energy Regulatory Board (AERB) of India. This study included patients who underwent low-dose radioiodine therapy using I-131. Patients were classified into two different groups, that is, group A and group B. Group A included patients receiving low dose I-131 for the treatment of thyrotoxicosis, whereas group B included patients receiving I-131 therapy for the ablation of residual thyroid tissue after total thyroidectomy. The radiation exposure rate was measured using a radiation detector in milli roentgen per hour (mR/h) at 5 cm distance of stomach and neck levels and with the patient standing at the distance of 1 m after oral administration of I-131 at 0, 1, and 2 hours. A total of 134 (17 males and 117 females) patients were included in the study. Group A comprised 102 (14 male and 88 females) patients and group B of 32 (3 males and 29 females) patients. At the neck level, the average exposure rate in group A versus group B after 0, 1, and 2 hours was observed to be 6.9 versus 22.27 mR/h, 33.67 versus 43.39 mR/h, and 41.75 versus 48.90 mR/h, respectively. At the stomach level, the exposure rate was 23.65 versus 71.32 mR/h, 13.27 versus 48.45 mR/h, and 9.91 versus 39.43 mR/h after 0, 1, and 2 hours, respectively. At a distance of 1 m, the exposure rate was 1.31 versus 2.99 mR/h, 1.05 versus 2.58 mR/h, and 0.92 versus 2.21 mR/h, respectively. Exposure rate measured for patients treated with up to 1,110 MBq (30 mCi) of I-131 was under permissible limits as per revised discharged limits, that is, 50 µSv/h (5 mR/h) prescribed by AERB, India. The patients undergoing radioiodine therapy I-131 (up to 1,110 MBq/30 mCi) can be discharged safely 2 hours postadministration following good work practice along with providing proper radiation safety instructions to patients.
PubMed: 37854087
DOI: 10.1055/s-0043-1771285 -
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 -
Biochimie Feb 2024Translation initiation consists in the assembly of the small and large ribosomal subunits on the start codon. This important step directly modulates the general proteome... (Review)
Review
Translation initiation consists in the assembly of the small and large ribosomal subunits on the start codon. This important step directly modulates the general proteome in living cells. Recently, genome wide studies revealed unexpected translation initiation events from unsuspected novel open reading frames resulting in the synthesis of a so-called 'dark proteome'. Indeed, the identification of the start codon by the translation machinery is a critical step that defines the translational landscape of the cell. Therefore, translation initiation is a highly regulated process in all organisms. In this review, we focus on the various cis- and trans-acting factors that rule the regulation of translation initiation in eukaryotes. Recent discoveries have shown that the guidance of the translation machinery for the choice of the start codon require sophisticated molecular mechanisms. In particular, the 5'UTR and the coding sequences contain cis-acting elements that trigger the use of AUG codons but also non-AUG codons to initiate protein synthesis. The use of these alternative start codons is also largely influenced by numerous trans-acting elements that drive selective mRNA translation in response to environmental changes.
Topics: Codon, Initiator; Eukaryota; Trans-Activators; RNA, Messenger; Proteome; Peptide Chain Initiation, Translational; Codon; Protein Biosynthesis; Open Reading Frames; 5' Untranslated Regions
PubMed: 37741547
DOI: 10.1016/j.biochi.2023.09.017 -
Academic Radiology Jan 2024In April 2023, the first American Roentgen Ray Society (ARRS) Wellness Summit was held in Honolulu, Hawaii. The Summit was a communal call to action bringing together...
In April 2023, the first American Roentgen Ray Society (ARRS) Wellness Summit was held in Honolulu, Hawaii. The Summit was a communal call to action bringing together professionals from the field of radiology to critically review our current state of wellness and reimagine the role of radiology and radiologists to further wellbeing. The in-person and virtual Summit was available free-of-cost to all meeting registrants and included 12 sessions with 44 invited moderators and panelists. The Summit aimed to move beyond simply rehashing the repeated issues and offering theoretical solutions, and instead focus on intentional practice evolution, identifying implementable strategies so that we as a field can start to walk our wellness talk. Here, we first summarize the thematic discussions from the 2023 ARRS Wellness Summit, and second, share several strategic action items that emerged.
Topics: United States; Humans; X-Rays; Radiologists; Radiology; Burnout, Professional
PubMed: 37718125
DOI: 10.1016/j.acra.2023.08.025 -
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 -
International Journal of Legal Medicine Nov 2023The AGFAD (Arbeitsgemeinschaft für Forensische Alterdiagnostik, Study Group on Forensic Age Diagnostics) has published several recommendations regarding both technical... (Review)
Review
The AGFAD (Arbeitsgemeinschaft für Forensische Alterdiagnostik, Study Group on Forensic Age Diagnostics) has published several recommendations regarding both technical aspects of computed tomography (CT) of the medial clavicular epiphysis (MCE) and the process of reading and interpreting the CT images for forensic age estimations (FAE). There are, however, no published recommendations regarding CT scan protocols and no dose reference values for CT of the MCE. The objective of this analysis was to assess adherence to AGFAD recommendations among practitioners of FAE and analyse reported dose-relevant CT scan parameters with the objective of helping to establish evidence-based dose reference values for FAE. A systematic literature search was conducted in PubMed and in Google Scholar with specific MeSH terms to identify original research articles on FAE with CT of the MCE from 1997 to 2022. A total of 48 studies were included. Adherence to AGFAD recommendations among practitioners of FAE is high regarding the use of Schmeling main stages (93%), bone window (79%), ≤ 1 mm CT slices (67%), axial/coronal CT images (65%), and Kellinghaus sub-stages (59%). The reporting of CT technique and CT dose-relevant scan parameters is heterogeneous and often incomplete in the current literature. Considering the success achieved by the AGFAD in creating standards of practice of FAE in living subjects, there is potential for the AGFAD to establish standards for radiation protection in FAE as well.
Topics: Humans; Age Determination by Skeleton; Clavicle; Epiphyses; Tomography, X-Ray Computed; Radiation Dosage; Guideline Adherence; Forensic Anthropology
PubMed: 37691040
DOI: 10.1007/s00414-023-03061-7