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Trends in Endocrinology and Metabolism:... Apr 2024Mitochondria play multiple critical roles in cellular activity. In particular, mitochondrial translation is pivotal in the regulation of mitochondrial and cellular...
Mitochondria play multiple critical roles in cellular activity. In particular, mitochondrial translation is pivotal in the regulation of mitochondrial and cellular homeostasis. In this forum article, we discuss human mitochondrial tRNA metabolism and highlight its tight connection with various mitochondrial diseases caused by mutations in aminoacyl-tRNA synthetases, tRNAs, and tRNA-modifying enzymes.
Topics: Humans; Mitochondria; Amino Acyl-tRNA Synthetases; RNA, Transfer
PubMed: 38307811
DOI: 10.1016/j.tem.2024.01.002 -
Radiology. Imaging Cancer Mar 2024Purpose To determine the pathologic features of nonmass enhancement (NME) directly adjacent to biopsy-proven malignant masses (index masses) at preoperative MRI and...
Purpose To determine the pathologic features of nonmass enhancement (NME) directly adjacent to biopsy-proven malignant masses (index masses) at preoperative MRI and determine imaging characteristics that are associated with a malignant pathologic condition. Materials and Methods This retrospective study involved the review of breast MRI and mammography examinations performed for evaluating disease extent in patients newly diagnosed with breast cancer from July 1, 2016, to September 30, 2019. Inclusion criteria were limited to patients with an index mass and the presence of NME extending directly from the mass margins. Wilcoxon rank sum test, Fisher exact test, and χ test were used to analyze cancer, patient, and imaging characteristics associated with the NME diagnosis. Results Fifty-eight patients (mean age, 58 years ± 12 [SD]; all women) were included. Malignant pathologic findings for mass-associated NME occurred in 64% (37 of 58) of patients, 43% (16 of 37) with ductal carcinoma in situ and 57% (21 of 37) with invasive carcinoma. NME was more likely to be malignant when associated with an index cancer that had a low Ki-67 index (<20%) ( = .04). The presence of calcifications at mammography correlating with mass-associated NME was not significantly associated with malignant pathologic conditions ( = .19). The span of suspicious enhancement measured at MRI overestimated the true span of disease at histologic evaluation ( < .001), while there was no evidence of a difference between span of calcifications at mammography and true span of disease at histologic evaluation ( = .27). Conclusion Mass-associated NME at preoperative MRI was malignant in most patients with newly diagnosed breast cancer. The span of suspicious enhancement measured at MRI overestimated the true span of disease found at histologic evaluation. Breast, Mammography © RSNA, 2024 See also the commentary by Newell in this issue.
Topics: Female; Humans; Middle Aged; Breast Neoplasms; Retrospective Studies; Breast; Mammography; Magnetic Resonance Imaging; Calcinosis
PubMed: 38305717
DOI: 10.1148/rycan.230060 -
Journal of the American Chemical Society Mar 2024Toehold-mediated strand displacement (TMSD) was tested as a tool to edit information in synthetic digital polymers. Uniform DNA-polymer biohybrid macromolecules were...
Toehold-mediated strand displacement (TMSD) was tested as a tool to edit information in synthetic digital polymers. Uniform DNA-polymer biohybrid macromolecules were first synthesized by automated phosphoramidite chemistry and characterized by HPLC, mass spectrometry, and polyacrylamide gel electrophoresis (PAGE). These precursors were diblock structures containing a synthetic poly(phosphodiester) (PPDE) segment covalently attached to a single-stranded DNA sequence. Three types of biohybrids were prepared herein: a substrate containing an accessible toehold as well as input and output macromolecules. The substrate and the input macromolecules contained noncoded PPDE homopolymers, whereas the output macromolecule contained a digitally encoded segment. After hybridization of the substrate with the output, incubation in the presence of the input led to efficient TMSD and the release of the digital segment. TMSD can therefore be used to erase or rewrite information in self-assembled biohybrid superstructures. Furthermore, it was found in this work that the conjugation of DNA single strands to synthetic segments of chosen lengths greatly facilitates the characterization and PAGE visualization of the TMSD process.
Topics: DNA; Polymers; DNA, Single-Stranded; Recombination, Genetic; Organophosphates
PubMed: 38286022
DOI: 10.1021/jacs.3c13953 -
Injury Mar 2024
Topics: Child; Humans; Humeral Fractures; Fracture Fixation, Internal; Radiation Exposure; Bone Wires; Treatment Outcome
PubMed: 38246014
DOI: 10.1016/j.injury.2024.111354 -
Physical Biology Jan 2024Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure...
Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the protein sequence landscape as defined by an effective energy that is a proxy of sequence foldability. This landscape shares characteristics with optimization challenges encountered in machine learning and constraint satisfaction problems. Our analysis reveals that natural proteins predominantly reside in wide, flat minima within this energy landscape. To investigate further, we employ statistical mechanics algorithms specifically designed to explore regions with high local entropy in relatively flat landscapes. Our findings indicate that these specialized algorithms can identify valleys with higher entropy compared to those found using traditional methods such as Monte Carlo Markov Chains. In a proof-of-concept case, we find that these highly entropic minima exhibit significant similarities to natural sequences, especially in critical key sites and local entropy. Additionally, evaluations through Molecular Dynamics suggests that the stability of these sequences closely resembles that of natural proteins. Our tool combines advancements in machine learning and statistical physics, providing new insights into the exploration of sequence landscapes where wide, flat minima coexist alongside a majority of narrower minima.
Topics: Protein Folding; Amino Acid Sequence; Proteins; Entropy; Molecular Dynamics Simulation; Algorithms; Protein Conformation; Thermodynamics
PubMed: 38237200
DOI: 10.1088/1478-3975/ad205c -
Skeletal Radiology Jul 2024To evaluate the distribution of intra- and extraarticular MRI findings in children and adolescents with clinically suspected intraarticular cause of hip pain in order to...
PURPOSE
To evaluate the distribution of intra- and extraarticular MRI findings in children and adolescents with clinically suspected intraarticular cause of hip pain in order to assess the need for additional intraarticular contrast administration.
MATERIAL AND METHODS
Database was searched over a period of 34 months retrospectively for consecutive hip MR arthrography in young patients (8-17 years) with suspected intraarticular cause of hip or groin pain. Exclusion criteria were prior hip surgery, follow-up examination due to known intraarticular pathology, incomplete examination, qualitatively non-diagnostic examinations, and missing informed consent. Reports of fellowship-trained MSK radiologists were searched for intraarticular versus extraarticular findings explaining hip or groin pain.
RESULTS
Seventy patients (68% female; median age: 14.5 years; range:10.8-16.9 years) were analyzed. No reason for pain was found in 30 (42.9%) hips, extraarticular reasons in 20 (28.6%) cases, intraarticular in 14 (20.0%), and both (intra- and extraarticular) in 6 (8.6%) hips. Most common extraarticular reasons were apophysitis (14.3%), other bony stress reactions (12.9%), intramuscular edema (7%), tendinitis (5.7%), and trochanteric bursitis (4.3%). Labral pathology was the most common intraarticular finding (overall:34.3%; partial tear:15.7%, complete tear:15.7%), most frequent at the anterosuperior position (81.8%). Cartilage defects (1.4%), intraarticular neoplasia (1.4%), and tear of the femoral head ligament (2.8%) were rarely found. Synovitis and loose bodies were not observed. Cam-(37.1%) and pincer-configurations (47.1%) were common while hip dysplasia was rare (5.7%).
CONCLUSION
MRI in children and adolescents with hip pain should be done primarily without intraarticular contrast administration since most cases show an extraarticular pain reason or no diagnosis detectable with MRI.
Topics: Humans; Adolescent; Female; Male; Child; Magnetic Resonance Imaging; Hip Joint; Arthralgia; Contrast Media; Reproducibility of Results; Arthrography; Sensitivity and Specificity; Retrospective Studies; Joint Diseases
PubMed: 38206356
DOI: 10.1007/s00256-023-04552-9 -
Brain : a Journal of Neurology Apr 2024Most research in Parkinson's disease focuses on improving motor symptoms. Yet, up to 80% of patients present with non-motor symptoms that often have a large impact on...
Most research in Parkinson's disease focuses on improving motor symptoms. Yet, up to 80% of patients present with non-motor symptoms that often have a large impact on patients' quality of life. Impairment in working memory, a fundamental cognitive process, is common in Parkinson's disease. While deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in Parkinson's disease, its impact on cognitive functions is less well studied. Here, we examine the effect of DBS in the theta, beta, low and high gamma frequency on working memory in 20 Parkinson's disease patients with bilateral STN-DBS. A linear mixed effects model demonstrates that STN-DBS in the theta frequency improves working memory performance. This effect is frequency-specific and was absent for beta and gamma frequency stimulation. Further, this effect is specific to cognitive performance, as theta frequency DBS did not affect motor function. A non-parametric cluster-based permutation analysis of whole-brain normative structural connectivity shows that working memory enhancement by theta frequency stimulation is associated with higher connectivity between the stimulated subthalamic area and the right middle frontal gyrus. Again, this association is frequency- and task-specific. These findings highlight the potential of theta frequency STN-DBS as a targeted intervention to improve working memory in patients with Parkinson's disease.
Topics: Humans; Parkinson Disease; Subthalamic Nucleus; Memory, Short-Term; Deep Brain Stimulation; Quality of Life
PubMed: 38193320
DOI: 10.1093/brain/awad433 -
Heliyon Jan 2024Esophageal cancer (EC) is a common and devastating tumor of the upper digestive tract. Unfortunately, by the time any symptoms have manifested, the disease has often... (Review)
Review
Esophageal cancer (EC) is a common and devastating tumor of the upper digestive tract. Unfortunately, by the time any symptoms have manifested, the disease has often progressed to an advanced stage and is accompanied by macro- and micrometastases, including in the bones. The treatment of esophageal cancer with bone metastases remains clinically challenging, given the poor prognosis associated with this condition. Effective prognostic biomarkers can help medical staff choose the appropriate operation and treatment plan, that is for most beneficial for making patients. Current treatments for esophageal cancer with bone metastases include pain-relieving drugs, surgical therapy, radiotherapy (RT), chemotherapy (CT, including molecular-targeted drug therapy), endocrine therapy (ET), bisphosphonates (BPs) and interventional therapy. Of these robust measures, radiotherapy has emerged as a particularly promising therapy for bone metastases from esophageal cancer. Substantial progress has been made in radiation therapy techniques since the discovery of X-rays by Roentgen in 1895. In its palliative capacity, the key goals of radiotherapy are to relieve the patients' bone pain and debilitate effects, including relieving spinal cord compression, correcting the spinal deformity and restoring spinal stability. However, it is worth mentioning that RT for esophageal cancer has various side effects. Currently, the available studies focused exclusively on radiotherapy for ECBM are too small to draw any definitive conclusions, and each of these studies has significant limitations. In this review, in addition to the epidemiology described at the beginning, we will explore the current prognostic biomarkers and radiotherapy for esophageal cancer, with a particular focus on those with bone metastases.
PubMed: 38170113
DOI: 10.1016/j.heliyon.2023.e23510 -
Radiology. Artificial Intelligence Jan 2024
Topics: Diagnostic Imaging; Archives; Radiography; Scotland
PubMed: 38166329
DOI: 10.1148/ryai.230466 -
Radiology Jan 2024While musculoskeletal imaging volumes are increasing, there is a relative shortage of subspecialized musculoskeletal radiologists to interpret the studies. Will... (Review)
Review
While musculoskeletal imaging volumes are increasing, there is a relative shortage of subspecialized musculoskeletal radiologists to interpret the studies. Will artificial intelligence (AI) be the solution? For AI to be the solution, the wide implementation of AI-supported data acquisition methods in clinical practice requires establishing trusted and reliable results. This implementation will demand close collaboration between core AI researchers and clinical radiologists. Upon successful clinical implementation, a wide variety of AI-based tools can improve the musculoskeletal radiologist's workflow by triaging imaging examinations, helping with image interpretation, and decreasing the reporting time. Additional AI applications may also be helpful for business, education, and research purposes if successfully integrated into the daily practice of musculoskeletal radiology. The question is not whether AI will replace radiologists, but rather how musculoskeletal radiologists can take advantage of AI to enhance their expert capabilities.
Topics: Humans; Artificial Intelligence; Radionuclide Imaging; Commerce; Physical Examination; Radiologists
PubMed: 38165245
DOI: 10.1148/radiol.230764