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Journal of the American Chemical Society Jul 2023The Hula-Twist (HT) photoreaction represents a fundamental photochemical pathway for bond isomerizations and is defined by the coupled motion of a double bond and an...
The Hula-Twist (HT) photoreaction represents a fundamental photochemical pathway for bond isomerizations and is defined by the coupled motion of a double bond and an adjacent single bond. This photoreaction has been suggested as the defining motion for a plethora of light-responsive chromophores such as retinal within opsins, coumaric acid within photoactive yellow protein, or vitamin D precursors, and stilbenes in solution. However, due to the fleeting character of HT photoproducts a direct experimental observation of this coupled molecular motion was severely hampered until recently. To solve this dilemma, the Dube group has designed a molecular framework able to deliver unambiguous experimental evidence of the HT photoreaction. Using sterically crowded atropisomeric hemithioindigo (HTI) the HT photoproducts are rendered thermally stable and can be observed directly after their formation. However, following the ultrafast excited state process of the HT photoreaction itself has not been achieved so far and thus crucial information for an elementary understanding is still missing. In this work, we present the first ultrafast spectroscopy study of the HT photoreaction in HTI and probe the competition between different excited state processes. Together with extensive excited state calculations a detailed mechanistic picture is developed explaining the significant solvent effects on the HT photoreaction and revealing the intricate interplay between productive isomerizations and unproductive twisted intramolecular charge transfer (TICT) processes. With this study essential insights are thus gained into the mechanism of complex multibond rotations in the excited state, which will be of primary importance for further developments in this field.
PubMed: 37364887
DOI: 10.1021/jacs.3c03536 -
BMC Medical Imaging Nov 2023To provide normative data and to determine accuracy and reliability of preoperative measurements of spondylolisthesis and kyphosis on supine static magnetic resonance...
BACKGROUND
To provide normative data and to determine accuracy and reliability of preoperative measurements of spondylolisthesis and kyphosis on supine static magnetic resonance imaging (MRI) of patients with degenerative cervical myelopathy.
METHODS
T2-weighted midsagittal images of the cervical spine were in 100 cases reviewed twice by one junior observer, with an interval of 3 months, and once by a senior observer. The spondylolisthesis slip (SSlip, mm) and the modified K-line interval (mK-line INT, mm) were assessed for accuracy with the standard error of measurement (SEm) and the minimum detectable change (MDC). Intraobserver and interobserver reliability levels were determined using the intraclass correlation coefficient (ICC).
RESULTS
The SEm was 0.5 mm (95% CI 0.4-0.6) for spondylolisthesis and 0.6 mm (95% CI 0.5-0.7) for kyphosis. The MDC, i.e., the smallest difference between two examinations that can be detected with statistical certainty, was 1.5 mm (95% CI 1.2-1.8) for spondylolisthesis and 1.6 mm (95% CI 1.3-1.8) for kyphosis. The highest reliability levels were seen between the second observation of the junior examiner and the senior observer (ICC = 0.80 [95% CI 0.70-0.87] and ICC = 0.96 [95% CI 0.94-0.98] for SSlip and mK-line INT, respectively).
CONCLUSIONS
This study provides normative values of alignment measurements of spondylolisthesis and kyphosis in DCM patients. It further shows the importance of taking measurement errors into account when defining cut-off values for cervical deformity parameters and their potential clinical application in surgical decision-making.
Topics: Humans; Spondylolisthesis; Reproducibility of Results; Kyphosis; Spinal Cord Diseases; Cervical Vertebrae; Magnetic Resonance Imaging
PubMed: 37946139
DOI: 10.1186/s12880-023-01151-x -
Brachytherapy 2023Target and organ delineation during prostate high-dose-rate (HDR) brachytherapy treatment planning can be improved by acquiring both a postimplant CT and MRI. However,...
PURPOSE
Target and organ delineation during prostate high-dose-rate (HDR) brachytherapy treatment planning can be improved by acquiring both a postimplant CT and MRI. However, this leads to a longer treatment delivery workflow and may introduce uncertainties due to anatomical motion between scans. We investigated the dosimetric and workflow impact of MRI synthesized from CT for prostate HDR brachytherapy.
METHODS AND MATERIALS
Seventy-eight CT and T2-weighted MRI datasets from patients treated with prostate HDR brachytherapy at our institution were retrospectively collected to train and validate our deep-learning-based image-synthesis method. Synthetic MRI was assessed against real MRI using the dice similarity coefficient (DSC) between prostate contours drawn using both image sets. The DSC between the same observer's synthetic and real MRI prostate contours was compared with the DSC between two different observers' real MRI prostate contours. New treatment plans were generated targeting the synthetic MRI-defined prostate and compared with the clinically delivered plans using target coverage and dose to critical organs.
RESULTS
Variability between the same observer's prostate contours from synthetic and real MRI was not significantly different from the variability between different observer's prostate contours on real MRI. Synthetic MRI-planned target coverage was not significantly different from that of the clinically delivered plans. There were no increases above organ institutional dose constraints in the synthetic MRI plans.
CONCLUSIONS
We developed and validated a method for synthesizing MRI from CT for prostate HDR brachytherapy treatment planning. Synthetic MRI use may lead to a workflow advantage and removal of CT-to-MRI registration uncertainty without loss of information needed for target delineation and treatment planning.
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Brachytherapy; Workflow; Retrospective Studies; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Magnetic Resonance Imaging
PubMed: 37316376
DOI: 10.1016/j.brachy.2023.05.005 -
ImmunoHorizons Nov 2023The polarization of naive Th cells into differentiated subsets in vitro was a powerful approach to define the development and function of Th cells in vivo. Th cell...
The polarization of naive Th cells into differentiated subsets in vitro was a powerful approach to define the development and function of Th cells in vivo. Th cell cultures identified cytokines that promote polarization and defined the phenotype and stability of differentiated cells. One of the limitations of this approach is the heterogeneity of the differentiated culture, essentially with regard to what proportion of the culture is secreting the hallmark cytokine of interest. This heterogeneity has always been puzzling because all cells in the culture have been exposed to identical culture conditions. We examined this phenomenon using an Il17f lineage-tracing allele (Cost, Cre on seventeen transcript) crossed to stop-flox Rosa-YFP (yellow fluorescent protein) mice. We found that less than half of the cells in a Th17 culture become lineage-positive during a differentiation culture and that it is primarily cells that are lineage-positive that produce cytokines when cultures are restimulated after differentiation. We sorted and analyzed YFP-positive and YFP-negative cells and found similar expression of many Th17 transcription factors, although YFP-negative cells had increased expression of other lineage-defining transcription factors. We observed that YFP-negative cells had diminished expression of Stat3 and Il6ra, as well as decreased STAT3 activation. YFP-negative cells transduced with active STAT3 had significant increases in IL-17A expression, without increases in Th17 transcription factors. Taken together, these data suggest that there is a threshold of STAT3 activation that is required for efficient Th17 differentiation, and that even in a culture of homogeneous naive T cells there is heterogeneity in the receipt of early cytokine signals.
Topics: Animals; Mice; Cytokines; Th17 Cells; Cell Differentiation; Alleles; Cell Movement
PubMed: 37938185
DOI: 10.4049/immunohorizons.2300072 -
Strabismus Dec 2023: Esotropia is a form of strabismus, a condition characterized by the misalignment of the eyes. Specifically, esotropia refers to inward deviation of one or both eyes.... (Review)
Review
: Esotropia is a form of strabismus, a condition characterized by the misalignment of the eyes. Specifically, esotropia refers to inward deviation of one or both eyes. It can manifest at different ages, ranging from infancy to adulthood, and can have varying degrees of severity. The false appearance of esotropia in the alignment of the visual axes is what defines pseudoesotropia. Halil Pasha was a Turkish painter known for his contributions to the art scene during the late 19th and early 20th centuries. His artistic talent, coupled with his influential position as a statesman, allowed him to leave a lasting impact on the cultural landscape of the Ottoman Empire. : In the present study, artistic depictions of esotropia or pseudoesotropia in Halil Pasha's "" were evaluated. A comprehensive literature review on strabismus in medicine and art was conducted. : "", translated as "", is one of the iconic paintings of Turkish art. It reflects the social dynamics and lifestyle of the time, offering a glimpse into the lives of women serving in Ottoman households. When we examine this painting as a physician, the first thing we notice is the old woman's eyes. An eye misalignment in the left eye of the old servant woman is noticed. : In medical humanities, which are addressed in medical education, medicine and art intersect with different perspectives and understandings. Although the evaluation of medical scenes in artworks seems to have been first observed by an art historian, today physicians and medical students need to examine artworks more carefully and develop their observational skills. Iconodiagnosis is the medical analysis of artworks that looks for clinical signs suggestive of medical disorders and diseases. The application of iconodiagnosis in medical education is an alternative and stimulating way to exercise students' observation skills; not only the physical examination of the patient is important, but also the information obtained from their posture, clothing, general demeanour and even physical aids.
Topics: Humans; Male; Esotropia; Strabismus
PubMed: 38031895
DOI: 10.1080/09273972.2023.2287854 -
PLoS Computational Biology Nov 2023In computational neuroscience, hypotheses are often formulated as bottom-up mechanistic models of the systems in question, consisting of differential equations that can...
In computational neuroscience, hypotheses are often formulated as bottom-up mechanistic models of the systems in question, consisting of differential equations that can be numerically integrated forward in time. Candidate models can then be validated by comparison against experimental data. The model outputs of neural network models depend on both neuron parameters, connectivity parameters and other model inputs. Successful model fitting requires sufficient exploration of the model parameter space, which can be computationally demanding. Additionally, identifying degeneracy in the parameters, i.e. different combinations of parameter values that produce similar outputs, is of interest, as they define the subset of parameter values consistent with the data. In this computational study, we apply metamodels to a two-population recurrent spiking network of point-neurons, the so-called Brunel network. Metamodels are data-driven approximations to more complex models with more desirable computational properties, which can be run considerably faster than the original model. Specifically, we apply and compare two different metamodelling techniques, masked autoregressive flows (MAF) and deep Gaussian process regression (DGPR), to estimate the power spectra of two different signals; the population spiking activities and the local field potential. We find that the metamodels are able to accurately model the power spectra in the asynchronous irregular regime, and that the DGPR metamodel provides a more accurate representation of the simulator compared to the MAF metamodel. Using the metamodels, we estimate the posterior probability distributions over parameters given observed simulator outputs separately for both LFP and population spiking activities. We find that these distributions correctly identify parameter combinations that give similar model outputs, and that some parameters are significantly more constrained by observing the LFP than by observing the population spiking activities.
Topics: Neural Networks, Computer; Neurons
PubMed: 38032904
DOI: 10.1371/journal.pcbi.1011625 -
Journal of Vision Mar 2024The ability of humans to identify and reproduce short time intervals (in the region of a second) may be affected by many factors ranging from the gender and personality...
The ability of humans to identify and reproduce short time intervals (in the region of a second) may be affected by many factors ranging from the gender and personality of the individual observer, through the attentional state, to the precise spatiotemporal structure of the stimulus. The relative roles of these very different factors are a challenge to describe and define; several methodological approaches have been used to achieve this to varying degrees of success. Here we describe and model the results of a paradigm affording not only a first-order measurement of the perceived duration of an interval but also a second-order metacognitive judgement of perceived time. This approach, we argue, expands the form of the data generally collected in duration-judgements and allows more detailed comparison of psychophysical behavior to the underlying theory. We also describe a hierarchical Bayesian measurement model that performs a quantitative analysis of the trial-by-trial data calculating the variability of the temporal estimates and the metacognitive judgments allowing direct comparison between an actual and an ideal observer. We fit the model to data collected for judgements of 750 ms (bisecting 1500 ms) and 1500 ms (bisecting 3000 ms) intervals across three stimulus modalities (visual, audio, and audiovisual). This enhanced form of data on a given interval judgement and the ability to track its progression on a trial-by-trial basis offers a way of looking at the different roles that subject-based, task-based and stimulus-based factors have on the perception of time.
Topics: Humans; Bayes Theorem; Judgment; Metacognition; Time Perception
PubMed: 38506794
DOI: 10.1167/jov.24.3.5 -
The Journal of Neuroscience : the... Nov 2023A common neuroscience application of Pavlovian fear conditioning is to manipulate neuron-type activity, pair a cue with foot shock, then measure cue-elicited freezing in...
A common neuroscience application of Pavlovian fear conditioning is to manipulate neuron-type activity, pair a cue with foot shock, then measure cue-elicited freezing in a novel context. If the manipulation reduces freezing, the neuron type is implicated in Pavlovian fear conditioning. This application reduces Pavlovian fear conditioning to a single concept. In this Viewpoint, I describe experiments supporting the view that Pavlovian fear conditioning refers to three distinct concepts: procedure, process, and behavior. An experimenter controls procedure, observes behavior, but infers process. Distinguishing these concepts is essential because: (1) a shock-paired cue can engage numerous processes and behaviors; (2) experimenter decisions about procedure influence the processes engaged and behaviors elicited; and (3) many processes are latent, imbuing the cue with properties that only manifest outside of the original conditioning setting. This means we could understand the complete neural basis of freezing, yet know little about the neural basis of fear. Neuroscientists can choose to use a variety of procedures to study a diversity of processes and behaviors. Manipulating neuron-type activity in multiple procedures can reveal specific, general, or complex neuron-type contributions to cue-elicited processes and behaviors. The results will be a broader and more detailed neural basis of fear with greater relevance to the spectrum of symptoms defining anxiety and stressor-related disorders.
Topics: Humans; Conditioning, Classical; Fear; Anxiety; Anxiety Disorders; Neurons
PubMed: 38030400
DOI: 10.1523/JNEUROSCI.0256-23.2023 -
Japanese Journal of Clinical Oncology Dec 2023Adult T-cell leukemia-lymphoma is defined as peripheral T-cell lymphoma caused by the human T-cell leukemia virus type I. Adult T-cell leukemia-lymphoma is classified... (Review)
Review
Adult T-cell leukemia-lymphoma is defined as peripheral T-cell lymphoma caused by the human T-cell leukemia virus type I. Adult T-cell leukemia-lymphoma is classified into indolent (favorable chronic or smoldering) or aggressive (acute, lymphoma or unfavorable chronic) types. This review discusses the therapeutic developments for patients with adult T-cell leukemia-lymphoma and unmet issues in treating adult T-cell leukemia-lymphoma. For indolent adult T-cell leukemia-lymphoma, a watchful waiting strategy is recommended until the disease progresses to aggressive adult T-cell leukemia-lymphoma. For aggressive adult T-cell leukemia-lymphoma, multi-agent chemotherapy with or without allogeneic hematopoietic stem cell transplantation has been recommended. However, many patients with adult T-cell leukemia-lymphoma relapse, and their prognosis is poor. Recently, novel agents, including mogamulizumab, lenalidomide, brentuximab vedotin, tucidinostat and valemetostat, have been approved for patients with relapsed or refractory aggressive adult T-cell leukemia-lymphoma, and the combination of mogamulizumab with multi-agent chemotherapy or brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone has been approved for patients with untreated aggressive adult T-cell leukemia-lymphoma in Japan. Importantly, the aging of patients with adult T-cell leukemia-lymphoma has recently been reported, and no standard of care for elderly patients with adult T-cell leukemia-lymphoma has been established. New evidence must be obtained from prospective clinical trials to improve the prognosis of patients with adult T-cell leukemia-lymphoma.
Topics: Adult; Humans; Aged; Leukemia-Lymphoma, Adult T-Cell; Brentuximab Vedotin; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Hematopoietic Stem Cell Transplantation
PubMed: 37592900
DOI: 10.1093/jjco/hyad108 -
PloS One 2023Small mammal species play an important role influencing vegetation primary productivity and plant species composition, seed dispersal, soil structure, and as predator...
Small mammal species play an important role influencing vegetation primary productivity and plant species composition, seed dispersal, soil structure, and as predator and/or prey species. Species which experience population dynamics cycles can, at high population phases, heavily impact agricultural sectors and promote rodent-borne disease transmission. To better understand the drivers behind small mammal distributions and abundances, and how these differ for individual species, it is necessary to characterise landscape variables important for the life cycles of the species in question. In this study, a suite of Earth observation derived metrics quantifying landscape characteristics and dynamics, and in-situ small mammal trapline and transect survey data, are used to generate random forest species distribution models for nine small mammal species for study sites in Narati, China and Sary Mogul, Kyrgyzstan. These species distribution models identify the important landscape proxy variables driving species abundance and distributions, in turn identifying the optimal conditions for each species. The observed relationships differed between species, with the number of landscape proxy variables identified as important for each species ranging from 3 for Microtus gregalis at Sary Mogul, to 26 for Ellobius tancrei at Narati. Results indicate that grasslands were predicted to hold higher abundances of Microtus obscurus, E. tancrei and Marmota baibacina, forest areas hold higher abundances of Myodes centralis and Sorex asper, with mixed forest-grassland boundary areas and areas close to watercourses predicted to hold higher abundances of Apodemus uralensis and Sicista tianshanica. Localised variability in vegetation and wetness conditions, as well as presence of certain habitat types, are also shown to influence these small mammal species abundances. Predictive application of the Random Forest (RF) models identified spatial hot-spots of high abundance, with model validation producing R2 values between 0.670 for M. gregalis transect data at Sary Mogul to 0.939 for E. tancrei transect data at Narati. This enhances previous work whereby optimal habitat was defined simply as presence of a given land cover type, and instead defines optimal habitat via a combination of important landscape dynamic variables, moving from a human-defined to species-defined perspective of optimal habitat. The species distribution models demonstrate differing distributions and abundances of host species across the study areas, utilising the strengths of Earth observation data to improve our understanding of landscape and ecological linkages to small mammal distributions and abundances.
Topics: Humans; Animals; Mammals; Advance Directives; Agriculture; Arvicolinae; Benchmarking; Marmota; Murinae
PubMed: 37590218
DOI: 10.1371/journal.pone.0289209