Anteromedial thalamus gates the selection and stabilization of long-term memories.

Memories initially formed in hippocampus gradually stabilize to cortex over weeks-to-months for long-term storage. The mechanistic details of this brain re-organization remain poorly understood. We recorded bulk neural activity in circuits that link hippocampus and cortex as mice performed a memory-guided virtual-reality task over weeks. We identified a prominent and sustained neural correlate of memory in anterior thalamus, whose inhibition substantially disrupted memory consolidation. More strikingly, gain amplification enhanced consolidation of otherwise unconsolidated memories. To gain mechanistic insights, we developed a technology for simultaneous cellular-resolution imaging of hippocampus, thalamus, and cortex throughout consolidation. We found that whereas hippocampus equally encodes multiple memories, the anteromedial thalamus preferentially encodes salient memories, and gradually increases correlations with cortex to facilitate tuning and synchronization of cortical ensembles. We thus identify a thalamo-cortical circuit that gates memory consolidation and propose a mechanism suitable for the selection and stabilization of hippocampal memories into longer-term cortical storage.

A Thalamic Orphan Receptor Drives Variability in Short-Term Memory.

Working memory is a form of short-term memory that involves maintaining and updating task-relevant information toward goal-directed pursuits. Classical models posit persistent activity in prefrontal cortex (PFC) as a primary neural correlate, but emerging views suggest additional mechanisms may exist. We screened ∼200 genetically diverse mice on a working memory task and identified a genetic locus on chromosome 5 that contributes to a substantial proportion (17%) of the phenotypic variance. Within the locus, we identified a gene encoding an orphan G-protein-coupled receptor, Gpr12, which is sufficient to drive substantial and bidirectional changes in working memory. Molecular, cellular, and imaging studies revealed that Gpr12 enables high thalamus-PFC synchrony to support memory maintenance and choice accuracy. These findings identify an orphan receptor as a potent modifier of short-term memory and supplement classical PFC-based models with an emerging thalamus-centric framework for the mechanistic understanding of working memory.

Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.

BACKGROUND: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate. METHODS: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice. RESULTS: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts. CONCLUSIONS: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

Semiquantitative evaluation of 68Ga-DOTANOC uptake in the normal myocardium: establishment of reference values.

BACKGROUND: To ascertain presence of physiological uptake and derive standardized uptake values (SUV) of 68Ga-DOTANOC in normal myocardium and establish reference values. METHODS AND RESULTS: Dedicated cardiac 68Ga-DOTANOC PET/CT studies of patients referred for evaluation of cardiac sarcoidosis (CS) or myocarditis and found to be normal on visual assessment and on cardiac MRI were analyzed semiquantitatively. The studies were acquired 45-60 minutes after intravenous injection of 111-185 MBq of 68Ga-DOTANOC. Myocardial SUVmax normalized to lean body mass (SUVmax_lbm) values for septum, anterior wall, proximal lateral wall, distal lateral wall, inferior wall, and apical region were 1.12 ± .39, 1.09 ± .42, 1.26 ± .49, 1.16 ± .40, 1.23 ± .39, and 1.05 ± .40, respectively. Myocardial SUVmax_lbm-to-blood pool SUVmean_lbm ratios were calculated for each region and 95th percentile values of these ratios were considered the upper limit of normal. 95th percentile values of myocardial SUVmax_lbm-to-blood pool SUVmean_lbm ratio for the corresponding regions were 1.70, 1.70, 2.00 1.95, 2.05, and 1.70, respectively. CONCLUSION: There can be physiological uptake of 68Ga-DOTANOC in normal myocardium and the reference values of semiquantitative parameters established in this study may be employed as a corroborative tool for visual assessment in patients undergoing 68Ga-DOTANOC PET/CT for suspected CS or myocarditis.

From NWChem to NWChemEx: Evolving with the Computational Chemistry Landscape.

Since the advent of the first computers, chemists have been at the forefront of using computers to understand and solve complex chemical problems. As the hardware and software have evolved, so have the theoretical and computational chemistry methods and algorithms. Parallel computers clearly changed the common computing paradigm in the late 1970s and 80s, and the field has again seen a paradigm shift with the advent of graphical processing units. This review explores the challenges and some of the solutions in transforming software from the terascale to the petascale and now to the upcoming exascale computers. While discussing the field in general, NWChem and its redesign, NWChemEx, will be highlighted as one of the early codesign projects to take advantage of massively parallel computers and emerging software standards to enable large scientific challenges to be tackled.

Lower Permian Gondwana sequence of Rajhara (Daltonganj Coalfield), Damodar Basin, India: floristic and geochemical records and their implications on marine ingressions and depositional environment.

Early Permian floral diversity and palaeodepositional environment of the Lower Permian Rajhara sequence of Damodar Basin have been studied based on mega-, microfossil and geochemical proxies. Even though Gondwana sediments are generally considered as fluvio-lacustrine deposits, recent studies indicate marine inundations with patchy records. Here in the present study, an attempt has been made to address the changeover from fluviatile to shallow marine conditions and also to address the palaeodepositional aspects. Luxuriant vegetation during deposition of the Lower Barakar Formation generated thick coal seams. The macroplant fossil assemblage shows Glossopteridales, Cordaitales and Equisetales comprising one palynoassemblage with the dominance of bisaccate pollen grains having glossopterid affinities. However, Lycopsids are absent in the megafloral record and are represented in megaspore assemblage. The present floral assemblage led to envisage the presence of dense forest with swampy conditions and prevalence of warm and humid climate during the deposition of Barakar sediments. Correlation with the coeval Indian assemblages and those from other Gondwanan continents also supports an Artinskian age and reveals a stronger affinity with flora of Africa than that of South America. Biomarker analysis reveals low pristane/phytane values (0.30-0.84), noticeable absence of hopanoid triterpenoids and long-chain n-alkanes that is attributed to the obliteration of organic compounds and subsequent alteration of composition due to thermal effect. The high chemical index of alteration, A-CN-K plot and PIA also suggest severe denudation under a warm/humid climate. The V/Al2O3 and P2O5/Al2O3 indicated freshwater-near-shore conditions. However, signature of possible marine influence is identified from Th/U and Sr/Ba ratios resulted from the eustatic fluctuations during Permian.

Kalman filter based short term prediction model for COVID-19 spread.

Corona Virus Disease 2019 (COVID19) has emerged as a global medical emergency in the contemporary time. The spread scenario of this pandemic has shown many variations. Keeping all this in mind, this article is written after various studies and analysis on the latest data on COVID19 spread, which also includes the demographic and environmental factors. After gathering data from various resources, all data is integrated and passed into different Machine Learning Models in order to check its appropriateness. Ensemble Learning Technique, Random Forest, gives a good evaluation score on the tested data. Through this technique, various important factors are recognized and their contribution to the spread is analyzed. Also, linear relationships between various features are plotted through the heat map of Pearson Correlation matrix. Finally, Kalman Filter is used to estimate future spread of SARS-Cov-2, which shows good results on the tested data. The inferences from the Random Forest feature importance and Pearson Correlation gives many similarities and few dissimilarities, and these techniques successfully identify the different contributing factors. The Kalman Filter gives a satisfying result for short term estimation, but not so good performance for long term forecasting. Overall, the analysis, plots, inferences and forecast are satisfying and can help a lot in fighting the spread of the virus.

Study of diffusionless and diffusional transformations using in situ cooling and heating techniques in a scanning electron microscope.

In situ electron microscopy can be an effective tool to investigate the underlying science of many transformation mechanisms in materials science. Useful utilization of these experimentations will provide greater insight into many of the existing theories, as microstructural changes can be visualized in real time under some applied constraints. In this study, we have investigated two basic phase transformation phenomena: diffusionless and diffusional mechanisms with the help of in situ cooling and heating techniques in scanning electron microscope (SEM). In situ cooling experiments have been carried out on secondary hardening ultra-high-strength steels to understand the diffusionless transformation of austenite to martensite. Nucleation and growth of the martensites have been observed with cooling in different steps to -194°C. Details of the formation of different variants of martensites in steel were studied with the help of orientation imaging microscopy. Diffusional transformations were studied in terms of oxidation of pure copper in SEM using in situ heating technique. Different heating cycles were adopted for different samples by in situ heating to a maximum temperature of 950°C for the oxidation study. Nucleation of copper oxides and subsequent growth of the copper oxides at different temperatures were studied systematically. Raman spectroscopy and orientation imaging were done to confirm the formation of oxides and their orientations. The thermal cycling phenomenon was replicated inside SEM with heating and cooling and it has been demonstrated how the nature of copper and its oxides changes with the thermal cycle. This article is part of a discussion meeting issue 'Dynamic in situ microscopy relating structure and function'.

Transadaptation and Standardization of Tinnitus Primary Function Questionnaire in Hindi.

The term tinnitus is derived from the Latin word tinnire, meaning to ring. Although it is often referred to as "ringing in the ears, tinnitus can be perceived as many different sounds including hissing, clicking or whistling. India being a multilingual country needs to develop and standardize tinnitus questionnaire in Indian language. There are no significant test materials available with respect to Indian context based on Hindi, which can be routinely used by the professionals to assess the primary effect of tinnitus in patients. Thus, a need was felt to develop instrument in Hindi that can be used as per the ICF (International Classification of Functioning, Disability and Health) classification system in all over the country. The study aims to evaluate the impact of tinnitus on quality of life of clients having tinnitus with and without hearing loss by using primary function questionnaire (TPF-Hindi). The present study attempts to transadapt and standardize Tinnitus Primary function Questionnaire in Hindi. And administer both the questionnaires (TPFQ-H vs THQ-H) on the tinnitus clients with and without hearing loss and compare the impact of tinnitus in terms of quality of life in subjects with tinnitus with hearing loss and without hearing loss. A 12-item questionnaire was administered to 50 patients (tinnitus with hearing loss and without hearing loss) and compared between two questionnaires Tinnitus Primary Function Questionnaire and Tinnitus Handicapped Questionnaire (TPFQ-H & THQ-H). The results of the current study were analysed by using Statistical Package for the Social Sciences (SPSSv 20.0). Scores were positively correlated with the Tinnitus Handicap Questionnaire. There is significant correlation between both the scales and reliability between the scales is also good.

Saturation Dynamics Measures Absolute Cross Section and Generates Contrast within a Neuron.

The intensity required to optically saturate a chromophore is a molecular property that is determined by its absorption cross section (σ) and the excited state lifetime. We present an analytical description of such a system and show that fluorescence around the onset of saturation is characterized by product of absorption cross section and lifetime. Using this approach we formulate a generalized method for measuring the multiphoton cross section of fluorophores and use it to obtain the absolute three-photon cross-section spectra of tryptophan. We find that the tryptophan three-photon cross section ranges from 0.28 S.I. units (m(6)s(2)photon(-2)) at 870 nm to 20 S.I. units at 740 nm. Further, we show that the product of molecular rate of excitation and de-excitation, denoted as ß, serves as a vital contrasting agent for imaging local environment. Our contrast parameter, ß, is related to fraction of the population present in the excited state and is independent of the fluorophore concentration. We show that ß-imaging can be carried out in a regular two-photon microscope setup through a series of intensity scans. Using enhanced green fluorescent protein (EGFP) fluorescence from the brain slices of Thy-1 EGFP transgenic mice, we show that there is an inherent, concentration independent, variation in contrast across the soma and the dendrite.

Epidemiological Profile of Tobacco Users at Tobacco Cessation Centre: An Indian Experience.

Objective. Tobacco consumption continues to rise in India with about 34.6% of adult population being tobacco users. This study was done to evaluate the epidemiological profile of the tobacco users presenting to a Tobacco Cessation Centre (TCC) in Delhi. Methods. This is a retrospective observational study of subjects seen over a period of 10 years (2001-2010) at TCC of Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. Information from a structured questionnaire filled by all tobacco users was pooled and analysed. Results. Of a total of 4493 subjects seen in the TCC, 4370 (97.3%) were males. 2704 (60.2%) subjects were smokers and remaining were users of smokeless tobacco. The highest number of subjects attending the clinic was between the age of 31 to 40 years. The mean age of starting tobacco use was 21 years. 2518 subjects started tobacco use due to "peer group pressure", while family history of tobacco use was observed in 2912 subjects. 3065 number of subjects attending the clinic were without any co-morbidity. Conclusions. Most of the subjects started tobacco use at a young age between 11 to 20 years. Peer pressure was the most common reason for initiation (56%). Most of the subjects (68.2%) had no co-morbidity. The present study observed that tobacco users probably want to quit smoking not only because of the consequences of co-morbidities but also because of the realisation of later harmful effects of continuing smoking.

Vaccine for Targeted Therapy of Lung Cancer: Advances and Developments.

Considering that lung cancer is a leading global perpetrator, novel treatment approaches must be investigated. Due to the broad spectrum of lung cancer, conventional therapies including chemotherapy, radiotherapy, and surgeries, are not always effective and can have adverse consequences. The present study's overarching objective was to enhance the development of a personalized vaccine for targeted lung cancer therapy. Vaccination functions by eliciting a strong and targeted immune response defense by taking advantage of the specific antigens that are expressed by lung cancer cells. Crucial antigens associated with tumor cells have been identified with the recognition of the genetic and immunological circumstances of lung cancer in this review. The vaccine includes these antigens to prime the immune system, directing it toward recognizing and attacking cancerous cells. In this review, we have addressed the possible benefits of a targeted vaccine strategy, which include a reduction in off-target effects and an improvement in health outcomes for patients. These studies highlight the promise of a tailored vaccine in a novel way for the treatment of lung cancer. The integration of molecular profiling and immunological insights offers a rationale for the design and implementation of personalized vaccines. While challenges exist, the promise of improved treatment outcomes and reduced side effects positions targeted vaccine therapy as a compelling avenue for advancing lung cancer treatment.

Incidental Detection of Lipomatous Hypertrophy of the Interventricular Septum on FDG PET/CT.

ABSTRACT: Cardiac lipomatous hypertrophy is a rare benign condition almost exclusively involving the interatrial septum. Interventricular septum involvement is seldom noted, with only a few documented case reports demonstrating the finding on various modalities such as ECHO, CT, and MRI. FDG PET can be a surrogate marker for lipomatous hypertrophy of the interventricular septum. Here, we describe a case of incidentally detected lipomatous hypertrophy of the interventricular septum on FDG PET/CT in a patient with squamous cell carcinoma of the oropharynx.

Role of 18F-FDG PET/CT for providing a targeted approach for etiology of PUO.

AIM: This study aimed to evaluate the potential role of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in providing a targeted approach for diagnosing the etiology of Pyrexia of Unknown Origin (PUO). METHODS: A total of 573 PUO patients were included in this ambispective study, with a mean age of 39.40 ±â€…4.6 years. Patients underwent FDG PET/CT scans using dedicated hybrid scanners. PET/CT data were interpreted by experienced nuclear medicine physicians. The study analyzed the guidance provided by FDG PET/CT for appropriate biopsy sites and assessed concordance between PET/CT findings and histopathological examination. RESULTS: Out of the 573 patients, a final diagnosis was reached for 219 patients, including malignancy, infectious causes, noninfectious inflammatory causes (NIID), and precancerous conditions. FDG PET/CT played a crucial role in guiding clinicians to appropriate biopsy sites, contributing to a higher diagnostic yield. Concordance between PET/CT findings and histopathological examination emphasized the noninvasive diagnostic potential of PET/CT in identifying underlying causes of PUO. Overall, FDG PET/CT contributed to guiding the appropriate site of biopsy or concordance of the first differential diagnosis with the final diagnosis in 50.05% of cases. CONCLUSION: This study highlights the valuable role of FDG PET/CT in providing a targeted approach for diagnosing PUO, showcasing its potential in guiding clinicians towards appropriate biopsy sites and improving the diagnostic yield. The findings underscore the importance of integrating FDG PET/CT into the diagnostic pathway for PUO, ultimately enhancing patient management and outcomes. Further prospective studies are necessary to validate these results and refine the integration of FDG PET/CT in the diagnosis of PUO.

FDG PET/CT in the Diagnosis and After Sunitinib Follow-up of Synchronous Base of Tongue and Thyroid Metastases From Renal Cell Carcinoma.

ABSTRACT: Renal cell carcinoma (RCC) is a leading cause of mortality among genitourinary malignancies with limited therapeutic options. The hematogenous route, lymphatic spread, and direct invasion have been documented in RCC. Usually, metastases are regional lymph nodes, lungs, bone, liver, adrenal glands, contralateral kidney, and brain. Metastases to the rare sites such as skin, breast, head and neck were documented in the literature. In the present case, we describe the synchronous metastases to the base of the tongue and thyroid gland in RCC and the response to sunitinib therapy on 18F-FDG PET/CT.

Strongly correlated multielectron bunches from interaction with quantum light.

Strongly correlated electron systems are a cornerstone of modern physics, being responsible for groundbreaking phenomena from superconducting magnets to quantum computing. In most cases, correlations in electrons arise exclusively because of Coulomb interactions. In this work, we reveal that free electrons interacting simultaneously with a light field can become highly correlated via mechanisms beyond Coulomb interactions. In the case of two electrons, the resulting Pearson correlation coefficient for the joint probability distribution of the output electron energies is enhanced by more than 13 orders of magnitude compared to that of electrons interacting with the light field in succession (one after another). These highly correlated electrons are the result of momentum and energy exchange between the participating electrons via the external quantum light field. Our findings pave the way to the creation and control of highly correlated free electrons for applications including quantum information and ultrafast imaging.

Free-electron crystals for enhanced X-ray radiation.

Bremsstrahlung-the spontaneous emission of broadband radiation from free electrons that are deflected by atomic nuclei-contributes to the majority of X-rays emitted from X-ray tubes and used in applications ranging from medical imaging to semiconductor chip inspection. Here, we show that the bremsstrahlung intensity can be enhanced significantly-by more than three orders of magnitude-through shaping the electron wavefunction to periodically overlap with atoms in crystalline materials. Furthermore, we show how to shape the bremsstrahlung X-ray emission pattern into arbitrary angular emission profiles for purposes such as unidirectionality and multi-directionality. Importantly, we find that these enhancements and shaped emission profiles cannot be attributed solely to the spatial overlap between the electron probability distribution and the atomic centers, as predicted by the paraxial and non-recoil theory for free electron light emission. Our work highlights an unprecedented regime of free electron light emission where electron waveshaping provides multi-dimensional control over practical radiation processes like bremsstrahlung. Our results pave the way towards greater versatility in table-top X-ray sources and improved fundamental understanding of quantum electron-light interactions.

Symmetrical peripheral gangrene and Roth spots in a patient with infective endocarditis.

We present a case of a young man with symmetrical peripheral gangrene (SPG) resulting from Streptococcus viridans-related infective endocarditis, an association which has not previously been reported. SPG is associated with up to 40% mortality and may necessitate amputation; early identification and treatment of the precipitating factors is very important.

Quantum Interference between Fundamentally Different Processes Is Enabled by Shaped Input Wavefunctions.

This work presents a general framework for quantum interference between processes that can involve different fundamental particles or quasi-particles. This framework shows that shaping input wavefunctions is a versatile and powerful tool for producing and controlling quantum interference between distinguishable pathways, beyond previously explored quantum interference between indistinguishable pathways. Two examples of quantum interference enabled by shaping in interactions between free electrons, bound electrons, and photons are presented: i) the vanishing of the zero-loss peak by destructive quantum interference when a shaped electron wavepacket couples to light, under conditions where the electron's zero-loss peak otherwise dominates; ii) quantum interference between free electron and atomic (bound electron) spontaneous emission processes, which can be significant even when the free electron and atom are far apart, breaking the common notion that a free electron and an atom must be close by to significantly affect each other's processes. Conclusions show that emerging quantum wave-shaping techniques unlock the door to greater versatility in light-matter interactions and other quantum processes in general.