bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Lung Structure and Regional Function Using 0.55 T MRI in Patients With Lymphangioleiomyomatosis
Authors: Bhattacharya Ipshita , Ramasawmy Rajiv , Javed Ahsan , Lowery Margaret , Henry Jennifer , Mancini Christine , Machado Tania , Jones Amanda , Julien-Williams Patricia , Lederman Robert J. , Balaban Robert S. , Chen Marcus Y. , Moss Joel , Campbell-Washburn Adrienne E. 
Published: October 2021

Objectives
Contemporary lower-field magnetic resonance imaging (MRI) may offer advantages for lung imaging by virtue of the improved field homogeneity. The aim of this study was to evaluate the utility of lower-field MRI for combined morphologic imaging and regional lung function assessment. We evaluate low-field MRI in patients with lymphangioleiomyomatosis (LAM), a rare lung disease associated with parenchymal cysts and respiratory failure.

Materials and Methods
We performed lung imaging on a prototype low-field (0.55 T) MRI system in 65 patients with LAM. T2-weighted imaging was used for assessment of lung morphology and to derive cyst scores, the percent of lung parenchyma occupied by cysts. Regional lung function was assessed using oxygen-enhanced MRI with breath-held ultrashort echo time imaging and inhaled 100% oxygen as a T1-shortening MR contrast agent. Measurements of percent signal enhancement from oxygen inhalation and percentage of lung with low oxygen enhancement, indicating functional deficits, were correlated with global pulmonary function test measurements taken within 2 days.

Results
We were able to image cystic abnormalities using T2-weighted MRI in this patient population and calculate cyst score with strong correlation to computed tomography measurements (R = 0.86, P < 0.0001). Oxygen-enhancement maps demonstrated regional deficits in lung function of patients with LAM. Heterogeneity of oxygen enhancement between cysts was observed within individual patients. The percent low-enhancement regions showed modest, but significant, correlation with FEV1 (R = −0.37, P = 0.007), FEV1/FVC (R = −0.33, P = 0.02), and cyst score (R = 0.40, P = 0.02). The measured arterial blood ΔT1 between normoxia and hyperoxia, used as a surrogate for dissolved oxygen in blood, correlated with DLCO (R = −0.28, P = 0.03).

Conclusions
Using high-performance 0.55 T MRI, we were able to perform simultaneous imaging of pulmonary structure and regional function in patients with LAM.
An Unusual Case of Bilateral Ureteric Metastasis on PSMA PET-CT Scan in Carcinoma Prostate
Authors: Dang Shreya , Pereira Melvika , Singh Natasha , Shivdasani Divya , Roy Debdip , Kesariya Jugal , Rungta Rachita 
Published: October 2021

Abstract
The most common locations for metastasis in adenocarcinoma of the prostate gland are lymph nodes, bone, lung, and liver. The involvement of the ureter as a site of metastasis in prostate carcinoma is quite rare in literature. Here we present a case involving bilateral ureters along with bilateral vesicoureteric junctions in a known case of prostate adenocarcinoma.
Excellent Response to Adapted Low-Dose 177Lu-PSMA-617 PSMA Therapy in Renal Compromise Patient
Authors: Usmani Sharjeel , Al Kandari Fareeda , Alrekhais Ibrahim , N. Khalaf Shatha , Ahmed Najeeb 
Published: October 2021

Abstract
Prostate-specific membrane antigen (PSMA)–targeted radioligand therapy with 177Lu-PSMA-617 has shown promising results in patients with metastasized castration-resistant prostate cancer. We report a case of a 74-year-old man with metastatic prostate cancer with comorbidities of diabetes mellitus, hypertension, and chronic kidney disease. In order to minimize radiation burden to kidneys, a lower dose of 4 GBq of 177Lu-PSMA-617 was prescribed instead of the usual 6 to 7 GBq. There was significant decrease in prostate-specific antigen levels and symptoms. Renal profile remained stable. This case highlights that compromised renal function is not a definite contraindication to radionuclide therapy, and doses can be modified based on risk versus benefits.
Epithelial-to-mesenchymal transition lowers the cholesterol pathway, which influences colon tumors differentiation
Authors: Aulas Anaïs , Liberatoscioli Maria Lucia , Finetti Pascal , Cabaud Olivier , Birnbaum David J. , Birnbaum Daniel , Bertucci François , Mamessier Emilie 
Published: October 2021

ABSTRACTColorectal cancer (CRC) is the second cause of death worldwide. Up to 70% of CRC patients will metastasize. Identify new biomarkers of progression to prevent/delay disease evolution is urgent. Epithelial-to-mesenchymal transition (EMT) is a major program engaged during metastasis. We aim at identifying a combination of new genes that further identify signs of EMT in cancer tissues. We treated HT-29 cells grown in 3D with an EMT Inducing cocktail, and collect them before during and after treatment. For each condition, pan-transcriptomic analyses were done. Genes that were both induced upon EMT induction and inhibited upon EMT release (mesenchymal-to-epithelial transition or MET) were selected. We identified new genes for EMT-MET programs. These genes were used to build a metagene that, when applied to a database of transcriptomic data from primary colorectal tumors (n= 2,239), had an independent prognosis value. Finally, we submitted this metagene to CMap and identified drugs that might affect EMT-MET programs. Statins, well-known inhibitors of cholesterol synthesis, were among them and effectively delayed MET. These data show that cholesterol and EMT pathways are opposite regulators and impact differently tumor differentiation and outcome.TRANSLATIONAL RELEVANCEMetastases are the main cause of death of colorectal cancer (CRC) and the major issue in CRC management. Understanding the chain of events that lead to metastasis occurrence is urgent to identify new biomarkers of progression and/or new potential targets. Epithelial to mesenchymal transition (EMT) is a major player in cancer dissemination that remains non-targetable due to its broad involvement in tissue homeostasis. Here, we used a relevant in vitro dynamic model to identify the pathways triggered during EMT in CRC and how this might improve tumors classification, prognosis and open therapeutic avenue for this deadly disease. The cholesterol pathway surprisingly popped-out from this model and turned out to be a good prognosis factor of disease-free survival for CRC. Altogether, our results showed that an active EMT program lowers the cholesterol pathway, which further influence the differentiation of colon tumor toward the most aggressive subtypes.
Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease
Authors: Wellens Judith , Edmans Matthew , Obolski Uri , McGregor Colleen GC , Simmonds Peter , Turner Marc , Jarvis Lisa , Skelley Donal , Dunachie Susanna , Barnes Eleanor , Eyre David W , Colombel Jean-Frederic , Wong Serre-Yu , Klenerman Paul , Lindsey James O , Satsangi Jack , Thompson Craig P 
Published: October 2021

AbstractThere is substantial interest regarding the perceived risk that immunomodulator and biologic therapy could have on COVID-19 disease severity among patients with inflammatory bowel disease (IBD) and clinicians. In this study, we show that infliximab/thiopurine combination therapy is associated with significantly lower IgA, a range of lower IgG responses as well as impaired neutralising antibody responses, compared to responses observed in healthy individuals. We also demonstrate that whilst IgG responses were significantly reduced in individuals with IBD treated with infliximab or vedolizumab monotherapy compared to healthy controls, there was no significant reduction in IgA and neutralising antibody responses. As neutralising antibody responses correlate with protection, this observation may provide the mechanistic explanation for the observation reported by the SECURE-IBD study that individuals on infliximab/thiopurine combination therapy were at greater risk of severe COVID-19 outcomes than patients on monotherapy.
Can individualized targets for transcranial magnetic stimulation increase treatment effectiveness in psychiatric disorders? A systematic review and meta-analysis
Authors: Zheng Yanbin , Zhang Zhaojie , Yang Bo , Zhou Weiran , Che Xianwei , Dong Guang-Heng 
Published: October 2021

ABSTRACTBackgroundTranscranial magnetic stimulation (TMS) techniques have developed in recent years in research and clinical treatment. The identification of targets for TMS treatment is increasingly individualized based on morphology or function; however, whether individualized TMS targets could increase the treatment effectiveness of psychiatric disorders remains controversial.MethodsA meta-analysis was conducted to explore whether individualized TMS targets are better than standard targets. A total of 3340 studies were identified in a systematic search, and twelve were included in the quantitative review. Among them, eight used a structure-based individualized target selection method, nine were on depression, and four compared unilateral and bilateral stimulant targets.ResultsMeta-analyses showed that: (1) individualized TMS targets increased the effectiveness in treating psychiatric disorders; (2) structural-based TMS targets brought additional treatment effectiveness, and PET-based structural selection methods proved to be valid; (3) there was no significant increase in the treatment effects of individualized targets in EEG-based and task-fMRI-based methods; (4) updated stimulant sequences did not increase the individualized target treatment effect; (5) individualized TMS targets showed increased treatment effectiveness in depression but not in schizophrenia; and (6) bilateral stimuli did not show additional effectiveness compared with unilateral stimuli.ConclusionsThe current findings revealed that individualized TMS targets show additional treatment effectiveness compared to standard targets in treating psychiatric disorders, and structure-based selection methods are effective in identifying TMS targets. The current conclusions provide directions for future TMS research and provide valuable references for clinicians treating psychiatric disorders.
SEIRDQ: A COVID-19 case projection modeling framework using ANN to model quarantine
Authors: Chandra Harish , Margaryan Arman , Meng Xianwei 
Published: October 2021

AbstractWe propose and implement a novel approach to model the evolution of COVID-19 pandemic and predict the daily COVID-19 cases (infected, recovered and dead). Our model builds on the classical SEIR-based framework by adding additional compartments to capture recovered, dead and quarantined cases. Quarantine impacts are modeled using an Artificial Neural Network (ANN), leveraging alternative data sources such as the Google mobility reports. Since our model captures the impact of lockdown policies through the quarantine functions we designed, it is able to model and predict future waves of COVID-19 cases. We also benchmark out-of-sample predictions from our model versus those from other popular COVID-19 case projection models.
Molecular and functional characterization of the mouse intracardiac nervous system
Authors: Lizot Guénaëlle , Pasqualin Côme , Tissot Audrey , Pagès Stephane , Faivre Jean-François , Chatelier Aurélien 
Published: October 2021

AbstractBackgroundThe intracardiac nervous system (ICNS) refers to clusters of neurons, located within the heart, which participate to the neuronal regulation of cardiac functions and which are involved in the initiation of cardiac arrhythmias. Therefore, deciphering its role in cardiac physiology and physiopathology is mandatory.ObjectiveThe aim of this study is to provide a phenotypic, electrophysiological and pharmacological characterization of the mouse ICNS, which is still poorly characterized.MethodsGlobal cardiac innervation and phenotypic diversity were investigated using immunohistochemistry on cleared murine heart and on tissue sections. Patch clamp technique was used for electrophysiological and pharmacological characterization of isolated mouse intracardiac neurons.ResultsWe have identified the expression of seven distinct neuronal markers within mouse ICNS, thus proving the neurochemical diversity of this network. Of note, it was the first time that the existence of neurons expressing the calcium binding protein calbindin, the neuropeptide Y (NPY) and the cocain and amphetamine regulated transcript (CART) peptide, was described in the mouse. Electrophysiological studies also revealed the existence of four different neuronal populations based on their electrical behavior. Finally, we showed that these neurons can be modulated by several neuromodulators.ConclusionThis study showed that mouse ICNS presents a molecular and functional complexity similar to other species, and is therefore a suitable model to decipher the role of individual neuronal subtypes regarding the modulation of cardiac function and the initiation of cardiac arrhythmias.
Adaptive coding of pain prediction error in the anterior insula
Authors: Hoskin R , Talmi D 
Published: October 2021

AbstractBackgroundUnderstanding the mechanisms behind the influence of expectation and context on pain perception is crucial for improving analgesic treatments. Prediction error (PE) signals how much a noxious stimulus deviates from expectation and is therefore crucial for our understanding of pain perception. It is thought that the brain engages in ‘adaptive coding’ of pain PE, such that sensitivity to unexpected outcomes is modulated by contextual information. While there is behavioural evidence that pain is coded adaptively, and evidence that reward PE signals are coded adaptively, controversy remains regarding the underlying neural mechanism of adaptively-coded pain PEs.MethodsA cued-pain task was performed by 19 healthy adults while undergoing FMRI scanning. BOLD responses to the task were tested using an axiomatic approach to identify areas that may code pain PE adaptively.ResultsThe left dorsal anterior insula demonstrated a pattern of response consistent with adaptively-coded pain PE. Signals from this area were sensitive to both predicted pain magnitudes on the instigation of expectation, and the unexpectedness of pain delivery. Crucially however, the response at pain delivery was consistent with the local context of the pain stimulation, rather than the absolute magnitude of delivered pain, a pattern suggestive of an adaptively-coded PE signal.ConclusionsThe study advances our understanding of the neural basis of pain prediction. Alongside existing evidence that the periaqueductal grey codes pain PE and the posterior insula codes pain magnitude, the results highlight a distinct contribution of the left dorsal anterior insula in the processing of pain.Significance statementAlthough there is behavioural evidence that pain is coded adaptively, the neural mechanisms serving this process are not well understood. This study used functional MRI to provide the first evidence that the left dorsal anterior insula, an area associated with aversive learning, responds to pain in a manner consistent with the adaptive coding of pain prediction error. This study aids our understanding of the neural basis of subjective pain representation, and thus can contribute to the advancement of analgesic treatments.
Genome scale modeling of the protein secretory pathway reveals novel targets for improved recombinant protein production in yeast
Authors: Li Feiran , Chen Yu , Qi Qi , Wang Yanyan , Yuan Le , Huang Mingtao , Elsemman Ibrahim E. , Feizi Amir , Kerkhoven Eduard J , Nielsen Jens 
Published: October 2021

AbstractEukaryal cells are used for the production of many recombinant pharmaceutical proteins, including several of the current top-selling products. The protein secretory pathway in eukaryal cells is complex and involves many different processes such as post-translational modifications, translocation, and folding. Furthermore, recombinant protein production competes with native secretory proteins for the limited energy and proteome resources allocated to the protein secretory pathway. Due to the complexity of this pathway, improvement through metabolic engineering has traditionally been relatively ad-hoc; and considering the industrial importance of this pathway, there is a need for more systematic approaches for novel design principles. Here, we present the first proteome-constrained genome-scale protein secretory model of a eukaryal cell, namely for the yeastSaccharomyces cerevisiae(pcSecYeast). The model contains all key processes of this pathway, i.e., protein translation, modification, and degradation coupled with metabolism. The model can capture delicate phenotypic changes such as the switch in the use of specific glucose transporters in response to changing extracellular glucose concentration. Furthermore, the model can also simulate the effects of protein misfolding on cellular growth, suggesting that retro-translocation of misfolded proteins contributes to protein retention in the Endoplasmic reticulum (ER). We used pcSecYeast to simulate various recombinant proteins production and identified overexpression targets for different recombinant proteins overproduction. We experimentally validated many of the predicted targets for α-amylase production in this study, and the results show that the secretory pathways have more limited capacity than metabolism in terms of protein secretion.
Cellular perception of growth rate and the mechanistic origin of bacterial growth law
Authors: Wu Chenhao , Balakrishnan Rohan , Braniff Nathan , Mori Matteo , Manzanarez Gabriel , Zhang Zhongge , Hwa Terence 
Published: October 2021

ABSTRACTBacteria organize many activities according to their grow rate via the ppGpp signaling system. Yet it is not clear how this signaling system “knows” how fast cells grow. Through quantitative experiments, we show that ppGpp responds inversely to the rate of translational elongation inE. coli. Together with its roles in inhibiting ribosome biogenesis and activity, ppGpp closes a key regulatory circuit that enables the cell to perceive and control the rate of its growth across conditions. The celebrated linear growth law relating the ribosome content and growth rate emerges as a consequence of keeping a supply of ribosome reserves while maintaining elongation rate in slow growth conditions. Further analysis suggests the elongation rate itself is detected by sensing the ratio of dwelling and translocating ribosomes, a strategy employed to collapse the complex, high-dimensional dynamics of the molecular processes underlying cell growth to perceive the physiological state of the whole.
PySOFI: an open source Python package for SOFI
Authors: Miao Yuting , Weiss Shimon , Yi Xiyu 
Published: October 2021

ABSTRACTSuper-resolution optical fluctuation imaging (SOFI) is a highly democratizable technique that provides optical super-resolution (SR) without requirement of sophisticated imaging instruments. An open source package for SOFI algorithm is needed to support not only the utilization of SOFI, but also the community adoption and participation for further development of SOFI. In this work, we developed PySOFI, an open source python package for SOFI analysis that offers the flexibility to inspect, test, modify, improve and extend the algorithm. We provide a complete documentation for the package and a collection of Jupyter Notebooks to demonstrate the usage of the package. We discuss the architecture of PySOFI, illustrate how to use each functional module, and demonstrate how to extend the PySOFI package with additional modules. We expect PySOFI to facilitate efficient adoption, testing, modification, dissemination and prototyping of new SOFI-relevant algorithms.
Prefrontal cortex supports speech perception in listeners with cochlear implants
Authors: Sherafati Arefeh , Dwyer Noel , Bajracharya Aahana , Hassanpour Mahlega S. , Eggebrecht Adam T. , Firszt Jill B. , Culver Joseph P. , Peelle Jonathan E. 
Published: October 2021

AbstractCochlear implants are neuroprosthetic devices that can restore hearing in people with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of acoustic detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging data in this population. In the current study, we assessed the brain regions supporting spoken word understanding in adult listeners with right unilateral cochlear implants (n=20) and matched controls (n=18) using high-density diffuse optical tomography (HD-DOT), a quiet and non-invasive imaging modality with spatial resolution comparable to that of functional MRI. We found that while listening to spoken words in quiet, listeners with cochlear implants showed greater activity in left prefrontal cortex than listeners with normal hearing, specifically in a region engaged in a separate spatial working memory task. These results suggest that listeners with cochlear implants require greater cognitive processing during speech understanding than listeners with normal hearing, supported by compensatory recruitment of left prefrontal cortex.
RNA Helix Thermodynamics: The End Game
Authors: Zuber Jeffrey , Schroeder Susan J. , Sun Hongying , Turner Douglas H. , Mathews David H. 
Published: October 2021

ABSTRACTNearest neighbor parameters for estimating the folding stability of RNA secondary structures are in widespread use. For helices, current parameters penalize terminal AU base pairs relative to terminal GC base pairs. We curated an expanded database of helix stabilities determined by optical melting experiments. Analysis of the updated database shows that terminal penalties depend on the sequence identity of the adjacent penultimate base pair. New nearest neighbor parameters that include this additional sequence dependence accurately predict the measured values of 271 helices in an updated database with a correlation coefficient of 0.982. This refined understanding of helix ends facilitates fitting terms for base pair stacks with GU pairs. Prior parameter sets treatedseparately from otherstacks. The improved understanding of helix end stability, however, makes the separate treatment unnecessary. Introduction of the additional terms was tested with three optical melting experiments. The average absolute difference between measured and predicted free energy changes at 37° C for these three duplexes containing terminal adjacent AU and GU pairs improved from 1.38 to 0.27 kcal/mol. This confirms the need for the additional sequence dependence in the model.