bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient PCA denoising of spatially correlated MRI data
Authors: Henriques Rafael Neto , Ianuş Andrada , Novello Lisa , Jovicich Jorge , Jespersen Sune N , Shemesh Noam 
Published: March 2023

AbstractMarčenko-Pastur (MP) PCA denoising is emerging as an effective means for noise suppression in MRI acquisitions with redundant dimensions. However, MP-PCA performance is severely compromised by spatially correlated noise – an issue typically affecting most modern MRI acquisitions – almost to the point of returning the original images with little or no noise removal. In this study, we develop and apply two new strategies that enable efficient and robust denoising even in the presence of severe spatial correlations. This is achieved by measuring a-priori information about the noise variance and combing these estimates with PCA denoising thresholding concepts. The two denoising strategies developed here are: 1) General PCA (GPCA) denoising that uses a-priori noise variance estimates without assuming specific noise distributions; and 2) Threshold PCA (TPCA) denoising which removes noise components with a threshold computed from a-priori estimated noise variance to determine the upper bound of the MP distribution. These strategies were tested in simulations with known ground truth and applied for denoising diffusion MRI data acquired using pre-clinical (16.4T) and clinical (3T) MRI scanners. In synthetic phantoms, MP-PCA failed to denoise spatially correlated data, while GPCA and TPCA correctly classified all signal/noise components. In cases where the noise variance was not accurately estimated (as can be the case in many practical scenarios), TPCA still provides excellent denoising performance. Our experiments in pre-clinical diffusion data with highly corrupted by spatial correlated noise revealed that both GPCA and TPCA robustly denoised the data while MP-PCA denoising failed. Inin vivodiffusion MRI data acquired on a clinical scanner in healthy subjects, MP-PCA weakly removed noised, while TPCA was found to have the best performance, likely due to misestimations of the noise variance. Thus, our work shows that these novel denoising approaches can strongly benefit future pre-clinical and clinical MRI applications.
The Kinship Formula: inferring the numbers of all kin from any structured population projection model
Authors: Coste Christophe F. D. 
Published: March 2023

AbstractStructured population projection models are fundamental to many fields of science. They enable abundance forecasting for populations categorized by various traits such as age (for demography), patch (for spatial ecology), genotype (for genetics), infectious stage (for epidemiology) or capital (economics). The demography of a structured population, determined by the transition rates (e.g., survival, fertility) between its various states, also shapes its relatedness – or kinship – structure. This structure (a probabilistic genealogy) is crucial for understanding how individuals are related to the rest of the population and affects effective population size, inclusive fitness, inbreeding, pedigrees, relatedness, familial structures, etc. Despite its significance, the relationship between demography and kinship remains under-explored. By incorporating the generation number as a trait into the population structure, we derive the Kinship Formula, yielding the expected number of any kin for any structured population. This formula is simple to implement and fast to compute, even for complex models. Most importantly, it promises significant theoretical advances. From the Kinship Formula, one can, for instance, assess the impact of embedded processes (e.g., dispersal, inheritance, growth) on kinship, compute mean population relatedness and the eventual number of kin (including kin already dead or not born yet). The Kinship Formula derived here stems from a one-sex constant environment framework. Its simplicity should allow for extensions to include environmental and demographic stochasticity as well as two-sex models.Data accessibility statementNo new data are used. All data used to illustrate the method are public. The code related to the main text (R and Matlab) can be found in Supplementary Materials (S.M.VIII)
Dynamics of mixed-ploidy populations under demographic and environmental stochasticities
Authors: Gaynor Michelle L. , Kortessis Nicholas , Soltis Douglas E. , Soltis Pamela S. , Ponciano José Miguel 
Published: March 2023

AbstractThe theoretical population dynamics of autopolyploids – organisms with more than two genome copies of a single ancestral species – and their diploid progenitors have been extensively studied. The acquisition of multiple genome copies, being in essence a stochastic process, strongly suggests a probabilistic approach to examine the long-term dynamics of a population with multiple cytotypes. Yet, our current understanding of empirical evidence on the dynamics of autopolyploid populations has not incorporated stochastic population dynamics. To investigate the factors contributing to the probability and stability of coexisting cytotypes, we designed a new population dynamics model with demographic and environmental stochasticities to simulate the formation, establishment, and persistence of diploids, triploids, and autotetraploids over time when gene flow is allowed among cytotypes. Contrary to previous research, increased selfing rates and pronounced reproductive isolation stabilized the long-run coexistence of multiple cyto-types. In stressful environments, these dynamics become much more complex, and our stochastic modeling approach helped reveal the resulting intricacies that give tetraploids competitive advantage over their diploid progenitors. Our work is fundamental to a better understanding of the dynamics of coexistence of multiple cytotypes and is a necessary step for further work modeling the dynamics between an autopolyploid and its diploid progenitor.
High-Dimensional Spectral Cytometry Reveals Therapeutically Relevant Immune Subtypes in Gastric Cancer
Authors: Abate Miseker , Fei Teng , Lin Ya Hui , Shimada Shoji , Drebin Harrison , Chen Eunise , Tang Laura , Strong Vivian E , Vardhana Santosha A. 
Published: March 2023

SummaryIdentification of locally advanced gastric cancer (GC) patients who might potentially benefit from immune-based strategies is limited by both the poor predictive quality of existing biomarkers, including molecular subtypes, tumor mutational burden, and PD-L1 expression, as well as inadequate understanding of the gastric cancer immune microenvironment. Here, we leveraged high-dimensional spectral cytometry to re-classify locally advanced gastric tumors based on immune composition. The gastric cancer microenvironment was comprised of a diverse immune infiltrate including high proportions of plasmablasts, macrophages, and myeloid-derived suppressor cells. Computational cell typing and sample clustering based on tiered broad immune and T-cell focused phenotyping identified three distinct immune subtypes. The most immunogenic subtype exhibited high proportions of activated CD4+ T-cells and plasmablasts and included tumors that would have been classified as non-immunogenic based on prior classifications. Analysis of gastric cancer patients treated with immune checkpoint blockade indicates that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to higher immune scores from our analysis. This work establishes a novel immunological classification of gastric cancer including identification of patients and immune networks likely to benefit from immune-based therapies.
HDAC11 inhibition triggers bimodal thermogenic pathways to circumvent adipocyte catecholamine resistance
Authors: Robinson Emma L. , Bagchi Rushita A. , Major Jennifer L. , Bergman Bryan C. , Madsuda Jennifer L. , McKinsey Timothy A. 
Published: March 2023

AbstractStimulation of adipocyte β-adrenergic receptors (β-ARs) induces expression of uncoupling protein 1 (UCP1), promoting non-shivering thermogenesis. Association of β-ARs with a lysine myristoylated form of A-kinase anchoring protein 12 (AKAP12)/gravin-α is required for downstream signaling that culminates in UCP1 induction. Conversely, demyristoylation of gravin-α by histone deacetylase 11 (HDAC11) suppresses this pathway. Whether inhibition of HDAC11 in adipocytes is sufficient to drive UCP1 expression independently of β-ARs is not known. Here, we demonstrate that adipocyte-specific deletion of HDAC11 in mice leads to robust induction of UCP1 in adipose tissue (AT), resulting in increased body temperature. These effects are mimicked by treating micein vivoor human ATex vivowith an HDAC11-selective inhibitor, FT895. FT895 triggers biphasic, gravin-α myristoylation-dependent induction of UCP1 protein expression, with a non-canonical acute response that is post-transcriptional and independent of protein kinase A (PKA), and a delayed response requiring PKA activity and newUcp1mRNA synthesis. Remarkably, HDAC11 inhibition promotes UCP1 expression even in models of adipocyte catecholamine resistance where β-AR signaling is blocked. These findings define cell autonomous, multi-modal roles for HDAC11 as a suppressor of thermogenesis, and highlight the potential of inhibiting HDAC11 to therapeutically alter AT phenotype independently of β-AR stimulation.
Trends in serotype distribution and disease severity in adults hospitalised withStreptococcus pneumoniaeinfection in Bristol and Bath: a retrospective cohort study, 2006-2022
Authors: Hyams Catherine , Challen Robert , Hettle David , Amin-Chowdhury Zahin , Grimes Charli , Ruffino Gabriella , Conway Rauri , Heath Robyn , North Paul , Malin Adam , Maskell Nick A , Williams Philip , Martin Williams O. , Ladhani Shamez N , Danon Leon , Finn Adam 
Published: March 2023

ABSTRACTOngoing surveillance is essential to inform policy decisions and monitor serotype replacement following pneumococcal conjugate vaccination (PCV) deployment. We report serotype and disease severity trends in this retrospective cohort of hospitalised adults in Bristol-Bath, 2006-22. Of 1686 invasive pneumococcal disease (IPD) cases, 1501 (89.0%) had known serotype. We also identified 2033/3719 cases of non-IPD. IPD declined sharply during the early COVID-19 pandemic. Over 2022 it gradually returned to pre-pandemic levels. Disease severity also changed throughout this period: CURB65 severity and inpatient mortality decreased whilst ICU admissions increased. PCV7 and PCV13-serotype IPD decreased from 2006-09 to 2021-22. However, significant residual PCV13-serotype IPD remains, representing 21.7% [15.5-29.6] of 2021-22 cases, highlighting that significant adult PCV-serotype disease still occurs despite 17-years of paediatric PCV usage in the UK. We found increased proportions of serotype 3 and 8 IPD, whilst 19F and 19A re-emerged. In 2020-22, 68.2% IPD cases were potentially covered by PCV20.Article SummaryWe observed significant serotype shifts but perseverance and re-emergence of some serotypes covered by PCVs over this 17-year retrospective study, which found considerable adult pneumococcal disease attributable to PCV-serotypes despite high uptake of paediatric PCV.
Impact of intestinal dysbiosis on clinical course in severe acute pancreatitis: a multicenter prospective observational study
Authors: Oami Takehiko , Ishida Shigenobu , Oshima Taku , Yamamoto Akinobu , Nakada Taka-aki 
Published: March 2023

AbstractBackgroundDysbiosis, an imbalance of the intestinal microbiota in critically ill patients, reportedly contributes to poor outcomes. Controlling the disruption of intestinal homeostasis could be promising tactics for infectious complications in acute pancreatitis. To improve the mortality rate of severe acute pancreatitis with high frequency of infectious complications, it is warranted to elucidate the pathophysiology for development of new treatment strategies. We hypothesized that patients with severe acute pancreatitis would demonstrate gut dysbiosis, leading to an onset of infectious complications and poor outcomes.MethodsWe will conduct a prospective study to compare the sequential changes in intestinal microbiota using 16s RNA metagenomics and metabolomics between patients with severe acute pancreatitis and mild acute pancreatitis. We will enroll adult patients (18 years of age or older) diagnosed with acute pancreatitis and newly admitted to the hospitals for 48 hours or longer. We will exclude patients with inflammatory bowel disease, patients with diarrhea prior to admission, patients who have received antimicrobial agents for more than 1 week in the 2 months prior to admission. We will collect stool and blood samples on day 1 and 6. The primary outcome is changes in various parameters of the intestinal microbiota, protein concentration in stool, and metabolite concentration. The secondary outcomes include relationship between each parameter and short- and long-term prognosis, correlation of each parameter with treatment details and clinical course during ICU stay, and associations among the amount of diarrhea and alpha-diversity parameters, protein concentration in each stool, and metabolite concentration.
Sociodemographic disparities in the use of GLP-1 receptor agonists and SGLT-2 inhibitors among US adults with type 2 diabetes: NHANES 2005-March 2020
Authors: Mittman Benjamin G. , Le Phuc , Payne Julia Y. , Ayers Gina , Rothberg Michael B. 
Published: March 2023

AbstractAimType 2 Diabetes (T2D) is a major cause of morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are highly effective but underutilized. We assessed racial/ethnic and other sociodemographic disparities in GLP-1/SGLT-2 use among US adults with T2D.Materials and MethodsWe conducted a retrospective analysis using nationally representative data from National Health and Nutrition Examination Survey 2005-March 2020. Participants were adults with T2D taking ≥1 diabetes medication, excluding pregnant women and adults with probable T1D. We performed univariate analyses to examine characteristics of patients using GLP-1/SGLT-2 and multivariable logistic regression to assess disparities in GLP-1/SGLT-2 use after adjusting for other patient factors.ResultsAmong 4,585 T2D patients (representing >18 million US adults) taking ≥1 medication, GLP-1/SGLT-2 usage increased from 1.4% in 2005-2006 to 13.3% in 2017-2020. In univariate analyses, patients using GLP-1/SGLT-2 vs. other T2D drugs were more likely to be white than nonwhite (72% vs. 60%, p = .001), but in multivariable analysis there was no significant difference in GLP-1/SGLT-2 use for nonwhite vs. white patients (aOR = 0.84, 95% CI [0.61, 1.16]). GLP-1/SGLT-2 use was higher for patients who completed some college (aOR = 1.83, 95% CI [1.06, 3.15]) or above (aOR = 2.06, 95% CI [1.28, 3.32]) vs. high school or less, and for those with an income-poverty ratio ≥4 vs. <2 (aOR = 2.11, 95% CI [1.30, 3.42]).ConclusionsUse of GLP-1/SGLT-2 drugs increased over time but remained low in March 2020. Higher education and income, but not race/ethnicity, were associated with GLP-1/SGLT-2 use.
Cognitive Intervention Effects Vary as a Function of Plasma Neurofilament Light Chain Levels: A PICMOR Randomized Controlled Trial
Authors: Otake-Matsuura Mihoko , Sugimoto Hikaru , Sekiguchi Takuya , Abe Masato S. , Miura Kumi W. , Tokunaga Seiki , Akamine Shoshin , Kishimoto Taishiro , Kudo Takashi 
Published: March 2023

AbstractBackgroundThere is a difference in the neuronal state of individuals. However, this has not been taken into consideration in most intervention studies. Recent advances in analytical technologies in hematological examination enabled us to evaluate neuronal states in a relatively convenient manner.ObjectiveUsing these advanced technologies, we aimed to investigate whether cognitive intervention effects vary as a function of levels of blood-based biomarkers, such as neurofilament light chain (NfL), since plasma NfL could be a biomarker of neurodegenerative diseases including Alzheimer’s disease.MethodsIn this study, we employed a group conversation-based intervention methodology named Photo-Integrated Conversation Moderated by Robots (PICMOR), which has been shown to improve verbal fluency in older adults. To examine the possibility of varying effects of this intervention method according to the neuronal state of each individual, we conducted a randomized controlled trial (UMIN Clinical Trials Registry number: UMIN000036599) and investigated how longitudinal changes in cognitive performance, such as verbal fluency, vary with the NfL level measured at the baseline.ResultsAs the main result, positive intervention effects of PICMOR on verbal fluency were observed in individuals with lower level of NfL, which indicate a relatively intact neuronal state, whereas negative intervention effects were identified in individuals with higher NfL level.ConclusionOur findings suggest that cognitive intervention effects vary depending on level of Nfl in the plasma. Thus, future intervention studies should take into account the neuronal status of the participants to examine intervention effects.
Disparities in Mortality Associated with Acute Myocardial Infarction and COVID-19 in the United States: A Nationwide Analysis
Authors: Muhyieddeen Amer , Cheng Susan , Mamas Mamas A , Beasley Dorian , Weins Galen Cook , Gulati Martha 
Published: March 2023

AbstractBackgroundThe impact of the COVID-19 pandemic on potential racial disparities in acute myocardial infarction (AMI) management and outcomes is unclear. We examined AMI patient management and outcomes during the pandemic’s initial nine months, comparing COVID-19 and non-COVID-19 cases.MethodsWe identified all patients hospitalized for AMI in 2020 using the National Inpatient Sample (NIS), identifying those with or without concurrent COVID-19. Logistic and linear regression was used for analyses of associations, with adjustment for potential confounders.ResultsPatients with both AMI and COVID-19 had higher in-hospital mortality rates (aOR 3.19, 95% CI 2.63-3.88), mechanical ventilation (aOR 1.90, 95% CI 1.54-2.33), and hemodialysis (aOR 1.38, 95% CI 1.05-1.89) compared to those without COVID-19. Black and Asian/Pacific Islander patients had higher in-hospital mortality than White patients, (aOR 2.13, 95% CI 1.35-3.59) and (aOR 3.41, 95% CI 1.5-8.37). Moreover, Black, Hispanic, and Asian/Pacific Islander patients had higher odds of initiating hemodialysis, (aOR 5.48, 95% CI 2.13-14.1), (aOR 2.99, 95% CI 1.13-7.97), and (aOR 7.84, 95% CI 1.55-39.5) and were less likely to receive PCI for AMI, (aOR 0.71, 95% CI 0.67-0.74), (aOR 0.81, 95% CI 0.77-0.86), and (aOR 0.82, 95% CI 0.75-0.90). Additionally, Black patients had a lower likelihood of undergoing CABG surgery for AMI (aOR 0.55, 95% CI 0.49-0.61).ConclusionOur study revealed increased mortality and complications in COVID-19 patients with AMI, highlighting significant racial disparities. Urgent measures addressing healthcare disparities, such as enhancing access and promoting culturally sensitive care, are needed to improve health equity.
Delineating the functional role of thePPE50 (Rv3135) - PPE51 (Rv3136)gene cluster in the pathophysiology ofMycobacterium tuberculosis
Authors: Mukku Ravi Prasad , Poornima Kokavalla , Yadav Sangya , Raghunand Tirumalai R. 
Published: March 2023

ABSTRACTThe extraordinary success ofMycobacterium tuberculosis(M. tb) has been attributed to its ability to modulate host immune responses. The genome ofM. tbencodes multiple immunomodulatory factors, including several proteins of the multigenic PE_PPE family, which comprise about 10% of its coding potential. The presence of these proteins in pathogenic mycobacteria strongly suggests that they play a role in disease pathogenesis. To understand its role inM. tbphysiology we have begun to characterise thePPE50 (Rv3135)-PPE51 (Rv3136)gene cluster, one of ninePPE-PPEclusters in theM. tbgenome. We demonstrate that this cluster encodes a co-transcriptional unit and that PPE50 and PPE51 interact bothin vitroandin vivo, the first demonstration of PPE-PPE interaction. THP-1 macrophages infected with recombinantM. smegmatisstrains expressingPPE50andPPE51showed less intracellular viability than the control strain containing the vector alone, the decline in viable counts correlating with an increase in transcript levels of inducible nitric oxide synthase (iNOS2). Macrophages infected with the recombinant strains exhibited an upregulation in levels of the anti-inflammatory cytokineIL-10, indicating an immunomodulatory role for these proteins. Using pull-down assays, we discovered TLR1 to be the cognate receptor for PPE50, with signalling through the receptor being indicated by an increase in IRAK1 phosphorylation. All the phenotypes observed on infection of THP-1 macrophages including the decrease in CFUs, the increase iniNOS2andIL-10levels, as well as signalling through the receptor, were reversed on treatment of macrophages with an anti-TLR1 antibody prior to infection, validating the functional outcome of PPE50-TLR1 interaction. Our data points to a TLR1 dependent role for thePPE50-PPE51cluster in promoting bacillary persistence,viaCFU reduction and a concomitant upregulation of the anti-inflammatory response - a two-pronged strategy to circumvent host immune surveillance.
β-helical protein PerA orchestrates antibiotic uptake across theCaulobacterouter membrane via converging stress signaling systems
Authors: Costafrolaz Jordan , Panis Gaël , Vallet Simon-Ulysse , Gomariz Manuel Velasco , Degeorges Laurence , Fröhlich Kathrin S. , Viollier Patrick H. 
Published: March 2023

ABSTRACTWhile large membrane-impermeable antibiotics cannot traverse a lipid barrier, spacious importers such as TonB-dependent receptors (TBDRs) can mistakenly ferry antibiotics across the bacterial outer membrane (OM). We discovered that loss of PerA, an enigmatic β-helix protein in the OM of the oligotrophic α-proteobacteriumCaulobacter crescentus, reprograms the OM TBDR proteome from ChvT that imports the glycopeptide antibiotic vancomycin to an uncharacterized TBDR (BugA) that confers sensitivity to the polypeptide antibiotic bacitracin. Both antibiotics are large zinc-binding molecules that target the peptidoglycan, echoing the zinc stress response induces destabilization of PerA. Inactivation of PerA launches two conserved and interwoven envelope stress programs that remodel the OM with TBDRs, a tripartite multidrug efflux pump and periplasmic proteases. Thus, unanticipated entry routes for antibiotics emerge in stressed diderm bacteria that may be treatable with membrane impermeable antimicrobials owing to an underlying transcriptional stress response pathways coordinated by a novel type of OM regulator.