bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropeptide Y gene polymorphisms and chronic kidney disease progression
Authors: Spoto Belinda , Mallamaci Francesca , Politi Cristina , Parlongo Rosa Maria Teresa , Leonardis Daniela , Capasso Giovambattista , Tripepi Giovanni , Zoccali Carmine 
Published: October 2023

Background:
Neuropeptide Y (NPY) is a neurotransmitter expressed in both the central and peripheral nervous systems, which is involved in regulating a multitude of physiological processes ranging from arterial pressure, energy balance, the immune response and inflammation and renal electrolyte transport. In a cohort of chronic kidney disease (CKD) patients, we recently showed that high plasma NPY levels predict renal disease progression independently of hypertension and other risk factors but the causal nature of this association remains unproven.

Methods:
In the same cohort of the previous study, we tested the relationship of NPY gene variability, as assessed by five single nucleotide polymorphisms (SNPs) that explained the whole gene variability, with the incidence rate of a predefined combined renal endpoint (dialysis/transplantation/estimated glomerular filtration rate reduction >30%) over a median follow up of 36 months (inter-quartile range 35–37 months) in 735 ethnically homogeneous patients with stage 2–5 CKD.

Results:
Two variants [rs16131 (recessive model for the T risk allele: TT, n = 563; CT + CC, n = 172) and rs16140 (dominant model for the G risk allele: GG + CG, n = 413; CC, n = 322)] were coherently associated with the incidence rate of renal events [hazard ratio (HR) ranging from 1.39 to 1.57, P ≤ 0.015] and this was also true when the two SNPs were jointly introduced into the same Cox model (P ≤ 0.043). The analysis of the biological interaction showed a significant synergism between the NPY rs16131 and rs16140 variants. Indeed, patients harboring NPY rs16131 TT and NPY rs16140 GG + CG risk genotypes had a much higher HR of renal events [HR: 1.80, 95% confidence interval (CI):1.16–2.79, P = 0.009] than that expected in the absence of biological interaction under both the additive and multiplicative models and the attributable proportion due to interaction (AP) was 25% and 38% on crude and adjusted analyses, respectively.

Conclusion:
This study, based on the Mendelian randomization approach and using NPY gene variants as instrumental variables to test the link between NPY and CKD progression, is in line with findings indicating that high plasma NPY levels predict an increased risk for renal events and lend support to the hypothesis that NPY is causally involved in renal disease progression.
Benign or painful? The interpretation of pain and fear of progression in rheumatoid arthritis
Authors: Boyse Jack B. , Sharpe Louise , Richmond Bethany , Dear Blake , Dudeney Joanne , Sesel Amy-Lee , Menzies Rachel E. 
Published: October 2023

AbstractPeople with chronic pain tend to interpret ambiguous information as health-related, more so than people without. In this study, we aimed to investigate whether people with rheumatoid arthritis (RA) exhibit this interpretation bias and whether it is associated with fear of disease progression (FoP). The interpretation biases of people with RA (n = 164) were compared with an age- and gender-matched control group. We hypothesized that (1) people with RA would have larger interpretation biases than people without; (2) those who scored in the clinical range for FoP would have larger interpretation bias than those who did not; (3) interpretation bias would moderate the relationship between pain severity and FoP; and (4) interpretation bias would explain variance in FoP above and beyond other established predictors. Our results confirmed that people with RA were more likely to interpret ambiguous information as health-related compared with people without RA. This effect was more pronounced for the RA subgroup with clinically significant FoP than those scoring in the normal range. We did not find evidence to suggest interpretation bias moderated the relationship between pain and FoP or that FoP added to the variance of other known predictors. Our results indicate that interpretation bias is common amongst people with RA and is associated with FoP. Further research is required to illuminate the exact nature of this relationship.
Measuring quality of life in patients with kidney stone disease: is it the future in endourology?
Authors: Vo Anh Khoi , Somani Bhaskar K. , Ulvik Øyvind , Beisland Christian , Seitz Christian , Juliebø-Jones Patrick 
Published: October 2023

Purpose of review
Kidney stone disease is recognized to negatively impact quality of life. This pertains to acute episodes, surgical interventions and even during asymptomatic periods. Over time there has been increased attention towards assessing this subjective parameter, including as a determinant of treatment success. Our aim was to evaluate the current status and emerging trends in this field.

Recent findings
Patient groups most affected appear to be recurrent stone formers, cystine stone formers, women, younger populations, non-Caucasians and low-income populations. Several stone specific patient reported outcome measures are now available of which, WISQol has been implemented the most in clinical research studies. More invasive interventions such as percutaneous nephrolithotomy impede quality of life to greater extent than alternatives such as shockwave lithotripsy.

Summary
There are certain patient groups who are more vulnerable to the negative impact of kidney stone disease on their quality of life. Urologists can improve patient care by recognizing these particular populations as well as by implemented patient reported outcome measures in their routine clinical practice and when performing research.
Association of Long-Term, New-Onset, and Postsurgical Diabetes With Survival in Patients With Resectable Pancreatic Cancer
Authors: Kanbour Sarah , Yenokyan Gayane , Abusamaan Mohammed , Laheru Daniel , Alam Ayman , El Asmar Marie Line , Virk Zunaira , Hardenbergh Dylan , Mathioudakis Nestoras 
Published: October 2023

Background
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Identifying modifiable risk factors, such as diabetes, is crucial. In the context of PDAC diagnosis, diabetes manifests as long-term (LTD), new-onset (NOD), or postsurgical (PSD) phenotypes. The link between these diabetes phenotypes and PDAC survival is debated.

Materials and Methods
We performed a retrospective study on patients with resectable PDAC who underwent pancreatectomy at Johns Hopkins Hospital from 2003 to 2017. We utilized the National Death Index and electronic medical records to determine vital status. We categorized diabetes as LTD, NOD, or PSD based on the timing of diagnosis relative to pancreatic resection. Using multivariable Cox models, we assessed hazard ratios (HRs) for survival times associated with each phenotype, considering known PDAC prognostic factors.

Results
Of 1556 patients, the 5-year survival was 19% (95% CI, 17–21). No significant survival differences were observed between diabetes phenotypes and non-diabetic patients. NOD and PSD presented nonsignificant increased risks of death (aHR: 1.14 [95% CI, 0.8–1.19] and 1.05 [95% CI, 0.89–1.25], respectively). LTD showed no survival difference (aHR, 0.98; 95% CI, 0.99–1.31).

Conclusions
No link was found between diabetes phenotypes and survival in resectable PDAC patients. Comprehensive prospective studies are required to validate these results.
Understanding the Impact of Mpox on Sexual Health Clinical Services: A National Knowledge, Attitudes, and Practices Survey – United States, 2022
Authors: Schubert Sara L. , Miele Kathryn , Quilter Laura , Agnew-Brune Christine , Coor Alexandra , Kachur Rachel , Lewis Felicia , Ard Kevin L. , Wendel Karen , Anderson Teri , Nagendra Gowri ,   National Network of STD Clinical Prevention Training Center Co-Authors, Tromble Erin 
Published: October 2023

Abstract

Background
During the 2022 mpox outbreak, most cases were associated with sexual contact and many people with mpox sought care from sexual health clinics and programs. The National Network of STD Clinical Prevention Training Centers (NNPTC), in partnership with Centers for Disease Control and Prevention, conducted a survey of United States sexual health clinics and programs to assess knowledge, practices, and experiences around mpox to inform a future public health response.

Methods
Between August 31–September 13, 2022, the NNPTC facilitated a web-based survey. Descriptive statistics were generated in R.

Results
Among 168 responses by clinicians (n = 131, 78%) and program staff (n = 37, 22%), more than half (51%) reported at least somewhat significant mpox-related clinical disruptions including burdensome paperwork requirements for mpox testing (40%) and tecovirimat use (88%). Long clinic visits (51%) added additional burden, the median mpox-related visit lasted one hour. Few clinicians felt comfortable with advanced pain management, and clinicians felt most uninformed about pre-exposure (19%) and post-exposure (24%) prophylaxis. Of 89 respondents involved in vaccination, 61% reported using equity strategies; however, accounts of these strategies revealed a focus on guideline or risk factor-based screenings instead of equity activities.

Conclusions
These findings highlight the substantial impact of the 2022 mpox outbreak on sexual health care in the United States. Critical gaps and barriers were identified that may inform additional mpox training and technical assistance, including challenges with testing, diagnosis, and management as well as a disconnect between programs’ stated goal of equity and operationalization of strategies to achieve equity.
Investigating the neural effects of typicality and predictability for face and object stimuli
Authors: Ficco Linda , Li Chenglin , Kaufmann Jürgen M. , Schweinberger Stefan R. , Kovács Gyula Z. 
Published: October 2023

AbstractThe brain calibrates itself based on the past stimulus diet, which makes frequently observed stimuli appear as typical (as opposed to uncommon stimuli, which appear as distinctive). Based on predictive processing theory, the brain should be more “prepared” for typical exemplars, because these contain information that has been encountered frequently, and allow to economically represent items of that category. Thus, one could ask whether predictability and typicality of visual stimuli interact, or rather act in an additive manner. We adapted the design by Egner and colleagues (2010), who used cues to induce expectations about stimulus category (face vs. chair) occurrence during an orthogonal inversion detection task. We measured BOLD responses with fMRI in 35 participants. First, distinctive stimuli always elicited stronger responses than typical ones in all ROIs, and our whole-brain directional contrasts for the effects of typicality and distinctiveness converge with previous findings. Second and importantly, we could not replicate the interaction between category and predictability reported by Egner et al. (2010), which casts doubt on whether cueing designs are ideal to elicit reliable predictability effects. Third, likely as a consequence of the lack of predictability effects, we found no interaction between predictability and typicality in any of the four tested regions (bilateral fusiform face areas, lateral occipital complexes) when considering both categories, nor in the whole brain. We discuss the issue of replicability in neuroscience and sketch an agenda for how future studies might address the same question.
Effect of Human Infant Gut Microbiota on Mouse Behavior, Dendritic Complexity, and Myelination
Authors: Dubey Harikesh , Roychoudhury Rohon , Alex Ann , Best Charlotte , Liu Sheng , White Antonio , Carlson Alexander , Azcarate-Peril M. Andrea , Mansfield Linda S. , Knickmeyer Rebecca 
Published: October 2023

AbstractThe mammalian gut microbiome influences numerous developmental processes. In human infants it has been linked with cognition, social skills, hormonal responses to stress, and brain connectivity. Yet, these associations are not necessarily causal. The present study tested whether two microbial stool communities, common in human infants, affected behavior, myelination, dendritic morphology, and spine density when used to colonize mouse models. Humanized animals were more like specific-pathogen free mice than germ-free mice for most phenotypes, although in males, both humanized groups were less social. Both humanized groups had thinner myelin sheaths in the hippocampus, than did germ-free animals. Humanized animals were similar to each other except for dendritic morphology and spine density where one group had greater dendritic length in the prefrontal cortex, greater dendritic volume in the nucleus accumbens, and greater spine density in both regions, compared to the other. Results add to a body of literature suggesting the gut microbiome impacts brain development.TeaserFecal transplants from human infants with highly abundantBifidobacterium, an important inhabitant of the intestinal tract of breastfed newborns, may promote brain connectivity in mice.
ZNF397 Loss Triggers TET2-driven Epigenetic Rewiring, Lineage Plasticity, and AR-targeted Therapy Resistance in AR-dependent Cancers
Authors: Xu Yaru , Wang Zhaoning , Sjöström Martin , Deng Su , Wang Choushi , Johnson Nickolas A , Gonzalez Julisa , Li Xiaoling , Metang Lauren A , Tirado Carla Rodriguez , Mukherji Atreyi , Wainwright Garrett , Yu Xinzhe , Yang Yuqiu , Barnes Spencer , Hofstad Mia , Zhu Hong , Hanker Ariella , He Housheng Hansen , Chen Yu , Wang Zhao , Raj Ganesh , Arteaga Carlos , Feng Felix , Wang Yunguan , Wang Tao , Mu Ping 
Published: October 2023

AbstractCancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as abona fideco-activator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that TET2 inhibitor can eliminate the AR targeted therapies resistance in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate and breast cancers acquire lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity.Statement of SignificanceThis study reveals a novel epigenetic mechanism regulating tumor lineage plasticity and therapy response, enhances understanding of drug resistance and unveils a new therapeutic strategy for prostate cancer and other malignancies. Our findings also illuminate TET2’s oncogenic role and mechanistically connect TET2-driven epigenetic rewiring to lineage plasticity and therapy resistance.
Multiple steps of prion strain adaptation to a new host
Authors: Bocharova Olga , Makarava Natallia , Pandit Narayan P. , Molesworth Kara , Baskakov Ilia V. 
Published: October 2023

AbstractThe transmission of prions across species is a critical aspect of their dissemination among mammalian hosts, including humans. This process often necessitates strain adaptation. In this study, we sought to investigate the mechanisms underlying prion adaptation while mitigating biases associated with the history of cross-species transmission of natural prion strains. To achieve this, we utilized the synthetic hamster prion strain S05. Propagation of S05 using mouse PrPCin Protein Misfolding Cyclic Amplification did not immediately overcome the species barrier. This finding underscores the involvement of factors beyond disparities in primary protein structures. Subsequently, we performed five serial passages to stabilize the incubation time to disease in mice. The levels of PrPScincreased with each passage, reaching a maximum at the third passage, and declining thereafter. This suggests that only the initial stage of adaptation is primarily driven by an acceleration in PrPScreplication. During the protracted adaptation to a new host, we observed significant alterations in the glycoform ratio and sialylation status of PrPScN-glycans. These changes support the notion that qualitative modifications in PrPSccontribute to a more rapid disease progression. Furthermore, consistent with the decline in sialylation, a cue for “eat me” signaling, the newly adapted strain exhibited preferential colocalization with microglia. In contrast to PrPScdynamics, the intensity of microglia activation continued to increase after the third passage in the new host. In summary, our study elucidates that the adaptation of a prion strain to a new host is a multi-step process driven by several factors.
Breast Cancer Macrophage Heterogeneity and Self-renewal are Determined by Spatial Localization
Authors: Ben-Chetrit Nir , Niu Xiang , Sotelo Jesus , Swett Ariel D. , Rajasekhar Vinagolu K. , Jiao Maria S. , Stewart Caitlin M. , Bhardwaj Priya , Kottapalli Sanjay , Ganesan Saravanan , Loyher Pierre-Louis , Potenski Catherine , Hannuna Assaf , Brown Kristy A. , Iyengar Neil M. , Giri Dilip D. , Lowe Scott W. , Healey John H. , Geissmann Frederic , Sagi Irit , Joyce Johanna A. , Landau Dan A. 
Published: October 2023

SummaryTumor-infiltrating macrophages support critical steps in tumor progression, and their accumulation in the tumor microenvironment (TME) is associated with adverse outcomes and therapeutic resistance across human cancers. In the TME, macrophages adopt diverse phenotypic alterations, giving rise to heterogeneous immune activation states and induction of cell cycle. While the transcriptional profiles of these activation states are well-annotated across human cancers, the underlying signals that regulate macrophage heterogeneity and accumulation remain incompletely understood. Here, we leveraged a novelex vivoorganotypic TME (oTME) model of breast cancer,in vivomurine models, and human samples to map the determinants of functional heterogeneity of TME macrophages. We identified a subset of F4/80highSca-1+ self-renewing macrophages maintained by type-I interferon (IFN) signaling and requiring physical contact with cancer-associated fibroblasts. We discovered that the contact-dependent self-renewal of TME macrophages is mediated via Notch4, and its inhibition abrogated tumor growth of breast and ovarian carcinomasin vivo, as well as lung dissemination in a PDX model of triple-negative breast cancer (TNBC). Through spatial multi-omic profiling of protein markers and transcriptomes, we found that the localization of macrophages further dictates functionally distinct but reversible phenotypes, regardless of their ontogeny. Whereas immune-stimulatory macrophages (CD11C+CD86+) populated the tumor epithelial nests, the stroma-associated macrophages (SAMs) were proliferative, immunosuppressive (Sca-1+CD206+PD-L1+), resistant to CSF-1R depletion, and associated with worse patient outcomes. Notably, following cessation of CSF-1R depletion, macrophages rebounded primarily to the SAM phenotype, which was associated with accelerated growth of mammary tumors. Our work reveals the spatial determinants of macrophage heterogeneity in breast cancer and highlights the disruption of macrophage self-renewal as a potential new therapeutic strategy.
A viral-specific CD4+T cell response protects female mice from Coxsackievirus B3 infection
Authors: Pattnaik Aryamav , Dhalech Adeeba H. , Condotta Stephanie A. , Corn Caleb , Richer Martin J. , Snell Laura M. , Robinson Christopher M. 
Published: October 2023

AbstractBiological sex plays an integral role in the immune response to various pathogens. The underlying basis for these sex differences is still not well defined. Here, we show that Coxsackievirus B3 (CVB3) induces a viral-specific CD4+T cell response that can protect female mice from mortality. We found that CVB3 can induce expansion of CD62LloCD4+T cells in the mesenteric lymph node and spleen of female but not male mice as early as 5 days post-inoculation, indicative of activation. Using a recombinant CVB3 virus expressing a model CD4+T cell epitope, we found that this response is due to viral antigen and not bystander activation. Finally, the depletion of CD4+T cells before infection increased mortality in female mice, indicating that CD4+T cells play a protective role against CVB3 in our model. Overall, these data demonstrated that CVB3 can induce an early CD4 response in female but not male mice and further emphasize how sex differences in immune responses to pathogens affect disease outcomes.
A generalised method for experiment design and model selection in the Bayesian framework
Authors: Jagadeesan Prem , Raman Karthik , Tangirala Arun K 
Published: October 2023

AbstractComputational modelling of dynamical systems often involves many free parameters estimated from experimental data. The information gained from an experiment plays a crucial role in the goodness of predictions and parameter estimates. Optimal Experiment Design (OED) is being used to choose an experiment containing maximum information from a set of possible experiments. This work presents a novel Bayesian Optimal Experiment Design principle for generalised parameter distributions. The generalization is archived by extending theβ-information gain to the discrete distributions. Theβ-information gain is based on what is known as the Bhattacharyya coefficient. We show that maximising theβ-information gain is equivalent to maximising the angle between the prior and posterior distributions, reducing the posterior’s uncertainty. Further, we apply the proposed BOED criteria for two realistic experiment designs in systems biology. Firstly, we use theβinformation gain to choose the best measurement method for parameter estimation in a Hes1 transcription model. The measurement method selected by theβ-information gain results in the minimum mean square error of the parameter estimates. In the second case, we employ the proposed information gained to select an optimal sampling schedule for HIV 1 2 LTR model. The sampling schedule chosen by the presented method reduces both prediction and parameter uncertainty. Finally, we propose a novel method for model selection usingβinformation gain and demonstrate the working of the proposed method in the model selection in compartmental models.