bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Use of Atenolol for the Treatment of Infantile Hemangiomas
Authors: Pathman Lydia , Simpson Jodie , Penington Anthony J , Phillips Roderic J
Published: September 2022

Introduction:

Infantile hemangiomas are common vascular tumours in infants. Propranolol is currently accepted as the first choice if systemic treatment is needed. Propranolol has an excellent record of safety in young children, but some concerns have been raised about possible longer-term neurocognitive effects and five recent unexpected infant deaths have been reported. An alternative beta blocker, atenolol, may be as effective at hemangioma treatment and may have a better side effect profile.

Objectives:

To report the efficacy, safety, and side effect profile of oral atenolol for infantile hemangiomas.

Design:

We conducted a prospective observational study of 219 infants with infantile hemangiomas who were prescribed oral atenolol (1 mg/kg bd) as outpatients. The primary outcome measure was the response of the hemangioma.

Results:

The median age at commencement was 3.6 months. The median duration of treatment was 8.5 months. An excellent response was seen in 59.0% of patients, good response in 30.5%, and poor response in 10.5%. There was no significant difference in the response to atenolol with location or type of hemangioma or age at the commencement of atenolol. Possible side effects were reported in 8% of patients, and sleep disturbance in 3%. No infant had any reported hypoglycaemic or cardiovascular events attributable to atenolol.

Conclusion:

Atenolol is effective in treating infantile hemangiomas in an outpatient setting with 90% of patients having a good or excellent response to treatment. Atenolol appears to have a more favorable side effect profile than propranolol. It is reasonable to consider atenolol as first-line therapy for infantile hemangiomas needing oral treatment.
Caring for the Pediatric Patient Post-Nuss Procedure
Authors: Duque Carmen R. , Altares Sarik Danielle , Buscemi Charles , Garlesky Cindy
Published: September 2022

Background

Surgical correction for pectus excavatum (PE) is often performed during adolescence for patients exhibiting cardiac and respiratory problems. The surgery to correct PE is a thoracoscopic-assisted minimally invasive repair of PE or Nuss procedure. The postoperative clinical management is largely related to addressing pain from the constant pressure from the bar(s) on the sternum. A quality improvement project was developed to improve nurses' knowledge of appropriate postoperative care for the pediatric patient undergoing a Nuss procedure.

Method

A literature search was conducted using CINAHL and MEDLINE (ProQuest) to identify research studies that have evaluated nurses' knowledge of postoperative care for patients undergoing surgical correction for PE. Six studies were identified that investigated nurses' knowledge and attitudes of postoperative pain management in the pediatric patient and the effectiveness of enhanced recovery pathways to improve patient outcomes. A pretest and posttest were developed from the findings of the literature review along with an educational intervention. The educational presentation focused on the postoperative care of the pediatric patient who undergoes a Nuss procedure. A complete supplemental care plan is provided, which includes an enhanced recovery after surgery pathway, recommended pain treatment plan, exercises, medication recording sheet, home management tips for pain control, and patient discharge information.

Results

Implementation of a targeted educational program for the care of the pediatric patient who undergoes a Nuss procedure improved the clinician's knowledge and attitudes, resulting in a positive impact on pain management practice and patient outcomes.

Conclusion

Targeted educational interventions to improve pain management knowledge in nurses can result in increased understanding of appropriate postoperative pain management. This increased knowledge has the possibility to improve pain management and significantly improve the nurse and patient experience.
Advances in Adrenal and Extra-adrenal Paraganglioma: Practical Synopsis for Pathologists
Authors: Juhlin Carl Christofer , Mete Ozgur
Published: September 2022

Adrenal paraganglioma (or “pheochromocytoma”) and extra-adrenal paraganglioma, collectively abbreviated PPGL, are rare but spectacular nonepithelial neuroendocrine neoplasms. These are the most inheritable neoplasia of all, with a metastatic potential in a varying degree. As of such, these lesions demand careful histologic, immunohistochemical, and genetic characterization to provide the clinical team with a detailed report taking into account the anticipated prognosis and risk of syndromic/inherited disease. While no histologic algorithm, immunohistochemical biomarker, or molecular aberration single-handedly can identify potentially lethal cases upfront, the combined analysis of various risk parameters may stratify PPGL patients more stringently than previously. Moreover, the novel 2022 WHO Classification of Endocrine and Neuroendocrine Tumors also brings some new concepts into play, not least the reclassification of special neuroendocrine neoplasms (cauda equina neuroendocrine tumor and composite gangliocytoma/neuroma-neuroendocrine tumor) previously thought to belong to the spectrum of PPGL. This review focuses on updated key diagnostic and prognostic concepts that will aid when facing this rather enigmatic tumor entity in clinical practice.
Differences in plasma lipoprotein profiles between patients with chronic peripheral neuropathic pain and healthy controls: an exploratory pilot study
Authors: Jönsson Mika , Bäckryd Emmanuel , Jonasson Lena , Gerdle Björn , Ghafouri Bijar
Published: September 2022

Introduction:

Little is still known about the underlying mechanisms that drive and maintain neuropathic pain (NeuP). Recently, lipids have been implicated as endogenous proalgesic ligands affecting onset and maintenance of pain; however, in the case of NeuP, the relationship is largely unexplored.

Objectives:

The aim of this study was to investigate the lipoprotein profile in patients with chronic peripheral NeuP compared with healthy controls.

Methods:

The concentrations of 112 lipoprotein fractions in plasma from patients with NeuP (n = 16) and healthy controls (n = 13) were analyzed using proton nuclear magnetic resonance spectroscopy. A multiplex immunoassay based on an electrochemiluminescent detection method was used to measure the concentration of 71 cytokines in plasma from patients with NeuP (n = 10) and healthy controls (n = 11). Multivariate data analysis was used to identify patterns of protein intercorrelations and proteins significant for group discrimination.

Results:

We found 23 lipoproteins that were significantly upregulated in patients with NeuP compared with healthy controls. When the influence of cytokines was included in a regression model, 30 proteins (8 cytokines and 22 lipoprotein fractions) were significantly upregulated or downregulated in patients with NeuP. Both conditions presented lipoprotein profiles consistent with inflammation. Body mass index did not affect lipoprotein profiles in either group. No relationship between age and lipoprotein pattern was found in NeuP, but a significant relationship was found in healthy controls.

Conclusion:

Patients with NeuP presented a lipoprotein profile consistent with systemic low-grade inflammation, like that seen in autoimmune, cardiometabolic, and neuroprogressive diseases. These preliminary results emphasize the importance of chronic low-grade inflammation in NeuP.
Single-cell analysis in endometrial research
Authors: CAO Dan-Dan , Wang Jue , Yao Yuan-Qing , Yeung William Shu-Biu
Published: September 2022

Human endometrium undergoes dynamic shedding, regeneration, and differentiation, with remarkable changes in gene expression across the menstrual cycle. The development of a receptive endometrium within a particular time frame (window of implantation) is critical for successful embryo implantation. To understand the role of the endometrium in human fertility and regenerative biology, transcriptomic characterization of the endometrium has traditionally been pursued at the tissue bulk level using microarray and next-generation sequencing. Owing to the rapid development of single-cell RNA sequencing technology, researchers have uncovered heterogeneous molecular activities in individual cells masked by bulk analysis. In this review, we opted to mainly focus on single-cell analysis in endometrial research and introduce basic knowledge of single-cell RNA sequencing and the isolation of single cells from endometrial cells. We also discussed how single-cell approaches are used to understand the transformation and regeneration of the endometrium in a physiological manner and uncover endometrial factors that contribute to uterine pathology.
The Perivascular Niche of Endometrial Mesenchymal Stromal/Stem Cells
Authors: Chan Rachel W.S , Li Tian-Qi , Zhang Si-Si , Fang Yuan , Xu Jing-Wen
Published: September 2022

Human endometrium is a unique adult tissue that undergoes cyclical shedding, repair, and regeneration during a woman’s reproductive life. Over the past two decades, tremendous progress has been made towards the identification and characterization of endometrial stromal stem/progenitor cells (ESCs). The substantial regeneration of vascularized stroma in the endometrium during the proliferative stages of each menstrual cycle is likely to be mediated by endometrial mesenchymal stromal/stem cells (eMSCs). This review focuses on the perivascular niche for CD140b+CD146+ pericytes and SUSD2+ perivascular cells. The identity, characteristics, and underlying mechanisms of uterine regeneration are also discussed.
Maximum Diameter of the Gallbladder Determined Presurgically Using Computed Tomography as a Risk Factor for Difficult Emergency Laparoscopic Cholecystectomy in Patients With Mild to Moderate Acute Cholecystitis
Authors: Sasaki Atsushi , Sakata Kazuhito , Nakano Koji , Tsutsumi Satoshi , Fujishima Hajime , Futsukaichi Takuro , Terashi Takahiro , Ikebe Masahiko , Bandoh Toshio , Utsunomiya Tohru
Published: September 2022

Background:

Early or emergency laparoscopic cholecystectomy (LC) was recommended in the 2018 Tokyo Guidelines for patients with mild to moderate acute cholecystitis (AC). Although surgical difficulty is frequently encountered during these surgeries, risk factors for predicting surgical difficulties have not been fully investigated, especially based on computed tomography (CT) findings.

Materials and Methods:

We investigated 72 patients who underwent emergency LC with mild (n=45) to moderate (n=27) AC. Patients who previously underwent presurgical percutaneous or endoscopic biliary drainage were excluded from this study. Difficult LC was defined using any of the following surgical factors: surgical duration ≥180 minutes, blood loss ≥300 g, or a conversion to open cholecystectomy. Subsequently, several presurgical clinical factors were analyzed, including sex, age at surgery, experience of the surgeon, interval between symptom onset and surgery, body mass index, diabetes history, presurgical white blood cell count, and C-reactive protein level. Moreover, stones in the cystic duct or perigallblader fluid and the maximum thickness and diameter of the gallbladders were evaluated via presurgical CT. Finally, logistic regression analysis was performed to compare the relationship between surgical difficulty and each clinical factor.

Results:

The average age at surgery of the included patients was 60.3 (range: 25 to 88 y), surgical duration was 112.2 (range: 29 to 296 min), and surgical blood loss was 55.2 (range: 0 to 530 g). Furthermore, 4 (5.6%) had to undergo open cholecystectomy, whereas postsurgical complications occurred in 5 (6.9%) patients. In addition, the mean postsurgical admission duration was 7 (range: 3 to 63 d). Thus, 12 patients experienced difficult LC, whereas 60 experienced nondifficult LC. Of the evaluated clinical factors, patients who experienced difficult LC showed higher presurgical C-reactive protein levels (10.78 vs. 6.76 mg/dL, P=0.01) and wider gallbladder diameters (48.4 vs. 41.8 mm, P<0.01) than those who experienced nondifficult LC. By univariate logistic regression analysis, results also showed that patients with a maximum gallbladder diameter had a higher risk of experiencing difficulty during emergency LC (P=0.02). Moreover, the gallbladder diameter’s cutoff value was 43 mm after the receiver operating characteristic curve analysis.

Conclusions:

In patients with mild to moderate AC, emergency LC can safely be performed. However, performing LC might be technically difficult in patients with AC after the identification of severe gallbladder swelling during presurgical CT.
Identifying vulnerable populations with symptomatic cholelithiasis at risk for increased health care utilization
Authors: Shenoy Rivfka , Kirkland Patrick , Jackson Nicholas , DeVirgilio Michael , Zingmond David , Russell Marcia M. , Maggard-Gibbons Melinda
Published: September 2022

BACKGROUND

Gallstones are a common problem in the United States with many patients suffering from symptomatic cholelithiasis (SC). Patients with SC may first present to the emergency department ED) and are often discharged for elective follow-up; however, it is unknown what system and patient factors are associated with increased risk for ED revisits. This study aimed to assess longitudinal ED utilization and cholecystectomy for patients with SC and identify patient, geographic, and hospital characteristics associated with ED revisits, specifically race/ethnicity and insurance status.

METHODS

Patients discharged from the ED with SC between July 1, 2016, and December 31, 2017, were identified from California administrative databases and followed for 1 year. Emergency department revisits and cholecystectomy after discharge were examined using logistic regression, clustering standard errors by hospital. Models adjusted for patient, geographic, and hospital variables using census and hospital administrative data.

RESULTS

Cohort included 34,427 patients who presented to the ED with SC and were discharged. There were 18.8% of the patients that had one or more biliary-related ED revisits within 1 year. In fully adjusted models, non-Hispanic Black patients had higher odds for any ED revisit (adjusted odds ratio 1.23; 95% confidence interval, 1.09–1.39) and for two more ED revisits (adjusted odds ratio 1.48; 95% confidence interval, 1.20–1.82). Insurance type was also associated with ED revisits.

CONCLUSION

Non-Hispanic Black patients experienced higher utilization of health care resources for SC after adjusting for other patient, geographic and hospital variables. Strategies to mitigate these disparities may include the development of standardized protocols regarding the follow-up and education for SC. Implementation of such strategies can ensure equitable treatment for all patients.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
The Impact of Nutritional Supplementation on Donor Kidneys During Oxygenated Ex Vivo Subnormothermic Preservation
Authors: Bhattacharjee Rabindra N. , Jackson Ashley , Ruthirakanthan Aushanth , Juriasingani Smriti , Levine Max A. , Jiang Larry , Patel Ram , Richard-Mohamed Mahms , Forrest Sheryl , Ravichandran Sevanthi , Sener Alp , Luke Patrick P.
Published: September 2022

Background.

Evidence suggests that nutritional supplementation during normothermic ex vivo perfusion improves organ preservation. However, it is unclear whether the same benefit is observed during room temperature (subnormothermic) oxygenated perfusion. In this study, we tested the impact of providing complete nutrition during subnormothermic perfusion on kidney outcomes.

Methods.

Porcine kidneys were recovered after 30 min of cross clamping the renal artery in situ to simulate warm ischemic injury. After flushing with preservation solution, paired kidneys were cannulated and randomly assigned to perfusion with either (1) hemoglobin-carrier hemoglobin-based oxygen carrier or (2) hemoglobin-based oxygen carrier + total parenteral nutrition (TPN) for 12 h at 22 °C. To mimic reperfusion injury, all kidneys were reperfused with whole blood for an additional 4 h at 37 °C. Kidney function and damage were assessed.

Results.

Kidneys preserved with or without TPN performed equally well, showing similar renal function postreperfusion. Histological findings indicated similar levels of damage from apoptosis staining and acute tubular necrosis scores in both groups. Additionally, markers of renal damage (KIM-1) and inflammation (IL-6; high-mobility group box 1) were similar between the groups.

Conclusions.

Unlike other studies using normothermic oxygenated perfusion platforms, nutritional supplementation does not appear to provide any additional benefit during ex vivo kidney preservation over 12 h evaluated by whole blood-based reperfusion method at subnormothermic temperature. Further study should include a kidney autotransplant model to assess the role of TPN in vivo.
Advances in the gut microbiome and mood disorders
Authors: Mörkl Sabrina , Butler Mary I. , Lackner Sonja
Published: September 2022

Purpose of review

The gut microbiome is in constant bidirectional communication with the brain through the microbiota-gut-brain-axis. Mood disorders are among the most common psychiatric disorders and include major depressive disorder and bipolar disorder. The gut microbiome is altered in individuals with mood disorders and has a role in its inflammatory pathophysiology. In this article, we performed a narrative review of clinical studies, randomized controlled trials and meta-analyses addressing advances in gut microbiome research in mood disorders and included articles that were published between 2021 and 2022.

Recent findings

Studies highlight transdiagnostic alterations of microbiota in mood disorders, with reductions of butyrate-producing bacteria. Participants with major depressive disorder showed altered beta-diversity, while participants with bipolar disorder showed reduced alpha-diversity. Both disorders exhibit alterations in the metabolome. Early pilot studies addressed the possibility of using the gut microbiome for the prediction of treatment response and the blood microbiome for the diagnosis of psychiatric disorders. Findings from clinical trials support the use of probiotics as an add-on therapy for major depressive disorder. The second published case report in the literature reported a favourable outcome of a patient with bipolar disorder after faecal microbiota transplantation.

Gut microbiome modulations allow new treatment strategies including the use of psychobiotics for the treatment and prevention of mood disorders. Well designed clinical trials aiming for personalized medicine are needed to investigate the efficacy and safety of psychobiotic interventions.
Ferruginibacter albus sp. nov., isolated from a mountain soil, and Mucilaginibacter robiniae sp. nov., isolated from a black locust flower, Robinia pseudoacacia
Authors: Won Miyoung , Weon Hang-Yeon , Heo Jun , Lee Daseul , Han Byeong-Hak , Hong Seung-Beom , Kwon Soon-Wo
Published: September 2022

Two bacterial strains, designated KIS38-8T and F39-2T, were isolated from a mountain soil sample and a black locust flower (Robinia pseudoacacia) in Republic of Korea, respectively. The phylogenetic tree based on 16S rRNA gene sequences showed that strain KIS38-8T was classified into the genus

Ferruginibacter

with the highest sequence similarity to

Ferruginibacter lapsinanis

HU1-HG42T (96.6 %), and strain F39-2T was grouped into the genus

Mucilaginibacter

with the highest sequence similarity to

Mucilaginibacter daejeonensis

Jip 10T (97.6 %). Orthologous average nucleotide identity and digital DNA–DNA hybridization values between strain KIS38-8T and closely related

Ferruginibacter

strains were less than 72 and 19 %, respectively, while those values between strain F39-2T and closely related

Mucilaginibacter

strains were less than 73 and 21 %, respectively. The DNA G+C contents of strain KIS38-8T and F39-2T were 36.4 and 41.4 mol%, respectively. On the basis of the phenotypic and genotypic evidence, strains KIS38-8T and F39-2T are considered to represent novel species of the genus

Ferruginibacter

and

Mucilaginibacter

, respectively, for which the names Ferruginibacter albus sp. nov. (type strain KIS38-8T=KACC 17328T=NBRC 113101T) and Mucilaginibacter robiniae sp. nov. (type strain F39-2T=KACC 19733T=JCM 33062T) have been proposed.
Naturally occurring Neisseria gonorrhoeae can have large deletions in housekeeping gene abcZ, making them untypable with multilocus sequence typing
Authors: Vollan Hilde Synnøve , Caugant Dominique A. , Eldholm Vegard , Alfsnes Kristian , Debech Nadia , Brynildsrud Ola
Published: September 2022

The abcZ gene is an essential housekeeping gene in all the

Neisseria

species. It is one of the seven genes used for multilocus sequence typing (MLST) this genus. It encodes the cytosolic component of an ATP-binding cassette (ABC) transporter complex of unknown function. We report here the finding of a strain of

Neisseria gonorrhoeae

with a 485 base pair deletion in the 5′ region of the abcZ gene that truncates the protein product from 636 amino acids to 89 amino acids. A second open reading frame (ORF), encoding the latter 388 amino acids of the abcZ gene, was predicted downstream. The deletion will affect MLST profiling; interrogation of genomic sequences from PubMLST revealed that this isolate is not an anomaly. Deletions in abcZ were identified in 256

Neisseria

genomes, roughly 0.6% of isolates. Furthermore, these deletions could leave the abcZ gene in a pseudogenized state. Our strain, isolated from a patient with symptoms of gonorrheal infection, nevertheless behaved normal in terms of growth and in vitro phenotypic properties.
Multimorbidity and its associated factors in Indonesia through universal health coverage scheme: A cross-sectional study based on national claims data
Authors: Mahmudah Noor Afif , Tessma Mesfin Kassaye , Mahendradhata Yodi
Published: September 2022

Multimorbidity has been increasing globally and is usually associated with higher health care utilization and costs. Indonesia has been implementing Universal Health Coverage (UHC) program since 2014. However, there is a limited study of the prevalence of multimorbidity and its impact on health care utilization and costs through the UHC scheme in Indonesia. This study aimed to determine the prevalence of multimorbidity and its associated factors, particularly the health care utilization and costs of patients with multimorbidity compared to patients with one chronic condition in the hospitals in Indonesia based on the UHC scheme. The study was a comparative cross-sectional design. The data was collected from the Social Security Agency for Health/Badan Penyelanggara Jaminan Sosial Kesehatan (BPJS Health) National Sample Data 2015-2016. All patients ≥60 years of age and have at least one chronic condition in the hospital were included. Descriptive statistics, bivariate analysis, and multivariable regression analysis were conducted to analyze the data. In a sample of 23,460 patients, the prevalence of multimorbidity was 44.4% among patients with chronic conditions in the hospital. We observed significant difference in gender, marital status, and membership segmentations between patients with multimorbidity and one chronic condition (p<0.05). Health care utilization and costs were significantly higher in multimorbid patients (p<0.001). This positive association between multimorbidity and health care utilization (OR: 1.70, 95% CI: 1.61-1.79) and health care costs (unstandardized coefficient 0.483, 95% CI: 0.443-0.524, p<0.001) remains significant after adjusting for age and gender. The analysis found that the prevalence of multimorbidity was high and positively associated with higher health care utilization and costs through the UHC scheme in Indonesia. Therefore, health policymakers and healthcare professionals need to consider the burden of multimorbidity more when structuring health care.
Computer generation of fruit shapes from DNA sequence
Authors: Pérez-Enciso M. , Pons C. , Granell A. , Soler S. , Picó B. , Monforte A.J. , Zingaretti L.M.
Published: September 2022

The generation of realistic plant and animal images from marker information could be a main contribution of artificial intelligence to genetics and breeding. Since morphological traits are highly variable and highly heritable, this must be possible. However, a suitable algorithm has not been proposed yet. This paper is a proof of concept demonstrating the feasibility of this proposal using ‘decoders’, a class of deep learning architecture. We apply it to Cucurbitaceae, perhaps the family harboring the largest variability in fruit shape in the plant kingdom, and to tomato, a species with high morphological diversity also. We generate Cucurbitaceae shapes assuming a hypothetical, but plausible, evolutive path along observed fruit shapes of C. melo. In tomato, we used 353 images from 129 crosses between 25 maternal and 7 paternal lines for which genotype data were available. In both instances, a simple decoder was able to recover expected shapes with large accuracy. For the tomato pedigree, we also show that the algorithm can be trained to generate offspring images from their parents’ shapes, bypassing genotype information. Data and code are available at https://github.com/miguelperezenciso/dna2image.
Characterizing subgroup performance of probabilistic phenotype algorithms within older adults: A case study for dementia, mild cognitive impairment, and Alzheimer’s and Parkinson’s diseases
Authors: Banda Juan M. , Shah Nigam H. , Periyakoil Vyjeyanthi S.
Published: September 2022

Objective

Biases within probabilistic electronic phenotyping algorithms are largely unexplored. In this work, we characterize differences in sub-group performance of phenotyping algorithms for Alzheimer’s Disease and Related Dementias (ADRD) in older adults.

Materials and methods

We created an experimental framework to characterize the performance of probabilistic phenotyping algorithms under different racial distributions allowing us to identify which algorithms may have differential performance, by how much, and under what conditions. We relied on rule-based phenotype definitions as reference to evaluate probabilistic phenotype algorithms created using the Automated PHenotype Routine for Observational Definition, Identification, Training and Evaluation (APHRODITE) framework.

Results

We demonstrate that some algorithms have performance variations anywhere from 3 to 30% for different populations, even when not using race as an input variable. We show that while performance differences in subgroups are not present for all phenotypes, they do affect some phenotypes and groups more disproportionately than others.

Discussion

Our analysis establishes the need for a robust evaluation framework for subgroup differences. The underlying patient populations for the algorithms showing subgroup performance differences have great variance between model features when compared to the phenotypes with little to no differences.

Conclusion

We have created a framework to identify systematic differences in the performance of probabilistic phenotyping algorithms specifically in the context of ADRD as a use case. Differences in subgroup performance of probabilistic phenotyping algorithms are not widespread nor do they occur consistently. This highlights the great need for careful ongoing monitoring to evaluate, measure, and try to mitigate such differences.
Multi-omics biomarkers aid prostate cancer prognostication
Authors: Xu Zhuoran , Omar Mohamed , Benedetti Elisa , Rosenthal Jacob , Umeton Renato , Krumsiek Jan , Pomerantz Mark , Imada Eddie , Loda Massimo , Marchionni Luigi
Published: September 2022

Effective biomarkers and diagnostic tools are urgently needed in clinical settings for improved management of prostate cancer patients, especially to reduce over-treatment of indolent tumors and for early identification of aggressive disease. Gene expression signatures are currently the “gold standard” to provide guide clinical decision, however their clinical utility and interpretability is questionable. Multi-modal molecular profiling provides an holistic approach to systematically unravel the biological complexity underlying cancer pathogenesis, hence biomarkers developed using such an integrated approach hold the potential to more accurately capture cancer-driving alterations than signatures based on a single omics modality. Currently, however, robust and reproducible multi-omics biomarkers are still lacking for prostate cancer. In this study, we analyzed transcriptomics and metabolomics profiles jointly in a prostate cancer cohort and identified two prognostic signatures with high statistical powers (signature 1: EGLN3, succinate, trans-4-hydroxyprolin; and signature 2: IL6, SLC22A2, histamine). Our approach leveraged a priori biological knowledge of the cellular metabolism and gene circuitry, enabling the identification of dysregulated network modules. Functional bioinformatics analyses suggest that these signatures can capture relevant molecular alterations in prostate cancer tissues, including dysregulations of cellular signaling, cell cycle progression, and immune system modulation, stratifying patients in distinct risk groups. Next, we trained two gene expression signatures as a proxy for the multi-omics ones, extending our investigation to publicly available data, further confirming their prognostic values in independent patient cohorts. In summary, the analysis of multi-modal molecular grounded in cellular network biology represents a promising approach for the development of robust prognostic biomarkers of detecting and discriminating high grade disease.
Generalization of contextual fear is sex-specifically affected by high salt intake
Authors: Beaver Jasmin N. , Weber Brady L. , Ford Matthew T. , Anello Anna E. , Ruffin Kaden M. , Kassis Sarah K. , Gilman T. Lee
Published: September 2022

A hallmark symptom of many anxiety disorders, and multiple neuropsychiatric disorders more broadly, is generalization of fearful responses to non-fearful stimuli. Anxiety disorders are often comorbid with cardiovascular diseases. One established, and modifiable, risk factor for cardiovascular diseases is salt intake. Yet, investigations into how excess salt consumption affects anxiety-relevant behaviors remains little explored. Moreover, no studies have yet assessed how high salt intake influences generalization of fear. Here, we used adult C57BL/6J mice of both sexes to evaluate the influence of two or six weeks of high salt consumption (4.0% NaCl), compared to controls (0.4% NaCl), on contextual fear acquisition, expression, and generalization. Further, we measured osmotic and physiological stress by quantifying serum osmolality and corticosterone levels, respectively. Consuming excess salt did not influence contextual fear acquisition nor discrimination between the context used for training and a novel, neutral context when training occurred 48 prior to testing. However, when a four week delay between training and testing was employed to induce natural fear generalization processes, we found that high salt intake selectively increases contextual fear generalization in females, but the same diet reduces contextual fear generalization in males. These sex-specific effects were independent of any changes in serum osmolality nor corticosterone levels, suggesting the behavioral shifts are a consequence of more subtle, neurophysiologic changes. This is the first evidence of salt consumption influencing contextual fear generalization, and adds information about sex-specific effects of salt that are largely missing from current literature.
Electroencephalogram Data Collection for Student Engagement Analysis with Audio-Visual Content
Authors: Singh Mansi , Mishra Shreya , Mehta Jayantika , Bansal Anusha , Baranwal Manoj , Upadhyay Rahul , Kumar Vinay
Published: September 2022

Recognizing and monitoring students’ attention during learning is crucial to successful knowledge acquisition since it influences cognitive function. As a result, gaining a precise picture of a learner’s mental state may enable interactive learning systems to alter tutoring content, devise effective help tactics, and improve learning outcomes. In computer-based learning environments, keeping track of students’ mental states is vital. Investigating the feasibility of utilizing active learning in enhancing student engagement index when exposed to various visual stimuli is the genesis of this work. The research includes collecting EEG data from 20 participants (ten males, ten females) while resting and being subjected to various virtual infotainment/educational content. The EEG data were collected using the Allengers Neuro PLOT, a 40-channel wet electrode system. The work includes raw and pre-processed EEG data under quiescent and audio-visual continuous cues. The recorded data is accommodated by a sophisticated EEG data pre-processing pipeline and will be available to the research community for usage.

Specifications Table
Choice seeking is motivated by the intrinsic need for personal control
Authors: Munuera Jérôme , Agost Marta Ribes , Bendetowicz David , Kerebel Adrien , Chambon Valérian , Lau Brian
Published: September 2022

When deciding between options that do or do not lead to future choices, humans often choose to choose. We studied choice seeking by asking subjects to decide between a choice opportunity or performing a computer-selected action. Subjects preferred choice when these options were equally rewarded, even deterministically, and were willing to trade extrinsic rewards for the opportunity to choose. We explained individual variability in choice seeking using reinforcement learning models incorporating risk sensitivity and overvaluation of rewards obtained through choice. Degrading perceived controllability diminished choice preference, although willingness to repeat selection of choice opportunities remained unchanged. In choices following these repeats, subjects were sensitive to rewards following freely chosen actions, but ignored environmental information in a manner consistent with a desire to maintain personal control. Choice seeking appears to reflect the intrinsic need for personal control, which competes with extrinsic reward properties and external information to motivate behavior.

Author summary

Human decisions can often be explained by the balancing of potential rewards and punishments. However, some research suggests that humans also prefer opportunities to choose, even when these have no impact on future rewards or punishments. Thus, opportunities to choose may be intrinsically motivating, although this has never been experimentally tested against alternative explanations such as cognitive dissonance or exploration. We conducted behavioral experiments and used computational modelling to provide compelling evidence that choice opportunities are indeed intrinsically rewarding. Moreover, we found that human choice preference varied according to individual risk attitudes, and expressed a need for personal control that competes with maximizing reward intake.
Ventral striatal dopamine encodes unique properties of visual stimuli in mice
Authors: Gonzalez L. Sofia , Fisher Austen A. , D’Souza Shane P. , Cotella Evelin M. , Lang Richard A. , Robinson J. Elliott
Published: September 2022

The mesolimbic dopamine system is an evolutionarily conserved set of brain circuits that plays a role in attention, appetitive behavior, and reward processing. In this circuitry, ascending dopaminergic projections from the ventral midbrain innervate targets throughout the limbic forebrain, such as the ventral striatum/nucleus accumbens (NAc). Dopaminergic signaling in the NAc has been widely studied for its role in behavioral reinforcement, reward prediction error encoding, and motivational salience. Less well characterized is the role of dopaminergic neurotransmission in the response to surprising or alerting sensory events. To address this, we used the genetically encoded dopamine sensor dLight1 and fiber photometry to explore the ability of striatal dopamine release in to encode the properties of salient sensory stimuli in mice, such as threatening looming discs. Here, we report that NAc lateral shell (LNAc) dopamine release encodes the rate and magnitude of environmental luminance changes rather than visual stimulus threat level. This encoding is highly sensitive, as LNAc dopamine could be evoked by light intensities that were imperceptible to human experimenters. We also found that light-evoked dopamine responses are wavelength-dependent at low irradiances, independent of the circadian cycle, robust to previous exposure history, and involve multiple phototransduction pathways. Thus, we have further elaborated the mesolimbic dopamine system’s ability to encode visual information in mice, which is likely relevant to a wide body of scientists employing light sources or optical methods in behavioral research involving rodents.
Hyperthermia elevates brain temperature and improves behavioural signs in animal models of Autism spectrum disorder
Authors: Lopez-Rodriguez Ana Belen , Murray Carol , Kealy John , Towns Clodagh , Nazmi Arshed , Arnold Logan , Doran Michelle , Lowry John , Cunningham Colm
Published: September 2022

Autism Spectrum Disorders (ASD) are predominantly developmental in nature and largely genetically determined. There are some human data supporting the idea that fever can improve symptoms in some individuals but the human data for this are limited and there are almost no data to support this from animal models. In the current study we used a whole body hyperthermia (WBH) protocol and systemic inflammation induced by bacterial endotoxin (LPS) to dissociate temperature and inflammatory elements of fever in order to examine the impact of these environmental stressors on behavioural signs in two animal models relevant to ASD: C58BL/6 and Shank3B- mice. While only LPS induced inflammatory signatures in the brain, WBH and LPS induced both overlapping and distinct neuronal cFos activation in several brain regions and modest effects on heat shock gene expression. In behavioural experiments LPS significantly suppressed most activities over 24-48 hours while WBH reduced repetitive behaviours and improved social interaction in C58BL/6 mice. In Shank3B- mice WBH significantly reduced compulsive grooming. The data are the first, to our knowledge, to demonstrate that elevated body temperature, in the absence of underpinning inflammation, can improve some behavioural signs in two distinct animal models of ASD. Given the developmental and genetic nature of ASD, evidence that symptoms may be ameliorated by environmental perturbations indicates that there are possibilities for improving function in these individuals.
Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell
Authors: Kelley Abigail M. , Del Valle Eric J. , Zaman Samin , Karkhanis Anushree N.
Published: September 2022

Excessive alcohol consumption in adolescence can disrupt neural development and may augment pain perception. Recent studies have shown that the nucleus accumbens (NAc) shell is involved in mediating pain sensitivity after peripheral inflammation in rodent models of chronic pain and alcohol use disorder (AUD). Interestingly, there have been very few studies examining the impact of chronic ethanol exposure during adolescence on pain sensitivity in adulthood. Therefore, in this project we investigated the impact of adolescent chronic intermittent ethanol (aCIE) exposure on mechanical allodynia and thermal hyperalgesia. Furthermore, given the involvement of the NAc shell in pain processing and chronic ethanol mediated changes, we measured changes in accumbal dopamine kinetics during protracted withdrawal. We found that both male and female aCIE rats show mechanical allodynia during withdrawal; however, only male rats exhibit thermal hyperalgesia during protracted withdrawal. Furthermore, male and female aCIE rats show greater evoked tonic dopamine release, maximal rate of dopamine reuptake, and dopamine affinity to the dopamine transporter in the NAc shell compared to controls. With phasic stimulation, aCIE rats also showed greater dopamine release compared to air exposed rats. These data suggest that aCIE exposure exacerbates pain sensitivity during withdrawal. Furthermore, based on prior literature, it is possible that the increased pain sensitivity may be driven, at least in part, by augmented dopamine kinetics in the NAc shell observed in the current study.
Combined DiI and antibody labeling reveals complex dysgenesis of hippocampal spine synapses in a mouse model of Fragile X Syndrome
Authors: Speranza Luisa , Filiz Kardelen Dalım , Goebel Sarah , Perrone-Capano Carla , Pulcrano Salvatore , Volpicelli Floriana , Francesconi Anna
Published: September 2022

Structural, functional, and molecular alterations in excitatory spine synapses are a common hall-mark of many neurodevelopmental disorders including intellectual disability and autism. Here, we describe an optimized methodology, based on combined use of DiI and immunofluorescence, for rapid and sensitive characterization of the structure and composition of spine synapses in native brain tissue. We successfully demonstrate the applicability of this approach by examining the properties of hippocampal spine synapses in juvenile Fmr1 KO mice, a mouse model of Fragile X Syndrome. We find that mutant mice display pervasive dysgenesis of spine synapses evidenced by an overabundance of both abnormally elongated thin spines and cup-shaped spines, in combination with reduced density of mushroom spines. We further find that mushroom spines expressing the actin-binding protein Synaptopodin – a marker for spine apparatus - are more prevalent in mutant mice. Previous work identified spines with Synaptopodin/spine apparatus as the locus of mGluR-LTD, which is abnormally elevated in Fmr1 KO mice. Altogether, our data suggest this enhancement may be linked to the preponderance of this subset of spines in the mutant. Overall, these findings demonstrate the sensitivity and versatility of the optimized methodology by uncovering a novel facet of spine dysgenesis in Fmr1 KO mice.
Prediction of RNA secondary structures in SARS-CoV-2 and comparison with contemporary predictions
Authors: Ziesel Alison , Jabbari Hosna
Published: September 2022

Abstract

SARS-CoV-2, the causative agent of covid-19, is known to exhibit secondary structure in its 5’ and 3’ untranslated regions, along with the frameshifting stimulatory element situated between ORF1a and 1b. To identify further regions containing conserved structure, multiple sequence alignment with related coronaviruses was used as a starting point from which to apply a modified computational pipeline developed to identify non-coding RNA elements in vertebrate eukaryotes. Three different RNA structural prediction approaches were employed in this modified pipeline. Forty genomic regions deemed likely to harbour structure were identified, ten of which exhibited three-way consensus substructure predictions amongst our predictive utilities. Intracomparison of the pipeline’s predictive utilities, along with intercomparison with three previously published SARS-CoV-2 structural datasets, were performed. Limited agreement as to precise structure was observed, although different approaches appear to agree upon regions likely to contain structure in the viral genome.
Modeling Breast Cancer Proliferation, Drug Synergies, and Alternating Therapies
Authors: He Wei , Demas Diane M. , Shajahan-Haq Ayesha N. , Baumann William T.
Published: September 2022

Estrogen receptor positive (ER+) breast cancer is responsive to a number of targeted therapies used clinically. Unfortunately, the continuous application of targeted therapy often results in resistance. Mathematical modeling of the dynamics of cancer cell drug responses can help find better therapies that not only hold proliferation in check but also potentially stave off resistance. Toward this end, we developed a mathematical model that can simulate various mono, combination and alternating therapies for ER+ breast cancer cells at different doses over long time scales. The model is used to look for optimal drug combinations and predicts a significant synergism between Cdk4/6 inhibitors in combination with the anti-estrogen fulvestrant, which may help explain the clinical success of adding CDK4/6 inhibitors to anti-estrogen therapy. Lastly, the model is used to optimize an alternating treatment protocol that works as well as monotherapy while using less total drug dose.
A unified framework of realistic in silico data generation and statistical model inference for single-cell and spatial omics
Authors: Song Dongyuan , Wang Qingyang , Yan Guanao , Liu Tianyang , Li Jingyi Jessica
Published: September 2022

In the single-cell and spatial omics field, computational challenges include method benchmarking, data interpretation, and in silico data generation. To address these challenges, we propose an all-in-one statistical simulator, scDesign3, to generate realistic single-cell and spatial omics data, including various cell states, experimental designs, and feature modalities, by learning interpretable parameters from real datasets. Furthermore, using a unified probabilistic model for single-cell and spatial omics data, scDesign3 can infer biologically meaningful parameters, assess the goodness-of-fit of inferred cell clusters, trajectories, and spatial locations, and generate in silico negative and positive controls for benchmarking computational tools.
Complete loss of RelA and SpoT homologs in Arabidopsis reveals the importance of the plastidial stringent response in the interplay between chloroplast metabolism and plant defense response
Authors: Inazu Masataka , Nemoto Takanari , Suzuki Sae , Ono Sumire , Kanno Yuri , Seo Mitsunori , Oikawa Akira , Masuda Shinji
Published: September 2022

The highly phosphorylated nucleotide, guanosine tetraphosphate (ppGpp), functions as a secondary messenger in bacteria and chloroplasts. The accumulation of ppGpp alters plastidial gene expression and metabolism, which are required for proper photosynthetic regulation and robust plant growth. However, because four plastid-localized ppGpp synthases/hydrolases function redundantly, the impact of the loss of ppGpp-dependent stringent response on plant physiology remains unclear. We used the CRISPR/Cas9 technology to generate an Arabidopsis thaliana mutant lacking all four ppGpp synthases/hydrolases, and characterized its phenotype. The mutant showed 20-fold less ppGpp levels than the wild type (WT) under normal growth conditions, and exhibited leaf chlorosis and increased expression of defense-related genes as well as salicylic acid and jasmonate levels upon transition to nitrogen-starvation conditions. These results demonstrate that proper levels of ppGpp in plastids are required for controlling not only plastid metabolism but also phytohormone signaling, which is essential for plant defense.