bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors
Authors: Upreti Chirag , Woodruff Caitlin M. , Zhang Xiao-Lei , Yim Michael J. , Zhou Zhen-yu , Pagano Andrew M. , Rehanian Dina S. , Yin Deqi , Kandel Eric R. , Stanton Patric K. , Nicholls Russell E. 
Published: March 2021

AbstractRetinoid X receptors are members of the nuclear receptor family that regulate gene expression in response to retinoic acid and related ligands. Group 1 metabotropic glutamate receptors are G-protein coupled transmembrane receptors that activate intracellular signaling cascades in response to the neurotransmitter, glutamate. These two classes of molecules have been studied independently and found to play important roles in regulating neuronal physiology with potential clinical implications for disorders such as depression, schizophrenia, Parkinson’s and Alzheimer’s disease. Here we show that mice lacking the retinoid X receptor subunit, RXRγ, exhibit impairments in group 1 mGluR-mediated electrophysiological responses at hippocampal Schaffer collateral-CA1 pyramidal cell synapses, including impaired group 1 mGluR-dependent long-term synaptic depression (LTD), reduced group 1 mGluR-induced calcium release, and loss of group 1 mGluR-activated voltage-sensitive currents. These animals also exhibit impairments in a subset of group 1 mGluR-dependent behaviors, including motor performance, spatial object recognition, and prepulse inhibition. Together, these observations demonstrate convergence between the RXRγ and group 1 mGluR signaling pathways that may function to coordinate their regulation of neuronal activity. They also identify RXRγ as a potential target for the treatment of disorders in which group 1 mGluR signaling has been implicated.
Mapping of the benzoate metabolism by human gut microbiome indicates food-derived metagenome evolution
Authors: Yadav Monika , Lomash Avinash , Kapoor Seema , Pandey Rajesh , Chauhan Nar Singh 
Published: March 2021

AbstractSodium benzoate is one of the widely used food preservatives and its metabolism in the human body has been studied only with the host perspective. Despite the human gut microbiome being considered as a virtual human organ, its role in benzoate metabolism is yet to be elucidated. The current study uses a multi-omic approach to rationalize the role of human gut microbes in benzoate metabolism. Microbial diversity analysis with multiple features synchronously indicates the dominance of Bacteroidetes followed by Firmicutes, Actinobacteria, and Proteobacteria. Metagenomic exploration highlights the presence of benzoate catabolic protein features. These features were mapped on to the aerobic and anaerobic pathways of benzoate catabolism. Benzoate catabolism assays identified statistically significant metabolites (P < 0.05) associated with the protocatechuate branch of the beta-ketoadipate pathway of the benzoate metabolism. Analysis of the 201 human gut metagenomic datasets across diverse populations indicates the omnipresence of these features. Enrichment of the benzoate catabolic protein features in human gut microbes rationalizes their role in benzoate catabolism, as well as indicates food-derived microbiome evolution.
Mutation analysis using cell-free DNA for endocrine therapy in patients with HR+ metastatic breast cancer
Authors: Sim Sung Hoon , Yang Han Na , Jeon Su Yeon , Lee Keun Seok , Park In Hae 
Published: March 2021

AbstractWe prospectively evaluated the utility of ESR1 and PIK3CA mutation analysis with cell-free DNA (cfDNA) using droplet digital PCR (ddPCR) for the efficacy of endocrine therapy (ET) in hormone receptive positive (HR+) metastatic breast cancer (MBC) patients. CfDNA was analyzed just before the start of ET for MBC. E380Q, Y537N, Y537S, and D538G were assessed for ESR1 mutations and H1047R, E545K, and E542K were assessed for PIK3CA mutations. A total of 75 patients were enrolled. Of those, 31 (41.3%) received letrozole with palbociclib, and 28 (37.3%) received exemestane and everolimus (EverX). ESR1 mutations were found in 36 (48.0%) patients, of which 16 (21.3%) had more than one variant. Seventeen (23.6%) patients had one PIK3CA mutation and 8 (11.1%) had two. In the total population, time to progression of the first ET after enrollment (TTP1) decreased significantly as the number of ESR1 mutations increased (p < 0.001). PIK3CA mutations were also significantly associated with shorter TTP1 (median TTP1: 16.2 months vs. 10.9 months, p = 0.03). In contrast, PIK3CA mutations were significantly associated with longer TTP in patients receiving EverX treatment (median TTP of EverX: 15.9 months vs. 5.2 months, p = 0.01) and remained a significant factor in multivariable analysis for TTP of EverX in this subgroup (hazard ratio = 0.2, 95% CI = 0.1– 0.8, p = 0.03). ESR1 and PIK3CA mutations in cfDNA were associated with clinical efficacies of ET in HR+ MBC patients.
Habenula GPR139 is associated with fear learning in the zebrafish
Authors: Roy Nisa , Ogawa Satoshi , Maniam Roshan , Parhar Ishwar 
Published: March 2021

AbstractG-protein coupled receptor 139 (GPR139) is an evolutionarily conserved orphan receptor, predominantly expressing in the habenula of vertebrate species. The habenula has recently been implicated in aversive response and its associated learning. Here, we tested the hypothesis that GPR139 signalling in the habenula may play a role in fear learning in the zebrafish. We examined the effect of intraperitoneal injections of a human GPR139-selective agonist (JNJ-63533054) on alarm substance-induced fear learning using conditioned place avoidance paradigm, where an aversive stimulus is paired with one compartment, while its absence is associated with the other compartment of the apparatus. The results indicate that fish treated with 1 µg/g body weight of GPR139 agonist displayed no difference in locomotor activity and alarm substance-induced fear response. However, avoidance to fear-conditioned compartment was diminished, which suggests that the agonist blocks the consolidation of contextual fear memory. On the other hand, fish treated with 0.1 µg/g body weight of GPR139 agonist spent a significantly longer time in the unconditioned neutral compartment as compared to the conditioned (punished and unpunished) compartments. These results suggest that activation of GPR139 signalling in the habenula may be involved in fear learning and the decision-making process in the zebrafish.
Age-dependent and region-specific alteration of parvalbumin neurons, perineuronal nets and microglia in the mouse prefrontal cortex and hippocampus following obesogenic diet consumption
Authors: Reichelt Amy C. , Lemieux Claire A. , Princz-Lebel Oren , Singh Ashmita , Bussey Timothy J. , Saksida Lisa M. 
Published: March 2021

AbstractEmergent evidence demonstrates that excessive consumption of high fat and high sugar (HFHS) diets has negative consequences on hippocampal and prefrontal cortex (PFC) function. Moreover, the delayed maturation of the PFC including the late development of parvalbumin-expressing (PV) interneurons and perineuronal nets (PNNs) may promote vulnerability to HFHS diet-induced nutritional stress. However, the young brain may have some resistance to diet-induced neuroinflammation. Thus, we examined the impact of a HFHS diet commencing either in adolescence or adulthood in male mice. PV interneurons, PNNs and microglia were assessed using immunohistochemistry. We observed greater numbers of PV neurons and PNNs in the hippocampus and the prelimbic and infralimbic PFC in adult mice in comparison to our younger cohort. Mice that consumed HFHS diet as adults had reduced numbers of hippocampal PV neurons and PNNs, which correlated with adiposity. However, we saw no effects of diet on PV and PNNs in the PFC. HFHS diet increased microgliosis in the adult cohort, and morphological changes to microglia were observed in the PFC and hippocampus of the adolescent cohort, with a shift to activated microglia phenotypes. Taken together, these findings demonstrate different regional and age-specific effects of obesogenic diets on PV neurons, PNNs and microglia.
Post translational modifications of milk proteins in geographically diverse goat breeds
Authors: Rout P. K. , Verma M. 
Published: March 2021

AbstractGoat milk is a source of nutrition in difficult areas and has lesser allerginicity than cow milk. It is leading in the area for nutraceutical formulation and drug development using goat mammary gland as a bioreactor. Post translational modifications of a protein regulate protein function, biological activity, stabilization and interactions. The protein variants of goat milk from 10 breeds were studied for the post translational modifications by combining highly sensitive 2DE and Q-Exactive LC-MS/MS. Here we observed high levels of post translational modifications in 201 peptides of 120 goat milk proteins. The phosphosites observed for CSN2, CSN1S1, CSN1S2, CSN3 were 11P, 13P, 17P and 6P, respectively in 105 casein phosphopeptides. Whey proteins BLG and LALBA showed 19 and 4 phosphosites respectively. Post translational modification was observed in 45 low abundant non-casein milk proteins mainly associated with signal transduction, immune system, developmental biology and metabolism pathways. Pasp is reported for the first time in 47 sites. The rare conserved peptide sequence of (SSSEE) was observed in αS1 and αS2 casein. The functional roles of identified phosphopeptides included anti-microbial, DPP-IV inhibitory, anti-inflammatory and ACE inhibitory. This is first report from tropics, investigating post translational modifications in casein and non-casein goat milk proteins and studies their interactions.
Potential of circulating tumor DNA as a predictor of therapeutic responses to immune checkpoint blockades in metastatic renal cell carcinoma
Authors: Kim Yeon Jeong , Kang Yumi , Kim Jun Seop , Sung Hyun Hwan , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Lee Hyun Moo , Park Donghyun , Park Woong-Yang , Kang Minyong 
Published: March 2021

AbstractWe evaluated the predictive role of circulating tumor DNA (ctDNA) detection by targeted deep sequencing in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockades (ICB). To determine the feasibility of ctDNA detection in our panel encompassing 40 genes, we collected 10 ml of blood from 20 patients at the time of radical nephrectomy. We analyzed somatic mutations in primary tumors and ctDNA samples from these patients. We finally collected 10 ml of blood before and after 1 month of treatment, respectively, from four patients with mRCC who received first-line ICB treatment. Variants were detected in primary tumors of 15 patients (75%) and ctDNA was detected in the plasma of 9 patients (45%). We examined the predictive role of ctDNA in four patients who received first-line ICB therapy. In two patients showing partial response, ctDNA levels decreased after 1 month of ICB treatment. However, in one patient who showed disease progression, ctDNA levels increased after 1 month of ICB treatment. Taken together, ctDNA detection in plasma by targeted deep sequencing was feasible in patients with RCC. Moreover, the levels of ctDNA could be an early predictor of treatment response in patients with mRCC who receive ICB therapy.
Validation of perinatal post-traumatic stress disorder questionnaire for Spanish women during the postpartum period
Authors: Hernández-Martínez Antonio , Martínez-Vázquez Sergio , Rodríguez-Almagro Julian , Khan Khalid Saeed , Delgado-Rodríguez Miguel , Martínez-Galiano Juan Miguel 
Published: March 2021

AbstractTo determine the psychometric properties of the Perinatal Post-Traumatic Stress Disorder (PTSD) Questionnaire (PPQ) in Spanish. A cross-sectional study of 432 Spanish puerperal women was conducted, following ethical approval. The PPQ was administered online through midwives' associations across Spain. The Edinburgh Postnatal Depression Scale was used to diagnose postnatal depression for examining criterion validity. Data were collected on sociodemographic, obstetric, and neonatal variables. An exploratory factorial analysis (EFA) was performed with convergence and criterion validation. Internal consistency was evaluated using Cronbach's α. The EFA identified three components that explained 63.3% of variance. The PPQ's convergence validation associated the risk of PTSD with variables including birth plan, type of birth, hospital length of stay, hospital readmission, admission of the newborn to care unit, skin-to-skin contact, maternal feeding at discharge, maternal perception of partner support, and respect shown by healthcare professionals during childbirth and puerperium. The area under the ROC curve for the risk of postnatal depression (criterion validity) was 0.86 (95% CI 0.82–0.91). Internal consistency with Cronbach's α value was 0.896. The PPQ used when screening for PTSD in postpartum Spanish women showed adequate psychometric properties.
Validating machine learning approaches for prediction of donor related complication in microsurgical breast reconstruction: a retrospective cohort study
Authors: Myung Yujin , Jeon Sungmi , Heo Chanyeong , Kim Eun-Kyu , Kang Eunyoung , Shin Hee-Chul , Yang Eun-Joo , Jeong Jae Hoon 
Published: March 2021

AbstractAutologous reconstruction using abdominal flaps remains the most popular method for breast reconstruction worldwide. We aimed to evaluate a prediction model using machine-learning methods and to determine which factors increase abdominal flap donor site complications with logistic regression. We evaluated the predictive ability of different machine learning packages, reviewing a cohort of breast reconstruction patients who underwent abdominal flaps. We analyzed 13 treatment variables for effects on the abdominal donor site complication rates. To overcome data imbalances, random over sampling example (ROSE) method was used. Data were divided into training and testing sets. Prediction accuracy, sensitivity, specificity, and predictive power (AUC) were measured by applying neuralnet, nnet, and RSNNS machine learning packages. A total of 568 patients were analyzed. The supervised learning package that performed the most effective prediction was neuralnet. Factors that significantly affected donor-related complication was size of the fascial defect, history of diabetes, muscle sparing type, and presence or absence of adjuvant chemotherapy. The risk cutoff value for fascial defect was 37.5 cm2. High-risk group complication rates analyzed by statistical method were significant compared to the low-risk group (26% vs 1.7%). These results may help surgeons to achieve better surgical outcomes and reduce postoperative burden.
The reasons for ceramic-on-ceramic revisions between the third- and fourth-generation bearings in total hip arthroplasty from multicentric registry data
Authors: Kim Sang-Min , Rhyu Kee Hyung , Yoo Jeong Joon , Lim Seung-Jae , Yoo Je Hyun , Kweon Suc Hyun , Lee Kyung-Jae , Han Seung-Beom 
Published: March 2021

AbstractThis study aimed to evaluate (1) the overall reasons for first revision in CoC THAs; (2) whether the reasons for revision differ between third-generation and fourth-generation CoC THAs; and (3) the specific factors associated with bearing-related problems as the reason for revision. We retrospectively reviewed 2045 patients (2194 hips) who underwent first revision THA between 2004 and 2013, among which 146 hips with CoC bearings underwent revision. There were 92 hips with third-generation ceramic bearings and 54 hips with fourth-generation ceramic bearings. The major reasons for CoC THA revisions were ceramic fracture and loosening of the cup or stem. When ceramic fracture, squeaking, incorrect ceramic insertion, and unexplained pain were defined as directly related or potentially related to ceramic use, 28.8% (42/146) of CoC revisions were associated with bearing-related problems. Among the third-generation ceramic bearings, revision was performed in 41.3% (38/92) of cases owing to bearing-related problems whereas revisions were performed for only 7.4% (4/54) of cases with fourth-generation ceramic bearings owing to bearing-related problems (p < 0.001). Younger age, lower American Society of Anesthesiologists (ASA) grade, and preoperative diagnosis of osteonecrosis were factors related to CoC THA revisions due to bearing-related problems.
Low serum levels of dehydroepiandrosterone sulfate and testosterone in Albanian female patients with allergic disease
Authors: Lokaj-Berisha Violeta , Gacaferri Lumezi Besa , Berisha Naser 
Published: March 2021

AbstractEvidence from several unrelated animal models and some studies conducted in humans, points to the immunomodulatory effects of androgens on various components of the immune system, especially on allergic disorders. This study evaluated the serum concentrations of sex hormones in women with allergy. For this purpose, blood samples were obtained from 78 participants in order to detect serum IgE concentrations, total testosterone, estradiol, progesterone, and DHEA-S. The majority of the subjects (54) in the study were consecutive patients with doctor-diagnosed allergic pathologies: 32 with allergic rhinitis, 10 with asthma and rhinitis, and 12 with skin allergies. In addition, 24 healthy volunteers were included in the research as the control group. The average age of the subjects was 32.54 years (SD ± 11.08 years, range between 4–59 years). All participants stated that they had not used any medical treatment to alleviate any of their symptoms prior to taking part in the research. They all underwent skin-prick tests for common aero-allergens, which was used as criterion for subject selection. Hence, the subjects were selected if they reacted positively to at least one aero-allergen. Their height and weight were measured in order to calculate the BMI. As a result, statistically significant differences between controls and allergic women in serum concentrations of androgens (testosterone, p = 0.0017; DHEA-S, p = 0.04) were found, which lead to the conclusion that the concentration of total serum testosterone and DHEA-S was lower in female patients with allergic diseases compared to controls.
Predictive model for the 5-year survival status of osteosarcoma patients based on the SEER database and XGBoost algorithm
Authors: Jiang Jiuzhou , Pan Hao , Li Mobai , Qian Bao , Lin Xianfeng , Fan Shunwu 
Published: March 2021

AbstractOsteosarcoma is the most common bone malignancy, with the highest incidence in children and adolescents. Survival rate prediction is important for improving prognosis and planning therapy. However, there is still no prediction model with a high accuracy rate for osteosarcoma. Therefore, we aimed to construct an artificial intelligence (AI) model for predicting the 5-year survival of osteosarcoma patients by using extreme gradient boosting (XGBoost), a large-scale machine-learning algorithm. We identified cases of osteosarcoma in the Surveillance, Epidemiology, and End Results (SEER) Research Database and excluded substandard samples. The study population was 835 and was divided into the training set (n = 668) and validation set (n = 167). Characteristics selected via survival analyses were used to construct the model. Receiver operating characteristic (ROC) curve and decision curve analyses were performed to evaluate the prediction. The accuracy of the prediction model was excellent both in the training set (area under the ROC curve [AUC] = 0.977) and the validation set (AUC = 0.911). Decision curve analyses proved the model could be used to support clinical decisions. XGBoost is an effective algorithm for predicting 5-year survival of osteosarcoma patients. Our prediction model had excellent accuracy and is therefore useful in clinical settings.
Pyrazinacenes exhibit on-surface oxidation-state-dependent conformational and self-assembly behaviours
Authors: Miklík David , Fatemeh Mousavi S. , Burešová Zuzana , Middleton Anna , Matsushita Yoshitaka , Labuta Jan , Ahsan Aisha , Buimaga-Iarinca Luiza , Karr Paul A. , Bureš Filip , Richards Gary J. , Švec Pavel , Mori Toshiyuki , Ariga Katsuhiko , Wakayama Yutaka , Morari Cristian , D’Souza Francis , Jung Thomas A. , Hill Jonathan P. 
Published: March 2021

AbstractAcenes and azaacenes lie at the core of molecular materials’ applications due to their important optical and electronic features. A critical aspect is provided by their heteroatom multiplicity, which can strongly affect their properties. Here we report pyrazinacenes containing the dihydro-decaazapentacene and dihydro-octaazatetracene chromophores and compare their properties/functions as a model case at an oxidizing metal substrate. We find a distinguished, oxidation-state-dependent conformational adaptation and self-assembly behaviour and discuss the analogies and differences of planar benzo-substituted decaazapentacene and octaazatetracene forms. Our broad experimental and theoretical study reveals that decaazapentacene is stable against oxidation but unstable against reduction, which is in contrast to pentacene, its C–H only analogue. Decaazapentacenes studied here combine a planar molecular backbone with conformationally flexible substituents. They provide a rich model case to understand the properties of a redox-switchable π-electronic system in solution and at interfaces. Pyrazinacenes represent an unusual class of redox-active chromophores.
Motor Speech Disorders and Communication Limitations in Progressive Supranuclear Palsy
Authors: Clark Heather M. , Utianski Rene L. , Ali Farwa , Botha Hugo , Whitwell Jennifer L. , Josephs Keith A. 
Published: March 2021

Purpose
This study describes motor speech disorders and associated communication limitations in six variants of progressive supranuclear palsy (PSP).

Method

The presence, nature, and severity of dysarthria and apraxia of speech (AOS) were documented, along with scores on the Apraxia of Speech Rating Scale–Version 3 (ASRS-3) for 77 (40 male and 37 female) patients with PSP. Clinician-estimated and patient-estimated communication limitations were rated using the Motor Speech Disorders Severity Rating (MSDSR) Scale and the Communicative Effectiveness Survey (CES), respectively. Descriptive statistics were calculated for each of these dependent variables. One-tailed
t
tests were conducted to test mean differences in ASRS-3 and CES between participants with and without AOS and between participants with and without dysarthria. Spearman rank correlations were calculated between ASRS-3 scores and clinical judgments of AOS and dysarthria severity and between MSDSR and CES ratings.

Results
Nine participants (12%) had normal speech. Eighty-seven percent exhibited dysarthria; hypokinetic and mixed hypokinetic–spastic dysarthria were observed most frequently. AOS was observed in 19.5% of participants across all variants, but in only 10% exclusive of the PSP speech and language variant. Nearly half presented with AOS in which neither phonetic nor prosodic features clearly predominated. The mean ASRS-3 score for participants with AOS was significantly higher than for those without and correlated strongly with clinician judgment of AOS severity. Mean ASRS-3 was higher for participants with dysarthria than for those without but correlated weakly with dysarthria severity. Mean MSDSR and CES ratings were lower in participants with AOS compared to those without and moderately correlated with each other.

Conclusions
Motor speech disorders that negatively impact communicative effectiveness are common in PSP and occur in many variants. This is the first description of motor speech disorders across PSP variants, setting the stage for future research characterizing neuroanatomical correlates, progression of motor speech disorders, and benefits of targeted interventions.

Supplemental Material

https://doi.org/10.23641/asha.14111837