Rate In Response Research Articles

Can carotid artery Doppler variations induced by the end-expiratory occlusion maneuver predict fluid responsiveness in septic shock patients?

BackgroundAn increase in cardiac index (CI) during an end-expiratory occlusion test (EEOt) predicts fluid responsiveness in ventilated patients. However, if CI monitoring is unavailable or the echocardiographic window is difficult, using the carotid Doppler (CD) could be a feasible alternative to track CI changes. This study investigates whether changes in CD peak velocity (CDPV) and corrected flow time (cFT) during an EEOt were correlated with CI changes and if CDPV and cFT changes predicted fluid responsiveness in patients with septic shock.MethodsProspective, single-center study in adults with hemodynamic instability. The CDPV and cFT on carotid artery Doppler and hemodynamic variables from the pulse contour analysis EV1000™ were recorded at baseline, during a 20-s EEOt, and after fluid challenge (500 mL). We defined responders as those who increased CI ≥ 15% after a fluid challenge.ResultsWe performed 44 measurements in 18 mechanically ventilated patients with septic shock and without arrhythmias. The fluid responsiveness rate was 43.2%. The changes in CDPV were significantly correlated with changes in CI during EEOt (r = 0.51 [0.26–0.71]). A significant, albeit lower correlation, was found for cFT (r = 0.35 [0.1–0.58]). An increase in CI ≥ 5.35% during EEOt predicted fluid responsiveness with 78.9% sensitivity and 91.7% specificity, with an area under the ROC curve (AUROC) of 0.85. An increase in CDPV ≥ 10.5% during an EEOt predicted fluid responsiveness with 96.2% specificity and 53.0% sensitivity with an AUROC of 0.74. Sixty-one percent of CDPV measurements (from − 13.5 to 9.5 cm/s) fell within the gray zone. The cFT changes during EEOt did not accurately predict fluid responsiveness.ConclusionsIn septic shock patients without arrhythmias, an increase in CDPV greater than 10.5% during a 20-s EEOt predicted fluid responsiveness with > 95% specificity. Carotid Doppler combined with EEOt may help optimize preload when invasive hemodynamic monitoring is unavailable. However, the 61% gray zone is a major limitation (retrospectively registered on Clinicaltrials.gov NCT04470856 on July 14, 2020).

Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors

Phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitors are currently evaluated for the therapy of esophageal squamous cell carcinoma (ESCC). It is of great importance to identify potential biomarkers to predict or monitor the efficacy of PI3Kα inhibitors in an aim to improve the clinical responsive rate in ESCC. Here, ESCC PDXs with CCND1 amplification were found to be more sensitive to CYH33, a novel PI3Kα-selective inhibitor currently in clinical trials for the treatment of advanced solid tumors including ESCC. Elevated level of cyclin D1, p21 and Rb was found in CYH33-sensitive ESCC cells compared to those in resistant cells. CYH33 significantly arrested sensitive cells but not resistant cells at G1 phase, which was associated with accumulation of p21 and suppression of Rb phosphorylation by CDK4/6 and CDK2. Hypo-phosphorylation of Rb attenuated the transcriptional activation of SKP2 by E2F1, which in turn hindered SKP2-mediated degradation of p21 and reinforced accumulation of p21. Moreover, CDK4/6 inhibitors sensitized resistant ESCC cells and PDXs to CYH33. These findings provided mechanistic rationale to evaluate PI3Kα inhibitors in ESCC patients harboring amplified CCND1 and the combined regimen with CDK4/6 inhibitors in ESCC with proficient Rb.

Outcomes for treatment of depression in the Veterans Health Administration: Rates of response and remission calculated from clinical and survey data

Healthcare Effectiveness Data and Information Set (HEDIS) quality measures for depression treatment aggregate Patient Health Questionnaire (PHQ)-9 data from routine clinical assessments recorded in electronic health records (EHR). To determine whether aggregated PHQ-9 data in US Veterans Health Administration (VHA) EHRs should be used to characterize the organization's performance, we compared rates for depression response and remission calculated from EHRs with rates calculated with data representing the underlying Veteran patient population estimated using Veterans Outcome Assessment (VOA) survey data. We analyzed data from initial assessments and 3-month follow-up for Veterans beginning treatment for depression. EHR data were available for only a minority of Veteran patients, and the group of Veterans with EHR data differed from the underlying Veteran patient population with respect to demographic and clinical characteristics. Aggregated rates of response and remission from EHR data were significantly different from estimates based on representative VOA data. The findings suggest that until patient-reported outcome from EHRs are available for a substantial majority of patients receiving care, aggregated measures of patient outcomes derived from these data cannot be assumed to be representative of the outcomes for the overall population, and they should not be used as outcome-based measures of quality or performance.

TRICHOSCOPIC COMPARISON BETWEEN TELOGEN EFFLUVIUM AND ANDROGENIC ALOPECIA

Background: Alopecia, is a major condition that affects both sexes and people of all ages. Hair loss is the most common reason for women to consult a dermatologist, apparently because of cosmetic reasons. Androgenetic alopecia and Telogen Effluvium have greater rates of occurrence and sensitive responsiveness to timely treatments. Trichoscopy helps in diagnosis, determining the biopsy location, and providing prognostic information. Dermatologists can examine the scalp with a handheld dermoscope (x10 magnification). Vascular patterns, follicular and perifollicular features, and hair shaft features are among the dermoscopy results.

Acute adaptation of central and peripheral motor unit features to exercise-induced fatigue differs with concentric and eccentric loading.

What is the central question of this study? Conflicting evidence exists on motor unit (MU) firing rate in response to exercise-induced fatigue, possibly due to the contraction modality used: Do MU properties adapt similarly following concentric and eccentric loading? What is the main finding and its importance? MU firing rate increased following eccentric loading only despite a decline in absolute force. Force steadiness deteriorated following both loading methods. Central and peripheral MU features are altered in a contraction type-dependant manner, which is an important consideration for training interventions. Force output of muscle is partly mediated by the adjustment of motor unit (MU) firing rate (FR). Disparities in MU features in response to fatigue may be influenced by contraction type, as concentric (CON) and eccentric (ECC) contractions demand variable amounts of neural input, which alters the response to fatigue. This study aimed to determine the effects of fatigue following CON and ECC loading on MU features of the vastus lateralis (VL). High-density surface (HD-sEMG) and intramuscular (iEMG) electromyography were used to record MU potentials (MUPs) from bilateral VLs of 12 young volunteers (six females) during sustained isometric contractions at 25% and 40% of the maximum voluntary contraction (MVC), before and after completing CON and ECC weighted stepping exercise. Multi-level mixed effects linear regression models were performed with significance assumed as P<0.05. MVC decreased in both CON and ECC legs post-exercise (P<0.0001), as did force steadiness at both 25% and 40% MVC (P<0.004). MU FR increased in ECC at both contraction levels (P<0.001) but did not change in CON. FR variability increased in both legs at 25% and 40% MVC following fatigue (P<0.01). From iEMG measures at 25% MVC, MUP shape did not change (P>0.1) but neuromuscular junction transmission instability increased in both legs (P<0.04), and markers of fibre membrane excitability increased following CON only (P=0.018). These data demonstrate that central and peripheral MU features are altered following exercise-induced fatigue and differ according to exercise modality. This is important when considering interventional strategies targeting MU function.

Prediction of the Efficacy of Lumbar Sympathetic Block in Patients with Lower Extremity Complex Regional Pain Syndrome Type 1 Based on the Sympathetic Skin Response.

Complex regional pain syndrome type 1 (CRPS-1) is prevalent after trauma, with intractable pain being the most prominent clinical symptom. The impact of sympathetic block on CRPS is unclear. The goal of this study was to explore the characteristics that predict successful symptom relief with lumbar sympathetic block (LSB) in patients with lower extremity CRPS-1. The study was designed as a prospective cohort study. Ninety-eight patients diagnosed with lower extremity CRPS-1 between March 2021 and March 2022 were enrolled as participants. All of the patients received two LSB treatments within a month. Sympthetic skin response (SSR) and numeric rating scale (NRS) were recorded before and after LSB treatment. The procedure was judged as a clinically positive response if the patients a 50% or greater reduction in NRS scores. Patients were divided into positive response and negative response groups after LSB treatment: LSB (+) and LSB (-), and the different characteristics and examination findings of the two groups of patients were compared. Furthermore, a multivariable logistic regression model was utilized to evaluate the predictors of successful symptom relief following LSB treatment. A total of 43.9% (43/98) of patients experienced successful symptom relief, while 56.1% (55/98) had unsuccessful symptom relief. After LSB treatment of all subjects, the overall NRS score decreased, the SSR amplitude increased, and the SSR latency shortened in the affected extremity (P < 0.05). There was a significant difference in the change in SSR amplitude between the LSB (-) and LSB (+) groups (P = 0.000). A 12-month disease duration had an OR (odds ratio) of 4.477 (P = 0.009), and a 510-µV baseline SSR amplitude of the affected extremity had an OR of 7.508 (P = 0.000) in the multivariable analysis that included these explanatory variables. Patients with lower extremity CRPS-1 can experience significant pain relief after LSB treatment. The predictors of successful symptom relief after LSB treatment were a baseline SSR amplitude of the affected extremity < 510µV and a disease duration < 12months. The study was registered in the Chinese Clinical Trial Registry (ID: ChiCTR2000037755, date of registration: September 4, 2020).

Abstract 1364: Profiling tumor microenvironment for therapeutic intervention to soft-tissue sarcomas

Abstract Soft-tissue sarcomas (STS) are mesenchymal tumors having remarkably diverse histological features. Genomic studies reported that STS have low frequencies of genetic mutation, but often harboring copy number variations (CNVs). For STS, CNVs frequently happen in essential tumor suppressor genes and oncogenic transcriptional genes, neither of which are easily “druggable” targets. Moreover, in concordance with low tumor mutation burden rate, STS show low immunogenicity with less cytotoxic TIL in the TME and is unfortunately linked to a lower responsive rate to PD1/PD-L1 ICB. Using a syngeneic mouse UPS model, we previously found that tumor-associated macrophages (TAM) in the TME are promoting the growth of sarcoma. We further identified specific tumor microenvironmental elements contributing to the pro-tumorigenicity of TAMs, which represent a promising novel clinical target for myeloid-related intervention. Therefore, we hypothesize that exploration of TME is beneficial to identify clinically promising targets for STS. To study the TME in STS, we performed bulk RNA-seq and scRNA-seq on human sarcoma samples which covered different histological subtypes of STS and compare them to normal samples. Our results show that, unlike carcinomas originating from epithelial cells, extracellular matrix (ECM)-related genes are highly upregulated in both cancer-associated fibroblast (CAF) and sarcoma tumor cells. Further analysis show that upregulation of these ECM genes is associated with a worse survival outcome in sarcoma patients. In order to further explore the STS and TME orchestra, we established several syngeneic mouse models according to the genetic aberrations reported in TCGA data. We are currently characterizing these syngeneic mouse models to find out whether they recapitulate human STS samples. Our goal is to utilize these mouse models to study the relationship of ECM-related genes in both CAF and tumor cells, find out the effect of upregulated ECM-related genes on the immune compartment in TME and search for potential therapeutic interventions. Citation Format: Jin-Fen Xiao, Marina Broz, Roberta Piras, Kristin Ishaya, Emily Ko, Jlenia Guarnerio. Profiling tumor microenvironment for therapeutic intervention to soft-tissue sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1364.

Albumin-to-fibrinogen ratio is an independent predictor of corticosteroid response and prognosis in patients with IgA nephropathy

BackgroundThe objective of this study was to investigate whether the albumin-to-fibrinogen ratio (AFR) can predict corticosteroid response and prognosis prediction among IgA nephropathy (IgAN) patients.MethodsEligible participants with diagnosed IgAN who were scheduled to receive corticosteroid therapy for persistent proteinuria were recruited. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of AFR or estimated glomerular filtration rate (eGFR) for corticosteroid response in IgAN patients. Risk factors for corticosteroid response and prognosis were validated using univariate and multivariate Cox proportional analyses.ResultsAFR and eGFR were both effective predictors of corticosteroid response in IgAN patients, with area under the curve (AUC) values of 0.686 and 0.643, respectively (P < 0.001 and P = 0.002). Baseline AFR level at biopsy was an independent risk factor for remission after corticosteroid therapy (HR: 2.38, 95% CI 1.32–4.07, P = 0.015), 50% decline in eGFR (HR: 0.78, 95% CI 0.69–0.89, P = 0.025), kidney failure (HR: 2.46, 95%CI 1.16–3.71, P = 0.016), and a composite event (HR: 2.13, 95%CI 1.28–3.34, P = 0.009) in IgAN patients.ConclusionsAFR level at biopsy was a potential predictor of corticosteroid response and prognosis among IgAN patients.

PD17-10 DISCOVERY OF A NOVEL MONOCLONAL PD-L1 ANTIBODY H1A THAT PROMOTES T-CELL MEDIATED TUMOR KILLING ACTIVITY IN RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023PD17-10 DISCOVERY OF A NOVEL MONOCLONAL PD-L1 ANTIBODY H1A THAT PROMOTES T-CELL MEDIATED TUMOR KILLING ACTIVITY IN RENAL CELL CARCINOMA Reza Nabavizadeh, Rodrigo Rodrigues Pessoa, Zesheng An, Joanina Gicobi, Susan Harrington, Henan Zhang, Tianxiao Xu, Jacob Hirdler, Christine Lohse, Bradley Leibovich, Haidong Dong, and Fabrice Lucien Reza NabavizadehReza Nabavizadeh More articles by this author , Rodrigo Rodrigues PessoaRodrigo Rodrigues Pessoa More articles by this author , Zesheng AnZesheng An More articles by this author , Joanina GicobiJoanina Gicobi More articles by this author , Susan HarringtonSusan Harrington More articles by this author , Henan ZhangHenan Zhang More articles by this author , Tianxiao XuTianxiao Xu More articles by this author , Jacob HirdlerJacob Hirdler More articles by this author , Christine LohseChristine Lohse More articles by this author , Bradley LeibovichBradley Leibovich More articles by this author , Haidong DongHaidong Dong More articles by this author , and Fabrice LucienFabrice Lucien More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immune checkpoint inhibitors (ICI) have shown conflicting outcomes in the adjuvant setting for high-risk clear cell renal cell carcinoma (ccRCC) patients. There is an unmet need to identify patients who would benefit from ICI treatment and to develop new therapies for those who progress on current anti PD1/PD-L1 treatments. Our group has recently created a novel monoclonal antibody (H1A) that induces PD-L1 destabilization at the cell surface resulting in its degradation. In this study, we evaluated the T-cell killing rate in response to current FDA approved treatments as well as H1A. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 13 subjects 3 months after nephrectomy for ccRCC. For treatment with ICI, antibodies were added at the time of activation with soluble anti-CD3 and at 20 μg/ml concentration. Human 786-O ccRCC cells was used as target cells and killing rates were measured by calcein release assay. Paired ANOVA test was used to compare efficacy of ICI. RESULTS: The median increase in T-cell killing rate for pembrolizumab, nivolumab and atezolizumab were 37.8% (range 17.4%-57.7%), 36.6% (range 6 22.7%-65.4%) and 29.9% (range 10%-52.5%), respectively. Individual response to immune checkpoint inhibitors was heterogeneous with some patients showing stronger response with nivolumab (n=9) while others had better killing activity with pembrolizumab (n=3) and one patient with no difference between different treatments. No best response was observed with atezolizumab across all patients. Median killing rate for H1A was 41.7% (range 25%-71.2%). Overall, median killing rate was significantly higher with H1A compared to the pembrolizumab (p=0.0003) and nivolumab (p=0.003) (Figure 1). In terms of individual response, all H1A-treated patients showed improved tumor cell killing efficiency compared to other treatment groups. CONCLUSIONS: In this proof-of-concept, we showed differential T-cell cytotoxic activity in response to various FDA-approved ICI. Additionally, we demonstrated the therapeutic value of a newly developed PD-L1 monoclonal antibody that induces stronger cytotoxic tumor cell killing from ccRCC patient-derived CD8 T cells compared to other ICI. Source of Funding: This work was supported by NIH R01CA256927 (HD) and R01AI095239 (HD) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e499 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Reza Nabavizadeh More articles by this author Rodrigo Rodrigues Pessoa More articles by this author Zesheng An More articles by this author Joanina Gicobi More articles by this author Susan Harrington More articles by this author Henan Zhang More articles by this author Tianxiao Xu More articles by this author Jacob Hirdler More articles by this author Christine Lohse More articles by this author Bradley Leibovich More articles by this author Haidong Dong More articles by this author Fabrice Lucien More articles by this author Expand All Advertisement PDF downloadLoading ...

Ortho‐ and Retronasal stimulations with specific food odours: Hedonic and familiarity ratings are related to chemosensory pleasure scale (CPS) scores

AbstractVolatile compounds can reach olfactory epithelium though the nose (orthonasal olfaction) or the mouth (retronasal olfaction). Although differences have been found between these two pathways in terms of odour sensitivity and identification, few studies have examined ortho‐ and retronasal differences taking into consideration the three main dimensions of olfactory perception (i.e. hedonicity, intensity and familiarity). Olfactory perception, and particularly odour hedonic perception, is influenced by several factors such as sex or age. Another variability factor worth considering, especially regarding food‐related odours, is the ability to experience pleasure simulated by smell or taste, which can be measured with the Chemosensory Pleasure Scale (CPS). Thus, the aims of this study were (1) to compare odour sensory ratings in response to ortho‐ and retronasal presentation and (2) to examine the relationship between CPS scores and odour sensory ratings in ortho‐ and retronasal pathways. Participants rated ten food odours in ortho‐ and retronasal conditions using visual analogue scales and were divided into two subgroups based on the median CPS score (CPS+ and CPS− groups). Results revealed similar sensory responses to food odours between ortho‐ and retronasal pathways for the three main dimensions of olfactory perception. Interestingly, when CPS scores were considered, clear differences in odour familiarity and hedonicity were shown, particularly for the retronasal pathway (i.e. odours were perceived as more pleasant and more familiar in CPS+ group than in CPS− group). Overall, these findings suggest that differences in odour perception between ortho‐and retronasal pathways may be related to specific individual characteristics such as chemosensory hedonic capacity.

MP29-14 PROSTATE-SPECIFIC ANTIGEN RESPONSE AND TIME-TO-CASTRATION RESISTANCE AMONG PATIENTS WITH METASTATIC CASTRATION SENSITIVE PROSTATE CANCER INITIATED ON APALUTAMIDE, ENZALUTAMIDE, OR ABIRATERONE ACETATE

You have accessJournal of UrologyCME1 Apr 2023MP29-14 PROSTATE-SPECIFIC ANTIGEN RESPONSE AND TIME-TO-CASTRATION RESISTANCE AMONG PATIENTS WITH METASTATIC CASTRATION SENSITIVE PROSTATE CANCER INITIATED ON APALUTAMIDE, ENZALUTAMIDE, OR ABIRATERONE ACETATE Benjamin Lowentritt, Shawn Du, Carmine Rossi, Frederic Kinkead, Dexter Waters, Bronwyn Moore, Patrick Lefebvre, Dominic Pilon, and Erik Muser Benjamin LowentrittBenjamin Lowentritt More articles by this author , Shawn DuShawn Du More articles by this author , Carmine RossiCarmine Rossi More articles by this author , Frederic KinkeadFrederic Kinkead More articles by this author , Dexter WatersDexter Waters More articles by this author , Bronwyn MooreBronwyn Moore More articles by this author , Patrick LefebvrePatrick Lefebvre More articles by this author , Dominic PilonDominic Pilon More articles by this author , and Erik MuserErik Muser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Next-generation androgen inhibitors (AI), including apalutamide (APA), enzalutamide (ENZ), and abiraterone acetate (ABI), are approved to treat patients with metastatic castration sensitive prostate cancer (mCSPC). Among patients with mCSPC, prostate-specific antigen (PSA) response is associated with increased overall survival and decreased castration resistance (CR), an important indicator of disease progression. This study described real-world PSA response and progression to CR among patients with mCSPC treated with APA, ENZ, or ABI in the US. METHODS: Data from 77 community-based urology practices (9/2018–4/2022) were used to evaluate patients with mCSPC newly initiated on APA, ENZ, or ABI using in-office dispensing data (index date is first dispensation date). On-treatment PSA response was defined as: 1) a post-index ≥90% decline in PSA (PSA90) from baseline (using the closest PSA value within 13 weeks prior to or on the index date) and 2) a post-index decline to ≤0.2 ng/mL (PSA0.2) among those with baseline PSA >0.2 ng/mL. The descriptive proportion of patients achieving a PSA response or progressing to CR was described separately for each cohort using Kaplan-Meier (KM) analysis up to 12- and 24-months post-index, respectively. RESULTS: A total of 589 APA, 597 ENZ, and 553 ABI patients were evaluated. Mean age at index was 76 years in each group. Mean baseline PSA was 19.2 ng/mL (APA), 18.8 ng/mL (ENZ), and 24.3 ng/mL (ABI). KM rates for PSA response and progression to CR are shown in the Table. PSA90 by 12 months was achieved by 72% (APA), 62% (ENZ), and 55% (ABI) of patients. PSA0.2 by 12 months was achieved by 81% (APA), 63% (ENZ), and 58% (ABI) of patients. By 24 months, progression to CR was observed in 34% (APA), 39% (ENZ), and 45% (ABI) of patients. CONCLUSIONS: This is among the first observational studies to describe real-world PSA response and progression to CR in mCSPC patients treated with AIs in US community urology practices. While AIs with higher proportions achieving PSA90 or PSA0.2 were observed to have lower rates of progression to CR, further studies adjusting for baseline characteristics are needed to understand this relationship. Source of Funding: Janssen Scientific Affairs, LLC. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e387 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin Lowentritt More articles by this author Shawn Du More articles by this author Carmine Rossi More articles by this author Frederic Kinkead More articles by this author Dexter Waters More articles by this author Bronwyn Moore More articles by this author Patrick Lefebvre More articles by this author Dominic Pilon More articles by this author Erik Muser More articles by this author Expand All Advertisement PDF downloadLoading ...

Shame on me for needing you: A multistudy examination of links between receiving interpersonal emotion regulation and experiencing shame.

Recent theory and research have drawn attention to interpersonal dimensions of emotion regulation. Yet, few empirical investigations of the outcomes of interpersonal emotion regulation have been conducted. We propose that one negative affective outcome of received interpersonal emotion regulation of conceptual and practical interest is shame. In the present series of studies, participants from six disparate samples reported on experiences of receiving interpersonal emotion regulation using autobiographical recall and ecological sampling paradigms (total analyzed n = 1,868; total analyzed k = 2,515 instances of receiving interpersonal emotion regulation). We sought to quantify the frequency and distinctiveness of shame as an outcome of receiving interpersonal emotion regulation. We used an exploratory-confirmatory approach to identify robust and generalizable correlates of shame. We considered individual (e.g., trait external shame-proneness), situational (e.g., desire for regulation), relational (e.g., perceived closeness with the provider), and interaction-specific (e.g., perceptions of provider hostility) variables. Our results indicate that it is not uncommon for people to experience receiving interpersonal emotion regulation as shame-inducing, and these perceptions are distinct from their evaluations of the overall helpfulness of the interaction. An internal mini meta-analysis showed that the strongest correlates of shame across studies and samples were individual differences in nonacceptance of negative emotions and expressive suppression and interaction-specific ratings of provider responsiveness and hostility. We discuss the conceptual, methodological, and practical implications of these findings for studying interpersonal emotion regulation and shame. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Recurrent and convolutional neural networks in structural dynamics: a modified attention steered encoder–decoder architecture versus LSTM versus GRU versus TCN topologies to predict the response of shock wave-loaded plates

The aim of the present study is to analyse and predict the structural deformations occurring during shock tube experiments with a series of recurrent and temporal convolutional neural networks. The goal is to determine the architecture that can best learn and predict physically and geometrically nonlinear deformations. For this approach, four different architectures are proposed. Firstly, the multi-layered long-short term memory is developed followed by the multi-layered gated recurrent unit (GRU). Both the RNNs allow accounting for history dependent behaviors through their corresponding internal variables. Further, a multilayered temporal convolutional network is initialized, where the dilated convolution operation is responsible for tracing the path dependent behavior. In the mentioned architectures a sequence of mechanical data is passed through the network and a transformation to corresponding displacements is established. These sequences and corresponding deflections belong to a wide range of strain rates in the dynamic response of structures consisting of steel, aluminum, and copper plates including geometrical and physical non-linearities. Finally, an encoder–decoder architecture consisting of GRU layers is introduced with a modified attention mechanism which showed the best result for predicting the dynamic response. Employing comparative calculations between the neural network (NN) enhanced predictions and the measurements, the nature of approximation of each mentioned NN architecture is discussed and the capabilities of these developed surrogate models are demonstrated by its prediction on validation experiments. These validation experiments have displacement and input data ranges beyond the range of data used for training the aforementioned models.

Team Barriers to Tacit Knowledge Sharing in Software Development Project Teams

Software Development Projects (SDPs) are being conducted at a rapid rate in response to the Fourth Industrial Revolution (4IR), even though SDPs are associated with very high failure rates. Their failure rate of SDPs has been declared as an International Crisis. SDPs are knowledge intensive in nature, whereby knowledge is essential when performing socio-technical tasks within SDPs. One of the reasons for the failure of SDPs is limited sharing of tacit knowledge within SDP teams. Limited tacit knowledge sharing within SDP teams results in the teams not being in position to perform their socio-technical tasks to the required standards which leads to success of SDPs. The main purpose of this research study was to identify the team-oriented barriers that limit the sharing of tacit knowledge within SDP teams. The researchers conducted a qualitative study and relied on qualitative data to achieve the objectives of the study. The qualitative data were collected through interviews and thematic data analysis was conducted to generate the results. A total of seven team-oriented barriers were identified includes team-culture, team-orientation, team-dispersion, team-cohesion, team-characteristics, trust, and communication. These issues are related to each other and influence one another in a positive way. These barriers stem from the entire SDP team, which is responsible for ensuring the success of SDPs.

Kinetic modeling of the chemotactic process in run-and-tumble bacteria.

The chemotactic process of run-and-tumble bacteria results from modulating the tumbling rate in response to changes in chemoattractant gradients felt by the bacteria. The response has a characteristic memory time and is subject to important fluctuations. These ingredients are considered in a kinetic description of chemotaxis, allowing the computation of the stationary mobility and the relaxation times needed to reach the steady state. For large memory times, these relaxation times become large, implying that finite-time measurements give rise to nonmonotonic currents as a function of the imposed chemoattractant gradient, contrary to the stationary regime where the response is monotonic. The case of an inhomogeneous signal is analyzed. Contrary to the usual Keller-Segel model, the response is nonlocal, and the bacterial profile is smoothed with a characteristic length that grows with the memory time. Finally, the case of traveling signals is considered, where appreciable differences appear compared to memoryless chemotactic descriptions.

Carbon Dots and Tumor Antigen Conjugates as Nanovaccines for Elevated Cancer Immunotherapy.

Cancer immunotherapy has become one of the current research hotspots. However, the deficiencies including restricted immunogenicity, insufficient antigen presentation, and low responsive rate limited their therapeutic applications. Own to the small size and excellent biocompatibility, carbon dots (CDs) can serve as nanovectors to improve the efficacy of cancer immunotherapy. Herein, a tumor antigen-based nanovaccines (GMal+B16F10-Ag and GMal+CT26-Ag) by the conjugation of CDs with the tumor cell-derived antigens (B16F10-Ag and CT26-Ag) is constructed. These nanovaccines can be effectively taken up by dendritic cells (DC2.4), promote DC cell maturation, cross-present the antigen to T cells, specifically target B16F10 melanoma or CT26 colon cancers, and inhibit tumor growth distinctly. This work illustrates the promise of CDs acting as versatile carriers for antigen delivery to achieve the optimal immunotherapeutic outcomes.

Background noise responding neurons in the inferior colliculus of the CF-FM bat, Hipposideros pratti

The Lombard effect, referring to an involuntary rise in vocal intensity, is a widespread vertebrate mechanism that aims to maintain signal efficiency in response to ambient noise. Previous studies showed that the Lombard effect could be sufficiently implemented at subcortical levels and operated by continuously monitoring background noise, requiring some subcortical auditory sensitive neurons to have continuous responses to background noise. However, such neurons have not been well characterized. The inferior colliculus (IC) is a major auditory integration center under the auditory cortex and provides projections to the putative vocal pattern generator in the brainstem. Thus, it is reasonable to speculate that the IC is a likely auditory nucleus candidate having background noise responding neurons (BNR neurons). In the present study, we isolated 183 sound-sensitive IC neurons in a constant frequency-frequency modulation bat, Hipposideros pratti, and found that around 19% of these IC neurons are BNR neurons when stimulated with 70 dB SPL background white noise. Their firing rates in response to noise increased with increasing noise intensity and could be suppressed by sound stimulation. Furthermore, compared to neurons with similar best frequencies, the BNR neurons had smaller Q10-dB values and lower noise-induced minimal threshold change, indicating that BNR neurons received fewer inhibitory inputs. These results suggested that the BNR neurons are ideal candidates for collecting information about background noise. We proposed that the BNR neurons synapsed with neurons in vocal-pattern-generating networks in the brainstem and initiated the Lombard effect by a feed-forward loop.

Dose-dependent tandem responses of osteoblasts during osteogenesis

Irisin, a myokine mainly secreted from contracted skeleton muscle, plays a profound role in bone formation and remodeling. Although irisin has been revealed to elevate bone mass in vivo, details whether there is a dose-dependent relationship between irisin and bone formation remain unclear. In this study, we explored the dose-dependent effects of irisin on osteoblast proliferation and differentiation. Our results first demonstrated a remarkable increase in cell proliferation rate and viability in response to elevated concentrations of r-irisin, which was further enhanced over time. Notably, this increase was subject to complex dose-response relationships as the proliferation-enhancing effects of r-irisin may have a saturation point between 10 ​ng/ml and 100 ​ng/ml. Furthermore, we determined that 1, 10, and 100 ​ng/ml r-irisin were able to upregulate the expression of osteogenic transcription factors (Runx2, Osx, and Atf4), as well as osteogenic markers (Alp, Col1a1 and Spp1), albeit without significant difference among these 3 concentrations. Interestingly, nutrient-depleted osteoblasts and those with standard culture showed distinct responses to higher doses of irisin regarding osteogenic differentiation. Further investigation is required to uncover the molecular mechanisms underlying the observed tandem effects of irisin on osteogenesis.

Did you get the joke? Physiological, subjective and behavioral responses to mirth.

Mirth is elicited by the perception of humor, which requires the resolution of an incongruity in an unexpected and playful manner. Previous psychophysiological research using affective pictures is scarce, and did not elucidate the cognitive and affective components of the humor process. In this study, the passive viewing paradigm is applied to mirthful, incongruent, neutral and erotic pictures to characterize the emotional response of mirth. Physiological (zygomaticus major [ZM] activity, skin conductance response [SCR] and heart rate [HR]), behavioral (free viewing time) and subjective responses (mirthful ratings) were recorded from 63 participants. The presence of an inflection change in the ZM response and mirthfulness ratings were used as markers of humor comprehension. Participants showed the greatest ZM and HR in response to mirthful compared to incongruent, erotic and neutral pictures, as well as a stronger SCR response to mirthful compared to incongruent and neutral pictures. The overall results shed light on the temporal course of the humor process, suggesting that humor comprehension (cognitive component) occurred around 1000-1500 ms after picture onset, according to the ZM and SCR responses; and the humor appreciation stage (emotional component) occurred at around 3500 ms after stimulus onset, according to the HR and SCR changes. Moreover, marked interindividual variability was observed in the number of smiles, and in the pictures that provoked them. This points to the complexity of the humor process, and suggests the need to develop methods to elicit mirth and elucidate the factors potentially underlying individual differences in humor.

Modulation of potassium conductances optimizes fidelity of auditory information.

Potassium channels in auditory neurons are rapidly modified by changes in the auditory environment. In response to elevated auditory stimulation, short-term mechanisms such as protein phosphorylation and longer-term mechanisms such as accelerated channel synthesis increase the amplitude of currents that promote high-frequency firing. It has been suggested that this allows neurons to fire at high rates in response to high sound levels. We have carried out simple simulations of the response to postsynaptic neurons to patterns of neurotransmitter release triggered by auditory stimuli. These demonstrate that the amplitudes of potassium currents required for optimal encoding of a low-amplitude auditory signal differ from those for louder sounds. Specifically, the cross-correlation of the output of a neuron with an auditory stimulus is improved by increasing potassium currents as sound amplitude increases. Temporal fidelity for low-frequency stimuli is improved by increasing potassium currents that activate at negative potentials, while that for high-frequency stimuli requires increases in currents that activate at positive membrane potentials. These effects are independent of the firing rate. Moreover, levels of potassium currents that maximize the fidelity of the output of an ensemble of neurons differ from those that maximize fidelity for a single neuron. This suggests that the modulatory mechanisms must coordinate channel activity in groups of neurons or an entire nucleus. The simulations provide an explanation for the modulation of the intrinsic excitability of auditory brainstem neurons by changes in environmental sound levels, and the results may extend to information processing in other neural systems.