bluuebunny/crossref_metadata_2025 huggingface dataset:
Tertiary structure and conformational dynamics of the anti-amyloidogenic chaperone DNAJB6b at atomistic resolution
Authors: Adupa Vasista , Ustyantseva Elizaveta , Kampinga Harm H. , Onck Patrick R.
Published: June 2023

DNAJB6b is a molecular chaperone of the heat shock protein network, shown to play a crucial role in preventing aggregation of several disease-related intrinsically disordered proteins. Despite its importance in maintaining cellular homeostasis, the structure-functional relationship of DNAJB6b is not yet known. Using homology modeling and microsecond-long all-atom molecular dynamics (MD) simulations, we show that monomeric DNAJB6b is a transiently interconverting protein cycling between three states: a closed state, an open state (both abundant), and a novel, less abundant extended state. Interestingly, the reported regulatory autoinhibitory anchor between helix V in the G/F1region and helices II/III of the J-domain, which obstructs the access of Hsp70 to the J-domain remains present in all three states. This possibly suggests a mechanistically intriguing regulation in which DNAJB6b only becomes exposed when loaded with substrates that require Hsp70 processing. Our MD results of DNAJB6b carrying mutations in the G/F1region that are linked to limb-girdle muscular dystrophy type D1 (LGMDD1) show that this G/F1region becomes highly dynamic, pointing towards a spontaneous release of the autoinhibitory helix V from helices II/III. This would increase the probability of non-functional Hsp70 interactions to DNAJB6b without substrates. Our cellular data indeed confirm that non-substrate loaded LGMDD1 mutants have aberrant interactions with Hsp70.
Dopamine D1-like receptors modulate synchronized oscillations in the hippocampal-prefrontal-amygdala circuit in contextual fear
Authors: Stubbendorff Christine , Hale Ed , Bast Tobias , Cassaday Helen J , Martin Stephen J , Suwansawang Sopapun , Halliday David M , Stevenson Carl W
Published: June 2023

Contextual fear conditioning (CFC) is mediated by a neural circuit that includes the hippocampus, prefrontal cortex, and amygdala, but the neurophysiological mechanisms underlying the regulation of CFC by neuromodulators remain unclear. Dopamine D1-like receptors (D1Rs) in this circuit regulate CFC and local synaptic plasticity, which is facilitated by synchronized oscillations between these areas. In rats, we determined the effects of systemic D1R blockade on CFC and oscillatory synchrony between dorsal hippocampus (DH), prelimbic (PL) cortex, basolateral amygdala (BLA), and ventral hippocampus (VH), which sends hippocampal projections to PL and BLA. D1R blockade altered DH-VH and reduced VH-PL and VH-BLA synchrony during CFC, as inferred from theta and gamma coherence and theta-gamma coupling. D1R blockade also impaired CFC, as indicated by decreased freezing at retrieval, which was characterized by altered DH-VH and reduced VH-PL, VH-BLA, and PL-BLA synchrony. This reduction in VH-PL-BLA synchrony was not fully accounted for by non-specific locomotor effects, as revealed by comparing between epochs of movement and freezing in the controls. These results suggest that D1Rs regulate CFC by modulating synchronized oscillations within the hippocampus-prefrontal-amygdala circuit. They also add to growing evidence indicating that this circuit synchrony at retrieval reflects a neural signature of learned fear.
Financial inclusion based on financial technology and risky behaviour of micro-finance institutes: evidence from South Asian micro-finance banks
Authors: Hussain Shahid , Rasheed Abdul
Published: June 2023

Purpose

The purpose of this paper financial technology (FinTech) revolutions are promptly remodelling the worldwide financial industry and facilitating financial inclusion initiatives with the aid of micro-finance institutions. Such hi-tech modifications are anticipated to sell the stableness of the financial system and lessen its predominant actors’ risk-taking behaviour. However, there needs to be more practical proof to guide the effect of financial inclusion based on financial technology on the risky behaviour of South Asia micro-finance institutes.

Design/methodology/approach

Therefore, the authors industrialised a fresh index to calculate financial inclusion based on financial technology and empirically measure its position in decreasing the risk-taking approach of micro-finance institutes. The use of numerous robustness examinations endorsed the rationality of the authors’ outcomes.

Findings

Z-scoring or standard scoring outcomes of FinInc support the extant studies displaying its incredible connection with economic stability, which interprets as a terrible courting with risky behaviour of micro-finance institutes. Consequently, the authors highlighted the significance of the universality and openness of financial technology solutions in minimising risk of micro-finance institutes. Moreover, the authors concluded that financial technology is greater related to small-size micro-finance institutes.

Originality/value

This study currently focusing South Asia, which has not been explored before, and it is the first time to research financial inclusion with Fintech in this area.
Fostering the sustainability of organizational learning: reviewing the role of Gen-Z employees
Authors: Pandita Deepika , Agarwal Yash , Vapiwala Fatima
Published: June 2023

Purpose

Organizations must be resilient to be agile and sensitive to numerous shifting situations due to the pandemic. There is limited research on how to bring the disparate perspectives and requirements of different generational cohorts in companies together to achieve outcomes that encourage organizational development and sustainability. Therefore, the purpose of the present study is to explore how Gen Z’s competencies can be banked upon to foster organizational learning to sustain.

Design/methodology/approach

Considering the constantly changing scenario in business organizations and the growing need for organizational learning to sustain, the authors have conducted an extensive review of the literature to understand how to sustain organizational learning for and through Gen Z. An integrative secondary search was carried out for specific and relevant work on the topic. The authors have considered both empirical and qualitative studies in their review to highlight the various themes that emerge from the extant literature.

Findings

The study indicates that much of the knowledge and experience is filtered through a generational lens, and organizations must encourage the development of Gen Z employees through e-learning, psychological contract, intrapreneurship and reverse mentoring. Based on the findings, the authors have proposed an ICES model which unifies the above four factors. The proposed ICES model encompasses specific interventions of having an Integrated 360 degrees learning experience (I), Coaching leadership for enabling intrapreneurship (C), revamping EVP for Gen Z-specific psychological contract (E) and building a Skill-will inventory for reverse mentoring (S).

Practical implications

There is limited research on how to bring the disparate perspectives and requirements of different generational cohorts in companies together to achieve outcomes that encourage organizational development and sustainability. This study will enable organizations to break down generational barriers, enhance organizational harmony, foster initiative and innovation and boost organizational performance through sustained organizational learning.

Originality/value

In view of the pandemic situation, organizations need to adapt not just their systems and processes but also to look for ways to engage their talent. The proposed ICES model will enable the sustainability of organizational learning for and through the Gen Z workforce by fostering individual development and organizational performance.
Last train timetable optimization for metro network to maximize the passenger accessibility over the end-of-service period
Authors: Wen Fang , Bai Yun , Zhang Xin , Chen Yao , Li Ninghai
Published: June 2023

Purpose

This study aims to improve the passenger accessibility of passenger demands in the end-of-operation period.

Design/methodology/approach

A mixed integer nonlinear programming model for last train timetable optimization of the metro was proposed considering the constraints such as the maximum headway, the minimum headway and the latest end-of-operation time. The objective of the model is to maximize the number of reachable passengers in the end-of-operation period. A solution method based on a preset train service is proposed, which significantly reduces the variables of deciding train services in the original model and reformulates it into a mixed integer linear programming model.

Findings

The results of the case study of Wuhan Metro show that the solution method can obtain high-quality solutions in a shorter time; and the shorter the time interval of passenger flow data, the more obvious the advantage of solution speed; after optimization, the number of passengers reaching the destination among the passengers who need to take the last train during the end-of-operation period can be increased by 10%.

Originality/value

Existing research results only consider the passengers who take the last train. Compared with previous research, considering the overall passenger demand during the end-of-operation period can make more passengers arrive at their destination. Appropriately delaying the end-of-operation time can increase the proportion of passengers who can reach the destination in the metro network, but due to the decrease in passenger demand, postponing the end-of-operation time has a bottleneck in increasing the proportion of passengers who can reach the destination.
Looking similar but all different: Phylogenetic signature of Brazilian rocky outcrops and the influence of temperature variability on their phylogenetic structure
Authors: Massante Jhonny Capichoni , Neri Andreza Viana , Villa Pedro Manuel , Fialho Izabela Ferreira , Pontara Vanessa , Bueno Marcelo , Gastauer Markus
Published: June 2023

Old, climatically buffered, infertile landscapes (OCBILs) have a disjunct yet wide distribution worldwide. Old lineages, rare and geographically restricted species, generally characterise these landscapes. Although the last decade provided evidence supporting the OCBIL theory, many studies are biased towards local scales, woody plants and specific OCBILs. Therefore, broad‐scale investigations across different types of OCBILs are needed.

We used 5186 flowering plant species (woody and herbaceous) distributed across 129 rocky outcrop sites in Brazil to investigate (1) the relative influence of climate on the phylogenetic diversity and structure of OCBILs; (2) their phylogenetic signature; (3) whether vegetation type influences phylogenetic diversity and structure of OCBILs after controlling for climate; and (4) the OCBILs' evolutionary median community age.

We found that rocky outcrops exhibit lower than expected phylogenetic diversity and are home to plant communities composed of closely related species (i.e. phylogenetic clustering) relative to the reference species pool, primarily due to temperature seasonality. Each rocky outcrop shows a distinct phylogenetic signature, indicated by plant families with more descendant species than expected by chance. Even after controlling for climate, phylogenetic diversity and structure remain low and clustered in most rocky outcrops. The median community age estimated at the species level is lower in campos de altitude than in other rocky outcrops.

Synthesis. We show that the influence of climate seasonality is pervasive in the phylogenetic diversity and structure of Brazilian rocky outcrops at different taxonomic levels. We also show that the phylogenetic signature of rocky outcrops comprises a mix of relatively old and young overrepresented plant families whose descendants contribute to their low phylogenetic diversity and phylogenetic clustering. Overall, the combination of low phylogenetic diversity, phylogenetic clustering and comparably low median community age across Brazilian rocky outcrops indicates that, on average, these OCBILs are subjected to strong environmental constraints and serve as arenas of recent diversification rather than a steady accumulation of taxa. Therefore, these findings indicate different OCBILs as hotspots for various plant lineages and species.
Postpartum readmission for hypertension and pre‐eclampsia: development and validation of a predictive model
Authors: Venkatesh Kartik Kailas , Jelovsek J. Eric , Hoffman Matthew , Beckham A. Jenna , Bitar Ghamar , Friedman Arielle M. , Boggess Kim A. , Stamilio David M.
Published: June 2023

Objective

To develop a model for predicting postpartum readmission for hypertension and pre‐eclampsia at delivery discharge and assess external validation or model transportability across clinical sites.

Design

Prediction model using data available in the electronic health record from two clinical sites.

Setting

Two tertiary care health systems from the Southern (2014–2015) and Northeastern USA (2017–2019).

Population

A total of 28 201 postpartum individuals: 10 100 in the South and 18 101 in the Northeast.

Methods

An internal‐external cross validation (IECV) approach was used to assess external validation or model transportability across the two sites. In IECV, data from each health system were first used to develop and internally validate a prediction model; each model was then externally validated using the other health system. Models were fit using penalised logistic regression, and accuracy was estimated using discrimination (concordance index), calibration curves and decision curves. Internal validation was performed using bootstrapping with bias‐corrected performance measures. Decision curve analysis was used to display potential cut points where the model provided net benefit for clinical decision‐making.

Main outcome measures

The outcome was postpartum readmission for either hypertension or pre‐eclampsia <6 weeks after delivery.

Results

The postpartum readmission rate for hypertension and pre‐eclampsia overall was 0.9% (0.3% and 1.2% by site, respectively). The final model included six variables: age, parity, maximum postpartum diastolic blood pressure, birthweight, pre‐eclampsia before discharge and delivery mode (and interaction between pre‐eclampsia × delivery mode). Discrimination was adequate at both health systems on internal validation (c‐statistic South: 0.88; 95% confidence interval [CI] 0.87–0.89; Northeast: 0.74; 95% CI 0.74–0.74). In IECV, discrimination was inconsistent across sites, with improved discrimination for the Northeastern model on the Southern cohort (c‐statistic 0.61 and 0.86, respectively), but calibration was not adequate. Next, model updating was performed using the combined dataset to develop a new model. This final model had adequate discrimination (c‐statistic: 0.80, 95% CI 0.80–0.80), moderate calibration (intercept −0.153, slope 0.960, Emax 0.042) and provided superior net benefit at clinical decision‐making thresholds between 1% and 7% for interventions preventing readmission. An online calculator is provided here.

Conclusions

Postpartum readmission for hypertension and pre‐eclampsia may be accurately predicted but further model validation is needed. Model updating using data from multiple sites will be needed before use across clinical settings.
Laryngeal edema in drug reaction with eosinophilia and systemic symptoms syndrome due to sulfasalazine
Authors: Shimada Yusuke , Suyama Yasuhiro , Koizumi Megumi , Hagiwara Kiyofumi
Published: June 2023

We present a case of a 47‐year‐old man with drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The patient had been diagnosed with rheumatoid arthritis and sulfasalazine was prescribed 4 weeks before admission. Initial symptoms with fever and rash worsened even after a discontinuation of the medication, and concomitant symptoms developed including typical manifestations of facial rash and edema sparing the periorbital area, as well as atypical laryngeal edema. Rheumatologists should be aware that sulfasalazine is derived from sulfonamide and can possibly induce DRESS syndrome, one of the life‐threatening drug eruptions.
The effectiveness of Tier 1 digital interventions for early reading: A meta‐analysis
Authors: Vanbecelaere Stefanie , Said‐Metwaly Sameh , Van den Noortgate Wim , Reynvoet Bert , Depaepe Fien
Published: June 2023

Reading is a fundamental skill to acquire during children's school career. The present meta‐analysis examined research on the effectiveness of digital technologies to foster early reading skills during Tier‐1 interventions (ie, high‐quality core reading instruction which is intended to promote learning for all children). Unlike previous meta‐analyses, this meta‐analysis investigated the effectiveness in a broad way, taking into account cognitive versus non‐cognitive learning outcomes, near versus far transfer outcomes and immediate versus delayed outcomes. Furthermore, different study characteristics were taken into account including participant characteristics, the targeted reading subskills, duration of intervention, type of technology and the level of integration. A total of 568 effect sizes from 72 studies encompassing 60,890 participants were analysed using a meta‐analytic three‐level model. A Hedges'g effect size of 0.37 was obtained, suggesting that using digital technologies generally have a positive, albeit small, effect compared to traditional teaching methods. Moderator analyses indicated that this effect was robust to cognitive and non‐cognitive outcomes, near and far transfer outcomes, and immediate and delayed outcomes, but differed by participants' age and study quality. Recommendations are formulated to push forward research on how digital interventions can be effectively implemented in the classroom.

Practitioner notes

What is already known about this topic

Digital technologies can foster (early) reading skills.

Meta‐analyses to date focus only on the effect of digital reading interventions in terms of cognitive outcomes.

Unclear how different factors moderate the effectiveness of digital reading interventions (eg, type of technology, trained content, level of integration).

What this paper adds

Results corroborate previous findings indicating a positive but small effect compared to traditional teaching methods.

This study provides some evidence that this effect was robust to cognitive and non‐cognitive outcomes, near and far transfer outcomes, and immediate and delayed outcomes.

The effect differed by participants' age and study quality.

Game elements, adaptivity and whether the intervention was well integrated made little difference to the effectiveness of the intervention.

Implications for practice and/or policy

The results confirm that digital reading interventions are effective in fostering cognitive, non‐cognitive and efficiency outcomes.

Call for more intervention studies investigating how game characteristics and the level of integration of a digital tool moderate the effectiveness.

There is a need for reports of pilot studies investigating the effectiveness of recent digital technologies such as AR and VR.
Discursive delegitimization of Rouhani's nuclear diplomacy and the Iran nuclear deal by Iranian conservatives on Twitter
Authors: Nourani Hossein , Mohammadian Mohammad , Sarhaddi Reza , Danesh Afsaneh , Latifi Farzaneh
Published: June 2023

The reformist‐moderate and the conservative discourses have co‐existed and contended for primacy in the Iranian foreign policy since the 1979 revolution. The 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran nuclear deal, has been at the core of this discursive contest in recent years. This article investigates how Iranian conservative tweeters delegitimized the JCPOA and President Rouhani's nuclear diplomacy. We use Van Leeuwen's discursive construction of legitimacy (2008) to analyze three popular conservative Twitter accounts. Findings show that the Iranian conservatives used the strategies of authorization, moral evaluation, and rationalization for legal and political criticism of the JCPOA, offending Rouhani's administration and allies, and questioning their political competence. This research partly reveals the conservatives' anti‐negotiation and anti‐West logic and their refusal to offer a diplomatic alternative to the JCPOA.
A Great Escape: resource availability and density‐dependence shape population dynamics along trailing range edges
Authors: Sirén Alexej , Zimova Marketa , Sutherland Chris S. , Finn John T. , Kilborn Jillian R. , Cliché Rachel M. , Prout Leighlan S. , Scott Mills L. , Lyn Morelli Toni
Published: June 2023

Populations along geographical range limits are often exposed to unsuitable climate and low resource availability relative to core populations. As such, there has been a renewed focus on understanding the factors that determine range limits to better predict how species will respond to global change. Using recent theory on range limits and classical understanding of density dependence, we evaluated the influence of resource availability on the snowshoe hareLepus americanusalong its trailing range edge. We estimated variation in population density, habitat use, survival, and parasite loads to test the Great Escape Hypothesis (GEH), i.e. that density dependence determines, in part, a species' persistence along trailing edges. We found that variability in resource availability affected density and population fluctuations and led to trade‐offs in survival for snowshoe hare populations in the northeastern USA. Hares living in resource‐limited environments had lower and less variable population density, yet higher survival and lower parasitism compared to populations living in resource‐rich environments. We suggest that density‐dependent dynamics, elicited by resource availability, provide hares a unique survival advantage and partly explain persistence along their trailing edge. We hypothesize that this low‐density escape from predation and parasitism occurs for other prey species along trailing edges, but the extent to which it occurs is likely conditional on the quality of matrix habitat. Our work indicates that biotic factors play an important role in shaping species' trailing edges and more detailed examination of non‐climatic factors is warranted to better inform conservation and management decisions.
Incubation with porcine urinary bladder matrix yields a late‐stage wound transcriptome in endothelial cells and keratinocytes isolated from both diabetic and non‐diabetic subjects
Authors: Paige John T. , Lightell Daniel J. , Douglas Hunter F. , Klingenberg Natasha C. , Pham Thaidan , Woods T. Cooper
Published: June 2023

Proper wound closure requires the functional coordination of endothelial cells (ECs) and keratinocytes. In the late stages of wound healing, keratinocytes become activated and ECs promote the maturation of nascent blood vessels. In diabetes mellitus, decreased keratinocyte activation and impaired angiogenic action of ECs delay wound healing. Porcine urinary bladder matrix (UBM) improves the rate of wound healing, but the effect of exposure to UBM under diabetic conditions remains unclear. We hypothesized that keratinocytes and ECs isolated from both diabetic and non‐diabetic donors would exhibit a similar transcriptome representative of the later stages of wound healing following incubation with UBM. Human keratinocytes and dermal ECs isolated from non‐diabetic and diabetic donors were incubated with and without UBM particulate. RNA‐Seq analysis was performed to identify changes in the transcriptome of these cells associated with exposure to UBM. While diabetic and non‐diabetic cells exhibited different transcriptomes, these differences were minimized following incubation with UBM. ECs exposed to UBM exhibited changes in the expression of transcripts suggesting an increase in the endothelial–mesenchymal transition (EndoMT) associated with vessel maturation. Keratinocytes incubated with UBM demonstrated an increase in markers of activation. Comparison of the whole transcriptomes with public datasets suggested increased EndoMT and keratinocyte activation following UBM exposure. Both cell types exhibited loss of pro‐inflammatory cytokines and adhesion molecules. These data suggest that application of UBM may accelerate healing by promoting a transition to the later stages of wound healing. This healing phenotype is achieved in cells isolated from both diabetic and non‐diabetic donors.
The surface and internal features of pubic hair: A comparative study with those of scalp hair
Authors: Ryu Soo Ryeon , Suh Jungwoo , Kim Hyeyoung , Shin Kwanwoo
Published: June 2023

Although pubic hair has been a subject of public interest, little is known about its structure or characteristics beyond its curly and coarse appearance. In this study, we investigated the surface and internal features of pubic hair from Korean males and compared them to those of scalp hair from the same donors. Our findings indicate that the cuticle layer of pubic hair has a greater number of scales than that of scalp hair, resulting in a thicker cuticle layer overall. Fourier‐transform infrared (FT‐IR) spectroscopy analysis showed that the protein in the cortex layer of pubic hair was less affected by exposure to urine or ammonia than the protein in the cortex layer of scalp hair. This suggests that the cuticle layer of pubic hair, which is thicker and composed of more scales, acts as a physical barrier that protects the hair's internal structure. Furthermore, we observed that the secondary and tertiary structures of keratin in the pubic hair cuticle layer are essentially different from those in scalp hair. Based on these findings, we hypothesize that the thickened cuticle layer in pubic hair may have evolved as a defence mechanism against chemical damage from urine, urea and ammonia.
Communication about children's origins among same‐gender adoptive parent families in Belgium, France, and Spain
Authors: Messina Roberta , Farr Rachel H. , Tasker Fiona
Published: June 2023

Objective

This study explored communication about children's origins among same‐gender parent adoptive families.

Background

Although this topic has been widely researched among different‐gender parent adoptive families, communication about origins among those with same‐gender parents, as well as sexual minority identity dynamics relevant to this crucial task, remain unexplored.

Method

A sample of same‐gender adoptive couples (N = 31) from Belgium, France, and Spain with children aged between 4 and 18 years (Mage = 8.9 years) participated in a semistructured interview and a graphic projective test aimed at explore their feelings and communication process about their adopted child's birth family.

Results

Inductive thematic analysis yielded a continuum of three main stances conveyed by adoptive parents regarding their child's origins: (a) critical/minimization, (b) cautious/uncertainty, and (c) open/validation. The first (critical/minimization) was associated with experiences of sexual minority stigma and poorer communication about children's origins and sexual minority family‐related issues, while the second (cautious/uncertainty) was characterized by mixed feelings (i.e., at times open, at times critical) in communicating about origins and parents' sexual minority experiences. The third (open/validation) was associated with positive feelings toward adoptive and sexual minority family statuses, as well as identity integration as a lesbian or gay parent and low internalized sexual stigma.

Conclusion

Our findings underline the importance of sexual minority identity issues in relation to communication about children's origins in same‐gender parent adoptive families.

Implications

These findings have important implications for both adoption assessment and therapeutic work with same‐gender adoptive parent families.
Comparing the Fried frailty phenotype versus the Veterans Affairs frailty index among dialysis dependent patients
Authors: Hamiduzzaman Anum , Wu Ruoxue , Murray Victoria , Kalantar‐Zadeh Kamyar , Streja Elani , Sy John
Published: June 2023

Introduction

Frailty in dialysis patients is a modifiable disease state which can increase mortality if left untreated but remains underdiagnosed as frailty evaluations can be arduous or time consuming. We evaluate the agreement between a clinical frailty construct (Fried frailty phenotype, FFP) against and an electronic health record‐based Veterans Affairs Frailty Index (VAFI) and their association with mortality.

Methods

A retrospective cohort analysis of 764 participants from the ACTIVE/ADIPOSE study was performed. Frailty as measured by VAFI and FFP was obtained and Kappa statistic estimating concordance between the two scores were calculated. Differences in mortality risk were analyzed according to presence or absence of frailty.

Findings

When assessing agreement between the VAFI and FFP, the kappa statistic was 0.09 (95% confidence interval [CI] 0.02–0.16) suggesting a low level of agreement. Frailty was independently associated with higher mortality risk (hazards ratio [HR] 1.40–1.42 in fully adjusted models depending upon frailty construct). Discordantly frail patients by construct had a higher risk of mortality though this was not statistically significant after adjustment. However, concordantly frail patients had much higher mortality risk compared to concordantly nonfrail (adjusted HR 2.08, 95% CI 1.44–3.01).

Discussion

Poor agreement between constructs is likely reflective of the multifactorial definition of frailty. While further longitudinal studies are needed to determine if the VAFI would be beneficial in the reassessment of frailty, it may be beneficial as a cue for further frailty testing (e.g., with FFP) with the combination of multiple frail constructs providing improved prognostic information.
The poor antitumor effect of pembrolizumab in advanced upper urothelial carcinoma with renal parenchymal invasion
Authors: Hara Takuto , Furukawa Junya , Okamura Yasuyoshi , Bando Yukari , Terakawa Tomoaki , Harada Kenichi , Takahashi Satoru , Nakano Yuzo , Fujisawa Masato
Published: June 2023

Objectives

We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI).

Methods

This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS.

Results

Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil‐lymphocyte ratio (NLR) ≥ 3, C‐reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI.

Conclusions

RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.
Realization of diversity in physical properties of Zr2Se(B1‐xSex) MAX phases through DFT approach
Authors: Hadi Mohammad A. , Akhter Mehnaj , Ahasan Mohammad Shamim , Ahmed Istiak , Kashem Mohammad A.
Published: June 2023

The discovery of a series of MAX phases, Zr2Se(B1‐xSex), with Se at both A‐ and X‐sites, drives a new chemical diversity to the MAX family. Here, we employed the density functional theory (DFT) approach to realize the diversity in physical properties of Zr2Se(B1‐xSex). All compositions of Zr2Se(B1‐xSex) are mechanically stable and the dynamical stability of the end member Zr2SeSe is confirmed. The elastic constant C33 and bulk moduli B show a decrease almost monotonically with Se‐content x while other constants and moduli change irregularly. All elastic constants and moduli except C12 and C13 are highest for the end member Zr2SeB. Additionally, the Vickers hardness, Debye temperature, minimum thermal conductivity, and lattice thermal conductivity are highest for Zr2SeB. The increase of Se‐content x at X‐site reduces most of the properties of Zr2Se(B1‐xSex). The electronic band structures change drastically with increasing Se‐content x. This diversity in electronic band structures is mainly the reason for the diversity in physical properties of Zr2Se(B1‐xSex). All compositions of Zr2Se(B1‐xSex) have the potential to be thermal barrier coating materials, and Zr2SeB has the potential to be etched into 2D MXene, Zr2B.
A detailed look at the European Medicines Agency's recommendations for use of Janus kinase inhibitors in patients with atopic dermatitis
Authors: Wollenberg Andreas , Thyssen Jacob P. , Bieber Thomas , Chan Gary , Kerkmann Urs
Published: June 2023

Background

Oral Janus kinase inhibitors (JAKi) have been approved for the treatment of several chronic inflammatory conditions, including rheumatoid arthritis (RA) and atopic dermatitis (AD). Prompted by new evidence, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recently reassessed the benefit–risk balance of oral JAKi. The PRAC recommended that oral JAKi should be used only if no suitable alternatives are available in patients ≥65 years of age, or who have a history of atherosclerotic cardiovascular (CV) disease, other CV risk factors (e.g. history of long‐term smoking) or have malignancy risk factors, and used with caution in patients at risk of pulmonary embolism or deep vein thrombosis. The European Commission's final decision was issued in March 2023.

Objectives

Our goal was to highlight the PRAC recommendations, especially in the context of oral JAKi use in AD.

Methods

Authors summarized the PRAC recommendations, the new clinical evidence on oral JAKi safety and key differences between patients with RA and AD.

Results

Risk of developing adverse events of special interest (e.g. cardiovascular events, malignancy) is higher in patients with RA than in patients with AD, because of the higher prevalence of the underlying risk factors.

Conclusions

The benefit–risk profile of JAKi approved for AD remains favourable, including use as first‐line systemic therapy for patients with AD <65 years of age and without CV or malignancy risk factors.
Evaluating a web‐based personalized decision report for total knee or hip replacement: Lessons learned from patients
Authors: Pila Sarah , Stern Brocha Z. , Rothrock Nan E. , Franklin Patricia D.
Published: June 2023

Rationale

Patient‐reported outcomes (PROs) are increasingly used in the context of clinical care, but evaluation of patients' perspectives of PRO‐based applications in routine care remains limited.

Aims and Objectives

This paper investigates patients' acceptability of a personalized web‐based decision report for total knee or hip replacement and identifies opportunities to refine the report.

Method

This qualitative evaluation was embedded in a pragmatic cluster randomized trial of the report. We interviewed 25 patients with knee and hip osteoarthritis about their experiences using the personalized decision report in the context of a surgical consultation. The web‐based report contained current descriptive PRO scores of pain, function and general physical health; tailored predicted postoperative PRO scores (i.e., personalized likely outcomes based on actual knee or hip replacement outcomes of similar patients in a national registry); and information about alternative nonoperative treatments. Two trained researchers analysed the interview data qualitatively using a combination of inductive and deductive coding.

Results

We identified three major categories for evaluation: content of report, presentation of data in report and engagement with report. Patients generally liked the report overall but specifically valued different pages of the report based on where they were in the surgical decision‐making process. Patients identified areas of confusion in data presentation related to graph orientation, terminology and interpretation of T‐scores. Patients also highlighted support needs to meaningfully engage with the information in the report.

Conclusion

Our findings highlight areas of opportunity to further refine this personalized web‐based decision report and similar patient‐facing PRO applications for routine clinical care. Specific examples include additional tailoring of reports via filterable web‐based dashboards and scalable educational supports to facilitate more independent patient understanding and use.
Insights from the judgement bias paradigm: social group and tank size do not affect mental state in female guppies
Authors: Epping Judith , Kotrschal Alexander , Kotrschal Séverine D.
Published: June 2023

Optimal holding conditions are key to animal welfare. How stressful husbandry is perceived by the animal can be determined via an assessment of an animal's mental state – where it is positioned on the continuum between optimistic and pessimistic states – and can be measured using the judgement bias paradigm. In this test, individuals are trained to distinguish a rewarded from an unrewarded cue before being presented an ambiguous, intermediate cue. The response time to the ambiguous cue is then indicative of mental state. A shorter latency suggests a more positive (optimistic) mental state and a longer latency a more negative (pessimistic) mental state. Here, the authors used the judgement bias paradigm to assess the impact of standard laboratory housing conditions on the mental states of female guppies (Poecilia reticulata). As it is debated which holding conditions confer optimal welfare, they tested the impact of husbandry on mental state by keeping animals for 3 weeks in small or large social groups in either small or large tanks. They found that the different standard housing conditions used did not lead to differences in mental state. As an unexpected side result, they found that female guppies seem lateral. Their findings of comparable mental state across housing conditions suggest either that guppies perceive the tested conditions as equally stressful or, alternatively, that guppies are relatively resilient to the combination of group and tank sizes tested in this study. The authors conclude that the judgement bias paradigm can be a useful tool to assess fish welfare.
Participatory development and implementation of a dementia care pathway with intervention bundles in acute care during the coronavirus pandemic: A process evaluation study
Authors: Petry Heidi , Ernst Jutta , Naef Rahel
Published: June 2023

Aims

To explore the implementation of a dementia care pathway in an acute care setting.

Background

Dementia care in acute settings is often constrained by contextual factors. We developed an evidence‐based care pathway with intervention bundles, and implemented it on two trauma units, with the aim to empower staff and improve quality care.

Design

Process evaluation using quantitative and qualitative methods.

Methods

Pre‐implementation, unit staff completed a survey (n = 72) assessing family and dementia care skills and level of evidence‐based dementia care. Post‐implementation, champions (n = 7) completed the same survey, with additional questions on acceptability, appropriateness and feasibility, and participated in a focus group interview. Data were analysed using descriptive statistics and content analysis guided by the Consolidated Framework for Implementation Research (CFIR).

Reporting Guideline

Standards for Reporting Qualitative Research Checklist.

Results

Pre‐implementation, staff's perceived skills in family and dementia care were moderate overall, with high skills in ‘building relationships’ and ‘sustaining personhood’. Evidence‐based interventions were delivered seldom to frequent, with ‘individualized care’ scoring lowest and ‘assessing cognition’ scoring highest. Implementation of the care pathway/intervention bundles was overshadowed by the pandemic, and failed due to major organisational‐ and process‐related barriers. Acceptability scored highest and feasibility lowest, with concerns relating to complexity and compatibility of pathways/bundles when introduced into clinical routines.

Conclusions

Our study implies that organisational and process factors are the most influential determinants to the implementation of dementia care in acute settings. Future implementation efforts should draw on the evolving evidence within implementation science and dementia care research to ensure effective integration and improvement process.

Relevance to Clinical Practice

Our study provides important learning around improving care for persons with dementia and their families in hospitals.

Patient or Public Contribution

A family caregiver was involved in the development of the education and training programme.
Take care of egotism, and redemption will take care of itself: Comments on Tracy Llanera's Richard Rorty: Outgrowing modern nihilism
Authors: Showler Paul D. G.
Published: June 2023

This commentary critically examines two facets of Tracy Llanera's recent book Richard Rorty: Outgrowing Modern Nihilism. First, it considers her interpretation of Richard Rorty's redemptive project. It argues that, while Llanera succeeds in resolving tensions in Rorty's public‐private distinction, her account downplays the role of abnormal discourse within projects of self‐creation. Second, it raises several questions about Llanera's strategy for situating this redemptive project within debates concerning existential nihilism. On her view, one ought to follow Rorty in addressing the problem of egotism instead of the problem of nihilism, since the former is prior to the latter. But it is not clear who counts as an egotist, or why egotists are especially prone to becoming nihilists. Moreover, there are reasons to think that egotism and nihilism are fundamentally different kinds of problems.
Presenting characteristics and progression of pediatric‐onset morphea: Interim analysis of a prospective registry
Authors: Ng Ashley T. , Brandling‐Bennett Heather A. , Drolet Beth A. , Siegel Dawn H. , Chiu Yvonne E.
Published: June 2023

Morphea is a rare fibrosing disorder with a highly variable disease course, which can complicate management. Here, we present a prospective cohort study describing the current treatments used in the management of pediatric‐onset morphea and assessing responses to systemic and topical therapies. Most patients demonstrated inactive disease by 1 year, regardless of treatment, though recurrences were common in our cohort overall (39%). Our results support the need for continuous monitoring of all children with morphea following the completion of treatment, including topical treatment, due to high rates of disease relapse.
Bilateralen coup de sabremorphea in a male child: A rare presentation
Authors: Bansal Shivani , Chojer Parul , Kaur Harmeet , Poonia Kavita
Published: June 2023

En coup de sabreis a rare subtype of morphea. Only a few bilateral cases have been reported to date. We report a case of a 12‐year‐old male child with two linear brownish depressed asymptomatic lesions over the forehead with hair loss on the scalp. After thorough clinical, ultrasonography and brain imaging, a diagnosis of bilateralen coup de sabremorphea was made and the patient was treated with oral steroids and weekly methotrexate.
Plasma exchange—A useful adjunct therapy to red cell exchange in patients with sickle cell disease and multiorgan dysfunction
Authors: Webb C. B. , Yates S. G. , Sarode R. , Kim J.
Published: June 2023

Background

Urgent red cell exchange (RBCx) is indicated for many complications of sickle cell disease (SCD), including acute chest syndrome, stroke, and hepatic/splenic sequestration. Many who receive RBCx remain hospitalized and develop further complications, including multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Therapeutic plasma exchange (TPE) has been advocated as an effective treatment of MODS, but its role in SCD compared with RBCx alone is not well studied.

Methods

We identified all ICU encounters from 2013 to 2019 involving RBCx procedures for MODS or SCD crisis that progressed to MODS, a total of 12 encounters. Data regarding hospital length of stay (LOS), survival, number of TPE procedures following RBCx, and procedure characteristics were collected. Surrogate laboratory markers of end‐organ damage and disease severity scores were recorded at the time of admission, post‐RBCx, post‐TPE, and at discharge.

Results

Eight encounters involved RBCx followed by TPE (TPE group) while four involved RBCx alone (RBCx group). The TPE group had a higher SOFA score at ICU admission (9.5 vs. 7.0), greater predicted mortality, and a statistical trend toward higher disease severity scores following RBCx relative to the RBCx group (p = 0.10). The TPE group showed a significantly greater decrease in SOFA score between RBCx and discharge (p = 0.04). No significant difference in mortality or hospital LOS was observed between the groups.

Conclusion

The findings suggest TPE may be considered as an adjunct treatment for patients with acute complications of SCD that progress to MODS, especially in cases where there is no significant improvement following RBCx.