bluuebunny/crossref_metadata_2025 huggingface dataset:
Resident training to optimize patient-focused menopause management: a multispecialty menopause curriculum to enhance knowledge and preparedness
Authors: Vesco Kimberly K. , Brooks Neon B. , Francisco Melanie C. , Leo Michael C. , Anderson Tovi M. , Kalter Marlene , Clark Amanda L.
Published: January 2024

Objective

Surveys of residents in obstetrics and gynecology, internal medicine, and family medicine have demonstrated low levels of knowledge and comfort in treating patients with menopausal symptoms, suggesting a need for improved training during residency. To address this problem, we used a flipped classroom design to deliver a novel menopause curriculum for medical residents. The curriculum included six podcast episodes followed by an interactive case-based classroom session. We then assessed effects of the curriculum on the residents' knowledge and preparedness to manage menopause symptoms.

Methods

We targeted 200 residents (43 obstetrics and gynecology, 86 internal medicine, and 71 family medicine) from six residency programs from 2019 to 2020. Of these, 115 (58%) completed both pre- and postcurriculum assessments, including a 15-item knowledge test and self-ratings of their knowledge, comfort, and preparedness to manage menopause.

Results

Following the curriculum, the proportion of correctly answered knowledge questions rose from 60.8% to 79.1% (+18.3%; 95% confidence interval, 15.4-21.2; Cohen's d = 1.2). Improvement did not significantly differ by specialty or year of residency. There were higher gains for residents who listened to the entirety of all six podcast episodes (b = 11.4, P < 0.001) and who attended the classroom session (b = 11.6, P = 0.003). Residents' self-ratings of knowledge, comfort, and preparedness also improved following the curriculum across all medical specialties (Cohen's d = 0.47-1.2). Residents rated the podcast format as convenient (73%) and effective (65%) compared with an equivalent amount of reading.

Conclusions

Pairing a podcast with a classroom discussion was found to be an effective combination for improving menopause knowledge.
INDETERMINATE CELL HISTIOCYTOSIS WITH OCULAR INVOLVEMENT IN A NEONATE: A CASE REPORT
Authors: Kassotis Alexis , Yeager Lauren , Bogomolny Dmitry , Marr Brian
Published: January 2024

Purpose:

The authors describe a case of Indeterminate cell histiocytosis, a rare disease of histiocytic proliferation on the spectrum of Langerhans cell histiocytosis.

Methods:

Data were collected through retrospective chart review.

Results:

The authors present a novel case of congenital Indeterminate cell histiocytosis with multisystem disease, including significant pan-ocular involvement. The neonate was successfully treated with the BRAF-kinase inhibitor dabrafenib, local anti-VEGF, and corticosteroid.

Conclusions:

The present case expands on the current ocular presentations of Indeterminate cell histiocytosis.
ASYMPTOMATIC RETINAL DYSFUNCTION AND RETINAL ABNORMALITIES IN A PATIENT WITH ALPHA-METHYLACYL-COA RACEMASE DEFICIENCY
Authors: Kalogeropoulos Dimitrios , Lagha Lilia , Lotery Andrew J.
Published: January 2024

Purpose:

The aim of this study was to present a case of a young female patient with asymptomatic retinal dysfunction associated with alpha-methylacyl-CoA (alpha-methylacyl-CoA racemase) racemase deficiency.

Methods:

This was a retrospective analysis of the medical notes of a single patient. Detailed slit-lamp examination was completed by Optos color fundus photography and enhanced depth imaging optical coherence tomography. Genetic testing was conducted to establish the diagnosis, and the patient was also referred to the Department of Neurology for further assessment.

Results:

Dilated fundoscopy and ophthalmic imaging revealed bilateral retinal pigment epithelium abnormalities that could be associated with a genetic retinal disorder. Indeed, genetic testing showed that this lady was homozygous for alpha-methylacyl-CoA racemase (OMIM 604489; Gene ID 23600) variant NM 014324.6: c.154T>C; p.(Ser52Pro). She had no detectable neurological deficit.

Conclusion:

Alpha-methylacyl-CoA racemase deficiency is a rare genetic condition that can potentially contribute to retinal dystrophy through various mechanisms. In addition, it may lead to a wide spectrum of systemic signs and symptoms. Interestingly, in contrast to other reported studies, the patient was completely asymptomatic, with no evidence of systemic disorders.
Reverse 4-Throw Pupilloplasty for Endothelial Keratoplasty
Authors: Narang Rhea , Agarwal Amar
Published: January 2024

Purpose:

The aim of this study was to describe the feasibility and applicability of a reverse 4-throw (RFT) pupilloplasty technique for endothelial keratoplasty.

Methods:

In RFT, the 9-0 polypropylene suture needle and a 26-Gauge needle pierce the iris tissue from the posterior surface to emerge on the anterior surface along the proximal and distal portion of iris tissue to be apposed, respectively. The 9-0 needle is threaded into the barrel of a 26-Gauge needle and is withdrawn from the eye. The suture loop is withdrawn and the suture end is passed through the loop 4 times. Both suture ends are pulled, which leads to the sliding of the loop inside the eye, thereby apposing the iris tissue with the knot lying on the posterior surface.

Results:

The procedure was performed in 11 eyes of 11 patients who were scheduled to undergo an endothelial keratoplasty procedure. The anterior segment optical coherence tomography image of the RFT pupilloplasty did not denote any presence of the suture in the anterior chamber or along the anterior surface of the iris plane. No incidence of primary graft failure or graft rejection during the entire follow-up period was reported in any of the eyes.

Conclusions:

RFT serves as an effective technique for performing pupilloplasty in endothelial keratoplasty cases without the presence of a knot or suture tail in the anterior chamber.
Caregivers’ and providers’ perspectives of social and medical care after pediatric liver transplant: Results from the multicenter SOCIAL-Tx study
Authors: Wadhwani Sharad I. , Alvarado Alejandra , Shifman Holly P. , Bautista Bethany , Yalung Jared , Squires James E. , Campbell Kathleen , Ebel Noelle H. , Hsu Evelyn , Vittorio Jennifer , Zielsdorf Shannon , Desai Dev M. , Bucuvalas John C. , Gottlieb Laura , Kotagal Uma , Lyles Courtney R. , Ackerman Sara L. , Lai Jennifer C.
Published: January 2024

Disparities exist in pediatric liver transplant (LT). We characterized barriers and facilitators to providing transplant and social care within pediatric LT clinics. This was a multicenter qualitative study. We oversampled caregivers reporting household financial strain, material economic hardship, or demonstrating poor health literacy. We also enrolled transplant team members. We conducted semistructured interviews with participants. Caregiver interviews focused on challenges addressing transplant and household needs. Transplant provider interviews focused on barriers and facilitators to providing social care within transplant teams. Interviews were recorded, transcribed, and coded according to the Capability, Opportunity, Motivation-Behavior model. We interviewed 27 caregivers and 27 transplant team members. Fifty-two percent of caregivers reported a household income <$60,000, and 62% reported financial resource strain. Caregivers reported experiencing (1) high financial burdens after LT, (2) added caregiving labor that compounds the financial burden, (3) dependency on their social network’s generosity for financial and logistical support, and (4) additional support being limited to the perioperative period. Transplant providers reported (1) relying on the pretransplant psychosocial assessment for identifying social risks, (2) discomfort initiating social risk discussions in the post-transplant period, (3) reliance on social workers to address new social risks, and (4) social workers feeling overburdened by quantity and quality of the social work referrals. We identified barriers to providing effective social care in pediatric LT, primarily a lack of comfort in assessing and addressing new social risks in the post-transplant period. Addressing these barriers should enhance social care delivery and improve outcomes for these children.
Videos for Psychiatric Education
Authors: Schildkrout Barbara
Published: January 2024

The field of psychiatry has been limited in its use of patient videos for educational purposes because essential facial information must be obscured to protect patient privacy, confidentiality, and dignity. This article calls attention to emerging technologies for deidentification of patients in video recordings while still preserving facial expression. Fully anonymized videos could be used to augment the education of psychiatric residents and for continuing education of the psychiatric workforce. This article suggests projects that deidentification technology could make possible; it also outlines some complex problems that would need to be addressed before the field could use this potentially transformative technology.
Nucleoid-associated proteins shape the global protein occupancy and transcriptional landscape of a clinical isolate ofVibrio cholerae
Authors: Rakibova Yulduz , Dunham Drew T. , Seed Kimberley D. , Freddolino P. Lydia
Published: January 2024

Vibrio cholerae, the causative agent of the diarrheal disease cholera, poses an ongoing health threat due to its wide repertoire of horizontally acquired elements (HAEs) and virulence factors. New clinical isolates of the bacterium with improved fitness abilities, often associated with HAEs, frequently emerge. The appropriate control and expression of such genetic elements is critical for the bacteria to thrive in the different environmental niches it occupies. H-NS, the histone-like nucleoid structuring protein, is the best studied xenogeneic silencer of HAEs in gamma-proteobacteria. Although H-NS and other highly abundant nucleoid-associated proteins (NAPs) have been shown to play important roles in regulating HAEs and virulence in model bacteria, we still lack a comprehensive understanding of how different NAPs modulate transcription inV. cholerae. By obtaining genome-wide measurements of protein occupancy and active transcription in a clinical isolate ofV. cholerae,harboring recently discovered HAEs encoding for phage defense systems, we show that a lack of H-NS causes a robust increase in the expression of genes found in many HAEs. We further found that TsrA, a protein with partial homology to H-NS, regulates virulence genes primarily through modulation of H-NS activity. We also identified a few sites that are affected by TsrA independently of H-NS, suggesting TsrA may act with diverse regulatory mechanisms. Our results demonstrate how the combinatorial activity of NAPs is employed by a clinical isolate of an important pathogen to regulate recently discovered HAEs.

Importance

New strains of the bacterial pathogenVibrio cholerae, bearing novel horizontally acquired elements (HAEs), frequently emerge. HAEs provide beneficial traits to the bacterium, such as antibiotic resistance and defense against invading bacteriophages. Xenogeneic silencers are proteins that help bacteria harness new HAEs and silence those HAEs until they are needed. H-NS is the best-studied xenogeneic silencer; it is one of the nucleoid-associated proteins (NAPs) in gamma-proteobacteria and is responsible for the proper regulation of HAEs within the bacterial transcriptional network. We studied the effects of H-NS and other NAPs on the HAEs of a clinical isolate ofV. cholerae. Importantly, we found that H-NS partners with a small and poorly characterized protein, TsrA, to help domesticate new HAEs involved in bacterial survival and in causing disease. Proper understanding of the regulatory state in emerging isolates ofV. choleraewill provide improved therapies against new isolates of the pathogen.
Spindle Oscillation Emerges at the Critical State of the Electrically Coupled Network in Thalamic Reticular Nucleus
Authors: Li Shangyang , Wang Chaoming , Wu Si
Published: January 2024

Spindle oscillation is a waxing-and-waning neural oscillation observed in the brain, initiated at the thalamic reticular nucleus (TRN) and typically occurring at 7-15 Hz. Experiments have shown that in the adult brain, electrical synapses, rather than chemical synapses, dominate between TRN neurons, suggesting that the traditional view of spindle generation via chemical synapses may need reconsideration. Based on known experimental data, we develop a computational model of the TRN network, where heterogeneous neurons are connected by electrical synapses. The model shows that the interplay between synchronizing electrical synapses and desynchronizing heterogeneity leads to multiple synchronized clusters with slightly different oscillation frequencies, whose summed activity produces spindle oscillation as seen in local field potentials. Our results suggest that during spindle oscillation, the network operates at the critical state, which is known for facilitating efficient information processing. This study provides insights into the underlying mechanism of spindle oscillation and its functional significance.
Pose analysis in free-swimming adult zebrafish,Danio rerio: “fishy” origins of movement design
Authors: Kanwal Jagmeet S. , Sanghera Bhavjeet , Dabbi Riya , Glasgow Eric
Published: January 2024

Movement requires maneuvers that generate thrust to either make turns or move the body forward in physical space. The computational space for perpetually controlling the relative position of every point on the body surface can be vast. We hypothesize the evolution of efficient design for movement that minimizes active (neural) control by leveraging the passive (reactive) forces between the body and the surrounding medium at play. To test our hypothesis, we investigate the presence of stereotypical postures during free-swimming in adult zebrafish,Danio rerio. We perform markerless tracking using DeepLabCut, a deep learning pose estimation toolkit, to track geometric relationships between body parts. To identify putative clusters of postural configurations obtained from twelve freely behaving zebrafish, we use unsupervised multivariate time-series analysis (B-SOiD machine learning software). When applied to single individuals, this method reveals a best-fit for 36 to 50 clusters in contrast 86 clusters for data pooled from all 12 animals. The centroids of each cluster obtained over 14,000 sequential frames recorded for a single fish represent anaprioriclassification into relatively stable “target body postures” and inter-pose “transitional postures” that lead to and away from a target pose. We use multidimensional scaling of mean parameter values for each cluster to map cluster-centroids within two dimensions of postural space. From apost-priorivisual analysis, we condense neighboring postural variants into 15 superclusters or core body configurations. We develop a nomenclature specifying the anteroposterior level/s (upper, mid and lower) and degree of bending. Our results suggest that constraining bends to mainly three levels in adult zebrafish preempts the neck, fore- and hindlimb design for maneuverability in land vertebrates.
The E3 ubiquitin ligase TRIM9 regulates synaptic function and actin dynamics
Authors: McCormick Laura E. , Evans Elliot B. , Barker Natalie K. , Herring Laura E. , Diering Graham H. , Gupton Stephanie L.
Published: January 2024

During neuronal development, dynamic filopodia emerge from dendrites and mature into functional dendritic spines during synaptogenesis. Dendritic filopodia and spines respond to extracellular cues, influencing dendritic spine shape and size as well as synaptic function. Previously, the E3 ubiquitin ligase TRIM9 was shown to regulate filopodia in early stages of neuronal development, including netrin-1 dependent axon guidance and branching. Here we demonstrate TRIM9 also localizes to dendritic filopodia and spines of murine cortical and hippocampal neurons during synaptogenesis and is required for synaptic responses to netrin. In particular, TRIM9 is enriched in the post-synaptic density (PSD) within dendritic spines and loss ofTrim9alters the PSD proteome, including the actin cytoskeleton landscape. While netrin exposure induces accumulation of the Arp2/3 complex and filamentous actin in dendritic spine heads, this response is disrupted by genetic deletion ofTrim9. In addition, we document changes in the synaptic receptors associated with loss ofTrim9. These defects converge on a loss of netrindependent increases in neuronal firing rates, indicating TRIM9 is required downstream of synaptic netrin-1 signaling. We propose TRIM9 regulates cytoskeletal dynamics in dendritic spines and is required for the proper response to synaptic stimuli.
Conditioned overconsumption is dependent on reinforcer type in lean, but not obese, mice
Authors: Lewis-Sanders Darielle , Bullich Sebastien , Olvera Maria Jose , Vo John , Hwang Yang-Sun , Stern Sarah A.
Published: January 2024

Associative learning can drive many different types of behaviors, including food consumption. Previous studies have shown that cues paired with food delivery while mice are hungry will lead increased consumption in the presence of those cues at later times. We previously showed that overconsumption can be driven in male mice by contextual cues, using chow pellets. Here we extended our findings by examining other parameters that may influence the outcome of context-conditioned overconsumption training. We found that the task worked equally well in males and females, and that palatable substances such as high-fat diet and Ensure chocolate milkshake supported learning and induced overconsumption. Surprisingly, mice did not overconsume when sucrose was used as the reinforcer during training, suggesting that nutritional content is a critical factor. Interestingly, we also observed that diet-induced obese mice did not learn the task. Overall, we find that context-conditioned overconsumption can be studied in lean males and female mice, and with multiple reinforcer types.
A food color based colorimetric assay forCryptococcus neoformanslaccase activity
Authors: Ramirez Lia Sanchez , Dragotakes Quigly , Casadevall Arturo
Published: January 2024

Cryptococcus neoformansis a fungal pathogen that causes cryptococcosis mostly in immune compromised patients, such as those with HIV/AIDS. One survival mechanism ofC. neoformansduring infection is melanin production, which catalyzed by laccase, and protects fungal cells against immune attack. Hence comparative assessment of laccase activity is useful for characterizing cryptococcal strains. We serendipitously observed that culturingC. neoformanswith food coloring resulted in the degradation of some dyes with phenolic structures. Consequently, we investigated the color changes for the food dyes metabolized byC. neoformanslaccase and explored using this effect for the development of a colorimetric assay to measure laccase activity. We developed several versions of a food dye based colorimetric laccase assay that can be used to compare the relative laccase activities between differentC. neoformansstrains. We found that phenolic color degradation was glucose dependent, which may reflect changes in the reduction properties of the media. Our food color based colorimetric assay has several advantages over the commonly used 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay for laccase activity, including lower cost, irreversibility, and does not require constant monitoring. This method has potential applications to bioremediation of water pollutants in addition to its use in determining laccase virulence factor expression.

Importance

Cryptococcus neoformansis present in the environment and while infection is common, disease occurs mostly in immunocompromised individuals.C. neoformansinfection in the lungs results in symptoms like pneumonia, and consequently cryptococcal meningitis occurs if the fungal infection spreads to the brain. The laccase enzyme catalyzes the melanization reaction that serves as a virulence factor ofC. neoformans. Developing a simple and less costly assay to determine laccase activity inC. neoformansstrains can be useful for a variety of procedures ranging from studying the relative virulence of cryptococci to environmental pollution studies.
Applied nonrelativistic conformal field theory: Scattering-length and effective-range corrections to rate of production of three neutrons at low relative momenta
Authors: Chowdhury Subham Dutta , Mishra Ruchira , Son Dam Thanh
Published: January 2024

Due to an accidentally large s-wave scattering length, in a relatively wide range of energy, neutrons are approximately described by the nonrelativistic conformal field theory of unitarity fermions, perturbed by one relevant and an infinite number of irrelevant operators. We develop a formalism which provides a nonperturbative definition of local operators in that nonrelativistic conformal field theory. We compute the scattering-length and effective-range corrections to the two-point functions of primary charge-three operators using the technique of conformal perturbation theory. These calculations allow us to find the first corrections to the scale-invariant behavior of the rate of nuclear reactions with three neutrons in the final state in the regime when the neutrons have small relative momenta.

Published by the American Physical Society
2024
Kinetic relaxation and nucleation of Bose stars in self-interacting wave dark matter
Authors: Jain Mudit , Wanichwecharungruang Wisha , Thomas Jonathan
Published: January 2024

We revisit kinetic relaxation and soliton/boson star nucleation in fuzzy scalar dark matter featuring short-ranged self-interactions Hint=−λ|ψ|4/2m2, alongside gravitational self-interactions. We map out the full curve of nucleation timescale for both repulsive (λ<0) and attractive (λ>0) short-ranged self-interaction strength and in doing so reveal two new points. Firstly, besides the two usual terms, ∝G2 and ∝λ2, in the total relaxation rate Γrelax, there is an additional cross term ∝Gλ arising due to interference between gravitational and short-ranged self-interaction scattering amplitudes. This yields a critical repulsive interaction strength λcr≃−2πGm2/v02, at which the relaxation rate is smallest and serves as the transition point between typical net attractive self-interaction (λ≳λcr) and net repulsive self-interaction (−λ≳−λcr). Secondly, while in the net attractive regime, nucleation timescale is similar to inverse relaxation timescale τnuc∼Γrelax−1; in the net repulsive regime, nucleation occurs at a delayed time τnuc∼(λ/λcr)Γrelax−1. We confirm our analytical understanding by performing 3D field simulations with varying average mass density ρ¯, box size L and grid size N.

Published by the American Physical Society
2024
Modeling the influence of online communities and social commerce
Authors: Patwa Nitin , Gupta Monika , Mittal Amit
Published: January 2024

Purpose

This paper aims to explain how Web 2.0, social connectedness online, has created incredible new business options. This research’s primary goal is to help businesses use these resources more effectively and perform better.

Design/methodology/approach

Variance-based structural equation modeling with the ADANCO program was used to examine the data. ADANCO software is used explicitly for variance-based structural equation modeling. To evaluate research models and test hypotheses, partial least square path modeling is used.

Findings

Theories encompassing social support and related approaches to “word of mouth” online, electronic purchasing and virtual communities mediated by technological platforms are the foundational frameworks for this research piece. It then produces a statistical model that enables users to predict how social commerce (s-commerce) building blocks, including forums, communities, ratings and reviews and recommendations, assist businesses in introducing innovative strategies to win in the digital markets. The results necessarily focus on trust, an essential component of e-commerce. Reciprocally, the study reverses engineer’s trust through the constructs of this moment mentioned.

Research limitations/implications

The present study describes the scope of empirical testing and validation of this framework and assists practitioners in further strengthening s-commerce strategy, an emerging and essential platform in the e-commerce industry.

Originality/value

Research highlights the dearth of current analysis in such conceptual domains while generating novel research insights aimed at e-commerce and digital business. From the viewpoint of potential and recurring customers who interact with online communities and product offerings, the study captures the essence of human interactions, often known as trade relationships, online.
An exploration of women entrepreneurs “doing context” in family business in the Gulf States
Authors: Hashim Sumaya , McAdam Maura , Nordqvist Mattias
Published: January 2024

Purpose

Drawing on indigenous theory of Ibn Khaldun, the rise and fall of States, this paper explores the agency of women entrepreneurs in family business in Bahrain and the underlying enablers in supporting and facilitating the exercise of this agency. This study attempts to move beyond the Western-centric studies to reflect and bring to light the unique institutional settings of the Gulf States.

Design/methodology/approach

The research builds on a rich qualitative single case of a family business based in Bahrain. The single case study methodology was motivated by the potential for generating rich contextual insights. Such an approach is particularly valuable to gain a more holistic and deeper understanding of the contextualized phenomenon and its complexity.

Findings

In this study the authors show how women entrepreneurs take two different paths to enter and become involved in the family business, the barriers they are subjected to and the active role they play in dismantling the challenges to the extent that they become the main mediators between the family business and central institutions in society.

Originality/value

By incorporating indigenous theory with Western family business concepts, the study extends existing understanding of women entrepreneurs in family business by underscoring the agency that women entrepreneurs have in “doing context” and the role that women play in strengthening common cause and destiny within the family and the business by building and drawing on different forms of loyalty.
Employees’ preferred extent for working from home – relationships with emotional job and childcare demands
Authors: Rashkovits Sarit , Unger-Aviram Esther
Published: January 2024

Purpose

To better understand employees’ preferred extent for working from home (WFH) setting that implies physical distance from clients and co-workers and enhanced physical proximity to others at home, this study, relying on job-demands resources (J-DR) theory, aims to investigate the relationships between this preference with both the perceived increase in emotional job demands and the exposure to childcare demands. Thus, this study aims to investigate the mediating role of perceived job difficulty in the relationship between emotional job demands and the preferred extent for WFH, and the moderating role of gender in the relationship between the number of children and the preferred extent for WFH.

Design/methodology/approach

A total of 239 employees who began WFH during the pandemic completed an online survey. Structural equation modelling was conducted to analyse the data and test the hypotheses.

Findings

As expected, an increase in emotional job demands had a significant negative indirect association with the preferred extent for WFH, through perceived increase in job difficulty. Furthermore, the number of children was negatively related to the preferred extent for WFH among male but not female employees.

Practical implications

The findings provide insights for promoting employees’ preferred extent for WFH.

Originality/value

The study points to a relationship between emotional job demands and employee attitudes towards WFH in terms of increased job difficulty and the preferred extent for WFH. It also points to the need to investigate the interaction between sex and number of children to understand employees’ preferred extent for WFH.
Implementing action competence teaching model as a framework for achieving sustainable development goals: insights from students
Authors: Xing Xiaojing , Ironsi Chinaza Solomon
Published: January 2024

Purpose

This paper aims to explore the potential of implementing an action competence teaching model as a framework for achieving sustainable development goals (SDGs) in higher education. The paper seeks to draw insights from the students on the potential of this teaching model.

Design/methodology/approach

The study adopted a quantitative research design in exploring the potential of an action competence teaching model. This study used self-report measures to obtain insights into the objective of the study.

Findings

The action competence teaching model was seen as useful in equipping students with knowledge about a problem, confidence and willingness to act. However, some issues like the design of the projects, teamwork and instructional practices were identified and discussed.

Originality/value

To the best of the authors’ knowledge, this study is the first to implement an action competence teaching model to help draw insights from students on its potential. This paper documents certain aspects of action competence that require attention before being implemented in higher education. This information so far lacking in scientific literature contributes to ongoing discussions on SDGs while unveiling strengths and weaknesses to be considered.
Propionate alleviates itch in murine models of atopic dermatitis by modulating sensory TRP channels of dorsal root ganglion
Authors: Xu Yao , Qiu Zhuoqiong , Gu Chaoying , Yu Su , Wang Shangshang , Li Changlin , Yao Xu , Li Wei
Published: January 2024

Background

Itch is the most common symptom of atopic dermatitis (AD) and significantly decreases the quality of life. Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism.

Methods

Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology/immunofluorescent analysis. Primary‐cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in vitro calcium imaging/in vivo miniature two‐photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism.

Results

Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro, attenuated the hyper‐excitability in sensory neurons in MC903‐induced AD model, and inhibited capsaicin‐evoked hTRPV1 currents (IC50 = 20.08 ± 1.11 μM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene‐related peptide by nerves in MC903‐induced AD mouse model, which further attenuated itch and skin inflammation.

Conclusion

Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD.
Relevance of different prognostic scores in primary CNS lymphoma in the era of intensified treatment regimens: A retrospective, multicenter analysis of 174 patients
Authors: Zeremski Vanja , Adolph Louisa , Beer Sina , Berisha Mirjeta , Jacobs Benedikt , Kahl Christoph , Koenecke Christian , Kropf Siegfried , Panse Jens , Petersen Judith , Schmidt‐Hieber Martin , Schneider Jessica , Vucinic Vladan , Walter Jeanette , Weigert Oliver , Witte Hanno M. , Mougiakakos Dimitrios
Published: January 2024

Objectives

Treatment intensification (including consolidative high‐dose chemotherapy with autologous stem cell transplantation [HDT‐ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients.

Methods

We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression‐free survival (PFS): Memorial Sloan‐Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three‐factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance.

Results

Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT‐ASCT. Two‐year OS and 2‐year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p = .003) and 3F score (p < .001), but not the IELSG score (p = .06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C‐index [0.71]) outperformed both the MSKCC (C‐index [0.64]) and IELSG (C‐index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C‐index (0.66).

Conclusion

The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches.
Current development of chimeric antigen receptor T‐cell therapy for diffuse large B‐cell lymphoma and high‐grade B‐cell lymphoma
Authors: Yamauchi Nobuhiko , Maruyama Dai
Published: January 2024

Chimeric antigen receptor (CAR) T‐cell therapy has become a commercially available treatment option for relapsed or refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) with two or more lines of prior therapies, and recently for high‐risk r/r DLBCL with one prior line of therapy. The successful development of CAR T‐cell therapy for multiple relapsed DLBCL has led to a boom in subsequent trials that investigated its utility in patients with other r/r B‐cell lymphoma subtypes. However, CAR T‐cell therapy is a multistep process that includes leukapheresis and manipulation which take several weeks. Therefore, patients with rapidly progressing or bulky disease may not be able to complete the therapeutic regimen involving CAR T‐cell products. This raises the question of the generalizability of the results of pivotal studies to the entire population. In this review, we summarize the development of CAR‐T cell therapy for B‐cell lymphoma and discuss strategies to further improve the clinical outcomes of this treatment.
Epilepsy and the risk of adverse cardiovascular events: A nationwide cohort study
Authors: Mayer Josephine , Fawzy Ameenathul M. , Bisson Arnaud , Pasi Marco , Bodin Alexandre , Vigny Pascal , Herbert Julien , Marson Anthony G. , Lip Gregory Y. H. , Fauchier Laurent
Published: January 2024

Background and purpose

Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross‐sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE).

Methods

Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow‐up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all‐cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest.

Results

A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all‐cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67–2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11–2.20), heart failure (IRR = 1.26, 95% CI = 1.25–1.28), IS (IRR = 2.08, 95% CI = 2.04–2.13), VT/VF (IRR = 1.10, 95% CI = 1.04–1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04–2.20). When accounting for all‐cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55–1.63) and for cardiac arrest of 1.73 (95% CI = 1.58–1.89) demonstrated higher risk in PWE.

Conclusions

The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE.
Pityriasis rosea: dermoscopic features in Uganda
Authors: Kiptis Paul K. , Mirembe Stephen K. , Aloyomola Gladys , Mulyowa Grace K.
Published: January 2024

Purpose

The study aimed to describe the dermoscopic features of pityriasis rosea among patients attending the skin clinic at Mbarara Regional Referral Hospital.

Patients and methods

A hospital‐based cross‐sectional descriptive study conducted for a 6‐month period in the skin clinic of MRRH in Southwestern Uganda. Data were collected from consecutively recruited patients using structured questionnaires. Patients with a clinical diagnosis of pityriasis rosea were examined using a dermoscope and subsequently sent for KOH and TPHA tests to rule out fungal skin infection and secondary syphilis, respectively, and then received routine care at the skin clinic.

Results

There were 54 patients with pityriasis rosea seen. Dermoscopy was done on a total of 162 lesions of which 19 were herald patches, 51 were truncal lesions, 52 on the extremities while 40 were on the face and neck regions. Common dermoscopic features consisted of a violaceous background noted in 145 (89.51%), white scales in 161 (99.38%), diffuse scale distribution in 57 (35.19%), perifollicular scale type in 61 (37.65%), and brown‐dotted pigmentary changes in 66 (40.74%). Other unique findings noted in a few lesions were cloudy structures, petechial spots, erosions, and punched out pits.

Conclusion

Most prevalent dermoscopic features included: a violaceous background, white scales, diffuse scale distribution, perifollicular scale type, brown‐dotted pigmentary changes with no visible blood vessels nor follicular changes. Other unique less frequently seen findings were cloudy structures, petechial spots, erosions, and punched out pits.
Analysis of the circumstances associated with death and predictors of mortality in Spanish adults with Down syndrome, 1997–2014
Authors: Aparicio Paloma , Alonso‐Babarro Alberto , Barba Raquel , Moldenhauer Fernando , Suárez Carmen , de Asúa Diego Real
Published: January 2024

Objectives

Characterise the circumstances associated with death during admission of adults with Down syndrome (DS) and to identify predictors of mortality.

Patients and Methods

Observational study based on data on all emergent admissions of adults with DS to hospitals of the Spanish National Health System between 1997 and 2014. We analysed epidemiological and clinical variables.

Results

We analysed admissions of 11,594 adults with DS, mean age 47 years. 1715 patients died (15%), being the highest mortality (35%) in individuals aged 50–59. A past medical history of cerebrovascular disease (aOR 2.95 [2.30–3.77]) or cancer (aOR 2.79 [2.07–3.75]), gross aspiration's admission (aOR 2.59 [2.20–3.04]), immobility (aOR 2.31 [1.46–3‐62]), and readmission within 30 days (aOR 2.43 [2.06–2.86]) were identified as predictors of mortality.

Conclusions

Adults with DS have a high in‐hospital mortality rate. The main predictors of death were cerebrovascular disease, cancer, early readmission, and conditions commonly associated with advanced dementia.
Online collaborative tools for science education: Boosting learning outcomes, motivation, and engagement
Authors: Ateş Hüseyin , Köroğlu Mustafa
Published: January 2024

Background

Online collaboration tools have been identified as potentially effective means for enhancing student learning, motivation, and engagement in science education. However, their effectiveness in improving science education outcomes among middle school students remains uncertain.

Objectives

The study aimed to investigate the impact of online collaboration tools on science education outcomes among middle school students, focusing on learning achievement, engagement, and motivation.

Methods

A quasi‐experimental design with a pretest‐posttest control group was used in this study. A total of 60 eighth‐grade middle school students were involved in the study, with both the experimental and control groups comprising 30 students each. The experimental group incorporated the use of digital collaboration platforms, including Asana, Slack, and Team Viewer, as instrumental components of group project execution and discussion in their science lessons. Conversely, the control group adhered to the current educational approach in Turkey, characterized by the employment of an inquiry‐based learning strategy in their science instruction. Data was collected over eight weeks using a science achievement test, engagement scale, and science motivation scale.

Results

The experimental group demonstrated significantly higher post‐test scores compared to the control group, suggesting that online collaboration tools positively impacted science education outcomes. Additionally, survey data indicated high levels of engagement and motivation among the experimental group students when using the online collaboration tools.

Conclusions

The findings support the notion that online collaboration tools can effectively enhance learning, motivation, and engagement in science education among middle school students. These results have significant implications for educators, educational institutions, policymakers, and curriculum developers. Further research is needed to examine the potential of these tools in various educational contexts and with different student populations. This will help broaden the understanding of how online collaboration tools can be integrated into diverse learning environments, potentially benefiting a larger number of students and further improving science education outcomes.
Exosome‐delivered miR‐410‐3p reverses epithelial‐mesenchymal transition, migration and invasion of trophoblasts in spontaneous abortion
Authors: Chen Zhen‐yue , Li Zhen , Zong Yun , Xia Bo , Luo Song‐ping , Deng Gao‐pi , Gao Jie
Published: January 2024

Current studies have indicated that insufficient trophoblast epithelial‐mesenchymal transition (EMT), migration and invasion are crucial for spontaneous abortion (SA) occurrence and development. Exosomal miRNAs play significant roles in embryonic development and cellular communication. Hereon, we explored the roles of serum exosomes derived from SA patients on trophoblast EMT, migration and invasion. Exosomes were isolated from normal control (NC) patients with abortion for unplanned pregnancy and SA patients, then characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. Exosomal miRNA profiles were identified by miRNA sequencing. The effects of serum exosomes on trophoblast migration and invasion were detected by scratch wound healing and transwell assays, and other potential mechanisms were revealed by quantitative real‐time PCR (RT‐PCR), western blotting and dual‐luciferase reporter assay. Finally, animal experiments were used to explore the effects of exosomal miR‐410‐3p on embryo absorption in mice. The serum exosomes from SA patients inhibited trophoblast EMT and reduced their migration and invasion ability in vitro. The miRNA sequencing showed that miR‐410‐3p was upregulated in SA serum exosomes. The functional experiments showed that SA serum exosomes restrained trophoblast EMT, migration and invasion by releasing miR‐410‐3p. Mechanistically, SA serum exosomal miR‐410‐3p inhibited trophoblast cell EMT, migration and invasion by targeting TNF receptor‐associated factor 6 (TRAF6) at the post‐transcriptional level. Besides, SA serum exosomal miR‐410‐3p inhibited the p38 MAPK signalling pathway by targeting TRAF6 in trophoblasts. Moreover, milk exosomes loaded with miR‐410‐3p mimic reached the maternal‐fetal interface and aggravated embryo absorption in female mice. Clinically, miR‐410‐3p and TRAF6 expression were abnormal and negatively correlated in the placental villi of SA patients. Our findings indicated that exosome‐derived miR‐410‐3p plays an important role between SA serum and trophoblasts in intercellular communication, suggesting a novel mechanism by which serum exosomal miRNA regulates trophoblasts in SA patients.
MicroRNA‐26a alleviates tubulointerstitial fibrosis in diabetic kidney disease by targeting PAR4
Authors: Qu Gaoting , Li Xingyue , Jin Ran , Guan Dian , Ji Jialing , Li Shanwen , Shi Huimin , Tong Pingfan , Gan Weihua , Zhang Aiqing
Published: January 2024

Our previous study found that miR‐26a alleviates aldosterone‐induced tubulointerstitial fibrosis (TIF). However, the effect of miR‐26a on TIF in diabetic kidney disease (DKD) remains unclear. This study clarifies the role and possible mechanism of exogenous miR‐26a in controlling the progression of TIF in DKD models. Firstly, we showed that miR‐26a was markedly decreased in type 2 diabetic db/db mice and mouse tubular epithelial cells (mTECs) treated with high glucose (HG, 30 mM) using RT‐qPCR. We then used adeno‐associated virus carrying miR‐26a and adenovirus miR‐26a to enhance the expression of miR‐26a in vivo and in vitro. Overexpressing miR‐26a alleviated the TIF in db/db mice and the extracellular matrix (ECM) deposition in HG‐stimulated mTECs. These protective effects were caused by reducing expression of protease‐activated receptor 4 (PAR4), which involved in multiple pro‐fibrotic pathways. The rescue of PAR4 expression reversed the anti‐fibrosis activity of miR‐26a. We conclude that miR‐26a alleviates TIF in DKD models by directly targeting PAR4, which may provide a novel molecular strategy for DKD therapy.
Complex adaptive organisations: How three‐dimensional visualisations can help to understand their structures and behaviours
Authors: Sturmberg Joachim P. , Gainsford Len
Published: January 2024

Many organisations struggle to achieve their true potential. In part it is a problem of organisational design, which is an outcome of a particularly common—command and control—leadership philosophy. The traditional linear hierarchical structure of organisations suggests that all knowledge and power concentrates at the top organisational layer, and that people in the lower layers need to be told what to do and when. These arrangements disempower people at the lower level, preventing them from providing the necessary feedback to pre‐emptively address emerging concerns. Systems and complexity thinking provide different ways of understanding organisations and their complex adaptive behaviours. In this paper, we first describe the key characteristics of complex adaptive organisations—their structure and dynamic behaviours—and then propose a three‐dimensional visualisation of a complex adaptive organisation that allows its members to clearly see and appreciate its interdependencies.