bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal degeneration and lumbar multifidus muscle quality may independently affect clinical outcomes in patients conservatively managed for low back or leg pain
Authors: Cooley Jeffrey R. , Jensen Tue S. , Kjaer Per , Jacques Angela , Theroux Jean , Hebert Jeffrey J.
Published: April 2024

Few non-surgical, longitudinal studies have evaluated the relations between spinal degeneration, lumbar multifidus muscle (LMM) quality, and clinical outcomes. None have assessed the potential mediating role of the LMM between degenerative pathology and 12-month clinical outcomes. This prospective cohort study used baseline and 12-month follow-up data from 569 patients conservatively managed for low back or back-related leg pain to estimate the effects of aggregate degenerative lumbar MRI findings and LMM quality on 12-month low back and leg pain intensity (0–10) and disability (0–23) outcomes, and explored the mediating role of LMM quality between degenerative findings and 12-month clinical outcomes. Adjusted mixed effects generalized linear models separately estimated the effect of aggregate spinal pathology and LMM quality. Mediation models estimated the direct and indirect effects of pathology on leg pain, and pathology and LMM quality on leg pain, respectively. Multivariable analysis identified a leg pain rating change of 0.99 [0.14; 1.84] (unstandardized beta coefficients [95% CI]) in the presence of ≥ 4 pathologies, and a disability rating change of − 0.65 [− 0.14; − 1.16] for each 10% increase in muscle quality, but no effect on back pain intensity. Muscle quality had a non-significant mediating role (13.4%) between pathology and leg pain intensity. The number of different pathologies present demonstrated a small effect on 12-month leg pain intensity outcomes, while higher LMM quality had a direct effect on 12-month disability ratings but no mediating effect between pathology and leg pain. The relations between degenerative pathology, LMM quality, and pain-related outcomes appear complex and may include independent pathways.
Research on optimization of basic rail top bending prediction model
Authors: Liu Chunjiang , Dong Zhikui , Ma Long , Hou Xinyu , Qiao Nanbing
Published: April 2024

Since the basic rail of the switch needs to have a certain bending angle when the train changes direction, top bending is an important link in the production process of the basic rail. The three-point pressure top bending method is simple, flexible and widely used. In this study, the traditional three-point pressure bending is optimized, the influence of the pick width in the model is considered, a corresponding rebound model is established, and the model is applied to the pressure bending process of the basic rail. The bilinear strengthening model of the material was used to construct the bending moment expressions at different positions during the top bending process, and the relationship between the load and bending deflection in the elastic stage and elastic-plastic stage was obtained. The final top bending prediction model was obtained by combining the load-deflection model in the bending stage and the rebound stage. The correctness of the theoretical mathematical model was verified by establishing finite element simulations, and the theoretical calculation results were compared with the experimental results. The results showed that the top bend prediction optimization model established in this study had high feasibility and met the machining accuracy requirements.
Multi-omics pan-cancer study of SPTBN2 and its value as a potential therapeutic target in pancreatic cancer
Authors: Chang Hongliang , Chen Hong , Ma Taiheng , Ma Kexin , Li Yi , Suo Lida , Liang Xiangnan , Jia Kunyu , Ma Jiahong , Li Jing , Sun Deguang
Published: April 2024

SPTBN2 is a protein-coding gene that is closely related to the development of malignant tumors. However, its prognostic value and biological function in pan-cancer, especially pancreatic cancer (PAAD), have not been reported. In the present study, a novel exploration of the value and potential mechanism of SPTBN2 in PAAD was conducted using multi-omics in the background of pan-cancer. Via various database analysis, up-regulated expression of SPTBN2 was detected in most of the tumor tissues examined. Overexpression of SPTBN2 in PAAD and kidney renal clear cell cancer patients potentially affected overall survival, disease-specific survival, and progression-free interval. In PAAD, SPTBN2 can be used as an independent factor affecting prognosis. Mutations and amplification of SPTBN2 were detected, with abnormal methylation of SPTBN2 affecting its expression and the survival outcome of PAAD patients. Immunoassay results demonstrate that SPTBN2 was a potential biomarker for predicting therapeutic response in PAAD, and may influence the immunotherapy efficacy of PAAD by regulating levels of CD8 + T cells and neutrophil infiltration. Results from an enrichment analysis indicated that SPTBN2 may regulate the development of PAAD via immune pathways. Thus, SPTBN2 is a potential prognostic biomarker and immunotherapy target based on its crucial role in the development of PAAD.
I2-Catalyzed three-component synthesis of 3-selenylated pyrazolo[1,5-a]pyrimidines
Authors: Choudhuri Tathagata , Paul Suvam , Sikdar Papiya , Das Sourav , Sawant Sanghapal D. , Bagdi Avik Kumar
Published: April 2024

A one-pot strategy has been developed for the synthesis of 3-selenylated pyrazolo[1,5-a]pyrimidines from amino pyrazoles, chalcones/enaminones, and diselenides through I2-catalyzed tandem cascade annulations/C–H selenylation.
Internal standard optimization advances sensitivity and robustness of ratiometric detection method
Authors: Jiang Yuning , Cao Jiaying , Hu Sen , Cheng Tao , Wang Hanyu , Guo Xiaoyu , Ying Ye , Liu Xinling , Wang Feng , Wen Ying , Wu Yiping , Yang Haifeng
Published: April 2024

We detect nitrite with pATP/Au/ITO chip via ratiometric SERS method. With the 1008 cm−1 SERS peak from ring deformation as the internal standard (replacing the traditional 1080 cm−1 C-S stretching peak), the detection sensitivity is 10-fold increase.
Correction: Influence of a neighbouring Cu centre on electro- and photocatalytic CO2 reduction by Fe-Mabiq
Authors: Rickmeyer Kerstin , Huber Matthias , Hess Corinna R.
Published: April 2024

Correction for ‘Influence of a neighbouring Cu centre on electro- and photocatalytic CO2 reduction by Fe-Mabiq’ by Kerstin Rickmeyer et al., Chem. Commun., 2024, 60, 819–822, https://doi.org/10.1039/D3CC04777F.
Vibrational energy transfer in collisions of molecules with metal surfaces
Authors: Rahinov Igor , Kandratsenka Alexander , Schäfer Tim , Shirhatti Pranav , Golibrzuch Kai , Wodtke Alec M.
Published: April 2024

A systematic perspective of the progress in observations and theory of electronically nonadiabatic vibrational energy transfer during molecule–metal surface collisions.
Antigen density and applied force control enrichment of nanobody-expressing yeast cells in microfluidics
Authors: Sanicas Merlin , Torro Rémy , Limozin Laurent , Chames Patrick
Published: April 2024

A method for force-based enrichment of yeasts displaying libraries of antibody fragments.
Retraction: Metal-ion batteries for electric vehicles: current state of the technology, issues and future perspectives
Authors: Verma Jaya , Kumar Deepak
Published: April 2024

Retraction of ‘Metal-ion batteries for electric vehicles: current state of the technology, issues and future perspectives' by Jaya Verma et al., Nanoscale Adv., 2021, 3, 3384–3394, https://doi.org/10.1039/D1NA00214G.
MOF-derived CoP/CuP hybrids as bifunctional electrocatalysts for zinc–air batteries
Authors: Liu Huimin , Zong Xing , Wang Yongfei , Hu Zhizhi , Zhang Zhiqiang
Published: April 2024

The finely distributed CoP/CuP nanoparticles and the distinctive supporting structure exhibit remarkable electrocatalytic performance in both the ORR and the OER.
Photocatalyst-free hydrothiolation of gem-difluoroalkenes with thiols
Authors: Zuo Lin , Zhang Zhiyang , Yuan Xiao-Ya , Sun Kai , Yu Bing
Published: April 2024

A photocatalyst-free hydrothiolation reaction of aromatic gem-difluoroalkenes was developed under the irradiation of blue light in dimethyl carbonate as a green solvent.
Radiolysis of bituminized radioactive waste: a comprehensive review
Authors: Millot Lucie , Houjeij Hanaa , Matta Georges , Ferrandis Jean-Yves , Laux Didier , Monsanglant Louvet Céline
Published: April 2024

In the realm of radioactive waste management, the impact of radiolysis on bitumen and bituminized radioactive waste also called bituminized waste product (BWP) is considered one of the most significant factors influencing structural changes and the generation of radiolysis gas bubbles. This review provides a comprehensive overview of several studies that have explored the intricate interaction between radiation and various types of bitumen, to gain a better understanding of how such waste ages when exposed to radiation. While these studies provide insights into the diverse effects of radiolysis on bitumen, they also highlight numerous unanswered questions. The absence of gas bubbles does not necessarily indicate an absence of gas production, leaving further research to be undertaken. The complexities of bitumen radiolysis offer multiple avenues for future investigation, aiming to enhance our understanding and provide comprehensive solutions for bituminous radioactive waste management. Among the studied types of bitumen, blown R85/40 bitumen and straight-run distilled bitumen with a penetration grade of 70/100 stands out due to their widespread use in immobilizing co-precipitated radioactive sludges. These bituminous matrices play an essential role in understanding the broader implications of radiolysis within the context of bituminous waste management. This review underscores the significance of further research into radiolysis and bitumen ageing, emphasizing the need for a more in-depth exploration of these complex phenomena and their implications for the long-term safety and efficacy of repositories and disposal facilities.
Thirsty for science? The Young Minds PONYS are here to “Parla Potabile”!
Authors: Almassu Serina , Di Meo Paolo
Published: April 2024

The Young Minds program has public-outreach of physics and science as one of its major goals as a global connecting hub for students and early-career physicists. Every year, many of our student-run chapters (sections) surprise us with astonishing new ideas for reaching out to people and specially school students, with a range of enjoyable, inspirational, and educational activities. In this issue we are proud to spotlight this unique grand science festival organized by the Physics and Optics Naples Young Students (PONYS) in its second edition.
Traffic flow from a physics perspective
Authors: Schadschneider Andreas
Published: April 2024

Physicists have been interested in traffic for a long time for various reasons. On the one hand, we all participate in traffic as pedestrians or drivers. On the other hand, traffic systems exhibit interesting, and sometimes counter-intuitive, collective phenomena. They are examples for nonequilibrium systems which allows to apply and test methods developed in statistical physics.
Zooming in on brownian motion with optical trapping microscopy
Authors: Raizen Mark G. , Forró László , Hillberry Logan E. , Macko Puhek Aleksandar M.
Published: April 2024

Optical trapping microscopy unravels open questions in statistical physics by making ultraprecise measurements of Brownian motion in diverse fluid environments. Moreover, the advent of pulsed lasers promises to push the boundaries even further, offering insights on how the compressibility of fluid flow affects Brownian particles at previously unexplored time scales.
« L’IA ? Un soutien à l’expertise humaine, une aide à la décision »
Authors: Chatila Raja
Published: April 2024

Un champ infini d’applications s’ouvre à nous en matière d’aide à la décision, de maintenance prédictive, d’inspection visuelle ou de traitement du signal… Partout où des données sont disponibles en nombre, l’intelligence artificielle peut apporter une puissance inédite pour assister les humains.
« L’IA n’est pas un système autonome qui prend le contrôle, mais bien un outil, aussi sophistiqué soit-il »
Authors: Dupin Ludovic , Le Gros Gaïc
Published: April 2024

Rencontre avec Nelly Ngoy Kubelwa, responsable des activités de contrôle-commande (I&C) dans la section ingénierie du département de l’énergie nucléaire de l’Agence internationale de l’énergie atomique et responsable du groupe de travail sur l’intelligence artificielle.
Effects of the three-child policy on the employment bias against professional women: evidence from 260 enterprises in Jiangxi province
Authors: Gao Qun , Zhao Mei , Chen Hengyang
Published: April 2024

Based on the samples from 260 enterprises in Jiangxi Province in 2022, this study examines the enterprises’ employment attitudes towards female employees from the perspective of HR managers. Through factor analysis, one-way analysis of variance, product-moment correlation analysis, and multiple regression analysis, this study investigates the female employment bias and its underlying mechanism across five dimensions: employee change, career development bias, policy impact, job competency and gender bias. The research findings confirm the employment bias against professional women by employers. The study reveals that the implementation of China’s three-child policy has exacerbated employment bias against female employees, especially in male-dominated enterprises. It is therefore recommended to provide more preferential policies for such enterprises. Furthermore, job competency has a significant negative correlation with gender employment bias. Continuing education and skills training are effective measures for professional women of childbearing age, particularly those in low-skilled jobs. With the further implementation of the three-child policy, this study anticipates a more challenging employment or promotion prospects for professional women. This study has also indirectly confirmed the employment dilemma of professional women of childbearing age, indicating potential obstacles in achieving the intended outcomes of the three-child policy.
Heat transfer improvement and drag force reduction around three heated square cylinders controlled by partitions
Authors: Admi Youssef , Lahmer El Bachir , Benhamou Jaouad , Moussaoui Mohammed Amine , Mezrhab Ahmed
Published: April 2024

Investigating the subject offers a pioneering approach to enhancing thermal performance and aerodynamic efficiency, unlocking novel strategies for optimizing energy utilization and air dynamics in engineering applications. In this research, a numerical study of airflow control coupled to heat transfer around several heated square cylinders is carried out at a fixed Reynolds number (Re=100). The effect of the positioning and length of the control partitions is examined. Numerical simulations are carried out using the lattice Boltzmann method with multiple relaxation times model. The obtained results reveal the existence of a critical position g=0 where a significant improvement in the Nusselt number is observed. This improvement amounts to 31.1% for the rear face of the top obstacle, 30.2% for the rear face of the central obstacle, and 36.65% for the rear face of the bottom obstacle compared to the uncontrolled case. Thus, a complete suppression of the vortex shedding is observed when the length of the partitions reaches a critical value (Lp=4D). Furthermore, a maximum percentage of drag reduction is achieved by around 6.03% for the central block and 16.67% for the two end blocks when the length of the control partitions reaches this critical value.
Charge transport and extrinsic absorption of two-dimensional defect-rich ZnIn2S4 semiconductor for below-bandgap photodetection
Authors: Wang Rui , Shao Wen-Zhu , Liu Yue , Xu Bo , Sun Zhao-Yuan , Li Hui , Zhang Chang-Jin , Xu Cheng-Yan , Li Yang , Zhen Liang
Published: April 2024

As a rediscovered ternary two-dimensional (2D) material, defect-rich Znln2S4 has great potential for energy-harvesting applications. However, the effect of defects on its physical properties and device performance remains elusive. Herein, we explored the influence of defects (S vacancies and In–Zn substitutions) in few-layer Znln2S4 on the charge transport and photoelectric performance. It is demonstrated that the defect-rich Znln2S4 device exhibits two-dimensional variable range hopping transport mechanism, with uniform charge transport along the channel and low contact resistance at the electrical contacts of Znln2S4/Au. Importantly, due to the contribution of the donor and acceptor energy levels inside the bandgap, the flake exhibits pronounced extrinsic absorption, leading to the competitive photodetector performance under sub-bandgap photo-excitation. Explicitly, the device exhibits a maximum responsivity of 4.08 × 104 A W−1, a photo-gain of >108 electrons per photon, and a specific detectivity of ∼1015 Jones under 532 nm laser excitation, with detection wavelength extending from 400 to 980 nm. Our findings underscore the significant potential of defect-engineering to enrich the functionalities of 2D semiconductors.
A Merningar Bardok family’s Noongar oral history of Two Peoples Bay Nature Reserve and surrounds
Authors: Knapp Lynette , Cummings Dion , Cummings Shandell , Fiedler Peggy L. , Hopper Stephen D.
Published: April 2024

Warning Aboriginal and Torres Strait Islander readers should be aware that this document may contain sensitive information, images or names of people who have since passed away. Context Two Peoples Bay Nature Reserve on Western Australia’s south coast is world renowned for its biodiversity, particularly its threatened fauna. Future co-management of the Reserve with Aboriginal peoples is likely, although very little information on the Noongar cultural heritage of the Reserve has been published and thus available for stewardship guidance. Methods This study used oral history interviews on Country based on open-ended questioning and respect for intellectual property. Comprehensive surveys for Noongar cultural heritage were conducted on foot on the Reserve. Key results A rich trove of women’s and men’s stories from the Knapp family about Two Peoples Bay is recalled and recorded. The Reserve features prominently in Wiernyert/Dreaming stories with classical human moral dilemmas, and transformations for wrong-doing are featured. Threatened animals and important plants are named as borongur/totems. Trading of gidj/spears of Taxandria juniperina is prominent. Use of fire traditionally was circumspect, and is confined to small areas and pathways in lowlands. Granite rocks are replete with lizard traps, standing stones, and stone arrangements. Conclusions The Reserve has a long and layered oral history for Merningar Bardok Noongars, exemplified here by the Knapp family, members of which have enjoyed continuous oral history for countless generations. Granite rocks, wetlands, flora, and fauna are vitally important vessels of such knowledge. Implications Cultural suppression has inhibited free cross-cultural exchange of kaatidjin/knowledge until recently. As respect for culture and Elders becomes paramount, positive co-stewardship of the Reserve will become a reality. Vibrant cultural interpretation and active management by Noongar guides and rangers is recommended.
The use of suboptimal antiretroviral therapy when applying for migration to Australia: a case series
Authors: Tran Daniel , Allan Brent , Stratigos Alexandra , O’Donnell Darryl , Heath-Paynter Dash , Cogle Aaron , Ong Jason J.
Published: April 2024

Background Australia imposes restrictions for people living with HIV (PLHIV) applying for permanent residency (PR), including spending less than AUD51,000 on medical costs over 10 years. Some PLHIV opted for suboptimal and cheaper antiretroviral therapy (ART) regimens to increase their chances of receiving PR. We collated a case series to examine PLHIV on suboptimal ART because of visa issues. Methods We identified all patients applying for a PR in Australia who obtained nevirapine, efavirenz or zidovudine between July 2022 and July 2023 from the Melbourne Sexual Health Centre. Pathology results and records detailing psychological issues relating to the patients’ wishes to remain on suboptimal ART were extracted from clinical records by two researchers. Results We identified six patients with a mean age of 39 years migrating from Asian and European countries. Three patients used efavirenz, and three used nevirapine. All desired to remain on cheaper, suboptimal ART to stay below visa cost thresholds, which they considered to aid favourably with their application. Four displayed stress and anxiety arising from visa rejections, appeal deadlines and the lengthy visa application process. Conclusions Despite access to more effective and safer ART, we identified patients who chose to remain on cheaper ART to improve chances of obtaining an Australian visa, potentially putting their health at risk. We found significant evidence of stress and anxiety among patients. There is a need to review and revise current migration policies and laws in Australia that discriminate against PLHIV and jeopardise public health.
β-catenin turnover is regulated by Nek10-mediated tyrosine phosphorylation in A549 lung adenocarcinoma cells
Authors: Dutt Previn , Haider Nasir , Mouaaz Samar , Podmore Lauren , Stambolic Vuk
Published: April 2024

β-catenin has influential roles affecting embryonic development, tissue homeostasis, and human diseases including cancer. Cellular β-catenin levels are exquisitely controlled by a variety of regulatory mechanisms. In the course of exploring the functions of the Nek10 tyrosine kinase, we observed that deletion of Nek10 in lung adenocarcinoma cells resulted in dramatic stabilization of β-catenin, suggestive of a Nek10 role in the control of β-catenin turnover. Nek10-deficient cells exhibited diminished ability to form tumorspheres in suspension, grow in soft agar, and colonize mouse lung tissue following tail vein injection. Mechanistically, Nek10 associates with the Axin complex, responsible for β-catenin degradation, where it phosphorylates β-catenin at Tyr30, located within the regulatory region governing β-catenin turnover. In the absence of Nek10 phosphorylation, GSK3-mediated phosphorylation of β-catenin, a prerequisite for its turnover, is impaired. This represents a divergent function within the Nek family, whose other members are serine-threonine kinases involved in different elements of the centrosomal cycle, primary cilia function, and DNA damage responses.
Proteolytic stability and aggregation in a key metabolic enzyme of bacteria
Authors: Pollack Dan , Nozoe Takashi , Kussell Edo
Published: April 2024

Proteins that are kinetically stable are thought to be less prone to both aggregation and proteolysis. We demonstrate that the classical
lac
system of
Escherichia coli
can be leveraged as a model system to study this relation. β-galactosidase (LacZ) plays a critical role in lactose metabolism and is an extremely stable protein that can persist in growing cells for multiple generations after expression has stopped. By attaching degradation tags to the LacZ protein, we find that LacZ can be transiently degraded during
lac
operon expression but once expression has stopped functional LacZ is protected from degradation. We reversibly destabilize its tetrameric assembly using α-complementation, and show that unassembled LacZ monomers and dimers can either be degraded or lead to formation of aggregates within cells, while the tetrameric state protects against proteolysis and aggregation. We show that the presence of aggregates is associated with cell death, and that these proteotoxic stress phenotypes can be alleviated by attaching an ssrA tag to LacZ monomers which leads to their degradation. We unify our findings using a biophysical model that enables the interplay of protein assembly, degradation, and aggregation to be studied quantitatively in vivo. This work may yield approaches to reversing and preventing protein-misfolding disease states, while elucidating the functions of proteolytic stability in constant and fluctuating environments.
Monocyte to macrophage differentiation and changes in cellular redox homeostasis promote cell type-specific HIV latency reactivation
Authors: Blanco Alexandra , Coronado Robert A. , Arun Neha , Ma Kelly , Dar Roy D. , Kieffer Collin
Published: April 2024

HIV latency regulation in monocytes and macrophages can vary according to signals directing differentiation, polarization, and function. To investigate these processes, we generated an HIV latency model in THP-1 monocytes and showed differential levels of HIV reactivation among clonal populations. Monocyte-to-macrophage differentiation of HIV-infected primary human CD14+ and THP-1 cells induced HIV reactivation and showed that virus production increased concomitant with macrophage differentiation. We applied the HIV-infected THP-1 monocyte-to-macrophage (MLat) model to assess the biological mechanisms regulating HIV latency dynamics during monocyte-to-macrophage differentiation. We pinpointed protein kinase C signaling pathway activation and Cyclin T1 upregulation as inherent differentiation mechanisms that regulate HIV latency reactivation. Macrophage polarization regulated latency, revealing proinflammatory M1 macrophages suppressed HIV reactivation while anti-inflammatory M2 macrophages promoted HIV reactivation. Because macrophages rely on reactive-oxygen species (ROS) to exert numerous cellular functions, we disrupted redox pathways and found that inhibitors of the thioredoxin (Trx) system acted as latency-promoting agents in T-cells and monocytes, but opposingly acted as latency-reversing agents in macrophages. We explored this mechanism with Auranofin, a clinical candidate for reducing HIV reservoirs, and demonstrated Trx reductase inhibition led to ROS induced NF-κB activity, which promoted HIV reactivation in macrophages, but not in T-cells and monocytes. Collectively, cell type-specific differences in HIV latency regulation could pose a barrier to HIV eradication strategies.
Correcting misperceptions of the material benefits associated with union membership increases Americans’ interest in joining unions
Authors: Kamphorst Jonne , Willer Robb
Published: April 2024

How accurate are Americans’ perceptions of the material benefits associated with union membership, and do these perceptions influence their support for, and interest in joining, unions? We explore these questions in a preregistered, survey experiment conducted on a national sample, representative of the US population on a number of demographic benchmarks (n= 1,430). We find that Americans exhibit large and consistent underestimates of the benefits associated with unionization, as compared to evidence from the Bureau of Labor Statistics and peer-reviewed academic research. For example, 89% of Americans underestimated the life-time income premium associated with union membership, 72% underestimated the percentage of union members who receive health insurance from their employer, and 97% overestimated the average union dues rate. We next randomly assigned half of the participants to receive a brief, informational correction conveying results of academic and government research on the material benefits associated with union membership, or not. Those who received the correction reported 11.6% greater interest in joining a union, 7.8% greater support for unions, and 6.9% greater interest in helping to organize a union in their workplace, as compared to the control group. These results suggest that, overall, Americans tend to underestimate the material benefits associated with unionization, misperceptions of these benefits are causally linked to Americans’ support for unionization, and correcting these misperceptions increases a range of pro-union sentiments in the American mass public.
The IL-17 pathway intertwines with neurotrophin and TLR/IL-1R pathways since its domain shuffling origin
Authors: Chen Shenghui , Fan Huiping , Ran Chenrui , Hong Yun , Feng Huixiong , Yue Zirui , Zhang Hao , Pontarotti Pierre , Xu Anlong , Huang Shengfeng
Published: April 2024

The IL-17 pathway displays remarkably diverse functional modes between different subphyla, classes, and even orders, yet its driving factors remains elusive. Here, we demonstrate that the IL-17 pathway originated through domain shuffling between a Toll-like receptor (TLR)/IL-1R pathway and a neurotrophin-RTK (receptor-tyrosine-kinase) pathway (a Trunk-Torso pathway). Unlike other new pathways that evolve independently, the IL-17 pathway remains intertwined with its donor pathways throughout later evolution. This intertwining not only influenced the gains and losses of domains and components in the pathway but also drove the diversification of the pathway’s functional modes among animal lineages. For instance, we reveal that the crustacean female sex hormone, a neurotrophin inducing sex differentiation, could interact with IL-17Rs and thus be classified as true IL-17s. Additionally, the insect prothoracicotropic hormone, a neurotrophin initiating ecdysis in
Drosophila
by binding to Torso, could bind to IL-17Rs in other insects. Furthermore, IL-17R and TLR/IL-1R pathways maintain crosstalk in amphioxus and zebrafish. Moreover, the loss of the Death domain in the pathway adaptor connection to IκB kinase and stress-activated protein kinase (CIKSs) dramatically reduced their abilities to activate nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) in amphioxus and zebrafish. Reinstating this Death domain not only enhanced NF-κB/AP-1 activation but also strengthened anti-bacterial immunity in zebrafish larvae. This could explain why the mammalian IL-17 pathway, whose CIKS also lacks Death, is considered a weak signaling activator, relying on synergies with other pathways. Our findings provide insights into the functional diversity of the IL-17 pathway and unveil evolutionary principles that could govern the pathway and be used to redesign and manipulate it.
Optimal analysis of finite element methods for the stochastic Stokes equations
Authors: Li Buyang , Ma Shu , Sun Weiwei
Published: April 2024

Numerical analysis for the stochastic Stokes equations is still challenging even though it has been well done for the corresponding deterministic equations. In particular, the pre-existing error estimates of finite element methods for the stochastic Stokes equations in theL∞(0,T;L2(Ω;L2))L^\infty (0, T; L^2(\Omega ; L^2))norm all suffer from the order reduction with respect to the spatial discretizations. The best convergence result obtained for these fully discrete schemes is only half-order in time and first-order in space, which is not optimal in space in the traditional sense. The objective of this article is to establish strong convergence ofO(τ1/2+h2)O(\tau ^{1/2}+ h^2)in theL∞(0,T;L2(Ω;L2))L^\infty (0, T; L^2(\Omega ; L^2))norm for approximating the velocity, and strong convergence ofO(τ1/2+h)O(\tau ^{1/2}+ h)in theL∞(0,T;L2(Ω;L2))L^{\infty }(0, T;L^2(\Omega ;L^2))norm for approximating the time integral of pressure, whereτ\tauandhhdenote the temporal step size and spatial mesh size, respectively. The error estimates are of optimal order for the spatial discretization considered in this article (with MINI element), and consistent with the numerical experiments. The analysis is based on the fully discrete Stokes semigroup technique and the corresponding new estimates.
Perceptions of Human Factors and patient safety education in undergraduate healthcare curricula: a pharmacy perspective
Authors: Sheehan P , Fleming A , Joy A , McCarthy S
Published: April 2024

Introduction

A recent systematic review identified a lack of formal patient safety (PS) education in undergraduate healthcare curricula1. Gaps were also identified in relation to teaching of Human Factors (HF) in this context.

Aim

This qualitative study aimed to examine the perceptions of School of Pharmacy faculty at an Irish university relating to PS/HF in undergraduate healthcare education.

Methods

Qualitative semi-structured interviews were conducted with seven School of Pharmacy faculty at an Irish university. Findings from a recent systematic review were used to inform research and interview questions.[1] Sampling was purposive and included lecturers from the disciplines of clinical pharmacy and pharmaceutics. Interviews were conducted, either in person or virtually, then transcribed and anonymised. Reflexive thematic analysis (TA) was chosen as the method of analysis, [2] conducted by the first author with input from the wider research team. Within the reflexive piece of this work was the drive to be informed by the lived experience of participants. In alignment with the principles of reflexive TA, an iterative approach was taken to data collection and analysis.[2] This approach informed a sample size which facilitated in-depth exploration of the topic.

Results

Seven interviews were conducted, and six key themes were derived from the analysis. These are presented in Table 1 along with the identified subthemes.

Conclusion

This study demonstrates gaps relating to HF/PS teaching in undergraduate pharmacy education in the Irish context. Findings of this study indicate that much PS learning is implicit and occurs while students are on clinical placement. Lack of synergy between the academic and clinical settings was identified as a gap. Interprofessional education was identified as a platform which may help bridge this gap. In agreement with previously published literature, there is a need for robust competency frameworks to underpin safety content.[1] These findings will inform future initiatives to develop HF and PS competency in undergraduate healthcare education.

A limitation of this research is that all data were collected at a single university. A strength is that this study captures the lived experience of PS education from the perspective of academic staff at an Irish school of pharmacy which in 2015 made the transition to a new MPharm programme.

References

1. Sheehan P, Joy A, Fleming A, Vosper H, McCarthy S. Human factors and patient safety in undergraduate healthcare education: a systematic review. Human Factors in Healthcare. 2022 Dec 1;2:100019.

2. Braun, V and Clarke, V. Conceptual and design thinking for thematic analysis. Qualitative Psychology. 2022;9(1):3.
Comprehensive Analysis of a Dendritic Cell Marker Genes Signature to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma
Authors: Song Peng , Li Yuan , Zhang Moyan , Lyu Baihan , Cui Yong , Gao Shugeng
Published: April 2024

With the development of immune checkpoints inhibitors (ICIs), immunotherapy has recently taken center stage in cancer treatment. Dendritic cells exert complicated and important functions in antitumor immunity. This study aims to construct a novel dendritic cell marker gene signature (DCMGS) to predict the prognosis and immunotherapy response of lung adenocarcinoma (LUAD). DC marker genes in LUAD were identified by analysis of single-cell RNA sequencing data. 6 genes (G0S2, KLF4, ALDH2, IER3, TXN, CD69) were screened as the most prognosis-related genes for constructing DCMGS on a training cohort from TCGA data set. Patients were divided into high-risk and low-risk groups by DCMGS risk score based on overall survival time. Then, the predictive ability of the risk model was validated in 6 independent cohorts. DCMGS was verified to be an independent prognostic factor in multivariate analysis. Furthermore, we performed pathway enrichment analysis to explore possible biological mechanisms of the powerful predictive ability of DCMGS, and immune cell infiltration landscape and inflammatory activities were exhibited to reflect the immune profile. Notably, we bridged DCMGS with expression of immune checkpoints and TCR/BCR repertoire diversity that can inflect immunotherapy response. Finally, the predictive ability of DCMGS in immunotherapy response was also validated by 2 cohorts that had received immunotherapy. As a result, the patients with lower DCMGS risk scores showed a better prognosis and immunotherapy response. In conclusion, DCMGS was suggested to be a promising prognostic indicator for LUAD and a desirable predictor for immunotherapy response.
Precise capture of circulating endometrial cells in endometriosis
Authors: Wang Shang , Cheng Hongyan , Zhu Honglan , Yu Xiaoming , Ye Xue , Chang Xiaohong
Published: April 2024

Background:

Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.

Methods:

Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients (n = 34) hospitalized in the Peking University People's Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics.

Results:

The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.

Conclusion:

The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.
Vitreous abnormalities in a patient with Gaucher disease
Authors: Mak Michael Y.K , Trask William M. , Huang Jordan J. , Huang Jaxon J. , Li Jasmine , Kulaga Andrzej , Adatia Feisal
Published: April 2024

Purpose:

To report a case and management of vitreous abnormalities in a patient with Gaucher disease.

Methods:

Case report.

Results:

A 28-year-old female with a known diagnosis of Gaucher disease presented to our retina service with complaints of “blurry” vision in both eyes. Ophthalmic examination revealed a Snellen visual acuity of 20/70 OD and 20/20 OS. The anterior segment examination was unremarkable bilaterally; however, the vitreous was notable for multiple yellowish-white vitreous opacifications in both eyes. Fluorescein angiography revealed the opacities but was otherwise unremarkable in terms of retinal vascular findings. Swept-source optical coherence tomography confirmed the position of these vitreous abnormalities to be directly anterior to and in contact with the retinal nerve fiber layer. She subsequently underwent 23-gauge pars plana vitrectomy to remove the vitreous debris; Triamcinolone Acetate (Kenalog) was used intraoperatively to visualize the posterior hyaloid. The cassette was sent for pathological analysis, which revealed amorphous vitreous material with occasional lymphocytes and histiocytes. Her post-vitrectomy Snellen visual acuity was 20/40 OD with pinhole to 20/25, and the patient reported resolution of her subjective symptoms. Her opacities had not recurred as of last follow-up.

Conclusion:

Vitreous abnormalities in Gaucher disease are an extremely rare and uncommon ophthalmologic finding. As our case demonstrates, vitrectomy can be an appropriate surgical approach for improving vision in these patients.
A Novel Pathogenic Variant of the PRPH2 Gene in Multifocal Pattern Dystrophy Simulating Stargardt Disease: A Case Report and Major Review
Authors: Alsumait Abdulaziz , Mahmoudzadeh Raziyeh , Couser Natario
Published: April 2024

Purpose:

To present a novel pathogenic variant in PRPH2 in a patient with multifocal pattern dystrophy simulating Stargardt Disease (MPDsSD) and provide a review of the literature summarizing the clinical findings of all presented cases of MPDsSD.

Methods:

We performed a systematic review of the literature to summarize the clinical findings in patients with MPDsSD. A PubMed search of “(multifocal pattern dystrophy simulating stargardt disease) OR (multifocal pattern dystrophy simulating fundus flavimaculatus) OR (PRPH2 associated retinal dystrophy)” retrieved a total of 152 articles on April 2023. Articles describing the clinical and ophthalmic characteristics of patients with MPDsSD were included. We also describe the case of a 42-year-old male presenting to the clinic with blurry vision and progressively worsening vision in both eyes who was found to have a novel pathogenic variant in the PRPH2 gene.

Results:

Genetic testing revealed a pathogenic variant in PRPH2, c.640T>C [p.(Cys214Arg)], which provided molecular confirmation of MPDsSD. Moreover, the systematic review, revealed 28 previously reported cases of MPDsSD. The most common presenting symptom among all patients was metamorphopsia (33% of cases). The most common finding on fundus exam was the presence of yellowish fleck-like deposits found in the posterior pole of the retina (83%). All cases of MPDsSD had hyper-autofluorescence of the yellow flecks on fundus autofluorescence. The mean age of onset was 41 years (28 – 65). Mean best corrected visual acuity (BCVA) at presentation was 0.27 (20/37) right eye (OD) and 0.26 (20/36) left eye (OS). Only 48% of the cases reported a known family history of PD.

Conclusion:

Molecular confirmation can help confirm a clinical suspicion of MPDsSD, as this condition may have overlapping features of other macular dystrophies, most notably Stargardt Disease.
Differential Rates of Toxicity Between Chloroquine and Hydroxychloroquine
Authors: Guttha Samyuktha , Choi Stephanie , Dedania Vaidehi S. , Mehta Nitish , Belmont H. Michael , Modi Yasha S.
Published: April 2024

Purpose:

To describe two cases of patients with systemic lupus erythematosus (SLE) who manifested differential rates of retinal toxicity progression on hydroxychloroquine (HCQ) and chloroquine (CQ), respectively.

Methods:

Retrospective case reports.

Results:

Case 1 is a 41-year-old woman with SLE and history of renal involvement, who had been managed on HCQ for 14 years and gradually progressed to moderate retinal toxicity over several years. Case 2 is a 59-year-old woman with SLE and history of renal involvement, who had been managed on quinacrine for 20 years followed by chloroquine for 5 years and initially presented without any evidence of retinal toxicity. One year later, she manifested moderate retinal toxicity. Both cases were screened regularly. In case 1, the diagnosis was missed and toxicity progressed predictably and slowly while on HQ. In case 2, there was no salient pathology on OCT or HVF testing at initial presentation. One year later, there was moderate toxicity.

Conclusion:

Given the dramatically different rate of progression of retinal toxicity in these two patients, these cases highlight potential gaps in our understanding of retinal toxicity and provide rationale to potentially study rates of retinal toxicity progression in patients on CQ or quinacrine.
Central Serous Chorioretinopathy in Nanophthalmos
Authors: Manayath George J , Ninan Rohan , Verghese Shishir , Narendran Venkatapathy
Published: April 2024

Purpose:

To report a case of bilateral central serous chorioretinopathy (CSC) occurring in a patient with nanophthalmos with long term follow up

Methods:

Case Report

Results:

A 37-year old male presented with diminution of vision in right eye (RE) since 3 days. On examination his best corrected visual acuity (BVCA) was 5/60 in RE and 6/18 in LE His refractive correction was +8.00D sphere. Anterior segment examination revealed small eyes with narrow palpebral fissures, shallow anterior chamber and clear lens. His axial length was 15.94mm in the RE and 15.89mm in the LE respectively. Fundus examination revealed a crowded disc with tortuous vessels in both eyes and the presence of subretinal fluid (SRF) in the macular area in the RE. Multimodal imaging included enhanced depth imaging spectral domain optical coherence tomography (EDI SD-OCT) and fundus fluorescein angiography (FFA) which revealed features suggestive of thick choroids BE, ink-blot leak on FFA suggestive of acute CSC in the RE and a pigment epithelial detachment (PED) in the left eye. Focal laser in RE lead to SRF resolution and visual improvement. He was on regular follow up and 5 years later he presented with a recurrence of CSC in the RE for which he underwent a repeat FFA guided focal laser.

Conclusion:

This case highlights the unique coexistence of CSC in the setting of Nanophthalmos and highlights a probable overlapping pathophysiology of choroidal venous overload as well as the importance of multimodal imaging in differentiating the mimicking entities.
Two Different Nuclear Mitochondrial DNA Mutations Associated with Retinal Abnormalities
Authors: Spaide Richard F.
Published: April 2024

Purpose:

To report the posterior pole imaging characteristics of two patients with pathogenic nuclear mitochondrial mutations.

Methods:

Case reports

Results:

The first case, a 61-year-old patient, initially diagnosed with age-related macular degeneration, exhibited focal hyperpigmentation and increased autofluorescence in the parafoveal macula, along with geographic atrophy and mild optic nerve pallor. Optical coherence tomography (OCT) showed ellipsoid zone (EZ) attenuation, hyperreflective foci colocalizing to the hyperpigmentation, subretinal deposits, and hypertransmission defects. He was found to have a pathogenic mutation of MFN2, a gene defect associated with Charcot-Marie-Tooth disease. The second case, a 65-year-old patient presented with loss of central vision with pallor of the optic nerve. OCT imaging showed widespread loss of the interdigitation zone and EZ attenuation peripheral to the foveal region. There was thinning of the ganglion cell and nerve fiber layers. A pathogenic OPA1 mutation, the leading cause of autosomal dominant optic atrophy, was found. Both MFN2 and OPA1 produce proteins integral in mitochondrial fusion.

Conclusions:

The findings of these cases suggest ocular examinations may be helpful in evaluating patients with nuclear mitochondrial mutations using the near microscopic resolution of OCT. Retinal imaging may highlight structural abnormalities related to mitochondrial problems and allows direct imaging of the EZ, a layer dominated by mitochondria and a place where direct imaging of mitochondria is possible, in vivo.