bluuebunny/crossref_metadata_2025 huggingface dataset:
External evaluation of intravenous vancomycin population pharmacokinetic models in adults receiving high‐flux intermittent haemodialysis
Authors: Ji Cheng , Garcia Jonathan , Sabuga Argem Joy , Ricard Maurane , Dion France , Rosu Vlad Alexandru , Legris Marie‐Ève , Marsot Amélie , Nguyen Van Dong
Published: November 2024

Aims

Patients undergoing haemodialysis (HD) are at greater risk of methicillin‐resistant Staphylococcus aureus infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model‐informed dosing is commonly used. This study aimed to perform an external evaluation of published vancomycin popPK models developed for adults undergoing high‐flux intermittent HD, and to create a dosing nomogram derived from the model that performed best.

Methods

A literature review was conducted through PubMed and EMBASE to identify relevant popPK models. an external dataset was collected retrospectively from patients of 2 healthcare centres in Quebec, Canada. Selected models were implemented in NONMEM (v7.5; ICON Development Solutions). Predictive performance was assessed through prediction and simulation‐based diagnostics.

Results

In total, 2386 vancomycin concentrations were collected from 274 patients and 476 antibiotic courses. Four vancomycin popPK models were selected for evaluation. None of the models demonstrated overall satisfactory or clinically acceptable predictive performance. Nonetheless, Bae et al.’s model performed best with a median prediction error of 16.25% and median absolute prediction error of 34.66%. Different predictive performance was also observed for vancomycin concentrations from samples collected during and between HD sessions.

Conclusion

All evaluated models presented poor overall predictive performance. Further studies are required, through existing popPK model parameter re‐estimation or new model development, to adequately describe vancomycin pharmacokinetics for our high‐flux intermittent HD patient cohort.
sGC stimulator (BAY 41‐8543) combined with PDE9 inhibitor (BAY 73‐6691) reduces renal fibrosis in 5/6 nephrectomized rats
Authors: Chen Xin , Delić Denis , Liu Yvonne , Cao Yaochen , Zhang Zeyu , Wu Hongwei , Gaballa Mohamed M. S. , Klein Thomas , Elitok Saban , Krämer Bernhard K. , Hocher Berthold
Published: November 2024

Renal fibrosis is closely related to the prognosis of chronic kidney disease (CKD). The increase in cGMP reduces renal fibrosis. Soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) are key enzymes that maintain cGMP levels. BAY 41–8543 (1 mg/kg/day) and/or BAY 73–6691 (1 mg/kg/day) were used to treat 5/6 nephrectomized rats for 13 weeks. 5/6 Nephrectomy caused an increase in cystatin C, proteinuria and glomerulosclerosis and renal interstitial fibrosis. Neither sGC stimulation nor PDE9 inhibition alone improved kidney function and morphology, whereas BAY 41–8543 in combination with BAY 73–6691 attenuated renal interstitial fibrosis. This beneficial effect could not be explained by alterations in blood pressure and the renal immune system. BAY 41–8543 in combination with BAY 73–6691 had no effect on renal macrophage, CD4 + T‐cell and CD8 + T‐cell in the late‐stage of 5/6 nephrectomy. RNA sequencing revealed BAY 41–8543 in combination with BAY 73–6691 down‐regulated the expression of fibrosis‐related genes such as Collagen Type I Alpha 1, Collagen Type III Alpha 1 Chain and Collagen Type XIV Alpha 1 Chain. sGC stimulator combined with PDE9 inhibitor attenuated renal fibrosis in 5/6 nephrectomized rats by down‐regulating fibrosis‐related gene expression. This novel approach of using low‐dose combination therapies to minimize side effects while maintaining therapeutic efficacy offers a promising strategy for the treatment of CKD.
A quasi‐continuous long‐term (5 Ma) Mid‐European mountain permafrost record based on fluvial magnetic susceptibility and its contribution to the explanation of Plio–Pleistocene glaciations
Authors: Püspöki Zoltán , Markos Gábor , Fancsik Tamás , Bereczki László , Kiss László Ferenc , Thamó‐Bozsó Edit , Krassay Zita , Kovács Péter , McIntosh Richard W. , Vári Zoltán , Stercel Ferenc , Lantos Zoltán , Maigut Vera , Sári Katalin , Rásonyi Miklós , Gibbard Philip L.
Published: November 2024

The low field magnetic susceptibility (χLF) measured in the 1116‐m‐long Dévaványa core (Pannonian Basin) is a quasi‐continuous record of the Plio–Pleistocene Mid‐European mountain permafrost development. The continuity of fluvial conditions is confirmed by seismic data, and the detrital origin of magnetite is indicated by frequency‐dependent susceptibility measurements, scanning electron microscope, and hysteresis investigations. The χLF record is correlated to the δ18O curve (LR04) supported by palaeomagnetic data. The colour of samples documents precession and obliquity cycles in local facies variations, but the χLF indicates the dominance of 100‐ka eccentricity cycles in the linked mountainous permafrost events. Comparison with orbital solutions revealed that the long‐term development of permafrost occurs as a result of amplitude modulation of the 100‐ka eccentricity cycles. Increases in amplitude of the 100‐ka cycles inhibits permafrost development due to shortened winters. Thus, if extremes are present, the permafrost regions are limited or disappear, but if the 100‐ka eccentricity cycles are attenuated, permanent frost can extend into the temperate zone. This amplitude modulation may also be responsible for the early glaciations during the Pliocene, for the intensification of Northern Hemisphere glaciation, foreshadows cooling in the forthcoming 405‐ka term, and allows the change from 41‐ka cycles to 100‐ka ones in the Mid‐Pleistocene Transition to be explained. The 41‐ka cycles are the result of obliquity‐controlled changes close to the polar cycles, while 100‐ka cycles occur when the amplitude attenuation of the 100‐ka eccentricity cycles enables extended glaciations that suppress the regular 41‐ka cycles. Higher mountains in the catchments enable higher resolution of permafrost records documenting even smaller glaciations. However, the similarities in the overall trends in χLF records of catchment areas with 1500‐m difference in their altitude is a potential counter‐argument when considering the role of tectonic elevations in the expansions of mountainous permafrost.
What do Lateglacial and Holocene land snail communities tell us about the palaeoenvironments of Mediterranean France?
Authors: Magnin Frédéric , Martin Sophie , Ollivier Vincent , Sirdeys Naïs
Published: November 2024

Southeastern France occupies a key biogeographical position on the lower Rhone corridor, at the interface between southern and northern Europe. It is also at the heart of long‐standing ecological debates about the respective roles of natural and human drivers in shaping the Mediterranean landscape. Molluscan analysis may represent a valuable contribution to this issue. In this paper, land snail assemblages from three calcareous tufa deposits in the Luberon mountain were used to reconstruct Lateglacial and Holocene palaeoenvironments. The Lateglacial communities only differ from the Pleniglacial ones by the development of hygrophilic snails. We note a high moisture budget at the end of the Lateglacial Interstadial (LGI). A patchy, steppe landscape is attested. A time lag in recolonization by woodland species during the LGI is conceivable. The postglacial woodland assemblages then trace a laborious reassembly of forest snail communities. It takes place mainly between c. 8000 and c. 6600 cal. a BP with spatial disparities and delayed recruitments. The French Mediterranean region has not benefitted from the macrorefugia that it would have sheltered or with which it would have been close. Woodlands, however, appear progressively more closed and complex c. 8000 cal. a BP. They reached their optimum c. 7500 to 7400 cal. a BP although their canopy seems to have stayed quite open. Anthropization remained weak during the Early Neolithic. A significant woodland opening is observed in the Early–Middle Neolithic. Human impact becomes clear from the Late Neolithic. Nevertheless, there are substantial differences compared with Basse‐Provence, where a more marked openness of the landscape from 7000 cal. a BP was accompanied by the development of Mediterranean synanthropic snails. The molluscan successions of the Luberon mountain should be a reference for the development of the Lateglacial and Holocene malacofauna in the SE of France, at the northern boundary of the western Mediterranean domain.
Patient‐reported outcomes after treatment for rectal cancer—A prospective nationwide study
Authors: Slørdahl Kathinka Schmidt , Balto Aina , Guren Marianne Grønlie , Wibe Arne , Kørner Hartwig , Norderval Stig , Gjelsvik Ylva Maria , Myklebust Tor Åge , Larsen Inger Kristin
Published: November 2024

Aim

While modern treatment has improved rectal cancer (RC) survival, it can cause late side effects that impact health‐related quality of life (HRQoL). The aim of this study was to evaluate HRQoL and late effects 1 year after diagnosis in patients who underwent major resection for Stage I–III RC.

Method

All patients with RC registered in the Cancer Registry of Norway between 1 January 2019 and 31 December 2020, aged ≥ 18 years, and a control group without colorectal cancer were invited to participate in the study by answering a questionnaire on HRQoL and late effects. Functional domains and symptoms were compared in different patient groups and between patients and controls.

Results

There were 558 patients and 1693 controls eligible for analysis. Response rates were 41% for patients and 23% for controls. Some differences in HRQoL were observed between treatment modalities. Major low anterior resection syndrome (LARS) was prevalent in 60.8% of patients, and was associated with lower functional and higher symptom scores compared with patients with no/minor LARS. Patients with major chronic pain [n = 86 (15.4%)] had significantly lower scores for most of the functional items and higher symptom scores than patients with no/minor chronic pain. Patients had some lower functional scores and several higher symptoms score compared with controls.

Conclusion

Patients who suffered from major LARS or major chronic pain had significantly impaired functions and more symptoms beyond change in bowel function and pain, respectively. Identification and treatment of these patient may hopefully be beneficial for their HRQoL.
Adults and Children Engage in Subtle and Fine‐Grained Action Interpretation and Evaluation in Moral Dilemmas
Authors: Blomberg Isa , Schünemann Britta , Proft Marina , Rakoczy Hannes
Published: November 2024

Understanding the actions of others is fundamental for human social life. It builds on a grasp of the subjective intentionality behind behavior: one action comprises different things simultaneously (e.g., moving their arm, turning on the light) but which of these constitute intentional actions, in contrast to merely foreseen side‐effects (e.g., increasing the electricity bill), depends on the description under which the agent represents the acts. She may be acting intentionally only under the description “turning on the light,” but did not turn on the light in order to increase the electricity bill. In preregistered studies (N = 620), we asked how adults and children engage in such complex subjective action interpretation and evaluation in moral dilemmas. To capture the deep structure of subjects' representations of the intentional structures of actions, we derived “act trees” from their response patterns to questions about the acts. Results suggest that people systematically distinguish between intended main and merely foreseen side‐effects in their moral and intentionality judgments, even when main and side‐effects were closely related and the latter were harmful. Additional experimental conditions suggest that, when given ambiguous information, the majority of subjects assume that agents act with beneficial main intentions. This “good intention prior” was so strong that participants attributed good intentions even when the harmful action was no longer necessary to resolve the dilemma (Study 2). These methods provide promising new ways to investigate in more subtle and fine‐grained ways how reasoners parse, interpret, and evaluate complex actions.
Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma
Authors: Bao Bin , Yu Xiaojun , Zheng Wujun , Sun Jiewei
Published: November 2024

Background

Kinesin family member 5A (KIF5A) has been reported to be closely related to cancer progression. The aim of this study was to investigate the effect of KIF5A on lung adenocarcinoma (LUAD) and its potential molecular mechanisms.

Methods

Using bioinformatics analysis methods and molecular experiments, the expression of KIF5A in LUAD was analyzed, with its expression in attached and detached tumor cells assessed. Gene set enrichment analysis (GSEA) of KIF5A was carried out. The small molecular drug with the highest affinity for KIF5A was screened out through molecular docking experiments, which was validated through cellular thermal shift assay (CETSA). Quantitative polymerase chain reaction (qPCR) was employed to measure the expression levels of anoikis‐repressing genes (BCL2, CAV1), as well as anoikis‐inducing gene (PDCD4). CCK‐8 assay was applied to examine cell viability. Cell colony formation experiments were utilized to evaluate cell proliferation ability.

Results

We observed that KIF5A was highly upregulated in LUAD tissues and cells, with a higher level detected in detached LUAD cells. By resorting to bioinformatics analysis, we discovered that KIF5A was abundant in the anoikis pathway. Knocking down KIF5A reinforced anoikis in LUAD. Further screening identified Ergotamine as the small molecular drug with the highest affinity for KIF5A. The CETSA confirmed the binding relationship between the two. In addition, Ergotamine has a promoting effect on the anoikis of LUAD, while overexpression of KIF5A reversed the effects of Ergotamine on LUAD cells.

Conclusion

This project uncovered that the small molecular drug Ergotamine targets and inhibits the expression of KIF5A. Downregulated KIF5A can enhance the anoikis of LUAD. Our results supported the inhibition of KIF5A as an attractive therapeutic strategy for LUAD. This finding provides a new innovative pathway for the treatment of LUAD and offers a strong theoretical basis for the development of therapeutic drugs targeting KIF5A.
Beyond Borders: International Immunosuppression Practices in Pediatric Lung Transplantation
Authors: Wong Erica , Brockmeyer Jake , Benden Christian , Avdimiretz Nicholas
Published: November 2024

Introduction

Current recommendations for lung transplantation immunosuppression do not explicitly target children, and many pharmacotherapies used in pediatrics are extrapolated from adults.

Methods

Data were collected from an anonymous survey distributed to International Pediatric Lung Transplant Collaborative (IPLTC) members from November 2023 to February 2024. Eligible participants included pediatric lung transplant physicians, pharmacists, or others with expertise in their lung transplant center's protocols. Participant and program demographics were surveyed, including location and transplant volume. Seventeen multiple‐choice questions, text responses, and Likert scale statements covered the following: induction immunosuppression, maintenance immunosuppression, drug monitoring, dose optimization, and expert guidance available in current literature.

Results

Among the 23 pediatric lung transplant healthcare professionals who responded, 13 respondents (57%) preferred using basiliximab as their standard induction immunosuppression. 3 (13%) prefer rabbit anti‐thymocyte globulin (rATG), while 7 (30%) consider either rATG or basiliximab for induction. Of 22 responses with 100% completion, 21 of 22 (95.2%) respondents reported a combination of tacrolimus, mycophenolate mofetil (MMF), and corticosteroids (CCS) as their preferred maintenance immunosuppression regimen, reflecting the suggested preferred regimen for pediatric lung transplantation. Feedback on the perception of available evidence‐based or established guidelines revealed the majority (90.0%) of respondents found them to be insufficient for pediatrics.

Conclusion

This international survey highlights the variability in immunosuppression practices across pediatric lung transplant programs around the world. The findings underscore a gap in unified, evidence‐based practice guidelines. With strong consensus among respondents on the lack of established guidelines, there is a clear directive for future research to establish standardized practices in pediatric lung transplantation.
Evaluation of skin cancer screening in Germany – a Microsimulation
Authors: Baltus Hannah , Hübner Joachim , Garbe Claudia , Hagenström Kristina , Rohr Maren , Hischke Sandra , Augustin Jobst , Augustin Matthias , Katalinic Alexander , Eisemann Nora
Published: November 2024

Background

Comprehensive skin cancer screening was introduced in Germany in 2008. It is unclear whether subsequently observed changes in the epidemiology of malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are due to the screening. Simulation models are used to compare different screening scenarios with each other and with observed incidence and mortality trends.

Methods

A microsimulation model for MM, SCC, and BCC was programmed and validated separately by sex on skin cancer‐specific mortality data. In addition to the currently practiced screening (biennial offer, annual participation probability 15%), triennial screening, screening with increased participation, e.g., via invitation, and no screening were simulated. Incidence, mortality, costs, and life‐years gained were simulated for 30 years from the start of screening.

Results

Compared with no screening, mortality is reduced by 13.8% in the simulation with current conditions. This effect occurs in the first years after screening starts before reaching a stable level. More screening allows for further increases in incidence, life‐years gained, and costs and decreases in mortality. Comparing simulated and observed effects shows little agreement.

Conclusions

The model is useful for comparing screening scenarios to identify potential optimization opportunities in SCS. Additional, especially risk‐adapted, screening scenarios should be investigated.
Genetic and Habitat Rescue Improve Population Viability in Self‐Incompatible Plants
Authors: Encinas‐Viso Francisco , Thrall Peter H. , Young Andrew G.
Published: November 2024

Habitat fragmentation and the acceleration of environmental change threaten the survival of many plant species. The problem is especially pronounced for plant species with self‐incompatibility mating systems, which are obligate outcrossers, thus requiring high mate availability to persist. In such situations, plant populations suffering decreased fitness could be rescued by: (a) improving local habitat conditions (habitat rescue), (b) increasing the number of individuals (demographic rescue), or (c) introducing new genetic variation (genetic rescue). In this study, we used a spatially and genetically explicit individual‐based model to approximate the demography of a small (N = 250) isolated self‐incompatible population using a timescale of 500 years. Using this model, we quantified the effectiveness of the different types of rescues described above, singly and in combination. Our results show that individual genetic rescue is the most effective type of rescue with respect to improving fitness and population viability. However, we found that introducing a high number of individuals (N > 30) to a small population (N = 50) at the brink of extinction through demographic rescue can also have a positive effect on viability, improving average fitness by 55% compared to introducing a low number of individuals (N = 10) over a long timescale (> 500 years). By itself, habitat rescue showed the lowest effects on viability. However, combining genetic and habitat rescue provided the best results overall, increasing both persistence (> 30%) and mate availability (> 50%). Interestingly, we found that the addition of even a small number of new S alleles (20%) can be highly beneficial to increase mate availability and persistence. We conclude that genetic rescue through the introduction of new S alleles and an increase in habitat suitability is the best management strategy to improve mate availability and population viability of small isolated SI plant populations to overcome the effects of demographic stochasticity and positive density dependence.
MeDi‐TODER: Medical Domain‐Incremental Task‐Oriented Dialogue Generator Using Experience Replay
Authors: Kim Minji , Yoo Joon , Jeong OkRan
Published: November 2024

Artificial intelligence (AI) technology has brought groundbreaking changes to the healthcare domain. Specifically, the integration of a medical dialogue system (MDS) has facilitated interactions with patients, identifying meaningful information such as symptoms and medications from their dialogue history to generate appropriate responses. However, shortcomings arise when MDS lacks access to the patient's cumulative history or prior domain knowledge, resulting in the generation of inaccurate responses. To address this challenge, we propose a medical domain‐incremental task‐oriented dialogue generator using experience replay (MeDi‐TODER) that applies the continual learning technique to the medical task‐oriented dialogue generator. By strategically sampling and storing exemplars from previous domains and rehearsing it as it learns, the model effectively retains knowledge and can respond to the novel domains. Extensive experiments demonstrated that MeDi‐TODER significantly outperforms other models that lack continual learning in both natural language generation and natural language understanding. Notably, our proposed method achieves the highest scores, surpassing the upper‐class benchmarks.
Dynamic Stakeholder Analysis Through Process Mapping
Authors: Rouse Paul , Sherkat Omid , O'Grady Winnie
Published: November 2024

Identification of stakeholders and their importance is critical to the design of accountability and performance management systems. Conventional stakeholder analysis approaches provide a static view of stakeholders and overlook that accountability is a dynamic process encompassing multiple temporally separated (or distinct) stages. We approach stakeholder analysis from a process perspective to ensure a more complete identification of stakeholders and to capture the dynamic nature of stakeholder emergence, retirement, and changes in relative importance. We used a participatory action research methodology to investigate contracting services in a community health setting and employed process mapping to reveal contracting activities undertaken in sequential stages of Deming's Plan–Do–Check–Act (PDCA) cycle. Stakeholders engage at different stages with different activities of a process so that in multi‐stage processes, stakeholder analysis needs to be repeated at each stage and is specific to each stage. Our use of the PDCA is broader than traditional applications and provides a suitable framework for a more complete identification of stakeholders across the entire process while aligning well with accountability and management control notions. The contribution is an approach that not only better identifies stakeholders but also recognizes the dynamics of multi‐stage processes for stakeholder interest and influence. The recurring nature of many processes (such as contracting) implies that roles remain the same even if an organization is restructured so that process mapping will still identify roles and stakeholders. This approach can be used by other organizations to better identify stakeholders and their dynamics in the planning and delivery processes.
The synergy between alkylating agents and ERCC1–XPF inhibitors is p53 dependent
Authors: Ciniero Gloria , Pedro Tiago Marques , Dumontet Charles , Elmenoufy Ahmed H. , West Frederick G. , Weinfeld Michael , Gentile Francesco , Tuszynski Jack A. , Cros‐Perrial Emeline , Jordheim Lars Petter
Published: November 2024

Background

DNA repair plays a major role in maintaining genomic stability, thus limiting the transformation of normal cells into cancer cells. However, in cancer patients treated with DNA‐targeting drugs, DNA repair can decrease efficacy by removing the damage generated by such molecules that is needed to induce pharmacological activity. Inhibiting DNA repair thus represents an interesting approach to potentiating the activity of chemotherapy in this setting.

Objectives

Here, we continue the characterization of an inhibitor of the interaction between Excision Repair Cross‐Complementing Rrodent repair deficiency complementation group 1 (ERCC1) and Xeroderma Pigmentousum group F (XPF) (B9), two key proteins of nucleotide excision repair.

Methods

We used various cell lines and co‐incubation studies for the determination of cell survival and DNA repair capacities.

Results

We show that it is synergistic with other platinum derivatives than previously described, and that synergy is lacking in cells not expressing ERCC1 or XPF. Finally, a series of experiments show that potentiation is observed only in cells expressing wild‐type p53.

Conclusion

Our results confirm the mechanism of action of our ERCC1–XPF inhibitor and give important additional data on this approach to enhance the activity of already existing cancer drugs.
Structure of human phospholipase D3, a single‐strand exonuclease associated with Alzheimer's disease
Authors: Bijelic Aleksandar , Macheroux Peter
Published: November 2024

Phospholipase D3 (PLD3) has emerged as an important 5′‐exonuclease in charge of removing single‐stranded DNA in lysosomes. Rare genetic variants of the gene encoding PLD3 have been implicated in late‐onset Alzheimer's disease (AD). Ishii et al. have produced the soluble domain of human PLD3 with the aim of determining its three‐dimensional structure using X‐ray crystallography. The high‐resolution structure (2.3 Å) provides new insights into the biochemical properties of the enzyme and paves the way to a deeper understanding of amino acid replacements affecting the stability and activity of the enzyme.
Association of PADI4 Gene Polymorphisms With Susceptibility to Rheumatoid Arthritis: Evidence From 24 Case–Control Studies
Authors: Karimian Mohammad , Mohammadzadeh Fatemeh Zahra
Published: November 2024

This study aims to investigate the association of rs11203366, rs11203367, rs874881, rs2240340 and rs1748033 polymorphisms of protein‐arginine deiminase type 4 (PADI4) gene with the risk of rheumatoid arthritis (RA) through a meta‐analysis that was followed with a bioinformatics approach. The data were collected from reputable articles and underwent quantitative analysis, followed by in silico analysis using some bioinformatics tools. The results showed that rs874881 polymorphism in Latino (G vs. C: OR = 1.35, 95% CI = 1.11–1.65, p = 0.003; GG + CG vs. CC: OR = 2.02, 95% CI = 1.41–2.89, p = 0.0001; CG vs. CC + GG: OR = 1.38, 95% CI = 1.04–1.83, p = 0.027; GG vs. CC: OR = 2.09, 95% CI = 1.35–3.23, p = 0.001; CG vs. CC: OR = 1.98, 95% CI = 1.36–2.87, p = 0.00033) and rs1748033 in Caucasian population (T vs. C: OR = 1.25, 95% CI = 1.07–1.45, p = 0.005; TT vs. CT + CC: OR = 1.34, 95% CI = 1.09–1.64, p = 0.005, TT + CT vs. CC: OR = 1.26, 95% CI = 1.09–1.44, p = 0.001; TT vs. CC: OR = 1.59, 95% CI = 1.13–2.23, p = 0.007; CT vs. CC: OR = 1.20, 95% CI: 1.04–1.39, p = 0.015) are associated with increased risk of RA. Moreover, rs11203366 (G vs. A: OR = 1.46, 95% CI = 1.19–1.78, p = 0.0002, GG vs. AG + AA: OR = 1.42, 95% CI = 1.01–2.01, p = 0.043; GG + AG vs. AA: OR = 2.03, 95% CI = 1.45–2.86, p = 0.00004; GG vs. AA: OR = 2.29, 95% CI = 1.49–3.51, p = 0.0002; AG vs. AA: OR = 1.93, 95% CI = 1.35–2.76, p = 0.0003) and rs11203367 (T vs. C: OR = 1.50, 95% CI = 1.23–1.83, p = 0.00007; TT vs. CT + CC: OR = 1.56, 95% CI = 1.12–2.18, p = 0.009; TT + CT vs. CC: OR = 2.02, 95% CI = 1.43–2.84, p = 0.00007, TT vs. CC: OR = 2.43, 95% CI = 1.59–3.71, p = 0.0004; CT vs. CC: OR = 1.86, 95% CI = 1.30–2.68, p = 0.0007) had an impact in the Latino population. Bioinformatics tools showed the effect of these polymorphisms on gene function. These findings suggest that rs11203366, rs11203367, rs874881 and rs1748033 polymorphisms may be genetic risk factors for RA. Moreover, differences between populations suggest that ethnicity may play an important role in the effect of these polymorphisms on RA risk.
The journey of young scientists in Brazil: challenges and perspectives
Authors: Corsi‐Zuelli Fabiana
Published: November 2024

As a young scientist in Brazil, my journey began with a modest education in a public school system that often lacked the resources needed to provide students with comprehensive support. However, with persistence and determination, I successfully gained admission to the University of São Paulo, a prestigious institution and one of the top universities in Latin America. My research focuses on the relationship between the nervous and immune systems in psychosis, a topic I am deeply passionate about. In this piece, I will discuss the systemic issues within the Brazilian education and research systems and delve deeper into my own challenges and achievements as a young scientist in Brazil, sharing insights that can inspire others in similar situations.
Unpacking reflexivity, psychological empowerment, and agile project dynamics among information systems professionals
Authors: Hekkala Riitta , Nordbäck Emma
Published: November 2024

In this study, we examine the reflexivity modes of information systems (IS) professionals and integrate the IS context—including structural, technological, and social properties—with IS professionals' biographical, inner dialogues to theorise about the role of reflexivity modes in their experiences of psychological empowerment. Through the lens of Archer's (2007) three‐stage model of reflexivity and different modes of reflexivity (communicative, autonomous, meta, and fractured), we investigate the experiences of psychological empowerment and project dynamics among IS professionals in IS development work by zooming in on 6 years of three IS professionals' work lives. Our findings make several contributions to theory and practice. First, we elucidate the interplay between reflexivity and psychological empowerment. Second, we show how different IS professionals' approach similar structural, technological, or social circumstances differently (such as agile work practices), depending on their reflexive inner dialogues. This includes showing how different reflexivity modes, focused on various properties of the IS context (structural, technological, and social), becomes entangled with interpersonal dynamics and IS project dynamics.
Application of the Actor–Partner Interdependence Model in Parent–Adolescent Mental Health Knowledge and Depression
Authors: Jiang Yu Lei , Lv Zi Yao , Zhou Yang , Hou Hao , Ao Meng Qin , Fu Yu‐Xin , Zou Huijing , Wang Xiao Qin , Luo Dan , Yang Bing Xiang
Published: November 2024

Aim

To explore the individual and interpersonal association between mental health knowledge (MHK) and depression in adolescents and one of their parents, and to explore whether gender differences exist between fathers and mothers in these associations.

Methods

Participants were 3456 father–adolescent dyads and 4478 mother–adolescent dyads, recruited from eight middle schools in Wuhan, who completed self‐report assessments of MHK and depression from September to October 2021.

Results

With the application of the actor–partner interdependence model, A positive actor effect between MHK and depression in adolescents was found. Adverse partner effects from fathers' MHK and mothers' MHK to adolescent depression were noted and showed no significant difference. Adolescents' depression was significantly associated with parental depression in both fathers and mothers.

Conclusion

It is implied that milder adolescent depression was associated with lower levels of adolescent MHK, along with higher levels of MHK in both fathers and mothers. For parents, it is important to emphasise the improvement of their own MHK and increase their attention to adolescent mental health problems, as this may contribute to enhancing the mental health of adolescents.

Implications for the Profession and/or Patient Care

This study is instructive and related to family‐based nursing interventions for mental health, emphasising the potential influence of parents in the family on adolescent depressive symptoms. The findings suggest that parental involvement should be encouraged and that the family's role in supporting the child's mental health should be recognised, contributing to the development of relevant policies.

Impact

This study highlights that higher parental MHK is associated with lower levels of adolescent depression, with no gender differences between fathers and mothers. Family‐based nursing interventions that emphasise mental health education for parents may have an impact on improving depression in adolescents.

Reporting Method

Guidelines were followed using the STROBE reporting method.

Patient or Public Contribution

None.
A Geological Imprint on Plant Biodiversity: Eastern Australia's Cenozoic Volcanic Flora
Authors: Nguyen Ngoc , Buettel Jessie C. , Brook Barry W.
Published: November 2024

Aim

Australia's distinct geological history provides key insights into the diversity of its flora. While previous studies have predominantly focused on climate as the main driver of species richness, growing evidence suggests that geological factors also play an important role. This study aims to investigate the influence of Cenozoic volcanic lithologies on terrestrial vascular plant diversity in eastern Australia, disentangling the relative contributions of climate and geology to biodiversity patterns.

Location

Eastern Australia.

Taxon

Terrestrial vascular plants.

Methods

We assessed the patterns of species richness in this region by examining whether sites with Cenozoic volcanic lithologies harbour greater vascular plant diversity, using a permutational multivariate analysis of variance (PERMANOVA). We then used a supervised machine learning algorithm (decision trees) coupled with partial canonical correspondence analysis (CCA) to discriminate the environmental variables influencing species richness and site composition in 230 sites in Queensland, New South Wales, Victoria and Tasmania.

Results

Soil profile variability and terrain ruggedness, influenced by underlying volcanic lithologies, emerged as primary predictors of species richness. We found species composition, indicative of distinct ecological communities, showed greater similarity within lithological types and varied significantly across volcanic complexes at different latitudes. Notably, areas of higher species richness corresponded with a greater diversity of stratigraphic units within protected zones.

Main Conclusions

Our study reveals a significant imprint of Cenozoic volcanic activity on present‐day plant species richness and distribution in eastern Australia. We show that geological features, particularly lithology and site complexity, play a crucial role in shaping species richness beyond previously recognised climatic factors. These findings highlight the importance of integrating geological and edaphic factors into conservation strategies, thereby broadening our understanding of ecological dynamics, and guiding more effective biodiversity conservation.
Impacts of interacting with an AI chatbot on preservice teachers' responsive teaching skills in math education
Authors: Lee Dabae , Son Taekwon , Yeo Sheunghyun
Published: November 2024

Background

Artificial Intelligence (AI) technologies offer unique capabilities for preservice teachers (PSTs) to engage in authentic and real‐time interactions using natural language. However, the impact of AI technology on PSTs' responsive teaching skills remains uncertain.

Objectives

The primary objective of this study is to examine whether interaction with a responsive AI‐based chatbot that acts as a virtual student improves pre‐service teachers' noticing abilities. The second objective is to compare how the presence or absence of chatbot responses affects changes in PSTs' questioning practices. Finally, the third objective is to investigate how the experience of interacting with the responsive virtual student affects PSTs' perceptions of the effectiveness of their questioning, their satisfaction with the interactions, and their confidence about interacting with a real student compared to the non‐responsive chatbot.

Methods

A randomised controlled pre‐ and post‐test design was used with 50 PSTs. PSTs' noticing, interaction with the chatbot, and post‐survey data were collected, and a t‐test was conducted to examine significant differences by group.

Results and Conclusion

In the experimental group, the virtual student responded to PSTs' questions, while in the control group, she did not. Notable differences were observed in their questioning practices.

Takeaways

Overall, AI‐based chatbots hold promise for enhancing PSTs' responsive teaching skills. Future research is needed to examine the long‐term impact of responsive chatbot use on PSTs' noticing skills.
Morphological analysis and cytotoxicity of acrylamide on SPC212 human mesothelioma cells: Do low doses induce proliferation, while high doses cause toxicity?
Authors: Kacar Sedat , Tomsuk Ozlem
Published: November 2024

Acrylamide is broadly utilized in numerous areas with different purposes including being an additive, flocculating, sealing, dry strength improver and polymerizing agent, and so forth. Furthermore, it forms in certain food products at high temperatures. It poses serious hazard since its readily water‐soluble and very reactive nature. Besides in vivo studies, several in vitro studies with various cell lines are carried out to evaluate its toxicity. However, of these cell line studies, there are no mesothelium or mesothelioma cell lines. To fill this lacuna, we aimed at examining various dose range of acrylamide on SPC212 human mesothelioma cell line. First, we executed MTT and neutral red cytotoxicity tests and ascertained IC50 dose. Next, we performed inverted, light (haematoxylin–eosin and May Grünwald), fluorescent (DAPI) and confocal microscope (AO/EB) analyses as well as immunohistochemistry for Bax, Bcl‐2 and PCNA proteins. As a result, we found IC50 of acrylamide at 2.65 mM. Starting from 3.13 mM of acrylamide dose, a deep decrease in cell proliferation was observed. Particularly in MTT assay, a proliferative action of acrylamide was detected at 0.39 and 0.78 mM, supported with inverted microscope images. In light microscope analysis, several cellular degenerations, including condensed and kidney‐shaped nucleus were evident. In AO/EB staining, cells with apoptotic characteristics augmented dose‐dependently, being upheld by a parallel uptick in Bax and a dimunition in Bcl‐2 staining. Besides, PCNA decreased at IC50 dose of acrylamide. This is the acrylamide‐associated first study conducted on SPC212 mesothelioma cells encompassing advanced morphological analysis. We believe this study to be an incentive for future studies.
Hydrogen sulfide alleviates neural degeneration probably by reducing oxidative stress and aldose reductase expression
Authors: Shen Wenqi , Hu Tingyu , Wang Xin , Zhang Xiaoyan , Lu Junxi , Lu Huijuan , Hu Yanyun , Liu Fang
Published: November 2024

We investigated the potential role of hydrogen sulfide (H2S) as a novel therapy for diabetic peripheral neuropathy in diabetic rats. A single dose of streptozotocin (60 mg/kg) was applied to the rats for the diabetic rat models. Sodium bisulfide (50 μmol/kg/d) was injected intraperitoneally daily for 2 weeks as H2S treatment. Electromyogram, haematoxylin eosin staining, transmission electron microscopy, western blotting and enzyme‐linked immunosorbent assay were then performed. H2S treatment did not affect body weights, blood glucose levels or liver function of diabetic rats, while the creatine levels of the H2S‐treated diabetic rats decreased compared with the diabetic control rats. H2S treatment for 2 weeks did not affect the sciatic nerve conduction velocity of the diabetic rats. However, H2S treatment relieved neurons loss and cell atrophy of dorsal root ganglion, and axon degeneration of sciatic nerve in diabetic rats. Serum super oxide dismutase (SOD) levels and SOD2 levels in the sciatic nerve of diabetic rats were lower than the non‐diabetic rats but were restored after H2S treatment. Serum and sciatic nerve homogenate malondialdehyde and aldose reductase expression were higher in diabetic rats but decreased significantly after H2S treatment. Our study revealed that H2S alleviates neural degeneration in diabetic rats probably by reducing oxidative stress and downregulating aldose reductase expression.
The regulation of ovarian degeneration in Pampus argenteus by heat shock protein genes under low‐temperature stress
Authors: Qin Chunlai , Li Chang , Ding Ming , Wang Yi , Li Yaya , Wang Yajun , Wang Xubo , Guo Chunyang
Published: November 2024

Temperature is a crucial environmental factor that significantly impacts the growth, development, metabolism, and physiological functions of fish. To study the effects of low‐temperature on the gonadal development of silver pomfret (Pampus argenteus), a cold period by gradually lowering the water temperature from 18°C to 9°C was simulated. The results showed that hsp70, hsp90a, and hsp90b were widely expressed in the tissues of P. argenteus, with hsp70 primarily expressed in the pituitary, hsp90a and hsp90b mainly expressed in the lateral. The hsps were involved in the development process of P. argenteus from 1 to 27 days post‐hatching (dph). The expression levels of hsp70 and hsp90b were highest at 17 dph, while the levels of hsp90a were at 25 dph. Under the condition of 9°C, regressed oocyte were observed in the ovaries, the oocyte diameter significantly decreased, and the ovaries degenerated 100% after low‐temperature stress. The expression levels of hsps in the ovaries were significantly higher than in the control group, while the expression levels in the testes were significantly lower than in the control group. Taken together, hsps may regulate the ovarian degeneration under low‐temperature stress. Male fish rapidly completed meiosis and maintained the testes in the prophase of meiosis to resist the low‐temperature stress.
Perinatal Loneliness and Isolation Early in the COVID‐19 Pandemic in New York City: A Qualitative Study
Authors: West Brooke S. , Ehteshami Lida , McCormack Clare , Beebe Beatrice , Atwood Ginger D. , Austin Judy , Chaves Vitoria , Hott Violet , Hu Yunzhe , Hussain Maha , Kyle Margaret H. , Kurman Georgia , Lanoff Marissa , Lavallée Andréane , Manning Jeremiah Q. , McKiernan Mary T. , Pini Nicolò , Smotrich Grace C. , Fifer William P. , Dumitriu Dani , Goldman Sylvie
Published: November 2024

Introduction

During the COVID‐19 pandemic, birthing parents were identified as a high‐risk group with greater vulnerability to the harms associated with SARS‐CoV‐2. This led to necessary changes in perinatal health policies but also to experiences of maternal isolation and loneliness, both in hospital settings, due to infection mitigation procedures, and once home, due to social distancing.

Methods

In this study, we qualitatively explored birthing and postpartum experiences in New York City during the early days of the pandemic when lockdowns were in effect and policies and practices were rapidly changing. Using thematic analysis, our focus was on experiences of isolation, navigating these experiences, and the potential impacts of isolation and loneliness on maternal health for 55 birthing people.

Results

Participants described numerous stressors related to isolation during the birthing process, including reconciling their hopes for their birth with the realities of the unknown and separation from partners, family, and friends in the hospital. During the postpartum period, loneliness manifested as having limited or no contact with family and friends, which led to feelings of a need for strengthened social support systems. The impact of these negative experiences shaped mental health. Overall, we found that solitary experiences during birthing and postpartum isolation were major sources of stress for participants in this study.

Discussion

To support impacted families and prepare for future crisis events, clinicians and researchers must prioritize the development of strong clinical and social support structures for perinatal people to ensure both maternal and child health.
Assessment of response to PRRT including anatomical and molecular imaging as well as novel biomarkers
Authors: Kong Grace , Noe Geertje , Chiang Cherie , Herrmann Ken , Hope Thomas A. , Michael Michael
Published: November 2024

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for both oncological and hormone control and is a widely accepted standard of care treatment for patients with neuroendocrine neoplasms (NEN). Its use is anticipated to increase significantly, and this demands accurate tools and paradigms to assess treatment response post PRRT. This article outlines the current role and future developments of anatomical, molecular imaging and biomarkers for response assessment to PRRT, highlighting the challenges and provides perspectives for the need to focus on a multimodality, multidisciplinary and individualised approach for patients with this complex heterogeneous disease.
Early‐life disadvantage and parent‐to‐child financial transfers
Authors: Cheng Kent Jason Go
Published: November 2024

Objective

To determine (1) how parental childhood disadvantage is associated with parent‐to‐child financial transfers for schooling and other unspecified purposes and (2) whether the association holds when parental socioeconomic status (years of education, family income, wealth) is considered.

Background

Cumulative inequality theory posits that early life disadvantage may not only adversely affect one's resource accumulation across the life course, but it may also shape one's ability to provide assistance to offspring.

Method

Data from the Panel Study of Income Dynamics were used to estimate zero‐inflated negative binomial regression models to predict the amount of parent‐to‐child transfers (N = 2364 for school transfers, N = 3618 for other transfers), controlling for parents' and children's sociodemographic factors. Childhood disadvantage score (0 as reference, 1, 2, 3, 4+) was constructed using 13 items that reflect the economic, psychosocial, environmental, and health domains of early life. The associations of each domain with financial transfers were also estimated.

Results

Parents with 4+ disadvantages gave about $2200 less for schooling. Economic and environmental disadvantage lessened levels of school transfers, while environmental disadvantage decreased the odds of being a non‐provider of other transfers. The disparity in transfer amounts generally narrowed when the mediating role of parental socioeconomic status was accounted for.

Conclusion

Higher education has become one of the major mechanisms through which class stratification, social inequality, and health disparities ensue. Educational outcomes among current cohorts of young adults could have been shaped by the preceding generation's childhood through intergenerational exchanges.