bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Significance of Chemotherapy Response Score in Patients Undergoing Interval Debulking Surgery and Attained Complete Cytoreduction for High-Grade Serous Tubal and Ovarian Carcinoma
Authors: Santhamma Anjana J. , Sambasivan Suchetha , Mohanan Simi C. , Nair Rema Prabhakaran , J. Siva Ranjith , James Francis V. , Zachariah Reba Ann , Mohanan Nair Jagathnath Krishna K.
Published: October 2024

Objectives The chemotherapy response score (CRS) has been described to assess the pathological response to chemotherapy in patients with high-grade serous tubal and ovarian carcinoma. The main aim of this study was to assess the prognostic significance of CRS in patients who underwent interval debulking surgery and attained complete cytoreduction.

Materials and Methods A retrospective study was conducted on patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIIC and IV high-grade serous tubal and ovarian carcinomas who had undergone surgery after three to four cycles of neoadjuvant chemotherapy and attained complete cytoreduction from January 2015 to July 2018.

Results A total of 125 patients were included in the study. The median age of the patients was 52 years. There were 21 patients (16.8%) with a CRS of 1, 53 patients (42.4%) with a CRS of 2, and 51 (40.8%) patients with a CRS of 3. The median follow-up period was 77 months. The CRS applied on the omental samples showed significant correlation with progression-free survival (PFS; CRS of 1 vs. 2: median PFS, 17 vs. 22 months; hazard ratio, 1.73; and CRS of 2 vs. 3: median PFS, 22 vs. 54 months; hazard ratio, 2.32) and overall survival (OS; CRS of 1 vs. 2: median OS, 19 vs. 40 months; hazard ratio, 2.13; CRS of 2 vs. 3: median OS, 40 months vs. not reached; hazard ratio, 2.19).

Conclusion Our study confirms that the omental CRS is significantly associated with PFS and OS in patients who attained complete cytoreduction during interval debulking surgery.
Pathological Insights into Non-Neoplastic Renal Parenchyma in Wilms Tumor: Implications for Nephron-Sparing Surgery
Authors: Huang Mingchuan , Shu Man , Xu Zhe , Wang Lin , Liu Longshan , Liu Juncheng , Zhang Huanxi , Yang Shicong , Wang Changxi , Gao Pengfei
Published: October 2024

Introduction This study aimed to evaluate the non-neoplastic renal parenchyma in Wilms tumor (WT) and investigate its impact on nephron-sparing surgery (NSS).

Materials and Methods The non-neoplastic renal parenchyma of WT patients was prospectively collected for pathological examination. The histology of non-neoplastic renal parenchyma was assessed from two perspectives: nephrogenic rests (NRs) and nephrons.

Results A total of 46 non-neoplastic renal parenchyma specimens were collected from 42 WT patients. The surgeons assessed the median proportion of non-neoplastic renal parenchyma as 30%, whereas using ellipsoid volume, it was calculated to be 27%. The Youden index of surgeons' assessment peaked at a 15% proportion of non-neoplastic renal parenchyma. The bilateral WT (BWT) group and NSS group exhibited significant differences compared with the unilateral WT group and radical nephrectomy group, respectively, with the BWT group showing a tendency toward thickened basement membrane.

Conclusion The presence of NRs and endogenous nephron alternations should be given due attention in WT. The probability of abnormalities is low when the proportion of non-neoplastic renal parenchyma exceeds 15%, providing pathological support for expanding the adaptation of NSS.
Reconceptualizing “feeling represented”: A new approach to measure how feelings of political representation are constructed
Authors: Vik Andrea , de Wilde Pieter
Published: October 2024

In political representation, the concept of feeling represented has garnered significant attention in recent years. However, the prevailing conceptualization of feeling represented is limited in its scope and has effectively conflated a perception of being represented with feeling represented. We argue that such a conflation undermines our understanding of political representation, especially in the face of the constructivist turn in representation. Constructivist scholars have theoretically elaborated that representation results from a process in which a linkage is created between represented and representative. We argue that feeling represented is an essential part of establishing this representative relationship. By drawing on the recent constructivist turn in representation and applying key insights from psychology, we develop and test a reconceptualization of feeling represented. Through an online survey, American prolific users ($$N=605$$

N
=
605

) were asked a number of questions related to feeling represented after witnessing representative claims by unelected representatives. Through both exploratory and confirmatory factor analysis, we establish that feeling represented is a multidimensional concept consisting of instrumental, expressive, and aversive dimensions. Thus, feeling represented is a subjective state consisting of clearly emotional components, and it can be measured as a response to unelected representation. Acknowledging this goes beyond the current constructivist account of representation and sets the stage for future research.
Severe hypersensitivity reactions to 2 immunotherapy agents in a patient with cutaneous squamous cell carcinoma
Authors: Liauw Justin C , Silveira Sabrina , Ribizzi-Akthar Iole
Published: October 2024

Purpose

There is currently limited data on cross-sensitivity between immunotherapy agents. In this case study, we report a case of severe anaphylaxis to both pembrolizumab and cemiplimab.

Pembrolizumab (Keytruda) and cemiplimab (Libtayo) are both approved for the treatment of metastatic cutaneous squamous cell carcinoma. Infusion reactions occur rarely with immunotherapy agents. However, if infusion reactions are severe, the treatment should be discontinued, and there is no guidance as to whether another immunotherapy agent may be used. An 87-year-old-male was diagnosed with metastatic cutaneous squamous cell carcinoma expressing a PD-L1 combined positive score of 81%-90%. He was treated with pembrolizumab and, 15 minutes after completion of the first infusion, developed swelling of the eyelids, ears, and tongue in addition to a whole-body rash without pruritus. Due to the severity of the reaction, pembrolizumab was permanently discontinued and the patient was then started on cemiplimab. The patient received a high-dose corticosteroid as premedication before the first infusion of cemiplimab and tolerated the treatment without any adverse effects. However, when the corticosteroid premedication dose was decreased before the second cycle, the patient had a severe infusion reaction to cemiplimab requiring discontinuation.

Conclusion

A patient with metastatic cutaneous squamous cell carcinoma developed a severe hypersensitivity reaction to pembrolizumab and subsequently to cemiplimab, despite premedication.
Twist-related protein 1 promotes transforming growth factor β receptor 1 in keloid fibroblasts via regulating the stability of myocyte enhancer factor 2A
Authors: Li Tianhao , Zhang Mingzi , Li Yunzhu , Sun Yixin , Huang Jiuzuo , Zeng Ang , Yu Nanze , Long Xiao
Published: October 2024

Background

Keloid scarring is caused by a fibroproliferative disorder due to abnormal activation of genes, the underlying mechanism of which is still unclear. The basic helix–loop–helix transcription factor Twist-related protein 1 (TWIST1) controls cell proliferation and differentiation in tissue development and disease processes. In this study, we aimed to clarify the essential role of TWIST1 in the pathogenesis of keloids.

Methods

Immunohistochemistry, cell counting kit-8 assays, western blotting, PCR, matrigel invasion assays and immunofluorescence assays were applied to demonstrate the effects and mechanisms of TWIST1 in fibroblasts derived from normal skin and keloids. Mass spectrometry, ubiquitination assays, chromatin immunoprecipitation and dual luciferase reporter assay were applied to explore the interaction of TWIST1 with downstream molecules.

Results

In the present study, we confirmed that TWIST1 was upregulated in keloid tissue of patients and in keloid-derived fibroblasts (KFBs). In vitro, TWIST1 inhibition prevented KFB proliferation, invasion and activation. We also discovered a link between TWIST1 and the transforming growth factor β (TGF-β) signaling related molecules TGF-β receptor 1 (TΒR1), SMAD family member 2 (Smad2) and Smad3, and the fibrosis markers α-smooth muscle actin, collagen type I and collagen type III in KFBs. Mechanistically, we uncovered a brand-new mechanism by which TWIST1 interacts with myocyte enhancer factor 2A (MEF2A) and suppresses its ubiquitination and degradation. Using chromatin immunoprecipitation and dual-luciferase reporter assay, TΒR1 was identified as a novel downstream target of MEF2A, which directly binds to its promoter. Overexpression of TWIST1 promoted the recruitment of MEF2A to the TΒR1 promoter and restored TΒR1 functional expression.

Conclusions

Our research highlights a significant function of TWIST1 in the development of keloid and its related fibroblasts, partially facilitated by elevated MEF2A-dependent TΒR1 expression. Blocking the expression of TWIST1 in KFBs could potentially pave a novel therapeutic avenue for keloid treatment.
Experimental investigation of the effects of different nanoparticles on the performance of single basin double-slope solar stills
Authors: Phukapak Chawisorn , Phukapak Sorawin , Pawaree Narathip
Published: October 2024

The study focuses on the development of a thermal model for a single basin double-slope solar still and compares the effects of varying volume concentrations of nanoparticles on its performance. The efficiency of single basin double-slope solar still is improved by using strip-grooved fin absorber shapes and a combination of nanoparticles (Al2O3, CuO, Ag, Fe2O3, and ZnO) in water depths from 0.01 to 0.05 m. The nanoparticles are present in different volume concentrations of 0.10%, 0.15%, 0.20%, 0.25%, and 0.30% in saline water within the basin. The strip-grooved fins are used to increase the surface area available for evaporation and serve as an important material for storing thermal energy, which is then transferred to the fluid mass in the basin, increasing its temperature. On the other hand, nanoparticles are used to improve the heat transfer of saline water in the basin and enhance its absorption of solar radiation. The experiment revealed that without the presence of nanofluid, the distillation efficiency of strip-grooved fin was 26.93%. The distillation production efficiency of strip-grooved fins combined with nanoparticles Al2O3, CuO, Ag, Fe2O3, and ZnO were 36.13%, 35.58%, 34.60%, 32.44%, and 29.71%, respectively. Furthermore, the economic analysis showed that the overall costs per liter of freshwater produced by single basin double-slope solar still with strip-grooved fin and the combination of single basin double-slope solar still with strip-grooved fin and Al2O3 were reduced by 0.0368 and 0.0309$/L, respectively.
Design and baseline characteristics of the STRIDE trial: evaluating semaglutide in people with symptomatic peripheral artery disease and type 2 diabetes
Authors: Bonaca Marc P , Catarig Andrei-Mircea , Hansen Yasemin , Houlind Kim , Ramesh Chethana Kalmady , Ludvik Bernhard , Nordanstig Joakim , Rasouli Neda , Sourij Harald , Verma Subodh
Published: October 2024

Background

People with lower extremity peripheral artery disease (PAD) suffer from a high burden of symptoms and significant functional impairment. There are few therapies that improve function and reduce symptoms in this population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to improve glycaemic control, reduce body weight, and reduce the risk of major adverse cardiovascular events in people with atherosclerotic cardiovascular disease and type 2 diabetes (T2D).

Methods and results

STRIDE (NCT04560998) is a randomized, placebo-controlled, double-blind phase 3b trial evaluating 1 mg once-weekly subcutaneous semaglutide (GLP-1 RA) vs. placebo, in people with symptomatic PAD (Fontaine IIa claudication) and T2D. Eligible participants were ≥18 years, had haemodynamically stable PAD, had no planned intervention, and were not receiving a GLP-1 RA. The primary endpoint is change in maximum walking distance on a constant-load treadmill (CLT). Secondary endpoints include quality of life and cardiometabolic assessments. A total of 792 participants were randomized in 20 countries. Participants’ median age was 68 and median T2D duration 12 years. Risk factors included 25.6% current smokers, 87.9% with hypertension, and 42.7% with coronary heart disease. The mean BMI was 29.6 kg/m2 and the mean HbA1C was 7.3%. Participants exhibited baseline functional impairment with a median maximum walking distance of 186 m on a CLT.

Conclusion

STRIDE has enrolled participants with symptomatic PAD and T2D, frequent risk factors and comorbidities, and functional impairment. The trial will provide evidence for the functional outcomes with semaglutide in people with PAD and T2D.
Macrophage-Derived Exosomes Promoted the Development and Stemness of Inflammatory Bowel Disease-Related Colorectal Cancer via nuclear paraspeckle assembly transcript 1-Mediated miRNA-34a-5p/phosphoprotein enriched in astrocytes 15 Axis
Authors: Liu Fen , Ai Feiyan , Tang Anliu , Yang Zhenyu , Li Zhaoqi , Liu Shaojun
Published: October 2024

Background

Inflammatory bowel disease (IBD) is closely associated with the development of colorectal cancer (CRC) due to the chronic inflammatory response. Macrophages play critical roles in regulating the microenvironment to facilitate tumor progression. Exosomes are key modulators for the communication between macrophages and tumor cells. The mechanism of macrophage-derived exosomes in IBD-related CRC development remains unclear.

Methods

The macrophages were isolated using fluorescence activating cell sorter (FACS). The RNA and protein expressions in exosomes and CRC cells were examined by quantitative real-time polymerase chain reaction and western blot assays, respectively. CRC cell development was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, BrdU staining, Transwell assay, and spheroid formation assay. The level of stemness was determined by detecting the proportion of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-positive CRC cells and the expression of LGR5, CD133, and CD44. Molecular interaction experiments were done using luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model in vivo and immunohistochemistry were used to observe the pathological changes.

Results

Macrophage-derived exosomes from IBD-related CRC tissues were enriched with nuclear paraspeckle assembly transcript 1 (NEAT1) and able to promote the progression and stemness of CRC both in vitro and in vivo. The exosomal NEAT1 could sponge miR-34a-5p, leading to the restoration of PEA15 expression in CRC cells and promoting the development of CRC. Inhibition of NEAT1 in exosomes could effectivity inhibit the tumor growth in the CRC xenograft model.

Conclusions

These findings provide novel insights into how macrophages affect CRC development and highlight exosomal NEAT1 as a therapeutic target for CRC treatment.
Regions and the European Union in times of crisis: A decline of the regional interest?
Authors: Solanes Mullor Joan
Published: October 2024

The article examines the evolving role of regions in the EU integration process, particularly in light of recent crises, such as the euro and COVID-19 crises. Historically, EU regional studies have emphasized the importance of regions in EU identity and integration, highlighting their role in regional and cohesion policies as key to a multilevel governance system. However, the euro crisis marked a significant shift, as the European Union’s response—focusing on fiscal discipline—curtailed regions’ budgetary autonomy, especially in Southern Europe. In contrast, the COVID-19 crisis prompted a different approach, with the EU relaxing fiscal controls and increasing public expenditure through initiatives like the Recovery Plan for Europe. Despite these measures, the article argues that state interests continue to dominate, sidelining regional voices in the new institutional structures. The article focuses on two critical aspects: the formal participation of regions in EU governance, particularly in the Economic and Monetary Union and the new pandemic-related frameworks, and the impact of these crises on EU regional policy. The findings suggest a decline in regional influence both in institutional participation and in regional policy resources, marking a regression from pre-crisis trends. While the article does not cover a broader multipolicy analysis or the national-level role of regions, it indicates that the post-crisis era has been challenging for regions in maintaining their relevance and influence within the EU framework. The article thus contributes to the discourse on whether the European Union’s interest in regions has diminished, signaling a potential shift in the balance of power within the EU integration process.
Global stochastic comprehensive sensitivity analysis based on robustness grouping and improved Pelican algorithm-optimized radial basis function neural network
Authors: Guan Tao , Xiao Yifeng , Ren Bingyu , Chen Purui , Yu Hao
Published: October 2024

Modeling analysis is one of the important means to analyze practical engineering, and as technology continues to evolve, various models are getting closer and closer to reality, while at the same time, there are more and more parameters in the models. It is important to analyze the impact of these parameters on the project to assist engineers in making plans or decisions. Sensitivity analysis (SA) can describe the effect of changes in these parameters on the model. However, complex models often have dozens or even hundreds of parameters, and most current SA methods struggle to deal reliably and effectively with these high-dimensional problems. In addition, it is difficult to obtain the sensitivity of continuous points in the parameter space with traditional SA methods. Therefore, this paper proposes a method that combines adaptive grouping and an improved pelican optimization algorithm for an optimal radial basis function (IPOA-RBF) agent model to solve these problems. Firstly, a clustering grouping method considering grouping robustness is established to obtain objective and stable parameter grouping results in high-dimensional SA. Secondly, a proxy model based on radial basis function neural network and an IPOA are proposed to capture the logic of the proxy model to obtain the parameter sensitivity of continuous points in the parameter space. Finally, the superiority and applicability of this method is verified using an arch dam simulation model.
An advanced RIME optimizer with random reselection and Powell mechanism for engineering design
Authors: Xu Shiqi , Jiang Wei , Chen Yi , Heidari Ali Asghar , Liu Lei , Chen Huiling , Liang Guoxi
Published: October 2024

RIME is a recently introduced optimization algorithm that draws inspiration from natural phenomena. However, RIME has certain limitations. For example, it is prone to falling into Local Optima, thus failing to find the Global Optima, and has the problem of slow convergence. To solve these problems, this paper introduces an improved RIME algorithm (PCRIME), which combines the random reselection strategy and the Powell mechanism. The random reselection strategy enhances population diversity and helps to escape Local Optima, while the Powell mechanism helps to improve the convergence accuracy and thus find the optimal solution. To verify the superior performance of PCRIME, we conducted a series of experiments at CEC 2017 and CEC 2022, including qualitative analysis, ablation studies, parameter sensitivity analysis, and comparison with various advanced algorithms. We used the Wilcoxon signed-rank test and the Friedman test to confirm the performance advantage of PCRIME over its peers. The experimental data show that PCRIME has superior optimization ability and robustness. Finally, this paper applies PCRIME to five real engineering problems and proposes feasible solutions and comprehensive performance index definitions for these five problems to prove the stability of the proposed algorithm. The results show that the PCRIME algorithm can not only effectively solve practical problems, but also has excellent stability, making it an excellent algorithm.
Bottom-up effects of nutrient solutions on grape–grape phylloxera (Daktulosphaira vitifoliae) interaction
Authors: Wu Hui , Huang Xiaoqing , Kong Fanfang , Wang Zhongyue , Song Yaqin , Liu Yongqiang
Published: October 2024

Fertilizers generally influence the nutritional quality or defense ability of the plants, which can indirectly cause an increase in populations of herbivorous insect pests such as grape phylloxera, Daktulosphaira vitifoliae (Homoptera: Phylloxeridae, Fitch). The effects of nutrient solutions on grape–grape phylloxera interactions were analyzed using five concentrations (nitrogen content: 15, 30, 60, 120, and 180 mg/L) of Hoagland’s nutrient solution to irrigate Vitis vinifera L. × Vitis labrusca L. (Kyoho). Life table variables and life history variables showed a hump-shaped or an inverted hump-shaped curve as nutrient input level increased. Sixty microgram per liter treatment resulted in the greatest longevity and egg incubation, shortened the nymph duration and significantly increased the adult lifespan. Overall, both excessive and insufficient nutrient inputs curbed growth and multiplication of D. vitifoliae. These results provide a theoretical basis for vineyards for amending fertilizer inputs to prioritize the prevention and control of this pest.
Evolution and screening of Trichoderma reesei mutants for secreted protein production at elevated temperature
Authors: Bodie Elizabeth , Chen Zhongqiang , Crotty Kirstin , Lin Cherry , Liu Chuanbin , Sunux Sergio , Ward Michael
Published: October 2024

The filamentous fungus Trichoderma reesei is a mesophilic ascomycete commercially used to produce industrial enzymes for a variety of applications. Strain improvement efforts over many years have resulted not only in more productive hosts, but also in undesirable traits such as the need for lower temperatures to achieve maximum protein secretion rates. Lower fermentation temperatures increase the need for cooling resulting in higher manufacturing costs. We used a droplet-based evolution strategy to increase the protein secretion temperature of a highly productive T. reesei whole cellulase strain from 25°C to 28°C by first isolating an improved mutant and subsequently tracing the causative high-temperature mutation to one gene designated gef1. An industrial host with a gef1 deletion was found to be capable of improved productivity at higher temperature under industrially relevant fermentation conditions.

One-Sentence Summary

High-temperature droplet-based evolution resulted in the identification of a mutation in Trichoderma reesei gef1 enabling high productivity at elevated temperatures.
A scoping review to determine if adverse human health effects are associated with use of organophosphates for mosquito control
Authors: Tai Zoe , Connelly C Roxanne , Kuczynski Lange Suzanne , Foley Nicole , De Leon Rivera Juan , Lozano Saul , Nett Randall J
Published: October 2024

Organophosphate insecticides are widely used for adult mosquito control. Although proven effective in reducing mosquito populations and limiting arbovirus transmission, public concern exists regarding potential human health effects associated with organophosphate exposure. The aim of this scoping review was to describe any reported human health conditions associated with organophosphates during their use for adult mosquito control in the United States and Canada. Original peer-reviewed articles published in English language journals from 1 January 2000 to 22 May 2024, were obtained by searching from the databases MEDLINE, EMBASE, Agricultural & Environmental Science Collection, CAB Abstracts, and Scopus. The search identified 6,154 screened articles. Following an independent review, 10 studies were identified that described human health conditions associated with organophosphate exposure during adult mosquito control applications. Of the 10 included studies, only two articles were published within the last 11 years (2013 to 22 May 2024). Three types of study design were represented in the included studies: cohort (n = 5), case study (n = 1), and risk assessment (n = 4). The included studies could not determine causality between exposure to adulticides and development of illness or adverse impacts. Exposure to organophosphates did not contribute to an observed increase in metabolic toxicity, hospitalization rates, or self-reported symptoms and exposure. The available and limited evidence indicates that organophosphates can be used safely to control nuisance mosquitoes or mosquitoes that transmit arboviruses. Continued research regarding the human health effects associated with organophosphate applications for adult mosquito control could help evaluate the basis of the public’s concerns and inform public health decision-making.
Use of a two-bag fluid administration protocol in the treatment of paediatric diabetic ketoacidosis: A retrospective review
Authors: Druken Rebecca , Harris Venita , Wong Elizabeth , Abdulsatar Farah , Ens Andrea , Metivier Emma , Miller Michael , Brar Jagraj
Published: October 2024

Objectives

The ‘two-bag method’ for the treatment of diabetic ketoacidosis (DKA) uses two intravenous fluid bags, only one of which contains 10% dextrose. The bags are run concurrently with rates adjusted according to a rate change table to allow the relative amount of dextrose administered to be adjusted over time, without the need for bag replacements. The Children’s Hospital at London Health Sciences Centre (CHLHSC) two-bag protocol is a simplified version of that used by other centres. The objective of this study was to ensure implementation of the CHLHSC two-bag protocol continues to provide safe and effective treatment of paediatric DKA and decreases resource utilization.

Methods

This retrospective chart review compared treatment pre- and post-protocol implementation.

Results

A total of 22 admissions were included. No significant differences in efficacy or safety outcomes were found between the protocol groups. There was no statistically significant difference between the two and one-bag protocols in time to normalization of serum bicarbonate (13.80 ± 7.68 versus 15.01 ± 7.53 h, P = 0.714), blood glucose correction (8.75 ± 4.86 versus 11.85 ± 4.92 h, P = 0.152), and critical care unit length of stay (24.26 ± 9.94 versus 32.30 ± 13.36, P = 0.399). The nursing staff appeared to appropriately implement the rate change table, but the chart documentation was poor.

Conclusions

The CHLHSC simplified two-bag protocol provides a safe and effective alternative to the one-bag protocol for DKA correction in paediatric patients and may also result in decreased resource utilization.
Health insurance for all children in Quebec? Ethical reflections on the implementation of PL 83
Authors: Liv Annie , Li Patricia , Chung Ryoa , Shaheen-Hussain Samir , Razack Saleem , Liu Joanne , Nathalie Gaucher
Published: October 2024

The adoption of Projet de loi 83 (PL83) in 2021 aimed to grant previously uninsured migrant children in Quebec access to provincial public health insurance. Three years later, health professionals continue to encounter children who should be eligible for provincial insurance through PL83 but remain uninsured and who face various structural barriers that contribute to this limited access (language, administrative navigation, and access to information). This commentary, based on the conceptual framework of the ethics of care, considers autonomy as the ability to make one’s own choices with support from others. Contrary to a conception of autonomy as self-sufficiency, the ethics of care encourages the design of policies and implementation measures capable of helping vulnerable individuals overcome barriers. In the case of access to healthcare for migrant children, we suggest presumptive eligibility and raising awareness among all key stakeholders who interact with parents, from admission and administrative staff to physicians.
Comparative analysis of tertiary lymphoid structures for predicting survival of colorectal cancer: a whole-slide images-based study
Authors: He Ming , Ye Huifen , Liu Liu , Yao Su , Li Zhenhui , Fan Xinjuan , Feng Lili , Tong Tong , Cui Yanfen , Yang Xiaotang , Wu Xiaomei , Mao Yun , Zhao Ke , Liu Zaiyi
Published: October 2024

Background

Tertiary lymphoid structures (TLS) are major components in the immune microenvironment, correlating with a favorable prognosis in colorectal cancer. However, the methods used to define and characterize TLS were not united, hindering its clinical application. This study aims to seek a more stable method to characterize TLS and clarify their prognostic value in larger multicenter cohorts.

Methods

A total of 1609 patients from four hospitals and The Cancer Genome Atlas database were analyzed. We quantified the number and maximum length of TLS along the invasive margin of tumor using hematoxylin and eosin-stained whole-slide images (WSIs). Additionally, the length of the invasive margin was determined to calculate the TLS density. The prognostic value of TLS for overall survival was evaluated. In addition, we examined the association between TLS density and immune cell infiltration using immunohistochemistry-stained WSIs. The performance for predicting overall survival was measured using hazard ratios (HR) with 95% confidence intervals (CI).

Results

Among the three TLS quantification methods, TLS density has the strongest discriminative performance. Survival analysis indicated that higher TLS density correlated with better overall survival [HR for high vs. low 0.57 (95% CI 0.42–0.78) in the primary cohort; 0.49 (0.35–0.69) in the validation cohort; 0.35 (0.18–0.67) in TCGA cohort]. A high TLS density was associated with a high level of CD3+ T cell infiltration.

Conclusions

Based on this comparative multicenter analysis, TLS density was identified as a simple, robust, and effective immune prognostic index for colorectal cancer.
Restricted Phase Space Thermodynamics of Nonlinear Electrodynamics-Anti-de Sitter Black Holes
Authors: Awal Mozib Bin , Phukon Prabwal
Published: October 2024

We study the Restricted Phase Space Thermodynamics (RPST) of magnetically charged anti-de Sitter (AdS) black holes sourced by nonlinear electrodynamics (NED). The first law and the corresponding Euler relation are examined using the scaling properties. While the mass is homogeneous in the first order, the intensive variables are observed to follow zeroth-order homogeneity. We use numerical and graphical techniques to find the critical points of the various thermodynamic quantities. By utilizing the rescaling properties of the equation of states, we study the thermodynamic processes using different pairs of variables. From our analysis, we infer that although the RPST of the NED-AdS black hole resembles those of Reissner–Nordström-AdS, Kerr-AdS, and Kerr–Sen-AdS black holes in most of its aspects, hinting at a possible universality, there exists one particular $\mu -C$ process that differs in its behavior from its counterparts in earlier reported works.
Impacts of agricultural production decisions on the safe and just operating space: A systematic literature review
Authors: Aladesuru Damilola T , Cechura Lukas , Neuenfeldt Sebastian , Kuhn Till , Kristkova Zuzana Smeets , Kroupová Zdeňka Žáková , Ratinger Tomas , Gocht Alexander , Müller Marc , Storm Hugo
Published: October 2024

Agricultural production decisions impact how agriculture navigates within the safe and just operating space (SJOS). The ability to model and assess these impacts is crucial for policy analysis. This study systematically explores the literature for links between agricultural production decisions and SJOS. As agricultural production decision categories, we examine on-farm technology usage, farm structural change, and field structural change. We identify the impact mechanisms of various aspects of these categories and discuss the scope of evidence available. Technology usage impacts the SJOS often through farmers’ choice of technology and its effect on yield. Farm structural change impacts the SJOS through economies of scale and scope, while field structural change impacts directly and through management efficiency. There is considerable knowledge of these relationships but also research gaps. The study provides fundamental insights for characterizing the decision properties of agricultural production and is useful for guiding policy modelling for improved SJOS outcomes.
Intergenerational family life courses and wealth accumulation in Norway
Authors: Hünteler Bettina , Nutz Theresa , Wörn Jonathan
Published: October 2024

While prior research has widely acknowledged the consequences of specific family transitions (e.g., parental death, parenthood, grandparenthood) for individual wealth holdings, the interplay of multiple family transitions and positions occurring at different life stages and in various orderings has received little attention. This is despite the fact that these transitions and positions most likely jointly shape wealth accumulation, both in the shorter and longer run. We apply (1) sequence analysis to identify typical family life course clusters defined by the timing of the death of the parent generation, the timing of the transition into parenthood, and grandparenthood and (2) regression analysis to describe how the accumulation of wealth between ages 40 and 64 differs by family life course cluster. Using Norwegian register data of individuals born in 1953 (N = 47,945), we identified six clusters of family trajectories ranging from childless individuals to individuals who were sandwiched between their parents, children, and grandchildren because of relatively early (grand)parenthood and late parental death. Individuals experiencing patterns with a later transition into (grand)parenthood occupied stable and high wealth positions over time. Individuals without children exhibited a steady increase in their wealth position. Additionally, experiencing parental death later in life was associated with increasing wealth, whereas early parental death was not. These results held net of gender and education. Pronounced and even increasing wealth differences over the life course seem to be associated with the interplay of multiple family transitions.
Fabrication of bio-inorganic metal nanoparticles by low-cost lychee extract for wastewater remediation: a mini-review
Authors: Naseem Khalida , Asghar Sana , Sembiring Kiky Corneliasari , Khan Mohammad Ehtisham , Hameed Asima , Massey Shazma , Hassan Warda , Anwar Aneela , Khan Haneef , Shair Faluk
Published: October 2024

Introduction: This review article gives an overview of the biogenic synthesis of metal nanoparticles (mNPs) while using Litchi chinensis extract as a reducing and stabilizing agent. The subtropical fruit tree i.e lychee contains phytochemicals such as flavonoids, terpenoids, and polyphenolic compounds which act as reducing agents and convert the metal ions into metal atoms that coagulate to form mNPs. Methodology: Different methodologies adopted for the synthesis of lychee extract and its use in the fabrication of mNPs under different reaction conditions such as solvent, extract amount, temperature, and pH of the medium have also been discussed critically in detail. Techniques: Different techniques such as FTIR, UV–visible, XRD, SEM, EDX, and TEM adopted for the analysis of biogenic synthesis of mNPs have also been discussed in detail.

Applications of mNPs: Applications of these prepared mNPs in various fields due to their antimicrobial, antiinflammatory, anticancer, and catalytic activities have also been described in detail.
Interpretation of Guidelines for Diagnosis, Management, and Prevention of Pertussis in China (2024 Edition)
Authors: Zeng Mei , Shao Zhujun , Xia Jun , Zhang Wenhong , Feng Tianxing , Cai Jiehao , Chen Mingliang
Published: October 2024

The resurgence of pertussis in China has recently attracted much attention. The incidence and burden of pertussis are largely underestimated in China owing to the lack of active pertussis surveillance and insufficient laboratory diagnosis. The high prevalence of macrolide-resistant Bordetella pertussis imposes a major challenge for the management of pertussis cases. To address a series of practice issues regarding pertussis diagnosis, treatment, and prevention, especially immunization practices, a multidisciplinary guideline development group (GDG) consisting of experts in the fields of infectious diseases, pediatric critical care medicine, clinical microbiology, epidemiology, and immunization planning jointly developed the first clinical practice guidelines for pertussis in China. Utilizing the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework recommended by the World Health Organization, the GDG formulated corresponding recommendations and suggestions. Good Practice Statements were created for issues not suitable for conventional evidence rating through the presentation of evidence and expert experience. The implementation suggestions for the 12 priority clinical questions given in this paper fully considered Chinese and international experiences as well as the national situation and policy. The primary target audience of these guidelines includes clinicians, microbiology laboratory staff, public health professionals, and policymakers.
Unveiling the spectrum of Respiratory Syncytial Virus disease in Adults: from Community to Hospital
Authors: Korsten Koos , Welkers Matthijs R.A. , van de Laar Thijs , Wagemakers Alex , van Hengel Peter , Wever Peter C. , Kolwijck Eva
Published: October 2024

Background

Respiratory syncytial virus can cause severe disease in the older adult population. Three vaccines for RSV are currently market approved but the risk of RSV-hospitalization in (older) adults from a community level remains elusive. We aimed to estimate the risk of RSV-hospitalization and characterize the patients that end up in hospital.

Methods

We manually analyzed records of adults aged ≥20 with RSV-infection between 2022-2024 in three hospitals in the Netherlands. These hospitals implemented routine RSV-testing at emergency departments. Using population-based data in combination with the in-hospital data, we estimated the population risk of RSV-hospitalization. Hospital records were analyzed to characterize the role RSV played in their course of disease.

Results

We analyzed 709 RSV cases of whom 503 (70.9%) were hospitalized. 526 patients were ≥60, and 183 were <60 years of age. The population risk of RSV-hospitalization was 0.006-0.02% for patients aged 20-59 years and 0.04-0.24% for those ≥60. The highest risks were seen in older patients with congestive heart disease (0.14-5.0%) and COPD (0.17-1.76%). RSV caused clinically relevant infection in 88% of hospitalized cases but was only mentioned using specific ICD-codes in 4.4%. Comorbidity was prevalent (88.5%) and exacerbation of underlying disease caused of 46.3% of RSV-related hospital admissions. ICU admittance was 11.2% and in-hospital mortality was 8.1%.

Conclusion

The risk of RSV-hospitalization from the community is low but is increased substantially in those with underlying disease. RSV is often clinically relevant in hospitalized patients by causing exacerbation of underlying disease but is infrequently mentioned in specific ICD-codes.
Correlates of behavioral and emotional disorders among school-going adolescents in Uganda
Authors: Bobholz Max , Dickson-Gomez Julia , Abbo Catherine , Kiconco Arthur , Shour Abdul , Kasasa Simon , Cassidy Laura , Anguzu Ronald
Published: October 2024

Background

Adolescence is a critical development transition period that increases vulnerability to poor mental health outcomes. Recent evidence suggests that 9.6% and 11.5% of adolescents in Uganda experienced behavioral and emotional disorders, respectively. We examined the factors associated with emotional and behavioral health outcomes among school-going adolescents in Uganda.

Methods

This cross-sectional study surveyed 1,953 students aged 10-24 enrolled in Central and Eastern Uganda secondary schools selected by stratified random sampling. Our outcome variables were (i) emotional and (ii) behavioral disorders that were measured using the Child and Adolescent Symptom Inventory-5 (CASI-5) diagnostic criteria outlined in the Diagnostic Statistical Manual-5 (DSM-5). Emotional disorders included major depressive disorder, generalized anxiety disorder, social anxiety disorder, and separation anxiety disorder. Attention deficit/hyperactivity disorder, conduct disorder, and oppositional defiant disorder were considered behavioral disorders. Covariates included socio-demographic, hardship-related experiences, and school-related characteristics. Modified Poisson and logistic regression models were appropriately run for the factors independently associated with respective outcomes. Prevalence ratios (PR), odds ratios (OR), and corresponding 95% confidence intervals (95%CI) were reported with p<0.05 considered significant.

Results

Participants’ mean age was 15.5 (SD=2.0) years; 54.7% were female, 5.7% had a behavioral disorder, and 17.4% had an emotional disorder. In the adjusted models, factors independently associated with higher odds of behavioral disorder were age (OR=1.2; 95%CI 1.1,1.4) and family history of mental illness (OR=1.9; 95%CI 1.2,3.3). Factors independently associated with a higher risk of emotional disorder were being female (PR=1.5; 95%CI 1.2,1.8), being enrolled in advanced education (PR=1.7; 95%CI 1.2,2.4), and attending private school (PR=1.4; 95%CI 1.1,1.8).

Conclusion

Behavioral and emotional disorders are prevalent among adolescents enrolled in secondary schools in Central and Eastern Uganda. Further inquiry using longitudinal designs is essential to understanding pathways for potential causality of the identified associations. School-based programs may consider routine screening for multi-level risk factors to improve the mental health of school-going adolescents.
A new phylogenetic framework for the genusKalanchoe(Crassulaceae) and implications for infrageneric classification
Authors: Rodewald Seraina E. , Klein David-Paul , Shtein Ronen , Smith Gideon F. , Joyce Elizabeth , Morales Briones Diego F. , Bernhard Sven , Letsara Rokiman , Mertes Hannah , Hühn Philipp , Kadereit Gudrun
Published: October 2024

Background and Aims

Kalanchoeis a diverse genus in the Crassulaceae, with a centre of diversity in Madagascar and sub-Saharan Africa. The genus is known for its popularity in horticulture, its use as a model system for research on CAM photosynthesis and vegetative reproduction, its high invasive potential, and its use in traditional medicine. The genus-rank circumscription and infrageneric classification ofKalanchoehas been the subject of debate for centuries, especially regarding the status and rank of what is now treated asK.subg.BryophyllumandK.subg.Kitchingia. We aim to generate a densely sampled phylogeny ofKalanchoe s.l.and evaluate the current infrageneric classification system.

Methods

We inferred a phylogenetic tree forKalanchoeusing a ddRAD sequencing approach, covering 70% of taxa and four out of five subgenera currently recognised in the genus.

Key Results

We recovered four well-supported clades, partially corresponding to the current subgeneric classification.Kalanchoesubg.Calophygiaresolves as sister to the rest of the genus. The relationships among the three remaining clades, however, receive less support. The predominantly mainland AfricanK.subg. Kalanchoeforms a strongly supported clade that resolves as sister toK.subg.Bryophyllum. These two clades are together sister to a clade containing mainly species fromK.subg.KitchingiaandK.sect.Pubescentes.

Conclusions

The current subgeneric classification ofKalanchoeis partially backed up by our phylogenetic tree but requires further refinement. The tree topology suggests a Malagasy origin of the genus and one dispersal event to the African mainland, with subsequent dispersal from continental Africa to the Arabian Peninsula and Southeast Asia. The formation of bulbils on the leaf margin is restricted to a larger clade withinK.subg.Bryophyllumand thus only evolved once. Our tree provides a framework for further taxonomic, evolutionary, and physiological research on the genus.
Mechanical control of germ cell specification in Arabidopsis anthers
Authors: Liu Chan , Shi Hui , Han Yuting , Wang Pan , Li Kexin , Zhang Zhishuai , Liu Jiazheng , Zheng Yafeng , Li Linlin , Lin Limei , Liang Chen , Qin Binjun , Han Hua , Bai Shunong , Liu Xiao , Chen Wenqian , Zhao Feng
Published: October 2024

A central question in developmental biology is how the germline is established. We have studied the specification of the male germ cells (GCs) within the anther1–3. Hereby, we have focused on the potential role of mechanics, an aspect of anther development which has been very poorly characterized2,4. Using a combination of live imaging and mechanical measurements, we provide evidence that GCs originate in a special micro-mechanical niche, where inner tissues exert ‘push’ on outer cell layers, placing them under compression. Mechanical perturbations significantly disrupted the GC specification and patterning. Moreover, we found that the master genetic regulator SPOROCYTELESS/NOZZLE (SPL/NZZ)5,6is central in establishing this micro-mechanical environment by softening the cell wall. The mechanical cues, in turn, stabilize the transcription ofSPL/NZZ. We propose here an intrinsic growth-derived mechano-chemical feedback loop that drives germ-cell fate acquisition.
Dissecting RNA Selectivity Mediated by Tandem RNA-Binding Domains
Authors: Harris Sarah E. , Hu Yue , Bridges Kaitlin , Guzmán Bryan B. , Cavazos Francisco F. , Martyr Justin G. , Murn Jernej , Aleman Maria M. , Dominguez Daniel
Published: October 2024

RNA-protein interactions are pivotal to proper gene regulation. Many RNA-binding proteins possess multiple RNA-binding domains; however, how these domains interplay to specify and regulate RNA targets remains poorly understood. Here, we investigate three multi-domain proteins, Musashi-1, Musashi-2, and Unkempt, three factors which share a high degree of RNA specificity. We use a combination of massively parallelin vitroassays with random or naturally derived RNA sequences and find that individual domains within a protein can have differing affinities, specificities, and spacing preferences. Further, we emphasize that while all three proteins have overlapping motif specificities, non-overlapping sequences may allow for target discrimination. We carry out large scale competition assays between these proteins and determine how individual protein specificities and affinities influence competitive binding. Integration ofin vivobinding and regulation within vitrospecificities shows that target selection involves a combination of the protein intrinsic specificities described here, but cellular context is critical to drive these proteins to motifs in specific transcript regions. Finally, evolutionarily conserved RNA regions display evidence of binding multiple RBPsin vivo, and these RNA regions recapitulate this trend with the highest affinityin vitro. We highlight the importance of understanding features of complex RNA-protein interactions and how protein-target discrimination can be established.