bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life and Relationships in Caregivers of People With Dementia. A Gender Perspective
Authors: Bjørge Heidi , Kvaal Kari , Ulstein Ingun
Published: August 2024

Home-dwelling people with dementia rely on their family members to be able to stay at home. This affects the family caregivers’ quality of life (QoL). However, less is known about how male and female caregivers differ in their QoL. Our study aimed to investigate gender differences in caregivers’ quality of life (QoL), whether emotional relationships influence QoL, and how their QoL changes over time. The study applied a cross-sectional and a longitudinal design to examine a total of 208 caregivers, 158 female and 50 male caregivers, and their family member with dementia. Regression analysis and t-tests were performed to identify what characteristics about caregivers and care receivers influence male and female QoL, and whether caregivers’ QoL developed after one year. Both male and female caregivers’ depression influenced their QoL. For females, their own social distress influenced their QoL, and for males, their experience of their care receivers’ overemotional attitude influenced their QoL. From baseline to one-year follow-up their QoL decreased while their distress and experience of care receivers’ emotional attitudes was stable. Significant gender-specific differences were found, indicating that gender must be considered when approving caregivers’ needs and planning interventions for caregivers.
Jianpi Jiedu Recipe Inhibits Proliferation through Reactive Oxygen Species-Induced Incomplete Autophagy and Reduces PD-L1 Expression in Colon Cancer
Authors: Cheng Lingling , Xu Liangfeng , Yuan Hua , Zhao Qihao , Yue Wei , Ma Shuang , Wu Xiaojing , Gu Dandan , Sun Yurong , Shi Haifeng , Xu Jianlin
Published: August 2024

Background:

Jianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear.

Methodology:

CCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. The RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. The xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo.

Results:

JPJDR has an excellent inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly, and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1. Meanwhile, JPJDR can exert an excellent therapeutic effect in xenograft tumor mice.

Conclusion:

JPJDR is a low-toxicity and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.
Space Games: Ecologies of Scale and Technologies of Hope in Taiwan's OPUS Game Trilogy
Authors: Inwood Heather
Published: August 2024

Extending ecocritical game studies to the Sinophone (or Chinese-speaking) world, this article offers a close playing of three OPUS-themed science fiction videogames produced between 2016 and 2021 by Taiwanese indie developer SIGONO, exploring the games’ function as environmental texts and their relationship to Taiwanese literary and cultural studies. By asking the player to engage in shifts in scale and perspective from human to nonhuman, life to death, past to present, and enclosed to boundless space, the OPUS games serve as an effective way of understanding ecological intervention that promotes multiscalar awareness and asks what still can be done and what hope can be found when all has already been lost. In doing so, they demonstrate the ecocritical potential of science fiction videogames that feature an in-game environment many millions of light-years away from our current earth-bound realities.
Redefining the exact roles and importance of carotid intima-media thickness and carotid plaque thickness in predicting cardiovascular events
Authors: Petrovic Dusan J.
Published: August 2024

Objective

The survey aimed to evaluate the precise roles and importance of carotid plaque thickness and carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) in future cardiovascular risk prediction.

Material and methods

188 respondents between the age of 46 and 87 divided into two groups (I group – 94 respondents without plaques with CIMT measurement and II Group 94 respondents with carotid plaques; 118 men and 70 women; mean age ± SD, 61.80 ± 5.49) were prospectively examined by the carotid ultrasound Doppler (carotid measurements included plaque thickness PT – nonstenotic plaques (carotid stenosis <50%) and stenotic culprit plaques (carotid stenosis ≥50%), mean CIMT and maximum CIMT). Subjects were followed for 36 months from the inclusion in the study (regular control examinations). Data were recorded on new cases of mortality (CV mortality) and adverse CV events (myocardial infarction – -MI, surgical or endovascular revascularization – coronary or stroke).

Results

In this study, CIMT values vary between 0.62 and 1.43 mm (mean CIMT = 1.21 ± 0.2 mm) while 52 subjects had nonstenotic plaques (14 respondents plaque ulceration, 22 type 2 diabetes mellitus, 38 arterial hypertension) and 38 subjects had stenotic culprit plaques (17 respondents plaque ulceration, 20 type 2 diabetes mellitus, 31 arterial hypertension). After 36 months of follow-up, 76 vascular events were noted (MI, transient ischaemic attack – TIA, stroke and cardiovascular angioplasty or surgery) in this period.

Conclusion

Respondents with carotid plaques had higher cardiovascular events occurrence ( p < .01, high statistical difference). Carotid plaques as a parameter have higher predictive vascular event value importance than CIMT. Of note, stenotic plaques, the presence of ulceration on the free surface of the plaque, type 2 diabetes mellitus and hypertension were connected with the highest events occurrence.
(Re)constructing sport memory with women: From having ‘muscles on your muscles’ to ‘feeling pretty special’ and beyond in early Australian triathlon memory
Authors: Hunt Jane Elizabeth
Published: August 2024

Contributions to Australian triathlon magazines and newsletters of the 1980s evoke competing images of the sport as macho and extreme, and organised and inclusive. Interpreting niche media texts as acts of social memory, this article aims to show that both themes in triathlon memory are discursively characterised by gendered and ageist athletic hierarchies. Positioning contemporary feminist histories by sportswomen as subjective acts that (re)construct networked sport memory with earlier sportswomen across time, this article adapts Frigga Haug’s notion of memory work in search of understanding of the disconnect between traditional notions of sport as immersive experience and the ways in which women subjectively construct themselves as triathletes. Drawing on feminist narrative and discourse analysis methodologies, it interrogates the ways in which many texts, as acts of social memory, contest the meaning of triathlon, including its gendered meaning, with cumulative impacts on triathlon memory and implications for triathlon as a sport.
Metabolic syndrome and psoriatic arthritis: the role of weight loss as a disease-modifying therapy
Authors: Williams Jacob Corum , Hum Ryan Malcolm , Rogers Kira , Maglio Cristina , Alam Uazman , Zhao Sizheng Steven
Published: August 2024

Psoriatic arthritis (PsA) is an inflammatory joint and entheseal disease associated with significant personal and public health burden. PsA has a prevalence of up to 1%, affecting ~20% of people suffering with psoriasis. PsA is frequently accompanied by metabolic syndrome (MetS), and both conditions are characterised by a chronic pro-inflammatory state, with several key cytokines in PsA (interleukin (IL)-17 and IL-23) also elevated in those with MetS. This narrative review aims to provide an update on MetS in PsA, focusing on its prevalence, pathogenesis, prognosis, treatment interactions and future therapeutic options. MetS is particularly prevalent in PsA compared to other inflammatory arthritides. Cohort studies indicate a higher risk of PsA in individuals with obesity, while Mendelian randomization studies link childhood obesity, insulin resistance, and dyslipidaemia to PsA. Weight loss interventions have been shown to reduce disease activity in PsA. Additionally, MetS negatively impacts the efficacy of tumour necrosis factor inhibitor (TNFi) drugs in treating PsA. Drugs given for PsA may also affect the conditions constituting MetS. Leflunomide has been shown to reduce body weight but also increase blood pressure. TNFi drugs lead to weight gain but reduce cardiovascular risk. Janus kinase inhibitors increase lipid levels and cardiovascular risk among high-risk groups. Anti-IL-17 and anti-IL-12/IL-23 drugs may cause a short-term increase in cardiovascular risk, although the long-term effects have yet to be established. Weight loss represents an unexplored avenue for disease modification in PsA, alongside a plethora of general health benefits. Dietary and exercise modifications are the cornerstone of weight management but vary substantially across individuals. Novel therapies to treat weight loss, such as glucagon-like peptide 1 agonists and sodium–glucose cotransporter 2 inhibitors, may prove useful alongside disease-modifying therapies for those with PsA and MetS and should be investigated as potential therapeutic adjuncts.
Russian internet news sites, 2008–2018: Fostering an informed citizenry?
Authors: von Seth Rutger
Published: August 2024

Since Perestroika, Russian journalism has gone through a liberalization. However, the short lived apex of journalistic freedom that took place in the late 1980s and early 1990s was followed by a setback in particular since Putin’s accession to power in 2000. The situation for the freedom of the daily press has stagnated. Despite this, the findings based on qualitative text analysis of news articles in some of the most important Russian news sites, strongly indicate that during 2008–2018 readers of news sites were being addressed as active and knowledgeable citizens. The methods focussing on perspectivation and the use of sources, exploring what voices that are used to get messages through and how they are represented, are applied to four case studies casting light on the period. The findings imply that a number of Russian Internet outlets had strengthened their role as advocates of the Fourth Estate. The results further indicate a sharp distinction between news sites that are utilizing traditional Western journalistic devices, and news sites employing a traditional Russian/Soviet journalistic approach. Thus, the roles of the audiences as active citizens were to a certain extent strengthened.
Nocturnal Hypoglycemia in the Era of Continuous Glucose Monitoring
Authors: Kulzer Bernhard , Freckmann Guido , Ziegler Ralph , Schnell Oliver , Glatzer Timor , Heinemann Lutz
Published: August 2024

Nocturnal hypoglycemia is a common acute complication of people with diabetes on insulin therapy. In particular, the inability to control glucose levels during sleep, the impact of external factors such as exercise, or alcohol and the influence of hormones are the main causes. Nocturnal hypoglycemia has several negative somatic, psychological, and social effects for people with diabetes, which are summarized in this article. With the advent of continuous glucose monitoring (CGM), it has been shown that the number of nocturnal hypoglycemic events was significantly underestimated when traditional blood glucose monitoring was used. The CGM can reduce the number of nocturnal hypoglycemia episodes with the help of alarms, trend arrows, and evaluation routines. In combination with CGM with an insulin pump and an algorithm, automatic glucose adjustment (AID) systems have their particular strength in nocturnal glucose regulation and the prevention of nocturnal hypoglycemia. Nevertheless, the problem of nocturnal hypoglycemia has not yet been solved completely with the technologies currently available. The CGM systems that use predictive models to warn of hypoglycemia, improved AID systems that recognize hypoglycemia patterns even better, and the increasing integration of artificial intelligence methods are promising approaches in the future to significantly minimize the risk of a side effect of insulin therapy that is burdensome for people with diabetes.
Fear of Hypoglycemia and Diabetes Distress: Expected Reduction by Glucose Prediction
Authors: Ehrmann Dominic , Laviola Luigi , Priesterroth Lilli-Sophie , Hermanns Norbert , Babion Nils , Glatzer Timor
Published: August 2024

Background:

Extended glucose predictions are novel in diabetes management. Currently, there is no solution widely available. People with diabetes mellitus (DM) are offered features like trend arrows and limited predictions linked to predefined situations. Thus, the impact of extended glucose predictions on the burden of diabetes and person-reported outcomes (PROs) is unclear.

Methods:

In this online survey, 206 people with type 1 and type 2 diabetes (T1D and T2D), 70.9% and 29.1%, respectively, who participated in the dia·link online panel and were current continuous glucose monitoring (CGM) users, were presented with different scenarios of hypothetical extended glucose predictions. They were asked to imagine how low glucose predictions of 30 minutes and overnight as well as glucose predictions up to 2 hours would influence their diabetes management. Subsequently, they completed the Hypoglycemia Fear Survey II (HFS-II) and the T1 Diabetes Distress Scale (T1-DDS) by rating each item on a 5-point scale (−2: strong deterioration to +2: strong improvement) according to the potential change due to using glucose predictions.

Results:

For all glucose prediction periods, 30 minutes, up to 2 hours, and at nighttime, the surveyed participants expected moderate improvements in both fear of hypoglycemia (HFS-II: 0.57 ± 0.49) and overall diabetes distress (T1-DDS = 0.44 ± 0.49). The T1-DDS did not differ for type of therapy or diabetes.

Conclusions:

People with T1D and T2D would see glucose predictions as a potential improvement regarding reduced fear of hypoglycemia and diabetes distress. Therefore, glucose predictions represent a value for them in lowering the burden of diabetes and its management.
Predicting Glucose Values: A New Era for Continuous Glucose Monitoring
Authors: Kulzer Bernhard , Heinemann Lutz
Published: August 2024

The last 25 years of CGM have been characterized above all by providing better and more accurate glucose values in real time and analyzing the measured glucose values. Trend arrows are the only way to look into the future, but they are often too imprecise for therapy adjustment. While AID systems provide algorithms to use glucose values for glucose control, this has not been possible with stand-alone CGM systems, which are most used by people with diabetes. By analyzing the measured values with algorithms, often supported by AI, this should be possible in the future. This provides the user with important information about the further course of the glucose level, such as during the night. Predictive approaches can be used by next-generation CGM systems. These systems can proactively prevent glucose events such as hypo- or hyperglycemia. With the Accu-Chek® SmartGuide Predict app, an integral part of a novel CGM system, and the Glucose Predict (GP) feature, people with diabetes have the first commercially available CGM system with predictive algorithms. It characterizes the CGM systems of the future, which not only analyze past values and current glucose values in the future, but also use these values to predict future glucose progression.
Remission of necrobiotic xanthogranuloma after intravenous immunoglobulin interruption: A case report
Authors: Gilbert-Falardeau Amélie , Drolet Anne-Marie
Published: August 2024

Necrobiotic xanthogranuloma is a rare non-Langerhans cell histiocytosis with the potential for multisystemic involvement. It’s a challenging disease to treat and multiple treatments have been reported in the literature with variable results. We present the case of a 92-year-old woman with multiple orange-brown papules and plaques on her face progressing for several years. The biopsy showed dermal xanthogranulomatous infiltration with multinucleated giant cells and necrobiosis, and she was diagnosed with necrobiotic xanthogranuloma. A complete response was obtained with intravenous immunoglobulins and she remained in remission despite treatment discontinuation.
Extended thoracotomy for main pulmonary artery access: Two lung cancer cases
Authors: Hayashi Kazuki , Kita Yusuke , Hanaoka Jun
Published: August 2024

This report details two cases of right upper-lobe lung cancer, of patients aged 62 and 56 years, requiring complex bronchoplasty and thoracoscopic surgeries. In both cases, owing to intraoperative complications, extended thoracotomies were performed to gain access to the right main pulmonary artery. The postoperative courses were uneventful, implying that this approach was safe. Uncomplicated postoperative recoveries underscore the need for adaptable surgical techniques, especially when traditional positioning fails. It emphasizes extending thoracotomy incisions for safer hilar structure access, offering insights for handling similar complex surgeries where standard methods falter.
Why the Anthropocene Epoch is a more pertinent concept than the Anthropocene event for understanding ongoing Earth system transition
Authors: Chakraborty Abhik
Published: August 2024

While the Anthropocene Working Group proposed in 2023 to formally recognize the Anthropocene Epoch with a lower boundary ~1950, the International Commission on Stratigraphy subsequently decided to reject the proposal. Instead, some scientists have argued, the Anthropocene is better understood as an ‘event’ with no temporal boundary. This article argues that the Anthropocene as an event idea is deeply problematic due to four major logical issues: (i) the heterogeneous term ‘event’ fails to provide clarity; (ii) the ‘-cene’ suffix is used consistently for epoch-level units of the Quaternary, so a temporally diffuse impact should be described with an altogether different term; (iii) it is misleading to put Earth system change caused by myriad organisms in the past on par with the impact of Homo sapiens (a single species) and (iv) a temporally diffuse event fails to address the qualitatively different nature of the Earth system change during the Great Acceleration.
Multidimensional factors correlated with population changes according to city size in Japan
Authors: Kato Haruka
Published: August 2024

Many developed countries need to plan urban policies based on multidimensional factors related to population change. However, empirical research has been inconsistent with respect to identifying these factors, including economic-, social-, and urban-planning-related factors. The purpose of this study is to clarify the nonlinear multidimensional factors that are correlated with population changes according to the city size. In the analysis, the population change rate was defined as the outcome variable, and 269 economic, social, and educational index (ESE index) were used as predictor variables. Data were stratified according to three city sizes. Using the ESE index, the XGBoost algorithm was used to analyze the nonlinear relationship between the population change rate and multidimensional data. As a key result, population changes were strongly correlated with social-related indicators, such as the population change rate among persons ages 0–14 years in small-sized cities, the natural population change rate in medium-sized cities, and the migration change rate in large-sized cities. Regarding the population decline, Japan has 1304 shrinking cities, which are primarily comprised of medium-sized and small-sized cities. In such cities, other than social-related factors, population changes correlated with the financial strength index as an economic-related factor in medium-sized cities and the designation of underpopulated areas as an urban-planning-related factor in small-sized cities. Among the multidimensional factors, cities of different sizes were characterized by factors other than social-related indicators. These multifaceted factors could provide preliminary insights for urban policymakers to explore various policy measures on which they need to focus, depending on the city’s size.
Create Model Cornerstone Assessment
Authors: Hatch Emily
Published: August 2024

Model Cornerstone Assessments (MCAs) are sample benchmark assessments that accompany the National Core Arts Standards. This column will examine the Create MCA. The Create artist process asks students to compose musical works with intention, and the MCA gives a sample assessment task to measure the Create standards. This column explores the makeup of the MCA document, looks at pre-knowledge requirements and cultural bias in the assessment, and then proposes ways that teachers can modify the assessment to better serve their learners and classroom environments.
Impact of PIK3CA gain and PTEN loss on mantle cell lymphoma biology and sensitivity to targeted therapies
Authors: Bettazova Nardjas , Senavova Jana , Kupcova Kristyna , Sovilj Dana , Rajmonova Anezka , Andera Ladislav , Svobodova Karla , Berkova Adela , Zemanova Zuzana , Daumova Lenka , Herman Vaclav , Dolníkova Alexandra , Davis R. Eric , Trneny Marek , Klener Pavel , Havranek Ondrej
Published: August 2024

Besides many other mutations in known cancer driver genes, mantle cell lymphoma (MCL) is characterized by recurrent genetic alterations of important regulators of the phosphoinositol-3-kinase (PI3K) cascade including PIK3CA gains and PTEN losses. To evaluate the biological and functional consequences of these aberrations in MCL, we have introduced transgenic expression of PIK3CA (PIK3CA UP) and performed knockout/knockdown of PTEN gene (PTEN KO/KD) in 5 MCL cell lines. The modified cell lines were tested for associated phenotypes including dependence on upstream B-cell receptor (BCR) signaling (by an additional BCR knockout). PIK3CA overexpression decreased the dependence of the tested MCL on prosurvival signaling from BCR, decreased levels of oxidative phosphorylation, and increased resistance to 2-deoxy-glucose, a glycolysis inhibitor. Unchanged protein kinase B (AKT) phosphorylation status and unchanged sensitivity to a battery of PI3K inhibitors suggested that PIK3CA gain might affect MCL cells in AKT-independent manner. PTEN KO was associated with a more distinct phenotype: AKT hyperphosphorylation and overactivation, increased resistance to multiple inhibitors (most of the tested PI3K inhibitors, Bruton tyrosine kinase inhibitor ibrutinib, and BCL2 inhibitor venetoclax), increased glycolytic rates with resistance to 2-deoxy-glucose, and significantly decreased dependence on prosurvival BCR signaling. Our results suggest that the frequent aberrations of the PI3K pathway may rewire associated signaling with lower dependence on BCR signaling, better metabolic and hypoxic adaptation, and targeted therapy resistance in MCL.
Polygenic polymorphism is associated with NKG2A repertoire and influences lymphocyte phenotype and function
Authors: Le Luduec Jean-Benoît , Kontopoulos Theodota , Panjwani M. Kazim , Sottile Rosa , Liu Hongtao , Schäfer Gesine , Massalski Carolin , Lange Vinzenz , Hsu Katharine C.
Published: August 2024

CD94/NKG2A is a heterodimeric receptor commonly found on natural killer (NK) and T cells, and its interaction with its ligand HLA-E on adjacent cells leads to inhibitory signaling and cell suppression. We have identified several killer cell lectin–like receptor (KLR)C1 (NKG2A) single nucleotide polymorphisms (SNPs) that are associated with NKG2A expression on NK cells, CD8+ T cells, and Vγ9/Vδ2+ T cells. Additionally, due to strong linkage disequilibrium, polymorphisms in KLRC2 (NKG2C) and KLRK1 (NKG2D) are also associated with NKG2A surface density and frequency. NKG2A surface expression correlates with single-cell NK responsiveness, and NKG2A+ NK cell frequency is associated with total NK repertoire response and inhibitability, making the identification of SNPs responsible for expression and frequency important for predicting the innate immune response. Because HLA-E expression is dependent on HLA class I signal peptides, we analyzed the relationship between peptide abundance and HLA-E expression levels. Our findings revealed a strong association between peptide availability and HLA-E expression. We identified the HLA-C killer immunoglobulin–like receptor ligand epitope as a predictive marker for HLA-ABC expression, with the HLA-C1 epitope associated with high HLA-E expression and the HLA-C2 epitope associated with low HLA-E expression. The relationship between HLA-C epitopes and HLA-E expression was independent of HLA-E allotypes and HLA-B leader peptides. Although HLA-E expression showed no significant influence on NKG2A-mediated NK education, it did affect NK cell inhibition. In summary, these findings underscore the importance of NKG2A SNPs and HLA-C epitopes as predictive markers of NK cell phenotype and function and should be evaluated as prognostic markers for diseases that express high levels of HLA-E.
Prediction of Coefficient of Restitution for Impact Elastoplastic Spheres Considering Finite Plate Thickness
Authors: Fan Yunfeng , Wang Hao , Zhou Tao , Zou Limin , Jiang Zhinong , Hu Minghui
Published: August 2024

Collisions between objects are a relatively common phenomenon in nature. Analyses of collision processes can greatly contribute to solving problems such as impact-rub faults and particle impacts. The coefficient of restitution is a critical parameter in the analysis of collision processes. Many experiments have shown that the coefficient of restitution is closely related to the plate thickness, and the smaller the plate thickness, the more inaccurate the coefficient of restitution predicted by the existing model, which seriously affects the process of collision analysis. To remedy this shortcoming, this paper proposes a plate thickness influence factor with the ratio of sphere diameter to plate thickness as the variable. The plate thickness influence factor can optimize the coefficient of restitution model to effectively predict the coefficient of restitution of impacting elastoplastic spheres with finite plate thickness. Finally, the validity of the new model is verified using a large amount of experimental data.
Greenhouse study and interviews indicate glyphosate residue via feed-feces-fertilizer route is a risk for horticultural producers using manure-based fertilizer
Authors: Birge Traci , Saloniemi Irma , Saikkonen Kari , Helander Marjo
Published: August 2024

Background

The herbicide glyphosate is the most widely used active ingredient in pesticides globally. Residues have been found in people, livestock, food and animal feed, and in the environment, but little is known about glyphosate residue in manure-based fertilizer. We describe a feed-feces-fertilizer route of glyphosate contamination with negative impacts for horticultural production. This exposure can harm sensitive plants, such as tomato, and pose a risk to effective waste disposal and nutrient cycling along principles of the circular economy.

We review the use and history of glyphosate and present a mixed methods research based on a real-world case from Finland where glyphosate residue in poultry manure fertilizer was suspected of inhibiting commercial organic tomato production. To test the fertilizer, we grew 72 ‘Encore’ variety tomato plants for 14 weeks in a climate-controlled greenhouse according to the practices of the commercial grower. To ascertain awareness and potential contamination mitigation measures, we contacted five fertilizer companies with sales of biogenic fertilizer in Finland, two farming organizations, a feed company, and two government organizations working on nutrient cycling and agricultural circular economy.

Results

The total harvest of tomatoes grown with fertilizer with the higher content of glyphosate residue was 35% smaller and the yield of first-class tomatoes 37% lower than that of the control, with lower glyphosate concentration. Two of the five fertilizer companies identified poultry manure as a source of glyphosate contamination. Companies with awareness of pesticide residues reported interest in establishing parameters for pesticide residues.

Conclusions

The extent of glyphosate contamination of recycled fertilizers is unknown, but this study shows that such contamination occurs with negative impacts on crop production. Lack of testing and regulation to ensure that recycled fertilizers are free from harmful levels of glyphosate or other pesticides creates risks for agricultural producers. The issue is particularly acute for certified organic producers dependent on these products, but also for sustainable transitions away from mineral fertilizers in conventional farming. The example from Finland shows that a model of co-production between fertilizer producers and state regulatory agencies to establish safe limits can benefit both fertilizer producers and their customers.
Exploring the Sublethal Impacts of Cu and Zn on Daphnia magna: a transcriptomic perspective
Authors: Paylar Berkay , Bezabhe Yared H. , Jass Jana , Olsson Per-Erik
Published: August 2024

Metal contamination of aquatic environments remains a major concern due to their persistence. The water flea Daphnia magna is an important model species for metal toxicity studies and water quality assessment. However, most research has focused on physiological endpoints such as mortality, growth, and reproduction in laboratory settings, as well as neglected toxicogenomic responses. Copper (Cu) and zinc (Zn) are essential trace elements that play crucial roles in many biological processes, including iron metabolism, connective tissue formation, neurotransmitter synthesis, DNA synthesis, and immune function. Excess amounts of these metals result in deviations from homeostasis and may induce toxic responses. In this study, we analyzed Daphnia magna transcriptomic responses to IC5 levels of Cu (120 µg/L) and Zn (300 µg/L) in environmental water obtained from a pristine lake with adjusted water hardness (150 mg/L CaCO3). The study was carried out to gain insights into the Cu and Zn regulated stress response mechanisms in Daphnia magna at transcriptome level. A total of 2,688 and 3,080 genes were found to be differentially expressed (DEG) between the control and Cu and the control and Zn, respectively. There were 1,793 differentially expressed genes in common for both Cu and Zn, whereas the number of unique DEGs for Cu and Zn were 895 and 1,287, respectively. Gene ontology and KEGG pathways enrichment were carried out to identify the molecular functions and biological processes affected by metal exposures. In addition to well-known biomarkers, novel targets for metal toxicity screening at the genomic level were identified.
Deliberate self-harm in adolescents screening positive for attention-deficit / hyperactivity disorder: a population-based study
Authors: Austgulen Amalie , Posserud Maj-Britt , Hysing Mari , Haavik Jan , Lundervold Astri J.
Published: August 2024

Background

Adolescents with attention-deficit / hyperactivity disorder (ADHD) have an increased risk of self-harm. The risk of self-harm among adolescents who display an elevated level of ADHD symptoms, but without a formal diagnosis, is not well-studied and understood.

Objective

To investigate the relationship between self-reported symptoms of ADHD and self-harm in a population-based sample of adolescents.

Methods

Adolescents in the population-based youth@hordaland study were invited to complete the Adult ADHD Self-Report Scale (ASRS) and the Short Mood and Feelings Questionnaire (SMFQ). They were asked whether they ever deliberately have taken an overdose or tried to harm themselves on purpose, once or multiple times, defined according to the code used in the Child and Adolescent Self-harm in Europe (CASE) Study. Adolescents reporting severe problems on ≥ four of six selected items on the ASRS-v 1.1 screener were defined as ADHD-screen positive (ADHD-SC+), and the remaining sample as ADHD-screen negative (ADHD-SC-). SMFQ score ≥ 12 was used to define a high level of depressive symptoms.

Results

A total of 9692 adolescents (mean age 17.4 years, 53.1% females) participated in the study, of which 2390 (24.7%) screened positive on the ASRS. ADHD-SC+ adolescents engaged in self-harm more often than the ADHD-SC- group (14.6% vs. 5.4%, OR = 3.02, 95%CI [2.57–3.24]). This remained significant after adjustment for demographic variables, SMFQ score ≥ 12, symptoms of conduct disorder and familial history of self-harm and suicide attempts (OR = 1.58, 95%CI [1.31–1.89]). They were also more likely to report an overdose as their method of self-harm (OR = 1.52, 95%CI [1.05–2.23]). Within the ADHD-SC+ group female sex, high levels of inattention and hyperactivity/impulsivity symptoms, SMFQ score ≥ 12, symptoms indicating conduct disorder and familial history of self-harm and suicide attempts increased the likelihood of engaging in deliberate self-harm.

Conclusion

Adolescents who screened positive for ADHD had increased risk of engaging in self-harm. Clinicians should consider the increased risk of such engagement in adolescents who present with high level of ADHD symptoms, even in the absence of a clinical ADHD diagnosis.
Updating a conceptual model of effective symptom management in palliative care to include patient and carer perspective: a qualitative study
Authors: Chapman Emma J. , Paley Carole A. , Pini Simon , Ziegler Lucy E.
Published: August 2024

Background

A conceptual model of effective symptom management was previously developed from interviews with multidisciplinary healthcare professionals (HCP) working in English hospices. Here we aimed to answer the question; does a HCP data-derived model represent the experience of patients and carers of people with advanced cancer?

Methods

Semi-structured interviews were undertaken with six patients with advanced cancer and six carers to gain an in-depth understanding of their experience of symptom management. Analysis was based on the framework method; transcription, familiarisation, coding, applying analytical framework (conceptual model), charting, interpretation. Inductive framework analysis was used to align data with themes in the existing model. A deductive approach was also used to identify new themes.

Results

The experience of patients and carers aligned with key steps of engagement, decision making, partnership and delivery in the HCP-based model. The data aligned with 18 of 23 themes. These were; Role definition and boundaries, Multidisciplinary team decision making, Availability of services/staff, Clinician-Patient relationship/rapport, Patient preferences, Patient characteristics, Quality of life versus treatment need, Staff time/burden, Psychological support -informal, Appropriate understanding, expectations, acceptance and goals- patients, Appropriate understanding, expectations, acceptance and goals-HCPs, Appropriate understanding, expectations, acceptance and goals- family friends, carers, Professional, service and referral factors, Continuity of care, Multidisciplinary team working, Palliative care philosophy and culture, Physical environment and facilities, Referral process and delays. Four additional patient and carer-derived themes were identified: Carer Burden, Communication, Medicines management and COVID-19. Constructs that did not align were Experience (of staff), Training (of staff), Guidelines and evidence, Psychological support (for staff) and Formal psychological support (for patients).

Conclusions

A healthcare professional-based conceptual model of effective symptom management aligned well with the experience of patients with advanced cancer and their carers. Additional domains were identified. We make four recommendations for change arising from this research. Routine appraisal and acknowledgement of carer burden, medicine management tasks and previous experience in healthcare roles; improved access to communication skills training for staff and review of patient communication needs. Further research should explore the symptom management experience of those living alone and how these people can be better supported.
Radiology education for medical students: a qualitative exploration of educational topics, teaching methods and future strategies
Authors: Harthoorn Frederike S. , Scharenborg Sascha W. J. , Brink Monique , Peters-Bax Liesbeth , Henssen Dylan
Published: August 2024

Background

Imaging techniques play a central role in modern medicine and therefore it would be beneficial for all medical students to incorporate radiology education in medical school curricula. However, a formal undergraduate radiology curriculum with well-defined learning objectives remains lacking in The Netherlands. This study aims to qualitatively ascertain opinions from clinicians (radiologists and non-radiologists) with regard to radiology education in the medical school curricula, including topics, teaching methods and strategies.

Methods

A qualitative study with in-depth semi-structured interviews was conducted. Inclusion was carried out until saturation was achieved, after which 2 additional interviews were held. Interviews were conducted using open-ended questions, following a predefined topic list. The constant comparative method was applied in order to include new questions when unexpected topics arose during the interviews. All interviews were transcribed verbatim and coded using a thematic analysis approach. Codes were organized into categories and themes by discussion between the researchers.

Results

Forty-four clinicians were interviewed (8 radiologists, 36 non-radiologists). The three main themes that were derived from the interviews were: (1) expectations of indispensable knowledge and skills on radiology, (2) organization of radiology education within the medical curriculum and (3) promising educational innovations for the radiology curriculum. The qualitative study design provides more in-depth knowledge on clinicians’ views on educational topics.

Conclusions

The themes and statements of this study provided new insights into educational methods, timing of radiology education and new topics to teach. More research is needed to gain consensus on these subjects and inclusion of the opinion of medical students with regard to radiology education is needed.
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era
Authors: Lara-Aguilar Violeta , Llamas-Adán Manuel , Brochado-Kith Óscar , Crespo-Bermejo Celia , Grande-García Sergio , Arca-Lafuente Sonia , de los Santos Ignacio , Prado Carmen , Alía Mario , Sainz-Pinós Coral , Fernández-Rodríguez Amanda , Martín-Carbonero Luz , Madrid Ricardo , Briz Verónica
Published: August 2024

Background

Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC).

Methods

Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen.

Results

The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups.

Conclusion

LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.
A cardiac-rehab behaviour intervention to reduce sedentary time in coronary artery disease patients: the SIT LESS randomized controlled trial
Authors: Kroesen Sophie H. , van Bakel Bram M. A. , de Bruin Marijn , Günal Arzu , Scheepmaker Arko , Aengevaeren Wim R. M. , Willems Frank F. , Wondergem Roderick , Pisters Martijn F. , Ortega Francisco B. , Hopman Maria T. E. , Thijssen Dick H. J. , Bakker Esmée A. , Eijsvogels Thijs M. H.
Published: August 2024

Background

High sedentary times (ST) is highly prevalent in patients with coronary artery disease (CAD), highlighting the need for behavioural change interventions that effectively reduce ST. We examined the immediate and medium-term effect of the SIT LESS intervention on changes in ST among CAD patients enrolled in cardiac rehabilitation (CR).

Methods

CAD patients participating in CR at 2 regional hospitals were included in this randomized controlled trial (1:1, stratified for gender and hospital). The control group received CR, whereas SIT LESS participants additionally received a 12-week hybrid behaviour change intervention. The primary outcome was the change in accelerometer-derived ST from pre-CR to post-CR and 3 months post-CR. Secondary outcomes included changes in ST and physical activity characteristics, subjective outcomes, and cardiovascular risk factors. A baseline constrained linear mixed-model was used.

Results

Participants (23% female; SIT LESS: n = 108, control: n = 104) were 63 ± 10 years. Greater ST reductions were found for SIT LESS compared to control post-CR (-1.7 (95% confidence interval (CI): -2.0; -1.4) versus − 1.1 (95% CI: -1.4; -0.8) h/day, pinteraction=0.009), but not at 3 months post-CR (pinteraction=0.61). Besides, larger light-intensity physical activity (LIPA) increases were found for SIT LESS compared to control post-CR (+ 1.4 (95% CI: +1.2; +1.6) versus + 1.0 (95% CI: +0.8; +1.3) h/day, pinteraction=0.020). Changes in other secondary outcomes did not differ among groups.

Conclusion

SIT LESS transiently reduced ST and increased LIPA, but group differences were no longer significant 3 months post-CR. These findings highlight the challenge to induce sustainable behaviour changes in CAD patients without any continued support.

Trial registration

Netherlands Trial Register: NL9263. Registration Date: 24 February 2021.
SelK promotes glioblastoma cell proliferation by inhibiting β-TrCP1 mediated ubiquitin-dependent degradation of CDK4
Authors: Li Jizhen , Zhao Lingling , Wu Zerui , Huang Shirui , Wang Junyu , Chang Yuanyuan , Liu Li , Jin Honglei , Lu Jianglong , Huang Chuanshu , Xie Qipeng , Huang Haishan , Su Zhipeng
Published: August 2024

Background

Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM.

Methods

Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4.

Results

SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of β-TrCP1 expression. Up-regulation of β-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells.

Conclusion

This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/β-TrCP1/CDK4 axis.
Weakly-supervised deep learning models enable HER2-low prediction from H &E stained slides
Authors: Valieris Renan , Martins Luan , Defelicibus Alexandre , Bueno Adriana Passos , de Toledo Osorio Cynthia Aparecida Bueno , Carraro Dirce , Dias-Neto Emmanuel , Rosales Rafael A. , de Figueiredo Jose Marcio Barros , Silva Israel Tojal da
Published: August 2024

Background

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a new subtype of tumor, for which novel antibody–drug conjugates have shown beneficial effects. Assessment of HER2 requires several immunohistochemistry tests with an additional in situ hybridization test if a case is classified as HER2 2+. Therefore, novel cost-effective methods to speed up the HER2 assessment are highly desirable.

Methods

We used a self-supervised attention-based weakly supervised method to predict HER2-low directly from 1437 histopathological images from 1351 breast cancer patients. We built six distinct models to explore the ability of classifiers to distinguish between the HER2-negative, HER2-low, and HER2-high classes in different scenarios. The attention-based model was used to comprehend the decision-making process aimed at relevant tissue regions.

Results

Our results indicate that the effectiveness of classification models hinges on the consistency and dependability of assay-based tests for HER2, as the outcomes from these tests are utilized as the baseline truth for training our models. Through the use of explainable AI, we reveal histologic patterns associated with the HER2 subtypes.

Conclusion

Our findings offer a demonstration of how deep learning technologies can be applied to identify HER2 subgroup statuses, potentially enriching the toolkit available for clinical decision-making in oncology.