bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes in residential aged care: Pharmacological management and concordance with clinical guidelines
Authors: Bhalla Hargun , Huang Guogui , Seaman Karla , Silva S. Sandun Malpriya , Wu Bosco , Wabe Nasir , Westbrook Johanna I. , Nguyen Amy D.
Published: July 2024

Objective

Existing studies have highlighted suboptimal diabetes management in residential aged care facilities (RACFs). However, understanding of diabetes management in Australian metropolitan RACFs has been limited. This retrospective cohort study aimed to explore the pharmacological management of diabetes in 25 RACFs in Sydney Australia and assess concordance with clinical practice guidelines (CPGs).

Methods

Data from 231 permanent RACF residents aged ≥65 years and over with type 2 diabetes mellitus over the period from 1 July 2016 to 31 December 2019 were used. Concordance was measured by assessing the medications and medical history data for each individual resident for concordance with evidence‐based CPGs. Multivariable logistic regression was used to estimate the effect of resident characteristics on concordance with CPGs.

Results

Of the 231 residents with diabetes, 87 (38%) were not taking any antidiabetic medication. Pharmacological management inconsistent with CPG recommendations was observed for 73 (32%) residents, with the most common reason for non‐concordance being the use of medications with significant adverse effects in older adults (47, 2%). Residents with hypertension or other heart diseases in addition to their diabetes had greater odds of their diabetes management being non‐concordant with CPGs (OR = 2.84 95% CI = 1.54, 5.3 and OR = 2.64, 95% CI = 1.07, 6.41, respectively).

Conclusions

Pharmacological diabetes management in metropolitan Australian RACFs is suboptimal, with a high prevalence of inconsistency with CPGs (32%) observed. Additionally, having hypertension or heart diseases significantly increased the possibility of non‐concordance among diabetic RACF residents. Further investigation into the underlying relationships with comorbidities is required to develop better strategies.
Revealing Properties of Citizenship through Landscape: Enacting “Block 16” through Dispossession and Displacement
Authors: Przybylinski Stephen
Published: July 2024

This paper examines the relationship between property and citizenship by engaging in a genealogy of one property in Portland, Oregon, “Block 16”, which details how this property was first enacted and then maintained into the 21st century. The paper foregrounds how normative definitions of liberal subjectivity were applied to Indigenous peoples originally living on this land, as well as valuations of citizenship for marginalised renters and the residents of a homeless encampment “illegally” occupying this property, to justify the dispossession and displacement of the groups using this same plot of land over time. I argue that the spatial enactment and maintenance of private property is contingent upon producing political subjects demarcated as “improper”, deviants from the normative or ideal liberal subject and citizen. To highlight how property shapes propriety, the paper engages in landscape analysis to reveal how the social relations producing land as property rely upon representations of impropriety and moral deficit to maintain the ownership model of private property against the historical use values of the land.
Risk factors for uveitis in a Finnish sarcoid population
Authors: Joukainen Elli , Antonen Jaakko , Leinonen Sanna
Published: July 2024

Purpose

To evaluate possible risk factors for uveitis among Finnish sarcoidosis patients.

Methods

Patient charts of patients with sarcoidosis, with (n = 97) or without (n = 255) uveitis, and with a comprehensive eye examination from January 2014 to January 2021 at Tays Eye Centre, Tampere University Hospital, Finland were studied.

Results

Sarcoidosis patients with uveitis had higher rate of lymphocytopenia (43% vs. 29%, p = 0.041) and lower serum lysozyme levels (2.0 mg/L vs. 2.3 mg/L, p = 0.049; 95% CI, −0.692 to −0.002). Lysozyme level or lymphocytopenia did not have a statistically significant effect on the probability of uveitis in a binary logistic regression analysis. No other differences in the potential risk factors with p‐values ≤0.05 were found, including bilateral hilar lymphadenopathy, serum angiotensin‐converting enzyme (ACE) levels, sex, age and history of smoking.

Conclusion

Lymphocytopenia and lower serum lysozyme levels present as possible risk factors for uveitis among patients with sarcoidosis. Systematic measurement of lymphocyte and lysozyme levels in sarcoidosis is needed to further understand their role as potential risk factors.
Evaluation of the cross‐protection of the Vero cell‐derived attenuated influenza vaccines with compound adjuvant, through intranasal immunization
Authors: Ze Liu , Shaohui Song , Jinhai Huang , Hui Gao
Published: July 2024

This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 105 PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 μg/mL of carbopol971P and 50 μg/mL of tetanus toxin. That vaccination was called catt‐flu. And it employed the GYZZ02 vaccine (commercialized freeze‐dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That catt‐flu program could induce more cross‐protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non‐inferiority titter compared with the chicken embryo‐derived GYZZ02 vaccine on safe and effect. The Vero cell‐derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as catt‐flu program.
Emergence and fixation of SARS‐CoV‐2 minority variants in a chronically infected patient receiving therapy in Denmark
Authors: Fonager Jannik , Nytofte Nikolaj Julian Skrøder , Schouw Christian Højte , Poulsen Christian B. , Wiese Lothar , Fomsgaard Anders , Bennedbæk Marc , Rasmussen Morten , Nielsen Xiaohui Chen
Published: July 2024

SARS‐CoV‐2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long‐term SARS‐CoV‐2 infection with the pre‐VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi‐species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS‐CoV‐2 among immunocpromised patients.
Letter: Helicobacter pylori and metabolic syndrome‐related von Willebrand factor and plasminogen activator inhibitor‐1 activity levels for outcome prediction of advanced chronic liver disease: Authors' reply
Authors: Scheiner Bernhard , Dominik Nina , Mandorfer Mattias
Published: July 2024

LINKED CONTENT

This article is linked to Dominik et al papers. To view these articles, visit https://doi.org/10.1111/apt.17945 and https://doi.org/10.1111/apt.18066
Unmasking luxury consumption and its psychology: An experimental approach to understanding the motivations behind ethical and sustainable brand preferences
Authors: Islam Tahir , Arya Vikas , Bodla Ali Ahmad , Palladino Rosa , Papa Armando
Published: July 2024

This research delved into the dynamics between pride, sustainability detectability, and product consciousness through three experimental studies conducted among Chinese millennials focusing on lavish brand. Grounded in the positive emotions theory, this study sought to discern the circumstances in which individuals with materialistic tendencies exhibit willingness to engage with sustainable luxury brands. The results of this meticulous experimental design indicate a positive relationship between materialism and the intention to purchase sustainable luxury brands, with pride identified as a mediating factor, and discussed the involvement of high conspicuousness of the product in the context of detectability of the brand's sustainability. Furthermore, this study offers insights through the positive emotion theory and examining the impact of self‐conscious emotions on buyer preferences regarding sustainable luxury brands. The findings from this theoretical research provide valuable insights for brand managers, scholars, and policymakers aiming to develop sustainable brands that resonate with the sentiments and values of conscientious consumers.
A 2‐year prospective evaluation of the Prostate Health Index in guiding biopsy decisions in a large cohort
Authors: Chiu Peter Ka‐Fung , Liu Alex Qinyang , Lau Sui‐Yan , Teoh Jeremy Yuen‐Chun , Ho Chi‐Chun , Yee Chi‐Hang , Hou See‐Ming , Chan Chi‐Kwok , Tang Wai‐Lun , Bangma Chris H. , Chu Peggy Sau‐Kwan , Poon Wing‐Tat , Ng Chi‐Fai , Roobol Monique J.
Published: July 2024

Objectives

To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real‐life setting for men with a prostate‐specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination.

Patients and Methods

Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow‐up plan was then decided via shared decision‐making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements.

Results

A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow‐up of 2.4 years.

Conclusion

In a real‐life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high‐grade prostate cancer detection rate when compared to PSA‐driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow‐up visits.
FOXM1 transcriptional regulation
Authors: Li Mengxi , Gao Xuzheng , Su Yanting , Shan Shigang , Qian Wenbin , Zhang Zhenwang , Zhu Dan
Published: July 2024

FOXM1 is a key transcriptional regulator involved in various biological processes in mammals, including carbohydrate and lipid metabolism, aging, immune regulation, development, and disease. Early studies have shown that FOXM1 acts as an oncogene by regulating cell proliferation, cell cycle, migration, metastasis, and apoptosis, as well as genes related to diagnosis, treatment, chemotherapy resistance, and prognosis. Researchers are increasingly focusing on FOXM1 functions in tumor microenvironment, epigenetics, and immune infiltration. However, researchers have not comprehensively described FOXM1's involvement in tumor microenvironment shaping, epigenetics, and immune cell infiltration. Here we review the role of FOXM1 in the formation and development of malignant tumors, and we will provide a comprehensive summary of the role of FOXM1 in transcriptional regulation, interacting proteins, tumor microenvironment, epigenetics, and immune infiltration, and suggest areas for further research.
Spexin inhibits excessive autophagy‐induced ferroptosis to alleviate doxorubicin‐induced cardiotoxicity by upregulating Beclin 1
Authors: Ou Wen , Liu Haiqiong , Chen Changhai , Yang Chaobo , Zhao Xiaoqing , Zhang Yu , Zhang Zhiyin , Huang Shuwen , Mo Huaqiang , Lu Weizhe , Wang Xianbao , Chen Aihua , Yan Jing , Song Xudong
Published: July 2024

Background and Purpose

Doxorubicin is widely used in the treatment of malignant tumours, but doxorubicin‐induced cardiotoxicity severely limits its clinical application. Spexin is a neuropeptide that acts as a novel biomarker in cardiovascular disease. However, the effects of spexin on doxorubicin‐induced cardiotoxicity is unclear.

Experimental Approach

We established a model of doxorubicin‐induced cardiotoxicity both in vivo and in vitro. Levels of cardiac damage in mice was assessed through cardiac function assessment, determination of serum cardiac troponin T and CKMB levels and histological examination. CCK8 and PI staining were used to assess the doxorubicin‐induced toxicity in cultures of cardiomyocytes in vitro. Ferroptosis was assessed using FerroOrange staining, determination of MDA and 4‐HNE content and ferroptosis‐associated proteins SLC7A11 and GPX4. Mitochondrial membrane potential and lipid peroxidation levels were measured using TMRE and C11‐BODIPY 581/591 probes, respectively. Myocardial autophagy was assessed by expression of P62 and Beclin1.

Key Results

Spexin treatment improved heart function of mice with doxorubicin‐induced cardiotoxicity, and attenuated doxorubicin‐induced cardiotoxicity by decreasing iron accumulation, abnormal lipid metabolism and inhibiting ferroptosis. Interestingly, doxorubicin caused excessive autophagy in cardiomyocyte in culture, which could be alleviated by treatment with spexin. Knockdown of Beclin 1 eliminated the protective effects of spexin in mice with DIC.

Conclusion and Implications

Spexin ameliorated doxorubicin‐induced cardiotoxicity by inhibiting excessive autophagy‐induced ferroptosis, suggesting that spexin could be a drug candidate against doxorubicin‐induced cardiotoxicity. Beclin 1 might be critical in mediating the protective effect of spexin against doxorubicin‐induced cardiotoxicity.
Effect of depression and the antidepressant fluoxetine on osseointegration—A pre‐clinical in vivo experimental study
Authors: Xiaowen Yundeng , Zhu Jingxuan , Gong Mingming , Meng Ge , Tan Renran , Zhang Yanbing , Chen Zhiyu
Published: July 2024

Objective

The aim of this study was to explore the effect of depression and selective serotonin reuptake inhibitors on implant osseointegration and bone healing.

Methods

Forty‐eight 6‐ to 8‐week‐old SPF Sprague–Dawley male rats were randomly divided into four groups: the Control group, the Fluoxetine group, the Depression group and the De&Flu group. The rats in the Depression group and the De&Flu group were subjected to a depression modelling process, and the rats in the Control group and the Fluoxetine group were raised normally. Then, a titanium implant was placed in the right tibia of each rat. In the Fluoxetine group and De&Flu group, fluoxetine was injected subcutaneously daily, while subcutaneously injecting physiological saline in the Control group and Depression group. Collecting serum from the rats used for ELISA. The surgical area was cut for microcomputed tomography and histology observation.

Results

After 12 weeks, bone mineral density was lower in the De&Flu group than in the Control group, Depression group and Fluoxetine group. Bone mineral density was also lower in the Depression group and the Fluoxetine group than in the Control group. The percentage of bone–implant contact (BIC%) in De&Flu rats was lower than in the Control, Depression and Fluoxetine groups. The BIC% in the Depression group and the Fluoxetine group was lower than in the Control group.

Conclusions

Depression and fluoxetine negatively affect bone density and implant osseointegration independently, and this damaging effect is exacerbated when both factors are present. The mechanism may be related to the dysregulation of the hypothalamic–pituitary–adrenal axis and inflammation in the body.
Sex differences in PD‐L1‐induced analgesia in paclitaxel‐induced peripheral neuropathy mice depend on TRPV1‐based inhibition of CGRP
Authors: Cao Yan , Jiang Wenqi , Yan Fang , Pan Yuyan , Gei Liba , Lu Simin , Chen Xiangnan , Huang Yang , Yan Yan , Feng Yan , Li Qiang , Zeng Weian , Xing Wei , Chen Dongtai
Published: July 2024

Aims

Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel‐induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions.

Methods

Male and female C57BL/6 mice (5–6 weeks and 12 months, weighing 18–30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD‐L1. On day 14 after PTX administration, PD‐L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno‐associated virus 9 (AAV9)‐Trpv1‐RNAi (5 μL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD‐L1, TRPV1 and CGRP were measured via Western blotting, RT–PCR, and immunofluorescence staining. The levels of TNF‐α and IL‐1β were measured via RT–PCR.

Results

TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX‐induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD‐L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717‐fold and 2.303‐fold, respectively. PD‐L1 and CGRP were partly co‐localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD‐L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9‐mediated spinal cord specific decreased TRPV1 expression.

Conclusions

PTX‐induced nociceptive behaviors and the analgesic effect of PD‐L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex‐specific therapeutic approaches.
The diverse socioeconomic contributions of wildlife ranching
Authors: Denner Candice , Clements Hayley S. , Child Matthew F. , De Vos Alta
Published: July 2024

The expansion of wildlife ranching has been broadly linked to conservation benefits, job creation, and economic contributions. However, a more nuanced understanding of the socioeconomic contributions of wildlife ranching accounting for the enterprise diversity in the sector remains a major limitation to assessing its potential to contribute to sustainable development. We assessed several important socioeconomic contributions of diverse wildlife‐based business models, defined by their main revenue‐generating activities, within the South African wildlife ranching industry, and the financial viability of these models. Owners and managers of privately‐owned wildlife ranches and conventional agricultural farms (for comparative purposes) were interviewed in the Eastern Cape (112 ranches; 24 farms) and Limpopo provinces (152 ranches; 4 farms). We used a hierarchical clustering analysis to delineate six wildlife ranching business models. These included three more specialized models: ecotourism, trophy hunting, and wildlife breeding, and three more mixed models: mixed hunting (i.e., both meat and trophy hunting), mixed wildlife‐agriculture, and trophy hunting‐game meat. In general, ecotourism‐focused ranches employed more people in total and per hectare (median = 23 jobs; 0.008/ha), and a higher proportion of women and skilled employees (41% and 45% of employees, respectively) than the other ranching models (median = 7–21 jobs; 0.002–0.005/ha) and conventional agriculture (median = 12 jobs; 0.004/ha). Trophy hunting‐focused ranches employed the second highest number of people per hectare (0.006) although on average, a third of these jobs were seasonal. Trophy hunting ranches tended to be more profitable (median profit margin = 33%) than ecotourism (−10%), wildlife breeding (0%) and mixed‐hunting (12%) ranches, though ecotourism ranches showed very high variability (interquartile range = −32% to 14%). These findings advance our understanding of the distinct socioeconomic contributions of diverse wildlife ranches, which benefits policy discourse and implementation surrounding the industry, promoting improved industry sustainability and inclusive growth.
Associations of body mass index, waist circumference and the weight‐adjusted waist index with daily living ability impairment in older Chinese people: A cross‐sectional study of the Chinese Longitudinal Healthy Longevity Survey
Authors: Sun Jie , Lin Jie , Shen Wenqin , Ding Pan , Yang Wenjuan , Huang Li , Chen Huajian
Published: July 2024

Aim

To investigate the associations of body mass index (BMI), waist circumference (WC) and the weight‐adjusted waist index (WWI) with the impairment of activities of daily living (ADL) in older Chinese people.

Methods

A total of 13 260 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey were included in this cross‐sectional study. BMI, WC and the WWI were calculated from measurements of height, weight and WC. Binary logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Non‐linear correlations were investigated using restricted cubic spline curves.

Results

In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between WC and WWI and ADL impairment, with adjusted ORs (95% CI) of 1.01 (1.00, 1.01) and 1.08 (1.03, 1.12), respectively. Meanwhile, participants with a high WWI had a higher risk of ADL impairment compared with those with a low WWI, with an adjusted OR (95% CI) of 1.12 (1.02, 1.23). Subgroup analyses showed that only the association between WWI and ADL impairment did not differ in any of the different populations. In addition, we found that BMI, WC and WWI were non‐linearly associated with ADL impairment.

Conclusions

There are significant associations between WC and WWI and ADL impairment in older Chinese people. The findings show the ability of the WWI to serve as a comprehensive and effective indicator of obesity in older Chinese people and emphasize the importance of assessing WWI in screening and preventing ADL impairment in older people.
Optimized ascospore ejection method for the evaluation of resistance to Teratosphaeria nubilosa in Eucalyptus
Authors: Freitas Camila S. , Almeida Rosiane F. , Fernandes Fernando M. , Alfenas Rafael F. , Badel Jorge L. , Silveira Silvaldo F. , Alfenas Acelino C.
Published: July 2024

Teratosphaeria nubilosa is the predominant causal agent of Teratosphaeria leaf disease (TLD) in experimental plantations of E. globulus in Brazil. It exhibits slow vegetative growth and lack of sporulation in in vitro culture, making it difficult to obtain enough ascospores for mass inoculation. This study aimed to establish an inoculation method based on ascospore ejection from naturally infected leaves and use it to assess the response to T. nubilosa of eucalypt species and interspecific hybrids. First, the optimal temperature and incubation time for ascospores ejection from naturally infected E. globulus leaves were determined in vitro. Then, these optimal conditions were used to assess the response of eight eucalypt genotypes to T. nubilosa inoculation using ejected ascospores. The infected leaves were placed above (T1), above and under (T2) or under (T3) the plants to be inoculated. Significant differences in disease incidence, disease severity and plant defoliation were observed among genotypes and inoculation treatments. Plants exhibited higher incidence, more severe symptoms and more defoliation when exposed to T2. E. globulus and E. globulus × E. nitens clones were the most susceptible whereas an E. benthamii clone was immune. The sources of resistance identified in this work can be used in hybridization programmes with E. globulus to obtain interspecific hybrids expressing resistance to T. nubilosa and retaining the desirable traits for planting in temperate climates. The inoculation method optimized in this work could be used for small and medium‐scale screening of Eucalyptus spp. resistant to TLD. However, periodic validation of the species and genotype of the fungus associated with the naturally infected leaves used for inoculation and confirmation of the resistant phenotype of the selected eucalypt clones or progenies through experimental replications over time must be conducted.
Vortioxetine improved schizophrenia‐like behavioral deficits in a Poly I:C‐induced maternal immune activation model of schizophrenia in rats
Authors: Taskiran Mehmet , Yildiz Taskiran Sacide , Unal Gokhan , Bozkurt Nuh Mehmet , Golgeli Asuman
Published: July 2024

Background

Several studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic‐polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring.

Objectives

The aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C‐induced schizophrenia‐like model in rats.

Methods

For this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL‐6 levels after 2 h. At postnatal days 83–86, behavioral tests were performed.

Results

Our results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open‐field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69–83) caused significant improvements in these deficits.

Conclusion

Overall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies.
Interacting effects of density and temperature on growth of wild and hatchery young‐of‐the‐year anadromous brown trout (Salmo trutta L.)
Authors: Lejk Adam M. , Smoliński Szymon , Łaszewski Maksym , Radtke Grzegorz
Published: July 2024

Stocking can affect population density but may influence fish growth responses to changes in environmental conditions. In a multi‐year field experiment, we investigated the interactive effects of density and temperature on the growth of young‐of‐the‐year anadromous brown trout in streams stocked with wild‐origin hatchery‐reared brown trout. Fish origin was the predominant factor influencing growth rate, thereby highlighting the importance of discriminating between wild and hatchery‐reared individuals. Growth was positively related to temperature (degree‐days) and negatively related to density, with the growth response to temperature modulated by density. Temperature had a more pronounced effect on juvenile growth at low density than at high density. The reduced growth response to temperature caused by density could reduce population resilience and should be considered in management and conservation strategies.
Altered metapopulation dynamics in a headwater specialist in geomorphically dynamic catchments
Authors: Stearman Loren W. , Schaefer Jacob F.
Published: July 2024

Human activities have widely disrupted the spatial ecological processes critical for population and ecosystem integrity. Local effects of altered sediment regimes in rivers are well explored, but how they impact connectivity at a catchment scale is less explored. In this paper we document evidence for altered metapopulation dynamics for a headwater specialist, blackspotted topminnow (Fundulus olivaceus) in catchments with geomorphically dynamic river mainstems.

We quantified decade‐scale patterns of fluvial geomorphic activity via planform analysis of historical and recent aerial imagery, and patterns of gene flow in F. olivaceus via analysis of single nucleotide polymorphisms, identified by genotype‐by‐sequencing.

Mainstem streams narrowed and increased in sinuosity, probably in recovery from historic flood events. Substantial variability in response indicated underlying differences due to differential disturbance history and catchment sensitivity to change.

Multiple analytical approaches all found geography to be a major factor in genetic structuring among catchments. Metrics of genetic differentiation and heterozygosity for F. olivaceus within catchments were related to the degree of geomorphic change inferred from a multivariate composite metric. Catchments with more geomorphic change tended to have more population structuring.

Five populations assigned to adjacent catchments. Analysis of heterozygosity in presumed donor, recipient, and mis‐assigned catchments indicated founder effects in recipient catchments and probable subsequent allopatric recolonisation following local extirpations.

Our results demonstrate complex nonlocal effects of channel evolution on metapopulation dynamics in a pool‐dwelling non‐lithophilous headwater specialist. Our integrative approach allows strong insight into deeper effects of geomorphic processes on aquatic ecosystems. F. olivaceus is ecologically dissimilar to taxa traditionally anticipated to respond to sediment‐related disturbances and demonstrates how broader channel morphological change can affect habitats beyond sedimentation of the stream bed.
Factors associated with potentially inappropriate prescribing in elderly patients with various degrees of chronic kidney disease
Authors: Nedin Rankovic Gorana G. , Pejcic Ana V. , Krtinic Dane A. , Stokanovic Dragana S. , Trajkovic Hristina S. , Jovanovic Hristina M. , Binic Iva I. , Jankovic Slobodan M.
Published: July 2024

Introduction

This study aimed to compare the prevalence of potentially inappropriately prescribed drugs in hemodialysis patients and patients with chronic kidney disease who did not require renal replacement therapy, as well as to identify risk factors associated with potentially inappropriate prescribing.

Methods

The study was designed as a cross‐sectional study conducted at the Department of Nephrology, Clinical Center in Nis, Serbia. The patients were divided into two groups: (1) patients on hemodialysis treatment and (2) patients with various degrees of chronic kidney disease without renal replacement therapy. The presence or absence of potentially inappropriate prescribing was determined using the 2015 AGS Beers criteria.

Findings

The study included a total of 218 patients aged 65 years and over. The number of patients with potentially inappropriate prescribed drugs did not differ significantly (chi‐square = 0.000, p = 1.000) between patients on hemodialysis (27 of 83, i.e., 32.5%) and patients with various degrees of chronic kidney disease without renal replacement therapy (44 of 135, i.e., 32.6%). Factors associated with potentially inappropriate prescribing in hemodialysis patients were the number of drugs (hazard ratio [HR] = 1.919, 95% confidence interval [CI]: 1.325–2.780) and number of comorbidities (HR = 1.743, 95% CI: 1.109–2.740). The number of drugs (HR = 1.438, 95% CI: 1.191–1.736) was the only independent factor associated with increased risk of potentially inappropriate prescribing in patients without renal replacement therapy.

Discussion

Our study showed that potentially inappropriate prescribing is a relatively frequent phenomenon present in about a third of patients in both study groups. The number of prescribed drugs was the main factor associated with the increased risk of potentially inappropriate prescribing in both groups.
Editor's Highlights — August 2024
Authors: Kemény Lajos
Published: July 2024

Pigmentary and hair disorders have a significant cosmetic and psychological impact. In the August issue of the Journal, we highlight the use of reflectance confocal microscopy in diagnosing and monitoring treatment responses in patients with melasma. We will also discuss new therapeutic approaches involving oral melatonin and a combination of glutathione and resveratrol for melasma. Additionally, the ongoing revolution in alopecia treatment with oral low‐dose minoxidil will be spotlighted, including the circumstances under which media attention has contributed to the growing interest in oral minoxidil prescriptions.
Efficacy and safety of dose‐dense gemcitabine plus cisplatin as neoadjuvant chemotherapy for muscle‐invasive bladder cancer
Authors: Hattori Yuto , Fujiwara Tasuku , Hagimoto Hiroki , Kokubun Hidetoshi , Murata Shiori , Makita Noriyuki , Abe Yohei , Kubota Masashi , Tohi Yoichiro , Tsutsumi Naofumi , Shibasaki Noboru , Inoue Koji , Kawakita Mutsushi , Yamasaki Toshinari
Published: July 2024

Objective

The objective of this study was to evaluate the efficacy and safety of dose‐dense gemcitabine and cisplatin (ddGC) as neoadjuvant chemotherapy for muscle‐invasive bladder cancer (MIBC).

Methods

Patients with locally advanced MIBC (cT2aN0M0‐cT4N1M0) who received ddGC between December 2017 and December 2023 were included. Regimens of ddGC with pegfilgrastim were administered every 2 weeks for 4 cycles, followed by radical cystectomy. The pathological complete response (CR) (pT0N0) and objective response (OR) (<pT2N0) rates were evaluated in patients who underwent radical cystectomy. Tolerability was assessed using relative dose intensity (RDI). Adverse events (AEs) were documented according to the Common Terminology Criteria for Adverse Events in all patients who received ddGC. Disease‐free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method.

Results

A total of 45 patients (cT2N0, 60%; cT3N0, 22%; cT4N0, 9%; and cTanyN1, 9%) were included. Of the 41 who underwent cystectomy, 38 (92.7%) completed all planned cycles, with a median RDI of 0.96 (interquartile range [IQR], 0.89–1.00). Overall, CR and OR were achieved in 12 (29.3%) and 17 (41.5%) patients, respectively, increasing to 32.4% and 45.9%, respectively, in cN0 patients. Severe AEs (grade ≥ 3) were observed in eight patients (17.8%), including four hematological toxicities. At a median follow‐up of 31 months, 2‐year DFS and OS were 70.8% and 89.2%, respectively.

Conclusion

Neoadjuvant ddGC demonstrated good tolerability, efficacy, and safety, suggesting its potential as a treatment option for MIBC.
Effects of poly (ADP‐ribose) polymerase 1 (PARP1) on silk proteins in the silkworm, Bombyx mori
Authors: Wu Mingke , Sun Hao , Wang Aoming , Lao Junjie , Liu Dan , Chen Chaojie , Zhang Yan , Xia Qingyou , Ma Sanyuan
Published: July 2024

Animal silk is economically important, while silk secretion is a complex and subtle mechanism regulated by many genes. We identified the poly (ADP‐ribose) polymerase (PARP1) gene of the silkworm and successfully cloned its coding sequence (CDS) sequence. Using clustered regularly interspaced short palindromic repeat (CRISPR/Cas9) technology, we screened single guide RNA (sgRNA) with high knockout efficiency by cellular experiments and obtained PARP1 mutants by knocking out the PARP1 gene of the silkworm at the individual level. We found that the mutants mainly exhibited phenotypes such as smaller cocoon size and reduced cocoon shell rate than the wild type. We also detected the expression of silk protein genes in the mutant by quantitative real‐time PCR (qPCR) and found that the expression of some silk protein genes was slightly down‐regulated. Meanwhile, together with the results of transcriptomic analysis, we hypothesized that PARP1 may affect the synthesis of silk proteins, resulting in their failure to function properly. Our study may provide an important reference for future in‐depth refinement of the molecular mechanism of silk protein expression in silk‐producing animals, as well as a potential idea for future development of molecular breeding lines of silkworms to improve silk production.
Stabilization of phase‐pure tetragonal zirconia ceramics with minimum CeO2 doping and associated benefits
Authors: Lakshya Annu Kumar , Jha Keshav Kumar , Chowdhury Anirban
Published: July 2024

In the quest of finding the minimum ceria doping for a stabilized zirconia matrix, we report a remarkable structure–property correlation for a high (> 99%) density, fine grained (∼100 nm), fully phase‐pure (confirmed via both slow scan X‐ray diffraction and Raman spectroscopy) tetragonal 10 mol.% CeO2‐doped zirconia ceramics (10Ce‐TZP). A starting near spherical, ultrafine (∼7 nm) powders with high surface area (∼170 m2/g) ensured the conventional pressureless sintering at 1150°C without the need of any additives, binders, and/or sintering aid to achieve this high density. No monoclinic phase was traced at the end of the low‐temperature degradation test for 100 h in boiling water; negligible (∼5% monoclinic phase) amounts showed up in the thermal quenching tests. The sintered 10Ce‐TZP ceramic recorded comparable/better hardness and indentation toughness value with respect to higher (i.e., 12 mol.%) ceria doped‐zirconia systems. For the first time, nanograined translucent 10Ce‐TZP ceramic portrayed a remarkable transmittance of ∼38% at 600 nm wavelength for 0.6 mm thick pellet.
The use of echocardiography compared to electrocardiogram when screening for left ventricular hypertrophy in hypertensive patients: A cross‐sectional study
Authors: Bult Marijn Marc , van de Ree Thomas Flint , Wind Anna Maria , Hurley Kai Morris , van de Ree Marcel Allard
Published: July 2024

Left ventricular hypertrophy (LVH) is often used as an indicator to assess hypertension‐mediated organ damage (HMOD), alongside hypertensive retinopathy (HR) and nephropathy. Assessment of HMOD is crucial when making decisions about treatment optimization. Despite longstanding debate over its reliability to detect LVH, it is common practice to perform an electrocardiogram (ECG) instead of directly assessing left ventricular mass with echocardiography. In this study, the presence of LVH was evaluated using both ECG and echocardiography among consecutive patients suspected of therapy‐resistant hypertension or secondary hypertension in the outpatient clinic of the Department of Internal Medicine at the Diakonessen Hospital, Utrecht, the Netherlands, between July 15, 2017, and July 31, 2020. The primary endpoints were the specificity and sensitivity of ECG as a diagnostic tool for LVH, with echocardiography serving as the reference method. Among the 329 participants, we identified 70 individuals (21.3%) with true LVH based on echocardiography. The ECG displayed a sensitivity of 47.9% and a specificity of 75.3%. Moreover, the area under the receiver operating characteristics curve was 0.604. In conclusion, ECG demonstrates limited value in identifying LVH. Considering the importance of accurately assessing HMOD for treatment optimization of hypertension, the role of ECG as a diagnostic tool for LVH is, therefore, questionable. Instead, we recommend employing standard echocardiography as a more reliable diagnostic.
The effect of ADAMTS13 on graft‐versus‐host disease
Authors: Li Dan , Cho Min Soon , Gonzalez‐Delgado Ricardo , Liang Xiaowen , Dong Jing‐Fei , Cruz Miguel A. , Ma Qing , Afshar‐Kharghan Vahid
Published: July 2024

Allogeneic haematopoietic stem cell transplantation (allo‐HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo‐HSCT is associated with significant complications. The most common and debilitating among them is graft‐versus‐host disease (GVHD). In GVHD, donor‐derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD‐targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non‐lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF‐cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF‐A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF‐A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD‐targeted organs in vivo. We identified LFA‐1 (αLβ2) as the binding site of VWF on T cells. Our results showed that blocking T‐cell homing by ADAMTS13 or VWF‐A2 peptide reduced the severity of the GVHD after allo‐HSCT, a potentially novel method for treating and preventing GVHD.
Immune‐related adverse events of antibody‐based biological medicines in cancer therapy
Authors: Rajagopal Deepa , MacLeod Elliot , Corogeanu Diana , Vessillier Sandrine
Published: July 2024

Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)‐based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab‐based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune‐related adverse event (irAE) associated with Ab‐based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life‐threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro‐inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab‐based novel cancer immunotherapeutics, namely immune checkpoint (IC)‐targeting Abs, bispecific Abs (BsAbs) and Ab‐drug‐conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab‐based biotherapeutics as an approach to support and refine clinical translation.
Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts
Authors: Gaudy‐Marqueste C. , Grob J. J. , Garbe C. , Ascierto P. A. , Arron S. , Basset‐Seguin N. , Bohne A. S. , Lenoir C. , Dummer R. , Fargnoli M. C. , Guminski A. , Hauschild A. , Kaufmann R. , Lallas A. , del Marmol V. , Migden M. , Penicaud M. , Rembielak A. , Stratigos A. , Tagliaferri L. , Zalaudek I. , Arance A. , Badinand D. , Bossi P. , Challapalli A. , Clementi M. , Di Stefani A. , Ferrándiz‐Pulido C. , Giuffrida R. , Gravina G. L. , Ha P. , Heinzerling L. , Mallet S. , Paradisi A. , Mohr P. , Piccerillo A. , Rutkowski D. , Saiag P. , Sollena P. , Trakatelli M. , Wojcieszek P. , Yom S. S. , Zelin E. , Peris K. , Malvehy J.
Published: July 2024

Background

There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision‐making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas.

Objectives

To generate a consensual and operational classification of cSCCs.

Methods

Unsupervised independent clustering of 248 cases of cSCCs considered difficult‐to‐treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K‐mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners.

Results

Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy‐to‐treat cSCC was included, resulting in a six‐group final classification: easy‐to‐treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases.

Conclusions

Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.