bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Caring for Grandchildren on Health and Well‐Being of Grandparents: Evidence From Vietnam
Authors: Le Duc Dung , Giang Long Thanh
Published: September 2024

To date, studies on the effects of grandparenting on grandparents' health and well‐being do not reach the same conclusion and most of them have been conducted in developed countries. We add to this literature by examining the causal relationship between grandparenting and grandparents' health and well‐being in Vietnam, where the social norm and reciprocal relationships between adult children and their older parents are strong. We used instrumental variable estimations to address the endogeneity issue of the decision to provide care. Using the national survey on older persons in Vietnam, we found that grandparenting care had positive effects on psychological well‐being, life satisfaction, and self‐rated health of grandparents. We also found that the effects were heterogenous by caregiver's gender, in which grandmothers were more beneficial from caregiving tasks than grandfathers. Further exploring the mechanisms underlying the effects revealed that improvements in memory and stronger social networks were potential channels through which grandparenting might improve the health and well‐being of grandparents. Our findings support the theory of role enhancement, suggesting that grandparents can have health and well‐being benefits from grandparenting. Policies aiming at strengthening old age protection and family relationships should be advocated to sustain the subjective well‐being of older adults.
A novel inhibitor of class IIa histone deacetylases attenuates collagen‐induced arthritis
Authors: Poon Eunice K. , Liu Ligong , Wu Kai‐Chen , Lim Junxian , Sweet Matthew J. , Lohman Rink‐Jan , Iyer Abishek , Fairlie David P.
Published: September 2024

Background and Purpose

Most inhibitors of histone deacetylases (HDACs) are not selective and are cytotoxic. Some have anti‐inflammatory activity in disease models, but cytotoxicity prevents long‐term uses in non‐fatal diseases. Inhibitors selective for class IIa HDACs are much less cytotoxic and may have applications in management of chronic inflammatory diseases.

Experimental Approach

LL87 is a novel HDAC inhibitor examined here for HDAC enzyme selectivity. It was also investigated in macrophages for cytotoxicity and for inhibition of lipopolysaccharide (LPS)‐stimulated cytokine secretion. In a rat model of collagen‐induced arthritis, LL87 was investigated for effects on joint inflammation in Dark Agouti rats. Histological, immunohistochemical, micro‐computed tomography and molecular analyses characterise developing arthritis and anti‐inflammatory efficacy.

Key Results

LL87 was significantly more inhibitory against class IIa than class I or IIb HDAC enzymes. In macrophages, LL87 was not cytotoxic and reduced both LPS‐induced secretion of pro‐inflammatory cytokines, and IL6‐induced class IIa HDAC activity. In rats, LL87 attenuated paw swelling and clinical signs of arthritis, reducing collagen loss and histological damage in ankle joints. LL87 decreased immune cell infiltration, especially pro‐inflammatory macrophages and osteoclasts, into synovial joints and significantly reduced expression of pro‐inflammatory cytokines and tissue‐degrading proteases.

Conclusion and Implications

A novel inhibitor of class IIa HDACs has been shown to have an anti‐inflammatory and anti‐arthritic profile distinct from current therapies. It is efficacious in reducing macrophage infiltration and joint inflammation in a chronic model of rat arthritis.
Neural Dynamic Principles for an Intentional Embodied Agent
Authors: Tekülve Jan , Schöner Gregor
Published: September 2024

How situated embodied agents may achieve goals using knowledge is the classical question of natural and artificial intelligence. How organisms achieve this with their nervous systems is a central challenge for a neural theory of embodied cognition. To structure this challenge, we borrow terms from Searle's analysis of intentionality in its two directions of fit and six psychological modes (perception, memory, belief, intention‐in‐action, prior intention, desire). We postulate that intentional states are instantiated by neural activation patterns that are stabilized by neural interaction. Dynamic instabilities provide the neural mechanism for initiating and terminating intentional states and are critical to organizing sequences of intentional states. Beliefs represented by networks of concept nodes are autonomously learned and activated in response to desired outcomes. The neural dynamic principles of an intentional agent are demonstrated in a toy scenario in which a robotic agent explores an environment and paints objects in desired colors based on learned color transformation rules.
Photodynamic therapy in dermatology: established and new indications
Authors: Balakirski Galina , Lehmann Percy , Szeimies Rolf‐Markus , Hofmann Silke C.
Published: September 2024

Photodynamic therapy (PDT) is internationally established as an approved treatment option for in situ forms of keratinocytic skin cancer (actinic keratoses, Bowen's disease, basal cell carcinoma). For these indications, there are standardized treatment protocols using narrow‐spectrum light sources or (artificial) daylight, the use of which is associated with successful healing, a low rate of lesion recurrence, and a very good cosmetic result.

Daylight PDT is superior to conventional PDT in terms of significantly less pain and associated higher patient acceptance.

Newer indications, for which no approval has yet been granted, but which nevertheless have sufficient evidence of efficacy according to the study situation, are inflammatory (lichen sclerosus, acne) and infectious dermatoses (viral warts, cutaneous leishmaniasis, atypical mycobacteriosis). In addition, PDT is increasingly being used in aesthetic dermatology with the aim of skin rejuvenation.
A phase‐field framework for stress corrosion cracking prediction in elastoplastic metallic materials
Authors: Wang Yuan‐Zuo , Liu Zi‐Han , Yang Lu , Du Xiu‐Li
Published: September 2024

To capture the stress corrosion cracking (SCC) in metallic materials, a phase‐field framework considering localized plastic deformation and stress states is established. A new function of critical energy release rate is proposed to describe the degradation of cracking resistance of materials in the SCC process. This proposed framework can reproduce SCC results consistent with experimental observations in C‐ring steel SCC tests, especially capturing the directionally characteristic of the cracks. Furthermore, the influences of localized plastic deformation and stress states on the SCC process are studied. This novel phase‐field framework can capture (1) the influences of coupled electricity, mechanics to the SCC mechanisms; (2) the contribution of plastic strain energy as the driving force for the phase‐field; (3) the potential and preferential crack initiation and propagation morphology within the complex stress and strain domain; and (4) the dependence of SCC rate and propagation direction on stress state and localized plastic deformation.
A diffusion‐driven model for deposit removal during water rinse
Authors: Fan Mengyuan , Kim Woo‐Ju , Heldman Dennis R.
Published: September 2024

The objective of this study is to develop a model that is based on water diffusion for predicting the cleaning procedure during water rinse of Clean‐in‐Place operation. The kinetics of dairy foulant generated by using dairy product was analysed. The foulants removal with three different moisture contents (6.7%, 13.4%, and 39.3%) and four different wall shear stresses (WSS, 0.013, 0.39, 0.84, and 2.42 Pa) were evaluated. It was found that the lag time decreased with increase of WSS. In addition, the maximal removal and cleaning rate was found to increase along with the elevation of the wall shear stress. Moisture contents of the deposit determines the minimum magnitude of the wall shear stress to initiate the removal process. By combining the water diffusion and removal kinetics obtained from the experiment, a model to describe the removal of the deposits has been developed. Diffusion assuming 1‐D infinite plate was used to simulate the change in moisture content. The model confirms that the foulants with a higher initial moisture content is more rapidly removed. Furthermore, the foulant removal is affected by the permeation of water into foulants as well as the wall shear stress.
MitoAMPK inhibits the Warburg effect by MZF1–SIRT6 with glycosis related genes in NSCLC
Authors: Li Shangyu , He Jinyao , Zhang Lijie , Zhao Qiaojiajie , Zhao Shuqi , Jiang Shanshan
Published: September 2024

MitoAMPK was proved to inhibit the Warburg effect, but the specific mechanisms on non‐small‐cell lung cancer remain unclear. Here, we selected SIRT6 and MZF1 to clarify the mechanism. By western blotting, quantitative polymerase chain reaction, the CCK‐8 assay, and immunohistochemistry assays, we found SIRT6 expression was lower in NSCLC tissues and cell lines than normal tissues and cells. Moreover, SIRT6 could inhibit the Warburg effect by regulating glycolysis‐related genes of SLC2A2, SLC2A4 and PKM2. Finally, we demonstrated the interaction between SIRT6 and MZF1 using ChIP‐qPCR. In conclusion, mitoAMPK inhibits the Warburg effect by regulating the expression of the MZF1–SIRT6 complex.
Experimental Periodontitis Worsens Dopaminergic Neuronal Degeneration
Authors: Jacob Gabrielle , Milan Bruna A. , Antonieto Livia Rodrigues , Levi Yara , Ribeiro Marcela Costa , Nassar Raquel , de Sousa‐Neto Manoel Damião , Mazzi‐Chaves Jardel Francisco , Messora Michel Reis , Furlaneto Flavia Aparecida Chaves , Nascimento Glauce C. , Del‐Bel Elaine
Published: September 2024

Aim

To investigate the hypothesis supporting the link between periodontitis and dopaminergic neuron degeneration.

Materials and Methods

Adult male Wistar rats were used to induce dopaminergic neuronal injury with 6‐hydroxydopamine (6‐OHDA) neurotoxin and experimental periodontitis via ligature placement. Motor function assessments were conducted before and after periodontitis induction in controls and 6‐OHDA‐injury‐induced rats. Tissue samples from the striatum, jaw and blood were collected for molecular analyses, encompassing immunohistochemistry of tyrosine hydroxylase, microglia and astrocyte, as well as micro‐computed tomography, to assess alveolar bone loss and for the analysis of striatal oxidative stress and plasma inflammatory markers.

Results

The results indicated motor impairment in 6‐OHDA‐injury‐induced rats exacerbated by periodontitis, worsening dopaminergic striatal degeneration. Periodontitis alone or in combination with 6‐OHDA‐induced lesion was able to increase striatal microglia, while astrocytes were increased by the combination only. Periodontitis increased striatal reactive oxygen species levels and plasma tumour necrosis factor‐alpha levels in rats with 6‐OHDA‐induced lesions and decreased the anti‐inflammatory interleukin‐10.

Conclusions

This study provides original insights into the association between periodontitis and a neurodegenerative condition. The increased inflammatory pathway associated with both 6‐OHDA‐induced dopaminergic neuron lesion and periodontal inflammatory processes corroborates that the periodontitis‐induced systemic inflammation may aggravate neuroinflammation in Parkinson's‐like disease, potentially hastening disease progression.
Sulfonylurea prescription patterns in elderly patients with type 2 diabetes mellitus: A comprehensive analysis of real‐world data from pharmacies in Japan
Authors: Yamazaki Michiko , Takebe Tohru , Hosokawa Masaya , Saika Tomoya , Nakao Yutaka , Ikeda Shunya , Sakamoto Masaya
Published: September 2024

Aims/Introduction

The study aim was to investigate sulfonylurea prescription patterns in elderly patients (age ≥65 years) with type 2 diabetes mellitus in Japan. Sulfonylurea use among older adults has been insufficiently examined, despite the associated risks of hypoglycemia.

Materials and Methods

This retrospective cross‐sectional survey entailed analysis of Japanese pharmacy data, extracted from the Musubi database, for patients (age 20–100 years) prescribed sulfonylureas between November 2022 and October 2023. Dose distribution, adherence to the Diabetes Treatment Guidelines for the Elderly 2023 and coprescription of other diabetes medications were investigated.

Results

Of the total 91,229 patients, 80.1% were prescribed glimepiride, 16.3% gliclazide and 3.6% glibenclamide. In patients aged ≥65 years, exceeding the recommended dose (>1 mg/day for glimepiride, >40 mg/day for gliclazide) was numerically higher for glimepiride (25.0%) than for gliclazide (7.8%). The most common prescribing patterns were quadruple therapy with a sulfonylurea, a dipeptidyl peptidase‐4 inhibitor, an sodium–glucose transporter 2 inhibitor and a biguanide in patients aged 65 to <75 years, and dual therapy with a sulfonylurea and a dipeptidyl peptidase‐4 inhibitor in patients aged ≥75 years. Unfortunately, glinide was coprescribed for 338 (0.5%) of elderly patients. Insulin was coprescribed for 3,682 (5.6%) of elderly patients.

Conclusions

Analysis of real‐world sulfonylurea prescription data found guideline non‐adherence, namely, excessive prescription of glimepiride, use of glibenclamide in elderly patients, and common coprescription with dipeptidyl peptidase‐4 inhibitors. These findings might provide an opportunity to reconsider the treatment of patients with type 2 diabetes mellitus who are over‐prescribed sulfonylureas to reduce residual risks, such as hypoglycemia.
Funny words on the screen: Exploring linguistic authority through subtitling practices
Authors: Wong Andrew D.
Published: September 2024

Linguistic authority, though generally understood as the right claimed by some people and institutions to regiment language use and representation, has also been conceptualized as the power of languages to command respect and attention from community members. To explore these two aspects of linguistic authority, this article examines how the producers of a popular Chinese talk show use on‐screen text to construct authority both for themselves and for Putonghua (standard Mandarin) in situated moments of interaction. It focuses on an episode of the show in which the Putonghua‐speaking host interviews a Hong Kong actor/director known for his Gangpu (Hong Kong Mandarin). Through the strategic use of traditional subtitles and impact captions, the show's producers position themselves as anonymous listening subjects who not only provide running commentary on what viewers hear, but also contrast Putonghua with Gangpu and Cantonese, and affirm its legitimacy by presenting it as the unmarked, anonymous language against which these minoritized varieties are compared. To fully understand the (de)legitimation of linguistic authority in media productions, we need to consider both aspects of linguistic authority, examine how they are connected to each other, and attend to the array of contrasting relations that subtitling practices create among linguistic varieties.
Prevalence, trends, and outcomes of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage in the USA
Authors: Qureshi Adnan I. , Bhatti Ibrahim A. , Gillani Syed A. , Beall Jonathan , Cassarly Christy N. , Gajewski Byron , Martin Renee H. , Suarez Jose I. , Kwok Chun Shing
Published: September 2024

Background and Purpose

Cerebral infarction remains an important cause of death or disability in patients with aneurysmal subarachnoid hemorrhage (SAH). The prevalence, trends, and outcomes of cerebral infarction in patients with aneurysmal SAH at a national level are not known.

Methods

We identified the proportion of patients who develop cerebral infarction (ascertained using validated methodology) among patients with aneurysmal SAH and annual trends using the Nationwide Inpatient Sample (NIS) from 2016 to 2021. We analyzed the effect of cerebral infarction on in‐hospital mortality, routine discharge without palliative care (based on discharge disposition), poor outcome defined by the NIS SAH outcome measure, and length and costs of hospitalization after adjusting for potential confounders.

Results

A total of 35,305 (53.6%) patients developed cerebral infarction among 65,840 patients with aneurysmal SAH over a 6‐year period. There was a trend toward an increase in the proportion of patients who developed cerebral infarction from 51.5% in 2016 to 56.1% in 2021 (p trend p<.001). Routine discharge was significantly lower (30.5% vs. 37.8%, odds ratio [OR] 0.82, 95% confidence interval [CI] 0.75‐0.89, p<.001), and poor outcome defined by NIS‐SAH outcome measure was significantly higher among patients with cerebral infarction compared with those without cerebral infarction (67.4% vs. 59.3%, OR 1.29, 95% CI 1.18‐1.40, p<.001). There was no difference in in‐hospital mortality (13.0% vs. 13.6%, OR 0.94, 95% CI 0.85‐1.05, p = .30). The length of stay (median 18 days [interquartile range [IQR] 13‐25] vs. 14 days [IQR 9‐20]), coefficient 3.04, 95% CI 2.44‐3.52 and hospitalization cost (median $96,823 vs. $71,311, coefficient 22,320, 95% CI 20,053‐24,587) were significantly higher among patients who developed cerebral infarction compared with those who did not develop cerebral infarction.

Conclusions

Cerebral infarction was seen in 54% of the patients with a trend toward an increase in the affected proportion of patients with aneurysmal SAH. Patients with cerebral infarction had higher rates of adverse outcomes and required higher resources during hospitalization.
Novel murine closed‐loop auditory stimulation paradigm elicits macrostructural sleep benefits in neurodegeneration
Authors: Dias Inês , Kollarik Sedef , Siegel Michelle , Baumann Christian R. , Moreira Carlos G. , Noain Daniela
Published: September 2024

Boosting slow‐wave activity (SWA) by modulating slow waves through closed‐loop auditory stimulation (CLAS) might provide a powerful non‐pharmacological tool to investigate the link between sleep and neurodegeneration. Here, we established mouse CLAS (mCLAS)‐mediated SWA enhancement and explored its effects on sleep deficits in neurodegeneration, by targeting the up‐phase of slow waves in mouse models of Alzheimer's disease (AD, Tg2576) and Parkinson's disease (PD, M83). We found that tracking a 2 Hz component of slow waves leads to highest precision of non‐rapid eye movement (NREM) sleep detection in mice, and that its combination with a 30° up‐phase target produces a significant 15–30% SWA increase from baseline in wild‐type (WTAD) and transgenic (TGAD) mice versus a mock stimulation group. Conversely, combining 2 Hz with a 40° phase target yields a significant increase ranging 30–35% in WTPD and TGPD mice. Interestingly, these phase‐target‐triggered SWA increases are not genotype dependent but strain specific. Sleep alterations that may contribute to disease progression and burden were described in AD and PD lines. Notably, pathological sleep traits were rescued by mCLAS, which elicited a 14% decrease of pathologically heightened NREM sleep fragmentation in TGAD mice, accompanied by a steep decrease in microarousal events during both light and dark periods. Overall, our results indicate that model‐tailored phase targeting is key to modulate SWA through mCLAS, prompting the acute alleviation of key neurodegeneration‐associated sleep phenotypes and potentiating sleep regulation and consolidation. Further experiments assessing the long‐term effect of mCLAS in neurodegeneration may majorly impact the establishment of sleep‐based therapies.
Evolving Characteristics of Decedents With Hepatitis A Listed as a Cause of Death, United States, 2011–2021
Authors: Hofmeister Megan G. , Ly Kathleen N. , Yin Shaoman , Spradling Philip R.
Published: September 2024

Hepatitis A is a vaccine‐preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person‐to‐person transmission have been widespread in the United States since 2016. We used public‐use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A‐listed deaths during non‐outbreak (2011–2015) and outbreak (2017–2021) periods and assessed the median age at death among decedents with and without hepatitis A‐listed deaths during the outbreak period. From the non‐outbreak period to the outbreak period, hepatitis A‐listed deaths more than doubled (from 369 to 801), while the hepatitis A‐listed age‐adjusted mortality rate increased 150% (p < 0.001). When compared with the non‐outbreak period, hepatitis A‐listed decedents during the outbreak period were more frequently male, aged 18–49 years, non‐Hispanic White, died in an inpatient setting, and had hepatitis A listed as their underlying cause of death. The median age at death for hepatitis A‐listed decedents was significantly younger during the outbreak period overall and among females (62 and 66 years, respectively) compared with the non‐outbreak period (64 and 72 years, respectively, p < 0.001). During the outbreak period, median age at death for hepatitis A‐listed decedents was 14 years younger than decedents without hepatitis A listed. Compared with the general US population, decedents with hepatitis A listed on the death certificate died at younger ages during 2017–2021. Efforts are needed to improve hepatitis A vaccination coverage among adults recommended for hepatitis A vaccination to prevent additional premature hepatitis A deaths.
Empowering youth as agents of change: Gaps and opportunities for meaningful youth engagement (MAYE) for sustainable nutrition, climate and public health programmes
Authors: Gaithuma Joseph , Chor Samuel , Natukunda Angela , Shahleen Pturgo , Kavle Justine A.
Published: September 2024

Addressing the intersection of food insecurity, malnutrition and climate change in Sub‐Saharan Africa requires meaningful adolescent and youth engagement to drive sustainable change. Drawing on empirical evidence and collective experiences from youth‐led initiatives and coalitions, four gaps and opportunities to better involve youth in programmes are discussed, including, the need to: (1) standardise the definition of youth to improve programme design and data harmonisation, (2) provide capacity building and mentorship for youth leadership in health service delivery, (3) foster youth leadership and multisectoral collaboration in food and health systems and (4) enhance capacity development for non‐youth actors to support genuine youth participation. This viewpoint underscores the importance of involving African youth in public health nutrition, climate change and food security programmes design and implementation—as drivers of change to addressing hunger and climate crises. By centering youth voices and experiences, programmes and policies can better address African communities' complex challenges, fostering inclusivity, sustainability and resilience in achieving better nutrition and public health programmes and outcomes.
A computer vision–aided methodology for bridge flexibility identification from ambient vibrations
Authors: Cheng Yuyao , Jia Siqi , Zhang Jianliang , Zhang Jian
Published: September 2024

This paper presents the implementation of a novel monitoring system in which video images and conventional sensor network data are simultaneously analyzed to identify the structural flexibility from the ambient vibrations. The magnitude ratio between the flexibility estimated from known/unknown input force are theoretically derived and decomposed into two parts: and . The first scale factor related to basic modal parameters can be acquired using the general modal identification methods. Aiming to tackle the difficulty in identifying the second scale factor related to the force intensity, a video stream of traffic is processed to detect and classify vehicles to determine the vehicle's location while displacement measurements are simultaneously collected. By integrating the toll station data, the vehicle loads are assigned to the vehicle on the bridge deck through the uniqueness of the license plate number. Thus, a structural input–output relationship is established to solve the second scale factor . Finally, the flexibility estimated from the ambient vibration are scaled by and , respectively to obtain the exact flexibility , which are same as the analytical ones . Both numerical example and a laboratory test are performed to demonstrate the accuracy of the proposed methodology. The algorithms, approaches, and results given in the paper demonstrate its effectiveness and shows great potential for its application on a real‐life bridge's condition assessment.
Interorgan, intraorgan and interplant communication mediated by nitric oxide and related species
Authors: Kolbert Zsuzsanna , Barroso Juan B. , Boscari Alexandre , Corpas Francisco J. , Gupta Kapuganti Jagadis , Hancock John T. , Lindermayr Christian , Palma José Manuel , Petřivalský Marek , Wendehenne David , Loake Gary J.
Published: September 2024

Plant survival to a potential plethora of diverse environmental insults is underpinned by coordinated communication amongst organs to help shape effective responses to these environmental challenges at the whole plant level. This interorgan communication is supported by a complex signal network that regulates growth, development and environmental responses. Nitric oxide (NO) has emerged as a key signalling molecule in plants. However, its potential role in interorgan communication has only recently started to come into view. Direct and indirect evidence has emerged supporting that NO and related species (S‐nitrosoglutathione, nitro‐linolenic acid) are mobile interorgan signals transmitting responses to stresses such as hypoxia and heat. Beyond their role as mobile signals, NO and related species are involved in mediating xylem development, thus contributing to efficient root–shoot communication. Moreover, NO and related species are regulators in intraorgan systemic defence responses aiming an effective, coordinated defence against pathogens. Beyond its in planta signalling role, NO and related species may act as ex planta signals coordinating external leaf‐to‐leaf, root‐to‐leaf but also plant‐to‐plant communication. Here, we discuss these exciting developments and emphasise how their manipulation may provide novel strategies for crop improvement.
Leaf stomatal configuration and photosynthetic traits jointly affect leaf water use efficiency in forests along climate gradients
Authors: Pan Shengnan , Wang Xin , Yan Zhengbing , Wu Jin , Guo Lulu , Peng Ziyang , Wu Yuntao , Li Jing , Wang Bin , Su Yanjun , Liu Lingli
Published: September 2024

Water use efficiency (WUE) represents the trade‐off between carbon assimilation and water loss in plants. It remains unclear how leaf stomatal and photosynthetic traits regulate the spatial variation of leaf WUE in different natural forest ecosystems.

We investigated 43 broad‐leaf tree species spanning from cold‐temperate to tropical forests in China. We quantified leaf WUE using leaf δ13C and measured stomatal traits, photosynthetic traits as well as maximum stomatal conductance () and maximum carboxylation capacity ().

We found that leaves in cold‐temperate forests displayed ‘fast’ carbon economics, characterized by higher leaf nitrogen, Chl, specific leaf area, and , as an adaptation to the shorter growing season. However, these leaves exhibited ‘slow’ hydraulic traits, with larger but fewer stomata and similar , resulting in higher leaf WUE. By contrast, leaves in tropical forests had smaller and denser stomata, enabling swift response to heterogeneous light conditions. However, this stomatal configuration increased potential water loss, and coupled with their low photosynthetic capacity, led to lower WUE.

Our findings contribute to understanding how plant photosynthetic and stomatal traits regulate carbon–water trade‐offs across climatic gradients, advancing our ability to predict the impacts of climate changes on forest carbon and water cycles.
On the Relationship Between Frailty, Nutritional Status, Depression and Quality of Life Among Older People
Authors: Kasa Ayele Semachew , Traynor Victoria , Lee Shu‐Chun , Drury Peta
Published: September 2024

Background

Frailty is a multidimensional geriatric syndrome associated with physical, psychological and social changes. There is a paucity of research on frailty in Sub‐Saharan African (SSA) countries, especially Ethiopia.

Objectives

To assess the initial correlations among frailty, nutritional status, depression and QOL (quality of life) in a group of older people in Ethiopia who are later enrolled in a study examining the effects of a nurse‐led community intervention on frailty and related health outcomes.

Methods

Data from 68 community‐dwelling individuals 60 years of age, or over, were collected. Frailty was measured using the Amharic version of the Tilburg Frailty Indicator. The statistical analysis included Spearman's rank correlation coefficient for degrees of association, Mann–Whitney U‐test for variables with two categories and Kruskal–Wallis for variables with three or more categories.

Results

The mean frailty score for participants was 7.3 (±1.9). Participants with higher frailty scores had lower nutritional status (rs = −0.46, p < 0.01). There was a statistically significant relationship (positive) between frailty scores and depression (rs = 0.39, p < 0.01). Depressed (Md = 9, n = 23) and non‐depressed frail older people (Md = 7, n = 45) showed a significant difference in their overall frailty score, U = 330.50, z = −2.49, p = 0.01, r = 0.30. There was an inverse significant association between the level of frailty across different domains in the QOL: physical (rs = −0.44, p < 0.01), psychological (rs = −0.45, p < 0.01), social relations (rs = −0.29, p < 0.05) and environmental (rs = −0.47, p < 0.01).

Conclusion

The findings from this study were consistent with those from across middle‐income and high‐income countries.

Implications for Practice

This research indicates that older people living in communities who are identified as frail often suffer from a poor nutritional status, depression and reduced QOL. It suggests that healthcare professionals in Sub‐Saharan countries would benefit from recognising the frailty in this population, and developing interventions aimed at enhancing nutrition, mental health and overall well‐being.
Visual impact of diffusion optic technology lenses for myopia control
Authors: Wolffsohn James S. , Hill Jennifer S. , Hunt Chris , Young Graeme
Published: September 2024

Purpose

To assess the visual impact of Diffusion Optics Technology™ 0.2 DOT lenses (SightGlass Vision Inc.) designed for myopia control on primary gaze. DOT spectacle lenses contain light scattering elements that scatter light as it passes through the lens which, in turn, reduces retinal image contrast.

Methods

Fifty‐one children (12.2 ± 1.3, range 10–14 years; 51% females) were randomly assigned to wear DOT spectacle (n = 27) or single vision lenses (n = 24) across six investigational sites in North America. Binocular high‐ and low‐contrast distant visual acuities, near visual acuity, reading speed, contrast sensitivity, stereoacuity and glare were assessed in primary gaze after at least 3 years of wear, with the study 95% powered in all metrics to detect significant differences between the groups.

Results

Mean binocular distance high‐contrast (−0.09 ± 0.02 vs. −0.08 ± 0.02 logMAR, p = 0.81), low‐contrast (0.05 ± 0.02 vs. 0.07 ± 0.02 logMAR, p = 0.52) and near visual acuity with glare sources (−0.06 ± 0.03 vs. −0.09 ± 0.03 logMAR, p = 0.32) were similar for DOT and single vision lens wearers, respectively. Contrast sensitivity was similar between children wearing DOT or single vision lenses across 11 of the 16 spatial frequencies (p > 0.05). Mean stereopsis was similar (p = 0.30) with the DOT lenses (33.2 ± 12.5″) and single vision lenses (38.1 ± 14.2″). Functional reading speed metrics were similar in both study groups, as was the objectively measured head tilt during reading (p > 0.05). The mean halo radius was 0.56° ± 0.17° with the DOT lenses compared with 0.50° ± 0.12° with single vision lenses (p = 0.02), but the statistically significant difference was smaller than the non‐inferiority bound of 0.4°.

Conclusion

Diffusion optics technology lenses provide a clinically equivalent visual experience to a standard single vision lens.
Medicago truncatula SOBIR1 controls pathogen immunity and specificity in the Rhizobium‐legume symbiosis
Authors: Sarrette Baptiste , Luu Thi‐Bich , Johansson Alexander , Fliegmann Judith , Pouzet Cécile , Pichereaux Carole , Remblière Céline , Sauviac Laurent , Carles Noémie , Amblard Emilie , Guyot Valentin , Bonhomme Maxime , Cullimore Julie , Gough Clare , Jacquet Christophe , Pauly Nicolas
Published: September 2024

Medicago truncatula Nod Factor Perception (MtNFP) plays a role in both the Rhizobium‐Legume (RL) symbiosis and plant immunity, and evidence suggests that the immune‐related function of MtNFP is relevant for symbiosis. To better understand these roles of MtNFP, we sought to identify new interacting partners. We screened a yeast‐2‐hybrid cDNA library from Aphanomyces euteiches infected and noninfected M. truncatula roots. The M. truncatula leucine‐rich repeat (LRR) receptor‐like kinase SUPPRESSOR OF BIR1 (MtSOBIR1) was identified as an interactor of MtNFP and was characterised for kinase activity, and potential roles in symbiosis and plant immunity. We showed that the kinase domain of MtSOBIR1 is active and can transphosphorylate the pseudo‐kinase domain of MtNFP. MtSOBIR1 could functionally complement Atsobir1 and Nbsobir1/sobir1‐like mutants for defence activation, and Mtsobir1 mutants were defective in immune responses to A. euteiches. For symbiosis, we showed that Mtsobir1 mutant plants had both a strong, early infection defect and defects in the defence suppression in nodules, and both effects were plant genotype‐ and rhizobial strain‐specific. This work highlights a conserved function for MtSOBIR1 in activating defence responses to pathogen attack, and potentially novel symbiotic functions of downregulating defence in association with the control of symbiotic specificity.
Personal experiences with the national healthcare system and institutional trust in times of COVID‐19
Authors: Cavazza Nicoletta , Roccato Michele
Published: September 2024

We conducted two studies to analyze the relations between dissatisfaction with experiences with the national healthcare system and trust in political (political parties and parliament), super partes (judiciary and police), and international (European Union [EU] and United Nations [UN]) institutions via the mediation of trust in the national healthcare system. Study 1 (longitudinal study on a quota sample of the Italian adult population, N = 689, surveyed in April 2021, T1, and in April 2022, T2) showed that dissatisfaction with experiences with the national healthcare system was negatively associated with trust in the national healthcare system, which, in turn, was positively associated with an increase in trust in political, super partes, and international institutions. Study 2 (between‐participant experimental design, N = 285) showed that priming a negative versus a positive experience with the national healthcare system decreased trust in this system, which, in turn, was positively associated with trust in political, super partes, and international institutions. The strengths, limitations, and possible development of this research are discussed.
MiRNAs profiles among three poplar varieties provide insights into different molecular responses in resistance to newly emerging bacterial pathogen
Authors: Yu Ruen , Yang Xiaoqian , Xiao Dandan , Bao Hai , Wang Yanwei
Published: September 2024

Canker caused by Lonsdalea populi has seriously reduced the economic and ecological benefits of poplar. MicroRNAs play vital roles in the response of plants to biotic stress. However, there is little research about the regulatory mechanism of miRNAs among different tree varieties upon pathogen infection. To dissect miRNAs involved in L. populi resistance, three poplar varieties, 2025 (susceptible), 107 (moderately resistant) and Populus. tomentosa cv ‘henan’ (resistant) were selected to elucidate the expression profiles of miRNAs using small RNA‐seq. A total of 227 miRNAs were identified from all varieties. Intriguingly, miR160, miR169, miR171 and miR482b‐5p were only identified in the resistant variety P. tomentosa upon pathogen infection, and these miRNAs might be important candidates for future investigation to improve the tolerance of poplar to L. populi. Among all identified miRNAs, 174 were differentially expressed in all varieties. Functional annotation analysis indicated that an array of miRNAs, including miR482, miR472, miR169, miR481, and miR172, should be involved in disease resistance and phytohormone signal transduction. Furthermore, correlation analysis of small RNA‐seq and RNA‐seq identified a handful of L. populi‐responsive miRNAs and target genes, which exhibited that miR159 and miR172 played key roles in resistant variety P. tomentosa by targeting MYB and ERF, while miR6462c‐5p and miR828 were related to the susceptibility of 2025 by targeting MYB. The comprehensive integration analysis in this research provides new insights into the regulatory pathways involved in the defence response of poplar to L. populi and offers crucial candidate miRNAs‐target genes modules for poplar resistance improvement.
Early seedling development and survival of seagrasses Posidonia australis and P. sinuosa using different seed‐based restoration methods
Authors: Maulidiyah Rizqi A. , Cambridge Marion L. , Austin Rachel , Kendrick Gary A.
Published: September 2024

Seagrass seed‐based restoration has been developed in several places worldwide, but disturbance at the vulnerable initial stages of seedling recruitment has proved to be a major bottleneck to successful restoration. A detailed investigation of seagrass seedling survival and growth at the earliest stages of seedling development is an important contribution to developing techniques to improve seedling establishment and survival. Here, we investigated the early seedling development of Posidonia australis and P. sinuosa as well as quantifying the variation in seedling survival and development under different seed‐based restoration methods. Early seedling development was documented in indoor aquaria during the first month after fruit dehiscence. In the second ex situ experiment, we determined the effects of three different restoration methods (surface sowing, seedling planting, and planting inside a hessian bag) on seedling survival and development over the first 2 months of life. In the first experiment, a primary root with the first root hairs developed after 7 days. After 1 month, roots were 20–60 mm in length, firmly establishing the seedling into the sediment. Compared to surface sowing, seedling planting and hessian bag restoration treatments did not significantly affect survival for P. australis but increased seedling mortality in P. sinuosa, although growth was greater (shoot and root lengths were approximately 50 and 40% longer, respectively). These aquarium‐scale experiments suggest that planting methods would enhance seedling establishment at larger scales in some species, promoting restoration of damaged seagrass habitats.
Real‐world experience in treatment of donor‐derived Hepatitis C virus in kidney transplant recipients with delayed initiation, shortened course glecaprevir/pibrentasvir versus standard of care
Authors: Papanikolla Johanna , McGowan Melissa , Chunduru Mythili , Winters Holli , Pesavento Todd , Smith Rachel , Singh Navdeep , Wellner Michael , Sobotka Lindsay , Nolan Annelise
Published: September 2024

Background

There is limited literature describing the real‐world practice of delayed initiation and shortened duration direct‐acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1‐week post‐transplant.

Methods

Retrospective study of HCV‐negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections.

Results:

102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups. 

Conclusion:

Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.

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A randomized, placebo‐controlled, dose‐escalation phase I/II multicenter trial of low‐dose cidofovir for BK polyomavirus nephropathy
Authors: Imlay Hannah , Gnann John W. , Rooney James , Peddi V. Ram , Wiseman Alexander C. , Josephson Michelle A. , Kew Clifton , Young Jo‐Anne H. , Adey Deborah B. , Samaniego‐Picota Milagros , Whitley Richard J. , Limaye Ajit P.
Published: September 2024

Background

BK polyomavirus‐associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV).

Methods

We report the results of a phase I/II, double‐blind, placebo‐controlled randomized dose‐escalation trial of cidofovir in KTRs with biopsy‐confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow‐up through day 49.

Results

The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log10 reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group).

Conclusions

These preliminary results indicate that low‐dose cidofovir was safe and tolerated but had no significant BKPyV‐specific antiviral effect in KTRs with BKPyVAN.

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Early clearance of BK polyomavirus‐DNAemia among kidney transplant recipients may lead to better graft survival
Authors: Breyer Isabel , Ptak Lucy , Stoy David , Mandelbrot Didier , Parajuli Sandesh
Published: September 2024

Introduction

BK polyomavirus (BKPyV)‐DNAemia is a common complication in kidney transplant recipients (KTRs). The significance of achieving viral clearance at different time intervals is not well understood.

Methods

All adult KTRs transplanted between January 1, 2015 and December 31, 2017 who developed BKPyV‐DNAemia were included. Outcomes were analyzed based on persistent clearance of BKPyV‐DNAemia at 3‐month intervals up to 2 years after initial detection, and for recipients with persistent BKPyV‐DNAemia at last follow‐up. Uncensored graft failure, death‐censored graft failure (DCGF), and a composite outcome of DCGF or fall in estimated glomerular filtration rate (eGFR) by ≥50% from the time of initial BKPyV‐DNAemia were outcomes of interest.

Results

Of 224 KTRs with BKPyV‐DNAemia, 58 recipients (26%) achieved viral clearance by 3 months after initial detection, 105 (47%) by 6 months, 120 (54%) by 9 months, 141 (63%) by 12 months, 155 (69%) by 15 months, 167 (75%) by 18 months, 180 (80%) by 21 months, and 193 (86%) by 24 months. Nine recipients (4%) had persistent BKPyV‐DNAemia at last follow‐up. Compared to recipients who achieved viral clearance by 3 months, those who achieved clearance by 6 months (adjusted odds ratio [aOR]: 3.15; 95% confidence interval [CI]: 1.22–8.12; p = .02) and 9 months (aOR: 3.69; 95% CI: 1.02–13.43; p = .04) had significantly increased risk for uncensored graft failure. There was no significant association between time to viral clearance and DCGF or composite outcomes.

Conclusions

We found a trend of increased risk for uncensored graft failure among those who cleared BKPyV‐DNAemia more slowly. Aiming to clear viremia early, without risking rejection, may be beneficial for allograft function and patient morbidity and mortality.

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Rapid induction of allergen‐blocking IgG in dogs vaccinated with plant‐based, Der f 2‐expressing bioparticles
Authors: Olivry Thierry , Mirande Lucie , Aglas Lorenz , Morel Bertrand , Mas‐Fontao Ana , Fitchette Anne‐Catherine , Holztrattner Lena , Stigler Maria , Roberge Joannie , Martel Caroline , Stordeur Virginie , Desgagnés Réjean , Vézina Louis , Favrot Claude , Gomord Véronique
Published: September 2024

Background

Allergen‐carrying virus‐like particles are effective and safe means of allergen immunotherapy (AIT) in rodent models.

Objective

To study the development of allergen‐blocking immunoglobulin (Ig)G in dogs injected with Der f 2‐carrying enveloped plant‐based bioparticles (eBPs).

Materials and Methods

Laboratory beagle dogs were injected intradermally (ID) or subcutaneously (SC) with Der f 2‐eBP three times at 2‐week intervals. A basophil mediator release assay was used to compare the reactivity of Der f 2‐eBPs to that of recombinant Der f 2. Allergen‐specific IgG serum levels were determined by immunoblotting and ELISA. The allergen‐blocking potential of postvaccination IgG was assessed by Pet Allergy Xplorer (PAX) macroarray and basophil mediator release inhibition assays.

Results

The amount of Der f 2 eBPs needed to induce basophil activation was 1000‐fold higher than that of the soluble natural allergen. In both immunisation groups, eBP injections caused no adverse events and induced Der f 2‐specific IgG, first detected on Day (D)14 and peaking on D41. The co‐incubation of sera with a Der f 2‐IgE‐rich canine serum pool resulted in a mean PAX inhibition of 70% (ID) to 80% (SC) on D41. For both groups, the inhibition of basophil mediator release reached 75% on D28 and D41. The percentage inhibition of PAX and mediator release correlated significantly with Der f 2 IgG levels.

Conclusion and Clinical Relevance

Intradermal and subcutaneous injections of Der f 2‐eBPs were safe and increased Der f 2‐specific IgG. The clinical benefit of immunotherapy will be evaluated in future trials enrolling atopic dogs allergic to house dust mites.