bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo optical imaging of tumor stromal cells with hypoxia‐inducible factor activity
Authors: Miyabara Hitomi , Hirano Ryuichiro , Watanabe Shigeaki , Soriano John Clyde Co , Watanabe Hitomi , Kuchimaru Takahiro , Kitada Nobuo , Kadonosono Tetsuya , Maki Shojiro A. , Kondoh Gen , Kizaka‐Kondoh Shinae
Published: July 2023

Tumors contain various stromal cells, such as immune cells, endothelial cells, and fibroblasts, which contribute to the development of a tumor‐specific microenvironment characterized by hypoxia and inflammation, and are associated with malignant progression. In this study, we investigated the activity of intratumoral hypoxia‐inducible factor (HIF), which functions as a master regulator of the cellular response to hypoxia and inflammation. We constructed the HIF activity‐monitoring reporter gene hypoxia‐response element‐Venus‐Akaluc (HVA) that expresses the green fluorescent protein Venus and modified firefly luciferase Akaluc in a HIF activity‐dependent manner, and created transgenic mice harboring HVA transgene (HVA‐Tg). In HVA‐Tg, HIF‐active cells can be visualized using AkaBLI, an ultra‐sensitive in vivo bioluminescence imaging technology that produces an intense near‐infrared light upon reaction of Akaluc with the D‐luciferin analog AkaLumine‐HCl. By orthotopic transplantation of E0771, a mouse triple negative breast cancer cell line without a reporter gene, into HVA‐Tg, we succeeded in noninvasively monitoring bioluminescence signals from HIF‐active stromal cells as early as 8 days after transplantation. The HIF‐active stromal cells initially clustered locally and then spread throughout the tumors with growth. Immunohistochemistry and flow cytometry analyses revealed that CD11b+F4/80+ macrophages were the predominant HIF‐active stromal cells in E0771 tumors. These results indicate that HVA‐Tg is a useful tool for spatiotemporal analysis of HIF‐active tumor stromal cells, facilitating investigation of the roles of HIF‐active tumor stromal cells in tumor growth and malignant progression.
Health care concerns in parents of children with different genetic developmental and epileptic encephalopathies: A qualitative study
Authors: Palacios‐Ceña Domingo , Güeita‐Rodríguez Javier , Gil‐Nagel Antonio , Jimenez‐Antona Carmen , García‐Bravo Cristina , Velarde‐García Juan Francisco , Cuenca‐Zaldivar Juan Nicolas , Aledo‐Serrano Ángel
Published: July 2023

Aim

To describe the experiences and unmet medical care needs of a group of parents of children with developmental and epileptic encephalopathies (DEEs) caused by the SCN1A, KCNQ2, CDKL5, PCDH19, and GNAO1 variants.

Method

A qualitative descriptive study was conducted. Participants were recruited using purposeful sampling. The inclusion criteria consisted of parents of children with DEEs caused by the SCN1A, KCNQ2, CDKL5, PCDH19, or GNAO1 variants, aged between 4 and 10 years old. In total, 21 parents were included. Data were acquired via researcher field notes and in‐depth interviews. A thematic analysis was performed.

Results

Three main themes were identified: (1) managing symptoms: epileptic seizures are experienced with great uncertainty and are accompanied by cognitive, behavioural, and motor symptoms; (2) accepting treatment: the ideal medication regimen is a challenge and the decision to withdraw or start a new therapy falls on the parents; and (3) therapeutic relationship and medical care: behaviours related to the health professional can hinder the therapeutic relationship with the parents. Parents are apprehensive about going to the emergency department.

Interpretation

Professionals in emergency departments should acquire better knowledge of DEEs, welcome parents, and improve treatment for the children. The results of this study can serve as a starting point for a roadmap of relevant caregiver‐reported outcomes in DEEs, to be implemented with new clinical trials and aetiology‐targeted therapies.

What this paper adds

Epileptic seizures are the symptom that is most experienced and feared by parents.

The medication regime has no defined protocol and the decision to withdraw a medication is frequently left to parents.
Female relatives and domestic service in nineteenth‐century England and Wales: Female kin servants revisited
Authors: You Xuesheng
Published: July 2023

This article uses the full sample of the 1851 census enumerators’ books (CEBs) to revisit and reanalyse the well‐known phenomenon of female kin servants in the British census. We find that the recording of female kin servants points to three distinct possibilities – day servants, domestic work at relatives’ homes, and work at relatives’ homes as part of the family business unit. Accordingly, we argue that female kin servants offer a rare opportunity to look into the interaction between gendered work, household economy, and market economy, and they should be considered as much in the labour force as classic servants. We further offer tentative methods to revise the number of female domestic servants. Our revision suggests that domestic service probably employed more women than manufacturing activities of all sorts put together. It highlights the limited impacts of industrialization on most women's work experiences as well as traditional sector's importance for women's employment, even as late as the mid‐nineteenth century.
Effect of the COVID‐19 pandemic on disease activity in multiple sclerosis patients treated with hematopoietic stem cell transplantation
Authors: Mariottini Alice , Lotti Antonio , Innocenti Chiara , Repice Anna Maria , Nozzoli Chiara , Boncompagni Riccardo , Fainardi Enrico , Saccardi Riccardo , Massacesi Luca
Published: July 2023

Background and purpose

It is still debated whether the COVID‐19 pandemic affected disease activity in people with autoimmune diseases, including multiple sclerosis (MS). The aim of this study, therefore, was to explore the impact of COVID‐19 in people with MS (pwMS) not receiving continuative disease‐modifying therapy (DMT) after previous treatment with autologous hematopoietic stem cell transplantation (AHSCT).

Materials and methods

We included pwMS treated with AHSCT who were in disease remission without receiving DMTs during the pandemic and who were followed up at our centre during the study period. Data on SARS‐CoV‐2 infection and vaccination were recorded, with details of adverse events and clinical‐radiological disease activity.

Results

A total of 36 pwMS (31 females; 86%) were included, of whom 23 (64%) had relapsing‐remitting (RR‐MS) and 13 had secondary progressive MS (SP‐MS). Thirty‐three pwMS (92%) received anti‐SARS‐CoV‐2 mRNA vaccines. Thirteen patients (36%) developed mild to moderate COVID‐19 a median (range) of 58 (4–224) months after AHSCT; seven (54%) of these patients were not yet vaccinated. Transient neurological symptoms after vaccination or infection were reported in 9% and 36% of the patients, respectively. The rate of new inflammatory events (relapses or asymptomatic magnetic resonance imaging [MRI] activity) after AHSCT increased from 0.006 (one asymptomatic new lesion/159 patient‐years) before the pandemic to 0.083 (five relapses plus two cases of asymptomatic MRI activity/84 patient‐years) since the pandemic start (p = 0.004).

Conclusions

People with MS with a history of highly active disease, who are untreated or receiving moderate‐efficacy DMTs might be more vulnerable to disease reactivation, possibly elicited by exogenous triggers. Careful monitoring and further investigation are warranted to ascertain whether special precautions are needed in these cases.
In vitro anti‐trypanosomal activity of synthetic nitrofurantoin‐triazole hybrids against Trypanosoma species causing human African trypanosomosis
Authors: Seetsi Anna , N'da David D. , Molefe‐Nyembe Nthatisi , Suganuma Keisuke , Ramatla Tsepo , Thekisoe Oriel
Published: July 2023

Human African trypanosomosis (HAT) which is also known as sleeping sickness is caused by Trypanosoma brucei gambiense that is endemic in western and central Africa and T. b. rhodesiense that is endemic in eastern and southern Africa. Drugs used for treatment against HAT first stage have limited effectiveness, and the second stage drugs have been reported to be toxic, expensive, and have time‐consuming administration, and parasitic resistance has developed against these drugs. The aim of this study was to evaluate the anti‐trypanosomal activity of nitrofurantoin‐triazole hybrids against T. b. gambiense and T. b. rhodesiense parasites in vitro. This study screened 19 synthesized nitrofurantoin‐triazole (NFT) hybrids on two strains of human trypanosomes, and cytotoxicity was evaluated on Madin‐Darby bovine kidney (MDBK) cells. The findings in this study showed that an increase in the chain length and the number of carbon atoms in some n‐alkyl hybrids influenced the increase in anti‐trypanosomal activity against T. b. gambiense and T. b. rhodesiense. The short‐chain n‐alkyl hybrids showed decreased activity compared to the long‐chain n‐alkyl hybrids, with increased activity against both T. b. gambiense and T. b. rhodesiense. Incorporation of additional electron‐donating substituents in some NFT hybrids showed increased anti‐trypanosomal activity than to electron‐withdrawing substituents in NFT hybrids. All 19 NFT hybrids tested displayed better anti‐trypanosomal activity against T. b. gambiense than T. b. rhodesiense. The NFT hybrid no. 16 was among the best performing hybrids against both T. b. gambiense (0.08 ± 0.04 μM) and T. b.rhodesiense (0.11 ± 0.06 μM), and its activity might be influenced by the introduction of fluorine in the para‐position on the benzyl ring. Remarkably, the NFT hybrids in this study displayed weak to moderate cytotoxicity on MDBK cells. All of the NFT hybrids in this study had selectivity index values ranging from 18 to greater than 915, meaning that they were up to 10–100 times fold selective in their anti‐trypanosomal activity. The synthesized NFT hybrids showed strong selectivity >10 to T. b. gambiense and T. b. rhodesiense, which indicates that they qualify from the initial selection criteria for potential hit drugs.
Greater physiological resistance to heat may favour an invasive freshwater turtle, enabling it to outcompete native species in a changing climate
Authors: Zhang Changyi , Xu Yuxuan , Hua Yijia , Li Peng , Storey Kenneth B. , Zhang Wenyi
Published: July 2023

Climate warming and biological invasion can interact to affect ecosystems, and the results of such interactions depend on whether invaders show physiological advantages in their responses to warming environments as compared with native species after the establishment and local adaptation. However, it has rarely been evaluated.

The present study compared the heat tolerance of a globally invasive turtle, the red‐eared slider Trachemys scripta elegans, and two co‐occurring native turtle species in China, the Chinese soft‐shelled turtle Pelodiscus sinensis and Chinese pond turtle Mauremys reevesii, after acclimation in the same thermal environment. The expression patterns of heat shock factor 1 (HSF1), multiple heat shock proteins (HSPs) and telomere reverse transcriptase (TERT), and changes in relative telomere length (RTL) were then evaluated in liver and muscle of turtles under thermal stress.

The results showed that T. scripta elegans had greater physiological resistance to heat than the co‐occurring native turtle species, and that this higher tolerance was accompanied by a higher temperature induction of the peak expression of inducible HSPs in liver and a higher onset temperature for the main inducible HSPs in muscle. During thermal stress, T. scripta elegans showed a better ability to maintain the expression levels of TERT under extremely hot conditions, whereas high temperatures inhibited TERT in muscles of native turtle species. Meanwhile, thermal stress did not cause telomere erosion in any of the three turtle species and some treatments can lead to slightly longer telomeres in T. scripta elegans or M. reevesii.

Overall, the invasive turtle species showed higher heat tolerance and physiological advantages in enduring hot weather in comparison to the co‐occurring native turtle species. This may favour these invaders in situations of climate warming. Our study highlights the role of physiological adaptations displayed by invaders in achieving advantages over native species under climate change.
Depth‐dependent effects of ericoid mycorrhizal shrubs on soil carbon and nitrogen pools are accentuated under arbuscular mycorrhizal trees
Authors: Ward Elisabeth B. , Polussa Alexander , Bradford Mark A.
Published: July 2023

Plant mycorrhizal associations influence the accumulation and persistence of soil organic matter and could therefore shape ecosystem biogeochemical responses to global changes that are altering forest composition. For instance, arbuscular mycorrhizal (AM) tree dominance is increasing in temperate forests, and ericoid mycorrhizal (ErM) shrubs can respond positively to canopy disturbances. Yet how shifts in the co‐occurrence of trees and shrubs with different mycorrhizal associations will affect soil organic matter pools remains largely unknown. We examine the effects of ErM shrubs on soil carbon and nitrogen stocks and indicators of microbial activity at different depths across gradients of AM versus ectomycorrhizal (EcM) tree dominance in three temperate forest sites. We find that ErM shrubs strongly modulate tree mycorrhizal dominance effects. In surface soils, ErM shrubs increase particulate organic matter accumulation and weaken the positive relationship between soil organic matter stocks and indicators of microbial activity. These effects are strongest under AM trees that lack fungal symbionts that can degrade organic matter. In subsurface soil organic matter pools, by contrast, tree mycorrhizal dominance effects are stronger than those of ErM shrubs. Ectomycorrhizal tree dominance has a negative influence on particulate and mineral‐associated soil organic matter pools, and these effects are stronger for nitrogen than for carbon stocks. Our findings suggest that increasing co‐occurrence of ErM shrubs and AM trees will enhance particulate organic matter accumulation in surface soils by suppressing microbial activity while having little influence on mineral‐associated organic matter in subsurface soils. Our study highlights the importance of considering interactions between co‐occurring plant mycorrhizal types, as well as their depth‐dependent effects, for projecting changes in soil carbon and nitrogen stocks in response to compositional shifts in temperate forests driven by disturbances and global change.
Under what circumstances can the forest sector contribute to 2050 climate change mitigation targets? A study from forest ecosystems to landfill methane emissions for the province of Quebec, Canada
Authors: Moreau Lucas , Thiffault Evelyne , Kurz Werner A. , Beauregard Robert
Published: July 2023

Meeting climate change mitigation targets by 2050, as outlined in international pledges, involves determining optimal strategies for forest management, wood supply, the substitution of greenhouse gas‐intensive materials and energy sources, and wood product disposal. Our study quantified the cumulative mitigation potential by 2050 of the forest sector in the province of Quebec, Canada, using several alternative strategies and assessed under what circumstances the sector could contribute to the targets. We used the Carbon Budget Model of the Canadian Forest Sector to project ecosystems emissions and sequestration of seven alternative and one baseline (business‐as‐usual [BaU]) forest management scenarios over the 2018–2050 period. Three baskets of wood products were used in a Harvested Wood Products model to predict wood product emissions. The mitigation potential was determined by comparing the cumulative CO2e budget of each alternative scenario to the BaU. The proportion of methane emissions from landfills (RCH4%) and the required displacement factor (RDF) to achieve mitigation benefits were assessed both independently and jointly. The fastest and most efficient way to improve mitigation outcomes of the forest sector of Quebec is to reduce end‐of‐life methane emissions from wood products. By reducing methane emissions, the RDF for achieving mitigation benefits through intensification strategies can be reduced from 1.2–2.3 to 0–0.9 tC/tC, thus reaching the current provincial mean DF threshold (0.9). Both a reduction and an increase in the harvested volume have the potential to provide mitigation benefits with adequate RCH4% and RDF. Increased carbon sequestration in ecosystems, innovations in long‐lived wood products, and optimal substitution in markets offer potential avenues for the forest sector to contribute to mitigation benefits but are subject to significant uncertainties. Methane emission reduction at the end of wood product service life is emerging as a valuable approach to enhance mitigation benefits of the forest sector.
Conceptualizing transnational disappearances: Polish missing abroad and the governance of the search
Authors: Matyska Anna
Published: July 2023

Transnational studies emphasize the continuous social presence of transnationally mobile people in their countries of origin. However, some of these individuals will disappear, bringing affective turmoil and uncertainty to the families left behind. Although research has focused on political indifference towards undocumented missing migrants, the effects of other mobility regimes on disappearances remain understudied. I explore patterns of Polish transnational disappearance. Poles as European Union citizens occupy a space of privileged mobility. Yet, I argue, they are also susceptible to disappearance and institutional disregard. I analyse four categories of Polish transnationally missing: temporary migrant workers, settled migrants, truck drivers and tourists. I show that each category carries a specific mobile status and an associated perception of vulnerability and traceability, both of which affect the governance of the search. The stratified reaction to Polish disappearances reflects a global mobility hierarchy and exemplifies the exclusionary practices of transnational governance.
Inorganic Hydrogeochemistry in the 21st Century
Authors: Zhu Chen , Fryar Alan E. , Apps John
Published: July 2023

Chemical and isotopic processes occur in every segment of the hydrological cycle. Hydrogeochemistry—the subdiscipline that studies these processes—has seen a transformation from “witch's brew” to credible science since 2000. Going forward, hydrogeochemical research and applications are critical to meeting urgent societal needs of climate change mitigation and clean energy, such as (1) removing CO2 from the atmosphere and storing gigatons of CO2 in soils and aquifers to achieve net‐zero emissions, (2) securing critical minerals in support of the transition from fossil fuels to renewable energies, and (3) protecting water resources by adapting to a warming climate. In the last two decades, we have seen extensive activity and progress in four research areas of hydrogeochemistry related to water‐rock interactions: arsenic contamination of groundwater; the use of isotopic and chemical tracers to quantify groundwater recharge and submarine groundwater discharge; the kinetics of chemical reactions and the mineral‐water interface's control of contaminant fate and transport; and the transformation of geochemical modeling from an expert‐only exercise to a widely accessible tool. In the future, embracing technological advances in machine learning, cyberinfrastructure, and isotope analytical tools will allow breakthrough research and expand the role of hydrogeochemistry in meeting society's needs for climate change mitigation and the transition from fossil fuels to renewable energies.
The objective and subjective impact of a daily self‐massage on visible signs of stress on the skin and emotional well‐being
Authors: Flament Frederic , Maudet Aurelie , Bayer‐Vanmoen Muriel
Published: July 2023

Introduction

Currently, levels of stress, worry and sadness are increasing worldwide. Considered a part of healthcare, massage is associated with morphological, biological and psychological benefits. Little is known about using daily facial self‐massage to improve skin quality and well‐being.

Objective

To evaluate the impact of a daily self‐massage on the visible signs of stress on facial skin and well‐being in women.

Materials and Methods

This open, prospective, clinical study was conducted in Paris, France. The visible signs of facial ageing were assessed with an objective 10‐point scale and a subjective skin and well‐being assessment with an online self‐questionnaire. Each day for 2 weeks, participants performed a prescribed, 3‐min self‐massage routine at‐home using a lubricant made of botanical oils. The prescribed massage included 14 gestures including stretching, flicking, deep typing, friction and smoothing on the face.

Results

Overall, 50 women, with Fitzpatrick skin type II or III, aged between 40 and 60 years were enrolled. Several statistically significant improvements on skin ageing signs were observed ptosis (p < 0.005, Student's t‐test, −4.9%), fine lines (p < 0.0001 Student's t‐test, −23.8%), plumpness (p < 0.005, Student's t‐test, +4.4%) and radiance (p < 0.0001 Student's t‐test, +16.7%). Subjective benefits were also declared. Most participants (>85%) agreed that their skin looks smoother, more bouncy and fine lines were reduced. Also, 100% of women declare that the massage boosts their feeling of well‐being.

Conclusion

This study showed that facial self‐massage provided significant, visible clinical, and self‐observed skin benefits, and feelings of well‐being.
Immunological mechanisms underlying clinical phenotypes and noninvasive diagnosis of immune checkpoint inhibitor‐induced kidney disease
Authors: Seethapathy Harish , Mistry Kavita , Sise Meghan E.
Published: July 2023

Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer therapy, with over 80 FDA‐approved indications. Used in a variety of settings and in combination with each other and with traditional chemotherapies, the hyperactive immune response induced by ICIs can often lead to immune‐related adverse events in bystander normal tissues such as the kidneys, lungs, and the heart. In the kidneys, this immune‐related adverse event manifests as acute interstitial nephritis (ICI‐AIN). In the era of widespread ICI use, it becomes vital to understand the clinical manifestations of ICI‐AIN and the importance of prompt diagnosis and management of these complications. In this review, we delve into the clinical phenotypes of ICI‐AIN and how they differ from traditional drug‐induced AIN. We also detail what is known about the mechanistic underpinnings of ICI‐AIN and the important diagnostic and therapeutic implications behind harnessing those mechanisms to further our understanding of these events and to formulate effective treatment plans to manage ICI‐AIN.
RETRACTED: Effect of Clindamycin compared with Ampicillin‐Sulbactam as prophylactic antibiotics for wound infections following major surgery for head and neck cancer: A meta‐analysis
Authors: Hu Yue , Yan Aihui , Jiang Feifei
Published: July 2023

A meta‐analysis examination was implemented to review the effect of Clindamycin compared with Ampicillin‐Sulbactam as prophylactic antibiotics (PAs) management for surgical site wound infections (SSWIs) following major surgery (MS) for head and neck cancer (H&NC). A comprehensive literature examination till May 2023 was done and 1296 interrelated examinations were reviewed. The six elected examinations, enclosed 4293 personals with MS for H&NC were in the utilized examinations' starting point, 1722 of them were utilizing Clindamycin, and 2571 were utilizing Ampicillin‐Sulbactam. Odds ratio (OR) and 95% confidence intervals (CIs) were utilized to appraise the consequence of Clindamycin compared with Ampicillin‐Sulbactam as PAs management for SSWIs following MS for H&NC by the dichotomous approach and a fixed or random model. Clindamycin had significantly higher SSWI compared with Ampicillin‐Sulbactam (OR, 2.65; 95% CI, 1.40–5.02, p = 0.003) in personals with MS for H&NC. Clindamycin had significantly higher SSWI compared with Ampicillin‐Sulbactam in personals with MS for H&NC. However, caution needs to be taken when interacting with its values because there was a low sample size of some of the chosen examinations and a low number of examinations found for the comparisons in the meta‐analysis.
Review and perspective on polyhedron model for estimating thermodynamic properties of oxides
Authors: Moosavi‐Khoonsari Elmira , Arias‐Hernandez Jesus Alejandro , Kwon Sun Yong
Published: July 2023

Knowledge of thermodynamics and phase equilibria of oxidic materials is crucial for advancement in the field of ceramics and glass. With the development of computational thermodynamics, predicting phase diagrams and chemical reactions of multicomponent systems has become possible. However, there are still plenty of oxides, the thermodynamic properties of which have not been identified due to the challenges in conducting experiments. Therefore, a key to the advancement in thermodynamic modeling would be to develop a universal model that can be used to estimate the thermodynamic properties of oxides with reliable extrapolation capacity. Atomistic (or molecular) scale models are still insufficient in predicting the thermodynamic properties of oxides at any scale. Alternatively, among group contribution–based methods, the polyhedron model has presented its potential in the estimation of the thermodynamic properties of ionic crystals. However, this model still demands improvements that increase the model's accuracy and extrapolation capacity. In this paper, the background and the state‐of‐the‐art of polyhedron model will be presented together with its strengths and shortcomings. Subsequently, it will be briefly discussed how the field of artificial intelligence could be exploited to devise the next generation of the polyhedron model, the modified polyhedron model.
Understanding the adsorption of calcium sulfate on tetracalcium aluminoferrite and tricalcium aluminate surfaces
Authors: Zhong Haoxuan , Yang Lu , Wang Fazhou
Published: July 2023

Calcium sulfate (CaSO4), an essential retarder in cement, retards the hydration of tricalcium aluminate (C3A) and tetracalcium aluminoferrite (C4AF) phases. However, its retarding mechanism remains unclear. This paper focused on the adsorption of CaSO4f on C4AF and C3A surfaces based on isothermal calorimetry, the measurement of the ionic concentrations in a diluted system, and density functional theory to enhance the understanding of the retardation mechanism. The results showed that the retarding effect of CaSO4 on C4AF was stronger than that on C3A due to the slower CaSO4 consumption rate, lower driving force for CaSO4 adsorption, and surface coverage of Fe(OH)3 gel. The adsorption of CaSO4 hindered Ca dissolution more markedly on C4AF than C3A, which was pronounced on Fe‐free C4AF surfaces. The adsorption of CaSO4 weakened the affinity of water on C4AF and C3A surfaces, lowering the driving force for H2O adsorption. The adsorption of H2O and CaSO4 promoted the dissolution of Al on the [AlO6] octahedral surface of C4AF, which may be responsible for the maintenance of a higher Al concentration in the solution. Based on the above results, the adsorption of CaSO4 on initial C4AF and C3A hydration was explained.
Utility of short‐time electrocardiogram to assess risk for atrial arrhythmia recurrence: Impact of atrial premature beat occurrence 1 day after pulmonary vein isolation for atrial fibrillation
Authors: Yamada Shinya , Kaneshiro Takashi , Nodera Minoru , Amami Kazuaki , Nehashi Takeshi , Horikoshi Yukiko , Yamadera Yukio , Takeishi Yasuchika
Published: July 2023

Introduction

Atrial premature beats (APBs) are the trigger for atrial fibrillation (AF). We sought to investigate the clinical significance of APB occurrence 1 day after pulmonary vein isolation (PVI) for AF using a short‐time electrocardiogram.

Methods

A total of 206 patients undergoing PVI for paroxysmal AF were included. Electrocardiogram recording for 100 consecutive beats was performed 1 day after PVI. The patients were divided into two groups: those with reproducible APBs (≥1 beat) during reassessment (APB group, n = 49) or those without (non‐APB group, n = 157). Late recurrence was defined as atrial tachyarrhythmia recurrence 3–12 months after PVI. The impact of APB occurrence on outcomes was investigated.

Results

Late recurrence occurred in 19 patients (9.2%). The presence of low‐voltage areas, left atrial volume, and recurrence rate were higher in the APB group than in the non‐APB group. In the APB group, the patients with recurrence had lower prematurity index (PI, coupling interval of APB/previous cycle length) compared to those without. Receiver‐operating characteristic analysis revealed PI (<59.3) to be a predictive factor of recurrence (area under the curve: 0.733). The study subjects were then reclassified into three groups according to the absence of APB occurrence (n = 157), presence thereof with PI ≥ 59.3 (n = 33), and presence with PI < 59.3 (n = 16). The multivariate Cox models revealed that APB with PI < 59.3 was an independent predictor for recurrence (hazard ratio, 8.735; p < 0.001).

Conclusion

A short‐time electrocardiogram enables risk assessment for arrhythmia recurrence, and APB with low PI 1 day after PVI is a powerful predictor.
FLRT2 suppresses bladder cancer progression through inducing ferroptosis
Authors: Jiang Pengcheng , Ning Jinzhuo , Yu Weimin , Rao Ting , Ruan Yuan , Cheng Fan
Published: July 2023

Bladder cancer is a common tumour worldwide and exhibits a poor prognosis. Fibronectin leucine rich transmembrane protein 2 (FLRT2) is associated with the regulation of multiple tumours; however, its function in human bladder cancer remain unclear. Herein, we found that FLRT2 level was reduced in human bladder cancer and that higher FLRT2 level predicted lower survival rate. FLRT2 overexpression inhibited, while FLRT2 silence facilitated tumour cell growth, migration and invasion. Mechanistic studies revealed that FLRT2 elevated acyl‐CoA synthetase long‐chain family member 4 (ACSL4) expression, increased lipid peroxidation and subsequently facilitated ferroptosis of human bladder cancer cells. In summary, we demonstrate that FLRT2 elevates ACSL4 expression to facilitate lipid peroxidation and subsequently triggers ferroptosis, thereby inhibiting the malignant phenotype of human bladder cancer cells. Overall, we identify FLRT2 as a tumour suppressor gene.
The role of PKN1 in glioma pathogenesis and the antiglioma effect of raloxifene targeting PKN1
Authors: Hao Yubing , Li Zelin , Zhang Anling , Sun Li , Wang Guangxiu , Wang Hu , Jia Zhifan
Published: July 2023

PKN1 (protein kinase N1), a serine/threonine protein kinase family member, is associated with various cancers. However, the role of PKN1 in gliomas has rarely been studied. We suggest that PKN1 expression in glioma specimens is considerably upregulated and positively correlates with the histopathological grading of gliomas. Knocking down PKN1 expression in glioblastoma (GBM) cells inhibits GBM cell proliferation, invasion and migration and promotes apoptosis. In addition, yes‐associated protein (YAP) expression, an essential effector of the Hippo pathway contributing to the oncogenic role of gliomagenesis, was also downregulated. In contrast, PKN1 upregulation enhances the malignant characteristics of GBM cells and simultaneously upregulates YAP expression. Therefore, PKN1 is a promising therapeutic target for gliomas. Raloxifene (Ralo), a commonly used selective oestrogen‐receptor modulator to treat osteoporosis in postmenopausal women, was predicted to target PKN1 according to the bioinformatics team from the School of Mathematics, Tianjin Nankai University. We showed that Ralo effectively targets PKN1, inhibits GBM cells proliferation and migration and sensitizes GBM cells to the major chemotherapeutic drug, Temozolomide. Ralo also reverses the effect of PKN1 on YAP activation. Thus, we confirm that PKN1 contributes to the pathogenesis of gliomas and may be a potential target for Ralo adjuvant glioma therapy.
MTHFD2 promotes PD‐L1 expression via activation of the JAK/STAT signalling pathway in bladder cancer
Authors: Li Linzhi , Zhang Yunlong , Hu Weimin , Zou Fan , Ning Jinzhuo , Rao Ting , Ruan Yuan , Yu Weimin , Cheng Fan
Published: July 2023

Although combination chemotherapy is widely used for bladder cancer (BC) treatment, the recurrence and progression rates remain high. Therefore, novel therapeutic targets are required. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) contributes to tumourigenesis and immune evasion in several cancers; however, its biological function in BC remains unknown. This study aimed to investigate the expression, prognostic value and protumoural function of MTHFD2 in BC and elucidate the mechanism of programmed death‐ligand 1 (PD‐L1) upregulation by MTHFD2. An analysis using publicly available databases revealed that a high MTHFD2 expression was correlated with clinical features and a poor prognosis in BC. Furthermore, MTHFD2 promoted the growth, migration, invasion and tumourigenicity and decreased the apoptosis of BC cells in vivo and in vitro. The results obtained from databases showed that MTHFD2 expression was correlated with immune infiltration levels, PD‐L1 expression, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. The expression of MTHFD2, PD‐L1 and JAK/STAT signalling pathway‐related proteins increased after interferon gamma treatment and decreased after MTHFD2 knockdown. Moreover, addition of a JAK/STAT pathway activator partially reduced the effect of MTHFD2 knockdown on BC cells. Collectively, our findings suggest that MTHFD2 promotes the expression of PD‐L1 through the JAK/STAT signalling pathway in BC.
Robust increase in glucagon secretion after oral protein intake, but not after glucose or lipid intake in Japanese people without diabetes
Authors: Ichikawa Raishi , Takano Koji , Fujimoto Kazumi , Kobayashi Masaki , Kitamura Tadahiro , Shichiri Masayoshi , Miyatsuka Takeshi
Published: July 2023

Few studies in Asian populations have analyzed how glucagon secretion is affected by ingested glucose, proteins or lipids, individually. To investigate the fluctuations of glucagon secretion after the intake of each of these nutrients, 10 healthy volunteers underwent oral loading tests using each of glucose, proteins and lipids, and blood levels of glucose, insulin and glucagon were measured every 30 min for 120 min. Whereas glucagon secretion was suppressed and minimally affected by oral glucose intake and lipid intake, respectively, oral protein intake robustly increased glucagon secretion, as well as insulin secretion. Further studies are needed to elucidate the mechanism by which protein loading increases glucagon secretion.
Dolichocolon (redundant colon) in a rhesus macaque (Macaca mulatta)
Authors: Celdran‐Bonafonte Diego , O'Connell Kathryn A. , Gothard Katalin M. , Ghaderi Iman , Besselsen David , Doane Cynthia J.
Published: July 2023

Dolichocolon (redundant colon) is an underdiagnosed cause of severe constipation in humans. The clinical presentation reported here in a rhesus macaque closely resembles that of intestinal adenocarcinoma, the most common neoplasia in macaques. Dolichocolon should be considered in differential diagnosis of macaques with anorexia, weight loss, and constipation.
Interprofessional collaboration in telemedicine for long‐term care: An exploratory qualitative study
Authors: Tan Apphia Jia Qi , Chua Wei Ling , McKenna Lisa , Tan Laurence Lean Chin , Lim Yu Jun , Liaw Sok Ying
Published: July 2023

Background

Widespread and sustained adoption of telemedicine in long‐term residential care is emerging. Nursing home (NH) nurses play a key role in collaborating with remote physicians to manage residents' medical conditions through videoconferencing. Therefore, understanding of interprofessional collaboration and effective communication between nurses and physicians is critical to ensure quality of care and safety during teleconsultations.

Aims

To explore NH nurses' and physicians' experiences of interprofessional collaboration and communication during teleconsultations.

Methods

A qualitative descriptive design was adopted. Purposive sampling was conducted to recruit 22 physicians and nurses involved in NH teleconsultations. Semi‐structured online interviews were conducted, and data were thematically analyzed.

Results

Three themes were identified: (1) Manner of communication in telemedicine, (2) sociocultural influences in collaborative practice, and (3) role expectations in telemedicine. Both nurses and physicians recognized the importance of building and maintaining trust as physicians heavily depended on nurses for provision of objective information for clinical decision‐making. However, practice differences were observed between nurses and physicians during teleconsultations. Sociocultural influences such as power relations and language barriers also affected the nurse–physician relationship and interpersonal communication. Additionally, different performance expectations were identified between nurses and physicians.

Conclusion

Interprofessional collaboration in teleconsultations is challenging because of lack of in‐person assessment and dependence on nurses for clinical information. In addition, expectations and communication styles differ among healthcare professionals. This study called for interprofessional telemedicine training with incorporation of shared mental models to improve role clarity and communication. Given the international‐dominated healthcare workforce in long‐term care, the development of cultural competency could also be considered in telemedicine training to enhance nurse–physician collaborative practice.

Clinical Relevance

Telemedicine is increasingly adopted in long‐term care settings, where multidisciplinary healthcare professionals from different health institutions are involved in resident care. Interprofessional collaboration should be incorporated into telehealth education for enhanced clinical practice in this care delivery model.
Characterization of causal agents of bacterial canker on apricot plantations and risk mapping using GIS in Aras Basin (Türkiye)
Authors: Akbaba Mustafa , Hürkan Kaan , Özcan Orkan
Published: July 2023

Bacterial canker of stone fruits caused by Pseudomonas syringae pv. syringae (Pss) and Pseudomonas syringae pv. morsprunorum (Psm race‐1/Psm race‐2) may lead to significant yield and crop losses in apricot (Prunus armeniaca L.) cultivation areas in Türkiye. Strains pathogenic to apricot were isolated from trees with symptoms (mainly necrotized buds and dieback) of bacterial canker in orchards in Aras Basin. Pathogens were characterized using pathogenicity tests, phenotypic assays, end‐point PCR and multilocus sequence analysis (MLSA). Fifteen Pseudomonas syringae strains were isolated from 205 plant samples collected from apricot orchards showing symptoms of bacterial canker. As a consequence of the diagnostic tests, all isolates were identified as P. syringae pv. syringae. In this study, Pss, Psm R1 and Psm R2 strains in stone fruits were separated into different phylogroups (Pg‐2, Pg‐3, sPg‐1b) based on MLSA. Turkish strains obtained from stone fruits, particularly apricot, showed genetic heterogeneity, and clustered in different sub‐phylogroups (sPg‐2b, sPg‐2c, sPg‐2d). All these strains except strain K258 are also clustered in the same sub‐phylogroups (sPg‐2b and sPg‐2d) with other strains from different countries especially Iran, Lebanon, etc. Strain K258 isolated from apricot was clustered in sPg‐2c with Pss strain 642 (USA). The risk of bacterial canker disease in apricot growing areas is considered using GIS in this study. It was determined that a significant part of the Iğdır Plain, the biggest agricultural area in the Aras Basin, is at very high risk.
Proposer and responder conceding in impunity bargaining
Authors: Di Cagno Daniela , Güth Werner , Panaccione Luca , Scarafile Maria Cristina
Published: July 2023

In impunity bargaining with concession, opportunistic proposers would not offer anything nor concede. Opportunistic responders should not accept first offers since second offers could be more generous, for example, due to random trembles. On the contrary, our experimental data, elicited via the strategy vector method, show that participants moderate initial claims and concede, albeit by small amounts. The considerable heterogeneity in behavior suggests that disagreement is unpleasant: participants avoid it by yielding (demanding firstly less than what can be shared) and conceding (lowering first demand). Overall agreement dominates interpersonally (one plays against another) and intrapersonally (as if one plays against oneself).
Staged pallidothalamic tractotomy and pallidotomy for chorea‐acanthocytosis
Authors: Saito Ryo , Horisawa Shiro , Nonaka Taku , Kim Kilsoo , Kawamata Takakazu , Taira Takaomi
Published: July 2023

Chorea‐acanthocytosis (ChAc) is a progressive degenerative disease, which manifests movement disorders including chorea and dystonia. Deep brain stimulation has been reported to successfully improve chorea and dystonia in ChAc. However, there are no reports of lesioning surgery for ChAc. The patient was a 47‐year‐old female with a mutation in VPS13A, which led to the diagnosis of ChAc, presenting with chorea in bilateral hands. The Unified Huntington's Disease Rating Scale‐Motor Score (UHDRS‐MS) was 51. The patient underwent staged bilateral pallidothalamic tractotomy and pallidotomy, which resulted in 60.8% improvement of UHDRS‐MS (20 at 3‐month postoperative evaluation). There was no perioperative complication. No chorea recurrence was observed during the 2‐year postoperative follow‐up period.
Plasticity of colonic enteric nervous system following spinal cord injury in male and female rats
Authors: Werner Claire M. , Willing Lisa B. , Goudsward Hannah J. , McBride Amanda R. , Stella Salvatore L. , Holmes Gregory M.
Published: July 2023

Background

Neurogenic bowel is a dysmotility disorder following spinal cord injury (SCI) that negatively impacts quality of life, social integration, and physical health. Colonic transit is directly modulated by the enteric nervous system. Interstitial Cells of Cajal (ICC) distributed throughout the small intestine and colon serve as specialized pacemaker cells, generating rhythmic electrical slow waves within intestinal smooth muscle, or serve as an interface between smooth muscle cells and enteric motor neurons of the myenteric plexus. Interstitial Cells of Cajal loss has been reported for other preclinical models of dysmotility, and our previous experimental SCI study provided evidence of reduced excitatory and inhibitory enteric neuronal count and smooth muscle neural control.

Methods

Immunohistochemistry for the ICC‐specific marker c‐Kit was utilized to examine neuromuscular remodeling of the distal colon in male and female rats with experimental SCI.

Key Results

Myenteric plexus ICC (ICC‐MP) exhibited increased cell counts 3 days following SCI in male rats, but did not significantly increase in females until 3 weeks after SCI. On average, ICC‐MP total primary arborization length increased significantly in male rats at 3‐day, 3‐week, and 6‐week time points, whereas in females, this increase occurred most frequently at 6 weeks post‐SCI. Conversely, circular muscle ICC (ICC‐CM) did not demonstrate post‐SCI changes.

Conclusions and Inferences

These data demonstrate resiliency of the ICC‐MP in neurogenic bowel following SCI, unlike seen in other related disease states. This plasticity underscores the need to further understand neuromuscular changes driving colonic dysmotility after SCI in order to advance therapeutic targets for neurogenic bowel treatment.
The consequences of limited training in disorders of gut‐brain interaction: Results from a national survey of gastroenterology trainees in the United Kingdom
Authors: Sasegbon Ayodele , Luo Yuying , Keefer Laurie A. , Vasant Dipesh H.
Published: July 2023

Background

Despite their high prevalence and burden, disorders of gut‐brain interaction (DGBI) are undertaught and underrepresented in medical curricula. We evaluated the exposure of UK gastroenterology trainees to DGBI and their comfort managing these conditions.

Methods

An electronic survey was distributed to trainees via UK training program directors. The survey included questions on stage of training; subspecialty interest; access to DGBI training opportunities, and comfort levels with DGBI diagnosis and management. Responses were compared between junior and senior trainees, by subspecialty interest (luminal and non‐luminal), by geographical region, and training program size.

Key Results

One hundred twelve trainees from across the UK participated (21.4% of national training post holders). Exposure to DGBI lectures (32.8% junior vs. 73.3% senior trainees, p = 0.00003) and clinics (9.0% junior vs. 42.2% senior trainees, p = 0.00003), increased with seniority. Regardless of seniority, most trainees were rarely comfortable making a DGBI diagnosis (39.5% senior vs. 33.9% junior trainees, p = 0.69), and were not comfortable initiating neuromodulators (50% senior vs. 25.8% junior trainees, p = 0.08). Trainees without a luminal subspecialty interest (50%) accessed fewer DGBI clinics (p = 0.04), had less communication skills training (p = 0.04) and were less likely to have been observed during DGBI consultations (p = 0.002). Responses were similar across UK regions and did not differ between smaller and larger programs.

Conclusions & Inferences

DGBI training opportunities are limited in UK gastroenterology training across training grades. Most trainees lack confidence with DGBI diagnosis and management. Urgent interventions need to be targeted at all stages of training to ensure DGBI competencies for future gastroenterologists and improve patient outcomes.
Exploring the identity of individual plant cells in space and time
Authors: Oliva Marina , Lister Ryan
Published: July 2023

In recent years, single‐cell genomics, coupled to imaging techniques, have become the state‐of‐the‐art approach for characterising biological systems. In plant sciences, a variety of tissues and species have been profiled, providing an enormous quantity of data on cell identity at an unprecedented resolution, but what biological insights can be gained from such data sets? Using recently published studies in plant sciences, we will highlight how single‐cell technologies have enabled a better comprehension of tissue organisation, cell fate dynamics in development or in response to various stimuli, as well as identifying key transcriptional regulators of cell identity. We discuss the limitations and technical hurdles to overcome, as well as future directions, and the promising use of single‐cell omics to understand, predict, and manipulate plant development and physiology.
Caregiving in academia: Examining educator well‐being and burnout during prolonged stressors
Authors: Bishop Rachael E. , High Andrew C.
Published: July 2023

In the face of prolonged stress, care professionals, including educators, often experience higher rates of burnout and worsened mental well‐being. As school systems across the United States reconsidered their instructional practices in an effort to curtail the spread of COVID‐19, educators have had to navigate a new academic landscape hallmarked by change, stress, burnout, and hopefully resilience. Guided by the theory of resilience and relational load (TRRL), this national study of educators (N = 449; Mage = 41.33 [14.49], 57.2% Female) illuminates the ways in which connectedness with colleagues, support gaps, and stress appraisals shape coping during the pandemic. Specifically, educators who reported higher levels of connection with their colleagues tended to experience enhanced mental well‐being and reduced levels of burnout because they perceived lower levels of stress and greater surpluses in support. Findings deepen our understanding of risk and protective factors contributing to burnout and well‐being within academia, underscore the value of relationships with colleagues, and refine the predictions of the TRRL.