bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of servant leadership and despotic leadership on employees’ happiness at work (HAW): the role of job crafting
Authors: Hamid Zeeshan
Published: May 2024

Purpose

Drawing on the conservation of resources (COR) theory, this study aims to examine the effects of servant leadership and despotic leadership on employees’ happiness at work (HAW) through job crafting.

Design/methodology/approach

To test the hypothesized relationships, the data were collected from 309 Pakistani employees. Structural equation modeling was used to analyze the data.

Findings

The findings showed that servant leadership is an optimal leadership style for creating employees’ HAW. In addition, job crafting was found to mediate the effects of servant leadership on employees’ broad-based positive attitudinal outcome (HAW). Moreover, results showed that despotic leadership negatively influences employees’ HAW through job crafting.

Originality/value

This study is novel as it investigates how newer forms of positive (servant) and negative (despotic) leadership styles influence employees’ multidimensional attitudinal outcome (HAW) via job crafting. By doing so, this research extends the nomological network of servant leadership, despotic leadership, job crafting and HAW.
How compulsive and impulsive buying affect consumer emotional regulation. Is anxiety a differential element?
Authors: Cachón-Rodríguez Gabriel , Blanco-González Alicia , Prado-Román Camilo , Fernández-Portillo Antonio
Published: May 2024

Purpose

Academic literature calls for research on the impact of psychological states derived from mental illness on detrimental consumer behaviour. The purpose of this study is to assess the impact of anxiety on the consumer’s buying processes (compulsive and impulsive) and emotional regulation.

Design/methodology/approach

To carry out the statistical analysis, the data were obtained through an online survey (n = 726) of supermarket consumers. The treatment of the data was using partial least squares structural equation modelling (PLS-SEM).

Findings

The results obtained show that anxiety influences the generation of harmful behaviour, as it has a positive impact on compulsive and impulsive buying. In addition, compulsive and impulsive buying generate higher levels of consumers’ emotional regulation.

Originality/value

This study contributes to the management of anxiety as a priority element to reduce harmful behaviour. Therefore, it provides useful information for marketing managers and professionals in psychological and healthy consumer processes.
Determinants and spatial spillover effects of inbound tourism in Chinese cities
Authors: Li Guangqin , Pu Kangyun
Published: May 2024

Purpose

By using a wide range of macro and micro factors, this paper aims to provide a new assessment of the recent literature on inbound tourism demand models.

Design/methodology/approach

This study examines the determinants and spatial effects of inbound tourism using Hausman–Taylor and spatial econometric models.

Findings

Several important factors were identified, including local economic growth, openness to the outside world, regional size, geographic distance, foreign direct investment, level of innovation and average annual temperature. In addition, the study found strong cross-city competition effects on tourism resource endowment and hotel infrastructure.

Originality/value

Inbound tourism is a crucial link in achieving high-quality economic development. However, previous studies have mainly focused on the analysis of single influencing factors, ignoring the spatial spillover effects of factors.
The implications of handwritten text recognition for accessing the past at scale
Authors: Nockels Joseph , Gooding Paul , Terras Melissa
Published: May 2024

Purpose

This paper focuses on image-to-text manuscript processing through Handwritten Text Recognition (HTR), a Machine Learning (ML) approach enabled by Artificial Intelligence (AI). With HTR now achieving high levels of accuracy, we consider its potential impact on our near-future information environment and knowledge of the past.

Design/methodology/approach

In undertaking a more constructivist analysis, we identified gaps in the current literature through a Grounded Theory Method (GTM). This guided an iterative process of concept mapping through writing sprints in workshop settings. We identified, explored and confirmed themes through group discussion and a further interrogation of relevant literature, until reaching saturation.

Findings

Catalogued as part of our GTM, 120 published texts underpin this paper. We found that HTR facilitates accurate transcription and dataset cleaning, while facilitating access to a variety of historical material. HTR contributes to a virtuous cycle of dataset production and can inform the development of online cataloguing. However, current limitations include dependency on digitisation pipelines, potential archival history omission and entrenchment of bias. We also cite near-future HTR considerations. These include encouraging open access, integrating advanced AI processes and metadata extraction; legal and moral issues surrounding copyright and data ethics; crediting individuals’ transcription contributions and HTR’s environmental costs.

Originality/value

Our research produces a set of best practice recommendations for researchers, data providers and memory institutions, surrounding HTR use. This forms an initial, though not comprehensive, blueprint for directing future HTR research. In pursuing this, the narrative that HTR’s speed and efficiency will simply transform scholarship in archives is deconstructed.
STEM authorship, user-generated reviews and their impact: legitimate or not?
Authors: Hajibayova Lala , McCorkhill Mallory , Bowman Timothy D.
Published: May 2024

Purpose

In this study, STEM resources reviewed in Goodreads were investigated to determine their authorship, linguistic characteristics and impact. The analysis reveals gender disparity favoring titles with male authors.

Design/methodology/approach

This paper applies theoretical concepts of knowledge commons to understand how individuals leverage the affordances of the Goodreads platform to share their perceptions of STEM-related books.

Findings

The analysis reveals gender disparity favoring titles with male authors. Female-authored STEM publications represent popular science nonfiction and juvenile genres. Analysis of the scholarly impact of the reviewed titles revealed that Google Scholar provides broader and more diverse coverage than Web of Science. Linguistic analysis of the reviews revealed the relatively low aesthetic disposition of reviewers with an emphasis on embodied experiences that emerged from the reading.

Originality/value

This study contributes to the understanding of the impact of popular STEM resources as well as the influence of the language of user-generated reviews on production, consumption and discoverability of STEM titles.
Is tax-related information value relevant? Empirical study in the Canadian setting
Authors: Zeng Tao
Published: May 2024

Purpose

This study aims at examining the value relevance of tax-related information in Canada. Tax-related information in this study includes taxable income, tax aggressiveness, and tax risk (i.e., unsustainable tax planning).

Design/methodology/approach

This study analyzes the Canadian listed firms covering the period of 2012–2021 using the Feltham–Ohlson valuation model.

Findings

The findings are: (1) taxable income provides incremental value relevance information; (2) tax risk reduces the value relevance of both taxable income and accounting income and (3) tax aggressiveness reduces the value relevance of accounting income but not of taxable income. Further tests show that the COVID-19 pandemic increases the value relevance of taxable income but decreases the value relevance of accounting income. An analysis of the association between stock price volatility and tax-related information documents that taxable income and accounting income are both informative. Tax risk reduces the informativeness of taxable income, but tax aggressiveness and the pandemic do not.

Research limitations/implications

The sample in this study covers the period up to 2021. Future research could use more recent data. Additionally, this study examines the Canadian setting. The results may not be generalized to other countries that have different accounting and tax rules.

Originality/value

This study sheds light on whether tax aggressiveness and tax risk affect the value relevance of taxable income and accounting income separately. In addition, to our knowledge, this is the first study that examines whether tax-related information is informative about stock price volatility.
Managing employee self-esteem in higher education: impact on individuals, organizations and society
Authors: Gómez-Jorge Fabiola , Díaz-Garrido Eloísa
Published: May 2024

Purpose

Organizations increasingly promote the health and well-being of their employees. There is a growing need for organizations to develop a long-term humanistic approach towards their workforce. This study aims to examine how self-esteem influences the organization, the employee and society within the context of higher education institutions.

Design/methodology/approach

The research has been carried out among the teaching and research staff of a higher education institution in Spain. For this, a structured questionnaire was used. Data analysis was conducted using 272 valid questionnaires. A linear regression analysis was used to examine the relationship between self-esteem and the variables of the model.

Findings

We identified a positive correlation between self-esteem and productivity, job satisfaction and altruism, where significant differences were observed according to gender, age, seniority and professional category of the teaching staff. The results revealed that teachers with high self-esteem are more productive, satisfied and participate in more altruistic activities than their counterparts with low self-esteem.

Originality/value

This study reveals the importance that worker self-esteem has on their behavior in the work environment and in society as a whole, to improve the overall results of the organization. We identified self-esteem as an attribute that improves productivity, job satisfaction and altruism, that can be used to reduce job turnover intention and improve job retention levels, positively affecting the organization. We also contribute to the achievement of some Sustainable Development Goals. This study offers a theoretical contribution by extending the application of social learning theory to the context of self-esteem within higher education institutions.
Experimental and numerical investigations on the thermoforming of 3D-printed polylactic acid parts
Authors: Alexandru Tudor George , Popescu Diana , Constantin Stochioiu , Baciu Florin
Published: May 2024

Purpose

The purpose of this study is to investigate the thermoforming process of 3D-printed parts made from polylactic acid (PLA) and explore its application in producing wrist-hand orthoses. These orthoses were 3D printed flat, heated and molded to fit the patient’s hand. The advantages of such an approach include reduced production time and cost.

Design/methodology/approach

The study used both experimental and numerical methods to analyze the thermoforming process of PLA parts. Thermal and mechanical characteristics were determined at different temperatures and infill densities. An equivalent material model that considers infill within a print is proposed. Its practical use was proven using a coupled finite-element analysis model. The simulation strategy enabled a comparative analysis of the thermoforming behavior of orthoses with two designs by considering the combined impact of natural convection cooling and imposed structural loads.

Findings

The experimental results indicated that at 27°C and 35°C, the tensile specimens exhibited brittle failure irrespective of the infill density, whereas ductile behavior was observed at 45°C, 50°C and 55°C. The thermal conductivity of the material was found to be linearly related to the temperature of the specimen. Orthoses with circular open pockets required more time to complete the thermoforming process than those with hexagonal pockets. Hexagonal cutouts have a lower peak stress owing to the reduced reaction forces, resulting in a smoother thermoforming process.

Originality/value

This study contributes to the existing literature by specifically focusing on the thermoforming process of 3D-printed parts made from PLA. Experimental tests were conducted to gather thermal and mechanical data on specimens with two infill densities, and a finite-element model was developed to address the thermoforming process. These findings were applied to a comparative analysis of 3D-printed thermoformed wrist-hand orthoses that included open pockets with different designs, demonstrating the practical implications of this study’s outcomes.
‘Normality in all the abnormality’—Older adults' experiences of holidays and celebrations from the COVID‐19 pandemic
Authors: Granbom Marianne , Jonsson Oskar , Carlsson Gunilla , Fristedt Sofi , Stormstege Elin , Martinsson Elvira , Kylén Maya
Published: May 2024

Introduction

The importance of holidays, traditions, and family celebrations to human culture and occupational engagement has been neglected. The aim of this study was to explore how older adults experienced holidays and celebrations with social and physical distancing during the COVID‐19 pandemic.

Methods

A secondary analysis was made on data from the At‐Risk Study. Seventeen community‐living adults (11 women and 6 men) aged 71–87 years, from Sweden participated. They were interviewed remotely four times during the first year of the pandemic. Data were analysed with qualitative content analysis. No consumer/community involvement occurred.

Findings

Three categories on how the participants hoped for, planned, decided, adapted, avoided, and experienced holidays and celebrations with social and physical distancing included expectations and preparations in unpredictable times; the constant need for re‐evaluation; and almost everything turned out differently.

Conclusions

The desire to celebrate despite pandemic restrictions shows the importance and meaning holidays hold for older adults. Celebrations can be disrupted for many reasons, not only as extreme as the ongoing pandemic. For wellbeing in later life health care, social care, and society need to understand the inherent components and acknowledge ways of supporting participation in occasional events such as holidays, traditions, and family celebrations.
Exerkine FNDC5/irisin‐enriched exosomes promote proliferation and inhibit ferroptosis of osteoblasts through interaction with Caveolin‐1
Authors: Tao Lin , Wang Jinpeng , Wang Ke , Liu Qichang , Li Hongyang , Xu Site , Gu Chunjian , Zhu Yue
Published: May 2024

Postmenopausal osteoporosis is a prevalent metabolic bone disorder characterized by a decrease in bone mineral density and deterioration of bone microstructure. Despite the high prevalence of this disease, no effective treatment for osteoporosis has been developed. Exercise has long been considered a potent anabolic factor that promotes bone mass via upregulation of myokines secreted by skeletal muscle, exerting long‐term osteoprotective effects and few side effects. Irisin was recently identified as a novel myokine that is significantly upregulated by exercise and could increase bone mass. However, the mechanisms underlying exercise‐induced muscle‐bone crosstalk remain unclear. Here, we identified that polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) are increased in skeletal muscles following a 10‐week treadmill exercise programme, which then promotes the expression and release of FNDC5/irisin. In osteoblasts, irisin binds directly to Cav1, which recruits and interacts with AMP‐activated protein kinase α (AMPKα) to activate the AMPK pathway. Nrf2 is the downstream target of the AMPK pathway and increases the transcription of HMOX1 and Fpn. HMOX1 is involved in regulating the cell cycle and promotes the proliferation of osteoblasts. Moreover, upregulation of Fpn in osteoblasts enhanced iron removal, thereby suppressing ferroptosis in osteoblasts. Additionally, we confirmed that myotube‐derived exosomes are involved in the transportation of irisin and enter osteoblasts through caveolae‐mediated endocytosis. In conclusion, our findings highlight the crucial role of irisin, present in myotube‐derived exosomes, as a crucial regulator of exercise‐induced protective effects on bone, which provides novel insights into the mechanisms underlying exercise‐dependent treatment of osteoporosis.
Influence of running on incidental and integral vitality and fatigue: An intensive longitudinal intervention in young Women's daily life
Authors: Buchner Laura , Moore Stephanie R. , Finkenzeller Thomas , Amesberger Günter , Rieser Harald , Würth Sabine
Published: May 2024

Exercise intensity and perceived autonomy are important factors for the affective response toward exercise and adherence. Dual‐mode theory suggests an inverted‐J response curve of affect with increased exercise intensity, but little is known about how different running programs affect the affective response and subsequent incidental affect in daily life. This ambulatory assessment study examines the short‐ to long‐term effects of two 8‐week running interventions (affect‐based vs. polarized‐prescribed) on subjective vitality and perceived fatigue in young female novices. Participants engaged in 3 × 30 minute running sessions weekly in their natural environments and completed electronic diaries three times daily. Autoregressive multilevel models indicate small effects of training intensity on immediate affective subjective vitality (ß = ‐2.37; p = .03; f2 = 0.02) but negligible non‐significant effects on fatigue (ß = 0.26; p = 0.12; f2 = 0.002). Novices experienced increased vitality throughout the day when their running was evaluated positively (ß = 0.23; p = .03; f2 = 0.04), with effects lasting over two days before returning to baseline (ß = ‐0.26; p < .001; f2 = 0.004). However, no significant long‐term effects were observed over 8 weeks in vitality or fatigue. Results indicate between‐ and within‐person variations, but limited sample power does not allow differentiating between programs. This study supports the dual‐mode theory and highlights the importance of distinguishing affective response from incidental affect.
Totally retroperitoneal approach for robot‐assisted nephroureterectomy with bladder cuff without repositioning
Authors: Hattori Yuto , Yamamoto Akihiro , Nagoshi Akihiko , Fujiwara Tasuku , Kambe Takanari , Igarashi Atsushi , Akagi Naoki , Shibasaki Noboru , Kawakita Mutsushi , Yamasaki Toshinari
Published: May 2024

Introduction

Robot‐assisted nephroureterectomy (RANU) for upper urinary tract urothelial carcinoma is typically performed via the transperitoneal approach because of limited surgical space. However, a retroperitoneal approach may be preferable in patients with a history of abdominal surgery or in those in whom pelvic lymph node dissection is unnecessary.

Materials and Surgical Techniques

RANU via the retroperitoneal approach was selected for two patients diagnosed with high‐grade upper urothelial carcinoma with a history of abdominal surgery. Nephrectomy was performed in the 90° flank position, and the bed was tilted at 20°. The retroperitoneal space was extended, and the robot trocar was subsequently repositioned in the left lower quadrant. After redocking the robot, the distal ureter was dissected, and the bladder cuff was resected en bloc along with the kidney and the ureter. Neither patient had any complications within 3 months postoperatively.

Discussion

By devising a new technique for trocar placement, total retroperitoneal RANU without repositioning was possible, even in a small patient.
Stocking and supplying naloxone: Findings from a representative sample of community pharmacies in Victoria, Australia
Authors: Karthikeyan Nandini , Xia Ting , Nielsen Suzanne , Picco Louisa
Published: May 2024

Introduction

Naloxone is an opioid receptor antagonist, which can rapidly reverse the effects of an opioid overdose. Community pharmacists may experience several barriers to stocking and supplying naloxone including a lack of confidence or knowledge and time constraints. The current study aimed to examine the extent to which Victorian community pharmacies stock and supply naloxone and determine specific characteristics associated with stocking naloxone.

Methods

A representative sample of community pharmacists (n = 558) in Victoria, Australia, were contacted between October and November 2020 and invited to participate in an online survey. Data related to pharmacy‐ and pharmacist‐related characteristics, including stocking and frequency of supplying naloxone in the past year. Multivariate logistic regression analysis was performed to examine the effect of various covariates on stocking naloxone.

Results

The sample comprised 265 pharmacists (response rate 47%). Most pharmacies were located in Melbourne (the capital city of Victoria, 59.6%) and were part of a pharmacy chain (61.5%). In total, 100 (38%) pharmacies stocked naloxone, a third of whom did not supply it in the past year. Pharmacies that provided opioid agonist treatment had 2.4 times higher odds of stocking naloxone (95% confidence interval 1.425–4.136; p = 0.001).

Discussion and Conclusion

Less than half of Victorian community pharmacies stock naloxone, with even fewer actually supplying it in the past year. Future efforts are needed to increase the number of pharmacies that stock naloxone and the frequency in which it is supplied, while also addressing possible barriers to stocking and supplying naloxone among community pharmacists.
Shifting boundaries, dismantling brick walls: Feminist knowledge in the struggles to transform economic thinking and policy
Authors: Lamberg Emma
Published: May 2024

This article contributes to ongoing debates on the politics of feminist knowledge transfer by considering how feminist professionals advocate transformative economic thinking and policies. I draw on interviews with an under‐researched group—feminist professionals with specialized knowledge about the economy—to argue that feminist economic experts' transformative politics is shaped by highly contextual efforts to lend credibility to feminist alternatives to conventional economic knowledge and policy. Combining feminist scholarship on scientific boundary‐work with theorizing on resistance to feminist institutional transformation, the article analyzes the practices that feminist experts use to reframe their knowledge claims to get their messages through to decision‐makers. I suggest that although feminist boundary‐work is likely to come up against ‘brick walls’ of institutional resistance, it can dismantle such walls by gradually shifting the boundaries of legitimate economic knowledge and policies.
Comparing QUBO models for quantum annealing: integer encodings for permutation problems
Authors: Codognet Philippe
Published: May 2024

QUBO (quadratic unconstrained binary optimization) has become the modeling language for quantum annealing and quantum‐inspired annealing solvers. We present different approaches in QUBO for the magic square problem and the quadratic assignment problem (QAP), which can be modeled by linear equations and a permutation constraint over integer variables. Different ways of encoding integers by Booleans in QUBO amount to models, the implementation of which could have very different performance. Experiments performed on the Fixstars Amplify Annealer Engine, a quantum‐inspired annealing solver, show that, compared to the classical one‐hot encoding, using unary encoding for integers performs slightly better for the QAP and much better for magic square.
Common anesthetic used in preclinical PET imaging inhibits metabolism of the PET tracer [18F]3F4AP
Authors: Ramos‐Torres Karla , Sun Yang , Takahashi Kazue , Zhou Yu‐Peng , Brugarolas Pedro
Published: May 2024

Positron emission tomography (PET) imaging studies in laboratory animals are almost always performed under isoflurane anesthesia to ensure that the subject stays still during the image acquisition. Isoflurane is effective, safe, and easy to use, and it is generally assumed to not have an impact on the imaging results. Motivated by marked differences observed in the brain uptake and metabolism of the PET tracer 3‐[18F]fluoro‐4‐aminopyridine [(18F]3F4AP) between human and nonhuman primate studies, this study investigates the possible effect of isoflurane on this process. Mice received [18F]3F4AP injection while awake or under anesthesia and the tracer brain uptake and metabolism was compared between groups. A separate group of mice received the known cytochrome P450 2E1 inhibitor disulfiram prior to tracer administration. Isoflurane was found to largely abolish tracer metabolism in mice (74.8 ± 1.6 vs. 17.7 ± 1.7% plasma parent fraction, % PF) resulting in a 4.0‐fold higher brain uptake in anesthetized mice at 35 min post‐radiotracer administration. Similar to anesthetized mice, animals that received disulfiram showed reduced metabolism (50.0 ± 6.9% PF) and a 2.2‐fold higher brain signal than control mice. The higher brain uptake and lower metabolism of [18F]3F4AP observed in anesthetized mice compared to awake mice are attributed to isoflurane's interference in the CYP2E1‐mediated breakdown of the tracer, which was confirmed by reproducing the effect upon treatment with the known CYP2E1 inhibitor disulfiram. These findings underscore the critical need to examine the effect of isoflurane in PET imaging studies before translating tracers to humans that will be scanned without anesthesia.

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Losing privacy versus losing choice: How consumers react to different costs of personalization
Authors: Moran Nora
Published: May 2024

This research investigates whether consumers anticipate any negative financial consequences arising from personalization practices, and examines how individuals respond to messages about its financial welfare implications, to see what factors increase blame toward firms for the impact their tactics can have on vulnerable populations. Results from a pilot study show that while privacy risks of personalization are highly accessible, few consider its potential to influence spending behavior. In addition, experimental studies reveal that individuals are more likely to blame firms for increases in teen consumer spending when they learn how online tactics limit and determine consumer choices, compared with when messages focus on firm's use of personal information. Additional studies also introduce a moderator for this effect. Overall, this research highlights limitations in consumers' ability to consider consequences of personalization, and provides guidance for advocates on how to better educate the public about potential issues associated with online marketing tactics.
Parkinson's disease – The dentist's role as part of the healthcare team
Authors: Camacho Liliana Ortiz , Jahangiri Leila , Iseringhausen Jenna , Goldstein Gary R.
Published: May 2024

Parkinson's disease is a neurodegenerative disease that results in patients exhibiting uncontrolled movements, changes in saliva production, and difficulty in swallowing and speech. Understanding the staging of the disease and the available therapies allows dentists to treat these patients safely and with compassion to meet their oral health care needs for an optimal quality of life. This appraisal discusses Parkinson's disease as it relates to clinically relevant facts to manage and treat the oral health care needs of these patients in the short and long term including general dental care recommendations. Important observations related to Parkinson's disease include disease causation,; stages, pharmacologic treatment, the effects on saliva, mastication, dysphagia, and aspiration pneumonia. Dental recommendations are made for the dentate, the partially edentulous, and the completely edentulous Parkinson's patients with a focus on late‐stage concerns. Optimizing dental health will help maintain the quality of life as the disease progresses. In late stages of Parkinson's disease, dental treatment should focus on keeping the patient comfortable and out of pain.  While benign neglect is an often‐used term, compassionate therapy in the late stages of Parkinson's disease is a more compelling term for defining the patient's needs.  Since dysphagia in Parkinson's patients has been underdiagnosed, neurologists must be aware of the important part that dentists play in the early diagnosis for these patients.  Early referral to a dentist is vital to mitigate the unfortunate consequence of the need for extensive dental care in late‐stage patients.
Long‐term effects of elevated CO2 on the nutrition provided to parasitoids by their herbivorous hosts
Authors: Najar‐Rodriguez Adriana Jeannette , Lacorazza Sara , Klaiber Jeannine , Avila Gonzalo Andres , Zhang Jinping , Ma Chun‐Sen , Ma Gang
Published: May 2024

Elevated concentrations of atmospheric carbon dioxide (CO2), a consequence of anthropogenic global change, may profoundly interfere with natural ecological processes, perhaps even interactions across trophic levels. Even the survival prospects of organisms at higher trophic levels could be affected, as follows. We showed previously that the endoparasitoid Diaeretiella rapae, a specialized parasitoid of the cabbage aphid Brevicoryne brassicae, exposed to elevated CO2 concentrations (800 ppm) for up to 10 weeks, performed far worse (e.g., lower survival and parasitism rates) compared with ambient CO2 (400 ppm). To investigate whether these CO2‐related effects in the parasitoids were mediated by changes in the quality of the aphids as hosts, we measured the nutritional and energy content of cabbage aphids under the above conditions. Specifically, we measured lipid, protein and water‐soluble carbohydrate concentrations. We tested the hypothesis that when insects feed from plants with altered nutritional content, they incur a cost in dealing with such biotic stresses. That cost reduces their metabolic well‐being and, thus, reduces their nutritional status with respect to parasitoids developing at their expense. We found that CO2 had significant effects on aphid body mass (i.e., wet weight) and chemical composition, with elevated CO2 concentrations reducing aphid mass by more than 50%. Aphids grown under elevated CO2 also had significantly reduced soluble carbohydrates but significantly more lipids, on a weight‐per‐weight basis, than aphids grown under ambient CO2. A significant decrease in total energy reserves (i.e., the sum of total proteins, lipids, and water‐soluble carbohydrates) thus typified aphids grown under elevated CO2. Our results contribute to explaining the impaired performance of the aphid B. brassicae and its parasitoid D. rapae previously reported under elevated CO2, and provide evidence that under future climate change, host plants might affect the development and performance of parasitoids through their impacts on the nutritional quality of their herbivorous hosts.
From primary HPV infection to carcinoma in situ: A mathematical approach to cervical intraepithelial neoplasia
Authors: Bitsouni Vasiliki , Gialelis Nikolaos , Stratis Ioannis G. , Tsilidis Vasilis
Published: May 2024

Cervical intraepithelial neoplasia (CIN) is the development of abnormal cells on the surface of the cervix, caused by a human papillomavirus (HPV) infection. Although in most of the cases it is resolved by the immune system, a small percentage of people might develop a more serious CIN which, if left untreated, can develop into cervical cancer. Cervical cancer is the fourth most common cancer in women globally, for which the World Health Organization (WHO) recently adopted the Global Strategy for cervical cancer elimination by 2030. With this research topic being more imperative than ever, in this paper, we develop a nonlinear mathematical model describing the CIN progression. The model consists of partial differential equations describing the dynamics of epithelial, dysplastic, and immune cells, as well as the dynamics of viral particles. We use our model to explore numerically three important factors of dysplasia progression, namely, the geometry of the cervix, the strength of the immune response, and the frequency of viral exposure.
TRPV3 activation by different agonists accompanied by lipid dissociation from the vanilloid site
Authors: Nadezhdin Kirill D. , Neuberger Arthur , Khosrof Lena S. , Talyzina Irina A. , Khau Jeffrey , Yelshanskaya Maria V. , Sobolevsky Alexander I.
Published: May 2024

TRPV3 represents both temperature- and ligand-activated transient receptor potential (TRP) channel. Physiologically relevant opening of TRPV3 channels by heat has been captured structurally, while opening by agonists has only been observed in structures of mutant channels. Here, we present cryo-EM structures that illuminate opening and inactivation of wild-type human TRPV3 in response to binding of two types of agonists: either the natural cannabinoid tetrahydrocannabivarin (THCV) or synthetic agonist 2-aminoethoxydiphenylborane (2-APB). We found that THCV binds to the vanilloid site, while 2-APB binds to the S1-S4 base and ARD-TMD linker sites. Despite binding to distally located sites, both agonists induce similar pore opening and cause dissociation of a lipid that occupies the vanilloid site in their absence. Our results uncover different but converging allosteric pathways through which small-molecule agonists activate TRPV3 and provide a framework for drug design and understanding the role of lipids in ion channel function.
Dehydrogenative synthesis of
N
-functionalized 2-aminophenols from cyclohexanones and amines: Molecular complexities via one-shot assembly
Authors: Xu Biping , Liu Xiaojie , Deng Lei , Shang Yaping , Jie Xiaoming , Su Weiping
Published: May 2024

Polyfunctionalized arenes are privileged structural motifs in both academic and industrial chemistry. Conventional methods for accessing this class of chemicals usually involve stepwise modification of phenyl rings, often necessitating expensive noble metal catalysts and suffering from low reactivity and selectivity when introducing multiple functionalities. We herein report dehydrogenative synthesis of
N
-functionalized 2-aminophenols from cyclohexanones and amines. The developed reaction system enables incorporating amino and hydroxyl groups into aromatic rings in a one-shot fashion, which simplifies polyfunctionalized 2-aminophenol synthesis by circumventing issues associated with traditional arene modifications. The wide substrate scope and excellent functional group tolerance are exemplified by late-stage modification of complex natural products and pharmaceuticals that are unattainable by existing methods. This dehydrogenative protocol benefits from using 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) as oxidant that offers interesting chemo- and regio-selective oxidation processes. More notably, the essential role of in situ generated water is disclosed, which protects aliphatic amine moieties from overoxidation via hydrogen bond–enabled interaction.
Electronic health record signatures identify undiagnosed patients with common variable immunodeficiency disease
Authors: Johnson Ruth , Stephens Alexis V. , Mester Rachel , Knyazev Sergey , Kohn Lisa A. , Freund Malika K. , Bondhus Leroy , Hill Brian L. , Schwarz Tommer , Zaitlen Noah , Arboleda Valerie A. , A. Bastarache Lisa , Pasaniuc Bogdan , Butte Manish J.
Published: May 2024

Human inborn errors of immunity include rare disorders entailing functional and quantitative antibody deficiencies due to impaired B cells called the common variable immunodeficiency (CVID) phenotype. Patients with CVID face delayed diagnoses and treatments for 5 to 15 years after symptom onset because the disorders are rare (prevalence of ~1/25,000), and there is extensive heterogeneity in CVID phenotypes, ranging from infections to autoimmunity to inflammatory conditions, overlapping with other more common disorders. The prolonged diagnostic odyssey drives excessive system-wide costs before diagnosis. Because there is no single causal mechanism, there are no genetic tests to definitively diagnose CVID. Here, we present PheNet, a machine learning algorithm that identifies patients with CVID from their electronic health records (EHRs). PheNet learns phenotypic patterns from verified CVID cases and uses this knowledge to rank patients by likelihood of having CVID. PheNet could have diagnosed more than half of our patients with CVID 1 or more years earlier than they had been diagnosed. When applied to a large EHR dataset, followed by blinded chart review of the top 100 patients ranked by PheNet, we found that 74% were highly probable to have CVID. We externally validated PheNet using >6 million records from disparate medical systems in California and Tennessee. As artificial intelligence and machine learning make their way into health care, we show that algorithms such as PheNet can offer clinical benefits by expediting the diagnosis of rare diseases.
Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome
Authors: Consiglieri Giulia , Tucci Francesca , De Pellegrin Maurizio , Guerrini Barbara , Cattoni Alessandro , Risca Giulia , Scarparo Stefano , Sarzana Marina , Pontesilli Silvia , Mellone Renata , Gasperini Serena , Galimberti Stefania , Silvani Paolo , Filisetti Chiara , Darin Silvia , Forni Giulia , Miglietta Simona , Santi Ludovica , Facchini Marcella , Corti Ambra , Fumagalli Francesca , Cicalese Maria Pia , Calbi Valeria , Migliavacca Maddalena , Barzaghi Federica , Ferrua Francesca , Gallo Vera , Recupero Salvatore , Canarutto Daniele , Doglio Matteo , Tedesco Lucia , Volpi Nicola , Rovelli Attilio , la Marca Giancarlo , Valsecchi Maria Grazia , Zancan Stefano , Ciceri Fabio , Naldini Luigi , Baldoli Cristina , Parini Rossella , Gentner Bernhard , Aiuti Alessandro , Bernardo Maria Ester
Published: May 2024

Mucopolysaccharidosis type I Hurler (MPSIH) is characterized by severe and progressive skeletal dysplasia that is not fully addressed by allogeneic hematopoietic stem cell transplantation (HSCT). Autologous hematopoietic stem progenitor cell–gene therapy (HSPC-GT) provides superior metabolic correction in patients with MPSIH compared with HSCT; however, its ability to affect skeletal manifestations is unknown. Eight patients with MPSIH (mean age at treatment: 1.9 years) received lentiviral-based HSPC-GT in a phase 1/2 clinical trial (NCT03488394). Clinical (growth, measures of kyphosis and genu velgum), functional (motor function, joint range of motion), and radiological [acetabular index (AI), migration percentage (MP) in hip x-rays and MRIs and spine MRI score] parameters of skeletal dysplasia were evaluated at baseline and multiple time points up to 4 years after treatment. Specific skeletal measures were retrospectively compared with an external cohort of HSCT-treated patients. At a median follow-up of 3.78 years after HSPC-GT, all patients treated with HSPC-GT exhibited longitudinal growth within WHO reference ranges and a median height gain greater than that observed in patients treated with HSCT after 3-year follow-up. Patients receiving HSPC-GT experienced complete and earlier normalization of joint mobility compared with patients treated with HSCT. Mean AI and MP showed progressive decreases after HSPC-GT, suggesting a reduction in acetabular dysplasia. Typical spine alterations measured through a spine MRI score stabilized after HSPC-GT. Clinical, functional, and radiological measures suggested an early beneficial effect of HSPC-GT on MPSIH-typical skeletal features. Longer follow-up is needed to draw definitive conclusions on HSPC-GT’s impact on MPSIH skeletal dysplasia.
Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness
Authors: Edlow Brian L. , Olchanyi Mark , Freeman Holly J. , Li Jian , Maffei Chiara , Snider Samuel B. , Zöllei Lilla , Iglesias J. Eugenio , Augustinack Jean , Bodien Yelena G. , Haynes Robin L. , Greve Douglas N. , Diamond Bram R. , Stevens Allison , Giacino Joseph T. , Destrieux Christophe , van der Kouwe Andre , Brown Emery N. , Folkerth Rebecca D. , Fischl Bruce , Kinney Hannah C.
Published: May 2024

Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness in the human brain, but knowledge about the subcortical networks that sustain arousal in humans is incomplete. Here, we aimed to map the connectivity of a proposed subcortical arousal network that sustains wakefulness in the human brain, analogous to the cortical default mode network (DMN) that has been shown to contribute to awareness. We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) of three human brains, obtained at autopsy from neurologically normal individuals, with immunohistochemical staining of subcortical brain sections. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. Deterministic and probabilistic tractography analyses of the ex vivo diffusion MRI data revealed projection, association, and commissural pathways linking dAAN nodes with one another and with DMN nodes. Complementary analyses of in vivo 7-tesla resting-state functional MRI data from the Human Connectome Project identified the dopaminergic ventral tegmental area in the midbrain as a widely connected hub node at the nexus of the subcortical arousal and cortical awareness networks. Our network-based autopsy methods and connectivity data provide a putative neuroanatomic architecture for the integration of arousal and awareness in human consciousness.
Vaccination for healthy aging
Authors: Bloom David E. , Pecetta Simone , Scorza Francesco Berlanda , Carfi Andrea , Carleton Bruce , Cipriano Mariateresa , Edwards Kathryn , Gasperini Gianmarco , Malley Richard , Nandi Arindam , Nguyen Aurelia , Stuart Lynda , Black Steve , Rappuoli Rino
Published: May 2024

As the world’s population grows older, vaccination is becoming a key strategy for promoting healthy aging. Despite scientific progress in adult vaccine development, obstacles such as immunosenescence and vaccine hesitancy remain. To unlock the potential of adult vaccines fully, we must enhance immunization programs, dispel misinformation, and invest in research that deepens our understanding of aging and immunity.
Insights into the activity of cefiderocol against PER-2 producing Enterobacterales
Authors: Ruggiero Melina , Briceño Muñoz Ivan , Gutkind Gabriel , Hujer Andrea M. , Bonomo Robert A. , Power Pablo
Published: May 2024

The PER-2 β-lactamase is a unique class A enzyme conferring broad spectrum cephalosporin resistance. In this study, we explored the stability of cefiderocol (FDC) against PER-2 β-lactamase to gain insights into structure activity relationships (SAR) of this synthetic siderophore-conjugated antibiotic. Herein, we show that the MICs of FDC for PER-2 producing isolates and transformants ranged between 0.125 and 64 µg/mL; diazabicyclooctanes (DBOs) reduced the MIC values. In PER-2 mutants, MIC values decreased up to 10–12 dilutions in agreement with previous observations especially in the case of Arg220 substitutions. Catalytic efficiency for PER-2 was 0.072 µM
−1
s
−1
, comparable with PER-1 (0.046 µM
−1
s
−1
) and NDM-1 (0.067 µM
−1
s
−1
).
In silico
models revealed that FDC within the active site of PER-2 demonstrates unique interactions as a result of the inverted Ω loop fold and extension of the β3-β4 connecting loop.
Pharmacological activation of TLR7 exerts inhibition on the replication of EV-D68 in respiratory cells
Authors: Li Huili , Huang Yuehan , Yang Qingran , Zhang Zhe , Shen Siyu , Guo Haoran , Wei Wei
Published: May 2024

The globally reemerging respiratory pathogen enterovirus D68 (EV-D68) is implicated in outbreaks of severe respiratory illness and associated with acute flaccid myelitis. However, there remains a lack of effective treatments for EV-D68 infection. In this work, we found that the host Toll-like receptor 7 (TLR7) proteins, which function as powerful innate immune sensors, were selectively elevated in expression in response to EV-D68 infection. Subsequently, we investigated the impact of Vesatolimod (GS-9620), a Toll-like receptor 7 agonist, on EV-D68 replication. Our findings revealed that EV-D68 infection resulted in increased mRNA levels of TLR7. Treatment with Vesatolimod significantly inhibited EV-D68 replication [half maximal effective concentration (EC
50
) = 0.1427 µM] without inducing significant cytotoxicity at virucidal concentrations. Although Vesatolimod exhibited limited impact on EV-D68 attachment, it suppressed RNA replication and viral protein synthesis after virus entry. Vesatolimod broadly inhibited the replication of circulating isolated strains of EV-D68. Furthermore, our findings demonstrated that treatment with Vesatolimod conferred resistance to both respiratory and neural cells against EV-D68 infection. Overall, these results present a promising strategy for drug development by pharmacologically activating TLR7 to initiate an antiviral state in EV-D68-infected cells selectively.

IMPORTANCE

Conventional strategies for antiviral drug development primarily focus on directly targeting viral proteases or key components, as well as host proteins involved in viral replication. In this study, based on our intriguing discovery that enterovirus D68 (EV-D68) infection specifically upregulates the expression of immune sensor Toll-like receptor 7 (TLR7) protein, which is either absent or expressed at low levels in respiratory cells, we propose a potential antiviral approach utilizing TLR7 agonists to activate EV-D68-infected cells into an anti-viral defense state. Notably, our findings demonstrate that pharmacological activation of TLR7 effectively suppresses EV-D68 replication in respiratory tract cells through a TLR7/MyD88-dependent mechanism. This study not only presents a promising drug candidate and target against EV-D68 dissemination but also highlights the potential to exploit unique alterations in cellular innate immune responses induced by viral infections, selectively inducing a defensive state in infected cells while safeguarding uninfected normal cells from potential adverse effects associated with therapeutic interventions.