bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Metformin for Idiopathic Intracranial Hypertension. A U.S-Based Real-World Data Retrospective Multicenter Cohort Study
Authors: Azzam Ahmed Y. , Nassar Mahmoud , Al Zomia Ahmed Saad , Elswedy Adam , Morsy Mahmoud M. , Mohamed Adham A. , Elamin Osman , Elsayed Omar S. , Azab Mohammed A. , Essibayi Muhammed Amir , Wu Jin , Dmytirw Adam A. , Altschul David J.
Published: September 2024

Introduction

Idiopathic intracranial hypertension (IIH) remains a challenging condition to manage, with limited therapeutic options. This study investigated the potential of metformin as a novel treatment for IIH, exploring its effects on disease outcomes and safety profile.

Methods

We conducted a retrospective cohort study using the TriNetX database, analyzing data from 2009 to August 2024. Patients diagnosed with IIH were included, with exclusions for other causes of elevated intracranial pressure and pre-existing diabetes. Propensity score matching was employed to balance cohorts according to age, sex, race, ethnicity, Hemoglobin A1C, and baseline body mass index (BMI) at the time of metformin initiation. Outcomes were assessed at various follow-up points up to 24 months.

Results

Our study initially comprised 1,268 patients in the metformin group and 49,262 in the control group, with notable disparities in several parameters. Post-matching, both cohorts were refined to 1,267 patients each after matching with metformin group. Metformin-treated patients showed significantly lower risks of papilledema, headache, and refractory IIH status at all follow-up points (p<0.0001). The metformin group also had reduced rates of therapeutic spinal punctures and acetazolamide continuation. BMI reductions were more pronounced in the metformin group, with significant differences observed from 6 months onward (p<0.0001). Notably, metformin’s beneficial effects persisted independently of BMI changes. The safety profile of metformin was favorable, with no significant differences in adverse events compared to the control group which did not receive metformin during the study timeframe.

Conclusions

Our study provides evidence for metformin’s potential as a disease-modifying therapeutic approach in IIH, demonstrating improvements across multiple outcomes. The benefits appear to extend beyond weight loss, suggesting complex mechanisms of action. These findings warrant further investigation through prospective clinical trials to establish metformin’s role in IIH management and explore its underlying therapeutic mechanisms.
Harnessing Random Peptide Mixtures to Overcome Multidrug-Resistant Fungal Infections
Authors: Adeoye John , Belo Yael , Rocha Marina , Hayby Hilla , Hayouka Zvi , Shlezinger Neta
Published: September 2024

Invasive fungal infections, characterized by high mortality rates, present a growing health concern due to the limited spectrum of effective drugs, escalating numbers of immunocompromised patients, and the rapid emergence of drug resistance. Addressing this challenge requires alternative therapeutic strategies. Candidate drugs should fulfill key requirements to qualify for clinical use, including negligible host toxicity, highin vitroandin vivoantifungal activity,in vivostability, and modes of actions that reduce the potential for the emergence of resistant strains. Antimicrobial peptides (AMPs) stand out as a promising class of compounds to combat antimicrobial resistance. Capitalizing on the unique characteristics of AMPs, we have developed a novel approach, to synthesize random peptide mixtures (RPMs) with robust bactericidal properties against drug-resistant bacteria. Here, we evaluate the antifungal potential of RPMs. Our findings demonstrate high potency of RPMs againstCandida auris, a newly emerged multidrug-resistant human fungal pathogen. In vitro studies demonstrated the effective eradication ofC. aurisby FK20 RPMs, with scanning electron microscopy revealing substantial damage to the fungal outer membrane, while confocal microscopy confirms their ability to penetrateC. auriscells. Importantly, our study elucidates that FK20 RPMs effectively hinder the development of resistance inC. auris, as confirmed by experimental evolution assays. Moreover, a synergistic effect is observed when combining FK20 RPMs with the antifungal drug caspofungin, effectively inhibiting biofilm formation. Lastly, we demonstrate the significant therapeutic potential of FK20 RPM in a murine model of systemic candidiasis. Our findings underscore the promise of RPMs as novel, efficacious, and safe treatment for drug-resistant fungal infections.
Model-guided gene circuit design for engineering genetically stable cell populations in diverse applications
Authors: Sechkar Kirill , Steel Harrison
Published: September 2024

Maintaining engineered cell populations’ genetic stability is a key challenge in synthetic biology. Synthetic genetic constructs compete with a host cell’s native genes for expression resources, burdening the cell and impairing its growth. This creates a selective pressure favouring mutations which alleviate this growth defect by removing synthetic gene expression. Non-functional mutants thus spread in cell populations, eventually making them lose engineered functions. Past work has attempted to limit mutation spread by coupling synthetic gene expression to survival. However, these approaches are highly context-dependent and must be tailor-made for each particular synthetic gene circuit to be retained.

In contrast, we develop and analyse a biomolecular controller which depresses mutant cell growth independently of the mutated synthetic gene’s identity. Modelling shows how our design can be deployed alongside various synthetic circuits without any re-engineering of its genetic components, outperforming extant gene-specific mutation spread mitigation strategies. Our controller’s performance is evaluated using a novel simulation approach which leverages resource-aware cell modelling to directly link a circuit’s design parameters to its population-level behaviour.

Our design’s adaptability promises to mitigate mutation spread in an expanded range of applications, whilst our analyses provide a blueprint for using resource-aware cell models in circuit design.
Transcriptomic profiling of ‘CandidatusLiberibacter asiaticus’ in different citrus tissues reveals novel insights into Huanglongbing pathogenesis
Authors: Lovelace Amelia H. , Wang Chunxia , Levy Amit , Ma Wenbo
Published: September 2024

‘CandidatusLiberibacter asiaticus’ (Las) is a gram-negative bacterial pathogen associated with citrus huanglongbing (HLB) or greening disease. Las is transmitted by the Asian citrus psyllid (ACP) where it colonizes the phloem tissue, resulting in substantial economic losses to citrus industry worldwide. Despite extensive efforts, effective management strategies against HLB remain elusive, necessitating a deeper understanding of the pathogen’ s biology. Las undergoes cell-to-cell movement through phloem flow and colonizes different tissues in which Las may have varying interactions with the host. Here, we investigate the transcriptomic landscape of Las in citrus seed coat vasculatures, enabling a complete gene expression profiling of Las genome and revealing unique transcriptomic patterns compared to previous studies using midrib tissues. Comparative transcriptomics between seed coat, midrib and ACP identified specific responses and metabolic states of Las in different host tissue. Two Las virulence factors that exhibit higher expression in seed coat can suppress callose deposition. Therefore, they may contribute to unclogging sieve plate pores during Las colonization in seed coat vasculature. Furthermore, analysis of regulatory elements uncovers a potential role of LuxR-type transcription factors in regulating Liberibacter effector gene expression during plant colonization. Together, this work provides novel insights into the pathogenesis of the devastating citrus HLB.

Funding

This work is supported by USDA National Institute of Food and Agriculture award No. 2020-70029-33197 to W.M and A.L.
A study of mediating and moderating effects on the relationship between audit quality and integrated reporting quality among Jordanian firms
Authors: Abu Afifa Malik , Saleh Isam , Abu Al-Nadi Rahaf
Published: September 2024

Purpose

The purpose of this research is to investigate the link between external audit quality and integrated reporting (IR) quality in the Jordanian market, a developing market. Furthermore, the research model considers the mediating effect of earnings management practices and the moderating effect of board gender diversity. As a result, it intends to provide further empirical evidence in this area.

Design/methodology/approach

This research investigates its model using data from Jordanian services companies listed on the Amman Stock Exchange (ASE) during the period 2013–2022. With 430 company-year observations, the current research’s sample includes all companies in the research population for which complete data were available during the period under investigation. Data relevant to the research setting were obtained from annual disclosures and the ASE's database.

Findings

The findings of this research show that audit firm size and audit firm specialty have a positive influence on IR quality, but audit firm tenure does not. External audit quality (as proxied by the size, specialty and turnover of the audit firm) had a negative impact on earnings management practices, while earnings management practices had a negative impact on IR quality. Additionally, the findings reveal that earnings management practices completely mediate the relationship between two external audit quality proxies (audit firm size and audit firm specialty) and IR quality. Furthermore, in terms of the moderating impact of board gender diversity, it is obvious that board gender diversity favorably moderates the relationships between all external audit quality proxies and IR quality.

Originality/value

Using agency theory and stakeholder theory, this investigation fills a gap in previous literature by adding scientific explanations and empirical evidence from the Jordanian market, a developing market, in the context of the impact of audit quality on IR quality, mediated by earnings management and moderated by board gender diversity.
Exploring opportunities and challenges in promoting interethnic tolerance as a social good through virtual influencers
Authors: Levkov Nikola , Santa Mijalche , Kitanovikj Bojan
Published: September 2024

Purpose

This paper aims to understand how virtual influencers (VIs) can promote interethnic tolerance, online, among youth as a social good.

Design/methodology/approach

This paper conducted qualitative research using interpretive analysis with RTA (Reflexive Thematic Analysis) on data collected through focus groups.

Findings

This paper revealed that the quality of the VI’s content is a leading factor influencing VI's ability to promote interethnic tolerance, but creating content that is constantly authentic, appealing and inclusive to diverse ethnic groups in a particular context is challenging.

Research limitations/implications

The study has some limitations related to the specific context on which it is focused and therefore transferring the findings to different contextual conditions requires caution, and also can be extended with positivist validation.

Practical implications

Findings from our study can drive future projects where real VI artifacts will play the role of a mediator in building strong relational trust among youth belonging to different ethnic groups. The findings indicate that VIs can be effectively used to foster interethnic tolerance if involve diverse team members who understand the ethnic culture deeply and social media experts, to create high-quality content to overcome some limitations.

Social implications

VIs can be used as social interventions to promote interethnic tolerance and to reduce prejudices and anxiety in online youth communication.

Originality/value

To the best of the authors’ knowledge, no known studies investigated the potential of VIs for promoting interethnic tolerance among ethnically diverse youth groups. Hence, this study paves the way for further refinement on using cutting-edge technology for social good, since it is highly challenging, often resulting in wasted money.
Exploring excellence: a comprehensive examination of professional development in library and information science
Authors: Margam Madhusudhan , Pandey Parbati
Published: September 2024

Purpose

This study aims to investigate future trends evident in the literature. It systematically reviews continuing professional development (CPD) practices, covering a range of CPD channels, benefits and challenges.

Design/methodology/approach

The study used a systematic literature review approach following the PRISMA 20 framework. Literature published between 2017 and 2023 was sourced from Scopus and Web of Science databases and the researcher's prior collection. An extensive search strategy was devised, yielding 1,740 results for initial screening. Finally, 25 studies were thoroughly scrutinized, each fulfilling the criteria for inclusive and exclusive with descriptive and interrogative analysis.

Findings

The trend observed in literature over the years indicates a dynamic professional development of library and information science (LIS) professionals. This evolution encompasses foundational qualitative studies, expansive global assessments and technology-driven interventions, reflecting the field's adaptability to the evolving needs of LIS professionals. However, several impediments hinder professionals from actively participating, such as financial constraints, lack of institutional and senior support, difficulties in the workplace, the absence of well-defined CPD policies, personal commitments, family obligations and diverse staff attitudes. The study proposes seamless integration of information and communication technology, a global perspective and well-structured CPD programs focusing on lifelong learning that will shape the future of LIS professionals.

Originality/value

This study offers valuable insights into the present state of professional development among LIS professionals toward global collaboration and a dedication to lifelong learning, aiming to aid stakeholders in formulating suitable strategies and policies.
An examination of COVID-19’s impact on student learning: a self-determination theory perspective
Authors: Hapke Holly , Lee-Post Anita , Dean Tereza , Huang Kun
Published: September 2024

Purpose

We propose and test a theoretically grounded structural model of our postulation, providing insights into how students’ COVID experiences affect their general learning experiences, specific learning experiences and specific class performance post-COVID.

Design/methodology/approach

Numerous studies have reported how COVID-19 has impacted student learning in higher education during the pandemic from Spring 2020 to Fall 2021. Students were found to be disengaged, unmotivated, isolated, anxious, having difficulty with emergency remote teaching (ERT) and dealing with financial, physical and/or mental health issues. Against this backdrop, we conduct our own investigation to ascertain what the lasting impacts of COVID-19 are on student learning using a survey instrument. Specifically, we postulate that the academic and social disruptions of COVID-19 affected students’ social connectedness and mental well-being, which in turn, affected their affective and cognitive learning outcomes. We used structural equation modeling to validate a structural model grounded in self-determination theory that capatures the complex relationships between genaral and specfiic COVID-19 impact factors on student learning as seven hypotheses.

Findings

All seven of our hypotheses are supported suggesting that both class-specific factors and broader general factors beyond the classroom affect student's satisfaction with and learning in the class, as postulated in our structural model.

Originality/value

We advance the work of self-determination theory by conceptualizing and modeling the roles that all three self-determination needs play in investigating COVID-19's impact on learning. Overall, our study confirms the value of considering affective factors such as anxiety and satisfaction in learning research.
Is monopoly truly effective for producers?
Authors: Moiseev Nikita
Published: September 2024

Purpose

The paper is devoted to modeling a pricing policy of competitive firms in a “closed” economy framework.

Design/methodology/approach

The proposed model can be regarded as an analog to CGE model and is based on the intersectoral balance methodology incorporating linear demand functions for goods and services.

Findings

By performing different model experiments, we show that a certain degree of competition can bring more profit to all competing firms, than in case of complete absence of such competition, what is also supported by empirical investigation. This finding implies that monopolies may perform worse than competitive firms, what contradicts with the modern provisions of economic theory, stating that monopoly is the most lucrative type of market structure for a producer. The discovered effect occurs due to the aggressive pricing policy, adopted by monopolies, spurring up the inflation spiral, which is most obvious if monopolies are strongly interdependent in terms of production matrix. This inflation spiral drives prices too high, what negatively reflects on firms’ costs and, consequently, results in monopolies receiving less profit.

Originality/value

The proposed model can also be useful for understanding and assessing various economic consequences after different external or internal shocks, what is especially crucial when conducting monetary or fiscal policy.
The impact of e-commerce platforms' quality on customer satisfaction and repurchase intention in post COVID-19 settings
Authors: Savastano Marco , Anagnoste Sorin , Biclesanu Isabelle , Amendola Carlo
Published: September 2024

Purpose

E-commerce expands product and service reach, emphasizing the need for strategic market approaches to enhance e-service quality and drive sales growth. This paper aims to assess the relationship between the perceived quality of e-commerce platforms (characterized by measures of order and return convenience), customer satisfaction with online shopping and repurchase intention from online stores as well as examine whether demographic variables such as age, gender and area of residency (urban/rural) influence the ratings of each of these variables.

Design/methodology/approach

An online, self-administered survey gathered 108 valid responses from e-commerce customers. Data were analyzed in Statistical Package for the Social Sciences (SPSS) and Analysis of Moment Structures (AMOS) through principal component analysis, confirmatory factor analysis and structural equation modeling (SEM) as well as correlation, descriptive statistics, difference of means tests and nonlinear regression.

Findings

Online shopping on e-commerce platforms is seen as convenient for both placing orders and managing returns. Additionally, consumers express satisfaction with their online shopping experiences and exhibit a strong intention to repurchase. The analysis revealed linear relationships between order convenience and customer satisfaction, between order convenience and repurchase intention and nonlinear relationships between return convenience, customer satisfaction and repurchase intention. No significant difference was found between the way the demographic variables rated the convenience, satisfaction and repurchase intention constructs.

Originality/value

This study contributes to the empirical literature on service quality in e-commerce by providing a streamlined model of the interactions among the factors as well as by isolating the nonlinear relationships and comparing results across three demographic variables. From a managerial standpoint, the findings suggest that strategies aimed at providing complete qualitative information and enhancing order and return convenience improve customer satisfaction and foster repurchase intention.
Transgenic silkworm expressing bioactive human ciliary neurotrophic factor for biomedical application
Authors: Lan Weiqun , Geng Wenjing , Jiang Xuechun , Chen Feng , Zhou Mingyi , Shen Guanwang , Lin Ping , Xia Qingyou , Zhao Ping , Li Zhiqing
Published: September 2024

Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective agent in neuronal survival and regeneration, and can also induce the differentiation of several stem cells into neurons, which highlights the broad application of CNTF in biomedicine. However, large‐scale production of bioactive recombinant human CNTF protein remains to be explored. Herein, this study aims to express a bioactive human CNTF protein on a large scale by genetically engineering a silk gland bioreactor of silkworm. Our results showed that CNTF protein was successfully expressed in the middle silk gland (MSG) of silkworm, which can be secreted into the silks with the amount of 3.2 mg/g cocoons. The fabrication of human CNTF‐functionalized silk material was able to promote proliferation and migration of neural cells when compared to the natural silk protein. Importantly, this functional silk material could also facilitate neurite outgrowth of mouse retinal ganglion cell (RGC‐5) cells. All these data demonstrated a high bioactivity of the recombinant human CNTF protein expressed in the MSG of silkworm. The further fabrication of different silk materials with CNTF bioactivity will give biomedical applications in tissue engineering and neuroregeneration.
Mounting an immune response reduces male attractiveness in a lizard
Authors: COMAS Mar , ZAMORA‐CAMACHO Francisco J. , GARRIDO‐BAUTISTA Jorge , MORENO‐RUEDA Gregorio , MARTÍN José , LÓPEZ Pilar
Published: September 2024

Parasites impact host fitness and constitute an important selective pressure on the host's life history. According to parasite‐mediated sexual selection, ornaments are presumed to honestly indicate immune capacity or resistance against parasites, and the chooser sex (typically females) obtains an advantage by selecting more ornamented, thus more immunocompetent mates. Therefore, signalers mounting an immune response must allocate resources from the sexual signal to the immune system, hence reducing the expression of the ornament and becoming less attractive to the choosing sex. Here, we test this idea in the lizard Psammodromus algirus. We inoculated a subsample of males with lipopolysaccharide (LPS) of the cell wall of Escherichia coli, while others served as sham controls. The inoculation of LPS decreased the proportion of ergosterol (pro‐vitamin D2) in femoral secretions, and chemosensory tests showed that the scent of LPS‐inoculated males was less attractive to females than the scent of control males. Given that ergosterol is a precursor of vitamin D, which has physiological functions as an immune modulator, immunocompromised males likely needed to divert vitamin D to the immune system, reducing the allocation of ergosterol to secretions. In this way, females could detect “sick” males, preferring the apparently healthy males. Overall, our study shows that mounting an immune response is costly in terms of reduced attractiveness. Moreover, we disentangle the underlying mechanism, which involves an honest signal based on vitamin D allocation.
Risks of segmentectomy for interstitial pneumonia with diffuse pulmonary ossification
Authors: Shimada Karin , Takamori Satoshi , Nakatsuka Marina , Endoh Makoto
Published: September 2024

An 84‐year‐old man with a history of progressive interstitial pneumonia presented to our department with lung cancer (cT2aN0M0‐IB) in right S6. Moreover, computed tomography revealed progressive diffuse pulmonary ossification in the bilateral lower pulmonary lobes. S6 segmentectomy was performed via video‐assisted thoracoscopic surgery. It was difficult to divide the intersegmental plane using a stapler because of severe fibrosis and pulmonary ossification with bone marrow formation. Pulmonary ossification may be an important finding for surgical planning because of severe fibrosis or inflammation associated with severe lung condition. We suggest that the surgical indications and approaches for such cases should be reconsidered because pulmonary ossification can be associated with severe lung conditions.
Peripheral facial palsy in children: Serum Borrelia antibodies may reduce the need for lumbar puncture
Authors: Bloch Joakim , Schmidt Lisbeth , Vissing Nadja , Nielsen Alex Christian Yde , Glenthøj Jonathan Peter , Smith Birgitte , Lisby Jan Gorm , Nielsen Lene , Tetens Malte , Lebech Anne‐Mette , Nygaard Ulrikka
Published: September 2024

Aim

We aimed to investigate the causes of acute peripheral facial palsy (PFP) in Danish children and to explore whether neuroborreliosis‐related PFP could be diagnosed without lumbar puncture using clinical symptoms and serum Borrelia burgdorferi (Bb) antibodies.

Methods

This retrospective population‐based cohort study included children undergoing lumbar puncture for PFP between 2019 and 2023 in Denmark's Capital Region. Diagnostic performance measures for neuroborreliosis‐related PFP were compared between serum Bb IgG alone and clinical risk scores combining Bb IgG with clinical parameters.

Results

Of the 326 patients with PFP, 137 (42%) were diagnosed with neuroborreliosis and 151 (46%) had Bell's palsy. Positive predictive value for serum Bb IgG alone was 88% (95% CI 79–93) and negative predictive value was 83% (95% CI 75–88). The positive predictive value of a risk score with seven additional parameters was 90% (95% CI 81–95) and negative predictive value 87% (95% CI 80–92).

Conclusion

The positive predictive value of serum Bb IgG alone was high in our setting, where nearly half of children with PFP had neuroborreliosis. In high endemic settings, lumbar punctures may be reduced by (i) treating all children with PFP with doxycycline or (ii) treating Bb IgG positive children and performing lumbar puncture in seronegative children.
Editorial: Non‐selective beta‐blockers: A lifesaving shield for critically ill patients with acute decompensation of cirrhosis?
Authors: Yang Ling , Liu Chuan , Lai Jimmy Che‐To , Qi Xiaolong
Published: September 2024

LINKED CONTENT

This article is linked to Kumar et al paper. To view this article, visit https://doi.org/10.1111/apt.18188
Safe and supportive prescribing in transgender and non‐binary patients with cancer
Authors: D'Elia Mariachiara , Nabhani‐Gebara Shereen , O'Callaghan Stewart
Published: September 2024

Global prevalence rates for transgender individuals vary with estimates ranging from 0.3% to 1%, translating to a potential global population of 24.3 million to 81 million. It is estimated that one in two people will develop cancer in their lifetime. Gender‐affirming hormone therapy (GAHT) is a common medical intervention for transgender and non‐binary individuals. GAHT requires careful consideration for concurrent medical care due to potential drug interactions and physiological changes. A multi‐disciplinary team with expertise in transgender health, oncology and pharmacy met to develop a document summarizing current knowledge on the topic for practical use. The team included trans and non‐binary authors who shaped the document's language and focus. The document gives a status update on the current understanding of GAHT and how this may intersect with the safe prescribing of systemic anti‐cancer therapies (SACT). The document underwent multiple review stages including internal review, review by the British Oncology Pharmacy Association (BOPA) EDI Subcommittee and, finally, BOPA Executive Committee review and final approval. Key recommendations of this document include the use of inclusive and effective communication, vigilant monitoring of kidney function and cardiovascular health, and considerations for hormone receptor‐positive cancers. The document also recognizes the multidisciplinary nature of transgender healthcare and where this relates to social prescribing.
Role of GABAA receptors of the dorsomedial periaqueductal grey on blood pressure and heart rate in the anesthetized rat
Authors: Baktashian Esfahani Mohammad Hossein , Sherkat Sogol , Shafei Mohammad Naser
Published: September 2024

The midbrain dorsomedial periaqueductal grey column (dmPAG) is involved in the regulation of cardiovascular responses. Due to the presence of Gamma‐Aminobutyric acid (GABA) receptors in the dmPAG, this study aimed to investigate the role of GABAA receptors in the dmPAG on cardiovascular parameters and its possible peripheral mechanisms. The left femoral artery was cannulated, and systolic arterial pressure (SAP), mean arterial pressure (MAP) and heart rate (HR) were recorded using a Power lab system. Microinjection of saline, muscimol and bicuculline (BIC) was done using a stereotaxic device. Also, the peripheral mechanisms dependent on GABAA receptors in the dmPAG were evaluated by intravenous (i.v.) injection of hexamethonium (Hexa) and atropine (Atr) 5 min before the BIC. Results showed that BIC significantly increased ∆SAP, ∆MAP and ∆HR than the control group, but muscimol had no significant effect. Injection of Hex significantly attenuates the effect of BIC on ∆SAP and ∆MAP. Atr (i.v) significantly increased the ∆HR, and when injected before BIC microinjection, it did not affect the cardiovascular responses induced by BIC. These findings show that GABAA receptors of the dmPAG have inhibitory effects on the cardiovascular system, which are mostly mediated by the sympathetic system.
Comparing GBA1‐Parkinson's disease and idiopathic Parkinson's disease: α‐Synuclein oligomers and synaptic density as biomarkers in the skin biopsy
Authors: Mazzetti Samanta , Contaldi Elena , Basellini Milo Jarno , Novello Claudia , Calogero Alessandra Maria , Straniero Letizia , Garrì Federica , Ferri Valentina , Calandrella Daniela , Del Sorbo Francesca , Asselta Rosanna , Cereda Emanuele , Cappelletti Graziella , Isaias Ioannis Ugo , Pezzoli Gianni
Published: September 2024

The main genetic risk factors for Parkinson's disease (PD) are presently represented by variants in GBA1 gene encoding for the β‐glucocerebrosidase (GCase). Searching for a peripheral biomarker that can be used for selecting and monitoring patients in clinical trials targeting GBA1‐associated PD (GBA1‐PD) is a current challenge. We previously demonstrated that α‐synuclein oligomers expressed as proximity ligation assay (PLA) score in synaptic terminals of skin biopsy are a reliable biomarker for distinguishing idiopathic PD (iPD) from healthy controls (HC). This cross‐sectional study investigates an unexplored cohort of GBA1‐PD (n = 27) compared to 28 HC, and 36 iPD cases to (i) analyze α‐synuclein oligomers and quantify them throughout PLA score, (ii) investigate GCase expression in brain and synaptic terminals targeting the sweat gland, (iii) unravel indicators that could differentiate patients with specific GBA1 mutations. PLA score discriminates GBA1‐PD from HC with sensitivity = 88.9% (95% CI 70.84–97.65), specificity = 88.5% (95% CI 69.85–97.55), and PPV = 88.9% (95% CI 73.24–95.90), AUC value = 0.927 (95% CI 0.859–0.996). No difference was found between GBA1‐PD patients and iPD, suggesting a common pathological pathway based on α‐synuclein oligomers. GCase score did not differ in GBA1‐PD, iPD, and HC in the synaptic terminals, whereas a positive correlation was found between PLA score and GCase score. Moreover, a significant increase in synaptic density was observed in GBA1‐PD compared to iPD and HC (P < 0.0001). Employing ROC curve to discriminate GBA1‐PD from iPD, we found an AUC value for synaptic density = 0.855 (95% CI 0.749–0.961) with sensitivity = 85.2% (95% CI 66.27%–95.81%), specificity = 77.1% (95% CI 59.86%–89.58%), and PPV = 74.19% (60.53%–84.35%). The highest synaptic density values were observed in p.N409S patients. This work points out to the value of both PLA score and synaptic density in distinguishing GBA1‐PD from iPD and to their potential to stratify and monitor patients in the context of new pathway‐specific therapeutic options.
The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors
Authors: Casar‐Borota Olivera , Burman Pia , Lopes M. Beatriz
Published: September 2024

The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology “atypical adenoma” for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established. The 2022 (5th Edition) WHO Classification of the Pituitary Tumors emphasizes the concept that morphological features distinguish indolent tumors from locally aggressive ones, however, the proposed histological subtypes are not consistent with the real life clinical characteristics of patients with aggressive tumors/carcinomas. So far, no single clinical, radiological or histological parameter can determine the risk of growth or malignant progression. Novel promising molecular prognostic markers, such as mutations in ATRX, TP53, SF3B1, and epigenetic DNA modifications, will need to be verified in larger tumor cohorts. In this review, we provide a critical analysis of the WHO guidelines for prognostic stratification and diagnosis of aggressive and metastatic PitNETs. In addition, we discuss the new WHO recommendations for changing ICD‐O and ICD‐11 codes for PitNET tumor behavior from a neoplasm either “benign” or “unspecified, borderline, or uncertain behavior” to “malignant” neoplasm regardless of the clinical presentation, histopathological subtype, and tumor location. We encourage multidisciplinary initiatives for integrated clinical, histological and molecular classification, which would enable early recognition of these challenging tumors and initiation of more appropriate and aggressive treatments, ultimately improving the outcome.
The effects of human‐caused mortality on mammalian cooperative breeders: a synthesis
Authors: Ausband David E. , Rebholz Peter F. , Petrillo Lindsay
Published: September 2024

Human‐caused mortality can be pervasive and even highly selective for individuals in groups of cooperative breeders. Many studies of cooperative breeders, however, do not address human‐caused mortality. Similarly, studies focused on the effects of human‐caused mortality on wildlife populations often do not consider the ecology of cooperative breeders. We searched the literature and identified 58 studies where human‐caused mortality affected a group characteristic, vital rate, or population state of a cooperative breeder. Of studies reporting population growth or decline, 80% reported a link between human‐caused mortality and population declines in cooperative breeders. Such studies often did not identify the mechanism behind population declines, but 28% identified concurrent declines in adult survival and another 21% reported concurrent declines in recruitment or reproduction. There was little overlap between the cooperative breeding and human‐caused mortality literatures, limiting our ability to accrue knowledge. Future work would be beneficial if it (i) identified the vital rate(s) causing population declines, (ii) leveraged management actions such as lethal removal to ask questions about the ecology of group‐living in cooperative breeders, and (iii) used insights from cooperative breeding theory to inform management actions and conservation of group‐living species.
Bending the curve of global freshwater biodiversity loss: what are the prospects?
Authors: Dudgeon David , Strayer David L.
Published: September 2024

Freshwater biodiversity conservation has received substantial attention in the scientific literature and is finally being recognized in policy frameworks such as the Global Biodiversity Framework and its associated targets for 2030. This is important progress. Nonetheless, freshwater species continue to be confronted with high levels of imperilment and widespread ecosystem degradation. An Emergency Recovery Plan (ERP) proposed in 2020 comprises six measures intended to “bend the curve” of freshwater biodiversity loss, if they are widely adopted and adequately supported. We review evidence suggesting that the combined intensity of persistent and emerging threats to freshwater biodiversity has become so serious that current and projected efforts to preserve, protect and restore inland‐water ecosystems may be insufficient to avert substantial biodiversity losses in the coming decades. In particular, climate change, with its complex and harmful impacts, will frustrate attempts to prevent biodiversity losses from freshwater ecosystems already affected by multiple threats. Interactions among these threats will limit recovery of populations and exacerbate declines resulting in local or even global extinctions, especially among low‐viability populations in degraded or fragmented ecosystems. In addition to impediments represented by climate change, we identify several other areas where the absolute scarcity of fresh water, inadequate scientific information or predictive capacity, and a widespread failure to mitigate anthropogenic stressors, are liable to set limits on the recovery of freshwater biodiversity. Implementation of the ERP rapidly and at scale through many widely dispersed local actions focused on regions of high freshwater biodiversity and intense threat, together with an intensification of ex‐situ conservation efforts, will be necessary to preserve native freshwater biodiversity during an increasingly uncertain climatic future in which poorly understood, emergent and interacting threats have become more influential. But implementation of the ERP must be accompanied by measures that will improve water, energy and food security for humans – without further compromising the condition of freshwater ecosystems. Unfortunately, the inadequate political implementation of policies to arrest widely recognized environmental challenges such as climate change do not inspire confidence about the possible success of the ERP. In many parts of the world, the Anthropocene future seems certain to include extended periods with an absolute scarcity of uncontaminated surface runoff that will inevitably be appropriated by humans. Unless there is a step‐change in societal awareness of – and commitment to – the conservation of freshwater biodiversity, together with necessary actions to arrest climate change, implementation of established methods for protecting freshwater biodiversity may not bend the curve enough to prevent continued ecosystem degradation and species loss.
Crosstalk between GBP2 and M2 macrophage promotes the ccRCC progression
Authors: Zheng Wei , Ye Shujiang , Liu Bin , Liu Dan , Yan Ruyu , Guo Hongjuan , Yu Hongtao , Hu Xudong , Zhao Huaiming , Zhou Kecheng , Li Guangyuan
Published: September 2024

Clear cell renal cell carcinoma (ccRCC) represents a highly heterogeneous kidney malignancy associated with the poorest prognosis. The metastatic potential of advanced ccRCC tumors is notably high, posing significant clinical challenges. There is an urgent imperative to develop novel therapeutic approaches to address ccRCC metastasis. Recent investigations indicated a potential association between GBP2 and tumor immunity. However, the precise functional role of GBP2 in the progression of ccRCC remains poorly understood. The present study revealed a strong correlation between GBP2 and M2 macrophages. Specifically, our findings demonstrated that the inhibition of GBP2 significantly impedes the migratory and invasive capabilities of ccRCC cells. We observed that the presence of M2 macrophages can reverse the effects of GBP2 knockdown on tumor cell migration and invasion. Mechanistically, we demonstrated that M2 macrophages promote the expression of the GBP2/p‐STAT3 and p‐ERK axis in tumor cells through the secretion of interleukin‐10 (IL‐10) and transforming growth factor‐β (TGF‐β), thereby substantially enhancing the migratory and invasive capacities of the tumor cells. Simultaneously, we have identified that GBP2 promotes the polarization of macrophages to the M2 phenotype by stimulating the secretion of interleukin‐18 (IL‐18). In summary, our investigation anticipates that the GBP2/IL‐18/M2 macrophages/IL‐10 and the TGF‐β/GBP2, p‐STAT3, p‐ERK loop plays a crucial role in ccRCC metastasis. The collective findings from our research underscore the significant role of GBP2 in tumor immunity and emphasize the potential for modulating GBP2 as a promising therapeutic strategy for targeting ccRCC metastasis.
Granzyme B inhibition reduces autoantibody‐induced dermal–epidermal separation in an ex vivo model of epidermolysis bullosa acquisita
Authors: Emtenani Shirin , Lebhar Hélène , Marquis Christopher P. , Ludwig Ralf J. , Schmidt Enno
Published: September 2024

The pemphigoid disease epidermolysis bullosa acquisita (EBA) is an autoimmune blistering skin disease characterized by autoantibodies against type VII collagen (COL7), immune cell infiltrates at the dermal–epidermal junction and subepidermal blistering. Proteases, particularly granzyme B (GzmB), have been established as therapeutic targets for the treatment of EBA and other pemphigoid diseases. We investigated the impact of the novel GzmB inhibitor SNT‐6935 on anti‐COL7 IgG‐induced subepidermal blistering in a well‐established EBA ex vivo model. Our findings demonstrate that pharmacological targeting of GzmB with its selective inhibitor SNT‐6935 significantly reduced autoantibody‐induced dermal–epidermal separation in human skin cryosections. Interestingly, treatment of skin cryosections with recombinant human GzmB alone did not cause dermal–epidermal separation, suggesting that additional mechanisms alongside GzmB are required for tissue damage in EBA. In conclusion, our study highlights the significant contribution of GzmB to the pathogenesis of EBA and supports the notion of GzmB as a therapeutic target in EBA and other pemphigoid diseases.
Deep learning‐based gesture recognition for surgical applications: A data augmentation approach
Authors: Santiago Sofía Sorbet , Cifuentes Jenny Alexandra
Published: September 2024

Hand gesture recognition and classification play a pivotal role in automating Human‐Computer Interaction (HCI) and have garnered substantial attention in research. In this study, the focus is placed on the application of gesture recognition in surgical settings to provide valuable feedback during medical training. A tool gesture classification system based on Deep Learning (DL) techniques is proposed, specifically employing a Long Short Term Memory (LSTM)‐based model with an attention mechanism. The research is structured in three key stages: data pre‐processing to eliminate outliers and smooth trajectories, addressing noise from surgical instrument data acquisition; data augmentation to overcome data scarcity by generating new trajectories through controlled spatial transformations; and the implementation and evaluation of the DL‐based classification strategy. The dataset used includes recordings from ten participants with varying surgical experience, covering three types of trajectories and involving both right and left arms. The proposed classifier, combined with the data augmentation strategy, is assessed for its effectiveness in classifying all acquired gestures. The performance of the proposed model is evaluated against other DL‐based methodologies commonly employed in surgical gesture classification. The results indicate that the proposed approach outperforms these benchmark methods, achieving higher classification accuracy and robustness in distinguishing diverse surgical gestures.
Parametric characterization of the Christopher–James–Patterson model for crack propagation in welded zone of A7N01 Aluminum alloys
Authors: Liu Xi , Lu Yaohui , Wang Qiushi , Lu Chuan , James Neil
Published: September 2024

Aluminum alloy is a widely used material in railway vehicle structures. In order to accurately analyze the crack propagation mechanism of Aluminum alloy welding structures and predict their crack propagation life, this study focuses on the A7N01 Aluminum alloy and proposes a full‐field strain solution method based on the least‐squares method. For the first time, digital image correlation (DIC) experimental measurements are combined with the finite element analysis method to determine the shape and size of the plastic zone at the crack tip of the compact tension (CT) specimen. And it also calculates the crack propagation driving force parameters of the Christopher–James–Patterson (CJP) model using traditional crack propagation driving parameters. The research results revealed that the plastic zone at the crack tip captured by DIC experiments is in good agreement with the finite element simulation results. Additionally, the crack growth rate curve of the A7N01 Aluminum alloy, fitted based on the CJP model, is insensitive to the stress ratio. The results offer an effective approach to utilizing the da/dN‐∆KCJP curve in analyzing A7N01 Aluminum alloy and welded structural failures, broadening the scope of engineering applications for the CJP model.
Impacts of improved transport on regional market access
Authors: O'Kelly M.E.
Published: September 2024

This article presents a pedagogic review and explanation of a core idea in location theory. Central to the analysis is the von Thünen model, a cornerstone of agricultural land use theory. The model is adapted to non‐uniform transport surfaces, enabling an exploration of how improved transport corridors, such as roads and canals, alter economic landscapes. The article explores the influence of enhanced transport corridors within agricultural growing regions and provides a conceptual framework for understanding the impacts of improved transport infrastructure. By examining incremental changes of varying effectiveness, we shed light on the multifaceted effects of these corridors. Using a spatial‐price equilibrium model, findings reveal and quantify how these improvements contribute to increased supply, price moderation, and cost reduction. Networks that provide full connectivity with large reductions in transport cost have the greatest effect, as might be expected, but there are subtle spatial zones displaying differential impacts.