bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-AIDS defining cancers in HIV-infected individuals: a concise review
Authors: Elendu Chukwuka
Published: October 2024

Non-acquired immunodeficiency syndrome (AIDS)-defining cancers (NADCs) present a growing concern in human immunodeficiency virus (HIV)-infected individuals, impacting morbidity and mortality rates. This paper synthesizes current epidemiological data and explores the multifaceted relationship between HIV infection and NADC risk. Epidemiological studies indicate a shifting landscape of cancer incidence among HIV-infected populations, with a notable rise in NADCs over recent decades. Factors such as prolonged life expectancy due to effective antiretroviral therapy (ART) and aging of the HIV-infected population contribute to this trend. Despite the overall decline in AIDS-defining cancers, NADCs have emerged as a significant cause of morbidity and mortality in HIV-infected individuals. Immunodeficiency, chronic inflammation, and oncogenic viral co-infections, such as human papillomavirus and hepatitis C virus, compound the risk of developing NADCs. Diagnostic challenges persist, with delayed detection and suboptimal management contributing to poor outcomes. Treatment modalities for NADCs in HIV-infected individuals require careful consideration, balancing cancer-directed therapy with potential interactions with ART and immune reconstitution. Prevention strategies, including cancer screening and lifestyle modifications, are crucial in mitigating the burden of NADCs in this population. As the landscape of HIV care continues to evolve, understanding the epidemiology and clinical characteristics of NADCs is imperative for optimizing clinical management and improving outcomes in HIV-infected individuals.
The need for biopsychosocial menopause care: a narrative review
Authors: Evans Subhadra , Van Niekerk Leesa , Orellana Liliana , O'Shea Melissa , Druitt Marilla I. , Jones Sara , Corrigan Sarah , Heggen Campbell , Arashiro Zuleika , Baber Rodney , Satyen Lata , Skvarc Dave , Mikocka-Walus Antonina
Published: October 2024

Importance and Objective

Menopause is a reproductive transition affecting half the world's population. Stigma and limited availability of evidence-based treatments that support biopsychosocial well-being mean that this life stage is often associated with challenging symptoms and reduced quality of life (QoL). The aim of this review was to examine the extent literature on psychological and mind-body interventions to manage perimenopausal and postmenopausal symptoms, and apply an interdisciplinary clinical, research, and cultural knowledge framework to guide recommendations for improving QoL and healthy aging in this population. We also aimed to understand the ideal delivery mode for such interventions.

Methods

Using Scopus, Medline, and PubMed, a review of systematic reviews, guidelines, and randomized controlled trials was undertaken to examine the use of psychological and mind-body interventions to improve menopause-related QoL and symptoms, including hot flushes, depression, anxiety, fatigue, pain, and sleep; conclusions were based on an analysis of this available evidence and linked to clinical and cultural considerations.

Discussion and Conclusion

Empirical support exists for a number of psychological and mind-body approaches to support QoL and symptoms during the menopause transition. The literature also identifies the need for menopause care that is culturally responsive.

An online multimodal model of menopause care is thus recommended, incorporating evidence-based treatments (eg, cognitive behavioral therapy, yoga, hypnosis) and treatment techniques (eg, mindfulness, and education including nutrition support), as well as First Nations wisdom. We also recommend financial well-being approaches to support people undergoing menopause. Integrated, multimodal approaches should be available online to remove time, location, and healthcare access barriers, and be designed with diverse consumers to ensure equity for those underserved due to region, LGBTIQ+ assigned female at birth status, and for multicultural and First Nations people.
Task-sharing with community health workers to treat hypertension: a scoping review
Authors: Inagaki Yoko , Matsushita Kunihiro , Appel Lawrence J. , Perry Henry B. , Neupane Dinesh
Published: October 2024

Many studies have implemented and evaluated task-sharing interventions with community health workers (CHWs) to manage hypertension. To identify gaps in research, we conducted a scoping review. We searched original articles published in PubMed and EMBASE between 2010 and 2022 and found 122 articles meeting our inclusion criteria. Only seven articles were from low-income countries (LICs), most of which were qualitative studies or mixed methods studies. In the identified 122 articles, CHWs often performed health education (61.3%) and measured blood pressure (60.4%). Whereas CHWs carried out pharmacological treatment in only three studies. Participant homes (75.0%) were the most common setting for receiving interventions. Our study identified specific needs for future research, specifically, studies in LICs that are experimental in design and that collect relevant qualitative information, and studies in which CHWs do advanced task. In addition, publications of CHW studies should provide a more comprehensive list of intervention features.
Establishing Vitreoretinal Surgery Capacity in Sierra Leone: Challenges and Opportunities to Address Retinal Health Disparities in Resource-limited Settings
Authors: Harrison-Williams Lloyd , Vandy Matthew Jusu , Mattia John G. , Hartley Caleb D. , Fashina Tolulope , Huang Ye , Choo Charlene , Yeh Caleb , Huang Crystal , Nguyen Nam , Conteh Ibrahim , Campbell Kenneth , Konneh Agnes , Hayek Brent R. , Shantha Jessica G. , Crozier Ian , Mwanza Jean-Claude , Conrady Christopher D. , Justin Grant A. , Yeh Steven , Mustapha Jalikatu ,   SMILE and EVICT-VR Study Investigators
Published: October 2024

A range of challenges exists regarding vitreoretinal (VR) surgical services in resource-limited settings, including Sierra Leone. As a result, retinal pathologies may contribute to vision loss and blindness. In the wake of the 2013 to 2016 outbreak of Ebola virus disease in West Africa, gaps in ophthalmic care were underscored as survivors were experiencing a constellation of sequelae, including uveitis and VR disease. Given the unmet needs in addressing VR disease, systems for retinal surgical care were required. To further understand long-term ocular complications in Ebola survivors and molecular and immunologic factors associated with this, research infrastructure was developed for retinal evaluation and surgery. The 5 “S’” framework was implemented and considered staff, space, stuff, systems, and social support. The ongoing development of retinal health infrastructure has helped to address challenges related to program implementation, development of surgical capacity, and alignment with local stakeholders and collaborator objectives. VR surgical services have been established in Sierra Leone through multidisciplinary partnerships and collaboration and serve patients in-country, as well as others in West Africa who have traveled for care. Continued engagement across stakeholders can aim to address challenges and promote effective care delivery.
Emerging Infectious Diseases and the Eye: Ophthalmic Manifestations, Pathogenesis, and One Health Perspectives
Authors: Blyden K’Mani , Thomas Joanne , Emami-Naeini Parisa , Fashina Tolulope , Conrady Christopher D. , Albini Thomas A. , Carag Jessica , Yeh Steven
Published: October 2024

Infectious diseases may lead to ocular complications including uveitis, an ocular inflammatory condition with potentially sight-threatening sequelae, and conjunctivitis, inflammation of the conjunctiva. Emerging infectious pathogens with known ocular findings include Ebola virus, Zika virus, Avian influenza virus, Nipah virus, severe acute respiratory syndrome coronaviruses, and Dengue virus. Re-emerging pathogens with ocular findings include Toxoplasma gondii and Plasmodium species that lead to malaria. The concept of One Health involves a collaborative and interdisciplinary approach to achieve optimal health outcomes by combining human, animal, and environmental health factors. This approach examines the interconnected and often complex human-pathogen-intermediate host interactions in infectious diseases that may also result in ocular disease, including uveitis and conjunctivitis. Through a comprehensive review of the literature, we review the ophthalmic findings of emerging infectious diseases, pathogenesis, and One Health perspectives that provide further insight into the disease state. While eye care providers and vision researchers may often focus on key local aspects of disease process and management, additional perspective on host-pathogen-reservoir life cycles and transmission considerations, including environmental factors, may offer greater insight to improve outcomes for affected individuals and stakeholders.
Forensic Mental Health Nurses' Perceptions and Experiences of Trauma-Informed Care in a High-Secure Hospital
Authors: Roberts Casey , Luder Michael , McMullen Crystal , Cole Rosalind , Dignam Paul , Ward Nicole , Ireland Michael
Published: October 2024

Background

Implementation of trauma-informed care (TIC) into forensic clinical practice may contribute to positive outcomes for both patients and staff.

Aim

The current study aimed to describe forensic mental health nurses' perceptions and experiences of using TIC within a high-secure forensic hospital.

Method

Twenty-seven forensic mental health nurses were interviewed regarding their experiences of using TIC within a high-secure hospital.

Results

Participants recognized the importance of understanding the past traumatic experiences of patients in their care but described a number of barriers to the implementation of TIC. A lack of organizational support, the negative impact of patient psychopathology on nurse well-being, and environmental factors were all perceived to negatively impact the successful delivery of TIC. Participants also discussed a widespread lack of knowledge and confidence in the application of TIC but expressed great desire for training to improve service delivery.

Implications for Clinical Forensic Nursing Practice

The application of TIC into daily clinical practice appears to be suboptimal. To support nurse and patient well-being and contribute to a highly skilled trauma-informed workforce, further training in this area is vital.

Conclusion

Training in TIC may contribute to enhanced patient outcomes and promote nurse well-being and should be supported organizationally with sufficient resources.
Efficacy and safety of stem cell therapy for fistula management: an overview of existing systematic reviews
Authors: Tripathi Tripti , Mohan Syam , Alfaifi Hassan A. , Farasani Abdullah , R Roopashree , Sharma Pawan , Sharma Abhishek , Koul Apurva , Prasad G. V. Siva , Rustagi Sarvesh , Anand Jigisha , Sah Sanjit , Gaidhane Shilpa , Bushi Ganesh , Jena Diptismita , Khatib Mahalaqua N. , Shabil Muhammed , Abdelwahab Siddig I. , Bhopte Kiran , Pant Manvi , Mehta Rachana , Pandey Sakshi , Brar Manvinder , Chilakam Nagavalli , Balaraman Ashok K.
Published: October 2024

Background:

Fistulas, abnormal connections between two anatomical structures, significantly impact the quality of life and can result from a variety of causes, including congenital defects, inflammatory conditions, and surgical complications. Stem cell therapy has emerged as a promising alternative due to its potential for regenerative and immunomodulatory effects. This overview of systematic reviews aimed to assess the safety and efficacy of stem cell therapy in managing fistulas, drawing on the evidence available.

Methods:

This umbrella review was conducted following the Joanna Briggs Institute (JBI) methodology to assess the efficacy and safety of stem cell therapy for treating various types of fistulas. A comprehensive search was performed across multiple electronic databases including PubMed, Embase, Cochrane Register, and Web of Science up to 5 May 2024. Systematic reviews focusing on stem cell therapy for fistulas were included, with data extracted on study design, stem cell types, administration methods, and outcomes. The quality of the reviews was assessed using the AMSTAR 2 tool, and meta-analyses were conducted using R software version 4.3.

Results:

Nineteen systematic reviews were included in our umbrella review. The stem cell therapy demonstrated by significant improvements in clinical remission rates, with a relative risk (RR) of 1.299 (95% CI: 1.192–1.420). Stem cell therapy enhanced fistula closure rates, both short-term (RR=1.481; 95% CI: 1.036–2.116) and long-term (RR=1.422; 95% CI: 1.091–1.854). The safety analysis revealed no significant increase in the risk of adverse events with stem cell therapy, showing a pooled RR of 0.972 (95% CI: 0.739–1.278) for general adverse events and 1.136 (95% CI: 0.821–1.572) for serious adverse events, both of which indicate a safety profile comparable to control treatments. Re-epithelialization rates also improved (RR=1.44; 95% CI: 1.322–1.572).

Conclusion:

Stem cell therapy shows promise as an effective and safe treatment for fistulas, particularly in inducing remission and promoting closure of complex fistulas. The findings advocate for further high-quality research to confirm these benefits and potentially incorporate stem cell therapy into standard clinical practice for fistula management. Future studies should focus on long-term outcomes and refining stem cell treatment protocols to optimize therapeutic efficacy.
Angular Insertion Depth in Inner Ear Malformations, Relationship to Cochlear Size, and Implications for Electrode Selection
Authors: Tellioğlu Burçay , Sennaroğlu Levent
Published: October 2024

Objective

The objectives were to determine the interrater agreement of the Skull AP X-ray in measuring angular insertion depth (AID), to provide descriptive information about the insertion depths of different electrodes used in inner ear malformations (IEMs), to investigate the effect of cochlear size and electrode length on AID, and to guide clinicians in electrode selection in IEMs.

Study Design

Retrospective case review.

Setting

Tertiary referral center.

Patients

A total of 198 IEMs (n = 169 patients) and 60 cochleae with normal anatomy (n = 60 patients) were selected from patients with severe mixed or sensorineural hearing loss who presented to our clinic and underwent cochlear implantation (CI) between January 2010 and December 2022.

Interventions

Three neurotologists independently measured AID on Skull AP X-rays. Basal turn length of the cochlea was measured in axial and coronal oblique reformatted sections on HRCT images.

Main Outcome Measures

Interrater reliability (ICC) of the AID measurements on Skull AP X-ray, determining the impact of cochlea size and electrode length on AID measurements.

Results

The interrater reliability (ICC) test showed a high level of consistency in measuring AID in the Skull AP X-ray (R = 0.906, p < 0.001). In the control group, a negative correlation was observed between the AID and the basal turn length of the cochlea, while a positive correlation was found between electrode length and AID (R = 0.947, p < 0.001).

Conclusions

The Skull AP X-ray appears to be a dependable tool for measuring AID. In cases of IEMs, it is important to select an electrode of appropriate length, considering the dimensions of the cochlea.
Grasping time – longevity of vascularized composite allografts
Authors: Messner Franka , Sardu Claudia , Petruzzo Palmina
Published: October 2024

Purpose of review

Despite significant advancements in the field of vascularized composite allotransplantation, challenges, particularly regarding the long-term viability and functionality of vascularized composite allotransplantation (VCA) grafts, persist. This paper provides a review of the current literature on the longevity of VCA grafts, focusing on factors influencing graft survival, immunological considerations and clinical outcomes.

Recent findings

Longevity of VCA grafts is influenced by a variety of peri- and postoperative factors including cold ischemia time, human leukocyte antigen matching, environmental exposure, psychosocial factors, adherence, immunosuppression, and complications. Due to the limited number of VCA transplants performed and heterogenous reporting, direct correlation of single factors with VCA outcomes remains inconclusive. Indirect evidence, however, supports their importance. High immunosuppressive burden, frequent occurrence of acute and accumulating cases of chronic rejection remain a significant challenge of the field.

Insights gained from this review aim to inform clinical practice and guide future research endeavors with the goal of ameliorating outcomes after VCA transplantation and facilitate wider use of VCA grafts for restoration of tissue defects.
Self-Leadership and Associated Factors in Nursing Students
Authors: Akdeniz Canberk , Duygulu Sergül
Published: October 2024

Background:

Nurse leaders face high pressure, but self-leadership can help them thrive. Nursing students, therefore, should develop this skill before graduation.

Purpose:

To investigate nursing students’ self-leadership perceptions and associated factors, and to reveal when and how self-leadership strategies are utilized.

Methods:

An explanatory sequential mixed-methods design with interpretative description; 943 nursing students were surveyed and 13 were selected for qualitative analysis. Descriptive data were collected, and self-leadership was assessed using the Revised Self-Leadership Questionnaire. Focus group interviews were analyzed through thematic and content analysis.

Results:

Students who were employed, were involved in student clubs or organizations, held managerial roles, and had career goals exhibited higher self-leadership perceptions. Qualitative findings revealed that staying in comfort zones, overthinking, and procrastination hinder self-leadership, while self-respect, self-awareness, and self-determination enhance it.

Conclusions:

Nurse educators should design interventions that enable students to take on planning roles, advance at their own pace, and engage in opportunities to develop their self-leadership skills.
Depictions of Aging in a Self-Portrait by David Bailly (1584–1657)
Authors: Hwang Kun
Published: October 2024

I present a case involving a portrait of David Bailly, containing 2 images portraying changes over a period of ∼40 years, and I compare the facial features that illustrate the aging process. He was 67 years old when he painted “Self-Portraits With Vanitas Symbols” (1651). By juxtaposing past representations with present reality, the painting suggests that the young artist is contemplating his future aging. The young man, appearing so vividly within the painting’s immediate reality, actually symbolizes a bygone era Compared with the young portrait, the older portrait exhibits a slightly drooped eyebrow tail, indicative of brow ptosis. In the young portrait, the lid margin is aligned with the upper border of the iris, whereas in the older portrait, it is aligned with the upper border of the pupil. The margin reflex distance 1 decreases with age. In addition, the older portrait shows baggy lower eyelids. The nasojugal groove is more pronounced, and the nasolabial fold is deeper. The beard and mustache are more extensive, and silver strands are interspersed among the black hairs. Presenting 2 images from a 40-year interval, the older portrait exhibits more pronounced signs of facial aging than the younger portrait. Portraits from that era, whether painted by western or eastern artists, demonstrate that the painters had an understanding of facial skin lines and the aging process. The process of creating portraits provides insights into historical contexts and remains significant in contemporary settings, particularly concerning perceptions and identity.
Qualitative Exploration of Abdominal Transplant Surgeon Perception of Retirement
Authors: Chumdermpadetsuk Ritah R , Montalvan Adriana , Canizares Stalin , Hsiao Ling , Sullivan Amy , Rivera Belen , Eckhoff Devin E , Lee David D
Published: October 2024

Background:

For many surgeons, retirement is an emotionally evocative subject, tied to a sense of loss. With minimal guidelines to facilitate a smooth transition, physicians tend to be inadequately prepared. There are few qualitative studies exploring surgeons’ perspectives and none focused on transplant surgeons, a population with arguably unique challenges. We set out to define an “ideal” retirement for transplant surgeons, and identify behavioral and cognitive patterns associated with optimism towards retirement.

Study Design:

We conducted 60-minute semi-structured interviews with 30 division chiefs of transplant surgery to explore their perceptions of retirement. Thematic analysis using a framework approach was performed to identify key themes.

Results:

The cohort was predominantly male (80.0%) and White (76.7%), with 24.8 years in practice on average (range 12-40 years). Participants expressed desires to retire at the peak of their career trajectory and maintain autonomy in this transition. However, when naming signs of impending retirement, they often cited indicators of burnout. Attributes separating those who were optimistic from others included 1) well-rounded sense of identity, 2) holistic attitude towards one’s health and well-being, 3) belief in the ability to exert autonomy over retirement process through long-range planning, 4) community centered mindset, and 5) multifaceted and evolving view of career identity.

Conclusion:

While surgeons aspire to “go out on top,” many envision working until they can no longer endure it. This discrepancy highlights the need for normalizing discussions around retirement. With their unique insights, we have the opportunity to develop supportive interventions, such that transplant surgeons retire in a manner which preserves dignity and celebrates their legacy.
Reproduction results in parallel changes of oxidative stress and immunocompetence in a wild long-living mammal—edible dormouse
Glis glis
Authors: Iwińska Karolina , Boratyński Jan S. , Książek Aneta , Błońska Joanna , Borowski Zbigniew , Konarzewski Marek
Published: October 2024

Oxidative stress (OS) and impaired immune function (IF) have been proposed as key physiological costs of reproduction. The relationship between OS and IF remains unresolved, particularly in long-living iteroparous species. We studied physiological markers of maintenance (OS, IF markers) in lactating, post-lactating and non-lactating females of edible dormice—a long-living rodent. We predicted the OS balance and IF to be compromised by lactation, especially in older females expected to face stronger trade-offs between life functions. We found that the age predictor (body size) correlated negatively with white blood cell level (WBC), positively with neutrophils to lymphocytes ratio and had no effect on OS markers. Oxidative damage markers (reactive oxygen metabolites (ROMs); but not antioxidant capacity) and body size-adjusted WBC were the lowest in lactating, higher in post-lactating and the highest in non-lactating females. Body size/age did not affect this correlation suggesting a similar age-independent allocation strategy during reproduction in this species. The path analysis testing the causal relationship between ROMs and WBC revealed that IF is more likely to affect OS than
vice versa
. Our study indicates the trade-off between crucial life functions during reproduction and suggests that immunosuppression reduces the risk of OS; therefore, mitigating oxidative costs of reproduction.
Frequency-dependent returns in nonlinear public goods games
Authors: Hauert Christoph , McAvoy Alex
Published: October 2024

When individuals interact in groups, the evolution of cooperation is traditionally modelled using the framework of public goods games. These models often assume that the return of the public goods depends linearly on the fraction of contributors. In contrast, in real-life public goods interactions, the return can depend on the size of the investor pool as well. Here, we consider a model in which the multiplication factor (marginal per capita return) for the public goods depends linearly on how many contribute, which results in a nonlinear model of public goods. This simple model breaks the curse of dominant defection found in linear public goods interactions and gives rise to richer dynamical outcomes in evolutionary settings. We provide an in-depth analysis of the more varied decisions by the classical rational player in nonlinear public goods interactions as well as a mechanistic, microscopic derivation of the evolutionary outcomes for the stochastic dynamics in finite populations and in the deterministic limit of infinite populations. This kind of nonlinearity provides a natural way to model public goods with diminishing returns as well as economies of scale.
Modelling human navigation and decision dynamics in a first-person herding task
Authors: bin Kamruddin Ayman , Sandison Hannah , Patil Gaurav , Musolesi Mirco , di Bernardo Mario , Richardson Michael J.
Published: October 2024

This study investigated whether dynamical perceptual-motor primitives (DPMPs) could also be used to capture human navigation in a first-person herding task. To achieve this aim, human participants played a first-person herding game, in which they were required to corral virtual cows, called targets, into a specified containment zone. In addition to recording and modelling participants’ movement trajectories during gameplay, participants’ target-selection decisions (i.e. the order in which participants corralled targets) were recorded and modelled. The results revealed that a simple DPMP navigation model could effectively reproduce the movement trajectories of participants and that almost 80% of the participants’ target-selection decisions could be captured by a simple heuristic policy. Importantly, when this policy was coupled to the DPMP navigation model, the resulting system could successfully simulate and predict the behavioural dynamics (movement trajectories and target-selection decisions) of participants in novel multi-target contexts. Implications of the findings for understanding complex human perceptual-motor behaviour and the development of artificial agents for robust human–machine interaction are discussed.
New specimens of
Bunaia woodwardi
Clarke, 1919 (Euchelicerata): a new member of Offacolidae providing insight supporting the Arachnomorpha
Authors: Lustri Lorenzo , Antcliffe Jonathan B. , Gueriau Pierre , Daley Allison C.
Published: October 2024

The rapid early diversification of arthropods has made understanding internal relationships within the group fiendish. Particularly unresolved is the origin of Euchelicerata, a clade consisting of the Prosomapoda (comprising the extant Xiphosura and Arachnida and the extinct Chasmataspidida, Eurypterida and synziphosurines) and the extinct Offacolidae. Here we describe new material of the Silurian ‘synziphosurine’
Bunaia woodwardi
Clarke, 1919 that reveals previously unknown features of its ventral anatomy: a pair of elongated chelicerae in the prosoma, followed posteriorly by five pairs of biramous appendages, a first pre-abdomen somite bearing a pair of paddle-like uniramous appendages (exopods) and a ventral pretelsonic process. Phylogenetic analyses retrieve
B. woodwardi
as a member of Offacolidae closely related to
Setapedites abundantis
from the Early Ordovician Fezouata Biota. An anatomical comparison of the pretelsonic process of
B. woodwardi
, also present in
Setapedites
, with the posterior trunk morphologies of other Offacolidae, Habeliida and Vicissicaudata, suggests a possible homologous appendicular origin. This proposed apomorphic character supports a monophyletic Arachnomorpha, formed of Vicissicaudata, Habeliida and Euchelicerata. The establishment of this new homology could help to clarify the highly enigmatic phylogeny at the base of the euchelicerates as well as the sequence of character acquisition during their early evolution.
Lagrangian gradient regression for the detection of coherent structures from sparse trajectory data
Authors: Harms Tanner D. , Brunton Steven L. , McKeon Beverley J.
Published: October 2024

Complex flows are often characterized using the theory of Lagrangian coherent structures (LCS), which leverages the motion of flow-embedded tracers to highlight features of interest. LCS are commonly employed to study fluid mechanical systems where flow tracers are readily observed, but they are broadly applicable to dynamical systems in general. A prevailing class of LCS analyses depends on reliable computation of flow gradients. The finite-time Lyapunov exponent (FTLE), for example, is derived from the Jacobian of the flow map, and the Lagrangian-averaged vorticity deviation (LAVD) relies on velocity gradients. Observational tracer data, however, are typically sparse (e.g. drifters in the ocean), making accurate computation of gradients difficult. While a variety of methods have been developed to address tracer sparsity, they do not provide the same information about the flow as gradient-based approaches. This work proposes a purely Lagrangian method, based on the data-driven machinery of regression, for computing instantaneous and finite-time flow gradients from sparse trajectories. The tool is demonstrated on a common analytical benchmark to provide intuition and demonstrate performance. The method is seen to effectively estimate gradients using data with sparsity representative of observable systems.
Astrocytes induce desynchronization and reduce predictability in neuron–astrocyte networks cultured on microelectrode arrays
Authors: Genocchi Barbara , Ahtiainen Annika , Niemi Annika , Barros Michael T. , Tanskanen Jarno M. A. , Lenk Kerstin , Hyttinen Jari , Puthanmadam Subramaniyam Narayan
Published: October 2024

In this article, we aim to study how astrocytes control electrophysiological activity during neuronal network formation. We used a combination of spike/burst analysis, classification of spike waveforms based on various signal properties and tools from information theory to demonstrate how astrocytes modulate the electrical activity of neurons using microelectrode array (MEA) signals. We cultured rat primary cortical neurons and astrocytes on 60-electrode MEAs with different neuron/astrocyte ratios ranging from ‘pure’ neuronal cultures to co-cultures containing 50% neurons and 50% astrocytes. Our results show that astrocytes desynchronize the network and reduce predictability in the signals and affect the repolarization phase of the action potentials. Our work highlights that it is crucial to go beyond standard MEA analysis to assess how astrocytes control neuronal cultures and investigate any dysfunction that could potentially result in neuronal hyperactivity.
β-Defensin gene copy number variation in cattle
Authors: Sidekli Ozge , Oketch John , Fair Sean , Meade Kieran G. , Hollox Edward J.
Published: October 2024

β-Defensins are peptides with antimicrobial roles, characterized by a conserved tertiary structure. Beyond antimicrobial functions, they exhibit diverse roles in both the immune response and fertility, including involvement in sperm maturation and function. Copy number variation (CNV) of β-defensin genes is extensive across mammals, including cattle, with possible implications for reproductive traits and disease resistance. In this study, we comprehensively catalogue 55 β-defensin genes in cattle. By constructing a phylogenetic tree to identify human orthologues and lineage-specific expansions, we identify 1 : 1 human orthologues for 35 bovine β-defensins. We also discover extensive β-defensin gene CNV across breeds, with
DEFB103,
in particular, showing extensive multi-allelic CNV. By comparing β-defensin expression levels in testis from calves and adult bulls, we find that 14 β-defensins, including
DEFB103
, increase in expression during sexual maturation. Analysis of β-defensin gene expression levels in the caput of adult bull epididymis, and β-defensin gene copy number, in 94 matched samples shows expression levels of four β-defensins are correlated with genomic copy numbers, including
DEFB103
. We therefore demonstrate extensive CNV in bovine β-defensin genes, in particular
DEFB103
, with potential functional consequences for fertility.
Skull sinuses precluded extinct crocodile relatives from cetacean-style deep diving as they transitioned from land to sea
Authors: Young Mark T. , Schwab Julia A. , Dufeau David , Racicot Rachel A. , Cowgill Thomas , Bowman Charlotte I. W. , Witmer Lawrence M. , Herrera Yanina , Higgins Robert , Zanno Lindsay , Xing Xu , Clark James , Brusatte Stephen L.
Published: October 2024

During major evolutionary transitions, groups develop radically new body plans and radiate into new habitats. A classic example is cetaceans which evolved from terrestrial ancestors to become pelagic swimmers. In doing so, they altered their air-filled sinuses, transitioning some of these spaces to allow for fluctuations in air capacity and storage via soft tissue borders. Other tetrapods independently underwent land-to-sea transitions, but it is unclear if they similarly changed their sinuses. We use computed tomography to study sinus changes in thalattosuchian crocodylomorphs that transformed from land-bound ancestors to become the only known aquatic swimming archosaurs. We find that thalattosuchian braincase sinuses reduced over their transition, similar to cetaceans, but their snout sinuses counterintuitively expanded, distinct from cetaceans, and that both trends were underpinned by high evolutionary rates. We hypothesize that aquatic thalattosuchians were ill suited to deep diving by their snout sinuses, which seem to have remained large to help drain their unusual salt glands. Thus, although convergent in general terms, thalattosuchians and cetaceans were subject to different constraints that shaped their transitions to water. Thalattosuchians attained a stage similar to less pelagic transitional forms in the cetacean lineage (late protocetid-basilosaurid) but did not become further specialized for ocean life.
Bacterial co-infections in mucormycosis in severely ill populations. An overlooked and complex challenge.
Authors: Corzo Leon Dora , Ahumada-Topete Victor Hugo , Ostrosky-Zeichner Luis
Published: October 2024

Mucormycosis is found in co-infection with bacteria in >50% of the cases. Most of these cases were reported among people with haematological diseases. The two most frequent bacteria found were Pseudomonas aeruginosa and Klebsiella pneumoniae. Almost 40% of the identified bacteria were reported as multidrug resistant (MDR).
A host shift as the origin of tomato bacterial canker caused by Clavibacter michiganensis
Authors: Yañez-Olvera Alan Guillermo , Gómez-Díaz Ambar Grissel , Sélem-Mojica Nelly , Rodríguez-Orduña Lorena , Lara-Ávila José Pablo , Varni Vanina , Alcoba Florencia , Croce Valentina , Legros Thierry , Torres Alberto , Torres Ruíz Alfonso , Tarrats Félix , Vermunt Adriaan , Looije Thorben , Cibrian-Jaramillo Angélica , Valenzuela Miryam , Siri María Inés , Barona-Gomez Francisco
Published: October 2024

The Actinomycetota (formerly Actinobacteria) genus Clavibacter includes phytopathogens with devasting effects in several crops. Clavibacter michiganensis, the causal agent of tomato bacterial canker, is the most notorious species of the genus. Yet, its origin and natural reservoirs remain elusive, and its populations show pathogenicity profiles with unpredictable plant disease outcomes. Here, we generate and analyse a decade-long genomic dataset of Clavibacter from wild and commercial tomato cultivars, providing evolutionary insights that directed phenotypic characterization. Our phylogeny situates the last common ancestor of C. michiganensis next to Clavibacter isolates from grasses rather than to the sole strain we could isolate from wild tomatoes. Pathogenicity profiling of C. michiganensis isolates, together with C. phaseoli and C. californiensis as sister taxa and the wild tomato strain, was found to be congruent with the proposed phylogenetic relationships. We then identified gene enrichment after the evolutionary event, leading to the appearance of the C. michiganesis clade, including known pathogenicity factors but also hitherto unnoticed genes with the ability to encode adaptive traits for a pathogenic lifestyle. The holistic perspective provided by our evolutionary analyses hints towards a host shift event as the origin of C. michiganensis as a tomato pathogen and the existence of pathogenic genes that remain to be characterized.
DNA Hanger: Surface Free Single-Molecule Blotting Platform
Authors: Seol Jincheol , Kim Byungju , Yu Eui-Sang , Jeong Cherlhyun , Lee Jong-Bong
Published: October 2024

Immunoblotting typically requires protein immobilization onto a membrane surface for quantification. Particularly, in real-time single-molecule blotting, stringent surface passivation is essential to prevent false-positive signals from nonspecific binding. In this study, we introduce a novel surface-free single-molecule blotting platform, termed the DNA Hanger. This platform employs a 3D structure of a quartz slide. Modifiedλ-phage DNA molecules are randomly biotinylated along their bases and suspended between 4 μm-high thin barriers, positioned away from the quartz slide surface. A light sheet, produced within the 3D structure, illuminates fluorophore-conjugated proteins bound to the biotinylated DNA, enabling single-molecule detection. The DNA Hanger assay significantly reduces nonspecific binding and enhances sensitivity to sub-picomolar concentrations, suggesting that this platform provides a novel, surface-condition-independent, and real-time approach in a wide range of single-molecule blotting.
Dissecting the Heterogeneity and Tumor-Associated Dynamics of Human Liver Group I ILC via scRNA Sequencing Data
Authors: Zhang Yumo , He Jitian , Li Xue , Chen Huaiyong , Yang Zhouxin , Wang Youwei
Published: October 2024

Single-cell transcriptome analysis has made outstanding contributions to the identification of new cell lineages and the study of cancer immune microenvironment. Yet, the characterization of human liver ILC1s and their dynamic changes in the tumor microenvironment have not been thoroughly studied at this detailed level. Here, we performed an integrated analysis of mouse and human liver immune cells to identify human liver ILC1 based on identified mouse liver ILC1 and to verify its functional similarity. Additionally, our findings highlighted the different expression patterns of the EOMES gene in human versus mouse group I ILCs, suggesting its reduced regulatory significance in human liver NK cells and ILC1 compared to murine models. A unique subset ofCD127hiintermediate ILCs (intILCs) was identified, exhibiting traits of both human liver NK cells and ILC1. Single-cell sequencing data analysis and TCGA were utilized to characterize the distinct alterations in the genes and functions of NK cells, ILC1, and intILCs in human hepatocellular carcinoma. It was found that the dynamic changes of ILC1 and intILCs, along with some of their subpopulations, may be key factors in tumor progression. This study provided new insights into the identification of ILC1 in human liver and the immunologic changes and mechanism of group I ILCs in the tumor microenvironment, and these findings may be applicable to improving the diagnosis and treatment of hepatocellular carcinoma.

Graphical Abstract
CIGB-300 reverses chemo-resistance in MDR1-transfected lung squamous cancer cells
Authors: Wang Meifeng , Tang Dongfang , Luo Xiaofang , Liu Wan , Xie Jiale , Yi Ying , Lan Yaqin , Li Wen , Perea Silvio E. , Dessie Wubliker , Perera Yasser , Qin Zuodong
Published: October 2024

Background

Inhibition of ABC transporter protein activity is considered to be the most effective method to reverse multidrug resistance (MDR). In this study, we evaluated the MDR reversal potential of CIGB-300, a potent CK2 kinase inhibitor.

Methods

ABCB1 overexpressing lung adenocarcinoma NCI-H226 cells were constructed using lentivirus, and the expression of ABCB1 gene and protein was detected by real-time fluorescence quantitative PCR and Western blotting. MTT assay was used to assess the cytotoxicity and MDR reversal effect of CIGB-300.The effect of CIGB-300 on ABCB1 expression was determined by Western Blotting. Cell surface expression and subcellular localization of ABCB1 were examined by Flow Cytometry and Immunofluorescence Staining. Rh123 efflux and accumulation were measured by Fluorescent Enzyme Labeler and Flow Cytometry.

Results

CIGB-300 significantly increased the sensitivity of drug-resistant cells overexpressing the ABCB1 drug efflux pump (NCI-H226-ABCB1), while it had no effect on their parental cell lines. At the same time, its mechanism of action may be related to the inhibition of ABCB1 expression, which was dose-dependent, Moreover, in addition, we demonstrated that CIGB-300 reduced the expression of NFKB and CDC37 proteins.

Conclusions

Our study elucidated that CIGB-300 reverses ABCB1-mediated MDR by inhibiting ABCB1 protein expression or intracellular signaling and provides a potential therapeutic strategy to improve tumor chemosensitivity.
Systemic inflammation and lymphocyte activation precede rheumatoid arthritis
Authors: He Ziyuan , Glass Marla C. , Venkatesan Pravina , Feser Marie L. , Lazaro Leander , Okada Lauren Y. , Tran Nhung T. T. , He Yudong D. , Rachid Zaim Samir , Bennett Christy E. , Ravisankar Padmapriyadarshini , Dornisch Elisabeth M. , Arishi Najeeb A. , Asamoah Ashley G. , Barzideh Saman , Becker Lynne A. , Bemis Elizabeth A. , Buckner Jane H. , Collora Christopher E. , Criley Megan A. L. , Demoruelle M. Kristen , Fleischer Chelsie L. , Garber Jessica , Genge Palak C. , Gong Qiuyu , Graybuck Lucas T. , Gustafson Claire E. , Hattel Brian C. , Hernandez Veronica , Heubeck Alexander T. , Kawelo Erin K. , Krishnan Upaasana , Kuan Emma L. , Kuhn Kristine A. , LaFrance Christian M. , Lee Kevin J. , Li Ruoxin , Lord Cara , Mettey Regina R. , Moss Laura , Musgrove Blessing , Nguyen Kathryn , Ochoa Andrea , Parthasarathy Vaishnavi , Pebworth Mark-Phillip , Pedrick Chong , Peng Tao , Phalen Cole G. , Reading Julian , Roll Charles R. , Seifert Jennifer A. , Siedschlag Marguerite D. , Speake Cate , Striebich Christopher C. , Stuckey Tyanna J. , Swanson Elliott G. , Takada Hideto , Thai Tylor , Thomson Zachary J. , Trieu Nguyen , Tsaltskan Vlad , Wang Wei , Weiss Morgan D. A. , Westermann Amy , Zhang Fan , Boyle David L. , Goldrath Ananda W. , Bumol Thomas F. , Li Xiao-jun , Holers V. Michael , Skene Peter J. , Savage Adam K. , Firestein Gary S. , Deane Kevin D. , Torgerson Troy R. , Gillespie Mark A.
Published: October 2024

Some autoimmune diseases, including rheumatoid arthritis (RA), are preceded by a critical subclinical phase of disease activity. Proactive clinical management is hampered by a lack of biological understanding of this subclinical ‘at-risk’ state and the changes underlying disease development. In a cross-sectional and longitudinal multi-omics study of peripheral immunity in the autoantibody-positive at-risk for RA period, we identified systemic inflammation, proinflammatory-skewed B cells, expanded Tfh17-like cells, epigenetic bias in naive T cells, TNF+IL1B+ monocytes resembling a synovial macrophage population, and CD4 T cell transcriptional features resembling those suppressed by abatacept (CTLA4-Ig) in RA patients. Our findings characterize pathogenesis prior to clinical diagnosis and suggest the at-risk state exhibits substantial immune alterations that could potentially be targeted for early intervention to delay or prevent autoimmunity. We provide a suite of tools athttps://apps.allenimmunology.org/aifi/insights/ra-progression/to facilitate exploration and enhance accessibility of this extensive dataset.

One Sentence Summary

ACPA+ at-risk individuals show RA-like inflammation and multi-compartment immune dysregulation during transition to clinically active RA
Predicting Immunogenic CD4+ T Cell Epitopes in Bacteria Using Antigen and Peptide Features
Authors: Marrama Daniel , Battey Hannah , Khaledian Ehdieh , Müller Miriam , Panda Sudhasini , da Silva Antunes Ricardo , Sette Alessandro , Arlehamn Cecilia S. Lindestam , Peters Bjoern
Published: October 2024

Background

T cell epitope prediction methods have been broadly utilized to facilitate epitope discovery in infectious agents and help design reagents, diagnostics, and vaccines. Current prediction methods are mainly focused on peptide presentation by MHC molecules, which is a necessary but not sufficient requirement for an epitope. For complex pathogens such as bacteria, it would be desirable to make such predictions more specific to limit the number of candidates that have to be experimentally tested.

Objective

To develop a machine learning-based prediction model that integrates both peptide-level and antigen-level features to improve the specificity of CD4+ T cell epitope predictions for bacteria.

Methods

We used a dataset of 20,216 peptides fromMycobacterium tuberculosis(Mtb), tested for T cell recognition in Mtb-infected participants, that led to the discovery of n = 144 peptide epitopes. For each peptide, we calculated six peptide-level features (e.g. MHC class II binding predictions and conservation scores) and six antigen-level features (e.g. including RNA expression levels and subcellular localization scores). Three machine learning algorithms—Random Forest, Gradient Boosting, and XGBoost—were trained using stratified, 5-fold cross-validation and combined into an ensemble model. Experimental validation was performed onStreptococcus pneumoniaepeptides, using ex vivo IFNγ assays to confirm the predictive performance.

Results

The ensemble model achieved an ROC-AUC of 0.91 in predicting immunogenic peptides in theMycobacterium tuberculosis(Mtb) dataset. Gene expression and conservation were identified as the most impactful features, followed by MHC class II binding predictions. When validated on an independentBordetella pertussisdataset, the model demonstrated accurate predictive capability, especially for peptides with broad recognition in the participant cohort (ROC-AUC up to 0.82). Prospectively applying the model toStreptococcus pneumoniae, we synthesized peptides predicted by our ensemble model to be immunogenic or non-immunogenic. Ex vivo testing with PBMCs from healthy participants showed that peptides predicted to be immunogenic elicited significantly higher IFNγ responses than non-immunogenic peptides, validating the model.

Conclusions

Our machine learning approach, integrating both peptide and antigen features, effectively predicts immunogenic CD4+ T cell epitopes across different bacterial pathogens. This method enhances epitope selection efficiency, aiding vaccine development and immunological research by reducing the need for extensive experimental screening.