bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR/Cas9 in the treatment of sickle cell disease (SCD) and its comparison with traditional treatment approaches: a review
Authors: Tariq Hamza , Khurshid Fatima , Khan Muhammad Hamza , Dilshad Aamna , Zain Ahmad , Rasool Warda , Jawaid Alishba , Kunwar Digbijay , Khanduja Sneha , Akbar Anum
Published: October 2024

Sickle cell disease (SCD) is a common hereditary blood disorder that profoundly impacts individuals’ health, causing chronic pain, anemia, organ damage, increased susceptibility to infections, and social and psychological effects. Over the years, advances in treatment have improved the long-term outcomes of SCD patients. However, problems such as limited access to hematopoietic stem cell transplantation (HSCT) and potential complications associated with the available therapies underscore the importance of continued research and development. The recent FDA approval of Casgevy (Exagamglogene autotemcel), a genetic therapy based on CRISPR/Cas9 technology, demonstrates a comprehensive effort to address the complexity of SCD using new technologies. This review explores the potential of CRISPR/Cas9 for treating SCD and evaluates its efficacy, safety, and long-term outcomes compared to traditional treatment approaches. Long-term research is needed to comprehensively assess the safety, effectiveness, and inclusion of CRISPR/Cas9, ensuring its overall efficacy.
TFE3-rearranged RCC with osseous metaplasia found on bone mass densitometry
Authors: Nasrallah Oussama G. , AlJardali Baraa , El Asmar Jose M. , El Kasti Abdallah , El Hajj Albert
Published: October 2024

Introduction and importance:

Renal cell carcinoma (RCC) is the most common primary renal malignancy in patients between the ages of 50 and 70. A rare described variant of RCC is transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) rearranged RCC. Osseous metaplasia, which refers to the occurrence of normal bone tissue in soft tissue, has been observed in all subtypes of renal cell carcinoma (RCC); however, only three previous case reports have documented the occurrence of osseous metaplasia in TFE3-rearranged RCC.

Case presentation:

We present a case of a 65-year-old woman presenting with an incidentally discovered calcified Bi-lobed renal mass detected on bone densitometry composed of a calcified thick-walled cyst measuring 7×6.5×6.5 cm showing intraluminal densities and heterogeneous content, and a lobulated partially exophytic renal mass measuring 4.5×5.5×4.5 cm. The patient underwent robotic-assisted radical nephrectomy confirming the diagnosis of RCC with osseous metaplasia extending into the pelvic calyces and renal sinus fat implicating a pathological stage of T3a.

Clinical discussion:

TFE3-rearranged RCCs represent a rare sub-classification in adult RCCs. It may be associated with unfavorable prognosis and aggressive patterns of disease in the presence of osseous metaplasia.

Conclusion:

This is the first case in the literature of TFE3-rearranged RCC with osseous metaplasia on bone mass densitometry scan and the fourth case of TFE3-rearranged RCC with osseous metaplasia. The patient is to be treated as a high-risk patient and to be monitored closely for recurrence of malignancy, as indicated in the EAU guidelines.
Improvements in Transitional Care Among Medicaid-Insured Patients With Serious Mental Illness
Authors: Nikpour Jacqueline , Langston Christine , Brom Heather , Sliwinski Kathy , Mason Aleigha , Garcia Dianne , Grantham-Murillo Marsha , Bennett Jovan , Cacchione Pamela Z. , Brooks Carthon J. Margo
Published: October 2024

Background:

The Thrive program is an evidenced-based care model for Medicaid-insured adults in the hospital-to-home transition. A substantial portion of Thrive participants live with serious mental illness (SMI), yet Thrive’s efficacy has not been tested among these patients.

Purpose:

To compare 30-day postdischarge outcomes between Thrive participants with and without SMI and explore Thrive’s appropriateness and acceptability among participants with SMI.

Methods:

We conducted a sequential explanatory mixed-methods study of 252 (62 with SMI) Thrive participants discharged from an academic medical center from February 2021 to August 2023. Interviews of participants with SMI were analyzed using rapid qualitative analysis.

Results:

Participants with and without SMI experienced similar rates of 30-day readmissions, emergency room visits, and postdischarge follow-up visits, with these differences being nonsignificant. Participants with SMI were highly satisfied with Thrive’s care coordination and attention to social needs, yet participants suggested stronger connections to behavioral health care.

Conclusions:

Participants with and without SMI benefit equitably from Thrive.
Sociodemographic Characteristics, Anxiety, Depression Levels, and Emotional and Behavioral Problems in Hospitalized COVID-19–Positive Children and Adolescents
Authors: Kizilyaprak Eda , Arslan Semiha Comertoglu , Altun Hatice , Gunes Hatice , Dincer Serpil
Published: October 2024

This study aimed to investigate anxiety, depression levels, and emotional/behavioral problems of children and adolescents while being treated in the COVID-19 unit. The present study included 50 children who were COVID-19 positive, aged 7–18 years, and 50 age- and gender-matched healthy controls. The sociodemographic data form and Revised Child Anxiety and Depression Scale–Child Version (RCADS-C) were applied to all children, and all families were asked sociodemographic data form, Revised Child Anxiety and Depression Scale–Parent Version (RCADS-P), and Strengths and Difficulties Questionnaire (SDQ). There was no significant difference between the patient and control groups in terms of anxiety, depression levels, and emotional/behavioral problems. The conduct problems subscale score of SDQ in the patient group was found to be significantly lower than the control group (p = 0.037). Separation anxiety subscale scores of RCADS (p = 0.034) and the rate of accompanying companions (p = 0.01) in the patient group were found to be significantly higher in preadolescents than in adolescents. In conclusion, this study demonstrated that children and adolescents who were COVID-19 positive were not different from healthy children in terms of anxiety and depression levels, and emotional and behavioral problems in the acute period during inpatient treatment.
The Mediating Role of Trauma Centrality in the Correlation Between Coping Self-Efficacy and Posttraumatic Growth Level of Disaster Volunteers
Authors: Arpacı Rabia , Ayar Duygu , Karasu Fatma
Published: October 2024

Volunteers who respond to disasters play a crucial role in disaster management. However, their indirect exposure to traumatic events during their duties can adversely affect their mental health. The aim of the study was to determine the correlation among trauma centrality, coping self-efficacy, and posttraumatic growth and trauma centrality as possible mediator role in this relationship. A total of 112 disaster volunteers participated. The data were collected with a Demographic Form, the Centrality of Events Scale, the Post-Traumatic Growth Scale, and the Coping Self-Efficacy Scale. Disaster volunteers exhibited above average event centrality, high levels of posttraumatic growth, and coping self-efficacy. A positive correlation was identified among trauma centrality, posttraumatic growth, and coping self-efficacy, with trauma centrality playing a full mediating role. This study will be instrumental in better understanding the posttraumatic processes of disaster volunteers and in strengthening coping capacities, guiding the implementation of preventive and protective psychosocial interventions.
Prognostic Value of IMP3 Expression in Squamous Cervical Cancer
Authors: Krešić Tanja , Klarić Marko , Eminović Senija , Kolobarić Anita , Dugandžić Šimić Ana , Bošković Ana
Published: October 2024

Cervical cancer remains one of the leading causes of death from malignant diseases in women worldwide. Primary and secondary prevention have led to better outcomes in developed countries, whereas in developing countries, cervical cancer continues to be responsible for an unjustifiably high number of fatalities. The discovery of new tumor biomarkers can lead to earlier diagnosis, better therapeutic decisions, and improved treatment methods. IMP3 is a protein responsible for invasiveness and other aggressive characteristics of tumor processes. Its highly specific expression has been proven in various malignant processes. The level of IMP3 expression in cervical cancer cells could be used as a prognostic factor for a worse disease course. In this study, IMP3 expression was examined in 80 patients who underwent surgery for squamous cell cervical cancer in the first FIGO stage of the disease, and its association with disease-free period and overall survival was investigated. Data analysis did not show a statistically significant association between IMP3 expression and the mentioned primary outcomes, despite its association with clinical-pathological indicators of advanced disease. In conclusion, the analysis of IMP3 protein expression in patients with early-stage cervical cancer is of limited utility.
Cytokine Signature Differences in Major Phenotypic Groups of Behçet Disease
Authors: Deniz Rabia , Emrence Zeliha , Punar Şeyma , İleri Berk , Arga Kazım Yalçın , Alibaz-Öner Fatma , Bes Cemal , Direskeneli Haner , Gül Ahmet , Erzik Can
Published: October 2024

Objectives

Behçet disease (BD) has heterogeneous presentations, mainly mucocutaneous, vascular, and ocular manifestations. The mechanisms associated with different phenotypes have not been clarified. We aimed to investigate the expression of innate and adaptive immunity–related cytokines in these 3 main BD phenotypes in active and untreated states and remission after treatment to be able to develop a cytokine-based treatment algorithm.

Methods

Serum samples were isolated from 41 patients with newly diagnosed active BD (aBD), which consisted of 19 mucocutaneous aBD, 11 ocular aBD (o-aBD), and 11 vascular aBD patients, 35 patients in remission (rBD), and 9 healthy controls (HC). Serum levels of each cytokine were measured with sandwich enzyme-linked immunosorbent assay and analyzed as both raw measurements and corrected levels for each 1 million white blood cells.

Results

The study included 41 aBD patients (female/male [F/M]: 9/32; median age, 29 years), 35 rBD patients (F/M: 9/26; median age, 29 years), and 9 HC (F/M: 3/6; median age, 28 years). The serum interferon γ level was significantly higher in the aBD group than in the rBD (116 vs. 92 pg/mL, p = 0.022). The serum interleukin 35 (IL-35) level was significantly higher in the HC group compared with aBD and rBD (p = 0.05). IL-17–related cytokines were lower in o-aBD. With treatment, they increased in o-aBD but decreased in mucocutaneous aBD and vascular aBD patients.

Conclusion

This study supports the involvement of both innate and TH1-predominated adaptive immune responses across all BD phenotypes. The IL-17 and TH17-related immune responses appear less prominent in ocular BD, which may explain the ineffectiveness of IL-17 blockade in treating ocular BD. These findings support the need for further studies using comprehensive gene expression analyses to develop targeted treatment strategies for BD phenotypes.
Influence of Preoperative Inflammatory Status on Outcomes of Alveolar Bone Grafting in Patients With Cleft Lip
Authors: Zhang Zhilu , Wang Yu , Di Wenjun , Ma Chenhao , Wang Yongqian
Published: October 2024

After secondary alveolar bone grafting, the outcome of bone formation is always a problem that leads to repeat surgery. Bone formation is closely related to the inflammatory and immune status of patients. To achieve better bone formation results, this study aimed to investigate the influence of preoperative inflammatory indicators on the bone survival ratio (BSR) of secondary alveolar bone grafting. A retrospective study was conducted on 62 patients who underwent surgery by the same surgeon between January 2016 to December 2022. Demographic and laboratory data were included as independent variables. The BSR calculated from computed tomography data was included as the dependent variable. Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression analysis were performed. The analysis results revealed significant correlations between BSR and preoperative inflammatory markers, including neutrophil percentage, neutrophil-to-lymphocyte ratio, lymphocyte percentage (L%), lymphocyte count, and monocyte-to-lymphocyte ratio. Multiple linear regression identified L% as an independent factor of BSR, with lower L% associated with higher BSR. Preoperative inflammatory markers may influence BSR after alveolar bone grating. A lower value of L% indicates a better postoperative bone formation outcome. Understanding these associations can aid clinicians in treatment planning and patient stratification.
Myoepithelial Carcinoma of the External Auditory Canal With Extension Into the Middle Ear and Mastoid
Authors: Fabry Milena , Cameron Nicholas , Smith Collin , Dietz Wolfgang
Published: October 2024

Myoepithelial carcinoma is a rare disease of the head and neck, with only a handful of cases reported occurring within the external auditory canal, middle ear, and mastoid. The patient discussed is a 67-year-old male with a prior history of a bilateral tympanomastoidectomy for cholesteatoma and a prior history of left parotidectomy and adjuvant radiation for pleomorphic sarcoma. Three years after the parotidectomy, the patient presented with contralateral ear fullness. During an intraoperative examination, a fibrous mass was encountered, which revealed an invasive salivary gland neoplasm, myoepithelial subtype. Definitive treatment consisted of a right radical mastoidectomy, temporal bone resection, and canal closure with adjuvant chemoradiation. This case serves to contribute to the established literature regarding this particular subtype of head and neck cancer, as well as provide the reader with a brief review of this rare entity.
Positional Plagiocephaly Side and Neurodevelopmental Delay: Study on 408 Infants
Authors: Pinyot Joan , Lacambra David , Garriga Maria , Pinyot Maria , Niubó Josep Maria
Published: October 2024

Objective:

Provide data on a cross-sectional study of neurodevelopmental delays in positional plagiocephaly (PP) based on severity and flattening side on early childhood patients.

Methods:

Neurodevelopment of 408 PP in patients with an age range of 3 to 59 months was assessed with Battelle Developmental Inventory (BDI) tests during and after their cranial orthotic treatment. Data obtained were compared with the cranial anthropometric measurements taken the same day the test was made, and results were segregated by flattening side, grouped by diagnosis and severity, segmented by age group, and split by sex.

Results:

From 3983 patients with positional skull deformities and simple craniosynostosis, 526 patients accepted to participate and took a total of 1261 BDI tests. Premature, patients with neurological diseases, cranial malformations, tests taken when positional skull deformity was corrected, and tests without plagiocephaly were excluded. The resulting database was made of 408 PP patients (300 boys and 108 girls) and 883 BDI tests (345 with left-side plagiocephaly and 538 with right-side plagiocephaly). Significant neurodevelopmental delay in more than one BDI domain on left-side plagiocephaly tests is observed in 76.4% of female and 92.2% of male patients and on right-side plagiocephaly tests in 75.5% of female and 95.5% of male patients. Neurodevelopmental delay difference between flattening sides, when both plagiocephaly sides presented significant delays, ranges from 0.2 to 3 months (BDI domain fine motor, Cephalic Index range ≥85 <100; BDI communication, age group 18–23).

Conclusion:

Neurological delay may vary depending on plagiocephaly side, thus when evaluating plagiocephaly patients the flattening side should be noted.
Immediate Injections of Botulinum Toxin A After Surgical Excision for Ear Keloids: A Retrospective Study
Authors: Li Shu Hua , Shan Xiu Juan , Wang Zhen Hua , Tao Shu Jie
Published: October 2024

Background:

Ear keloids are pathologic scar hyperplasia in the ear region. The most therapeutic approach was surgical shave excision with radiation therapy. However, radiation therapy is easily delivered to healthy surrounding tissues. In the last years, injections with botulinum toxin type A (BTX-A) have been proven to improve surgical scars effectively in clinical trials. This study aimed to evaluate the effect of immediate injections of BTX-A after surgical excision for ear keloids.

Methods:

From January 2020 to January 2023, 33 consecutive patients with ear keloids were enrolled. All patients underwent scar excision and revision at the same time when they needed BTX-A. It was injected into surgical wound closure immediately after surgery. The results of this study were evaluated at follow-up from 7 to 18 months using the Vancouver Scar Scale (VSS) and the Visual Analogue Scale (VAS).

Results:

From January 2020 to January 2023, 33 patients received concomitant therapy of immediate injections of BTX-A after surgery for ear keloids. The patients were evaluated at follow-ups lasting 7 to 18 months. Only one case recurred within the follow-up period, and no adverse effects were reported.

Conclusion:

This study demonstrates that significant cosmetic outcomes in ear keloid treatment were achieved after early postsurgical BTX-A injections. The patients reported high satisfaction and few complications.
Application of Indocyanine Green Fluorescence Imaging During Laparoscopic Reoperations of the Biliary Tract Enhances Surgical Precision and Efficiency
Authors: Xu Ding-Wei , Li Xin-Cheng , Li Ao , Zhang Yan , Hu Manqin , Huang Jie
Published: October 2024

Background:

A history of abdominal surgery is considered a contraindication for laparoscopic procedures. However, the advancements in laparoscopic instruments and techniques have facilitated the performance of increasingly intricate operations, even in patients with prior abdominal surgeries. ICG fluorescence imaging technology offers advantages in terms of convenient operation and clearer intraoperative bile duct imaging, as confirmed by numerous international clinical studies on its feasibility and safety. The application of ICG fluorescence imaging technology in repeat laparoscopic biliary surgery, however, lacks sufficient reports.

Methods:

The clinical data of patients who underwent elective reoperation of the biliary tract in our department between January 2020 and June 2022 were retrospectively analyzed. ICG was injected peripherally before the operation, and near-infrared light was used for 3-dimensional imaging of the bile duct during the operation.

Results:

Altogether, 143 patients were included in this study and divided into the fluorescence and nonfluorescence groups according to the inclusion criteria. Among the 26 patients in the fluorescence group, cholangiography was successfully performed in 24 cases, and the success rate of intraoperative biliary ICG fluorescence imaging was 92.31%. The intraoperative biliary tract identification time was significantly different between the fluorescence and nonfluorescence groups, but no statistical difference was observed in the final operation method, operative time, and intraoperative blood loss between the 2 groups. Although there was no significant difference in the postoperative ventilation rate, incidence of bile leakage, and stone recurrence rate at 6 months postoperatively between the 2 groups (P>0.05), a significant difference in postoperative hospitalization days was observed (P=0.032).

Conclusion:

The application of ICG fluorescence imaging technology in laparoscopic reoperation of the biliary tract is useful for the early identification of the biliary tract during operation, thereby shortening the operative time and reducing the risk of damage to nonoperative areas. This approach also enhances the visualization of the biliary system and avoids secondary injury intraoperatively due to poor identification of the biliary system. This technique is safe for repeat biliary tract surgery and has a good application prospect.
Are new pediatric trauma centers located close to the high-risk populations? A geolocation study
Authors: Williams Keyonna M. , Scholtz Nicole O. , Plagens Connor , Tubbs Darrell , Ehrlich Peter F.
Published: October 2024

BACKGROUND

Higher rates of injury occur in children who live in low socioeconomic areas. Since 2010, the number of verified Level I and Level II pediatric trauma centers (PTCs) has doubled. The purpose of this study is to look at the location of new verified PTC in relation to children living in high-risk areas.

METHODS

Historical and recent data about verified Level I and Level II PTCs were obtained from the American College of Surgeons (ACS), the American Trauma Society, and State Data where available. Census data were obtained from the US Census Bureau's American Community Survey for 2010 and 2020 for children younger than 18 years. The pediatric population was stratified by (1) poverty threshold and (2) living within 30 miles of PTC. The census data and trauma center locations were geocoded using the ArcGIS Pro program. Data analysis was performed at the census tract level.

RESULTS

A total of 55 Level I or Level II ACS-verified PTCs were in the United States in 2010 and 116 in 2020. In 2010, there were 14.5 million children (19.6%) below the poverty threshold and 12.9 million (17.8%) in 2020. In 2010, 23 states did not have an ACS-verified PTC either in the state or in a neighboring state within 30 miles. By 2020, only nine states did not have an ACS-verified PTC or a center in a neighboring state within 30 miles. When state level data were included, this dropped to four. The 19 states who had new verified PTCs covered between 14% and 21% of children below the poverty level. The percentage of children below the poverty threshold and less than 30-mile access to a Level I or Level II PTC in 2010 was 74.56% compared with children above poverty and less than 30-mile access, which was 70.34% (p< 0.0001). In 2020, children below poverty without 30-mile access had been reduced to 52% and 45.54% for children above poverty level (p< 0.0001). Thus, there was a greater increase in 30-mile access for children above the poverty level than for those below the poverty level (24.8% vs. 22.6%,p< 0.001).

CONCLUSION

On a national level, despite doubling the number of PTC, it has not improved 30-mile access for high-risk children. Alternatively, 19 states now have better access.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Decoding burst swimming performance: a scaling perspective on time-to-fatigue
Authors: Ashraf Muhammad Usama , Nyqvist Daniel , Comoglio Claudio , Nikora Vladimir , Marion Andrea , Domenici Paolo , Manes Costantino
Published: October 2024

Fatigue curves quantify fish swimming performance, providing information about the time (

T

f

) fish can swim against a steady flow velocity (

U
f

) before fatiguing. Such curves represent a key tool for many applications in ecological engineering, especially for fish pass design and management. Despite years of research, though, our current ability to model fatigue curves still lacks theoretical foundations and relies primarily on fitting empirical data, as obtained from time-consuming and costly experiments. In the present article, we address this shortcoming by proposing a theoretical analysis that builds upon concepts of fish hydrodynamics to derive scaling laws linking statistical properties of

T

f

to velocities

U
f

, pertaining to the so-called burst range. Theoretical arguments, in the present study, suggest that the proposed scaling laws may hold true for all fish species and sizes. A new experimental database obtained from over 800 trials and five small-sized Cypriniformes support theoretical predictions satisfactorily and calls for further experiments on more fish species and sizes to confirm their general validity.
Effect of infusion direction on convection-enhanced drug delivery to anisotropic tissue
Authors: Yang Yi , Yuan Tian , Rodriguez y Baena Ferdinando , Dini Daniele , Zhan Wenbo
Published: October 2024

Convection-enhanced delivery (CED) can effectively overcome the blood–brain barrier by infusing drugs directly into diseased sites in the brain using a catheter, but its clinical performance still needs to be improved. This is strongly related to the highly anisotropic characteristics of brain white matter, which results in difficulties in controlling drug transport and distribution in space. In this study, the potential to improve the delivery of six drugs by adjusting the placement of the infusion catheter is examined using a mathematical model and accurate numerical simulations that account simultaneously for the interstitial fluid (ISF) flow and drug transport processes in CED. The results demonstrate the ability of this direct infusion to enhance ISF flow and therefore facilitate drug transport. However, this enhancement is highly anisotropic, subject to the orientation of local axon bundles and is limited within a small region close to the infusion site. Drugs respond in different ways to infusion direction: the results of our simulations show that while some drugs are almost insensitive to infusion direction, this strongly affects other compounds in terms of isotropy of drug distribution from the catheter. These findings can serve as a reference for planning treatments using CED.
Bounded risk disposition explains Turing patterns and tipping points during spatial contagions
Authors: Jamerlan C. M. , Prokopenko M.
Published: October 2024

Spatial contagions, such as pandemics, opinion polarization, infodemics and civil unrest, exhibit non-trivial spatio-temporal patterns and dynamics driven by complex human behaviours and population mobility. Here, we propose a concise generic framework to model different contagion types within a suitably defined contagion vulnerability space. This space comprises risk disposition, considered in terms of bounded risk aversion and adaptive responsiveness and a generalized susceptibility acquisition. We show that resultant geospatial contagion configurations follow intricate Turing patterns observed in reaction–diffusion systems. Pattern formation is shown to be highly sensitive to changes in underlying vulnerability parameters. The identified critical regimes (tipping points) imply that slight changes in susceptibility acquisition and perceived local risks can significantly alter the population flow and resultant contagion patterns. We examine several case studies using Australian datasets (COVID-19 pandemic; crime incidence; conflict exposure during COVID-19 protests; real estate businesses and residential building approvals) and demonstrate that these spatial contagions generated Turing patterns in accordance with the proposed model.
Using mangrove and field observation data to identify fine-scale species distributions: a case study in bockadams (Serpentes: Homalopsidae:
Cerberus
)
Authors: Bernstein Justin M. , Bautista Joward B. , Clores Michael A. , Brown Rafe M. , Ruane Sara , Sanguila Marites B. , Alis-Besenio Mary Grace Joyce , Pejo Cory Lyn F. , Cuesta Michael A.
Published: October 2024

Characterization of species distributions is a fundamental challenge in biodiversity science, with particular significance for downstream evolutionary studies, conservation efforts, field-based faunal studies and estimates of species diversity. Checklists and phylogenetic studies often focus on poorly known, rare taxa with limited ranges. However, studies of widely distributed, ecologically important species that are abundant in their preferred microhabitats are also important for systematics and local conservation efforts, but less often studied. We collected novel natural history data during fieldwork (2019–2023) for Philippine populations of bockadams (Homalopsidae:
Cerberus
), one of the most abundant vertebrates in Southeast Asian aquatic systems. Considered a coastal snake, many studies report
Cerberus
inland. We report the frequency of encounters of
Cerberus schneiderii
, and the IUCN data-deficient, Philippine-endemic
Cerberus microlepis
during six expeditions (62 days; 1041 person-hours). We report new occurrence data for 69
C. schneiderii
and
6 C. microlepis
for coastal and inland populations, water measurements and dietary observations. Regression analyses and ecological niche models show the importance of coastal and mangrove habitats for
Cerberus
. Our study is the most comprehensive assessment of Philippine
Cerberus
populations to date and provides critical baseline natural history data for downstream research on widespread and range-restricted species of Southeast Asian snakes.
Causal evidence for social group sizes from Wikipedia editing data
Authors: Burgess M. , Dunbar R. I. M.
Published: October 2024

Human communities have self-organizing properties in which specific Dunbar Numbers may be invoked to explain group attachments. By analysing Wikipedia editing histories across a wide range of subject pages, we show that there is an emergent coherence in the size of transient groups formed to edit the content of subject texts, with two peaks averaging at around

N
=
8

for the size corresponding to maximal contention, and at around

N
=
4

as a regular team. These values are consistent with the observed sizes of conversational groups, as well as the hierarchical structuring of Dunbar graphs. We use a model of bipartite trust to derive a scaling law that fits the data and may apply to all group size distributions when these are based on attraction to a seeded group process. In addition to providing further evidence that even spontaneous communities of strangers are self-organizing, the results have important implications for the governance of the Wikipedia commons and for the security of all online social platforms and associations.
Probability of early infection extinction depends linearly on the virus clearance rate
Authors: Juhász N. , Bartha F. A. , Marzban S. , Han R. , Röst G.
Published: October 2024

We provide an
in silico
study of stochastic viral infection extinction from a pharmacokinetical viewpoint. Our work considers a non-specific antiviral drug that increases the virus clearance rate, and we investigate the effect of this drug on early infection extinction. Infection extinction data are generated by a hybrid multiscale framework that applies both continuous and discrete mathematical approaches. The central result of our paper is the observation, analysis and explanation of a linear relationship between the virus clearance rate and the probability of early infection extinction. The derivation behind this simple relationship is given by merging different mathematical toolboxes.
Life-history and genetic relationships in cooperatively breeding dwarf mongoose groups
Authors: Arbon Josh J. , Morris-Drake Amy , Kern Julie M. , Howell Gabrielle M. K. , Wentzel Jeanette , Radford Andrew N. , Nichols Hazel J.
Published: October 2024

Cooperatively breeding societies show distinct interspecific variations in social and genetic organization. Long-term studies provide invaluable data to further our understanding of the evolution and maintenance of cooperative breeding but have also demonstrated how variation exists within species. Here we integrate life-history, behavioural and genetic data from a long-term study of dwarf mongooses
Helogale parvula
in South Africa to document mating, breeding, dispersal and relatedness patterns in this population and compare them to those found in a Tanzanian population at the other extreme of the species’ range. Our genetic data reveal high levels of reproductive skew, above that expected through observational data. Dispersal was male-biased and was seen more frequently towards the onset of the breeding season, but females also regularly switched between groups. These patterns of breeding and dispersal resulted in a genetically structured population: individuals were more related to groupmates than outsiders, apart from the unrelated dominant pair, ultimately resulting in reduced inbreeding risk. Our results also demonstrate that dwarf mongooses are largely consistent in their social structure across their sub-Saharan distribution. This work demonstrates the direct and indirect pathways to reproductive success for dwarf mongooses and helps to explain the maintenance of cooperative breeding in the species.
Existence and uniqueness of periodic pseudospherical surfaces emanating from Cauchy problems
Authors: Duruk Mutlubas Nilay , Freire Igor Leite
Published: October 2024

We study implications and consequences of well-posed solutions of Cauchy problems of a Novikov equation describing pseudospherical surfaces. We show that if the co-frame of dual one-forms satisfies certain conditions for a given periodic initial datum, then there exist exactly two families of periodic one-forms satisfying the structural equations for a surface. Each pair then defines a metric of constant Gaussian curvature and a corresponding Levi-Civita connection form. We prove the existence of universal connection forms giving rise to second fundamental forms compatible with the metric. The main tool to prove our geometrical results is the Kato’s semi-group approach, which is used to establish well-posedness of solutions of the Cauchy problem involved and ensure

C
1

regularity for the first fundamental form and the Levi-Civita connection form.
Asymptotic limits of transient patterns in a continuous-space interacting particle system
Authors: González-Tokman Cecilia , Oelz Dietmar B.
Published: October 2024

We study a discrete-time interacting particle system with continuous state space, which is motivated by a mathematical model for turnover through branching in actin filament networks. It gives rise to transient clusters reminiscent of actin filament assemblies in the cortex of living cells. We reformulate the process in terms of the inter-particle distances and characterize their marginal and joint distributions. We construct a recurrence relation for the associated characteristic functions and pass to the large population limit, reminiscent of the Fleming–Viot super processes. The precise characterization of all marginal distributions established in this work opens the way to a detailed analysis of cluster dynamics. We also obtain a recurrence relation that enables us to compute the moments of the asymptotic single particle distribution characterizing the transient aggregates. Our results indicate that aggregates have a fat-tailed distribution.
Interannual Magneto–Coriolis modes and their sensitivity on the magnetic field within the Earth’s core
Authors: Gerick F. , Livermore P. W.
Published: October 2024

Linear modes for which the Coriolis acceleration is almost entirely in balance with the Lorentz force are called Magneto–Coriolis (MC) modes. These MC modes are thought to exist in Earth’s liquid outer core and could therefore contribute to the variations observed in Earth’s magnetic field. The background state on which these waves ride is assumed here to be static and defined by a prescribed magnetic field and zero flow. We introduce a new computational tool to efficiently compute solutions to the related eigenvalue problem, and study the effect of a range of both axisymmetric and non-axisymmetric background magnetic fields on the MC modes. We focus on a hierarchy of conditions that sequentially partition the numerous computed modes into those which are: (i) in principle observable, (ii) those which match a proxy for interannual geomagnetic signal over 1999–2023, and (iii) those which align with core-flows based on recent geomagnetic data. We found that the background field plays a crucial role in determining the structure of the modes. In particular, we found no examples of axisymmetric background fields that support modes consistent with recent geomagnetic changes, but that some non-axisymmetric background fields do support geomagnetically consistent modes.
Nanocluster-Mediated Signaling Crosstalk between FcγR and TLR4 in Macrophage Inflammatory Responses
Authors: Lee Seonik , Yu Yan
Published: October 2024

Receptor crosstalk, the interaction between different receptors to modulate signaling, is crucial for fine-tuning the inflammatory responses of innate immune cells. Although the synergistic crosstalk between Toll-like receptor (TLR)4 and Fc gamma receptor (FcγR) is well documented, the detailed mechanism underlying this synergy remains unclear. In this study, we addressed this knowledge gap by imaging the molecular organization of TLR4 and FcγR on the macrophage cell surface and correlating it with their synergistic co-activation using ligands functionalized on lipid bilayers. We confirmed that co-activation of TLR4 and FcγR enhances whole-cell pro-inflammatory responses and tyrosine phosphorylation at the receptor level. Super-resolution microscopy revealed that TLR4 and FcγR each form discrete nanoclusters after ligand stimulation, and their synergistic co-activation significantly increases both the size and spatial overlap of these nanoclusters, leading to amplified immune signaling. Contrary to previous assumptions that TLR4 and FcγR form heterodimers during their crosstalk, our results emphasize the critical role of receptor nanocluster interactions in modulating innate immune responses. Additionally, these findings align with similar receptor interaction mechanisms that we previously reported in other receptor pairs, such as Dectin-1/TLR2 and FcγR/TLR2, suggesting that nanocluster interactions may represent a predominant mechanism governing crosstalk between TLRs and ITAM-containing receptors.
Effect of the Environmental Mechanical Heterogeneity on T Cell Function
Authors: Pandit Jatin Jawhir , Yassin Abed Al-Kader , Martin Carlos Ureña , Le Saux Guillaume , Porgador Angel , Schvartzman Mark
Published: October 2024

T cells, key players in the immune system, recognize antigens via T-cell receptors (TCRs) and require additional costimulatory and cytokine signals for full activation. Beyond biochemical signals, T cells also respond to mechanical cues such as tissue stiffness. Traditionalex-vivomechanostimulating platforms, however, present a uniform mechanical environment, unlike the heterogeneous conditions T cells encounterin-vivo. This work introduces a novel mechanically heterogeneous environment, with alternating soft and stiff microdomains, to mimic the complex mechanical signals T cells face. Results show that T cells exposed to this heterogeneous environment do not average the mechanical signals but instead respond similarly to those on a homogeneously soft surface, leading to lower activation compared to those on a stiff surface. Interestingly, long-term exposure to these patterns enhances the proliferation of central memory and effector T cell phenotypes, similar to stiff environments. These findings reveal the non-linear nature of T cell mechanosensing and suggest that mechanical heterogeneity plays a critical role in modulating T cell responses, providing new insights into T cell activation and potential implications for immunotherapies.
FragLlama: Next-fragment prediction for molecular design
Authors: Shen Jian , Zhou Shengmin , Che Xing
Published: October 2024

The emergence of ChatGPT has drawn significant attention to Large Language Models (LLMs) due to their impressive performance. While LLMs primarily focus on next token/word prediction, we apply this principle to molecular design by reframing the task as predicting the next token/fragment. We present FragLlama, a large language model trained for molecular design, featuring custom tokens that represent molecular fragments and functional groups. The model is for generating molecules given one or two fragments, for application scenarios like general hit-to-lead and lead optimization stage drug design, PROTAC linker design; mapping to commonly used drug design strategies like fragment growing and scaffold hopping. In the pre-training stage, we adapted the Llama 3 architecture to create FragLlama, training it to learn conditional probabilities of these fragment-level tokens. The subsequent alignment stage employed fine-tuning to guide the model towards generating molecules with desired properties. The effectiveness of FragLlama is demonstrated through its applications in designing molecular glue libraries, PROTAC linkers and EGFR binders. FragLlama demonstrates proficiency in reproducing expert-level designs while also exploring novel and promising chemical spaces, highlighting its potential to augment the capabilities of medicinal chemists in drug design.
Global patterns, drivers and impacts of metabolic traits across amniotes
Authors: Yang Qi , Wang Ziyi , Fan Liqing , Wang Dehua , Lei Fumin , Xiong Ying
Published: October 2024

Metabolism and climate are thought to influence species richness and diversification, yet few studies have examined whether global patterns of metabolic traits are linked to climate and diversification rate. Here we investigate the drivers of global metabolic rates and their impacts on biodiversity across 2,633 amniote vertebrates. We found consistent distribution patterns of metabolic rates in terrestrial amniotes and marine birds, with metabolic rates increasing with distance from the equator across latitudes. Temperature is a primary climatic variable affecting metabolic rates in birds and mammals, whereas precipitation dominates in terrestrial reptiles. Furthermore, elevated metabolic rates promote diversification rates and reduce extinction risks in birds and terrestrial mammals. Conversely, high metabolic rates decrease diversification rates and increase extinction risks in reptiles. Our results show that global patterns of metabolic rates are driven by various climate variables and may shape diversification and extinction patterns among amniotes in the context of climate change.
Tissue-Targeted Prime/Pull/Keep Therapeutic Herpes Simplex Virus Vaccine Protect Against Recurrent Ocular Herpes Diseases in HLA-A*0201 Transgenic Rabbits
Authors: Chentoufi Aziz A , Prakash Swayam , Vahed Hawa , Quadiri Afshana , BenMohamed Lbachir
Published: October 2024

Herpes Simplex Virus type 1 (HSV-1) continues to be one of the most prevalent viral infections globally, with approximately 3.72 billion individuals affected worldwide. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull/keep vaccine was tested in Human Leukocyte Antigen transgenic rabbit model of ocular herpes (HLA-A*0201 Tg rabbit). Ten asymptomatic (ASYMP) CD8+ T cell peptide epitopes and 3 CD4+ T-cell epitopes were selected from the HSV-1 glycoproteins D and B (gD and gB), viral tegument proteins (VP11/12 and VP13/14) and the DNA replication binding helicase (UL9), all preferentially recognized by CD8+and CD4+T-cells from “naturally protected” HSV-1-seropositive healthy ASYMP individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were ocularly infected with HSV-1 then during latency at day 30 post-infection, the rabbits were ocularly vaccinated with a recombinant neurotropic AAV8 vector (107GC/ eye) encoding for the 10 CD8+ T cell peptide and 4 CD4+ T cells peptide (prime), T cell-attracting CXCL-11 (Pull) and T-cell keeping IL-2/IL-15 cytokines (keep). The rabbits were followed up for eye disease and viral loads in tears for 28 days. The frequency, function and protective efficacy of HSV-specific CD8+T cells induced by the prime/pull/keep vaccine were assessed in the trigeminal ganglia (TG), cornea, Spleen, and peripheral blood. Compared to the mock group (unvaccinated), the peptides/CXCL11/IL-2/IL-15 vaccine generated frequent resident CD8+T cells that infiltrated the TG. CD8+T cells mobilization and retention into TG of prime/pull/keep vaccinated rabbits was associated with a significant reduction in corneal herpes infection and disease after an ocular HSV-1 challenge (McKrae). These findings draw attention to the novel prime/pull/keep therapeutic vaccine strategy to mobilize and retain anti-viral T cells into tissues protecting them against herpetic infection and disease.

IMPORTANCE

There is an urgent need for a vaccine against widespread human herpes simplex virus infections. The present study demonstrates that immunization of humanized HLA-A*0201 transgenic rabbits with CD8+ and CD4+ T-cell epitope peptides (prime)/ CXCL11 (pull)/ IL-2/IL-15 (Keep) AAV8-based vaccine triggered mobilization ad retention of HSV-1-specific CD8+T cells locally in the cornea and TG, the sites of acute and latent herpes infections. Mobilization and retention of antiviral CD8+T cells into cornea and TG of HSV-1 infected rabbits that received the prime/pull/keep vaccine was associated with protection against ocular herpes infection and disease. These results highlight the importance of the prime/pull/keep vaccine strategy to bolster the number and function of protective CD8+T cells within infected tissues.
Population genomics for coral reef restoration - a case study of staghorn corals in Micronesia
Authors: Rios Dareon , Torrado Hector , Lemer Sarah , Drury Crawford , Burdick David , Raymundo Laurie , Combosch David J.
Published: October 2024

StaghornAcroporacorals are ecological keystone species in shallow lagoons and back reef habitats throughout the tropics. Their widespread decline coupled with their amenability for asexual propagation propelled them to the forefront of global coral restoration efforts - albeit frequently without much scientific input. To guide these efforts and as a blueprint for similar projects, we conducted a comprehensive population genomic study ofAcropora cf. pulchra, a major restoration target species in the Indo-Pacific. Our results revealed thatA.cf.pulchrapopulations in the Mariana Islands are characterized by large clonal clusters and extremely low levels of genetic diversity. Differentiation among populations followed a significant isolation-by-distance pattern and delineated two distinct metapopulations on Guam. Our investigation identified critical population genetic parameters, necessitating targeted management strategies, and provides actionable guidelines for effective conservation efforts. For management and conservation, two populations emerged as pivotal connectivity hubs with elevated genetic diversity. For restoration, we show thatA. cf.pulchrapopulations demonstrated a suitability for extensive asexual propagation and provide guidelines how to best apply that. To preserve and augment genetic diversity, strategies to mitigate inbreeding are crucial until sexual reproduction can be fully integrated into restoration protocols. Critical sites for restoration include local connectivity hubs, fringing lagoons that connect metapopulations, and back reefs around a particularly isolated population. These findings offer crucial insights into the genetic landscape of a keystone coral species and provide actionable recommendations for coral conservation and restoration. By advocating for the preservation of population connectivity and the promotion of genotypic, genetic, and symbiont diversity in coral restoration, our study serves as a blueprint for leveraging population genomic studies to enhance the efficacy and resilience of restoration projects on remote islands.