bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vitro assessment of cutaneous immune responses to aedes mosquito salivary gland extract and dengue virus in Cambodian individuals
Authors: Guerrero David , Lay Sokchea , Piv Eakpor , Chhin Chansophea , Leng Sokkeang , Meng Ratana , Mam Kim Eng , Pean Polidy , Vantaux Amelie , Boyer Sebastien , Missé Dorothée , Cantaert Tineke 
Published: April 2024

Abstract
Dengue virus (DENV) poses a global health threat, affecting millions individuals annually with no specific therapy and limited vaccines. Mosquitoes, mainly Aedes aegypti and Aedes albopictus worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how Aedes mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from three different mosquito strains: Ae. aegypti USDA strain, Ae. aegypti and Ae. albopictus wild type (WT) in the presence/absence of DENV. We observed notable alterations in skin immune cell phenotypes subsequent to exposure to Aedes salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of Aedes SGE. Differences in cellular responses were observed when Aedes SGE of three distinct mosquito strains were compared. Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.
Size Discount and Size Penalty: Trading Costs in Bond Markets
Authors: Pinter Gabor , Wang Chaojun , Zou Junyuan 
Published: April 2024

Abstract
We show that larger trades incur lower trading costs in government bond markets (“size discount”), but costs increase in trade size after controlling for client identity (“size penalty”). The size discount is driven by the cross-client variation of larger traders obtaining better prices, consistent with theories of trading with imperfect competition. The size penalty, driven by the within-client variation, is larger for corporate bonds, during major macroeconomic surprises and during COVID-19. These differences are larger among more sophisticated clients, consistent with information-based theories.
Stem cell dynamics and cellular heterogeneity across lineage subtypes of castrate-resistant prostate cancer
Authors: Beshiri Michael L , Capaldo Brian J , Lake Ross , Ku Anson T , Burner Danielle , Tice Caitlin M , Tran Crystal , Kostas Julianna , Alilin Aian Neil , Yin JuanJuan , Agarwal Supreet , Morris Samantha A , Karzai Fatima H , Lotan Tamara L , Dahut William L , Sowalsky Adam G , Kelly Kathleen 
Published: April 2024

Abstract
To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. Castrate-resistant prostate adenocarcinoma can transition to neuroendocrine (NE) and occasionally to amphicrine, co-expressed luminal and NE, phenotypes. We developed castrate-resistant prostate cancer (CRPC) patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine model displaying a range of luminal and NE phenotypes. To gain biological insight and to identify potential treatment targets within heterogeneous tumor cell populations, we assessed the lineage hierarchy and molecular characteristics of various CRPC tumor subpopulations. Transcriptionally similar stem/progenitor (St/Pr) cells were identified for all lineage populations. Lineage tracing in amphicrine CRPC showed that heterogeneity originated from distinct subclones of infrequent St/Pr cells that produced mainly quiescent differentiated amphicrine progeny. By contrast, adenocarcinoma CRPC progeny originated from St/Pr cells and self-renewing differentiated luminal cells. Neuroendocrine prostate cancer (NEPC) was composed almost exclusively of self-renewing St/Pr cells. Amphicrine subpopulations were enriched for secretory luminal, mesenchymal, and enzalutamide treatment persistent signatures that characterize clinical progression. Finally, the amphicrine St/Pr subpopulation was specifically depleted with an AURKA inhibitor, which blocked tumor growth. These data illuminate distinct stem cell (SC) characteristics for subtype-specific CRPC in addition to demonstrating a context for targeting differentiation-competent prostate SCs.
The Unidroit Principles and the inflexibility of code as law: reconciling smart contracts with general clauses
Authors: Meyer Olaf , Ortolani Pietro 
Published: April 2024

Abstract
Smart contracts are a set of digital technologies enabling the automation of certain aspects of contractual performance and/or remedies. These technologies follow a deterministic, if/then logic that is often difficult to reconcile with the inherent malleability of contract law. This article scrutinizes this tension, with specific reference to the International Institute for the Unification of Private Law’s (Unidroit) Principles of International Commercial Contracts (PICC). The article argues that some recurring PICC general clauses (such as good faith and reasonableness) play a crucial role in ensuring fairness. Therefore, their operation should not be constrained by smart contracts. To the contrary, the parties to an international commercial contract should use technology to empower arbitrators to make full use of the flexibility inherent to the PICC and issue (partially) self-enforcing awards.
Availability in ECMO Reduces the Failure to Rescue in Patients With Pulmonary Embolism After Major Surgery: A Nationwide Analysis of 2.4 Million Cases
Authors: Diers Johannes , Baumann Nikolas , Baum Philip , Uttinger Konstantin L. , Wagner Johanna C. , Kranke Peter , Meybohm Patrick , Germer Christoph-Thomas , Wiegering Armin 
Published: April 2024

Objective:
Postoperative pulmonary embolism (PE) is a rare but potentially life-threatening complication, which can be treated with extracorporeal membrane oxygenation (ECMO) therapy, a novel therapy option for acute cardiorespiratory failure. We postulate that hospitals with ECMO availability have more experienced staff, technical capabilities, and expertise in treating cardiorespiratory failure.

Design:
A retrospective analysis of surgical procedures in Germany between 2012 and 2019 was performed using hospital billing data. High-risk surgical procedures for postoperative PE were analyzed according to the availability of and expertise in ECMO therapy and its effect on outcome, regardless of whether ECMO was used in patients with PE.

Methods:
Descriptive, univariate, and multivariate analyses were applied to identify possible associations and correct for confounding factors (complications, complication management, and mortality).

Results:
A total of 13,976,606 surgical procedures were analyzed, of which 2,407,805 were defined as high-risk surgeries. The overall failure to rescue (FtR) rate was 24.4% and increased significantly with patient age, as well as type of surgery. The availability of and experience in ECMO therapy (defined as at least 20 ECMO applications per year; ECMO centers) are associated with a significantly reduced FtR in patients with PE after high-risk surgical procedures. In a multivariate analysis, the odds ratio (OR) for FtR after postoperative PE was significantly lower in ECMO centers (OR, 0.75 [0.70–0.81], P < 0.001).

Conclusions:
The availability of and expertise in ECMO therapy lead to a significantly reduced FtR rate of postoperative PE. This improved outcome is independent of the use of ECMO in these patients.
Trauma-Informed Care as a Universal Precaution: A Brief, Case-Based, Educational Primer Featuring Role-Playing and Individual Self-Reflection Exercises
Authors: Kopstick Avi J. , Aly Aly M. , Zientek Emily , Williams Cydni N. , Hall Trevor A. , Macauley Robert C. , Duffee James H. 
Published: April 2024

Abstract:
Despite its growing popularity, the implementation of Trauma-Informed Care (TIC) in standard medical practices remains insufficient. A workshop, featuring role-playing scenarios and individual self-reflection exercises, was developed to enhance compassion among health care providers. The workshop was created by a multidisciplinary team of community pediatricians, pediatric intensivists, psychologists, and palliative care physicians, was structured around key elements and principles of TIC, and was based on actual patient encounters. The 90-minute session included didactics, role-playing, writing and self-reflection exercises, and large-group debriefings, and it was presented at two academic meetings. It is currently available as an open-sourced, freely accessible website. The workshop was attended by individuals with varying levels of training and experience. Of approximated 80 participants, 39 responded to surveys about baseline knowledge and workshop satisfaction, and 24 completed self-perceived pre- and postknowledge surveys. Nearly 90% had limited prior exposure to TIC. All rated the workshop highly, with no significant differences based on workshop facilitation. Nearly 95% felt that they learned something that would impact their day-to-day practices. Self-perceived pre–post knowledge showed statistically significant improvements. This workshop is feasible and can potentially increase health care professionals' capacity to care, decrease moral injury, and alleviate burnout from difficult cases.
Design of OASIS 1 and 2: phase 3 clinical trials assessing the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause
Authors: Pinkerton JoAnn V. , Simon James , Panay Nick , Seitz Christian , Parke Susanne , Caetano Cecilia , Mellinger Uwe , Haseli Mashhadi Nazanin , Haberland Claudia , Atanackovic Gordana , Holz Cornelia , Mao Guangping , Morrison Marina , Nisius Sven , Schaefers Matthias , Zuurman Lineke 
Published: April 2024

Abstract

Objective
Elinzanetant is a selective neurokinin-1,3 receptor antagonist in development for the treatment of vasomotor symptoms (VMS) associated with menopause. The pivotal, double-blind, randomized, placebo-controlled phase 3 studies Overall Assessment of efficacy and Safety of elinzanetant In patients with vasomotor Symptoms (OASIS) 1 and 2 will assess the efficacy and safety of elinzanetant in women with VMS.

Methods
The OASIS 1 and 2 pivotal studies are designed in accordance with regulatory guidance. Postmenopausal women with moderate/severe VMS are randomized to receive 120 mg elinzanetant or placebo once daily for 12 weeks, followed by a 14-week active treatment extension. Primary endpoints are the mean change in frequency and severity of moderate/severe VMS from baseline to weeks 4 and 12. Key secondary endpoints will assess the onset of action and effects on sleep disturbance and menopause-related quality of life. Primary and key secondary endpoints will be analyzed using a mixed model with repeated measures. Feedback from postmenopausal women with VMS was used during protocol development.

Results
Women confirmed the relevance of endpoints that assess the impact of VMS, sleep disturbance, and mood changes, and the need for new nonhormone treatments. Educational materials around study design, conduct and expected assessments and procedures were developed based on questions and concerns raised by women.

Conclusions
The OASIS 1 and 2 pivotal phase 3 studies will enable assessment of the efficacy and safety of elinzanetant as a treatment for VMS, together with its effect on sleep disturbances, depressive symptoms, and menopause-related quality of life. Feedback from postmenopausal women with VMS was used to maximize patient centricity in the trials.
Conserved long noncoding RNA TILAM promotes liver fibrosis through interaction with PML in HSCs
Authors: Sun Cheng , Zhou Chan , Daneshvar Kaveh , Ben Saad Amel , Kratkiewicz Arcadia J. , Toles Benjamin J. , Arghiani Nahid , Hess Anja , Chen Jennifer Y. , Pondick Joshua V. , York Samuel R. , Li Wenyang , Moran Sean P. , Gentile Stefan D. , Rahman Raza Ur , Li Zixiu , Zhou Peng , Sparks Robert P. , Habboub Tim , Kim Byeong-Moo , Choi Michael Y. , Affo Silvia , Schwabe Robert F. , Popov Yury V. , Mullen Alan C. 
Published: April 2024

Background and Aims:
Fibrosis is the common end point for all forms of chronic liver injury, and the progression of fibrosis leads to the development of end-stage liver disease. Activation of HSCs and their transdifferentiation into myofibroblasts results in the accumulation of extracellular matrix proteins that form the fibrotic scar. Long noncoding RNAs regulate the activity of HSCs and provide targets for fibrotic therapies.

Approach and Results:
We identified long noncoding RNA TILAM located near COL1A1, expressed in HSCs, and induced with liver fibrosis in humans and mice. Loss-of-function studies in human HSCs and human liver organoids revealed that TILAM regulates the expression of COL1A1 and other extracellular matrix genes. To determine the role of TILAM in vivo, we annotated the mouse ortholog (Tilam), generated Tilam-deficient green fluorescent protein-reporter mice, and challenged these mice in 2 different models of liver fibrosis. Single-cell data and analysis of single-data and analysis of Tilam-deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Tilam-deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Furthermore, loss of Tilam expression attenuated the development of fibrosis in the setting of in vivo liver injury. Finally, we found that TILAM interacts with promyelocytic leukemia nuclear body scaffold protein to regulate a feedback loop by which TGF-β2 reinforces TILAM expression and nuclear localization of promyelocytic leukemia nuclear body scaffold protein to promote the fibrotic activity of HSCs.

Conclusions:

TILAM is activated in HSCs with liver injury and interacts with promyelocytic leukemia nuclear body scaffold protein to drive the development of fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end-stage liver disease.
Reverse 4-Flanged Technique for Intrascleral Fixation of a Foldable Hydrophobic Intraocular Lens in the Absence of Capsular Support Through a 2.2-mm Corneal Incision
Authors: Romero-Valero Daniel , Martínez Toldos Jose Juan 
Published: April 2024

Purpose:
The purpose of this study was to describe a modified technique for sutureless intrascleral intraocular lens fixation in patients without capsular support: the reverse 4-flanged technique.

Methods:
A 2.2-mm corneal incision was made for aphakic patients. The 6-0 polypropylene sutures were threaded through a 30-gauge needle outside the eye. An MDJ injector was employed to insert the intraocular lens into the eye. A suture-needle snare with 7-0 polypropylene was used to exteriorize the superior end of the sutures through the sclerotomy. The 6-0 polypropylene was heated with a cautery to create the flanges.

Results:
Nine eyes of nine patients underwent the reverse 4-flanged technique. The median follow-up time was 182 days (range 174–195). Best-corrected distance visual acuity improved from 20/400 [hand movement—20/33] to 20/120 [20/400–20/21]. No vitreous hemorrhage, retinal detachment, endophthalmitis, intraocular lens luxation, or flange exposure was recorded during the follow-up.

Conclusion:
The reverse 4-flanged technique maintains the advantages of the original 4-flanged technique in terms of intraocular lens stability while reducing the incision size and surgical maneuvers performed inside the eye. This modification promises to be a reliable, safe, and relatively simple technique to correct aphakia in the absence of capsular support.
Directional Optical Coherence Tomography Imaging of Macular Pathology
Authors: Lujan Brandon J. , Griffin Shane , Makhijani Vikram S. , Antony Bhavna J. , Chew Emily Y. , Roorda Austin , McDonald H. Richard 
Published: April 2024

Purpose:
To survey the impact of directional reflectivity on structures within optical coherence tomography (OCT) images in retinal pathology.

Methods:
Sets of commercial OCT images taken from multiple pupil positions were analyzed. These Directional OCT (D-OCT) sets revealed directionally reflective structures within the retina. After ensuring sufficient image quality, resulting hybrid and composite images were characterized by assessing the Henle Fiber Layer (HFL), Outer Nuclear Layer (ONL), Ellipsoid Zone (EZ), and Interdigitation Zone (IZ). Additionally, hybrid images were reviewed for novel directionally reflective pathological features.

Results:
Cross-sectional D-OCT image sets were obtained in 75 eyes of 58 subjects having a broad range of retinal pathologies. All cases showed improved visualization of the ONL/Henle fiber layer interface, and ONL thinning was therefore more apparent in several cases. The EZ and IZ also demonstrated attenuation where a geometric impact of underlying pathology affected their orientation. Misdirected photoreceptors were also noted as a consistent direction-dependent change in EZ reflectivity between regions of normal and absent EZ.

Conclusion:
D-OCT enhances the understanding of retinal anatomy and pathology. This optical contrast yields more accurate identification of retinal structures and possible imaging biomarkers for photoreceptor-related pathology.
FOVEAL AVASCULAR ZONE IN ADULTS BORN PRETERM WITH AND WITHOUT RETINOPATHY OF PREMATURITY
Authors: Fieß Achim , Zange Maria , Gißler Sandra , Mildenberger Eva , Urschitz Michael S. , Laspas Panagiotis , Stoffelns Bernhard , Pfeiffer Norbert , Schuster Alexander K. 
Published: April 2024

Purpose:
To examine potential changes in the foveal avascular zone (FAZ) during adulthood due to prematurity and retinopathy of prematurity (ROP), as assessed by measurements of the FAZ area and circularity.

Methods:
The Gutenberg Prematurity Eye Study is a retrospective German cohort study with a prospective ophthalmologic examination of adults aged 18 years to 52 years, born either preterm or full-term, using spectral-domain optical coherence tomography angiography. Participants were categorized into groups based on gestational age and postnatal ROP status. The study conducted multivariable linear regression analyses to explore associations with the FAZ.

Results:
The study cohort comprised 380 right eyes from individuals born both preterm and full-term, with an average age of 28.4 years ± 8.6 years, including 214 women. The FAZ area decreased as gestational age decreased: FAZ was 0.28 mm2 ± 0.12 mm2 in the control group, 0.21 ± 0.10 mm2 at GA 33 weeks to 36 weeks, 0.18 mm2 ± 0.10 mm2 at GA 29 weeks to 32 weeks, 0.11 mm2 ± 0.10 mm2 at GA ≤28 weeks, 0.11 mm2 ± 0.10 mm2 in ROP without treatment, and 0.11 mm2 ± 0.10 mm2 in those requiring ROP treatment. In the multivariable analyses, smaller FAZ was independently associated with gestational age (P < 0.05), increased foveal retinal thickness (P < 0.05), and foveal hypoplasia (P < 0.05). Moreover, no association was seen between visual acuity and FAZ.

Conclusion:
The main perinatal factor associated with a smaller FAZ in this German cohort is preterm birth, while ROP, ROP treatment, or other perinatal factors do not affect FAZ observed in adulthood. A smaller FAZ shape in preterm individuals might be an indicator of foveal hypoplasia.
Is Meibomian Gland Dysfunction One Disease? Heterogeneity Among Phenotypes
Authors: Kim Colin K. , Locatelli Elyana V. T. , Prislovsky Amanda , Cabrera Kimberly , Gary Ashlyn A. , Mandal Nawajes , Galor Anat 
Published: April 2024

Purpose:
The purpose of this study was to examine ocular surface symptoms, tear metrics, and tear cytokines by Meibomian gland dysfunction (MGD) features.

Methods:
Symptom questionnaires and an ocular surface evaluation were performed on 40 individuals with varied MGD signs (Meibomian gland [MG] plugging, eyelid vascularity, meibum quality, and MG dropout). Tear proteins were extracted off Schirmer strips and analyzed for 23 human inflammation-related proteins. Statistical analysis was performed to examine associations between dry eye metrics inflammatory proteins and MGD features.

Results:
The study involved 40 South Florida veterans with a mean age of 61 ± 13 years; most individuals were male (95%), White (31%), and non-Hispanic (85%). MGD features differentially related to dry eye signs. Eyelid vascularity, meibum quality, and MG dropout, but not MG plugging, correlated with higher corneal staining and lower tear production. MGD features also differentially related to tear cytokines. Eyelid vascularity most closely related to inflammation with significant correlations for interferon-gamma-γ (r = 0.36, P = 0.02), interleukin-4 (IL-4) (r = 0.43, P = 0.006), IL-17A (r = 0.42, P = 0.007), matrix metalloproteinase-2 (r = 0.39, P = 0.01), C-X-C motif chemokine ligand 5 (Regulated upon Activation, Normal T-Cell Expressed and presumably Secreted [RANTES]) (r = 0.32, P = 0.04), and tumor necrosis factor α (r = 0.36, P = 0.02). The other 3 MGD signs were less related to inflammation. Multivariable models revealed IL-4 to be most closely related to eyelid vascularity (standardized β = 0.39, P < 0.0001).

Conclusions:
Eyelid vascularity was the MGD sign most closely related to inflammatory cytokines, suggesting that different MGD features may be driven by different pathophysiological mechanisms.
Mediastinal Nontuberculous Mycobacterial Infection in Children: A Multidisciplinary Approach
Authors: Wiener Jonathan , Wanaguru Dylan , Currie Bruce , Grant Peter , Russell Carolyn , Palasanthiran Pamela , Williams Phoebe , Belessis Yvonne , Soma Marlene 
Published: April 2024

Background:
Mediastinal infections due to nontuberculous mycobacteria remain an exceedingly rare entity. Most cases in the published literature do not include pediatric patients. Due to their clinical infrequency, poor response to antimicrobial therapy and often precarious anatomical location, the optimal management of these lesions can be challenging.

Methods:
Retrospective medical record review of 4 pediatric cases of mediastinal nontuberculous mycobacteria infection was undertaken. Each child presented with nonspecific respiratory symptoms, including significant acute airway obstruction and required a range of investigations to confirm the diagnosis. Nonresponsiveness to conservative measures and antimycobacterial therapy ultimately resulted in surgical intervention to obtain clinical improvement.

Results:
All 4 children had extensive evaluation and multidisciplinary involvement in otolaryngology, respiratory medicine, pediatric surgery, infectious diseases and cardiothoracic surgery. They all eventually had their disease debulked via thoracotomy in addition to prolonged antimycobacterial therapy, with successful clinical outcomes.

Conclusions:
Mediastinal nontuberculous mycobacteria infections in the pediatric population are rare and diagnostically challenging. A high clinical suspicion should be maintained, and multidisciplinary input sought. Targeted surgery with adjuvant medical therapy can reduce disease burden with minimal long-term morbidity.