bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitreous abnormalities in a patient with Gaucher disease
Authors: Mak Michael Y.K , Trask William M. , Huang Jordan J. , Huang Jaxon J. , Li Jasmine , Kulaga Andrzej , Adatia Feisal 
Published: April 2024

Purpose:
To report a case and management of vitreous abnormalities in a patient with Gaucher disease.

Methods:
Case report.

Results:
A 28-year-old female with a known diagnosis of Gaucher disease presented to our retina service with complaints of “blurry” vision in both eyes. Ophthalmic examination revealed a Snellen visual acuity of 20/70 OD and 20/20 OS. The anterior segment examination was unremarkable bilaterally; however, the vitreous was notable for multiple yellowish-white vitreous opacifications in both eyes. Fluorescein angiography revealed the opacities but was otherwise unremarkable in terms of retinal vascular findings. Swept-source optical coherence tomography confirmed the position of these vitreous abnormalities to be directly anterior to and in contact with the retinal nerve fiber layer. She subsequently underwent 23-gauge pars plana vitrectomy to remove the vitreous debris; Triamcinolone Acetate (Kenalog) was used intraoperatively to visualize the posterior hyaloid. The cassette was sent for pathological analysis, which revealed amorphous vitreous material with occasional lymphocytes and histiocytes. Her post-vitrectomy Snellen visual acuity was 20/40 OD with pinhole to 20/25, and the patient reported resolution of her subjective symptoms. Her opacities had not recurred as of last follow-up.

Conclusion:
Vitreous abnormalities in Gaucher disease are an extremely rare and uncommon ophthalmologic finding. As our case demonstrates, vitrectomy can be an appropriate surgical approach for improving vision in these patients.
A Novel Pathogenic Variant of the PRPH2 Gene in Multifocal Pattern Dystrophy Simulating Stargardt Disease: A Case Report and Major Review
Authors: Alsumait Abdulaziz , Mahmoudzadeh Raziyeh , Couser Natario 
Published: April 2024

Purpose:
To present a novel pathogenic variant in PRPH2 in a patient with multifocal pattern dystrophy simulating Stargardt Disease (MPDsSD) and provide a review of the literature summarizing the clinical findings of all presented cases of MPDsSD.

Methods:
We performed a systematic review of the literature to summarize the clinical findings in patients with MPDsSD. A PubMed search of “(multifocal pattern dystrophy simulating stargardt disease) OR (multifocal pattern dystrophy simulating fundus flavimaculatus) OR (PRPH2 associated retinal dystrophy)” retrieved a total of 152 articles on April 2023. Articles describing the clinical and ophthalmic characteristics of patients with MPDsSD were included. We also describe the case of a 42-year-old male presenting to the clinic with blurry vision and progressively worsening vision in both eyes who was found to have a novel pathogenic variant in the PRPH2 gene.

Results:
Genetic testing revealed a pathogenic variant in PRPH2, c.640T>C [p.(Cys214Arg)], which provided molecular confirmation of MPDsSD. Moreover, the systematic review, revealed 28 previously reported cases of MPDsSD. The most common presenting symptom among all patients was metamorphopsia (33% of cases). The most common finding on fundus exam was the presence of yellowish fleck-like deposits found in the posterior pole of the retina (83%). All cases of MPDsSD had hyper-autofluorescence of the yellow flecks on fundus autofluorescence. The mean age of onset was 41 years (28 – 65). Mean best corrected visual acuity (BCVA) at presentation was 0.27 (20/37) right eye (OD) and 0.26 (20/36) left eye (OS). Only 48% of the cases reported a known family history of PD.

Conclusion:
Molecular confirmation can help confirm a clinical suspicion of MPDsSD, as this condition may have overlapping features of other macular dystrophies, most notably Stargardt Disease.
Differential Rates of Toxicity Between Chloroquine and Hydroxychloroquine
Authors: Guttha Samyuktha , Choi Stephanie , Dedania Vaidehi S. , Mehta Nitish , Belmont H. Michael , Modi Yasha S. 
Published: April 2024

Purpose:
To describe two cases of patients with systemic lupus erythematosus (SLE) who manifested differential rates of retinal toxicity progression on hydroxychloroquine (HCQ) and chloroquine (CQ), respectively.

Methods:
Retrospective case reports.

Results:
Case 1 is a 41-year-old woman with SLE and history of renal involvement, who had been managed on HCQ for 14 years and gradually progressed to moderate retinal toxicity over several years. Case 2 is a 59-year-old woman with SLE and history of renal involvement, who had been managed on quinacrine for 20 years followed by chloroquine for 5 years and initially presented without any evidence of retinal toxicity. One year later, she manifested moderate retinal toxicity. Both cases were screened regularly. In case 1, the diagnosis was missed and toxicity progressed predictably and slowly while on HQ. In case 2, there was no salient pathology on OCT or HVF testing at initial presentation. One year later, there was moderate toxicity.

Conclusion:
Given the dramatically different rate of progression of retinal toxicity in these two patients, these cases highlight potential gaps in our understanding of retinal toxicity and provide rationale to potentially study rates of retinal toxicity progression in patients on CQ or quinacrine.
Central Serous Chorioretinopathy in Nanophthalmos
Authors: Manayath George J , Ninan Rohan , Verghese Shishir , Narendran Venkatapathy 
Published: April 2024

Purpose:
To report a case of bilateral central serous chorioretinopathy (CSC) occurring in a patient with nanophthalmos with long term follow up

Methods:
Case Report

Results:
A 37-year old male presented with diminution of vision in right eye (RE) since 3 days. On examination his best corrected visual acuity (BVCA) was 5/60 in RE and 6/18 in LE His refractive correction was +8.00D sphere. Anterior segment examination revealed small eyes with narrow palpebral fissures, shallow anterior chamber and clear lens. His axial length was 15.94mm in the RE and 15.89mm in the LE respectively. Fundus examination revealed a crowded disc with tortuous vessels in both eyes and the presence of subretinal fluid (SRF) in the macular area in the RE. Multimodal imaging included enhanced depth imaging spectral domain optical coherence tomography (EDI SD-OCT) and fundus fluorescein angiography (FFA) which revealed features suggestive of thick choroids BE, ink-blot leak on FFA suggestive of acute CSC in the RE and a pigment epithelial detachment (PED) in the left eye. Focal laser in RE lead to SRF resolution and visual improvement. He was on regular follow up and 5 years later he presented with a recurrence of CSC in the RE for which he underwent a repeat FFA guided focal laser.

Conclusion:
This case highlights the unique coexistence of CSC in the setting of Nanophthalmos and highlights a probable overlapping pathophysiology of choroidal venous overload as well as the importance of multimodal imaging in differentiating the mimicking entities.
Two Different Nuclear Mitochondrial DNA Mutations Associated with Retinal Abnormalities
Authors: Spaide Richard F. 
Published: April 2024

Purpose:
To report the posterior pole imaging characteristics of two patients with pathogenic nuclear mitochondrial mutations.

Methods:
Case reports

Results:
The first case, a 61-year-old patient, initially diagnosed with age-related macular degeneration, exhibited focal hyperpigmentation and increased autofluorescence in the parafoveal macula, along with geographic atrophy and mild optic nerve pallor. Optical coherence tomography (OCT) showed ellipsoid zone (EZ) attenuation, hyperreflective foci colocalizing to the hyperpigmentation, subretinal deposits, and hypertransmission defects. He was found to have a pathogenic mutation of MFN2, a gene defect associated with Charcot-Marie-Tooth disease. The second case, a 65-year-old patient presented with loss of central vision with pallor of the optic nerve. OCT imaging showed widespread loss of the interdigitation zone and EZ attenuation peripheral to the foveal region. There was thinning of the ganglion cell and nerve fiber layers. A pathogenic OPA1 mutation, the leading cause of autosomal dominant optic atrophy, was found. Both MFN2 and OPA1 produce proteins integral in mitochondrial fusion.

Conclusions:
The findings of these cases suggest ocular examinations may be helpful in evaluating patients with nuclear mitochondrial mutations using the near microscopic resolution of OCT. Retinal imaging may highlight structural abnormalities related to mitochondrial problems and allows direct imaging of the EZ, a layer dominated by mitochondria and a place where direct imaging of mitochondria is possible, in vivo.
The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens
Authors: Stream Alexandra , Corriden Ross , Döhrmann Simon , Gallo Richard L. , Nizet Victor , Anderson Ericka L. 
Published: April 2024

Abstract
Vitamin A and its biologically active derivative, retinoic acid (RA), are important for many immune processes. RA, in particular, is essential for the development of immune cells, including neutrophils, which serve as a front-line defense against infection. While vitamin A deficiency has been linked to higher susceptibility to infections, the precise role of vitamin A/RA in host-pathogen interactions remains poorly understood. Here, we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus (MRSA). RA treatment stimulated primary human neutrophils to produce reactive oxygen species, neutrophil extracellular traps, and the antimicrobial peptide cathelicidin (LL-37). Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection, we expanded our analysis to other infectious agents. RA did not affect the growth of a number of common bacterial pathogens, including MRSA, Escherichia coli K1 and Pseudomonas aeruginosa; however, RA directly inhibited the growth of group A Streptococcus (GAS). This antimicrobial effect, likely in combination with RA-mediated neutrophil boosting, resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of RA. Furthermore, in a murine model of GAS skin infection, topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial burden. These findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.
Effect of hemoglobin A1c change on 24-month clinical outcomes in patients with diabetes after acute myocardial infarction
Authors: Park Sangshin , Choi Woong Gil , Bae Dae-Hwan , Kim Min , Lee Ju-Hee , Kim Sangmin , Bae Jang-Whan , Kim Dong-Woon , Cho Myeong-Chan , Kim Chong-Jin , Chae Shung-Chull , Jeong Myung-Ho , Hwang Kyung-Kuk ,   on behalf of the KAMIR-NIH Registry
Published: April 2024

Background
The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI.

Methods
We enrolled patients with diabetes (n = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined.

Results
The baseline HbA1c levels were 8.55 ± 0.85, 7.00 ± 0.98 and 7.07 ± 1.05 (P = 0.001) and HbA1c levels after 1 year were 6.62 ± 0.73, 7.05 ± 0.98 and 9.26 ± 1.59 (P = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization.

Conclusions
Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.
Mycotic Aneurysms: Uncommon Pathogens and Treatment Conundrums
Authors: Ravindra Akshatha , Naguthevar Santhanam , Kumar Deepak , Rajagopal Rengarajan , Khera Pushpinder Singh , Tak Vibhor , Ramankutty Neetha Thayil , Meena Durga Shankar , Midha Naresh , Bohra Gopal Krishana , Garg Mahendra Kumar 
Published: April 2024

Introduction

Mycotic aneurysms, characterized by vessel wall dilation resulting from infections including bacteria, fungi, and viruses, are a rare yet severe consequence of systemic infections.These aneurysms, accounting for 0.6% of Western countries' aneurysms, carry a higher risk of rupture compared to uninfected conditions. While the femoral artery, aorta, and intracranial visceral arteries are commonly affected, pathogens causing mycotic aneurysms vary across regions. Diagnostic challenges arise from nonspecific symptoms such as fever, pulsatile mass, local discomfort, and arterial inflammation.

Materials & Methods:
The case series involves three patients diagnosed with mycotic aneurysms due to unusual pathogens. We describe each patient's clinical presentation, medical history, physical examination findings, laboratory results, imaging studies, and the diagnostic process leading to the identification of the causative pathogens.

Results

The first case depicts a 70-year-old male with a ruptured infra-renal abdominal aortic pseudoaneurysm caused by Salmonella Paratyphi A. The second case involves a 66-year-old male with a Streptococcus pneumoniae-associated descending thoracic aortic pseudoaneurysm. The third case pertains to a 70-year-old male with a ruptured descending thoracic aortic aneurysm into the esophagus due to Pseudomonas aeruginosa infection. Each case highlights unique clinical features, laboratory findings, imaging results, and the management approaches undertaken.

Conclusion

Mycotic aneurysms, stemming from infections involving diverse pathogens, pose diagnostic challenges due to their nonspecific symptoms. Early identification and intervention are essential to mitigate the severe complications associated with these aneurysms. The presented cases underscore the need for a comprehensive approach to diagnosis and management, ensuring optimal outcomes for patients affected by mycotic aneurysms.
Australian vertebrate hosts of Japanese encephalitis virus; a review of the evidence
Authors: Moore Kevin T. , Mangan Madelyn J. , Linnegar Belinda , Athni Tejas S. , McCallum Hamish I. , Trewin Brendan J. , Skinner Eloise 
Published: April 2024

AbstractJapanese Encephalitis Virus (JEV) transmission in temperate Australia has underscored a critical need to characterise transmission pathways and identify probable hosts of infection within the country. This systematic review consolidates existing research on the vertebrate hosts of JEV that are known to exist in Australia. Specifically, we aim to identify probable species for JEV transmission, their potential role as either a spillover or maintenance host and identify critical knowledge gaps. Data were extracted from studies involving experimental infection, seroprevalence, and virus isolation and were available for 22 vertebrate species known to reside in Australia. A host competence score was calculated to assess the potential for a given species to infect JEV vectors and to quantity their possible role in JEV transmission. Based on the host competence score and ecology of each species, we find ardeid birds, feral pigs, and flying foxes have potential as maintenance hosts for JEV in the Australian context. We also note that brushtail possums and domestic pigs have potential as spillover hosts under certain outbreak conditions. However, evidence to confirm these roles in localized transmission or outbreaks is sparse, emphasizing the need for further targeted research. This review provides a foundation for future investigations into JEV transmission in Australia, advocating for enhanced surveillance and standardized research methodologies to better understand and mitigate the virus’s impact.
Tissue inflammation induced by constitutively active STING is mediated by enhanced TNF signaling
Authors: Luksch Hella , Schulze Felix , Geißler-Lösch David , Sprott David , Höfs Lennart , Szegö Eva M. , Tonnus Wulf , Winkler Stefan , Günther Claudia , Linkermann Andreas , Behrendt Rayk , Teichmann Lino L. , Falkenburger Björn H. , Rösen-Wolff Angela 
Published: April 2024

AbstractConstitutive activation of STING by gain-of-function mutations triggers manifestation of the systemic autoinflammatory disease STING-associated vasculopathy with onset in infancy (SAVI). In order to investigate the role of signaling by tumor necrosis factor (TNF) in SAVI, we used pharmacological inhibition and genetic inactivation of TNF receptors 1 and 2 in murine SAVI, which is characterized by T cell lymphopenia, inflammatory lung disease and neurodegeneration. Pharmacologic inhibition of TNF signaling improved T cell lymphopenia, but had no effect on interstitial lung disease. Genetic inactivation of TNFR1 and TNFR2, however, rescued the loss of thymocytes, reduced interstitial lung disease and neurodegeneration. Furthermore, genetic inactivation of TNFR1 and TNFR2 blunted transcription of cytokines, chemokines and adhesions proteins, which result from chronic STING activation in SAVI mice. In addition, increased transendothelial migration of neutrophils was ameliorated. Taken together, our results demonstrate a pivotal role of TNFR-signaling in the pathogenesis of SAVI in mice and suggest that available TNFR antagonists could ameliorate SAVI in patients.Graphic Abstract
Medical Diagnosis Coding Automation: Similarity Search vs. Generative AI
Authors: Klotzman Vanessa 
Published: April 2024

AbstractObjectiveThis study aims to predict ICD-10-CM codes for medical diagnoses from short diagnosis descriptions and compare two distinct approaches: similarity search and using a generative model with few-shot learning.Materials and MethodsThe text-embedding-ada-002 model was used to embed textual descriptions of 2023 ICD-10-CM diagnosis codes, provided by the Centers provided for Medicare & Medicaid Services. GPT-4 used few-shot learning. Both models underwent performance testing on 666 data points from the eICU Collaborative Research Database.ResultsThe text-embedding-ada-002 model successfully identified the relevant code from a set of similar codes 80% of the time, while GPT-4 achieved a 50 % accuracy in predicting the correct code.DiscussionThe work implies that text-embedding-ada-002 could automate medical coding better than GPT-4, highlighting potential limitations of generative language models for complicated tasks like this.ConclusionThe research shows that text-embedding-ada-002 outperforms GPT-4 in medical coding, highlighting embedding models’ usefulness in the domain of medical coding.
Order among chaos: high throughput MYCroplanters can distinguish interacting drivers of host infection in a highly stochastic system
Authors: Chen Melissa Y , Fulton Leah , Huang Ivie , Liman Aileen , Hossain Sarzana , Hamilton Corri , Song Siyu , Geissmann Quentin , King Kayla C. , Haney Cara H 
Published: April 2024

ABSTRACTWhile microbiomes provide diverse benefits for their host, they are notoriously variable in structure and function. As a result, substantial experimental replication and scalability are required to identify the contributions of and interactions between microbiota, the host and the environment. Here, we describe a novel high throughput plant growth system (MYCroplanters) to test how multiple host, microbiota, and pathogen variables predict host health. Using an Arabidopsis-Pseudomonashost-microbiome-pathogen model, we found that host genotype and order of arrival predict competition outcome between strains in the rhizosphere, but pathogen and microbiota dose can overwhelm these effects. Regardless of host or inoculation conditions, final microbial community structure emerged as a consistent predictor of host health. We demonstrate that high-throughput tools like MYCroplanters can isolate interacting drivers of host health. Increasing the scale at which we can screen components of microbiome-mediated host benefits will facilitate building microbiome engineering solutions for medicine and agricultural applications.
Drosophila Models Uncover Substrate Channeling Effects on Phospholipids and Sphingolipids in Peroxisomal Biogenesis Disorders
Authors: Wangler Michael F , Chao Yu-Hsin , Roth Mary , Welti Ruth , McNew James A. 
Published: April 2024

AbstractPeroxisomal Biogenesis Disorders Zellweger Spectrum (PBD-ZSD) disorders are a group of autosomal recessive defects in peroxisome formation that produce a multi-systemic disease presenting at birth or in childhood. Well documented clinical biomarkers such as elevated very long chain fatty acids (VLCFA) are key biochemical diagnostic findings in these conditions. Additional, secondary biochemical alterations such as elevated very long chain lysophosphatidylcholines are allowing newborn screening for peroxisomal disease. In addition, a more widespread impact on metabolism and lipids is increasingly being documented by metabolomic and lipidomic studies. Here we utilizeDrosophilamodels ofpex2andpex16as well as human plasma from individuals withPEX1mutations. We identify phospholipid abnormalities inDrosophilalarvae and brain characterized by differences in the quantities of phosphatidylcholine (PC) and phosphatidylethanolamines (PE) with long chain lengths and reduced levels of intermediate chain lengths. For diacylglycerol (DAG) the precursor of PE and PC through the Kennedy pathway, the intermediate chain lengths are increased suggesting an imbalance between DAGs and PE and PC that suggests the two acyl chain pools are not in equilibrium. Altered acyl chain lengths are also observed in PE ceramides in the fly models. Interestingly, plasma from human subjects exhibit phospholipid alterations similar to the fly model. Moreover, human plasma shows reduced levels of sphingomyelin with 18 and 22 carbon lengths but normal levels of C24. Our results suggest that peroxisomal biogenesis defects alter shuttling of the acyl chains of multiple phospholipid and ceramide lipid classes, whereas DAG species with intermediate fatty acids are more abundant. These data suggest an imbalance betweende novosynthesis of PC and PE through the Kennedy pathway and remodeling of existing PC and PE through the Lands cycle. This imbalance is likely due to overabundance of very long and long acyl chains in PBD and a subsequent imbalance due to substrate channeling effects. Given the fundamental role of phospholipid and sphingolipids in nervous system functions, these observations suggest PBD-ZSD are diseases characterized by widespread cell membrane lipid abnormalities.