bluuebunny/crossref_metadata_2025_split huggingface dataset:
RESOLUTION OF CHOROIDAL METASTASIS AND ASSOCIATED SUBRETINAL EXUDATION OF METASTATIC CUTANEOUS MELANOMA 15 DAYS AFTER TREATMENT WITH COMBINED TARGETED THERAPY
Authors: Wanten Victor , Vanhonsebrouck Eva , Jacob Julie 
Published: September 2023

Purpose:
The purpose of this study was to report a case of metastatic cutaneous melanoma to the choroid with rapid and complete resolution of associated choroidal elevation and subretinal fluid after the initiation of combined targeted therapy.

Methods:
We describe a case of a 41-year-old man diagnosed with a metastatic cutaneous melanoma to the choroid of his right eye, for which treatment with dabrafenib/trametinib was initiated.

Results:
A 41-year-old man with a medical history of a BRAF V600E/V600E2/V600D-mutated invasive superficial spreading cutaneous melanoma presented with acute metamorphopsia and blurred vision in his right eye. Examination revealed a best-corrected visual acuity (BCVA) of 20/22 and two elevated choroidal lesions temporal to the fovea with subretinal exudation to the fovea on fundoscopy. On repeat examination 3 days later, his vision had further decreased to 20/50 with an increase of subretinal fluid. Treatment with BRAF/MEK inhibitor dabrafenib/trametinib was initiated, with complete resolution of the choroidal masses and subretinal exudation and improvement of the BCVA to 20/22 after only 15 days. An 8-week follow-up after the start of therapy showed stable fundoscopic and tomographic findings, with further improvement of BCVA to 20/17 and no ocular side effects.

Conclusion:
A case of metastatic cutaneous melanoma to the choroid with choroidal elevation and subretinal exudation to the fovea, for which treatment with dabrafenib/trametinib was initiated. Rapid and complete resolution of choroidal metastasis and the associated subretinal exudation after the initiation of combined targeted therapy was seen, without any ocular side effects.
Moyamoya disease mimicking primary central nervous system vasculitis: A case report
Authors: Morikawa Ryo , Suzuki Junichiro , Nakai Noriyoshi , Takasu Syuntaro , Itoh Takayuki , Ito Yasuhiro 
Published: September 2023

Rationale:
Both Moyamoya disease (MMD) and primary central nervous system vasculitis (PCNSV) cause cerebrovascular stenosis resulting in similar ischemic neurological events, although therapeutic approaches are distinct from each other. High-resonance vascular wall imaging (HRVWI) with contrast-enhanced magnetic resonance imaging (MRI) is believed to be useful to differentiate PCNSV from MMD by detecting enhancement of cerebral vascular walls. However, recent studies have reported that the vascular walls of major arteries and superficial cerebral arteries are also enhanced by HRVWI in some MMD cases.

Patient concerns:
A 40-year-old Chinese woman admitted to our hospital with transient weakness of the right hand for a week. A cerebral infarction of the left frontal lobe was detected by diffusion-weighted brain MRI. Magnetic resonance angiography demonstrated severe stenosis of the left middle cerebral artery (MCA) and extensive vascular narrowing. Magnetic resonance angiography incidentally taken 3 years before admission showed only a mild stenosis at the proximal portion of right MCA with intact left internal carotid artery (ICA) and MCA. Moreover, on HRVWI with contrast-enhanced MRI after admission, the wall of ICA was strongly enhanced, and the superficial cerebral arteries were also highly enhanced, which initially suggested PCNSV. Despite these findings, reticular blood vessels were confirmed by digital subtraction angiography, and p.R4810K polymorphism in the ring finger protein 213 gene was detected.

Diagnosis:
Based on these result, the patient was diagnosed with MMD.

Interventions:
Bypass surgery was performed.

Outcomes:
Ischemic events have never been experienced since surgery.

Lessons:
Our MMD case demonstrated marked asymmetrical progression of cerebral artery stenosis, and enhanced vascular walls of ICA and superficial cerebral arteries by HRVWI, which made differential diagnosis from PCNSV difficult. Genetic analysis of SNP in the ring finger protein 213 gene should be performed to rule out MMD to avoid misdiagnosis of PCNSV particularly in Asian population.
Propiverine induced pure visual hallucinations without cognitive impairment: A case report
Authors: Selçuk Mahmut 
Published: September 2023

Rationale:
Propiverine is believed to have fewer adverse effects on the central nervous system than other anticholinergic medications since it penetrates the blood–brain barrier less deeply. In daily practice, no evidence links propiverine use to neuropsychiatric adverse effects. To our knowledge, this is the first report of psychotic symptoms being linked to propiverine use.

Patient concerns:
A urologist prescribed 30 mg/day of propiverine capsules to a 62-year-old male patient who complained of urine incontinence and visited the urology outpatient clinic. The patient returned to the urology outpatient clinic a week later because he was experiencing visual hallucinations.

Interventions:
In the psychiatry outpatient clinic, the patient was conscious, cooperative, and oriented during the mental state examination. He spoke about daylong visual hallucinations that included visions of numerous animals and geometric forms. His mood was somewhat anxious as a result of these images, which started appearing 3 days after taking the propiverine capsule and persisted for 4 days. His cognitive functions were normal. Physical examination, blood chemistry, endocrinology, and brain exams using cranial tomography and electroencephalogram revealed no abnormalities. We advised stopping the medication since visual hallucinations started soon after taking propiverine capsules.

Outcomes:
After discontinuation of propiverine capsules, the patient’s visual hallucinations disappeared.

Lessons:
Health practitioners should be aware that adverse effects like visual hallucinations can happen even with anticholinergic medications like propiverine that have a low level of penetration into the blood–brain barrier.
Regional Social Vulnerability is Associated with Geographic Disparity in Waitlist Outcomes for Patients with Non-HCC MELD Exceptions in the United States
Authors: Cannon Robert M. , Goldberg David S. , Sheikh Saulat S. , Anderson Douglas J. , Pozo Marcos , Rabbani Umaid , Locke Jayme E. 
Published: September 2023

Background:
This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplant with non-HCC MELD exceptions.

Methods:
Adults listed at a single center for a first time liver only transplant without HCC after June 18, 2013 in the SRTR database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplant were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control’s Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health.

Results:
There were 49,494 candidates in the cohort, of whom 4,337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n=78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 vs. 0.53 in non-advantaged HRRs (P=0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI vs. 40.7% of non-advantaged HRRs, while 44.6% of advantaged HRRs were in spatial clusters of low SVI vs.38.0% of non-advantaged HRRs (P=0.037).

Conclusion:
Advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity.
Digital thErapy For Improved tiNnitus carE Study (DEFINE): Protocol for a Randomised Controlled Trial
Authors: Smith Matthew E , Sharma Dhiraj , Rivero-Arias Oliver , Rand Kim , Barrack Lucy , Ogburn Emma , Young Michael , Field Polly , Multmeier Jan , Muzaffar Jameel 
Published: September 2023

AbstractTinnitus is a common health condition, affecting approximately 15% of the UK population. The tinnitus treatment with the strongest evidence base is Cognitive Behavioural Therapy (CBT), with standard tinnitus therapy typically augmented with education, relaxation and other techniques. Availability of CBT and conventional tinnitus therapy more broadly is limited for tinnitus sufferers.The DEFINE trial aims to assess whether smartphone-delivered tinnitus therapy, the Oto app, is as effective as current standard care, one-to-one therapist-delivered tinnitus treatment for the treatment of tinnitus in adults. The trial is registered in the ISRCTN Registry:ISRCTN99577932.DEFINE is an open-label, non-inferiority, prospective, parallel design, randomised-controlled trial. Recruitment, interventions and assessments will be remote, enabling UK-wide participant involvement.198 participants aged 18 years or more will be recruited via social media advertisement or via primary care physicians. A screening process will identify those with tinnitus that impacts health-related quality of life, and following consent smartphone-based audiometry will be performed. Randomisation 1:1 to the Oto app or one-to-one therapist-led tinnitus therapy will be performed centrally by computer, matching groups for age, sex and hearing level. Following participant allocation, the Oto app will be provided for immediate use, or a one-to-one remote therapy appointment booked to occur within approximately 1 week, with up to 6 sessions delivered.Participant outcomes will be collected at 4,12, 26 and 52 weeks via questionnaire and phone call. The primary outcome is the change in Tinnitus Functional Index (TFI) total score measured at 26 weeks following allocation. Adverse events will be recorded. A health economic evaluation in the form of a cost-utility analysis will be performed using data from participant submitted EuroQol 5D-5L and Health Utilities Index Mark 3 scores and resource use data.Trial results will be made publicly available, including a plain English summary.
Determinants of anti-retroviral therapy adherence among adolescents living with HIV in the Kingdom of Eswatini
Authors: Hlophe Londiwe D. , Shumba Constance S. , Bedada Diribsa T. , Nyasulu Peter S. 
Published: September 2023

AbstractBackgroundThe success of antiretroviral therapy (ART) depends on a high level of adherence to the life-long therapy of 95% and above. However, in Eswatini, adolescents and young people aged 15 to 24 years, have poor ART adherence as evidenced by low viral load (VL) suppression rates (76% and 63% among female and males respectively) compared to the general population (96%). The wide age-band of 15 to 24 years in reporting viral suppression rates means that adolescent specific data is limited, and younger adolescents aged 10-14 years are excluded. This study explored the level of ART adherence and associated factors among adolescents living with HIV (ALHIV) aged 10 to 19 years on ART in Eswatini.MethodsWe performed a retrospective analysis of 911 medical records of ALHIV aged 10 to 19 years on ART for at least a month in Eswatini for the period 1stJanuary 2017 to 30thSeptember 2022. Bivariate logistic regression was fitted for each predictor variable. Missing values were imputed using multiple imputation by chained equation (MICE). Statistically significant (p-value ≤0.2) predictor variables were included in a multivariable logistic regression model. P-value ≤0.05 was used to declare statistical significance in the final regression model.ResultsART adherence of 88.5% was recorded with higher adherence among males (88.9%) than females (87.8%). Hhohho region had highest adherence (90.7%) while Shiselweni region had lowest adherence (82%). Adherence was low among ALHIV with a non-suppressed baseline VL result (65.3%) and those assigned to multi-month ART model of care at ART initiation (66.7%). The Shiselweni region (OR 0.47; 95%CI 0.26-2.78), suppressed baseline VL result (OR 5.49; 95%CI 3.36-8,96) and assigned to the main-stream ART care model (OR 0.22; 95%CI 0.05-0.95) were statistically associated with ART adherence. In the multivariable regression analysis, only Shiselweni region and suppressed baseline VL result were statistically associated with ART adherence.ConclusionEswatini ALHIV have a low ART adherence compared to general population. Shiselweni region is negatively associated with ART adherence among ALHIV while a suppressed baseline VL is positively associated with improved ART adherence. There is therefore a need to intensify interventions aimed at early ART initiation and intensive follow-up and support among ALHIV especially in the Shiselweni region.
A new cell culture resource for investigations of reptilian gene function
Authors: Samudra Sukhada P. , Park Sungdae , Esser Elizabeth A. , McDonald Tryggvi P. , Borges Arianna M. , Eggenschwiler Jonathan , Menke Douglas B. 
Published: September 2023

AbstractThe recent establishment of CRISPR/Cas9 gene editing inA. sagreilizards makes it a powerful model system for studies of reptilian gene function. To enhance the versatility of this model, we developed an immortalized lizard fibroblast cell line (ASEC-1) for the exploration of reptilian gene function in cellular processes. We demonstrate the use of thisin vitrosystem by scrutinizing the role of primary cilia in lizard Hedgehog (Hh) signaling. Through CRISPR/Cas9 mutagenesis we disrupted theift88gene, which is required for ciliogenesis in diverse organisms. We find that the loss ofitf88from lizard cells results in an absence of primary cilia, a partial derepression ofgli1transcription, and an inability of the cells to respond to the Smoothened agonist, SAG. Through a cross-species analysis of SAG-induced transcriptional responses in cultured limb bud cells, we further determined that ∼46% of genes induced as a response to Hh pathway activation inA. sagrei,are also SAG-responsive inM. musculuslimb bud cells. Our results highlight conserved and diverged aspects of Hh signaling in anoles and establish a new resource for investigations of reptilian gene function.
Using a function-first ‘scout fragment’-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes
Authors: Ramsey Jared R. , Shelton Patrick M.M , Heiss Tyler K. , Olinares Paul Dominic B. , Vostal Lauren E. , Soileau Heather , Grasso Michael , Warrington Sara , Adaniya Stephanie , Miller Michael , Sun Shan , Huggins David J. , Myers Robert W. , Chait Brian T. , Vinogradova Ekaterina V. , Kapoor Tarun M. 
Published: September 2023

ABSTRACTHelicases, classified into six superfamilies, are mechanoenzymes that utilize energy derived from ATP hydrolysis to remodel DNA and RNA substrates. These enzymes have key roles in diverse cellular processes, such as genome replication and maintenance, ribosome assembly and translation. Helicases with essential functions only in certain cancer cells have been identified and helicases expressed by certain viruses are required for their pathogenicity. As a result, helicases are important targets for chemical probes and therapeutics. However, it has been very challenging to develop selective chemical inhibitors for helicases, enzymes with highly dynamic conformations. We envisioned that electrophilic ‘scout fragments’, which have been used for chemical proteomic based profiling, could be leveraged to develop covalent inhibitors of helicases. We adopted a function-first approach, combining enzymatic assays with enantiomeric probe pairs and mass spectrometry, to develop a covalent inhibitor that selectively targets an allosteric site in SARS-CoV-2 nsp13, a superfamily-1 helicase. Further, we demonstrate that scout fragments inhibit the activity of two human superfamily-2 helicases, BLM and WRN, involved in genome maintenance. Together, our findings suggest a covalent inhibitor discovery approach to target helicases and potentially other conformationally dynamic mechanoenzymes.
AccessPD - a ‘next generation’ registry to accelerate Parkinson’s disease research
Authors: Chang Yun-Hsuan , Periñan Maria Teresa , Wilson Matt , Noyce Alastair J 
Published: September 2023

AbstractObjectiveTo create a registry of patients with Parkinson’s disease (PD) and a rich database of PD-relevant information that can be used to stratify participants for precision opportunities.BackgroundRecruitment to studies and trials is a major rate-limiting factor in PD research. Participants from lower socioeconomic backgrounds or geographically remote areas often have restricted access to clinical research opportunities. AccessPD is a novel platform that aims to accelerate progress of PD research.Design/MethodsPotential participants are identified using electronic health records (EHRs) held by their primary care providers. They are contacted via a text message with an individualized link to the study portal. Electronic patient-reported outcomes (ePRO) are collected via regular online questionnaires and integrated with existing EHR.Results200 participants were recruited within the first 6 months, with an average age of 70.8 years at the time of enrollment. When re-engaged, 191 participants answered the follow-up questionnaire. Here, to showcase the potential of AccessPD, we described the most common diagnoses before and after the diagnosis of PD, the most commonly prescribed drugs, and we used a case study to demonstrate how precision opportunities for research can be created by identifying participants who could benefit from device-aided therapies using consensus criteria.ConclusionsAccessPD will enroll a minimum of 2000 patients. Early-stage analysis using ePROs and EHR data demonstrated AccessPD’s unique ability to link different data sources that could be used to stratify patients for longitudinal observational studies or recruit patients into clinical trials most suited to them.
Discovery of Urinary Metabolite Biomarkers of Psychiatric Disorders Using Two-Sample Mendelian Randomization
Authors: Zaki Jihan K. , Tomasik Jakub , McCune Jade , Scherman Oren A. , Bahn Sabine 
Published: September 2023

AbstractBackgroundPsychiatric disorders cause substantial patient suffering world-wide, which could be alleviated through the discovery of early diagnostic biomarkers. Urinary markers have promising practical applications; however, no robust urine biomarkers exist currently for psychiatric disorders. While the traditional biomarker discovery process is costly and time-consuming, genetic methods utilizing existing data from large-scale studies, such as Mendelian randomization, may provide an alternative, cost-effective approach to identifying such biomarkers.MethodsA two-sample Mendelian randomization analysis was conducted in R using GWAS data for seven psychiatric disorders from the Psychiatrics Genomics Consortium, as well as a meta-analysis of urinary metabolite GWAS studies and the GWAS Catalog. Mendelian randomization assumptions were assessed using the MR-Egger intercept, P-values, and genetic associations from the PhenoScanner database.OutcomesThe Mendelian randomization analysis revealed 67 analyte-disorder associations, of which 21 were exclusive to a single disorder. Most notable associations were observed between tyrosine and schizophrenia (β=−0.041, SE=0.013, Q=0.027), and creatine and bipolar disorder (β=−0.077, SE=0.019, Q=0.002), which validated across multiple studies, as well as that of pyridoxal (β=0.10, SE=0.03, Q=0.042) and ferulic acid 4-sulfate (β=0.077, SE=0.025, Q=0.037) to anorexia nervosa, and N,N-dimethylglycine to attention deficit hyperactivity disorder (β=−0.39, SE=0.11, Q=0.008).InterpretationThese results indicate an association between bipolar disorder, schizophrenia, anorexia nervosa, and attention deficit hyperactivity disorder with urinary metabolite marker alterations. Most of the findings were supported by previous literature. The results provide a roadmap for future experimental and clinical validation of the identified biomarker candidates and demonstrate the utility of using genetic instruments for urinary biomarker discovery.
A novel ultrasensitive assay for plasma p-tau217: performance in individuals with subjective cognitive decline and early Alzheimer’s disease
Authors: Gonzalez-Ortiz Fernando , Ferreira Pamela C L , Gonzalez Armand , Montoliu-Gaya Laia , Ortiz-Romero Paula , Kac Przemyslaw R. , Turton Michael , Kvartsberg Hlin , Ashton Nicholas J. , Zetterberg Henrik , Harrison Peter , Bellaver Bruna , Povala Guilherme , Villemagne Victor L. , Pascoal Tharick A. , Ganguli Mary , Cohen Anne D. , Miguillon Carolina , Contador Jose , Suarez-Calvet Marc , Karikari Thomas K. , Blennow Kaj 
Published: September 2023

ABSTRACTINTRODUCTIONDetection of Alzheimer’s disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.METHODSWe employed a novel p-tau217 immunoassay (UGOT p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (β-AARC).RESULTSUGOT p-tau217 showed high accuracy (AUC= 0.80-0.91) identifying Aβ pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC= 0.91).DISCUSSIONUGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.
A Retrospective Case Study of Successful Translational Research: Cardiovascular Disease Risk Assessment, Experiences in Community Engagement
Authors: Bales Michael E. , Zhu Jifeng , Ganzer Christine A. , Aboharb Farid , Keeler Allegra , Ryon Krista A. , Ehrmann Brett J. , Imperato-McGinley Julianne ,   the H2H Consortium
Published: September 2023

AbstractIn underserved communities in New York City, uninsured adults encounter a greater risk of cardiovascular disease and diabetes. The Heart-to-Heart Community Outreach Program (H2H) is addressing these disparities by providing screenings for diabetes and other cardiovascular disease risk factors, fostering community engagement in translational research at our CTSC. Screening events are hosted in partnership with community faith-based institutions. Participants provide medical history, complete a survey, and receive individualized counseling by clinicians with referrals for follow-up care. The population served is disproportionately non-white, uninsured, with low-income, and underserved. The program empowers participants to make beneficial lifestyle changes using myriad strategies to reach those most in need. This required strong foundational program leadership, effective inter-institutional collaboration, and maintaining of community trust. Leveraging partnerships with faith-based institutions and community centers in at-risk NYC neighborhoods, H2H addresses the increasing burden of diabetes and cardiovascular disease risk factors in vulnerable individuals and provides a model for similar initiatives.