bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular Surface Squamous Neoplasia: Changes in the Standard of Care 2003 to 2022
Authors: Greenfield Jason A. , Cohen Adam K. , Galor Anat , Chodosh James , Stone Donald , Karp Carol L. 
Published: January 2024

Purpose:
The aim of this review was to elucidate treatment preferences for ocular surface squamous neoplasia and to examine the changes in treatment modalities over the past 2 decades.

Methods:
An electronic survey was distributed to members of The Cornea Society, Ocular Microbiology and Immunology Group, and 4 international corneal specialist listservs. Questions examined medical and surgical treatment preferences, and results were compared with surveys administered in 2003 and 2012.

Results:
A total of 285 individuals responded to the survey; 90% of respondents were self-classified as corneal specialists. Seventy-three percent reported using primary topical monotherapy to treat ocular surface squamous neoplasia as compared with 58% in 2012 (P = 0.008). Compared with 2003, the percentage use of topical interferon significantly increased (P < 0.0001) from 14% to 55%, 5-fluorouracil increased (P < 0.0001) from 5% to 23%, and mitomycin C decreased (P < 0.0001) from 76% to 19% as a primary monotherapy. The frequency of performing excision without the use of postoperative adjunctive medical therapy decreased significantly (P < 0.0001), from 66% to 26% for lesions <2 mm, 64% to 12% for lesions between 2 and 8 mm, and 47% to 5% for lesions >8 mm from 2003 to 2022. More clinicians initiated topical immuno/chemotherapy without performing a biopsy as compared to 2003 (31% vs. 11%, P < 0.0001).

Conclusions:
These results demonstrate a paradigm shift in the management of ocular surface squamous neoplasia. The use of primary medical therapy as a first approach has significantly increased, with a reduction in the frequency of performing surgical excision alone.
Artificial Endothelial Layer Implantation After Multiple Failed Keratoplasties
Authors: Rens Jasmien , Krolo Iva , Koppen Carina , Ni Dhubhghaill Sorcha 
Published: January 2024

Purpose:
Presenting the first case of noncellular corneal endothelial substitute after multiple failed penetrating keratoplasty (PK) and lamellar endothelial keratoplasty.

Methods:
Our case presented with pseudophakic bullous keratopathy after a history of 2 rejected PKs and 1 rejected Descemet stripping automated endothelial keratoplasty. We implanted an artificial endothelial layer.

Results:
The implant remained fully attached for a follow-up period of 12 months, and central corneal thickness decreased significantly. The patient reported improvement in her subjective vision, although ocular comorbidities limited the visual potential.

Conclusions:
This new device could serve as an alternative to lamellar endothelial corneal transplantation in cases where tissue rejection has occurred and is highly likely to recur. The technique is simple, and the deswelling effect on the cornea persisted, although the visual results require further validation in patients with a higher visual potential.
Characterizing glare effects associated with diffractive optics in presbyopia-correcting intraocular lenses
Authors: Łabuz Grzegorz , Khoramnia Ramin , Yan Weijia , van den Berg Thomas J.T.P. , Auffarth Gerd U. , Naujokaitis Tadas , Tandogan Tamer 
Published: January 2024

Purpose:
To objectively quantify glare of intraocular lenses (IOLs) using a diffractive principle to extend the visual range and to identify models with increased susceptibility to inducing glare.

Setting:
David J Apple Laboratory, Heidelberg, Germany.

Design:
Laboratory investigation.

Methods:
Glare was assessed by means of a straylight parameter with a standard C-Quant intended for 7 degrees. In addition, 2 C-Quant modifications were used to test lower angles (ie, 2.5 degrees and 3.5 degrees). The following IOL models were assessed: PanOptix, AT Lisa Tri, Synergy, and Triumf, the latter 2 with chromatic aberration correction at distance. Straylight from trifocal IOLs was compared against a monofocal W-60R lens. The C-Quant test was performed through the studied IOLs by using additional optical components attached to their ocular.

Results:
Straylight (deg2sr−1) of the control was <1 at all tested angles, with the trifocal models showing comparable straylight at 7 degrees. At 3.5 degrees, Triumf's straylight increased to 15.5 ± 0.6, followed by Synergy (6.2 ± 1.1), PanOptix (4.1 ± 0.3), and AT Lisa Tri (2.0 ± 0.8). The chromatic aberration–correcting models demonstrated correspondingly higher straylight (Synergy: 18.8 ± 1.3; Triumf: 17.3 ± 0.5) at 2.5 degrees compared with PanOptix (4.3 ± 0.4), AT Lisa Tri (2.1 ± 0.1), and monofocal IOLs yielding minimal or no increase.

Conclusions:
Trifocal IOLs induced increased straylight, but it was limited to lower angles, which may cause difficulties detecting these effects using a standard clinical approach. The latest IOL designs featuring chromatic aberration correction at far focus seem more susceptible than the established trifocal IOLs to inducing a glare phenomenon.
Subclinical Measures of Cardiovascular Health Among Wildland Firefighters
Authors: Hasan Md Zahid , Semmens Erin O. , Navarro DuBose Kathleen , McCray L. Kaili , Noonan Curtis W. 
Published: January 2024

Objective
The aim of the study is to compare subclinical measures of cardiovascular health among wildland firefighters (WFFs) to the US general population.

Methods
Our cross-sectional study compared body mass index, total cholesterol, and blood pressure in 11,051 WFFs aged 17 to 64 years using Department of the Interior Medical Screening Program clinical screening examinations between 2014–2018 to National Health and Nutrition Examination Survey of 2015–2016 cycle using adjusted logistic regression analyses.

Results
The logistic regression model shows significantly higher odds of hypertension and prehypertension in WFFs (2.84 times more with 95% CI: 2.28–3.53) than US general population. There were no consistent differences in body mass index or total cholesterol between the two population.

Conclusions
Hypertension and prehypertension were more prevalent in WFFs compared with the US general population, which suggests the need for actions for protecting against cardiovascular disease among WFFs.
Somatic mosaicism in focal epilepsies
Authors: Gooley Samuel , Perucca Piero , Tubb Caitlin , Hildebrand Michael S. , Berkovic Samuel F. 
Published: January 2024

Purpose of review
Over the past decade, it has become clear that brain somatic mosaicism is an important contributor to many focal epilepsies. The number of cases and the range of underlying pathologies with somatic mosaicism are rapidly increasing. This growth in somatic variant discovery is revealing dysfunction in distinct molecular pathways in different focal epilepsies.

Recent findings
We briefly summarize the current diagnostic yield of pathogenic somatic variants across all types of focal epilepsy where somatic mosaicism has been implicated and outline the specific molecular pathways affected by these variants. We will highlight the recent findings that have increased diagnostic yields such as the discovery of pathogenic somatic variants in novel genes, and new techniques that allow the discovery of somatic variants at much lower variant allele fractions.

Summary
A major focus will be on the emerging evidence that somatic mosaicism may contribute to some of the more common focal epilepsies such as temporal lobe epilepsy with hippocampal sclerosis, which could lead to it being re-conceptualized as a genetic disorder.
Hidden stories of caregivers with children living with sickle cell disease in Uganda: experiences, coping strategies and outcomes
Authors: Alinda Isaac , Kabiri Lydia 
Published: January 2024

AbstractBackgroundSickle Cell Disease (SCD) poses a substantial public health challenge in Uganda, exhibiting distinct regional variations in prevalence. The Uganda Sickle Cell Surveillance Study has estimated an overall SCD prevalence of 13.3%. Notably, this prevalence diverges significantly across the country’s regions, reaching its highest in the northern region at 22.2% and it’s lowest in the central region at 5.3%. This variation reflects the diverse impact of SCD and underscores the need for a comprehensive understanding of its regional implications.SCD places substantial physical, social, and psychological burdens on caregivers, potentially leading to heightened parental stress. However, limited research has focused on the daily challenges and experiences of SCD caregivers, despite evidence showing the detrimental impact on their emotional well-being, personal lives, employability, and socioeconomic status. This study explored the undisclosed struggles of Ugandan caregivers tending to children with SCD, uncovering their coping strategies and subsequent outcomes.MethodsFrom June 23rd to July 30th, 2023, we engaged in the recruitment of participants for our study, we conducted in-depth interviews with caregivers at Mulago sickle cell clinic after obtaining their informed consent. An interview guide was used as the primary data collection tool, with interviews lasting 30-45 minutes. Twelve participants were recruited, ensuring comprehensive data collection by following the data saturation principle. We analyzed the collected data using open coding.ResultsThree key themes emerged: caregiver experiences, coping strategies, and outcomes. Initially, caregivers grappled with confusion and uncertainty before a formal diagnosis. Financial strain and inadequate support posed persistent challenges, affecting their emotional well-being. Coping strategies varied, encompassing traditional remedies and modern medical treatments for symptom relief. Coping outcomes were complex, reflecting caregivers’ resilience alongside substantial emotional distress and sleep disturbances. The substantial financial burden further exacerbated their overall well-being.ConclusionElevating awareness and knowledge about sickle cell disease within communities is essential. Such awareness can empower caregivers of children living with sickle cell disease, promoting emotional resilience and mitigating family disruptions.
Exposure to angiotensin-converting enzyme inhibitors that cross the blood-brain barrier and the risk of dementia among patients with human immunodeficiency virus
Authors: Cummings Tammy H. , Magagnoli Joseph , Sikirzhytskaya Aliaksandra , Tyagin Ilya , Safro Ilya , Wyatt Michael D. , Shtutman Michael , Sutton S. Scott 
Published: January 2024

ABSTRACTMore than one million people in the United States and over 38 million people worldwide are living with human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) greatly improves the health of people living with HIV (PLWH); however, the increased life longevity of PLWH has revealed consequences of HIV-associated comorbidities. HIV can enter the brain and cause inflammation even in individuals with well-controlled HIV infection. The quality of life for PLWH can be compromised by cognitive deficits and memory loss, termed HIV-associated neurological disorders (HAND). HIV-associated dementia is a related but distinct diagnosis. Common causes of dementia in PLWH are similar to the general population and can affect cognition. There is an urgent need to identify treatments for the aging PWLH population. We previously developed AI-based biomedical literature mining systems to uncover a potential novel connection between HAND the renin-angiotensin system (RAAS), which is a pharmacological target for hypertension. RAAS-targeting anti-hypertensives are gaining attention for their protective benefits in several neurocognitive disorders. To our knowledge, the effect of RAAS-targeting drugs on the cognition of PLWH development of dementia has not previously been analyzed. We hypothesized that exposure to angiotensin-converting enzyme inhibitors (ACEi) that cross the blood brain barrier (BBB) reduces the risk/occurrence of dementia in PLWH. We report a retrospective cohort study of electronic health records (EHRs) to examine the proposed hypothesis using data from the United States Department of Veterans Affairs, in which a primary outcome of dementia was measured in controlled cohorts of patients exposed to BBB-penetrant ACEi versus those unexposed to BBB-penetrant ACEi. The results reveal a statistically significant reduction in dementia diagnosis for PLWH exposed to BBB-penetrant ACEi. These results suggest there is a potential protective effect of BBB ACE inhibitor exposure against dementia in PLWH that warrants further investigation.
Conventional electrode catheter placement can miss crucial atypical atrioventricular nodal reentrant tachycardia circuit details. -New insights into the retrograde slow pathways-
Authors: Kawabata Mihoko , Maeda Shingo , Okishige Kaoru , Shirai Yasuhiro , Kamata Tatsuaki , Kawashima Tomoyuki , Yonai Ryo , Atarashi Hirotsugu , Hirao Kenzo 
Published: January 2024

AbstractBackgroundDuring atypical atrioventricular nodal reentrant tachycardia (AVNRT), the earliest atrial activation site following retrograde slow pathway (SP) conduction is at the atrial exit of the left inferior extension of the compact node (LIE) in the coronary sinus (CS) or the right inferior extension (RIE) on the tricuspid annulus (TA). We tested the validity of conventional electrode placement-based mapping of the atrial ends of these extensions.MethodsWe retrospectively evaluated the efficiency of the two catheter (His bundle and CS) mapping method for localization of LIE and RIE in atypical AVNRT patient using electroanatomical 3D mapping validation.ResultsAmong 19 atypical AVNRTs (15 fast/slow and 4 slow/slow) in 14 patients (9 females, age 59±17), 8 AVNRTs had LIE involvement and 11 had RIE. The 8 LIE exits were inside the CS, and localization by 3D mapping and CS electrode catheter matched in all. In contrast, RIE exits were on the posterior TA where electrode catheters are conventionally not placed. All RIE exits required 3D mapping for accurate localization. During retrograde RIE conduction, comparison of the activation time of the CS ostium and HBE showed that the CS ostium was earlier in 7 RIEs, HBE was earlier in 1, and they were simultaneous in 3, resulting in the presence of RIE being missed in 4/11 (36%) AVNRTs using current diagnostic criteria. Activation time of the CS ostium and His bundle were determined by their relative closeness to the RIE exit.ConclusionsConventionally placed electrode catheter mapping in atypical AVNRT was able to identify 100% of LIE, but only 64% of RIE. It is critical to place a catheter on or use a 3D mapping system for the posterior TA in cases of suspected atypical AVNRT, so that all inferior extensions of the AV node can be identified and targeted for treatment.
DNA damage-induced PARP/ALC1 activation leads to Epithelial-to-Mesenchymal transition stimulating homologous recombination
Authors: Rajabi Fatemeh , Smith Rebecca , Liu-Bordes Win-Yan , Schertzer Michael , Huet Sebastien , Londoño-Vallejo Arturo 
Published: January 2024

AbstractEpithelial-to-mesenchymal transition (EMT) allows cancer cells to metastasize while acquiring resistance to apoptosis and to chemotherapeutic agents with significant implications in patients’ prognosis and survival. Despite its clinical relevance, the mechanisms initiating EMT during cancer progression remain poorly understood. We demonstrate that DNA damage triggers EMT by activating PARP and the PARP-dependent chromatin remodeler ALC1 (CHD1L). We show that this activation directly facilitates the access to chromatin of EMT transcriptional factors (TFs) which then initiate cell reprogramming. We also show that EMT-TFs bind to the RAD51 promoter to stimulate its expression and to promote DNA repair by recombination. Importantly, a clinically relevant PARP inhibitor totally reversed or prevented EMT in response to DNA damage while resensitizing tumor cells to other genotoxic agents. Overall, our observations shed light on the intricate relationship between EMT, DNA damage response and PARP inhibitors, providing valuable insights for future therapeutic strategies in cancer treatment.
Root-specific secondary metabolism at the single-cell level: a case study of theanine metabolism and regulation in the roots of tea plants (Camellia sinensis)
Authors: Lin Shijia , Zhang Yiwen , Zhang Shupei , Wei Yijie , Han Mengxue , Deng Yamei , Guo Jiayi , Zhu Biying , Yang Tianyuan , Xia Enhua , Wan Xiaochun , Lucas William J. , Zhang Zhaoliang 
Published: January 2024

AbstractRoot-synthesized secondary metabolites are critical quality-conferring compounds of foods, plant-derived medicines, and beverages. However, information at a single-cell level on root-specific secondary metabolism remains largely unexplored. L-theanine, an important quality component of tea, is primarily synthesized in roots, from which it is then transported to new shoots of tea plant. In this study, we present a single-cell RNA sequencing (scRNA-seq)-derived map for the tea plant root, which enabled cell-type-specific analysis of glutamate and ethylamine (two precursors of theanine biosynthesis) metabolism, and theanine biosynthesis, storage, and transport. Our findings support a model in which the theanine biosynthesis pathway occurs via multicellular compartmentation and does not require high co-expression levels of transcription factors and their target genes within the same cell cluster. This study provides novel insights into theanine metabolism and regulation, at the single-cell level, and offers an example for studying root-specific secondary metabolism in other plant systems.
Chromosome-scale genome assembly of bread wheat’s wild relativeTriticum timopheevii
Authors: Grewal Surbhi , Yang Cai-yun , Scholefield Duncan , Ashling Stephen , Ghosh Sreya , Swarbreck David , Collins Joanna , Yao Eric , Sen Taner Z. , Wilson Michael , Yant Levi , King Ian P. , King Julie 
Published: January 2024

AbstractWheat (Triticum aestivum) is one of the most important food crops with an urgent need for increase in its production to feed the growing world.Triticum timopheevii(2n = 4x = 28) is an allotetraploid wheat wild relative species containing the Atand G genomes that has been exploited in many pre-breeding programmes for wheat improvement. In this study, we report the generation of a chromosome-scale reference genome assembly ofT. timopheeviiaccession PI 94760 based on PacBio HiFi reads and chromosome conformation capture (Hi-C). The assembly comprised a total size of 9.35 Gb, featuring a contig N50 of 42.4 Mb, and 166,325 predicted gene models. DNA methylation analysis showed that the G genome had on average more methylated bases than the Atgenome. The G genome was also more closely related to the S genome ofAegilops speltoidesthan to the B genome of hexaploid or tetraploid wheat. In summary, theT. timopheeviigenome assembly provides a valuable resource for genome-informed discovery of agronomically important genes for food security.
The general transcription factor TFIIB is a target for transcriptome control during cellular stress and viral infection
Authors: Gulyas Leah , Glaunsinger Britt A. 
Published: January 2024

AbstractMany stressors, including viral infection, induce a widespread suppression of cellular RNA polymerase II (RNAPII) transcription, yet the mechanisms underlying transcriptional repression are not well understood. Here we find that a crucial component of the RNA polymerase II holoenzyme, general transcription factor IIB (TFIIB), is targeted for post-translational turnover by two pathways, each of which contribute to its depletion during stress. Upon DNA damage, translational stress, apoptosis, or replication of the oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV), TFIIB is cleaved by activated caspase-3, leading to preferential downregulation of pro-survival genes. TFIIB is further targeted for rapid proteasome-mediated turnover by the E3 ubiquitin ligase TRIM28. KSHV counteracts proteasome-mediated turnover of TFIIB, thereby preserving a sufficient pool of TFIIB for transcription of viral genes. Thus, TFIIB may be a lynchpin for transcriptional outcomes during stress and a key target for nuclear replicating DNA viruses that rely on host transcriptional machinery.Graphical AbstractSignificance StatementTranscription by RNA polymerase II (RNAPII) synthesizes all cellular protein-coding mRNA. Many cellular stressors and viral infections dampen RNAPII activity, though the processes underlying this are not fully understood. Here we describe a two-pronged degradation strategy by which cells respond to stress by depleting the abundance of the key RNAPII general transcription factor, TFIIB. We further demonstrate that an oncogenic human gammaherpesvirus antagonizes this process, retaining enough TFIIB to support its own robust viral transcription. Thus, modulation of RNAPII machinery plays a crucial role in dictating the outcome of cellular perturbation.
Alcohol Use Disorder-Associated DNA Methylation in the Nucleus Accumbens and Dorsolateral Prefrontal Cortex
Authors: White Julie D. , Minto Melyssa S. , Willis Caryn , Quach Bryan C. , Han Shizhong , Tao Ran , Deep-Soboslay Amy , Zillich Lea , Clark Shaunna L. , van den Oord Edwin J. C. G. , Hyde Thomas M. , Mayfield R. Dayne , Webb Bradley T. , Johnson Eric O. , Kleinman Joel E. , Bierut Laura J. , Hancock Dana B. 
Published: January 2024

AbstractBackgroundAlcohol use disorder (AUD) has a profound public health impact. However, understanding of the molecular mechanisms underlying the development and progression of AUD remain limited. Here, we interrogate AUD-associated DNA methylation (DNAm) changes within and across addiction-relevant brain regions: the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC).MethodsIllumina HumanMethylation EPIC array data from 119 decedents of European ancestry (61 cases, 58 controls) were analyzed using robust linear regression, with adjustment for technical and biological variables. Associations were characterized using integrative analyses of public gene regulatory data and published genetic and epigenetic studies. We additionally tested for brain region-shared and -specific associations using mixed effects modeling and assessed implications of these results using public gene expression data.ResultsAt a false discovery rate ≤ 0.05, we identified 53 CpGs significantly associated with AUD status for NAc and 31 CpGs for DLPFC. In a meta-analysis across the regions, we identified an additional 21 CpGs associated with AUD, for a total of 105 unique AUD-associated CpGs (120 genes). AUD-associated CpGs were enriched in histone marks that tag active promoters and our strongest signals were specific to a single brain region. Of the 120 genes, 23 overlapped with previous genetic associations for substance use behaviors; all others represent novel associations.ConclusionsOur findings identify AUD-associated methylation signals, the majority of which are specific within NAc or DLPFC. Some signals may constitute predisposing genetic and epigenetic variation, though more work is needed to further disentangle the neurobiological gene regulatory differences associated with AUD.