bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent and Severe Mpox Keratitis Despite Systemic and Topical Treatment
Authors: Domínguez García Laura , Gutierrez-Arroyo Almudena , Miguel-Buckley Rosa , Martin Ucero Ana , Cantizani Juan , Boto-de-los-Bueis Ana 
Published: March 2024

Purpose:
The purpose of this study was to report a case of peripheral ulcerative keratitis in a patient diagnosed with corneal polymerase chain reaction (PCR) and a positive mpox culture.

Methods:
This is a case report.

Results:
An immunocompetent 54-year-old man was diagnosed with conjunctivitis in his left eye 15 days after being diagnosed with mucocutaneous monkeypox. He received treatment with dexamethasone 0.1% and tobramycin 0.3% eye drops for 2 weeks. Two weeks after discontinuing this treatment, he developed peripheral ulcerative keratitis and a paracentral epithelial defect. Mpox keratitis was diagnosed by corneal culture and PCR. Corneal inflammation persisted for more than 6 months, manifested as corneal epithelial defect, limbitis, endotheliitis, neurotrophic changes, and trabeculitis. This persistence was observed alongside positive corneal PCR results, despite undergoing 2 courses of trifluorothymidine, 2 courses of oral tecovirimat, and intravenous cidofovir. An amniotic membrane transplantation was then performed.

Conclusions:
Persistent corneal pain and replication are possible with the mpox virus, even in immunocompetent patients. Having received treatment with topical corticosteroids before antiviral treatment for the pox virus may have contributed to the severity and persistence of the clinical condition. Cycle threshold PCR values can be used to support the diagnosis and monitor treatment effectiveness.
Punctal and Canalicular Stenosis Following Topical 1% 5-Fluorouracil Eye Drop Therapy for Ocular Surface Squamous Neoplasia
Authors: Alvarez Osmel P. , Zein Mike , Serrano Andres , Galor Anat , Karp Carol L. 
Published: March 2024

Purpose:
To present the first known cases of punctal and canalicular stenosis following topical 5-fluorouracil (5-FU) eye drops for ocular surface squamous neoplasia (OSSN).

Methods:
A retrospective chart review of patients with OSSN receiving topical 1% 5-FU eye drops as a primary or adjuvant treatment between 2013 and 2021 was performed. Individuals diagnosed with punctal or canalicular stenosis during or after topical 5-FU use were included in this study. Four individuals met these criteria; we report clinical findings and treatment course for each patient.

Results:
We reviewed 303 patients (316 eyes) with OSSN. All patients were treated with topical 1% 5-FU eye drops in cycles, given 4 times daily for 1 week with 3 weeks off. Four patients (5 eyes) developed punctal stenosis, for a frequency of 1.3%. The mean age at 5-FU initiation in the 4 individuals was 61 years (range 53–69). Most individuals were male (75%), White (75%), and non-Hispanic (100%). The most common presenting symptom of stenosis was epiphora, noted 4.6 ± 3 months after initiating topical 5-FU (after 4.9 ± 2.0 cycles). This occurred in 4 eyes while on therapy (3, 2, 4, and 4 months since 5-FU initiation) and in 1 eye after stopping therapy (10.3 months since 5-FU initiation). In 1 eye, punctal stenosis and epiphora resolved spontaneously after stopping 5-FU. Punctal dilation led to symptom resolution in 2 eyes. Surgical intervention (punctoplasty and external dacryocystorhinostomy) was needed in 2 eyes for punctal and canalicular stenosis, respectively.

Conclusions:
Punctal or canalicular stenosis is a rare and previously unreported adverse effect of topical 5-FU that may require surgical treatment.
Demographic and Psychiatric Associations With Dry Eye in a Medicare Population
Authors: Li Gavin , Garzon Catalina , Klawe Janek , Akpek Esen Karamursel , Ahmad Sumayya 
Published: March 2024

Purpose:
The purpose of this study was to investigate the impact of demographic characteristics and psychiatric comorbidity on the prevalence of dry eye disease in the American geriatric population.

Methods:
Data were collected from a 2011 nationwide sample of Medicare beneficiaries aged 65 years and older (N = 1,321,000). Age, sex, race/ethnicity, residential area, climate region, and income, along with psychiatric comorbidities including depression and anxiety, were collected. Multivariable logistic regression models were used to assess the relationship between demographic and psychiatric factors and the prevalence of dry eye disease.

Results:
Among 21,059 patients with clinically significant dry eye, women had higher odds of having dry eye compared with men [odds ratio (OR) 2.03, 95% confidence interval (1.97–2.10)]. Asian and Native American patients had increased odds of having dry eye compared with White patients [OR 1.85 (1.69–2.02) and OR 1.51 (1.19–1.93)], while Black patients were less likely to have dry eye [OR 0.83 (0.79–0.87)]. Patients aged 75 to 84 years and 85+ were more likely to have dry eye compared with those aged 65 to 74 years [OR 1.49 (0.45–1.53) and OR 1.54 (1.48–1.60)]. Having both depression and anxiety were associated with higher odds of having dry eye [OR 2.38 (2.22–2.55)] compared with having depression alone [OR 1.95 (1.86–2.04)] or anxiety alone [OR 2.22 (2.10–2.35)].

Conclusions:
Significant racial and regional disparities in dry eye prevalence were found. Psychiatric association with dry eye varied with age, sex, race, and residence region. Further research is needed to comprehend the underlying mechanisms, implications, and to address disparities in the diagnosis and management of dry eye.
Unregulated Decorative Lenses: A Brief Definitive Review
Authors: Han Elaine , Rhee Michelle K. 
Published: March 2024

Abstract:
Contact lenses are US Food and Drug Administration-regulated medical devices that are a safe and effective method for the correction of refractive error. They are worn by an estimated 45 million Americans. Decorative contact lenses (DCLs) can be used for patients with medical conditions such as failed corneas or aniridia. However, DCLs have also gained popularity in the young, contact lens-naïve population. DCL users often buy lenses through unregulated sources without a clinical examination and education on proper use by an eye care professional. These lenses have a significantly higher risk of infection when compared with contact lenses for the correction of refractive error. To reduce the incidence of microbial keratitis, regulators and eye care professionals must make coordinated efforts to generate and disseminate prevention messages to all contact lens users. In addition, physician and patient reporting of contact lens-related complications to regulatory agencies enhances the pathway to risk reduction. This article reviews DCL use and supply, with a specific focus on the increased risk of contact lens-related complications in unsupervised DCL use.
Therapeutic Response to Treatment of a Papillomatous Ocular Surface Squamous Neoplasia With Intramuscular Human Papillomavirus Vaccine
Authors: Zein Mike , De Arrigunaga Sofia , Amer Mona M. , Galor Anat , Nichols Anna J. , Ioannides Tim , Dubovy Sander R. , Karp Carol L. 
Published: March 2024

Purpose:
The purpose of this study was to describe the response of a papillomatous ocular surface squamous neoplasia (OSSN) to the intramuscular (IM) 9-valent human papillomavirus (HPV) vaccine after failed medical and surgical interventions.

Methods:
A 79-year-old White man with a conjunctival lesion underwent a biopsy which revealed OSSN and positivity for high-risk HPV. Initially treated with medical therapy and surgical excisions, the patient developed a recurrence and refused further surgery. He was given 4 doses of IM HPV vaccine at the 6-week interval.

Results:
A dramatic reduction in lesion size and reduced epithelial thickening and hyperreflectivity was noted on slitlamp examination and high-resolution anterior segment optical coherence tomography after receiving the IM HPV vaccine. Although lesion size was markedly reduced, the therapy did not achieve total resolution, resulting in further treatment with topical 1% 5-fluorouracil (5-FU) eye drops and later 0.04% mitomycin C eye drops. The patient then elected to discontinue further treatment and solely observe.

Conclusions:
This case report adds to the growing literature demonstrating the potential therapeutic use of vaccines in cancer treatment. Although HPV vaccination is currently approved for prophylaxis, the use of HPV vaccines as a therapeutic option for various HPV-mediated diseases, including OSSN, should be further explored. The HPV vaccine yielded significant initial improvement in this patient who refused further surgical interventions. The use of IM HPV vaccine as an adjunctive treatment of papillomatous OSSN may represent a potential therapeutic option in cases refractory to standard treatment modalities.
Phase 3 Safety and Immunogenicity Study of a Three-dose Series of Twenty-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers
Authors: Korbal Piotr , Wysocki Jacek , Jackowska Teresa , Kline Mary , Tamimi Noor , Drozd Jelena , Lei Lanyu , Peng Yahong , Giardina Peter C. , Gruber William , Scott Daniel , Watson Wendy 
Published: March 2024

Background:
Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains.

Methods:
This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events.

Results:
Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48–0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13.

Conclusions:
PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.
Aggressiveness in systemic anticancer therapy at the end of life in an oncology center
Authors: Ferraz-Gonçalves José António , Silva Inês , Redondo Patrícia , Luís Michael Sapateiro 
Published: March 2024

Introduction:
An increasing aggressiveness in cancer treatment at the end of life (EoL) has been reported in several, but not all, countries. This study aimed to see how aggressive cancer treatment is at the EoL in an oncology center.

Methods:
Retrospective study of patients 18 years or older with a solid cancer diagnosis who died in 2017. The focus was systemic anticancer therapy (SACT), excluding hormonotherapy.

Results:
In 2017, 2024 patients with solid tumors died. Of those patients, 1262 (62%) were male, and the median age was 69 (range 19–97) years. The most frequent primary cancer was lung cancer, followed by colorectal and stomach cancers, and 740 (37%) patients had metastatic disease. The median interval between SACT and death was 61 days. Of the patients undergoing SACT, 216 (27%) did it in the last month of life, 174 (22%) between 8 and 30 days from death, and 42 (5%) in the last week. On multivariable analysis, head and neck, colorectal, breast, and melanoma primaries; age group (older than 65 years); and metastatic disease had statistical significance associated with SACT. Of these variables, only metastatic disease is more likely to undergo SACT.

Conclusion:
This study confirms the relatively frequent aggressiveness in cancer treatment at the EoL. Taking into consideration previously published data, it can be tentatively concluded that the use of SACT increased in the last month and the last week of life.
On Merit and Equity in Admission to US Physical Therapist Education Programs: A Qualitative Analysis of Faculty Habitus
Authors: Nuciforo Matthew A. 
Published: March 2024

Introduction.
In contrast to the increased diversity of the US population, historically excluded racial and ethnic groups remain underrepresented in the physical therapist profession. As decision-makers, faculty exert direct influence on enrollment through evaluating applications and determining which applicants are deserving of admission to physical therapist programs.

Review of Literature.
Faculty decision-making in admissions is a cultural process which can reproduce inequities and perpetuate underrepresentation if faculty fail to recognize systemic disparities in legitimized forms of merit. No studies within physical therapist education have directly investigated faculty habitus and patterns of thought and behavior which reinforce admissions decision-making. The purpose of this study was to describe patterns of faculty habitus which influence judgments of admission merit and equity in US physical therapist education programs.

Subjects.
Sixteen physical therapy faculty across 3 physical therapist education programs.

Methods.
Using interpretative research methodology and a constructivist approach, semistructured interviews were conducted with each participant. Faculty social actions were also observed during field observations. Thematic analysis using Bourdieu's social reproduction theory was used for coding and establishment of themes.

Results.
Two predominant patterns of faculty habitus with corresponding themes emerged from the data: Transformative habitus oriented faculty toward a sense of responsibility to promote equity, construct a more contextualized understanding of merit, and formulate compelling applicant storylines; gatekeeping habitus positioned faculty to support a meritocratic process, reinforce traditional notions of academic rigor, and support the necessity of adjusting standards to address underrepresentation.

Discussion and Conclusion.
Findings revealed contrasting patterns of faculty habitus which legitimized certain criteria, knowledge, and experiences on which decisions of merit were based. Attention to the individual dispositions of faculty decision-makers in addition to criteria and processes used in holistic review may shape equitable access to physical therapist education programs.
The impact of teach-back training method (TBTM) on treatment adherence in hemodialysis patients: a randomized controlled trial
Authors: Alilu Leyla , Pazirofteh Sonia , Habibzadeh Hossein , Rasouli Javad 
Published: March 2024

Introduction:
Ensuring adherence to treatment is vital for individuals undergoing haemodialysis. The demanding treatment frequency and duration often present challenges for patients in maintaining a consistent routine. Non-adherence can result in adverse health effects and an increased risk of hospitalization. This study aimed to evaluate the impact of teach-back training on treatment adherence among haemodialysis patients.

Method:
A randomized controlled trial involved 60 end-stage kidney disease patients undergoing haemodialysis. Participants were randomly assigned to either the control or intervention group. Data were collected using the End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ), assessing adherence in four dimensions: HD incidence, medication use, fluid restriction, and diet recommendations. The intervention group received feedback-based training on diet and fluid restriction during four 45–60-min sessions, while the control group received regular indoor training.

Result:
Following the intervention, significant differences in mean scores for HD frequency, medication use, and fluid restriction were observed between the two groups (P<0.001). However, there was no significant difference in the mean score for food recommendations (P=0.108).

Conclusion:
The teach-back training method (TBTM) is an effective communication strategy that enhances treatment adherence in haemodialysis patients. This intervention has the potential to improve patient outcomes and overall quality of life by simplifying medical information and encouraging patient engagement.
Canadian Anatomic Kidney Score: Quantitative Macroscopic Assessment of Donor Kidney Quality for Transplantation
Authors: Matti Danny , Offerni Juliano , Roshanov Pavel S. , Lu Jirong , Guo Yanbo , Lebedeva Victoria , Ai Li Erica , Abed Haider , Luke William , Sener Alp , Luke Patrick P. 
Published: March 2024

Background.
The Canadian Anatomic Kidney Score (CAKS) is a novel 6-point grading system that standardizes the gross description of a donor kidney across 3 components—vessels, anatomy, and sticky fat. We hypothesized that the CAKS predicts allograft functional outcomes and provides additional information to the Kidney Donor Profile Index (KDPI) and histologic assessment of the donor kidney.

Methods.
Single-center cohort of 145 patients who underwent renal transplantation with CAKS analysis between 2018 and 2021. CAKS was prospectively determined before transplantation. Preimplantation core biopsies were assessed according to the Remuzzi score (RS). The primary outcome was 1-y allograft function represented by an estimated glomerular filtration rate (eGFR).

Results.
Linear regression without adjustment for KDPI or RS showed a significant association between the CAKS and 1-y eGFR (−8.7 mL/min/1.73 m2 per point increase in CAKS; 95% CI, −13.0 to −4.4; P < 0.001). Most of that association was attributed to the vessel component (−12.1; −19.4 to −4.8; P = 0.002). Adjustment for KDPI and RS attenuated the relationship between 1-y function and CAKS (−4.6; −9.5 to 0.3; P = 0.065) and vessel component (−7.4; −15.2 to 0.5; P = 0.068).

Conclusions.
Anatomic assessment of donor kidneys at the time of transplantation associates with allograft function at 1 y. Vascular assessment appears to make the dominant contribution.
Dual targeting of EZH2 and Histone Deacetylases in hematological malignancies promotes transcriptional and metabolic deregulation leading to ferroptosis
Authors: Veloso Alexandra , Slegers Thomas , Schoenaker Jente , Demeyer Sofie , den Bergh Stef Van , Aertgeerts Margo , Verhoeft Krista , Schoenmaekers Yilke , Meeuws Nienke , Bischops Ilan , Renard Félicien , Boogaerts Lien , Mentens Nicole , Gielen Olga , Jacobs Kris , Segers Heidi , Cools Jan , Dierickx Daan , Bempt Marlies Vanden 
Published: March 2024

AbstractThe methyltransferase EZH2 functions as the enzymatic component of the PRC2 complex, which deposits methyl groups on H3K27, leading to chromatin condensation and gene repression. Recent studies have shown that EZH2 can also act as a transcriptional modulator outside of the PRC2 complex and thus, independent of its methyltransferase activity. In this study, we first aimed to investigate the effects of EZH2 enzymatic inhibition versus protein degradation in hematological malignancies. We demonstrate that EZH2 degradation is more effective in blocking cellular proliferation compared to EZH2 enzymatic inhibition, and that EZH2 targeting upregulates the cholesterol biosynthesis pathway. Secondly, combined targeting of EZH2 and HDACs showed synergistic effects in a broader spectrum of hematological malignancies. Mechanistically, combined targeting of EZH2 and HDACs induced increased levels of H3K27 acetylation and strong upregulation of cholesterol biosynthesis. This leads to metabolic stress due to acetyl-CoA depletion, ultimately inducing ferroptotic cell death.Statement of significanceWe show that combined EZH2 and HDAC targeting is a promising therapeutic strategy for a broad spectrum of hematological malignancies. We uncover that EZH2 targeting induces upregulation of cholesterol biosynthesis, which is crucial for the synergistic effect with HDAC inhibition, ultimately leading to ferroptosis induction.
Nociceptive neurons interact directly with gastric cancer cells via a CGRP/Ramp1 axis to promote tumor progression
Authors: Zhi Xiaofei , Wu Feijing , Qian Jin , Ochiai Yosuke , Lian Guodong , Malagola Ermanno , Chen Duan , Ryeom Sandra W , Wang Timothy C 
Published: March 2024

SummaryCancer cells have been shown to exploit neurons to modulate their survival and growth, including through establishment of neural circuits within the central nervous system (CNS)1–3. Here, we report a distinct pattern of cancer-nerve interactions between the peripheral nervous system (PNS) and gastric cancer (GC). In multiple GC mouse models, nociceptive nerves demonstrated the greatest degree of nerve expansion in an NGF-dependent manner. Neural tracing identified CGRP+ peptidergic neurons as the primary gastric sensory neurons. Three-dimensional co-culture models showed that sensory neurons directly connect with gastric cancer spheroids through synapse-like structures. Chemogenetic activation of sensory neurons induced the release of calcium into the cytoplasm of cancer cells, promoting tumor growth and metastasis. Pharmacological ablation of sensory neurons or treatment with CGRP inhibitors suppressed tumor growth and extended survival. Depolarization of gastric tumor membranes throughin vivooptogenetic activation led to enhanced calcium flux in nodose ganglia and CGRP release, defining a cancer cell-peptidergic neuronal circuit. Together, these findings establish the functional connectivity between cancer and sensory neurons, identifying this pathway as a potential therapeutic target.
An anti-depressant drug vortioxetine suppresses malignant glioblastoma cell growth
Authors: Devare Mayur Nimbadas , Kaeberlein Matt 
Published: March 2024

AbstractGlioblastoma (GBM) stands as the predominant primary malignant brain tumor in adults, characterized by an exceedingly grim prognosis. Urgent efforts are essential to pioneer effective therapeutics capable of addressing both the intrinsic and acquired resistance exhibited by GBM towards existing treatments. This study employs a drug repurposing strategy to explore the anti-cancer potential of vortioxetine in malignant U251 and T98G glioblastoma cells. Findings from WST-8 cell counting assay and clonogenic assays indicated that vortioxetine effectively suppressed the short-term viability and long-term survival of glioblastoma cells. We also showed that vortioxetine inhibited migration of glioblastoma cells as compared to the control. Our findings encourage further exploration and validation of the use of vortioxetine in the treatment of glioblastoma.