bluuebunny/crossref_metadata_2025 huggingface dataset:
A new obstacle for phenomenal contrast
Authors: Fulkerson Matthew , Cohen Jonathan
Published: February 2025

Phenomenal Contrast Arguments (PCAs) are a prominent method in philosophy of mind for, among other uses, investigating how specific mental features shape the phenomenal character of experience. This paper identifies a general and underexplored obstacle to the success of PCAs: The necessity of demonstrating that the contrasts employed in these arguments are genuinely phenomenal, rather than merely cognitive or otherwise non-phenomenal. We contend that proponents of PCAs often assume a phenomenal difference without adequately ruling out these alternative explanations for the available contrast. While we do not preclude the possibility of successful PCAs, our arguments suggest that many existing instances fail to meet this burden.
A New Copy of Shakespeare’s Sonnet 116: A Cavalier Cover Version
Authors: Veronese Leah S
Published: February 2025

This article records a new witness of Shakespeare’s Sonnet 116 in Bodleian MS Ashmole 36, 37. The poem is a copy of Henry Lawes’ song-setting which adds six new lines to the poem. The song-setting can also be found in NYPL Drexel MS 4257, although there are significant variations between the two copies. The sonnet takes on new political relevance when read in the context of the Royalist Elias Ashmole’s miscellany, Bodleian MS Ashmole 36, 37, amongst material from the early 1640s: Shakespeare’s text is transformed from praise of romantic constancy to political constancy. This article provides a transcription of the new witness, reads the text in the local context of Bodleian MS Ashmole 36, 37, and then considers the setting in the wider context of the circulation of Shakespearean songs in manuscript and domestic musical performance during the Interregnum. The text is politicized at a local level in the context of Bodleian MS Ashmole 36, 37 and in the wider context of domestic performance during the Interregnum when the public performance of music was banned. This new copy contributes to our understanding of the circulation of Shakespeare’s poetry in manuscript, Shakespearean reception during the mid-seventeenth century, and Royalist counterculture.
Evaluation of patient-based disease activity score (PDAS) in the Japanese rheumatoid arthritis patient registry (NinJa registry)
Authors: Shoda Hirofumi , Matsui Toshihiro , Tohma Shigeto , Sawada Tetsuji
Published: February 2025

Objective

Patient-reported outcomes (PROs) should be regarded as an important factor in the management of rheumatic diseases. The Patient-based disease activity score (PDAS) was developed as a clinically reliable composite measure for evaluating PROs in rheumatoid arthritis (RA) patients. To replicate and further characterize PDAS, we analyzed PDAS and its clinical relevancy in the National Database of Rheumatic Diseases in Japan (NinJa).

Methods

Clinical data from the 2022 version of NinJa were analyzed. PDAS1 was calculated for each patient, and statistical analyses, including correlation analyses and multiple regression analysis, were conducted to evaluate the relationship between PDAS1 and other clinical measures. Propensity score (PS) matching was used to compare patients treated with different types of disease-modifying anti-rheumatic drugs (DMARDs).

Results

The number of included patients was 11983. PDAS1 demonstrated strong correlations with DAS28(ESR) (R = 0.89, p< 2.2x1016) and CDAI, indicating its utility in assessing disease activity. The majority of patients (71.8%) achieved PDAS1-defined remission, aligning closely with DAS28 and CDAI remission. PDAS1 was significantly associated with serum rheumatoid factor (RF) titers (R = 0.25, p< 0.001), and RF-positive patients exhibited higher PDAS1 scores. Notably, PS matched comparison revealed that PDAS1 was lower in patients treated with IL-6 inhibitors, compared with those treated with TNF inhibitors, reflecting differences in lower patient global assessment.

Conclusion

PDAS1 is a reliable and useful tool for evaluating both disease activity and the functional state of RA patients, particularly from the perspective of PROs. Additionally, PDAS1 can be used for conducting clinical studies in RA patients.
Does the level of cash always increase with firm size? Theory and evidence from small firms
Authors: Kakhbod Ali , Reppen A Max , Umar Tarik , Xing Hao
Published: February 2025

Large firms typically increase their cash holdings as they grow to buffer against greater cash flow volatility. However, data on 11.2 million small firms show the opposite: cash levels decline as firms expand. We explain this phenomenon through a liquidity management model. Small firms with limited cash flows rely on cash reserves for investment due to costly external financing. As they grow, they do not fully replenish their cash reserves because investment incentives decrease, and increased cash flows support more of their anticipated investments. This mechanism generates a negative correlation between cash holdings and firm size among small firms.
An Immersive Virtual Reality Simulation Scenario to Improve Empathy in Nursing Students
Authors: Collier Rosemary , Darling Rosa , Browne Karen
Published: February 2025

Empathy is essential in nursing practice and can be taught throughout nursing curriculum using a variety of methods including clinical experiences, in-person simulation, virtual reality, and didactic lecture. Empathy can also change over time, often decreasing the longer nurses practice. A cohort of upper-level nursing students viewed a short immersive virtual reality simulation as part of routine curriculum and completed the Toronto Empathy Questionnaire before viewing (time 1), 2 weeks later (time 2), and, for a small cohort, several months later (time 3). The sample included 110 undergraduate nursing students. There were no improvements in Toronto Empathy Questionnaire scores from time 1 to time 2. There was no improvement from time 1 to time 3 for the cohort who completed the Toronto Empathy Questionnaire three times. There were no significant differences in Toronto Empathy Questionnaire scores between cohorts for any measurement times. Total mean empathy scores were comparatively high in this study and did not decline over time. Although this virtual reality simulation scenario appears to have protected against decline in empathy, it may have been insufficient to foster an increase in empathy scores. Empathic training needs to be immersed throughout their nursing education in both didactic and clinical settings.
Effect of a Nurse-Led Omaha System–Based Mobile Health Application in Managing Symptoms and Enhancing Quality of Life in Patients With a Communicable Disease
Authors: Torun Gizemnur , Seçginli Selda
Published: February 2025

This study investigated the effects of a nurse-led Omaha System–based mobile health application on physical, psychosocial, and cognitive symptoms and quality of life in patients with COVID-19 followed at home. This randomized control trial was conducted on 60 patients followed at home (30 in each intervention and control group). The intervention group received a nurse-led Omaha System–based mobile health application named COVOS, and the control group received usual care. Compared with the control group, the physical symptoms of the intervention group were significantly reduced at all follow-ups (first, second, and third months; P < .05). Psychosocial symptoms (depression, anxiety, stress) were significantly reduced, respectively, in the intervention group at all follow-ups: first and third months and second and third months (P < .05). Cognitive symptoms were significantly reduced in the first month in the intervention group (P = .014). Similarly, the physical component score of quality of life significantly improved in the first month, and the mental component score of quality of life significantly improved in the second and third months (P < .05) in the intervention group. Results suggest that the COVOS had the potential to reduce effectively the physical, psychosocial, and cognitive symptoms of patients with COVID-19 and improve the quality of life of patients with COVID-19 followed at home.
Socioeconomic Factors Associated With Differential Access to Treatment in Patients With Keratoconus at a US Urban Safety-Net Hospital
Authors: Ihionu Oluchi C. , Samra Jasmeet K. , Rashad Ramy M. , Arsiwala Mohsin A. , Del Plato Nedda S. , Lee Hyunjoo J.
Published: February 2025

Purpose:

The purpose of this study was to examine the effects of area deprivation index (ADI)—a measure of overall socioeconomic status—as well as insurance status, race, and preferred language, on patients’ odds of receiving corneal cross-linking (CXL) or medical contact lenses (CL), and the association of these factors with keratoconus severity at presentation.

Methods:

We reviewed the records of 540 patients with keratoconus presenting to Boston Medical Center (Boston, MA) between 2012 and 2020. CXL and CL treatment odds based on ADI and other socioeconomic factors were calculated using logistic regression. Amsler–Krumeich (AK) classification and keratoplasty rates were used to classify severity at presentation, and associations with socioeconomic factors were evaluated by logistic regression and the Chi-square test.

Results:

We did not find a significant association between ADI and CXL treatment (P = 0.440) or CL treatment (P = 0.823), nor did we find a significant association between insurance status and CXL treatment in multivariate analysis (OR = 2.26, 95% CI, 0.91–5.48, P = 0.079). However, patients whose preferred language was not English were less likely to receive CL treatment (OR = 0.63, 95% CI, 0.42–0.96, P = 0.031). In addition, when adjusted for all other factors, White patients were more likely to receive CXL relative to Black/African American patients (OR = 7.44, 95% CI, 2.20–27.02, P = 0.028). We also found that White patients presented with less severe disease than Black/African American patients (OR = 0.33, 95% CI, 0.13–0.75, P = 0.027).

Conclusions:

Although we did not find associations between ADI and keratoconus treatment access, we found lower rates of CXL and CL treatment of keratoconus and worse severity on presentation for commonly disadvantaged groups. Further studies are warranted to investigate these disparities to more equitably reduce disease burden.
Rho Kinase Inhibitor–Induced Visually Significant Vortex Keratopathy
Authors: Ciulla Lauren , Nottage Jennifer
Published: February 2025

Purpose:

The purpose of this case report is to describe a case of visually significant vortex keratopathy in a patient using a Rho kinase inhibitor.

Methods:

A 69-year-old male patient was found to have bilateral vortex keratopathy while taking a Rho kinase inhibitor. The case was reviewed and detailed in this report.

Results:

Approximately 5 months after starting netarsudil/latanoprost, the patient complained of ongoing right worse than left blurred vision and glare. Best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/20 in the left eye. Corneal exam was significant for vortex keratopathy with iron deposition diffusely in the right eye and mildly in the left eye. The patient underwent superficial keratectomy with diamond burr debridement in his right eye. One month after procedure, the BCVA improved to 20/25. The patient subsequently underwent the same procedure in his left eye and BCVA remained stable at 1 month. At 13 months after right eye procedure, the patient returned complaining of declined vision. There was moderate recurrent pigmented vortex keratopathy in the central visual axis in the right eye. The patient underwent repeat superficial keratectomy/diamond burr debridement in the right eye and the Rho kinase inhibitor was discontinued. The patient has been followed for approximately 31 months after stopping the medication without further recurrence of the vortex keratopathy.

Conclusions:

We present a case of visually significant and reoccurring vortex keratopathy in a patient taking a Rho kinase inhibitor. This case is notable as Rho kinase inhibitor–associated vortex keratopathy is typically not visually significant.
Evaluation of factors related to the need for surgery in patients with intestinal obstruction due to adhesions in a third-level clinic in Bogotá, Colombia. A case control study
Authors: Brito Rojas Isabel Cristina , Padrón Pardo Oscar Luis , Pilar Montilla María Del
Published: February 2025

Introduction and importance:

Intestinal obstruction due to adhesions is a common reason for emergency department visits. Initial management includes bowel rest, nasogastric tube placement, hydration optimization, and pain control, among other measures. Patients who do not respond adequately to conservative treatment are candidates for surgical management. However, delays in identifying patients in need of surgery can lead to increased morbidity, mortality, and costs.

Materials and methods:

An analytical observational case-control study was conducted, involving 102 patients diagnosed with intestinal obstruction due to adhesions, evaluated in the emergency department of a third-level clinic in Bogotá between 2019 and 2023. The patients were divided into two groups: Intervention and non-operative intervention. Clinical, paraclinical, and radiological data were obtained from the electronic review of medical records and entered into an Excel database. Statistical analysis was performed based on this data. This work has been reported in line with the STROCSS criteria.

Clinical discussion:

The mean age of the patients included in the study was 58.57 years, with a predominance of males. Patients with a history of laparotomy were less frequently taken to surgical management. Similarly, a history of infraumbilical open surgery and colorectal surgery was associated with a reduced need for surgery. On the other hand, the presence of complete obstruction was associated with a OR 16.74-fold increase (95% CI 3.98-97.86) in the likelihood of operative intervention.

Conclusion:

The presence of complete intestinal obstruction is associated with the need for operative intervention, in contrast to a history of infraumbilical open surgery and colorectal surgery, which reduce the risk of surgery.
Deletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH
Authors: Parthasarathy Gopanandan , Venkatesan Nanditha , Sidhu Guneet Singh , Song Myeong Jun , Liao Chieh-Yu , Barrow Fanta , Mauer Amy , Sehrawat Tejasav , Nakao Yasuhiko , Daniel P. Vineeth , Dasgupta Debanjali , Pavelko Kevin , Revelo Xavier S. , Malhi Harmeet
Published: February 2025

Background:

Immune cell–driven inflammation is a key mediator of metabolic dysfunction–associated steatohepatitis (MASH) progression. We have previously demonstrated that pharmacological sphingosine 1-phosphate (S1P) receptor modulation ameliorates MASH and is associated with attenuated accumulation of intrahepatic macrophage and T-cell subsets. Although S1P receptors are expressed on several immune cell types, given the prominent role of monocyte-derived recruited macrophages in the sterile inflammation of MASH, we hypothesized that deletion of S1P receptor 1 (S1P1) on myeloid cells may ameliorate MASH by reducing the accumulation of proinflammatory monocyte-derived macrophages in the liver.

Methods:

The LyzMCre approach was used to generate myeloid cell–specific knockout mice, termed S1pr1

MKO
. Littermate S1pr1

loxp/loxp
mice were used as wild-type controls. MASH was established by feeding mice a high-fat, -fructose, and -cholesterol (FFC) diet for 24 weeks, which led to the development of steatohepatitis and MASH-defining cardiometabolic risk factors. Liver injury and inflammation were determined by histological and gene expression analyses. Intrahepatic leukocyte populations were analyzed by mass cytometry and immunohistochemistry.

Results:

Histological examination demonstrated a reduction in liver inflammatory infiltrates and fibrosis in high-fat, -fructose, and -cholesterol–fed S1pr1

MKO
compared to wild-type. There was a corresponding reduction in alanine aminotransferase, a sensitive marker for liver injury. As determined by mass cytometry, a significant decrease in recruited macrophages was noted in the livers of high-fat, -fructose, and -cholesterol–fed S1pr1

MKO
mice compared to wild-type. Gene ontology pathway analysis revealed significant suppression of the peroxisome proliferator–activated receptor gamma and mitogen-activated protein kinase pathways in S1pr1

MKO
consistent with attenuated MASH in mice.

Conclusions:

Deletion of S1P1 in myeloid cells is sufficient to attenuate intrahepatic accumulation of monocyte-derived macrophages and ameliorate murine MASH.
Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay
Authors: Steg Saban Or , Vandriel Shannon M. , Fatima Syeda Aiman , Bourdon Celine , Mundh Amrita , Ng Vicky L. , Ling Simon C. , Bandsma Robert H.J. , Kamath Binita M.
Published: February 2025

Background:

Standard-of-care therapy in children with autoimmune hepatitis (AIH) includes induction with prednisone 1–2 mg/kg daily with gradual weaning of the dose. We aimed to test the hypothesis that children with AIH receiving standard-of-care treatment have altered growth trajectories.

Methods:

Children diagnosed with AIH between 1997 and 2023 at SickKids had serial growth measurements. Mixed effect models assessed the impact of time and daily steroid exposure on z-scores. Kaplan-Meier survival methods were used to estimate the cumulative incidence of new-onset growth impairments. A time-dependent Cox proportional hazards model was constructed to determine predictors for growth impairments.

Results:

Sixty-one children (66% females, median age at diagnosis 11.5 y) were included. BMIz showed a sharp increase, and HAZ declined significantly without returning to baseline. Each 1 mg/kg/d prednisone exposure increased BMIz gain in the first 6 months by 0.27 ([95% CI: 0.11, 0.42], p = 0.001), and decreased HAZ by −0.02 ([95% CI: −0.03, −0.01], p = 0.005). Children diagnosed before puberty exhibited a higher occurrence of excessive weight gain (72.2% vs. 49.3%; log-rank p < 0.01) and obesity (63% vs. 31.5%; log-rank p < 0.01) compared to those diagnosed during puberty. In a Cox proportional-hazards model, young age at diagnosis and daily prednisone dose >10 mg 6 months after diagnosis were predictors for linear growth delay.

Conclusions:

This study demonstrates that children with AIH receiving standard-of-care therapy demonstrate altered growth trajectories, long-term excess weight gain, obesity, and linear growth delay. Young age at diagnosis and >10 mg of daily prednisone at 6 months are predictors for linear growth delay. These data indicate the need to re-evaluate standard treatment algorithms for pediatric AIH in terms of steroid dosing and potential nonsteroid alternatives.
The Link Between Perceived Racism and Health Services Utilization Among Older Adults
Authors: Ambade Preshit N. , Hoffman Zachary , Mehra Kaamya , Gunja Munira , Moore Justin X.
Published: February 2025

Objectives:

To understand the link between perceived racial/ethnic discrimination among older adults and 2 health service utilization processes: (1) visiting health care providers or emergency room (ER), and (2) repeated visits after the first encounter.

Methods:

Analysis of 2021 Commonwealth Fund International Health Policy Survey of Older Adults—a nationally representative, self-reported, and cross-sectional survey from Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, the United Kingdom, and the United States. We used a 2-part multivariable hurdle model.

Results:

Perceived discrimination was associated with 18% reduced odds of visiting at least 1 primary care provider (OR: 0.82; 95% CI: 0.68–0.99). Among those who have visited at least 1 provider, those who perceived discrimination were more likely to visit different providers when compared with those who did not (RR: 1.06; 95% CI: 1.01–1.11). Perceived racism was associated with first (OR: 1.13; 95% CI: 1.01–1.27) and frequent (RR: 1.14; 95% CI: 1.01–1.29) ER visits.

Conclusions:

Perceived racial discrimination is linked with higher health service utilization among older adults in high-income countries.

Policy Implications:

A multilevel policy response that includes workforce sensitization and diversification, system transparency and accountability, and addressing structural barriers to accessing health care is warranted.
The Effect of Three Different Local Cold Applications on Pain Severity, Anxiety Level, and Physiological Parameters in Intra-Articular Injections for Knee Osteoarthritis Treatment
Authors: Çulha Yeliz , Büyükyılmaz Funda , Avşar Murat Tolga , Karagöz Esra
Published: February 2025

Minimizing pain and anxiety associated with intra-articular injection interventions is important for patient satisfaction and comfort. The sample of this quasi-experimental study consisted of 120 patients who received intra-articular knee injections for the first time. Patients were divided into four study groups before injection. The inter-group comparisons of the vital signs and mean pain and anxiety scores obtained immediately after the injection (0th minutes) and after 30 minutes indicated that mean systolic blood pressure, diastolic blood pressure, and pain scores were lower in the icepack application group, mean pulse rate score was lower in the cold spray group, and mean respiratory rate score was lower in the buzzy device group, with differences being statistically significant (p < .05). We conclude that icepack application is effective in reducing pain severity in intra-articular injections.
Factors Affecting Pain Intensity Among Korean Women With Rheumatoid Arthritis
Authors: Oh Hyunjin , Boo Sunjoo
Published: February 2025

This cross-sectional study investigated the factors affecting pain intensity among Korean women with rheumatoid arthritis (RA) (n = 246). Data included pain site and intensity, physical function, fatigue, medication attitudes, and learned helplessness (LH) from patient self-report, and Disease Activity Score 28 (DAS28) from chart review. The overall pain intensity was 3.59 out of 10, with a median of 3. The mean number of painful joints was 8.4, with the most commonly reported painful joint groups being the fingers, wrists, and knees. Higher DAS28, impaired physical function, eight or more painful joints, higher levels of fatigue, and higher levels of LH were significantly associated with pain intensity. Our results suggest that pain in women with RA is closely associated with cognitive or psychological variables such as fatigue and LH in addition to inflammation itself. For improved pain management, patients with RA should receive regular counseling to address their feelings of LH and fatigue.
Repeatability of tear film lipid layer interferometry measurements: A randomized, crossover study
Authors: Wang Michael T. M. , Misra Stuti L. , Gokul Akilesh , Kim Ji Soo , Kim Andy D. , Xue Ally L. , Cruzat Andrea , Craig Jennifer P.
Published: February 2025

SIGNIFICANCE

Tear film lipid layer interferometry is one of the most sensitive diagnostic markers for evaporative dry eye disease. However, the dynamic structure breaks up and reforms rapidly during each blink cycle, and it remains yet to be established whether there may be significant intrasessional, diurnal, or day-to-day variability.

PURPOSE

This study aimed to assess intrasession repeatability, diurnal intravisit and day-to-day intervisit reproducibility of qualitative tear film lipid layer interferometry grading obtained from the Keratograph 5M (Oculus Optikgeräte GmbH, Wetzlar, Germany), and automated quantitative layer thickness measurements obtained from the TearScience LipiView II Ocular Surface Interferometer (Johnson & Johnson Vision, Milpitas, CA), in community residents, not stratified by dry eye or blepharitis status.

METHODS

Forty community residents (24 women, 16 men; age mean ± standard deviation, 36 ± 14 years) were recruited in an investigator-masked, randomized, crossover study. Participants attended two sessions 6 hours apart on the same day and a third session on a separate day. During each session, tear film lipid layer grading and thickness measurements were performed in triplicate, in a masked manner, with 10-minute intervals between each measurement.

RESULTS

There were no significant differences in lipid layer grading and thickness measurements in all pairwise intrasession, diurnal intravisit, and day-to-day intervisit comparisons (all p≥0.19), and positive correlations were observed in all cases (all p<0.001). The weighted Cohen κ coefficients for intrasession repeatability and diurnal intravisit and day-to-day intervisit reproducibility of qualitative lipid layer grading ranged from 0.670 to 0.867. The test-retest repeatability of quantitative lipid layer thickness measurements ranged from 4.5 to 11.7 nm, and the Bland-Altman biases were within the order of 3 nm in all pairwise comparisons. The intraclass correlation coefficients for lipid layer thickness measurements exceeded 0.80 for all intrasession comparisons and were between 0.60 and 0.80 for all diurnal intravisit and day-to-day intervisit comparisons.

CONCLUSIONS

Both qualitative grading and automated quantitative thickness measurements of tear film lipid layer interferometry demonstrated relatively favorable levels of intrasession repeatability and diurnal intravisit and day-to-day intervisit reproducibility. The study findings would support the use of either qualitative or quantitative measurement in clinical and research settings, as a reliable tool for assessing lipid layer interferometry.
Claudin 18.2 Immunohistochemistry Expression in Gastric Cancer: A Systematic Review
Authors: Lop Gros Joan , Santiago Díaz Pablo , Larrubia Loring Mónica , Patriarca Maria E. , Lloveras Belen , Iglesias Mar
Published: February 2025

Claudin 18.2 is a transmembrane protein, part of the tight-junction complex, selectively expressed in gastric epithelium. It is showing promising results as a target in advanced gastric cancer in phase 3 clinical trials using a monoclonal antibody against claudin 18.2. A systematic review on expression of claudin 18.2 in gastric cancer was performed using the PubMed database. The following search expression was used: (“Stomach Neoplasms” [Mesh]) AND ((“claudin-18[TIAB]”) OR (“CLDN18[TIAB]”)). A total of n=99 articles were retrieved. Of those, 17 preclinical studies about claudin 18.2 expression by immunohistochemistry were selected. The results of those studies showed great variability in the criteria used for defining the thresholds for positivity of the stain. The proportion of claudin 18.2 positive cases varied between 24% and 83%. In works using a positivity threshold set at >40% or >70% of cells with membranous/cytoplasmic﻿ staining at 2+/3+ intensity, the average rate of positive cases was 50% or 30%, respectively (similar with clones 43-14A and EPR19202). Positivity of claudin 18.2 was associated with advanced stage, diffuse phenotype and PD-L1 and EBV positivity in some of the studies. Variability in criteria used to define claudin 18.2 positivity, as well as methodological differences, could explain the variation in the proportion of positive cases described, as well as the inconsistency of the association with clinical, molecular, and survival variables. The upcoming anticlaudin 18.2 therapy in advanced gastric cancer should prompt pathology laboratories to adjust their staining protocols and evaluation criteria in their series of patients, to further establish the association of claudin expression with clinical and molecular variables.
The Diagnostic Spectrum of Myelodysplastic Syndromes and Acute Myeloid Leukemia
Authors: Arber Daniel A. , Orazi Attilio
Published: February 2025

The International Consensus Classification (ICC) of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) expands on the work of prior classifications to refine the diagnostic criteria for MDS and AML and to identify specific genetic disease subtypes. This review summarizes the approach to the diagnosis of MDS and AML from the ICC perspective. For MDS, the significance of detecting mutations in SF3B1, usually associated with ring sideroblasts, as well as the poor prognosis of mutations of TP53 are now included. For AML, new genetic categories are included, and the classification now incorporates additional clinically significant gene mutations by recognizing AML with TP53 mutation and AML with mutations in genes associated with prior therapy or MDS. Finally, the new category of MDS/AML is introduced for adult patients without recurrent de novo genetic abnormalities with 10% to 19% peripheral blood or bone marrow blasts that allow for more treatment flexibility based on clinical findings. While the increase in genetic categories and changes in blast cell requirements can be confusing, a stepwise approach is provided to allow easy use of the classification.
POCUS the Pelvis: A Case Series of Timely Diagnoses in Pediatric Patients With Abdominal Pain
Authors: Leviter Julie , Shah Rahul D. , Constantine Erika , Riera Antonio
Published: February 2025

Abdominal pain is a frequent presenting complaint in the pediatric emergency department (PED). Point-of-care ultrasound (POCUS) can expedite the diagnosis and management of patients in the PED with abdominal pain. We present a series of 6 patient cases in which a “POCUS the pelvis” approach expedited diagnosis of undifferentiated abdominal pain in the PED, and thus facilitated definitive management.
Peritoneal Scintigraphy Identified the Reason for Scrotal Edema in a Patient Undergoing Peritoneal Dialysis
Authors: Sun Hui , Chen Suyun , Cheng Weiwei
Published: February 2025

Scrotal edema is a complication in continuous ambulatory peritoneal dialysis patients, and its etiology can be challenging to determine. We performed peritoneal scintigraphy in a case of a patient who developed pronounced scrotal edema following peritoneal dialysis. The imaging revealed clear visualization of the right inguinal canal and right scrotum, suggesting the usefulness of peritoneal scintigraphy in identifying the etiology of scrotal edema in continuous ambulatory peritoneal dialysis patients.
Detection of the Cingulate Island Sign by Early Perfusion Imaging in Dopamine Transporter SPECT With Multiple-Pinhole Collimators
Authors: Karimzadeh Amir , Burkhardt Anne , Klutmann Susanne , Apostolova Ivayla , Buchert Ralph
Published: February 2025

Multiple-pinhole collimators provide considerable improvement of SPECT system count sensitivity. This case report suggests that SPECT with brain-specific multiple-pinhole collimators enables cerebral perfusion imaging with diagnostic quality by an early 12 minutes scan immediately after injection of a standard dose of the dopamine transporter ligand 123I-FP-CIT. Thus, 123I-FP-CIT SPECT with multiple-pinhole collimators could assess nigrostriatal degeneration (late image) and extrastriatal involvement (early perfusion image) during the same imaging session. The early image may serve as an alternative to FDG PET in patients with suspicion of an atypical neurodegenerative parkinsonian syndrome. This could streamline diagnostic workflows by reducing the need for additional imaging modalities.
Diverse Applications of Saphenous Vein Graft in Oral and Maxillofacial Reconstruction
Authors: Mustakim Kezia Rachellea , Eo Mi Young , Lee Jong Ho , Kim Soung Min
Published: February 2025

The greater saphenous vein (GSV) is widely used as an autologous graft in reconstructive surgeries, particularly in coronary artery bypass grafting and peripheral vascular interventions. This study explores the applicability of the GSV as a valuable graft option in oral and maxillofacial reconstructions, focusing on complex head and neck cases. Given the unique anatomic challenges of these areas, including proximity to vital structures and the need for extensive tissue resection, the GSV serves as an effective conduit in reconstructive strategies. This article provides a detailed overview of the typical GSV harvesting technique and presents case studies demonstrating the diverse applications of GSV grafts, including mandibular defect reconstruction, replacement of the internal jugular vein after radical neck dissection, and maxillary reconstruction after oncologic resection. The discussion addresses common anatomic and technical considerations, such as variable GSV diameters, vessel size mismatches, and donor site morbidity. A number of advanced anastomotic techniques is evaluated to address graft–recipient vessel discrepancies, ensuring optimal outcomes. Emphasizing careful patient evaluation and precise surgical techniques, this study concludes that the GSV is a reliable autogenous graft option, extending its versatility to challenging head and neck reconstructions. Preoperative anatomic assessment through Doppler analysis, patient consultation, and meticulous graft handling are essential to optimize graft function and minimize complications.
Endoscopic Papillary Balloon Dilation Versus Small Endoscopic Sphincterotomy for Endoscopic Retrograde Cholangiopancreatography–Related Adverse Events in Patients With Non–Dilated Distal Bile Duct
Authors: Gao Lili , Yan Huafang , Bu Limei , Zhang Hao
Published: February 2025

Objective:

Endoscopic papillary balloon dilation (EPBD), small endoscopic sphincterotomy (EST), and small EST plus EPBD are commonly used as rescue techniques to remove bile duct stones. However, we often encountered challenging cases with non–dilated distal bile ducts, especially in those undergoing EPBD. We aimed to explore the reasons by assessing whether patients without the dilated bile duct had a higher risk of early complications and whether it was impacted by the rescue techniques.

Methods:

We performed a retrospective cohort study by frequency matching design in patients diagnosed with stones in non–dilated distal bile duct who received rescue techniques from July 2016 to June 2022. Besides, patients with stones and without dilatation of the distal bile duct (DDBD) were divided into 3 subgroups according to the rescue technique received. Outcomes were compared between the subgroups.

Results:

The non-DDBD group was more likely to develop post–endoscopic retrograde cholangiopancreatography pancreatitis (PEP) and hyperamylasemia (HP) than the DDBD group (P < 0.05). Some cases had mild or moderate pancreatitis, but no one in either group developed severe pancreatitis. For subgroup analysis, each technique resulted in complete stone removal; the EPBD group had a higher HP rate than the other subgroups and reached statistical significance: the EPBD group versus the small EST group (P = 0.013) and the EPBD group versus the EPBD plus small EST group (P = 0.008). Although there was no statistical significance, PEP incidence in the EPBD group was 13.7% higher than in other subgroups (P > 0.05/3).

Conclusion:

Non-DDBD patients have a higher risk for endoscopic retrograde cholangiopancreatography-related pancreatic inflammation. EPBD should be used cautiously due to the significant association with increased rates of PEP and HP. Conversely, small EST and combination therapy are suitable for non–dilated bile duct stones because of their high safety profile and efficacy.
Accuracy of SEEG Source Localization: A Pilot Study Using Corticocortical Evoked Potentials
Authors: Cox Benjamin C. , Smith Rachel J. , Mohamed Ismail , Donohue Jenna V. , Rostamihosseinkhani Mahtab , Szaflarski Jerzy P. , Chatfield Rebekah J.
Published: February 2025

Introduction:

EEG source localization is an established technique for localizing scalp EEG in medically refractory epilepsy but has not been adequately studied with intracranial EEG (iEEG). Differences in sensor location and spatial sampling may affect the accuracy of EEG source localization with iEEG. Corticocortical evoked potentials can be used to evaluate EEG source localization algorithms for iEEG given the known source location.

Methods:

We recorded 205 sets of corticocortical evoked potentials using low-frequency single-pulse electrical stimulation in four patients with iEEG. Averaged corticocortical evoked potentials were analyzed using 11 distributed source algorithms and compared using the Wilcoxon signed-rank test (P < 0.05). We measured the localization error from stimulated electrodes and the spatial dispersion of each solution.

Results:

Minimum norm, standard low-resolution electromagnetic tomography (sLORETA), LP Norm, sLORETA-weighted accurate minimum norm (SWARM), exact LORETA (eLORETA), standardized weighted LORETA (swLORETA), and standardized shrinking LORETA-FOCUSS (ssLOFO) had the least localization error (13.3–15.7 mm) and were superior to focal underdetermined system solver (FOCUSS), logistic autoregressive average (LAURA, and LORETA, 17.9–21.7, P < 0.001). The FOCUSS solution had the smallest spatial dispersion (7.4 mm), followed by minimum norm, L1 norm, LP norm, and SWARM (20.8–28.3 mm). Gray matter stimulations had less localization error than white matter (median differences 3.1–6.1 mm) across all algorithms except SWARM, LORETA, and logistic autoregressive average. A multivariate linear regression showed that distance from the source to sensors and gray/white matter stimulation had a significant effect on localization error for some algorithms but not SWARM, minimum norm, focal underdetermined system solver, logistic autoregressive average, and LORETA.

Conclusions:

Our study demonstrated that minimum norm, L1 norm, LP norm, and SWARM localize iEEG corticocortical evoked potentials well with lower localization error and spatial dispersion. Larger studies are needed to confirm these findings.
Electroconvulsive Therapy for Treatment-Resistant Depression in a Patient With Wolff-Parkinson-White Syndrome
Authors: Gutiérrez-Alzate María Paula , López-Ospino Sebastián , Suárez-Chacón Andrea Marcela , Coral-Sánchez Gina Tatiana , Acero-González Ángela R.
Published: February 2025

Electroconvulsive therapy (ECT) has been recognized as an effective treatment option in severe major depression and treatment-resistant depression. However, its use has been associated with an initial increase in parasympathetic and subsequently sympathetic tone; this has relevance in the context of patients with arrhythmias or pre-excitation syndromes in which some adverse effects have been reported. We present the case of a young female with treatment-resistant depression and a history of Wolff Parkinson White Syndrome admitted for modified ECT. To date, there is no evidence of the anesthetic management of patients with pre-excitation syndromes who require ECT treatment. Therefore, doubts arose regarding the management prior to the procedure. After performing 12 modified ECT sessions an improvement in depressive symptoms was evidenced without any adverse event.
USP7 inhibition perturbs proteostasis and tumorigenesis in triple negative breast cancer
Authors: Kim Ahhyun , Gopalakrishnan Priya , Chen Claire C. , Umesh Nikita , Mordant Angie , Barker Natalie K. , Herring Laura E. , Suárez-Pizarro Marina , Kakati Rasha T. , Spanheimer Philip M. , Emanuele Michael J. , Benavente Claudia A.
Published: February 2025

The deubiquitinase USP7 is a critical regulator of tumorigenesis, known for stabilizing the MDM2-p53 pathway. Emerging evidence highlights USP7’s p53-independent roles in proliferation and tumorigenesis. Triple negative breast cancers frequently inactivate p53 and this disease subtype remains difficult to treat and in need of new therapeutic options. Our study reveals that USP7 is upregulated in TNBC patient tumors. Importantly, genetic and pharmacologic USP7 inactivation impaired tumor progression in TNBC models. To explore USP7’s role in p53-mutant TNBCs, we performed deep quantitative proteomics across TNBC cell lines, identifying shared USP7 targets involved in cell proliferation, genome stability, and proteostasis. Acute USP7 inactivation allowed us to infer proximally controlled proteins which are likely direct targets. Surprisingly, many of the proteins downregulated by USP7 inhibition are E3 ubiquitin ligases. Thus, a key USP7 function in TNBC is to antagonize the degradation of ubiquitinating enzymes, since these enzymes are often susceptible to auto-ubiquitination and degradation. Notably, we identified TOPORS, a dual ubiquitin- and SUMO-ligase, among novel USP7 substrates. TOPORS interacts with the BRCA1-A DNA damage repair complex suggesting a USP7-TOPORS-BRAC1-A axis that might further explain the continued proliferation of genomically unstable TNBCs. Collectively, these data nominate USP7 as a potential therapeutic in TNBC.
Factors associated with newly diagnosed ischemic stroke among people in Thailand: A population-based case-control study
Authors: Phasom Junjira , Ungcharoen Ratchadaporn , Pusuwan Pakorn , Phoosuwan Nitikorn
Published: February 2025

Background

Stroke is a leading cause of death and disability-adjusted life years globally. The incidence of stroke is increasing in Asia, with ischemic stroke accounting for approximately 80% of stroke cases in Thailand. Stroke often results in long-term disabilities, including impairments in speech, communication, and concentration.

Objective

This study aimed to investigate factors associated with newly diagnosed ischemic stroke.

Methods

A matched case-control study was conducted, including 154 newly diagnosed ischemic stroke cases and 183 non-stroke individuals with type 2 diabetes mellitus (T2DM) as controls. Data were collected between February and September 2022 (post-COVID-19 period) using a structured questionnaire covering (1) socio-demographics, (2) lifestyle factors, (3) perceived social support, and (4) self-care management (SCM). Multivariable logistic regression models were employed to calculate adjusted odds ratios (aOR) with 95% confidence intervals (CI).

Results

Most participants were female (60.8%), Buddhists (92.9%), and agriculturists (66.5%), with a mean age of 58.9 (±9.9) years. Factors associated with ischemic stroke included male sex (aOR=3.533, 95%CI 1.732–7.206), Buddhism (aOR=3.529, 95%CI 1.107–11.250), sedentary occupation (aOR=5.785, 95%CI 2.613–12.807), and having T2DM for over 10 years (aOR=6.194, 95%CI 3.553–10.798). Protective factors included age ≥ 60 years (aOR=0.553, 95%CI 0.312–0.982) and moderate SCM levels (aOR=0.453, 95%CI 0.256–0.802).

Conclusion

Prolonged T2DM and sedentary occupations significantly contribute to ischemic stroke incidence. Effective prevention programs, including lifestyle modifications and diabetes self-care management education, may help reduce the burden of ischemic stroke.
SEPSIS-INDUCED LIPID DROPLET ACCUMULATION ENHANCES ANTIBACTERIAL INNATE IMMUNITY
Authors: Pereira-Dutra Filipe S. , Santos Julia Cunha , Souza Ellen Kiarely , Savi Rodrigo Vieira , Souza Tamyris S. , Espinheira-Silva Hugo , Ferraro-Moreira Felipe , Iack Guilherme , Cunha-Fernandes Tamires , Igreja-Silva Tathiany , Palhinha Lohanna , Campos Mariana Macedo , Oliveira Douglas Mathias , Cardoso Vinicius Soares , Rajão Matheus A. , Teixeira Livia , Souza-Moreira Luciana , Costa Maria Fernanda Souza , Reis Patrícia Alves , Bozza Patrícia T.
Published: February 2025

Lipid droplets (LDs) are lipid-rich organelles recognized as central players in lipid homeostasis, signaling, and inflammation. While their functions in inflammation are well-documented, the role of LDs in antibacterial immunity and infection resistance remains less understood. In this study, we investigated triglyceride synthesis and LD accumulation in the context of antibacterial innate immunity during sepsis. Our results show that LD accumulation is part of immunometabolic reprogramming inE. coli-infected macrophages. Pharmacological inhibition or genetic knockdown of DGAT1, a key enzyme in triglyceride synthesis, reduced LD formation, bacterial clearance, and pro-inflammatory responses (nitric oxide, PGE2, CCL2, IL-6, IFN-β). Notably, DGAT1 inhibition impaired the expression of several interferon-stimulated genes (ISGs), including viperin, iNOS, cathelicidin, and IGTP, inE. coli-infected macrophages. In a sepsis model, DGAT1 inhibition reduced sepsis-induced LD accumulation in peritoneal cells and decreased levels of CCL2, IFN-β, nitric oxide, and lipid mediators (PGE2, LTB4, and RvD1). Furthermore, DGAT1 inhibition accelerated sepsis-related mortality, coinciding with elevated bacterial loads in the peritoneum and bloodstream at 6 and 24 hours post-sepsis. Our results demonstrate that tryglicerides synthesis and LDs are critical regulators of infection resistance, contributing to both bacterial clearance and the coordination of a protective proinflammatory response during sepsis.
Systematic position of edible tropical oysters and first record of genusTalonostrea(Ostreidae) in the Myeik coastal area, Myanmar
Authors: Toyokawa Masaya , Yurimoto Tatsuya , Kang Bong Jung , Sultana Zakea , Aung Cherry
Published: February 2025

Belcher’s (Magallana belcheri) and hooded (Saccostrea cuccullata) oysters are edible species in Myeik, Myanmar. Belcher’s oyster is particularly desirable for aquaculture because of its high price and potential value as export products. Previous studies have noted a mismatch between oyster spat settlement patterns and the maturity of the species’ gonads, suggesting the possible settling of unintended oyster species in the Myeik coastal area. To address this issue, DNA barcoding was used to identify oyster species collected from the Myeik coast. Genetic analysis of mitochondrial DNA sequences from various sources of oysters sampled from mangrove roots, experimental cultivation rafts, and settled natural spat revealed an abundance of unidentified species of the genusTalonostreain addition to Belcher’s and hooded oysters. Therefore, this study suggested that collecting aquaculture target oysters from natural spat is inefficient because only a low percentage is found in coastal areas.
Altered endothelial mitochondrial Opa1-related fusion in mouse amplifies age-associated vascular and kidney damages
Authors: Turnaturi Carlotta , L’Hoste Loïck , Proux Coralyne , Grimaud Linda , Vessieres Emilie , Zorzano Antonio , Teissier Anne , Reynier Pascal , Sorrentino Raffaella , Lenaers Guy , Loufrani Laurent , Henrion Daniel
Published: February 2025

Background

Cardiovascular diseases are the major cause of death worldwide and their frequency increases with age in association with progressive kidney damages. Endothelial cells (ECs) are early affected in cardiovascular diseases. Although energy production in ECs involves glycolysis, endothelial mitochondria play a role in modulating cellular signalling. A reduction in fusion protein Opa1 level in ECs decreases the vascular response to flow and increased oxidative stress in perfused kidneys. Thus, we hypothesized that reduced Opa1 expression contributes to vascular aging.

Methods

We used male and female mice with ECs specific Opa1 knock-out (EC-Opa1), and littermate wild-type (EC-WT) mice aged 6 (young) and 20 months (old). Mesenteric resistance arteries (MRA) and kidneys were collected for vascular reactivity and Western-blot analysis.

Results

In old EC-Opa1 mice blood urea was greater than in age-matched EC-WT mice and MRA showed hypercontractilty and reduced endothelium-dependent relaxation. In kidneys, the mitochondria fission protein Fis-1 and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were increase in old EC-Opa1 mice. The level of eNOS expression was greater in young EC-Opa1 mice and caveolin-1 expression greater in old EC-Opa1 mice. Moreover, in kidneys from EC-Opa1 old mice, NADPH-oxidase subunits gp91, p47 and p67 expression was greater than in age-matched EC-WT mice. No difference was observed between old and young EC-WT mice.

Conclusion

Reduced mitochondrial fusion in mouse ECs altered mesenteric vascular reactivity and increased oxidative stress in aging kidneys. Thus, Opa1 might protect the vascular tree in target organs such as the kidney during aging.