bluuebunny/crossref_metadata_2025 huggingface dataset:
Endovascular treatment of a giant arteria lusoria aneurysm in a young female with Marfan syndrome
Authors: Fraund-Cremer Sandra , Rusch Rene , Uebing Anselm , Voges Inga , Schäfer Philipp
Published: February 2025

Aneurysms of an aberrant right subclavian artery (ARSA) are rare, but constitute a potentially lethal condition, especially with concomitant Marfan syndrome (MFS).

A 27-year-old female with confirmed MFS presented with a relevant progression of a known aneurysm of an ARSA in magnetic resonance imaging. The patient had undergone valve-sparing aortic root replacement (David procedure) 4 months prior. After interdisciplinary discussion, she underwent endovascular exclusion of the aneurysm using a combination of established vascular plugs and novel shape memory polymer embolization plugs to fill the large ARSA aneurysm volume. The shape memory polymer embolization plugs expand in the vessel to a porous scaffold, designed to support thrombus formation throughout its structure. The polymer is also radiolucent, which minimizes artifact and facilitates follow-up imaging.

Development of a strategy for the treatment of ARSA aneurysms is challenging and different surgical, endovascular, and combined approaches have been published. Interdisciplinary discussion is crucial to minimize the overall risk and trauma. In our case of a young female and new mother, an endovascular approach was successfully and safely performed. The future need for surgery due to concomitant MFS is expected.
AnnCovDB: a manually curated annotation database for mutations in SARS-CoV-2 spike protein
Authors: Zhang Xiaomin , Lei Zhongyi , Zhang Jiarong , Yang Tingting , Liu Xian , Xue Jiguo , Ni Ming
Published: February 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been circulating and adapting within the human population for >4 years. A large number of mutations have occurred in the viral genome, resulting in significant variants known as variants of concern (VOCs) and variants of interest (VOIs). The spike (S) protein harbors many of the characteristic mutations of VOCs and VOIs, and significant efforts have been made to explore functional effects of the mutations in the S protein, which can cause or contribute to viral infection, transmission, immune evasion, pathogenicity, and illness severity. However, the knowledge and understanding are dispersed throughout various publications, and there is a lack of a well-structured database for functional annotation that is based on manual curation. AnnCovDB is a database that provides manually curated functional annotations for mutations in the S protein of SARS-CoV-2. Mutations in the S protein carried by at least 8000 variants in the GISAID were chosen, and the mutations were then utilized as query keywords to search in the PubMed database. The searched publications revealed that 2093 annotation entities for 205 single mutations and 93 multiple mutations were manually curated. These entities were organized into multilevel hierarchical categories for user convenience. For example, one annotation entity of N501Y mutation was ‘Infectious cycle➔Attachment➔ACE2 binding affinity➔Increase’. AnnCovDB can be used to query specific mutations and browse through function annotation entities.

Database URL: https://AnnCovDB.app.bio-it.tech/
Apolipoprotein C3 and risk of cardiovascular events and death in patients on optimized statin treatment after recent acute coronary syndrome
Authors: Schwartz Gregory G , Szarek Michael , Reijnders Esther , Jukema J Wouter , Bhatt Deepak L , Bittner Vera A , Fazio Sergio , Garon Genevieve , Goodman Shaun G , Harrington Robert A , White Harvey D , Ruhaak L Renee , Stevanovic Irena , Cobbaert Christa M , Steg Philippe Gabriel
Published: February 2025

Aims

Apolipoprotein (Apo) C3 has been associated with incident coronary heart disease and major adverse cardiovascular events (MACE). Whether ApoC3 levels predict risk in patients with acute coronary syndrome (ACS) on optimized statin treatment is unknown.

Methods

ApoC3 was measured by mass spectrometry at baseline (n=11,956) and after 4 months’ treatment (M4; n=11 176) with alirocumab or placebo in the ODYSSEY OUTCOMES trial. Patients with fasting triglycerides >400 mg/dL were excluded. The association of baseline ApoC3 with risk of MACE or death was assessed in post hoc adjusted Cox regression models and spline analyses adjusted for treatment and ApoB. In adjusted models in the alirocumab group we determined association of ApoC3 change from baseline to M4 with subsequent risk of MACE and death.

Results

Median (Q1, Q3) baseline ApoC3 concentration was 85 (65, 113) mg/L. With adjustment for ApoB, baseline ApoC3 showed no clinically meaningful relationship to risk of MACE or death in spline analyses and no association with MACE (P=0.89) or death (P=0.70) in Cox regression analyses. Alirocumab reduced ApoC3 modestly by median –10 (–27, –5) mg/L (P<0.0001) and reduced MACE (10.1% vs 12.1%; P=0.0006) and death (3.5% vs 4.2%; P=0.045) versus placebo. However, the change in ApoC3 on alirocumab did not predict subsequent MACE or death.

Conclusion

In patients with recent ACS on optimized statins without severe hypertriglyceridemia, neither baseline ApoC3 (accounting for ApoB) nor ApoC3 change with alirocumab predicted MACE or death. It is uncertain whether targeted therapies producing larger reductions in ApoC3 from higher baseline levels will affect cardiovascular risk.
Differentiating mechanism from outcome for ancestry-assortative mating in admixed human populations
Authors: Massey Dashiell J , Szpiech Zachary A , Goldberg Amy
Published: February 2025

Population genetic theory, and the empirical methods built upon it, often assumes that individuals pair randomly for reproduction. However, natural populations frequently violate this assumption, which may potentially confound genome-wide association studies, selection scans, and demographic inference. Within several recently admixed human populations, empirical genetic studies have reported a correlation in global ancestry proportion between spouses, referred to as ancestry-assortative mating. Here, we use forward genomic simulations to link correlations in global ancestry proportion between mates to the underlying mechanistic mate choice process. We consider the impacts of 2 types of mate choice model, using either ancestry-based preferences or social groups as the basis for mate pairing. We find that multiple mate choice models can produce the same correlations in global ancestry proportion between spouses; however, we also highlight alternative analytic approaches and circumstances in which these models may be distinguished. With this work, we seek to highlight potential pitfalls when interpreting correlations in empirical data as evidence for a particular model of human mating practices and to offer suggestions toward development of new best practices for analysis of human ancestry-assortative mating.
Building a Collaborative Environmental Governance for Sustainable Management of Volcanic Lake at The Dieng Plateau-Central Java Indonesia
Authors: Wahyono Ari , Yoga Gunawan Pratama , Subehi Luki , Rustini Hadiid Agita , Fakhrudin Muh , Apip Apip , Ridwansyah Iwan , Samir Octavianto
Published: February 2025

The Dieng Plateau in Central Java, Indonesia, is home to unique volcanic lakes with significant ecological and economic value. Effective environmental governance is critical for the sustainable management of volcanic lakes, particularly in regions prone to natural hazards like the Dieng Plateau. Several hazards have been reported, including phreatic explosions. This paper explores a multidisciplinary approach to environmental governance, integrating ecological sciences and social sciences, to ensure the sustainable management of these lakes. We investigated the necessity and challenges of establishing collaborative environmental governance mechanisms to address the complex issues surrounding Lake Menjer as volcanic lake management in the region. Based on an investigation of water quality and biodiversity, all nutrient inputs from anthropogenic activities promoted this lake’s degradation. The environmental degradation of the lake showed the absence of management institutions. Drawing upon multidisciplinary research and stakeholder engagement, this study aims to: 1) to analyze the trend of environmental degradation in Lake Menjer in terms of eutrophication; and 2) to evaluate the current governance structures and propose strategies for enhancing collaboration among the various stakeholders. We analyzed existing policies, institutional frameworks, and community participation models to identify gaps and opportunities for improving environmental governance practices. We also advocate for a holistic and sustainable approach to volcanic lake management that balances ecological conservation and socio-economic development in Lake Menjer by fostering collaboration and co-management approaches. Key recommendations include fostering inclusive decision-making processes and promoting knowledge exchange and capacity-building initiatives with collaborative environmental governance approaches.
Taylor’s Critique of Secularism from a Naturalist Perspective
Authors: Nicholson Hugh
Published: February 2025

This article argues that Charles Taylor’s apologetic for religious belief in A Secular Age—in particular, his argument for the equivalence of the closed and open interpretations of the “immanent frame” of nature—is persuasive to the extent that the reader shares Taylor’s conviction that human-level structures of meaning are not subject to the standards of truth and verification operative in the natural sciences. Absent this assumption, an acceptance of a self-sufficient immanent order, although it does not lead inexorably to atheism, nevertheless contains an inherent bias away from the metaphysical claims of traditional religions. The article concludes by identifying a current in contemporary scientific thought that expands the conception of science beyond the classical nomothetic and reductionistic model presupposed in Taylor’s analysis at the same time that it challenges, as effectively as Taylor’s appeal to a premodern religious worldview, the modern “ethic of rational control” that is the dubious legacy of Descartes.
Structural insights into human PNPase in health and disease
Authors: Li Yi-Ching , Wang Chun-Hsiung , Patra Malay , Chen Yi-Ping , Yang Wei-Zen , Yuan Hanna S
Published: February 2025

Human polynucleotide phosphorylase (hPNPase) is a 3′-to-5′ exoribonuclease located in mitochondria, where it plays crucial roles in RNA degradation and RNA import. Mutations in hPNPase can impair these functions, leading to various mitochondrial dysfunctions and diseases. However, the mechanisms by which hPNPase switches between its roles as an RNA-degrading enzyme and an RNA carrier, as well as how disease-associated mutations may affect these distinct functions, remain unclear. In this study, we present cryo-electron microscopy structures of hPNPase, highlighting the flexibility of its S1 domains, which cap the ring-like RNA-degradation chamber and shift between two distinctive open and closed conformations. We further demonstrate by small-angle X-ray scattering and biochemical analyses that the disease-associated mutations P467S and G499R impair hPNPase’s stem-loop RNA-binding and degradation activities by limiting the S1 domain’s ability to transition from an open to closed state. Conversely, the D713Y mutation, located within the S1 domain, does not affect the RNA-binding affinity of hPNPase, but diminishes its interaction with Suv3 helicase for cooperative degradation of structured RNA. Collectively, these findings underscore the critical role of S1 domain mobility in capturing structured RNA for degradation and import, as well as its involvement in mitochondrial degradosome assembly. Our study thereby reveals the molecular mechanism of hPNPase in RNA binding and degradation, and the multiple molecular defects that could be induced by disease-linked mutations in hPNPase.
A C2H2 Zinc Finger Protein, OsZOS2-19, Modulates ABA Sensitivity and Cold Response in Rice
Authors: Zhang Di , Ding Xiaoping , Wang Zhijun , Li Wenyu , Li Lingling , Liu Ling , Zhou Huang , Yu Jianghui , Zheng Cheng , Wu HouXiong , Yuan Dingyang , Duan Meijuan , Liu Citao
Published: February 2025

Cold stress is a major factor limiting rice (Oryza sativa L.) productivity, making it crucial to understand the molecular mechanisms underlying stress responses to develop resilient crops. In this study, we characterized OsZOS2-19, a cold- and abscisic acid (ABA) -responsive C2H2 zinc finger protein, which functions as a transcriptional repressor. Overexpression of OsZOS2-19 in rice lines increases sensitivity both cold and ABA, reducing cold tolerance, disrupting osmotic balance, and impairing reactive oxygen species (ROS) scavenging. RNA sequencing revealed that OsZOS2-19 overexpression interfered with key stress-response pathways, including those associated with sugar metabolism and glutathione biosynthesis. These findings suggest that OsZOS2-19 negatively regulates cold tolerance and ABA sensitivity by modulating ROS accumulation and osmotic balance, offering new insights into cold adaptation in rice.
An alternative pathway to starch granule initiation unraveled in Chlamydomonas reinhardtii.
Authors: Courseaux Adeline , Deschamps Philippe , Dauvillée David
Published: February 2025

The initiation of starch granule synthesis remains a relatively poorly understood phenomenon. Recent advances enabled the establishment of a model explaining the synthesis of new starch granules in Arabidopsis thaliana. These characterizations revealed the involvement of both a specific starch synthase isoform (SS4) and of several non-enzymatic proteins in this process. In this work, we investigated whether the initiation of starch synthesis in the green microalgae Chlamydomonas reinhardtii involves the same machinery as those uncovered in the plant model. Our extensive phylogenetic analysis revealed that most of the key players that were identified in higher plants are not found in microalgae suggesting that a different pathway is taking place. We showed that restoration of ADP-glucose synthesis in a mutant strain devoid of any endogenous primers allowed normal starch synthesis, revealing the existence of an initiation mechanism in Chlamydomonas. Our biochemical characterizations revealed that starch synthase isoform 3 possesses the intrinsic capacity to initiate polysaccharide synthesis in vitro and could be one of the functions involved in starch initiation. Our work suggests that the initiation of starch synthesis in Chlamydomonas involves a different pathway to that described in Arabidopsis and that further efforts will be required to identify the proteins involved in this process.
Occupational history questionnaire for job coding and exposure assessment in systemic autoimmune rheumatic diseases
Authors: Dens Anne-Catherine , Celen Hannelore , Michiels Stijn , Doumen Michaël , Pazmino Sofia , Godderis Lode , Verschueren Patrick , Kromhout Hans , Ronsmans Steven , De Langhe Ellen
Published: February 2025

Objectives

Systemic autoimmune rheumatic diseases (SARDs) develop in genetically susceptible individuals when exposed to environmental factors, such as respirable crystalline silica (RCS) particles. Assessing occupational exposure in population-based studies is critical but resource-intensive, often requiring expert interviews. This study aimed to develop and validate a self-administered occupational history questionnaire that allows for International Standard Classification of Occupations (ISCO-68) coding and exposure assessment, as a cost-effective alternative to traditional interviews.

Methods

Seventy rheumatoid arthritis patients participated by completing a standardized telephone interview and the newly developed self-administered questionnaire. Participants were also asked to recruit two gender- and age-matched family members for comparison. Independent observers assigned ISCO-68 codes to the reported jobs, and a job exposure matrix was used to link each job to RCS exposure. Agreement between the interview and questionnaire was assessed by comparing reported working years, ISCO-68 job codes, and RCS exposure. Cohen’s κ and intraclass correlation were calculated to evaluate agreement and interobserver variability.

Results

Patient response rate was 77%, but family member controls had a low response rate (6.45%), likely impacted by the COVID-19 pandemic. Agreement for reported working years was 91%, with Cohen’s κ of 0.87 for ever/never RCS exposure. Manual ISCO coding introduced variability, but interobserver reliability remained high (ICC = 0.91).

Conclusion

In conclusion, the self-administered occupational history questionnaire provides a valid, cost-effective, and time-efficient alternative to telephone interviews for assessing occupational history and estimating RCS exposure in epidemiological research. Future studies should explore automated coding systems and improved strategies for control recruitment.
Cancer risk of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs among older Americans with rheumatoid arthritis
Authors: Ahmed Shyfuddin , Pfeiffer Ruth M , Jackson Sarah S , Song Minkyo , Mariette Xavier , Seror Raphaèle , Engels Eric A
Published: February 2025

Objective

To examine cancer risk associated with Janus kinase inhibitors (JAKis) and biological DMARDs (bDMARDs) in patients with RA.

Methods

Case–control study of patients with RA age 65 years or older in the US Surveillance, Epidemiology, and End Results (SEER)-Medicare database during 2014–2019. Cases were individuals with a first cancer diagnosed in SEER registries (N = 12 463). Cancer-free controls (N = 38 345) were Medicare beneficiaries residing in SEER areas. Exposure to JAKis, tumour necrosis factor inhibitors (TNFis) and other bDMARDs was ascertained using prescription claims. Logistic regression was used to estimate adjusted odds ratios (ORs).

Results

1.9% of cases and 2.0% of controls were prescribed a JAKi. Among patients prescribed a JAKi, the median duration of documented exposure was 1.8 years. Overall cancer risk was not associated with exposure to JAKis (adjusted OR 1.04, 95% CI 0.87–1.26), TNFis (0.98, 0.92–1.05) or other bDMARDs (0.98, 0.90–1.07). However, JAKi exposure was associated with significantly increased risk of lung cancer (OR 1.40, 95% CI 1.06–1.87), especially in males (2.12, 1.14–3.94) and with >2 years of JAKi exposure (1.52, 1.01–2.28). Among females, JAKi exposure was associated with lower risk of breast cancer (OR 0.62, 95% CI 0.39–0.97).

Conclusions

Among older adults with RA, JAKi exposure over a median of 1.8 years was not associated with an overall increase in cancer risk. However, lung cancer risk was elevated, supporting clinical caution in prescribing this medication class to smokers. Further research is needed to understand the role of the JAK/STAT pathway in cancer.
Rigid Corneal Lenses for Visual Rehabilitation in Infants With Unilateral Aphakia After Cataract Surgery: A Longitudinal Case Series
Authors: Yan Honggai , Li Li , Liang Tianwei
Published: February 2025

Objectives:

This study investigated the safety of rigid corneal lenses in children with unilateral aphakia after cataract surgery and observed the visual rehabilitation longitudinally.

Methods:

This retrospective cohort study performed a 3-year follow-up of 21 infants (age 5.9±3.3 months) with unilateral congenital cataracts who started wearing rigid corneal contact lenses after cataract surgery. The basic presurgical patient information included chief complaint, intraocular pressure (IOP), axial length, corneal width, anterior segment, and fundus examination. The postsurgical visual acuity, IOP, and anterior segment were examined during regular postoperative follow-up visits. Keratometry was performed when contact lenses had to be changed.

Results:

Of the 21 patients, 15 were male and 6 were female. Before surgery, the affected and nonaffected eyes had similar IOP (9.5±3.5 vs. 9.2±2.8 mm Hg; P=0.502) and axial length (19.2±1.5 vs. 19.4±0.96; P=0.333). The corneal diameter in the affected eyes was smaller than in the nonaffected eyes (10.2±0.7 vs. 10.6±0.6 mm; P=0.002). After surgery, the logarithm of the minimum angle of resolution vision of the affected eyes improved gradually, showing values of 1.12±0.28, 0.78±0.37, and 0.62±0.38 at 1, 2, and 3 years after surgery, respectively. The respective values in the unaffected eyes were 0.58±0.14, 0.40±0.13, and 0.33±0.16. The mean keratometric astigmatism and keratometry 1 and 3 years after surgery were statistically similar (2.09±1.21 vs. 1.73±1.16 D, P=0.272; 44.82±3.15 vs. 44.39±2.75 D, P=0.324, respectively). No serious complications occurred during the follow-up.

Conclusion:

The rigid corneal lens is well tolerated and safe in aphakic eyes and can effectively improve children's visual acuity after unilateral cataract surgery. For patients able to receive rigid corneal lenses, intraocular lens implantation can be delayed until after the age of three.
Vasopressor Requirements in Antipsychotic Overdose
Authors: Tobarran Natasha , Kershner Emily K. , Cumpston Kirk L. , Chambers Andrew , Michienzi Avery , Rose S. Rutherfoord , Charlton Nathan , Wills Brandon K.
Published: February 2025

Purpose/Background

The antipsychotic class of medications has a varying degree of peripheral alpha antagonism resulting vasodilation and potentially hypotension. These hemodynamic changes may require treatment with crystalloids and vasopressors. The primary aim of this study was to evaluate the occurrence of hypotension after antipsychotic overdose and characterize vasopressor use.

Methods/Procedures

A retrospective cohort study was conducted by chart review of electronic records from 2 regional poison centers from January 1, 2004, to December 31, 2020. Inclusion criteria were single acute antipsychotic exposures evaluated in a health care facility and age >15. Exclusion criteria included missing data, minor or no effect outcomes, and polypharmacy overdose. The primary outcome was hypotension, which was defined as systolic blood pressure <90 mm Hg and/or MAP <65.

Findings/Results

There were 4488 single acute antipsychotic overdoses that presented to a healthcare facility after the initial search was conducted. After exclusions, there were 2070 cases with moderate or severe outcomes. The mean age was 42 (SD = 16), and 70% were female. There were 169 cases with hypotension. Of the hypotensive cases, 92% involved atypical antipsychotics, with quetiapine being the most common (n = 128, 76%). Vasopressor therapy was administered in 16/169 cases (9.9%). In the cases where vasopressor use was recorded, norepinephrine was used 12 times, dopamine 3 times, and phenylephrine once. No deaths were reported.

Implications/Conclusions

In antipsychotic overdoses that presented to a healthcare facility, hypotension was present in n = 169 (3.8%).

Conclusions

Among patient reports to 2 regional poison centers, we found that hypotension following acute antipsychotic overdose was infrequent and vasopressors are rarely administered.
Electronic Clinical Quality Measures for Prosthetic Joint Infection Diagnosis: Pitfalls and Potential
Authors: Miller Andy O. , Chin Amy S. , Carli Alberto V. , Sayegh George , Chee Diana , Buchalter Daniel B. , Simon Sam , Maclean Catherine H.
Published: February 2025

Introduction:

Prosthetic joint infection (PJI) after total hip and knee arthroplasty (TJA) is a major cause of morbidity in orthopedics. Fully specified quality measures for PJI diagnosis are lacking. We aimed to specify and evaluate electronic clinical quality measures (eCQM) across different healthcare institutions.

Methods:

Measures were specified using an iterative process through which elements in the measures were identified and evaluated, and their capture optimized in the electronic health record (EHR). Measures were then retrospectively tested at three institutions. Performance on the measures at each institution, and across surgeons at one, was also assessed. Qualitative interviews with each institution identified technical, structural, and clinical reasons for poor performance on the measures.

Results:

Four of the five eCQMs could be implemented within the EHRs. Wide variations were found in measure performance. Qualitative interviews revealed differences in EHR coding, data not being shared within institutions, and focus on specific tests within the testing set as reasons for poor performance.

Conclusions:

Significant variability in posthetic joint infection eCQMs exists, driven both by variations in data availability and clinical practice. Electronic clinical quality measures hold significant potential to enhance diagnostic quality measurement, but successful implementation is highly dependent on process standardization, data accuracy, and adaptation of measures across healthcare settings.
Massive transfusion protocol prediction decision aids in an Australian trauma setting
Authors: Wangoo Kush , Nguyen Vinh Dat David , Byth Karen , Malik Rajesh , Coggins Andrew
Published: February 2025

Background

Trauma patients may require activation of an emergent massive transfusion protocol (MTP). Several decision aids are designed to predict massive transfusion requirements but have not been widely studied in the Australasian setting.

Methods

Commonly used MTP decision aids were assessed for accuracy in injured patients at an urban Level 1 trauma centre. Consecutive cases were prospectively enrolled to a complete registry of thromboelastogram assays in trauma patients. Analysis was undertaken using receiver operating characteristic (ROC) curves, sensitivity and specificity.

Results

A total of 114 patients met inclusion criteria (56 received MTP). More detailed and military derived scores including McLaughlin and Larson demonstrated >90% specificity. Area under ROC curve results were similar to prior reports, but the ABC score performed less accurately than expected.

Conclusion

In the setting of traumatic haemorrhage, the available MTP prediction decision aids should be applied cautiously and used only in combination with on-going clinical judgement.
Rare coagulation factor deficiencies: a five-year experience from a single tertiary care center in South India
Authors: Suresh Nivedita , Kurian Bitty , Jeladharan Reshma , Sao Amrita , Sidharthan Neeraj , Abraham Reema Miria
Published: February 2025

Objective

Rare coagulation factor deficiencies (RCFD) comprise a heterogeneous class of coagulation disorders due to deficiencies/abnormalities in coagulation factors other than factors VIII, IX and von Willebrand factor (VWF). Due to its rarity and varying geographic prevalence, bleeding characteristics and behaviour pattern are not known. Our aim was to study the frequency and clinical profile of RCFD, assess the severity of deficiency, evaluate blood component requirements and surgical outcomes.

Methods

This is a retrospective cohort study done at Advanced Coagulation Laboratory, Amrita Hospital, Kerala from September 2018 to October 2023. Clinical characteristics including bleeding phenotype were noted. The patients were diagnosed based on their complete coagulation workup.

Results

Total of 1019 patients were evaluated, 93 (9.1%) patients had RCFD. Males and females were 60 (64.5%) and 33 (35.5%), respectively (M : F ratio 2 : 1). Median age at diagnosis was 26 years (range: 2 months–74 years). Half the patients (47) had bleeding episodes, 23 (25%) patients were detected incidentally and 23 (25%) patients as a part of preoperative evaluation. Mucocutaneous bleeding was the commonest symptom. The most common RCFD was factor VII deficiency (40%). Transfusion/hemostatic support was required for 29 (31.2%) patients during their life time. No adverse outcome was noted in 27 (29%) patients who underwent surgeries.

Conclusion

Factor VII deficiency was the commonest RCFD. Only half of the patients with RCFD were symptomatic. RCFDs generally have a favorable surgical/ pregnancy outcome. Data from resource limited settings are lacking; more studies are required to formulate management guidelines.
The role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as venous thromboembolism predictors in breast cancer patients pre- and post-therapy
Authors: Qian Alyssa , Zandi Armita , Bucciol Regan , Othman Maha
Published: February 2025

Objectives

Breast cancer (BC) accounts for 12.3% of all cancer-associated venous thromboembolism (VTE). Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are recognized inflammatory biomarkers but have not been incorporated into thrombosis risk stratification models. We evaluated NLR and PLR as predictive biomarkers for VTE in BC patients to determine their optimal predictive cutoffs and net predictive value before and after treatment.

Methods

We conducted a prospective pilot study that involved 56 women with BC, recruited prior to treatment (chemotherapy and immunotherapy) initiation with at least 6-month monitoring for VTE. NLR and PLR were assessed pre and posttreatment.

Results

Five patients (8.9%) developed VTE. NLR and PLR increased significantly posttreatment (P = 0.001). Post, not pretreatment, NLR (P = 0.029) and PLR (P = 0.033) were significantly associated with VTE occurrence. Receiver Operating curve analysis indicated enhanced predictive capacity for VTE postimmunotherapy. Optimal posttreatment cutoffs were 3.6 for NLR and 280 for PLR, aligning with existing literature, with slightly elevated NLR.

Conclusions

Posttreatment NLR and PLR have higher predictability for VTE in patients receiving immunotherapy compared to chemotherapy. NLR outperforms PLR, particularly postimmunotherapy. This data holds promise for thrombosis risk stratification in the context of immunotherapy but requires evaluation in larger studies.
Demographics and Clinical Characteristics of Patients With Cpue
Authors: Stathopoulos Anna G. , Hylind Linda M. , Giardiello Francis M. , Foda Zachariah H.
Published: February 2025

Goals:

This study examines the demographic and clinical characteristics of patients with CPUE (colonic polyposis of unknown etiology) to determine who may benefit from increased surveillance.

Background:

CPUE refers to individuals with 10 or more colonic adenomas with no identifiable genetic mutation as determined by multigene panel testing. Unlike hereditary syndromes, such as familial adenomatous polyposis, CPUE lacks well-established guidelines for polyp and colorectal cancer surveillance, relying heavily on expert opinion.

Study:

This single-center retrospective study included 75 individuals over the age of 18. Data on demographics, medical history, social history, and endoscopic data were collected via chart review. Patients were stratified by total number of polyps (10 to 19, 20 to 29, and over 30). Data were analyzed using the Pearson χ2 test for categorical variables and ANOVA to compare means.

Results:

Among all CPUE patients, 58.7% were male, and 89.3% were white. Tobacco use was reported in 44.0% of patients. Nearly half had hypertension (49.3%) or hyperlipidemia (49.3%). The total prevalence of CRC was 10.7%. Of the 44 patients who underwent EGD, 25.0% had at least one gastric polyp. No statistically significant differences were found between the 3 groups.

Conclusions:

The NCCN recommends exercising clinical judgment for the management of those with 10 to 19 adenomas; however, these findings suggest that individuals in that group do not significantly differ from patients with 20 or more adenomas and may therefore benefit from similar management.
The use of simple tests to predict biopsy-proven steatohepatitis in people with type 2 diabetes
Authors: Machado-Silva Lilian , Terra Carlos , Campos Carlos Frederico , Lanzoni Valeria , Miguez Marcio , Perazzo Hugo , Gomes Marilia Brito , Perez Renata M.
Published: February 2025

Background/aims

Metabolic-associated steatotic liver disease (MASLD) has become the most common chronic liver disease, especially in people with type 2 diabetes mellitus (T2DM). Liver biopsy remains the gold standard method for diagnosis of MASLD subtypes, but prevalences may be under or overestimated when biopsy is performed with selection bias. The aims of this study were to define prevalence of MASLD subtypes by liver biopsy in T2DM participants not selected by abnormal exams, determine variables associated with metabolic-associated steatohepatitis (MASH), and analyze performance of aminotransferases and abdominal ultrasound in diagnosis.

Methods

T2DM participants from 18 to 70 years were considered for enrollment. Of the 396 participants, 85 were included and submitted to clinical, laboratory examinations, and ultrasound. Eighty-three performed liver biopsy evaluated by two independent pathologists. Factors independently associated to MASH and significant fibrosis were assessed by hierarchical multivariate logistic regression.

Results

Prevalence of MASLD was 92% (50% simple steatosis, 42% MASH) and kappa = 0.78. Steatosis was mild in 76% of participants with simple steatosis and severe in 65% of MASH (P < 0.001). Presence of MASH or fibrosis was associated with BMI and alanine aminotransferase (ALT) [threshold of 33.5 mg/dl in predicting MASH (area under the curve = 0.82, P = 0.001)].

Conclusion

Prevalence of MASLD by liver biopsy in T2DM regardless of ultrasound or ALT elevation is almost 100%, with 42% of MASH. MASH was associated to severe steatosis on histology. BMI and ALT were independently associated with MASH and ALT close to the upper limit of normal gave the best cutoff point for MASH detection.
Management of sporotrichosis in patients with inflammatory bowel disease using biological therapy (antitumor necrosis factor)
Authors: Godoy Finger Ana Paula , Tavares Ferreira de Oliveira Cruz Lívia , Rosevics Leticia , de Queiroz-Telles Flavio , Beiral Hammerle Marcia , Breda Giovanni , Kowalski Furlan Thaisa , Castro Tavares Gabriel , Cuzzi Tullia , Zaltman Cyrla , Ramos Junior Odery
Published: February 2025

Antitumor necrosis factor (TNF)-alpha (TNFa) drugs are crucial for treating inflammatory bowel disease (IBD) but may increase opportunistic infection risk. Among such infections, sporotrichosis is a chronic granulomatous disease caused by saprophytic dimorphic fungi of the genus Sporothrix, which occurs worldwide. To date, there have been no reports of sporotrichosis in immunosuppressed IBD patients. The main objectives are to discuss clinical, diagnostic, and therapeutic aspects of sporotrichosis in IBD patients on anti-TNF therapy. We describe three patients with IBD on TNFa therapy who contracted cutaneous-disseminated and extracutaneous sporotrichosis and discuss strategies for managing sporotrichosis and IBD therapy in this scenario. The first case is a patient with ulcerative colitis with mild lymphocutaneous sporotrichosis who did not require discontinuation of anti-TNF agents and methotrexate. The other two patients had rapidly progressive extensive lymphocutaneous disease and disseminated sporotrichosis. These patients required hospitalization, a temporary discontinuation of their biological therapy, and a subsequent switch to vedolizumab. In all cases, the sporotrichosis was successfully treated and none of them experienced serious complications. Sporotrichosis should be considered in anti-TNF IBD patients with opportunistic infections. Early diagnosis, infection treatment, education of cat owners, and population control programs are necessary.
Reversal of Roe v. Wade and implications of legal restrictions for neonatal care
Authors: Bishop Christine E. , Manian Maya
Published: February 2025

Purpose of review

This review examines the implications of the 2022 Dobbs v. Jackson Women's Health Organization decision on neonatal care and explores how legal restrictions on abortion are influencing medical practices for neonates and the broader healthcare landscape for neonates.

Recent Findings

The Dobbs decision has led to increased uncertainty and challenges in both maternal and neonatal healthcare. Restrictive abortion laws are associated with higher infant mortality rates, increased health disparity, and increased care provider ethical dilemmas and moral distress due to legal uncertainty surrounding the care of infants. However, current changes in federal and state law regarding abortion do not change the previously established standard of care for neonates. Other federal legal statutes potentially addressing the care of neonates have existed for over 20 years and have had minimal effect on the practice of neonatology, because there is no record of federal enforcement actions or federal case law to clarify how the law should be interpreted.

While restrictive abortion laws primarily affect women and pregnant people's health care, indirect effects on neonatal care are becoming more common. There are other laws and policies with greater potential to regulate care for infants at the federal and state level. Professional medical standards remain the guiding framework in neonatal care. Clinicians can mitigate legal concerns through knowledge and advocacy.
Deep Learning Reconstruction Combined With Conventional Acceleration Improves Image Quality of 3 T Brain MRI and Does Not Impact Quantitative Diffusion Metrics
Authors: Wilpert Caroline , Russe Maximilian Frederic , Weiss Jakob , Voss Christian , Rau Stephan , Strecker Ralph , Reisert Marco , Bedin Ricardo , Urbach Horst , Zaitsev Maxim , Bamberg Fabian , Rau Alexander
Published: February 2025

Objectives

Deep learning reconstruction of magnetic resonance imaging (MRI) allows to either improve image quality of accelerated sequences or to generate high-resolution data. We evaluated the interaction of conventional acceleration and Deep Resolve Boost (DRB)–based reconstruction techniques of a single-shot echo-planar imaging (ssEPI) diffusion-weighted imaging (DWI) on image quality features in cerebral 3 T brain MRI and compared it with a state-of-the-art DWI sequence.

Materials and Methods

In this prospective study, 24 patients received a standard of care ssEPI DWI and 5 additional adapted ssEPI DWI sequences, 3 of those with DRB reconstruction. Qualitative analysis encompassed rating of image quality, noise, sharpness, and artifacts. Quantitative analysis compared apparent diffusion coefficient (ADC) values region-wise between the different DWI sequences. Intraclass correlations, paired sampled t test, Wilcoxon signed rank test, and weighted Cohen κ were used.

Results

Compared with the reference standard, the acquisition time was significantly improved in accelerated DWI from 75 seconds up to 50% (39 seconds; P < 0.001). All tested DRB-reconstructed sequences showed significantly improved image quality, sharpness, and reduced noise (P < 0.001). Highest image quality was observed for the combination of conventional acceleration and DL reconstruction. In singular slices, more artifacts were observed for DRB-reconstructed sequences (P < 0.001). While in general high consistency was found between ADC values, increasing differences in ADC values were noted with increasing acceleration and application of DRB. Falsely pathological ADCs were rarely observed near frontal poles and optic chiasm attributable to susceptibility-related artifacts due to adjacent sinuses.

Conclusions

In this comparative study, we found that the combination of conventional acceleration and DRB reconstruction improves image quality and enables faster acquisition of ssEPI DWI. Nevertheless, a tradeoff between increased acceleration with risk of stronger artifacts and high-resolution with longer acquisition time needs to be considered, especially for application in cerebral MRI.
68Ga-FAPI PET/CT in a Patient With Multiple Aneurysms Due to Idiopathic Hypereosinophilic Syndrome
Authors: Li Puhao , Liang Juan , Chen Yue , Ding Haoyuan
Published: February 2025

Idiopathic hypereosinophilic syndrome is a group of unexplained diseases characterized by a persistent increase in eosinophils with multiple organs damage. Herein, we describe the 68Ga-FAPI PET/CT findings of idiopathic hypereosinophilic syndrome in a 56-year-old woman. 68Ga-FAPI PET/CT showed multiple aneurysms with increased FAPI uptake. In addition, myocardial uptake of FAPI was observed.
Imaging Spectrum of Extrathyroidal Neck Masses
Authors: Patel Naiya , Gharai Sean , Brindle Kathleen A. , Khati Nadia J.
Published: February 2025

Extrathyroidal masses in the anterolateral neck are frequently encountered in the adult population and may represent a diagnostic dilemma. These neck masses can result from a diverse array of pathologies including congenital, inflammatory, infectious, and neoplastic causes. Relevant medical history and physical examination are essential to complement the imaging findings. Ultrasound (US) plays an important role in the initial evaluation of neck masses due to its reliability, availability, safety and cost-effectiveness. It can confirm or exclude the presence of a mass and initially characterize it as solid or cystic. Sonographically assessing the relationship of a mass to adjacent cervical anatomy can facilitate a more targeted differential diagnosis. US also effectively guides fine needle aspirations and/or biopsies of accessible lesions. Multimodality imaging is reserved for problem-solving complex cases and presurgical planning. The anterolateral neck masses are categorized into midline/paramedian lesions, salivary gland pathologies, and other soft tissue lesions. Midline and paramedian lesions include thyroglossal duct pathologies, ectopic thyroid tissue, and parathyroid adenomas. Salivary gland pathologies include obstructive/inflammatory processes, benign and malignant neoplasms, and systemic diseases. This pictorial essay presents clinical features and sonographic characteristics of extrathyroidal masses in the anterolateral neck with a brief discussion of other imaging modalities.
ACS NSQIP Surgical Risk Calculator Accuracy When Operative Risk is Represented by the Principal CPT® code Versus Many Codes
Authors: Cohen Mark E. , Liu Yaoming , Hall Bruce L. , Ko Clifford Y.
Published: February 2025

Objective:

To determine whether ACS NSQIP risk calculator (RC) accuracy can be improved by incorporating CPT codes beyond the principal code.

Background:

Because of technical limitations, past and current RC algorithms have relied only on the principal CPT code, represented as a logit score, to adjust for procedure-related risk. RC performance was evaluated when using a new machine learning (ML) algorithm capable of incorporating an indeterminate number of high cardinality categorical variables (in this case, multiple CPT codes).

Methods:

ACS-NSQIP data from 5,020,713 patients from 2016-2020 were used. Predictive accuracy, for 13 outcomes, was assessed when the RC relied on, in addition to standard predictors, a logit score associated with the principal CPT code (extreme gradient boosting ML, XGB), or up to 21 codes in native categorical form (CatBoost ML, CATB). 80% of cases were used for training and 20% for validation. Discrimination (area under the receiver operator characteristic curve and area under the precision recall curve) and calibration (Hosmer-Lemeshow statistics) were assessed on the entire validation dataset and on a subset of that data that included only patients who had at least 1 CPT code recorded beyond the principal code.

Results:

There was no consistent accuracy advantage of CATB over XGB with respect to discrimination. XGB tended to have slightly better calibration than CATB when evaluated on the complete validation dataset but tended to have slightly worse calibration compared to CATB when the validation dataset was limited to the subset of 34.8% of cases where there was at least one code in addition to the principal CPT code. However, there was a subset of patients with 4 or more CPTs (about 8% of all patients) where CATB provided meaningfully more accurate estimates than XGB.

Conclusions:

While the current RC, relying on XGB and the principal CPT code, remains a viable approach to routine surgical risk assessment, an advanced version of the RC, based on the CATB algorithm and accommodating multiple CPT codes, may provide more accurate estimates.
The Utility of Follow-up Transthoracic Echocardiogram to Screen for Severe Portopulmonary Hypertension (POPH) in Patients Granted POPH Model for End-stage Liver Disease (MELD) Exceptions
Authors: del Valle Kathryn T. , Kay Dana , Krowka Michael J. , Runo James R. , Sadd Corey , Heimbach Julie K. , Cartin-Ceba Rodrigo , Cajigas Hector R. , Burger Charles D. , Moss John E. , DuBrock Hilary M.
Published: February 2025

Background.

The current model for end-stage liver disease (MELD) exception policies for portopulmonary hypertension (POPH) require serial right heart catheterizations (RHCs) every 3 mo to maintain exception points. RHC is necessary for the initial diagnosis of POPH, but the utility of serial catheterizations has not been studied. In patients with POPH MELD exceptions, we sought to compare noninvasive and invasive hemodynamics and determine the sensitivity of echocardiography for the detection of hemodynamically severe POPH that would preclude liver transplant.

Methods.

We performed a single-center retrospective cohort study of patients with POPH MELD exceptions who underwent liver transplant from December 2008 to January 2024. Results were validated at an external center. Echocardiograms and RHCs performed within 1 mo were compared. Pearson correlation coefficient and Bland-Altman plots assessed the association between echocardiogram and RHC variables. We examined varied echocardiographic parameters to optimize sensitivity for the detection of hemodynamically severe POPH.

Results.

Twenty-two individuals underwent 60 follow-up RHCs with paired echocardiograms. Right ventricular systolic pressure (RVSP) and cardiac index estimated with echocardiogram were not strongly correlated with RHC measurements at follow-up (RVSP and RHC pulmonary artery systolic pressure: R = 0.30, P = 0.02; cardiac index: R = 0.17, P = 0.21). However, echocardiograms with RVSP ≥48 mm Hg had 100% sensitivity for detecting hemodynamically severe POPH, with 100% negative predictive value. In external validation of 13 paired echocardiograms and RHCs, our algorithm had 64% specificity and 100% negative predictive value.

Conclusions.

Although echocardiogram and RHC hemodynamic estimates were not strongly correlated, these results could potentially negate the current requirement for repeat RHC every 3 mo to maintain POPH MELD exception.
State-of-the-art gene therapy in epilepsy
Authors: Walker Matthew C.
Published: February 2025

Purpose of review

Gene therapy in epilepsy has undergone a rapid expansion in recent years. This has largely been driven by both advances in our understanding of epilepsy genetics and mechanisms, and also significant advances in gene therapy tools, in particular safe and effective viral vectors. Epilepsy remains an ideal target disease for gene therapy and this review highlights recent developments in this area.

Recent findings

There have been continued advances in the development of antisense oligonucleotide therapies to knock down genes in the treatment of monogenic epilepsies with some now entering clinical trial. However, the greatest recent advances have been in vector gene therapy, which offers a more permanent solution by delivering therapeutic genes directly to the brain as a one-off therapy. In particular, there has been a growth in methods that target focal epilepsy. Such promising approaches close to or in clinical trial include expressing NPY and its Y2 receptor, knocking-down GluK5, a kainate receptor subunit, and the over-expression of Kv1.1, an endogenous potassium channel.

In the future, it is likely that we will take advantage of approaches of regulating more precisely network excitability by using methods such as optogenetics, designer receptors exclusively activated by designer drugs (DREADDs), ‘inhibitory’ glutamate receptors activated by excessive glutamate spill-over, and activity-dependent promoters, which target gene expression to the ‘hyperactive’ neurons.

Gene therapies offer a novel approach to the treatment of not just genetic epilepsies but any form of epilepsy and may in the future offer an alternative to drug and surgical therapies, allowing more precise, permanent and targeted treatment with fewer adverse effects.