bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Role of Gynecomastia Surgery in Improving Sexual Function and Hormonal Profiles
Authors: Akdag Tansu , Akdag Abdullah , Ozkan Mustafa , Aydin Osman Enver 
Published: February 2025

Abstract

Background
Patients with gynecomastia may experience hormonal imbalances and sexual dysfunctions such as erectile and ejaculatory disorders.

Objectives
This study evaluates the changes in hormonal parameters and sexual function following gynecomastia surgery.

Methods
Thirty-two male patients (aged 15–65) without systemic or genetic comorbidities underwent gynecomastia surgery. Preoperative and postoperative hormonal parameters free and total testosterone, estrogen, prolactin, follicle-stimulating hormone [FSH], luteinizing hormone [LH], sex hormone-binding globulin [SHBG], and sexual function scores (International Index of Erectile Function [IIEF], Premature Ejaculation Diagnostic Tool [PEDT]) were assessed. A urologist blinded to the study evaluated patients andrologically.

Results
The mean age of the patients was 25.69 ± 10.37 years. Postoperative prolactin and estrogen levels significantly decreased (p=0.03 and p&lt;0.001, respectively). All IIEF subscale scores showed significant postoperative improvements (p-values ranging from &lt;0.001 to 0.006). PEDT scores significantly decreased postoperatively (p&lt;0.001).

Conclusions
Surgical treatment of gynecomastia leads to significant improvements in hormonal parameters and sexual function. These benefits should be considered in surgical planning.
Autosomal dominant SLURP1 variants cause palmoplantar keratoderma and progressive symmetric erythrokeratoderma
Authors: Jiang Xingyuan , Mortlock Ryland D , Lomakin Ivan B , Zhou Jing , Hu Ronghua , Cossio María Laura , Bunick Christopher G , Choate Keith A 
Published: February 2025

Abstract

Background
Epidermal differentiation disorders (EDDs, a.k.a. ichthyosis and palmoplantar keratoderma) are severe heritable skin conditions characterized by localized or generalized skin scaling and erythema.

Objectives
To identify novel genetic variants causing palmoplantar keratoderma (PPK) and progressive symmetric erythrokeratoderma (PSEK) phenotypes.

Methods
We performed whole exome sequencing in a large EDD cohort including PPK and PSEK phenotypes to identify novel genetic variants. We investigated the variant consequence using in silico predictions, assays in patient keratinocytes, high-resolution spatial transcriptomics, and quantitative cytokine profiling.

Results
We identified three unrelated kindreds with autosomal dominant transmission of heterozygous SLURP1 variants affecting the same amino acid within the signal peptide (c.65C&gt;A, p.A22D, and c.65C&gt;T, p.A22V). One (p.A22V) had isolated PPK, and two others (p.A22D) had PSEK and PPK. In silico modeling suggested that both variants alter pro-SLURP1 cleavage, appending two amino acids to the secreted protein, which we subsequently confirmed with mass spectrometry. In patient keratinocytes we found increased differentiation-induced SLURP1 expression and secretion compared to healthy control cells. Spatial transcriptomics revealed increased NF-κB signaling and innate immune activity which may contribute to epidermal hyperproliferation in dominant SLURP1-PPK/PSEK.

Conclusions
Our results expand the phenotypic spectrum of EDD due to SLURP1 pathogenic variants. While autosomal recessive Mal de Meleda is due to biallelic loss-of-function SLURP1 variants, our finding of autosomal dominant SLURP1 pathogenic variants in kindreds with PPK and PSEK suggests a novel mechanism of action. We found that heterozygous p.A22V and p.A22D SLURP1 variants append two amino acids to secreted SLURP1, increase differentiation-induced SLURP1 expression and secretion, and upregulate NF-κB signaling in PSEK cases.
Cross-fitted empirical likelihood on semiparametric models
Authors: Qiu Chen 
Published: February 2025

Abstract
We propose a new cross-fitted empirical likelihood (CFEL) inference procedure for low dimensional parameters in the presence of complex, infinite dimensional nuisance parameters that may be estimated by modern machine learning methods. Relying on the Neyman orthogonal moment condition and cross-fitting as a sample-splitting procedure, we show that our CFEL statistic is asymptotically pivotal under weak conditions often invoked in Wald-type approaches. Three examples show how these can be established using low-level conditions on the quality of the estimated nuisance parameters. Simulation evidence suggests that the Wald approach may undercover more compared to our CFEL approach, especially when the estimating equation is nonlinear in the low-dimensional parameter and the first-step estimators have larger finite-sample estimation errors. We illustrate the value of our approach by revisiting the Pennsylvania Reemployment Bonus experiment that studied the effect of cash bonuses on unemployment duration.
Organic food consumption and the incidence of atherosclerotic cardiovascular disease in the Danish Diet, Cancer and Health cohort
Authors: Andersen Julie L M , Frederiksen Kirsten , Kyrø Cecilie , Hansen Johnni , Raaschou-Nielsen Ole , Bork Christian S , Dahm Christina C , Tjønneland Anne , Olsen Anja 
Published: February 2025

Abstract

Aims
We investigated associations between overall organic food consumption and consumption of specific organic food groups with the risk of developing atherosclerotic cardiovascular disease (ASCVD).

Methods
The study was based on a prospective cohort of middle-aged women and men from the Danish Diet, Cancer and Health study. Information about organic food consumption of vegetables, fruit, dairy products, eggs, meat, and bread and cereal products was obtained from a food frequency questionnaire. The frequency consumption of the six food groups was summarized into a total organic food score evaluated in categories (never, low, medium and high intake) and as a continuous variable. A total of 41,407 study participants were followed for a median of 16 years during which 5,365 developed ASCVD.

Results
Overall organic food consumption was associated with a 6% lower incidence rate of ASCVD per 6-point increment in the total organic food score (HR: 0.94, 95% CI: 0.89-0.99). Organic consumption of eggs was associated with lower incidence of ASCVD for both women (HR, 0.95, 95% CI 0.91-0.99) and men (HR: 0.96, 95% CI: 0.93-0.99), and organic consumption of bread and cereal products were associated with a lower incidence of ASCVD among men (HR: 0.95, 95% CI: 0.91-0.99).

Conclusions
We found that organic food consumption was associated with a lower incidence of ASCVD in a cohort of middle-aged Danish women and men.
Prenatal and Postnatal Nutritional Mismatch, Reflected by Birth Weight and Adult BMI, and Cardiometabolic Disease Risk
Authors: Chen Shuhao , Ding Ding , Cui Qingmei , Zhao Xirui , Feng Anping , Xia Yuhan , Xu Qian , Li Jie 
Published: February 2025

Abstract

Aims
This study aimed to investigate how nutritional exposures in early life, represented by birth weight (BW), and in later life, indicated by adult body mass index (BMI), interact to influence cardiometabolic disease (CMD) risk and to examine the underlying causal relationships.

Methods
Included were 254,224 participants of White European ancestry from the UK Biobank. To evaluate the joint associations of BW and adult BMI with CMD risk, BW was categorized as low (LBW, &lt;2.5 kg) or high (HBW, ≥2.5 kg), and BMI as low (LBMI, &lt;30 kg/m²) or high (HBMI, ≥30 kg/m²). Multivariable Cox proportional hazards models and 2x2 factorial Mendelian randomization (MR) analyses were employed to assess these associations and the underlying causality.

Results
Compared to the participants with HBW-LBMI, the hazard ratio (HR) for atherosclerotic cardiovascular disease (ASCVD) was 1.19 (95% CI: 1.12 to 1.26) in the LBW-LBMI group, 1.33 (1.28 to 1.38) in the HBW-HBMI group, and 1.62 (1.50 to 1.75) in the LBW-HBMI group. The LBW-HBMI group also exhibited higher risks for hypertension (HR: 2.42 [2.26–2.59]), diabetes (HR: 5.16 [4.73–5.63]), and hyperlipidemia (HR: 1.95 [1.81–2.10]). Additive interactions between LBW and HBMI were identified for metabolic diseases but not for ASCVD. The causality of these associations was confirmed by MR analysis.

Conclusions
Combined exposure to LBW and HBMI was most strongly associated with an elevated risk of CMD, underscoring the critical role of the mismatch between early-life and adult nutritional status in shaping long-term cardiometabolic health.
Occurrence of “under-the-radar” antibiotic resistance in anthropogenically affected produce
Authors: Davidovich Chagai , Erokhina Kseniia , Gupta Chhedi Lal , Zhu Yong-Guan , Su Jian-Qiang , Djordjevic Steven P , Wyrsch Ethan R , Blum Shlomo E , Cytryn Eddie 
Published: February 2025

Abstract
With global climate change, treated-wastewater irrigation and manure amendment are becoming increasingly important in sustainable agriculture in water- and nutrient-stressed regions. Yet, these practices can potentially disseminate pathogens and antimicrobial resistance determinants to crops, resulting in serious health risks to humans through the food chain. Previous studies demonstrated that pathogen and antimicrobial resistance indicators from wastewater and manure survive poorly in the environment, suggesting that ecological barriers prevent their dissemination. However, we recently found that these elements can persist below detection levels in low quality treated wastewater-irrigated soil, and potentially proliferate under favorable conditions. This “under-the-radar” phenomenon was further investigated here, in treated wastewater-irrigated and poultry litter-amended lettuce plants, using an enrichment platform that resembles gut conditions, and an analytical approach that combined molecular and cultivation-based techniques. Enrichment uncovered clinically relevant multidrug-resistant pathogen indicators and a myriad of antibiotic resistance genes in the litter amended and treated wastewater-irrigated lettuce that were not detected by direct analyses, or in the enriched freshwater irrigated samples. Selected resistant E. coli isolates were capable of horizontally transferring plasmids carrying multiple resistance genes to a susceptible strain. Overall, our study underlines the hidden risks of under-the-radar pathogen and antimicrobial resistance determinants in anthropogenically affected agroenvironments, providing a platform to improve quantitative microbial risk assessment models in the future.
Locating ‘country of origin’ in a borderless world: assessing Article 5(3) of the Berne Convention in the context of global platforms and social media
Authors: Glynn Cameron 
Published: February 2025

Abstract
The paper assesses Article 5(3) of the Berne Convention in an era of digital networks, social media, and globally operating platforms. Of primary focus is the significance and meaning of a ‘country of origin’ provision in these contexts, where cross-border communication and the removal of territorial limitations are defining features. Resolving this tension seems critical if the Berne Convention is to maintain its relevance today, and into the future, where digital spaces seem only to be strengthening in scope and universality. This paper evaluates these challenges and proposes a novel interpretation of Article 5(3), fitting for the developing digital environment.
A genetically encoded secreted toxin potentiates synaptic NMDA receptors in hippocampal neurons and confers neuroprotection
Authors: Carmi Ido , Zoabi Shaden , Bittan Asaf M , Kellner Shai , Oz Shimrit , Heinrich Ronit , Berlin Shai 
Published: February 2025

Abstract
NMDA receptors (NMDARs) play essential roles in neuronal development, survival, and synaptic plasticity, to name a few. However, dysregulation in receptors' activity can lead to neuronal and synaptic damage, contributing to the development of various brain pathologies. Current pharmacological treatments targeting NMDARs remain limited, for instance due to insufficient receptor selectivity and poor spatial targeting. Genetic approaches hold promise to overcome some of these issues; however, require genetically encodable NMDAR-modulating peptides, which are scarce. Here, we explored NMDAR-selective peptide toxins from marine cone snails, which resulted in the necessary engineering of a posttranslational modification-free variant of Conantokin-P (naked Con-P). The naked form is essential for expression in mammalian cells. We systematically explored the naked variant and discovered that naked Con-P maintains its ability to inhibit GluN2B-containing receptors, but uniquely acquired the ability to potentiate GluN2A-containing synaptic receptors. We then engineered a secreted naked Con-P that readily enhances NMDAR-mediated synaptic events in primary hippocampal neurons, and mitigates neuronal damage induced by staurosporine. We therefore provide a genetically encodable, subtype selective, and secreted bimodulator of NMDARs. This new variant and approach should pave the way for the development of additional genetic tools, specifically tailored to target NMDARs within distinct cellular populations in the brain.
Intravascular Large B-Cell Lymphoma With Exclusively Cutaneous Involvement, Colonizing Pre-Existing Hemangiomas: A Rare Case With Aberrant HMB45 Expression
Authors: García de Sola-Llamas Carmen , Pérez-Pérez Manuel , Morillo-Andújar Mercedes , Ríos-Martín Juan J. 
Published: February 2025

Abstract:
Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. It is characterized by the presence of neoplastic lymphoid cells within blood vessels. We report a rare case of IVLBCL with exclusively cutaneous involvement colonization of hemangiomas. A 55-year-old man with a history of cutaneous angioma consulted dermatology because of the growth of some of the hemangiomas in recent months. Histologic examination revealed a dermal proliferation of small- and medium-sized vessels with lumina occupied by large pleomorphic cells with B immunophenotype and aberrant expression of HMB-45. Biopsy of a pre-existing hemangioma may be useful in the diagnosis of suspected cutaneous IVLBCL. The cutaneous variant has a better prognosis. It is also important to note that unexpected protein expression or loss of expression in malignant tumors may be a risk factor for misdiagnosis.
Clinicopathologic Features of PRAME-Positive Common Melanocytic Nevi: A Case-Control Study
Authors: Knittel Ronan J. , Harvey Nathan T. , Ardakani Nima Mesbah , O'Brien Blake , Lee Stephen , Wood Benjamin A. 
Published: February 2025

Abstract:
Preferentially Expressed Antigen in Melanoma (PRAME) immunohistochemistry has been found to be relatively sensitive and specific for the diagnosis of melanoma, although the detection of PRAME positivity in some melanocytic nevi is a significant limitation. This study was designed to investigate the features of common melanocytic nevi showing PRAME staining, encountered in routine community practice. We reviewed all pathology reports on common melanocytic nevi seen in routine practice for a 1-month period and found that 7.1% of nevi stained with PRAME were considered positive by the original reporting pathologist. A total of 41 PRAME-positive nevi (representing 4.7% of nevi) and a control group of 43 PRAME-negative nevi collected during the same period were identified. The histologic features were reviewed, and the diagnosis and PRAME staining were recorded in a masked fashion by 3 dermatopathologists. Our results suggest that caution is warranted in the interpretation of PRAME in the assessment of small lentiginous melanocytic nevi with a low level of suspicion for melanoma, because these are not infrequently PRAME positive. We found a statistically significant association between the presence of solar elastosis and lentiginous growth pattern, and PRAME status (P < 0.01). When comparing the original diagnosis with the reviewer's diagnosis, the original diagnosis was severely atypical in 54% of PRAME-positive cases, while only 7% were considered to show severe atypia on review masked to PRAME status (P < 0.001). There was no such discrepancy among PRAME-negative cases (9% vs. 19%, considered severely atypical). This finding provides evidence of a “PRAME bias” in the interpretation of melanocytic lesions with no or mild atypia, whereby such lesions are classified as severely atypical when PRAME is positive, likely with the intention of prompting re-excision.
Rhabdomyosarcoma Harboring NRAS or HRAS Mutation Arising in Giant Congenital Melanocytic Nevus: Report of 2 Cases
Authors: Kletskaya Irina , Konovalov Dmitry , Druy Alexander , Abasov Ruslan , Salomatina Anastasia , Zaitseva Margarita , Kazaryan Guzel , Pishchayeva Nadezhda , Belousova Irena , Kazakov Dmitry V. 
Published: February 2025

Abstract:
Nonmelanoma malignancies associated with congenital melanocytic nevi (CMN) are extremely rare, with only 12 reported cases of rhabdomyosarcoma (RMS) to date. We present 2 additional cases of RMS arising in giant CMN, with immunohistochemical and molecular biologic investigations. The first case was a 32-year-old woman with a personal history of melanoma in giant CMN who, after successful treatment and long remission, presented with a new 1-cm nodule within the CMN. Microscopically, the atypical areas exhibited a round cell/alveolar morphology with immunoreactivity for desmin and myogenin, and lacked PAX3/7::FOXO1 fusions typical for alveolar RMS on a reverse transcription polymerase chain reaction analysis. An identical NRAS p.Q61R mutation with comparable variant allele frequency (32% and 44%) was identified in both the nevus and the RMS tissue by next-generation sequencing. The second patient was a 5-year-old girl with a rapidly growing, bleeding, ulcerated 3 × 4 cm interscapular mass within a giant CMN that histologically seemed as a proliferation of pleomorphic spindle, polygonal and epithelioid cells with marked pleomorphism immunoreactive for myogenin, muscle-specific actin, and smooth muscle actin. Next-generation sequencing yielded an HRAS p.Q61R mutation with limited variant allele frequency (7%) in the RMS component, while ATRX p.Q2193* variant was detected in the nevus. Our study is apparently the first report of NRAS and HRAS mutations in tumors with RMS phenotype arisen in CMN.
Acral Cutaneous Intraneural Pseudoperineurioma
Authors: AbdullGaffar Badr , Farhan Rabiah 
Published: February 2025

Abstract:
Several cutaneous neurovascular stromal lesions are clinically and pathologically ill-defined entities. They are known by different nomenclatures, often unrecognized, misinterpreted, and confused with other skin lesions. Reports have documented cases of palmar and oral lesions in both children and adults. There is uncertainty regarding their true prevalence, clinicopathologic characteristics, and classification. Our aim is to highlight the salient histopathologic, histochemical, and immunohistochemical features of acral nodular tumors showing perineuriomatous differentiation. We found 3 teenagers (0.2%) [2 females, 1 male, average age: 13 years] with hand nodules out of 1331 patients with cutaneous and oral polypoid lesions. They were isolated, asymptomatic, nontraumatic, subcentimetric, palmar, digital nodules with an average duration of 5 years. They demonstrated dermal-based anomalous growths composed of thick tortuous neurovascular bundles and collagenous fibrovascular stroma. Masson trichome demarcated micronodular and plexiform neurovascular bundles showing concentric onion-bulb whorls ensheathed in collagenous fibrovascular stroma. Elastic fibers were absent. Alcian blue demonstrated intraneural mucinous alteration and loose interstitial myxoid mesenchyme. CD31, ERG, and smooth muscle actin highlighted small intraneural capillary-sized, and larger venous and arteriolar interstitial vasculatures. CD34 decorated the interstitial mesenchyme. S100, SOX10, and neurofilament revealed sparse neural components, whereas EMA and GLUT1 highlighted prominent perineurial components within the neurovascular bundles and onion-bulb micronodules. The findings suggest that cutaneous intraneural pseudoperineurioma nodules may represent a distinct clinicopathologic entity among traumatic neuromas, resembling cutaneous intraneural perineurioma. Further validation studies are necessary because of the small size of the case series and the lack of molecular genetic studies.
Comparison of the IHC Expression of p16, p53, and MIB-1 in Extragenital Skin Bowenoid Lesions With High- and Low- Chronic Sun Damage
Authors: Gil-Pallares Pedro , Gil-Pallares Maria E. , Navarro-Bielsa Alba , Figueroa-Silva Olalla , Taboada-Paz Laura , Suárez-Peñaranda José M. 
Published: February 2025

Background:
Bowen disease and bowenoid actinic keratosis are difficult to distinguish due to overlapping histopathology. This study evaluates the role of p16, p53, and MIB-1 staining patterns in differentiating high-chronic sun damage (H-CSD) and low-chronic sun damage bowenoid lesions.

Methods:
Sixty extragenital in situ squamous cell carcinomas were included. Lesions with elastosis were considered H-CSD. P16, p53, and MIB-1 staining patterns were classified as block, gradient, or focal.

Results:
Seventy-two percent of lesions were H-CSD. Full-thickness dysplasia was observed in all lesions, and basal layer involvement in 97%. P16 staining was positive in 80%, matching areas of higher atypia, with block pattern more frequent in H-CSD (58% vs. 47%, P = 0.047). P53 was positive in 47%, with block pattern more common in H-CSD (40% vs. 18%, P = 0.02). MIB-1 was positive in all cases. P16 and MIB-1 patterns coincided in 75%, independently of sun exposure.

Conclusions:
P16 and p53 expression may be less frequent in bowenoid lesions than previously described. Histopathological features like basal layer and adnexal or follicular involvement may not differentiate H-CSD from low-chronic sun damage lesions or Bowen disease from bowenoid actinic keratosis. Variations in p16, p53, and MIB-1 staining could indicate different dysplasia pathways, although further studies are needed to clarify their prognostic significance.
“Eventually…Your Body Just Can't No More”
Authors: Keirns Natalie G. , Rosen Rochelle K. , Burg Matthew , Gathright Emily , Ouaddi Sara , Tripolone Janice , Breault Christopher , Salmoirago-Blotcher Elena 
Published: February 2025

Background
Takotsubo syndrome (TS) is preceded by emotional/physical triggers in two-thirds of cases and no trigger in one-third. Information on triggers is typically obtained in the emergency room, and patients rarely have the opportunity to describe in detail the event(s) leading to TS onset.

Objective
This study aimed to conduct a qualitative exploration of patients' narratives regarding the events preceding their TS episode.

Methods
Semistructured interviews inquiring about the presence, type (physical vs emotional), and timing of contiguous events/circumstances relative to symptoms onset were conducted within 2 to 12 weeks of hospital discharge for a TS episode. Interview recordings were transcribed, coded, and analyzed with applied thematic content analysis.

Results
Participants (n = 30; 97% women, 93% White; age, 63 ± 8 years) described equal proportions of acute events (onset < 4 days before admission, 43%) and chronic circumstances (onset > 4 days before admission, 43%) preceding their TS episodes. Acute events included emotional, physical, and mixed (ie, emotional and physical) factors. Chronic circumstances included emotional and mixed factors. Seventy percent of participants perceived these events/circumstances as contributing to their onset of TS.

Conclusions
Patients' narratives of the events contiguous to the TS episode are complex and often include factors that are chronic and/or emotional in nature. Future research should explore the potential importance of emotional aspects and chronic stress in the development of TS.