bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, Effectiveness, and Participant Satisfaction With Multiple Simultaneous Cryolipolysis Treatments Using a Dual-Applicator Cryolipolysis System
Authors: Bachelor Eric , Moradi Amir , Stevens Grant , Scott-Shemon Deja , Ostrowski Rafael , Madere Tonia , Gamio Sylvia 
Published: February 2025

BACKGROUND
Cryolipolysis is a safe, effective, and noninvasive treatment for subcutaneous fat reduction.

OBJECTIVE
Assess safety, effectiveness, and participant satisfaction with multiple simultaneous dual-applicator cryolipolysis treatments on the torso.

MATERIALS AND METHODS
Adult participants received multiple simultaneous treatments to the torso (i.e., flanks, abdomen, back/bra area). Primary effectiveness end point was ≥70% correct identification of baseline versus week 12 post–final treatment photographs by ≥2 of 3 independent reviewers; safety end point was frequency of adverse device effects (ADEs). Secondary end points included fat layer thickness reduction and participant satisfaction/comfort.

RESULTS
Mean participant age (N = 35) was 40.4 years, 77.1% were female, and mean body mass index was 24.9 kg/m2. A mean of 20.8 treatment cycles were received over 2 treatment sessions. The primary effectiveness end point was met; 75% of pretreatment images were correctly identified. Mean reduction in fat layer thickness was 0.33 cm. Most ADEs were mild, with no serious events. Mean overall participant satisfaction with the procedure was 82.8%. Mean maximum pain scores were 2.6 and 4.1 (scale of 10) during treatment sessions 1 and 2, respectively.

CONCLUSION
Multiple simultaneous cryolipolysis treatments on the torso using a dual-applicator system were safe and effective, with high overall participant satisfaction.
Targeting protein hyperSUMOylation halts cholangiocarcinoma progression by impairing cancer cell viability and tumor-stroma crosstalk
Authors: Olaizola Paula , Olaizola Irene , Lapitz Ainhoa , Val Beatriz , Izquierdo-Sanchez Laura , Fernandez-Barrena Maite G. , O’Rourke Colm J. , Lee-Law Pui Y. , Gradinaru Andreea , Jimenez-Agüero Raul , La Casta Adelaida , Riaño Ioana , Macias Rocio I.R. , Marin Jose J.G. , Martinez-Chantar Maria L. , Avila Matias A. , Aspichueta Patricia , Andersen Jesper B. , Boulter Luke , Bujanda Luis , Rodrigues Pedro M. , Perugorria Maria J. , Banales Jesus M. 
Published: February 2025

Background and Rationale:
Cholangiocarcinoma (CCA) includes a diverse group of biliary malignancies with poor prognosis. Alterations in post-translational modifications contribute to disrupted protein dynamics, cellular disturbances, and disease. This study investigates the role of protein SUMOylation in cholangiocarcinogenesis and its potential as a therapeutic target.

Approach and Results:
Analysis of CCA tumors from four patient cohorts and CCA cell lines, revealed increased expression of the SUMOylation machinery genes SAE1 and UBE2I, regardless of the tumor’s molecular profile, resulting in elevated levels of SUMO1-conjugated proteins. Higher SAE1 and UBE2I levels were both indicative of unfavorable clinical outcomes. Deregulated SUMOylated proteins in CCA, mostly linked to cell proliferation, survival, and homeostasis, were identified through immunoprecipitation and mass spectrometry. Genetic (UBE2I-knockdown) and pharmacological (ML792 and SAMe) inhibition of SUMOylation effectively suppressed tumorigenesis in subcutaneous and oncogene-driven CCA models, reducing the presence of cancer-associated fibroblasts (CAFs) and increasing the recruitment of anti-tumor immune cells. In vitro, targeting SUMOylation induced CCA cell death and reduced cell proliferation, colony formation, and spheroid growth. Importantly, ML792 and SAMe did not adversely affect normal human cholangiocytes. Moreover, co-culture of wild-type or UBE2I-knockdown CCA cells with CAFs revealed that depleting SUMOylation in CCA cells impaired CAF cell growth and altered their protein secretome, ultimately disrupting CCA growth through a regulatory feedback loop.

Conclusion:
Aberrant SUMOylation drives CCA progression by enhancing cell survival, proliferation, and shaping the tumor microenvironment. Targeting SUMOylation shows potential in inhibiting CCA growth, representing a promising therapeutic strategy.
Ciliary Neurotrophic Factor Implant in Geographic Atrophy from Age-related Macular Degeneration: A Long-Term Case Study
Authors: Shiromani Sakshi , Leef Donna , Jain Nieraj , Yan Jiong 
Published: February 2025

Purpose:
To report a case of thirteen-year long progression of geographic atrophy (GA) from dry age-related macular degeneration (AMD) with ciliary neurotrophic factor (CNTF) implant, NT-501, in one eye, compared to the untreated contralateral eye.

Methods:
Using sequential images from 2012 to 2024, the macular GA and peripapillary atrophy was identified as areas of definitely decreased autofluorescence on fundus autofluorescence (FAF) and clearly delineated areas of hyperreflectivity on near infrared reflectance (NIR-R). Optical coherence tomography B scans confirmed areas of complete retinal pigment epithelium and outer retinal atrophy to support FAF grading.

Results:
A 76-year-old male received the CNTF implant in the right eye in August 2011. Macular GA area on short wavelength FAF exhibited growth from 4.51 mm2 (8/2012) to 14.46 mm2 (6/2020), in the treated right eye, and from 3.2 mm2 to 14.92 mm2 in the untreated left eye. The linearized growth rates were 0.21 mm/y (right) and 0.26 mm/y (left), showing a 16.3% difference. A similar pattern was seen on green laser FAF from 2018 to 2024, with peripapillary atrophy progression rates of 0.2 mm2/y (right) and 1.03 mm2/y (left).

Conclusions:
Notably, the implanted eye, exhibited less progression of macular GA and peripapillary atrophy. While acknowledging the limitations of a single case, we highlight the potential benefits of using the CNTF implant, a one-time surgical procedure, in reducing the treatment burden for atrophic AMD patients. We hope to see further reports from other sites that participated in this compassionate use protocol for NT-501 in atrophic AMD.
Choroidal Synphlebia in a Patient with Central Serous Chorioretinopathy
Authors: Naderi Amirreza , Spaide Richard 
Published: February 2025

Purpose:
To describe the choroidal vascular abnormality of conjoined choroidal vessels, synphlebia, in a patient with central serous chorioretinopathy (CSC).

Methods:
A patient initially referred for pigmentary retinal dystrophy later developed central serous retinopathy and underwent a comprehensive examination with multimodal imaging.

Results:
A 30-year-old man had an undiagnosed pigmentary retinopathy and nyctalopia was found to have a DHDDS mutation, confirming a retinitis pigmentosa diagnosis. A year later, he presented with bilateral central serous chorioretinopathy. During the venous phase of indocyanine green angiography individual vessels could not be differentiated in the posterior pole. Swept-source optical coherence tomography revealed an abnormally thick choroid with enormous vascular channels that did not appear to have separation into individual tubular structures. These abnormal vessels nearly occupied the entire thickness of the choroid in the macular region. There was little sign of any intermediate-sized choroidal vessels in the posterior pole. A review of other patients with DHDDS mutation showed no similar choroidal vascular changes.

Conclusion:
Large, conjoined veins, which we termed synphlebia, were seen in an eye with CSC. Loading of the choriocapillaris from these enlarged vascular channels may have contributed to hyperpermeability and formation of serous fluid. Observation of this choroidal vascular pattern suggests that a CSC phenotype may develop through more than one pathway.
Cellulosimicrobium spp. – A novel cause of endogenous endophthalmitis diagnosed on DNA sequencing
Authors: Shettigar Manoj P. , Sheba Esther , Joseph Joveeta , Dave Vivek Pravin 
Published: February 2025

Purpose:
To report two cases of Cellulosimicrobium. spp – A novel cause of endogenous endophthalmitis diagnosed on DNA sequencing

Methods:
Our non-comparative retrospective descriptive case series included two clinically diagnosed cases of endogenous endophthalmitis. We noted the clinical presentations, management outcomes, and microbiological workup. The patients underwent pars plana vitrectomy with intravitreal empirical antibiotics and microbiological investigation of the vitreous sample. The vitreous biopsy samples from both cases underwent routine microbiological evaluation, PCR, and DNA sequencing, which played a crucial role in the diagnosis.

Results:
Both cases were of young males aged 12 and 13 years, respectively, who presented with painful diminution in vision and redness. The mode of infection was deemed endogenous, given the spontaneous occurrence of endophthalmitis. Both patients underwent pars plana vitrectomy followed by intravitreal empirical antibiotics injection (Vancomycin and Ceftazidime). Vitreous biopsy demonstrated thick Gram-positive beaded bacilli. DNA sequencing revealed Cellulosimicrobium spp. The organism was found to be multi-drug resistant but was susceptible to Vancomycin. Post vitrectomy, a rhegmatogenous retinal detachment was noted. Both patients underwent silicone oil injections and, over the next month, showed complete resolution of endophthalmitis. Snellen's best-corrected visual acuity in Case 1 remained at counting fingers close to face due to a recurrent retinal detachment, while in Case 2, it improved to 20/50 from baseline.

Conclusion:

Cellulosimicrobium spp. can cause endogenous endophthalmitis, and the infection can be multi-drug-resistant. Organism identification may be elusive using routine smear culture techniques but can be confirmed by DNA sequencing.
Psychometric Properties and Measurement Invariance of the Patient Health Questionnaire 9 in an Italian Coronary Heart Disease Population
Authors: Di Matteo Roberta , Bolgeo Tatiana , Simonelli Niccolò , Dal Molin Alberto , Bassola Barbara , Lusignani Maura , Maconi Antonio , Rasero Laura , Vellone Ercole , Iovino Paolo 
Published: February 2025

Background
Depression is common in patients with coronary heart disease (CHD). The 9-item patient health questionnaire (PHQ-9) is an instrument for screening depression. However, evidence on the psychometric properties of the PHQ-9 in Italian populations with CHD is still lacking.

Objective
The objective of this study was to examine the psychometric properties and measurement invariance of the PHQ-9 in a large CHD sample.

Methods
This is a secondary analysis of 3-month follow-up data collected from a multicenter longitudinal study. Patients completed a battery of self-reported instruments that included the PHQ-9 and the generalized anxiety disorder scale-7 (GAD-7). Factorial validity was assessed with confirmatory factor analysis. Convergent validity was tested by inspecting the correlations between the PHQ-9 and GAD-7 scores, and other sociodemographic factors. Internal consistency was investigated with the model-based internal consistency reliability index. Measurement invariance was tested across sex and age (≥65 vs <65 years) with confirmatory multigroup factor analysis.

Results
We enrolled 427 patients (mean age, 64.41 years; 78.9% male; 66.7% married). The confirmatory factor analysis supported a bi-dimensional factor structure with the factors measuring somatic and cognitive symptoms. Convergent validity testing showed significant positive correlations of the PHQ-9 scores with the GAD-7 scores, gender, and perceived financial status. The model-based internal consistency reliability index was adequate at 0.80. Measurement invariance across age was confirmed at the scalar level, whereas invariance across sex was achieved at the metric level.

Conclusion
The PHQ-9 shows adequate psychometric and invariance properties across age groups in patients with CHD. Hence, this instrument can be used in clinical practice and research to assess the severity of depression in patients with CHD and to compare depression scores between younger and older individuals.
Expression of human immunodeficiency virus envelope protein in the human central nervous system
Authors: Agbey Christy , Walton Sofia , Campbell Lee Antony , Nath Avindra , Smith Bryan , Snow Joseph , Wiebold Amanda , Hou Chunyan , Ma Junfeng , Mocchetti Italo ,   the NIH-Neuro-HIV Research Consortium
Published: February 2025

Objective/Design:
The human immunodeficiency virus (HIV) envelope glycoprotein gp120 contributes to neuronal damage that could lead to human immunodeficiency virus-mediated neurocognitive disorder. However, it is debated whether gp120 could promote direct neurotoxicity to synapses because it may not be present in the central nervous system of people living with human immunodeficiency virus (PLWH) on antiretroviral therapy (ART). This study sought to establish whether gp120 is expressed in the human central nervous system in the pre- and post- ART era.

Methods:
We utilized real-time polymerase chain reaction (PCR) to detect the envelope mRNA in postmortem caudate nucleus from pre-ART era. HIV negative samples were used as controls. We then used RNAscope fluorescence multiplex to identify which cells express the envelope mRNA. To determine whether gp120 is present despite ART, we analyzed cerebrospinal fluid (CSF) samples from PLWH on ART using mass spectrometry.

Results:
Using PCR, we detected the envelope mRNA in the caudate nucleus from PLWH with neurocognitive impairment but not in control samples. With RNAscope, we detected the envelope mRNA in microglia and astrocytes in the frontal cortex and caudate nucleus from HIV-positive tissue. With mass spectrometry, we identified a gp120 peptide in the CSF of PLWH on antiretroviral therapy (n = 20) but not in control subjects (n = 7).

Conclusion:
Our data suggest that despite antiretroviral therapy, gp120 is expressed and likely released by infected cells, suggesting that gp120 could be one of the key factors in the neuropathology observed in people living with human immunodeficiency virus.
Comparative Analysis of Dynamic Esthetic Characteristics in Spontaneous Smiles Among Hani and Han Youths in Yunnan Province, China
Authors: Liang Hongrun , Lin Yunhong , Ren Xiaoxue , Fu Wanni , Li Xingxing 
Published: February 2025

Objective:
The aim of this study is to examine the dynamic esthetic characteristics of spontaneous smiles in Hani and Han youths in Yunnan Province.

Methods:
Employing a multistage stratified cluster random sampling approach, participants from the Hani and Han ethnic groups in Yunnan Province were recruited. Digital videography was used to capture facial characteristics at both rest and during spontaneous smiles. Subsequently, selected images were analyzed for dynamic esthetic parameters concerning the lips, teeth, and gingiva using image measurement software.

Results:
The study included youths from the Hani (n = 68) and Han (n = 59) ethnic groups in Yunnan Province. During spontaneous smiles, the exposure of maxillary central incisors was more pronounced compared with maxillary lateral incisors and canines in both ethnic groups. Variations in gingival display of central incisors were observed among males in the 2 ethnic groups (P < 0.05). The mobility of the mouth corner’s width was significantly greater in Han males compared with Hani males (P < 0.05). Conversely, the width of the mouth corner during spontaneous smiles was greater in Hani females than in Han females (P < 0.05). Regarding the relationship between the gingival line and the upper lip, the unexposed type was predominant among males of both ethnicities, whereas the parallel type was predominant among females. Parallel and straight smile arcs were commonly observed among participants from both ethnicities.

Conclusion:
The dynamic esthetic characteristics of the lips, teeth, and gingiva exhibit similarities between the youth of Hani and Han ethnicities in Yunnan Province. However, notable differences in certain dynamic smile esthetic traits exist between the sexes.
How Autism Impacts Children’s Working Memory for Faces
Authors: Esfahan Shahrzad M. , Sepahi Narges , Rezayat Ehsan 
Published: February 2025

AbstractThis study investigates how visual working memory (WM) functions in children with Autism Spectrum Disorder (ASD) compared to typically developing (TD) children aged 7 to 12, focusing on their ability to remember faces. The primary goal was to understand the differences in visual WM performance between these two groups and identify the sources of memory recall errors. Findings indicate that children with ASD demonstrated significantly poorer visual WM compared to their TD counterparts, particularly in the precision of memory recall. Despite this difference, both groups exhibited similar rates of random guessing, suggesting that the challenges faced by children with ASD are more about accuracy than guessing strategy. This research sheds light on the specific deficits in visual WM associated with ASD, enhancing our understanding of the cognitive mechanisms at play and highlighting potential areas for targeted interventions to support these children.
ZSeeker: An optimized algorithm for Z-DNA detection in genomic sequences
Authors: Wang Guliang , Mouratidis Ioannis , Provatas Kimonas , Chantzi Nikol , Patsakis Michail , Georgakopoulos-Soares Ilias , Vasquez Karen 
Published: February 2025

AbstractZ-DNA is an alternative left-handed helical form of DNA with a zigzag-shaped backbone that differs from the right-handed canonical B-DNA helix. Z-DNA has been implicated in various biological processes, including transcription, replication, and DNA repair, and can induce genetic instability. Repetitive sequences of alternating purines and pyrimidines have the potential to adopt Z-DNA structures. ZSeeker is a novel computational tool developed for the accurate detection of potential Z-DNA-forming sequences in genomes, addressing limitations of prior methods. By introducing a novel methodology informed and validated by experimental data, ZSeeker enables the refined detection of potential Z-DNA-forming sequences. Built both as a standalone Python package and as an accessible web interface, ZSeeker allows users to input genomic sequences, adjust detection parameters, and view potential Z-DNA sequence distributions and Z-scores via downloadable visualizations. Our Web Platform provides a no-code solution for Z-DNA identification, with a focus on accessibility, user-friendliness, speed and customizability. By providing efficient, high-throughput analysis and enhanced detection accuracy, ZSeeker has the potential to support significant advancements in understanding the roles of Z-DNA in normal cellular functions, genetic instability, and its implications in human diseases.AvailabilityZSeeker is released as a Python package under the GPL license as a multi-platform application and is available at:https://github.com/Georgakopoulos-Soares-lab/ZSeeker. A web-interface of ZSeeker is publicly available athttps://zseeker.netlify.app/.
Glycosylphosphatidylinositol biosynthesis restricts coronavirus infection via the regulation of LY6E
Authors: Ma Yanlong , Feng Fei , Feng Hui , Ma Xue , Wang Ziqiao , Han Yutong , Zhu Yunkai , Wang Yuyan , Gao Zhichao , Zhang Yuyuan , Zhao Jincun , Zhang Rong 
Published: February 2025

ABSTRACTCoronaviruses, including SARS-CoV-2, rely on host factors for their replication and pathogenesis, while hosts deploy defense mechanisms to counteract viral infections. Although numerous host proviral factors have been identified, the landscape of host restriction factors and their underlying mechanisms remain less explored. Here, we conducted genome-wide CRISPR knockout screens using three distinct coronaviruses—SARS-CoV-2, HCoV-OC43 (a common cold human virus from the genusBetacoronavirus) and porcine epidemic diarrhea virus (Alphacoronavirus) to identify conserved host restriction factors. We identified glycosylphosphatidylinositol (GPI) biosynthesis as the pan-coronavirus host factor that restrict viral entry by disrupting spike protein-mediated membrane fusion at both endosomal and plasma membranes. GPI biosynthesis generates GPI moieties that covalently anchor proteins (GPI-anchored proteins [GPI-APs]) to the cell membrane, playing essential roles in various cellular processes. Through focused CRISPR knockout screens targeting 193 GPI-APs, we identified LY6E as the key downstream effector mediating the antiviral activity of the GPI biosynthesis pathway. These findings reveal a novel role for GPI biosynthesis as a conserved host defense mechanism against coronaviruses and highlight LY6E as a critical antiviral effector. This study provides new insights into virus-host interactions and the development of host-directed antiviral therapies.
Functional connectivity of thalamic nuclei during sensorimotor task-based fMRI at 9.4 Tesla
Authors: Charyasz Edyta , Erb Michael , Bause Jonas , Heule Rahel , Bender Benjamin , Kumar Vinod Jungir , Grodd Wolfgang , Scheffler Klaus 
Published: February 2025

ABSTRACTThe thalamus is the brain’s central communication hub, playing a key role in processing and relaying sensorimotor and cognitive information between the cerebral cortex and other brain regions. It consists of specific and non-specific nuclei, each with a different role. Specific thalamic nuclei relay sensory and motor information to specific cortical and subcortical regions to ensure precise communication. In contrast, non-specific thalamic nuclei are involved in general functions such as attention or consciousness through broader and less targeted connections. In the present study, we aimed to investigate the functional connectivity patterns of the thalamic nuclei identified in our previous study as being involved in motor (finger-tapping) and sensory (finger-touch) tasks. The results of this study show that thalamic nuclei are not static hubs with a predefined role in neural signal processing, as they show different task-specific functional connectivity patterns in the anterior, middle, lateral, and posterior thalamic nuclei. Instead, they are all functional hubs that can flexibly change their connections to other brain regions in response to task demands. This work has important implications for understanding task-dependent functional connectivity between thalamic nuclei and different brain regions using task-based fMRI at 9.4 Tesla.
ANTIBACTERIAL ACTIVITY OF LEAVES AND STEM OFBryohyllum Pinnatum(MIRACLE LEAF) IN SOKOTO STATE, NIGERIA
Authors: Dantani Maryam , Rabe Amina Musa , Dantani Abdulmalik 
Published: February 2025

AbstractThis study aimed to evaluate the antibacterial activity ofBryophyllum pinnatumleaves and stems against selected bacterial isolates from Sokoto State, Nigeria. Aqueous and ethanol solvents were used to extract bioactive compounds, and the extracts were tested at concentrations of 200, 140, and 60 mg/ml againstStaphylococcus aureus, Pseudomonas aeruginosa, andMicrococcus spp. The results revealed no inhibitory effects from theBryophyllum pinnatumextracts on the tested bacterial strains, irrespective of solvent type or concentration. In contrast, the standard antibiotic Tetracycline exhibited significant antibacterial activity, with inhibition zones of 20 mm, 16 mm, and 9 mm forStaphylococcus aureus, Micrococcus spp., andPseudomonas aeruginosa, respectively.These findings suggest thatBryophyllum pinnatumextracts, under the tested conditions, lack antibacterial activity against the evaluated bacterial isolates. However, this does not exclude the plant’s potential for other therapeutic applications. Future studies should investigate alternative extraction methods, diverse solvent systems, and a broader range of bacterial strains to comprehensively evaluate the bioactivity ofBryophyllum pinnatum.