bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine-learning–based plasma metabolomic profiles for predicting long-term complications of cirrhosis
Authors: Guo Chengnan , Liu Zhenqiu , Fan Hong , Wang Haili , Zhang Xin , Zhao Shuzhen , Li Yi , Han Xinyu , Wang Tianye , Chen Xingdong , Zhang Tiejun 
Published: April 2024

Background and Aims:
The complications of liver cirrhosis occur after long asymptomatic stages of progressive fibrosis and are generally diagnosed late. We aimed to develop a plasma metabolomic–based score tool to predict these events.

Approach and Results:
We enrolled 64,005 UK biobank participants with metabolomic profiles. Participants were randomly divided into the training (n=43,734) and validation cohorts (n=20,271). Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with HCC. An interpretable machine-learning framework was applied to learn the metabolomic states extracted from 168 circulating metabolites in the training cohort. An integrated nomogram was developed and compared to conventional and genetic risk scores. We created 3 groups: low-risk, middle-risk, and high-risk through selected cutoffs of the nomogram. The predictive performance was validated through the area under a time-dependent receiver operating characteristic curve (time-dependent AUC), calibration curves, and decision curve analysis. The metabolomic state model could accurately predict the 10-year risk of liver cirrhosis complications in the training cohort (time-dependent AUC: 0.84 [95% CI: 0.82–0.86]), and outperform the fibrosis-4 index (time-dependent AUC difference: 0.06 [0.03–0.10]) and polygenic risk score (0.25 [0.21–0.29]). The nomogram, integrating metabolomic state, aspartate aminotransferase, platelet count, waist/hip ratio, and smoking status showed a time-dependent AUC of 0.930 at 3 years, 0.889 at 5 years, and 0.861 at 10 years in the validation cohort, respectively. The HR in the high-risk group was 43.58 (95% CI: 27.08–70.12) compared with the low-risk group.

Conclusions:
We developed a metabolomic state–integrated nomogram, which enables risk stratification and personalized administration of liver-related events.
SUPERFICIAL AND DEEP VASCULAR COMPLEXES DAMAGED TO DIFFERENT EXTENTS IN ADVANCED STAGES OF DIABETIC RETINOPATHY
Authors: Lee Min-Woo , Jun Ji-Ho , Yu Hwa-Young , Kim Jung-Tae , Song Yong-Yeon 
Published: April 2024

Purpose:
To identify the extent of damage to the superficial vascular complex and deep vascular complex as the stage of diabetic retinopathy (DR) increases.

Methods:
Subjects were divided into four groups: patients with type 2 diabetes without DR (Group 1), those with mild-to-moderate nonproliferative DR (Group 2), those with severe-to-very severe nonproliferative DR (Group 3), and those with proliferative DR (Group 4). The vessel densities of the superficial vascular complex (superficial vessel density, SVD) and deep vascular complex (deep vessel density, DVD) and their ratios were compared. Linear regression analyses were used to identify factors associated with the SVD/DVD ratio.

Results:
The SVDs were 25.5% ± 6.1%, 25.1% ± 7.0%, 24.5% ± 9.0%, and 21.6% ± 6.9% (P = 0.048); the DVDs 25.6% ± 5.3%, 23.0% ± 7.0%, 22.3% ± 8.8%, and 17.5% ± 5.0% (P < 0.001); and the SVD/DVD ratios 1.00 ± 0.16, 1.12 ± 0.20, 1.14 ± 0.33, and 1.24 ± 0.27 (P < 0.001) in Groups 1 to 4, respectively. In multivariate analysis, DR severity (B = 7.16, P < 0.001) and the HbA1c level (B = 1.57, P = 0.042) were significantly associated with the SVD/DVD ratio.

Conclusion:
Both the SVD and DVD tended to decrease in the advanced stages of DR, and the SVD/DVD ratio increased, indicating more severe damage to the deep vascular complex than the superficial vascular complex. The ratio was positively associated with the HbA1c level, indicating a significant relationship between that level and DVD rather than SVD damage.
AMALRIC TRIANGULAR SIGN AND CAROTID DOPPLER ULTRASONOGRAPHIC FINDINGS IN CENTRAL RETINAL ARTERY OCCLUSION
Authors: Okubo Maki , Mano Fukutaro , Hashimoto Ryuya , Maeno Takatoshi , Kuniyoshi Kazuki , Kusaka Shunji 
Published: April 2024

Purpose:
The aim of this study was to determine the incidence of the Amalric triangular sign (ATS) in patients with central retinal artery occlusion and investigate its association with visual function and carotid Doppler ultrasonography findings.

Methods:
A retrospective chart review was conducted on 21 eyes from 21 patients with complete central retinal artery occlusion. Best-corrected visual acuity and carotid Doppler ultrasonography findings [peak systolic velocity, end-diastolic velocity, and resistance index (RI) = (PSV − EDV)/PSV] were investigated.

Results:
Three patients (14%) exhibited the ATS. Best-corrected visual acuity at first visit was significantly worse in ATS-positive patients than in ATS-negative patients (P = 0.024). Doppler waveform analysis of the common carotid artery showed that ATS-positive patients had a significantly lower end-diastolic velocity [P = 0.009, median 10 (range 9–10) vs. 17 (13–24) m/second] and significantly higher resistance index [P = 0.021, median 0.80 (range 0.79–0.83) vs. 0.72 (0.66–0.82)] than did ATS-negative.

Conclusion:
The Amalric triangular sign was observed in three patients with central retinal artery occlusion, who showed worse best-corrected visual acuity at the first visit than did those without the ATS. Carotid Doppler ultrasonography revealed that ATS-positive patients had a significantly higher resistance index and lower end-diastolic velocity at the common carotid artery than did ATS-negative, indicating steno-occlusive changes in the internal carotid artery.
Hyalinizing clear cell carcinoma of the left main bronchus diagnosed with Ewing sarcoma breakpoint region 1::activating transcription factor 1 fusion: A case report
Authors: Kawachi Riken , Obikane Hiyo , Satoh Daisuke , Shimamura Mie , Nagao Toshitaka , Masuda Shinobu , Sakurai Hiroyuki 
Published: April 2024

Rationale:
Hyalinizing clear cell carcinoma (HCCC) of the bronchus is extremely rare. In addition, its rarity makes an accurate histological diagnosis difficult. Herein, we report a case of HCCC in the left main bronchus diagnosed by the detection of Ewing sarcoma breakpoint region 1::activating transcription factor 1 (EWSR1::ATF1) fusion transcript using reverse transcription-polymerase chain reaction (RT-PCR).

Patient concerns:
A 56-year-old woman presented with a tumor obstructing the left main bronchus on physical examination computed tomography. A bronchoscopic biopsy confirmed a malignant tumor but did not provide a definitive diagnosis.

Interventions:
Sleeve resection of the left main bronchus was performed. The intraoperative frozen section was negative for cancer in both the proximal and distal bronchial stumps.

Diagnosis:
General immunohistochemical staining was performed, and mucoepidermoid carcinoma and HCCC were suspected. RT-PCR revealed positive results for EWSR1::ATF1 fusion transcript, and the tumor was finally diagnosed as HCCC.

Outcomes:
The patient was discharged without any postoperative complications. Sixty-five months have passed since surgery, and no cancer recurrence has been observed.

Lessons:
Although hematoxylin and eosin staining and immunostaining alone were not sufficient to distinguish HCCC from mucoepidermoid carcinoma and other malignant tumors, adding genetic testing for EWSR1 rearrangement led to a definitive pathological diagnosis.
Discovering Provider Awareness of Mobility Assistive Technologies and Clinical Guidelines—A Comparative Analysis With Consumer Responses
Authors: Lee Chang Dae , Peterson Sara , Joseph James , McKernan Gina , Cooper Rosemarie , Koontz Alicia M. , Dicianno Brad E. , Cooper Rory A. 
Published: April 2024

Objective
This study aims to enhance the accessibility and quality of mobility-assistive technology by investigating and bridging knowledge gaps between mobility-assistive technology providers and consumers with ambulatory limitations.

Design
A survey was conducted among mobility-assistive technology providers in the United States, consisting of sections on awareness, knowledge importance and desire, and knowledge sources. The responses were compared to data collected from consumers in a previous study.

Results
A total of 144 mobility-assistive technology providers participated, with 60% having received academic or professional training in relevant fields. Analysis revealed significant knowledge gaps between providers and consumers, particularly in assistive technology assessment tools and knowledge sources. Moderate gaps were also observed in areas such as clinical practice guidelines, desired mobility-assistive technology information, and knowledge sources. However, the gaps in other areas were relatively small.

Conclusions
This study highlights the knowledge gaps between mobility-assistive technology providers and consumers, hindering the optimal utilization and fulfillment of user needs. Providers possess valuable information that consumers may lack, positioning them as primary knowledge sources. Addressing these gaps through targeted interventions, improved communication channels, and enhanced education can enhance the utilization of mobility-assistive technology and improve outcomes for individuals with ambulatory limitations.
Effect of Extracorporeal Shock Wave on Upper Trapezius Trigger Points in Patients With Cervicogenic Headache
Authors: Hammam Radwa F. , Alshimy Ahmed M. , Elabd Omar M. , Elabd Aliaa M. 
Published: April 2024

Objective
A recent study was designed to ascertain the impact of extracorporeal shock wave therapy on upper trapezius trigger points in cervicogenic headaches patients.

Design
A double-blinded randomized controlled trial study, in which 50 participants (11 male and 39 female) aged between 20–40 with cervicogenic headache were subdivided with randomization to group (A), which received traditional physical therapy and sham shock wave therapy, and group (B), which received traditional physical therapy and actual shock wave therapy. All assessments were performed by a therapist before and after the treatment program (4 wks).

Results
There was a significant difference of headache disability index, visual analog scale scores, and upper trapezius electromyographic characteristics with P value <0.05 in both groups, in favor of the shock wave group.

Conclusions
Extracorporeal shock wave therapy could be used for clinical and research concerns because its positive effects on pain suppression, reduction of headache intensity, and restoration of muscle regular activity in cervicogenic headache patients.
Relationship of Body Mass Index on Patient-Reported Outcomes After Platelet-Rich Plasma Versus Microfragmented Adipose Tissue for Knee Osteoarthritis
Authors: Baria Michael , George Reshma , Barker Tyler , Flanigan David , Kaeding Christopher , Magnussen Robert A. 
Published: April 2024

Abstract

Objective
Body mass index is known to contribute to outcomes for patients with knee osteoarthritis. Furthermore, body mass index influences the protein expression of orthobiologic treatments like platelet-rich plasma and microfragmented adipose tissue. We performed a secondary analysis of the association of body mass index with patient-reported outcomes for patients with knee osteoarthritis who received either platelet-rich plasma or microfragmented adipose tissue injections.

Methods
Seventy-one patients with knee osteoarthritis were randomized to receive a single ultrasound-guided injection of platelet-rich plasma or microfragmented adipose tissue. Platelet-rich plasma was created from 180 cc of anticoagulated blood and processed using a double-spin, buffy-coat concentration system. Microfragmented adipose tissue was created using autologous lipoaspirate that was processed according to minimal manipulation guidelines. Patient-reported outcomes and osteoarthritis outcome scores (Knee Osteoarthritis and injury Outcome Score) were tracked for 12 mos.

Results
Forty-nine patients (platelet-rich plasma = 23, microfragmented adipose tissue = 26) completed 12-mo follow-up. Knee Osteoarthritis and injury Outcome Score quality of life and activity of daily living subscores were inversely correlated (both P < 0.05) with body mass index in the microfragmented adipose tissue but not platelet-rich plasmagroup. Knee Osteoarthritis and injury Outcome Score pain and sport subscores showed a trend toward inverse correlation with body mass index in the microfragmented adipose tissue group (P = 0.07 and P = 0.06, respectively), but not platelet-rich plasma.

Conclusions
Body mass index was negatively associated with patient-reported outcomes in patients who received microfragmented adipose tissue injections for knee osteoarthritis, but not for patients receiving platelet-rich plasma.
Missed Opportunities – Characteristics of People who Received a Concurrent HIV/AIDS Diagnosis in New York State from 2016 – 2021
Authors: Rosenthal Mark , Patterson Wendy , Rajulu Deepa T. 
Published: April 2024

Background:
Late HIV diagnosis is associated with a wide range of negative outcomes. This study aims to identify characteristics of individuals who received a concurrent diagnosis (CDX) in New York State (NYS) so that more effective interventions can be developed to encourage earlier testing among these populations.

Methods:
The NYS HIV registry was used to identify people who received a CDX from 2016 – 2021. A CDX was a diagnosis that met the criteria for a stage 3 HIV infection within 30 days of the initial HIV diagnosis. Sex at birth, race/ethnicity, transmission risk group, age at diagnosis, region of residence at diagnosis, urbanicity of zip code of diagnosis, and type of diagnosing facility were used as covariates. Bivariate and multivariate risk ratios were calculated to quantify associations between CDX and covariates.

Results:
There were 14,866 people newly diagnosed with HIV in NYS from 2016 – 2021, of which 19.0% had a CDX. Those with female sex at birth, IDU, or MSM/IDU risk were less likely to have a CDX. Increased age, Asian race/ethnicity, residence outside of New York City, and diagnosis at inpatient facilities or emergency rooms were associated with an increased likelihood of a CDX.

Conclusion:
Populations with the highest proportions of CDX were ones that made up a small percentage of all new HIV diagnoses and may not be benefiting as much from current HIV prevention efforts. There are complex interactions between many factors including geographic and social characteristics which may lead to delayed diagnostic testing.
Solitary Pulmonary Perivascular Epithelial Cell Tumor Mimicking Pulmonary Metastasis on 68Ga-DOTATATE PET/CT in a Patient With Pancreatic Neuroendocrine Tumor
Authors: Liang Shuang , Chen Xiaoliang 
Published: April 2024

Abstract
We report the findings of 68Ga-DOTATATE PET/CT in a 56-year-old woman with solitary pulmonary perivascular epithelioid cell tumor. 68Ga-DOTATATE PET/CT showed a lesion with intense uptake in the region of pancreatic head and a solitary nodule with moderate uptake in the left lung. Pancreatic neuroendocrine tumor with pulmonary metastasis was considered. The postoperative pathological results showed a benign perivascular epithelioid cell tumor of the lung. This case emphasizes the need to increase awareness of benign perivascular epithelioid cell tumors in the differential diagnosis of solitary pulmonary nodule with moderate DOTATATE activity.
BRAIN-MAGNET: A novel functional genomics atlas coupled with convolutional neural networks facilitates clinical interpretation of disease relevant variants in non-coding regulatory elements
Authors: Deng Ruizhi , Perenthaler Elena , Nikoncuk Anita , Yousefi Soheil , Lanko Kristina , Schot Rachel , Maresca Michela , Medico-Salsench Eva , Sanderson Leslie E. , Parker Michael J. , van Ijcken Wilfred F.J. , Park Joohyun , Sturm Marc , Haack Tobias B. ,   Genomics England Research Consortium, Roshchupkin Gennady V , Mulugeta Eskeatnaf , Barakat Tahsin Stefan 
Published: April 2024

AbstractGenome-wide assessment of genetic variation is becoming routine in human genetics, but functional interpretation of non-coding variants both in common and rare diseases remains extremely challenging. Here, we employed the massively parallel reporter assay ChIP- STARR-seq to functionally annotate the activity of >145 thousand non-coding regulatory elements (NCREs) in human neural stem cells, modelling early brain development. Highly active NCREs show increased sequence constraint and harbourde novovariants in individuals affected by neurodevelopmental disorders. They are enriched for transcription factor (TF) motifs including YY1 and p53 family members and for primate-specific transposable elements, providing insights on gene regulatory mechanisms in NSCs. Examining episomal NCRE activity of the same sequences in human embryonic stem cells identified cell type differential activity and primed NCREs, accompanied by a rewiring of the epigenome landscape. Leveraging the experimentally measured NCRE activity and nucleotide composition of the assessed sequences, we built BRAIN-MAGNET, a functionally validated convolutional neural network that predicts NCRE activity based on DNA sequence composition and identifies functionally relevant nucleotides required for NCRE function. The application of BRAIN-MAGNET allows fine-mapping of GWAS loci identified for common neurological traits and prioritizing of possible disease-causing rare non-coding variants in currently genetically unexplained individuals with neurogenetic disorders, including those from the Genomics England 100,000 Genomes project, identifying novel enhanceropathies. We foresee that this NCRE atlas and BRAIN-MAGNET will help reduce missing heritability in human genetics by limiting the search space for functionally relevant non-coding genetic variation.
Insights into Professional Preferences and Rationale for Surgical Sequencing in Managing Hip-Spine Syndrome
Authors: Breuning Carolina , Tian Xinggui , Goronzy Jens , Günther Klaus-Peter , Platz Uwe , Beyer Franziska , Disch Alexander Carl , Lachiewicz Paul F. , Liu Ning , Goodman Stuart B. , Wood Kirkham B. , Zwingenberger Stefan 
Published: April 2024

AbstractBackgroundThe optimal sequence of hip and spine surgeries for hip-spine syndrome management remains a contentious issue. This study aimed to investigate the preferences and rationale behind the sequence of surgical treatments across various hip-spine syndrome scenarios among potential specialist interviewees.MethodsA questionnaire survey, featuring five fictional clinical presentations encompassing symptomatic hip osteoarthritis and diverse spinal pathologies, was conducted among German hip and spine surgeons, alongside conducting a cross-national comparison with previous US survey.ResultsGerman hip and spine surgeons preferred spine-first surgery in hip-spine syndrome scenarios involving neurological deficits, while preferred hip-first in scenarios without such deficits. In contrast, US surgeons demonstrated differing sequencing patterns, highlighting differences between nations. Notably, distinct surgical order preferences were observed among different specialists. Surgeons’ decision-making was primarily influenced by symptom severity and urgency, spine-pelvis-hip biomechanics, and treatment efficacy.ConclusionThe sequence of hip and spine surgery in various hip-spine syndrome scenarios has different preference patterns, with professional preferences and cross-nation differences, and is guided by the multifaceted considerations involved in surgical decision-making.
Characterising the Modulatory Role of Ikebana in Flower-Dependent Cell Competition
Authors: Marques-Reis Mariana , Gutiérrez-García Andrés , Flores Clara Carlos , Argudo Irene , Stefan Eggel Matthias , Hauert Barbara , Brás-Pereira Catarina , Moreno Eduardo 
Published: April 2024

AbstractTissues encompass a quality control mechanism that promotes their optimal state. This mechanism, designated cell competition, is characterised by the elimination of suboptimal yet viable cells when they are near healthier cells within the same tissue compartment.This study explores Flower-dependent cell competition and introduces Ikebana as a novel player. The differential expression of theflowerisoforms labels cells as winners or losers, influencing their fate in diverse contexts, including eye development, traumatic brain injury, and Alzheimer’s disease. Ikebana, ubiquitously produced in wing imaginal discs and adult brains, modulates loser cell elimination. Reduction ofikebanaexpression correlates with an increased number of loser cells, while its overexpression in the Alzheimer’s disease model reduces the number of Flower LoseB-positive cells.We suggest that Ikebana protects loser cell elimination, particularly when excessive elimination of loser cells can compromise tissue function. Thus, Ikebana might be a potential therapeutic target for modulating Flower LoseB expression.
A negatively-charged region within carboxy-terminal domain maintains proper CTCF DNA binding
Authors: Liu Lian , Tang Yuanxiao , Zhang Yan , Wu Qiang 
Published: April 2024

SUMMARYAs an essential regulator of higher-order chromatin structures, CTCF is a highly-conserved DNA binding protein with a central DNA-binding domain of 11 tandem zinc fingers, which are flanked by amino (N-) and carboxy (C-) terminal domains of intrinsically disordered regions. Here we report that CRISPR deletion of the entire C-terminal domain of alternating charge blocks decreases CTCF DNA binding but deletion of the C-terminal fragment of 116 amino acids results in increased CTCF DNA binding and aberrant gene regulation. Through a series of genetic targeting experiments, in conjunction with EMSA, 4C, qPCR, ChIP-seq, and ATAC-seq, we uncovered a negatively-charged region (NCR) responsible for weakening CTCF DNA binding and chromatin accessibility. AlphaFold prediction suggests an autoinhibitory mechanism of CTCF via NCR as a flexible DNA mimic domain, possibly competing with DNA binding for the positively-charged ZF surface area. Thus, the unstructured C-terminal domain plays an intricate role in maintaining proper CTCF-DNA interactions and 3D genome organization.