bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Review of the Protective Effects of Alkaloids against Alpha-synuclein Toxicity in Parkinson's Disease
Authors: Khodadadi Mahdi , Javadi Behjat 
Published: June 2024

Background:
Alpha-synuclein (α-syn) aggregation products may cause neural injury and
several neurodegenerative disorders (NDs) known as α-synucleinopathies. Alkaloids are secondary
metabolites present in a variety of plant species and may positively affect human health, particularly
α-synucleinopathy-associated NDs.

Aim:
To summarize the latest scientific data on the inhibitory properties of alkaloids in α-
synucleinopathies, especially in Parkinson’s disease.

Methods:
Literature search was performed using web-based databases including Web of Science,
PubMed, and Scopus up to January 2024, in the English language.

Results:
Harmala alkaloids, caffein, lycorine, piperin, acetylcorynoline, berberin, papaverine, squalamine,
trodusquemine and nicotin have been found to be the most active natural alkaloids against
synucleinopathy. The underlying mechanisms that contribute to this effect would be the inhibition
of α-syn aggregation; elimination of formed aggregates; improvement in autophagy activation; promotion
of the activity and expression of antioxidative enzymes; and prevention of oxidative injury
and apoptosis in dopaminergic neurons.

Conclusion:
The findings of the present study highlight the inhibitory activities of alkaloids against
synucleinopathy. However, no clinical data supports the reported activities in humans, which calls
attention to the need for conducting clinical trials to elucidate the efficacy, safety, proper dosage,
unwanted effects and pharmacokinetics aspects of alkaloids in humans.
Bosentan and Pulmonary Hypertension Caused by COVID-19: A Pilot Randomized Double-blind Clinical Study
Authors: Shokrollahi Fahime , Pazoki Ali , Allami Abbas , Aliakbari Shahin , Ardali Kimia Rahimi 
Published: June 2024

Introduction/Objective:
Coronavirus disease 2019 (COVID-19) has been the biggest
pandemic in history, with severe complications, such as acute respiratory distress syndrome and
pulmonary hypertension (PH). An endothelin-1 (ET-1) receptor antagonist, such as bosentan, may
be beneficial in treating elevated ET-1 levels. Hence, our study aimed to evaluate the therapeutic
effects of bosentan in patients with COVID-19-induced PH.

Methods:
A single-centre, randomized, double-blind study involving 72 participants was carried
out; 36 received bosentan and the other 36 received a placebo. Pulmonary arterial pressure, tricuspid
valve pressure gradient, and right atrial pressure were measured using echocardiography. The
Cox proportional hazards regression model was used to investigate the impact of bosentan and patients'
age on mortality during a 6-month follow-up period.

Results:
In-hospital mortality was significantly lower in the case group (13%) compared with the
control group (33.3%) (P=0.003). Additionally, bosentan improved echocardiographic parameters,
such as systolic pulmonary artery pressure and tricuspid regurgitation gradient (P=0.011 and
P=0.003, respectively). Bosentan use was a significant predictor of long-term mortality rates for
600 days [age-adjusted hazard ratio of 5.24 (95% CI 1.34 to 20.46)].

Conclusion:
This study provided a mixed perspective on the use of bosentan therapy in patients
with COVID-19-related PH. Bosentan effectively reduced in-hospital mortality and improved
echocardiographic measures. However, the treatment group showed an increased requirement for
supplemental oxygen therapy and long-term mortality. Further studies with larger sample sizes are
necessary to elucidate the effects of bosentan in PH following COVID-19.
Prevalence and Causes of Vitamin D Deficiency in a Cohort of Greek HIV-Infected Individuals: A Prospective, Single Center, Observational Study
Authors: Androutsakos Theodoros , Politou Marianna , Boti Sofia , Pittaras Theodoros , Kontos Athanasios , Kordossis Theodore , Pouliakis Abraham , Panayiotakopoulos George 
Published: June 2024

Background:
Vitamin D deficiency and/or insufficiency (hypovitaminosis D) has been
associated with several disorders including autoimmune diseases, like type 1 diabetes mellitus;
cardiovascular diseases; neoplasms; obesity; insulin resistance, and type 2 diabetes mellitus. This
problem is common in southern European countries, especially in elderly and institutionalized persons.
In HIV-infected individuals, hypovitaminosis D has been correlated with various complications
like tuberculosis, hyperparathyroidism, bone mass loss, premature atherosclerosis, and systemic
arterial hypertension, deterioration of immune function, progression of the disease and overall
mortality.

Objective:
The objective of this study was to examine the prevalence and causes of hypovitaminosis
D in a cohort of Greek HIV-infected patients, the factors, and possible complications associated
with it.

Methods:
All patients attending our HIV unit for a period of 5 months were included in this study.
Vitamin D status, medical anamnes, and laboratory tests were obtained at baseline; patients were
followed for 3 years and HIV-related complications were noted. No patient received vitamin D
supplementation during the follow-up period.

Results:
Hypovitaminosis D was common, with 83.7% of the patients showing levels below
30ng/dl and 55.4% below 20ng/dl. After multivariable analysis, age and duration of treatment
were the only significant factors for low vitamin D levels. During follow-up, 26 patients exhibited
a total of 34 HIV-related complications, the most common being pneumonocystis jiroveci pneumonia
(PCP). Hypovitaminosis D showed a positive correlation with overall complications, PCP
as well as wasting syndrome.

Conclusion:
Overall, our study shows that hypovitaminosis D is common in HIV-infected individuals
and should probably be treated as soon as possible to protect these patients from serious HIVrelated
complications like PCP or wasting syndrome.
Accurate Recognition of Vascular Lumen Region from 2D Ultrasound Cine Loops for Bubble Detection
Authors: Wang Ziyi , Yang Zhuochang , Chen Ziye , Huang Xiaoyu , Xu Lifan , Zhou Chang , Zhou Yingjie , Zhu Baoliang , Zhang Kun , Gong Deren , Xu Weigang , Chen Jiangang 
Published: June 2024

Background:
Accurate identification of vascular lumen region founded the base of bubble detection and bubble grading, which played a significant role in the
detection of vascular gas emboli for the diagnosis of decompression sickness.

Objectives:
To assist in the detection of vascular bubbles, it is crucial to develop an automatic algorithm that could identify vascular lumen areas in ultrasound
videos with the interference of bubble presence.

Methods:
This article proposed an automated vascular lumen region recognition (VLRR) algorithm that could sketch the accurate boundary between vessel
lumen and tissues from dynamic 2D ultrasound videos. It adopts 2D ultrasound videos of the lumen area as input and outputs the frames with
circled vascular lumen boundary of the videos. Normalized cross-correlation method, distance transform technique, and region growing technique
were adopted in this algorithm.

Results:
A double-blind test was carried out to test the recognition accuracy of the algorithm on 180 samples in the images of 6 different grades of bubble
videos, during which, intersection over union and pixel accuracy were adopted as evaluation metrics. The average IOU on the images of different
bubble grades reached 0.76. The mean PA on 6 of the images of bubble grades reached 0.82.

Conclusion:
It is concluded that the proposed method could identify the vascular lumen with high accuracy, potentially applicable to assist clinicians in the
measurement of the severity of vascular gas emboli in clinics.
Messenger Use and Video Calls as Correlates of Depressive and Anxiety Symptoms: Results From the Corona Health App Study of German Adults During the COVID-19 Pandemic
Authors: Edler Johanna-Sophie , Terhorst Yannik , Pryss Rüdiger , Baumeister Harald , Cohrdes Caroline 
Published: June 2024

Background
Specialized studies have shown that smartphone-based social interaction data are predictors of depressive and anxiety symptoms. Moreover, at times during the COVID-19 pandemic, social interaction took place primarily remotely. To appropriately test these objective data for their added value for epidemiological research during the pandemic, it is necessary to include established predictors.

Objective
Using a comprehensive model, we investigated the extent to which smartphone-based social interaction data contribute to the prediction of depressive and anxiety symptoms, while also taking into account well-established predictors and relevant pandemic-specific factors.

Methods
We developed the Corona Health App and obtained participation from 490 Android smartphone users who agreed to allow us to collect smartphone-based social interaction data between July 2020 and February 2021. Using a cross-sectional design, we automatically collected data concerning average app use in terms of the categories video calls and telephony, messenger use, social media use, and SMS text messaging use, as well as pandemic-specific predictors and sociodemographic covariates. We statistically predicted depressive and anxiety symptoms using elastic net regression. To exclude overfitting, we used 10-fold cross-validation.

Results
The amount of variance explained (R2) was 0.61 for the prediction of depressive symptoms and 0.57 for the prediction of anxiety symptoms. Of the smartphone-based social interaction data included, only messenger use proved to be a significant negative predictor of depressive and anxiety symptoms. Video calls were negative predictors only for depressive symptoms, and SMS text messaging use was a negative predictor only for anxiety symptoms.

Conclusions
The results show the relevance of smartphone-based social interaction data in predicting depressive and anxiety symptoms. However, even taken together in the context of a comprehensive model with well-established predictors, the data only add a small amount of value.
Morphological Variation of <i>Diospyros</i> spp. Native to Sulawesi Based on Vegetative Organ Characters
Authors: Wulandari Aprilia Ayu , Khotimperwati Lilih , Wanda Irvan Fadli 
Published: June 2024

Researchers about Diospyros have not extensively conducted studies on the morphological characteristics to enhance information for taxonomic hierarchy purposes. Diospyros in Indonesia has great potential for in-depth research due to its unique characteristics, particularly in Sulawesi. This research aims to fill the knowledge gap regarding investigating phenotypic variations in Diospyros, specifically in the Sulawesi region. Nine species of Diospyros from the BBG collection will be observed and described for their morphological characteristics. The results indicate 25 variations of 50 characters in morphological characteristics. Variations in morphological characters can suggest that each species adapts to the surrounding environmental conditions.
Diversity and Phenetic Relationship of Mountain Papaya (<i>Vasconcellea Pubescens</i>) in Dieng Plateau Based on Morphological Marker
Authors: Rifqi Muhammad Said , Chasani Abdul Razaq 
Published: June 2024

Vasconcellea pubescens A. DC., commonly referred to as mountain papaya, belongs to the Caricaceae family and is native to the Andean highlands. In Indonesia, mountain papaya can be found on the Dieng Plateau and has become one of the typical processed products from the Dieng area. The aim of the study is to explore the diversity and phenetic relationship of mountain papaya from the Dieng Plateau based on morphological markers. This study is important to provide information in guiding future conservation efforts. 18 samples were collected from three areas with different altitudes in the Dieng Plateau. In addition, it proved valuable results by elucidating patterns of variation, enabling the identification of distinct groups. A total of 18 samples were collected from three areas with varying altitudes in the Dieng Plateau. Morphological analysis used 22 characters with The Clustering Analysis Method, Principal Component Analysis (PCA), and Diversity Analysis using Multivariate Statistical Package (MVSP) software version 3.1A. The results of cluster analysis showed that mountain papaya accessions were grouped into two main clusters and five sub-clusters. Cluster grouping based on sex distribution characters, flower stalk length, and inflorescence density; there is no grouping based on geographical location or altitude. The Shannon's Index Value (H') for mountain papaya shows moderate phenetic diversity. This suggests that the mountain papaya community remains stable within its substrate and its environmental parameters.
10-OR: Diffusion Tensor Imaging and T2 Mapping of the Tibial Nerve Can Detect Nerve Damage in Type 2 Diabetes
Authors: PARK HYEONG-KYU 
Published: June 2024

Magnetic resonance imaging (MRI) has played little role for the study of peripheral nerve disease. However, recent technological advances in MRI have provided us more information about neural microstructure and higher resolution in peripheral nerves. The aim of this study is to evaluate whether diffusion tensor imaging (DTI) in MRI can detect peripheral nerve abnormalities in patients with type 2 diabetes (T2D).In this prospective, single-center study, 33 T2D patients (mean age, 60.5 ± 7.0 yr; 16 M/ 17F) and 12 healthy controls (61.8 ± 5.3 yr, 5M / 7 F) were included. All T2D patients underwent Michigan Neuropathy Screening Instrument questionnaire and quantitative sensory testing. MRI including DTI and axial T2-weight Dixon sequence was performed for each participant. DTI parameters of the tibial nerves such as fractional anisotropy (FA) and diffusivity (mean (MD), axial (AD), and radial (RD)) and T2 relaxation time were calculated. FA of the tibial nerves was significantly lower in T2D patients than healthy controls at both level 1 (0.42 ± 0.07 vs. 0.57 ± 0.09, P&lt;0.001) and level 2 (0.44 ± 0.07 vs. 0.55 ± 0.08, P&lt;0.001). AD was also significantly lower in T2D patients than controls at both level 1 (1.97 ± 0.43 vs. 2.40 ± 0.63, P&lt;0.05) and level 2 (2.18 ± 0.37 vs. 2.59 ± 0.47, P&lt;0.05). RD was significantly higher in T2D patients than controls at level 1 (0.97 ± 0.21 vs. 0.83 ± 0.13, P&lt;0.05). However, there were no differences in DTI parameters between T2D patients with peripheral neuropathy (PN) and those without PN. T2D patients with and without PN had significantly longer T2 relaxation time for the tibial nerve compared to healthy controls. In summary, we demonstrated that DTI and T2 relaxation time can detect microstructural alterations of peripheral nerves in T2D patients with PN as well as those without PN, suggesting that the structural nerve damage can occur before the development of PN in T2D patients.

Disclosure
H. Park: None.
10-PUB: Single Nuclei RNA-seq to Map Adipose Cellular Populations and Senescent Cells in Response to a Lifestyle or Senolytic Intervention in Older Adults with Obesity—A Double-Blind, Placebo-Controlled, Randomized Trial
Authors: CONNOLLY GAVIN , ASLAMY ARIANNE , NIE JIA , KABIR MORVARID , SERRA MONICA C. , ESPINOZA SARA E. , MUSI NICOLAS 
Published: June 2024

Introduction & Objective: Older adults with obesity are at an increased risk for metabolic diseases and diabetes. The underlying molecular mechanisms by which increased adiposity and aging predispose individuals to metabolic diseases are not well understood. Recent data suggests that variations in adipocyte cellular subpopulations influence whole-body metabolism, and an increased burden of adipocyte senescent cells has been implicated in metabolic diseases. The purpose of this study is to conduct a double-blinded, placebo-controlled, randomized trial investigating the relations between adipose molecular signatures and cellular senescence on metabolic outcomes.
Methods: Using single nuclei RNA sequencing (SnRNA-seq), we will develop a transcriptomic atlas of human adipose tissue and analyze molecular profiles pre- and post-intervention. We will recruit a cohort of older adults with obesity (≥65 years of age; BMI=30-39.9 kg/m2; n=72). We will obtain adipose biopsies to analyze cellular/molecular profiling via snRNA-seq as it relates to phenotypic measures of insulin sensitivity, glucose tolerance, beta cell function, and hepatic lipid content compared to cohorts of younger lean (18-30 years of age; BMI=18.5-24.9 kg/m2; n = 24) and older lean (≥65 years of age; BMI=18.5-24.9 kg/m2; n=24) participants. The cohort of older adults with obesity will be randomized to one of three groups for 10 weeks: lifestyle (diet- and exercise-induced weight loss of 8-10% of body mass), senolytic (dasatinib and quercetin), or placebo.
Results & Conclusion: The findings from this study will help elucidate whether changes in global adipose molecular signatures and cellular senescence are mechanisms by which lifestyle or senolytic therapy intervention improves metabolic parameters. This information may help identify molecular targets for treating metabolic diseases.

Disclosure
G. Connolly: None. A. Aslamy: None. J. Nie: None. M. Kabir: None. M.C. Serra: None. S.E. Espinoza: None. N. Musi: None.

Funding
National Institutes of Health/National Institute on Aging (R01AG075684)
1001-P: Improvements in Data Availability with the G7 CGM System
Authors: JEPSON LAUREN H. , ANDRADE SARAH B. , WELSH JOHN 
Published: June 2024

Introduction & Objective: The G6 CGM system offers a 2-hour warmup and a 10-day lifespan; the G7 system (both from Dexcom) offers a 30-minute warmup and a 12-hour grace period of functionality after 10 days. We examined data gaps and alert availability with the two systems.
Methods: Real-world data were analyzed from 59,285 users in the US and Europe who uploaded ≥60 days of data from G6, transitioned to G7, and then uploaded ≥60 days of data from G7. Comparisons between the last 60 days of G6 use and the first 60 days of G7 use were analyzed.
Results: After switching to G7, the median between-session data gap duration decreased by 1.8 hours, and the proportion of gaps lasting ≥1 hour increased from 0.1% to 54.3% (Table). Most G7 sessions exceeded the 10-day lifespan and extended into the 12-hour grace period. Median time between sensor replacements was 14 minutes shorter with G7 than with G6.
Conclusion: The simpler sensor insertion and shorter warm-up time for G7 provide users with access to the CGM data sooner for more timely diabetes management decisions and the 12-hour grace period provides users flexibility in their schedules with continued access to CGM data.

Disclosure
L.H. Jepson: Employee; Dexcom, Inc. Stock/Shareholder; Dexcom, Inc. S.B. Andrade: Employee; Dexcom, Inc. J. Welsh: Employee; Dexcom, Inc.
1016-P: Development of Highly Accurate Measurement Method of Salivary Glycated Albumin by HPLC
Authors: AIHARA MASAKAZU , KUBOTA NAOTO , YAMAUCHI TOSHIMASA 
Published: June 2024

Objective: Measurements diabetes-related biomarkers are necessary to determine glycemic management, however commonly used home finger-prick blood glucose test and HbA1c measurements at hospital are invasive. Blood glycated albumin (GA) is also commonly measured in an invasive manner. This study aimed to develop a non-invasive method for evaluating glycemic control: measurement of salivary GA using high-performance liquid chromatography (HPLC) method with high accuracy.
Research Design & Methods: Participants with diabetes mellitus, who admitted to The University of Tokyo Hospital for glycemic management, were recruited for this study. Blood and saliva samples were collected three times (fasting and 2-hour postprandial on admission and fasting on discharge). Blood and saliva samples after the partial purification using antibody-based column were measured for GA levels using HPLC method.
Results: We enrolled 56 participants with diabetes mellitus in the study. There was a correlation between GA levels in blood and saliva collected fasting and 2-hour postprandial on admission and fasting on discharge. Multiple regression analysis revealed the associations were maintained even after adjustments for age, BMI, and nephropathy stage.
Conclusions: In this study, preprocessed saliva samples were measured for GA levels using HPLC method. Salivary GA levels measured by this method were so accurate to replace blood GA measurement. In the future, we would like to develop post-in or home salivary GA measurement method so that people with diabetes can easily and non-invasively monitor and improve their own glycemic management status.

Disclosure
M. Aihara: None. N. Kubota: None. T. Yamauchi: Research Support; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Covidien Japan Inc. (Medtronic Japan Co., Ltd.). Research Support; Novo Nordisk. Other Relationship; Astellas Pharma Inc., AstraZeneca K.K. Research Support; Ono Pharmaceutical Co., Ltd. Other Relationship; Novartis International AG. Research Support; Boehringer Ingelheim GmbH Japan. Other Relationship; Kyowa Kirin Co., Ltd. Research Support; Kowa Company, Ltd. Other Relationship; Merck Sharp & Dohme Corp., Sanofi, SANWA KAGAKU KENKYUSHO CO., LTD., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd. Research Support; Eli Lilly and Company, Sumitomo Pharma Co., Ltd., Asahi Mutual Life Insurance Company, Nipro Corporation, Otsuka Pharmaceutical Co., Ltd., Teijin Pharma Limited, Shionogi & Co., Ltd. Other Relationship; Abbott Japan Co., Ltd. Research Support; Boehringer Ingelheim GmbH. Other Relationship; Terumo Corporation, Viatris Inc., LifeScan Japan Co., Ltd., Roche DC Japan Co., Ltd., Cosmic Corporation Co., Ltd., ARKRAY Marketing Co., Ltd.
102-OR: A Novel Strategy for Detecting In Vivo Functional ß-Cells Using Positron Emission Tomography (PET) Imaging
Authors: LI JUNFENG , YIN RUNKAI , RAWSON JEFFREY , KANDEEL FOUAD R. 
Published: June 2024

Introduction & Objective: Autopsy studies in individuals with T1D demonstrated residual β cells. There are significant challenges in accurately evaluating in vivo insulin secretion from functional β-cells, hampering therapeutic translations of β-cell regeneration to human. Zn2+ is an excellent biomarker of β-cell insulin release. Tracking pancreatic free Zn2+ could provide a window to detect β-cell function. We aimed to investigate if a chelating-zinc PET probe could detect Zn2+ released from β-cells to evaluate their insulin secretion.
Methods: 18F-labeled Tripicolylamine (TPA) demonstrated high specific affinity to Zn2+. We evaluated 18F-TPA PET imaging in two mice models with/without glucose stimulation: in vivo healthy NODscid mice and ex vivo STZ-induced diabetic mice. Following PET imaging, biodistribution and immunostaining were conducted and analyzed.
Results: 18F-TPA PET imaging could efficiently detect change in healthy mice without/with glucose stimulation (Figure). There was low imaging interference from organs adjacent to pancreas. 18F-TPA could detect the functional residue β-cells in diabetic mice. Biodistribution and immunostaining validated PET imaging results.
Conclusion: 18F-TPA PET imaging detected Zn2+ released from β-cells, reflecting insulin secretion capacity. It can be valuable for tracking in vivo β-cell function in future T1D treatment strategies.

Disclosure
J. Li: None. R. Yin: None. J. Rawson: None. F.R. Kandeel: Advisory Panel; Vertex Pharmaceuticals Incorporated.

Funding
the Oxnard Foundation (50214-2012049); WFP Mid-Term Innovative Award (10014-2011440)