bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting multiple sclerosis severity with multimodal deep neural networks
Authors: Zhang Kai , Lincoln John A. , Jiang Xiaoqian , Bernstam Elmer V. , Shams Shayan 
Published: November 2023

AbstractMultiple Sclerosis (MS) is a chronic disease developed in the human brain and spinal cord, which can cause permanent damage or deterioration of the nerves. The severity of MS disease is monitored by the Expanded Disability Status Scale, composed of several functional sub-scores. Early and accurate classification of MS disease severity is critical for slowing down or preventing disease progression via applying early therapeutic intervention strategies. Recent advances in deep learning and the wide use of Electronic Health Records (EHR) create opportunities to apply data-driven and predictive modeling tools for this goal. Previous studies focusing on using single-modal machine learning and deep learning algorithms were limited in terms of prediction accuracy due to data insufficiency or model simplicity. In this paper, we proposed the idea of using patients’ multimodal longitudinal and longitudinal EHR data to predict multiple sclerosis disease severity in the future. Our contribution has two main facets. First, we describe a pioneering effort to integrate structured EHR data, neuroimaging data and clinical notes to build a multi-modal deep learning framework to predict patient’s MS severity. The proposed pipeline demonstrates up to 19% increase in terms of the area under the Area Under the Receiver Operating Characteristic curve (AUROC) compared to models using single-modal data. Second, the study also provides valuable insights regarding the amount useful signal embedded in each data modality with respect to MS disease prediction, which may improve data collection processes.
Knowledge, attitudes and intentions of the Syrian pregnant women toward labour analgesia, and its associated factors: a cross sectional study in Syria (2022)
Authors: Bohsas Haidara , Alibrahim Hidar , Swed Sarya , Abouainain Yasmeen , Nasif Mohamad Nour , Jawish Nagham , Almarja Mohammad Bani , Aldarwish Sara , Ghareeb Carol , Sawaf Bisher , Hafez Wael 
Published: November 2023

Abstract
Background
During the reproductive period among pregnant women, the worst pain a woman can experience is labour pain. Untreated labour pain has many detrimental effects on the mother and the fetus. Then, the inadequate levels of awareness and attitudes toward labour analgesia among pregnant women are considered a serious concern that influences no-healthy results for both the mother and the baby. Therefore, this research aimed to define the degree of Awareness, Attitude, and intent to use labour analgesia among pregnant women in Syria.

Methods
We conducted a cross-sectional study from 7 September to 23 October 2022, in which we included Pregnant Syrian women aged 18 and above. The questionnaire was based on a prior study that included verified and validated scales, which consisted of 23 questions separated into four sections. The sample size was calculated using Fisher’s formula; however, our study included 638 participants. The data was analyzed using IBM SPSS Version 28.0, using descriptive and binary logistic regression methods.

Results
Among those who had previous deliveries, 39.4% performed a caesarian delivery, and only 1.9% had a delivery at home. Nearly half of the study participants (50.4%) reported adequate knowledge about analgesia for obstetric pain. The inquired pregnant women who had children had more odds of knowledge than participants who had not. Respondents who were childbearing at the health center were more likely to have a good attitude (Adjusted Odds ratio = 4.728, P-value < 0.05, 95%CI: 1.035–21.589) than those who were childbearing at a national referral hospital. Also, the respondents above 31 years were less likely to desire labour analgesia than those aged 18–24.

Conclusion
Our results revealed that Syrian pregnant women have a moderated awareness, attitudes, and desire regarding labour analgesia, indicating a serious health problem among this population group. It is recommended that local and global health organizations address the current condition relevant to this issue by implementing healthy educational programmes for Syrian women through coordination with obstetric and gynaecological professionals.
Integrative single-cell RNA-seq analysis of vascularized cerebral organoids
Authors: Sato Yuya , Asahi Toru , Kataoka Kosuke 
Published: November 2023

Abstract
Background
Cerebral organoids are three-dimensional in vitro cultured brains that mimic the function and structure of the human brain. One of the major challenges for cerebral organoids is the lack of functional vasculature. Without perfusable vessels, oxygen and nutrient supplies may be insufficient for long-term culture, hindering the investigation of the neurovascular interactions. Recently, several strategies for the vascularization of human cerebral organoids have been reported. However, the generalizable trends and variability among different strategies are unclear due to the lack of a comprehensive characterization and comparison of these vascularization strategies. In this study, we aimed to explore the effect of different vascularization strategies on the nervous system and vasculature in human cerebral organoids.

Results
We integrated single-cell RNA sequencing data of multiple vascularized and vascular organoids and fetal brains from publicly available datasets and assessed the protocol-dependent and culture-day-dependent effects on the cell composition and transcriptomic profiles in neuronal and vascular cells. We revealed the similarities and uniqueness of multiple vascularization strategies and demonstrated the transcriptomic effects of vascular induction on neuronal and mesodermal-like cell populations. Moreover, our data suggested that the interaction between neurons and mesodermal-like cell populations is important for the cerebrovascular-specific profile of endothelial-like cells.

Conclusions
This study highlights the current challenges to vascularization strategies in human cerebral organoids and offers a benchmark for the future fabrication of vascularized organoids.
Changing turn-over rates regulate abundance of tryptophan, GS biosynthesis, IAA transport and photosynthesis proteins in Arabidopsis growth defense transitions
Authors: Abukhalaf Mohammad , Proksch Carsten , Thieme Domenika , Ziegler Jörg , Hoehenwarter Wolfgang 
Published: November 2023

Abstract
Background
Shifts in dynamic equilibria of the abundance of cellular molecules in plant-pathogen interactions need further exploration. We induced PTI in optimally growing Arabidopsis thaliana seedlings for 16 h, returning them to growth conditions for another 16 h.

Methods
Turn-over and abundance of 99 flg22 responding proteins were measured chronologically using a stable heavy nitrogen isotope partial labeling strategy and targeted liquid chromatography coupled to mass spectrometry (PRM LC–MS). These experiments were complemented by measurements of mRNA and phytohormone levels.

Results
Changes in synthesis and degradation rate constants (Ks and Kd) regulated tryptophane and glucosinolate, IAA transport, and photosynthesis-associated protein (PAP) homeostasis in growth/PTI transitions independently of mRNA levels. Ks values increased after elicitation while protein and mRNA levels became uncorrelated. mRNA returned to pre-elicitation levels, yet protein abundance remained at PTI levels even 16 h after media exchange, indicating protein levels were robust and unresponsive to transition back to growth. The abundance of 23 PAPs including FERREDOXIN-NADP( +)-OXIDOREDUCTASE (FNR1) decreased 16 h after PAMP exposure, their depletion was nearly abolished in the myc234 mutant. FNR1 Kd increased as mRNA levels decreased early in PTI, its Ks decreased in prolonged PTI. FNR1 Kd was lower in myc234, mRNA levels decreased as in wild type.

Conclusions
Protein Kd and Ks values change in response to flg22 exposure and constitute an additional layer of protein abundance regulation in growth defense transitions next to changes in mRNA levels. Our results suggest photosystem remodeling in PTI to direct electron flow away from the photosynthetic carbon reaction towards ROS production as an active defense mechanism controlled post-transcriptionally and by MYC2 and homologs. Target proteins accumulated later and PAP and auxin/IAA depletion was repressed in myc234 indicating a positive effect of the transcription factors in the establishment of PTI.
Deep transcriptome profiling reveals limited conservation of A-to-I RNA editing in Xenopus
Authors: Nguyen Tram Anh , Heng Jia Wei Joel , Ng Yan Ting , Sun Rui , Fisher Shira , Oguz Gokce , Kaewsapsak Pornchai , Xue Shifeng , Reversade Bruno , Ramasamy Adaikalavan , Eisenberg Eli , Tan Meng How 
Published: November 2023

Abstract
Background
Xenopus has served as a valuable model system for biomedical research over the past decades. Notably, ADAR was first detected in frog oocytes and embryos as an activity that unwinds RNA duplexes. However, the scope of A-to-I RNA editing by the ADAR enzymes in Xenopus remains underexplored.

Results
Here, we identify millions of editing events in Xenopus with high accuracy and systematically map the editome across developmental stages, adult organs, and species. We report diverse spatiotemporal patterns of editing with deamination activity highest in early embryogenesis before zygotic genome activation and in the ovary. Strikingly, editing events are poorly conserved across different Xenopus species. Even sites that are detected in both X. laevis and X. tropicalis show largely divergent editing levels or developmental profiles. In protein-coding regions, only a small subset of sites that are found mostly in the brain are well conserved between frogs and mammals.

Conclusions
Collectively, our work provides fresh insights into ADAR activity in vertebrates and suggest that species-specific editing may play a role in each animal’s unique physiology or environmental adaptation.
Deletion in 1p36.33-p36.32 is associated with pancytopenia: a case report
Authors: Yang Huanhuan , Huang Jun , Zheng Hao , Zhang Yunfan , Zhang Yuanzhen , Liu Wei , Wu Jinrong , Chen Xiaobin , Lin Jinfeng , Ni Yanna , Nie Xiaojing 
Published: November 2023

Abstract
Background
1P36 deletion syndrome is recognized as the most common terminal microdeletion syndrome in humans, characterized by early developmental delay and consequent intellectual disability, seizure disorder, and distinctive facial features. Variable deletion locations may attributed to phenotypic variability. However, the abnormal phenotypes of hematology are rarely reported in 1P36 deletion syndrome patients.

Case presentation
We present a case of postnatal intellectual disability accompanied by pancytopenia. Copy number variation analysis revealed a pathogenic deletion in 1p36.331p36.32 with a deletion size of 2.21 Mb. Following successful treatment with glucocorticoids, the patient was diagnosed with immuno-related hemocytopenia (IRH).

Discussion
The patient experienced IRH, an uncommon characteristic of 1p36 deletion syndrome. The deletion fragment of 1p36.33-p36.32, particularly the loss of GNB1 gene, has been associated with the development of pancytopenia. Genotype-phenotype correlations are valuable in identifying the genes responsible for various clinical characteristics of the syndrome by associating phenotypic variation with specific genes located within the chromosome deletion region. Genome sequencing is recommended in cases where clinical manifestations indicate the presence of a genetic disorder but pose diagnostic challenges.
Cardiometabolic Index (CMI), Lipid Accumulation Products (LAP), Waist Triglyceride Index (WTI) and the risk of acute pancreatitis: a prospective study in adults of North China
Authors: Sun Qiu , Ren Qingshuai , Du Liming , Chen Shuohua , Wu Shouling , Zhang Bing , Wang Bangmao 
Published: November 2023

Abstract
Objective
To investigate the correlation between anthropometric indexes [cardiometabolic index (CMI), lipid accumulation products (LAP), waist triglyceride index (WTI), and body mass index (BMI)] and acute pancreatitis (AP) in a Chinese adult population.

Methodology
The present investigation consisted of a prospective group including 117,326 subjects who were enrolled in the Kailuan investigation. The individuals were categorized into quartiles based on their baseline levels of CMI, LAP, and WIT. BMI was categorized into three distinctive groups: normal weight group (BMI < 24 kg/m2), overweight group (BMI 24–28 kg /m2), and obesity group (BMI ≥ 28 kg/m2). The data were subjected to analysis in order to investigate the correlation between these anthropometric indexes and the incidence of AP. Cox regression models were employed to assess the relative risk of AP while accounting for known risk factors through appropriate adjustments.

Outcomes
Over the course of a median follow-up duration of 12.59 ± 0.98 years, we documented 401 incident AP cases. Incidence density and cumulative incidence rates of AP increased with the increase of CMI, LAP, and WTI. After multivariate adjustment, the fourth quartile of CMI, LAP, and WTI exhibited the greatest risk of AP [CMI: hazard ratio (HR) 1.93, 95% confidential interval (CI) (1.45–2.57); LAP: HR 2.00, 95% CI(1.49–2.68); WTI: HR 2.13,95% CI (1.59–2.83)]. In comparison to the normal weight group, the obesity group (BMI ≥ 28 kg/m2) had an elevated risk of AP (HR = 1.58, 95% CI: 1.21–2.05). Furthermore, the incremental effect of BMI combined with CMI on the prognostic value of AP was greater than that of BMI alone (the C statistics demonstrated a result of 0.607 versus 0.546; the integrated discrimination improvement revealed a result of 0.321%; net reclassification improvement was 1.975%).

Conclusion
We found that CMI, LAP, and WTI were positively and independently connected to the risk of AP. Additionally, CMI demonstrates a superior prognostic capacity than other indexes in anticipating AP.
Aptamer-based self-assembled nanomicelle enables efficient and targeted drug delivery
Authors: Chen Ganghui , Mao Dongsheng , Wang Xuan , Chen Jingqi , Gu Chao , Huang Shuqin , Yang Yu , Zhang Fang , Tan Weihong 
Published: November 2023

AbstractNucleic acid aptamer-based nanomicelles have great potential for nanomedicine and nanotechnology applications. However, amphiphilic aptamer micelles are known to be inherently unstable upon interaction with cell membranes in the physiological environment, thus potentially compromising their specific targeting against cancer cells. This flaw is addressed in the present work which reports a superstable micellar nanodelivery system as an amphiphilic copolymer self-assembled micelle composed of nucleic acid aptamer and polyvalent hydrophobic poly(maleic anhydride-alt-1-octadecene) (C18PMH). Using Ce6 as a drug model, these C18-aptamer micelles exhibit efficient tumor-targeting and -binding ability, facilitating the entry of Ce6 into targeted cells for photodynamic therapy. In addition, they can be loaded with other hydrophobic drugs and still demonstrate favorable therapeutic effects. As such, these C18-aptamer micelles can serve as a universal platform for loading multiple drugs, providing a safer and more effective solution for treating cancer.
Characteristics of hemoglobin distributions in preschool children and non-pregnant women of reproductive age and their implications for establishing quality control criteria for hemoglobin data in field surveys: evidence from 483 surveys conducted in refugee settings worldwide
Authors: Bilukha Oleg , Kianian Behzad , Samson Kaitlyn L. I. 
Published: November 2023

Abstract
Background
Currently, there is a lack of clear guidance on hemoglobin (Hb) data quality parameters and plausible flagging ranges for population-representative surveys. There is a need to determine which properties of Hb data indicate lower data quality and increased measurement error and which represent intrinsic statistical properties of Hb distributions rather than quality problems.

Methods
We explored statistical characteristics of Hb distributions and plausible exclusion ranges in population-representative surveys of non-pregnant women of reproductive age (WRA) (15–49 years, n = 401 surveys) and children (6–59 months, n = 461 surveys) conducted in refugee settings by the United Nations High Commissioner for Refugees (UNHCR). Hb distribution characteristics [standard deviation (SD), skewness and kurtosis] were compared to those from Demographic and Health Surveys (DHS).

Results
Overall, 0.08% of child and 0.14% of WRA Hb values were outside of the previously proposed 4.0–18.0 g/dL plausible range. Surveys conducted in Uganda tended to have unusually high SD compared with surveys from other settings, possibly an indication of problematic measurement quality. We therefore used summary results on SD, skewness and kurtosis excluding surveys from Uganda when comparing with DHS results or proposing plausible ranges. Both WRA and child Hb distributions tended to be left-skewed and had excess positive kurtosis. Mean survey-level SD was greater, mean skewness more negative, and mean kurtosis more positive in WRA surveys compared to child surveys. All these findings were broadly similar to those from DHS surveys. Mean SD in DHS surveys was higher than that in our data for both children (1.48 vs. 1.34) and WRA (1.58 vs. 1.43).

Conclusions
We observed several statistical characteristics of Hb distributions that may not necessarily be indicative of data quality problems and bear strong similarities with the characteristics found in DHS surveys. Hb distributions tended to be negatively skewed and positively kurtotic, and SD in many surveys exceeded 1.5 (previously proposed upper plausible range). Based on our empirical evidence, surveys with skewness above + 0.2 and kurtosis below -0.5 or Hb SD outside the range of 1.1–1.55 g/dL for children (6–59 mo) or 1.1–1.65 g/dL for non-pregnant WRA (15–49 y) may require further quality investigation.
A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer
Authors: Kalantari Leila , Ghotbabadi Zahra Rostami , Gholipour Arsalan , Ehymayed Hadi Mohammed , Najafiyan Behnam , Amirlou Parsa , Yasamineh Saman , Gholizadeh Omid , Emtiazi Nikoo 
Published: November 2023

AbstractAccording to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV.
Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats
Authors: Liu Baoer , Korkmaz Brice , Kraft Patricia , Mayer Tobias , Sayour Alex A. , Grundl Marc A. , Domain Roxane , Karck Matthias , Szabó Gábor , Korkmaz-Icöz Sevil 
Published: November 2023

Abstract
Background
Heart transplantation (HTX) is the standard treatment for end-stage heart failure. However, reperfusion following an ischemic period can contribute to myocardial injury. Neutrophil infiltration, along with the subsequent release of tissue-degrading neutrophil elastase (NE)-related serine proteases and oxygen-derived radicals, is associated with adverse graft outcomes. The inhibition of cathepsin C (CatC) has been shown to block NE-related protease activation. We hypothesized that the CatC inhibitor BI-9740 improves graft function after HTX.

Methods
In a rat model of HTX, the recipient Lewis rats were orally administered with either a placebo (n = 12) or BI-9740 (n = 11, 20 mg/kg) once daily for 12 days. Donor hearts from untreated Lewis rats were explanted, preserved in a cardioplegic solution, and subsequently heterotopically implanted. In vivo left-ventricular (LV) graft function was assessed after 1 h of reperfusion. The proteolytic activity of neutrophil serine proteases was determined in bone marrow lysates from BI-9740-treated and control rats. Additionally, myocardial morphological changes were examined, and heart samples underwent immunohistochemistry and western blot analysis.

Results
The NE-related proteolytic activity in bone marrow cell lysates was markedly decreased in the BI-9740-treated rats compared to those of the placebo group. Histopathological lesions, elevated CatC and myeloperoxidase-positive cell infiltration, and nitrotyrosine immunoreactivity with an increased number of poly(ADP-ribose) polymerase (PARP)-1-positive cells were lowered in the hearts of animals treated with BI-9740 compared to placebo groups. Regarding the functional parameters of the implanted graft, improvements were observed in both systolic function (LV systolic pressure 110 ± 6 vs 74 ± 6 mmHg; dP/dtmax 2782 ± 149 vs 2076 ± 167 mmHg/s, LV developed pressure, at an intraventricular volume of 200 µl, p < 0.05) and diastolic function in the hearts of BI-9740 treated animals compared with those receiving the only placebo. Furthermore, the administration of BI-9740 resulted in a shorter graft re-beating time compared to the placebo group. However, this study did not provide evidence of DNA fragmentation, the generation of both superoxide anions and hydrogen peroxide, correlating with the absence of protein alterations related to apoptosis, as evidenced by western blot in grafts after HTX.

Conclusions
We provided experimental evidence that pharmacological inhibition of CatC improves graft function following HTX in rats.