bluuebunny/crossref_metadata_2025 huggingface dataset:
Representational shifts: increasing motivation for bottled water through simulation-enhancing advertisements
Authors: Claassen Maria Almudena , Papies Esther Katharina
Published: November 2023

Background

Despite its numerous health benefits, consumers’ daily water consumption is below recommend levels while soft drink consumption remains high. Previous research has shown that the degree to which drinks are cognitively represented in terms of consumption and enjoyment (i.e., through simulations of consumption and reward) predicts desire and intake. Here, we examined whether simulation-enhancing advertisements that frame water in terms of consumption and reward change cognitive representations and increase motivation for a fictitious bottled water.

Methods

In three pre-registered online experiments (Nexp1 = 984; Nexp2 = 786; Nexp3 = 907), UK participants viewed three advertisements that either highlighted the rewarding consumption experience of water (e.g., “Refresh all your senses with this smooth, cool water”; simulation-enhancing ads), the health consequences of drinking water (e.g., “This water takes care of your health”; health-focused ads), or control ads. We assessed cognitive representations of the bottled water with a semantic feature production task, and we coded the words used as consumption and reward features or positive long-term health consequences features. We assessed motivation through ratings of the attractiveness of the water (Exp. 1 only), desire to drink it, and willingness to pay for it (WTP).

Results

In line with our hypotheses, participants represented the bottled water more in terms of consumption and reward after viewing simulation-enhancing advertisements, and more in terms of positive long-term health consequences after viewing health-focused advertisements. There was no direct effect of advertisement condition on motivation ratings. However, significant indirect effects showed that simulation-enhancing advertisements increased desire and WTP through the proportion of consumption and reward features, whereas health-focused advertisements increased motivation through an increase in the proportion of positive long-term health consequences features. The effects through consumption and reward were stronger.

Conclusions

These findings are consistent with research suggesting that the experience of immediate reward from drinking water underlies intake. Public health interventions should emphasize the enjoyment of drinking water, rather than the long-term health benefits.
PTSD, FOMO and fake news beliefs: a cross-sectional study of Wenchuan earthquake survivors
Authors: Gong Chen , Ren Yijin
Published: November 2023

Background

Post-traumatic stress disorder (PTSD) sufferers show problematic patterns of Internet use such as fear of missing out (FOMO) and sharing misinformation and fake news. This study aimed to investigate these associations in survivors of the 2008 earthquake in Wenchuan, China.

Methods

A self-reported survey was completed by 356 survivors of the Wenchuan earthquake. A mediated structural equation model was constructed to test a proposed pattern of associations with FOMO as a mediator of the relationship between PTSD symptoms and belief in fake news, as well as moderators of this pathway.

Results

PTSD was directly associated with believing fake news (β = 0.444, p < .001) and with FOMO (β = 0.347, p < .001). FOMO mediated the association between PTSD and fake news belief (β = 0.373, p < .001). Age moderated the direct (β = 0.148, t = 3.097, p = .002) and indirect (β = 0.145, t = 3.122, p = .002) pathways, with effects more pronounced with increasing age. Gender was also a moderator, with the indirect effect present in females but not in males (β = 0.281, t = 6.737, p < .001).

Conclusion

Those with higher PTSD symptoms are more likely to believe fake news and this is partly explained by FOMO. This effect is present in females and not males and is stronger in older people. Findings extend knowledge of the role of psychological variables in problematic Internet use among those with PTSD.
Association between P-pulmonale and respiratory morbidity in COPD: a secondary analysis of the BLOCK-COPD trial
Authors: Wade R. Chad , Mkorombindo Takudzwa , Ling Sharon X. , Helgeson Erika. S. , MacDonald David M. , Pew Krystle , Voelker Helen , Bittner Vera , Kunisaki Ken M. , Lammi Matthew R. , Dransfield Mark. T.
Published: November 2023

Rationale

Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms.

Objective

We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH.

Methods

ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ).

Results

We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45–5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77–1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32–6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61).

Conclusions

In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.
Antitumor effect of toosendanin on oral squamous cell carcinoma via suppression of p-STAT3
Authors: Wu Ye , Chen Lingling , Feng Cheng , Wang Tao , He Shaohai , Zheng Dali , Lin Lisong
Published: November 2023

Background

Toosendanin (TSN) exhibits potent antitumor activity against various tumor cell lines. However, its efficacy against oral squamous cell carcinoma (OSCC) remains unknown. Here, we investigated the effects of TSN on OSCC cells in vitro and verified them in vivo using a patient-derived xenograft (PDX) model.

Methods

The effect of TSN on OSCC cells was investigated by cytotoxicity assays and flow cytometry. The expression of proteins was detected by western blotting. An OSCC PDX model was constructed to further investigate the role of TSN in regulating the function of OSCC.

Results

The cell viability of CAL27 and HN6 cells decreased as the concentration of TSN increased within the experimental range. Compared with controls, TSN at lower doses inhibited cell proliferation and induced apoptosis through S-phase cell cycle arrest. TSN inhibited OSCC cell proliferation by downregulating the STAT3 pathway through the inhibition of STAT3 phosphorylation. After successful construction of the OSCC PDX model with high pathological homology to the primary tumor and treatment with an intraperitoneal injection of TSN, we showed that TSN significantly reduced the tumor size of the PDX model mice without obvious toxicity.

Conclusions

Both in vitro and in vivo, TSN significantly inhibits the proliferation and promoted apoptosis of OSCC cells. Furthermore, TSN demonstrates potent inhibition of STAT3 phosphorylation, indicating its potential as a promising therapeutic agent for OSCC. Therefore, TSN holds great promise as a viable drug candidate for the treatment of OSCC.
“It kinda helped us to be there”: students’ perspectives on the use of virtual patient software in psychiatry posting
Authors: Woon Luke Sy-Cherng , Mohd Daud Tuti Iryani , Tong Seng Fah
Published: November 2023

Background

At the Faculty of Medicine of the National University of Malaysia, a virtual patient software program, DxR Clinician, was utilised for the teaching of neurocognitive disorder topics during the psychiatry posting of undergraduate medical students in a modified team-based learning (TBL) module. This study aimed to explore medical students’ learning experiences with virtual patient.

Methods

Ten students who previously underwent the learning module were recruited through purposive sampling. The inclusion criteria were: (a) Fourth-year medical students; and (b) Completed psychiatry posting with the new module. Students who dropped out or were unable to participate in data collection were excluded. Two online focus group discussions (FGDs) with five participants each were conducted by an independent facilitator, guided by a questioning route. The data were transcribed verbatim and coded using the thematic analysis approach to identify themes.

Results

Three main themes of their learning experience were identified: (1) fulfilment of the desired pedagogy (2), realism of the clinical case, and (3) ease of use related to technical settings. The pedagogy theme was further divided into the following subthemes: level of entry for students, flexibility of presentation of content, provision of learning guidance, collaboration with peers, provision of feedback, and assessment of performance. The realism theme had two subthemes: how much the virtual patient experience mimicked an actual patient and how much the case scenario reflected real conditions in the Malaysian context. The technical setting theme entailed two subthemes: access to the software and appearance of the user interface. The study findings are considered in the light of learning formats, pedagogical and learning theories, and technological frameworks.

Conclusions

The findings shed light on both positive and negative aspects of using virtual patients for medical students’ psychiatry posting, which opens room for further improvement of their usage in undergraduate psychiatry education.
The consequences of data dispersion in genomics: a comparative analysis of data sources for precision medicine
Authors: Costa Mireia , García S. Alberto , Pastor Oscar
Published: November 2023

Background

Genomics-based clinical diagnosis has emerged as a novel medical approach to improve diagnosis and treatment. However, advances in sequencing techniques have increased the generation of genomics data dramatically. This has led to several data management problems, one of which is data dispersion (i.e., genomics data is scattered across hundreds of data repositories). In this context, geneticists try to remediate the above-mentioned problem by limiting the scope of their work to a single data source they know and trust. This work has studied the consequences of focusing on a single data source rather than considering the many different existing genomics data sources.

Methods

The analysis is based on the data associated with two groups of disorders (i.e., oncology and cardiology) accessible from six well-known genomic data sources (i.e., ClinVar, Ensembl, GWAS Catalog, LOVD, CIViC, and CardioDB). Two dimensions have been considered in this analysis, namely, completeness and concordance. Completeness has been evaluated at two levels. First, by analyzing the information provided by each data source with regard to a conceptual schema data model (i.e., the schema level). Second, by analyzing the DNA variations provided by each data source as related to any of the disorders selected (i.e., the data level). Concordance has been evaluated by comparing the consensus among the data sources regarding the clinical relevance of each variation and disorder.

Results

The data sources with the highest completeness at the schema level are ClinVar, Ensembl, and CIViC. ClinVar has the highest completeness at the data level data source for the oncology and cardiology disorders. However, there are clinically relevant variations that are exclusive to other data sources, and they must be considered in order to provide the best clinical diagnosis. Although the information available in the data sources is predominantly concordant, discordance among the analyzed data exist. This can lead to inaccurate diagnoses.

Conclusion

Precision medicine analyses using a single genomics data source leads to incomplete results. Also, there are concordance problems that threaten the correctness of the genomics-based diagnosis results.
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

Multiple 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

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

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

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

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

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

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

Nucleic 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

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

According 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

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.
Reverse complete heart block using transcutaneous pacing and repeated plasmapheresis in a neonate with lupus: a case report
Authors: Liu Yanfei , Li Wanwei , Zhou Kun , Hu Zhangxue
Published: November 2023

Background

It has been reported that the complete heart block (CHB) in neonatal lupus (NL) cannot be reversed. This study reported a case of NL-CHB that was reversed by transcutaneous pacing and repeated plasmapheresis.

Case presentation

A 35+ 6-week male preterm baby was transferred to the neonatal intensive care unit of the Army Medical Center in May 2020 for slight cyanosis around the lips and nose. Two days after birth, a sudden decrease in heart rate was observed during electrocardiogram (EGG) monitoring. Physical examination revealed a bluish-purple discoloration around the lips and an irregular heartbeat. EGG showed the presence of isolated P (142 bpm) and QRS (78 bpm) waves, ventricular escape beats, and a diagnosis of NL-CHB. To reverse the condition, transcutaneous pacing and five sessions of plasmapheresis were performed. At a 1.5-year follow-up, the baby exhibited well-developed cardiac structure and normal neurodevelopment.

Conclusions

Transcutaneous pacing and repeated plasmapheresis might be possible to reverse CHB in NL.
A pelvic kinematic approach for calculating hip angles for active hip disarticulation prosthesis control
Authors: Golshan Farshad , Baddour Natalie , Gholizadeh Hossein , Lemaire Edward D.
Published: November 2023

Background

Control system design for a microprocessor-controlled hip–knee–ankle–foot (HKAF) prosthesis is a challenge since hip disarticulation amputees lack the entire leg and, therefore, only have pelvis movement as user-guided input. This research proposes a method for determining hip joint angles from pelvis movement in a control system for the next generation of powered prostheses.

Method

Three-dimensional pelvic motion and stance time of 10 transfemoral (TF) prosthetic users were used to identify important features and to develop an algorithm to calculate hip angles from pelvis movement based on correlation and linear regression results. The algorithm was then applied to a separate (independent) TF group to validate algorithm performance.

Results

The proposed algorithm calculated viable hip angles during walking by utilizing pelvic rotation, pelvic tilt, and stance time. Small angular differences were found between the algorithm results and motion capture data. The greatest difference was for hip maximum extension angle (2.5 ± 2.0°).

Conclusions

Since differences between algorithm output and motion data were within participant standard deviations, the developed algorithm could be used to determine the desired hip angle from pelvis movements. This study will aid the future development of gait control systems for new active HKAF prostheses.
One hundred years of neurosciences in the arts and humanities, a bibliometric review
Authors: Cebral-Loureda Manuel , Sanabria-Z Jorge , Ramírez-Moreno Mauricio A. , Kaminsky-Castillo Irina
Published: November 2023

Background

Neuroscientific approaches have historically triggered changes in the conception of creativity and artistic experience, which can be revealed by noting the intersection of these fields of study in terms of variables such as global trends, methodologies, objects of study, or application of new technologies; however, these neuroscientific approaches are still often considered as disciplines detached from the arts and humanities. In this light, the question arises as to what evidence the history of neurotechnologies provides at the intersection of creativity and aesthetic experience.

Methods

We conducted a century-long bibliometric analysis of key parameters in multidisciplinary studies published in the Scopus database. Screening techniques based on the PRISMA method and advanced data analysis techniques were applied to 3612 documents metadata from the years 1922 to 2022. We made graphical representations of the results applying algorithmic and clusterization processes to keywords and authors relationships.

Results

From the analyses, we found a) a shift from a personality-focus quantitative analysis to a field-focus qualitative approach, considering topics such as art, perception, aesthetics and beauty; b) The locus of interest in fMRI-supported neuroanatomy has been shifting toward EEG technologies and models based on machine learning and deep learning in recent years; c) four main clusters were identified in the study approaches: humanistic, creative, neuroaesthetic and medical; d) the neuroaesthetics cluster is the most central and relevant, mediating between creativity and neuroscience; e) neuroaesthetics and neuroethics are two of the neologism that better characterizes the challenges that this convergence of studies will have in the next years.

Conclusions

Through a longitudinal analysis, we evidenced the great influence that neuroscience is having on the thematic direction of the arts and humanities. The perspective presented shows how this field is being consolidated and helps to define it as a new opportunity of great potential for future researchers.
iTRAQ-based proteomics reveals potential markers and treatment pathways for acute Achilles tendon rupture
Authors: Qianman Bayixiati , Wupuer Aikeremu , Jiasharete Tuomilisi , Luo Biao , Nihemaiti Meihua , Jielile Jiasharete
Published: November 2023

Background

Due to its limited blood supply and irregular mechanical loading, the Achilles tendon is the most frequently ruptured tendon. Despite the rising incidence of acute Achilles tendon rupture (AATR), the optimal treatment remains controversial. Missed diagnoses and delayed treatments lead to poor outcomes and limited treatment options. This study aimed to identify potential biomarkers for diagnosing and developing therapies for AATR.

Methods

We employed the coupled isobaric tag for relative and absolute quantitation-liquid chromatography–electrospray ionization-tandem mass spectrometry approach to investigate protein expression in tissues from AATR patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify differentially expressed proteins (DEPs) between AATR patients and healthy individuals. A protein–protein interaction (PPI) network of DEPs was constructed using the Search Tool for the Retrieval of Interacting Genes. The screened hub genes were selectively verified by immunohistochemical staining.

Results

We identified 410 DEPs between AATR patients and controls. The DEPs were significantly enriched in GO terms such as the extracellular region, extracellular region part, and defense response, as well as KEGG pathways, including complement and coagulation cascades, focal adhesion, and regulation of actin cytoskeleton. The main hub nodes in the PPI network comprised fibronectin 1 (FN1), major histocompatibility complex, class I, B (HLA-B), filamin A (FLNA), heat shock 27-kDa protein 1 (HSPB1), heat shock protein family A member 5 (HSPA5), apolipoprotein A4 (APOA4), and myosin IC (MYO1C). Although APOA4 and collagens I, II, and III were detectable in healthy tendons, immunohistochemical staining confirmed higher expression of these proteins in the acutely ruptured Achilles tendon.

Conclusions

Our findings lay a foundation for further molecular studies of AATR. Inflammation and age-related degeneration may contribute to the pathogenesis of AATR. Moreover, the identified DEPs could be potential biomarkers for AATR diagnosis and treatment.
International Undiagnosed Diseases Programs (UDPs): components and outcomes
Authors: Curic Ela , Ewans Lisa , Pysar Ryan , Taylan Fulya , Botto Lorenzo D. , Nordgren Ann , Gahl William , Palmer Elizabeth Emma
Published: November 2023

Over the last 15 years, Undiagnosed Diseases Programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases, integrating research and clinical care to optimize diagnostic outcomes. This narrative review summarizes the published literature surrounding Undiagnosed Diseases Programs worldwide, including thirteen studies that evaluate outcomes and two commentary papers. Commonalities in the diagnostic and research process of Undiagnosed Diseases Programs are explored through an appraisal of available literature. This exploration allowed for an assessment of the strengths and limitations of each of the six common steps, namely enrollment, comprehensive clinical phenotyping, research diagnostics, data sharing and matchmaking, results, and follow-up. Current literature highlights the potential utility of Undiagnosed Diseases Programs in research diagnostics. Since participants have often had extensive previous genetic studies, research pipelines allow for diagnostic approaches beyond exome or whole genome sequencing, through reanalysis using research-grade bioinformatics tools and multi-omics technologies. The overall diagnostic yield is presented by study, since different selection criteria at enrollment and reporting processes make comparisons challenging and not particularly informative. Nonetheless, diagnostic yield in an undiagnosed cohort reflects the potential of an Undiagnosed Diseases Program. Further comparisons and exploration of the outcomes of Undiagnosed Diseases Programs worldwide will allow for the development and improvement of the diagnostic and research process and in turn improve the value and utility of an Undiagnosed Diseases Program.
Epidemiology of ischemic stroke and hemorrhagic stroke in venoarterial extracorporeal membrane oxygenation
Authors: Hwang Jaeho , Kalra Andrew , Shou Benjamin L. , Whitman Glenn , Wilcox Christopher , Brodie Daniel , Zaaqoq Akram M. , Lorusso Roberto , Uchino Ken , Cho Sung-Min
Published: November 2023

Background

While venoarterial extracorporeal membrane oxygenation (V-A ECMO) provides lifesaving support for cardiopulmonary failure, complications may increase mortality, with few studies focusing on ischemic/hemorrhagic stroke. We aimed to determine the trends and associations of stroke incidence and mortality, and their risk factors, including the effects of annual case volumes of ECMO centers.

Methods

Retrospective analysis was performed on the Extracorporeal Life Support Organization (ELSO) registry, including adult V-A ECMO patients from 534 international centers between 2012 and 2021, excluding extracorporeal cardiopulmonary resuscitation. Temporal trend analyses were performed for stroke incidence and mortality. Univariate testing, multivariable regression, and survival analysis were used to evaluate the associations of stroke, 90-day mortality, and impact of annual center volume.

Results

Of 33,041 patients, 20,297 had mortality data, and 12,327 were included in the logistic regression. Between 2012 and 2021, ischemic stroke incidence increased (p < 0.0001), hemorrhagic stroke incidence remained stable, and overall 90-day mortality declined (p < 0.0001). Higher 24-h PaO2 and greater decrease between pre-ECMO PaCO2 and post-cannulation 24-h PaCO2 were associated with greater ischemic stroke incidence, while annual case volume was not. Ischemic/hemorrhagic strokes were associated with increased 90-day mortality (both p < 0.0001), while higher annual case volume was associated with lower 90-day mortality (p = 0.001). Hazard of death was highest in the first several days of V-A ECMO.

Conclusion

In V-A ECMO patients between 2012 and 2021, 90-day mortality decreased, while ischemic stroke incidence increased. ELSO centers with higher annual case volumes had lower mortality, but were not associated with ischemic/hemorrhagic stroke incidence. Both ischemic/hemorrhagic strokes were associated with increased mortality.