bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further evidence of biallelic variants in KCNK18 as a cause of intellectual disability and epilepsy with febrile seizure plus
Authors: Majethia Purvi , Harish Rhea , Narayanan Dhanya Lakshmi , B L Yatheesha , Sharma Suvasini , Shukla Anju 
Published: May 2023

Introduction

KCNK18, a potassium channel subfamily K member 18 (MIM*613655), encodes for TWIK-related spinal cord K+ channel (TRESK) and is important for maintaining neuronal excitability. Monoallelic variants in KCNK18 are known to cause autosomal dominant migraine, with or without aura, susceptibility to, 13 (MIM#613656). Recently, biallelic missense variants in KCNK18 have been reported in three individuals from a non-consanguineous family with intellectual disability, developmental delay, autism spectrum disorder (ASD), and seizure.

Methods
Singleton exome sequencing was performed for the proband after detailed clinical evaluation to identify the disease-causing variants in concordance with the phenotype.

Results
We herein report an individual with intellectual disability, developmental delay, ASD, and epilepsy with febrile seizure plus with a novel homozygous stopgain variant, c.499C>T p.(Arg167Ter) in KCNK18.

Conclusion
This report further validates KCNK18 as a cause of autosomal recessive intellectual disability, epilepsy, and ASD.
Nanomedicine in kidney disease
Authors: Bishop Boaz , Sharma Swagat , Scott Evan A. 
Published: May 2023

Purpose of review
The pathophysiological understanding of kidney-related disorders has profoundly increased; however, tissue-specific and cell-specific treatments in this field remain scarce. Advances in nanomedicine enable alteration of pharmacokinetics and targeted treatments improving efficiency and reducing toxicity. This review addresses recent developments of nanocarriers used for various purposes in the broad field of kidney disease, which may pave a path to therapeutic and diagnostic solutions for kidney disease.

Recent findings
Controlled delivery of antiproliferative medications enables improved treatment of polycystic kidney disease and fibrosis. Directed anti-inflammatory treatment mitigated glomerulonephritis and tubulointerstitial nephritis. Multiple injury pathways in AKI have been targeted, with therapeutic solutions for oxidative stress, mitochondrial dysfunction, local inflammation and improving self-repair mechanisms. In addition to such treatment development, noninvasive early detection methods (minutes after ischemic insult) have been demonstrated as well. Sustained release of therapies that reduce ischemia–reperfusion injury as well as new aspects for immunosuppression bring hope to improving kidney transplant outcomes. The latest breakthroughs in gene therapy are made achievable by engineering the targeted delivery of nucleic acids for new treatments of kidney disease.

Summary
Recent advances in nanotechnology and pathophysiological understanding of kidney diseases show potential for translatable therapeutic and diagnostic interventions in multiple etiologies of kidney disease.
Kidney clearance of fibroblast growth factor-23 in humans
Authors: Sharma Shilpa , Ix Joachim H. 
Published: May 2023

Purpose of review
Recent studies have shed light on factors influencing FGF23 regulation in terms of its production and cleavage. However, less is known about FGF23 elimination from circulation. The kidney's role in FGF23 elimination will be the focus of this review.

Recent findings
Marked abnormalities in FGF23 physiology have been observed in persons with reduced kidney function compared with healthy persons and raise the question of whether the kidney may be directly regulating FGF23 concentrations. FGF23 concentrations rise dramatically after onset of acute kidney injury and early chronic kidney disease and are associated with poor clinical outcomes. New studies leveraging measurements of FGF23 in the aorta and renal veins concurrently demonstrate that the human kidney efficiently extracts both intact and C-terminal FGF23 from the circulation independent of kidney function and catabolize the hormone. Additionally, the kidney's reduction of PTH predicts the amount it will reduce both C-terminal and intact FGF23.

Summary
The human kidney removes both intact FGF23 and its C-terminal fragments. FGF23 catabolism within the kidney may be influenced by PTH concentrations, and other factors. Future studies to understand regulation of these hormones and the kidney's role in this interplay are timely.
A Targeted Analysis of Serial Cytokine Measures and Nonpulmonary Organ System Failure in Children With Acute Respiratory Failure: Individual Measures and Trajectories Over Time
Authors: Ardila Silvia M. , Weeks Heidi M. , Dahmer Mary K. , Kaciroti Niko , Quasney Michael , Sapru Anil , Curley Martha A. Q. , Flori Heidi R. ,   for the Biomarkers in Children with Acute Lung Injury (BALI) and Randomized Evaluation for Sedation Titration for Respiratory Failure (RESTORE) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: May 2023

OBJECTIVES:
There is a need for research exploring the temporal trends of nonpulmonary organ dysfunction (NPOD) and biomarkers in order to identify unique predictive or prognostic phenotypes. We examined the associations between the number and trajectories of NPODs and plasma biomarkers of early and late inflammatory cascade activation, specifically plasma interleukin-1 receptor antagonist (IL-1ra) and interleukin-8 (IL-8), respectively, in the setting of acute respiratory failure (ARF).

DESIGN:
Secondary analysis of the Randomized Evaluation for Sedation Titration for Respiratory Failure clinical trial and Biomarkers in Acute Lung Injury (BALI) ancillary study.

SETTING:
Multicenter.

PATIENTS:
Intubated pediatric patients with ARF.

INTERVENTIONS:
NPODs were evaluated against plasma IL-1ra and IL-8 levels on individual days (1 to 4 d after intubation) and longitudinally across days.

MEASUREMENTS AND MAIN RESULTS:
Within the BALI cohort, 432 patients had at least one value for IL-1ra or IL-8 within days 0 through 5. 36.6% had a primary diagnosis of pneumonia, 18.5% had a primary diagnosis of sepsis and 8.1% died. Multivariable logistic regression models showed that increasing levels of both plasma IL-1ra and IL-8 were statistically significantly associated with increasing numbers of NPODs (IL-1ra: days 1–3; IL-8: days 1–4), independent of sepsis diagnosis, severity of oxygenation defect, age, and race/ethnicity. Longitudinal trajectory analysis identified four distinct NPOD trajectories and seven distinct plasma IL-1ra and IL-8 trajectories. Multivariable ordinal logistic regression revealed that specific IL-1ra and IL-8 trajectory groups were associated with greater NPOD trajectory group (p = 0.004 and p < 0.0001, respectively), independent of severity of oxygenation defect, age, sepsis diagnosis, and race/ethnicity.

CONCLUSIONS:
Both the inflammatory biomarkers and number of NPODs exhibit distinct trajectories over time with strong associations with one another. These biomarkers and their trajectory patterns may be useful in evaluating the severity of multiple organ dysfunction syndrome in critically ill children and identifying those phenotypes with time-sensitive, treatable traits.
Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndromes
Authors: Sabile Jean , Pavletic Steven , Migdady Yazan 
Published: May 2023

Abstract
Myelodysplastic syndromes (MDSs) are characterized by a clonal proliferation of hematopoietic stem cells with potential life-threatening cytopenia(s) and transformation to acute myeloid leukemia. Individualized risk stratification is evolving with new molecular models, such as the Molecular International Prognostic Scoring System, for better estimation of leukemic transformation and overall survival. The only potential cure for MDSs is allogeneic transplant, although it is underutilized in MDSs because of advanced patient age and multiple comorbidities. Optimization of transplant relies on improved identification of high-risk patients pretransplant, using targeted therapies leading to deeper molecular response, developing lower toxicity conditioning regimens, engineering better molecular tools for early detection and relapse monitoring, and adding maintenance treatment strategies for high-risk patients posttransplant. This review provides an overview of transplant in MDSs with updates, future directions, and role for novel therapies.
Changing Characteristics of HIV-Positive Gay and Bisexual Men's Relationships in the Era of Biomedical Prevention
Authors: Broady Timothy R. , Chan Curtis , MacGibbon James , Mao Limin , Prestage Garrett , Clifton Brent , Paynter Heath , Bavinton Benjamin R. , Holt Martin 
Published: May 2023

Objective:
To assess changes in personal and relationship characteristics among HIV-positive Australian gay and bisexual men (GBM) as rates of antiretroviral therapy and knowledge and confidence regarding the effectiveness of viral suppression in preventing HIV transmission have increased.

Design:
Repeated behavioral surveillance of GBM recruited from venues, events, and online in 7 Australian states and territories.

Methods:
HIV-positive participants were included. Trends in demographics, HIV treatment, and relationship characteristics were assessed with binary and multivariable logistic regression.

Results:
A total of 3643 survey responses (2016–2020) were included. Over time, HIV-positive GBM became less likely to identify as gay or report an Anglo-Australian ethnicity. The average length of time since HIV diagnosis increased and the frequency of attending HIV-related clinical appointments decreased. There were no changes in the reported number of recent sex partners or proportion reporting regular male partners over time. Among HIV-positive GBM in relationships, the proportion reporting HIV-positive partners decreased and the proportion reporting HIV-negative partners increased. Levels of condomless sex with regular partners increased over time; however, this was concentrated among HIV-positive GBM in serodiscordant relationships.

Conclusion:
Findings suggest that increased accessibility and trust in biomedical prevention strategies have contributed to broader relationship and sexual opportunities for HIV-positive GBM in Australia. Our findings suggest that future health promotion activities could highlight the social and relationship benefits of treatment as prevention to further increase trust in it as an HIV prevention strategy among GBM.
Traditional and faith-based healthcare in the management of psychotic disorders in Africa: in search for synergy
Authors: van der Zeijst Martine C.E. , Veling Wim , Chiliza Bonginkosi , Hoek Hans W. 
Published: May 2023

Purpose of review
This review summarizes the current literature on the role of traditional and faith-based healthcare in the management of psychotic disorders in Africa.

Recent findings
In contemporary Africa, individuals with psychosis and traditional and faith healers (TFH) are pluralistic towards their understanding of psychosis and their help-seeking behaviour. Traditional healing is perceived to be helpful to patients with psychotic disorders and their family members and may have a positive influence on the course of psychosis in some selected individuals. Studies show that potentially harmful practices are commonly used by African TFH, but that these are associated with a lack of resources and are susceptible to training. Although various TFH and biomedical practitioners are open to collaboration, the many identified obstacles hinder actual partnerships. However, the few studies that have been conducted on collaborative care for patients with psychotic disorders on the continent, show positive outcomes.

Summary
Rather than harmonizing the two healing paradigms, synergistic collaboration between traditional/faith-based and biomedical mental healthcare in the management of individuals with psychosis seems to be possible within certain limits. Synergistic collaboration is more culturally syntonic and may actually contribute to bridging the treatment gap for mental disorders in present-day Africa.
Analysis of lncRNA, miRNA, mRNA-associated ceRNA networks in Autism
Authors: Azad Asal Tabatabaei , Mehrabi Mohammad-Reza , Zarinzad Yasamin , Noori Atefeh , Nemati Hossein , Shahbazi Amir , Badameh Parisa , Mohammadnezad kenari Seyed Roham , Arabzadeh Parham , Javanmard Amir-Reza 
Published: May 2023

AbstractAutism is a multifactorial behavioral disease, which is caused by different environmental and genetic alterations. In this disease, various molecular pathways such as inflammation and cell-cell connections are affected. In this study, by analyzing RNA-seq data and bioinformatics approaches, candidate genes were selected for further analysis, and the expression of candidate genes in the blood samples of autistic people was compared to normal. Finally, the candidate genes showed potential as biological markers for prognosis in autism. Through the analysis of these candidate genes, the researchers were able to identify changes in the expression of certain genes that were associated with the disease. By understanding how these genes are involved in the disease, researchers can develop better treatments and diagnose the disease earlier.
Mechanism Underlying the Immune Responses of a Sublingual Vaccine for SARS-CoV-2 with RBD Antigen and Adjuvant, Poly(I:C) or AddaS03, in Non-human Primates
Authors: Yamamoto Tetsuro , Mitsunaga Fusako , Wasaki Kunihiko , Kotani Atsushi , Tajima Kazuki , Tanji Masanori , Nakamura Shin 
Published: May 2023

AbstractA sublingual vaccine formulated with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and Poly(I:C)) adjuvant was assessed for its safety in non-human primates. This Poly(I:C)-adjuvanted sublingual vaccine was safe compared to the AddaS03-adjuvanted vaccine in blood tests and plasma CRP. The safety of the vaccine was also confirmed through quantitative reverse transcription PCR of six genes and ELISA of four cytokines associated with inflammation and related reactions. The Poly(I:C)- or AddaS03-adjuvanted sublingual vaccine produced RBD-specific IgA antibodies in nasal washings, saliva, and plasma. SARS-CoV-2 neutralizing antibodies were detected in plasma, suggesting that adjuvanted-sublingual vaccines protect against SARS-CoV-2 infection. “Yin and Yang”-like unique transcriptional regulation was observed through DNA microarray analyses of white blood cell RNAs from both vaccines, suppressing and enhancing immune responses and up- or downregulating genes associated with these immune responses. Poly(I:C) adjuvanted sublingual vaccination induced atypical up- or downregulation of genes related to immune suppression or tolerance; Treg differentiation; and T-cell exhaustion. Therefore, Poly(I:C) adjuvant is safe and favorable for sublingual vaccination and can induce a balanced “Yin/Yang” -like effect on immune responses.
Clonal Hematopoiesis of Indeterminate Potential in Patients with Chronic Thromboembolic Pulmonary Hypertension
Authors: Liu Chao , Cheng Chun-Yan , Lian Tian-Yu , Zhou Yu-Ping , Yang Yin-Jian , Zhang Si-Jin , Wei Yun-Peng , Zhu Yong-Jian , Qiu Lu-Hong , Qiu Bao-Chen , Ren Li-Yan , Ma Jing-Si , Li Ruo-Nan , Wang Jia , Shen Ying-Hui-Zi , Han Zhi-Yan , Li Jing-Hui , Zhao Qin-Hua , Wang Lan , Xu Xi-Qi , Sun Kai , Wang Duo-Lao , Zhang Ze-Jian , Jing Zhi-Cheng 
Published: May 2023

AbstractBackgroundThe pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex and multifactorial, with growing evidence indicating the involvement of hematologic disorders. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with increased risks of both hematologic malignancies and cardiovascular diseases. The CHIP in patients with CTEPH and its clinical relevance remain undetermined.MethodsWe performed a step-wise calling method on the next-generation sequencing data from 499 CTEPH patients referred to three centers between October 2006 and December 2021 to identify CHIP mutations. We associated CHIP with all-cause mortality in patients with CTEPH. To provide potential mechanistic insights, the associations between CHIP and inflammation characteristics reflected by circulating cytokines and IgG galactosylation, a hallmark of inflammatory state in diseases were also determined.ResultsTotal 51 (10.2%) patients with CTEPH carried at least one CHIP mutation at a variant allele frequency of ≥ 2%, and the most common mutations were amongDNMT3A,RUN1andSTAG2. During a mean follow-up time of 55 months, deaths occurred in 21 patients (42.9%) in the CHIP group and 105 patients (24.3%) in the non-CHIP group, contributing to the 5-year survival rate of 65.3% in the CHIP group and 81.9% in the non-CHIP group (P< 0.001 for log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (HR: 3.447; 95% CI: 1.747 – 6.803;P< 0.001). Besides, patients in the CHIP group showed higher circulating IL-1beta and IL-6 and lower IL-4 and IgG galactosylation compared with the non-CHIP group.ConclusionsCHIP is enriched in CTEPH patients and is associated with a worse prognosis in CTEPH. Mechanically, patients in the CHIP group showed a more severe inflammatory state.Clinical PerspectiveWhat is new?Clonal hematopoiesis of indeterminate potential (CHIP) mutations are enriched in chronic thromboembolic pulmonary hypertension (CTEPH) patients, with most common mutated genes beingDNMT3A,RUN1andSTAG2.CHIP is associated with worse clinical outcomes in CTEPH.CHIP is associated with more severe inflammation state mediated by myeloid as well as lymphoid cells in patients with CTEPH.What are the clinical implications?CHIP might be a risk factor for CTEPH, suggesting a relationship between CTEPH and hematopoietic disorders.CHIP represented an additional disease component in CTEPH that independently impacts prognosis.CHIP might be a potential target for personalized medicine and an indicator of benefit from anti-inflammatory therapies for CTEPH patients.
Intravenous thrombolysis prior to endovascular treatment in posterior circulation occlusions; a MR CLEAN Registry study
Authors: Knapen R.R.M.M. , Pirson F.A.V. , Langezaal L.C.M. , Brouwer J. , Majoie C.B. , Emmer B.J. , Vos J.A. , van Doormaal P.J. , Yoo A.J. , Bruggeman A.A.E. , Nijeholt G.J. Lycklama à , van der Leij C. , van Oostenbrugge R.J. , van Zwam W.H. , Schonewille W.J. 
Published: May 2023

AbstractBackground and aimsThe effectiveness of intravenous thrombolysis (IVT) prior to endovascular treatment (EVT) has been investigated in randomized trials and meta-analyses. These studies mainly concerned anterior circulation occlusions. We aimed to investigate clinical, technical, and safety outcomes of IVT prior to EVT in posterior circulation occlusions in a nationwide registry.MethodsPatients were included from the MR CLEAN Registry: a nationwide, prospective, multicenter registry of patients with acute ischemic stroke (AIS) due to a large intracranial vessel occlusion receiving EVT between 2014 and 2019. All patients with a posterior circulation occlusion were included. Primary outcome was a shift towards better functional outcome on the modified Rankin scale (mRS) at 90 days. Secondary outcomes were favorable functional outcome (mRS 0-3), occurrence of symptomatic intracranial hemorrhages (sICH), successful reperfusion (eTICI≥2B), first-attempt successful reperfusion, and mortality at 90 days. Regression analyses with adjustments based on univariate analyses and literature were applied.ResultsA total of 248 patients were included, who received either IVT (n=125) or no IVT (n=123) prior to EVT. Results show no differences in a shift on the mRS (acOR:1.04, 95%CI:0.61-1.76). Although sICH occurred more often in the IVT group (4.8% versus 2.4%), regression analysis did not show a significant difference (aOR:1.65, 95%CI:0.33-8.35). Successful reperfusion, favorable functional outcome, first-attempt successful reperfusion, and mortality did not differ between patients treated with and without IVT.ConclusionsWe found no significant differences in clinical, technical and safety outcomes between patients with a large vessel occlusion in the posterior circulation treated with or without IVT prior to endovascular therapy. Our results are in line with the literature on the anterior circulation.
Predicting structures of large protein assemblies using combinatorial assembly algorithm and AlphaFold2
Authors: Shor Ben , Schneidman-Duhovny Dina 
Published: May 2023

AbstractDeep learning models, such as AlphaFold2 and RosettaFold, enable high-accuracy protein structure prediction. However, large protein complexes are still challenging to predict due to their size and the complexity of interactions between multiple subunits. Here we present CombFold, a combinatorial and hierarchical assembly algorithm for predicting structures of large protein complexes utilizing pairwise interactions between subunits predicted by AlphaFold2. CombFold accurately predicted (TM-score > 0.7) 72% of the complexes among the Top-10 predictions in two datasets of 60 large, asymmetric assemblies. Moreover, the structural coverage of predicted complexes was 20% higher compared to corresponding PDB entries. We applied the method on complexes from Complex Portal with known stoichiometry but without known structure and obtained high-confidence predictions. CombFold supports the integration of distance restraints based on crosslinking mass spectrometry and fast enumeration of possible complex stoichiometries. CombFold’s high accuracy makes it a promising tool for expanding structural coverage beyond monomeric proteins.
The performance of major airports in the Europe, North America and Asia
Authors: Park Jae-Woo , Roh Saeyeon , Jang Hyunmi , Seo Young-Joon 
Published: May 2023

Purpose This study aims to provide a meaningful comparison of airports’ performance and better understand the differences observed in the analysed airport performance by presenting a model to analyse the relationship between operational and financial performance and airport characteristics.Design/methodology/approach This study uses a quantitative analysis approach. The Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) and entropy weight were utilised to analyse 17 airports in three Airports Council International regions: Asia, Europe and North America. Through operational and financial factors, these sample airports identified the most efficiently operated airports from 2016 to 2019.Findings Overall, Asian airports were superior in operational and financial efficiency. Unlike operating performance, the sample airport’s financial and total performance results show a similar trend. There were no noticeable changes in operational factors. Therefore, differences in financial variables for each airport may affect the total performance.Practical implications This study provides insightful implications for airport policymakers to establish a standardised information disclosure foundation for consistent analysis and encourage airports to provide this information.Originality/value The adoption of Earnings Before Interest, Taxes, Depreciation, and Amortisation (EBITDA) to debt ratio and EBITDA per passenger, which had previously been underutilised in the previous study as financial factors, demonstrated differences between airports for airport stakeholders. In addition, the study presented a model that facilitates producing more intuitive results using TOPSIS, which was relatively underutilised compared to other methodologies such as date envelopment analysis.