bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prognostic Predictors of Airway Stenting in Malignant Airway Involvement From Esophageal Carcinoma
Authors: Leelayuwatanakul Nophol , Thanthitaweewat Vorawut , Wongsrichanalai Virissorn , Lertbutsayanukul Chawalit , Prayongrat Anussara , Kitpanit Sarin , Sriprasart Thitiwat 
Published: July 2022

Background:
In locoregional esophageal carcinoma (EC), airway involvement is the most common route of extraesophageal metastasis. The prognosis remains poor even with a multimodality approach. Although airway stenting is well known for restoration of the airway, the survival benefit is still lacking.

Methods:
A total of 37 of patients with airway involvement from EC who underwent airway stenting at a single institution from 2015 to 2020 were retrospectively reviewed. Survival curves after stent placement among different groups were analyzed using Kaplan-Meier method.

Results:
Of 37 patients, 34 were male, and the mean age was 58.9 years (42 to 80). EC was commonly located at midesophagus (51.4%). The site of airway involvement was left main bronchus (48.6%), trachea (32.4%), multiple sites (16.2%), and right main bronchus (2.7%). The nature of airway involvement was tumor invasion (91.9%), compression (62.2%), and fistula (37.8%). Twenty-three patients (62.2%) had airway involvement at the time of esophageal cancer diagnosis. Only 4 patients underwent esophageal stenting. The median survival time after stent placement was 97 days (5 to 539). Chemotherapy and/or radiotherapy were given before stent placement in 18 patients (48.6%). Treatment-naive before airway stenting and diagnosis of airway involvement at the same time of EC diagnosis were independent predictors for the increased survival after stent placement (P<0.05). Poststent treatment was associated with improved survival (P=0.002).

Conclusion:
In patients with malignant airway involvement from EC who underwent airway stenting, the prognostic predictors for improved survival were treatment-naive status, receiving treatment after airway stenting, and early-onset of airway involvement.
Synbiotics in the Management of Pediatric Gastrointestinal Disorders
Authors: Hojsak Iva , Kolaček Sanja , Mihatsch Walter , Mosca Alexis , Shamir Raanan , Szajewska Hania , Vandenplas Yvan ,   Working Group on Probiotics and Prebiotics of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, van den Akker Chris H. P. , Berni Canani Roberto , Dinleyici Ener Cagri , Domellof Magnus , van Goudoever Johannes B. , Guarino Alfredo , Gutierrez‐Castrellon Pedro , Indrio Flavia , Orel Rok , Salvatore Silvia , Weizman Zvi 
Published: July 2022

Background:Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders.Aim:The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.Methods:From existing literature databases, we searched and appraised all systematic reviews and/or meta‐analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well‐defined synbiotic were available.Results:Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children.Conclusions:There is a need for more, well‐designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter‐studies comparisons.
SARS-CoV-2 Non-Structural Protein 1(NSP1) Mutation Virulence and Natural Selection: Evolutionary Trends in the Six Continents
Authors: Salami Ghaleh Samira , Rahimian Karim , Mahmanzar Mohammadamin , Mahdavi Bahar , Tokhanbigli Samaneh , Mollapour Sisakht Mahsa , Farhadi Amin , Mousakhan Bakhtiari Mahsa , Lee Kuehu Donna , Deng Youping 
Published: July 2022

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unsegmented positivesense single-stranded RNA virus that belongs to the β-coronavirus. This virus was the cause of a novel severe acute respiratory syndrome in 2019 (COVID-19) that emerged in Wuhan, China at the early stage of the pandemic and rapidly spread around the world. Rapid transmission and reproduction of SARS-CoV-2 threaten worldwide health with a high mortality rate from the virus. According to the significant role of non-structural protein 1 (NSP1) in inhibiting host mRNA translation, this study focuses on the link between amino acid sequences of NSP1 and alterations of them spreading around the world. The SARS-CoV-2 NSP1 protein sequences were analyzed and FASTA files were processed by Python language programming libraries. Reference sequences compared with each NSP1 sample to identify every mutation and categorize them were based on continents and frequencies. NSP1 mutations rate divided into continents were different. Based on continental studies, E87D in global vision and also in Europe notably increased. The E87D mutation has significantly risen especially in the last months of the study as the first frequent mutation observed. The remarkable mutations, H110Y and R24C, have the second and third frequencies, respectively. Based on this mutational information, despite NSP1 being a conserved sequence occurrence, these mutations change the rate of flexibility and stability of the NSP1 protein, which can eventually affect inhibiting the host translation.IMPORTANCEIn this study, we analyzed 6,510,947 sequences of non-structural protein 1 as a conserved region of SARS-CoV-2. According to the obtained results, 93.4819% of samples had no mutant regions on their amino acid sequences. Heat map data of mutational samples demonstrated high percentages of mutations that occurred in the region of 72 to 126 amino acids indicating a hot spot region of the protein. Increased rates of E87D, H110Y, and R24C mutations in the timeline of our study were reported as significant compared to available mutant samples. Analyzing the details of replacing amino acids in the most frequent E87D mutation reveals the role of this alteration in increasing molecule flexibility and destabilizing the structure of the protein.
Trophoblast glycoprotein is required for efficient synaptic vesicle exocytosis from retinal rod bipolar cells
Authors: Wakeham Colin M , Shi Qing , Ren Gaoying , Haley Tammie L , Duvoisin Robert M , von Gersdorff Henrique , Morgans Catherine W 
Published: July 2022

AbstractRod bipolar cells (RBCs) faithfully transmit light-driven signals from rod photoreceptors in the outer retina to third order neurons in the inner retina. Recently, significant work has focused on the role of leucine-rich repeat (LRR) proteins in synaptic development and signal transduction at RBC synapses. We previously identified trophoblast glycoprotein (TPBG) as a novel transmembrane LRR protein localized to the dendrites and axon terminals of RBCs. We now examine the effects on RBC physiology and retinal processing of TPBG genetic knockout in mice using immunofluorescence and electrophysiological techniques. The scotopic electroretinogram showed a modest increase in the b-wave and a marked attenuation in oscillatory potentials in the TPBG knockout. No effect of TPBG knockout was observed on the RBC dendritic morphology, TRPM1 currents, or RBC excitability. Because scotopic oscillatory potentials primarily reflect RBC-driven rhythmic activity of the inner retina, we investigated the contribution of TPBG to downstream transmission from RBCs to third-order neurons. Using electron microscopy, we found shorter synaptic ribbons in TPBG knockout axon terminals in RBCs. Time-resolved capacitance measurements indicated that TPBG knockout reduces synaptic vesicle exocytosis and subsequent GABAergic reciprocal feedback without altering voltage-gated Ca2+currents. Thus, TPBG is required for normal synaptic ribbon development and efficient neurotransmitter release from RBCs to downstream cells. Our results highlight a novel synaptic role for TPBG at RBC ribbon synapses and support further examination into the mechanisms by which TPBG regulates RBC physiology.Graphical abstract
A Markov constraint to uniquely identify elementary flux mode weights in unimolecular metabolic networks
Authors: Chitpin Justin G. , Perkins Theodore J. 
Published: July 2022

AbstractElementary flux modes (EFMs) are minimal, steady state pathways characterizing a flux network. Fundamentally, all steady state fluxes in a network are decomposable into a linear combination of EFMs. While there is typically no unique set of EFM weights that reconstructs these fluxes, several optimization-based methods have been proposed to constrain the solution space by enforcing some notion of parsimony. However, it has long been recognized that optimization-based approaches may fail to uniquely identify EFM weights and return different feasible solutions across objective functions and solvers. Here we show that, for flux networks only involving single molecule transformations, these problems can be avoided by imposing a Markovian constraint on EFM weights. Our Markovian constraint guarantees a unique solution to the flux decomposition problem, and that solution is arguably more biophysically plausible than other solutions. We describe an algorithm for computing Markovian EFM weights via steady state analysis of a certain discrete-time Markov chain, based on the flux network, which we call the cycle-history Markov chain. We demonstrate our method with a differential analysis of EFM activity in a lipid metabolic network comparing healthy and Alzheimer’s disease patients. Our method is the first to uniquely decompose steady state fluxes into EFM weights for any unimolecular metabolic network.
Rho of plant GTPase MxROP1 regulates Fe deficiency responses by targeting Zinc Ribbon 3 in apple rootstock
Authors: Li Keting , Zhai Longmei , Jiang Lizhong , Sun Qiran , Wu Ting , Zhang Xinzhong , Xu Xuefeng , Han Zhenhai , Wang Yi 
Published: July 2022

ABSTRACTSmall G protein is a multifunctional molecular switch that can regulate plant growth, development and responses to the environment. However, how Rho-related GTPase of plants (ROPs) regulates the response to Fe deficiency has not been well clarified. Here, we found that Fe deficiency induced MxROP1 in Malus xiaojinensis at both the transcriptional and translational levels. The overexpression of MxROP1, MxROP1DN (inactive form) and MxROP1CA (active form) in apple roots increased the activity of ferric chelate reductase and the ability to acidify the rhizosphere, and lines that overexpressed MxROP1DN exhibited the strongest reaction to enhance Fe uptake. Yeast two-hybrid library screening indicated that MxROP1 interacted with ZR3.1, a DNL zinc finger protein that negatively regulates Fe deficiency responses. We further identified their interaction in vitro and in vivo using pull-down and bimolecular fluorescence complementation assays, respectively, and MxROP1DN-MxZR3.1 interacted the most strongly. Furthermore, MxROP1 negatively affected the stability of MxZR3.1 protein in vitro as shown by a cell semi-degradation assay, and the application of MG132 inhibited the degradation of MxZR3.1-HIS proteins. This indicated that MxROP1 caused the degradation of MxZR3.1 protein through the 26S proteasome pathway. Similar results were found in OE-MxROP1+OE-MxZR3.1 transgenic apple callus compared with those in the OE-MxZR3.1 callus. We also demonstrated that MxZR3.1 interacted with MxbHLH39, a known positive transcription factor and core component of Fe deficiency, and MxROP1 affected the interaction of MxZR3.1-MxbHLH39 using a competitive binding assay. This illuminated one MxROP1-MxZR3.1-MxbHLH39 pathway that maintains Fe homeostasis in M. xiaojinensis.
Examining the Influence of the Budget Execution Processes on the Efficiency of County Health Systems in Kenya
Authors: Musiega Anita , Tsofa Benjamin , Nyawira Lizah , Njuguna Rebecca G , Munywoki Joshua , Hanson Kara , Mulwa Andrew , Molyneux Sassy , Maina Isabel , Normand Charles , Jemutai Julie , Barasa Edwine 
Published: July 2022

ABSTRACTPublic Financial Management (PFM) processes are a driver of health system efficiency. The budget execution process is the stage in the PFM cycle where health system inputs are translated into outputs and outcomes. This study examined how the budget execution process influenced the efficiency of county health systems in Kenya. We conducted a concurrent mixed methods case study using counties classified as relatively efficient (n=2) and relatively inefficient (n=2) in a related quantitative analysis as our cases. We developed a conceptual framework from a literature review to guide the development of tools and analysis. We collected qualitative data through document reviews, and in-depth interviews (n=70) with actors from health and finance sectors at the national and county level. We collected quantitative data from secondary sources, including budgets and budget reports. We analyzed qualitative data using the thematic approach and carried out descriptive analyses on quantitative data. The budget execution processes within counties in Kenya were characterized by poor budget credibility, cash disbursement delays, limited provider autonomy, and poor procurement practices. These challenges were linked to an inappropriate input mix that compromised the capacity of county health systems to deliver healthcare services, misalignment between county health needs and the use of resources, reduced staff motivation and productivity, procurement inefficiencies, and reduced county accountability for finances and performance. The efficiency of county health systems in Kenya can be enhanced by improving budget credibility, cash disbursement processes, procurement processes and improved provider autonomy.
Epigenome-wide meta-analysis of BMI in nine cohorts: examining the utility of epigenetic BMI in predicting metabolic health
Authors: Do Whitney L. , Sun Dianjianyi , Meeks Karlijn , Dugue Pierre-Antoine , Demerath Ellen , Guan Weihua , Li Shengxu , Chen Wei , Milne Roger , Adeyemo Abedowale , Agyemang Charles , Nassir Rami , Manson JoAnn , Shadyab Aladdin H , Hou Lifang , Horvath Steve , Assimes Themistocles L. , Bhatti Parveen , Jordahl Kristina , Baccarelli Andrea , Smith Alicia , Staimez Lisa R. , Stein Aryeh , Whitsel Eric A. , Venkat Narayan K.M. , Conneely Karen 
Published: July 2022

AbstractThis study sought to examine the association between DNA methylation and body mass index (BMI) and the potential utility of these cytosine-phosphate-guanine (CpG) sites in predicting metabolic health. We pooled summary statistics from six trans-ethnic EWAS of BMI representing nine cohorts (n=17058), replicated these findings in the Women’s Health Initiative (WHI, n=4822) and developed an epigenetic prediction score of BMI. In the pooled EWAS, 1265 CpG sites were associated with BMI (p<1E-7), and 1238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European descent and individuals of African descent. We found five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log normalized BMI in the WHI (80% training/20% testing). This model found 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides, and lower HDL-cholesterol and LDL-cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL-cholesterol and lower glucose and triglycerides. This study identified 553 previously identified and 685 novel CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.
Accurate sex prediction of cisgender and transgender individuals without brain size bias
Authors: Wiersch Lisa , Hamdan Sami , Hoffstaedter Felix , Votinov Mikhail , Habel Ute , Clemens Benjamin , Derntl Birgit , Eickhoff Simon B. , Patil Kaustubh R. , Weis Susanne 
Published: July 2022

AbstractBrain size differs substantially between human males and females. This difference in total intracranial volume (TIV) can cause bias when employing machine-learning approaches for the investigation of sex differences in brain morphology. TIV-biased models will likely not capture actual qualitative sex differences in brain organization but rather learn to classify an individual’s sex based on brain size differences, thus leading to spurious and misleading conclusions, for example when comparing brain morphology between cisgender- and transgender individuals. Here, TIV bias in sex classification models applied to cis- and transgender individuals was systematically investigated by controlling for brain size either through featurewise confound removal or by matching training samples for TIV. Our results provide evidence that non-TIV-biased models can classify the sex of both cis- and transgender individuals with high accuracy, highlighting the importance of appropriate modelling to avoid bias in automated decision making.TeaserAccurate non-biased structural sex classification in cis- and transgender individuals by matching training samples for TIV
REDIRECTION: Generating drug repurposing hypotheses using link prediction with DISNET data
Authors: Ayuso Muñoz Adrián , Carro Esther Ugarte , Prieto Santamaría Lucía , Carrasco Belén Otero , Ruiz Ernestina Menasalvas , Pérez Gallardo Yuliana , Rodríguez-González Alejandro 
Published: July 2022

AbstractIn the recent years and due to COVID-19 pandemic, drug repurposing or repositioning has been placed in the spotlight. Giving new therapeutic uses to already existing drugs, this discipline allows to streamline the drug discovery process, reducing the costs and risks inherent to de novo development. Computational approaches have gained momentum, and emerging techniques from the machine learning domain have proved themselves as highly exploitable means for repurposing prediction. Against this backdrop, one can find that biomedical data can be represented in terms of graphs, which allow depicting in a very expressive manner the underlying structure of the information. Combining these graph data structures with deep learning models enhances the prediction of new links, such as potential disease-drug connections. In this paper, we present a new model named REDIRECTION, which aim is to predict new disease-drug links in the context of drug repurposing. It has been trained with a part of the DISNET biomedical graph, formed by diseases, symptoms, drugs, and their relationships. The reserved testing graph for the evaluation has yielded to an AUROC of 0.93 and an AUPRC of 0.90. We have performed a secondary validation of REDIRECTION using RepoDB data as the testing set, which has led to an AUROC of 0.87 and a AUPRC of 0.83. In the light of these results, we believe that REDIRECTION can be a meaningful and promising tool to generate drug repurposing hypotheses.
Distinctive chaperonopathy in skeletal muscle associated with the dominant variant inDNAJB4
Authors: Inoue Michio , Noguchi Satoru , Inoue Yukiko U. , Iida Aritoshi , Ogawa Megumu , Bengoechea Rocio , Pittman Sara K. , Hayashi Shinichiro , Watanabe Kazuki , Hosoi Yasushi , Sano Terunori , Takao Masaki , Oya Yasushi , Takahashi Yuji , Miyajima Hiroaki , Weihl Conrad C. , Inoue Takayoshi , Nishino Ichizo 
Published: July 2022

AbstractDnaJ homolog, subfamily B, member 4, a member of the heat shock protein 40 chaperones encoded byDNAJB4, is highly expressed in myofibers. We identified a heterozygous c.270 T>A (p.F90L) variant inDNAJB4in a family with a dominantly inherited distal myopathy, in which affected members have specific features on muscle pathology represented by the presence of cytoplasmic inclusions and the accumulation of desmin, p62, HSP70 and DNAJB4 predominantly in type 1 fibers. Both Dnajb4- F90L knock-in and knockout mice developed muscle weakness and recapitulated the patient muscle pathology in the soleus muscle, where DNAJB4 has the highest expression. These data indicate that the identified variant is causative resulting in defective chaperone function and selective muscle degeneration in specific muscle fibers. This study demonstrates the importance of DNAJB4 in skeletal muscle proteostasis by identifying the associated chaperonopathy.
Polycomb repression during S/G2 phases restrain initiation of cell differentiation to the G1 phase of the cell cycle
Authors: Asenjo Helena G. , Alcazar-Fabra María , Espinosa Mencía , Lopez-Onieva Lourdes , Gallardo Amador , Dimitrova Emilia , Feldmann Angelika , Pachano Tomas , Martorell-Marugán Jordi , Carmona-Sáez Pedro , Sanchez-Pozo Antonio , Rada-Iglesias Álvaro , Klose Robert J. , Landeira David 
Published: July 2022

AbstractThe potential of pluripotent cells to respond to developmental cues and trigger cell differentiation is enhanced during the G1 phase of the cell cycle, but the molecular mechanisms involved are poorly understood. Variations in polycomb activity during interphase progression have been hypothesized to regulate the cell-cycle-phase-dependent transcriptional activation of differentiation genes during lineage transition in pluripotent cells. Here, we asked whether the Polycomb Repressive Complex 1 (PRC1) modulates the ability of mouse embryonic stem cells (ESCs) to differentially respond to developmental cues depending on the phase of the cell cycle in which they are found. We discovered that recruitment of PRC1 complexes and their associated molecular functions, ubiquitination of H2AK119 and three-dimensional chromatin interactions, are enhanced during S and G2 phases compared to the G1 phase. In agreement with the accumulation of PRC1 at target promoters upon G1 phase exit, cells in S and G2 phases show firmer transcriptional repression of developmental regulator genes that is drastically perturbed upon genetic ablation of the PRC1 catalytic subunit Ring1b. Importantly, depletion of Ring1b during retinoic acid stimulation interferes with the preference of mESCs to induce the transcriptional activation of differentiation genes in G1 phase. We propose that incremental enrolment of polycomb repressive activity during interphase progression reduces the tendency of cells to respond to developmental cues during S and G2 phases, facilitating activation of cell differentiation in the G1 phase of the pluripotent cell cycle.