bluuebunny/crossref_metadata_2025_split huggingface dataset:
A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening
Authors: Chitale Shalaka , Wu Wenxuan , Mukherjee Avik , Lannon Herbert , Suresh Pooja , Nag Ishan , Ambrosi Christina M. , Gertner Rona S. , Melo Hendrick , Powers Brendan , Wilkins Hollin , Hinton Henry , Cheah Mickey , Boynton Zachariah , Alexeyev Alexander , Sword Duane , Basan Markus , Park Hongkun , Ham Donhee , Abbott Jeffrey 
Published: June 2023

AbstractProfiling compounds and genetic perturbations via high-content imaging has become increasingly popular for drug discovery, but the technique is limited to endpoint images of fixed cells. In contrast, electronic-based devices offer label-free, functional information of live cells, yet current approaches suffer from low-spatial resolution or single-well throughput. Here, we report a semiconductor 96-microplate platform designed for high-resolution real-time impedance “imaging” at scale. Each well features 4,096 electrodes at 25 µm spatial resolution while a miniaturized data interface allows 8× parallel plate operation (768 total wells) within each incubator for enhanced throughputs. New electric field-based, multi-frequency measurement techniques capture >20 parameter images including tissue barrier, cell-surface attachment, cell flatness, and motility every 15 min throughout experiments. Using these real-time readouts, we characterized 16 cell types, ranging from primary epithelial to suspension, and quantified heterogeneity in mixed epithelial and mesenchymal co-cultures. A proof-of-concept screen of 904 diverse compounds using 13 semiconductor microplates demonstrates the platform’s capability for mechanism of action (MOA) profiling with 25 distinct responses identified. The scalability of the semiconductor platform combined with the translatability of the high dimensional live-cell functional parameters expands high-throughput MOA profiling and phenotypic drug discovery applications.
Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma
Authors: Jacobse Justin , Aziz Zaryab , Sun Lili , Chaparro Jasmine , Pilat Jennifer M. , Kwag Aaron , Buendia Matthew , Wimbiscus Mae , Nasu Motomi , Saito Tsuyoshi , Mine Shinji , Orita Hajime , Revetta Frank , Short Sarah P. , Washington M. Kay , Hiremath Girish , Gibson Michael K. , Coburn Lori , Koyama Tatsuki , Goettel Jeremy A. , Williams Christopher S. , Choksi Yash A. 
Published: June 2023

AbstractBackground/AimsEosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown.MethodsEosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient (ΔdblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (Ccl11-/-). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils.ResultsActivated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cellCcl11expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models (Ccl11-/-mice, ΔdblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer.In vitroco-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. ΔdblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways.ConclusionEosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.
Learning Peptide Properties with Positive Examples Only
Authors: Ansari Mehrad , White Andrew D. 
Published: June 2023

AbstractDeep learning can create accurate predictive models by exploiting existing large-scale experimental data, and guide the design of molecules. However, a major barrier is the requirement of both positive and negative examples in the classical supervised learning frameworks. Notably, most peptide databases come with missing information and low number of observations on negative examples, as such sequences are hard to obtain using high-throughput screening methods. To address this challenge, we solely exploit the limited known positive examples in a semi-supervised setting, and discover peptide sequences that are likely to map to certain antimicrobial properties via positive-unlabeled learning (PU). In particular, we use the two learning strategies of adapting base classifier and reliable negative identification to build deep learning models for inferring solubility, hemolysis, binding against SHP-2, and non-fouling activity of peptides, given their sequence. We evaluate the predictive performance of our PU learning method and show that by only using the positive data, it can achieve competitive performance when compared with the classical positive-negative (PN) classification approach, where there is access to both positive and negative examples.
Can Quantum Chemistry Improve the understanding of Protein-Ligand Interactions? Implications for Structure Based Drug Discovery
Authors: Menezes Filipe , Fröhlich Tony , Popowicz Grzegorz M. 
Published: June 2023

ABSTRACTWe introduce an Energy Decomposition Analysis suitable for understanding the nature of non-covalent binding in large chemical systems, like those of drug-protein complexes. The method is atom specific, thus allowing rationalization of the role that each atom or functional group plays for the interaction. Visual representations are constructed in the form of interaction maps, depicting the different contributions for electrostatics, polarization, dispersion (lipophilicity),etc. This marks the departure from atomistic models towards electronic interaction ones, that better correlate with experimental data. The maps provide a quick access to the driving forces behind the formation of intermolecular complexes, and the key contributors for each interaction. This allows constructing quantum mechanical models of binding. The presented method is validated against experimental binding data for the difficult to target protein-protein interface for PEX14-PEX5 and its inhibitors.
scATAnno: Automated Cell Type Annotation for single-cell ATAC Sequencing Data
Authors: Jiang Yijia , Hu Zhirui , Lynch Allen W. , Jiang Junchen , Zhu Alexander , Zeng Ziqi , Zhang Yi , Wu Gongwei , Xie Yingtian , Li Rong , Zhou Ningxuan , Meyer Cliff , Cejas Paloma , Brown Myles , Long Henry W. , Qiu Xintao 
Published: June 2023

AbstractRecent advances in single-cell epigenomic techniques have created a growing demand for scATAC-seq analysis. One key analysis task is to determine cell type identity based on the epigenetic data. We introduce scATAnno, a python package designed to automatically annotate scATAC-seq data using large-scale scATAC-seq reference atlases. This workflow generates the reference atlases from publicly available datasets enabling accurate cell type annotation by integrating query data with reference atlases, without the use of scRNA-seq data. To enhance annotation accuracy, we have incorporated KNN-based and weighted distance-based uncertainty scores to effectively detect cell populations within the query data that are distinct from all cell types in the reference data. We compare and benchmark scATAnno against 7 other published approaches for cell annotation and show superior performance in multiple data sets and metrics. We showcase the utility of scATAnno across multiple datasets, including peripheral blood mononuclear cell (PBMC), Triple Negative Breast Cancer (TNBC), and basal cell carcinoma (BCC), and demonstrate that scATAnno accurately annotates cell types across conditions. Overall, scATAnno is a useful tool for scATAC-seq reference building and cell type annotation in scATAC-seq data and can aid in the interpretation of new scATAC-seq datasets in complex biological systems.
Catalytic activity of the Bin3/MEPCE methyltransferase domain is dispensable for 7SK snRNP function inDrosophila melanogaster
Authors: Palumbo Ryan J , Hanes Steven D 
Published: June 2023

ABSTRACTMethylphosphate Capping Enzyme (MEPCE) monomethylates the gamma phosphate at the 5’ end of the 7SK noncoding RNA, a modification thought to protect 7SK from degradation. 7SK serves as a scaffold for assembly of a snRNP complex that inhibits transcription by sequestering the positive elongation factor P-TEFb. While much is known about the biochemical activity of MEPCEin vitro, little is known about its functionsin vivo, or what roles— if any—there are for regions outside the conserved methyltransferase domain. Here, we investigated the role of Bin3, theDrosophilaortholog of MEPCE, and its conserved functional domains inDrosophiladevelopment. We found thatbin3mutant females had strongly reduced rates of egg-laying, which was rescued by genetic reduction of P-TEFb activity, suggesting that Bin3 promotes fecundity by repressing P-TEFb.bin3mutants also exhibited neuromuscular defects, analogous to a patient withMEPCEhaploinsufficiency. These defects were also rescued by genetic reduction of P-TEFb activity, suggesting that Bin3 and MEPCE have conserved roles in promoting neuromuscular function by repressing P-TEFb. Unexpectedly, we found that a Bin3 catalytic mutant (Bin3Y795A) could still bind and stabilize 7SK and rescue allbin3mutant phenotypes, indicating that Bin3 catalytic activity is dispensable for 7SK stability and snRNP functionin vivo. Finally, we identified a metazoan-specific motif (MSM) outside of the methyltransferase domain and generated mutant flies lacking this motif (Bin3ΔMSM). Bin3ΔMSMmutant flies exhibited some—but not all—bin3mutant phenotypes, suggesting that the MSM is required for a 7SK-independent, tissue-specific function of Bin3.
Zoledronic acid improves bone quality and muscle function in a high bone turnover state
Authors: Trivedi Trupti , Manaa Mohamed , John Sutha , Reiken Steven , Murthy Sreemala , Pagnotti Gabriel M. , Dole Neha S. , She Yun , Suresh Sukanya , Hain Brian A. , Regan Jenna , Ofer Rachel , Wright Laura , Robling Alex , Cao Xu , Alliston Tamara , Marks Andrew R. , Waning David L. , Mohammad Khalid S. , Guise Theresa A. 
Published: June 2023

SUMMARYZoledronic acid (ZA) prevents muscle weakness in mice with bone metastases; however, its role in muscle weakness in non-tumor-associated metabolic bone diseases and as an effective treatment modality for the prevention of muscle weakness associated with bone disorders, is unknown. We demonstrate the role of ZA-treatment on bone and muscle using a mouse model of accelerated bone remodeling, which represents the clinical manifestation of non-tumor associated metabolic bone disease. ZA increased bone mass and strength and rescued osteocyte lacunocanalicular organization. Short-term ZA treatment increased muscle mass, whereas prolonged, preventive treatment improved muscle mass and function. In these mice, muscle fiber-type shifted from oxidative to glycolytic and ZA restored normal muscle fiber distribution. By blocking TGFβ release from bone, ZA improved muscle function, promoted myoblast differentiation and stabilized Ryanodine Receptor-1 calcium channel. These data demonstrate the beneficial effects of ZA in maintaining bone health and preserving muscle mass and function in a model of metabolic bone disease.Context and significanceTGFβ is a bone regulatory molecule which is stored in bone matrix, released during bone remodeling, and must be maintained at an optimal level for the good health of the bone. Excess TGFβ causes several bone disorders and skeletal muscle weakness. Reducing excess TGFβ release from bone using zoledronic acid in mice not only improved bone volume and strength but also increased muscle mass, and muscle function. Progressive muscle weakness coexists with bone disorders, decreasing quality of life and increasing morbidity and mortality. Currently, there is a critical need for treatments improving muscle mass and function in patients with debilitating weakness. Zoledronic acid’s benefit extends beyond bone and could also be useful in treating muscle weakness associated with bone disorders.
Mapping theArabidopsis thalianaproteome in PeptideAtlas and the nature of the unobserved (dark) proteome; strategies towards a complete proteome
Authors: van Wijk Klaas J. , Leppert Tami , Sun Zhi , Kearly Alyssa , Li Margaret , Mendoza Luis , Guzchenko Isabell , Debley Erica , Sauermann Georgia , Routray Pratyush , Malhotra Sagunya , Nelson Andrew , Sun Qi , Deutsch Eric W. 
Published: June 2023

ABSTRACTThis study describes a new release of theArabidopsis thalianaPeptideAtlas proteomics resource providing protein sequence coverage, matched mass spectrometry (MS) spectra, selected PTMs, and metadata. 70 million MS/MS spectra were matched to the Araport11 annotation, identifying ∼0.6 million unique peptides and 18267 proteins at the highest confidence level and 3396 lower confidence proteins, together representing 78.6% of the predicted proteome. Additional identified proteins not predicted in Araport11 should be considered for building the next Arabidopsis genome annotation. This release identified 5198 phosphorylated proteins, 668 ubiquitinated proteins, 3050 N-terminally acetylated proteins and 864 lysine-acetylated proteins and mapped their PTM sites. MS support was lacking for 21.4% (5896 proteins) of the predicted Araport11 proteome – the ‘dark’ proteome. This dark proteome is highly enriched for certain (e.g.CLE, CEP, IDA, PSY) but not other (e.g.THIONIN, CAP,) signaling peptides families, E3 ligases, TFs, and other proteins with unfavorable physicochemical properties. A machine learning model trained on RNA expression data and protein properties predicts the probability for proteins to be detected. The model aids in discovery of proteins with short-half life (e.g.SIG1,3 and ERF-VII TFs) and completing the proteome. PeptideAtlas is linked to TAIR, JBrowse, PPDB, SUBA, UniProtKB and Plant PTM Viewer.
Combining Procedural and Behavioral Treatments for Chronic Low Back Pain: A Pilot Feasibility Randomized Controlled Trial
Authors: Tanus Adrienne D. , Nishio Isuta , Williams Rhonda , Friedly Janna , Soares Bosco , Anderson Derek , Bambara Jennifer , Dawson Timothy , Hsu Amy , Kim Peggy Y. , Krashin Daniel , Piero Larissa Del , Korpak Anna , Timmons Andrew , Suri Pradeep 
Published: June 2023

AbstractIndividual treatments for chronic low back pain (CLBP) have small magnitude effects. Combining different types of treatments may produce larger effects. This study used a 2×2 factorial randomized controlled trial (RCT) design to combine procedural and behavioral treatments for CLBP. The study aims were to: (1) assess feasibility of conducting a factorial RCT of these treatments; and (2) estimate individual and combined treatment effects of (a) lumbar radiofrequency ablation (LRFA) of the dorsal ramus medial branch nerves (vs. a simulated LRFA control procedure) and (b) Activity Tracker-Informed Video-Enabled Cognitive Behavioral Therapy program for CLBP (AcTIVE-CBT) (vs. an educational control treatment) on back-related disability at 3 months post-randomization. Participants (n=13) were randomized in a 1:1:1:1 ratio. Feasibility goals included an enrollment proportion ≥30%, a randomization proportion ≥80%, and a ≥80% proportion of randomized participants completing the 3-month Roland-Morris Disability Questionnaire (RMDQ) primary outcome endpoint. An intent-to-treat analysis was used. The enrollment proportion was 62%, the randomization proportion was 81%, and all randomized participants completed the primary outcome. Though not statistically significant, there was a beneficial, moderate-magnitude effect of LRFA vs. control on 3-month RMDQ (−3.25 RMDQ points; 95% CI: -10.18, 3.67). There was a significant, beneficial, large-magnitude effect of AcTIVE-CBT vs. control (−6.29, 95% CI: -10.97, -1.60). Though not statistically significant, there was a beneficial, large effect of LRFA+AcTIVE-CBT vs. control (−8.37; 95% CI: -21.47, 4.74). We conclude that it is feasible to conduct an RCT combining procedural and behavioral treatments for CLBP.ClinicalTrials.gov Registration:https://clinicaltrials.gov/ct2/show/NCT03520387
Awareness and use of Tranexamic Acid in the management of Postpartum Haemorrhage among health care providers in Enugu, Nigeria
Authors: Onwujekwe Ogochukwu , Mosanya Adaobi Uchenna , Ekwuazi Kingsley , Iyoke Chukwuemeka 
Published: June 2023

ABSTRACTObjectivesThis study was carried out to determine the knowledge, practice and barriers regarding the use of Tranexamic acid for the prevention and treatment of postpartum hemorrhage among health care providers in Enugu, Nigeria.MethodsA cross sectional study was carried out among health professionals (Doctors, Pharmacists and Nurses) in two Nigerian tertiary teaching hospitals. One is Federal and the other is State. A total of 220 questionnaires were distributed, 207 were collected back (response rate: 94%) and analyzed using SPSS for inferential statistics with level of significance at p < 0.05.ResultsOnly 23.7% of the respondents had good Knowledge (p<0.001). Good awareness of the recent WHO recommendation on the use of Tranexamic acid for Postpartum Haemorrhage was low (19.8%, <0.001). Majority of the respondents have neither prescribed nor dispensed it (30%; <0.001). Very few respondents use it for all cases of Postpartum Haemorrhage (16.4%; p<0.001). Barriers against its use include non-awareness of the latest WHO recommendation, preference for other utero-tonics and cost of the drug.ConclusionsThere was poor knowledge of Tranexamic acid, poor awareness of its recommendation and low use for Postpartum Haemorrhage among different cadres of health care providers.SynopsisThere was poor knowledge of Tranexamic acid, poor awareness of its recommendation and low use for Postpartum Haemorrhage among different cadres of health care providers.
A NEW PERSPECTIVE ON ISOTRETINOIN IN PREGNANCY: PREGNANCY OUTCOMES, EVALUATION OF COMPLEX PHENOTYPES, AND IMPORTANCE OF TERATOLOGICAL COUNSELLING
Authors: Alay Mustafa Tarık , Yiğin Aysel Kalaycı , Seven Mehmet 
Published: June 2023

ABSTRACTBackgroundTeratogens are responsible for 5% of all known causes of congenital anomalies. Isotretinoin, a retinoic acid–derived agent, leads to congenital anomalies in 21-52% of cases when exposure occurs during pregnancy according to studies conducted before 2006. However, rates of congenital anomalies were much lower in later studies.ObjectivesTo investigate the rates of congenital anomalies in isotretinoin exposure during pregnancy, isotretinoin exposure before pregnancy, and a control group unexposed to any teratogenic agents.MethodsIn this cohort study, we divided pregnant women admitted to our center between 2009 and 2020 into two groups: isotretinoin exposure during the pregnancy (n=77) and isotretinoin exposure before the pregnancy (n=75). We selected the control group from among the non-teratogen exposed pregnant women with a simple random sampling method. Obstetricians calculated the ages of all pregnancies via ultrasound (USG) (crown-rump diameter for the first trimester; biparietal diameter and femur length for the second trimester). After birth, a pediatric genetics specialist examined all babies.ResultsAmong the isotretinoin exposure during the pregnancy, isotretinoin exposure before the pregnancy, and the control groups, there were statistically significant differences in live births (respectively, 64.3%, 88%, 93.3%), congenital anomalies (respectively, 28.6%, 6.1%, 1.4%), miscarriages (respectively, 13%, 2.7%, 4%), terminations (respectively, 32.5%, 9.3%, 2.7%), prematurities (11.9%, 16.7%, 2.9%) (respectively, p < 0.001, p<0.001, p=0.014, p<0.001). We detected novel phenotypical features in five patients.ConclusionsOur study demonstrated that study design, long-term follow-up, teratological counseling, and implementing advanced molecular analysis in complex phenotypes with novel phenotypical features are beneficial for understanding the association of congenital anomalies with isotretinoin exposure. While evaluating congenital anomalies, we detected statistically significant differences between isotretinoin exposure vs control, but we did not detect any statistical differences between isotretinoin exposure before the pregnancy and controls. This conflict between our study and previous studies might be caused by no evident differentiation between isotretinoin exposure before the pregnancy and during the pregnancy and higher termination rates in previous studies.
Tafenoquine following G6PD screening versus primaquine for the treatment of vivax malaria in Brazil: a cost-effectiveness analysis using a transmission model
Authors: Price David J , Nekkab Narimane , Monteiro Wuelton M , Villela Daniel AM , Simpson Julie A. , Lacerda Marcus VG , White Michael T , Devine Angela 
Published: June 2023

ABSTRACTBackgroundMalaria transmission modelling has demonstrated the potential impact of semi-quantitative glucose-6-phosphate dehydrogenase (G6PD) testing and treatment with single-dose tafenoquine forPlasmodium vivaxradical cure. This modelling has focused on predicting the number of vivax cases averted, rather than its cost-effectiveness.MethodsWe explored the cost-effectiveness of using tafenoquine after G6PD screening as compared to usual practice (7-day low-dose primaquine (0.5 mg/kg/day) without G6PD screening) in Brazil using a 10-year time horizon with 5% discounting considering four scenarios: 1) tafenoquine for adults only assuming 66.7% primaquine treatment adherence, 2) tafenoquine for adults and children aged >2 years assuming 66.7% primaquine adherence, 3) tafenoquine for adults only assuming 90% primaquine adherence, 4) tafenoquine for adults only assuming 30% primaquine adherence. The incremental cost-effectiveness ratios (ICERs) were estimated by dividing the incremental costs by the disability-adjusted life-years (DALYs) averted. These were compared to a willingness to pay threshold of US$7,800 for Brazil, and one-way and probabilistic sensitivity analyses were performed.ResultsAll four scenarios were cost-effective using this willingness to pay threshold with ICERs ranging from US$154–1836. One-way sensitivity analyses showed that the results were most sensitive to severity and mortality due to vivax malaria, the lifetime and number of semi-quantitative G6PD analysers needed, cost per malaria episode and per G6PD test strips, and life expectancy. All scenarios had a 100% likelihood of being cost-effective at the willingness to pay threshold.ConclusionsTafenoquine prescribed after a semi-quantitative G6PD testing is highly likely to be cost-effective in Brazil.