bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment Noncompliance Level Among Patients with Type 2 Diabetes Mellitus: A Hospital Based Cross-Sectional Study in Bangladesh
Authors: Khan Ishtiakul Islam , Pulock Orindom Shing , Barua Biddhuth , Dola Taslima Ahmed , Chowdhury Pratik , Seal Tapan , Salekin Sanzida , Quader Md. Tarek Ul , Mitra Ambarish , Chowdhury M A Hassan , Siddiqui Sayeda Rumman Aktar 
Published: January 2022

AbstractIntroductionThe consequence of good diabetic treatment depends on the patient’s commitment to a large degree. Noncompliance leads to inadequacy of metabolic control, which strengthens the advancement and speeds up diabetic complications.MethodologyThis descriptive cross-sectional study was conducted at Medical Center Hospital, Chattogram, Bangladesh. The study included two hundred and fifty-nine patients with T2DM. Data regarding sociodemographic factors, patient’s characteristics, medication factors, physician-related factors, and noncompliance were collected using a pretested and structured questionnaire. Treatment adherence was assessed by Morisky Medication Adherence Scales (MMAS-8). Data analyses were conducted on SPSS v23.0 Software. The study’s main goal was to assess the treatment noncompliance level among patients with type-2 diabetes mellitus (T2DM) in Bangladesh.ResultThe majority of the participants (56%) were in the 40-45 years of age group, followed by 32% in the older age group (≥60 years), and 62.5% of them were male. One hundred and sixty-eight (64.86%) patients were considered low adherent as per the response of the MMAS-8 scale (score <6), followed by 57 (22.0%) patients were regarded as high adherent (score 8) and 34 (13.13%) patients were considered medium adherent (score 6-7) to treatment. Observing the frequency distribution for noncompliance, financial concerns (32.3 %), forgetfulness (27.7%), a busy daily schedule (17.7%), and fear of antihyperglycemic drug side effects were all identified as significant explanations. On multivariate analysis, participants aged 60 years or more, monthly family incomes of <30,000BDT or 30,000 – 50,000 BDT, smoking, and uncontrolled glycemic status showed higher chances of noncompliance than their counterparts.ConclusionPatient counseling and awareness programs may enhance treatment adherence among people with T2DM. Our findings will help physicians and public health workers to develop targeted strategies to increase awareness of the same among their patients.HighlightsOne of the most preventable causes of treatment failure is noncompliance with treatment.Age group, educational level, and monthly family income had a significant association with the compliance to treatment in diabetic patientsMajority of the respondents (64.86%) were low adherent to the medications as per MMA-8 scale.Financial issues (32.3 percent), forgetfulness (27.7%), a hectic daily schedule (17.7%), and fear of antidiabetic medicine side effects were all cited as key causes for noncompliance with antidiabetic treatment.Aged participants (≥ 60 years), monthly family income of (30,000-50,000) BDT, uncontrolled glycemic status and smokers portrayed higher frequency of noncompliance.
COVID infection severity in children under 5 years old before and after Omicron emergence in the US
Authors: Wang Lindsey , Berger Nathan A. , Kaelber David C. , Davis Pamela B. , Volkow Nora D. , Xu Rong 
Published: January 2022

AbstractImportancePediatric SARS-CoV-2 infections and hospitalizations are rising in the US and other countries after the emergence of Omicron variant. However data on disease severity from Omicron compared with Delta in children under 5 in the US is lacking.ObjectivesTo compare severity of clinic outcomes in children under 5 who contracted COVID infection for the first time before and after the emergence of Omicron in the US.Design, Setting, and ParticipantsThis is a retrospective cohort study of electronic health record (EHR) data of 79,592 children under 5 who contracted SARS-CoV-2 infection for the first time, including 7,201 infected between 12/26/2021-1/6/2022 when the Omicron predominated (Omicron cohort), 63,203 infected between 9/1/2021-11/15/2021 when the Delta predominated (Delta cohort), and another 9,188 infected between 11/16/2021-11/30/2021 when the Delta predominated but immediately before the Omicron variant was detected in the US (Delta-2 cohort).ExposuresFirst time infection of SARS-CoV-2.Main Outcomes and MeasuresAfter propensity-score matching, severity of COVID infections including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and mechanical ventilation use in the 3-day time-window following SARS-CoV-2 infection were compared between Omicron and Delta cohorts, and between Delta-2 and Delta cohorts. Risk ratios, and 95% confidence intervals (CI) were calculated.ResultsAmong 7,201 infected children in the Omicron cohort (average age, 1.49 ± 1.42 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. Before propensity score matching, the Omicron cohort were younger than the Delta cohort (average age 1.49 vs 1.73 years), comprised of more Black children, and had fewer comorbidities. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67% (risk ratio or RR: 0.71 [0.66-0.75]); hospitalizations: 1.04% vs. 3.14% (RR: 0.33 [0.26-0.43]); ICU admissions: 0.14% vs. 0.43% (RR: 0.32 [0.16-0.66]); mechanical ventilation: 0.33% vs. 1.15% (RR: 0.29 [0.18-0.46]). Control studies comparing Delta-2 to Delta cohorts show no difference.Conclusions and RelevanceFor children under age 5, first time SARS-CoV-2 infections occurring when the Omicron predominated (prevalence >92%) was associated with significantly less severe outcomes than first-time infections in similar children when the Delta variant predominated.
MT-MAG: Accurate and interpretable machine learning for complete or partial taxonomic assignments of metagenome-assembled genomes
Authors: Li Wanxin , Kari Lila , Yu Yaoliang , Hug Laura A. 
Published: January 2022

AbstractWe propose MT-MAG, a novel machine learning-based software tool for the complete or partial hierarchically-structured taxonomic classification of metagenome-assembled genomes (MAGs). MT-MAG is alignment-free, withk-mer frequencies being the only feature used to distinguish a DNA sequence from another (hereink= 7). MT-MAG is capable of classifying large and diverse metagenomic datasets: a total of 245.68 Gbp in the training sets, and 9.6 Gbp in the test sets analyzed in this study. In addition to complete classifications, MT-MAG offers a “partial classification” option, whereby a classification at a higher taxonomic level is provided for MAGs that cannot be classified to the Species level. MT-MAG outputs complete or partial classification paths, and interpretable numerical classification confidences of its classifications, at all taxonomic ranks. To assess the performance of MT-MAG, we define a “weighted classification accuracy,” with a weighting scheme reflecting the fact that partial classifications at different ranks are not equally informative. For the two benchmarking datasets analyzed (genomes from human gut microbiome species, and bacterial and archaeal genomes assembled from cow rumen metagenomic sequences), MT-MAG achieves an average of 87.32% in weighted classification accuracy. At the Species level, MT-MAG outperforms DeepMicrobes, the only other comparable software tool, by an average of 34.79% in weighted classification accuracy. In addition, MT-MAG is able to completely classify an average of 67.70% of the sequences at the Species level, compared with DeepMicrobes which only classifies 47.45%. Moreover, MT-MAG provides additional information for sequences that it could not classify at the Species level, resulting in the partial or complete classification of 95.13%, of the genomes in the datasets analyzed. Lastly, unlike other taxonomic assignment tools (e.g., GDTB-Tk), MT-MAG is an alignment-free and genetic marker-free tool, able to provide additional bioinformatics analysis to confirm existing or tentative taxonomic assignments.
Sex-specific evolution of a Drosophila sensory system via interacting cis- and trans-regulatory changes
Authors: Luecke David , Rice Gavin , Kopp Artyom 
Published: January 2022

AbstractThe evolution of gene expression via cis-regulatory changes is well established as a major driver of phenotypic evolution. However, relatively little is known about the influence of enhancer architecture and intergenic interactions on regulatory evolution. We address this question by examining chemosensory system evolution in Drosophila. D. prolongata males show a massively increased number of chemosensory bristles compared to females and males of sibling species. This increase is driven by sex-specific transformation of ancestrally mechanosensory organs. Consistent with this phenotype, the Pox neuro transcription factor (Poxn), which specifies chemosensory bristle identity, shows expanded expression in D. prolongata males. Poxn expression is controlled by non-additive interactions among widely dispersed enhancers. Although some D. prolongata Poxn enhancers show increased activity, the additive component of this increase is slight, suggesting most changes in Poxn expression are due to epistatic interactions between Poxn enhancers and trans-regulatory factors. Indeed, the expansion of D. prolongata Poxn enhancer activity is only observed in cells that express doublesex (dsx), the gene that controls sexual differentiation in Drosophila and also shows increased expression in D. prolongata males due to cis-regulatory changes. Although expanded dsx expression may contribute to increased activity of D. prolongata Poxn enhancers, this interaction is not sufficient to explain the full expansion of Poxn expression, suggesting that cis-trans interactions between Poxn, dsx, and additional unknown genes are necessary to produce the derived D. prolongata phenotype. Overall, our results demonstrate the importance of epistatic gene interactions for evolution, particularly when pivotal genes have complex regulatory architecture.Research HighlightsIn Drosophila prolongata males, many mechanosensory organs are transformed into chemosensory. This is due in part to interacting regulatory changes in Poxn, which controls chemosensory organ development, and dsx, which controls sexual differentiation.Graphical Abstract
A Systematic, Complexity-Reduction Approach to Dissect Microbiome: the Kombucha Tea Microbiome as an Example
Authors: Huang Xiaoning , Xin Yongping , Lu Ting 
Published: January 2022

AbstractOne defining goal of microbiome research is to uncover mechanistic causation that dictates the emergence of structural and functional traits of microbiomes. However, the extraordinary degree of ecosystem complexity has hampered the realization of the goal. Here we developed a systematic, complexity-reducing strategy to mechanistically elucidate the compositional and metabolic characteristics of microbiome by using the kombucha tea microbiome as an example. The strategy centered around a two-species core that was abstracted from but recapitulated the native counterpart. The core was convergent in its composition, coordinated on temporal metabolic patterns, and capable for pellicle formation. Controlled fermentations uncovered the drivers of these characteristics, which were also demonstrated translatable to provide insights into the properties of communities with increased complexity and altered conditions. This work unravels the pattern and process underlying the kombucha tea microbiome, providing a potential conceptual framework for mechanistic investigation of microbiome behaviors.
Complement facilitates developmental microglial pruning of astrocyte and vascular networks
Authors: Gnanaguru Gopalan , Tabor Steven J. , Bonilla Gracia M. , Sadreyev Ruslan , Yuda Kentaro , Köhl Jörg , Connor Kip M. 
Published: January 2022

AbstractMicroglia, the resident immune cell of the central nervous system (CNS), play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. This current work resolves a previously unknown role for microglia in facilitating the developmental pruning of the astrocytic template resulting in a spatially organized retinal superficial vascular bed. Mechanistically, our study identified that local microglial expression of complement (C)3 and C3aR is necessary for the regulation of astrocyte patterning and vascular growth during retinal development. Ablation of retinal microglia and deficiency of C3 or C3aR reduced developmental pruning and clearance of astrocytic bodies leading to increased astrocyte density, altered vascular patterning, and elevated gene expression levels of extracellular matrix proteins involved in vascular growth during retinal development. These data demonstrate that C3/C3aR signaling is an important checkpoint required for the finetuning of vascular density during neuroretinal development.
Optimal protein production by a synthetic microbial consortium: Coexistence, distribution of labor, and syntrophy
Authors: Martínez Carlos , Cinquemani Eugenio , Jong Hidde de , Gouzé Jean-Luc 
Published: January 2022

AbstractThe bacterium E. coli is widely used to produce recombinant proteins such as growth hormone and insulin. One inconvenience with E. coli cultures is the secretion of acetate through overflow metabolism. Acetate inhibits cell growth and represents a carbon diversion, which results in several negative effects on protein production. One way to over-come this problem is the use of a synthetic consortium of two different E. coli strains, one producing recombinant proteins and one reducing the acetate concentration. In this paper, we study a chemostat model of such a synthetic community where both strains are allowed to produce recombinant proteins. We give necessary and sufficient conditions for the existence of a coexistence equilibrium and show that it is unique. Based on this equilibrium, we define a multi-objective optimization problem for the maximization of two important bioprocess performance metrics, process yield and productivity. Solving numerically this problem, we find the best available trade-offs between the metrics. Under optimal operation of the mixed community, both strains must produce the protein of interest, and not only one (distribution instead of division of labor). Moreover, in this regime acetate secretion by one strain is necessary for the survival of the other (syntrophy). The results thus illustrate how complex multi-level dynamics shape the optimal production of recombinant proteins by synthetic microbial consortia.
A neural network model of hippocampal contributions to category learning
Authors: Sučević Jelena , Schapiro Anna C. 
Published: January 2022

AbstractIn addition to its critical role in encoding individual episodes, the hippocampus is capable of extracting regularities across experiences. This ability is central to category learning, and a growing literature indicates that the hippocampus indeed makes important contributions to this form of learning. Using a neural network model that mirrors the anatomy of the hippocampus, we investigated the mechanisms by which the hippocampus may support novel category learning. We simulated three category learning paradigms and evaluated the network’s ability to categorize and to recognize specific exemplars in each. We found that the trisynaptic pathway within the hippocampus—connecting entorhinal cortex to dentate gyrus, CA3, and CA1—was critical for remembering exemplar-specific information, reflecting the rapid binding and pattern separation capabilities of this circuit. The monosynaptic pathway from entorhinal cortex to CA1, in contrast, specialized in detecting the regularities that define category structure across exemplars, supported by the use of distributed representations and a relatively slower learning rate. Together, the simulations provide an account of how the hippocampus and its constituent pathways support novel category learning.
Real time, in vivo measurement of neuronal and peripheral clocks in Drosophila melanogaster
Authors: Johnstone Peter S. , Ogueta Maite , Top Inan , Syed Sheyum , Stanewsky Ralf , Top Deniz 
Published: January 2022

ABSTRACTCircadian clocks are highly conserved transcriptional regulators that control 24-hour oscillations in gene expression, physiological function, and behavior. Circadian clocks exist in almost every tissue and are thought to control tissue-specific gene expression and function, synchronized by the brain clock. Many disease states are associated with loss of circadian regulation. How and when circadian clocks fail during pathogenesis remains largely unknown because it is currently difficult to monitor tissue-specific clock function in intact organisms. Here, we developed a method to directly measure the transcriptional oscillation of distinct neuronal and peripheral clocks in live, intact Drosophila, which we term Locally Activatable BioLuminescence or LABL. Using this method, we observed that specific neuronal and peripheral clocks exhibit distinct transcription properties. Loss of the receptor for PDF, a circadian neurotransmitter critical for the function of the brain clock, disrupts circadian locomotor activity but not all tissue-specific circadian clocks; we found that, while peripheral clocks in non-neuronal tissues were less stable after the loss of PDF signaling, they continued to oscillate. This result suggests that the presumed dominance of the brain clock in regulating peripheral clocks needs to be re-examined. This result further demonstrates that LABL allows rapid, affordable, and direct real-time monitoring of clocks in vivo.
The Mechanisms of GPR55 Receptor Functonal Selectivity
Authors: Akimov Mikhail G. , Gretskaya Natalia M. , Dudina Polina V. , Sherstyanykh Galina D. , Zinchenko Galina N. , Serova Oksana V. , Degtyaryova Ksenia O. , Deyev Igor E. , Bezuglov Vladimir V. 
Published: January 2022

AbstractThe objective of the study was to establish the mechanisms of multidirectional signal transmission through the same G-protein coupled receptor GPR55. Using the CRISPR-Cas9 system, clones of the MDA-MB-231 line knockout for the GPR55, CB1, CB2, GPR18, and TRPV1 receptor genes were obtained. On clones of the MDA-MB-231 line with a knockout CB2 receptor, the cytotoxic activity of the pro-apoptotic ligand docosahexaenoyldopamine (DHA-DA) did not change or slightly increased, while the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor (ML-184) completely disappeared. On the original line MDA-MB-231, the stimulatory effect of ML-184 is removed by the CB2 receptor blocker, but not by GPR55. At the same time, the stimulating effect of ML-184 is practically not manifested on cell lines knockout at the GPR55 receptor. Thus, it can be confidently assumed that when proliferation is stimulated with the participation of the GPR55 receptor, a signal is transmitted from the CB2 receptor to the GPR55 receptor due to the formation of a heterodimer. GPR18 and TRPV1 receptors are additionally involved in the implementation of the cytotoxic effect of DHA-DA, while the CB1 receptor is not involved. In the implementation of the cytotoxic action of DHA-DA, the predominant participation of one of the Gα subunits was not found, but the Gα13 subunit plays a decisive role in the implementation of the proproliferative action.
Cisplatin neurotoxicity targets specific subpopulations and K+ channels in tyrosine-hydroxylase positive dorsal root ganglia neurons
Authors: Finno Carrie J. , Chen Yingying , Park Seojin , Lee Jeong H. , Perez-Flores Cristina M. , Yamoah Ebenezer N. 
Published: January 2022

AbstractAmong the features of cisplatin chemotherapy-induced peripheral neuropathy are chronic pain and innocuous mechanical hypersensitivity. The complete etiology of the latter remains unknown. Here, we show that cisplatin targets a heterogeneous population of tyrosine hydroxylase-positive (TH+) primary afferent dorsal root ganglion neurons (DRGNs) within the primary afferent dorsal root ganglia in mice, determined using single-cell transcriptome and electrophysiological analyses. TH+ DRGNs regulate innocuous mechanical sensation through C-low threshold mechanoreceptors. A differential assessment of wild-type and vitamin E deficient TH+ DRGNs revealed heterogeneity and specific functional phenotypes. The TH+ DRGNs comprise; fast-adapting eliciting one action potential (AP; 1-AP), moderately-adapting (≥ 2-APs), in responses to square-pulse current injection, and spontaneously firing (SF). Cisplatin increased the input resistance and AP frequency but reduced the temporal coding feature of 1-AP and ≥ 2-APs neurons. By contrast, cisplatin has no measurable effect on the SF neurons. Vitamin E reduced the cisplatin-mediated increased excitability, but did not improve the TH+ neuron temporal coding properties. Cisplatin mediates its effect by targeting outward K+ current, likely carried by through K2P18.1 (Kcnk18), discovered through the differential transcriptome studies and heterologous expression. Studies show a potential new cellular target for chemotherapy-induced peripheral neuropathy and implicate the possible neuroprotective effects of vitamin E in cisplatin chemotherapy.
Flexible cue anchoring strategies enable stable head direction coding in both sighted and blind animals
Authors: Asumbisa Kadjita , Peyrache Adrien , Trenholm Stuart 
Published: January 2022

AbstractVision plays a crucial role in instructing the brain’s spatial navigation systems. However, little is known about how vision loss affects the neuronal encoding of spatial information. Here, recording from head direction (HD) cells in the anterior dorsal nucleus of the thalamus in mice, we find stable and robust HD tuning in blind animals. In contrast, placing sighted animals in darkness significantly impairs HD cell tuning. We find that blind mice use olfactory cues to maintain stable HD tuning and that prior visual experience leads to refined HD cell tuning in blind adult mice compared to congenitally blind animals. Finally, in the absence of both visual and olfactory cues, the HD attractor network remains intact but the preferred firing direction of HD cells continuously drifts over time. We thus demonstrate remarkable flexibility in how the brain uses diverse sensory information to generate a stable directional representation of space.HighlightsHead direction (HD) cell tuning in ADn is robust in blind animals, but unstable in sighted animals placed in the darkBlind mice use olfaction to stabilize HD cell tuningPrior visual experience leads to refined HD cell tuning in blind adult miceIn the absence of both vision and olfaction, the HD attractor network in ADn remains intact but the preferred firing direction of HD cells continuously drifts