bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hippocampal–Ventral Medial Prefrontal Cortex Neurocircuitry Involvement in the Association of Daily Life Stress With Acute Perceived Stress and Cortisol Responses
Authors: Ren Xi , Zhao Xiaolin , Li Jiwen , Liu Yadong , Ren Yipeng , Pruessner Jens C. , Yang Juan 
Published: February 2022

ABSTRACT

Objective
Daily life stressors include everyday irritants, hassles, and inconveniences, such as problems in traffic and unexpected work deadlines. A growing body of research has suggested higher daily stress is associated with blunted cortisol response to acute psychosocial stressors. However, so far, the neural mechanism underlying this association has not been elucidated. The current study aimed to examine the role of stress neurocircuitry between the hippocampus and the ventral medial prefrontal cortex in this relationship.

Methods
To this end, as an index of daily stress in 44 young healthy individuals (23 females; mean [standard deviation] age = 19.07 [1.11] years), the total stressful rating score of daily life stress events that occurred in a 24-hour period was quantified. Individuals were then administered a modified version of the Montreal Imaging Stress Task while undergoing functional magnetic resonance imaging scans, and their saliva samples were collected for assessment of the stress hormone cortisol.

Results
Results revealed that a higher level of daily stress was associated with lower salivary cortisol secretion (r = −0.39, p = .008) and lower activation of the left hippocampus (t
peak = −5.51) in response to the Montreal Imaging Stress Task. Furthermore, a higher level of daily stress was associated with stronger functional connectivity between the left hippocampus and the ventral medial prefrontal cortex/subgenual anterior cingulate cortex (t
peak = 4.91, R
2
= 0.365).

Conclusions
Taken together, the current study suggested a possible neurocircuitry of the hippocampus and ventral medial prefrontal cortex in the relationship between daily life stress and acute psychosocial stress.
A Pragmatic Method for Measuring Inpatient Complications and Complication-Specific Mortality
Authors: Blike George T. , Perreard Irina M. , McGovern Krystal M. , McGrath Susan P. 
Published: February 2022

Objectives
The primary objective of this study was to develop hospital-level metrics of major complications associated with mortality that allows for the identification of opportunities for improvement. The secondary objective is to improve upon current metrics for failure to rescue (i.e., death from serious but treatable complications.)

Methods
Agency for Healthcare Research and Quality metrics served as the basis for identifying specific complications related to major organ system morbidity associated with death. Complication-specific occurrence rates, observed mortality, and risk-adjusted mortality indices were calculated for the study institution and 182 peer organizations using component International Classification of Disease, Tenth Revision codes. Data were included for adults over a 4-year period, with exclusion of hospice patients and complications present on admission. Temporal visualizations of each metric were used to compare past and recent performance at the study hospital and in comparison to peers.

Results
The complication-specific method showed statistically significant differences in the study hospital occurrence rates and associated mortality rates compared with peer institutions. The monthly control-chart presentation of these metrics provides assessment of hospital-level interventions to prevent complications and/or reduce failure to rescue deaths.

Conclusions
The method described supplements existing metrics of serious complications that occur during the course of acute hospitalization allowing for enhanced visualization of opportunities to improve care delivery systems. This method leverages existing measure components to minimize reporting burden. Monthly time-series data allow interventions to prevent and/or rescue patients to be rapidly assessed for impact.
Use of Online Information in Musculoskeletal Conditions
Authors: Fritsch Carolina G. , Duong Vicky , Chen Lingxiao , Hunter David J. , McLachlan Andrew J. , Ferreira Paulo H. , Ferreira Manuela L. 
Published: February 2022

Background/Objective
We aimed to investigate the yearly online public interest for gout, low back pain, neck pain, osteoarthritis, and rheumatoid arthritis, the most popular topics searched for these conditions, and the association between the change in their interest over time and the sociodemographic index of the search location.

Methods
We conducted online searches in Google Trends for the aforementioned conditions between 2004 and 2020. The search volumes for each condition (relative to all searches conducted in the period) and the top and rising related queries and topics were downloaded and summarized.

Results
There was a rise in the online interest for musculoskeletal conditions between 2008 and 2020, with low back pain (annual percent change, 7.4; 95% confidence interval [CI], 7.1–7.7) and neck pain (annual percent change, 7.2; 95% CI, 6.9–7.5) presenting the highest increases. There was a negative, statistically significant, but small association between change in online interest and the country's sociodemographic index for low back pain (−0.007; 95% CI, −0.011 to−0.003), neck pain (−0.005; 95% CI, 0.009 to −0.001), and rheumatoid arthritis (−0.009; 95% CI, −0.017 to −0.001) between 2013 and 2020. The interest for the cause and symptoms of the selected conditions increased over time, except for gout. The proportion of queries and topics related to treatment of all conditions decreased over time.

Conclusions
The worldwide interest in musculoskeletal conditions increased between 2008 and 2020. The public seems more interested in understanding what musculoskeletal conditions are and less interested in which treatment options are available. The results can guide the development of educational campaigns for musculoskeletal conditions.
Hybrid Preservation Rhinoplasty: Combining Mix-Down and Semi Let-Push Down Techniques
Authors: Öztürk Güncel 
Published: February 2022

Abstract:
Rhinoplasty is 1 of the most applied procedures among aesthetic and plastic surgery areas. Dorsal hump deformity is a common deformity among Caucasians based on the natural anatomy of the nose. Dorsal preservation techniques arose as a necessity for overcoming the negative outcomes of traditional hump reduction surgery in patients with hump deformity. Beside the strong advantages of dorsal preservation techniques such as push-down and let-down techniques in the fixation of dorsal hump deformity, innovations on these procedures would bring better outcomes in terms of aesthetic and functional manners. In present research, the author defines a new technique, which combines new procedures as mix-down and semi let-down and semi push-down techniques. This study was designed as a retrospective. According to the inclusion and exclusion criteria, 36 patients (26 females and 10 males) were included in the study. The author applied to patients hybrid preservation rhinoplasty approach, which is a combination of mix-down and semi let-down and semi push-down techniques. All patients completed the Rhinoplasty Outcome Evaluation (ROE) questionnaire before surgery and at their 1-year follow-up appointment. The follow-up period ranged between 13 and 28 months (median of 19.8months). The initial median ROE score was 55.5, and it increased to 91.00 points at 12 months after surgery (P < 0.001). According to the ROE scale, patients’ satisfaction was found as excellent in 91.6% of patients. Present study showed satisfactory outcomes of hybrid dorsal preservation technique, which is a combination of mix-down and semi-let down and semi-push down approaches. This new approach will be suitable for selected patients and easy to perform by the surgeons. Moreover, patients who have concomitant hump and deviation deformities will benefit from hybrid dorsal preservation technique.

Level of Evidence: 3
Phototherapy with physically and molecularly produced light for Alzheimer’s disease
Authors: Kuang Shi , Zhu Biyue , Zhang Jing , Yang Fan , Wu Bo , Ding Weihua , Shen Shiqian , Zhang Can , Ran Chongzhao 
Published: February 2022

AbstractOver the past decades, classical drug development approaches for Alzheimer’s disease have yielded limited success, and this futileness has prompted scientists to seek non-classical approaches. In this report, we demonstrated that, with irradiation of LED light or with molecularly generated light (dubbed as “molecular light”) from chemiluminescence probe ADLumin-4, photolabile curcumin analogue CRANAD-147 could change properties, structures (sequences) and neurotoxicity of amyloid beta (Aβ) species in vitro. We further demonstrated that, with the assistance from molecular chemiluminescence imaging, the combination of CRANAD-147/LED or CRANAD-147/ADLumin-4 (molecular light) could slow down the accumulation of Aβs in transgenic 5xFAD mice in vivo. Due to the unlimited capacity of tissue penetration of molecular light in vivo, phototherapy with the combination of photolabile Aβ ligand and molecular light has great potential as an alternative approach for AD drug discovery.
Predicting Math Ability using Working Memory, Number Sense, and Neurophysiology in Children and Adults
Authors: van Bueren Nienke E. R. , van der Ven Sanne H. G. , Roelofs Karin , Kadosh Roi Cohen , Kroesbergen Evelyn H. 
Published: February 2022

AbstractPrevious work has shown relations between domain-general processes, domain-specific processes, and mathematical ability. However, the underlying neurophysiological effects of mathematical ability are less clear. Recent evidence highlighted the potential role of beta oscillations in mathematical ability. Here we investigate whether domain-general (working memory) and domain-specific (number sense) mediate the relation between resting-state beta oscillations and mathematical ability, and how this may differ as a function of development (children vs. adults). We compared a traditional analysis method normally used in EEG studies with a more recently developed parameterization method that separates periodic from aperiodic activity. Regardless of methods chosen, we found no support for mediation of working memory and number sense, neither for children nor for adults. However, we found subtle differences between the methods. Additionally, we showed that the traditional EEG analysis method conflates periodic activity with aperiodic activity, and the latter is strongly related to mathematical ability and this relation differs between children and adults. At the cognitive level, our findings do not support previous suggestions of a mediation of working memory and number sense. At the neurophysiological level our findings suggest that aperiodic, rather than periodic, activity is linked to mathematical ability as a function of development.
MIAMI: Mutual Information-based Analysis of Multiplex Imaging data
Authors: Seal Souvik , Ghosh Debashis 
Published: February 2022

AbstractMotivationStudying the interaction or co-expression of the proteins or markers in the tumor microenvironment (TME) of cancer subjects can be crucial in the assessment of risks, such as death or recurrence. In the conventional approach, the cells need to be declared positive or negative for a marker based on its intensity. For multiple markers, manual thresholds are required for each marker, which can become cumbersome. The performance of the subsequent analysis relies heavily on this step and thus suffers from subjectivity and lacks robustness.ResultsWe present a new method where different marker intensities are viewed as dependent random variables, and the mutual information (MI) between them is considered to be a metric of co-expression. Estimation of the joint density, as required in the traditional form of MI, becomes increasingly challenging as the number of markers increases. We consider an alternative formulation of MI which is conceptually similar but has an efficient estimation technique for which we develop a new generalization. With the proposed method, we analyzed a lung cancer dataset finding the co-expression of the markers, HLA-DR and CK to be associated with survival. We also analyzed a triple negative breast cancer dataset finding the co-expression of the immuno-regulatory proteins, PD1, PD-L1, Lag3 and IDO, to be associated with disease recurrence. We demonstrated the robustness of our method through different simulation studies.AvailabilityThe associatedRpackage can be found here,https://github.com/sealx017/MIAMI.Contactsouvik.seal@cuanschutz.eduSupplementary informationThe Supplementary Material is attached.
HIV, Pathology and epigenetic age acceleration in different human tissues
Authors: Horvath Steve , Lin David T.S. , Kobor Michael S. , Said Jonathan W. , Morgello Susan , Singer Elyse , Yong William H. , Jamieson Beth D. , Levine Andrew J. 
Published: February 2022

ABSTRACTBackgroundEpigenetic clocks based on patterns of DNA methylation have great importance in understanding aging and disease; however, there are basic questions to be resolved in their application. It remains unknown whether epigenetic age acceleration (EAA) within an individual shows strong correlation between different primary tissue sites, the extent to which tissue pathology and clinical illness correlates with EAA in the target organ, and if EAA variability across tissues differs according to sex. Considering the outsized role of age-related illness in Human Immunodeficiency Virus-1 (HIV), these questions were pursued in a sample enriched for tissue from HIV-infected individuals.MethodsWe used a custom methylation array to generate DNA methylation data from 661 samples representing 11 human tissues (adipose, blood, bone marrow, heart, kidney, liver, lung, lymph node, muscle, spleen, and pituitary gland) from 133 clinically-characterized, deceased individuals, including 75 infected with HIV. We developed a multimorbidity index based on the clinical disease history.ResultsEpigenetic age was moderately correlated across tissues. Blood had the greatest number and degree of correlation, most notably with spleen and bone marrow. However, blood did not correlate with epigenetic age of liver. EAA in liver was weakly correlated with EAA in kidney, adipose, lung, and bone marrow. Clinically, hypertension was associated with EAA in several tissues, consistent with the multi-organ impacts of this illness. HIV infection was associated with positive age acceleration in kidney and spleen. Male sex was associated with increased epigenetic acceleration in several tissues. Preliminary evidence indicates that Amyotrophic Lateral Sclerosis is associated with positive EAA in muscle tissue. Finally, greater multimorbidity was associated with greater EAA across all tissues.ConclusionBlood alone will often fail to detect EAA in other tissues. While hypertension is associated with increased EAA in several tissues, many pathologies are associated with organ-specific age acceleration.
The First Inhibitor of Meso-Diaminopimelate Biosynthesis with Antibacterial Activity Against Multi-Drug Resistant Bacteria
Authors: Soares da Costa Tatiana P. , Wyllie Jessica A. , Ghardi Chamodi K. , Hulett Mark D. , Abbott Belinda M. , Sutton J. Mark , Perugini Matthew A. 
Published: February 2022

AbstractAntibiotic resistance represents one of the biggest threats to global health. While several of our current antibiotics target the peptidoglycan within the bacterial cell wall, only a fraction of its components has been explored for antibiotic development. A component that remains under-exploited is meso-diaminopimelate (meso-DAP), a constituent of the cross-linking peptide in Gram-negative bacteria. In this study, we employed a high throughput chemical screen to identify the first inhibitor of meso-DAP biosynthesis with antibacterial activity. Indeed, the compound was shown to have minimum inhibitory concentration values of 8–16 μg/mL against a panel of multi-drug resistant Acinetobacter baumannii strains, including those resistant to the last resort antibiotic carbapenem. Importantly, the compound targets the meso-DAP biosynthesis pathway specifically, with no off-target effects observed in human cell lines, and no resistance exhibited upon continuous treatment, under the conditions tested. Furthermore, we revealed for the first time that meso-DAP biosynthesis inhibition prevents biofilm formation and disrupts established biofilms in A. baumannii. Using a Galleria mellonella model, we showed that this compound improves survival rates against A. baumannii infection by up to 40% relative to the no treatment controls. Lastly, we determined that the inhibitor potentiates the activity of several antibiotic classes, including carbapenems. Thus, this study provides proof-of-concept that meso-DAP biosynthesis represents a promising target for the development of standalone antibacterial agents with a new mode of action as well as adjuvants to be used in combinatorial regimens to rejuvenate our current antibiotic arsenal to combat resistance.ImportanceResistance levels to available antibiotics continues to rise, with a growing number of Gram-negative bacterial infections, in particular A. baumannii infections, becoming life-threatening. Despite this, there have been no new classes of antibiotics against Gram-negative bacteria introduced to the market over the last 40 years. Hence, new targets and therapeutics are urgently required to combat these clinically important pathogens. One such target is meso-DAP, a critical component of the cross-linking peptides in the cell walls of Gram-negative bacteria. Here, we describe the first inhibitor of bacterial meso-DAP biosynthesis, with antibacterial activity against multi-drug resistant Gram-negative bacterial strains, including carbapenem-resistant A. baumannii. We also reveal that meso-DAP biosynthesis inhibition affects biofilm stability and potentiates the activity of several antibiotic classes. This study highlights the need to further explore meso-DAP biosynthesis and other unexploited targets in the search for antibiotics with new modes of action.
A single-cell resolution gene expression atlas of the larval zebrafish brain
Authors: Shainer Inbal , Kuehn Enrico , Laurell Eva , Kassar Mariam Al , Mokayes Nouwar , Sherman Shachar , Larsch Johannes , Kunst Michael , Baier Herwig 
Published: February 2022

AbstractThe advent of multimodal brain atlases promises to accelerate discoveries in neuroscience by offering in silico queries of cell types, connectivity and gene expression in regions of interest. We employed multiplexed fluorescent in situ RNA hybridization chain reaction (HCR) to generate expression maps for an initial set of 200 marker genes across the larval zebrafish brain. The data were registered to the Max Planck Zebrafish Brain (mapzebrain) atlas, thus allowing co-visualization of gene expression patterns, single-neuron tracings, transgenic lines and anatomical segmentations. Additionally, brain activity maps of freely swimming larvae were generated at single-cell resolution using HCR labeling of the immediate-early gene cfos and integrated into the atlas. As a proof of concept, we identified a novel class of cerebellar eurydendroid cells that express calb2a, project to the hypothalamus and are activated in animals that have recently ingested food. Thus, a cellular-resolution gene expression atlas will not only help with rapid identification of marker genes for neuronal populations of interest, but also bridge the molecular and circuit levels by anchoring genetic information to functional activity maps and synaptic connectivity.
BORIS/CTCFL-mediated chromatin accessibility alterations promote a pro-invasive transcriptional signature in melanoma cells
Authors: Moscona Roy , Janssen Sanne Marlijn , Elchebly Mounib , Papadakis Andreas Ioannis , Rubin Eitan , Spatz Alan 
Published: February 2022

AbstractMelanoma is the deadliest form of skin cancer, due to its tendency to metastasize early. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcription regulator that becomes ectopically expressed in melanoma. We recently showed that BORIS contributes to melanoma phenotype switching by altering the gene expression program of proliferative melanoma cells in favor of a more invasive phenotype. However, how BORIS alters the transcriptome remains unclear. Here, ATAC-seq was used to study BORIS-mediated chromatin accessibility alterations in proliferative melanoma cells. Genes that gained promoter accessibility following ectopic BORIS expression, were enriched for melanoma-specific invasive genes as well as invasion-associated biological processes, while promoters of genes associated with proliferation show reduce accessibility. Integration of ATAC-Seq and RNA-Seq data demonstrates that increased chromatin accessibility is associated with transcriptional upregulation of genes involved in tumor progression processes, and the aberrant activation of oncogenic transcription factors, while reduced chromatin accessibility and downregulated genes, were associated with repressed activity of tumor suppressors. Together, these findings indicate that BORIS mediates transcriptional reprogramming in melanoma cells by altering chromatin accessibility and gene expression, shifting the cellular transcription landscape of proliferative melanoma cells towards a pro-invasive genetic signature.SignificanceWe recently reported that BORIS contributes to melanoma phenotype switching by altering the transcriptional landscape of melanoma cells from a proliferative to an invasive state. In this study, using ATAC-Seq, we demonstrate that ectopic BORIS expression in proliferative melanoma cells leads to increased chromatin accessibility at promoters of upregulated invasion-associated genes. Importantly, by integrating the ATAC-Seq data with RNA-Seq data, we were able to identify key cancer-associated transcription factors that become aberrantly activated or repressed following ectopic BORIS expression. Taken together, this study sheds light on the mechanisms by which BORIS mediates phenotype switching in melanoma cells.
Whole-Genome Sequencing and Comparative Genomic Analysis of Potential Biotechnological Strains of Trichoderma harzianum, Trichoderma atroviride, andTrichoderma reesei
Authors: Rosolen Rafaela Rossi , Horta Maria Augusta Crivelente , de Azevedo Paulo Henrique Campiteli , da Silva Carla Cristina , Sforca Danilo Augusto , Goldman Gustavo Henrique , de Souza Anete Pereira 
Published: February 2022

AbstractTrichoderma atrovirideandTrichoderma harzianumare widely used as commercial biocontrol agents against plant diseases. Recently,T. harzianumIOC-3844 (Th3844) andT. harzianumCBMAI-0179 (Th0179) demonstrated great potential in the enzymatic conversion of lignocellulose into fermentable sugars. Herein, we performed whole-genome sequencing and assembly of the Th3844 and Th0179 strains. To assess the genetic diversity within the genusTrichoderma, the results of both strains were compared with strains ofT. atrovirideCBMAI-00020 (Ta0020) andT. reeseiCBMAI-0711 (Tr0711). The sequencing coverage value of all genomes evaluated in this study was higher than that of previously reported genomes for the same species ofTrichoderma. The resulting assembly revealed total lengths of 40 Mb (Th3844), 39 Mb (Th0179), 36 Mb (Ta0020), and 32 Mb (Tr0711). A genome-wide phylogenetic analysis provided details on the relationships of the newly sequenced species with otherTrichodermaspecies. Structural variants revealed genomic rearrangements among Th3844, Th0179, Ta0020, and Tr0711 relative to theT. reeseiQM6a reference genome and showed the functional effects of such variants. In conclusion, the findings presented herein allow the visualization of genetic diversity in the evaluated strains and offer opportunities to explore such fungal genomes in future biotechnological and industrial applications.