bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Upper Cervical Spine Alignment on Patient-reported Outcome Measures in Anterior Cervical Decompression and Fusion
Authors: Divi Srikanth N. , Karamian Brian A. , Canseco Jose A. , Chang Michael , Toci Gregory R. , Goyal Dhruv K.C. , Nicholson Kristen J. , Mujica Victor E. , Bronson Wesley , Kaye I. David , Kurd Mark F. , Woods Barrett I. , Radcliff Kris E. , Rihn Jeffrey A. , Anderson D. Greg , Hilibrand Alan S. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D. 
Published: March 2022

Study Design:
This was a retrospective cohort study.

Objective:
To determine the extent to which the upper cervical spine compensates for malalignment in the subaxial cervical spine, and how changes in upper cervical spine sagittal alignment affect patient-reported outcomes.

Summary of Background Data:
Previous research has investigated the relationship between clinical outcomes and radiographic parameters in the subaxial cervical spine following anterior cervical discectomy and fusion (ACDF). However, limited research exists regarding the upper cervical spine (occiput to C2), which accounts for up to 40% of neck movement and has been hypothesized to compensate for subaxial dysfunction.

Materials and Methods:
Patients undergoing ACDF for cervical radiculopathy and/or myelopathy at a single center with minimum 1-year follow-up were included. Radiographic parameters including cervical sagittal vertical axis, C0 angle, C1 inclination angle, C2 slope, Occiput-C1 angle (Oc–C1 degrees), Oc–C2 degrees, Oc–C7 degrees, C1–C2 degrees, C1–C7 degrees, and C2–C7 degrees cervical lordosis (CL) were recorded preoperatively and postoperatively. Delta (Δ) values were calculated by subtracting preoperative values from postoperative values. Correlation analysis as well as multiple linear regression analysis was used to determine relationships between radiographic and clinical outcomes. Alpha was set at 0.05.

Results:
A total of 264 patients were included (mean follow-up 20 mo). C2 slope significantly decreased for patients after surgery (Δ=−0.8, P=0.02), as did parameters of regional cervical lordosis (Oc–C7 degrees, C1–C7 degrees, and C2–C7 degrees; P<0.001, <0.001, and 0.01, respectively). Weak to moderate associations were observed between postoperative CL and C1 inclination (r=−0.24, P<0.001), Oc–C1 degrees (r=0.59, P<0.001), and C1–C2 degrees (r=−0.23, P<0.001). Increased preoperative C1–C2 degrees and Oc–C2 degrees inversely correlated with preoperative SF-12 Mental Composite Score (MCS-12) scores (r=−0.16, P=0.01 and r=−0.13, P=0.04). Cervical sagittal vertical axis was found to have weak but significant associations with Short Form-12 (SF-12) Physical Composite Score (PCS-12) (r=−0.13, P=0.03) and MCS-12 (r=0.12, P=0.05).

Conclusion:
No clinically significant relationship between upper cervical and subaxial cervical alignment was detected for patients undergoing ACDF for neurological symptoms. Upper cervical spine alignment was not found to be a significant predictor of patient-reported outcomes after ACDF.

Level of Evidence:
Level III.
Pattern and risk factors of menstrual regulation service use among ever-married women in Bangladesh: evidence from a nationally representative cross-sectional survey
Authors: Alam Md. Rashed , Khan Md. Nuruzzaman , Sawangdee Yothin 
Published: March 2022

AbstractBackgroundAround 47% of the total conceptions in Bangladesh are unintended which leads to several adverse consequences, including maternal and child mortality. Availability of menstrual regulation (MR) service and its use can help women to end conception at an earlier stage, as such, reducing adverse consequences related to the unintended pregnancy. We explored the prevalence and determinants of MR service knowledge and its use among ever-married women in Bangladesh.MethodsA total of 20 127 ever-married women data from the 2017 Bangladesh Demographic and Health Survey were analyzed. Knowledge about menstrual regulation (MR) and its use were our outcomes of interest. Several individual, household and community-level factors were considered as explanatory variables. The multilevel mixed-effects Poisson regression model was used to determine the factors associated with MR service knowledge and its use in Bangladesh.ResultsAround 71% of the total analyzed women reported they know about MR service while only 7% of them reported they used this service within three years of the survey date. MR service knowledge was found to be higher among women with increased age and education and engaged in income-generating employment. Knowledge about MR service was also found to be higher among women whose husbands were higher educated and engaged in physical work or business. Rural women and women who resided in the community with lower poverty and higher illiteracy were reported lower knowledge of MR service. MR service use was found higher among higher-aged women, women whose husbands were either physical workers or businessmen, women who have an increased number of children and inherent in the community with lower poverty. Lower use of MR service was found among women who resided in the Chattogram, Khulna, and Mymensingh divisions and women who resided in the community with increased illiteracy.ConclusionUse of MR service is very low in Bangladesh. This could be responsible for higher adverse consequences related to unintended pregnancy including higher maternal and child mortality. Policies and programs are important to aware women of MR.
Beyond inappropriate fire regimes: a synthesis of fire-driven declines of threatened mammals in Australia
Authors: Santos Julianna L. , Hradsky Bronwyn A. , Keith David A. , Rowe Kevin , Senior Katharine L. , Sitters Holly , Kelly Luke T. 
Published: March 2022

ABSTRACTFire can promote biodiversity but changing patterns of fire threaten species worldwide. While scientific literature often describes ‘inappropriate fire regimes’ as a significant threat to biodiversity, less attention has been paid to the characteristics that make a fire regime inappropriate. We go beyond this generic description and synthesize how inappropriate fire regimes contribute to declines of animal populations, using threatened mammals as a case study. We developed a demographic framework for classifying mechanisms by which fire regimes cause population decline, and applied the framework in a systematic review to identify fire characteristics and interacting threats associated with population declines in Australian threatened land mammals (n=99). Inappropriate fire regimes threaten 88% of Australian threatened land mammals. Our review indicates that intense, large, and frequent fires are the primary cause of fire-related population declines, particularly through their influence on survival rates. However, several species are threatened by a lack of fire and there is considerable uncertainty in the evidence base for fire-related declines. Climate change and predation are documented or predicted to interact with fire to exacerbate mammalian declines. This demographic framework will help target conservation actions globally and would be enhanced by empirical studies of animal survival, dispersal, and reproduction.
NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion
Authors: Tillé Laure , Cropp Daniela , Bodley Gabrielle , Andreatta Massimo , Charmoy Mélanie , Crespo Isaac , Nassiri Sina , Lourenco Joao , Leblond Marine , Lopez-Rodriguez Cristina , Speiser Daniel E. , Carmona Santiago J. , Held Werner , Verdeil Grégory 
Published: March 2022

AbstractPersistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. We discovered that NFAT5, an NFAT family member lacking an AP-1 docking site, is highly expressed in exhausted T cells from murine and human tumors and is a central player in tumor-induced exhaustion. While NFAT5 overexpression reduced tumor control, NFAT5 deletion improved tumor control by promoting the accumulation of tumor-specific CD8+ T cells that expressed less TOX and PD-1 and produced more cytokines particularly among precursor exhausted cells. Conversely, NFAT5 had no effect on chronic infection-induced T cell exhaustion. Mechanistically we found that TCR triggering induced NFAT5 expression and that hyperosmolarity stimulated transcriptional activity of NFAT5. We propose that NFAT5 takes over NFAT1/2 to promote exhaustion specifically in tumor-infiltrating CD8+ T cells.
Sea anemone Frizzled receptors play partially redundant roles in the oral-aboral axis patterning
Authors: Niedermoser Isabell , Lebedeva Tatiana , Genikhovich Grigory 
Published: March 2022

AbstractCanonical Wnt (cWnt) signaling is involved in a plethora of basic developmental processes such as endomesoderm specification, gastrulation and patterning the main body axis. To activate the signal, Wnt ligands form complexes with LRP5/6 and Frizzled receptors, which leads to nuclear translocation of β-catenin and transcriptional response. In Bilateria, the expression of different Frizzled genes is often partially overlapping, and their functions are known to be redundant in several developmental contexts. Here we demonstrate that all four Frizzled receptors take part in the cWnt-mediated oral-aboral axis patterning in the cnidarian Nematostella vectensis but show partially redundant functions. However, we do not see evidence for their involvement in the specification of the endoderm – an earlier event likely relying on maternal, intracellular β-catenin signaling components. Finally, we demonstrate that the main Wnt ligands crucial for the early oral-aboral patterning are Wnt3 and Wnt4. Comparison of our data to the knowledge from other models suggests that distinct but overlapping expression domains and partial functional redundancy of cnidarian and bilaterian Frizzled genes may represent a shared ancestral trait.
Tempo: an unsupervised Bayesian algorithm for circadian phase inference in single-cell transcriptomics
Authors: Auerbach Benjamin J. , FitzGerald Garret A. , Li Mingyao 
Published: March 2022

AbstractThe circadian clock is a 24-hour cellular timekeeping mechanism that temporally regulates human physiology. Answering several fundamental questions in circadian biology will require joint measures of single-cell circadian phases and transcriptomes. However, no widespread experimental approaches exist for this purpose. While computational approaches exist to infer cell phase directly from single-cell RNA-sequencing (scRNA-seq) data, existing methods yield poor circadian phase estimates, and do not quantify estimation uncertainty, which is essential for interpretation of results from highly sparse scRNA-seq data. To address these unmet needs, we developed Tempo, a Bayesian variational inference approach that incorporates domain knowledge of the clock and quantifies phase estimation uncertainty. Through simulations and analyses of real data, we demonstrate that Tempo yields more accurate estimates of circadian phase than existing methods and provides well-calibrated uncertainty quantifications. We further demonstrate that these properties generalize to the cell cycle. Tempo will facilitate large-scale studies of single-cell circadian transcription.
Drug mechanism enrichment analysis improves prioritization of therapeutics for repurposing
Authors: Garana Belinda B. , Joly James H. , Delfarah Alireza , Hong Hyunjun , Graham Nicholas A. 
Published: March 2022

ABSTRACTBACKGROUNDThere is a pressing need for improved methods to identify effective therapeutics for disease. Many computational approaches have been developed to repurpose existing drugs to meet this need. However, these tools often output long lists of candidate drugs that are difficult to interpret, and individual drug candidates may suffer from unknown off-target effects. We reasoned that an approach which aggregates information from multiple drugs that share a common mechanism of action (MOA) would increase on-target signal compared to evaluating drugs on an individual basis. In this study, we present Drug Mechanism Enrichment Analysis (DMEA), an adaptation of Gene Set Enrichment Analysis (GSEA), which groups drugs with shared MOAs to improve the prioritization of drug repurposing candidates.RESULTSFirst, we tested DMEA on simulated data and showed that it can sensitively and robustly identify an enriched drug MOA. Next, we used DMEA on three types of rank-ordered drug lists: (1) perturbagen signatures based on gene expression data, (2) drug sensitivity scores based on high-throughput cancer cell line screening, and (3) molecular classification scores of intrinsic and acquired drug resistance. In each case, DMEA detected the expected MOA as well as other relevant MOAs. Furthermore, the rankings of MOAs generated by DMEA were better than the original single-drug rankings in all tested data sets. Finally, in a drug discovery experiment, we identified potential senescence-inducing and senolytic drug MOAs for primary human mammary epithelial cells and then experimentally validated the senolytic effects of EGFR inhibitors.CONCLUSIONSDMEA is a fast and versatile bioinformatic tool that can improve the prioritization of candidates for drug repurposing. By grouping drugs with a shared MOA, DMEA increases on-target signal and reduces off-target effects compared to analysis of individual drugs. DMEA is publicly available as both a web application and an R package athttps://belindabgarana.github.io/DMEA.
Unsupervised discovery of tissue architecture in multiplexed imaging
Authors: Kim Junbum , Rustam Samir , Mosquera Juan Miguel , Randell Scott H. , Shaykhiev Renat , Rendeiro André F. , Elemento Olivier 
Published: March 2022

AbstractMultiplexed imaging and spatial transcriptomics enable highly resolved spatial characterization of cellular phenotypes, but still largely depend on laborious manual annotation to understand higher-order patterns of tissue organization. As a result, higher-order patterns of tissue organization are poorly understood and not systematically connected to disease pathology or clinical outcomes. To address this gap, we developed UTAG, a novel method to identify and quantify microanatomical tissue structures in multiplexed images without human intervention. Our method combines information on cellular phenotypes with the physical proximity of cells to accurately identify organ-specific microanatomical domains in healthy and diseased tissue. We apply our method to various types of images across physiological and disease states to show that it can consistently detect higher level architectures in human organs, quantify structural differences between healthy and diseased tissue, and reveal tissue organization patterns with relevance to clinical outcomes in cancer patients.
Targeted Anatomical and Functional Identification of Antinociceptive and Pronociceptive Serotonergic Neurons that Project to the Spinal Dorsal Horn
Authors: Ganley Robert P. , Magalhaes de Sousa Marília , Werder Kira , Öztürk Tugce , Mendes Raquel , Ranucci Matteo , Wildner Hendrik , Zeilhofer Hanns Ulrich 
Published: March 2022

AbstractSpinally-projecting serotonergic neurons play a key role in controlling pain sensitivity and can either increase or decrease nociception depending on physiological context. It is currently unknown how serotonergic neurons mediate these opposing effects. Utilizing virus-based strategies, we identified two anatomically separated populations of serotonergic hindbrain neurons located in the lateral paragigantocellularis (LPGi) and the medial hindbrain, which respectively innervate the superficial and deep spinal dorsal horn and have contrasting effects on sensory perception. Our tracing experiments revealed that serotonergic neurons of the LPGi were much more susceptible to transduction with spinally injected AAV2retro vectors than medial hindbrain serotonergic neurons. Taking advantage of this difference, we employed intersectional chemogenetic approaches to demonstrate that activation of the LPGi serotonergic projections decreases thermal sensitivity, whereas activation of medial serotonergic neurons increases sensitivity to mechanical von Frey stimulation. Together these results suggest that there are functionally distinct classes of serotonergic hindbrain neurons that differ in their anatomical location in the hindbrain, their postsynaptic targets in the spinal cord, and their impact on nociceptive sensitivity. The LPGi neurons that give rise to rather global and bilateral projections throughout the rostrocaudal extent of the spinal cord appear to be ideally posed to contribute to widespread systemic pain control.
Deep Learning-Derived Myocardial Strain
Authors: Kwan Alan C. , Tokodi Márton , Jain Ishan , Chang Ernest , Theurer John , Tang Xiu , Francisco Nadia , Haddad Francois , Liang David , Yuan Neal , Merkely Béla , Siegel Robert , Cheng Susan , Kovács Attila , Ouyang David 
Published: March 2022

ABSTRACTBackgroundEchocardiographic strain measurements require extensive operator experience and have significant inter-vendor variability. This study sought to develop an automated deep learning strain (DLS) analysis pipeline and validate its performance both externally and prospectively.MethodsThe DLS pipeline takes blood pool semantic segmentation results from the EchoNet-Dynamic network and derives longitudinal strain from the frame-by-frame change in the length of the left ventricular endocardial contour. The pipeline was developed using 7,465 echocardiographic videos, with preprocessing steps optimized to determine the change in endocardial length from systole to diastole. It was evaluated on a large external retrospective dataset and was prospectively compared with manual within-patient acquisition of repeated measures by two experienced sonographers and two separate vendor speckle-tracking methods on different machines.ResultsIn the external validation set, the DLS method maintained moderate agreement (intraclass correlation coefficient (ICC) 0.58, p<0.001) with a bias of -2.33% (limits of agreement -10.61 to 5.93%). The absolute difference in measurements was independent of subjective image quality (ß: 0.12, SE: 0.10, p=0.21). Compared to readers on repeated measures, our method has reduced variability (standard deviation: 1.35 vs. 2.55%) and better inter-vendor agreement (ICC: 0.45 vs. 0.29).ConclusionsThe DLS measurement provides lower variance than human measurements and similar quantitative results. The method is rapid, consistent, vendor-agnostic, publicly released, and robust across a wide range of imaging qualities.
COVID-19 Vaccine Hesitancy in Ghana: The Roles of Political Allegiance, Misinformation Beliefs, and Sociodemographic Factors
Authors: Brackstone Ken , Atengble Kirchuffs , Head Michael G , Boateng Laud A 
Published: March 2022

AbstractThe vast majority of people in the world who are unvaccinated against COVID-19 reside in LMIC countries in sub-Saharan Africa. This includes Ghana, where only 15.9% of the country are fully vaccinated as of April 2022. A key factor negatively impacting vaccination campaigns is vaccine hesitancy, defined as the delay in the acceptance, or blunt refusal, of vaccines. Four online cross-sectional surveys of Ghanaian citizens were conducted in August 2020 (N = 3048), March 2021 (N = 1558), June 2021 (N = 1295), and February 2022 (N = 424) to observe temporal trends of vaccine hesitancy in Ghana, and to examine key groups associated with hesitancy. Overall hesitancy decreased from 36.8% (95% CI: 35.1%-38.5%) in August 2020 to 17.2% (95% CI: 15.3%-19.1%) in March 2021. However, hesitancy increased to 23.8% (95% CI: 21.5%-26.1%) in June 2021, and then again to 52.2% (95% CI: 47.4%-57.0%) in February 2022. Key reasons included not having enough vaccine-related information (50.6%) and concerns over vaccine safety (32.0%). Hesitant groups included Christians, urban dwellers, opposition political party voters, people with more years of education, females, people who received COVID-19 information from internet sources, and people who expressed uncertainty about COVID-19 misinformation beliefs.
Outdoor long-range transmission of COVID-19 and patient zero
Authors: Rowe B.R. , Mitchell J.B.A. , Canosa A. , Draxler R. 
Published: March 2022

AbstractFollowing the outdoor model of risk assessment developed in one of our previous studies, we demonstrate in the present work that long-range transport of infectious aerosols could initiate patient “zero” creation at distances downwind beyond one hundred kilometers. The very low probability of this outdoor transmission can be compensated by high numbers and densities of infected and susceptible people such as it occurs in large cities, respectively in the source and the target.
Acceptance of COVID 19 vaccine among sub-Sahara African (SSA): a comparative study of residents and diaspora dwellers
Authors: Miner Chundung Asabe , Timothy Chikasirimobi G. , Mashige Khathutshelo Percy , Osuagwu Uchechukwu Levi , Envuladu Esther Awazzi , Amiebenomo Onyekachukwu Mary-Anne , Ovenseri-Ogbomo Godwin , Charwe Deborah Donald , Goson Piwuna Christopher , Ekpenyong Bernadine N , Abu Emmanuel Kwasi , Langsi Raymond , Oloruntoba Richard , Ishaya Tanko , Agho Kingsley 
Published: March 2022

AbstractThe COVID-19 vaccines are being rolled out across all the Sub-Saharan Africa (SSA) countries, with countries setting targets for achieving full vaccination rates. The aim of this study was to compare the uptake of, resistance and hesitancy to the COVID-19 vaccine between SSA locally residents and in the diaspora. This was a cross-sectional study conducted using a web and paper-based questionnaire to obtain relevant information on COVID-19 vaccine acceptance. The survey items included questions on demography, uptake and planned acceptance or non-acceptance of the COVID-19 vaccines among SSAs. Multinomial logistic regression was used to determine probabilities of outcomes for factors associated with COVID-19 vaccination resistance and hesitancy among SSA respondents residing within and outside Africa. Uptake of COVID-19 vaccines varied among the local (14.2%) and diaspora (25.3%) residents. There was more resistance to COVID-19 vaccine among locals (68.1%) and across the sociodemographic variables of sex [ adjusted Relative Risk (ARR) =0.73, 95% CI; 0.58 – 0.93], primary/less [ARR =0.22, 95% CI; 0.12 – 0.40] and bachelor’s degree [ARR =0.58, 95% CI; 0.43 – 0.77] educational levels, occupation [ARR =0.32, 95% CI; 0.25 - 0.40] and working status [ARR =1.40, 95%CI; 1.06 - 1.84]. COVID-19 vaccine hesitancy was almost similar between locals and diasporas (17.7% and 17.8% respectively) significant only among healthcare workers [ARR =0.46, 95% CI; 0.16 – 1.35] in the diaspora after adjusting for the variables. Similarly, knowledge and perception of COVID-19 vaccine among locals were substantial, but only perception was remarkable to resistance [ARR =0.86, 95% CI; 0.82 – 0.90] and hesitancy [ARR =0.85, 95% CI; 0.80 – 0.90] of the vaccine. Differences exist in the factors that influence COVID-19 vaccine acceptance between local SSA residents and those in the diaspora. Knowledge about COVID-19 vaccines affects the uptake, resistance, and hesitancy to the COVID-19 vaccine. Information campaigns focusing on the efficacy and safety of vaccines could lead to improved acceptance of COVID-19 vaccines.
Monoclonal antibody and antiviral therapy for treatment of mild-to-moderate COVID-19 in pediatric patients
Authors: Vora Surabhi B. , Englund Janet A. , Trehan Indi , Waghmare Alpana , Kong Ada , Adler Amanda , Zerr Danielle M. 
Published: March 2022

AbstractThe recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options for mild-to-moderate Covid-19 in high-risk adolescents and adults. In this report we describe patient characteristics, treatment-related process measures and outcomes associated with early Covid-19 therapy in high-risk pediatric patients.