bluuebunny/crossref_metadata_2025_split huggingface dataset:
0460 First-line treatment patterns in patients with insomnia: a large-scale, real-world cohort study
Authors: Grandner Michael , Ahuja Ajay , Meijer Paulien , Büsser Alexander , McCall William , Lettieri Christopher 
Published: May 2022

Abstract

Introduction
Current pharmacologic treatments for insomnia are not universally effective, are associated with a range of adverse events, can cause daytime impairment, and have the potential to be abused. With no consistent standard of care, many patients with insomnia experience multiple dose changes and medication switches. The current study leveraged large-scale, real-world data to investigate the pharmacological treatment patterns of patients with insomnia.

Methods
Exploratory analyses were performed on claims data from the HealthVerity US primary care claims database. Data from 10/2015 to 3/2020 were obtained for patients aged 18+. Prescribing patterns, including initial treatment, switching, concomitant treatment, and discontinuation were explored.

Results
Of approximately 1.4 million individuals, 265,382 (~19%) had an insomnia diagnosis and 42.4% of that group were prescribed hypnotic medications. Among those, first prescriptions were most frequently a Z-drug (zolpidem, eszopiclone, zaleplon; 35.8%), trazodone (25.0%), a benzodiazepine (15.6%), or another class (23.6%; includes orexin receptor antagonists, antidepressants, melatonin agonists, etc.). For those receiving a benzodiazepine first, median treatment duration was 55 days, 80.4% of subjects discontinued, 11.6% were switched to a different medication, and 7.9% received concomitant treatment with another sleep medicine. For those first receiving a Z-drug, median treatment duration was 81 days, 87.3% discontinued, 8.2% were switched, and 4.4% received concomitant treatment. For those receiving trazodone first, median treatment duration was 104 days, 85.8% of patients eventually discontinued, 5.8% of patients received concomitant treatment with an additional hypnotic agent, and 8.4% switched to a different hypnotic. Furthermore, of those switched from trazodone, 22% were switched to a benzodiazepine, 31% to a Z-drug, and 47% to a medication of another class.

Conclusion
These results demonstrate a lack of a standard first-line treatment approach for insomnia; it is likely that physicians have their own preferences, or that they might tailor treatment choice to individual patient characteristics. Additionally, more insomnia patients are discontinued from medical treatment than are switched to a different medicine. Further study is needed to determine what proportion of treatment discontinuation is due to successful treatment, versus being due to adverse events or lack of efficacy.

Support (If Any)
Idorsia Pharmaceuticals, Ltd.
0495 Sleep Disturbance Features Differentially Influence Inflammatory Markers in Adolescents
Authors: Chiem Emily , O'Hora Kathleen , Grigoryan Vardui , Amir Carolyn , Irwin Michael , Chiang Jessica , Bearden Carrie 
Published: May 2022

Abstract

Introduction
Sleep disruption has profound effects on immune function. Many adolescents do not get adequate amounts of sleep each night, and chronic sleep disturbance has been associated with increased risk of several inflammatory diseases. However, the relationship between sleep disturbances and inflammation during adolescence is not well understood. In this study, we examined the relationship between specific features of sleep disruption and cytokine levels in adolescents.

Methods
A total of 88 adolescents (18.36 ± 0.51 years, 56.8% female) completed the Pittsburgh Sleep Quality Index (PSQI), a self-reported questionnaire used to assess subjective sleep quality over a 1-month time period. Blood plasma samples were obtained for each participant at the same timepoint to measure levels of pro-inflammatory cytokines (Interleukin (IL)-6, IL-8, tumor-necrosis factor (TNF)-alpha, and interferon (IFN)-gamma), anti-inflammatory cytokine (IL-10), and C-reactive protein (CRP). Samples were assayed using a Meso Scale Discovery multiplex immunoassay. Linear regression models were used to test the effect of PSQI sleep latency, duration, efficiency, quality, disturbance, and total score on each cytokine level, while covarying for sex and body mass index. We corrected for multiple comparisons using a False Discovery Rate (FDR) correction.

Results
Overall, disruption in sleep was associated with distinct cytokine differences. Worse sleep, reflected by the PSQI total score and greater sleep disturbance, was associated with lower IL-6 levels (p=0.013, p=0.015, respectively), however theses associations were attenuated to a trend after FDR correction (q=0.083, q=0.092, respectively). Longer sleep latency was also associated with lower IL-6 (p=0.028), and IFN (p=0.016) levels, however these effects were also attenuated after FDR correction (q=0.138, q=0.094, respectively). Reduced sleep efficiency was associated with higher TNF (q=0.046) and CRP (q=0.021) levels.

Conclusion
Our findings show that different components of sleep disruption have varying effects on cytokine release, resulting in an overall blunted immune response. This underscores the significant impact of sleep disturbances on perturbing immune function during this critical developmental period.

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0587 Sleep Problems are Associated with Treatment for Anemia in the US Population
Authors: Shah Sayani , Mason Brooke , Wills Chloe , Tubbs Andrew , Killgore William , Grandner Michael 
Published: May 2022

Abstract

Introduction
Anemia is characterized as low circulating hemoglobin and is often treated with an increase in iron consumption. Previous studies have linked anemia with Restless Legs Syndrome. Regarding other sleep disorders, Insomnia has been found to be associated with anemia in children, but the relationship has been understudied in adults.

Methods
A multinomial logistic regression was conducted on the data collected from 2017 to March 2020 for the National Health and Nutrition Examination Survey, to explore a relationship between those with self-assessed sleep problems and whether the participant was treated for anemia. Sleep problems were assessed using a item asking participants how often they have been bothered by difficulties “falling asleep, staying asleep, or sleeping too much,” categorized as “Never,” “Several Days,” “More Than Half the Days” and “Nearly Every Day” in the past 2 weeks. Anemia treatment was characterized as “yes” or “no” based on self-report, with any form of treatment in the past 3 months was considered as “yes.” Reported results were unweighted; weighted results forthcoming.

Results
Unadjusted results indicate that those being treated for anemia show an increased likelihood of sleep difficulties several days (OR:1.36, [1.07,1.73] p=0.011), more than half the days (OR: 1.59, [1.13,2.25] p=0.008), and nearly every day (OR: 1.85, [1.37,2.50] p&lt;0.001), compared to those who report that they never have sleep difficulties. When adjusted for sex, age, race/ethnicity, education, and marital status, those being treated for anemia show significant increased odds of sleep problems several days (OR: 1.29, [1.01,1.65] p=0.041), more than half the days (OR: 1.50, [1.06,2.14] p=0.024), and nearly every day (OR: 1.55, [1.13,2.13] p=0.006), compared to never. Those being treated for anemia also had a higher likelihood of having short sleep (≤ 6 hours) during the week (OR: 1.56, [1.13,2.15], p=0.007) as well as long sleep( ≥ 9 hours) (OR: 1.75, [1.30,2.36], p&lt;0.001) compared to those that slept a healthy amount, 6.5-8.5 hours a night.

Conclusion
There was a significant relationship between those treated for anemia the presence of sleep difficulties, as well as short and long sleep. Future studies should assess the associations between anemia and specific sleep characteristics, as sleep problems may be a cause, a consequence, or a marker of anemia. Also, the degree to which these sleep difficulties represent overlap with Restless Legs symptoms should be explored at the population level.

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0721 Correlation between Oxygen Desaturation Index and Apnea Hypopnea Index for Diagnosis of Obstructive Sleep Apnea
Authors: Jamil Saad Bin , Kachechian Talar , Armache Maria , Alapati Rahul , Tsao Jaime , Huntley Colin , Fast Zhanna 
Published: May 2022

Abstract

Introduction
Obstructive sleep apnea (OSA) is diagnosed through polysomnography (PSG) which can be done in lab or outpatient. PSG is conventionally not approved by insurance companies’ in-patient which can result in delay in diagnosis and treatment of OSA. High resolution pulse oximetry (HRPO) done inpatient is easy to perform and calculates oxygen desaturation index (ODI) to asses’ nocturnal desaturations which solely, is insufficient for diagnoses of OSA according to current treatment guidelines. We hypothesize that there may be a correlation between ODI and apnea hypopnea index (AHI) which can facilitate in earlier diagnosis of OSA.

Methods
We conducted a retrospective chart review to compare patients who underwent HRPO resulting in a sleep medicine consult inpatient followed by polysomnography outpatient over a 2-year period at a tertiary care academic center. Demographic data, ODI, AHI and oxygen nadir levels were collected.

Results
Sixty-five patients (47 males, 18 females; mean age of 59.1 years) with suspected OSA underwent inpatient HRPO during their hospital stay, followed by a PSG in the outpatient setting. The strength of association between ODI and AHI was determined using a Pearson’s analysis after adjusting to a logarithmic scale. There was a statistically significant weakly positive association between ODI and AHI (Pearson correlation=0.33, p=0.008). Linear regression analysis demonstrated a predictive value of 0.419 (p=0.008) between AHI and ODI. However, there was no statistically significant predictive value between ODI and AHI when adjusted for age, sex, body mass index (BMI) and ethnicity (beta =0.169; p=0.330). This may be limited by small sample size. HRPO nadir oxygen saturation (NOS) also correlated with polysomnography NOS with a Pearson correlation coefficient of 0.353 (p=0.006). Linear regression analysis showed a predictive value beta of 0.149 (p=0.006). When adjusted for age, sex, BMI and race, beta was equal to 0.156 (p=0.007).

Conclusion
ODI calculated through HRPO may be correlated with AHI. NOS determined through HRPO is weakly positively predictive of NOS calculated through PSG. To initiate treatment of OSA sooner, HRPO may be considered for screening or diagnostic purposes. The correlation between ODI and AHI needs to establish further in randomized controlled setting.

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0782 Changes in markers of ventricular repolarization and positive airway pressure therapy: A pilot study
Authors: Perez Karolina , Zareba Wojciech , LaFleur Bonnie , Xia Xiaojuan , Woosley Raymond , Patel Imran , Quan Stuart , Grandner Michael , Youngstedt Shawn , Miller Jerod , Parthasarathy Sairam , Patel Salma 
Published: May 2022

Abstract

Introduction
Positive airway pressure (PAP) therapy is the mainstay treatment for obstructive sleep apnea (OSA). Continuous PAP (CPAP) therapy has been shown to decrease QTc length in electrocardiograms in patients with OSA in small studies. The impact of higher pressures of CPAP and Bilevel PAP (BPAP) on ventricular repolarization—QTc length and QT variability in OSA is unknown. The goal of this pilot study is to explore this relationship.

Methods
10 consecutive patients who underwent polysomnography during which they had a diagnostic, CPAP titration, and BPAP titration portion were included for analysis. Bazett’s heart rate correction was used to calculate QTc. QT variability was measured as short-term interval QT variability (STVQT) and normalized QT interval variance (QTVN). All variables were analyzed for the entire duration of the diagnostic period, on the highest CPAP pressure and highest BPAP pressure delivered.

Results
The patients were 49 ± 15 years of age and 60% women. Median CPAP pressure was 14.5 cm H2O (mean 13.5 ± 5 cm H2O). For BPAP, the median inspiratory PAP was 21.5 cm H2O (mean 20.5 ± 5 cm H2O) and EPAP median was 16 cm H2O (mean 15.9 ± 4 cm H2O). Mean QTc for the diagnostic portion, highest CPAP pressure and highest BPAP pressure were 430 ± 17 ms, 445 ± 15 ms and 441 ± 21 ms, respectively (p=0.141). Mean QTVN for the diagnostic portion, highest CPAP pressure and highest BPAP pressure settings were 0.0011 ± 0.0008 dimensionless units (du), 0.0012± 0.0008 du and 0.002 ± 0.0012 du, respectively (p=0.127). STVQT for the diagnostic portion, highest CPAP pressure and highest BPAP pressure settings were 6.62 ± 4.13 ms, 9.12 ± 4.7271 ms and 12.62 ± 4.99 ms, respectively (P=0.041). Post-hoc pairwise comparisons between BPAP and diagnostic portions of the study were significant for STVQT (P=0.034).

Conclusion
Short-term QT variability, STVQT, was significantly increased on BPAP when compared to the diagnostic portion of the study.

Support (If Any)
American Academy of Sleep Medicine Foundation (203-JF-18), National Institutes of Health (HL126140, 2L30HL154400-023) University of Arizona Health Sciences Career Development Award (5299903), and University of Arizona Faculty Seed Grant (5833261)
How brain networks tic: predicting tic severity through rs-fMRI dynamics in Tourette syndrome
Authors: Ramkiran Shukti , Veselinović Tanja , Dammers Jürgen , Rajkumar Ravichandran , Shah N. Jon , Neuner Irene 
Published: May 2022

AbstractTourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and phonic tics, which several different theories, such as basal ganglia-thalamo-cortical loop dysfunction and amygdala hypersensitivity, have sought to explain. Previous research has shown dynamic changes in the brain prior to tic onset leading to tics, and this study aims to investigate the contribution of network dynamics to them. For this, we have employed three methods of functional connectivity to resting-state fMRI data - namely the static, the sliding window dynamic and the ICA based estimated dynamic; followed by an examination of the static and dynamic network topological properties. A leave-one-out (LOO-) validated regression model with LASSO regularization was used to identify the key predictors. Most relevant predictors were related to regions belonging to the amygdala-mediated visual social processing network. This is in line with a recently proposed social decision-making dysfunction hypothesis, opening new horizons in understanding tic pathophysiology.
Characterization and Profiling of Gut Bacterial Microbiome and Pathobionts among HIV-negative and HIV-infected individuals in Cameroon
Authors: Ako Simon Eyongabane , Nkenfou Celine N. , Assob Jules N. , Pokam Thumamo Benjamin , Njopin Christopher , Eteneneng Enoh Jude , Nchang Cho Frederick , Mbanya Mbanya Gladice , Gilles-Fils Woguia , Franck Ngoume Moukoma Y. , Akum Eric Achidi 
Published: May 2022

ABSTRACTBackgroundKnowledge of the core gut microbiome among Cameroonians is a preliminary step for a better implementation of treatment strategies to correct dysbiosis and improve health care management. HIV infection has continued to cause high mortality among those infected, but the types and frequency of human gut microbiota associated with or without HIV/AIDS presence have not been identified in the adult populations in Cameroon.MethodsThis was a case-control and comparative study design that ran from June 2018 to September 2019. Stool Samples were purposively collected from 40 participants (15 HIV-negative and 25 HIV-positive) for the 16S rRNA gene sequencing on the next-generation Illumina® MiSeq™ sequencer. Blood samples were collected for HIV determine testing, CD4 Tcell count and HIV viral load. Sequences were clustered into operational taxonomic units (OTUs) at ninety-nine percent identity and their representatives were accustomed to using a phylogenetic approach.ResultsThe study showed a phylogenetic taxonomy of the gut microbiome communities in two kingdoms (Archea and Bacteria) and eight Phylum [Firmicutes (44.7%), Bacteroidetes (43.7%), Proteobacteria (8.7%), Actinobacteria (1%), Fusobacteria (0.2%), Euryarchaeota (0.01%), Synergistetes (0.01%), Verrucomicrobia (0.01%) and unclassified phylum (1.7%)]. A total of 347 gut microbiota species were identified, 55 unique species/oligotypes and 28 pathobionts from the study population. HIV infection was characterized by significant gut microbiota compositional changes with HIV-positive less diverse (56 strains absent) with significant increased OTUs of the butyrate-producing microbiome species as compared to HIV-negative individuals (p=0.001).ConclusionsA profile of 347 gut microbiome bacterial species where identified in the Cameroonian community. Particularly, from the 347 gut microbiome bacterial species profiled, eight phyla were identified, with 55 unique species/oligotypes containing more than one sequence and 28 pathobionts. A host of unknown/unclassified gut microbiome bacterial species were also noted circulating among the study population.Key PointsThere is high diversity and specie uniqueness of the gut microbiome in Cameroon. Functionality of the gut microbiome needs to be investigated.There are gut pathobionts circulating among HIV-infected and HIV-negative individuals in Cameroon. The origin of pathobionts is a call for concern.Unique gut microbiome OTU sequences are significantly high among HIV-infected. Emerging strains of new microorganisms are on a rise.
Coregistered transcranial optoacoustic and magnetic resonance angiography of the human brain
Authors: Ni Ruiqing , Dean-Ben Xose Luis , Treyer Valarie , Gietl Anton , Hock Christoph , Klohs Jan , Nitsch Roger M. , Razansky Daniel 
Published: May 2022

AbstractImaging modalities capable of visualizing the human brain have led to major advances in neurology and brain research. Multi-spectral optoacoustic tomography (MSOT) has gained importance for studying cerebral function in rodent models due to its unique capability to map changes in multiple hemodynamic parameters and to directly visualize neural activity within the brain. The technique further provides molecular imaging capabilities that can facilitate early disease diagnosis and treatment monitoring. However, transcranial imaging of the human brain is hampered by acoustic attenuation and other distortions introduced by the skull. Here, we demonstrate noninvasive transcranial MSOT angiography through the temporal bone of an adult healthy volunteer. Time-of-flight (TOF) magnetic resonance angiography (MRA) and T1-weighted structural MRI were further acquired to facilitate anatomical registration and interpretation. The superior middle cerebral vein in the temporal cortex was identified in the MSOT images, matching its location observed in the TOF-MRA images. These initial results pave the way toward the application of MSOT in clinical brain imaging.
Development and scaling of a sequencing pipeline for genomic surveillance of SARS-CoV-2 in New York City
Authors: Hammerling Michael J. , Kang Shinyoung Clair , Ward William , Escapa Isabel F. , Bugga Pradeep , Del Castillo Cybill , Hopkins Melissa , Chase Steven , Rey Sol , Law Dylan , Carpio Alexander , Nelson Katharine , Chhabria Simran , Gupta Simran , Rivera Tiara , Laurent Jon M. , Hao Haiping , Lee Henry H. 
Published: May 2022

ABSTRACTIn the ongoing COVID-19 pandemic, detecting the appearance and spread of variants of concern (VOC) is a critical capability in the fight to quell the virus and return to normalcy. Genomic surveillance of the emergence, propagation, and geographical spread of VOCs is thus an important tool for public health officials and government leaders to make policy decisions and advise the public. As part of our role as a major SARS-CoV-2 diagnostic testing facility in New York City, the Pandemic Response Lab (PRL) has been performing genomic surveillance on the large number of positive samples processed by the facility on a daily basis from throughout the New York metropolitan area. Here we describe the development and optimization of a high-throughput SARS-CoV-2 genome sequencing facility at PRL serving New York City.
Active remodeling of the chromatin landscape directs extravillous trophoblast cell lineage development
Authors: Varberg Kaela M. , Dominguez Esteban M. , Koseva Boryana , Varberg Joseph M. , McNally Ross P. , Moreno-Irusta Ayelen , Wesley Emily R. , Iqbal Khursheed , Cheung Warren A. , Schwendinger-Schreck Carl , Smail Craig , Okae Hiroaki , Arima Takahiro , Lydic Michael , Holoch Kristin , Marsh Courtney , Soares Michael J. , Grundberg Elin 
Published: May 2022

ABSTRACTThe extravillous trophoblast (EVT) cell lineage is a key feature of placentation and successful pregnancy. Knowledge of transcriptional regulation driving EVT cell development is limited. Here, we mapped the transcriptome and epigenome landscape as well as chromatin interactions of human trophoblast stem (TS) cells and their transition into EVT cells. Integration of chromatin accessibility, long-range chromatin interactions, transcriptomic, and transcription factor (TF) binding motif enrichment enabled identification of TFs and regulatory mechanisms associated with EVT cell development. Functional roles forTFAP2C,SNAI1,andEPAS1in the regulation of EVT cell development were elucidated.EPAS1was identified as an upstream regulator of key EVT cell TFs, includingASCL2andSNAI1and together with its target genes, was linked to pregnancy loss and birth weight. Collectively, we have revealed activation of a dynamic regulatory network that provides a framework for understanding EVT cell specification in trophoblast cell lineage development and human placentation.
SARS-CoV-2 variants in the making: Sequential intrahost evolution and forward transmissions in the context of persistent infections
Authors: Gonzalez-Reiche Ana S. , Alshammary Hala , Schaefer Sarah , Patel Gopi , Polanco Jose , Carreño Juan Manuel , Amoako Angela A. , Rooker Aria , Cognigni Christian , Floda Daniel , van de Guchte Adriana , Khalil Zain , Farrugia Keith , Assad Nima , Zhang Jian , Alburquerque Bremy ,   PARIS/PSP study group, Sominsky Levy , Gleason Charles , Srivastava Komal , Sebra Robert , Ramirez Juan David , Banu Radhika , Shrestha Paras , Krammer Florian , Paniz-Mondolfi Alberto , Sordillo Emilia Mia , Simon Viviana , van Bakel Harm 
Published: May 2022

AbstractPersistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, to our knowledge, no direct evidence of subsequent transmission and stepwise adaptation is available.Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins.Our findings demonstrate that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome during persistent infection in more than one host, and also document ongoing transmission of these novel variants. There is an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.