bluuebunny/crossref_metadata_2025 huggingface dataset:
State and County-Level Factors Associated with the Effectiveness of Stay-At-Home Orders Issued in the United States in Response to COVID-19
Authors: Barker Forrest DL , Mirzadadeh Ali , Feachem Neelam Sekhri
Published: May 2023

Title

State and County-Level Factors Associated with the Effectiveness of Stay-At-Home Orders Issued in the United States in Response to COVID-19

Background

To slow the spread of COVID-19 and protect medical facilities from overflowing, Stay-At-Home Orders (SAHOs) were issued in the United States during the spring of 2020. These orders had variable levels of effectiveness and profound consequences that continue to manifest long after their termination. This study aimed to assess if state and county-level population characteristics could explain variability in SAHO effectiveness as measured by the effective reproductive number (Rt).

Methods

We calculated the Rtfor the 40 states which enacted SAHOs, and also for a sample of 289 counties that issued SAHOs in 2020, using EpiEstim R Package based on the states’ and counties’ daily case data. We determined SAHOs to be effective if, three weeks after their implementation, Rtwas equal to or less than one. Wilcoxon rank sum tests and logistic regression were used to determine if population characteristics (age, income, level of education, political orientation, percent of non-English speaking people, racial and ethnic compositions), and percentage of frontline workers, percent of eligible people vaccinated by July 2021, level of viral transmission, and other Non-Pharmaceutical-Interventions (NPI) enacted before the SAHO, were associated with effectiveness of SAHOs.

Results

SAHOs were effective in 20 (50%) states. No significant differences were found in the characteristics studied between states with effective and ineffective SAHOs. SAHOs were effective in 54% of counties. Counties with effective SAHOs had fewer days of NPIs before the SAHOs in comparison to counties with ineffective SAHOs (Median 24 vs. 34, p-value 0.005). All other characteristics considered showed non-significant differences. In multivariate analysis, days of NPIs before the SAHOs remained the only significant factor for effective SAHOs in studied counties.

Conclusion

Our analysis suggests that SAHO effectiveness may be influenced by the implementation of prior public health interventions but is not likely to be related to the other characteristics studied. These findings should be considered when assessing when and how to implement SAHOs in future epidemics to limit the spread of an infectious respiratory disease.
Impact of the COVID-19 Pandemic, Stratified by Transfer and COVID-19 Infection Status, on Inpatient Mortality in ST-Elevation Myocardial Infarction Patients, Using a Nationally Representative Database
Authors: Gill Ahmad , Al-Taweel Omar , Massey Blaine , Mohammed Salman , Ren Jie , Al-Baghdadi Yousif , Parida Akash , Fakhra Sadaf , Rahimi Osman , Badial Tajinder , Patibandla Saikrishna , Wineinger Tracy , Alkhatib Deya , Mubder Mohamad , Ahsan Chowdhury
Published: May 2023

Introduction

The coronavirus disease 2019 (COVID-19) pandemic has impacted various aspects of healthcare, including the management of ST-elevation myocardial infarction (STEMI) patients. Our study investigates the in-hospital outcomes and the impact of transfer and COVID-19 infection status on mortality in STEMI patients.

Methods

We conducted a retrospective cohort study to compare the inpatient outcomes of STEMI patients in 2020 with STEMI patients from 2016 to 2019 using the National Inpatient Sample database. We performed 1:1 greedy nearest neighbor matching and utilized logistic regression to compare mortality.

Results

In our matched cohort, there was no difference in overall mortality between STEMI patients in 2020 and those from 2016 to 2019 (OR 1.00, 95% CI: 0.94-1.05; p = 0.87). When stratified by COVID-19 infection status, regularly admitted STEMI patients with concurrent COVID-19 infection in 2020 had 2.11 times higher odds of inpatient mortality compared to regularly admitted STEMI patients from 2016 to 2019 (OR 2.11, 95% CI: 1.55-2.87; p < 0.001). STEMI acute care transfers with concurrent COVID-19 infection in 2020 had 3.17 times higher odds of inpatient mortality than those from 2016 to 2019 (OR 3.17, 95% CI: 1.83-5.50; p < 0.001). STEMI non-acute care transfers with concurrent COVID-19 infection in 2020 had 5.13 times higher odds of inpatient mortality than those from 2016 to 2019 (OR 5.13, 95% CI: 1.87-14.06; p = 0.001).

Conclusion

The COVID-19 pandemic exacerbated many longstanding disparities within our healthcare system. Moving forward, it is crucial to engage in further discussions addressing the national physician shortage, the patient transfer system and healthcare in underserved regions.
KOunt – A reproducible KEGG orthologue abundance workflow
Authors: Mattock Jennifer , Martínez-Álvaro Marina , Cleveland Matthew A. , Roehe Rainer , Watson Mick
Published: May 2023

Accurate gene prediction is essential for successful metagenome analysis. We present KOunt, a Snake-make pipeline, that precisely quantifies KEGG orthologue abundance.

Availability and implementation

KOunt is available on GitHub:https://github.com/WatsonLab/KOunt. The KOunt reference database is available on figshare:https://figshare.com/s/72fe3ed7dfbbdcd8b1e5. Test data are available athttps://figshare.com/ndownloader/files/39545968and version 1.1.0 of KOunt athttps://figshare.com/ndown-loader/files/39547273.

Contact

jennifer.mattock@roslin.ed.ac.uk

Supplementary information

Supplementary data are available atBioinformaticsonline.
Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients
Authors: Lii Theresa R. , Smith Ashleigh E. , Flohr Josephine R. , Okada Robin L. , Nyongesa Cynthia A. , Cianfichi Lisa J. , Hack Laura M. , Schatzberg Alan F. , Heifets Boris D.
Published: May 2023

BACKGROUND

Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials.

METHODS

In a triple-masked, randomized, placebo-controlled trial, 40 adult patients with major depressive disorder were randomized to a single infusion of ketamine (0.5 mg/kg) or placebo (saline) during anesthesia as usual for routine surgery. The primary outcome was depression severity measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 1, 2, and 3 days post-infusion. The secondary outcome was the proportion of participants with clinical response (≥50% reduction in MADRS scores) at 1, 2, and 3 days post-infusion. After all follow-up visits, participants were asked to guess which intervention they received.

RESULTS

Mean MADRS scores did not differ between groups at screening or pre-infusion baseline. The mixed-effects model showed no evidence of effect of group assignment on post-infusion MADRS scores at 1 to 3 days post-infusion (−5.82, 95% CI −13.3 to 1.64, p=0.13). Clinical response rates were similar between groups (60% versus 50% on day 1) and comparable to previous studies of ketamine in depressed populations. Secondary and exploratory outcomes did not find statistical separation of ketamine from placebo. 36.8% of participants guessed their treatment assignment correctly; both groups allocated their guesses in similar proportions. One serious adverse event occurred in each group, unrelated to ketamine administration.

CONCLUSION

In adults with major depressive disorder, a single dose of intravenous ketamine delivered during surgical anesthesia had no greater effect than placebo in acutely reducing the severity of depressive symptoms. This trial successfully masked treatment allocation in moderate-to-severely depressed patients using surgical anesthesia. While it is impractical to use surgical anesthesia for most placebo-controlled trials, future studies of novel antidepressants with acute psychoactive effects should make efforts to fully mask treatment assignment in order to minimize subject-expectancy bias. (ClinicalTrials.govnumber,NCT03861988)
Factors Associated with Overweight and Obesity among Women of Reproductive Age in Cambodia: Analysis of Cambodia Demographic and Health Survey
Authors: Um Samnang , An Yom
Published: May 2023

Overweight and obesity are associated with increased chronic disease and death rates globally. In Cambodia, the prevalence of overweight and obesity among women is high and may grow. This study aimed to determine the prevalence and factors associated with overweight and obesity among women of reproductive age (WRA) in Cambodia. We analyzed data from the 2021-2022 Cambodia Demographic and Health Survey (CDHS) that used a two-stage stratified cluster sampling design. Data analysis was restricted to non-pregnant women, resulting in an analytic sample of 9,417 WRA. Multivariable logistic regressions were performed using STATA V17 to examine factors associated with overweight and obesity. Prevalence of overweight and obesity among non-pregnant women of reproductive age was 22.56%, and 5.61% were overweight and obese, respectively. Factors independently associated with increased odds of overweight and obesity included women aged 20-29 years [AOR=1.85; 95% CI: 1.22 - 2.80], 30-39 years [AOR=3.34; 95% CI: 2.21 - 5.04], and 40-49 years [AOR=5.57; 95% CI: 3.76 - 8.25], married women [AOR=2.49; 95% CI: 1.71-3.62], women from middle wealth quintile [AOR=1.21; 95% CI: 1.02-1.44], and rich wealth quintile [AOR=1.44; 95% C: 1.19 - 1.73], having at least three children or more [AOR=1.40; 95% CI: 1.00 - 1.95], ever drink alcohol [AOR=1.24; 95% CI: 1.04 - 1.47], and current drink alcohol [AOR=1.2; 95% CI: 1.01 - 1.45]. On the contrary, the following factors were independently associated with decreased odds of having overweight and obese: women with at least secondary education [AOR=0.73; 95% CI: 0.58-0.91] and working in manual labor jobs [AOR=0.76; 95% CI: (0.64 - 0.90]. Increased age, married women, having at least three children, and alcohol consumption were the main risk factors associated with overweight and obesity. Conversely, higher education and manual labor were negatively associated with overweight and obesity. Cambodia’s non-communicable disease (NCD) public health programs should consider these characteristics for targeting interventions further to reduce overweight and obesity in the coming years.
Genetic influences on alcohol flushing in East Asian populations
Authors: Cho Yoonsu , Lin Kuang , Lee Su-Hyun , Yu Canqing , Valle Dan Schmidt , Avery Daniel , Lv Jun , Jung Keumji , Li Liming , Smith George Davey ,   China Kadoorie Biobank Collaborative Group, Chen Zhengming , Millwood Iona Y. , Hemani Gibran , Walters Robin G.
Published: May 2023

Background

Although it is known that variation in thealdehyde dehydrogenase 2(ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.

Methods

We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake.

Results

We identified variants in the region ofALDH2strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 andADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke).

Conclusion

This study confirms thatALDH2-rs671 andADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.

Trial registration

This study only used secondary data.
Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron Variants in Mice and Hamsters
Authors: Case James Brett , Scheaffer Suzanne M. , Darling Tamarand L. , Bricker Traci L. , Adams Lucas J. , Harastani Houda , Trende Reed , Sanapala Shilpa , Fremont Daved H. , Boon Adrianus C. M. , Diamond Michael S.
Published: May 2023

The continued evolution and emergence of novel SARS-CoV-2 variants has resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a currently circulating SARS-CoV-2 Omicron lineage variant, BQ.1.1, in multiple rodent models including K18-hACE2 transgenic, C57BL/6J, and 129S2 mice, and Syrian golden hamsters. In contrast to a previously dominant BA.5.5 Omicron variant, inoculation of K18-hACE2 mice with BQ.1.1 resulted in a substantial weight loss, a characteristic seen in pre-Omicron variants. BQ.1.1 also replicated to higher levels in the lungs of K18-hACE2 mice and caused greater lung pathology than the BA.5.5 variant. However, C57BL/6J mice, 129S2 mice, and Syrian hamsters inoculated with BQ.1.1 showed no differences in respiratory tract infection or disease compared to animals administered BA.5.5. Airborne or direct contact transmission in hamsters was observed more frequently after BQ.1.1 than BA.5.5 infection. Together, these data suggest that the BQ.1.1 Omicron variant has increased virulence in some rodent species, possibly due to the acquisition of unique spike mutations relative to other Omicron variants.

IMPORTANCE

As SARS-CoV-2 continues to evolve, there is a need to rapidly assess the efficacy of vaccines and antiviral therapeutics against newly emergent variants. To do so, the commonly used animal models must also be reevaluated. Here, we determined the pathogenicity of the circulating BQ.1.1 SARS-CoV-2 variant in multiple SARS-CoV-2 animal models including transgenic mice expressing human ACE2, two strains of conventional laboratory mice, and Syrian hamsters. While BQ.1.1 infection resulted in similar levels of viral burden and clinical disease in the conventional laboratory mice tested, increases in lung infection were detected in human ACE2-expressing transgenic mice, which corresponded with greater levels of pro-inflammatory cytokines and lung pathology. Moreover, we observed a trend towards greater animal-to-animal transmission of BQ.1.1 than BA.5.5 in Syrian hamsters. Together, our data highlight important differences in two closely related Omicron SARS-CoV-2 variant strains and provide a foundation for evaluating countermeasures.
Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS
Authors: Woods Scott W. , Parker Sophie , Kerr Melissa J. , Walsh Barbara C. , Wijtenburg S. Andrea , Prunier Nicholas , Nunez Angela R. , Buccilli Kate , Mourgues-Codern Catalina , Brummitt Kali , Kinney Kyle S. , Trankler Carli , Szacilo Julia , Colton Beau-Luke , Ali Munaza , Haidar Anastasia , Billah Tashrif , Huynh Kevin , Ahmed Uzair , Adery Laura L. , Corcoran Cheryl M. , Perkins Diana O. , Schiffman Jason , Perez Jesus , Mamah Daniel , Ellman Lauren M. , Powers Albert R. , Coleman Michael J. , Anticevic Alan , Fusar-Poli Paolo , Kane John M. , Kahn Rene S. , McGorry Patrick D. , Bearden Carrie E. , Shenton Martha E. , Nelson Barnaby , Calkins Monica E. , Hendricks Larry , Bouix Sylvain , Addington Jean , McGlashan Thomas H. , Yung Alison R. ,   the Accelerating Medicines Partnership Schizophrenia,   AMP SCZ Working Group and Subgroup leaders (not previously listed):, Allott Kelly , Clark Scott R. , Kapur Tina , Lavoie S. , Lewandowski Kathryn E. , Mathalon Daniel H. , Pasternak Ofer , Stone William S. , Torous John ,   National Institute of Mental Health Project Scientists:, Rowland Laura M. , Zhan Ming ,   Research Network and DPACC Investigators (not previously listed):, Amminger Paul , Arango Celso , Broome Matthew R. , Cadenhead Kristin S. , Chen Eric Y.H. , Choi Jimmy , Kevin Cho Kang Ik , Conus Philippe , Cornblatt Barbara A. , Glenthøj Louise Birkedal , Horton Leslie E. , Kambeitz Joseph , Keshavan Matcheri S. , Koutsouleris Nikolaos , Langbein Kerstin , Diaz-Caneja Covadonga Martinez , Mittal Vijay A. , Nordentoft Merete , Gaspar Ramos Pablo A. , Pearlson Godfrey D. , Shah Jai L. , Smesny Stefan , Strauss Gregory P. , Wang Jijun ,   Study Coordinators and Project Managers (not previously listed):, Marcy Patricia J. , Matneja Priya , Phassouliotis Christina , Ray Susan , Snowball Collum , Spark Jessica , Tod Sophie ,   Individual names of AMP SCZ collaborators are listed in the Acknowledgment
Published: May 2023

Aim

To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS).

Methods

The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences.

Results

Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and partial harmonization for CHR-P criteria. The semi-structured interview, namedPositiveSYmptoms and Diagnostic Criteria for theCAARMSHarmonized with theSIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS.

Conclusion

Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.
The use of a Multi-morbidity Index (MMI) in Patients Receiving Home Parenteral Nutrition (HPN)
Authors: Rothkopf Michael M. , Rothkopf Zachary S. , Pant Mohan D. , Brown Rebecca , Haselhorst Jamie , Gagliardotto Francine , Stevenson Debbie , DePalma Andrew , Saracco Michael
Published: May 2023

Introduction

Although HPN patients often have concomitant medical conditions, little has been done to assess the role of multi-morbidity in relation to HPN care (1-3). A validated method for determining multi-morbidity in HPN patients could be beneficial in determining the needs and risks for each HPN patient.

We previously studied the effect of a multidisciplinary nutritional support team (MNST) on quality improvement HPN care (QIP-PN) (4). In a secondary analysis, we explored the options for measuring multi-morbidity of patients in the QIP-PN study. In this report, we describe the results of a pilot study on measuring multi-morbidity in HPN patients to determine its value in HPN care.

Objective

Determine the role of multi-morbidity scoring in HPN care.

Methods

60 HPN patients (30 study patients and 30 case-matched controls) were reviewed for demographics, CIRS Score, number of PN formula changes, hospitalizations and hospital length of stay. Histograms were produced to visually examine the data and cutoffs were selected for CIRS scores based on this information. A matrix plot was drawn showing Spearman correlations among the three variables of interest. The data was then subjected to Kruskal-Wallis and Wilcoxon Rank Sum Tests and Negative Binomial Regression Models to determine if the groups differed significantly.

Results

28 patients had CIRS scores <17, while 32 patients had CIRS scores ≥17. The results of negative binomial regression indicate that the number of hospitalizations was a significant predictor of total hospital LOS at the 5% alpha level and that the total hospital LOS of patients with a CIRS Score <17 was significantly different from that of patients with a CIRS≥17 at 5% alpha level.

Conclusion

We found the CIRS method was well suited to use in HPN patients. It was easy to learn and perform. It provided a single variable which could be used a summary statement of patient multimorbidity. When the CIRS data on 60 long term HPN patients was analyzed, a trend emerged wherein a higher CIRS score was associated with greater hospital LOS. This approach requires greater study and validation.

Key Messages Box

1.

What is already known on this topic?

The risk of HPN complications is known to relate to patient demographics, length of functional bowel, duration of HPN therapy and macronutrient content. A validated method for determining multi-morbidity in HPN patients could be beneficial in determining the needs of and risk for each HPN patient.

2.

What this study adds

The study the explores the role of measuring multi-morbidity scoring in HPN care to determine the risk of adverse effects during therapy.

3.

How this study might affect research, practice or policy?

The study suggests that using CIRS scoring for HPN patients could help healthcare providers and payors allocate resources based on risk analysis.
Digital markers of motor speech impairments in natural speech of patients with ALS-FTD spectrum disorders
Authors: Shellikeri Sanjana , Cho Sunghye , Ash Sharon , Gonzalez-Recober Carmen , McMillan Corey T. , Elman Lauren , Quinn Colin , Amado Defne A. , Baer Michael , Irwin David J , Massimo Lauren , Olm Chris , Liberman Mark , Grossman Murray , Nevler Naomi
Published: May 2023

Background and objectives

Patients with ALS-FTD spectrum disorders (ALS-FTSD) have mixed motor and cognitive impairments and require valid and quantitative assessment tools to support diagnosis and tracking of bulbar motor disease. This study aimed to validate a novel automated digital speech tool that analyzes vowel acoustics from natural, connected speech as a marker for impaired articulation due to bulbar motor disease in ALS-FTSD.

Methods

We used an automatic algorithm called Forced Alignment Vowel Extraction (FAVE) to detect spoken vowels and extract vowel acoustics from 1 minute audio-recorded picture descriptions. Using automated acoustic analysis scripts, we derived two articulatory-acoustic measures: vowel space area (VSA, in Bark2) which represents tongue range-of-motion (size), and average second formant slope of vowel trajectories (F2 slope) which represents tongue movement speed. We compared vowel measures between ALS with and without clinically-evident bulbar motor disease (ALS+bulbar vs. ALS-bulbar), behavioral variant frontotemporal dementia (bvFTD) without a motor syndrome, and healthy controls (HC). We correlated impaired vowel measures with bulbar disease severity, estimated by clinical bulbar scores and perceived listener effort, and with MRI cortical thickness of the orobuccal part of the primary motor cortex innervating the tongue (oralPMC). We also tested correlations with respiratory capacity and cognitive impairment.

Results

Participants were 45 ALS+bulbar (30 males, mean age=61±11), 22 ALS-nonbulbar (11 males, age=62±10), 22 bvFTD (13 males, age=63±7), and 34 HC (14 males, age=69±8). ALS+bulbar had smaller VSA and shallower average F2 slopes than ALS-bulbar (VSA: |d|=0.86,p=0.0088; F2 slope: |d|=0.98,p=0.0054), bvFTD (VSA: |d|=0.67,p=0.043; F2 slope: |d|=1.4,p<0.001), and HC (VSA: |d|=0.73,p=0.024; F2 slope: |d|=1.0,p<0.001). Vowel measures declined with worsening bulbar clinical scores (VSA: R=0.33,p=0.033; F2 slope: R=0.25,p=0.048), and smaller VSA was associated with greater listener effort (R=-0.43,p=0.041). Shallower F2 slopes were related to cortical thinning in oralPMC (R=0.50,p=0.03). Neither vowel measure was associated with respiratory nor cognitive test scores.

Conclusions

Vowel measures extracted with automatic processing from natural speech are sensitive to bulbar motor disease in ALS-FTD and are robust to cognitive impairment.
Feasibility of multicomponent exercise training with beat-accentuated music among community-dwelling older adults with mild-to-moderate cognitive decline
Authors: Park Kyoung Shin , Buseth Lake , Hong Jiyeong , Etnier Jennifer L.
Published: May 2023

Objectives

This study explored the feasibility and preliminary efficacy of a music-based, multicomponent exercise intervention among community-dwelling older adults with mild-to-moderate cognitive impairment.

Methods

13 older adults aged 85±9 years with mild-to-moderate cognitive impairment completed multicomponent exercise training for 20 weeks at an independent living facility. Participants received aerobic, resistance, and balance training paired with beat-accentuated music stimulation (BMS). Participants’ adherence to the training was tracked down and their cognitive and physical functioning and quality of life were assessed at pre- and post-test.

Results

13 participants attended an average of 4.6 days/week over 20 weeks and reported high satisfaction with the intervention (90.6%). Participants showed significant improvement in global cognition, cognitive processing speed, and walking endurance/aerobic fitness at post-test.

Conclusions

These findings support the feasibility of music-based, multicomponent exercise training for older adults in an independent living facility and set the stage for future studies to test the efficacy of music on physical activity and ensuing health outcomes.

Clinical Implications

Music-based, multicomponent exercise training can be beneficial for community-dwelling older adults with mild-to-moderate cognitive decline. BMS can be combined with exercise training to manipulate exercise tempo and may provide a source of motivation to help older adults adhere to exercise.
Individual Differences in the Effects of Neighborhood Socioeconomic Deprivation on Economic Decision Making and Psychotic Risk in Children
Authors: Park Junghoon , Cho Minje , Lee Eunji , Kim Bo-Gyeom , Kim Gakyung , Joo Yoonjung Yoonie , Cha Jiook
Published: May 2023

Understanding how a child’s social and economic surroundings influence their mental development and potential for psychological disorders is essential for unpacking the origins of mental health issues. This study, using up-to-date machine learning-based causal inference methods, tested the relationships between neighborhood socioeconomic deprivation, delay discounting, and psychotic-like experiences (PLEs) in 2,135 children considering the wide range of covariates. We found that a greater neighborhood deprivation led to steeper future reward discounting and a higher psychosis risk, evident over 1-year and 2-year follow- ups. We also discovered, across children, significant individual differences in the effect of neighborhood adversity on childhood PLEs, particularly hallucinational symptoms. Children particularly vulnerable to PLEs in adverse neighborhoods exhibited steeper future reward discounting, higher cognitive performance polygenic scores, notable neuroanatomical alterations, including reduced volume, surface area, and white matter in limbic regions. Furthermore, these children displayed increased BOLD reactivity within the prefrontal-limbic system during Monetary Incentive Delay tasks across various reward/loss versus neutral conditions. These findings underscore the intricate interaction between the brain’s reward processing mechanisms and external socioeconomic elements in shaping the risk of psychosis in children.
Application of the Robson Classification in Assessing Cesarean Section Rates: An Audit of a Tertiary Care Hospital’s Gynecology Department in Karachi, Pakistan
Authors: Abidi Syed Muhammad Aqeel , Abbas Shahida , Abidi Syeda Tayyaba Fatima , Hussain Namayah , Haresh Sonia
Published: May 2023

Objective

The increasing rate of cesarean sections (CS) is a significant concern for healthcare providers worldwide. The World Health Organization (WHO) recommends that CS rates should not exceed 10-15% at the population level. The Robson classification system is a widely used tool for assessing and comparing CS rates based on the indications and patient population across different hospitals and obstetric populations. This audit report will help identify areas for improvement in obstetric care practices and facilitate the development of strategies to optimize obstetric care and reduce CS rates, thereby improving maternal and neonatal outcomes.

Methods

This retrospective study utilizing hospital records was conducted from January 1st, 2022, to December 31st, 2022, at the Department of Obstetrics and Gynecology in Holy Family Hospital, Karachi, Pakistan. During the study period of one year, a total of 449 cesarean sections were conducted, which were classified into the ten groups of The Robson Classification. Group CS rate, Group size, Relative contribution of group to overall CS rate, and Absolute group contribution to overall CS rate was calculated for each group. Overall indications of CS in all groups was analyzed and based on the results interventions were suggested to be implemented to optimize CS.

Results

1464 women were delivered during this one year period. A total of 507 CS were our ‘population of interest’. Of the cesarean sections performed, 48.8% (247) were elective and 51.2% (260) were emergency. The Robson classification group 5 (51.9%), group 2 (18.5%), and group 10 (14.4%) respectively were the major contributor to the overall CS rate. The main indications for CS were previous history of caesarean section (32.3%), non-progress of labor (21.15%), and cephalopelvic disproportion (16.92%).

Conclusion

It is crucial to develop strategies to decrease the unnecessary CS rate while ensuring safe and appropriate obstetric care. Furthermore, there is a need for further research to identify the underlying factors contributing to the high CS rates and to develop effective interventions to address this issue. Implementation of these strategies may lead to improved maternal and fetal outcomes, reduced healthcare costs, and increased patient satisfaction.
HOW COMPLETE ARE TOBACCO SALES DATA? ASSESSING THE COMPREHENSIVENESS OF TOBACCO PRODUCT RETAIL SALES DATA THROUGH COMPARISONS TO EXCISE TAX COLLECTIONS
Authors: Liber Alex C. , Faraji Maryam , Ranganathan Radhika , Friedman Abigail S.
Published: May 2023

Introduction

Sales data analyses are increasingly used to guide tobacco regulatory science. However, such data do not cover specialist retailers like vape shops or tobacconists. Understanding the extent of the cigarette and electronic nicotine delivery system (ENDS) markets covered by sales data is critical to establishing such analyses’ generalizability and potential biases.

Methods

Sales data from Information Resources Incorporated (IRI) and Nielsen Retail Scanner data are used to conduct a tax gap analysis, comparing state tax collections based on cigarette and ENDS sales data to states’ annual 2018-2020 cigarette tax collections and monthly ENDS and cigarette tax revenue data for January 2018 to October 2021. Cigarette analyses consider the 23 US states covered by both IRI and Nielsen. ENDS analyses consider the subset of those states with per unit ENDS taxes: Louisiana, North Carolina, Ohio, and Washington.

Results

Across states covered by both sales datasets, IRI’s mean cigarette sales coverage was 92.3% (95% CI 88.3-96.2%), while Nielsen’s was 84.0% (95% CI 79.3-88.7%). Coverage rates for average ENDS sales were lower, ranging from 42.3% to 86.1% for IRI and 43.6% to 88.5% for Nielsen, but remained stable over time.

Conclusions

IRI and Nielsen sales data capture almost the entire US cigarette market and, while coverage rates are lower, a substantial portion of the US market for ENDS as well. Coverage rates are relatively stable over time. Thus, with proper care to address shortcomings, sales data analyses can capture changes in the US market for these tobacco products.

Implications

Policy evaluations and analyses using e-cigarette and cigarette sales data are often criticized because these data do not cover online sales or sales by specialty retailers like tobacconists.

Cigarette sales data consistently cover nearly 90% of taxed sales, while e-cigarette sales data cover around 50% of taxed volumes.

Retail sales data capture nearly all cigarette sales and a substantial portion of ENDS sales with relatively stable rates of coverage over time, supporting their continued use in tobacco surveillance and policy evaluation work.
Adrenomedullin promotes interneuron migration in a dual human model for hypoxic interneuronopathy of prematurity
Authors: Michno Wojciech P. , Puno Alyssa , Li Li , Everitt Amanda , McCluskey Kate , Birey Fikri , Htun Saw , Nagar Dhriti , Dai Yuqin , Gurwitz Emily , Willsey A. Jeremy , Pasca Anca M.
Published: May 2023

Extremely preterm born individuals at < 28 postconceptional weeks (PCW) are at high risk for encephalopathy of prematurity and life-long neuropsychiatric conditions. Clinical studies and animal models of preterm brain injury suggest that encephalopathy of prematurity is strongly associated with exposure to hypoxia and/or inflammation in the perinatal period. Histologic examination of postmortem brain tissue from children born preterm demonstrates decreased numbers of cortical GABAergic interneurons in the cerebral cortex. However, the cellular and molecular mechanisms underlying the decreased numbers of GABAergic interneurons in the cerebral cortex of extremely preterm individuals remain unclear. Here, we developed a dual, complementary human cellular model to study hypoxia-induced interneuronopathies using human forebrain assembloids (hFA) derived from human induced pluripotent stem cells (hiPSCs) andex vivohuman prenatal cerebral cortex at mid-gestation. The hFA are generated through the integration of region-specific neural organoids containing either dorsal forebrain (excitatory) glutamatergic neurons or ventral forebrain (inhibitory) GABAergic interneurons. We discover a substantial reduction in migration of cortical interneurons during exposure to hypoxic stress in both hFA andex vivohuman prenatal cerebral cortex. Next, we identify that this migration defect is restored by supplementation of hypoxic cell culture media with exogenous adrenomedullin (ADM), a peptide hormone member of the calcitonin gene related peptide (CGRP) family. Lastly, we demonstrate that the rescue is mediated through increased activity of the PKA molecular pathway and increased pCREB-dependent expression of GABA receptors. Overall, these findings provide important insights into the cellular mechanisms contributing to cortical interneuron depletion in preterm infants, and pinpoint novel therapeutic molecular pathways with high translational potential for hypoxic encephalopathy of prematurity.
ClearX9™: an efficient alternative to fetal bovine serum for growing animal cells in vitro
Authors: Gautam Sumit , Verma Neeraj , Manvati Siddharth , Dhar Pawan K.
Published: May 2023

Fetal Bovine Serum (FBS) is a nutrient-rich fluid that contains nutritional and macromolecular factors essential for cell growth. Every year millions of pregnant cows are slaughtered in search of FBS leading to huge environmental consequences. Here we report ClearX9™ - an affordable, sustainable, ethical, and effective replacement for FBS. ClearX9™ cell culture medium was used to grow HeLa (cervical cancer cells), HEK293T (embryonic kidney transformed cells) and Nthy Ori-3-1 (primary thyroid follicular transformed epithelial cells) and showed encouraging growth patterns and good cellular health. Compared with the FBS-enriched cell culture medium, ClearX9™ scored positive on all the parameters suggesting ClearX9™ as a credible alternative to FBS. In future, more work is required to establish the efficacy of ClearX9™ in toxicology testing, bio-manufacturing, regenerative medicine, and vaccine research.

HIGHLIGHTS

ClearX9™ provides good nutritional support for the growth of animal cells

ClearX9™ cell growth performance is comparable to the serum-enriched medium

ClearX9™ maintains a healthy morphological profile of cells during division

ClearX9™ generates a stress-free environment within cells

ClearX9™ does not require animal slaughter and reduces carbon footprint

ClearX9™ has applications in biotechnology and cell cultivated meat industry
Brain-wide Correspondence Between Neuronal Epigenomics and Long-Distance Projections
Authors: Zhou Jingtian , Zhang Zhuzhu , Wu May , Liu Hanqing , Pang Yan , Bartlett Anna , Rivkin Angeline , Lagos Will N. , Williams Elora , Lee Cheng-Ta , Miyazaki Paula Assakura , Aldridge Andrew , Zeng Qiurui , Salinda J.L. Angelo , Claffey Naomi , Liem Michelle , Fitzpatrick Conor , Boggeman Lara , Yao Zizhen , Smith Kimberly A. , Tasic Bosiljka , Altshul Jordan , Kenworthy Mia A. , Valadon Cynthia , Nery Joseph R. , Castanon Rosa G. , Patne Neelakshi S. , Vu Minh , Rashid Mohammad , Jacobs Matthew , Ito Tony , Osteen Julia , Emerson Nora , Lee Jasper , Cho Silvia , Rink Jon , Huang Hsiang-Hsuan , Pinto-Duartec António , Dominguez Bertha , Smith Jared B. , O’Connor Carolyn , Zeng Hongkui , Lee Kuo-Fen , Mukamel Eran A. , Jin Xin , Behrens M. Margarita , Ecker Joseph R. , Callaway Edward M.
Published: May 2023

Single-cell genetic and epigenetic analyses parse the brain’s billions of neurons into thousands of “cell-type” clusters, each residing in different brain structures. Many of these cell types mediate their unique functions by virtue of targeted long-distance axonal projections to allow interactions between specific cell types. Here we have used Epi-Retro-Seq to link single cell epigenomes and associated cell types to their long-distance projections for 33,034 neurons dissected from 32 different source regions projecting to 24 different targets (225 source →target combinations) across the whole mouse brain. We highlight uses of this large data set for interrogating both overarching principles relating projection cell types to their transcriptomic and epigenomic properties and for addressing and developing specific hypotheses about cell types and connections as they relate to genetics. We provide an overall synthesis of the data set with 926 statistical comparisons of the discriminability of neurons projecting to each target for every dissected source region. We integrate this dataset into the larger, annotated BICCN cell type atlas composed of millions of neurons to link projection cell types to consensus clusters. Integration with spatial transcriptomic data further assigns projection-enriched clusters to much smaller source regions than afforded by the original dissections. We exemplify these capabilities by presenting in-depth analyses of neurons with identified projections from the hypothalamus, thalamus, hindbrain, amygdala, and midbrain to provide new insights into the properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription factor binding motifs, and neurotransmitter usage.
High performance anion exchange chromatography purification of probiotic bacterial extracellular vesicles enhances purity and anti-inflammatory efficacy
Authors: Piroli Nicholas H. , Reus Laura Samantha C. , Mamczarz Zuzanna , Khan Sulayman , Bentley William E. , Jay Steven M.
Published: May 2023

Bacterial extracellular vesicles (BEVs), including outer membrane vesicles (OMVs), have emerged as a promising new class of vaccines and therapeutics to treat cancer and inflammatory diseases, among other applications. However, clinical translation of BEVs is hindered by a current lack of scalable and efficient purification methods. Here, we address downstream BEV biomanufacturing limitations by developing a method for orthogonal size- and charge-based BEV enrichment using tangential flow filtration (TFF) in tandem with high performance anion exchange chromatography (HPAEC). The data show that size-based separation co-isolated protein contaminants, whereas size-based TFF with charged-based HPAEC dramatically improved purity of BEVs produced by probiotic Gram-negativeEscherichia coliand Gram-positive lactic acid bacteria (LAB).E. coliBEV purity was quantified using established biochemical markers while improved LAB BEV purity was assessed via observed potentiation of anti-inflammatory bioactivity. Overall, this work establishes orthogonal TFF + HPAEC as a scalable and efficient method for BEV purification that holds promise for future large-scale biomanufacturing of therapeutic BEV products.
HDAC-6 inhibition ameliorates the early neuropathology in a mouse model of Krabbe disease
Authors: Braz Sandra O. , Morgado Marlene M. , Pereira Marta I. , Monteiro Ana C. , Golonzhka Olga , Jarpe Matthew , Brites Pedro , Sousa Monica M. , Nogueira-Rodrigues Joana
Published: May 2023

In Krabbe disease (KD), mutations in β-galactosylceramidase (GALC), a lysosomal enzyme responsible for the catabolism of galactolipids, lead to the accumulation of its substrates galactocerebroside and psychosine. This neurologic condition is characterized by a severe and progressive demyelination together with neuron-autonomous defects and degeneration. Twitcher mice mimic the infantile form of KD, which is the most common form of the human disease. The Twitcher CNS and PNS present demyelination, axonal loss and neuronal defects including decreased levels of acetylated tubulin, decreased microtubule stability and impaired axonal transport. Here, we tested whether inhibiting the α-tubulin deacetylase HDAC6 with a specific inhibitor, ACY-738, was able to counteract the early neuropathology and neuronal defects of Twitcher mice. Our data show that delivery of ACY-738 corrects the low levels of acetylated tubulin in the Twitcher nervous system. Furthermore, it reverts the loss myelinated axons in the sciatic nerve and in the optic nerve when administered from birth to postnatal day 9, suggesting that the drug holds neuroprotective properties. The extended delivery of ACY-738 to Twitcher mice delayed axonal degeneration in the CNS and ameliorated the general presentation of the disease. ACY-738 was effective in rescuing neuronal defects of Twitcher neurons, stabilizing microtubule dynamics and increasing the axonal transport of mitochondria. Overall, our results support that ACY-738 has a neuroprotective effect in KD and should be considered as an add-on therapy combined with strategies targeting metabolic correction.
Optimisation of asymmetric field pulses for transcranial magnetic stimulation
Authors: Ma Ke , Goetz Stephan M.
Published: May 2023

Transcranial magnetic stimulation (TMS) is a widely-used noninvasive brain stimulation technique through electromagnetic induction. Nowadays commercial TMS devices routinely use conventional biphasic pulses for repetitive TMS protocols and monophasic pulses for single-pulse stimulation. They respectively generate underdamped or damped cosinusoidal electric field pulses that have been proven to be power-inefficient. Recently, symmetric field pulses with near-rectangular electric fields show great potential in terms of energy loss and coil heating, but only limited studies have investigated asymmetric field pulses with different asymmetry levels for the induced electric field waveforms. Thus, this paper optimises and searches a wide range of potential current waveforms with the goal of minimising energy loss and coil heating. The optimised results demonstrated that asymmetric field pulses with near-rectangular electric fields have significantly lower power consumption than conventional ones. These optimised waveforms commonly consist of an initial falling phase followed by rapidly rising and falling phases, trailed by a slow decay to zero. Interestingly, the initial phase has a decay time constant around 260 µs and introduces a pulse-duration-dependent negative bias for the current baseline to minimise the energy loss and coil heating. Thus, it is possible to directly design asymmetric field pulses with various asymmetry ratios by using several prediction equations rather than running optimisation. These results also suggest that introducing such an initial current phase could likely significantly reduce the coil heating of most TMS pulse shapes to improve their power efficiencies.
Meta-learning in head fixed mice navigating in virtual reality: A Behavioral Analysis
Authors: Zhao Xinyu , Gattoni Rachel , Kozlosky Andrea , Jacobs Angela , Morrow Colin , Lindo Sarah , Spruston Nelson
Published: May 2023

Animals can learn general task structures and use them to solve new problems with novel sensory specifics. This capacity of ‘learning to learn’, or meta-learning, is difficult to achieve in artificial systems, and the mechanisms by which it is achieved in animals are unknown. As a step toward enabling mechanistic studies, we developed a behavioral paradigm that demonstrates meta-learning in head-fixed mice. We trained mice to perform a two-alternative forced-choice task in virtual reality (VR), and successively changed the visual cues that signaled reward location. Mice showed increased learning speed in both cue generalization and serial reversal tasks. During reversal learning, behavior exhibited sharp transitions, with the transition occurring earlier in each successive reversal. Analysis of motor patterns revealed that animals utilized similar motor programs to execute the same actions in response to different cues but modified the motor programs during reversal learning. Our study demonstrates that mice can perform meta-learning tasks in VR, thus opening up opportunities for future mechanistic studies.
Characterization of an evolutionarily distinct bacterial ceramide kinase fromCaulobacter crescentus
Authors: Dhakephalkar Tanisha , Stukey Geordan , Guan Ziqiang , Carman George M. , Klein Eric A.
Published: May 2023

A common feature among nearly all Gram-negative bacteria is the requirement for lipopolysaccharide (LPS) in the outer leaflet of the outer membrane. LPS provides structural integrity to the bacterial membrane which aids bacteria in maintaining their shape and acts as a barrier from environmental stress and harmful substances such as detergents and antibiotics. Recent work has demonstrated thatCaulobacter crescentuscan survive without LPS due to the presence of the anionic sphingolipid ceramide-phosphoglycerate. Based on genetic evidence, we predicted that protein CpgB functions as a ceramide kinase and performs the first step in generating the phosphoglycerate head group. Here, we characterized the kinase activity of recombinantly expressed CpgB and demonstrated that it can phosphorylate ceramide to form ceramide 1-phosphate. The pH optimum for CpgB was 7.5, and the enzyme required Mg2+as a cofactor. Mn2+, but not other divalent cations, could substitute for Mg2+. Under these conditions, the enzyme exhibited typical Michaelis-Menten kinetics with respect to NBD-C6-ceramide (Km,app=19.2 ± 5.5 μM; Vmax,app=2586.29 ± 231.99 pmol/min/mg enzyme) and ATP (Km,app=0.29 ± 0.07 mM; Vmax,app=10067.57 ± 996.85 pmol/min/mg enzyme). Phylogenetic analysis of CpgB revealed that CpgB belongs to a new class of ceramide kinases which is distinct from its eukaryotic counterpart; furthermore, the pharmacological inhibitor of human ceramide kinase (NVP-231) had no effect on CpgB. The characterization of a new bacterial ceramide kinase opens avenues for understanding the structure and function of the various microbial phosphorylated sphingolipids.