bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronodisruption during Pregnancy Mediates the Relationship between Social Disadvantage and Reduced Brain Maturation in Neonates
Authors: Hoyniak Caroline P. , Whalen Diana J. , Luby Joan L. , Barch Deanna M. , Miller J. Philip , Zhao Peinan , Triplett Regina L. , Ju Yo-El , Smyser Christopher D. , Warner Barbara , Rogers Cynthia E. , Herzog Erik D. , England Sarah K.
Published: May 2022

Prenatal exposure to adversity profoundly impacts offspring development. Well-documented disparities in sleep and circadian health are known to be related, and exposure to disrupted maternal sleep and circadian rhythms during pregnancy may have an effect on offspring neurodevelopment. The current study explored the association between maternal sleep and circadian rhythm disruption during pregnancy and infant brain outcomes at birth, examining sleep and circadian rhythm disruptions as a possible mediator of the effect of adversity during pregnancy on infant structural brain outcomes in 148 mother-child dyads. Maternal sleep was quantified using actigraphy data collected during each trimester of pregnancy and quantified using a measure of chronodisruption (irregularity in the sleep schedule) and a measure of chronotype (sleep timing). Adversity was quantified using a latent factor of several metrics of social disadvantage (e.g., income-to-needs ratio). Infant structural brain outcomes at birth including cortical gray matter, subcortical gray matter, and white matter volumes along with a measure of cortical folding reflecting the total surface area of the cortex. Findings indicated that chronodisruption during pregnancy was associated with smaller infant cortical gray matter, subcortical gray matter, and white matter volumes and less cortical folding at birth, with infants of mothers with later chronotypes evidencing smaller subcortical gray matter volumes. Chronodisruption during pregnancy mediated the association between maternal social disadvantage and structural brain outcomes. Findings highlight the importance of regularity and rhythmicity in sleep schedules during pregnancy and highlight the role of chronodisruption as a mechanism of the deleterious neurodevelopmental effects of prenatal adversity.

Significance Statement

This study examined the effect of exposure to maternal sleep and circadian rhythm disruptions during pregnancy on neonatal brain structure. Sleep and circadian disruptions were associated with global differences in neonatal brain structure. Mothers who had more irregular sleep schedules during pregnancy had infants who had smaller total cortical gray matter, subcortical gray matter, and white matter volumes and less cortical folding at birth. Irregular maternal sleep schedules during pregnancy mediated the association between adversity and structural brain outcomes, suggesting that sleep and daily rhythm disturbances may be one pathway through which adversity shapes offspring neurodevelopment. Findings imply that modifying the work schedules of pregnant women to avoid swing or night shifts might be beneficial for enhancing child neurodevelopment.
Temporal and frontal lobe contributions to neural synchronization dysfunction and auditory attention in Fragile X Syndrome
Authors: Pedapati Ernest V , Ethridge Lauren E. , DeStefano Lisa , Liu Yanchen , Miyakoshi Makoto , Sweeney John A , Schmitt Lauren M. , Gilbert Donald L. , Wu Steve W. , Liu Rui , Smith Elizabeth , Shaffer Rebecca C. , Dominick Kelli C. , Horn Paul S. , Binder Devin , Erickson Craig A.
Published: May 2022

Fragile X syndrome (FXS) is a trinucleotide repeat disorder and the most common hereditary form of intellectual disability. Patients with FXS are commonly impaired by sensory hypersensitivity. Compared to cognition, neural correlates of sensory responses can be studied more objectively and across species. Alterations in auditory processing in FXS measured by scalp electroencephalography (EEG) are well documented. However, the orientation of the auditory cortex in humans introduces significant confounding between temporal and frontal sources. Herein, we conducted EEG source analysis in 36 participants with FXS and 39 matched controls to localize known alterations to the auditory chirp stimulus. The key findings in participants with FXS include 1) distinct contributions of frontal and temporal sources to the onset and intrastimulus neural synchronization, 2) moderation of abnormal neural responses in females with FXS, 3) evidence of deep brain sources contributing to impairments in synchronization, and 4) presence of robust region-specific clinical correlations. The synchronous and asynchronous gamma activity (SA ratio) ratio may further represent a clinically relevant biomarker of the efficiency of auditory processing in FXS. Findings from this study have implications for back translation and relevance for signal-to-noise conceptual frameworks in understanding neural activity in neurodevelopmental disorders.
A Deterministic Agent-based Model with Antibody Dynamics Information in COVID-19 Epidemic Simulation
Authors: Xu Zhaobin , Zhang Hongmei
Published: May 2022

Accurate prediction of the temporal and spatial characteristics of COVID-19 infection can provide favorable guidance for epidemic prevention and control. We first introduce individual antibody dynamics into an agent-based model. Antibody dynamics model can well explain the antibody fading effects through time. Based on this model, we further developed an agent-based approach which considers the dynamic behaviors of each individual antibodies. The method can effectively reflect the dynamic interaction between the antibody and the virus in each host body in the overall population. Using this method, we can accurately predict the temporal and spatial characteristics of the epidemic. It can quantitatively calculate the number and spatial distribution of infected persons with different symptoms at different times. At the same time, our model can predict the prevention and control effect of different prevention and control measures. At present, China’s dynamic zero strategies mainly include large-scale nucleic acid test, isolation of positive infected persons and their close contacts. Our model demonstrates that for a less infectious and more virulent variant, this approach can achieve good preventive effect. The effect of reducing social contacts and quarantining only positive infected persons is relatively weaker on epidemic control. This can explain why China’s targeted epidemic-control measures had an excellent performance in 2020 and 2021. However, our model also warns that for the highly infectious and less virulent variant, targeted epidemic-control measures can no longer achieve effective control of the epidemic. Therefore, we must choose to quarantine potential infected groups in a wider range (such as the quarantine of secondary close contact and tertiary close contact) or coexist with the virus. Furthermore, our model has a strong traceability ability, which can effectively conduct epidemiological investigation to unearth patient number zero based on the early epidemic distribution. In the end, our model expands the traditional approaches of epidemiological simulation and provides an alternative in epidemic modeling.

Major findings

First, a method was developed to integrate the characteristics of individual antibody dynamics into epidemic prediction;

Second, this model can effectively predict the spatiotemporal characteristics of patients with different symptoms (including asymptomatic patients, mild and severe patients, etc.);

Thirdly, this model proves that China’s dynamic zero strategy which include the quarantine of close contact people is more efficient than just isolating positive cases;

Fourth: This model also reflects the limitations of targeted epidemic-control strategies and warns that for the highly infectious and less virulent variant, targeted epidemic-control measures can no longer achieve effective control of the epidemic;

Fifth, this model can help epidemiological research and find out patient zero according to the early incidence of the epidemic.
Single center blind testing of a US multi-center validated diagnostic algorithm for Kawasaki disease in Asia
Authors: Kuo Ho-Chang , Hao Shiying , Jin Bo , Chou C. James , Han Zhi , Chang Ling-Sai , Huang Ying-Hsien , Hwa KuoYuan , Whitin John C. , Sylvester Karl G. , Reddy Charitha D. , Chubb Henry , Ceresnak Scott R. , Kanegaye John T. , Tremoulet Adriana H. , Burns Jane C. , McElhinney Doff , Cohen Harvey J. , Ling Xuefeng B.
Published: May 2022

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. A key objective of research in KD is to reduce the risk of long-term cardiovascular sequelae by expediting timely diagnosis. The major challenge in KD diagnosis is that it shares clinical signs with other childhood febrile illnesses. Our previously single-center developed computer-based two-step algorithm was further tested by a five-center validation in US. This first blinded multi-center trial validated our approach, with sufficient sensitivity and positive predictive value, to identify most patients with KD diagnosed at centers across the US.

We sought to determine if our algorithmic approach applied to an Asian cohort. This study involved 418 KD and 259 febrile controls (FC) from the Chang Gung Memorial Hospital in Taiwan. Our diagnostic algorithm retained sensitivity (379 of 418; 90.7%), specificity (223 of 259; 86.1%), PPV (379 of 409; 92.7%), and NPV (223 of 247; 90.3%) comparable to previous US 2016 single center and US 2020 fiver center results. Only 4.7% (15 of 418) of KD and 2.3% (6 of 259) of FC patients were identified as indeterminate. The algorithm identified 18 of 50 (36%) KD patients who presented 2 or 3 principal criteria. Of 418 KD patients, 157 were infants younger than one year and 89.2% (140 of 157) were classified correctly. Of the 44 patients with KD who had coronary artery abnormalities, our diagnostic algorithm correctly identified 43 (97.7%) including all patients with dilated coronary artery but one who found to resolve in 8 weeks.

We assessed the performance of our KD diagnostic algorithm with a single center Asian cohort. This work demonstrates the applicability of our algorithmic approach and diagnostic portability, providing evidence to support the launch of an adequately powered, multicenter study for future Asian application in the emergency department setting. If deployed in Asia, our tool promises a cost-effective diagnostic approach to allow the timely management of Asian KD patients even in the absence of KD experts, to potentially enhance the outcome for KD patients and reduce the risk of coronary artery aneurysms.
Social media discourse and internet search queries on cannabis as a medicine: A systematic scoping review
Authors: Hallinan Christine Mary , Habibabadi Sedigheh Khademi , Conway Mike , Bonomo Yvonne Ann
Published: May 2022

The use of cannabis for medicinal purposes has increased globally over the past decade since patient access to medicinal cannabis has been legislated. Yet, evidence of cannabis efficacy for a suite of conditions is only just emerging. Although there is considerable engagement from many stakeholders to add to the evidence base through randomized control trials, many gaps in the literature remain. Data from real-world and patient reported sources can provide opportunities to address this evidence deficit. This real-world data can be captured from a variety of sources such as found in routinely collected health care and health services records that include but are not limited to patient generated data from medical, administrative and claims data, patient reported data from surveys, wearable trackers, patient registries, and social media. In this systematic scoping review, we seek to understand the utility of online user generated text into the use of cannabis as a medicine. The objective of this scoping review is to synthesize primary research that uses social media discourse and internet search engine queries to answer the following questions: (i) Does online user-generated text provide a useful data source for studying cannabis as a medicine? (ii) What are the aims, data sources, and research themes of studies using online user-generated text to discuss the medicinal use of cannabis? For this scoping review we used a framework for systematic reviews and meta-analyses, the PRISMA guidelines to inform our methods. We conducted a manual search of primary research studies which used online user-generated text as a data source using the MEDLINE, Embase, Web of Science, and Scopus databases in October 2022. Editorials, letters, commentaries, surveys, protocols, and book chapters were excluded from the review. Forty-two studies were included in this review, 22 studies used manually labelled data, four studies used existing meta-data (Google trends/geo-location data), two studies used data that was manually coded using crowdsourcing services, and two used automated coding supplied by a social media analytics company, 15 used computational methods for annotating data. Our review reflects a growing interest in the use of user-generated content for public health surveillance. It also demonstrates the need for the development of a systematic approach for evaluating the quality of social media studies and highlights the utility of automatic processing and computational methods (machine learning technologies) for large social media datasets. This systematic scoping review has shown that user-generated content as a data source for studying cannabis as a medicine provides another means to understand how cannabis is perceived and used in the community. As such, it provides another potential ‘tool’ with which to engage in pharmacovigilance of, not only cannabis as a medicine, but also other novel therapeutics as they enter the market.
Unilateral cathodal transcranial direct current stimulation over the parietal area modulates on postural control depending with eyes open and closed
Authors: Oka Shinichiro , Ikeda Takuro , Mitsutake Tsubasa , Ogata Katsuya , Goto Yoshinobu
Published: May 2022

Cathodal transcranial direct current stimulation (C-tDCS) is generally assumed to inhibit cortical excitability. The parietal cortex contributes to multisensory information processing in the postural control system, and this processing is proposed to be different between the right and left hemispheres and sensory modality. However, previous studies did not clarify whether the effects of unilateral C-tDCS of the parietal cortex on the postural control system differ depending on the hemisphere. We investigated the changes in static postural stability after unilateral C-tDCS of the parietal cortex. Ten healthy right-handed participants were recruited for right- and left-hemisphere tDCS and sham stimulation, respectively. The cathodal electrode was placed on either the right or left parietal area, whereas the anodal electrode was placed on the contralateral forehead. We evaluated static standing balance by measuring the sway path length, mediolateral (ML) sway, anteroposterior (AP) sway, sway area, and the sway path length per unit area (L/A) after 15-minute C-tDCS under eyes open (EO) and closed (EC) conditions. C-tDCS over the right hemisphere significantly increased the sway path length, ML sway, and sway area in the EO condition. In contrast, C-tDCS over the left hemisphere significantly increased the L/A in both the EC and EO condition. These results suggest that the right parietal region contributes to static standing balance through chiefly visual information processing during the EO condition. On the other hand, L/A increase during EC and EO by tDCS over the left parietal region depends more on somatosensory information to maintain static standing balance during the EC condition.
COVID-19 booster dose antibody response in pregnant, lactating, and nonpregnant women
Authors: Atyeo Caroline , Shook Lydia L. , Nziza Nadege , Deriso Elizabeth A. , Muir Cordelia , Baez Arantxa Medina , Lima Rosiane S. , Demidkin Stepan , Brigida Sara , De Guzman Rose M. , Burns Madeleine D. , Balazs Alejandro B. , Fasano Alessio , Yonker Lael M. , Gray Kathryn J. , Alter Galit , Edlow Andrea G.
Published: May 2022

BACKGROUND

While emerging data during the SARS-CoV-2 pandemic have demonstrated robust mRNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence of variants of concern motivated the use of mRNA vaccine booster doses. Whether all populations, including pregnant and lactating individuals, will mount a comparable response to a booster dose is not known.

OBJECTIVE

We sought to profile the humoral immune response to a COVID-19 mRNA booster dose in a cohort of pregnant, lactating, and age-matched nonpregnant women.

STUDY DESIGN

We characterized the antibody response against ancestral Spike and Omicron in a cohort of 31 pregnant, 12 lactating and 20 nonpregnant age-matched controls who received a BNT162b2 or mRNA-1273 booster dose after primary COVID-19 vaccination. We also examined the vaccine-induced antibody profiles of 15 maternal:cord dyads at delivery.

RESULTS

Receipt of a booster dose during pregnancy resulted in increased IgG1 against Omicron Spike (post-primary vaccination vs post-booster, p = 0.03). Pregnant and lactating individuals exhibited equivalent Spike-specific total IgG1, IgM and IgA levels and neutralizing titers against Omicron compared to nonpregnant women. Subtle differences in Fc-receptor binding and antibody subclass profiles were observed in the immune response to a booster dose in pregnant compared to nonpregnant individuals. Analysis of maternal and cord antibody profiles at delivery demonstrated equivalent total Spike-specific IgG1 in maternal and cord blood, yet higher Spike-specific FcγR3a-binding antibodies in the cord relative to maternal blood (p = 0.002), consistent with preferential transfer of highly functional IgG. Spike-specific IgG1 levels in the cord were positively correlated with time elapsed since receipt of the booster dose (Spearman R 0.574, p = 0.035).

CONCLUSIONS

These data suggest that receipt of a booster dose during pregnancy induces a robust Spike-specific humoral immune response, including against Omicron. If boosting occurs in the third trimester, higher Spike-specific cord IgG1 levels are achieved with greater time elapsed between receipt of the booster and delivery. Receipt of a booster dose has the potential to augment maternal and neonatal immunity.
Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: a Specific Hormonal, or a General Autoimmune Comorbidity
Authors: Soheili-Nezhad Sourena , Sprooten Emma , Tendolkar Indira , Medici Marco
Published: May 2022

Background

The hypothalamus-pituitary-thyroid axis coordinates brain development and post-developmental function. Thyroid hormone variations, even within the normal range, have been associated with the risk of developing common psychiatric disorders, although the underlying mechanisms remain poorly understood.

Materials and methods

To get new insight into the potentially shared mechanisms underlying thyroid dysfunction and psychiatric disorders, we performed a comprehensive analysis of multiple phenotypic and genotypic databases. We investigated the relationship of thyroid disorders with depression, bipolar disorder, and anxiety disorders in 502,480 subjects from UK Biobank. We subsequently investigated genetic correlations between thyroid disorders, thyroid stimulating hormone (TSH) and free T4 (FT4) levels, with the genome-wide factors that predispose to psychiatric disorders. Finally, the observed global genetic correlations were furthermore pinpointed to specific local genomic regions.

Results

Hypothyroidism was positively associated with an increased risk of major depressive disorder (OR=1.51, p<10−16) and bipolar disorder (OR=1.99, p=2.1×10−6). Genetically, strong coheritability was observed between autoimmune hypothyroidism and both major depressive (rg=0.17, p=2.7×10−4) and anxiety disorders (rg=0.17, p=6.7×10−6). This genetic correlation was particularly strong at the Major Histocompatibility Complex (MHC) locus on chromosome six (p<10−5), but further analysis showed that other parts of the genome also contributed to this global effect. Importantly, neither TSH nor FT4 levels were genetically correlated with mood disorders.

Conclusion

Our findings highlight an underlying association between autoimmune hypothyroidism and mood disorders, which is not mediated via thyroid hormones, and in which autoimmunity plays a prominent role. While these findings could shed new light on the potential ineffectiveness of treating (minor) variations in thyroid function in psychiatric disorders, further research is needed to identify the exact underlying molecular mechanisms.
Gender differences in the prevalence of Parkinson’s disease
Authors: Zirra Alexandra , Rao Shilpa C , Bestwick Jonathan , Rajalingam Rajasumi , Marras Connie , Blauwendraat Cornelis , Mata Ignacio , Noyce Alastair J
Published: May 2022

Background

It is generally recognized that Parkinson’s disease (PD) affects males more commonly than females. The reasons for the difference in PD prevalence by gender remain unclear.

Methods

In this systematic review and meta-analysis, we updated previous work by searching MEDLINE, SCOPUS, and OVID for articles reporting PD prevalence for both genders between 2011-2021. We calculated overall male/female prevalence ratios (OPR) and investigated heterogeneity in effect estimates.

Results

19 new and 13 previous articles were included. The OPR was 1.18, 95% CI [1.03, 1.36]. The OPR was lowest in Asia and appeared to be decreasing over time. Study design, national wealth, and participant age did not explain heterogeneity in OPR.

Conclusion

Gender differences in PD prevalence may not be as stark as previously thought, but still remain. Studies are needed to understand the role of genetic, environmental, and societal determinants of gender differences in prevalence.
Exploring barriers and facilitators to physical activity during the COVID-19 pandemic: a qualitative study
Authors: Roche Charlotte , Fisher Abigail , Fancourt Daisy , Burton Alexandra
Published: May 2022

Objectives

Quantitative data show that physical activity (PA) reduced during the COVID-19 pandemic, with differential impacts across demographic groups. Qualitative research is limited, so reasons for this have not been explored in-depth. This study aimed to understand barriers and facilitators to PA during the pandemic, focusing on groups more likely to have been affected by restrictions, and to map these onto the Capability, Opportunity, Motivation Model of Behaviour (COM-B).

Design

Semi-structured qualitative interview study.

Methods

One-to-one telephone/videocall interviews were conducted with younger (aged 18-24) and older adults (aged 70+), those with long-term physical health conditions or mental health conditions, and parents of young children, probing about their experiences of PA. Barriers and facilitators were identified using reflexive thematic analysis, and themes were mapped onto COM-B dimensions.

Results

116 participants were included (18-93 years old, 61% female, 71% White British). Key themes were the importance of the outdoor environment, impact of COVID-19 restrictions, fear of contracting COVID-19, and level of engagement with home exercise. Caring responsibilities and conflicting priorities were a barrier. PA as a method of socialising, establishing new routines, and the importance of PA for protecting mental health were motivators. Most themes mapped onto the physical opportunity (environmental factors) and reflective motivation (evaluations and plans) COM-B domains.

Conclusions

Future interventions should increase physical opportunity and reflective motivation for PA during pandemics, to avoid further negative health outcomes following periods of lockdown. Strategies could include tailoring PA guidance depending on location and giving education on the health benefits of PA.

Statement of Contribution

What is already known on this subject?

Physical activity (PA) levels reduced during the COVID-19 pandemic.

The extent of this reduction varied across demographic groups.

Very few qualitative studies have explored reasons for these changes.

What does this study add?

Novel interview data, giving context to existing quantitative data.

Insight into which themes were important for different demographic groups.

Suggestions for increasing PA in future pandemics, by mapping findings to a theoretical framework.
Building Medical Rehabilitation System with Safety and Without Interruption for the Patients with Coronavirus Disease 2019 Using the Functional Resonance Analysis Method (FRAM)
Authors: Sasanuma Naoki , Takahashi Keiko , Yanagida Ai , Miyagi Yohei , Yamakawa Seiya , Seo Tetsu , Uchiyama Yuki , Kodama Norihiko , Domen Kazuhisa
Published: May 2022

Introduction

Coronavirus disease 2019 (COVID-19) is an indication for rehabilitation medicine, especially in severe cases. However, there has been no systematic development of a safe and uninterrupted provision system of medical rehabilitation for patients and medical staff with COVID-19. The Functional Resonance Analysis method (FRAM) is used to analyze performance in a socio-technical system. In FRAM, each “Function” is viewed from six aspects : Input, Output, Preconditions, Resources, Control, and Time. These aspects define each Function and reveal connections between Functions. In this study, we analyzed a safe and uninterrupted provision system for medical rehabilitation—for severely ill COVID-19 patients using FRAM to prepare for possible problems in the future.

Methods

The subject of analysis was the provision system for medical rehabilitation for patients with COVID-19 at the Rehabilitation Center of Hyogo College of Medicine College Hospital. The analysis was conducted by dividing a 21-month rehabilitation period beginning April 2020 into 5 phases, and analyzing each phase using FRAM. The first four phases were retrospective analyses, and the fifth phase was a prospective analysis.

Results

Our results showed that the number of rehabilitation physicians, consultation systems, and full-time therapists was adjusted and the system providing rehabilitation was modified during each phase.

Discussion

Elements of Function, such as preconditions, control, and resources, require modification in each phase. In the process of adding and deleting these elements, it became clear that it was necessary to deal with new characteristics of SARS-CoV-2 infection. Retrospective system analysis using FRAM may contribute to the planning of measures necessary for the implementation of rehabilitation medicine prospectively.
Safety of anti-thrombotic therapy in acute aortic dissection; single center, observational study
Authors: Hori Kensuke , Morikawa Nagisa , Tayama Eiki , Fukumoto Yoshihiro
Published: May 2022

Background

Acute aortic dissection occurs due to a primary tear in aortic intima, with blood from aortic lumen penetrating into diseased media, in which anti-thrombotic therapies may be harmful. We examined the prognosis in patients, who had already taken antithrombotic therapies at the onset of acute aortic dissection, and the safety to administer anti-thrombotic drugs in acute phase during hospitalization.

Methods and Results

We retrospectively enrolled 685 patients with acute aortic dissection (type A/B: 454/231), who were transferred to Kurume University Hospital from 2004 to 2020. In both type A and B, there were no significant differences in in-hospital mortality between with and without antithrombotic therapies at the onset. Patients, who survived more than a day and administered anti-thrombotic drugs during hospitalization, had significantly lower in-hospital mortality than those who had no anti-thrombosis in acute phase in type A, while there was no significant difference in in-hospital mortality between the 2 groups in type B.

Conclusions

We demonstrated that anti-thrombotic drugs did not worsen the prognosis in patients with acute aortic dissection, indicating that we should not hesitate anti-thrombotic drugs if indicated.
Investigating relations between the NICU speech environment and weight gain in infants born very preterm
Authors: Kumar Komal , Marchman Virginia A. , Morales Maya Chan , Scala Melissa , Travis Katherine E.
Published: May 2022

Background

Children born very preterm (< 32 weeks gestational age), are at risk for poor growth and adverse neurodevelopmental outcomes. Poor outcomes in preterm children have been attributed to the aversive sounds and relative speech paucity of the neonatal intensive care unit (NICU). Experimental studies that directly expose preterm infants to speech sounds in the NICU find significant improvements in health factors relevant for neurodevelopment. Few studies have examined whether natural variations in the speech environment of the NICU are related to short-term health outcomes in preterm infants. Such data are important for optimizing the sound environment of the NICU.

Objective

Examine relations between the NICU speech environment and rate of weight gain during hospitalization, an important determinant of physical health and neurodevelopmental outcomes for preterm infants.

Methods

Participants were infants born very preterm (n = 20). The speech environment of each infant was assessed at 32-36 weeks postmenstrual age using a speech-counting device known as a Starling. Speech rates were averaged for each infant over the 4-week period. Average rates of weight gain (g/kg/day) were ascertained over the same period. Calories were derived from charted intake (kcals/kg/day). Linear regressions examined associations between weight gain and both caloric intake and speech counts. Control analyses explored whether effects remained after controlling for family visitation, time in incubator, and health acuity.

Results

Infants who received more calories gained more weight, accounting for more than 30% of the variance. Importantly, speech counts accounted for nearly 29% additional variance (p < .001). These effects were not reduced when controlling for family visitation, time in incubator, or health acuity.

Conclusions

Enhancing speech exposure in the NICU may be beneficial for physical growth. NICU infant care plans should consider opportunities to increase speech exposure.
A Comparative Effectiveness Study on Opioid Use Disorder Prediction Using Artificial Intelligence and Existing Risk Models
Authors: Fouladvand Sajjad , Talbert Jeffery , Dwoskin Linda P. , Bush Heather , Meadows Amy L. , Peterson Lars E. , Mishra Yash R. , Roggenkamp Steven K. , Wang Fei , Kavuluru Ramakanth , Chen Jin
Published: May 2022

Objective

To compare the effectiveness of multiple artificial intelligence (AI) models with unweighted Opioid Risk Tool (ORT) in opioid use disorder (OUD) prediction.

Materials and Methods

This is a retrospective cohort study of deidentified claims data from 2009 to 2020. The study cohort includes 474,208 patients. Cases are prescription opioid users with at least one diagnosis of OUD or at least one prescription for buprenorphine or methadone. Controls are prescription opioid users with no OUD diagnoses or buprenorphine or methadone prescriptions. Cases and controls are matched based on age, sex, opioid use duration and longitudinal data availability. OUD prediction performance of logistic regression (LR), random forest (RF), XGBoost, long short-term memory (LSTM), transformer, our proposed AI model for OUD prediction (MUPOD), and the unweighted ORT were assessed using accuracy, precision, recall, F1-score and AUC.

Results

Data includes 474,208 patients; 269,748 were females with an average age of 56.78 years. On 100 randomly selected test sets including 47,396 patients, MUPOD can predict OUD more efficiently (AUC=0.742±0.021) compared to LR (AUC=0.651±0.025), RF (AUC=0.679±0.026), XGBoost (AUC=0.690±0.027), LSTM (AUC=0.706±0.026), transformer (AUC=0.725±0.024) as well as the unweighted ORT model (AUC=0.559±0.025).

Discussion

OUD is a leading cause of death in the United States. AI can be harnessed with available claims data to produce automated OUD prediction tools. We compared the effectiveness of AI models for OUD prediction and showed that AI can predict OUD more effectively than the unweighted ORT tool.

Conclusion

Embedding AI algorithms into clinical care may assist clinicians in risk stratification and management of patients receiving opioid therapy.
BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children
Authors: Bartsch Yannic C , Chen Jessica W , Kang Jaewon , Burns Madeline D , St Denis Kerri J , Sheehan Maegan L , Davis Jameson P , Balazs Alejandro B , Yonker Lael M , Alter Galit
Published: May 2022

Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of novel variants of concerns has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of variants of concern that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine induced antibody titers in children 5-11 years receiving two doses of the age recommended 10 μg dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12-15 years) or adults receiving the 30 μg dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-variants of concern responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to variants of concern (VOCs) in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2 induced antibody response in children, vaccine induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to attenuation of disease.
An audit of antibiotic prescriptions at the Base Hospital of Wathupitiwala in Sri Lanka
Authors: Samaranayake WAMP , Jayawardhana GPC , Sampath Perera UAAS , Roshan ALL , Vidanagamage U , Wijayawardana M , Halpagamage N , Rannolu P
Published: May 2022

Antimicrobial resistance is a serious global public threat. A retrospective audit was conducted in December 2021 in seven units to identify the prevalence and antibiotic prescription patterns at Base Hospital Wathupitiwala, Sri Lanka. Data on antibiotic use was extracted from randomly selected 30 bead head tickets (BHTs) from each unit using a standard questionnaire form. A total of 210 patient records were examined, 107 (50.95%) were females, and the mean age was 41.43 years. Ninety-five patients (45.23%) were on antibiotics, and approximately one-third of them (33.68%) were found to be wrong choices. The prevalence of antimicrobial use varied across the ward types, with the highest being in surgical units (86.66%), followed by pediatric units (55.66%). Community-acquired infections were responsible for the majority (97.89%) of prescriptions. Skin and soft tissue infections are the most common reason (23.35%) for starting antibiotics, followed by respiratory tract infections (16.84%). The majority of prescriptions 90 (70.53%) were made empirically, and 16.4% were related to surgical or medical prophylaxis. Amoxicillin-clavulanate and third-generation cephalosporin were the most commonly used antibiotics, while the duplicate anaerobic cover and two beta-lactam therapies were most widely prescribed as combination therapy. The reason for antibiotics was not documented in 11 (11.58%) patients, while 4 (4.21%) patients had received sub-therapeutic doses. Appropriate microbiological cultures were not sent in the vast majority (71.87%) of prescriptions. Implementation of an antimicrobial stewardship program with the help of all stakeholders is crucial to curbing antimicrobial resistance and inappropriate antimicrobial therapy at Base Hospital Wathupitiwala.
How Should COVID-19 Vaccines be Distributed between the Global North and South? A Discrete Choice Experiment in Six European Countries
Authors: Steinert JI , Sternberg H , Veltri GA , Büthe T
Published: May 2022

Background

The global distribution of COVID-19 vaccinations remains highly unequal. We examine public preferences in six European countries regarding the allocation of COVID-19 vaccines between the Global South and Global North.

Methods

We conducted online discrete choice experiments with adult participants in France (n=766), Germany (n=1964), Italy (n=767), Poland (n=670), Spain (n=925), and Sweden (n=938). Respondents were asked to decide which one of two candidates, who varied along four attributes: age, mortality risk, employment, and living in a low- or high-income country, should receive the vaccine first. We analysed the relevance of each attribute in allocation decisions using a conditional logit regression.

Results

Across countries, respondents selected candidates with a high mortality and infection risk, irrespective of whether the candidate lived in their own country. All else equal, respondents in Italy, France, Spain, and Sweden gave priority to a candidate from a low-income country, whereas German respondents were significantly more likely to choose the candidate from their own country. Female, younger, and more educated respondents were more favourable of an equitable vaccine distribution.

Conclusions

Given these preferences for global solidarity, European governments should promote vaccine transfers to poorer world regions.

Funding

Funding was provided by the European Union’s Horizon H2020 research and innovation programme under grant agreement 101016233 (PERISCOPE).
Assessing Cellular and Transcriptional diversity of IIeal Mucosa amongst Treatment Naïve and Treated Crohn’s disease
Authors: Maddipatla Sushma Chowdary , Kolachala Vasantha L , Venkateswaran Suresh , Dodd Anne F , Pelia Ranjit Singh , Geem Duke , Yin Hong , Sun Yutong , Xu Congmin , Mo Angela , Kosters Astrid , Yang Junkai , Matthews Jason D. , Ghosn Eliver , Kugathasan Subra , Qiu Peng
Published: May 2022

Background and Aims

Crohn’s disease is a life-long disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn’s.

Methods

Ileal biopsies were obtained from (i) controls (n=6), (ii) treatment-naïve (n=7), and (iii) established (n=14) Crohn’s patients along with remission (n=3) and refractory (n=11) treatment groups. The biopsies were processed using 10x Genomics single cell 5’ yielded 139,906 cells. Gene expression count matrices of all samples were analyzed by reciprocal principal component integration, followed by clustering analysis. Manual annotations of the clusters were performed using canonical gene markers. Cell-type proportions, differential expression analysis and gene ontology enrichment were carried out for each cell type.

Results

We identified 3 cellular compartments with 9 epithelial, 1 stromal, and 5 immune cell subtypes. We observed differences in the cellular composition between ctrl, treatment-naive and established groups, with the significant changes in the epithelial subtypes of the treatment-naive patients, including microfold, tuft, goblet, enterocytes and BEST4+ cells. Surprisingly, fewer changes in the composition of the immune compartment were observed, however gene expression in the epithelial and immune compartment was different between Crohn’s phenotypes indicating changes in cellular activity.

Conclusions

Our study identified cellular and transcriptional signatures associated with treatment-naive that collectively points to dysfunction of the intestinal barrier with an increase in inflammatory cellular activity. Our analysis also highlights the heterogeneity amongst patients within the same disease phenotype, shinning new light on personalized treatment responses and strategies.
Shift work and evening chronotype are related to prevalent non-alcoholic fatty liver disease in 282,303 UK biobank participants
Authors: Maidstone Robert , Rutter Martin K. , Marjot Thomas , Ray David W. , Baxter Matthew
Published: May 2022

Background & Aims

Non-alcoholic fatty liver disease (NAFLD) is globally prevalent and confers a high risk of morbidity via progression to non-alcoholic steatohepatitis (NASH). Circadian disruption in mouse models contributes to the development of hepatic steatosis and inflammation, however evidence in humans is lacking. We investigated how shift working and chronotype were associated with NAFLD/NASH in UK Biobank participants.

Methods

We stratified 282,303 UK Biobank participants into day, irregular-shift, and permanent night-shift workers. We compared the likelihood of NAFLD/NASH in these groups using: a) Dallas Steatosis Index (DSI), b) NAFLD/NASH ICD10 codes, and c) liver proton density fat fraction (PDFF) after serially adjusting for age, sex, ethnicity, sleep, alcohol, smoking, and body mass index. We further assessed the relationship of baseline chronotype with likelihood of NAFLD/NASH using the same outcomes and covariates.

Results

Compared to day workers, irregular-shift workers were more likely to have NAFLD/NASH defined by high DSI (odds ratio (OR) 1.29 (95% CI 1.18–1.4)) after adjusting for all covariates excluding BMI, with some attenuation after additional adjustment for BMI (OR 1.12 (1.03-1.22)). Likelihood of DSI-defined NAFLD/NASH was also higher in permanent night-shift workers (OR 1.08 (0.9–1.29)) in the fully-adjusted model. Compared to participants with intermediate chronotype, those with extreme late chronotype had a higher likelihood of DSI-defined NAFLD/NASH (OR 1.45 (1.34–1.56)) and a higher likelihood of NAFLD/NASH by ICD10 code (OR 1.23 (1.09–1.39)). Liver PDFF was elevated in irregular shift workers, but not permanent night shift workers.

Conclusions

Irregular-shift work and chronotype are associated with NAFLD/NASH, suggesting circadian misalignment as an underlying mechanism. These findings have implications for health interventions to mitigate the detrimental effect of shift work.
Optimizing next-generation RSV prevention in Mali: a cost-effectiveness analysis of pediatric vaccination, maternal vaccination, and extended half-life monoclonal antibody immunoprophylaxis
Authors: Laufer Rachel S. , Baral Ranju , Buchwald Andrea G. , Campbell James D. , Coulibaly Flanon , Diallo Fatoumata , Doumbia Moussa , Driscoll Amanda J. , Galvani Alison P. , Keita Adama M. , Neuzil Kathleen M. , Sow Samba , Pecenka Clint , Ortiz Justin R. , Fitzpatrick Meagan C.
Published: May 2022

Background

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children.

Methods

We conducted an analysis of both health and economic impacts of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years of life, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios.

Finding

We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. In an optimization analysis incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months.

Interpretation

At prices comparable to existing vaccine products, public health programs using extended half-life RSV mAbs alone or in combination with pediatric RSV vaccines would be impactful and efficient components of prevention strategies in LMICs such as Mali.
Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian Multiple Sclerosis patients, a follow-up study
Authors: Idda Maria Laura , Pitzalis Maristella , Lodde Valeria , Loizedda Annalisa , Frau Jessica , Lobina Monia , Zoledziewska Magdalena , Virdis Francesca , Delogu Giuseppe , Marini Maria Giuseppina , Mingoia Maura , Masala Marco , Lorefice Lorena , Fronza Marzia , Carmagnini Daniele , Carta Elisa , Pilotto Silvy , Castiglia Paolo , Chessa Paola , Uzzau Sergio , Farina Gabriele , Solla Paolo , Steri Maristella , Devoto Marcella , Fiorillo Edoardo , Floris Matteo , Zarbo Roberto Ignazio , Cocco Eleonora , Cucca Francesco
Published: May 2022

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations of the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and a month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. And although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.
The time is ripe to harmonize global acute febrile illness etiologic investigations
Authors: Moreira José , Fernando-Carballo B. Leticia , Escadafal Camille , Dittrich Sabine , Brasil Patrícia , M Siqueira André
Published: May 2022

We investigated the impact of considering different case definitions of fever as inclusion criteria among participants enrolling in an acute febrile illness investigation and observed that adopting a subjective assessment of fever regardless of specific fever cut-off value accounted for the diversity of clinical fever phenotypes and did not mischaracterize the febrile population.