bluuebunny/crossref_metadata_2025 huggingface dataset:
0967 Network Analysis of Depression and Insomnia Among Pregnant Women
Authors: Li Xiao , Sit Hao Fong , Ng Denise Ching Yiu , Wong Natalie Yuk Ching , Leung Wing Cheong , Lau So-ling , Chan Joey , Chan Ngan Yin , Lee Antoinette , Wing Yun Kwok , Manber Rachel , Li Shirley Xin
Published: April 2024

Introduction

Pregnancy is a vulnerable period of lifespan characterized by a myriad of physiological and psychological changes and challenges. Whilst the existing research has documented the intricate relationship between insomnia and depression among expectant mothers, the use of sum scores of the measures in previous studies might have limited the understanding of the underlying mechanisms and key symptoms contributing to the development and persistence of these conditions. The current study aimed to examine the inter-relationship between the symptoms of insomnia and depression during the antenatal period using a networking approach.

Methods

A total of 480 pregnant women were recruited from the outpatient clinics of local hospitals and the community in Hong Kong. Insomnia and depressive symptoms were assessed by the Insomnia Severity Index (ISI) and the Edinburgh Postnatal Depression Scale (EPDS), respectively. A cutoff score ≥ 10 on the ISI indicated probable insomnia, and a cutoff ≥ 13 on EPDS indicated probable depression. Network analyses, utilizing expected influence (EI) and bridge expected influence (BEI), were conducted to determine central symptoms and bridge symptoms.

Results

Among the 480 expectant mothers (mean age: 33.0 ± 4.4 years, mean gestation week: 24.2 ± 5.9), the prevalence of probable insomnia and depression was 73.95% and 45.83%, respectively. The values of skewness and kurtosis of all symptoms were acceptable (skewness: -0.74 - 1.21, kurtosis: 1.91 - 3.47). Distress about sleep problems (ISI5) had the highest EI value, followed by Sadness (EPDS8), Unable to enjoy things (anhedonia) (EPDS2), and Feeling scared or panicky (EPDS5). Four bridge symptoms were identified: Difficulty initiating sleep (ISI-DIS), Difficulty sleeping (EPDS7), Feeling anxious/worried (EPDS4), and Distress about sleep problems (ISI5), suggesting that these symptoms exert simultaneous influence on both antenatal insomnia and depression, acting as a bridge connecting these two sets of symptoms.

Conclusion

Central symptoms and bridge symptoms identified in this network analysis should be targeted in the development of prevention and intervention strategies to address insomnia and depression among pregnant women.

Support (if any)

This work was funded by the Health and Medical Research Fund (HMRF, Ref. 20212091), the Food and Health Bureau, Hong Kong SAR, China.
0974 Sleep Characteristics and Depression and Anxiety Symptoms Among Adults with Inflammatory Bowel Disease
Authors: Zhang Xiaoyu , Yoo Linda , Conley Samantha , Kamp Kendra
Published: April 2024

Introduction

Inflammatory Bowel Disease (IBD) is a chronic, immune-mediated condition, encompassing Crohn's disease (CD) and ulcerative colitis (UC). Up to 80% of individuals with IBD report poor sleep quality. However, there is limited information on factors that predict sleep characteristics in this population. This study aims to explore the associations between demographic, clinical, and psychological factors with sleep characteristics in adults with IBD.

Methods

We conducted a retrospective analysis of two IBD sleep studies. Participants aged 18-64 years old with a diagnosis of IBD were recruited from two academic medical centers and completed Patient-Reported Outcomes Measure Information System (PROMIS) depression and anxiety questionnaires and wore a wrist actigraph for 10 days continuously. We employed Independent T-Tests and Pearson’s correlation to assess the association of biologic treatment, IBD type, sex, depression, and anxiety on sleep efficiency (SE), total sleep time (TST), and sleep onset latency (SOL).

Results

We included 58 participants with a mean age of 35.6 years (SD=12.1). 60.3% were female, and 60.3% were diagnosed with CD. The mean depression score was 51.3 (SD = 10.2) and the anxiety score was 52.2 (SD = 15.5). The mean SOL was 19.3 minutes (SD = 15.5), TST was 413.3 minutes (SD = 53.2), and SE was 83.5% (SD = 5.7). TST was significantly longer in females compared to males (427.4 vs. 391.9 minutes , p< 0.05). SE was significantly higher among females compared to males (85.1% vs. 81.0%, p< 0.001) and among individuals with Crohn's disease compared to Ulcerative colitis ((85.1% vs. 81.0%, p< 0.01). SOL was longer among individuals with Ulcerative colitis compared to Crohn's disease (15.6 vs.25.0minutes , p< 0.05). Depression and anxiety scores were not significantly correlated with any sleep characteristic.

Conclusion

Sleep continuity was poor in people with IBD. Given that we found sex and IBD type impacted sleep continuity, these factors should be considered in future precision sleep health interventions for this population.

Support (if any)

This study was funded by the University of Washington School of Nursing, NINR (K23 NR020044) (Kendra Kamp, and the American Nurses Foundation (Samantha Conley).
0976 A Brief Non-Pharmacological Insomnia Treatment for Military Suicidal Behaviors: A Sham-Controlled, Randomized Trial
Authors: Bernert Rebecca , Soltani Shamsi , Pham Savannah , Hom Melanie , Schatzberg Alan , Manber Rachel , Germain Anne , Krakow Barry , Brown Gregory , Neri Eric , Jo Booil , Tomlinson Megan , Hilberg Amanda
Published: April 2024

Introduction

Suicide represents a public health emergency among veterans, who die by suicide at alarming rates and show elevated sleep disturbances. Selective interventions for military suicide indication are scarce, and available treatments remains mismatched to the acute nature of a suicidal crisis. We sought to develop and test preliminary efficacy of a fast-acting, behavioral insomnia intervention for antisuicidal response in the context of a sham-controlled, randomized trial among veterans.

Methods

A multicomponent behavioral sleep intervention was developed, integrating: CBT for Insomnia (CBTi) and Imagery Rehearsal Treatment (IRT) within a rapid (4-session) format (SERVE: Sleep Enhancement for Returning Veterans). This was compared to active control, Arousal-Based Treatment of Insomnia (ABTI). Treatments were manualized and matched for therapist contact, materials (manuals, powerpoints, guidesheets), and passage of time. Raters were blind to treatment assignment. Inclusion criteria: (a) age>18, (b) clinically-significant sleep disturbance (Insomnia Severity Index (ISI>10)), (c) DSM-V-Defined Depression, or (d) current suicidal ideation (Columbia Suicidal Severity Rating Scale (CSSRS>1)). A comprehensive data and safety monitoring plan supported standardized risk assessment, safety planning, and triage. Outcomes were assessed at Baseline and Posttreatment (1,3 mos) according to primary (suicidal ideation), secondary (sleep indices), and exploratory (mood, stress indices) outcomes.

Results

Recruitment occurred by way of comprehensive military partnerships, clinic referrals, and community flyering. Of n=753 new contacts, n=436 participants were screened for inclusion. Of these, n=112 were interviewed by full-battery eligibility assessment, resulting in n=77 veterans enrolled and randomized to: Active Treatment (n=39) vs. Active Control (n=38). Feasibility analyses supported high rates of acceptance, tolerability, and safety. For the full sample, t-tests revealed large posttreatment reductions in suicidal ideation (CSSRS, p<.001; Depressive Symptom Inventory Suicidality Subscale (DSISS)), p<.001), sleep, mood, and stress outcomes (ISI, p<.01; DDNSI, p<.01; QIDS-SR, p<.01; PCL, p<.001). Effects were significant compared to control (DSISS, p<.01; ISI, p<.01).

Conclusion

A brief, non-pharmacological insomnia intervention resulted in antisuicidal response and large posttreatment improvements in sleep and well-being. This is the first known report testing non-medication insomnia treatment within a sham-controlled, randomized trial for military suicidal behaviors, where results support feasibility, safety, and therapeutic impact to suicidal risk.

Support (if any)

Work was supported by NIH (K23MH093490), DOD/MOMRP/MSRC funding (W81XWH-10-2-0178)
0982 Quadratic Association Between Ecologically Assessed Sleep Duration and Next-day Suicidal Ideation in Youth
Authors: Kudinova Anastacia , Nesi Jacqueline , Ryan Sarah , Diab Ella , Carskadon Mary
Published: April 2024

Introduction

Sleeping too little or too much has been linked to adverse mental health outcomes in youth. Most studies that described the link between sleep duration and suicide risk in youth, however, relied on a single assessment of sleep and suicidal ideation, with considerable temporal gaps in between. Characterizing the proximal link between sleep duration and suicide risk in children and adolescents is essential for developing informative, early mobile interventions. We examined the association between ecologically assessed suicidal ideation (SI) and sleep duration in youth recruited after a partial hospitalization program. We also examined contextual factors in relation to sleep duration that are particularly salient for youth, including nighttime social media use and social media use-related self-referential cognitions.

Methods

We used ecological momentary assessment (EMA) 3 times/day over two weeks in discharged partial hospital patients to assess their levels of SI at home (n=79; 62% assigned F at birth; ages 12-15; mean 13.52; sd 1.14 yr). We also asked youth to report their bedtimes and waketimes every morning for two weeks. Social media use was assessed once via a questionnaire.

Results

Using generalized linear mixed models, we showed a significant quadratic effect of sleep duration on next-day SI (B=–0.04, SE =0.01, p< 0.001). The turning point of the quadratic function was the sleep duration of 10 hours. Specifically, longer sleep was linked to lower next-day SI, with this association reversing at 10 hours of sleep. Nighttime social media use (B=–0.18, SE =0.05, p< 0.001) and engaging in social media use-related self-criticism (B=–0.10, SE =0.05, p< 0.05) were both linked to shorter sleep duration, whereas daytime social media use was not associated with sleep duration (p>0.05).

Conclusion

These preliminary findings point to a curvilinear association between how long children and adolescents sleep and how much they think about suicide the following day and highlight the significance of social media use at bedtime. The findings emphasize the potential clinical relevance of daily assessment of sleep duration in developing adaptive, just-in-time interventions to decrease suicide risk in youth.

Support (if any)

NIMH Career Development (K23MH122587) Award; Bradley Hospital COBRE Center (P20GM139743).
0983 Reciprocal Relations Between Sleep and Alcohol Use
Authors: Tussey Emma , Wong Maria
Published: April 2024

Introduction

Prior studies have established a longitudinal association between sleep disturbance and the development of alcohol use disorder. Experimental research also shows that alcohol intake negatively impacts sleep. The present study evaluated the reciprocal relationship between sleep and alcohol use with intensive longitudinal methods. We hypothesized that sleep disturbance would predict greater next-day alcohol intake and that greater alcohol intake would predict greater same-night sleep disturbance.

Methods

50 college students (70% female, mean age 24) participated in a two-week study assessing their daily sleep and alcohol use patterns. Participants wore the Phillips Actiwatch Spectrum and completed daily diaries capturing self-reported sleep and alcohol intake. Multi-level zero-inflated binomial models assessed whether prior sleep predicted next-day alcohol use, including the likelihood of abstaining from alcohol the next day and alcohol intake amongst individuals who do drink. Linear multi-level models assessed whether alcohol use predicted daily sleep. All models assessed both within-subject (daily) and between-subject (average) effects because daily variations in sleep may influence alcohol use separately from average patterns and vice versa—models controlled for race, age, and gender.

Results

Participants with greater average sleep onset latency (SOL) were less likely to drink the next day (OR: 1.02 p < .05). Among those who drank, greater average wake after sleep onset (WASO) and SOL and shorter daily total sleep time (TST) predicted greater next-day alcohol intake (WASO IR: 1.01; SOL IR: 1.01; TST IR: 0.998; p < .05). Higher average alcohol intake predicted increased daily WASO (B = 10.3, SE = 4.4, p < .05), TST (B = 15.0, SE = 5.1, p < .05), and decreased daily sleep quality (B = -0.13, SE = .06, p < .05). Daily alcohol intake did not predict sleep variables.

Conclusion

These results suggest there is a dynamic reciprocal relationship between sleep and alcohol use. Individuals with worse average sleep continuity were less likely to drink alcohol. However, among those who chose to drink, lower average sleep continuity and shorter daily sleep duration predicted greater alcohol intake. These results suggest that sleep disturbance is a risk factor for developing excessive alcohol use.

Support (if any)

Idaho State University, Graduate School; PSI CHI; INBRE.
0987 Physical Activity as a Tool to Improve Sleep Quality for Secure Psychiatric Inpatients: A Pilot Feasibility Study
Authors: Gardiner Poppy , Kinnafick Florence , Breen Kieran , Hartescu Iuliana
Published: April 2024

Introduction

People with severe mental illness (SMI) may receive inpatient care in a secure facility. Due to highly prevalent sleep disorders such as insomnia, and common daytime behaviours such as napping and inactivity, many of these patients experience disrupted sleep/wake cycles. Sleep/wake cycles can be retrained by increasing daytime physical activity (PA), however, patients with SMI are highly sedentary. For sedentary groups, engaging in multiple short bouts of PA across the day may feel more attainable than completing one longer bout. Therefore, we conducted a pilot study to investigate the feasibility of an intermittent PA intervention to improve sleep quality for psychiatric inpatients residing in secure healthcare.

Methods

N=22 inpatients (40.0±16.9y, 16 males) from a secure psychiatric hospital (England) participated in a ten-week, theory-informed, PA intervention. Participants were instructed to engage in three ten-minute bouts of PA/day, five days/week, completed at a self-selected intensity. At baseline, mid-point (week 5), and post-intervention, inpatients completed questionnaires, including the Insomnia Severity Index (ISI) (primary outcome). The wrist-worn Motionwatch8 actigraph was used to record sleep and PA data (including total sleep time (TST), sleep efficiency (SE), and moderate-to-vigorous PA (MVPA)).

Results

Pre-to-post intervention, mean ISI scores decreased from 12.14 (SD=4.98) to 11.38 (SD=6.18) (t(20)=0.65,p=0.53). Actigraphy data was used to derive five time-points across the sleep/wake cycle. Mean wake time advanced by 34min (SE=15.92min), time to get out of bed advanced 34min (SE=14.31min), and mid-point of sleep advanced 38min (SE=15.93min). These advances were significant (p< 0.05). Mean time to bed and time to sleep also advanced (both p>0.05). Mean MVPA increased by 17min/day (T=1.17, p>0.05). Other sleep indices (including TST, SE) did not change significantly. PA adherence scores were highly variable person-to-person. All participants remained in the trial from intervention week 1 to post-intervention.

Conclusion

Intermittent PA can decrease insomnia symptoms and significantly advance sleep phase in secure psychiatric inpatients. Though habitually sedentary, MVPA can be increased in this population. The impact of age, gender, or diagnosis could not be specified due to small sample size. Future research with larger, more diverse samples would be beneficial to support these promising early results.

Support (if any)

Loughborough University (UK), St Andrew’s Healthcare (UK)
0991 Fear of Missing out and Sleep Health: A Systematic Review and Meta-analysis
Authors: Brombach Ruth , Dietch Jessica
Published: April 2024

Introduction

Fear of missing out (FoMO) refers to anxiety and apprehension an individual feels when they believe they are missing out on rewarding experience, social interaction, or information. FoMO has been associated with negative psychological and behavioral symptoms and might also impact sleep health. This meta-analysis therefore aimed to examine the existing literature on the relationship between FoMO and dimensions of sleep health.

Methods

A systematic literature search across PubMed, PsycINFO, and Web of Science was conducted in August 2023. Primary inclusion criteria were original research studies that test the relationship between FoMO and a dimension of sleep health. Of the primary 268 studies identified, 16 were included in the final analysis.

Results

Meta-analytic results of the random-effects model applied to a total of 3 independent samples showed a positive correlation between FoMO and Bedtime Procrastination (Fisher’s Z = 0.250; 95% CI 0.137, 0.362; Z = 4.348; p <.001). Additionally, meta-analytic results of the random-effects model applied to a total of 5 independent samples showed a positive correlation between FoMO and Sleep Hygiene (Fisher’s Z = 0.268; 95% CI 0.186, 0.350; Z = 6.419; p <.001) and Sleep Quality (Fisher’s Z = 0.305; 95% CI 0.038, 0.572; Z = 2.240; p = 0.025). Additionally, two or less independent samples showed positive significant relations between FoMO and insomnia, later lights out time, problematic sleep, sleep-deprivation, SOL and TST.

Conclusion

FoMO seems to be related to different dimensions of sleep health. It seems like the constant urge to stay connected or engaged can lead to sacrificing essential sleep hours, resulting in decreased sleep quality and procrastinated bedtime. This can have effects on various aspects of physical and mental health. Therefore, addressing FoMO may be relevant in improving sleep health. While our findings are significant, it's crucial to acknowledge the limitations of drawing conclusions from some of our results, which were based on findings from just one study. This highlights the need for further comprehensive research to establish a better understanding of the relationship between FoMO and sleep health. Future research should additionally focus on conducting longitudinal studies to understand the direction of the relationships better

Support (if any)
0992 Hippocampal Response to Sleep Sound Moderates Impact of Depressed Mood on Daytime Sleepiness in Shift Workers
Authors: Shin Jiyoon , Lee Kyung Hwa , Seo Won Woo , Jeon Jeong Eun , Lee Ha Young , Yoo Jin Hyuk , Kim Sun-Young , Kim Seog Ju , Lee Yu Jin
Published: April 2024

Introduction

Shift workers (SW) commonly experience mood symptoms, which is known to be linked to sleep disturbances and disrupted 24-hour rest-activity rhythm (RAR). Altered brain response to sleep-related sound (SS) were reported to be associated with dysfunctional appraisals of sleep and sleep disturbances. In current study, we aimed to investigate differences in brain activity in response to SS between SW and control participants (CON). Furthermore, we explored the moderation effects of brain response to SS on the relationships between daytime sleepiness, mood symptoms and 24-hour RAR in SW.

Methods

SW (n=57, female 75.4%) and CON (n=56, female 71.4%) completed questionnaires (Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory). Participants also underwent one-night polysomnography and actigraphy with sleep diary for one week. We calculated 24-hour RAR with cosinor analysis on actigraphy parameters. Functional magnetic resonance imaging was performed while listening to SS and control sounds (CS). We compared brain activation in response to SS (vs. CS) between SW and CON. In addition, we conducted a moderation analysis with ESS as a dependent variable and BDI, BAI, and 24-hour RAR as independent variables. Brain activities with significant differences between SW and CON were used as moderators.

Results

SW showed higher ESS score (t = 2.28, p = 0.025) and lower interdaily stability, relative amplitude, and higher least active 5-hour period (all-ps < 0.001). SW also showed higher activity to SS in right hippocampus (t = 3.61, p < 0.001) and MFG (t = 3.57, p < 0.001) compared to CON. In SW, right hippocampus activity (HA) in response to SS moderated the relationship between BDI and ESS (F = 7.61, adjusted R-squared = 0.265, p < 0.001, high HA; r = 0.433, low HA; r = 0.051).

Conclusion

Current results suggested differential brain activity to sleep-related stimuli in SW. Moreover, the findings indicate that decreased right HA in SW can be associated with increased impact of depression on daytime sleepiness. Therefore, modulating HA and managing depressive symptoms can be helpful in reduction in excessive daytime sleepiness among SW.

Support (if any)

National Research Foundation (No. 2016M3C7A1904338 and No. 2022R1A2C1008209).
0997 Preliminary Analyses of Sleep and Psychotic-like Experiences in a Clinical High-Risk Sample
Authors: Kelly Brennan , Akhras Sarah , Orellana Stephanie , Lott Morgan , Koesterer Sophia , Banik Nandita , McCleery Amanda , Baran Bengi
Published: April 2024

Introduction

While sleep disturbances are common in individuals with psychotic disorders, and are shown to exacerbate symptoms and cognitive deficits, less is known about sleep in youth at heightened clinical high risk (CHR) for psychosis. The goals of the present study were to identify CHR individuals using well-established clinical criteria, quantify sleep using wearable technology, and investigate the relations between objective measures of sleep with endorsed psychotic-like experiences (PLEs) and associated distress.

Methods

Participants were recruited from the Psychosis-risk Intervention, Education, and Research (PIER) Program. While data collection is ongoing for this longitudinal study, current analyses were based on 9 participants (67% female, 11% male, 22% non-binary, ages 13-33). Self-reports on the Prodromal Questionnaire-Brief were used to quantify PLEs and associated distress. Sleep was measured at home with an EEG headband (Sleep Profiler) and scored according to standard AASM criteria.

Results

Preliminary analyses reveal great variability in sleep efficiency (56-97%) and Wake After Sleep Onset (5-101 min). Contrary to our predictions, we observed no significant relations between sleep duration, efficiency, or architecture and PLEs (all p’s >.5).

Conclusion

In this group of help-seeking individuals we did not observe significant relations between sleep indices and self-reported PLEs. The current study has several limitations such as a small sample size and clinical heterogeneity, and relied on self-reported measures of PLEs completed by participants online. With data collection still under way, future plans include obtaining objective clinical phenotypes (e.g., utilizing the Structured Interview of Psychosis-risk Syndromes to categorize clinical high risk status) and investigating how sleep and PLEs change over time.

Support (if any)
Effectiveness of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Acute Myocardial Infarction With or Without Type 2 Diabetes: A Systematic Review and Meta-analysis
Authors: Zhang Xuefang , Sun Gang , Li Zhiquan , Gao Weidong , Tan Wenfeng , Liu Jinxue , Zhang Bin , Wu Juan , Chen Rong , Li Xiu Juan , Zhang Gaoxing
Published: April 2024

Recent studies have revealed the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) in heart failure patients. However, their effects on acute myocardial infarction (AMI) remain uncertain. Therefore, we conducted this meta-analysis to assess the effectiveness of SGLT2i in patients with AMI with or without diabetes. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library encompassing data from inception until November 30, 2023. Relevant studies comparing SGLT2i with placebo or non-SGLT2i in patients with AMI were included. The mean difference and/or odds ratio (OR) with 95% confidence intervals were pooled using a fixed-effects model when the heterogeneity statistic (I2) was less than 50%; otherwise, a random-effects model was employed. Four randomized controlled trials and 4 observational studies involving 9397 patients with AMI were included in this meta-analysis. Patients treated with SGLT2i exhibited a significantly lower rate of hospitalization for heart failure (OR = 0.50, 95% CI: 0.32–0.80) and all-cause death (OR = 0.65, 95% CI: 0.44–0.95) compared with those treated with placebo or non-SGLT2i. Furthermore, the use of SGLT2i was associated with a significant increase in left ventricular ejection fraction (mean difference = 1.90, 95% CI: 1.62–2.17) and a greater reduction of N-terminal prohormone of brain natriuretic peptide (OR = 0.88, 95% CI 0.82–0.94). Subgroup analysis revealed that in patients with diabetes, SGLT2i exhibited similar effects. The present meta-analysis provided evidence indicating the effectiveness of SGLT2i in patients with AMI; SGLT2i may serve as an additional therapeutic option for patients with AMI, regardless of the presence or absence of diabetes.
Resistance phenotype and virulence potential of Leclercia adecarboxylata strains isolated from different sources
Authors: Yescas-Zazueta Viviana , Rocha-Gracia Rosa del Carmen , González-Bonilla Cesar R. , Ayala-Zavala J. Fernando , Enciso-Martínez Yessica , Carreón-León Eder A. , González Corona Brigitte A. , Valencia Dora , Ballesteros-Monrreal Manuel G. , Barrios-Villa Edwin
Published: April 2024

Introduction.
Leclercia adecarboxylata is a member of Enterobacterales, often considered an opportunistic pathogen. Recent reports have highlighted L. adecarboxylata as an emerging pathogen harbouring virulence and resistance determinants.

Gap statement. Little information exists on virulence and resistance determinants in L. adecarboxylata strains isolated from environmental, food, and clinical samples.

Aim. To determine the presence of resistance and virulence determinants and plasmid features in L. adecarboxylata strains isolated from environmental, food, and clinical samples, as well as their phylogenetic relationship.

Results. All strains tested showed resistance to β-lactams and quinolones but were sensitive to aminoglycosides and nitrofurans. However, even though fosfomycin resistance is considered a characteristic trait of L. adecarboxylata, the resistance phenotype was only observed in 50 % of the strains; bla
TEM was the most prevalent BLEE gene (70 %), while the quinolone qnrB gene was observed in 60 % of the strains. Virulence genes were differentially observed in the strains, with adhesion-related genes being the most abundant, followed by toxin genes. Finally, all strains carried one to seven plasmid bands ranging from 7 to 125 kbps and harboured several plasmid addiction systems, such as ParDE, VagCD, and CcdAB in 80 % of the strains.

Conclusions.
L. adecarboxylata is an important emerging pathogen that may harbour resistance and virulence genes. Additionally, it has mobilizable genetic elements that may contribute to the dissemination of genetic determinants to other bacterial genera.
Palaeoproteomic identification of a whale bone tool from Bronze Age Heiloo, the Netherlands
Authors: Dekker Joannes A. A. , Mylopotamitaki Dorothea , Verbaas Annemieke , Sinet-Mathiot Virginie , Presslee Samantha , McCarthy Morgan L. , Olsen Morten Tange , Olsen Jesper V. , Hurk Youri van den , Brattinga Joris , Welker Frido
Published: April 2024

Identification of the taxonomic origin of bone tools is an important, but often complicated, component of studying past societies. The species used for bone tool production provide insight into what species were exploited, potentially how, and for what purpose. Additionally, the choice of species may have important implications for the place of the tool within the larger toolkit. However, the taxonomic identification of bone tools is often unsuccessful based on morphology. Here we apply three palaeoproteomic techniques, ZooMS, SPIN-like data analysis and a targeted database search to narrow down the taxonomic identification of an unusually large Bronze Age bone tool from Heiloo, the Netherlands, to the North Atlantic right whale (Eubalaena glacialis). Additionally, the tool was investigated for use-wear, which showed that it was likely used for the processing of plant fibres. The assignment of the tool as whale bone adds support to the exploitation of whales by coastal Bronze Age populations, not just for meat, as previously suggested, but also for bone as a resource for tool production. We know of no other parallel of a bone tool such as this in terms of size, use, hafting, and taxonomic identity.
Optimization of an adeno-associated viral vector for epidermal keratinocytesin vitroandin vivo
Authors: Shen Qi , Suga Shogo , Moriwaki Yuta , Zening Du , Aizawa Emi , Okazaki Mutsumi , Izpisua Belmonte Juan Carlos , Hirabayashi Yusuke , Suzuki Keiichiro , Kurita Masakazu
Published: April 2024

Background: Local gene therapies, including in vivo genome editing, are highly anticipated for the treatment of genetic diseases in skin, especially the epidermis. While the adeno-associated virus (AAV) is a potent vector for in vivo gene delivery, the lack of efficient gene delivery methods has limited its clinical applications. Objective: To optimize the AAV gene delivery system with higher gene delivery efficiency and specificity for epidermis and keratinocytes (KCs), using AAV capsid and promoter engineering technologies. Methods: AAV variants with mutations in residues reported to be critical to determine the tropism of AAV2 for KCs were generated by site-directed mutagenesis of AAVDJ. The infection efficiency and specificity for KCs of these variants were compared with those of previously reported AAVs considered to be suitable for gene delivery to KCs in vitro and in vivo. Additionally, we generated an epidermis-specific promoter using the most recent short-core promoter and compared its specificity with existing promoters. Results: A novel AAVDJ variant capsid termed AAVDJK2 was superior to the existing AAVs in terms of gene transduction efficiency and specificity for epidermis and KCs in vitro and in vivo. A novel tissue-specific promoter, termed the K14 SCP3 promoter, was superior to the existing promoters in terms of gene transduction efficiency and specificity for KCs. Conclusion: The combination of the AAVDJK2 capsid and K14 SCP3 promoter improves gene delivery to epidermis in vivo and KCs in vitro. The novel AAV system may benefit experimental research and development of new epidermis-targeted gene therapies.
Evolutionary paleoecology of European rhinocerotids across the Oligocene-Miocene transition
Authors: Hullot Manon , Martin Céline , Blondel Cécile , Becker Damien , Rössner Gertrud E.
Published: April 2024

The Oligocene-Miocene transition witnessed great environmental and faunal changes, spanning from late Oligocene to early Miocene (MP28-MN3). Its drivers and consequences on mammals are however poorly understood. Rhinocerotoids are among the most affected taxa, reflected by great taxonomical and morphological changes. However, potential associated changes in ecology have not been explored. Here, we investigated the paleoecology of 10 rhinocerotid species coming from 15 localities across Western Europe and ranging from MP28 to MN3. We explored evolutionary trends for diet, physiology, and habitat via dental wear, hypoplasia, body mass, and stable isotopy. All rhinocerotids studied were C3 feeders, whether browsing or mixed-feeding, but clear dietary differences were observed at some localities and between Oligocene and Miocene rhinocerotids. The prevalence of hypoplasia was low (< 10 %) to moderate (< 20 %), but there were great differences by loci, species, and localities. Body mass co-variated with hypoplasia prevalence, suggesting that larger species might be more susceptible to stresses and environmental changes. We reconstructed similar warm conditions at all localities except Gaimersheim, but found greater variations in precipitation. Indeed, a clear shift in δ13C values was noticed at the end of the Oligocene, consistent with climatic and vegetation changes reported at that time.
Functional and antigenic landscape of the Nipah virus receptor binding protein
Authors: Larsen Brendan B. , McMahon Teagan , Brown Jack T. , Wang Zhaoqian , Radford Caelan E. , Crowe James E. , Veesler David , Bloom Jesse D.
Published: April 2024

Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.
Phenotypic overlap between rare disease patients and variant carriers in a large population cohort informs biological mechanisms
Authors: Fitzsimmons Lane ,   Undiagnosed Diseases Network, Beaulieu-Jones Brett K , Kobren Shilpa Nadimpalli
Published: April 2024

The biological mechanisms giving rise to the extreme symptoms exhibited by rare disease patients are complex, heterogenous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional biological mechanisms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population. Seizures are a common, extreme phenotype that can result from diverse and often elusive biological pathways in patients with ultrarare or undiagnosed disorders. In this pilot study, we present an approach to understand the biological pathways leading to seizures in patients from the Undiagnosed Diseases Network (UDN) by analyzing aggregated genotype and phenotype data from the UK Biobank (UKB). Specifically, we look for enriched phenotypes across UKB participants who harbor rare variants in the same gene known or suspected to be causally implicated in a UDN patient's recessively manifesting disorder. Analyzing these milder but related associated phenotypes in UKB participants can provide insight into the disease-causing molecular mechanisms at play in the rare disease UDN patient. We present six vignettes of undiagnosed patients experiencing seizures as part of their recessive genetic condition, and we discuss the potential mechanisms underlying the spectrum of symptoms associated with UKB participants to the severe presentations exhibited by UDN patients. We find that in our set of rare disease patients, seizures may result from diverse, multi-step pathways that involve multiple body systems. Analyses of large-scale population cohorts such as the UKB can be a critical tool to further our understanding of rare diseases in general.
Cardiovascular Health Effects and Synthetic Cooling Agents in E-cigarettes Labeled as ‘clear’ Marketed in Massachusetts After the Tobacco Product Flavoring Ban
Authors: Minetti Erika T. , Erythropel Hanno C. , Keith Rachel , Davis Danielle R. , Zimmerman Julie B. , Krishnan-Sarin Suchitra , Hamburg Naomi M.
Published: April 2024

Introduction

Massachusetts (MA) enacted statewide regulation on all flavored tobacco products in June 2020. Thereafter, electronic cigarettes (e-cigarettes) labeled ‘clear’ emerged on the market. We aimed to combine cardiovascular health effects with chemical analysis of ‘clear’ e-cigarettes.

Methods

We measured acute changes in blood pressure and heart rate following a 10-minute structured use of participants’ own e-cigarette, comparing ‘clear’ e-cigarette users with other flavored e-cigarette users and non-users. Chemical characterization and quantification of relevant flavorings and cooling agents (WS-3, WS-23) of 19 ‘clear’-labeled disposable e-cigarette liquids was carried out by GC/MS.

Results

After the ban, participants that used ‘clear’ labeled e-cigarettes increased from 0% to 21%. Increase in diastolic blood pressure and heart rate was significantly greater in ‘clear’ e-cigarettes users (n=22) compared to both non-’clear’ flavored e-cigarette users (n=114) and non-users (n=72). We saw similar results in heart rate when comparing Juul e-cigarette and ‘clear’ users; Juul was used as a reference as synthetic coolants WS-3 or WS-23 were not detected in these.

All (19/19) ‘clear’ e-liquids were found to contain synthetic cooling agents WS-23 and/or WS-3, menthol (18/19), as well as other flavorings (12/19).

Discussion

The detected presence of menthol alongside other flavorings in tested ‘clear’ products is a direct violation of the MA flavored tobacco product regulation, warranting stricter monitoring for new products and constituents. ‘clear’ e-cigarette use led to greater hemodynamic effects compared to other flavored e-cigarettes and Juul, which raises questions about the effect of cooling agents on users.
Multiparametric MRI Along with Machine Learning Informs on Molecular Underpinnings, Prognosis, and Treatment Response in Pediatric Low-Grade Glioma
Authors: Fathi Kazerooni Anahita , Kraya Adam , Rathi Komal S. , Kim Meen Chul , Vossough Arastoo , Khalili Nastaran , Familiar Ariana , Gandhi Deep , Khalili Neda , Kesherwani Varun , Haldar Debanjan , Anderson Hannah , Jin Run , Mahtabfar Aria , Bagheri Sina , Guo Yiran , Li Qi , Huang Xiaoyan , Zhu Yuankun , Sickler Alex , Lueder Matthew R. , Phul Saksham , Koptyra Mateusz , Storm Phillip B. , Ware Jeffrey B. , Song Yuanquan , Davatzikos Christos , Foster Jessica , Mueller Sabine , Fisher Michael J. , Resnick Adam C. , Nabavizadeh Ali
Published: April 2024

In this study, we present a comprehensive radiogenomic analysis of pediatric low-grade gliomas (pLGGs), combining treatment-naïve multiparametric MRI and RNA sequencing. We identified three immunological clusters using XCell enrichment scores, highlighting an ‘immune-hot’ group correlating with poorer prognosis, suggesting potential benefits from immunotherapies. A radiomic signature predicting immunological profiles showed balanced accuracies of 81.5% and 84.4% across discovery and replication cohorts, respectively. Our clinicoradiomic model predicted progression-free survival with concordance indices of 0.71 and 0.77 in these cohorts, and the clinicoradiomic scores correlated with treatment response (p = 0.001). We also explored germline variants and transcriptomic pathways related to clinicoradiomic risk, identifying those involved in tumor growth and immune responses. This is the first radiogenomic analysis in pLGGs that enhances prognostication by prediction of immunological profiles, assessment of patients’ risk of progression, prediction of treatment response to standard-of-care therapies, and early stratification of patients to identify potential candidates for novel therapies targeting specific pathways.
Source-to-Tap Investigation of the Occurrence of Nontuberculous Mycobacteria in a Full-Scale Chloraminated Drinking Water System
Authors: Dowdell Katherine Shea , Potgieter Sarah C , Olsen Kirk , Lee Soojung , Vedrin Matthew , Caverly Lindsay J , LiPuma John J , Raskin Lutgarde
Published: April 2024

Nontuberculous mycobacteria (NTM) in drinking water are a significant public health concern. However, an incomplete understanding of the factors that influence the occurrence of NTM in drinking water limits our ability to characterize risk and prevent infection. This study sought to evaluate the influence of season and water treatment, distribution, and stagnation on NTM in drinking water. Samples were collected source-to-tap in a full-scale, chloraminated drinking water system approximately monthly from December 2019 to November 2020. NTM were characterized using culture-dependent (plate culture with matrix-assisted laser desorption ionization-time of flight mass spectrometry [MALDI-TOF MS] isolate analysis) and culture-independent methods (quantitative PCR and genome resolved metagenomics). Sampling locations included source waters, three locations within the treatment plant, and five buildings receiving water from the distribution system. Building plumbing samples consisted of first draw, five-minute flush, and full flush cold-water samples. As the study took place during the COVID-19 pandemic, the influence of reduced water usage in three of the five buildings was also investigated. The highest concentrations of NTM source-to-tap were found in the summer first draw building water samples (107gene copies/L), which also had the lowest chloramine concentrations. Flushing was found to be effective for reducing NTM and restoring disinfectant residuals, though flush times necessary to improve water quality varied by building. Clinically-relevant NTM species, includingMycobacterium avium, were recovered via plate culture, with increased occurrence observed in buildings with higher water age. Four of five NTM metagenome-assembled genomes were identified to the species level and matched identified isolates.
An efficient gene targeting system using Δku80and functional analysis of Cyp51A inTrichophyton rubrum
Authors: Ishii Masaki , Yamada Tsuyoshi , Ohata Shinya
Published: April 2024

Trichophyton rubrumis one of the most frequently isolated fungi in patients with dermatophytosis. Despite its clinical significance, the molecular mechanisms of drug resistance and pathogenicity ofT. rubrumremain to be elucidated because of the lack of genetic tools, such as efficient gene targeting systems. In this study, we generated aT. rubrumstrain that lacks the nonhomologous end-joining-related geneku80(Δku80) and then developed a highly efficient genetic recombination system with gene targeting efficiency that was 46 times higher than that using the wild-type strain. Cyp51A and Cyp51B are 14-α-lanosterol demethylase isozymes inT. rubrumthat promote ergosterol biosynthesis and are the targets of azole antifungal drugs. The expression ofcyp51AmRNA was induced by the addition of the azole antifungal drug efinaconazole, whereas no such induction was detected forcyp51B, suggesting that Cyp51A functions as an azole-responsive Cyp51 isozyme. To explore the contribution of Cyp51A to susceptibility to azole drugs, the neomycin phosphotransferase (nptII) gene cassette was inserted into thecyp51A3′-UTR region of Δku80to destabilize the mRNA ofcyp51A. In this mutant, although the expression level ofcyp51AmRNA was comparable to that of the parent strain, the induction ofcyp51AmRNA expression by efinaconazole was diminished. The minimum inhibitory concentration for several azole drugs of this strain was reduced, suggesting that dermatophyte Cyp51A contributes to the tolerance for azole drugs. These findings suggest that an efficient gene targeting system using Δku80inT. rubrumis applicable for analyzing genes encoding drug targets.

Key Points

A novel gene targeting system using Δku80strain was established inT. rubrum

Cyp51A inT. rubrumresponds to the azole antifungal drug efinaconazole

Cyp51A contributes to azole drug tolerance inT. rubrum
Jumbo phages possess independent synthesis and utilization systems of NAD+
Authors: Li Cunyuan , Liu Kaiping , Gu Chengxiang , Li Ming , Zhou Ping , Chen Linxing , Sun Shize , Li Xiaoyue , Wang Limin , Ni Wei , Li Meng , Hu Shengwei
Published: April 2024

Jumbo phages, phages with genomes >200 kbp, contain some unique genes for successful reproduction in their bacterial hosts. Due to complex and massive genomes analogous to those of small-celled bacteria, how do jumbo phages complete their life cycle remain largely undefined. In this study, we assembled 668 high-quality jumbo phage genomes from over 15 TB of intestinal metagenomic data from 955 samples of five animal species (cow, sheep, pig, horse, and deer). Within them, we obtained a complete genome of 716 kbp in length, which is the largest phage genome so far reported in the gut environments. Interestingly, 174 out of the 668 jumbo phages were found to encode all genes required for synthesis of NAD+by the salvage pathway or Preiss-Handler pathway, referred as NAD-jumbo phage. Besides synthesis genes of NAD+, these NAD-jumbo phages also encode at least 15 types of NAD+-consuming enzyme genes involved in DNA replication, DNA repair, and counterdefense, suggesting that these phages not only have the capacity to synthesize NAD+but also redirect NAD+metabolism towards phage propagation need in hosts. Phylogenetic analysis and environmental survey indicated NAD-jumbo phages are widely present in the Earth’s ecosystems, including the human gut, lakes, salt ponds, mine tailings, and seawater. In summary, this study expands our understanding of the diversity and survival strategies of phages, and in-depth study of the NAD-jumbo phages is crucial for understanding their role in ecological regulation.
Safety of Repeated Low-Level Red-Light Therapy for Myopia: A Systematic Review
Authors: Chen Yanping , Chen Shida , Xiong Ruilin , Yang Shaopeng , Liu Riqian , Zhu Ziyu , Xiang Kaidi , Congdon Nathan , Wang Wei
Published: April 2024

Topic

Existing evidence for the safety of repeated low-level red-light (RLRL) therapy for myopia control.

Clinical relevance

Recent trials show RLRL therapy is effective in the prevention and control of myopia. Establishing its safety profile is necessary prior to widespread clinical implementation.

Methods

We conducted a systematic review (International Prospective Register of Systematic Reviews, CRD42024516676) of articles across seven databases from inception through February 10, 2024, with keywords related to myopia and RLRL therapy. Pooled safety outcomes and risk-to-benefit ratios were reported, and incidence of side effects was compared with other anti-myopia interventions. Quality appraisal was performed using the Cochrane Risk of Bias Tool.

Results

Among 689 screened articles, 20 studies (2.90%; eleven randomized controlled trials, four non-randomized controlled trials, one post-trial study, one single-arm study, one retrospective study and two case reports of identical patient.; median duration 9 months, longest 24 months) were analysed, encompassing 2,380 participants aged 3-18 years and 1,436 individuals undergoing RLRL therapy. Two case reports described an identical patient with reversible decline in visual acuity and optical coherence tomography (OCT) abnormalities, completely resolved 4 months after treatment cessation. No cases of permanent vision loss were reported. Temporary afterimage was the most common ocular symptom following treatment, resolving within 6 minutes in reported studies. The number needed to harm outweighed the number needed to treat by a ratio of 12.7-21.4 for a person with −3D to −8D myopia treated with RLRL therapy. Incidence of side effects from RLRL was 0.088 per 100 patient-years (95% confidence interval [CI], 0.02-0.50), comparable to spectacles designed for myopia reduction (0.22; 95% CI, 0.09-0.51; P=0.385), and significantly lower than for low-dose atropine (7.32; 95% CI, 6.65-8.05; P<0.001), orthokeratology (20.6; 95% CI, 16.7-25.0; P<0.001), other anti-myopia contact lens (19.3; 95% CI, 17.6-21.1; P<0.001).

Conclusion

No irreversible visual function loss or ocular structural damage was identified with RLRL. Fundus photography and OCT before and during therapy, alongside home monitoring of visual acuity and duration of afterimages, are necessary to identify side effects. Further adequately-powered studies of longer duration are needed to evaluate long-term safety of RLRL.