bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian analysis reveals the influence of maternal effect on pre-weaning body weights in Landlly piglets
Authors: Ahmad Sheikh Firdous , Gaur Gyanendra Kumar , Panda Snehasmita , Chauhan Anuj , Dutt Triveni , Bhushan Bharat
Published: April 2022

The present study was undertaken to estimate the (co)variance components and genetic parameters of body weights recorded in Landlly piglets from birth to weaning at weekly intervals (w0 to w6). The data pertained to body weights of 2462 piglets, born to 91 sires and 159 dams across different generations during a 7-year period from 2014 to 2020. Five animal models (I–V), differentiated by inclusion or exclusion of maternal effects with or without covariance between maternal and direct genetic effects, were fitted on the data using the Bayesian algorithm. The analyses were implemented by Gibbs sampling in the BLUPF90 program and Markov chain Monte Carlo (MCMC) methodology was used to draw samples of posterior distribution pertaining to (co)variance components. Based on deviance information criteria (DIC), model V with inclusion of direct additive genetic, direct maternal genetic and permanent environmental effect of dam as random factors along with covariance between direct additive and maternal effects best fitted the data on pre-weaning traits (w0 to w5). Whereas, model I incorporating only the direct additive genetic effect best fitted the weaning weight (w6) data in Landlly piglets. The posterior mean estimates of direct heritability under the best models for W0 to W6 were 0.13, 0.19, 0.29, 0.13, 0.26, 0.32 and 0.46, respectively. Inclusion of the maternal component helped in better partitioning of variance for different body weights in Landlly piglets. The maternal heritability ranged from 0.06 to 0.14, while the litter heritability ranged from 0.11 to 0.15 for pre-weaning weights (W0 to W5) under the best-fit models. The influence of maternal environment was greater than maternal genetic effect from birth to 4th week of age. The results implied that variations in body weight of Landlly pigs were genetically controlled to moderate levels (especially w2 and w4) with contributions from direct additive and maternal genotype that can be exploited by designing efficient breeding programmes.
Infection profile of patients with extracorporeal membrane oxygenation in paediatric cardiac surgery ICU
Authors: Işık Mehmet Emirhan , Arslanoğlu Ergin , Menekşe Şirin , Uygun-Kızmaz Yeşim , Şavluk Ömer Faruk , Kara Kenan Abdurrahman , Türkmen-Karaağaç Aysu , Ceyran Hakan
Published: April 2022

Aim:

We investigated the risk of increased nosocomial infections and the associated pathogens in patients who underwent paediatric cardiovascular surgery and were put on extracorporeal membrane oxygenation support. We studied the duration of extracorporeal membrane oxygenation use and other variables that may be associated with increased nosocomial infection risk.

Methods:

Patients who were treated with an extracorporeal membrane oxygenation in paediatric cardiovascular surgery ICU between 2010 and 2020 were included in this retrospective study. We analysed the site of infection and microbiological profile of infections occurring in these patients according to CDC and National Healthcare Safety Network criteria.

Results:

The onset of infection development in patients after extracorporeal membrane oxygenation was found to be median 8 (3–15, 25–75 IQR) days in the whole group, and median 11 (3–16, 25–75 IQR) days in those who developed infection without being put on extracorporeal membrane oxygenation. When patients were divided into those with and without infection, duration of ICU was found to be 19 (16–28, IQR 25–75) days in patients with infection vs. 8 (2–16, IQR 25–75; p: <0.001) days in patients without infection. Duration of extracorporeal membrane oxygenation support was found to be 14 (10–25, IQR 25–75) days in patients with infection versus 5 (2–10, IQR 25–75; p: <0.001) days in patients without infection and total hospital stay was 26 (18–33, IQR 25–75) days in patients with infection versus 8 (2–23, IQR 25–75) days in those without infection. A total of 24 patients out of the 70 patients experienced 32 infectious episodes during extracorporeal membrane oxygenation support. Culture-positive infections were detected at a single site in 19 patients, and multiple sites in 5 patients.

Conclusion:

We propose that prolonged extracorporeal membrane oxygenation support is associated with an increased risk of infection. Although extracorporeal membrane oxygenation is a life-saving treatment method, prolonged extracorporeal membrane oxygenation may increase the development of infectious complications and the associated mortality and morbidity of the patient.
Assessing the Risk of Health, Social, and Fiscal Events in Schizophrenia According to Remission or Relapse Status Using Real World Data from a SCZ Survey in the US
Authors: Kadakia Aditi , Martins Rui , Fan Angela , Dembek Carole , Connolly Mark , Shepherd Jason , Williams Rhys
Published: April 2022

Background

Schizophrenia-related, health, social, and fiscal consequences are substantial, affecting patients, caregivers, and society. The incidence of health, social, and fiscal outcomes are frequently reported for the overall schizophrenia population, not stratified by remission or relapse status.

Objectives

This study aimed to assess healthcare resource use, employment status, and housing circumstances for patients with schizophrenia in remission or relapse, compared to the overall schizophrenia population.

Methods

The Adelphi Schizophrenia Disease Specific Programme was a point-in-time survey conducted across the USA between July and October 2019. Remission was defined using Clinical Global Impression-Severity (CGI-S) score of 1-3 (stable), with relapse defined as a CGI-S score of 4-7 (unstable). Outcome-specific rate ratios were calculated by dividing the cumulative incidence for those in remission or relapse by the cumulative incidence of the overall schizophrenia population. Ratios greater than 1 indicate a higher probability of the event.

Results

Psychiatrists (n = 124) provided data for 409 patients in remission and 609 patients in relapse. Patients with schizophrenia in remission were more likely to be employed (1.66, 95% confidence interval [1.46-1.90]) and to live with a partner or family (1.08 [1.01-1.17]) compared to the overall schizophrenia population, whereas patients in relapse were more likely to experience hospitalizations in the previous 12 months (1.34 [1.19-1.15]), disability-related unemployment (1.38 [1.25-1.51]), sick leave absences (1.23 [0.66-2.31]), need to support housing (1.39 [1.08-1.79]), and homelessness (1.47 [0.95-2.27]).

Conclusions

Schizophrenia patients in relapse were more likely to experience hospitalizations, unemployment, and have unfavorable housing circumstances compared to the overall schizophrenia population. Identifying patients at risk of relapse may aid physicians in targeting interventional support, thereby reducing the burden of schizophrenia.

Funding

Sunovion Pharmaceuticals
The Incidence and Economic Burden of Extrapyramidal Symptoms in Patients with Schizophrenia Initiating Atypical Antipsychotics in a Commercially Insured Population
Authors: Kadakia Aditi , Brady Brenna , Dembek Carole , Williams Rhys , Kent Justine
Published: April 2022

Background

Extrapyramidal symptoms (EPS) affect 15% to 30% of patients with schizophrenia treated with antipsychotics and have been associated with poor patient outcomes.

Objectives

To examine the incidence and economic burden of EPS in patients with schizophrenia initiating treatment with atypical antipsychotics (AAPs).

Methods

Patients with schizophrenia newly initiating AAPs with no prior EPS were identified in the MarketScan Commercial and Medicare Supplemental database from January 1, 2012 to December 31, 2018. Incidence of EPS (new diagnosis or medication) was assessed in the year following AAP initiation. Patients were classified as developing (EPS cohort) or not developing (non-EPS cohort) EPS. All-cause and schizophrenia-related healthcare resource use and costs were compared between cohorts over the year following the first EPS claim (EPS) or randomly assigned index date (non-EPS). Multivariate models were developed for total healthcare costs and inpatient admissions.

Results

A total of 3558 patients qualified for the study; 22.1% developed EPS in the year following AAP initiation (incidence: 26.9 cases/100-person-years). Multivariate analyses demonstrated that EPS patients had a 34% higher odds of all-cause (OR:1.3361, 95% CI:1.0770-1.6575, P < .01) and 84% increased odds of schizophrenia-related (OR:1.8436, 95% CI:1.0434-2.4219, P < .0001) inpatient admissions, as well as significantly higher all-cause (EPS: $26,632 vs non-EPS: $21,273, P < .001) and schizophrenia-related (EPS: $9018 vs non-EPS: $4475, P < .0001) total costs compared to the non-EPS cohort.

Conclusions

Approximately 20% of patients developed EPS in the year following AAP initiation. The significant increases in healthcare resource utilization and costs in the EPS cohorts highlight the need for treatments that effectively target schizophrenia symptoms while reducing the risk of EPS.

Funding

Sunovion Pharmaceuticals
d-Amphetamine Transdermal System in Treatment of Children and Adolescents with ADHD: Secondary Endpoint Results from a Phase 2 Trial
Authors: Cutler Andrew J. , Suzuki Katsumi , Starling Brittney , Balakrishnan Kanan , Komaroff Marina , Castelli Mariacristina
Published: April 2022

Background

Amphetamines are a first-line treatment for ADHD. The dextroamphetamine transdermal system (d-ATS) was developed as an alternative to oral amphetamine formulations. A randomized controlled trial of d-ATS in children and adolescents with ADHD was conducted, and its primary and key secondary endpoints were met. Here, we report secondary endpoints of the study, further assessing the efficacy and safety of d-ATS.

Methods

This study comprised a 5-week, open-label dose optimization period (DOP) followed by a 2-week, randomized, cross-over double-blind treatment period (DBP). All eligible patients received d-ATS 5 mg/9 h and were evaluated weekly for a possible dose increase to 10 mg/9 h, 15 mg/9 h, and 20 mg/9 h. Once reached, the optimal dose was maintained for the DOP and utilized during the DBP. Secondary objectives for this study included assessment of efficacy via Permanent Product Measure of Performance-Attempted and -Correct (PERMP-A, PERMP-C), ADHD-RS-IV, Conners Parent Rating Scale Revised Short Form (CPRS-R:S), and Clinical Global Impression (CGI) scores in a laboratory classroom setting. Efficacy was analyzed using a mixed-model repeated-measures (MMRM) approach. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal safety.

Results

In total, 110 patients were enrolled in the DOP, and 106 patients were randomized in the DBP. Patients receiving d-ATS demonstrated significant improvement vs placebo in PERMP-A and -C scores in the DBP consistently from 2 to 12 hours post-dose (P < .001 for all timepoints). ADHD-RS-IV total scores improved during the DOP and improved further during the DBP, with a least-squares mean (95% CI) difference for d-ATS vs placebo of −13.1 (−16.2, −10.0; P < .001). Significant differences between placebo and d-ATS in the DBP were also observed for the CPRS-R:S and CGI scales (P < .001). Most TEAEs were mild or moderate, with 3 TEAEs (abdominal pain, irritated mood, and appetite loss) leading to study discontinuation in the DOP and none in the DBP. No patients were discontinued due to dermal reactions in either phase.

Conclusions

d-ATS was effective in the treatment of ADHD in children and adolescents, meeting its primary endpoint (reported elsewhere) and all secondary endpoints. d-ATS was safe and well-tolerated, with minimal dermal reactions.

Funding

Noven Pharmaceuticals, Inc.
Alliaceous Axilla as a Manifestation of Olfactory Reference Syndrome
Authors: Lima Anton S. , Patel Jenish V. , Chang Tiffany , Hirsch Alan R.
Published: April 2022

Introduction

Olfactory reference syndrome (ORS) is a delusion in which a person believes that he or she exudes a displeasing body aroma that others perceive negatively. The axilla has been reported as a single primary source in only one patient. Furthermore, ORS is rarely reported to be associated with food odor. In these instances, the food is not edible. Delusions of ORS presenting as alliaceous edible food aromas have not heretofore been described.

Case Report

One week after undergoing catheter ablation for atrial fibrillation, this 42-year-old right-handed male experienced a sudden onset of loss of smell and taste. This has persisted on presentation and he described a complete lack of smell, only being able to smell different spices and herbs. Over time, his sense of smell selectively improved such that he was able to smell alliaceous substances, including onion and garlic, as well as a few other aromas. At the same time his smell returned, he noted that his own body exuded a smell of garlic. This occurred especially while weightlifting at the gym. He noticed that the shirts he had worn working out, in the axillary regions, were encumbered with a garlic/onion miasma. He was fearful that this mephitic aroma was being secreted through his armpits, and that others would recognize his tragomaschalia. As a result, he restricted his activities. Over a few months, his smell ability gradually worsened back to the condition he was in after the ablation. Coincident with this, his perception that he was exuding an alliaceous aroma resolved.

Results

Motor examination: Drift testing: mild left pronator drift. Left abductor digiti minimal sign. Olfactory testing prior to the development of ORS: Alcohol Sniff Test (AST): 0 (anosmia). Brief Smell Identification Test (B-SIT): 3 (anosmia). Olfactory testing during ORS: AST: 16 (hyposmia). B-SIT: 9 (hyposmia). Olfactory testing after resolution of ORS: AST: 0 (anosmia).

Discussion

This could be explained by a physiologic axillary odor or malodor, which he could not detect before or after the ORS. During the ORS, the odor may have been misperceived in a dysosmic manner due to his underlying olfactory deficit. Such dysosmia may have then been interpreted as the aroma of an alliaceous vegetable. The intensity of the aroma may have been greatest at the axillary area if compared to the other sources, but due to his underlying hyposmia, he was able to perceive only the axilla as a sole source of the aroma. Besides, psychodynamic preoccupation with bodily physique may have explained his hypersensitivity to minor flaws and his excessive preoccupation with possible harassment from others. He may have consequently misinterpreted individuals’ benign observations and attitudes to presume the presence of aroma. In individuals with olfactory deficit, this investigation for the presence of ORS with traditionally unpleasant food aromas or the presence of ORS in those with chemosensory dysfunction is warranted.

Funding

No funding
Effect of the HP-3070 Transdermal System (Secuado ) on Symptoms of Hostility in Adults with Schizophrenia
Authors: Citrome Leslie , Komaroff Marina , Starling Brittney , Byreddy Sandeep , Terahara Takaaki , Hasabe Masami
Published: April 2022

Background

Patients with schizophrenia may exhibit symptoms of hostility. HP-3070, a once-daily asenapine transdermal system, is the first antipsychotic patch approved by the FDA for use in adults with schizophrenia, and its efficacy in this indication has been demonstrated. This post hoc analysis of a phase 3 randomized study investigated the efficacy of HP-3070 in treating hostility in patients with schizophrenia.

Methods

In the pivotal phase 3 study, adults with schizophrenia were randomized 1:1:1 to once-daily treatment with HP-3070 3.8 mg/24 h, 7.6 mg/24 h, or placebo for 6 weeks. Least-squares mean (LSM) changes in the PANSS hostility item score (P7) and PANSS-Excited Component (PANSS-EC), the sum of items P4 (Excitement), P7 (Hostility), G4 (Tension), G8 (Uncooperativeness), and G14 (Poor impulse control), from baseline to week 6 were assessed post hoc. Efficacy was analyzed with a mixed-effects model for repeated measures (MMRM) adjusted for PANSS-positive symptoms, items P1 (Delusions), P2 (Conceptual disorganization), P3 (Hallucinatory behavior), P5 (Grandiosity), P6 (Suspiciousness/persecution), and G9 (Unusual thought content) and presence of somnolence (including hypersomnia, hypersomnolence, or sedation) or akathisia.

Results

Among the 369 patients with a baseline PANSS hostility item score >1 and hostility scores collected at both baseline and week 6 (126 HP-3070 7.6 mg/24 h; 123 3.8 mg/24 h; 120 placebo), the week 6 LSM (95% CI) change from baseline in PANSS hostility item score was significantly better with HP-3070 than placebo for 7.6 mg/24 h (−0.4 [−0.6, −0.2]; P < .001) and 3.8 mg/24 h (−0.3 [−0.6, −0.1]; P < .01). Similar results were observed after adjusting for covariates (P < .01 for both doses). The week 6 PANSS-EC LSM change from baseline was also greater for HP-3070 7.6 mg/24 h (−1.1 [−1.9, −0.4]; n = 164; P < .01) and 3.8 mg/24 h (−1.3 [−2.0, −0.6]; n = 168; P < .001) compared with placebo (n = 165).

Conclusions

In this post hoc analysis, HP-3070 was superior to placebo in reducing hostility in patients with schizophrenia, even after adjusting for covariates, suggesting that these effects are at least partially independent of general antipsychotic effects or of effects on sedation or akathisia. These findings suggest that HP-3070 may have a specific anti-hostility effect in patients with schizophrenia.

Funding

Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical, Co.
Hyponatremia Secondary Treatment with SSRI Antidepressants in Adults and Elderly
Authors: Mazzoglio y Nabar Martin J. , Muniz Milagros M. , Montivero Christian A. , Schraier Gabriel , Leidi Terren Emmanuel E.
Published: April 2022

Introduction

Hyponatremia is an electrolyte disorder that can be caused by multiple factors, among which the syndrome of inappropriate antidiuretic hormone secretion (SIAHS) is one of the most frequent causes. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressant drugs in all age groups for efficacy, safety, and adverse effects, although they can cause serious and undesirable side effects.

Objective

Report of a series of cases of patients with SIAHS secondary to the use of SSRIs.

Materials and Methods

We report 21 cases of patients between 52 and 76 years of age, of both sexes, undergoing treatment for depressive disorder with SSRI antidepressants and anxiolytics, concomitant with other clinical treatments (ACEI, thiazides, and carbamazepine). Biochemical laboratory and electrocardiogram studies were performed prior to the start of treatment.

Results

In the first weeks (mean = 2.5) after starting psychopharmacological treatment, hyponatremia (mean = 126 mEq/L) was recorded in 9 symptomatic patients, and Inadequate Antidiuretic Hormone Secretion Syndrome (SIAHS) was diagnosed with referral to Nephrology and Endocrinology. The SSRI was withdrawn, achieving normalization of the biochemical values (plasma and urinary sodium, plasma, and urinary osmolarity), psychotherapy was reinforced until the rotation of another antidepressant. The mean time of suspension of the antidepressant was 7.1 days, the time of disappearance of symptoms after the suspension was 4.3 days and the normalization of biochemical values was 21.68 days. Only one case was severe and 5 required hospitalization.

Conclusions

In the cases presented, the SSRI antidepressants were associated with hyponatremia caused by the syndrome of inappropriate antidiuretic hormone secretion. This adverse event was more significant in elderly patients and in those treated with other drugs that cause the disease, such as antineoplastic, diuretic, and antiepileptic drugs, due to synergism between the causative mechanisms.

Funding

No funding
COVID-19 Induced Psychosis in Patients with Underlying Mental Health Disorder: Case Report
Authors: Bhimanadham Narmada Neerja , Ali Ornela , Hossain Asghar
Published: April 2022

The COVID-19 pandemic confronted the world with an unknown reality whose challenges extend beyond the immediate threat to human health posed by the virus itself. Numerous stressors such as fear of the disease gravity and absence of proper treatment protocols, prolonged social isolation, anxiety, and financial burden lead to increased risk of developing psychiatric disorders in patients with underlying mental health problems. We present a case of a 23-year-old female, with a history of anxiety and depression who presents with psychosis and mania after contracting 2019 novel coronavirus. The patient was asymptomatic for the infection. The purpose of this case report is to highlight the fact that COVID-19 can increase the risk of mania and new-onset psychosis in patients with a previous psychiatric history.

Funding

No funding
Error-Related Brain Activity in ADHD: A Systematic Review and Meta-Analysis of Electroencephalography Markers of Cognitive Control Performance
Authors: Awasthi Pranjali
Published: April 2022

Background

Deviant cognitive control performance is implicated in Attention-Deficit-Hyperactivity-Disorder (ADHD). It is also conjectured to be a potential diagnoser and differentiator between the Inattentive and Hyperactive-Impulsive ADHD types. Reliable measures have not been established due to the variation in published results.

Methods

We performed a systematic review and meta-analysis of the literature published up to May 2021 with data on electrophysiological correlates, that is, EEG correlates of cognitive control monitoring (error-related negativity, ERN; error positivity, Pe; correct-response negativity, CRN) in ADHD patients and the efficiency of EEG recordings in differentiating between ADHD types. Multiple databases including PubMed, Scopus, Google Scholar, bioRxiv, and medRxiv were searched for eligible literature. Meta-Analyses were performed through statistical tools provided by the open-source metafor package and separately using the Hedge’s g standardized mean differences.

Results

Meta-Analyses were performed on a shortlisted set of 125 studies involving 7248 participants. To avoid extraneous variables, the sex ratio was maintained at 50:50, and the age groups of participants were equally varied between early teenagers (12-15 years), late teenagers (15-18 years), young adults (21-25), and middle-aged adults (29-37). The ADHD-afflicted group showed reduced ERN (Hedge’s g = −0.58 [CIs: −0.76, −0.35]) and reduced Pe (Hedge’s g = −0.65 [CIs: −0.79, −0.44). The Hyperactive-Impulsive ADHD types (2574/7248 participants) showed an increased CRN (Hedge’s g = 0.68 [CIs: 0.71, 0.29]), while the Inattentive ADHD Types (4674/7248 participants) showed a slightly reduced CRN (Hedge’s g = −0.25 [CIs: −0.31, −0.28]. The prevalence of counted task errors was higher in the teenagers’ group (12-18 years) than the adults’ group (21-37 years).

Conclusions

Results suggest that EEG Pattern Markers (especially Pe and CRN) can act as strong differentiators/diagnosers between the Hyperactive-Impulsive and Inattentive ADHD types. In further development, deep learning classifiers can be built for ADHD types using EEG Markers as Features and statistical values as weights.

Not Part of Abstract, Additional Notes

Pranjali Awasthi is a 14-year-old researcher working on the overlap of neuroimaging and machine learning at the Neural Dynamics of Control Lab, FIU. She is an avid speaker on topics of AI Awareness and Ethics. Here is a recent feature by the Analytics India Magazine: https://analyticsindiamag.com/how-this-15-year-old-created-a-research-career-in-machine-learning.

Funding

New York Institute of Technology MRGA Committee
Incarceration: An Unrecognized Public Health Crisis
Authors: DuWors Robert , Lang Peter , Derry James , Hoffman Peter , Wolford Robert , Donovan-Dorval Christopher , Capece Jesse
Published: April 2022

Background

The current study involved decades of research and a Systematic Literature Review.

Methods

Six hundred and seventy-two former prisoners were interviewed, shortly upon release from incarceration. Multiple variables experienced while incarcerated were reviewed. Animal models around overcrowding and sustained levels of stress were also considered. The neurological underpinnings and relatedness to the concept of hypervigilance, thought to be an effective survival technique and PTSD were comprehensively researched. Hypervigilance is a well-regarded survival technique that is likened to the marine in a forward foxhole who hears a twig snap in the middle of the night and responds directly and decisively. The loading placed on the neuronal pathways and related brain regions is seen as a precursor to PTSD and otherwise burdensome to the overstimulated nervous system attempting to maintain an emotional equilibrium.

Results

A particular area of inquiry was around the presence of early parental/adult absence, recognized as a precursor to Complex PTSD (see World Health Organization ICD 11). But not delineated in DSM 5 (American Psychiatric Association). Significant rates of PTSD symptoms were identified in individuals experiencing early developmental trauma. All subjects met the criteria for Subthreshold PTSD at a minimum, and others (193) Posttraumatic Stress Disorder. Complex PTSD was descriptive of the findings of 179 of 193 subjects diagnosed with PTSD. These findings suggest that preexisting subthreshold Complex PTSD prior to incarceration predicts the development of Complex PTSD while incarcerated.

Conclusion

The social cost of American Corrections incubates PTSD and subthreshold PTSD, releasing to society individuals more at risk to themselves and society than prior to the Correctional experience is incalculable. A philosophical reconsideration of the American Correctional experience at this time is long overdue. This philosophy is grounded on the concepts of Incapacitation; Punishment and Deterrence, v the European model generally of Rehabilitation and Reintegration.

Funding

No funding
Relationships between maternal body mass index and child cognitive outcomes at 3 years of age are buffered by specific early environments in a prospective Canadian birth cohort
Authors: West Zoe , Demchenko Iryna , Clark Lee , White Marina , MacFarlane Amanda J. , Fraser William D. , Arbuckle Tye E. , Connor Kristin L. ,   the MIREC Study Group
Published: April 2022

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler’s Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother−child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; −2.01 [−3.43, −0.59],p= 0.006), verbal composite (−1.93 [−3.33, −0.53],p= 0.007), and information scale (−0.41 [−0.70, −0.14],p= 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%–41% and 7%–22%, respectively, and accounted for approximately 5%–10% greater variation in male children’s cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.
Participation of Women in the Annual Lunar and Planetary Science Conferences
Authors: Zellner N. E. B. , Rathbun J. A. , Martindale N. L. , Seidel A. M.
Published: April 2022

In recent years, conversations about the low representation of marginalized groups in most science, technology, engineering, and mathematics fields are occurring more frequently. Multiple studies reported that members of these groups are underrepresented as conference attendees, as members of conference organizing committees, and as speakers at conferences, where presenting research is important for career advancement. Planetary science has benefited from two workforce studies, and as the number of women in planetary science is increasing, their conference participation should, too. Through analyses of conference abstract author data, and to interpret the data from the workforce studies in the context of meeting participation, we studied the representation of scientists perceived to be women at the annual Lunar and Planetary Science Conference between 1999 and 2017. In the most recent five years, we find that the percentages of attendees with talks were nearly identical for men and women, and that, in general, women were represented as speakers in proportion to their numbers in the field of planetary science. This is in contrast to other professional conferences that draw from the same population of scientists and may be the result of the way the conference program is organized by a centralized committee rather than by separate session conveners. While representation of people perceived to be women has improved, we have limited data on members of other marginalized groups, including nonbinary scientists and scientists of color. In order to enable an understanding of challenges and barriers to success for members of all groups, especially those who identify along multiple axes, conferences should solicit self‐identified gender, race, career stage, and other information.
The Transience of Channel‐Spanning Logjams in Mountain Streams
Authors: Wohl Ellen , Iskin Emily P.
Published: April 2022

We use 11 years of annual surveys in streams of the Southern Rockies of Colorado, USA, to examine the persistence and geomorphic effects of logjams. Each year’s survey includes ∼300 logjams along more than 21 km of four mountain streams in primarily old‐growth subalpine forest. Streams alternate longitudinally between laterally confined reaches with a single channel and wider reaches with multithread‐channel planform. We distinguish logjam persistence and site persistence. Logjam persistence is the median timespan over which an individual jam is present. Site persistence describes the tendency for jams to disappear and then re‐form at the same site. We hypothesize that (a) site persistence is greatest in multithread reaches, (b) logjam persistence is greatest in multithread reaches, and (c) average backwater storage at each jam is greater in multithread reaches. We find that spatial and temporal metrics of site persistence differ significantly between single and multithread reaches. Individual logjam persistence does not differ significantly. Backwater storage is significantly greater in multithread reaches. Varying combinations of riparian forest age and average logjams per channel length explain variation in jam and site persistence and backwater storage via multivariate linear regression analyses. Over the 11 years of survey, a total of 429 distinct logjams were observed. Only 2.1% of the population was present for all 11 annual surveys. Median jam persistence is 1–2.5 years; median site persistence is 6–10 years. Despite the transience of most channel‐spanning logjams in the population, these jams create persistent effects in channel planform and backwater storage.
Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons
Authors: Wagle Mahendra , Zarei Mahdi , Lovett-Barron Matthew , Poston Kristina Tyler , Xu Jin , Ramey Vince , Pollard Katherine S. , Prober David A. , Schulkin Jay , Deisseroth Karl , Guo Su
Published: April 2022

Salient sensory stimuli are perceived by the brain, which guides both the timing and outcome of behaviors in a context-dependent manner. Light is such a stimulus, which is used in treating mood disorders often associated with a dysregulated hypothalamic-pituitary-adrenal stress axis. Relationships between the emotional valence of light and the hypothalamus, and how they interact to exert brain-wide impacts remain unclear. Employing larval zebrafish with analogous hypothalamic systems to mammals, we show in free-swimming animals that hypothalamic corticotropin releasing factor (CRFHy) neurons promote dark avoidance, and such role is not shared by other hypothalamic peptidergic neurons. Single-neuron projection analyses uncover processes extended by individual CRFHy neurons to multiple targets including sensorimotor and decision-making areas. In vivo calcium imaging uncovers a complex and heterogeneous response of individual CRFHy neurons to the light or dark stimulus, with a reduced overall sum of CRF neuronal activity in the presence of light. Brain-wide calcium imaging under alternating light/dark stimuli further identifies distinct and distributed photic response neuronal types. CRFHy neuronal ablation increases an overall representation of light in the brain and broadly enhances the functional connectivity associated with an exploratory brain state. These findings delineate brain-wide photic perception, uncover a previously unknown role of CRFHy neurons in regulating the perception and emotional valence of light, and suggest that light therapy may alleviate mood disorders through reducing an overall sum of CRF neuronal activity.
Apolipoprotein E potently inhibits ferroptosis by blocking ferritinophagy
Authors: Belaidi Abdel Ali , Masaldan Shashank , Southon Adam , Kalinowski Pawel , Acevedo Karla , Appukuttan Ambili T. , Portbury Stuart , Lei Peng , Agarwal Puja , Leurgans Sue E. , Schneider Julie , Conrad Marcus , Bush Ashley I. , Ayton Scott
Published: April 2022

Allelic variation to the APOE gene confers the greatest genetic risk for sporadic Alzheimer’s disease (AD). Independent of genotype, low abundance of apolipoprotein E (apoE), is characteristic of AD CSF, and predicts cognitive decline. The mechanisms underlying the genotype and apoE level risks are uncertain. Recent fluid and imaging biomarker studies have revealed an unexpected link between apoE and brain iron, which also forecasts disease progression, possibly through ferroptosis, an iron-dependent regulated cell death pathway. Here, we report that apoE is a potent inhibitor of ferroptosis (EC50 ≈ 10 nM; N27 neurons). We demonstrate that apoE signals to activate the PI3K/AKT pathway that then inhibits the autophagic degradation of ferritin (ferritinophagy), thus averting iron-dependent lipid peroxidation. Using postmortem inferior temporal brain cortex tissue from deceased subjects from the Rush Memory and Aging Project (MAP) (N = 608), we found that the association of iron with pathologically confirmed clinical Alzheimer’s disease was stronger among those with the adverse APOE-ε4 allele. While protection against ferroptosis did not differ between apoE isoforms in vitro, other features of ε4 carriers, such as low abundance of apoE protein and higher levels of polyunsaturated fatty acids (which fuel ferroptosis) could mediate the ε4 allele’s heighted risk of AD. These data support ferroptosis as a putative pathway to explain the major genetic risk associated with late onset AD.
Global population attributable fraction of potentially modifiable risk factors for mental disorders: a meta-umbrella systematic review
Authors: Dragioti Elena , Radua Joaquim , Solmi Marco , Arango Celso , Oliver Dominic , Cortese Samuele , Jones Peter B. , Il Shin Jae , Correll Christoph U. , Fusar-Poli Paolo
Published: April 2022

Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these risk factors. This study quantifies the Population Attributable Fraction (PAF) of potentially modifiable risk factors for mental disorders. We conducted a PRISMA 2020-compliant (Protocol: https://osf.io/hk2ag) meta-umbrella systematic review (Web of Science/PubMed/Cochrane Central Register of Reviews/Ovid/PsycINFO, until 05/12/2021) of umbrella reviews reporting associations between potentially modifiable risk factors and ICD/DSM mental disorders, restricted to highly convincing (class I) and convincing (class II) evidence from prospective cohorts. The primary outcome was the global meta-analytical PAF, complemented by sensitivity analyses across different settings, the meta-analytical Generalised Impact Fraction (GIF), and study quality assessment (AMSTAR). Seven umbrella reviews (including 295 meta-analyses and 547 associations) identified 28 class I–II risk associations (23 risk factors; AMSTAR: 45.0% high-, 35.0% medium-, 20.0% low quality). The largest global PAFs not confounded by indication were 37.84% (95% CI = 26.77–48.40%) for childhood adversities and schizophrenia spectrum disorders, 24.76% (95% CI = 13.98–36.49%) for tobacco smoking and opioid use disorders, 17.88% (95% CI = not available) for job strain and depression, 14.60% (95% CI = 9.46–20.52%) for insufficient physical activity and Alzheimer’s disease, 13.40% (95% CI = 7.75–20.15%) for childhood sexual abuse and depressive disorders, 12.37% (95% CI = 5.37–25.34%) for clinical high-risk state for psychosis and any non-organic psychotic disorders, 10.00% (95% CI = 5.62–15.95%) for three metabolic factors and depression, 9.73% (95% CI = 4.50–17.30%) for cannabis use and schizophrenia spectrum disorders, and 9.30% (95% CI = 7.36–11.38%) for maternal pre-pregnancy obesity and ADHD. The GIFs confirmed the preventive capacity for these factors. Addressing several potentially modifiable risk factors, particularly childhood adversities, can reduce the global population-level incidence of mental disorders.
Returning individual research results in international direct-to-participant genomic research: results from a 31-country study
Authors: Lang Michael , Zawati Ma’n H.
Published: April 2022

This paper summarizes the results of a 31-country qualitative study of expert perspectives on the regulation of international “direct-to-participant” (DTP) genomic research. We outline how the practice of directly recruiting participants for genomic studies online complicates ethics and regulatory considerations for the return of individual research results. As part of a larger project supported by the National Human Genome Research Institute, National Institutes of Health, we prepared and distributed to 31 global legal experts a questionnaire intended to ascertain opinions and perspectives on the way international DTP genomic research is likely to be regulated. We found significant disagreement across jurisdictions on the most favorable approach to managing such results, with some countries favoring return by default and others preferring to return only with the express consent of research participants. We conclude by outlining policy considerations that should guide researcher practices in this context. As international DTP genomic research evolves, jurists and ethicists should be attentive to the ways novel approaches to subject recruitment align with existing ethical and regulatory norms in research with human participants. This paper is a preliminary step toward documenting such alignment in the context of the return of individual research results.
A parallel randomised controlled trial of the Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised self-care (HARPdoc)
Authors: Amiel Stephanie A. , Potts Laura , Goldsmith Kimberley , Jacob Peter , Smith Emma L. , Gonder-Frederick Linda , Heller Simon , Toschi Elena , Brooks Augustin , Kariyawasam Dulmini , Choudhary Pratik , Stadler Marietta , Rogers Helen , Kendall Mike , Sevdalis Nick , Bakolis Ioannis , de Zoysa Nicole
Published: April 2022

Impaired awareness of hypoglycaemia (IAH) is a major risk for severe hypoglycaemia in insulin treatment of type 1 diabetes (T1D). To explore the hypothesis that unhelpful health beliefs create barriers to regaining awareness, we conducted a multi-centre, randomised, parallel, two-arm trial (ClinicalTrials.gov NCT02940873) in adults with T1D and treatment-resistant IAH and severe hypoglycaemia, with blinded analysis of 12-month recall of severe hypoglycaemia at 12 and/or 24 months the primary outcome. Secondary outcomes included cognitive and emotional measures. Adults with T1D, IAH and severe hypoglycaemia despite structured education in insulin adjustment, +/− diabetes technologies, were randomised to the “Hypoglycaemia Awareness Restoration Programme despite optimised self-care” (HARPdoc, n = 49), a psychoeducation programme uniquely focussing on changing cognitive barriers to avoiding hypoglycaemia, or the evidence-based “Blood Glucose Awareness Training” (BGAT, n = 50), both delivered over six weeks. Median [IQR] severe hypoglycaemia at baseline was 5[2–12] per patient/year, 1[0–5] at 12 months and 0[0–2] at 24 months, with no superiority for HARPdoc (HARPdoc vs BGAT incident rate ratios [95% CI] 1.25[0.51, 3.09], p = 0.62 and 1.26[0.48, 3.35], p = 0.64 respectively), nor for changes in hypoglycaemia awareness scores or fear. Compared to BGAT, HARPdoc significantly reduced endorsement of unhelpful cognitions (Estimated Mean Difference for Attitudes to Awareness scores at 24 months, −2.07 [−3.37,−0.560], p = 0.01) and reduced scores for diabetes distress (−6.70[−12.50,−0.89], p = 0.02); depression (−1.86[−3.30, −0.43], p = 0.01) and anxiety (−1.89[−3.32, −0.47], p = 0.01). Despite positive impact on cognitive barriers around hypoglycaemia avoidance and on diabetes-related and general emotional distress scores, HARPdoc was not more effective than BGAT at reducing severe hypoglycaemia.
Somatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression
Authors: Paulson Thomas G. , Galipeau Patricia C. , Oman Kenji M. , Sanchez Carissa A. , Kuhner Mary K. , Smith Lucian P. , Hadi Kevin , Shah Minita , Arora Kanika , Shelton Jennifer , Johnson Molly , Corvelo Andre , Maley Carlo C. , Yao Xiaotong , Sanghvi Rashesh , Venturini Elisa , Emde Anne-Katrin , Hubert Benjamin , Imielinski Marcin , Robine Nicolas , Reid Brian J. , Li Xiaohong
Published: April 2022

While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett’s esophagus compared to 40 Barrett’s patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett’s tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures. The critical distinction between stable Barrett’s versus those who progress to cancer is acquisition and expansion ofTP53−/− cell populations having complex structural variants and high-level amplifications, which are detectable up to six years prior to a cancer diagnosis. These findings reveal the timing of common somatic genome dynamics in stable Barrett’s esophagus and define key genomic features specific to progression to esophageal adenocarcinoma, both of which are critical for cancer prevention and early detection strategies.
A strength inversion origin for non-volcanic tremor
Authors: Vannucchi Paola , Clarke Alexander , de Montserrat Albert , Ougier-Simonin Audrey , Aldega Luca , Morgan Jason P.
Published: April 2022

Non-volcanic tremor is a particularly enigmatic form of seismic activity. In its most studied subduction zone setting, tremor typically occurs within the plate interface at or near the shallow and deep edges of the interseismically locked zone. Detailed seismic observations have shown that tremor is composed of repeating small low-frequency earthquakes, often accompanied by very-low-frequency earthquakes, all involving shear failure and slip. However, low-frequency earthquakes and very-low-frequency earthquakes within each cluster show nearly constant source durations for all observed magnitudes, which implies characteristic tremor sub-event sources of near-constant size. Here we integrate geological observations and geomechanical lab measurements on heterogeneous rock assemblages representative of the shallow tremor region offshore the Middle America Trench with numerical simulations to demonstrate that these tremor events are consistent with the seismic failure of relatively weaker blocks within a stronger matrix. In these subducting rocks, hydrothermalism has led to a strength-inversion from a weak matrix with relatively stronger blocks to a stronger matrix with embedded relatively weaker blocks. Tremor naturally occurs as the now-weaker blocks fail seismically while their surrounding matrix has not yet reached a state of general seismic failure.
An efficient approach to angular tricyclic molecular architecture via Nazarov-like cyclization and double ring-expansion cascade
Authors: Wang Yun-Peng , Fang Kun , Tu Yong-Qiang , Yin Jun-Jie , Zhao Qi , Ke Tian
Published: April 2022

A modular and efficient method for constructing angular tri-carbocyclic architectures containing quaternary carbon center(s) from 1,3-dicycloalkylidenyl ketones is established, which involves an unconventional synergistic cascade of a Nazarov cyclization and two ring expansions. It features high selectivity, mild conditions and convenient operation, wide scope and easy availability of substrate. Substitution with R1 and R2 at the 4πe-system with electron-donating group favors this reaction, while that with electron-withdrawing group or proton disfavors. The electron-donating group as R1 directs the initial ring expansion at its own site, while the p-π- or n-π- associated substituent as R2 favors selectively the later ring expansion near its location because of the beneficial maintenance of an original conjugated system. The stereoselectivity has proved to be governed by either the steric effect of R3 and R4 at the expanded rings, or the migration ability of the migrating atom. Density Functional Theory calculation suggests the initial Nazarov cyclization would be the rate-determining step. A racemic total synthesis of the natural (±)-waihoensene is realized in 18 steps by use of this methodology.