bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Response to Immunotherapy Using Pembrolizumab in a Patient With Conjunctival Squamous Cell Carcinoma With Nodal Metastasis
Authors: Fan Janet , Goldberg Hila , Torres-Cabala Carlos A. , Stewart John , Nagarajan Priyadharsini , Debnam Matthew , Crouse Eloisa Catherine , Lu Tracy , Ferrarotto Renata , Esmaeli Bita
Published: April 2024

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden. She was treated with pembrolizumab and had complete resolution of the conjunctival mass and the associated parotid metastasis after just 2 cycles of treatment. This case underscores the promising role of immune checkpoint inhibitors in the treatment of conjunctival squamous cell carcinoma, especially when surgery is associated with significant ocular morbidity, in patients who may not be good surgical candidates, or in patients with metastasis.
Depression in Persons With Epilepsy
Authors: Abell Kathryn , Sit Dorothy K. , Wisner Katherine L.
Published: April 2024

Background

Major depressive disorder is highly prevalent among persons with epilepsy (PWEs). Between 30% and 50% of PWEs suffer from depression. Many factors contribute to this prevalence, including the psychosocial impact of the diagnosis, restrictions on driving and certain types of work, and adverse effects associated with antiseizure medications. Without proper treatment, depressed PWEs have increased risks for suicide, strained relationships, lowered seizure control, and impairment in functioning. Our objective was to use the existing literature and insights from our experience in treating depression and anxiety in PWEs within an academic mood disorders center. We aimed to provide practical guidance for health care professionals who treat depression in this population.

Methods

Persons with epilepsy and depression were identified by their treating psychiatrists. Their electronic health records were reviewed and compiled for this report, with a total of 12 included in this review. Records were reviewed regarding antiseizure medications, psychotropic medications, light therapy, psychotherapy, other interventions, and treatment response.

Results

Based on our review of literature, as well as review of cases of individuals with epilepsy and comorbid psychiatric conditions, we recommend a step-wise evidence-based approach of optimizing psychiatric medication doses, augmenting with additional medication and/or implementing nonpharmacological interventions such as light therapy and psychotherapy.

Conclusions

In PWEs, improvement in depression, other psychiatric symptoms, and function are the goals of drug and nondrug interventions. Depression care has the potential to significantly improve the quality of life of PWEs and reduce both morbidity and mortality.
Navigating Pre-exposure Prophylaxis Access: Qualitative Insights From Black Women at a Northeastern Historically Black College and University
Authors: Robinson Marissa , Aidoo-Frimpong Gloria , Nelson LaRon , Sandoval-Rosario Michelle , Williams Brittany , Chandler Rasheeta
Published: April 2024

Black women are essential to ending the HIV epidemic in the United States; yet prevention, access, testing, and structural racism affect how HIV disproportionately affects them. Limited public health research focuses on Black women attending Historically Black Colleges and Universities (HBCUs) and the ability to address HIV prevention, such as pre-exposure prophylaxis (PrEP) uptake. PrEP is a once-daily oral pill used to prevent HIV transmission and has suboptimal uptake within the Black community. This generic qualitative descriptive analysis identifies the barriers and facilitators of PrEP uptake among Black women attending an HBCU using the health belief model. Overall, 22 Black college women participated in a 60-minute focus group. Emergent categories were as follows: (a) Barriers—stigma, cost, and side effects; (b) Facilitators—PrEP's effectiveness, exposure to HIV, and unprotected sex. Our findings can inform future efforts to increase PrEP uptake among Black women attending an HBCU.
HIV Diagnosis in the Context of Stable Relationships: A Qualitative Study With Women Living in Portugal
Authors: Gonçalves Mariana , Moraes Lais , Maia Ângela Costa
Published: April 2024

The purpose of this phenomenological study is to explore the acceptance of HIV diagnosis of women in stable relationships. Based on eight semistructured interviews with cisgender Portuguese women, thematic analysis identified four interrelated themes that illustrated the emotional and psychosocial dynamics involved in this journey. Following an HIV diagnosis, participants grappled with complex emotions, societal perceptions, and the internalization of stigma. Marital relationships underwent profound changes, with trust breakdown and emotional distancing. Coping mechanisms ranged from seeking support to living in secrecy, which impacted psychological well-being. Acceptance of HIV diagnosis is influenced by self-stigmatization, societal perceptions of HIV, and gender dynamics. The findings contribute to the development of tailored interventions, emphasizing the interconnected nature of physical and psychological well-being in the diagnosis acceptance process.
In Vitro Testing of Trichomonas vaginalis Drug Susceptibility: Evaluation of Minimal Lethal Concentration for Secnidazole That Correlates With Treatment Success
Authors: Graves Keonte J. , Novak Jan , Tiwari Hemant K. , Secor W. Evan , Augostini Peter , Muzny Christina A.
Published: April 2024

We determined the in vitro minimum lethal concentration of secnidazole and assessed the correlation with clinical susceptibility among Trichomonas vaginalis isolates obtained from 71 women, of whom 66 were successfully treated with this medication. A minimum lethal concentration ≤12.5 μg/mL correlated with clinical susceptibility in this study.
Deep Learning Synthesis of White-Blood From Dark-Blood Late Gadolinium Enhancement Cardiac Magnetic Resonance
Authors: Jaspers Tim J.M. , Martens Bibi , Crawley Richard , Jada Lamis , Amirrajab Sina , Breeuwer Marcel , Holtackers Robert J. , Chiribiri Amedeo , Scannell Cian M.
Published: April 2024

Objectives

Dark-blood late gadolinium enhancement (DB-LGE) cardiac magnetic resonance has been proposed as an alternative to standard white-blood LGE (WB-LGE) imaging protocols to enhance scar-to-blood contrast without compromising scar-to-myocardium contrast. In practice, both DB and WB contrasts may have clinical utility, but acquiring both has the drawback of additional acquisition time. The aim of this study was to develop and evaluate a deep learning method to generate synthetic WB-LGE images from DB-LGE, allowing the assessment of both contrasts without additional scan time.

Materials and Methods

DB-LGE and WB-LGE data from 215 patients were used to train 2 types of unpaired image-to-image translation deep learning models, cycle-consistent generative adversarial network (CycleGAN) and contrastive unpaired translation, with 5 different loss function hyperparameter settings each. Initially, the best hyperparameter setting was determined for each model type based on the Fréchet inception distance and the visual assessment of expert readers. Then, the CycleGAN and contrastive unpaired translation models with the optimal hyperparameters were directly compared. Finally, with the best model chosen, the quantification of scar based on the synthetic WB-LGE images was compared with the truly acquired WB-LGE.

Results

The CycleGAN architecture for unpaired image-to-image translation was found to provide the most realistic synthetic WB-LGE images from DB-LGE images. The results showed that it was difficult for visual readers to distinguish if an image was true or synthetic (55% correctly classified). In addition, scar burden quantification with the synthetic data was highly correlated with the analysis of the truly acquired images. Bland-Altman analysis found a mean bias in percentage scar burden between the quantification of the real WB and synthetic white-blood images of 0.44% with limits of agreement from −10.85% to 11.74%. The mean image quality of the real WB images (3.53/5) was scored higher than the synthetic white-blood images (3.03), P = 0.009.

Conclusions

This study proposed a CycleGAN model to generate synthetic WB-LGE from DB-LGE images to allow assessment of both image contrasts without additional scan time. This work represents a clinically focused assessment of synthetic medical images generated by artificial intelligence, a topic with significant potential for a multitude of applications. However, further evaluation is warranted before clinical adoption.
Clinical Outcomes of Surgical Revascularization Strategies Guided by Quantitative Flow Ratio in Primary Noncoronary Cardiac Surgery
Authors: Li Linlin , Zhang Heng , Rao Chenfei , Meng Jian , Zhou Xingtong , Liu Chang , Fan Hongguang
Published: April 2024

Purpose:

Information regarding quantitative flow ratio (QFR) usage in coronary artery bypass grafting (CABG) is lacking. We compared the incidence of postoperative long-term adverse cardiovascular and cerebrovascular events after QFR-guided or coronary angiography-guided adult cardiac surgery with concurrent bypass surgery.

Materials and Methods:

This study included 432 patients who underwent cardiopulmonary bypass (CPB) at our institution with at least 1 angiographical coronary artery lesion (diameter stenosis: 30% to 90%) between January 2015 and January 2016. The QFR of each patient was calculated. Patients who only underwent intraoperative coronary revascularization following the principles of optimal revascularization strategy were assigned to group A. Patients with coronary lesions not meeting the above criteria were placed in group B.

Results:

The average number of distal anastomoses of patients with combined CABG in group B was similar to that in Group A (1.9±1.0 vs. 1.7±0.9; P=0.081). Group A had a shorter CPB duration (114.4±49.2 vs 135.8±55.2 minutes; P<0.001) and shorter aortic cross-clamping time (83.6±36.2 vs 101.1±40.6 minutes; P<0.001). The rates of perioperative mortality and major complications did not differ between groups. Long-term major adverse cardiovascular and cerebrovascular events (MACCEs) were less common in group A than in group B (14.7% vs 29.5%; P<0.001).

Conclusions:

In primary noncoronary cardiac surgery, despite the similar average numbers of distal anastomoses, the group with target vessels treated using an optimal coronary revascularization strategy presented shorter CPB time and aortic cross-clamping time than the other group. Multivariate analyses also showed a lower incidence of long-term MACCEs.
Harnessing extracellular cold-inducible RNA binding protein by PS-OMe miR130: A promising shield against hemorrhage-induced lung injury
Authors: Hu Zhijian , Li Jingsong , Jacob Asha , Wang Ping
Published: April 2024

INTRODUCTION

Hemorrhagic shock (HS) poses a life-threatening condition with the lungs being one of the most susceptible organs to its deleterious effects. Extracellular cold-inducible RNA binding protein has emerged as a pivotal mediator of inflammation, and its release has been observed as a case of HS-induced tissue injury. Previous studies unveiled a promising engineered microRNA, designated PS-OMe miR130, which inhibits extracellular cold-inducible RNA binding protein, thereby safeguarding vital organs. In this study, we hypothesized that PS-OMe miR130 serves as a protective shield against HS-induced lung injury by curtailing the overzealous inflammatory immune response.

METHODS

Hemorrhagic shock was induced in male C57BL6 mice by withdrawing blood via a femoral artery cannula to a mean arterial pressure of 30 mm Hg for 90 minutes. The mice were resuscitated with twice the shed blood volume with Ringer's lactate solution. They were then treated intravenously with either phosphate-buffered saline (vehicle) or 62.5 nmol PS-OMe miR130. At 4 hours later, blood and lungs were harvested.

RESULTS

Following PS-OMe miR130 treatment in HS mice, a substantial decrease was observed in serum injury markers including aspartate aminotransferase, alanine transaminase, lactate dehydrogenase, and blood urea nitrogen. Serum interleukin (IL)-6 exhibited a similar reduction. In lung tissues, PS-OMe miR130 led to a significant decrease in the messenger RNA expressions of pro-inflammatory cytokines (IL-6, IL-1β, and tumor necrosis factor α), chemokines (keratinocyte-derived chemokine and macrophage inflammatory protein 2), and an endothelial injury marker, E-selectin. PS-OMe miR130 also produced substantial inhibition of lung myeloperoxidase activity and resulted in a marked reduction in lung injury as evidenced by histological evaluation. This was further confirmed by the observation that PS-OMe miR130 significantly reduced the presence of lymphocyte antigen 6 family member G–positive neutrophils and terminal deoxynucleotidyl transferase dUTP nick end labeling–positive apoptotic cells.

CONCLUSION

PS-OMe miR130 emerges as a potent safeguard against HS-induced lung injury by effectively inhibiting pro-inflammation and injuries, offering a promising therapeutic strategy in such critical clinical condition.
Effect of contextual prediction on emotional word processing: an evidence from ERPNR-D-24-00189
Authors: Li Yulin , Sui Xue , Li Yutong
Published: April 2024

Objective

This study examined the effect of context on the prediction of emotional words with varying valences. It investigated the neural mechanisms underlying the processing differences of emotion words with different valences in both predictable and unpredictable contexts. Additionally, it aimed to address the conflicting results regarding the processing time in predictive contexts reported in previous studies.

Methods

Participants were instructed to carefully read the text that included the specified emotion words. Event-related potentials elicited by emotional words were measured. To ensure that the participants can read the text carefully, 33% of the texts are followed by comprehension problems. After reading the text, the comprehension questions were answered based on the text content.

Results

The study revealed that the N400 amplitude elicited by an unpredictable context was greater than that elicited by a predictable context. Additionally, the N400 amplitude triggered by positive emotion words was larger than that triggered by negative emotion words. However, there was no significant difference in late positive component amplitude observed between contextual prediction and emotional word valence.

Conclusion

The present study suggests that predictive processing takes place at an intermediate stage of speech processing, approximately 400 ms after stimulus onset. Furthermore, the presence of a predictive context enhances the processing of emotional information. Notably, brain activity is more pronounced during the processing of positive emotional stimuli compared to negative emotional stimuli. Additionally, the facilitative effect of a predictable context diminishes in the advanced phase of Chinese speech comprehension.
The Relationship between microbial population adenosine triphosphate and quantitative polymerase chain reaction bioburdens in diesel fuel microcosms
Authors: Passman Frederick J. , Schmidt Jordan , Nicoletti Danika
Published: April 2024

Historically, fuel microbiology studies have relied on culture data.  Potentially relevant but unculturable were not detected.  Although adenosine triphosphate (ATP) can quantify total microbial bioburdens in fuels, it cannot differentiate among the taxa present.  Quantitative polymerase chain reaction (qPCR) testing promises to fill this gap by quantifying targeted amplicon sequences and thereby detecting both culturable and non-culturable taxa and quantifying specifically targeted taxa.  In this study, fluid samples drawn from the fuel, interface, and water phases of fuel over water microcosms were tested for cellular ATP concentration ([cATP]), and qPCR bioburdens.  Additionally, surface swab samples from steel corrosion coupon surfaces exposed to each of these three phases were collected and tested for total ATP concentration ([tATP]) and qPCR bioburdens.  Statistical relationships between ATP and qPCR bioburdens were examined.  Correlation coefficients between the two variables were matrix dependent and ranged from negligible (|r| = 0.2) to strong (|r| = 0.7).  When results were categorized into negligible, moderate, and heavy bioburdens, parameter agreement was again matrix dependent.  Percent agreement between [ATP] and qPCR gene copies ranged from 11 % to 89 % – with qPCR-bioburden ratings typically being greater than ATP-bioburden ratings.
The Role of Genomic-Informed Risk Assessments in Predicting Dementia Outcomes
Authors: Andrews Shea J. , Jonson Caroline , Fulton-Howard Brian , Renton Alan E , Yokoyama Jennifer S , Yaffe Kristine ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2024

Importance

By integrating genetic and clinical risk factors into genomic-informed dementia risk reports, healthcare providers can offer patients detailed risk profiles to facilitate understanding of individual risk and support the implementation of personalized strategies for promoting brain health.

Objective

To develop a genomic-informed risk assessment composed of family history, genetic, and clinical risk factors and, in turn, evaluate how the risk assessment predicted incident dementia.

Design

This longitudinal study included data from two clinical case-control cohorts with an average of 6.6 visits. Secondary analyses were conducted from July 2023 - March 2024.

Setting

Data were previously collected across multiple US locations from 1994 to 2023.

Participants

Older adults aged 55+ with whole-genome sequencing and dementia-free at baseline.

Exposures

An additive score comprising the modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (mCAIDE), family history of dementia, APOEgenotype, and an AD polygenic risk score.

Main Outcome(s) and Measure(s)

The risk of progression to all-cause dementia was evaluated using Cox-proportional hazard models (hazard ratios with 95% confidence intervals [OR 9%CI]).

Results

A total of 3,429 older adults were included (aged 75 ± 7 years; 59% female; 75% non-Latino White, 15% Black, 5.2% Latino, 3.6% other, and 0.4% Asian; 27% MCI), with 751 participants progressing to dementia. The most common high-risk indicator was a family history of dementia (56%), followed byAPOE*ε4 genotype (36%), high mCAIDE score (34%), and high AD-PRS (11%). Most participants had at least one high-risk indicator, with 39% having one, 32% two, 9.8% three, and 1% four. The presence of 1, 2, 3, or 4 risk indicators was associated with a doubling (HR = 1.72, CI: 1.34-2.22, p = 2.5e-05), tripling (HR = 3.09, CI: 2.41-3.95, p = 4.4e-19), quadrupling (HR = 4.46, CI: 3.34-5.94, p = 2.2e-24), and a twelvefold increase (HR = 12.15, CI: 7.33-20.14, p = 3.2e-22) in dementia risk.

Conclusion & Relevance

We found that most participants in memory and aging clinics had at least one high-risk indicator for dementia. Furthermore, we observed a dose-response relationship where a greater number of risk indicators was associated with an increased risk of incident dementia.
Light Exposure Differs by Gender in the US: Women Have Less Bright Light Exposure than Men
Authors: Wallace Danielle A.
Published: April 2024

Light is a salient environmental exposure, serving as the primary entraining cue for the circadian system and having other, non-circadian, effects on health. Gender differences in light exposure patterns could contribute to gender differences in health outcomes and would have important implications for sleep and circadian research. Gender differences in real-world light exposure (measured over a week with wrist-worn ActiGraph GT3X+ devices) were investigated in cross- sectional data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Measures of time above light threshold (TALT), individual photoperiod (IP), first and last timing of light (FTL and LTL, respectively), and mean light timing revised (MLiTR) at different light intensity thresholds were derived. Gender differences in light exposure were tested using two-sample t-tests, Watson’s two-sample test of homogeneity, and linear regression models. Exploratory analyses to investigate work and physical activity-related factors in relation to bright light exposure were also conducted. A total of 11,318 NHANES participants (age range: 3-80+, 52.2% women) with 6 days of valid actigraphy and light data were included in the analysis. The findings suggest that for every 60 minutes of bright light (≥1,000 lux) that men receive, women receive 39.6 minutes. Men spend approximately 52% more time in bright light than women and this gender difference begins in childhood. The IP of bright light exposure is also longer for men, with earlier first and later last timing of bright light exposure compared to women. These gender differences were robust across ages and between race and ethnicity groups. While further research is needed, these gender differences in light exposure may be due to gender differences in indoor vs. outdoor activities. Future studies of gender differences in response to light exposure should consider light exposure history in study design and analysis. The results of this study may inform future health disparities research and support the importance of the study of light as an important environmental exposure and component of the human exposome.
Clostridioides difficiletransmission: a compartmental model accounting for environmental spore persistence
Authors: Edman-Wallér Jon , Rizzardi Kristina , Jacobsson Gunnar , Gerlee Philip
Published: April 2024

Objective

To set up a compartmental model, including environmental spore levels, forC. difficiletransmission dynamics in a hospital and determine the effect of preventive interventions on infection and colonization rates.

Design

Intervention study within a compartmental mathematical modeling framework.

Setting

A simulated Swedish 500-bed secondary care hospital.

Interventions modeled

Antibiotic stewardship, improved isolation of infected patients, improved general cleaning and disinfection.

Results

Antibiotic stewardship had the largest effect on infections, with a 30.6% decrease in infection prevalence. Improved general cleaning and disinfection had the largest effect on colonization (–22.5%) and environmental spore levels (–39.7%). Improved isolation of infected patients had modest effects in comparison.

Conclusions

Modeling that includes the dynamics of environmental spores can aid our understanding ofC. difficiletransmission within hospitals. Antibiotic stewardship and improved general cleaning and disinfection showed the largest potential for prevention in our modeled setting.
Unveiling Peripheral Immune Dysfunction in Parkinson’s Disease through Analysis of Blood-based Mitochondrial DNA Copy Number
Authors: Wang Longfei , Han Jiru , Fearnley Liam G. , Milton Michael , Rafehi Haloom , Reid Joshua , Gerring Zachary , Masaldan Shashank , Lang Tali , Speed Terence P. , Bahlo Melanie
Published: April 2024

Mitochondrial dysfunction plays an important role in Parkinson’s disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. Our study aimed to assess the association between blood mtDNA-CN and PD, as well as to uncover the underlying mechanisms. Introducing mitoCN, a novel mtDNA-CN estimator adjusting for coverage bias, suitable for large-scale whole-genome sequencing data, we applied it across six cohorts within the Accelerating Medicines Partnership program for Parkinson’s Disease dataset. We investigated the links between blood mtDNA-CN and both PD risk and severity, leveraging comprehensive clinical assessments. Our findings reveal that reduced blood mtDNA-CN levels are associated with heightened PD risk and increased severity of motor symptoms and olfactory dysfunction. However, upon adjusting for blood composition, these associations largely disappeared, indicating a predominant influence of changes in blood variables. Furthermore, using bidirectional Mendelian randomization, we explored causal relationships, finding no evidence of a direct causal relationship between blood mtDNA-CN and PD susceptibility. Thus, even though blood bulk mtDNA-CN correlates with an elevated risk of PD and more severe PD symptoms, our refined analyses and results suggest that peripheral immune dysfunction rather than mitochondrial dysfunction underpins these previously identified associations.
Quality of life, symptom burden and associated factors among lung cancer patients: baseline study of three public hospitals across sub- Saharan Africa
Authors: Ratshikana Mpho , Malale Kija , Murunga Lawrence Atundo , Sayed Abdul-Rauf , Ayeni Oluwatosin , Ginindza Themba G , Dlamini Xolisile , Busakhala Naftali , Mathiba Rofhiwa , Blanchard Charmaine , Tsitsi Merika , Msomi Sabelo , Masalu Nestory , Dhudha Herry O. , Ruff Paul , Graham Anita , Osei-Fofie Daniel
Published: April 2024

Background

Cancer patients in Sub-Saharan Africa (SSA) are diagnosed late partly due to community lack of knowledge about the disease, social and cultural factors, health system challenges, and inadequate health care worker knowledge. These delays in diagnosis as well as inadequate treatment options contribute to the high mortality from lung cancer in SSA. Quality of life (QoL) is an important outcome measure for cancer patients undergoing treatment.

Objective

To describe the quality of life among lung cancer patients in three teaching hospitals in SSA.

Methods

This is a prospective cross-sectional study of lung cancer patients at three teaching hospitals in Sub-Saharan Africa (SSA-Kenya (BMC), Tanzania (MTRH) and South Africa (The Lung Laboratory Research and Intervention Unit Helen Joseph Hospital). Trained interviewers collected data on demographics, clinical information and performance status using the Eastern Cooperative Oncological Group Performance Scale (ECOG-PS). Patients’ QoL was assessed using the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).

Results

A total of 210 lung cancer patients consented and were enrolled across the three sites. Global Health Status in this cohort is low, the median score was 41.7 (range: 0-100) and differed between sites. Wits Core patients had higher social functioning, while BMC and MTRH had higher financial difficulty scores. Poor ECOG-PS score (3-4) was associated with poorer Global QoL (GqoL) score (aOR = 2.9; 95% CI: 1.4 - 5.9), and patients with higher symptom burden had poorer GQoL.

Conclusion

The QoL among lung cancer patients in the three sites is low. Poor QOL in the study is associated with level of education, performance status, fatigue, pain, dyspnoea, insomnia, loss of appetite and constipation.
Trends in fetal alcohol spectrum disorder (FASD) research: a systematic scoping review and bibliometric analysis
Authors: McQuire Cheryl , Frennessen Nessie Felicia , Parsonage James , Van der Heiden Molly , Troy David , Zuccolo Luisa
Published: April 2024

Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disability globally. International health and policy organisations have highlighted an urgent need for improved prevention, diagnosis, and support. However, the evidence base needed to inform this is thought to be limited. We conducted a systematic scoping review and bibliometric analysis to describe trends in the volume and characteristics of original research on FASD published between 2000–2023 (Review 1). We compared the volume of published research on FASD to that of other neurodevelopmental disorders (Review 2). Searches were conducted in MEDLINE, Embase, CINAHL, PsychInfo (Review 1) and PubMed (Review 2). Eligible studies were original research articles with FASD terms in the title (Review 1) and all records with FASD, autism, or attention-deficit-hyperactivity disorder terms in the title (Review 2) published between 2000–2023. Data were summarised using descriptive statistics, narrative syntheses, and time-series plots to depict trends in common themes, countries of publication, sample characteristics, and research volume. This review found that FASD remains significantly under-researched. While there has been an increase in the number of original FASD research articles published annually over the last 23-years, this is significantly lower than what would be expected based on comparison with publication trends for other neurodevelopmental conditions, and the wider scientific literature. Further research is needed to understand the needs and impact of FASD across the lifespan and within different populations, to inform evidence-based prevention, policy, and support, and to advance progress in strength-based, stigma-reducing approaches to FASD research and practice.

Statements and Declarations

The authors declare no conflicts of interest
Discovery of a synthetic small molecule targeting the central regulator ofSalmonellapathogenicity
Authors: Boudrioua Abdelhakim , Joiner Joe D. , Grin Iwan , Kronenberger Thales , Korotkov Vadim S. , Steinchen Wieland , Kohler Alexander , Schminke Sophie , Schulte Julia-Christina , Pietsch Michael , Naini Arun , Kalverkamp Simon , Hotop Sven-Kevin , Coyle Travis , Piselli Claudio , Coles Murray , Rox Katharina , Marschal Matthias , Bange Gert , Flieger Antje , Poso Antti , Brönstrup Mark , Hartmann Marcus D. , Wagner Samuel
Published: April 2024

The enteric pathogenSalmonella entericaserovar Typhimurium relies on the activity of effector proteins to invade, replicate, and disseminate into host epithelial cells and other tissues, thereby causing disease. Secretion and injection of effector proteins into host cells is mediated by dedicated secretion systems, which hence represent major virulence determinants. Here, we report the identification of a synthetic small molecule with drug-like properties, C26, which suppresses the secretion of effector proteins, and consequently hinders bacterial invasion of eukaryotic cells. C26 binds to and inhibits HilD, the transcriptional regulator of the major secretion systems. While sharing the same binding pocket as the previously described long-chain fatty acid ligands, C26 inhibits HilD with a unique binding mode and a distinct mechanism. We provide evidence for target engagement within infected eukaryotic cells and present analogs with improved potency and suitability as scaffolds to develop anti-virulence agents againstSalmonellainfections in humans and animals.
IPMK regulates HDAC3 activity and histone H4 acetylation in human cells
Authors: Sowd Gregory A. , Stivison Elizabeth A. , Chapagain Pratima , Hale Andrew T. , Poland James C. , Rameh Lucia E. , Blind Raymond D.
Published: April 2024

Histone deacetylases (HDACs) repress transcription by catalyzing the removal of acetyl groups from histones. Class 1 HDACs are activated by inositol phosphate signaling moleculesin vitro, but it is unclear if this regulation occurs in human cells. Inositol Polyphosphate Multikinase (IPMK) is required for production of inositol hexakisphosphate (IP6), pentakisphosphate (IP5) and certain tetrakisphosphate (IP4) species, all known activators of Class 1 HDACsin vitro. Here, we generated IPMK knockout (IKO) human U251 glioblastoma cells, which decreased cellular inositol phosphate levels and increased histone H4-acetylation by mass spectrometry. ChIP-seq showed IKO increased H4-acetylation at IKO-upregulated genes, but H4-acetylation was unchanged at IKO-downregulated genes, suggesting gene-specific responses to IPMK knockout. HDAC deacetylase enzyme activity was decreased in HDAC3 immunoprecipitates from IKOvs. wild-type cells, while deacetylase activity of other Class 1 HDACs had no detectable changes in activity. Wild-type IPMK expression in IKO cells fully rescued HDAC3 deacetylase activity, while kinase-dead IPMK expression had no effect. Further, the deficiency in HDAC3 activity in immunoprecipitates from IKO cells could be fully rescued by addition of synthesized IP4 (Ins(1,4,5,6)P4) to the enzyme assay, while control inositol had no effect. These data suggest that cellular IPMK-dependent inositol phosphates are required for full HDAC3 enzyme activity and proper histone H4-acetylation. Implications for targeting IPMK in HDAC3-dependent diseases are discussed.
Testing models of cell cortex wave generation by Rho GTPases
Authors: Chomchai Dom , Leda Marcin , Golding Adriana , von Dassow George , Bement William M. , Goryachev Andrew B.
Published: April 2024

The Rho GTPases pattern the cell cortex in a variety of fundamental cell-morphogenetic processes including division, wound repair, and locomotion. It has recently become apparent that this patterning arises from the ability of the Rho GTPases to self-organize into static and migrating spots, contractile pulses, and propagating waves in cells from yeasts to mammals1. These self-organizing Rho GTPase patterns have been explained by a variety of theoretical models which require multiple interacting positive and negative feedback loops. However, it is often difficult, if not impossible, to discriminate between different models simply because the available experimental data do not simultaneously capture the dynamics of multiple molecular concentrations and biomechanical variables at fine spatial and temporal resolution. Specifically, most studies typically provide either the total Rho GTPase signal or the Rho GTPase activity as reported by various sensors, but not both. Therefore, it remains largely unknown how membrane accumulation of Rho GTPases (i.e., Rho membrane enrichment) is related to Rho activity. Here we dissect the dynamics of RhoA by simultaneously imaging both total RhoA and active RhoA in the regime of acute cortical excitability2, characterized by pronounced waves of Rho activity and F-actin polymerization3-5. We find that within nascent waves, accumulation of active RhoA precedes that of total RhoA, and we exploit this finding to distinguish between two popular theoretical models previously used to explain propagating cortical Rho waves.
Post-transcriptional regulatory pre-complex assembly drives timely cell-state transitions during differentiation
Authors: Komori Hideyuki , Rastogi Geeta , Bugay John Paul , Luo Hua , Lin Sichun , Angers Stephane , Smibert Craig A. , Lipshitz Howard D. , Lee Cheng-Yu
Published: April 2024

Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. TheDrosophilaRNA-binding protein Brain tumor (Brat) promotes degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and in uncommitted intermediate neural progenitors (immature INPs). We identified Ubiquitin-specific protease 5 (Usp5) as a Brat interactor essential for the degradation of Brat target mRNAs in both cell types. Usp5 promotes Brat-dedadenylase pre-complex assembly in mitotic neural stem cells (neuroblasts) by bridging Brat and the scaffolding components of deadenylase complexes lacking their catalytic subunits. The adaptor protein Miranda binds the RNA-binding domain of Brat, limiting its ability to bind target mRNAs in mitotic neuroblasts. Cortical displacement of Miranda activates Brat-mediated mRNA decay in immature INPs. We propose that the assembly of an enzymatically inactive and RNA-binding-deficient pre-complex poises mRNA degradation machineries for rapid activation driving timely developmental transitions.
ESCRT recruitment to damaged lysosomes is dependent on the ATG8 E3-like ligases
Authors: Corkery Dale P. , Li Shuang , Wijayatunga Deerada , Herzog Laura K. , Knyazeva Anastasia , Wu Yao-Wen
Published: April 2024

The endosomal sorting complex required for transport (ESCRT) machinery plays an essential role in the sealing of endolysosomal membranes damaged by pathogenic, chemical or physical stress. How membrane damage is sensed by the cell and then translated into the recruitment of the ESCRT machinery is largely unknown. Here, we show that damage-dependent translocation of the autophagy ATG8 E3-like ligases to lysosomal membranes acts as the catalyst for ESCRT recruitment. Leakage of protons or calcium from perforated lysosomes induces V-ATPase-dependent or sphingomyelin-dependent recruitment of the ATG16L1-ATG5-ATG12 or TECPR1-ATG5-ATG12 E3-like complex, respectively. We show that E3-like complex-dependent recruitment of the ATG5-ATG12 conjugate to the damaged membrane is an essential prerequisite to ESCRT recruitment. At the damaged membrane ATG5-ATG12 plays both a conjugation-dependent and conjugation-independent role in stabilizing the calcium sensor, ALG-2, and recruiting the downstream repair complex. For the former scenario, we demonstrate that LC3B binds directly to ALG-2 in a Ca2+dependent manner. This places the ATG8 E3-like ligases in the role of damage sensors for ESCRT- mediated membrane repair.

GRAPHICAL ABSTRACT
The lncRNAMalat1is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons
Authors: Xiao Wen , Halabi Reem , Lin Chia-Ho , Nazim Mohammad , Yeom Kyu-Hyeon , Black Douglas L.
Published: April 2024

Synaptic function in neurons is modulated by local translation of mRNAs that are transported to distal portions of axons and dendrites. The metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is broadly expressed across cell types, almost exclusively as a nuclear long noncoding RNA. We found that in differentiating neurons, a portion ofMalat1RNA redistributes to the cytoplasm. Depletion ofMalat1using antisense oligonucleotides (ASOs) stimulates the expression of particular pre- and postsynaptic proteins, implicatingMalat1in their regulation. NeuronalMalat1is localized in puncta of both axons and dendrites that costain with Staufen1 protein, similar to neuronal RNA granules formed by locally translated mRNAs. Ribosome profiling of cultured mouse cortical neurons identified ribosome footprints within a 5′ region ofMalat1containing short open reading frames. The upstream-most reading frame (M1) of theMalat1locus was linked to the GFP-coding sequence in mouse embryonic stem cells. When these gene-edited cells were differentiated into glutamatergic neurons, the M1-GFP fusion protein was expressed. Antibody staining for the M1 peptide confirmed its presence in wild-type neurons and showed that M1 expression was enhanced by synaptic stimulation with KCl. Our results indicate thatMalat1serves as a cytoplasmic coding RNA in the brain that is both modulated by and modulates synaptic function.
Remembering what we imagine: the role of event schemas in shaping how imagined autobiographical events are recalled
Authors: Fenerci Can , Adjei Bianca , Sheldon Signy
Published: April 2024

Much like recalling autobiographical memories, constructing imagined autobiographical events depends on episodic memory processes. The ability to imagine events contributes to several future-oriented behaviors (e.g., decision-making, problem solving), which relies, in part, on the ability to remember the imagined events. A factor affecting the memorability of such events is their adherence to event schemas—conceptualizations of how events generally unfold. In the current study, we examined how two aspects of event schemas—event expectancy and familiarity—affect the ability to recall imagined events. Participants first imagined and described in detail autobiographical events that either aligned with or deviated from an event, expected to occur in a context (e.g., a kitchen) that was either familiar or unfamiliar. This resulted in imaginations ranging from maximally schema-congruent (expected events in a familiar context) to maximally novel (unexpected events in an unfamiliar context). Twenty-four hours later, participants recalled these imagined events. Recollections were scored for the number of reinstated details from the imaginations and the number of newly added details. We found greater reinstatement of details for both the maximally congruent and maximally novel events, while maximally novel events were recalled more precisely than other events (i.e., fewer added details). Our results indicate a complementary benefit to remembering schematic and novel imagined events, which may guide equally important but distinct future-oriented behaviors.
Mass spectrum of spin-one hadrons in dense two-color QCD: Novel predictions by extended linear sigma model
Authors: Suenaga Daiki , Murakami Kotaro , Itou Etsuko , Iida Kei
Published: April 2024

We construct an extended version of the linear sigma model in such a way as to describe spin-1 hadrons as well as spin-0 hadrons in two-color QCD (QC2D) by respecting the Pauli-Gürsey SU(4) symmetry. Within a mean-field approximation, we therefrom examine a mass spectrum of the spin-1 hadrons at finite quark chemical potential (μq) and zero temperature. Not only mean fields of scalar mesons and scalar-diquark baryons but also of vector mesons and vector-diquark baryons are incorporated. As a result, we find that, unless all of those four types of mean fields are taken into account, neither lattice result for the critical μq that corresponds to the onset of baryon superfluidity nor for μq dependence of the pion mass can be reproduced. We also find that a slight suppression of the ρ meson mass in the superfluid phase, which was suggested by the lattice simulation, is reproduced by subtle mixing effects between spin-0 and spin-1 hadrons. Moreover, we demonstrate the emergence of an axial-vector condensed phase and possibly of a vector condensed phase by identifying the values of

μ

q

at which the corresponding hadron masses vanish. The possible presence of isotriplet 1− diquarks that may be denoted by a tensor-type quark bilinear field is also discussed.

Published by the American Physical Society
2024
Extraction of the neutron
F2
structure function from inclusive proton and deuteron deep-inelastic scattering data
Authors: Li S. , Accardi A. , Cerutti M. , Fernando I. P. , Keppel C. E. , Melnitchouk W. , Monaghan P. , Niculescu G. , Niculescu M. I. , Owens J. F.
Published: April 2024

The available world deep-inelastic scattering (DIS) data on proton and deuteron structure functions F2p, F2d, and their ratios are leveraged to extract the free neutron F2n structure function, the F2n/F2p ratio, and associated uncertainties using the latest nuclear effect calculations in the deuteron. Special attention is devoted to the normalization of the proton and deuteron experimental datasets and to the treatment of correlated systematic errors, as well as the quantification of procedural and theoretical uncertainties. The extracted F2n dataset is utilized to evaluate the Q2 dependence of the Gottfried sum rule and the nonsinglet F2p−F2n moments. To facilitate replication of our study, as well as for general applications, we provide a comprehensive DIS database including all recent Jefferson Lab 6 GeV measurements, the extracted Fn2, a modified CTEQ-JLab global parton distribution function fit named CJ15nlo_mod, and grids with calculated proton, neutron, and deuteron DIS structure functions.

Published by the American Physical Society
2024
Spin-flip gluon generalized transverse-momentum-dependent parton distribution
F1,2
at small
x
Authors: Agrawal Sanskriti , Vasim Nahid , Abir Raktim
Published: April 2024

Until recently the spin-flip processes in the deep inelastic scatterings are thought to be suppressed in the high energy. We found a positive intercept for the spin-flip generalized transverse momentum-dependent parton distribution (GTMDs) Re(F1,2) as Re(F1,2)∼(1x)α¯s(4 ln2−8/3)(cos3ϕkΔ+cosϕkΔ). This is done by analytically solving the integro-differential evolution equation for Re(F1,2), recently proposed by Hatta and Zhou, in the dilute regime. Interestingly, the surviving solution corresponds to conformal spin n=2 and carries an explicit cos3ϕkΔ+cosϕkΔ azimuthal dependence. As the imaginary part of F1,2, is related to the spin-dependent odderon or gluon Siver function and scales as Im(F1,2)∼x0, the positive intercept for Re(F1,2) implies that it is expected to dominate over the gluon Siver function in the small-x limit and may directly impact the modeling of unpolarized GTMDs and associated spin-flip processes.

Published by the American Physical Society
2024
Possible
Σc*Σ¯
molecular states
Authors: Wu Bing , Dong Xiang-Kun , Guo Feng-Kun , Zou Bing-Song
Published: April 2024

We investigate the possibility of deuteronlike Σc*Σ¯ bound states within the one-boson-exchange model and systematically analyze the effects of the contact range δ3(r→) potential, the tensor term from the vector-meson exchange, and nonlocal potentials due to the dependence on the sum of the initial and final state center-of-mass momenta. We find that the pion-exchange potential including the δ3(r→) term and the tensor term of the ρ-exchange potential exhibit comparable magnitudes but opposite signs for any S-wave baryon-antibaryon systems. For the Σc*Σ¯ system, it is most likely to form bound states with mass around 3.7 GeV in the I(JP)=0(2−) and 1(2−) channels.

Published by the American Physical Society
2024
Q
-balls and charged
Q
-balls in a two-scalar field theory with generalized Henon-Heiles potential
Authors: Brihaye Y. , Buisseret F.
Published: April 2024

We construct Q-ball solutions from a model consisting of one massive scalar field ξ and one massive complex scalar field ϕ interacting via the cubic couplings g1ξϕ*ϕ+g2ξ3, typical of Henon-Heiles-like potentials. Although being formally simple, these couplings allow for Q-balls. In one spatial dimension, analytical solutions exist, either with vanishing or nonvanishing ϕ. In three spatial dimensions, we numerically build Q-ball solutions and investigate their behaviors when changing the relatives values of g1 and g2. For g1g2. We then extend the former solutions by gauging the U(1) symmetry of ϕ and show that charged Q-balls exist.

Published by the American Physical Society
2024
Cosmological implications of inflaton-mediated dark and visible matter scatterings after reheating
Authors: Ghosh Deep , Gope Sourav , Mukhopadhyay Satyanarayan
Published: April 2024

The initial density of dark matter (DM) particles, otherwise secluded from the standard model (SM), may be generated at reheating, with an initial temperature ratio for internal thermalizations, ξi=TDM,i/TSM,i. This scenario necessarily implies inflaton-mediated scatterings between DM and SM after reheating, with a rate fixed by the relic abundance of DM and the reheat temperature. These scatterings can be important for an inflaton mass and reheat temperature as high as O(107  GeV) and O(109  GeV), respectively, since the thermally averaged collision terms become approximately independent of the inflaton mass when the bath temperature is larger than the mass. The impact of these scatterings on DM cosmology is studied modeling the perturbative reheating physics by a gauge-invariant set of inflaton interactions up to dimension 5 with the SM gauge bosons, fermions, and the Higgs fields. It is observed that an initially lower (higher) DM temperature will rapidly increase (decrease), even with very small couplings to the inflaton. There is a sharp lower bound on the DM mass below which the relic abundance cannot be satisfied due to faster backscatterings depleting DM quanta to SM particles. For low DM masses, the cosmic microwave background constraints become stronger due to the collisions for ξi<1, probing values as small as O(10−4), and weaker for ξi>1. The big-bang nucleosynthesis constraints become stronger due to the collisions for lower DM masses, probing ξi as small as O(0.1), and weaker for higher DM mass. Thus inflaton-mediated collisions with predictable rates, relevant even for high-scale inflation models, can significantly impact the cosmology of light DM.

Published by the American Physical Society
2024