bluuebunny/crossref_metadata_2025 huggingface dataset:
Charting epimutation dynamics in human hematopoietic differentiation
Authors: Qin Xiaohuan , Lu Jiayi , Wu Peng , Zhang Chunyong , Shi Lei , Zhu Ping
Published: June 2024

DNA methylation plays a critical role in hematopoietic differentiation. Epimutation is a stochastic variation in DNA methylation that induces epigenetic heterogeneity. However, the effects of epimutations on normal hematopoiesis and hematopoietic diseases remain unclear. In this study, we developed a Julia package called EpiMut that enabled rapid and accurate quantification of epimutations. EpiMut was used to evaluate and provide an epimutation landscape in steady-state hematopoietic differentiation involving 13 types of blood cells ranging from hematopoietic stem/progenitor cells to mature cells. We showed that substantial genomic regions exhibited epigenetic variations rather than significant differences in DNA methylation levels between the myeloid and lymphoid lineages. Stepwise dynamics of epimutations were observed during the differentiation of each lineage. Importantly, we found that epimutation significantly enriched signals associated with lineage differentiation. Furthermore, epimutations in hematopoietic stem cells (HSCs) derived from various sources and acute myeloid leukemia were related to the function of HSCs and malignant cell disorders. Taken together, our study comprehensively documented an epimutation map and uncovered its important roles in human hematopoiesis, thereby offering insights into hematopoietic regulation.
Effect of Keloid Properties on Treatment Efficacy: A Systematic Review
Authors: Bekkers Vazula , Barsoum Paul , Yin Qi , Niessen Frank , van Zuijlen Paul , Lapid Oren , van Doorn Martijn , Wolkerstorfer Albert
Published: June 2024

BACKGROUND

The efficacy of keloid treatment in randomized studies is highly variable. However, no systematic review has been performed to evaluate the effect of different keloid properties on treatment efficacy.

OBJECTIVE

To identify clinically relevant keloid properties that may influence treatment efficacy.

MATERIALS AND METHODS

An electronic database search was conducted. Two reviewers independently selected randomized controlled trials (RCTs) and performed a methodologic quality assessment using the Cochrane risk-of-bias 2.0 tool.

RESULTS

One thousand five hundred twenty studies were screened, and 16 RCTs, involving 1,113 patients, were included. The authors found lower efficacy in older keloids (n = 3), keloids located on the chest, extremities, pinna, and shoulder (n = 3), larger keloids (n = 2), lower baseline Vancouver Scar Scale score (n = 1), and keloids with history of recurrence (n = 1). Overall, most studies had a high risk of bias.

CONCLUSION

Only a minority of studies specifically addressed keloid properties, which makes comparisons between studies challenging. The authors' results suggest that keloid location, duration prior to treatment, size, history of recurrence, and severity are clinically relevant keloid properties that affect treatment efficacy. Further studies are crucial to corroborate the authors' findings, establish a clinically relevant keloid classification, and ultimately develop an evidence-based treatment algorithm that takes these properties into account.
Association of Arterial Carbon Dioxide Tension Following In-Hospital Cardiac Arrest With Survival and Favorable Neurologic Outcome
Authors: Millet Natalie , Parnia Sam , Genchanok Yevgeniy , Parikh Puja B. , Hou Wei , Patel Jignesh K.
Published: June 2024

Background:

In-hospital cardiac arrest (IHCA) continues to be associated with high morbidity and mortality. The objective of this study was to study the association of arterial carbon dioxide tension (PaCO2) on survival to discharge and favorable neurologic outcomes in adults with IHCA.

Methods:

The study population included 353 adults who underwent resuscitation from 2011 to 2019 for IHCA at an academic tertiary care medical center with arterial blood gas testing done within 24 hours of arrest. Outcomes of interest included survival to discharge and favorable neurologic outcome, defined as Glasgow outcome score of 4–5.

Results:

Of the 353 patients studied, PaCO2 classification included: hypocapnia (PaCO2 <35 mm Hg, n = 89), normocapnia (PaCO2 35–45 mm Hg, n = 151), and hypercapnia (PaCO2 >45 mm Hg, n = 113). Hypercapnic patients were further divided into mild (45 mm Hg < PaCO2 ≤55 mm Hg, n = 62) and moderate/severe hypercapnia (PaCO2 > 55 mm Hg, n = 51). Patients with normocapnia had the highest rates of survival to hospital discharge (52.3% vs. 32.6% vs. 30.1%, P < 0.001) and favorable neurologic outcome (35.8% vs. 25.8% vs. 17.9%, P = 0.005) compared those with hypocapnia and hypercapnia respectively. In multivariable analysis, compared to normocapnia, hypocapnia [odds ratio (OR), 2.06; 95% confidence interval (CI), 1.15–3.70] and hypercapnia (OR, 2.67; 95% CI, 1.53–4.66) were both found to be independently associated with higher rates of in-hospital mortality. Compared to normocapnia, while mild hypercapnia (OR, 2.53; 95% CI, 1.29–4.97) and moderate/severe hypercapnia (OR, 2.86; 95% CI, 1.35–6.06) were both independently associated with higher in-hospital mortality compared to normocapnia, moderate/severe hypercapnia was also independently associated with lower rates of favorable neurologic outcome (OR, 0.28; 95% CI, 0.11–0.73), while mild hypercapnia was not.

Conclusions:

In this prospective registry of adults with IHCA, hypercapnia noted within 24 hours after arrest was independently associated with lower rates of survival to discharge and favorable neurologic outcome.
Characterizing Adaptive Changes and Patient Survival After 2018 Donor Allocation Restructuring: A UNOS Database Analysis
Authors: Miyamoto Takuma , Pritting Christopher David , Tatum Rob , Ahmad Danial , Brailovsky Yevgeniy , Shah Mahek K. , Rajapreyar Indranee , Rame J. Eduardo , Alvarez Rene J. , Entwistle John W. , Massey Howard Todd , Tchantchaleishvili Vakhtang
Published: June 2024

Purpose:

We sought to characterize adaptive changes to the revised United Network for Organ Sharing donor heart allocation policy and estimate long-term survival trends for heart transplant (HTx) recipients.

Methods:

Patients listed for HTx between October 17, 2013 and September 30, 2021 were identified from the United Network for Organ Sharing database, and stratified into pre- and postpolicy revision groups. Subanalyses were performed to examine trends in device utilization for extracorporeal membranous oxygenation (ECMO), durable left ventricular assist device (LVAD), intra-aortic balloon pump (IABP), microaxial support (Impella), and no mechanical circulatory support (non-MCS). Survival data post-HTx were fitted to parametric distributions and extrapolated to 5 years.

Results:

We identified 27,523 HTx waitlist candidates during the study period, most of whom (n = 16,376) were waitlisted in the prepolicy change period. Overall, 19,554 patients underwent HTx during the study period (pre: 12,037 and post: 7517). Listings increased after the policy change for ECMO (P < 0.01), Impella (P < 0.01), and IABP (P < 0.01) patients. Listings for LVAD (P < 0.01) and non-MCS (P < 0.01) patients decreased. HTx increased for ECMO (P < 0.01), Impella (P < 0.01), and IABP (P < 0.01) patients after the policy change and decreased for LVAD (P < 0.01) and non-MCS (P < 0.01) patients. Waitlist survival increased for the overall (P < 0.01), ECMO (P < 0.01), IABP (P < 0.01), and non-MCS (P < 0.01) groups. Waitlist survival did not differ for the LVAD (P = 0.8) and Impella (P = 0.1) groups. Post-transplant survival decreased for the overall (P < 0.01), LVAD (P < 0.01), and non-MCS (P < 0.01) populations.

Conclusions:

Allocation policy revisions have contributed to greater utilization of ECMO, Impella, and IABP, decreased utilization of LVADs and non-MCS, increased waitlist survival, and decreased post-HTx survival.
Determinants of Mortality in COVID-19–Associated Opportunistic Fungal Infections
Authors: Rewri Parveen , Pandey Surya Mani , Singal Rohit , Khatri Ritika , Bishnoi Mamta
Published: June 2024

Background

COVID-19–associated mucormycosis (CAM) affected over 50,000 people during the second wave of the pandemic in India. Epidemiological aspects of CAM were reported, but there is a lack of published literature on mortality and its determinants in CAM and other fungal infections. The present study investigated patterns and determinants of mortality in these patients.

Methods

The retrospective study reviewed case records of 390 patients, with at least 1 year of follow-up, for information related to demographics, epidemiology, clinical features, laboratory investigations, and treatment. The association between categorical variables was studied using the chi-square test of independence and logistic regression between 2 groups of those who survived and those who died during hospitalization or after discharge.

Results

A total of 157 (40%) patients did not survive; of these, 112 (29%) died during hospitalization and 45 (11%) had postdischarge mortality. The risk of mortality was associated with higher age, use of corticosteroids (odds ratio, 1.38; 95% confidence interval, 0.87–2.16), visual acuity <3/60 at presentation, palate involvement, and abnormal levels of white blood cells and red blood cells.

Conclusions

The demographic, clinical, laboratory, and microbiological parameters may be predictors of mortality in patients of rhino-orbital-cerebral mucormycosis.
Effectiveness and safety of a novel crosslinked hyaluronate canalicular gel occlusive device for dry eye
Authors: Packer Mark , Lindstrom Richard , Thompson Vance , Parekh Jai G. , Gupta Preeya , Nijm Lisa M. , Donnenfeld Eric
Published: June 2024

Purpose:

To evaluate the effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared with a commercially available hydrogel canalicular plug (Form Fit).

Setting:

5 sites in the United States.

Design:

Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug).

Methods:

Adults (≥22 years) with the Schirmer test (with anesthesia) ≤10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of ≥23 with ≤3 responses of “not applicable,” patent lacrimal drainage system, and bilateral corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was noninferiority of the mean within subject change from baseline to month 3 in Schirmer score for patients receiving filler compared with plugs. The key secondary effectiveness endpoint was noninferiority of the proportion of patients with filler achieving improvement from baseline to month 3 in OSDI by a minimal clinically important difference. Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear breakup time, and safety.

Results:

157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was noninferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI.

Conclusions:

Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months.
The enteroendocrine axis and its effect on gastrointestinal function, nutrition, and inflammation
Authors: Philpott Jordan D. , Rodriguez Hovnanian K. Marco , Stefater-Richards Margaret , Mehta Nilesh M. , Martinez Enid E.
Published: June 2024

Purpose of review

Gastrointestinal (GI) dysfunction limits enteral nutrition (EN) delivery in critical illness and contributes to systemic inflammation. The enteroendocrine (EE) axis plays an integral role in this interface between nutrition, inflammation, and GI function in critical illness. In this review, we present an overview of the EE system with a focus on its role in GI inflammation and function.

Recent findings

Enteroendocrine cells have been primarily described in their role in macronutrient digestion and absorption. Recent research has expanded on the diverse functions of EE cells including their ability to sense microbial peptides and metabolites and regulate immune function and inflammation. Therefore, EE cells may be both affected by and contribute to many pathophysiologic states and interventions of critical illness such as dysbiosis, inflammation, and alternative EN strategies. In this review, we present an overview of EE cells including their growing role in nonnutrient functions and integrate this understanding into relevant aspects of critical illness with a focus on EN.

The EE system is key in maintaining GI homeostasis in critical illness, and how it is impacted and contributes to outcomes in the setting of dysbiosis, inflammation and different feeding strategies in critical illness should be considered.
Education and Age in Return to Work After Ischemic Stroke
Authors: Rosendahl Eva , Carlson Nicholas , Kragholm Kristian , Butt Jawad H. , Fosbøl Emil L. , Gislason Gunnar , Torp-Pedersen Christian , Christiansen Christine Benn
Published: June 2024

Objectives:

To investigate return to work and workforce detachment in ischemic stroke, including the association with age and level of education.

Methods:

Patients in the workforce aged 18 to 60 with first-time ischemic stroke between 1997 and 2017 were identified in Danish registers and followed for 5 years. The cumulative incidence of return to work and subsequent workforce detachment was computed overall and stratified according to age group and education level. Cox regression analysis was used for multivariate analysis.

Results:

A total of 28,325 patients were included (median age 52.3 (interquartile range (IQR) 46.1 to 56.6) and 64.3% male). After 1 year, 62.0% were in the workforce, highest in age group 18 to 30 (80.0%) and lowest in patients aged 51 to 60 (58.5%). One-year cumulative incidence of return to work overall was 73.4% (20,475), highest in the young age group (87.0%, 76.7%, 74.5%, and 71.3% for age group 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high education (80.3%, 72.1%, and 71.3% for long higher, basic or vocational education, respectively). One-year cumulative incidence of subsequent workforce detachment was 25.6% (5248), lowest in young age (22.4%, 23.1%, 24.1%, and 27.2% for age groups 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high level of education (13.0%, 28.4%, and 27.2% for long higher, basic, and vocational education, respectively). During the full follow-up, 10,855 (53.0%) left the workforce again.

Conclusions:

A high proportion of patients returned to work within 1 year, but more than half left the workforce again. Young age and long education were associated with a higher incidence of return to work and lower subsequent workforce detachment.
Gene therapies for CMT neuropathies: from the bench to the clinic
Authors: Stavrou Marina , Kleopa Kleopas A.
Published: June 2024

Purpose of review

Charcot-Marie-Tooth (CMT) neuropathies are rare, genetically heterogeneous and progressive diseases for which there are no approved treatments and their management remains mostly supportive and symptomatic. This review is intended to provide an update on recent developments in gene therapies for different CMT neuropathies.

Recent findings

Increasing knowledge of disease pathomechanisms underlying several CMT types has facilitated the development of promising viral and nonviral gene therapy approaches. Some of these therapies are currently approaching the crucial step of moving from the bench to the clinic, having passed the proof-of-concept stage in rodent models and some also in larger animals. However, questions of optimal delivery route and dose, off-target effects, and possible payload toxicity remain to be clarified for several of these approaches. Furthermore, limited resources, the rarity of most CMT subtypes, and issues of safety and regulatory requirements, create the need for consensus guidelines and optimal clinical trial design.

Promising gene therapies have been developed for several CMT neuropathies, with proof-of-principle demonstrated in relevant disease models. Advantages and drawbacks of each approach are discussed and remaining challenges are highlighted. Furthermore, we suggest important parameters that should be considered in order to successfully translate them into the clinic.
Comparative analysis of virulence gene profiles of Escherichia coli from human and non-human sources in Rivers State, Nigeria

Authors: Abeni Barira Azeez , Frank-Peterside Nnenna , Otokunefor Kome
Published: June 2024

Traditionally, the presence of virulence features have been thought to be a key factor in differentiating pathogenic from commensal strains. An understanding of virulence potential of Escherichia coli isolates from various sources is essential to help shed light on potential contamination/transmission rates between the various sources. This study was therefore aimed at exploring the occurrence of specific virulence genes and gene profiles associated with Escherichia coli from human and non-human sources in Rivers State, Nigeria.
Two hundred samples from human (urine and feces) and non-human (soil and poultry droppings) sources (50 each) were analyzed using standard microbiological procedures. DNA was extracted from isolates presumptively identified as Escherichia coli using PrestoTM Mini gDNA Bacteria-Kit Quick protocol following the manufacturer’s instructions. Isolate identities were confirmed using E. coli specific 16S rRNA primers and confirmed isolates screened for the presence of six virulence genes (Afimbriae binding adhesin (afa), type 1 fimbriae (fimH), P-fimbrial Usher Protein (papC)), iron acquisition systems: aerobactin (aer), Cytotoxic necrotizing factor I (cnf1) and alpha hemolysin (hly).
Results showed that all isolates haboured at least one of the tested virulence genes, with fimH (97%) as the most prevalent virulence gene and papC the least commonly occurring (35%). A higher occurrence of virulence genes was noted in non-human isolates though hly and cnf were not detected at all in any of the isolates studied (0%). Ten different profiles were observed with the afaCc-aer-fimH profile the most commonly occurring virulence gene profile in general (33.3%). For non-human isolates however, the aer-afaCc-fimH-papC was the most commonly occurring profile (42.9%).
This study shows that the test Escherichia coli from human and non-human sources do not carry distinct virulence gene profiles. Studies on a larger subset of isolates would however be necessary to determine if indeed the virulence genes tested for in this study really cannot be used to tell whether an isolate is from a human source or not in the South-South of Nigeria.
Incorporating Microbial Pilin-Based Nanowires into a Water-Stable Electronic Polymer Composite
Authors: Sonawane Jayesh M. , Chia Eric , Ueki Toshiyuki , Greener Jesse , Nonnenmann Stephen S. , Yao Jun , Lovley Derek R.
Published: June 2024

Electrically conductive protein nanowires (e-PNs), microbially produced from a pilin monomer, are a novel, sustainable electronic material that can be genetically tailored for specific functions. e-PNs, expressed withEscherichia coligrown on the biodiesel byproduct glycerol, and mixed with polyvinyl butyral yielded a transparent, electrically conductive water-stable composite.Composite conductivity was adjusted by modifying the e-PN concentration or incorporating e-PNs genetically tuned for different conductivities. Electronic devices in which composites were the sensor component differentially responded to dissolved ammonia over a wide concentration range (1µM-1M). Genetically modifying e-PNs to display an ammonia-binding peptide on their outer surface increased the sensor response to ammonia 10-fold. These results, coupled with the flexibility to design peptides for specific binding of diverse analytes, demonstrate that sustainably produced e-PNs offer the possibility of incorporating multiple sensor components, each specifically designed to detect different analytes with high sensitivity and selectivity, within one small sensor device.
15-Lipoxygenase-Mediated Lipid Peroxidation Regulates LRRK2 Kinase Activity
Authors: Keeney Matthew T. , Hoffman Eric K. , Weir Julie , Wagner Weston G. , Rocha Emily M. , Castro Sandra , Farmer Kyle , Fazzari Marco , Di Maio Roberto , Konradi Andrei , Hastings Teresa G. , Pintchovski Sean A. , Shrader William D. , Greenamyre J. Timothy
Published: June 2024

Mutations inleucine-rich repeat kinase 2 (LRRK2)that increase its kinase activity are strongly linked to genetic forms of Parkinson’s disease (PD). However, the regulation of endogenous wild-type (WT) LRRK2 kinase activity remains poorly understood, despite its frequent elevation in idiopathic PD (iPD) patients. Various stressors such as mitochondrial dysfunction, lysosomal dyshomeostasis, or vesicle trafficking deficits can activate WT LRRK2 kinase, but the specific molecular mechanisms are not fully understood. We found that the production of 4-hydroxynonenal (4-HNE), a lipid hydroperoxidation end-product, is a common biochemical response to these diverse stimuli. 4-HNE forms post-translational adducts with Cys2024 and Cys2025 in the kinase activation loop of WT LRRK2, significantly increasing its kinase activity. Additionally, we discovered that the 4-HNE responsible for regulating LRRK2 is generated by the action of 15-lipoxygenase (15-LO), making 15-LO an upstream regulator of the pathogenic hyperactivation of LRRK2 kinase activity. Pharmacological inhibition or genetic ablation of 15-LO prevents 4-HNE post-translational modification of LRRK2 kinase and its subsequent pathogenic hyperactivation. Therefore, 15-LO inhibitors, or methods to lower 4-HNE levels, or the targeting of Cys2024/2025 could provide new therapeutic strategies to modulate LRRK2 kinase activity and treat PD.
Consistency of affective responses to naturalistic stimuli across individuals using intersubject correlation analysis based on neuroimaging data
Authors: Jang Junhyeok , Kim Jongwan
Published: June 2024

In this study, we used functional magnetic resonance imaging (fMRI) data obtained for naturalistic emotional stimuli to examine the consistency of neural responses among participants in specific regions related to valence. We reanalyzed fMRI data from 17 participants as they watched episodes of “Sherlock” and used emotional ratings from 125 participants. To determine regions where neural response patterns were synchronized across participants based on the pattern of valence changes, intersubject correlation analysis was conducted. As a validation analysis, multidimensional scaling was conducted to investigate emotional representation for significant regions of interest. The results revealed that the ventromedial prefrontal cortex, bilateral superior frontal cortices, left posterior cingulate cortex, thalamus, right anterior cingulate cortex, and bilateral inferior frontal cortices showed increased neural synchrony as positive scenes were presented. Also, the bilateral superior temporal gyrus and bilateral medial temporal gyrus exhibited increased neural synchrony as negative scenes were presented. Moreover, the left inferior frontal cortex and right superior frontal gyrus were found to be engaged in emotion representation and display increased neural synchrony. These findings provide insights into the differential neural responses to emotionally evocative naturalistic stimuli as compared to conventional experimental stimuli. Also, this study highlights the future potential for using intersubject correlation analysis for examining consistency of neural responses to naturalistic stimuli.
Benchmarking of a multi-biomarker low-volume panel for Alzheimer’s Disease and related dementia research
Authors: Ibanez Laura , Liu Menghan , Beric Aleksandra , Timsina Jigyasha , Kholfeld Pat , Bergmann Kristy , Lowery Joey , Sykora Nick , Sanchez-Montejo Brenda , Brock Will , Budde John P. , Bateman Randall J. , Barthelemy Nicolas , Schindler Suzanne E. , Holtzman David M , Benzinger Tammie L. S. , Xiong Chengjie , Tarawneh Rawan , Moulder Krista , Morris John C. , Sung Yun Ju , Cruchaga Carlos
Published: June 2024

Alzheimer’s Disease (AD) biomarker measurement is key to aid in the diagnosis and prognosis of the disease. In the research setting, participant recruitment and retention and optimization of sample use, is one of the main challenges that observational studies face. Thus, obtaining accurate established biomarker measurements for stratification and maximizing use of the precious samples is key. Accurate technologies are currently available for established biomarkers, mainly immunoassays and immunoprecipitation liquid chromatography-mass spectrometry (IP-MS), and some of them are already being used in clinical settings. Although some immunoassays- and IP-MS based platforms provide multiplexing for several different coding proteins there is not a current platform that can measure all the stablished and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) is a mid-throughput platform with antibody-based measurements with a sequencing output that requires 15µL of sample volume to measure more than 100 analytes, including those typically assayed for AD. Here we benchmarked and compared the AD-relevant biomarkers including in the NULISA against validated assays, in both CSF and plasma. Overall, we have found that CSF measures of Aß42/40, NfL, GFAP, and p-tau217 are highly correlated and have similar predictive performance when measured by immunoassay, mass-spectrometry or NULISA. In plasma, p-tau217 shows a performance similar to that reported with other technologies when predicting amyloidosis. Other established and exploratory biomarkers (total tau, p-tau181, NRGN, YKL40, sTREM2, VILIP1 among other) show a wide range of correlation values depending on the fluid and the platform. Our results indicate that the multiplexed immunoassay platform produces reliable results for established biomarkers in CSF that are useful in research settings, with the advantage of measuring additional novel biomarkers using minimal sample volume.
Ultra-processed foods and hypertension incidence in RaNCD cohort project
Authors: Amirian Parsa , Zarpoosh Mahsa , Pasdar Yahya
Published: June 2024

Background

Due to rapid population growth and, subsequently, large-scale food production methods, ultra-processed food consumption is in parabolic growth. By affecting 1.28 billion adults globally, hypertension is a major risk factor and cause of premature death. In order to find the relation between ultra-processed food consumption and other covariates with hypertension incidence, this study was conducted in the western part of Iran using RaNCD prospective cohort data.

Methods

We included 8150 participants at the risk of hypertension in the final analysis. Using the data obtained from the Iranian food frequency questionnaire and the NOVA food classification, we assessed the ultra-processed food consumption of each participant in a day. Logistic regression models and the Cox proportional hazards regression model were used to assess the association between ultra-processed food consumption and hypertension in the main model and sensitivity analysis.

Results

The mean age of participants was 46.25y ± 7.94 (47.58% males); the mean follow-up time was 7.65y ± 1.62, and the mean daily UPF intake in g/d among participants was 88.07 ± 84.96. During the follow-up period, 862 cases of hypertension were recorded. We adjusted the main model for several confounders, including age, gender, residence type, marital status, socioeconomic status, physical activity, body mass index, familial history of hypertension, fasting blood sugar, and waist-to-hip ratio. The odds ratio and 95% confidence interval (95% CI) of the second and third tertile of UPFs were 1.15 (95% CI, 0.96-1.37) and 1.03 (95%CI, 0.85-1.24), respectively, compared to the first tertile with insignificant p-value & p-trend.

Conclusion

To the best of our knowledge, our study is the first to assess the association between hypertension and ultra-processed foods in the Middle East region. Significant associations between hypertension incidence and some confounders were also identified.
Metabolism-Disrupting Chemical Mixtures during Pregnancy, Folic Acid Supplementation, and Liver Injury in Mother-Child Pairs
Authors: India-Aldana Sandra , Midya Vishal , Betanzos-Robledo Larissa , Yao Meizhen , Alcalá Cecilia , Andra Syam S. , Arora Manish , Calafat Antonia M. , Chu Jaime , Deierlein Andrea , Estrada-Gutierrez Guadalupe , Jagani Ravikumar , Just Allan C. , Kloog Itai , Landero Julio , Oulhote Youssef , Walker Ryan W. , Yelamanchili Shirisha , Baccarelli Andrea A. , Wright Robert O. , Téllez Rojo Martha María , Colicino Elena , Cantoral Alejandra , Valvi Damaskini
Published: June 2024

Background and Aims

Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs.

Methods

We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation.

Results

In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations (p-interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day (p-interactions<0.05).

Conclusions

Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.
Female Brain and Endocrinological Research – Veteran (FemBER-Vet) Study: A study protocol for identifying endocrinological, lifestyle and psychosocial determinants of brain health outcomes in female veterans for future intervention success
Authors: Watermeyer Tamlyn , Atkinson Elliott , Howatson Glyn , McGill Gill , Dodds Christina , Ansdell Paul , Udeh-Momoh Chinedu
Published: June 2024

Background

Recent studies have demonstrated a greater risk of dementia in female veterans compared to civilians; with the highest prevalence noted for former service women with a diagnosis of psychiatric (trauma, alcoholism, depression), and/or a physical health condition (brain injury, insomnia, diabetes). Such findings highlight the need for increased and early screening of medical and psychiatric conditions, and indeed dementia, in the female veteran population. Further, they call for a better understanding of the underlying biopsychosocial mechanisms that might confer heightened risk for female veterans, to tailor preventative and interventional strategies that support brain health across the lifespan.

Methods

The Female Brain and Endocrinological Research – Veteran (FemBER-Vet) Study will create a highly-phenotyped readiness cohort of ex-service persons as well as non-veterans to assess the impacts of, and risks associated with, military service on brain health, using state-of-the-art non-invasive cognitive, physiological and biomarker capture techniques. FEMBER-Vet will include 90 participants across three study groups (30 female veterans, 30 male veterans, 30 female civilians) to delineate the precise biological, socio-demographic, health, lifestyle, military-related, and life-course determinants of brain health outcomes (psychosocial, cognitive, neurophysiological, and other biomarkers).

Discussion

This work addresses the poorly understood biopsychosocial outcomes that female veterans experience compared to their male counterparts and the general female population. Ultimately, it will provide evidence to support the development of tailored interventions for an emerging health priority that currently lacks sufficient evidence for screening and therapeutic intervention.
Tripartite organization of brain state dynamics underlying spoken narrative comprehension
Authors: Liu Lanfang , Jiang Jiahao , Li Hehui , Ding Guosheng
Published: June 2024

Speech comprehension involves the dynamic interplay of multiple cognitive processes, from basic sound perception, to linguistic encoding, and finally to complex semantic-conceptual interpretations. How the brain handles the diverse streams of information processing remains poorly understood. Applying Hidden Markov Modeling to fMRI data obtained during spoken narrative comprehension, we reveal that the whole brain networks predominantly oscillate within a tripartite latent state space. These states are respectively characterized by high activities in the sensory-motor (State #1), bilateral temporal (State #2), and DMN (State #3) regions, with State #2 acting as a transitional hub. The three states are selectively modulated by the acoustic, word-level semantic and clause-level semantic properties of the narrative. Moreover, the alignment with the best performer in brain state expression can predict participants’ narrative comprehension scores. These results are reproducible with different brain network atlas and generalizable to two datasets consisting of young and older adults. Our study suggests that the brain underlies narrative comprehension by switching through a tripartite state space, with each state probably dedicated to a specific component of language faculty, and effective narrative comprehension relies on engaging those states in a timely manner.
Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease
Authors: Malla Sulochan , Bryant Annie G. , Jayakumar Rojashree , Woost Benjamin , Wolf Nina , Li Andrew , Das Sudeshna , van Veluw Susanne J. , Bennett Rachel E.
Published: June 2024

White matter hyperintensities (WMHs) are commonly detected on T2-weighted magnetic resonance imaging (MRI) scans, occurring in both typical aging and Alzheimer’s disease. Despite their frequent appearance and their association with cognitive decline, the molecular factors contributing to WMHs remain unclear. In this study, we investigated the transcriptomic profiles of two commonly affected brain regions with coincident AD pathology—frontal subcortical white matter (frontal-WM) and occipital subcortical white matter (occipital-WM)—and compared with age-matched healthy controls. Through RNA-sequencing in frontal- and occipital-WM bulk tissues, we identified an upregulation of genes associated with brain vasculature function in AD white matter. To further elucidate vasculature-specific transcriptomic features, we performed RNA-seq analysis on blood vessels isolated from these white matter regions, which revealed an upregulation of genes related to protein folding pathways. Finally, comparing gene expression profiles between AD individuals with high-versus low-WMH burden showed an increased expression of pathways associated with immune function. Taken together, our study characterizes the diverse molecular profiles of white matter changes in AD compared to normal aging and provides new mechanistic insights processes underlying AD-related WMHs.
Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience
Authors: Nicholas Christopher R. , Banks Matthew I. , Lennertz Richard L. , Wenthur Cody J. , Krause Bryan M. , Riedner Brady A. , Smith Richard F. , Hutson Paul R. , Sauder Christina J. , Dunne John D. , Roseman Leor , Raison Charles L.
Published: June 2024

Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.
A NEW POSTURAL MOTOR RESPONSE TO SPINAL CORD STIMULATION: POST-STIMULATION REBOUND EXTENSION
Authors: Mahrous Amr A. , Chardon Matthieu , Johnson Michael , Miller Jack , Heckman CJ
Published: June 2024

Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.
Revisiting signatures of thermal axions in nonstandard cosmologies
Authors: Arias Paola , Bernal Nicolás , Osiński Jacek K. , Roszkowski Leszek , Venegas Moira
Published: June 2024

We revisit the formation of a thermal population of hadronic axions in nonstandard cosmologies, in light of the recent developments in obtaining continuous and smooth interaction rates for both the gluon and photon couplings. For certain cosmological histories, such as low-temperature reheating (LTR) and kinationlike scenarios, the thermalization of the axion can be severely delayed to higher masses. In the case that thermal equilibrium is achieved, we improve the constraints on LTR for axion masses around the eV scale with respect to previous works and we constrain for the first time early matter-dominated cosmologies. We also point out the possibility of having the coexistence of cold and warm dark matter populations of axions in kinationlike scenarios in the eV mass range.

Published by the American Physical Society
2024
Variational Adiabatic Transport of Tensor Networks
Authors: Kim Hyeongjin , Fishman Matthew , Sels Dries
Published: June 2024

We discuss a tensor network method for constructing the adiabatic gauge potential—the generator of adiabatic transformations—as a matrix product operator, which allows us to adiabatically transport matrix product states. Adiabatic evolution of tensor networks offers a wide range of applications, of which two are explored in this paper: improving tensor network optimization and scanning phase diagrams. By efficiently transporting eigenstates to quantum criticality and performing intermediary density-matrix renormalization group (DMRG) optimizations along the way, we demonstrate that we can compute ground and low-lying excited states faster and more reliably than a standard DMRG method at or near quantum criticality. We demonstrate a simple automated step size adjustment and detection of the critical point based on the norm of the adiabatic gauge potential. Remarkably, we are able to reliably transport states through the critical point of the models we study.

Published by the American Physical Society
2024
Robust fault-tolerant preview control for automatic landing of carrier-based aircraft
Authors: Xiao Huiyunuo , Zhen Ziyang , Zhang Zhibing , Zheng Fengying
Published: June 2024

Purpose

This paper aims to propose the automatic carrier landing system with the fault-tolerant ability for carrier-based aircraft in the presence of deck motion, external airwake disturbance and actuator fault, which consists of the reference trajectory generation module and flight control module.

Design/methodology/approach

The longitudinal and lateral basic controllers are designed based on the optimal preview control (OPC), which can ensure favorable tracking performance and anti-disturbance ability of system. Furthermore, based on the OPC, the robust fault-tolerant preview control scheme is proposed to attenuate the impact of actuator fault on system, which ensures the safe landing of carrier-based aircraft in case of actuator failure.

Findings

Both the Lyapunov method and simulations prove that the tracking errors can converge to zero and system states can be asymptotically stable both in normal and fault operations.

Originality/value

The fault-tolerant control strategy is introduced into preview control to deal with actuator fault, which combines feedforward control based on future previewable information and feedback control based on current information to improve the system performance.
Gabapentin treatment for challenging behaviors in autism spectrum disorder and coexisting intellectual disability: a case report
Authors: Marini Stefano , D'Agostino Lucia , Ciamarra Carla , De Berardis Domenico , Gentile Alessandro
Published: June 2024

Purpose

The purpose of this case report is to report the clinical experience of the use of gabapentin in the management of problem behaviors in a person with autism spectrum disorder and comorbid intellectual disability. Autism spectrum disorder is a neurodevelopmental disorder with a high prevalence of intellectual disability. Challenging behaviors in autism spectrum disorder are very common. In recent years, the hypothesis that the symptoms of autism derive from a deficiency of the inhibitory neurotransmission of gamma-aminobutyric acid is gaining considerable weight.

Design/methodology/approach

Exploring behavioral symptoms improvement in an adult man with ASD and severe intellectual disability taking gabapentin.

Findings

The rating scales used show improvement in challenging behaviors and aggressions. No side effects were observed.

Originality/value

Currently, there are no authorized drugs for the treatment of the symptomatic features of autism spectrum disorder, but drugs are used for comorbid psychopathological aspects. The authors want to speculate on a hypothetical function of gabapentin in remodeling the expression of alpha-2-delta subunits in people with autism and the processing of neural information.
Industry 4.0 and sustainability: the case of the Italian textile district of Prato
Authors: Ferlito Rosaria
Published: June 2024

Purpose

The purpose of this paper is to analyze the twin transition of textile firms operating in an industrial district. The twin transition comprises two interconnected but distinct processes: the sustainable transition and the digital transition. The study specifically considers sustainability goals in terms of the triple bottom line and digitalization as the adoption of Industry 4.0 (I4.0) technologies. The study aims to understand how the characteristics of Italian districts influence the choices related to the twin transition and how it affects textile industrial firms.

Design/methodology/approach

The author conducts a multiple-case study involving five firms of industrial textile district of Prato.

Findings

The results show the relationship between the characteristics of the district, such as fragmentation of the supply chain, lean manufacturing, territorial proximity and attachment to origins and traditions and the sustainable goals and I4.0 technologies adoption. Moreover, the study proposes a framework for twin transition. Market and technology drive the process in which sustainability represents the aim, I4.0 serves as enablers and the relevant outcome is the implementation of the business model innovation.

Practical implications

These findings offer valuable insights for textile firms, policymakers and stakeholders seeking to navigate the complexities of twin transition.

Originality/value

The study contributes to the broader topic of twin transition. In particular, it links the particular context represented by the industrial district in which the textile firms operate to their conduct, and the two interconnected and distinct processes, sustainable transition and digital transition, with the business model innovation topic.
Emerging from COVID-19: the perceptions of university students to part-time working and its impact on their transferable skill development
Authors: Evans Carl , Lean Jonathan , Sen Ali , Yusof Zatun Najahah
Published: June 2024

Purpose

The purpose of this study is to examine university students’ behaviours and perceptions relating to part-time working, particularly the impact of external factors such as COVID-19, on their work activity.

Design/methodology/approach

A structured, online questionnaire was issued to Business Management students at a UK university. A total of 123 responses were received.

Findings

The study offers a unique insight into the effects of Covid-19 on students’ perceptions regarding part-time work.

Research limitations/implications

It is important for universities to understand the motivations of students and their current circumstances, since these could affect students’ academic performance and wellbeing and well as their employability, and as a consequence, influence university policy.

Originality/value

The study offers a unique insight into the effects of prevailing external factors in particular Covid-19 on students’ perceptions regarding part-time work.