bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking Yi’an (Medical Cases) as a Tool for Narrative Medicine in China
Authors: GUI Ting
Published: April 2023

When narrative medicine (NM) was introduced into China, traditional Chinese medicine scholars found that the core concepts advocated by NM are manifested in Chinese yi’an. But why NM echoes with ancient Chinese yi’an? How can we better integrate NM into Chinese medical practices? To answer those questions, this article first investigates how NM establishes itself as a remedy to biomedicine by taking traditional healing models including TCM as its ideal Other. Then, the narrative traditions of both case histories and yi’an are examined respectively. This article argues that NM is searching for a lost tradition of narrative case histories, but yi’an functions as a living tradition of TCM. The Parallel Chart in NM, designed as a complement to the dehumanized hospital chart, is still based on a dichotomy of science and art and a conflictual doctor-patient model. But yi’an exemplifies the holistic and humane healthcare that NM hopes to achieve. A comparison of both genres also inspired us to rethink the genre of yi’an in NM. Thus, it is concluded that yi’an should be viewed as an epistemic genre integrating individualization and generalization, a bridge linking medicine and literature. And narrative yi’an can well serve as a tool for NM in China. It is also proposed that a thick description of yi’an be encouraged to further promote a pluralistic NM in China.
How to recognize and treat rumination syndrome
Authors: Sawada Akinari , Sifrim Daniel
Published: April 2023

Purpose of review

Rumination syndrome (RS) is a functional gastroduodenal disorder characterized by repeated effortless regurgitation or vomiting of recently ingested food without retching. RS generally has been considered a rare entity. However, it has been increasingly recognized that many RS patients are likely to be underdiagnosed. This review discusses how to recognize and manage RS patients in clinical practice.

Recent findings

A recent epidemiological study that included over 50,000 individuals found that the prevalence of RS around the world is 3.1%. In patients with proton pump inhibitor (PPI)-refractory reflux symptoms, postprandial high-resolution manometry combined with impedance (HRM/Z) reveals that RS accounts for up to 20% of those cases. HRM/Z can be a gold standard for objective RS diagnosis. In addition, off-PPI 24-h impedance pH monitoring can suggest the possibility of RS when it reveals frequent postprandial, non-acid reflux with a high symptom index. Modulated cognitive behavioral therapy (CBT) targeting secondary psychological maintaining mechanisms almost eliminates regurgitation.

The prevalence of RS is higher than generally thought. For patients suspected of RS, HRM/Z is useful to distinguish RS from gastroesophageal reflux disease. CBT can be a highly effective therapeutic option.
Transgender and gender-diverse youth: an update on standard medical treatments for gender dysphoria and the sociopolitical climate
Authors: Arnold Jacob C. , McNamara Meredithe
Published: April 2023

Purpose of review

Transgender and gender-diverse (TGD) youth experience a discordance between their binary sex assigned at birth and gender identity. All TGD youth benefit from compassionate care delivered by clinicians who are informed in matters of gender diversity. Some of TGD youth experience clinically significant distress, termed gender dysphoria (GD), and may benefit from additional psychological support and medical treatments. Discrimination and stigma fuel minority stress in TGD youth and thus many struggle with mental health and psychosocial functioning. This review summarizes the current state of research on TGD youth and essential medical treatments for gender dysphoria. These concepts are highly relevant in the current sociopolitical climate. Pediatric providers of all disciplines are stakeholders in the care of TGD youth and should be aware of updates in this field.

Recent findings

Children who express gender-diverse identities continue to express these identities into adolescence. Medical treatments for GD have a positive effect on mental health, suicidality, psychosocial functioning, and body satisfaction. The overwhelming majority of TGD youth with gender dysphoria who receive medical aspects of gender affirming care continue these treatments into early adulthood. Political targeting and legal interference into social inclusion for TGD youth and medical treatments for GD are rooted in scientific misinformation and have negative impacts on their well being.

All youth-serving health professionals are likely to care for TGD youth. To provide optimal care, these professionals should remain apprised of best practices and understand basic principles of medical treatments for GD.
Chronic Mucosal Inflammation in Pediatric Intestinal Failure Patients—A Unique Phenomenon
Authors: Moran-Lev Hadar , Kocoshis Samuel A. , Oliveira Stephanie B. , Helmrath Michael , Cole Conrad R.
Published: April 2023

Introduction/Objectives:

As intestinal failure (IF) management improves and long-term survival rate increases, its physiological complications have become more apparent. The development of chronic intestinal inflammation resembling inflammatory bowel disease (IBD) in this population has been reported, but the literature describing it in detail is sparse. The present study was designed to characterize children with IF who developed chronic intestinal inflammation and identify the potential predisposing clinical factors.

Methods:

This retrospective study was based on the electronic medical records of pediatric patients seen at the Cincinnati Children’s Hospital Medical Center between January 2000 and July 2022. Demographic and medical history data were collected and compared between children with IF that developed chronic intestinal inflammation and children with IF that did not develop chronic intestinal inflammation.

Results:

During the follow-up period, 23 children were diagnosed with chronic intestinal inflammation. Of these, 12 (52%) were males, with a median age of 4.5 (3–7) years at diagnosis. Nearly one-third of the patients had gastroschisis (31%), followed by necrotizing enterocolitis (26%), and malrotation and volvulus (21.7%). More children in the chronic intestinal inflammation group lacked an ileocecal valve (ICV) and adjoining distal ileum as compared to the short bowel syndrome (SBS)-IF control group (15 patients, 65% vs 8 patients, 33%). Moreover, more children in the chronic intestinal inflammation group had undergone a prior lengthening procedure than the SBS-IF control group (5 patients, 21.7% vs. 0, respectively).

Discussion:

SBS patients are at risk of relatively early onset chronic intestinal inflammation. The absence of an ICV (and adjoin ileum) and prior lengthening procedures emerge as factors associated with the risk of IBD in these patients.
Accurate anatomic repair of obstetric anal sphincter damage or rectovaginal fistula aided by prior ultrasonograghy: a cohort study
Authors: Mokoena Taole , Abdool Zeelha
Published: April 2023

Background:

Anorectal obstetric injuries resulting in anal sphincter damage (ASD) and rectovaginal fistula (RVF) remain a major problem. The resulting flatus or faecal incontinence is devastating. Surgical repair remains a challenge. Postpartum RVF primarily results from ischaemic pressure necrosis following obstructed labour. The fistula tract is surrounded by a fibrous scar. ASD usually results from precipitous labour. The injury heals by fibrous scar leading to varying degrees of anal incontinence. Contraction and retraction of muscles around the injury renders the defect and fibrous scar larger than the primary injury. Anorectal ultrasonography has been used to define RVF and ASD, and the associated fibrous scar.

Patients and methods:

A retrospective review of patients who underwent transvaginal surgical repair of RVF and ASD was undertaken. Patients were preoperatively assessed for pathology and incontinence degree. Anorectal ultrasonography was used to define ASD or RVF and the associated scar preoperatively. Repair of RVF or ASD entails total excision of the scar with accurate anatomical layers reconstruction of healthy tissues.

Results:

There were 23 patients, 8 RVF with a mean (SD) age 29 (6.78) years and 17 ASD with a mean (SD) age 35.25 (15.90). Twenty followed obstetric trauma (6RVF, 14 ASD), 1 prior rectocoele repair (ASD), 2 rape (1RVF + 1 ASD) and 1 was idiopathic (RVF). All patients had 1 or more prior repairs except for idiopathic RVF. Operative technique entailed transvaginal complete excision of the fibrous scar and accurate anatomical reconstruction of healthy tissue layers. A colostomy was not routinely used. There were three significant postoperative complications: ASD breakdown from an infected haematoma; perianal abscess, later a sinus after drainage; and RVF repair dehiscence during early coitus. All patients had full continence after 8 months minimum follow-up.

Conclusion:

Complete excision of the fibrous scar and accurate anatomical tissue layers reconstruction of the obstetric RVF or ASD, aided by prior ultrasonography, yielded good results.
Myopia Control Dose Delivered to Treated Eyes by a Dual Focus Myopia Control Contact Lens
Authors: Ramasubramanian Viswanathan , Logan Nicola S. , Jones Susie , Meyer Dawn , Jaskulski Matt , Rickert Martin , Chamberlain Paul , Arumugam Baskar , Bradley Arthur , Kollbaum Pete S.
Published: April 2023

Significance

Consistent with closed loop models of regulated eye growth, a successful dual-focus (DF) myopia control contact lens focused a significant proportion of light anterior to the central retina in eyes of treated children viewing near and distant targets.

Purpose

This study examined the optical impact of a DF contact lens during near viewing in a sample of habitual DF lens wearing children.

Methods

Seventeen myopic children aged 14 to 18 years who had completed 3 or 6 years of treatment with a DF contact lens (MiSight 1 day, CooperVision, Inc.) were recruited and fit bilaterally with the DF and a single vision (SV, Proclear 1 day, CooperVision, Inc.) contact lens. Right eye wavefronts were measured using a pyramidal aberrometer (Osiris, CSO) while children accommodated binocularly to high contrast letter stimuli at 5 target vergences. Wavefront error data were used to compute pupil maps of refractive state.

Results

During near viewing, children wearing SV lenses accommodated on average to achieve approximate focus in the pupil center but due to combined accommodative lag and negative spherical aberration experienced up to 2.00 D of hyperopic defocus in the pupil margins. With DF lenses, children accommodated similarly achieving approximate focus in the pupil center. When viewing three near distances (0.48, 0.31 and 0.23 m), the added +2.00 D within the DF lens treatment optics shifted the mean defocus from +0.75 D to -1.00 D. The DF lens reduced the % of hyperopic defocus (≥ +0.75 D) in the retinal image from 52% to 25% over these target distances, leading to an increase in myopic defocus (≤ -0.50 D) from 17% to 42%.

Conclusions

The DF contact lens did not alter the accommodative behavior of children. The treatment optics introduced myopic defocus and decreased the amount of hyperopically defocused light in the retinal image.
Operationalizing Appropriate Sepsis Definitions in Children Worldwide: Considerations for the Pediatric Sepsis Definition Taskforce
Authors: Carrol Enitan D. , Ranjit Suchitra , Menon Kusum , Bennett Tellen D. , Sanchez-Pinto L. Nelson , Zimmerman Jerry J. , Souza Daniela C. , Sorce Lauren R. , Randolph Adrienne G. , Ishimine Paul , Flauzino de Oliveira Claudio , Lodha Rakesh , Harmon Lori , Watson R. Scott , Schlapbach Luregn J. , Kissoon Niranjan , Argent Andrew C. ,   on behalf of the Society of Critical Care Medicine’s Pediatric Sepsis Definition Taskforce
Published: April 2023

Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a “Think globally, act locally” approach is required.
Evaluation of Health Promotion Program at the Community Level in Mexico: Is the Program Efficient and Effective?
Authors: Alcalde-Rabanal Jacqueline E. , Flores-Loera Yuliana , Chivardi Carlos , Ruelas-González Ma. Guadalupe , Macías Nayeli , González-Robledo María Cecilia
Published: April 2023

Context:

Health promotion programs have been encouraged in the Americas since 1990. In Mexico, health program promotion at the community level was implemented by the Ministry of Health in 2001 to encourage community health status improvement. Despite the longtime of its implementation, evaluations of its efficiency and effectiveness are scarce.

Objective:

To evaluate the efficiency of the Healthy Environments and Communities Program (HECP) through 2 means: (1) efficiency of the implementation and (2) technical efficiency, as well as to evaluate its effectiveness.

Setting:

Target communities of the HECP of 32 Mexican states during 2013-2017. The HECP developed community interventions to improve community organization, health behaviors, and family and communitarian sanitation.

Methodology:

We conducted a cross-sectional study to evaluate the efficiency of HECP implementation and estimated the inclusion of target communities (focalization index), the retention of communities (continuity index), and the desertion of communities in the program (desertion index). To evaluate the adequate use of the program resources (technical efficiency), we used data-enveloped analysis and the Tobit regression model to identify external factors that can influence results. Finally, to evaluate the program's effectiveness, we estimated the index of the communities that improved their health indicators and were certified as healthy (community certification).

Results:

The median rate of focalization was 3.44 (1.31-85.13); the continuity of communities' rate was 0.50 (0.16-2.67). Regarding technical efficiency to reach healthy communities, only 2 states reached the optimal efficiency (score 1); where the efficiency was adjusted for external factors, 6 states reached a score of 1. The median of global effectiveness was 0.19 (0.01-0.78). We found differences in efficiency and effectiveness scores among states.

Conclusion:

We found lower efficiency of the implementation and technical efficiency, as well as poor effectiveness of the program to reach healthy communities. To achieve HECP purpose, it is necessary to revise its guidelines, improve its strategies to work in communities, and establish the right mechanisms to monitor its implementation. It is essential to focus on the resources used to enhance technical efficiency and effectiveness at the community level.
Child Maltreatment: A Comparison of Wisconsin Children Identified in Health Care and Child Protective Services (CPS) Records, 2018-2019
Authors: Imm Pamela , Pac Jessica
Published: April 2023

Context:

Child Protective Services (CPS) reports and health records (hospital inpatient and emergency department visits) are the primary data sources to measure child maltreatment; yet, they are not linked at the state or national level. Linking provides novel insight into the demographic characteristics of the populations served by one or both agencies, thus informing opportunities for prevention and intervention.

Objective:

This study compares children identified as maltreated in health records (based on International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes indicating suspected or confirmed child maltreatment) and/or CPS reports.

Design:

Three mutually exclusive comparison groups were created: group 1- children with a nonfatal hospitalization and/or emergency department visit with a maltreatment ICD-10-CM code and an investigated CPS report; group 2- children with a maltreatment ICD-10-CM code in a health record without an investigated CPS report; and group 3- children with an investigated CPS report without a health record with a maltreatment ICD-10-CM code. Descriptive statistics and tests for statistically significant differences were conducted.

Setting and Participants:

Wisconsin children with maltreatment ICD-10-CM code in health record and/or CPS-investigated report from 2018 to 2019.

Main Outcome Measure:

Demographic and maltreatment type differences between groups.

Results:

Group 1 children were significantly younger than those in other groups (P <. 001), and group 2 children were significantly more female (69.6%; P < .001). Black children were overrepresented in all groups and most disproportionate among group 1 (39.5%; P < .001). Maltreatment type also differed significantly across groups.

Conclusions:

CPS staff and health providers encounter overlapping and nonoverlapping populations of children experiencing different types of maltreatment. Although interventions may be tailored toward the type of maltreatment and other relevant child characteristics, all populations could benefit from referrals and access to supportive social services. Agency contact provides an opportunity to intervene and support at-risk children and families.
Trauma history predicts decoupling of C-reactive protein and somatic symptoms: Results from a cohort study of sexual and gender minority youth
Authors: Schrock Joshua M. , Nusslock Robin , McDade Thomas W. , Mustanski Brian
Published: April 2023

Objective

Systemic inflammation can induce somatic symptoms (e.g., pain, nausea, fatigue) through neuroimmune signaling pathways. Previous research suggests that early-life adversity amplifies signaling between peripheral inflammation and the brain. We therefore hypothesized that greater lifetime trauma exposure at baseline would predict stronger associations between systemic inflammation and somatic symptoms at 2.5-year follow-up in a cohort study of sexual and gender minority youth assigned male at birth (SGM-AMAB youth, n = 694).

Methods

We measured prior trauma exposure (lifetime count of traumatic event types reported at baseline), somatic symptoms (Brief Symptom Inventory somatization score), and systemic inflammation (C-reactive protein, interleukin-6, interleukin-1β, and tumor necrosis factor-α). All models included age, gender, education, recent trauma exposure, substance use, BMI, and HIV status as covariates.

Results

Higher C-reactive protein concentrations were associated with greater somatic symptoms in the main effects model (β = 0.019, 95% CI: 0.006, 0.031). Contrary to our hypothesis, we observed a negative interaction between prior trauma exposure and C-reactive protein levels in predicting somatic symptoms (β = -0.017, 95% CI: -0.030, -0.004). Higher C-reactive protein was associated with greater somatic symptoms only in participants without prior trauma exposure at baseline (β = 0.044, 95% CI: 0.026, 0.062). Specificity analyses revealed similar patterns when non-somatic depressive symptoms were used as the outcome variable.

Conclusions

These results suggest that SGM-AMAB youth who have a history of prior trauma exposure may experience decoupling of systemic inflammation and somatic symptoms. The absence of inflammation-related symptoms may prevent individuals from seeking necessary medical care by reducing interoceptive awareness of pathological states.
The circuit basis for chronic pain and its comorbidities
Authors: Patel Ryan
Published: April 2023

Purpose of review

Chronic pain is poorly treated with many developing disabling comorbidities such as anxiety, depression and insomnia. Considerable evidence supports the idea that pain and anxiodepressive disorders share a common neurobiology and can mutually reinforce, which has significant long-term implications as the development of comorbidities leads to poorer treatment outcomes for both pain and mood disorders. This article will review recent advances in the understanding of the circuit basis for comorbidities in chronic pain.

Recent findings

A growing number of studies have aimed to determine the mechanisms underlying chronic pain and comorbid mood disorders by using modern viral tracing tools for precise circuit manipulation with optogenetics and chemogenetics. These have revealed critical ascending and descending circuits, which advance the understanding of the interconnected pathways that modulate the sensory dimension of pain and the long-term emotional consequences of chronic pain.

Comorbid pain and mood disorders can produce circuit-specific maladaptive plasticity; however, several translational issues require addressing to maximise future therapeutic potential. These include the validity of preclinical models, the translatability of endpoints and expanding analysis to the molecular and system levels.
Dexmedetomidine alleviates propofol-induced pyroptosis of hippocampal neurons through NLRP3 inflammasome pathway
Authors: Wang Xin , Wan Zhenzhen
Published: April 2023

Propofol is neurotoxic to trigger neuronal pyroptosis and dexmedetomidine possesses the ability to suppress proptosis. This study expounded on the protective functions of dexmedetomidine on propofol-induced pyroptosis of primary hippocampal neurons via NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway. At first, primary hippocampal neurons underwent separation and identification and were treated with different concentrations of propofol (1, 10, and 100 μM). The toxicity of propofol in the neurons was evaluated. Prior to propofol treatment, the neurons were treated with different concentrations of dexmedetomidine (0.01, 0.1, 1, 5, and 10 μM). The viability of neurons with different treatments was detected. The mRNA expressions of homeobox A5 (HOXA5) and NLRP3 were identified. The protein levels of intracellular HOXA5, NLRP3, the N-terminal fragment of gasdermin D (GSDMD-N), and cleaved-caspase-1 and the concentrations of interleukin (IL)-1β and IL-18 were examined. Subsequently, the binding of HOXA5 to the NLRP3 promoter was detected. Joint experiments were conducted with pcDNA3.1-HOXA5 or pcDNA3.1-NLRP3 in dexmedetomidine-treated neurons. Dexmedetomidine pretreatment attenuated propofol-induced pyroptosis of hippocampal neurons, increased cell viability, and repressed NLRP3, GSDMD-N, and cleaved-caspase-1 protein levels and IL-1β and IL-18 concentrations. Dexmedetomidine pretreatment inhibited intracellular HOXA5 expression, and HOXA5 bound to the NLRP3 promoter region to promote NLRP3 expression. Overexpressing HOXA5 or NLRP3 reversed anti-pyroptosis role of dexmedetomidine pretreatment in hippocampal neurons. Dexmedetomidine pretreatment suppressed NLRP3 expression by downregulating HOXA5 expression, inhibiting propofol-induced pyroptosis in primary hippocampal neurons.
Cerebrovascular and cardiovascular autonomic regulation in sickle cell patients with white matter lesions
Authors: Ferreira De Matos Christophe , Cougoul Pierre , Zaharie Oana Maria , Kermorgant Marc , Pavy-Le Traon Anne , Gales Celine , Senard Jean-Michel , Strumia Mathilde , Bonneville Fabrice , Nasr Nathalie
Published: April 2023

Background

The prevalence of asymptomatic white matter lesions (WML) in patients with sickle cell disease (SCD) has been described to be very frequent in young adults. Cerebrovascular regulation and cardiovascular autonomic regulation, more specifically the sympatho-vagal balance can be altered in SCD.

In this study we assessed the association between WML, cerebrovascular regulation and sympatho-vagal balance in SCD.

Method

Adults with no history of stroke from a cohort of SCD patients were prospectively evaluated for, cerebrovascular regulation using Mx for autoregulation, breath holding test for cerebrovascular reactivity and cerebral arterial compliance calculated from arterial blood pressure and cerebral velocities. Sympatho-vagal balance was assessed using heart rate variability parameters. WML was assessed with MRI using Fazekas score grading and the presence of lacunar lesions.

Results

Forty-one patients (F/M:25/16) were included. Median age was 37.5 (range 19-65). Twenty-nine (70,7%) patients had SS genotype, 7 patients (17,1%) had SC genotype and 5 (12,2%) patients had Sß° genotype. Among the 41 patients included, 11 patients had WML (26,8%). Patients with WML were significantly older (44.5 vs 30.6 years; p<0.001), had a lower HF (HF 157 ms2vs HF 467.6 ms2; p<0.005) and impaired cerebral arterial compliance (CaBVR 15.4 vs 37.3 cm3/mmHg; p<0.014). Cerebral blood flow velocities, reactivity to breath holding test and cerebral autoregulation parameters did not significantly differ between the two groups.

Conclusions

Lower parasympathetic activity and impaired cerebral arterial compliance were associated with WML in adults with SCD. This could potentially yield to a better understanding of pathophysiological parameters leading to premature cerebrovascular ageing in SCD patients.
Decoding the role of transcriptomic clocks in the human prefrontal cortex
Authors: Martínez-Magaña José J. , Krystal John H. , Girgenti Matthew J. , Núnez-Ríos Diana L. , Nagamatsu Sheila T. , Andrade-Brito Diego E. ,   Traumatic Stress Brain Research Group, Montalvo-Ortiz Janitza L.
Published: April 2023

Aging is a complex process with interindividual variability, which can be measured by aging biological clocks. Aging clocks are machine-learning algorithms guided by biological information and associated with mortality risk and a wide range of health outcomes. One of these aging clocks are transcriptomic clocks, which uses gene expression data to predict biological age; however, their functional role is unknown. Here, we profiled two transcriptomic clocks (RNAAgeCalc and knowledge-based deep neural network clock) in a large dataset of human postmortem prefrontal cortex (PFC) samples. We identified that deep-learning transcriptomic clock outperforms RNAAgeCalc to predict transcriptomic age in the human PFC. We identified associations of transcriptomic clocks with psychiatric-related traits. Further, we applied system biology algorithms to identify common gene networks among both clocks and performed pathways enrichment analyses to assess its functionality and prioritize genes involved in the aging processes. Identified gene networks showed enrichment for diseases of signal transduction by growth factor receptors and second messenger pathways. We also observed enrichment of genome-wide signals of mental and physical health outcomes and identified genes previously associated with human brain aging. Our findings suggest a link between transcriptomic aging and health disorders, including psychiatric traits. Further, it reveals functional genes within the human PFC that may play an important role in aging and health risk.
Profiling the effect of micronutrient levels on vital cardiac markers
Authors: Krishnamurthy Hari Krishnan , Reddy Swarnkumar , Jayaraman Vasanth , Krishna Karthik , Song Qi , Wang Tianhao , Bei Kang , Rajasekaran John J.
Published: April 2023

Cardiovascular diseases (CVD) are among the most preventable chronic disorders accounting for about one-third of general mortality around the globe. Micronutrients have been shown to have a significant impact on cardiovascular health. Micronutrients have been looked at as the most adoptable lifestyle choice which could reduce the burden of disease around the world. In this context, it is important to study the levels of micronutrients and see their correlation to cardiac disease biomarkers. The present study, has attempted to investigate the relationship between the diverse class of micronutrients and serum levels of the key lipids and lipoproteins. A retrospective analysis was carried out between the serum levels of micronutrients and vital cardiovascular markers. The study was carried out in a group of 358 individuals tested for the Cardio Health and Micronutrients Panel at Vibrant America Clinical Laboratory. The study population was categorized based on the serum concentration of lipids and lipoproteins into 3 groups ‘Low’ ‘Normal’ and ‘High’ and the levels of micronutrients were compared among these groups. The results revealed a significant association of several cardiovascular markers with vitamins including Vit D, Vit E, Vit K, and minerals including zinc, iron, calcium, magnesium, and amino acids including leucine, isoleucine, and valine. Quantitative analysis by Pearson’s correlation exhibited a negative correlation of asparagine with serum levels of cholesterol and LDL. Amino acids such as cysteine, isoleucine, and valine were found to have a significant negative correlation with HDL. A positive correlation was observed between valine and serum levels of LDL and Apo B. Vitamins such as Vit A, Vit D3, Vit E, and Vit K1 were found to have a strong positive correlation with levels of total cholesterol and triglycerides. The study summarizes micronutrients and modulation of several lipid markers which are critical for the management of cardiovascular diseases. Micronutrients such as vitamins B1, B3, asparagine, and glutamine have a strong positive association, and fat-soluble vitamins, and BCAA has a strong negative association with cardiovascular health.
IntroducingSoNHR– Reporting guidelines for social networks in health research
Authors: Luke Douglas A. , Tsai Edward , Carothers Bobbi J. , Malone Sara , Prusaczyk Beth , Combs Todd B. , Vogel Mia T. , Neal Jennifer Watling , Neal Zachary P.
Published: April 2023

Objective

The overall goal of this work is to produce a set of recommendations (SoNHR– Social Networks in Health Research) that will improve the reporting and dissemination of social network concepts, methods, data, and analytic results within health sciences research.

Methods

This study used a modified-Delphi approach for recommendation development consistent with best practices suggested by the EQUATOR health sciences reporting guidelines network. An initial set of 28 reporting recommendations was developed by the author team. A group of 67 (of 147 surveyed) experienced network and health scientists participated in an online feedback survey. They rated the clarity and importance of the individual recommendations, and provided qualitative feedback on the coverage, usability, and dissemination opportunities of the full set of recommendations. After examining the feedback, a final set of 18 recommendations was produced.

Results

The final SoNHR reporting guidelines are comprised of 18 recommendations organized within five domains:conceptualization(how study research questions are linked to network conceptions or theories),operationalization(how network science portions of the study are defined and operationalized),data collection & management(how network data are collected and managed),analyses & results(how network results are analyzed, visualized, and reported), andethics & equity(how network-specific human subjects, equity, and social justice concerns are reported). We also present a set of exemplar published network studies which can be helpful for seeing how to apply the SoNHR recommendations in research papers. Finally, we discuss how different audiences can use these reporting guidelines.

Conclusions

These are the first set of formal reporting recommendations of network methods in the health sciences. Consistent with EQUATOR goals, these network reporting recommendations may in time improve the quality, consistency, and replicability of network science across a wide variety of important health research areas.
Air pollution and emotional behavior in adolescents across the U.S.
Authors: Campbell Claire E. , Cotter Devyn L. , Bottenhorn Katherine L. , Burnor Elisabeth , Ahmadi Hedyeh , Gauderman W. James , Cardenas-Iniguez Carlos , Hackman Daniel , McConnell Rob , Berhane Kiros , Schwartz Joel , Chen Jiu-Chiuan , Herting Megan M.
Published: April 2023

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence – a vulnerable time for developing mental health difficulties. This study examines how annual average PM2.5and NO2exposure at ages 9-10 years relates to internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at baseline and annually for two follow-up sessions for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Overall, the pollution effects moderated the main effects of age with higher levels of PM2.5and NO2leading to an even greater likelihood of having no behavioral problems (i.e., score of zero) with age over time, as well as fewer problems when problems are present as the child ages. Albeit this was on the order equal to or less than a 1-point change. Thus, one year of annual exposure at 9-10 years is linked with very small change in emotional behaviors in early adolescence, which may be of little clinical relevance.
The Impact of Intensive Blood Pressure Management in the Post-Thrombolysis Setting: a real-world observational study
Authors: Harper Bethan , Ranta Syrah , McNaughton Harry , Ranta Anna
Published: April 2023

Introduction

Systolic Blood pressure (SBP) >180mmHg following stroke thrombolysis has been associated with increased bleeding and poorer outcome. Aiming for the guideline SBP of <180mmHg often leads to SBP overshoot as treatment is only triggered if this threshold is passed. We tested whether a lower target would result in fewer high SBP protocol violations.

Methods

This is a prospective, single centre, sequential comparison of two blood pressure protocols. Between 2013 and 2017, the guideline based post-thrombolysis SBP target of <180mmHg was compared with a new protocol aiming for 140-160mmHg. Primary outcome was rate of patients with SBPs >180 mmHg. Secondary outcomes included rate of SBP <120 mmHg, antihypertensive infusion use, symptomatic intracerebral haemorrhage (sICH), and 3-month functional independence (mRS 0-2). Results were adjusted for age, baseline function, and stroke severity using regression analysis.

Results

During the 23 months preceding and 18 months following the transition to the new protocol 68 and 100 patients were thrombolysed respectively. Baseline characteristics were similar between groups. The odds of one or more SBPs >180mmHg trended lower in the intensive group (adjusted odds ratio (aOR) 0.61; 95% CI 0.32-1.17; p=0.14). There was a higher rate of SBPs <120mmHg (aOR 3.09; 95% CI 1.49-6.40; p=0.002) in the intensive BP protocol group. sICH rate and 3-month mRS 0-2 were similar between groups.

Conclusions

The more intensive post-thrombolysis BP protocol led to a significant increase in sub-optimally low BP events with a non-significant trend toward fewer high BP protocol violations and unaffected patient outcomes.
Prehospital Stroke Scales Outperform National Institutes of Health Stroke Scale in Predicting Large Vessel Occlusion in a Large Academic Telestroke Network
Authors: English Stephen W. , Chhabra Nikita , Hanus Abigail E. , Basharath Rida , Miller Monet , Butterfield Richard J. , Zhang Nan , Demaerschalk Bart M.
Published: April 2023

Background

With growing emphasis on prehospital identification of large vessel occlusion (LVO), some experts have advocated for prehospital involvement of vascular neurologists. Prehospital telestroke may improve triage and in-hospital treatment, but the accuracy of prehospital LVO scales in telestroke has not been investigated.

Methods

We performed a retrospective study of telestroke consultations in a large academic telestroke network from 2019 to 2020. We assessed performance of 7 LVO scales using the NIHSS score at presentation (RACE, C-STAT, FAST-ED, 3I-SS, PASS, VAN, and G-FAST). We performed two analyses using different LVO definitions: (1) anterior LVO including occlusion of the internal carotid (ICA), middle cerebral (M1 or M2), or anterior cerebral (A1 or A2) arteries; and (2) any LVO including occlusion sites above plus basilar artery or posterior cerebral artery (P1 or P2). Diagnostic performance was assessed via sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and accuracy using established thresholds of each scale. These results were compared to NIHSS at thresholds of 6, 8, and 10. Area under curve (AUC) was calculated using c-statistics by treating scales as continuous variables.

Results

A total of 625 patients were included; 111 (17.8%) patients had an anterior LVO, 118 (18.9%) patients had any LVO, and 182 (29.1%) patients had stroke mimic diagnosis. Mean age (SD) was 67.9 (15.9), 48.3% were female, and 93.4% were white. Mean NIHSS (SD) was 14.9 (8.4) for patients with anterior LVO, 4.7 (5.0) for patients with non-LVO ischemic stroke, and 4.4 (5.8) for stroke mimic (p<0.001). Compared to the NIHSS, FAST-ED and RACE scales demonstrated higher accuracy and AUC for LVO detection.

Conclusions

Both the FAST-ED and RACE scales outperformed the NIHSS for LVO detection in patients evaluated by telestroke. These scales may be valid alternatives to the NIHSS examination in this setting.
Donor Bone Marrow Derived Macrophage Engraftment into the Central Nervous System of Allogeneic Transplant Patients
Authors: Loeb Anisha M. , Pattwell Siobhan S. , Meshinchi Soheil , Bedalov Antonio , Loeb Keith R.
Published: April 2023

Hematopoietic stem cell transplantation is a well known treatment of hematologic malignancies wherein nascent stem cells provide a regenerating marrow and immunotherapy against the tumor. The progeny of hematopoietic stem cells also populate a wide spectrum of tissues, including the brain, as bone marrow derived macrophages similar to microglial cells. We developed a sensitive and novel combined IHC and XY FISH assay to detect, quantify and characterize donor cells in the cerebral cortex of 19 female allogeneic stem cell transplant patients. We show that the number of male donor cells ranged from 0.14-3.0% of total cells or 1.2-25% of microglial cells. Using tyramide based fluorescent IHC we found at least 80% of the donor cells express the microglial marker Iba1 consistent with being bone marrow derived macrophages. The percentage of donor cells was related to pretransplant conditioning; donor cells from radiation based myeloablative cases averaged 8.1% of microglial cells, while those from non-myeloablative cases averaged only 1.3%. The number of donor cells in patients conditioned with Busulfan or Treosulfan based myeloablation were similar to TBI based conditioning; donor cells averaged 6.8% of microglial cells. Notably, patients who received multiple transplants and those with the longest post-transplant survival had the highest level of donor engraftment, with donor cells averaging 16.3% of microglial cells. Our work represents the largest study characterizing bone marrow-derived macrophages in post-transplant patients. The efficiency of engraftment observed in our study warrants future research on microglial replacement as a therapeutic option for disorders of the central nervous system.

Key Points

We developed a sensitive Iba1 IHC and XY FISH co-stain assay to detect bone marrow derived donor cells in the brain of HSCT patients.

Donor cells in the CNS express Iba1 and average 8% of microglia after myeloablative HSCT; double transplants increase engraftment up to 25%.
Exploring the Performance and Explainability of BERT for Medical Image Protocol Assignment
Authors: Talebi Salmonn , Tong Elizabeth , Mofrad Mohammad R. K.
Published: April 2023

Although deep learning has become state of the art for numerous tasks, it remains untouched for many specialized domains. High stake environments such as medical settings pose more challenges due to trust and safety issues for deep learning algorithms. In this work, we propose to address these issues by evaluating the performance and explanability of a Bidirectional Encoder Representations from Transformers (BERT) model for the task of medical image protocol assignment. Specifically, we evaluate the performance and explainability on this medical image protocol classification task by fine tuning a pre-trained BERT model and measuring the word importance by attributing the classification output to every word through a gradient based method. We then have a trained radiologist review the resulting word importance scores and assess the validity of the model’s decision-making process in comparison to that of a human. Our results indicate that the BERT model is able to identify relevant words that are highly indicative of the target protocol. Furthermore, through the analysis of important words in misclassifications, we are able to reveal potential systematic errors in the model that may be addressed to improve its safety and suitability for use in a clinical setting.
Investigating the role of commoncis-regulatory variants in modifying penetrance of putatively damaging, inherited variants in severe neurodevelopmental disorders
Authors: Wigdor Emilie M. , Samocha Kaitlin E. , Eberhardt Ruth Y. , Chundru V. Kartik , Firth Helen V. , Wright Caroline F. , Hurles Matthew E. , Martin Hilary C.
Published: April 2023

Recent work has revealed an important role for rare, incompletely penetrant inherited coding variants in neurodevelopmental disorders (NDDs). Additionally, we have previously shown that common variants contribute to risk for rare NDDs. Here, we investigate whether common variants exert their effects by modifying gene expression, using multi-cis-expression quantitative trait loci (cis-eQTL) prediction models. We first performed a transcriptome-wide association study for NDDs using 6,987 probands from the Deciphering Developmental Disorders (DDD) study and 9,720 controls, and found one gene,RAB2A, that passed multiple testing correction (p = 6.7×10−7). We then investigated whethercis-eQTLs modify the penetrance of putatively damaging, rare coding variants inherited by NDD probands from their unaffected parents in a set of 1,700 trios. We found no evidence that unaffected parents transmitting putatively damaging coding variants had higher genetically-predicted expression of the variant-harboring gene than their child. In probands carrying putatively damaging variants in constrained genes, the genetically-predicted expression of these genes in blood was lower than in controls (p = 2.7×10−3). However, results for proband-control comparisons were inconsistent across different sets of genes, variant filters and tissues. We find limited evidence that commoncis-eQTLs modify penetrance of rare coding variants in a large cohort of NDD probands.
Gene fusions during the early evolution of mesothelioma correlate with impaired DNA repair and Hippo pathways
Authors: Jama Maymun , Zhang Min , Poile Charlotte , Nakas Apostolos , Sharkey Annabel , Dzialo Joanna , Dawson Alan , Kutywayo Kudazyi , Fennell Dean A. , Hollox Edward J
Published: April 2023

Malignant pleural mesothelioma (MPM), a rare cancer a long latency period (up to 40 years) between asbestos exposure and disease presentation. The mechanisms coupling asbestos to recurrent somatic alterations are poorly defined. Gene-fusions arising through genomic instability may create novel drivers during early MPM evolution. We explored the gene fusions that occurred early in the evolutionary history. We conducted multiregional whole exome sequencing (WES) of 106 samples from 20 patients undergoing pleurectomy decortication and identified 24 clonal non-recurrent fusions, three of which were novel (FMO9P-OR2W5,GBA3andSP9). The number of early gene fusion events detected varied from zero to eight per tumour, and presence of gene fusions was associated with clonal SCNAs involving the Hippo pathway genes and homologous recombination DNA repair genes. Fusions involved known tumour suppressorsBAP1,MTAP, andLRP1B,and a clonal oncogenic fusion involvingCACNA1D-ERC2, PARD3B-NT5DC2andSTAB2-NT5DC2fusions were also identified as clonal fusions. Gene fusions events occur early during MPM evolution. Individual fusions are rare as no recurrent truncal fusions event were found. This suggests the importance of early disruption of these pathways in generating genomic rearrangements resulting in potentially oncogenic gene fusions.
SecretoMyc, a web-based database on mycobacteria secreted proteins and structure-based homology identification using bio-informatics tools
Authors: Gracy Jérôme , Vallejos-Sanchez Katherine , Cohen-Gonsaud Martin
Published: April 2023

To better understand the interaction between the host and theMycobacterium tuberculosispathogen, it is critical to identify its potential secreted proteins. While various experimental methods have been successful in identifying proteins under specific culture conditions, they have not provided a comprehensive characterisation of the secreted proteome. We utilized a combination of bioinformatics servers and in-house software to identify all potentially secreted proteins from six mycobacterial genomes through the three secretion systems: SEC, TAT, and T7SS. The results are presented in a database that can be crossed with selected proteomics and transcriptomics studies (https://secretomyc.cbs.cnrs.fr/myc). In addition, thanks to the recent availability of Alphafold models, we developed a tool in order to identify the structural homologues among the mycobacterial genomes.