bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating T-lymphocyte subsets as promising biomarkers for the identification of sepsis-induced acute kidney injury
Authors: Guo Xue-Ling , Lu Cheng-Xiang , Luo Yan , Wang Ping-Ping , Su Wen-Song , Yang Si-Jiu , Zhan Ling-Hui
Published: October 2024

Background:

This retrospective study investigated whether disturbances in circulating T-lymphocyte subsets could predict the incidence of acute kidney injury (AKI) and in-hospital mortality in patients with sepsis.

Methods:

Clinical data from patients with sepsis admitted to the intensive care unit were reviewed. Logistic regression analyses were used to identify independent predictors of in-hospital mortality and the development of AKI.

Results:

Of 81 patients with sepsis, 50 developed AKI. Both nonsurvivors and patients with septic AKI exhibited higher Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Nonsurvivors exhibited more organ damage, with significantly lower levels of peripheral T-lymphocyte subsets, including total circulating lymphocytes, and CD3+, CD3+CD4+, and CD3+CD8+ T-lymphocytes. Patients with septic AKI exhibited fewer total peripheral lymphocytes and fewer CD3+, CD3+CD4+, and CD3+CD8+ T-lymphocytes, with higher serum lactate levels and lower nadir platelet counts. Independent predictors of 30-day hospital mortality included maximum SOFA and APACHE II scores, occurrence of encephalopathy, and peripheral CD3+ and CD3+CD8+ T-lymphocyte counts. Moreover, the maximum SOFA score and CD3+ and CD3+CD8+ T-lymphocyte counts demonstrated good predictive power for AKI in receiver operating characteristic (ROC) curve analyses, with an area under the ROC curve of 0.810 (95% confidence interval [CI], 0.712-0.908) for SOFA score, 0.849 (95% CI, 0.764-0.934) for CD3+ T-lymphocytes, and 0.856 (95% CI, 0.772-0.941) for CD3+CD8+ T-lymphocytes.

Conclusion:

Patients with sepsis-induced AKI experienced T lymphopenia and increased in-hospital mortality. Higher maximum SOFA scores and reduced peripheral CD3+ and CD3+CD8+ T-lymphocyte levels were associated with in-hospital mortality and the development of AKI in patients with sepsis.
Topical Steroids Are Effective and Safe in Patients With Eosinophilic Esophagitis Over a Median of 6.5 Years of Chronic Use
Authors: McCallen Justin D. , Dave Mili , LaFata Sean S. , Cameron Brenderia A. , Xue Angela Z. , Kiran Akshatha , Ocampo Adolfo A. , Lee Christopher J. , Borinsky Stephanie A. , Redd Walker D. , Cotton Cary C. , Eluri Swathi , Reed Craig C. , Dellon Evan S.
Published: October 2024

Goals:

To determine long-term efficacy and safety of tCS for treatment of EoE.

Background:

Maintenance therapy with topical corticosteroids (tCS) is recommended for eosinophilic esophagitis (EoE), but data for long-term use are still needed.

Study:

This retrospective cohort study assessed newly diagnosed patients with EoE who were treated with a tCS and had a follow-up endoscopy with biopsy after at least 5 years. Histologic symptomatic and endoscopic responses were extracted from medical records. Patients who did and did not have long-term tCS treatment were compared at baseline, and outcomes for patients were assessed at their last endoscopy while on tCS.

Results:

Of 431 patients with EoE treated with tCS, 104 met inclusion criteria for long-term use. For patients with long-term tCS use, the median time (IQR) on tCS was 6.5 years (5.4 to 8.8 y). At the last endoscopy, 54% had histologic response (<15 eos/hpf), but those with excellent adherence had a histologic response of 64%. Endoscopic severity also decreased with improved adherence which was strongly associated with EREFS (1.7 vs. 2.8 vs. 4.0 for excellent, good, and poor adherence;P<0.001). Symptomatic response was 68% overall, but only 40% in those with poor adherence (P=0.07). Complications of taking tCS were uncommon (adrenal insufficiency: 1%; osteopenia: 1%; and esophageal candidiasis: 4% at final endoscopy).

Conclusions:

Long-term tCS (median 6.5 y) were generally effective, especially with better adherence, and also safe, with only rare serious complications. These data can be used to help patients make clinical decisions about chronic tCS use in EoE.
Low false-positive lymph nodes for 18F-fibroblast activation protein inhibitors PET/computed tomography in preoperative staging of patients with nonsmall cell lung cancer
Authors: Mu Xingyu , Lu Ludeng , Li Jingze , Zhang Lei , Deng Yanyun , Fu Wei
Published: October 2024

Objective

This study aimed to evaluate the diagnostic accuracy of 18F-fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in identifying primary tumors and mediastinal lymph node metastases in nonsmall cell lung cancer (NSCLC), with histopathological findings serving as the reference standard.

Methods

Nineteen patients underwent preoperative 18F-FAPI PET/CT and subsequent surgery; of these, 13 also underwent 18F-fluorodeoxyglucose (FDG) PET/CT within 1 week. The diagnostic accuracy of primary tumors and lymph node metastases was evaluated for both modalities. Semiquantitative parameters, including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBRs), for both primary tumors and lymph node metastases were assessed for both modalities.

Results

For primary tumors, 18 of 19 (94.7%) showed positive results on 18F-FAPI PET/CT scans. In 13 patients who also underwent 18F-FDG PET/CT, 18F-FAPI PET/CT demonstrated a higher detection rate compared with 18F-FDG PET/CT (100% vs. 69.1%). The overall accuracy of lymph node assessment with 18F-FAPI PET/CT (95.9–97.1%) was significantly higher compared to 18F-FDG PET/CT (51.0%). Malignant lymph nodes exhibited significantly higher SUVmax and TBR on 18F-FAPI scans (SUVmax: 7.0 vs. 0.9, P < 0.001; TBRmuscle: 5.0 vs. 0.8, P < 0.001) than on 18F-FDG scans (SUVmax: 3.9 vs. 1.8, P = 0.01), except for the liver TBR on 18F-FDG scans (TBRliver: 1.8 vs. 1.0, P = 0.055).

Conclusion

18F-FAPI could be utilized in the preoperative staging of NSCLC to mitigate the incidence of false positives associated with 18F-FDG, due to its higher accuracy in identifying mediastinal lymph node metastasis.
Hearing preservation in pediatric cochlear implantation
Authors: Marinelli John P. , Carlson Matthew L.
Published: October 2024

Purpose of review

Pediatric cochlear implantation has evolved considerably over the past three decades to include more patients at earlier ages with greater degrees of residual hearing. As an extension, a significant focus of research over the past decade has surrounded preservation of existing acoustic hearing.

Recent findings

Multiple studies published within the last 5 years demonstrate aidable acoustic hearing preservation in 60–90% of pediatric patients, with 40–60% experiencing complete hearing preservation following cochlear implantation. Durability of preserved hearing varies among patients, with some patients losing residual hearing within 1 year of surgery whereas others maintain acoustic hearing through at least 5 years of follow-up. Speech outcomes appear superior among patients with preserved acoustic hearing, particularly in the presence of background noise. Several recent studies suggest a music appreciation advantage in children with preserved acoustic hearing following cochlear implantation.

Hearing preservation rates during cochlear implantation in children matches, if not often exceeds, hearing preservation rates observed among adults. Preservation of acoustic hearing during cochlear implantation confers multiple advantages for the pediatric population. Beyond improved speech understanding and music appreciation, minimizing intracochlear trauma and resultant scarring facilitates potential future regenerative treatments or revision surgery.
Acute renal failure requiring renal replacement therapy secondary to rhabdomyolysis due to rosuvastatin
Authors: Yadav Kundan K. , Shah Bikash K. , Yadav Srijana K. , Sherpali Aakash , Pourkamali Yesamin , Kantha Adesh , Timilsaina Manoj K.
Published: October 2024

Introduction and importance:

Statins are the group of medicines that lower the level of low-density lipoprotein cholesterol. One of the life-threatening complications is rhabdomyolysis as the use of these drugs.

Case presentation:

Here, we report a case of a 69-year-old female who was diagnosed with non-ST elevation myocardial infarction one month and was on regular medication before presentation with generalized weakness and decreased urine output. Proximal muscle weakness was greater than distal muscle on the bilateral lower limb, and power at the hip, knee, and ankle was 3/5 in the bilateral area, with absent reflex at the knee and ankle bilateral area.

Clinical discussion:

A total of four hemodialysis sessions were performed; the first three sessions were performed at an interval of 24 h, then the last maintenance hemodialysis after 48 h of three sessions. The patient’s weakness in the bilateral lower limb returns to normal condition.

Conclusion:

Physicians need to be aware of the potential of developing severe rhabdomyolysis in patients taking rosuvastatin to prevent morbidity, extended hospital stay, and financial loss.
Evaluation of a Drug Checking Training Program for Frontline Harm Reduction Workers and Implications for Practice
Authors: Teal Taylor , Wallace Bruce , Hore Dennis
Published: October 2024

Context

Drug checking, defined as the use of instruments (e.g. spectrometers), test strips, and other technologies to provide information on drug composition for harm reduction purposes, has emerged as a promising intervention to reduce harms of illicit drugs linked to overdose deaths. While demonstrating potential, these interventions remain limited in reach amid questions of how to reach the full population of people who use drugs and are at risk of overdose, including those outside urban areas. In response to these limitations, Substance, a drug checking project based in Victoria, Canada, developed a Distributed Model of Drug Checking and a concomitant training program.

Program

The Distributed Drug Checking Training program eliminates need for point-of-care spectrometry technicians, instead capacitating harm reduction workers to provide drug checking using software developed by the project, infrared spectrometers, and immunoassay test strips. The training includes 5 hours of group content that can be delivered virtually, and 2 hours of practice time per learner.

Implementation

Training and data collection took place between May 2022 and March 2024 with learners from 6 locations across Vancouver Island, Canada. We offered 13 training sessions, with evaluation data collected from 54 learners.

Evaluation

The training was evaluated across Kirkpatrick’s 4 levels of training evaluation. The training was highly acceptable to learners, attributable to intended changes in knowledge and skill related to drug checking, resulted in competence to deliver drug checking through the project’s Distributed Model, and facilitated expansion of drug checking services to 6 geographically distant locations.

Discussion

After completing the 7-hour training program, harm reduction workers were able to deliver drug checking without need for on-site drug checking technicians. The short duration of the training and its demonstrated success with the Distributed Model of Drug Checking make this a promising approach for expanding the reach of drug checking services.
Routine discussion of previous trauma in the perinatal period: Insights from interviews with women, voluntary sector representatives, and maternity care providers
Authors: Cull Joanne , Thomson Gill , Downe Soo , Fine Michelle , Topalidou Anastasia
Published: October 2024

Background

Many pregnant women have a history of trauma, such as abuse or violence, which can significantly impact their mental and physical health. Discussing these experiences in maternity care presents an opportunity to support women, reduce stigma, and connect them with resources. However, concerns persist about stigmatisation, re-traumatisation and unwarranted safeguarding referrals. As part of a larger study that aimed to develop a methodology for conducting trauma discussions, interviews were carried out with a range of stakeholders.

Methods

Semi-structured interviews were conducted with women with trauma histories (experts by experience; n=4), representatives of voluntary sector organisations (n=7), and healthcare providers (n=12). Reflexive thematic analysis was used to analyse the data. The study employed a critical participatory action research approach, supported by a Patient and Public Involvement & Engagement group (named as the ‘Research Collective’ for this study) comprising experts by experience, maternity care professionals, and voluntary sector practitioners. The group contributed to both the design and analysis phases of the research.

Findings

Five key themes emerged from the interviews, exploring both the benefits and challenges of trauma discussion in maternity care. Participants reflected on who should lead these discussions, the appropriate settings and timings, and strategies for effective communication. The emotional and training needs of care providers conducting trauma discussions were also highlighted.

Conclusion

Trauma discussions in maternity care are a complex but necessary intervention that require careful consideration of timing, communication, and referral pathways. This paper offers concrete steps towards creating a more empathetic and supportive maternity care environment.

Statement of Significance

Problem

Traumatic experiences such as abuse or violence contribute to long term mental and physical health problems.

What is already known

Raising the issue of previous trauma within maternity care offers an opportunity to provide support, but if handled insensitively can be distressing to women.

What this paper adds

This paper shows that discussing trauma is complex and requires a system-wide approach which addresses when, where, and how to talk about trauma, referral pathways, and the need for training and support for maternity care providers. It also offers insights on conducting these discussions sensitively and effectively.
Clinical signatures ofSYNGAP1-related disorders through data integration
Authors: McKee Jillian L. , Magielski Jan H. , Xian Julie , Cohen Stacey , Toib Jonathan , Chen Chen , Kim Dan , Rathod Aakash , Brimble Elise , Fitter Nasha , Graglia J. Michael , Helde Kathryn A. , Boland Michael J. , Ruggiero Sarah McKeown , Sederman Rob , Helbig Ingo
Published: October 2024

Objective

To characterize the longitudinal disease and treatment histories of individuals withSYNGAP1-related disorders.

Methods

Participants withSYNGAP1were identified from a range data data sources, including insurance claims data by ICD-10 diagnosis codes (n=246), a specialized medical record registry and a local cohort followed at a single tertiatry health care institution (n=158).

Results

Compared to a broader population of individuals with epilepsy, phenotypes associated withSYNGAP1disorders included behavioral abnormalities (Odds ratio (OR) 12.35, 95% CI 9.21–16.78), generalized-onset seizures (OR 1.56, CI 1.20–2.02), and autism (OR 12.23, CI 9.29–16.24). A wide range of clinical features showed distinct age-related patterns, such as a more than five-fold risk of autistic behavior emerging between 27 and 30 months. Generalized-onset seizures became significantly enriched (OR 4.05, CI 2.02–7.59) after 3 years of age and persisted over time. Valproic acid (OR 2.26, CI 1.29–3.70) and clobazam (OR 2.58, CI 1.55–4.09) were commonly used for epilepsy management, which contrasted significantly from treatment strategies in the broader epilepsy cohort. Furthermore, valproate and lamotrigine were more effective at reducing seizure frequencies or maintaining seizure freedom than other anti-seizure medications. Risperidone, aripiprazole, and guanfacine were commonly used for behavioral features.

Interpretation

Phenotypic features specific toSYNGAP1included a predominance and age-dependence of generalized seizures, a more than ten-fold risk of behavioral abnormalities, and a developmental profile with prominent deficits in verbal skill acquisition. Clear delineation of trajectories ofSYNGAP1-related disorders will improve diagnosis, prognosis, and clinical care, facilitating clinical trial readiness.
Investigating Mood and Cognition in People with Multiple Sclerosis: A Prospective Study Protocol
Authors: Cooper Elena C. , Schindler Matthew K. , Bar-Or Amit , Brandstadter Rachel B. , Calkins Monica E. , Gur Ruben C. , Jacobs Dina A. , Markowitz Clyde E. , Moore Tyler M. , Naydovich Laura R. , Perrone Christopher M. , Ruparel Kosha , Spangler Bailey C. , Troyan Scott , Shinohara Russell T. , Satterthwaite Theodore D. , Baller Erica B.
Published: October 2024

Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects one million people in the United States. Up to 50% of people with MS experience depression, yet the mechanisms of depression in MS remain under-investigated. Studies of medically healthy participants with depression have described associations between white matter variability and depressive symptoms, but frequently exclude participants with medical comorbidities and thus cannot be extrapolated to people with intracranial diseases. White matter lesions are a key pathologic feature of MS and could disrupt pathways involved in depression symptoms. The purpose of this study is to investigate the impact of brain network disruption on depression using MS as a model. We will obtain structured clinical and cognitive assessments from two hundred fifty participants with MS and prospectively evaluate white matter lesion burden as a predictor of depressive symptoms. Ethics approval was obtained from The University of Pennsylvania Institutional Review Board (Protocol #853883). The results of this study will be presented at scientific meetings and conferences and published in peer-reviewed journals.

ARTICLE SUMMARY

Strengths and Limitations of this Study

We will use MS as a model to study how white matter disease contributes to both the pathophysiology of depression in MS and to general network mechanisms of depression.

We will leverage research-grade 3-tesla (3T) MRIs acquired as part of routine MS care and maximize scalability by using the Method for Inter-Modal Segmentation Analysis (MIMoSA) for automated white matter lesion segmentation.

Our study will include participants with medical comorbidities, creating a more representative population and more broadly applicable results.

We will obtain detailed clinical and cognitive assessments from each participant to evaluate the inter-relationship of mood symptoms, anxiety symptoms, and cognitive deficits, and relate them to white matter disease.

This is a single-center study.
Medical Risk Factors Associated with Listening Difficulties in Children
Authors: Moore David R. , Vesole Adam S. , Lin Li , Caldwell-Kurtzman Jody , Hunter Lisa L.
Published: October 2024

abstract

OBJECTIVES

Listening difficulty refers to difficulty hearing speech despite normal pure-tone audiometry. It is as prevalent as clinical hearing loss among adults, but incidence, causes and treatment remain poorly understood in children. We hypothesized that four medical risk factors would be associated with listening difficulty in children.

METHODS

A prospective, case-control study was conducted in a tertiary care children’s hospital. Children (6-13 years old) with clinically normal hearing divided into listening difficulty (n=68) and typically developing (n=84) groups based on a validated caregiver report. All children were native English users without reported conditions restricting participation. Testing included extended high frequency (EHF) audiometry, speech and spatial perception, and cognitive function. Caregiver reports, electronic medical records, and testing ascertained risk of prematurity, head injury, otitis media and EHF hearing loss. Logistic regression, chi-square, correlation, and odds ratios determined associations of listening difficulty with risk factors.

RESULTS

Prevalence and risk of prematurity (18%, OR 3.39 [95% CI, 1.1-10.2]), head injury (21%, 3.37 [1.2-9.3]), and high frequency hearing loss (32%, 2.42 [1.1-5.5]) were significantly greater for children with listening difficulty than typically developing children. Ventilation tubes were no more common in the listening difficulty group (25%, 1.14 [0.5-2.4]). EHF hearing loss was associated with prematurity and tubes. Prematurity, tubes, and EHF loss were significantly related to poorer competing speech perception and dichotic listening.

CONCLUSIONS

Children with a history of prematurity, head injury or EHF loss were at increased risk of listening difficulties. Early intervention to boost communication skills could potentially improve poorer long-term outcomes.
Evaluating generative artificial intelligence’s limitations in health policy identification and interpretation
Authors: Wilson Rory , Weets Ciara M. , Rosner Amanda , Katz Rebecca
Published: October 2024

Policy epidemiology utilizes human subject-matter experts (SMEs) to systematically surface, analyze, and categorize legally-enforceable policies. The Analysis and Mapping of Policies for Emerging Infectious Diseases project systematically collects and assesses health-related policies from all United Nations Member States. The recent proliferation of generative artificial intelligence (GAI) tools powered by large language models have led to suggestions that such technologies be incorporated into our project and similar research efforts to decrease the human resources required. To test the accuracy and precision of GAI in identifying and interpreting health policies, we designed a study to systematically assess the responses produced by a GAI tool versus those produced by a SME.

We used two validated policy datasets, on emergency and childhood vaccination policy and quarantine and isolation policy in each United Nations Member State. We found that the SME and GAI tool were concordant 78.09% and 67.01% of the time respectively. It also significantly hastened the data collection processes.

However, our analysis of non-concordant results revealed systematic inaccuracies and imprecision across different World Health Organization regions. Regarding vaccination, over 50% of countries in the African, Southeast Asian, and Eastern Mediterranean regions were inaccurately represented in GAI responses. This trend was similar for quarantine and isolation, with the African and Eastern Mediterranean regions least concordant. Furthermore, GAI responses only provided laws or information missed by the SME 2.14% and 2.48% of the time for the vaccination dataset and for the quarantine and isolation dataset, respectively. Notably, the GAI was least concordant with the SME when tasked with policy interpretation.

These results suggest that GAI tools require further development to accurately identify policies across diverse global regions and interpret context-specific information. However, we found that GAI is a useful tool for quality assurance and quality control processes in health policy identification.
Right caudate deactivation during reward anticipation predicts elevated risk for psychosis in adolescents
Authors: Sen Pritha , Knolle Franziska
Published: October 2024

Background: Schizophrenia is associated with abnormalities in neurodevelopmental processes. Furthermore, dysfunctional neural circuits involved in reward processing may be linked to the development of symptoms in schizophrenia and are predictive of long-term functional outcome. It is however unknown whether neural signatures of reward processing are detectable in children with an increased risk of psychosis and/or predictive of their prodromal psychosis score. Methods: Using data from the ABCD study 4.1, we defined a healthy control (N=50) and a risk for psychosis (N=50) group with a Prodromal Psychosis Syndrome (PPS) score>3 at baseline (9-10 years) and 2nd-year-follow-up (11-12 years). While undergoing functional MR-imaging, all children completed the Monetary Incentive Delay task. Using the preprocessed ABCD-data, we explore whether behaviour and brain activations for reward and loss anticipation in areas underlying reward processing differed between groups and time-points. Furthermore, we investigated whether those brain activations that showed differences between the groups were predictive of later PPS scores. Results: While behavioural results did not differ, we found that at-risk children demonstrated lower activation during reward anticipation in the caudate for both timepoints, and the nucleus accumbens, the putamen, the dorsolateral and the ventral medial prefrontal cortex for the 2nd-year-follow-up compared to controls. Regression analysis revealed that right caudate deactivation for both timepoints was predictive of later PPS scores. Conclusion: This study reveals that neural alterations during reward anticipation are detectable in children at-risk of psychosis. These dysfunctions in neural activation patterns may serve as a potential predictive biomarker for psychosis.
Co-expression-wide association studies link genetically regulated interactions with complex traits
Authors: Malakhov Mykhaylo M. , Pan Wei
Published: October 2024

Transcriptome- and proteome-wide association studies (TWAS/PWAS) have proven successful in prioritizing genes and proteins whose genetically regulated expression modulates disease risk, but they ignore potential co-expression and interaction effects. To address this limitation, we introduce the co-expression-wide association study (COWAS) method, which can identify pairs of genes or proteins whose genetically regulated co-expression is associated with complex traits. COWAS first trains models to predict expression and co-expression conditional on genetic variation, and then tests for association between imputed co-expression and the trait of interest while also accounting for direct effects from each exposure. We applied our method to plasma proteomic concentrations from the UK Biobank, identifying dozens of interacting protein pairs associated with cholesterol levels, Alzheimer’s disease, and Parkinson’s disease. Notably, our results demonstrate that co-expression between proteins may affect complex traits even if neither protein is detected to influence the trait when considered on its own. We also show how COWAS can help disentangle direct and interaction effects, providing a richer picture of the molecular networks that mediate genetic effects on disease outcomes.
Noninvasive Optical Monitoring of Cerebral Hemodynamics Immediately after Birth in Neonates with Congenital Heart Disease
Authors: Winston Chloe N. , Bowe Madison E. , Lee Sura , Ranieri Nicolina R. , Ades Anne , Gebb Juliana , Rychik Jack , Naim Maryam Y. , Bostwick Anna , Forti Rodrigo M. , Ko Tiffany S , Foglia Elizabeth E. , Baker Wesley B. , Lynch Jennifer M.
Published: October 2024

Objective

Critical congenital heart disease (CHD) is associated with neuropsychiatric impairment that may stem from altered cerebral hemodynamics. While cerebral hemodynamics are shown to differ in neonates with CHD, the effect of CHD on cerebral physiology earlier in life during the fetal to neonatal transition period is yet to be elucidated. This period of neonatal resuscitation could represent an opportunity for intervention in critical CHD, so we aimed to characterize cerebral physiology immediately after birth in neonates with critical CHD using noninvasive optical monitoring.

Methods

This case series analysis included term neonates with hypoplastic left heart syndrome (HLHS; n=2) and with transposition of the great arteries (TGA; n=2) who were born at Children’s Hospital of Philadelphia. Continuous measurements of cerebral hemodynamics were acquired during the first hour after birth with novel non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS), as well as commercial near-infrared spectroscopy (NIRS). NIRS measures cerebral oxygenation, and the combined FD-DOS/DCS device measures cerebral oxygenation, blood flow, and metabolism.

Results

In all four patients, cerebral oxygen saturation was lower than reference values in the literature. Additionally, we observed decreases in cerebral blood flow and oxygen metabolism during postnatal transition that were not reflected by peripheral oxygen saturation. The decreases were spontaneous in infants with HLHS and temporally associated with invasive respiratory support in infants with TGA.

Conclusion

This study demonstrates periods of neurological vulnerability during postnatal transition in CHD and motivates further research on the use of noninvasive optical monitoring during neonatal resuscitation.

Clinical Perspective

What is New?

An advanced noninvasive hybrid FD-DOS/DCS system detects periods of neurological vulnerability during neonatal resuscitation in patients with critical CHD that are not reflected by peripheral oxygen saturation trends.

Invasive respiratory support is associated with cerebral desaturations.

What Are the Clinical Implications?

These findings suggest the utility of noninvasive cerebral monitoring during neonatal resuscitation in neonates with critical CHD and motivate further studies to assess this.
Unravelling the Impact of Tumor Location on Patient Survival in Glioblastoma: A Genomics and Radiomics Approach
Authors: Kundal Kavita , Kumar Neeraj , Kumar Rahul
Published: October 2024

Glioblastoma (GBM), the most aggressive form of brain tumor, has a median survival rate of 12-15 months. Understanding the relationship between genetics and tumor location, as well as identifying non-invasive biomarkers, is crucial for improving treatment strategies and survival outcomes in GBM. In this study, we investigated the impact of tumor location on survival outcome of GBM patients along with genetic factors that influence tumor behaviour in different brain regions. Interestingly, we found that patients with parietal lobe tumors had significantly poor survival outcome compared to those with tumors in other brain regions, particularly the frontal lobe. In a comprehensive genomic analysis, we identified genetic factors, seemingly contributing to the poor survival outcomes in parietal lobe patients. We found the enrichment ofPTENloss-of-function mutations in parietal lobe tumors and interestingly these mutations are known to be associated with chemoresistance and poor patient survival. We also found two fusion genes i.e.,FGFR3-TACC3andEGFR-SEPT14, exclusively in parietal lobe tumors, which are known to play crucial roles in tumorigenesis. Differential gene expression analysis revealed the upregulation of genes likePITX2, HOXB13, andDTHD1, which could be responsible for tumor progression in parietal lobe tumors. Conversely, the downregulation ofALOX15increased relapse risk. Copy number alterations, such as deletions in tumor suppressor gene (LINC00290), were linked to the aggressive nature of parietal lobe tumors. Radiomic analysis revealed two key features, lowerLLL_GLDM_DependanceEntropyand higherHLL_firstorder_Mean, both of which show a significant correlation with increased risk and poorer survival outcome. These findings suggest the potential for targeted therapies and personalized treatments based on tumor location, genetic profile, and radiomic markers. We anticipate that as the size of the datasets will increase for radiogenomics based studies, it will further strengthen these findings and our understanding of molecular drivers for GBM progression, treatment resistance and survival outcome.
Serum proteomics reveals high-affinity and convergent antibodies by tracking SARS-CoV2 hybrid immunity to emerging variants of concern
Authors: Patel Anand , Lima Thiago , Carson Richard , Huang Qiulong , Bonissone Stefano R. , Castellana Natalie
Published: October 2024

The rapid spread of SARS-CoV2 and continuing impact on human health has prompted the need for effective and rapid development of monoclonal antibody therapeutics. In this study, we interrogate polyclonal antibodies in serum and B cells from whole blood of three donors with SARS-CoV2 immunity to find high-affinity anti-SARS-CoV2 antibodies to escape variants. Serum IgG antibodies were selected by affinity to the receptor-binding domain (RBD) and non-RBD sites on the spike protein of Omicron subvariant B.1.1.529 from each donor. Antibodies were analyzed by bottom-up mass spectrometry, and matched to single- and bulk-cell sequenced repertoires for each donor. Antibodies observed in serum were recombinantly expressed, and characterized to assess domain binding, cross-reactivity between different variants, and capacity to inhibit RBD binding to host protein. Donors infected with early Omicron subvariants had serum antibodies with subnanomolar affinity to RBD that show binding activity to a newer Omicron subvariant BQ.1.1. The donors also showed a convergent immune response. Serum antibodies and other single- and bulk-cell sequences were similar to publicly reported anti-SARS-CoV-2 antibodies, and characterized serum antibodies had the same variant-binding and neutralization profiles as their reported public sequence. The serum antibodies analyzed were a subset of anti-SARS-CoV2 antibodies in the B cell repertoire, which demonstrates significant dynamics between the B cells and circulating antibodies in peripheral blood.
Non-Invasive Systemic Blood Pressure Measurement Wait Period Error Mitigation
Authors: McMahon Seán , Morrow Paul
Published: October 2024

World Health Organisation blood pressure measurement guidelines stipulate that a patient should be seated, back straight and legs uncrossed, for five minutes prior to blood pressure measurement. A study shows that in the majority of cases, the wait period is disregarded by the physician and consequently, the patient may be exposed to the risk of missed diagnosis or misdiagnosis. Modern oscillometric blood pressure measurement devices do not enforce a wait period or monitor patients to gauge their readiness for a measurement. This study investigates whether the electrocardiogram (ECG) or photoplethysmography (PPG) data of a patient could be used as a determinant of readiness for blood pressure measurement. The results indicate that the standard deviation of the interpeak difference of a patient’s ECG bio-signal could be used as a trigger for blood pressure measurement. In this single participant study, the wait period could be reduced from five minutes to 35 seconds. A follow up clinical investigation is recommended to validate the result on broader populations and a list of improvements are provided for such a follow up investigation.
Investigating the Prevalence and Risk Determinants of Ovarian Cancer in Women from Bauchi State North-East, Nigeria
Authors: Jibril Murtala Muhammad , Baffah Maryam Dalhatu , Mohammed Mohammed Bello
Published: October 2024

Ovarian cancer posed a significant health challenge, particularly in low-resource settings where late diagnosis and limited healthcare access contribute to high mortality rates. This cross- sectional study assessed the prevalence and risk factors for ovarian cancer among women attending General Hospital Azare, North-eastern Nigeria. Data were collected from women of reproductive age 18 and above through structured questionnaires and medical records. The study found an ovarian cancer prevalence of 7.2%, with key risk factors including family history of cancer (17.5%), early menarche, and nulliparity (66%). Despite access to healthcare, only 11.3% of participants had undergone ovarian cancer screening, and 58.8% lacked adequate knowledge of its risk factors. Urban residence (80.4%) and student status (71.1%) were linked to better healthcare access, but a significant gap in awareness persisted. Family history had the strongest association with ovarian cancer (Chi-square = 24.621, p < 0.001), although a counterintuitive negative coefficient suggested the need for further investigation. Alcohol consumption (Chi- square = 27.086, p < 0.001) and hormonal contraceptive use (Chi-square = 12.855, p = 0.0016) were also significantly associated with increased risk. Smoking (Chi-square = 8.57, p = 0.0034) further elevated the risk, while physical activity indicated no significant association. These findings highlighted the need for public health interventions, including education, awareness programs, and improved access to diagnostic services. Efforts to promote early detection and address healthcare disparities are crucial in reducing ovarian cancer risks in this population.
Changes in population immunity to omicron SARS-CoV-2 variants and selected Sarbecoviruses from 2020 to 2023 in urban Colombo, Sri Lanka
Authors: Bary Farha , Karunananda Maneshka Vindesh , Jeewandara Chandima , Danasekara Saubhagya , Guruge Dinuka , Rizan Rizna , Aberathna Inoka Sepali , Ranasinghe Thushali , Kuruppu Heshan , Jayamali Jeewantha , Perera Lahiru , Chathurangika Harshani , Gunaratne Amaya , Dasanthi Naduni , Ranatunga Chathura , Ishara A.W. Shashini , Yatiwelle Sathsara , Wijayamuni Ruwan , Tan Tiong Kit , Townsend Alain , Ogg Graham S. , Malavige Gathsaurie Neelika
Published: October 2024

Background

To understand how the population immunity evolved over time and possible susceptibility of the Sri Lankan population to emerging SARS-CoV-2 variants, we proceeded to evaluate the changes in antibody positivity rates to omicron variants BA.2.75 and XBB.1.5 and for selected sarbecoviruses.

Methods

The haemagglutination test (HAT) was carried out to determine the presence of antibodies against the RBD of the SARS-CoV-2 omicron variants XBB.1.5 and BA.2.75 and the RBD of the Sabecoviruses RaTG13, WIV1, Khosta-2 and SARS-CoV-1, in individuals aged 5 to 80 years of age in years 2020 (n=381), 2022 (n=432) and 2023 (n=382).

Results

The highest positivity rates for BA.2.75, RaTG13, WIV1, Khosta-2 and SARS-CoV-1 were seen in 2022, with positivity rates significantly declining to many of the viruses except XBB.1.5 and Khosta-2 by 2023. The positivity rates for Khosta-2 (p<0.001) and WIVI (p<0.001) were significantly lower in children <14 years age, but not for XBB.1.5, BA.2.75 and RaTG13. Children <14 years who were SARS-CoV-2 unvaccinated had the lowest positivity rates for all tested viruses except BA.2.75. <20% of individuals in all age groups had antibody titres equivalent to 1:80, which correspond to neutralising antibody titres by 2023.

Conclusions

Population immunity to omicron SARS-CoV-2 variants and selected sarbecoviruses had significantly declined in Colombo, Sri Lanka by 2023. Therefore, although T cells might still offer some protection against severe disease, immunizing vulnerable individuals in the community with protective vaccine designs, might be important to consider at this stage.
Sex-specific Metabolic Signatures of Insulin Resistance, Body Mass Index, and Visceral Adiposity in Fasting and Postprandial States
Authors: Shojaeifard Zahra , Chahibakhsh Negar , Horner David , Schoos Ann-Marie M , Thorsen Jonathan , Stokholm Jakob , Vinding Rebecca , Bønnelykke Klaus , Rasmussen Morten A. , Ebrahimi Parvaneh
Published: October 2024

The rising prevalence of obesity and insulin resistance, a risk factor for type 2 diabetes (T2D), among adolescents is a growing public health concern. Understanding the metabolic underpinnings of adiposity and insulin resistance in adolescence can provide insights into the development of metabolic dysfunction, and potentially facilitate early intervention strategies to prevent the progression of these conditions into more severe metabolic disorders in adulthood. We explored the metabolic signatures of insulin resistance, Body Mass Index (BMI), and visceral adiposity in adolescents, in both fasting and postprandial states. A meal challenge was undertaken on 18-year-olds (154 females; 144 males), and their blood metabolites were profiled using Nuclear Magnetic Resonance spectroscopy (NMR). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for modeling and variable selection, in a sex-stratified manner. The results show distinct metabolic patterns between sexes, with males showing more pronounced postprandial responses and stronger associations between blood metabolome and insulin resistance, BMI, and visceral adiposity. Key metabolites such as lipid metabolites, Branched-Chain Amino Acids (BCAAs), glucose, and Glycoprotein Acetylation (GlycA) were selected as important metabolic entities in predicting insulin resistance and adiposity in adolescence. The findings underscore the complex interplay of metabolites with metabolic health and sex, and can pave the way for developing targeted interventions and preventive strategies specifically tailored to adolescents. Such interventions can potentially mitigate the risk of progression to more severe metabolic disorders.
Analysis of clinical characteristics of invasive non-typhoidalSalmonellainfections in children: a 5-year dual-center retrospective study
Authors: Lu Chenggang , Xie Yongping , Li Yan , Cheng Fangfang , Huang Lisu , Hua Wang
Published: October 2024

Objective

To investigate the incidence, microbiological characteristics, clinical manifestations, and antibiotic resistance of invasive non-typhoidalSalmonella(iNTS) infections in children.

Methods

A retrospective study was conducted from January 2018 to December 2022 at two large teaching hospitals: Zhejiang University School of Medicine Children’s Hospital (ZCH) and Children’s Hospital of Soochow University (SCH). Medical records of culture-confirmed iNTS cases were reviewed, and a standardized case report form was used to collect demographic, clinical, and microbiological data.

Results

A total of 109 cases of iNTS infection were included, with 40 cases from SCH and 69 cases from ZCH. 71 cases (65.1%) were boys.. Infants under 1 year old accounted for 30.3% of the cases. Among the cases, 38 cases (34.9%) had underlying diseases, mainly tumors (55.3%,21/38). The most common sites of infection were the bloodstream (84.4%) and bones and joints (12.8%). The most common serogroups were B (36.8%), C (44.7%) and D (38.2%). The overall resistance rate of ampicillin was 53.6%, ceftriaxone resistance rate was 17.8%, and carbapenem resistance rate was 0%. Seasonal trends indicated higher incidence rates during the summer.

Conclusion

iNTS infections in children primarily affect the bloodstream and bones/joints, with a significant proportion of cases in those with underlying medical conditions. Ceftriaxone remains the first-line antibiotic, but increasing resistance highlights the need for vigilant antimicrobial stewardship. Carbapenems can be considered as second-line antibiotics in severe cases. Further studies are needed to understand the molecular characteristics and improve treatment strategies for iNTS infections in pediatric patients.
The Viability, Necessity, and Acceptability of Text Message Group Therapy Among Low-Income Racial-Ethnic Minority Mothers: A Qualitative Study
Authors: Guiroy Ilang M. , Caicedo Brianna I. , Nouri Roya , Kuhn Eric , Semple Randye J.
Published: October 2024

Purpose

This qualitative focus group study conceptually explored the viability, necessity, and acceptability of a proposed text message group therapy (TMGT) intervention as a psychotherapy delivery format among racial-ethnic minority, low-income peripartum mothers.

Method

Three semi-structured, virtual focus groups facilitated in-depth interviews with 12 adults who gave birth in the previous 24 months, self-identified as a racial-ethnic minority, had at least mild depression (PHQ-9 >5), participated in a government program requiring low-income (e.g. Special Supplemental Nutrition Program for Women, Infants, and Children [WIC]), and were fluent in English. Recruitment, data collection, and analyses were performed concurrently. This allowed theme saturation (no emergence of new themes) to determine the sample size of 12 participants. The qualitative analysis framework was Grounded Theory. Krippendorff’s alpha was set to > 0.8 for interrater reliability.

Results

Ten of the 12 participants were willing to engage in the proposed TMGT. Participants reported a need for psychotherapy tailored to motherhood that was not met by their current support system or healthcare providers, which the proposed TMGT could meet. While all participants communicated via text messaging about motherhood and baby care, they varied in terms of how much. Text messaging has the unique strength of being resilient to interruptions by young children and allowing for multitasking. Text messaging can be a less emotionally stimulating form of communication for an often overstimulated parent. Some mothers found it easier to share their emotions via text message, whereas others found it more difficult. Drawbacks include that information could be lost (increasing frustration or making it possible to hide their true feelings), conversational turns could take too long, and keeping track of the conversation and mobile devices could increase the mental load.

Conclusion

These racial-ethnic minority, low-income mothers with peripartum depression expressed a strong need for a safe space to share their lived experiences of motherhood, receive emotional support, and obtain high-quality information about motherhood and baby care tailored to their situation. The proposed text message group therapy is viable, acceptable, and necessary and could meet the needs of many women and increase access to group psychotherapy for this important, underserved population.
Advancing maternal and newborn health care measurement: Developing quality of care indices for postnatal and small and/or sick newborn care in low- and middle-income countries
Authors: Sheffel Ashley , King Shannon , Day Louise Tina , Marchant Tanya , Muzigaba Moise , Requejo Jennifer , Carter Emily , Munos Melinda K.
Published: October 2024

Background

High-quality healthcare for pregnant women and newborns, particularly postnatal care (PNC) and small and/or sick newborn care (SSNC), is essential to reducing maternal and newborn morbidity and mortality in low- and middle-income countries (LMICs). Poor quality of care is a major contributor to preventable morbidity and mortality, emphasizing the need for improvements in health service delivery, which requires measuring and monitoring quality of care (QoC). Although indicators measuring QoC have been identified, there is a current gap in the availability of composite indicators that can summarize the complex, multidimensional nature of QoC. This study systematically developed three composite QoC indices for maternal PNC, newborn PNC, and SSNC feasible to measure using existing data in LMICs.

Methods

A four-step process was used to define the indices: (1) Intervention selection: Key interventions were identified by reviewing global clinical guidelines and QoC frameworks; (2) Guideline review and item identification: Discrete items recommended for delivery of each of the selected interventions were extracted from intervention-specific guidelines; (3) Data mapping: These items were mapped to health facility survey data to assess their alignment with standardized tools; and (4) Final index development: A quality readiness index (QRI) was developed for each service area based on QoC frameworks, available data, and clinical guidelines.

Results

The maternal PNC-QRI includes 12 interventions and contains 24 items. The newborn PNC-QRI includes 3 interventions and contains 16 items. The SSNC-QRI includes 8 interventions and contains 48 items. Data gaps for maternal PNC, newborn PNC, and SSNC led to the exclusion of some evidence-based interventions and limited item inclusion. No data on provision/experience of care were available for PNC or SSNC, thus the indices reflect only facility readiness.

Conclusions

The three QRIs developed provide composite measures for PNC and SSNC readiness and can be adapted at country level and operationalized using health facility assessment survey data, facilitating their use by decision-makers for planning and resource allocation. Revision of existing health facility assessments to address gaps in readiness and provision/experience of care measurement for PNC and SSNC would bolster efforts to monitor and improve QoC for mothers and newborns.