bluuebunny/crossref_metadata_2025 huggingface dataset:
43 Etiology of community-acquired bacterial meningitis in children seen in the emergency department in Canada
Authors: Besner Anne-Sophie , Renaud Christian , Gravel Jocelyn
Published: October 2024

Background

Bacterial meningitis poses a significant threat to paediatric health, resulting in substantial morbidity and mortality in children. Though previous studies have delineated the causative agents behind community-acquired meningitis, recent vaccination initiatives may have reshaped its underlying etiology.

Objectives

This study aimed to identify the bacteria responsible for community-acquired bacterial meningitis in children in Canada.

Design/Methods

This was a retrospective cohort study including children aged 1 day-18 years with confirmed bacterial meningitis, evaluated at a tertiary-care, Canadian emergency department between July 1st 2014 and December 31st 2022. The primary outcome was the pathogen identified. Other variables of interest were mortality, complications, age, sex, and diagnostic method. Medical charts were identified via the hospital’s archives and reviewed by a single co-author. A random sample of 20 (23%) medical charts were independently reviewed by a second co-author to assess inter-rater reliability. We set a target of evaluating at least 50 cases to allow narrow confidence intervals (+/- 13%) for proportions.

Results

All variables showed excellent inter-rater reliability with Kappa scores and intraclass correlation coefficients higher than 0.60. All 79 eligible cases were included. The main causal agents were Group B Streptococcus (GBS) (n=20; 25%), Streptococcus pneumoniae (n=16; 20%), Neisseria meningitidis (n=16; 20%) and Haemophilus influenzae (n=9; 11%). Etiology exhibited age-dependent variations, with 85% of GBS and 100% of E. coli infections identified in children under two months, while all pneumococcal and Group A Streptococcus cases were in children older than six months. All children infected by S. pneumoniae were vaccinated against pneumococcal infection but the serotype was not covered by vaccination in 7/8 infections. All children with N. meningitidis were either too young to be vaccinated (n=10) or infected by a serotype not covered by the vaccine. Six (7%) patients died and 29 (34%) suffered complications, including hearing impairment (n=5), cerebral ischemia (n=4), seizures (n=4), and subdural abscess (n=3). Fifty-nine bacterias were identified by cerebrospinal fluid culture, 13 by PCR and 7 by both methods.

Conclusion

GBS is the leading etiology of paediatric community-acquired bacterial meningitis in Canada. Causal agents of bacterial meningitis vary greatly by age. Future studies should work on improving the serotype spectrum of vaccines, prophylaxis in mothers who are GBS carriers, and use of PCR as a diagnostic tool for timely clinical interventions.
47 Association between unmet social needs and parental stress in a paediatric asthma clinic
Authors: Botella Mathilde , Drouin Olivier , Perez Tamara , Smyrnova Anna , Islam Mahisa , Ducharme Francine Monique , Fleegler Eric , Lavoie Kim L , Sultan Serge , Tse Sze Man , Zhao Jiaying
Published: October 2024

Background

There are well documented associations between unmet social needs and undesirable health outcomes, but little data exist on the association between unmet social needs and stress in families of children with asthma.

Objectives

To document the relationship between unmet social needs and parental stress in a Canadian paediatric asthma clinic.

Design/Methods

Ongoing prospective observational study to determine the association between unmet social needs and parental stress was conducted in a tertiary care paediatric asthma clinic, between September 2022 and September 2023. Participants were parents of children with a diagnosis of asthma, treated with at least one controller medication. Unmet social needs were collected by parental self-report using a questionnaire assessing 8 domains: employment, housing, ability to pay for utilities, financial resources, food security, transportation, childcare, and education. The four-item Perceived Stress Scale was used to assess how parents perceived stress and how they felt they were able to manage situations in their lives. Chi-square tests compared our independent variable, the presence vs. absence of unmet social needs, to our dependent variables; each measure of stress (control over important aspects of ones’ life, confidence in ability to overcome problems, feeling that everything was going well, ability to overcome too many accumulated difficulties).

Results

Of 162 participants, seventy-seven (48%) reported at least one unmet social need. Compared to participants without unmet social needs, those with unmet needs were more likely to report having no control over important aspect of their work or main activity (p< 0.001); less likely to report having confidence in their ability to overcome problems (p< 0.001); less likely to report having the feeling that everything was going well (p< 0.001); and less likely to report having the ability to overcome too many accumulated difficulties (p< 0.001).

Conclusion

Findings suggest significant association between unmet social needs and parental stress of asthmatic children. Parental stress and unmet needs may concomitantly increase the burden of adhering to asthma controller medication, making adherence more challenging through pathways related to the interactions between cognitive burden and precarious living situations. This ongoing Canadian study seeks to elucidate the mechanisms by which these factors make adherence to asthma medication more challenging for families, so these challenges can be addressed.
51 Feasibility of paediatric postoperative telemedicine in Nunavik
Authors: Bugra Adalet , Kabbes Nour , Janssen Ricky , Wissanji Hussein , Osmanlliu Esli
Published: October 2024

Background

To access surgical care, Inuit children from Nunavik are relocated by plane to an urban tertiary hospital. Current processes that require an in-person follow-up appointment extend their stay away from home despite an overall low rate of postoperative complications. Telemedicine presents the opportunity to reduce this delay, but little is known about its feasibility for paediatric postoperative care in Nunavik.

Objectives

To determine the feasibility of paediatric postoperative telemedicine in Nunavik.

Design/Methods

In this mixed methods study using a convergent parallel design (August 2022 – May 2023), we recruited eleven healthcare providers who regularly interact with Inuit families of Nunavik. We conducted individual semi-structured in-depth interviews about postoperative care in this setting and analyzed the data thematically. In parallel, we conducted a narrative synthesis of the literature and gathered input from collaborators to assess the potential resources needed to enable postoperative telemedicine in the region. We then determined the capability for telemedicine in each of the fourteen villages of Nunavik using data provided by the regional health board. A meeting with specialists responsible for telemedicine in the region was held to discuss findings and future steps. We analyzed and compared qualitative and quantitative results to determine the degree of postoperative telemedicine readiness in the region.

Results

The main themes influencing the feasibility of telemedicine were general considerations for telemedicine use as a follow-up modality, patient characteristics most suitable for postoperative telemedicine, resources needed for telemedicine use as a follow-up modality, and the feasibility of postoperative telemedicine as determined by healthcare providers. All interviewees deemed paediatric postoperative telemedicine in this region feasible but highlighted conditions for its success. The narrative review uncovered limited literature on telemedicine use in Nunavik. As of January 2023, the two regional hospitals and three health centers had full capabilities for postoperative telemedicine. The nine other health centers had partial capabilities, mainly due to limited access to stable high-speed Internet and Internet bandwidth. Only regional hospitals had access to hospitalization, imaging, readaptation, and laboratory departments. The participating specialists deemed telemedicine feasible if patient load and burden of administrative work are manageable.

Conclusion

Postoperative paediatric telemedicine in Nunavik is feasible from a resource, healthcare providers and specialists standpoint. Leveraging centers with appropriate capacity would allow the increase in telemedicine usage in Nunavik. Next steps in this research program include interviews with families to evaluate their needs, preferences and attitudes toward postoperative paediatric telemedicine.
55 Post-pandemic paediatric asthma admissions: Clinical characteristics and outcomes of children hospitalized with asthma in 2022: The READAPT-Kids study cohort
Authors: Kim Min Jung , Gill Peter J , Mtaweh Haifa , Freire Gabrielle , Yang Connie L , Rayment Jonathan H , Mahant Sanjay , Morris Shaun K , Seaton Claire
Published: October 2024

Background

Asthma exacerbations triggered by acute respiratory infections (ARIs) are a major cause of hospitalizations in children. There were large reductions in asthma admission during the SARS-CoV2 pandemic. Following the relaxation of public health interventions, there was a resurgence in admissions for ARIs. The effect of this rebound in ARIs on asthma management practices and outcomes is not well understood.

Objectives

To describe sociodemographic characteristics, etiology, management, and clinical outcomes of children and youth under the age of 18 years admitted to a tertiary care paediatric hospital with an acute asthma exacerbation from July 1, 2022 to Dec 31, 2022.

Design/Methods

An observational cohort study of children and youth less than 18 years, hospitalized with an acute asthma exacerbation from July 1, 2022 to Dec 31, 2022 at a single large Canadian children’s hospital. This was a subgroup analysis of the READAPT-Kids study cohort (Clinical chaRacteristics and outcomEs of hospitAlized children with Acute resPiratory infecTions.) Cases were identified using ICD-10-CA codes, then manually screened for inclusion. Detailed clinical and demographic information was extracted.

Results

Among 551 patients hospitalized with an ARI, 29.2% (n=161) were diagnosed with an asthma exacerbation. 99 were male (61.5%) with a median age of 3.8 years (IQR 2.2-6.3). 41.3% (n=64) had a previously documented asthma history, and of those, only 16.9% were taking any form of asthma therapy at admission. In hospital, 91.4% were given systemic corticosteroids, 86.5% had at least 1 viral pathogen identified, 72.2% had a chest x ray, 42.1% received antibiotics, and 23.7% had high flow nasal cannula oxygen outside of the paediatric intensive care (PICU). 22.4% (n=36), were admitted to the PICU, and 3.7% required invasive mechanical ventilation, there were no patient deaths. Median length of stay was 2.6 days (IQR 1.7–4.6 days). At discharge, 79.5% were prescribed regular inhaled corticosteroid therapy.

Conclusion

Asthma admissions accounted for a significant proportion of children hospitalized with ARIs in the post-pandemic era, with one fifth requiring transfer to PICU. CXR and antibiotic usage were high. Over 80% of those with a previous diagnosis of asthma were not taking inhaled corticosteroids at the time of admission.
56 Iron deficiency is common in extreme preterm infants despite prophylactic iron supplementation
Authors: Barr Hudson , Morrison Lisa , Ketan Kulkarni , Ghotra Satvinder
Published: October 2024

Background

Iron deficiency (ID) in childhood is linked to adverse neurodevelopmental outcomes in the long-term. Extremely premature infants (EPI; born < 28 weeks gestation) are more susceptible to ID due to a multitude of factors including lower iron reserves at birth, rapid growth, immature erythropoiesis, and multiple phlebotomy tests during hospital stay. Therefore, professional societies advise prophylactic iron therapy for these infants from 2-6 weeks age until 6-12 months. However, there is paucity of data on the iron status in EPI receiving this prophylactic iron supplementation.

Objectives

To investigate the prevalence and risk factors associated with ID in EPI.

Design/Methods

A retrospective cohort study analyzed a Provincial database of EPIs born between 2005-2018. Infants with congenital malformations, chromosomal anomalies and blood disorders were excluded. All included infants received prophylactic iron supplementation from 2-4 weeks of chronological age that was recommended to continue at discharge until 9-12 months corrected age (CA). At 4-6 months CA, these infants underwent blood testing. ID was defined as serum ferritin < 20mcg/L at 4 months CA or SF < 12mcg/L at 6 months CA. Through a univariate analysis using single-variable logistic regression, factors linked to ID were identified. Those with a p-value < 0.20 progressed to a multivariable model, retaining variables with a p-value < 0.05.

Results

Of 146 infants, 45.9% had ID. ID group had lower mean ferritin (16.4 µg/L vs 50.0 µg/L, p < .001) and reticulocyte hemoglobin equivalent (28.4pg vs 31.6pg, p < .001) compared to the non-ID group. ID prevalence reduced from 59.7% in 2005-2011 to 40.3% in 2012-2018 cohort. Exclusive or partial breastfeeding at 4-6 months CA was protective against ID (Odds: 0.2, p = 0.003). Iron therapy at 4-6 months CA was not protective in the final model. Notably, 27.4% stopped iron therapy before 4-6 months CA, and exclusive formula-fed infants had notably lower iron intake than breastfed infants (66.1% vs 99.1%, p = 0.006).

Conclusion

Nearly half of the EPI exhibited ID at 4-6 months CA despite prophylactic iron supplementation. About a quarter discontinued therapy before reaching this age. Breastfeeding at this age was protective against ID. This high prevalence of ID in EPI underscores the need of future studies to discern strategies to mitigate ID in this vulnerable population.
67 A population-based cohort study of endocrine outcomes within the first 5 years of life in children born preterm
Authors: Lam Carol , Shen Ye , Richter Lindsay , Ting Joseph
Published: October 2024

Background

Preterm birth (<37 weeks’ gestational age [GA]) occurs in 8% of live births in Canada. While advancements in neonatal medicine have led to increased survival in preterm births, infants born preterm continue to sustain short- and long-term health sequelae. There is paucity of large population studies evaluating childhood health care outcomes, including endocrine-related outcomes, in recent birth cohorts.

Objectives

To evaluate the rates of endocrine conditions during the first 5 years of life in children born preterm and term.

Design/Methods

The study cohort included liveborn infants at 22-44 weeks’ GA in British Columbia, Canada between 2004-2014. Follow-up data to December 2019 included linked health services use information from four BC provincial databases (perinatal database, hospitalizations, outpatient services, and outpatient prescriptions). Rates of outcomes were compared by GA at birth (37-44 weeks reference category) using robust Poisson regression.

Results

There were 455,960 children included in this study with 42,820 (9.4%) born at <37 weeks GA. Results are summarized in Table 1 and Table 2. Compared to children born at 37-44 weeks’ gestations, infants born at 36 weeks’ gestation or younger have an increased rate of thyroid disorders between 0 months and 5 years (rate ratio [RR]: 1.45, 95% confidence interval [CI]: 0.78-2.43; RR: 1.83, 95% CI 1.51-2.20; RR: 1.41 95% CI 1.26-1.57 for 22-27 weeks, 28-33 weeks and 34-36 weeks GA, respectively). Similarly, infants born at 36 weeks’ gestation or younger have a higher rate of conditions in growth and development (RR: 3.05, 95% CI: 0.76-7.96; RR: 3.20, 95% CI 2.04-4.76; RR: 1.42 95% CI 1.02-1.94 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively) and bone health conditions (RR: 1.38, 95% CI: 1.27-1.49; RR: 1.04, 95% CI 1.00-1.08; RR: 1.05 95% CI 1.03-1.07 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively). There was no difference in rates of conditions related to glucose metabolism such as diabetes mellitus or hypoglycemia.

Conclusion

Children born preterm have increased rates of endocrine conditions by age 5. Disorders of thyroid, growth and development are increased in infants born preterm. Children born preterm have an increase rate of bone-related disorders, including those born late-preterm. These results provide useful prognostic information for follow-up care for preterm children and for healthcare resource planning. Furthermore, these results highlight areas of future research in endocrine health among preterm infants.
71 Development and validation of the COCINL scale assessing family resilience in the NICU among parents of preterm infants
Authors: Laporte Geneviève , Gélinas Céline , Genest Christine , Aita Marilyn
Published: October 2024

Background

Given the negative impact of parental distress on preterm infants and their families, examining the role of family resilience in the neonatal intensive care unit (NICU) is a promising avenue for promoting parental mental health while remaining consistent with family-centered care. A tool to assess NICU family resilience is essential to guide care and research, yet none specifically adapted for the neonatal context exists to date according to a recent systematic review.

Objectives

Therefore, the aim of this study was to develop and validate a new scale, the COCINL scale, designed to measure family resilience in the context of neonatal care among French-speaking parents of preterm infants.

Design/Methods

This methodological design study was carried out in four successive phases: (I) compilation of an item pool (II) mixed-method evaluation of content validity (clarity, relevance, representativeness) involving 12 experts, (III) pre-testing and electronic administration of the COCINL scale, along with a measure of psychological distress (Kessler-6) and an open-ended self-report question on family resilience to parents of preterm infants (n=88) and (IV) psychometric testing of the COCINL scale (internal consistency, construct validity, exploratory sensitivity and specificity). Parents of preterm infants and experts were recruited by convenience sampling from two urban, level III NICUs.

Results

From a pool of 112 items, 55 items were favorably evaluated after content validation (S-CVI>0.95). Based on preliminary interitem correlations and internal consistency results, the COCINL scale was shortened to 42 items and divided in four subscales. High internal consistency is also shown in subscales (0.796 to 0.908) and total scale (0.937) Cronbach’s alphas. The COCINL scale displays adequate construct validity, as determined by the Pearson correlation obtained between scores of family resilience and psychological distress (r=-0.236, p=0.027). Strong in between correlations of the four subscales and with the COCINL total score (0.732 to 0.851), further indicated good construct validity. Exploratory sensitivity and specificity analysis revealed the COCINL scale compares to participants' self-reported perception of family resilience (AUC 0.754).

Conclusion

The COCINL scale has shown strong evidence of validity and internal consistency. Thus, the scale can be recommended for research use as a measure of family resilience in the neonatal context. Still, additional evidence of its validity and reliability should be compiled before clinical use is considered. The COCINL scale could potentially support the development, evaluation and implementation of nursing interventions consistent with the family-centered care approach being promoted in NICUs across Canada and worldwide.
72 Hospital level of service, rural-urban hospital location, and neonatal resuscitation interventions at birth: A population-based study in Alberta, Canada from 2000-2020
Authors: Pickett Breanna , Crawford Susan , McNeil Deborah , Schmolzer Georg , Soraisham Amuchou , Pan Bo , Shonoski Heather , Aziz Khalid , Law Brenda
Published: October 2024

Background

Advanced neonatal resuscitation interventions (ANRIs: endotracheal intubation, chest compressions, and epinephrine) are rarely needed for infants born at ≥34 weeks gestational age (GA). However, healthcare providers (HCPs) in community hospitals can encounter the need for ANRIs, while having less experience and resources than HCPs in centers with neonatal intensive care units (NICUs). Understanding practice differences between hospitals of different levels of service (LofS) and rural/urban location can inform quality improvement to reduce health disparities.

Objectives

To examine how hospital level of service and rural/urban location relate to ANRI rates in Alberta, Canada, a universal public health system with standardized Neonatal Resuscitation Program (NRP) training.

Design/Methods

All live births ≥34 weeks GA in Alberta from 2000-2020 inclusive were examined using retrospective, population-level administrative data from the Alberta Perinatal Health Program (APHP). Hospitals (n=97) were contacted to determine annual LofS during the study period, with levels (0,1A/B/C,2,3) based on provincial obstetrical triage for availability of delivery support, cesarean-sections, obstetricians, paediatricians/neonatologists, and NICUs. Hospitals were further subcategorized by population and proximity to metropolitan centers.(Table 1) Rates of individual interventions or any ANRI were compared.

Results

There were 971,403 live births during the study period with a mean GA of 38.9 weeks; 1.6% were missing ANRI data, 955,835 births were included. Most occurred in hospitals with level 2 (57.4%) or level 3 (21.8%) NICUs; few occurred at sites with no delivery support (Level 0, 0.1%). ANRI rates were intubation (0.8%), chest compression (0.2%), and epinephrine (0.02%), any ANRI (0.96%, ~1/1000 live births). However, chest compression rates progressively decrease, and intubation rates progressively increase as LofS increases.(Table 1, Figure 1) When considering rural/urban location, there were outliers in chest compression rates in remote 0 (25.4/1000 live births) and metro-influenced 1A (30.2/1000 live births), intubation in remote 1C (33.3/1000 live births) and metro 0 (193.5/1000 live births) and epinephrine in metro 0 (64.5/1000 live births).

Conclusion

In this population-based cohort study of ≥34 weeks births, there were higher chest compressions rates and lower intubations rates at hospitals without NICUs despite standardized training. Reasons for this difference require further investigation; potential solutions such as targeted outreach education and introduction of laryngeal mask airways could be explored.
79 Using artificial intelligence and machine learning to automate injury prevention surveillance data
Authors: Singh Devin , Celik Alper , Zhang Evangeline , Rosenfield Daniel
Published: October 2024

Background

The Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) is a pan-Canadian injury and poisoning surveillance system that tracks patients presenting to Canadian Emergency Departments (EDs). Like many surveillance systems, data is input in a manual fashion with humans screening all charts. Natural language processing algorithms using transformer models can analyze text from triage notes of previous CHIRPP-positive patients to train models to predict future CHIRPP patients. We sought to automate these functions using machine learning and artificial intelligence.

Objectives

The objective of this initiative is to automate detection of injured patients using artificial intelligence. Once charts are identified, a further summarization model will automatically generate a narrative of the events surrounding the injury, as required for the surveillance system.

Design/Methods

ED notes were obtained from an electronic health record for all patients visiting the ED from October 2018 to December 2021 (n =203626). All charts were manually reviewed to determine if patients met the criteria for CHIRPP. CHIRPP-positive patients made up 24.8% (n = 50499) of the total presentations. Patient charts were randomly split into train (70%) and validation (30%) datasets. Pre-trained distilbert-base-uncased model from Huggingface was utilized. The best model according to AUROC was selected for further development. For note summarization, we fine-tuned a multi-task model (t5-small) from the Huggingface repository. We used human summaries from the same dataset (October 2018-December 2021) as training data (49,078 note, summary pairs). A 70/30 train/validation split was performed.

Results

Our model captured 90% of all positive cases while reducing the total number of charts for review by 77%, 75% and 63% for train, validation and test sets respectively. See AUC curve (figure 1). Based on 2022 volumes this is a reduction to 24,027 from 64,938 charts. For note summarization, when we compared the cosine similarities of human summaries to actual note text vs t5-small summaries to note text we saw remarkable similarity implying high model performance.

Conclusion

Our model has shown that high volumes of charts that were previously screened manually can utilize natural language processing to automate the task with minimal sacrifices in terms of data capture and accuracy, dramatically reducing cost while improving speed to reporting. Our summarization model also showed potential for further automating this process. This application to an injury prevention program has wide scale applicability and scalability.
83 What is social paediatrics and how do we teach it? A scoping review of social medicine curricula in the child and youth health context across health disciplines
Authors: Rosenkrantz Maya , Schrewe Brett , Jassemi Sara
Published: October 2024

Background

Social paediatrics is a field that focuses on addressing social and environmental factors that affect children’s health and wellbeing1. Over recent years in medical education, social paediatrics has become increasingly recognized as foundational to undergraduate and postgraduate paediatrics curricula. Paediatric residency programs worldwide have been developing and offering social paediatrics curricula, yet we lack understanding of effective strategies for teaching it to medical trainees.

1. Spencer N, Colomer C, Alperstein G, et al. Social paediatrics. J Epidemiol Community Health. 2005;59(2):106-108. doi:10.1136/jech.2003.017681

Objectives

We conducted a scoping review to describe the various educational interventions used to teach content and practice related to social paediatrics.

Design/Methods

We conducted a scoping review to describe the various educational interventions used to teach content and practice related to social paediatrics. Our literature search first drew upon Ovid MEDLINE and MedEd PORTAL, with subsequent studies identified through reference searching in relevant articles. We included studies that described and/or evaluated educational interventions aimed to teach elements of social paediatrics. We excluded studies published before 2000. We extracted data from the selected articles and conducted thematic analysis.

Results

Our search yielded 443 articles. Initial screen by title and/or abstract and subsequent screen by abstract and/or full text yielded 28 papers. Where it was unclear if studies met inclusion criteria, two additional researchers reviewed the full text. With the addition of articles found in references of the provisional articles, a total of 36 papers were included in the review. Of those, 17 (47%) described curricular interventions at the level of paediatric residency, 7 (19%) described medical school curricula, and 8 (22%) included non-medicine fields such as dentistry, nursing, research, and others. Fifty percent of curricula required self-directed learning, while a different 50% subset had a formal reflection process as part of learning consolidation. We organized the literature thematically into the following themes: interdisciplinary collaboration, community partnership, advocacy training, and experiential learning.

Conclusion

Our scoping review describes a variety of curricular interventions aimed to teach elements of social paediatrics, with a large focus on social determinants of health, primarily poverty, and a relative lack of focus on the underlying structural, systemic, and social justice issues underpinning these health determinants. We need to consider how the pedagogical strategies on offer can be purposed towards the development of more robust social paediatrics curricula at the postgraduate level.
Labor-inclusive corporatism after democratic transitions: Institutionalization in South Africa and Brazil
Authors: Castro Henrique A
Published: October 2024

Under what conditions has corporatist policymaking become institutionalized in newly transitioned democracies? I argue that transitions have provided temporary opportunities for unions to push for laws they can later use to protect their place in economic councils. The relevant sets of legal rules, which I call compulsory deliberation, enable non-‘State official’ members to resist governmental disruption of such councils despite them composing the Executive’s structure. I compare South Africa and Brazil, two ‘most similar’ cases that featured sequences of chronically unstable labor-excluding councils under authoritarian regimes. I argue that the former broke out of this trajectory while the latter did not because South African unions developed aspirations for durable policy influence before the transition, whereas Brazilian ones only did so afterward and thus mobilized too late. Although Brazilian governments have enacted dozens of regulations covering as many councils, these have only served as short-term instruments for marketing policies.
Pharmacological inhibition of histamine N-methyltransferase extends wakefulness and suppresses cataplexy in a mouse model of narcolepsy
Authors: Naganuma Fumito , Girgin Birkan , Agu Anne Bernadette S , Hirano Kyosuke , Nakamura Tadaho , Yanai Kazuhiko , Vetrivelan Ramalingam , Mochizuki Takatoshi , Yanagisawa Masashi , Yoshikawa Takeo
Published: October 2024

Histamine, a neurotransmitter, plays a predominant role in maintaining wakefulness. Furthermore, our previous studies showed that histamine N-methyltransferase (HNMT), a histamine-metabolizing enzyme, is important for regulating brain histamine concentration. However, the effects of pharmacological HNMT inhibition on mouse behavior, including the sleep–wake cycle and cataplexy, in a mouse model of narcolepsy have not yet been investigated. In the present study, we investigated the effects of metoprine, an HNMT inhibitor with high blood-brain barrier permeability, in wild-type (WT) and orexin-deficient (OxKO) narcoleptic mice. Metoprine increased brain histamine concentration in a time- and dose-dependent manner without affecting peripheral histamine concentrations. Behavioral tests showed that metoprine increased locomotor activity in both novel and familiar environments, but did not alter anxiety-like behavior. Sleep analysis showed that metoprine increased wakefulness and decreased non-rapid eye movement (NREM) sleep through the activation of the histamine H1 receptor (H1R) in WT mice. In contrast, the reduction of rapid eye movement (REM) sleep by metoprine occurred independent of H1R. In OxKO mice, metoprine was found to prolong wakefulness and robustly suppress cataplexy. In addition, metoprine has a greater therapeutic effect on cataplexy than pitolisant, which induces histamine release in the brain and has been approved for patients with narcolepsy. These data demonstrate that HNMT inhibition has a strong effect on wakefulness, demonstrating therapeutic potential against cataplexy in narcolepsy.
The evaluation of a novel single-lead biopotential device for home sleep testing
Authors: Massie Frederik , Vits Steven , Verbraecken Johan , Bergmann Jeroen
Published: October 2024

Study Objectives

This paper reports on the clinical evaluation of the sleep staging performance of a novel single-lead biopotential device.

Methods

One hundred and thirty-three patients suspected of obstructive sleep apnea were included in a multi-site cohort. All patients underwent polysomnography and received the study device, a single-lead biopotential measurement device attached to the forehead. Clinical endpoint parameters were selected to evaluate the device’s ability to determine sleep stages. Finally, the device’s performance was compared to the clinical study results of comparable devices.

Results

Concurrent PSG and study device data were successfully acquired for 106 of the 133 included patients. The results of this study demonstrated significant similarity in overall sleep staging performance (five-stage Cohen’s Kappa of 0.70) to the best-performing reduced-lead biopotential device to which it was compared (five-stage Cohen’s Kappa of 0.73). Contrary to the comparator devices, the study device reported a higher Cohen’s Kappa for rapid eye movement (REM) (0.78) compared to N3 (0.61), which can be explained by its particular measuring electrode placement (diagonally across the lateral cross-section of the eye). This placement was optimized to ensure the polarity of rapid eye movements could be adequately captured, enhancing the capacity to discriminate between N3 and REM sleep when using only a single-lead setup.

Conclusions

The results of this study demonstrate the feasibility of incorporating a single-lead biopotential extension in a reduced-channel home sleep apnea testing setup. Such incorporation could narrow the gap in the functionality of reduced-channel home sleep testing and in-lab polysomnography without compromising the patient’s ease of use and comfort.

Clinical Trials

NCT05035992, A Validation Study of the NightOwl Head Sensor

https://clinicaltrials.gov/ct2/show/NCT05035992
Dissecting the role of transcription factor AP2‐M in Babesia asexual replication
Authors: Wang Jinming , Chai Yijun , Yang Jifei , Ye Yuxin , Luo Jianxun , Yin Hong , Guan Guiquan
Published: October 2024

Babesia spp. are obligate intracellular parasites that invade host cells to complete their asexual development and transmission. Here, we identified a transcription factor AP2‐M (BXIN_0799) in Babesia sp. Xinjiang (Bxj), a member of the Apicomplexan AP2 family, which regulates gene expression related to red blood cell (RBC) invasion and cell cycle progression. Our genome‐wide analysis of (Cut‐Tag) data shows that AP2‐M specifically recognized DNA motifs in the promoters of target genes. AP2‐M target genes included other AP2 gene family members and epigenetic markers, which could modulate gene expression involved in RBC invasion, merozoite morphology, and cell cycle phases, as indicated by RNA sequencing, proteomics, and single‐cell RNA sequencing (scRNA‐seq) data from an ap2‐m gene disrupted strain (AP2‐M (−)). We conclude that AP2‐M appeared to contribute to the process of red blood cell invasion, maintain merozoite morphology, and cell cycle progression through GS and MS phases.
m6A demethylase FTO transcriptionally activated by SP1 improves ischemia reperfusion‐triggered acute kidney injury by activating Ambra1/ULK1‐mediated autophagy
Authors: Chen Yan , Liu Yuanfei , Tu Weiping , Chen Yanxia , Xu Chengyun , Huang Chong
Published: October 2024

Ischemia reperfusion (I/R) was considered as one of main causes of acute kidney injury (AKI). However, the exact mechanism remains unclear. Here, this study aimed to investigate the role and mechanism of the m6A demethylase fat mass and obesity‐associated (FTO) protein in I/R‐induced AKI. HK‐2 cells and SD rats were utilized to establish hypoxia/reoxygenation (H/R) or I/R induced AKI models. The changes of RNAs and proteins were quantified using RT‐qPCR, western blot, and immunofluorescence assays, respectively. Cell proliferation and apoptosis were assessed by CCK‐8 and flow cytometry. Interactions between molecules were investigated using RIP, ChIP, Co‐IP, RNA pull‐down, and dual luciferase reporter assays. Global m6A quantification was evaluated by kits. TUNEL and HE staining were employed for histopathological examinations. Oxidative stress‐related indicators and renal function were determined using ELISA assays. The FTO expression was downregulated in H/R‐induced HK‐2 cells and renal tissues from I/R‐induced rats. Overexpression of FTO improved the cell viability but repressed apoptosis and oxidative stress in H/R‐treated HK‐2 cells, as well as enhanced renal function and alleviated kidney injury in I/R rats. Notably, the FTO overexpression significantly increased autophagy‐related LC3 and ULK1 levels. When autophagy was inhibited, the protective effects of FTO in AKI were diminished. Notably, Ambra1, a crucial regulator of autophagy, was repressed in H/R‐induced HK‐2 cells. However, the FTO overexpression restored the Ambra1 expression by reducing m6A modification of its mRNA. SP1, acting as an upstream transcription factor, directly interacts with the FTO promoter to enhance FTO expression. Knockdown of SP1 or Ambra1 suppressed the beneficial effects of FTO upregulation on autophagy and oxidative stress injury in H/R‐stimulated cells. FTO, transcriptionally activated by SP1, promoted autophagy by upregulating Ambra1/ULK1 signaling, thereby inhibiting oxidative stress and kidney injury. These findings may provide some novel insights for AKI treatment.
Surgical Management of Early Metacarpophalangeal Joint Silicone Implant Fracture in Patient With Rheumatoid Arthritis
Authors: Pasha Mehreen , Baldino Joshua B. , Rodner Craig M.
Published: October 2024

Introduction:

Metacarpophalangeal (MCP) joint arthroplasty is a common treatment modality to correct ulnar drift, pain, and functional deficits in patients with rheumatoid arthritis, an autoimmune condition targeting the synovium of joints. While silicone MCP joint implants are susceptible to revision in the long term, there is a lack of literature discussing their early breakage. The present case illustrates silicone implant fracture only 10 weeks after MCP arthroplasty—the first instance in the literature to the authors’ knowledge.

Materials and Methods:

The patient is a 64-year-old female with stage 4 rheumatoid arthritis who underwent right index and middle finger MCP joint arthroplasties using 0-degree silicone implants, radial sagittal band imbrication on these digits, and right ring and small finger extensor tendon centralization at the MCP joint.

Results:

During the 10th postoperative week, the patient presented with atraumatic middle finger pain and ulnar deviation. Imaging revealed a right middle finger MCP implant fracture at the distal stem, which underwent successful revision using a 30-degree flexed implant and index and middle extensor tendon centralization.

Discussion:

Nineteen months after revision surgery, the patient continues to have no pain and an improved range of motion. Ultimately, we are hopeful that the flexed silicone implant will last the patient's lifetime.
Long-Term Prospective Quality-of-Life Outcomes in 445 Patients with Sporadic Vestibular Schwannoma
Authors: Carlson Matthew L. , Babajanian Eric E. , Lohse Christine M. , Tombers Nicole M. , Link Michael J.
Published: October 2024

Objective

To evaluate the long-term changes in sporadic vestibular schwannoma (VS) disease-specific quality-of-life (QOL) outcomes.

Study Design

Prospective longitudinal study using the Penn Acoustic Neuroma Quality of Life (PANQOL) Scale.

Setting

National survey.

Patients

Patients with sporadic VS who completed a baseline survey before treatment and at least one follow-up survey recruited through the authors’ center and through the Acoustic Neuroma Association.

Interventions

Observation, microsurgery, radiosurgery.

Main Outcome Measures

Changes in PANQOL scores from baseline to most recent survey.

Results

Among 445 eligible patients the mean duration of follow-up was 4.4 (SD, 2.3) years, including 122, 218, and 105 in the observation, microsurgery, and radiosurgery groups, respectively. Patients managed with observation (p = 0.03) or microsurgery (p < 0.001) demonstrated improvement in anxiety scores. Changes in facial function scores differed significantly by management group (p = 0.01), with patients undergoing microsurgery demonstrating a mean decline of 10 points in facial function scores compared with mean declines of 3 for those managed with observation or radiosurgery. Hearing loss scores decreased similarly over time for all three groups (p = 0.3). There were minimal changes in total PANQOL scores over time across all management groups (p = 0.5).

Conclusions

Long-term changes in total QOL among VS management groups are not significantly different. Microsurgery may continue to confer an advantage regarding improvement in anxiety postoperatively, but with a greater decline in facial function when compared to observation or radiosurgery. Long-term declines in hearing loss scores were not statistically significantly different among groups.
Residual Vestibular Schwannomas: Proposed Age-Tumor-Residual (ATR) Staging System to Predict Future Growth
Authors: Totten Douglas J. , Cumpston Evan C. , Schneider William , Yates Charles W. , Shah Mitesh V. , Nelson Rick F.
Published: October 2024

Objective

To assess growth rates of residual vestibular schwannoma after subtotal and near-total surgical resection and establishing staging system for risk of residual tumor growth.

Study Design

Retrospective cohort study.

Setting

Tertiary referral center.

Patients

Patients with residual vestibular schwannoma after surgical resection from 2011 to 2023 identified on postoperative MRI defined as near-total resection (NTR, less than 5 mm of remaining tumor), subtotal resection (STR; 5–10 mm) and debulking (>10 mm).

Main Outcome Measures

Tumor growth of 2 mm or more after subtotal or near-total surgical resection of vestibular schwannoma.

Results

A total of 56 patients (54% female; mean, standard deviation [SD] age 51 [17] yr) had residual tumor. Mean preoperative tumor size was 3.0 (1.1) cm, and residual tumors involved both sides with similar frequency (right: 52%). Quantitatively, 29% were NTR, 32% were STR, and 39% were debulking. With an average follow-up of 27 (SD 31) months, tumor growth occurred in 11 (20%), tumor shrinkage occurred in 16 (29%), and tumors were unchanged in 29 (51%) cases. Growing residual tumors were treated with radiation (7 patients) or a second surgical resection (4 patients). Multivariable analysis identified lower patient age, larger preoperative tumor size, and larger residual tumor size in risk of residual growth. A residual VS tumor staging system (Age, Tumor, Residual [ATR]) is proposed with most tumors in stage II (22, 42%) or stage III (23, 44%), whereas 7 (14%) tumors are stage I.

Conclusions

Approximately 80% of residual VS are stable or shrink in size. Initial observation is advocated after incomplete resection and long-term follow up is needed. Patient age less than 55 years, larger preoperative tumor size, and larger postoperative residual tumor size appear predictive of residual tumor growth.

Level of Evidence: 4
Optimization and Protection of Kidney Health in Liver Transplant Recipients: Intra- and Postoperative Approaches
Authors: Jan Muhammad Y. , Patidar Kavish R. , Ghabril Marwan S. , Kubal Chandrashekhar A.
Published: October 2024

Postoperative acute kidney injury after liver transplant (LT) has long-term implications for kidney health. LT recipients are at risk of acute kidney injury due to a number of factors related to the donor liver, intraoperative factors including surgical technique, as well as recipient factors, such as pre-LT kidney function and postoperative complications. This review discusses these factors in detail and their impact on posttransplant kidney function. Long-term risk factors such as calcineurin inhibitors have also been discussed. Additionally, the impact of liver allocation policies on pre- and post-LT kidney health is discussed.
Complete sequences of pIJ101-based Streptomyces-Escherichia coli shuttle vectors
Authors: Brown Katelyn V. , Nybo S. Eric
Published: October 2024

High-copy-number plasmids are indispensable tools for gene overexpression studies in prokaryotes to engineer pathways or probe phenotypes of interest. The development of genetic tools for the industrially relevant Actinobacteria is of special interest, given their utility in producing keratolytic enzymes and biologically active natural products. Within the Actinobacteria, Streptomyces–Escherichia coli shuttle vectors based on the SCP2* and pIJ101 incompatibility groups are widely employed for molecular cloning and gene expression studies. Here, the sequences of two commonly used pIJ101-based Streptomyces–E. coli shuttle vectors, pEM4 and pUWL201, were determined using next-generation sequencing. These plasmids drive the expression of heterologous genes using the constitutive ermE*p promoter. pEM4 was found to be 8.3 kbp long, containing a β-lactamase gene, thiostrepton resistance marker, the lacZɑ fragment, a ColE1 origin of replication and the Streptomyces pIJ101 origin of replication. pUWL201 was found to be 6.78 kbp long, containing a β-lactamase gene, thiostrepton resistance marker, the lacZɑ fragment, a ColE1 origin of replication and the Streptomyces pIJ101 origin of replication. Interestingly, the sequences for both pEM4 and pUWL201 exceed their previously reported size by 1.1 and 0.4 kbp, respectively. This report updates the literature with the corrected sequences for these shuttle vectors, ensuring their compatibility with modern synthetic biology cloning methodologies.
Rag2Mol: Structure-based drug design based on Retrieval Augmented Generation
Authors: Zhang Peidong , Peng Xingang , Han Rong , Chen Ting , Ma Jianzhu
Published: October 2024

Artificial intelligence (AI) has brought tremendous progress to drug discovery, yet identifying hit and lead compounds with optimal physicochemical and pharmacological properties remains a significant challenge. Structure-based drug design (SBDD) has emerged as a promising paradigm, but the inherent data biases and ignorance of synthetic accessibility render SBDD models disconnected from practical drug discovery. In this work, we explore two methodologies, Rag2Mol-G and Rag2Mol-R, both based on retrieval-augmented generation (RAG) to design small molecules to fit a 3D pocket. These two methods involve searching for similar small molecules that are purchasable in the database based on the generated ones, or creating new molecules from those in the database that can fit into a 3D pocket. Experimental results demonstrate that Rag2Mol methods consistently produce drug candidates with superior binding affinities and drug-likeness. We find that Rag2Mol-R provides a broader coverage of the chemical landscapes and more precise targeting capability than advanced virtual screening models. Notably, both workflows identified promising inhibitors for the challenging target PTPN2, which was considered undruggable because of structural characteristics of phosphatases. Our highly extensible framework can integrate diverse SBDD methods, marking a significant advancement in AI-driven SBDD. The codes are available at:https://github.com/CQ-zhang-2016/Rag2Mol.