Breastfeeding in US working mothers: A systematic review.

BACKGROUND: Previous studies demonstrate that exclusive breastfeeding has positive long-term health effects on the mother and infant, but research has shown that nearly 50% of mothers do not breastfeed for the recommended amount of time. OBJECTIVE: This article systematizes previous quantitative research on the impact of work on breastfeeding practices to identify the factors that correlate to the cessation of breastfeeding in working mothers. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements, we performed a systematic review that screened PubMed, CINAHL, PsycINFO, and Academic Search Complete databases for articles relating to maternal employment and breastfeeding. RESULTS: Of the 13,106 articles assessed for eligibility, 21 studies met all requirements and were included in this systematic review. The 21 articles were divided into study type and methods, participant demographics, study outcomes, and additional factors that included stressors and stress levels, factors that increased or decreased rates of breastfeeding, and feeding methods. Articles outside of the United States were excluded due to differences in maternity leave policies of other countries impacting the data. CONCLUSION: Cessation of breastfeeding and breastfeeding outcomes were seen to have a strong association with maternal employment, specifically with the policies and employer support in the workplace. Other factors such as race, level of education, and stress were also shown to relate to breastfeeding outcomes and are important to consider in future public health interventions and workplace policies.

Utility of artificial intelligence in the diagnosis and management of keratoconus: a systematic review.

Introduction: The application of artificial intelligence (AI) systems in ophthalmology is rapidly expanding. Early detection and management of keratoconus is important for preventing disease progression and the need for corneal transplant. We review studies regarding the utility of AI in the diagnosis and management of keratoconus and other corneal ectasias. Methods: We conducted a systematic search for relevant original, English-language research studies in the PubMed, Web of Science, Embase, and Cochrane databases from inception to October 31, 2023, using a combination of the following keywords: artificial intelligence, deep learning, machine learning, keratoconus, and corneal ectasia. Case reports, literature reviews, conference proceedings, and editorials were excluded. We extracted the following data from each eligible study: type of AI, input used for training, output, ground truth or reference, dataset size, availability of algorithm/model, availability of dataset, and major study findings. Results: Ninety-three original research studies were included in this review, with the date of publication ranging from 1994 to 2023. The majority of studies were regarding the use of AI in detecting keratoconus or subclinical keratoconus (n=61). Among studies regarding keratoconus diagnosis, the most common inputs were corneal topography, Scheimpflug-based corneal tomography, and anterior segment-optical coherence tomography. This review also summarized 16 original research studies regarding AI-based assessment of severity and clinical features, 7 studies regarding the prediction of disease progression, and 6 studies regarding the characterization of treatment response. There were only three studies regarding the use of AI in identifying susceptibility genes involved in the etiology and pathogenesis of keratoconus. Discussion: Algorithms trained on Scheimpflug-based tomography seem promising tools for the early diagnosis of keratoconus that can be particularly applied in low-resource communities. Future studies could investigate the application of AI models trained on multimodal patient information for staging keratoconus severity and tracking disease progression.

Vernal keratoconjunctivitis in adults: a narrative review of prevalence, pathogenesis, and management.

Vernal keratoconjunctivitis (VKC) is a chronic, progressive, allergic ocular surface disorder that can lead to sight-threatening complications. VKC occurs primarily in children and generally resolves about the time of puberty; however, case series and retrospective analyses indicate that approximately 10% of patients with VKC are adults, and that a subset of adult cases develop after puberty. Consequently, two age-related variants of VKC have recently been described: early-onset VKC-which manifests during childhood and persists into adult life-and late-onset disease, which emerges de novo after puberty. Although the signs and symptoms of adult and childhood VKC are similar, adult VKC is a long-lasting disease characterized by severe inflammation and increased risk of conjunctival fibrosis, which may place adult patients at higher risk for sight-threatening complications and adverse impacts on daily life. This review discusses the epidemiology, signs, symptoms, immunopathogenesis of adult VKC variants, and highlights current gaps in research and management of patients with this condition.

Impact of CYP3A5 Polymorphisms on Pediatric Asthma Outcomes.

Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2-18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes. A subset of patients provided saliva samples for SNP analysis and participated in a pharmacokinetic study. Multivariable regression analysis adjusted for age, sex, race, and ethnicity was used to evaluate the impact of CYP3A5 SNPs on asthma outcomes, including asthma control (measured using the asthma symptom tracker, a modified version of the asthma control test or ACT), exacerbations, and hospital admissions. Plasma corticosteroid and cortisol concentrations post-ICS dosing were also assayed using liquid chromatography-tandem mass spectrometry. Of the 751 patients using the e-AT, 166 (22.1%) provided saliva samples and 16 completed the PK study. The e-AT cohort was 65.1% male, and 89.6% White, 6.0% Native Hawaiian, 1.2% Black, 1.2% Native American, 1.8% of unknown race, and 15.7% Hispanic/Latino; the median age was 8.35 (IQR: 5.51-11.3) years. CYP3A5*3/*3 frequency was 75.8% in White subjects, 50% in Native Hawaiians and 76.9% in Hispanic/Latino subjects. Compared with CYP3A5*3/*3, the CYP3A5*1/*x genotype was associated with reduced weekly asthma control (OR: 0.98; 95% CI: 0.97-0.98; p < 0.001), increased exacerbations (OR: 6.43; 95% CI: 4.56-9.07; p < 0.001), and increased asthma hospitalizations (OR: 1.66; 95% CI: 1.43-1.93; p < 0.001); analysis of 3/*3, *1/*1 and *1/*3 separately showed an allelic copy effect. Finally, PK analysis post-ICS dosing suggested muted changes in cortisol concentrations for patients with the CYP3A5*3/*3 genotype, as opposed to an effect on ICS PK. Detection of CYP3A5*3/3, CYPA35*1/*3, and CYP3A5*1/*1 could impact inhaled steroid treatment strategies for asthma in the future.

Foveal photoreceptor atrophy, persistent fetal vasculature, congenital cataracts, and microphthalmia in a pediatric patient with BCOR-associated oculo-facio-cardio-dental (OFCD) syndrome.

Purpose: To report a case of oculo-facio-cardio-dental (OFCD) syndrome secondary to a novel BCOR variant in a pediatric patient with congenital cataracts, microphthalmia, persistent fetal vasculature (PFV), focal chorioretinal hyperpigmentation, peripheral retinal avascularity, and foveal photoreceptor atrophy. Observations: A 3-month-old female patient was referred for bilateral congenital cataracts with microphthalmia. Her past medical history was significant for syndactyly of the toes, left bifid rib, atrial septal defect, patent ductus arteriosus, mitral regurgitation, pulmonary hypertension, anemia of prematurity, vesicoureteral reflux, and duodenal atresia. Examination under anesthesia revealed persistent fetal vasculature (PFV) with peripheral avascularity, foveal photoreceptor atrophy, and focal chorioretinal hyperpigmentation. A bilateral lensectomy with anterior vitrectomy and posterior capsulotomy were performed. Genetic testing identified a novel heterozygous pathogenic variant in the BCOR gene (c.1612C > T (p.Gln538Ter)), confirming a diagnosis of OFCD syndrome. Conclusions and importance: This case describes novel posterior segment findings in a patient with OFCD. A detailed examination of both anterior and posterior segments in combination with multimodal imaging should be performed in patients suspected of having OFCD, as this may be critical in determining visual potential and appropriate surgical management.

Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.

Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance. Here, we report the development of antibody fusion proteins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The complementary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell activation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic antibodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes.

Leveraging baseline covariates to analyze small cluster-randomized trials with a rare binary outcome.

Cluster-randomized trials (CRTs) involve randomizing entire groups of participants-called clusters-to treatment arms but are often comprised of a limited or fixed number of available clusters. While covariate adjustment can account for chance imbalances between treatment arms and increase statistical efficiency in individually randomized trials, analytical methods for individual-level covariate adjustment in small CRTs have received little attention to date. In this paper, we systematically investigate, through extensive simulations, the operating characteristics of propensity score weighting and multivariable regression as two individual-level covariate adjustment strategies for estimating the participant-average causal effect in small CRTs with a rare binary outcome and identify scenarios where each adjustment strategy has a relative efficiency advantage over the other to make practical recommendations. We also examine the finite-sample performance of the bias-corrected sandwich variance estimators associated with propensity score weighting and multivariable regression for quantifying the uncertainty in estimating the participant-average treatment effect. To illustrate the methods for individual-level covariate adjustment, we reanalyze a recent CRT testing a sedation protocol in 31 pediatric intensive care units.

Propensity score stratified MAP prior and posterior inference for incorporating information across multiple potentially heterogeneous data sources.

Incorporation of external information is becoming increasingly common when designing clinical trials. Availability of multiple sources of information has inspired the development of methodologies that account for potential heterogeneity not only between the prospective trial and the pooled external data sources but also between the different external data sources themselves. Our approach proposes an intuitive way of handling such a scenario for the continuous outcomes setting by using propensity score-based stratification and then utilizing robust meta-analytic predictive priors for each stratum to incorporate the prior data to distinguish among different external data sources in each stratum. Through extensive simulations, our approach proves to be more efficient and less biased than the currently available methods. A real case study using clinical trials that study schizophrenia from multiple different sources is also included.

Association of Emergency Department Evaluation With Public Insurance Use and Treatment Delays for ACL Injury.

Background: Utilization of an emergency department (ED) visit for anterior cruciate ligament (ACL) injury is associated with high cost and diagnostic unreliability. Hypothesis: Patients initially evaluated at an ED for an ACL injury would be more likely to be from a lower income quartile, use public insurance, and experience a delay in treatment. Study Design: Cohort study; Level of evidence, 3. Methods: Patients in the Rhode Island All Payers Claims Database who underwent ACL reconstruction (ACLR) between 2012 and 2021 were identified using the Current Procedure Terminology (CPT) code 29888. Patients were stratified into 2 cohorts based on CPT codes for ED or in-office services within 1 year of ACLR. A chi-square analysis was used to test for differences between cohorts in patient and surgical characteristics. Multivariable linear and logistic regression were used to determine how ED evaluation affected timing and outcome variables. Results: While adjusting for patient and operative characteristics, patients in the ED cohort were more likely to have Medicaid (29% vs 12.5%; P < .001) and be in the lowest income quartile (44.6% vs 32.1%; P < .001). ED visit and Medicaid status were associated with increased time to (1) diagnostic magnetic resonance imaging, adding 7.97 days on average (95% CI, 4.14-11.79 days; P < .001) and 8.40 days (95% CI, 3.44-13.37 days; P = .001), respectively; and (2) surgery, adding 20.30 days (95% CI, 14.10-26.49 days; P < .001) and 12.88 days (95% CI, 5.15-20.60 days; P = .001), respectively. Patients >40 years who were evaluated in the ED were 2.5 times more likely to require subsequent ACLR (odds ratio, 2.50 [95% CI, 1.01-6.21]; P = .049). Conclusion: In this study, patients who visited the ED within 1 year before ACLR were more likely to have a lower income, public insurance, increased time to diagnostic imaging, and increased time to surgery, as well as decreased postoperative physical therapy use and increased subsequent ACLR rates in the 40-49 years age-group.

Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (SBRT).

PURPOSE/OBJECTIVES: Patients with lung cancer sometimes present with multiple primary lung cancers (MPLCs), either simultaneously (synchronous) or after treatment of an initial lesion (metachronous). Although open surgery remains a treatment mainstay for patients with stage I-II non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) is an acceptable alternative for patients who are medically unfit for or who refuse surgery. In this study, we retrospectively examine the outcome among patients with early-stage MPLCs treated at our institution with SBRT. MATERIALS/METHODS: Patients at our institution receiving SBRT for MPLC between June 2011 and March 2020 were reviewed retrospectively. Prior to undergoing definitive SBRT, the imaging, and pathology for every patient were reviewed in a multi-disciplinary thoracic/pulmonary tumor board. Dose and fractionation varied with the most common prescriptions being 50 Gy/5 fractions, 56 Gy/4 fractions, and 55 Gy/5 fractions. RESULTS: A total of 38 patients with a total of 80 MPLCs were treated, among which 68 were T1 lesions and 12 were T2 lesions. Median follow-up was 25.9 months, with local control (LC) rates calculated per lesion to be 98.6%, 93.3%, and 88.2% at one, two, and three years. Median overall survival (OS) was 43.5 months; 83.6%, 67.8%, and 52.3% at one, two, and three years, respectively. Sixty-two of the 80 (77.5%) treated lesions were not associated with any subsequent acute or late toxicity. The 18 (22.5%) lesions associated with toxicity included nine acute and nine late events. All toxicity was either grade 1 (13 of 18) or grade 2 (five of 18). CONCLUSIONS: SBRT for early-stage MPLC achieves high control rates with limited toxicity. MPLC patients deemed unfit for open surgical management should be considered for definitive SBRT.

Genome Mining and Discovery of Imiditides, a Family of RiPPs with a Class-Defining Aspartimide Modification.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large and diverse class of natural products of ribosomal origin. In the past decade, various sophisticated machine-learning-based software packages have been established to discover novel RiPPs that do not resemble the known families. Here, we show that tailoring enzymes that cluster with various RiPP families can serve as effective bioinformatic seeds, providing a complementary approach for novel RiPP discovery. Leveraging the fact that O-methyltransferases homologous to protein isoaspartyl methyltransferases (PIMTs) are associated with lasso peptide, graspetide, and lanthipeptide biosynthetic gene clusters (BGCs), we utilized a C-terminal motif unique to RiPP-associated O-methyltransferases as the search query to discover a novel family of RiPPs, the imiditides. Our genome-mining algorithm reveals a total of 670 imiditide BGCs, distributed across Gram-positive bacterial genomes. In addition, we demonstrate the heterologous production of the founding member of the imiditide family, mNmaAM, encoded in the genome of Nonomuraea maritima. In contrast to other RiPP-associated PIMTs that recognize constrained peptides as substrates, the PIMT homologue in the mNmaAM BGC, NmaM, methylates a specific Asp residue on the linear precursor peptide, NmaA. The methyl ester is then turned into an aspartimide spontaneously. Substrate specificity is achieved by extensive charge-charge interactions between the precursor NmaA and the modifying enzyme NmaM suggested by both experiments and an AlphaFold model prediction. Our study shows that PIMT-mediated aspartimide formation is an emerging backbone modification strategy in the biosynthesis of multiple RiPP families.

Association of multi-criteria derived air toxics hazard score with lung cancer incidence in a major metropolitan area.

Background: Lung cancer remains a major health problem world-wide. Environmental exposure to lung cancer carcinogens can affect lung cancer incidence. We investigated the association between lung cancer incidence and an air toxics hazard score of environmental carcinogen exposures derived previously under the exposome concept. Methods: Lung cancer cases diagnosed in Philadelphia and the surrounding counties between 2008 and 2017 were identified from the Pennsylvania Cancer Registry. Age-adjusted incidence rates at the ZIP code level were calculated based on the residential address at diagnosis. The air toxics hazard score, an aggregate measure for lung cancer carcinogen exposures, was derived using the criteria of toxicity, persistence, and occurrence. Areas with high incidence or hazard score were identified. Spatial autoregressive models were fitted to evaluate the association, with and without adjusting for confounders. Stratified analysis by smoking prevalence was performed to examine potential interactions. Results: We observed significantly higher age-adjusted incidence rates in ZIP codes that had higher air toxics hazard score values after controlling for demographic variables, smoking prevalence, and proximity to major highways. Analyzes stratified by smoking prevalence suggested that exposure to environmental lung carcinogens had a larger effect on cancer incidence in locations with higher smoking prevalence. Conclusion: The positive association between the multi-criteria derived air toxics hazard score and lung cancer incidence provides the initial evidence to validate the hazard score as an aggregate measure of carcinogenic exposures in the environment. The hazard score can be used to supplement the existing risk factors in identifying high risk individuals. Communities with higher incidence/hazard score may benefit from greater awareness of lung cancer risk factors and targeted screening programs.

Alternatives to transvenous lead placement in a patient undergoing surgical tricuspid valve repair.

Tricuspid regurgitation is a widely recognised phenomenon in patients with transvenous cardiac rhythm management (CRM) devices. If tricuspid valve repair or replacement is to be considered, what to do with the existing CRM system requires scrutiny with multidisciplinary input. We present a case of multifactorial tricuspid regurgitation in a 48-year-old female with giant cell myocarditis and a transvenous implantable cardioverter-defibrillator (ICD). Key considerations in management and alternative CRM options are discussed.

Role of the ocular surface microbiome in allergic eye diseases.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on emerging literature on the role of the ocular surface microbiome (OSM) in allergic eye diseases. RECENT FINDINGS: Findings in the literature suggest that the ocular surface microbiome plays a role in the pathophysiology and course of allergic disease of the ocular surface. SUMMARY: Knowledge regarding the role of the ocular surface microbiome in allergic disease is important to guide development of targets for future therapeutic interventions.

E-commerce development and its contribution to agricultural non-point source pollution control: Evidence from 283 cities in China.

Agricultural non-point source (ANPS) pollution is a pressing environmental issue in developing countries that poses a substantial threat to sustainable development. With the rapid growth of e-commerce and its great penetration and transformation in many socioeconomic sectors, e-commerce plus agriculture is widely regarded as the solution to sustainable agricultural development. However, the environmental impacts of e-commerce on agriculture, as well as the underlying mechanisms have yet to be fully explored and verified. Based on China's practices of e-commerce development and its integration with agriculture, a panel dataset of 283 prefecture-level cities from 2009 to 2019 was collected, and a spatial difference in difference (SDID) model combined with a Durbin model was constructed to examine the local and spatial spillover effects of e-commerce development on ANPS pollution. It is found out that e-commerce development has significant positive environmental impacts achieved by stimulating industrial structure upgrading and promoting green technology innovation, while the mechanism of cultivation scaling up tends to aggravate the ANPS pollution. Spatial analysis demonstrates that e-commerce development also helps alleviate the ANPS pollution of neighboring regions with a decayed effect over a distance. Meanwhile, the impact of e-commerce on mitigating ANPS pollution shows regional heterogeneity. Those developed regions present significant positive effects, while those regions dominated by agriculture economy and without sufficient supporting facilities for e-commerce development, show significant negative effects. Therefore, we argue that the positive environmental contribution of e-commerce is not bound to happen but instead is contingent, while policies should be adapted to local conditions and enhanced to encourage the integration of e-commerce and other socioeconomic sectors, in order to develop beyond the immature pioneering stage.

Subcutaneous defibrillator use with unipolar pacemakers: Cautiously possible.

Implantation of subcutaneous implantable cardioverter-defibrillator in a patient with existing unipolar pacemaker is against manufacturer recommendations. We report the case of a successful subcutaneous implantable cardioverter-defibrillator implantation in a patient with Fontan circulation and concomitant active unipolar pacing and present a summary of recommendations when considering subcutaneous implantable cardioverter-defibrillator implantation with unipolar pacing. Recommendations included: pre-procedure screening, rescreening during implantation and ventricular fibrillation induction, pacemaker programming, and post-procedure investigations.

Genome Mining and Discovery of Imiditides, a Novel Family of RiPPs with a Class-defining Aspartimide Modification.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a fascinating class of natural products of ribosomal origins. In the past decade, various sophisticated machine learning-based software packages have been established to discover novel RiPPs that do not resemble the known families. Instead, we argue that tailoring enzymes that cluster with various RiPP families can serve as effective bioinformatic seeds for novel RiPP discovery. Leveraging that O -methyltransferases homologous to protein isoaspartyl methyltransferases (PIMTs) are associated with lasso peptide, graspetide, and lanthipeptide biosynthetic gene clusters (BGCs), we utilized the C-terminal motif unique to RiPP-associated O -methyltransferases as the search query to discover a novel family of RiPPs, imiditides. Our genome-mining algorithm reveals a total of 670 imiditide BGCs, widely distributed in Gram-positive bacterial genomes. In addition, we demonstrate the heterologous production of the founding member of the imiditide family, mNmaA M , encoded in the genome of Nonomuraea maritima . In contrast to other RiPP associated PIMTs that recognize constrained peptides as substrates, the PIMT homolog in mNmaA M BGC, NmaM, methylates a specific Asp residue on the linear precursor peptide, NmaA. The methyl ester is then turned into an aspartimide spontaneously. The aspartimide moiety formed is unusually stable, leading to the accumulation of the aspartimidylated product in vivo . The substrate specificity is achieved by extensive charge-charge interactions between the precursor NmaA and the modifying enzyme NmaM suggested by both experimental validations as well as an AlphaFold model prediction. Our study suggests that PIMT-mediated aspartimide formation is an underappreciated backbone modification strategy in RiPP biosynthesis, compared to the well-studied backbone rigidification chemistries, such as thiazol(in)e and oxazol(in)e formations. Additionally, our findings suggest that aspartimide formation in Gram-positive bacterial proteomes are not limited to spontaneous protein aging and degradation.

Objectively-Assessed Ultraviolet Radiation Exposure and Sunburn Occurrence.

Ultraviolet radiation (UVR) exposure is the primary modifiable risk factor for melanoma. Wearable UVR sensors provide a means of quantifying UVR exposure objectively and with a lower burden than self-report measures used in most research. The purpose of this study was to evaluate the relationship between detected UVR exposure and reported sunburn occurrence. In this study, a UVR monitoring device was worn by 97 parent-child dyads during waking hours for 14 days to measure instantaneous and accumulated UVR exposure. The results showed that the participants' total UVR exposure was associated with reported sunburn after adjusting for Fitzpatrick skin type and geographic location. It was observed that one standard erythemal dose (SED) increase in the participants' daily total UVR exposure was associated with reported sunburn (an odds ratio (OR) of 1.26 with a 95% CI of 1.13 and 1.41, and p < 0.001 for parents and an OR of 1.28 with a 95% CI of 1.12 and 1.47, and p < 0.001 for children). A one-SED increase in the participants' UVR exposure from 10 am to 4 pm was also associated with reported sunburn (an OR of 1.31 with a 95% CI of 1.15 and 1.49, and p < 0.001 for parents and an OR of 1.33 with a 95% CI of 1.12 and 1.59, and p = 0.001 for children). We found that elevated UVR exposure recordings measured by the UVR sensor were associated with reported sunburn occurrence. Future directions for wearable UVR sensors may include their use as an intervention tool to support in-the-moment sunburn prevention.

Predictors of Citations for Original Research in Ophthalmology.

There is a dearth of literature on factors associated with citation of publications in ophthalmology. We investigated predictors of citations for original ophthalmologic research articles based on author, study, and journal characteristics. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), we extracted articles that studied the leading cause of vision impairment in the United States (cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma) and were published in the top fifteen ophthalmology journals with the highest impact factors that accepted original research. Descriptive statistics, one-way analysis of variance (ANOVA) tests, and negative binomial regression were used to compare citation counts based on author, study, and journal characteristics. In this study, author research productivity, journal impact factor, study funding, and location in high-income countries were predictors of increased citation in ophthalmology.