bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study
Authors: Jayasinghe Sanjay , Williams Phoebe C M , Macartney Kristine K , Crawford Nigel W , Blyth Christopher C 
Published: August 2024

Abstract

Background
In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged &gt;12 months. This study assessed the impact of this change using national IPD surveillance data.

Methods
Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged &lt;12 years were compared to that expected if the 3+0 schedule were continued.

Findings
Over 2012–2022, rate of 3-dose breakthrough cases in children aged &gt;12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%–4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28–.84] and 1.12 [0.71–1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, −60.9 to −40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (−9.6 to 39.7).

Interpretations
The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.
The geometry of admixture in population genetics: the blessing of dimensionality
Authors: Oteo José-Angel , Oteo-García Gonzalo 
Published: August 2024

Abstract
We present a geometry-based interpretation of the f-statistics framework, commonly used in population genetics to estimate phylogenetic relationships from genomic data. The focus is on the determination of the mixing coefficients in population admixture events subject to post-admixture drift. The interpretation takes advantage of the high dimension of the dataset and analyzes the problem as a dimensional reduction issue. We show that it is possible to think of the f-statistics technique as an implicit transformation of the genomic data from a phase space into a subspace where the mapped data structure is more similar to the ancestral admixture configuration. The 2-way mixing coefficient is, as a matter of fact, carried out implicitly in this subspace. In addition, we propose the admixture test to be evaluated in the subspace because the comparison with the conventional one provides an important assessment of the admixture model. The overarching geometric framework provides slightly more general formulas than the f-formalism by using a different rationale as a starting point. Explicitly addressed are 2- and 3-way admixtures. The mixture proportions are provided by suitable linear fits, in 2 or 3 dimensions, that can be easily visualized. The difficulties encountered with introgression and gene flow are also addressed. The developments and findings are illustrated with numerical simulations and real-world cases.
Direct inference of the distribution of fitness effects of spontaneous mutations from recombinant inbred Caenorhabditis elegans mutation accumulation lines
Authors: Crombie Timothy A , Rajaei Moein , Saxena Ayush Shekhar , Johnson Lindsay M , Saber Sayran , Tanny Robyn E , Ponciano José Miguel , Andersen Erik C , Zhou Juannan , Baer Charles F 
Published: August 2024

Abstract
The distribution of fitness effects of new mutations plays a central role in evolutionary biology. Estimates of the distribution of fitness effect from experimental mutation accumulation lines are compromised by the complete linkage disequilibrium between mutations in different lines. To reduce the linkage disequilibrium, we constructed 2 sets of recombinant inbred lines from a cross of 2 Caenorhabditis elegans mutation accumulation lines. One set of lines (“RIAILs”) was intercrossed for 10 generations prior to 10 generations of selfing; the second set of lines (“RILs”) omitted the intercrossing. Residual linkage disequilibrium in the RIAILs is much less than in the RILs, which affects the inferred distribution of fitness effect when the sets of lines are analyzed separately. The best-fit model estimated from all lines (RIAILs + RILs) infers a large fraction of mutations with positive effects (∼40%); models that constrain mutations to have negative effects fit much worse. The conclusion is the same using only the RILs. For the RIAILs, however, models that constrain mutations to have negative effects fit nearly as well as models that allow positive effects. When mutations in high linkage disequilibrium are pooled into haplotypes, the inferred distribution of fitness effect becomes increasingly negative-skewed and leptokurtic. We conclude that the conventional wisdom—most mutations have effects near 0, a handful of mutations have effects that are substantially negative, and mutations with positive effects are very rare—is likely correct, and that unless it can be shown otherwise, estimates of the distribution of fitness effect that infer a substantial fraction of mutations with positive effects are likely confounded by linkage disequilibrium.
A Rapid and Scalable Multiplex PCR-Based Next-Generation Amplicon Sequencing Method for Familial Hypercholesterolemia Genetic Screening
Authors: Imran Mohamed , Arvinden V R , Mehanathan Pabithadevi Balaiah , Rajagopal Raskin Erusan , Muthu Suriya Prabha , Arunachalam Arul Subbiah , Bhoyar Rahul C , Vignesh Harie , Mitra Samya , Jha Ganga Nath , Gupta Aayush , Kumar Manoj , Bhowmick Rohit , Bhunia Niladri Sekhar , Dutta Atanu Kumar , Scaria Vinod , Sivasubbu Sridhar 
Published: August 2024

Abstract

Background
Familial hypercholesterolemia (FH) is a frequently underdiagnosed genetic disorder characterized by elevated low-density lipoprotein (LDL) levels. Genetic testing of LDLR, APOB, and PCSK9 genes can identify variants in up to 80% of clinically diagnosed patients. However, limitations in time, scalability, and cost have hindered effective next-generation sequencing of these genes. Additionally, pharmacogenomic variants are associated with statin-induced adverse effects in FH patients. To address these challenges, we developed a multiplex primer-based amplicon sequencing approach for FH genetic testing

Methods
Multiplex primers were designed for the exons of the LDLR, APOB, and PCSK9 genes, as well as for pharmacogenomic variants rs4149056 (SLCO1B1:c.521T &gt; A), rs2306283 (SLCO1B1:c.388A &gt; G), and rs2231142 (ABCG2:c.421C &gt; A). Analytical validation using samples with known pathogenic variants and clinical validation with 12 FH-suspected probands were conducted. Library preparation was based on a bead-based tagmentation method, and sequencing was conducted on the NovaSeq 6000 platform.

Results
Our approach ensured no amplicon dropouts, with over 100× coverage on each amplicon. Known variants in 2 samples were successfully detected. Further, we identified one heterozygous LDLR (p.Glu228Ter) variant and 2 homozygous cases of LDLR (p.Lys294Ter) and LDLR (p.Ser177Leu) variants in patients. Pharmacogenomic analysis revealed that overall 3 patients may require reduced statin doses. Our approach offered reduced library preparation time (approximately 3 h), greater scalability, and lower costs (under $50) for FH genetic testing.

Conclusions
Our method effectively sequences LDLR, APOB, and PCSK9 genes including pharmacogenomic variants that will guide appropriate screening and statin dosing, thus increasing both efficiency and affordability.
Cancer information and population health resource: a resource for catchment area data and cancer outcomes research
Authors: Baggett Christopher D , Jackson Bradford E , Green Laura , Kuo Tzy-Mey , Kim KyungSu , Zhou Xi , Reeder-Hayes Katherine E , Lund Jennifer L , Wheeler Stephanie B , Olshan Andrew F 
Published: August 2024

Abstract

Background
The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center has developed a novel data resource, the Cancer Information and Population Health Resource (CIPHR), for conducting catchment area evaluation and cancer population health research that links the North Carolina Central Cancer Registry (NCCCR) to medical and pharmacy claims data from Medicare, Medicaid, and private plans operating within North Carolina. This study’s aim was to describe the CIPHR data and provide examples of potential cohorts available in those data.

Methods
We present the underlying populations included in the NCCCR and claims data before linkage and demonstrate estimated sample sizes when these data are linked and commonly used insurance enrollment criteria are applied.

Results
Data for the years 2003-2020 are present in CIPHR and include 947 977 cancer cases from the NCCCR and 21.6 million enrollees in public and private health insurance (cancer and noncancer cases). When limited to first or only cancers (n = 672 377), 86% could be linked to insurance enrollment for at least 1 month during 2003-2020 (n = 582 638), with 62% of individuals linking to enrollment during the month of cancer diagnosis. Among all registry cancer cases, 47% (n = 317 898) had continuous insurance enrollment for at least 12 months before and after cancer diagnosis.

Conclusion
CIPHR illustrates the utility of establishing and maintaining a statewide, comprehensive cancer population health database. This resource serves to characterize the cancer center catchment area and aids in tracking cancer outcomes and trends in care delivery as well as identifying disparities that require intervention and policy focus.
Immune checkpoint inhibitor–associated nephritis—treatment standard
Authors: Barbir Elena-Bianca , Kitchlu Abhijat , Herrmann Sandra M 
Published: August 2024

ABSTRACT
Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAEs) more frequently. Renal irAEs, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2%–5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 and its ligand (PD1/PDL-1) blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management and prognostication of ICI-AKI.
An image-domain deep-learning denoising technique for accelerated parallel brain MRI: prospective clinical evaluation
Authors: Onac Laura , Dobai Lorand , Mouraviev Andrei , Badila Mihai A , Yap Denise , Kennedy Samantha , Nguyen Annie , Gal Emi , Sodickson Daniel K 
Published: August 2024

Abstract

Background
Parallel imaging can accelerate MRI acquisitions, but excessive accelerations can introduce amplified noise and aliasing artifacts.

Purpose
To evaluate a vendor-agnostic AI-based approach to remove image degradation artifacts in highly accelerated MRI scans, improving image quality and reducing scan time.

Materials and methods
Training was performed by retrospectively degrading standard accelerated images. Evaluation was performed with both retrospective and prospectively-collected highly accelerated images. Retrospective data were taken from ∼2000 MRI studies obtained between August 2016 and October 2022, and prospective data were collected in &gt;200 subjects between June and November 2022, using scanners from multiple vendors and locations. Scan time data were collected from prospective studies and used to compute time savings per sequence and per protocol for each vendor. Images were evaluated qualitatively by 5 board-certified radiologists and quantitatively by assessing noise, contrast, and spatial resolution. Paired Wilcoxon signed-rank tests were used to compare model outputs to model inputs and low-acceleration images.

Results
Images from 101 adults from 5 sites and 6 scanner models from different vendors were enrolled. 89% of imaged subjects had noteworthy imaging features or pathology. Model outputs were rated superior to model inputs (P &lt; .001) and most were either non-inferior (Pinf &gt; .05) or superior (Psup &lt; .05) to baseline images in qualitative metrics of image quality and feature visibility. Quantitative evaluation of signal-to-noise ratio and contrast-to-noise ratio improved for model outputs compared to inputs (P &lt; .001) or baseline images (P &lt; .005). Apparent resolution measured using the full width at half maximum or minimum was either enhanced (Psup &lt; .05) or preserved (non-superior Psup &gt; .05 and non-inferior Pinf &gt; .05). The scan time was reduced by an average of 29% (19%-41% per sequence).

Conclusion
This vendor-agnostic AI-based method achieved robust scan time savings without loss of image quality, potentially allowing for reduced cost and improved patient experience.
Interferon‐gamma signaling drives epithelial TNF‐alpha receptor‐2 expression during colonic tissue repair
Authors: Watson Sean , Cabrera‐Silva Rodolfo I. , Parkos Charles A. , Nusrat Asma , Quiros Miguel 
Published: August 2024

AbstractInterferon‐gamma (IFNγ) is traditionally recognized for its pro‐inflammatory role during intestinal inflammation. Here, we demonstrate that IFNγ also functions as a pro‐repair molecule by increasing TNFα receptor 2 (TNFR2 protein/TNFRSF1B gene) expression on intestinal epithelial cells (IEC) following injury in vitro and in vivo. In silico analyses identified binding sites for the IFNγ signaling transcription factor STAT1 in the promoter region of TNFRSF1B. Scratch‐wounded IEC exposed to IFNγ exhibited a STAT1‐dependent increase in TNFR2 expression. In situ hybridization revealed elevated Tnfrsf1b mRNA levels in biopsy‐induced colonic mucosal wounds, while intraperitoneal administration of IFNγ neutralizing antibodies following mucosal injury resulted in impaired IEC Tnfrsf1b mRNA and inhibited colonic mucosal repair. These findings challenge conventional notions that “pro‐inflammatory” mediators solely exacerbate damage by highlighting latent pro‐repair functions. Moreover, these results emphasize the critical importance of timing and amount in the synthesis and release of IFNγ and TNFα during the inflammatory process, as they are pivotal in restoring tissue homeostasis.
Fetomaternal Hemorrhage and Choriocarcinoma
Authors: Farmer Meredith 
Published: August 2024

Background:
This case describes chronic anemia of a late preterm infant secondary to maternal–fetal hemorrhage and subsequent findings of maternal choriocarcinoma.

Clinical Findings:
This infant was born at 35 6/7 weeks gestational age via cesarean section for non-reassuring fetal heart tones. The mother presented with decreased fetal movement and the biophysical profile was 4/8. Following delivery, the infant did not require respiratory support, was vigorous with extreme pallor, and had a hemoglobin of less than 5 on cord gas.

Primary Diagnosis:
Chronic anemia secondary to fetomaternal hemorrhage.

Interventions:
The infant’s initial hemoglobin was 2.4 and hematocrit was 8.1. The mother’s Kleihauer-Betke test was elevated at 7%. The infant required a partial exchange transfusion following admission to the neonatal intensive care unit. Following the partial exchange transfusion, the infant began to experience increasing respiratory distress and required respiratory support. An echocardiogram showed severe persistent pulmonary hypertension of the neonate. The mother was subsequently diagnosed with choriocarcinoma.

Outcomes:
The infant fully recovered from chronic anemia and persistent pulmonary hypertension of the neonate and was discharged home with the mother. The infant required follow-up testing for choriocarcinoma outpatient.

Practice Recommendations:
Newborns diagnosed with early chronic anemia should be evaluated, the cause investigated, and appropriate treatment considered. If the cause of blood loss is unknown, a maternal Kleihauer-Betke test should be considered. In this case, a partial exchange transfusion was performed to avoid cardiovascular volume overload, but another course of treatment could include small aliquots of packed red blood cell transfusions.
The Effect of Oral Colostrum Application on the Condition of the Mouth and Incidence of Late-Onset Sepsis Among Premature Infants
Authors: Barizeh Leila , Jabraeili Mahnaz , Hoseini Mohammad Bagher , Rahkar Farshi Mahni , Martyn Julie-Anne , Thapa Deependra Kaji , Cleary Michelle 
Published: August 2024

Background:
Premature infants have higher risks of infection due to their underdeveloped immune systems and changes to the oral cavity’s normal flora colonization.

Purpose:
To assess the effect of oral colostrum application on the condition of the mouth and the incidence of late-onset sepsis (LOS) among premature infants.

Methods:
In this randomized controlled trial, 70 newborn premature infants were randomly allocated to colostrum or sterile water groups. The Mouth Care Assessment Tool was used to evaluate the condition of the mouth for 5 days after oral colostrum application. The incidence of LOS was measured using clinical and laboratory indicators from 72 hours after birth until discharge.

Results:
The condition of the mouth was significantly different on days 4 and 5, demonstrating that the colostrum group had less need for oral care (P < .001) compared to the control group. There was no significant difference between the 2 groups in clinical symptoms and laboratory values related to LOS (P > .05).

Implications for practice:
Oral colostrum application can benefit oral mucosal health and reduce the need for oral care among premature infants. It is also safe alternative oral care for premature infants who cannot breastfeed during the first few days of life. Future research should include infants of different gestational ages and mechanically ventilated infants to assess the effect of oral colostrum application on serum immune factors.
Hearing Loss and Annual Earnings Over a 20-Year Period: The HUNT Cohort Study
Authors: Jørgensen Astrid Ytrehus , Engdahl Bo , Bratsberg Bernt , Mehlum Ingrid Sivesind , Hoffman Howard J. , Aarhus Lisa 
Published: August 2024

Objectives:
The association between hearing loss and income has only been examined in cross-sectional studies. We aim to study annual increase in earnings over 20 years, comparing people with and without hearing loss.

Design:
We used data from a population-based hearing study in Norway (The Trøndelag Health Study, 1996–1998), including 14,825 persons (46.2% men, mean age at baseline 30.6 years, age range 20 to 40 years). Hearing loss was defined as the pure-tone average threshold of 0.5 to 4 kHz in the better hearing ear ≥20 dB HL (n = 230). Annual earnings were assessed from 1997 to 2017. Longitudinal analyses were performed with linear mixed models adjusted for age, sex, and education.

Results:
People without hearing loss at baseline (before age 40) had a greater annual increase in earnings over a 20-year follow-up period compared with people with hearing loss. For people with normal hearing, annual earnings over 20 years increased by 453 Euro (EUR) (95% confidence interval [CI] = 384 to 522) or 13.2% more per year than for people with hearing loss, adjusted for age and sex. The difference in annual earnings over 20 year was greater among women (462 EUR, 95% CI = 376 to 547) than men (424 EUR, 95% CI = 315 to 533), greater among younger than older adults, and greater among lower than higher educated persons. When including adjustment for education in the model, in addition to age and sex, the difference in annual earnings over 20 years between persons with and without hearing loss was reduced (337 EUR, 95% CI = 269 to 405).

Conclusions:
The results from this large population-based study indicates that people with hearing loss experience lower long-term earnings growth compared with people with normal hearing. The findings highlight the need for increased interventions in the workplace for people with hearing loss.
Granulomatous Folliculotropic Secondary Syphilis: An Unusual Histopathological Clue
Authors: Sánchez-Martínez Eva , Schaller Jörg 
Published: August 2024

Abstract:
Syphilis is a sexually transmitted disease that can present a wide variety of clinical and histopathological manifestations. We present the case of a 75-year-old patient with a persistent maculopapular rash on the trunk and extremities, in which the biopsy showed an exclusively perifollicular granulomatous infiltrate. In the immunohistochemical staining with anti-Treponema pallidum antibodies, spirochetes scattered within the perifollicular inflammatory infiltrate were identified. These findings together with the serological analysis allowed the diagnosis of secondary syphilis. Folliculotropic nonalopecic syphilis is rare, and the pathogenic mechanisms that cause this specific tropism are unknown. On the other hand, granulomatous inflammation is a pattern typically described in tertiary syphilis but also occasionally found in secondary syphilis. We present a case of secondary syphilis with the combination of both histopathological findings, an uncommon constellation for dermatopathologists to consider.