bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural genomic variants in thoracic aortic disease
Authors: Meester Josephina A.N. , Hebert Anne , Loeys Bart L. 
Published: February 2023

Purpose of review
Structural genomic variants have emerged as a relevant cause for several disorders, including intellectual disability, neuropsychiatric disorders, cancer and congenital heart disease. In this review, we will discuss the current knowledge about the involvement of structural genomic variants and, in particular, copy number variants in the development of thoracic aortic and aortic valve disease.

Recent findings
There is a growing interest in the identification of structural variants in aortopathy. Copy number variants identified in thoracic aortic aneurysms and dissections, bicuspid aortic valve related aortopathy, Williams-Beuren syndrome and Turner syndrome are discussed in detail. Most recently, the first inversion disrupting FBN1 has been reported as a cause for Marfan syndrome.

Summary
During the past 15 years, the knowledge on the role of copy number variants as a cause for aortopathy has grown significantly, which is partially due to the development of novel technologies including next-generation sequencing. Although copy number variants are now often investigated on a routine basis in diagnostic laboratories, more complex structural variants such as inversions, which require the use of whole genome sequencing, are still relatively new to the field of thoracic aortic and aortic valve disease.
LONG-TERM EVOLUTION OF MYOPIC RETINOSCHISIS WITH A DOME-SHAPED MACULA AND PREDICTORS OF PROGRESSION AND VISUAL PROGNOSIS
Authors: Shiwei Li  , Li Tingting , Long Da , Lu Bin , Chen Yan , Zhang Xueyan , Hu Jianyan , WU Qiang 
Published: February 2023

Purpose:
To study the long-term natural course of myopic retinoschisis (MRS) with a dome-shaped macula (DSM) and to identify the factors affecting its development and visual prognosis.

Methods:
In this retrospective case series study, we followed 25 MRS eyes with a DSM and 68 MRS eyes without a DSM for at least two years and observed changes in optical coherence tomography morphologic features and best-corrected visual acuity.

Results:
During the mean follow-up of 48.3 ± 13.24 months, the difference in the rate of MRS progression between the DSM and non-DSM groups was not significant (P = 0.7462). In the DSM group, the patients whose MRS progressed were older and had a higher refractive error than those whose MRS was stable or improved (P = 0.0301 and 0.0166, respectively). The patients whose DSM was located in the central fovea had a significantly higher progression rate than those whose DSM was located in the parafovea (P = 0.0421). For all DSM eyes, BCVA did not decrease significantly in eyes with extrafoveal retinoschisis (P = 0.2500), patients whose best-corrected visual acuity decreased more than two lines had a greater central foveal thickness initially than those whose best-corrected visual acuity decreased less than two lines during the follow-up period (P = 0.0478).

Conclusion:
A DSM did not delay the progression of MRS. The development of MRS in DSM eyes was associated with age, myopic degree, and DSM location. A higher schisis cavity predicted visual deterioration, and a DSM protected visual function in extrafoveal MRS eyes during the follow-up period.
The Contribution of Viruses and Bacteria to Childhood Community-acquired Pneumonia: 11-Year Observational Study From Norway
Authors: Smyrnaios Anastasios , Risnes Kari , Krokstad Sidsel , Nordbø Svein Arne , Heimdal Inger , Christensen Andreas , Døllner Henrik 
Published: February 2023

Background:
Viruses are associated with pediatric community-acquired pneumonia (CAP) but are also common in the upper airways of healthy children. We have determined the contribution of respiratory viruses and bacteria by comparing children with CAP and hospital controls.

Methods:
Children less than 16 years old with radiologically confirmed CAP (n = 715) were enrolled over an 11-year period. Children admitted for elective surgery during the same period served as controls (n = 673). Nasopharyngeal aspirates were tested for 20 respiratory pathogens by semiquantitative polymerase chain reaction tests and cultivated for bacteria and viruses. We used logistic regression to calculate adjusted odds ratios [aOR; 95% confidence intervals (CIs)], and estimated population-attributable fractions (95% CI).

Results:
At least 1 virus was detected in 85% of cases and 76% of controls, and greater than or equal to 1 bacterium was detected in 70% of cases and controls. The presence of respiratory syncytial virus (RSV) (aOR, 16.6; 95% CI: 9.81–28.2), human metapneumovirus (HMPV) (13.0; 6.17–27.5) and Mycoplasma pneumoniae (27.7; 8.37–91.6) were most strongly associated with CAP. For RSV and HMPV, there were significant trends between lower cycle-threshold values indicating higher viral genomic loads, and higher aORs for CAP. The population-attributable fraction estimates of RSV, HMPV, human parainfluenza virus, influenza virus and M. pneumoniae were 33.3% (32.2–34.5), 11.2% (10.5–11.9), 3.7% (1.0–6.3), 2.3% (1.0–3.6) and 4.2% (4.1–4.4), respectively.

Conclusions:
RSV, HMPV and M. pneumoniae were most strongly related to pediatric CAP and accounted for half of all cases. There were positive trends between increasing viral genomic loads of RSV and HMPV, and higher odds for CAP.
Demographic Characteristics Influence Treatment Costs of Invasive Melanoma in Florida
Authors: Avila Francisco R. , Spaulding Aaron C. , Rinker Brian D. , Huayllani Maria T. , Boczar Daniel , Torres-Guzman Ricardo A. , Maita Karla C. , Ho Olivia A. , Forte Antonio J. 
Published: February 2023

Background
Demographic characteristics are known to influence the treatment and outcomes of patients with invasive melanoma. Whether these characteristics influence treatment costs is unknown. We aimed to analyze whether patient demographics and tumor characteristics influence treatment costs for patients with invasive cutaneous melanoma in Florida.

Methods
This was a cross-sectional study in which the Florida Inpatient and Outpatient Dataset of the Agency for Health Care Administration was analyzed for patients with a diagnosis of invasive melanoma between January 1, 2013 and December 31, 2018. Categorical variables were assessed using Pearson χ2 tests, and continuous variables were evaluated using Kruskal-Wallis tests. Logistic regression analysis was conducted to identify the association between patient demographics and total costs. All analyses were done using SAS 9.4 statistical software (SAS Institute, Inc).

Results
Multivariate analysis showed that sex (P < 0.001), hospital setting (P < 0.001), race/ethnicity (P < 0.01), patient region (P < 0.01), Elixhauser Comorbidity Index score (P < 0.001), presence of metastasis (P < 0.01), total number of procedures (P < 0.001), and length of stay (P < 0.001) were correlated with the cost of treatment of invasive cutaneous melanoma. After stratification, the association between cost and race/ethnicity disappeared for inpatients but remained for Black patients in the outpatient setting (P < 0.001). The association between cost and patient residence regions also differed when the cohort was stratified.

Conclusions
Strategies addressing disparities in treatment cost of invasive melanoma should differ, depending on the hospital setting where the patient is being treated.
Transcutaneous and Direct Electrical Stimulation of Mouse Sciatic Nerve Accelerates Functional Recovery After Nerve Transection and Immediate Repair
Authors: Pion Anne-Marie , Roy Andrée-Anne , Ma Xiya , Beaumont Eric , Lin Jenny C. 
Published: February 2023

Background
Electrical stimulation can accelerate peripheral nerve regeneration after injury and repair. Clinically, direct electrical stimulation (DES) may involve longer operating times, increasing risks of perioperative complications. Transcutaneous electrical stimulation (TCES) is a noninvasive alternative. In this study, we investigate how transcutaneous and DES compare for accelerating functional nerve recovery in a mouse sciatic nerve model.

Methods
Twenty-eight mice were divided into sham (n = 4), axotomy (n = 8), DES (n = 8), and TCES (n = 8) groups. After sciatic nerve transection and repair, the proximal nerve was subjected to DES or TCES at 20 Hz for 1 hour. Sciatic functional index was measured before the injury, and at weeks 1, 2, 4, 6, 8, 10, and 12 by walking-track analysis. Electrophysiological measures were taken at week 12.

Results
Kinematic studies showed significant improvement from the 8th week to the 12th week for both electrical stimulation groups compared with the axotomy group (P < 0.05), with no difference between the electrical stimulation groups. At the 12th week, both DES and TCES groups had significantly faster average conduction velocity than the axotomy group.

Conclusions
Functional recovery was significantly better from 8 weeks onward in mice receiving either DES or TCES stimulation when compared with axotomy and repair alone. Transcutaneous electrical stimulation is a minimally invasive alternative treatment for accelerating functional recovery after peripheral nerve injury.
Heart Transplantation in Patients Less Than 18 Years of Age: Comparison of 2 Eras Over 36 Years and 323 Transplants at a Single Institution
Authors: Bleiweis Mark S , Fricker Frederick Jay , Upchurch Gilbert R , Peek Giles J , Stukov Yuriy , Gupta Dipankar , Shih Renata , Pietra Biagio , Sharaf Omar M , Jacobs Jeffrey P 
Published: February 2023

BACKGROUND:We reviewed our management strategy and outcome data for all 311 patients less than 18 years of age who underwent 323 heart transplants at our institution (1986 to 2022) in order to assess changes in patterns of practice and outcomes over time and to compare two consecutive eras: era 1 (154 heart transplants [1986 to 2010]) and era 2 (169 heart transplants [2011 to 2022]).STUDY DESIGN:Descriptive comparisons between the two eras were performed at the level of the heart transplant for all 323 transplants. Kaplan-Meier survival analyses were performed at the level of the patient for all 311 patients, and log-rank tests were used to compare groups.RESULTS:Transplants in era 2 were younger (6.6 ± 6.5 years vs 8.7 ± 6.1 years, p = 0.003). More transplants in era 2 were in infants (37.9% vs 17.5%, p < 0.0001), had congenital heart disease (53.8% vs 39.0%, p < 0.010), had high panel reactive antibody (32.1% vs 11.9%, p < 0.0001), were ABO-incompatible (11.2% vs 0.6%, p < 0.0001), had prior sternotomy (69.2% vs 39.0%, p < 0.0001), had prior Norwood (17.8% vs 0%, p < 0.0001), had prior Fontan (13.6% vs 0%, p < 0.0001), and were in patients supported with a ventricular assist device at the time of heart transplant (33.7% vs 9.1%, p < 0.0001). Survival at 1, 3, 5, and 10 years after transplant was as follows: era 1 = 82.4% (76.5 to 88.8), 76.9% (70.4 to 84.0), 70.7% (63.7 to 78.5), and 58.8% (51.3 to 67.4), respectively; era 2 = 90.3% (85.7 to 95.1), 85.4% (79.7 to 91.5), 83.0% (76.7 to 89.8), and 66.0% (49.0 to 88.8), respectively. Overall Kaplan-Meier survival in era 2 was better (log-rank p = 0.03).CONCLUSIONS:Patients undergoing cardiac transplantation in the most recent era are higher risk but have better survival.
APRI score is not predictive of post-surgical outcomes in cholangiocarcinoma patients
Authors: Aslam Faaiq N , Loveday Tristan A , Uson Junior Pedro Luiz Serrano , Truty Mark , Smoot Rory , Bekaii-Saab Tanios , Ahn Daniel , Sonbol Mohamad Bassam , Wu Christina , Stucky Chee-Chee , Babiker Hani , Borad Mitesh J 
Published: February 2023

AbstractObjectiveTo assess the utility of aminotransferase-platelet ratio index (APRI) score in prognosticating post-surgical outcomes in cholangiocarcinoma patients.Methods152 cholangiocarcinoma patients at the Mayo Clinic that underwent surgical resection were retrospectively analyzed. Statistical analyses were done to determine the relationship between APRI score and demographic factors, laboratory values, pathological features, and outcomes data.ResultsNo relationship between APRI score and demographic factors was identified. There was a correlation between APRI score and ALT, albumin, and bilirubin, but the remaining laboratory parameters showed no correlation. APRI score did not prove to be useful as a prognostic tool as it did not correlate with tumor pathology features and did not correlate with post-surgical recurrence and mortality.ConclusionWe found that APRI score was not a prognostic tool for post-surgical outcomes in cholangiocarcinoma patients.
Ethnic inequalities during clinical placement: a qualitative study of student nurses’ experiences within the London National Health Service
Authors: Walker Chenel R , Gunasinghe Cerisse , Harwood Hannah , Ehsan Annahita , Ahmed Farah , Dorrington Sarah , Onwumere Juliana , Meriez Paula , Stanley Nathan , Stoll Nkasi , Woodhead Charlotte , Hatch Stephani L , Rhead Rebecca 
Published: February 2023

AbstractAimTo understand how student nurse experiences on clinical placement, within NHS hospitals, differ for ethnic minority and White British groups.DesignA qualitative thematic analysis with an inductive approach.MethodsData from semi-structured interviews with 21 London (United Kingdom) hospital-based student nurses were examined using thematic analysis. Participants were interviewed as part of theTackling Inequalities and Discrimination Experiences in health Services(TIDES) study and asked about their experiences during clinical placement.ResultsFive main themes were identified: 1) Role of mentors, 2) Discrimination and unfair treatment, 3) Speaking up/out, 4) Career progression, and 5) Consequences of adverse experiences. All themes were linked, with the social dynamics and workplace environment (referred to as ‘ward culture’) providing a context that normalises mistreatment experienced by nursing students. Students from ethnic minority backgrounds reported racism as well as cultural and/or religious microaggressions. While being valued for their race and ethnicity, White British students also experienced discrimination and inequity due to their age, sex, gender, and sexual orientation. Students from both White British and ethnic minority groups acknowledged that being treated badly was a barrier to career progression. Ethnic minority students also noted that the lack of diverse representation within senior nursing positions discouraged career progression within the UK National Health Service (NHS).ConclusionThese initial experiences of inequality and discrimination are liable to shape a student’s perspective of their profession and ability to progress within nursing. The NHS is responsible for ensuring that student nurses’ developmental opportunities are equal, irrespective of ethnicity.ImpactWard culture is perpetuated through the action of others to normalise mistreatment and concurrently disadvantage ethnic minority students making them feel unvalued, which in turn impacts both staff retention and career progression within the NHS. Training assessors should be aware of the existing culture of discrimination within clinical placements and work to eradicate it.
Universal health coverage in the context of population ageing: Catastrophic health expenditure and unmet need for healthcare
Authors: Okamoto Shohei , Sata Mizuki , Rosenberg Megumi , Nakagoshi Natsuko , Kamimura Kazuki , Komamura Kohei , Kobayashi Erika , Sano Junko , Hirazawa Yuzuki , Okamura Tomonori , Iso Hiroyasu 
Published: February 2023

AbstractObjectivesThis study investigates the incidence/prevalence, determinants, and consequences of catastrophic health expenditure (CHE) and unmet need for healthcare and assesses the potential heterogeneity between younger (≤ 64 years) and older people (65 years≤).MethodsUtilising an annual nationally representative survey of Japanese aged 20 years and over, we estimated the incidence of CHE and unmet need for healthcare using disaggregated estimates by household members’ age (i.e. ≤ 64 years vs. 65 years≤) between 2004–2020. Using a fixed-effects model, we assessed the determinants of CHE and unmet need along with the consequences of CHE. We also assessed the heterogeneity by age.ResultsHouseholds with older members were more likely to have their healthcare needs met but experienced CHE more so than households without older members. The financial consequences of CHE were heterogeneous by age, suggesting that households with older members responded to CHE by reducing food and social expenditures more so than households without older members reducing expenditure on education. Households without older members experienced an income decline in the year following the occurrence of CHE, while this was not found among households with older members. A U-shaped relationship was observed between age and the probability of experiencing unmet healthcare need.ConclusionsHouseholds with older members are more likely to experience CHE with different financial consequences compared to those with younger members. Unmet need for healthcare is more common among younger and older members than among their middle-aged counterparts, though the health consequences of this unmet need could not be determined.
Genotype and Clinical Characteristics of Patients with Wolfram Syndrome and WFS1-related Disorders
Authors: Lee Evan M. , Verma Megha , Palaniappan Nila , Pope Emiko M. , Lee Sammie , Blacher Lindsey , Neerumalla Pooja , An William , Campbell Toko , Brown Cris , Hurst Stacy , Marshall Bess , Hershey Tamara , Nunes Virginia , de Heredia Miguel López , Urano Fumihiko 
Published: February 2023

AbstractObjectiveWolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity and prognosis of Wolfram syndrome more accurately.ApproachPatient data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and patient case reports were analyzed to select for patients with two recessive mutations in the WFS1 gene. Mutations were classified as being either nonsense/frameshift variants or missense/in-frame insertion/deletion variants and statistical analysis was performed using unpaired and paired t-tests and one- and two-way ANOVA with Tukey’s or Dunnett’s tests.ResultsA greater number of genotype variants correlated with earlier onset and a more severe presentation of Wolfram syndrome. Secondly, non-sense and frameshift variants had more severe phenotypic presentations than missense variants, as evidenced by optic atrophy emerging significantly earlier in patients with 2 nonsense/frameshift alleles compared with 0 missense transmembrane variants. In addition, the number of transmembrane in-frame variants demonstrated a statistically significant dose-effect on age of onset of diabetes mellitus and optic atrophy.Summary / ConclusionsThe results contribute to our current understanding of the genotype-phenotype relationship of Wolfram syndrome, suggesting that alterations in coding sequences result in significant changes in the presentation and severity of Wolfram. The impact of these findings is significant, as the results will aid clinicians in predicting more accurate prognoses and pave the way for personalized treatments for Wolfram syndrome.
Semi-conservative transmission of DNA N6-adenine methylation in a unicellular eukaryote
Authors: Sheng Yalan , Wang Yuanyuan , Yang Wentao , Wang Xue Qing , Lu Jiuwei , Pan Bo , Nan Bei , Liu Yongqiang , Li Chun , Song Jikui , Dou Yali , Gao Shan , Liu Yifan 
Published: February 2023

AbstractWhile DNA N6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has generated great interest recently. Biochemical and genetic evidence supports that AMT1, a MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, 6mA transmission mechanism remains to be elucidated. Taking advantage of Single Molecule Real-Time Circular Consensus Sequencing (SMRT CCS), here we provide definitive evidence for semi-conservative transmission of 6mA, showcased in the unicellular eukaryoteTetrahymena thermophila. In wildtype (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); hemi-methylation (hemi-6mApT) is transiently present on the parental strand of newly replicated DNA. In ΔAMT1cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and likely processive, whilede novo6mA deposition in ΔAMT1cells is slow and sporadic. InTetrahymena, regularly spaced 6mA clusters coincide with linker DNA of the canonical nucleosome arrays in the gene body. Importantly,in vitromethylation of human chromatin by reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1’s intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semi-conservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independentde novomethylation, reveals a molecular pathway for 6mA transmission with striking similarity to 5-methyl cytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as abona fideeukaryotic epigenetic mark.
Downregulation of stromal syntenin sustains AML development
Authors: Leblanc Raphael , Ghossoub Rania , Goubard Armelle , Castellano Rémy , Fares Joanna , Camoin Luc , Audebert Stephane , Balzano Marielle , Bou-Tayeh Berna , Fauriat Cyril , Vey Norbert , Borg Jean-Paul , Collette Yves , Aurrand-Lions Michel , David Guido , Zimmermann Pascale 
Published: February 2023

AbstractThe crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC), stromal syntenin deficiency, in turn, generating a pro-tumoral microenvironment. From serial transplantations in mice and co-culture experiments, we conclude that syntenin-deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro-tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, whichin transstimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML-stroma crosstalk and unsuspected tumor-suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.