Tag: pubmed

Mamm Genome. 2022 Jan 8. doi: 10.1007/s00335-021-09941-w. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome, previously known as Stein-Leventhal syndrome, is associated with altered reproductive endocrinology, predisposing a young woman towards the risk of PCOS. It has a prevalence of 6-20% among the reproductive-age women. Progesterone is a key hormone in the pathophysiology of PCOS and patients show diminished response (progesterone resistance), implicating the role of progesterone receptor (PR) as a factor in the disease etiology and prognosis. In this case-control study, we have used mutation-specific PCR (confirmed by Sanger sequencing) to detect the presence of a pathologically significant PR polymorphic variant called as PROGINS. The variant has an Alu insertion in intron G and has two SNPs in exon 4 and exon 5, with all the three aberrations in complete disequilibrium. Our results demonstrated a statistically significant difference in the frequencies of PROGINS between the PCOS patients and healthy controls (p = 0.047). The frequencies of the genotypes CC (A1/A1), CT (A1/A2), and TT (A2/A2) in patients were 74.50%, 20.58%, and 4.90%, and in healthy controls they were 87.28%, 11%, and 1.69%, respectively. Our results put forward two determining factors with regard to PCOS: (i) the frequency of PROGINS allele was significantly higher among PCOS patients compared to the healthy matched controls (0.15 vs 0.07) in the studied population, (ii) the PROGIN allele was significantly associated with the lower levels of serum progesterone in PCOS patients (p < 0.003). The findings are conspicuous as these relate the PROGINS variant to the increased susceptibility of PCOS and might explain the progesterone resistance in patients.

PMID:34997844 | DOI:10.1007/s00335-021-09941-w

Pediatr Blood Cancer. 2022 Jan 8:e29457. doi: 10.1002/pbc.29457. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LLy) commonly present with critical features such as hyperleukocytosis and mediastinal mass, which complicates completing a diagnostic and staging workup and prevents clinical trial enrollment.

PROCEDURE: Consecutive patients with T-ALL/LLy from 1999 to 2019 at the Children’s Hospital of Philadelphia were analyzed for pediatric intensive care unit (PICU) admission and various high-risk features as well as clinical trial enrollment and outcome.

RESULTS: We identified 153 patients newly diagnosed with T-ALL/LLy, 53 (35%) required PICU-level care within 24 hours and 73 (48%) within 7 days. Non-PICU patients had a significantly higher clinical trial enrollment rate (79.4%) versus PICU patients (56.1%, P = 0.016). Patients who enrolled on a clinical trial had similar relapse risk to those who did not enroll (relapse rate 20% vs 29%, P = 0.523). Nineteen patients were precluded from trial participation. Risk of relapse was increased for patients admitted to the PICU within 24 hours (26% vs 13%, P = 0.048). Forty-four patients with T-ALL presented with hyperleukocytosis, of which 30% relapsed versus 14% without (P = 0.082). Patients who underwent apheresis for hyperleukocytosis were statistically more likely to relapse (47% vs 15%, P = 0.007). Patients with elevated uric acid (20% vs 16%, P = 0.278), mediastinal mass (20% vs 14%, P = 0.501), or required emergent steroids (20% vs 16%, P = 0.626) had a similar relapse risk. A single second relapse patient survived.

CONCLUSIONS: Almost half of T-ALL/LLy patients required PICU-level care at diagnosis, making enrollment on clinical trials challenging, but trial enrollment predicted better outcome. Physicians should balance maintaining eligibility with safety to offer patients all options.

PMID:34997812 | DOI:10.1002/pbc.29457

Int J Lang Commun Disord. 2022 Jan 8. doi: 10.1111/1460-6984.12686. Online ahead of print.

ABSTRACT

BACKGROUND: Difficulties in language development are related to social and emotional problems, lower academic outcomes, and lower quality of life from childhood to adolescence. These grave consequences might be significantly reduced by timely identification and professional support. The introduction of systematic screening for language delay (LD) in 3-year-old children in Hungary was based on the recent adaptation of the MacArthur-Bates CDI-III (HCDI-III).

AIMS: To explore the relevant psychometric properties of the HCDI-III; to identify factors characteristic of the families and children influencing language development at the age group under investigation; and to evaluate the adequacy of the tool for the purpose of screening LD in kindergarten at the age of 3 years.

METHODS & PROCEDURES: The norming study of the HCDI-III was conducted in a collaborative research project with the Metropolitan Pedagogical Services in Budapest. HCDI-III parent report forms along with a demographic survey form were distributed to parents of all Hungarian-speaking children between the ages of 2;0 and 4;2 without special education needs. The normative sample comprised data from 1424 children aged 2;0-4;2 with 51.1% boys and 48.9% girls. The data set contained information including language skills, basic demographics, birth conditions, health issues and socio-economic status (SES).

OUTCOMES & RESULTS: In the HCDI-III form, six outcome variables were created to cover the domains of expressive vocabulary, morphosyntax and language use. Statistical analyses revealed appropriate psychometric properties of five outcome variables that showed a normal distribution and were strongly correlated to age. Outcomes of girls were slightly (but significantly) higher on scales corresponding to vocabulary, syntax, language use and productivity. Most variables were highly correlated with one another even with age partialled out. Multiple regression analyses revealed significant effect of age, gender and parental education on all main outcome variables. Neither one of the other eight predictors, including familial and birth-related factors, affected linguistic outcomes in our sample.

CONCLUSIONS & IMPLICATIONS: The results are consistent with the majority of Communicative Development Inventory (CDI) studies, and support the psychometric eligibility of the instrument for screening purposes between 30 and 50 months. As certain regions of Hungary are characterised by a high prevalence of low-SES families, more research is needed to adapt the screening procedure and subsequent measures to their needs.

WHAT THIS PAPER ADDS: What is already known on the subject Difficulties in language development are related to lower social and academic outcomes and lower quality of life from childhood to adolescence. These grave consequences might be significantly reduced by timely identification and professional support. Structured parent report forms such as the MacArthur-Bates CDI are widely accepted methods for screening children with LD. What this paper adds to existing knowledge This study reports the Hungarian adaptation and norming of the CDI-III form. Statistical analyses revealed appropriate psychometric properties of most of its sections. Language outcomes were affected by age, gender and parental education on all main outcome variables in children between 2 and 4 years of age. What are the potential or actual clinical implications of this work? The results support the psychometric eligibility of the HCDI-III instrument for screening purposes. The introduction of the screening procedure in clinical practice is expected to improve early support of children with language difficulties and reduce risks of developmental problems related to language disorders.

PMID:34997807 | DOI:10.1111/1460-6984.12686

Cytometry A. 2022 Jan;101(1):7. doi: 10.1002/cyto.a.24526.

NO ABSTRACT

PMID:34997809 | DOI:10.1002/cyto.a.24526

Am J Med Genet B Neuropsychiatr Genet. 2022 Jan 8. doi: 10.1002/ajmg.b.32885. Online ahead of print.

ABSTRACT

The year 1900 saw not only the rediscovery of Mendel’s hybridization studies but also the publication by Karl Pearson of his newly developed tetrachoric correlation which he used to study the parent-offspring resemblance for the “insane diathesis” in 1905. This was followed by more detailed reports by two of his students/associates: Heron in 1907 and Goring in 1909. Both calculated the tetrachoric correlation for insanity in parent-offspring and Heron for sib-sib pairs. Estimates ranged from approximately +0.30 to +0.60. These papers were statistically sophisticated but demonstrated minimal interest in the phenotype being studied. They are of historical interest because they laid the groundwork for biometrical psychiatric genetics which emerged as a major research paradigm in latter third of the 20th century. In a biting critique of Heron’s paper by a young Ernst Rüdin, we see the beginnings of a long-running argument in psychiatric genetics about the relative value of detailed phenotyping versus novel statistical methods and of Mendelian versus Biometrical methods. While much interest has focused on the eugenic orientation of German psychiatric genetics in the early 20th century, these early British biometrical geneticists, like the majority of geneticists of that day, were also ardent advocates of the eugenic application of their research results.

PMID:34997802 | DOI:10.1002/ajmg.b.32885

J Magn Reson Imaging. 2022 Jan 8. doi: 10.1002/jmri.28048. Online ahead of print.

ABSTRACT

BACKGROUND: Determining the absence or presence of peripancreatic lymph nodal metastasis (PLNM) is important to the pathologic staging, prognostication, and guidance of treatment in pancreatic ductal adenocarcinoma (PDAC) patients. Computed tomography and MRI had a poor sensitivity and diagnostic accuracy in the assessment of PLNM.

PURPOSES: To develop and validate a 3 T MRI primary tumor radiomics-based nomogram from multicenter datasets for pretreatment prediction of the PLNM in PDAC patients.

STUDY TYPE: Retrospective.

SUBJECTS: A total of 251 patients (156 men and 95 women; mean age, 60.85 ± 8.23 years) with histologically confirmed pancreatic ductal adenocarcinoma from three hospitals.

FIELD STRENGTH AND SEQUENCES: A 3.0 T and fat-suppressed T1-weighted imaging.

ASSESSMENT: Quantitative imaging features were extracted from fat-suppressed T1-weighted (FS T1WI) images at the arterial phase.

STATISTICAL TESTS: Normally distributed data were compared by using t-tests, while the Mann-Whitney U test was used to evaluate non-normally distributed data. The diagnostic performances of the preoperative and postoperative nomograms were assessed in the external validation cohort with the area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis (DCA). AUCs were compared with the De Long test. A p value below 0.05 was considered to be statistically significant.

RESULTS: The AUCs of magnetic resonance imaging (MRI) Rad-score were 0.868 (95% confidence level [CI]: 0.613-0.852) and 0.772 (95% CI: 0.659-0.879) in the training and internal validation cohort, respectively. The preoperative and postoperative nomograms could accurately predict PLNM in the training cohort (AUC = 0.909 and 0.851) and were validated in both the internal and external cohorts (AUC = 0.835 and 0.805, 0.808 and 0.733, respectively). DCA indicated that the two novel nomograms are of similar clinical usefulness.

DATA CONCLUSION: Pre-/postoperative nomograms and the constructed radiomics signature from primary tumor based on FS T1WI of arterial phase could serve as a potential tool to predict PLNM in patients with PDAC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:34997795 | DOI:10.1002/jmri.28048

Microsc Res Tech. 2022 Jan 8. doi: 10.1002/jemt.24049. Online ahead of print.

ABSTRACT

Several mechanical and biological factors may change the orthodontic wire frictional resistance (FR). Titanium dioxide (TiO₂ ) and silica dioxide (SiO₂ ) nanoparticle (NP) coatings may be used to improve the characteristics of materials, reducing FR between archwire and bracket. This in vitro study aimed to evaluate the FR of orthodontic wires with and without coating in both dry and wet environments and measure the surface roughness (SR). One hundred and eighty segments of rectangular Cr-Ni orthodontic wires (Morelli Co, Brazil) were divided into three groups according to the NP coating applied: TiO₂ group; SiO₂ group; and control group. The SR parameters were measured in an optical profilometer, the surface morphology was analyzed with scanning electron microscopy (SEM), and FR was performed in a universal testing machine in dry and wet environments (n = 30). The statistical analysis was performed using the Generalized Estimated Equations model with a Bonferroni post-test (α = 0.05). It was observed that SiO₂ NP coating decreased FR significantly when compared to the TiO₂ and control groups, in both environments (p < .001). The SiO₂ and TiO₂ groups presented statistically lower SR than the control group and were similar to each other (p < .001). The SiO₂ group presented the lower depth of Valley parameter than the TiO₂ group (p < .001). The SEM showed that the TiO₂ coating had the most heterogeneous surface morphology than the SiO₂ and control groups. The orthodontic wires with NP coating modified the FR and morphology. The SiO₂ coating reduced FR in both dry and wet environments and decreased SR.

PMID:34997799 | DOI:10.1002/jemt.24049

J Magn Reson Imaging. 2022 Jan 8. doi: 10.1002/jmri.28046. Online ahead of print.

ABSTRACT

BACKGROUND: Preferential publication of studies with positive findings can lead to overestimation of diagnostic test accuracy (i.e. publication bias). Understanding the contribution of the editorial process to publication bias could inform interventions to optimize the evidence guiding clinical decisions.

PURPOSE/HYPOTHESIS: To evaluate whether accuracy estimates, abstract conclusion positivity, and completeness of abstract reporting are associated with acceptance to radiology conferences and journals.

STUDY TYPE: Meta-research.

POPULATION: Abstracts submitted to radiology conferences (European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and International Society for Magnetic Resonance in Medicine (ISMRM)) from 2008 to 2018 and manuscripts submitted to radiology journals (Radiology, Journal of Magnetic Resonance Imaging [JMRI]) from 2017 to 2018. Primary clinical studies evaluating sensitivity and specificity of a diagnostic imaging test in humans with available editorial decisions were included.

ASSESSMENT: Primary variables (Youden’s index [YI > 0.8 vs. <0.8], abstract conclusion positivity [positive vs. neutral/negative], number of reported items on the Standards for Reporting of Diagnostic Accuracy Studies [STARD] for Abstract guideline) and confounding variables (prospective vs. retrospective/unreported, sample size, study duration, interobserver agreement assessment, subspecialty, modality) were extracted.

STATISTICAL TESTS: Multivariable logistic regression to obtain adjusted odds ratio (OR) as a measure of the association between the primary variables and acceptance by radiology conferences and journals; 95% confidence intervals (CIs) and P-values were obtained; the threshold for statistical significance was P < 0.05.

RESULTS: A total of 1000 conference abstracts (500 ESGAR and 500 ISMRM) and 1000 journal manuscripts (505 Radiology and 495 JMRI) were included. Conference abstract acceptance was not significantly associated with YI (adjusted OR = 0.97 for YI > 0.8; CI = 0.70-1.35), conclusion positivity (OR = 1.21 for positive conclusions; CI = 0.75-1.90) or STARD for Abstracts adherence (OR = 0.96 per unit increase in reported items; CI = 0.82-1.18). Manuscripts with positive abstract conclusions were less likely to be accepted by radiology journals (OR = 0.45; CI = 0.24-0.86), while YI (OR = 0.85; CI = 0.56-1.29) and STARD for Abstracts adherence (OR = 1.06; CI = 0.87-1.30) showed no significant association. Positive conclusions were present in 86.7% of submitted conference abstracts and 90.2% of journal manuscripts.

DATA CONCLUSION: Diagnostic test accuracy studies with positive findings were not preferentially accepted by the evaluated radiology conferences or journals.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:34997786 | DOI:10.1002/jmri.28046

J Pineal Res. 2022 Jan 8:e12780. doi: 10.1111/jpi.12780. Online ahead of print.

ABSTRACT

Light at night in adults suppresses melatonin in a nonlinear intensity-dependent manner. In children, bright light of a single intensity before bedtime has a robust melatonin suppressing effect. To our knowledge, whether evening light of different intensities is related to melatonin suppression in young children is unknown. Healthy, good-sleeping children (n = 36; 3.0-4.9 years; 39% male) maintained a stable sleep schedule for 7 days followed by a 29.5-h in-home dim-light circadian assessment (~1.5 lux). On the final night of the protocol, children received a 1-h light exposure (randomized to one of 15 light levels, ranging 5-5000 lux, with ≥2 participants assigned to each light level) in the hour before habitual bedtime. Salivary melatonin was measured to calculate the magnitude of melatonin suppression during light exposure compared with baseline levels from the previous evening, as well as the degree of melatonin recovery 50 min after the end of light exposure. Melatonin levels were suppressed between 69.4% and 98.7% (M = 85.4 ± 7.2%) during light exposure across the full range of intensities examined. Overall, we did not observe a light intensity-dependent melatonin suppression response; however, children exposed to the lowest quartile of light intensities (5-40 lux) had an average melatonin suppression (77.5 ± 7.0%) which was significantly lower than that observed at each of the three higher quartiles of light intensities (86.4 ± 5.6%, 89.2 ± 6.3%, and 87.1 ± 5.0%, respectively). We further found that melatonin levels remained below 50% baseline for at least 50 min after the end of light exposure for the majority (62%) of participants, and recovery was not influenced by light intensity. These findings indicate that preschool-aged children are highly sensitive to light exposure in the hour before bedtime and suggest the lighting environment may play a crucial role in the development and the maintenance of behavioral sleep problems through impacts on the circadian timing system.

PMID:34997782 | DOI:10.1111/jpi.12780

Br J Haematol. 2022 Jan 8. doi: 10.1111/bjh.18026. Online ahead of print.

ABSTRACT

The clinical outcome of chronic myeloid leukaemia patients has vastly improved since the introduction of tyrosine kinase inhibitor treatment, with a significant proportion of patients able to achieve treatment-free remission. However, studies have shown that patients with the e13a2 transcript were less likely to achieve major molecular response compared to those with e14a2 transcripts. Most quantitative polymerase chain reaction (PCR) assays for detection of the BCR-ABL1 fusion gene do not differentiate between the two transcripts and we therefore hypothesised that technical bias linked to the qPCR assay could partially explain the discrepancy in outcomes. We designed an e14a2-specific assay and identified no difference in results compared to an e13a2 standard assay. We then demonstrated that the commercial e14a2 standards were causing a significant overestimation of the e13a2 transcripts. Finally, we reviewed patient management after the qPCR values were corrected, using our new evaluation. We concluded that despite statistically significant differences in qPCR results, there was no impact on patient management or outcome. We conclude that, at least in our institution, it would be inappropriate to perform separate assays for patients with e13a2 or e14a2.

PMID:34997766 | DOI:10.1111/bjh.18026