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Κυριακή 6 Νοεμβρίου 2022

Testing different sources of environmental unpredictability on adolescent functioning: ancestral cue versus statistical learning and the role of temperament

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Background

The dimensional model of environmental adversity highlighted the effects of an unpredictable environment in promoting risky development. Toward gaining greater specificity in understanding, this multimethod, longitudinal study investigated the role of two sources of environmental unpredictability—ancestral cues versus statistical learning, and their interaction with dove temperament conceptualized within the evolutionary model of temperament, in shaping adolescent functioning.

Methods

Participants were 192 families with an adolescent (M age = 12.4) followed for two annual waves. We measured unpredictability within the ancestral-cue approach as incidents of disruptive family events, and statistical-learning unpredictability as the random variability in observed moment-to-moment maternal hostility during parent–child interaction. We focused on dove temperament, which characterizes strategies of cautious and inhibited behavior in novel contexts and persistence and intrinsic engagement in benign contexts.

Results

Findings indicated unique effects of ancestral-cue versus statistical-learning unpredictability—in interaction with dove temperament—in association with adolescent functioning. Ancestral-cue unpredictability interacted with dove temperament in association with vagal stress reactivity, and the interactive effects of statistical-learning unpredictability were only associated with set-shifting. Furthermore, the family instability-x-dove temperament interaction was linked to adolescent adjustment via vagal reactivity. Adolescents with lower dove temperament showed dampened vagal reactivity within the more unpredictable environments, which was in turn associated with a greater decrease in social withdrawal over time.

Conclusions

The findings highlighted the specificity in different sources of environmental unpredictability in shaping adolescent development.

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Improving Methods of Identifying Anaphylaxis for Medical Product Safety Surveillance Using Natural Language Processing and Machine Learning

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Abstract
We sought to determine whether machine learning and natural language processing (NLP) applied to electronic medical records could improve performance of automated healthcare claims-based algorithms to identify anaphylaxis events using data on 516 patients with outpatient, emergency department, or inpatient anaphylaxis diagnosis codes during 2015-2019 in two integrated healthcare institutions in the Northwest United States. We used one site's manually reviewed gold standard outcomes data for model development and the other's for external validation based on cross-validated (cv) area under the receiver operating characteristic curve (cv AUC), positive predictive value (PPV), and sensitivity. In the development site 154 (64%) of 239 potential events met adjudication criteria for anaphylaxis compared to 180 (65%) of 277 in the validation site. Logistic regression models using only structured claims data achieved a cv-AUC of 0.58 (95% CI: 0.54, 0. 63). Machine learning improved cv-AUC to 0.62 (0.58, 0.66); incorporating NLP-derived covariates further increased cv AUCs to 0.70 (0.66, 0.75) in development and 0.67 (0.63, 0.71) in external validation data. A classification threshold with cv-PPV of 79% and cv-sensitivity of 66% in development data had cv-PPV of 78% and cv-sensitivity of 56% in external data. Machine learning and NLP-derived data improved identification of validated anaphylaxis events.
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Transcriptional analysis of the mfa‐cluster genes in Porphyromonas gingivalis strains with one and two mfa5 genes

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Abstract

The Porphyromonas gingivalis Mfa1 fimbria is composed of the Mfa1 to Mfa5 proteins, encoded by the mfa1 to mfa5 genes, respectively, which are tandemly arranged on chromosomes. A recent study discovered that many P. gingivalis strains possess two mfa5 genes (called herein mfa5-1 and mfa5-2), which are also in tandem. This study examined the transcriptional unit and activity of mfa-cluster genes in strains with one (the ATCC 33277 and TDC60 strains) and two (the HG66 and A7436 strains) mfa5 genes. Complementary DNA was prepared from the total RNA extracted from the bacterial cells in the logarithmic growth phase using a random primer. PCR analysis for the intergenic regions from mfa1 to mfa5 or mfa5-2 showed that mfa1 to mfa5 or mfa5-2 formed a polycistronic gene cluster. Quantitative real-time PCR showed that the mfa1 transcription was 5–10 times higher than tha t of mfa2 in all the strains. However, mfa2 to mfa5 mostly showed a comparable expression. Both mfa5 genes were comparably transcribed in HG66 and A7436 strains. The transcriptional levels were almost consistent with the respective protein expression levels. In silico analysis identified a transcriptional terminator structure in the intergenic region between mfa1 and mfa2 that was probably responsible for the decreased transcription rate of mfa2 and the downstream genes.

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Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C

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Abstract
Background
The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.
Methods
An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenance TMZ for two years (arm B). The primary endpoint was overall survival (OS).
Results
Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, two-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95 to 4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response.
Conclusions
This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.
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Remimazolam versus propofol for deep sedation/anaesthesia in upper gastrointestinal endoscopy in elderly patients: A multicenter, randomized controlled trial

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Remimazolam versus propofol for deep sedation/anaesthesia in upper gastrointestinal endoscopy in elderly patients: A multicenter, randomized controlled trial

The rate of hypotension was 36.5% in the remimazolam group and 69.6% in the propofol group (p < 0.001). The remimazolam group also had a lower rate of bradycardia (1.5% vs. 8.5%, p < 0.001) and respiratory depression (4.5% vs. 10.0%, p < 0.05).


Abstract

Background and Objective

Propofol is the most commonly used sedative in gastrointestinal endoscopic procedures, but is associated with cardiorespiratory suppression, particularly in elderly patients. Remimazolam is a new short-acting GABA(A) receptor agonist with minimal impact on cardiorespiratory suppression, and may be a viable alternative in elderly patients undergoing endoscopic procedures.

Methods

This multicenter, randomized controlled trial was conducted between September 2020 and September 2021. Elderly patients (65–85 years of age) scheduled to undergo upper gastrointestinal endoscopy were randomized in 1:1 ratio to receive remimazolam tosilate (300 mg/h) or propofol (3 g/h) in addition to 50-μg fentanyl, until the Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) reached ≤1. MOAA/S was maintained at 0 or 1 throughout the procedure using 2.5 mg remimazolam or 0.5 mg/kg propofol boluses in the two groups, respectively. The primary outcome was the rate of hypotension (defined as systolic blood pressure at ≤90 mmHg or > 30% decline vs. the baseline). Bradycardia was defined as heart rate ≤50 per minute; respiratory depression was defined as respiratory rate <8 per minute and/or SpO2 < 90%.

Results

A total of 400 patients (161 men and 239 women; 70.4 ± 4.6 years of age) were enrolled (200 patients per group). Average body mass index was 22.2 ± 2.4 kg/m2. The rate of hypotension was 36.5% in the remimazolam group and 69.6% in the propofol group (p < 0.001). The remimazolam group also had a lower rate of bradycardia (1.5% vs. 8.5%, p < 0.001), respiratory depression (4.5% vs. 10.0%, p < 0.05) and pain at the injection site (0% vs. 12.0%, p < 0.001).

Conclusion

Remimazolam was associated with a lower rate of hypotension in elderly patients undergoing upper gastrointestinal endoscopy under deep sedation/anaesthesia than propofol.

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Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients

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Journal of Human Genetics, Published online: 07 November 2022; doi:10.1038/s10038-022-01095-0

Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients
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