Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical, Emotional/Behavioral, and Neurocognitive Developmental Outcomes From 2 to 4 Years After PICU Admission: A Secondary Analysis of the Early Versus Late Parenteral Nutrition Randomized Controlled Trial Cohort*

OBJECTIVES: PICU patients face long-term developmental impairments, partially attributable to early parenteral nutrition (PN) versus late-PN. We investigated how this legacy and harm by early-PN evolve over time. DESIGN: Preplanned secondary analysis of the multicenter PEPaNIC-RCT (ClinicalTrials.gov, NCT01536275) that enrolled 1,440 critically ill children from 2012 to 2015 and its 2- (2014–2018) and 4-year (2016–2019) cross-sectional follow-up studies. SETTING: PICUs of Leuven (Belgium), Rotterdam (The Netherlands), and Edmonton (Canada). PATIENTS: Patients and demographically matched healthy control children that underwent longitudinal assessment for physical/emotional/behavioral/neurocognitive functions at both follow-up time points. INTERVENTIONS: In the PEPaNIC-RCT, patients were randomly allocated to early-PN versus late-PN. MEASUREMENTS AND MAIN RESULTS: This within-individual longitudinal study investigated changes in physical/emotional/behavioral/neurocognitive functions from 2 to 4 years after PICU admission for 614 patients (297 early-PN and 317 late-PN, tested at mean ± sd age 5.4 ± 4.2 and 7.3 ± 4.3 yr) and for 357 demographically matched healthy children tested at age 5.6 ± 4.3 and 7.5 ± 4.3 years. We determined within-group time-courses, interaction between time and group, and independent impact of critical illness and early-PN on these time-courses. Most deficits in patients versus healthy children remained prominent over the 2 years (p ≤ 0.01). Deficits further aggravated for height, body mass index, the executive function metacognition, intelligence, motor coordination (alternating/synchronous tapping), and memory learning-index, whereas verbal memory deficits became smaller (working/immediate/delayed memory) (p ≤ 0.05). Adjustment for risk factors confirmed most findings and revealed that patients “grew-into-deficit” for additional executive functions (flexibility/emotional control/total executive functioning) and “grew-out-of-deficit” for additional memory functions (recognition/pictures) (p ≤ 0.05). Time-courses were largely unaffected by early-PN versus late-PN, except for weight loss and limited catch-up for visual-motor integration and alertness in early-PN patients (p ≤ 0.05). CONCLUSIONS: From 2- to 4-year post-PICU admission, developmental impairments remained prominent. Within that time-window, impaired growth in height, executive functioning and intelligence aggravated, and impaired memory and harm by early-PN only partially recovered. Impact on development into adulthood requires further investigation.
Emergent ferroelectricity in subnanometer binary oxide films on silicon

The critical size limit of voltage-switchable electric dipoles has extensive implications for energy-efficient electronics, underlying the importance of ferroelectric order stabilized at reduced dimensionality. We report on the thickness-dependent antiferroelectric-to-ferroelectric phase transition in zirconium dioxide (ZrO2) thin films on silicon. The emergent ferroelectricity and hysteretic polarization switching in ultrathin ZrO2, conventionally a paraelectric material, notably persists down to a film thickness of 5 angstroms, the fluorite-structure unit-cell size. This approach to exploit three-dimensional centrosymmetric materials deposited down to the two-dimensional thickness limit, particularly within this model fluorite-structure system that possesses unconventional ferroelectric size effects, offers substantial promise for electronics, demonstrated by proof-of-principle atomic-scale nonvolatile ferroelectric memory on silicon. Additionally, it is also indicative of hidden electronic phenomena that are achievable across a wide class of simple binary materials. Description Ultrathin ferroelectric films The electrical properties of ferroelectrics can be changed with an electric field, making them attractive materials for computer hardware applications. Cheema et al. show that extremely thin films of zirconium dioxide on a silica substrate have ferroelectric order down to the unit cell scale. Whereas in many other materials the ferroelectric behavior is suppressed at the few-nanometer scale, a ferroelectric phase transition occurs if zirconium dioxide is thinner than two nanometers. This property might be true for any fluorite-structured binary oxide, making these types of thin films attractive for next-generation electronics. —BG Decreasing the thickness of zirconium dioxide on a silicon substrate creates ferroelectric ordering.
The Effects of Automatic Segmentations on Preoperative Lymph Node Status Prediction Models With Ultrasound Radiomics for Patients With Early Stage Cervical Cancer

Introduction: The purpose of this study is to investigate the effects of automatic segmentation algorithms on the performance of ultrasound (US) radiomics models in predicting the status of lymph node metastasis (LNM) for patients with early stage cervical cancer preoperatively. Methods: US images of 148 cervical cancer patients were collected and manually contoured by two senior radiologists. The four deep learning-based automatic segmentation models, namely U-net, context encoder network (CE-net), Resnet, and attention U-net were constructed to segment the tumor volumes automatically. Radiomics features were extracted and selected from manual and automatically segmented regions of interest (ROIs) to predict the LNM of these cervical cancer patients preoperatively. The reliability and reproducibility of radiomics features and the performances of prediction models were evaluated. Results: A total of 449 radiomics features were extracted from manual and automatic segmented ROIs with Pyradiomics. Features with an intraclass coefficient (ICC) > 0.9 were all 257 (57.2%) from manual and automatic segmented contours. The area under the curve (AUCs) of validation models with radiomics features extracted from manual, attention U-net, CE-net, Resnet, and U-net were 0.692, 0.755, 0.696, 0.689, and 0.710, respectively. Attention U-net showed best performance in the LNM prediction model with a lowest discrepancy between training and validation. The AUCs of models with automatic segmentation features from attention U-net, CE-net, Resnet, and U-net were 9.11%, 0.58%, –0.44%, and 2.61% higher than AUC of model with manual contoured features, respectively. Conclusion: The reliability and reproducibility of radiomics features, as well as the performance of radiomics models, were affected by manual segmentation and automatic segmentations.
Innate Immune Responses to RSV Infection Facilitated by OGG1, an Enzyme Repairing Oxidatively Modified DNA Base Lesions

The primary cause of morbidity and mortality from infection with respiratory syncytial virus (RSV) is the excessive innate immune response(s) (IIR) in which reactive oxygen species (ROS) play key role(s). However, the mechanisms for these processes are not fully understood. We hypothesized that expressions of IIR genes are controlled by the ROS-generated epigenetic-like mark 7,8-dihydro-8-oxo(d)guanine (8-oxo(d)Gua) and 8-oxoguanine DNA glycosylase1 (OGG1). Here, we report that ROS not only generates intrahelical 8-oxo(d)Gua, but also enzymatically disables OGG1 in RSV-infected human airway epithelial cells and mouse lungs. OGG1 bound to 8-oxo(d)Gua in gene regulatory sequences promotes expression of IIR genes, and consequently exacerbates lung inflammation, histological changes, and body weight loss of experimental animals. Pharmacological inhibition of OGG1 substrate binding decreased expression of RSV-induced chemokine and cytokines and significantly lessened clinical symptoms. Results of mechanistic studies show that OGG1 binding at 8-oxo(d)Gua promoter regions modulated loading of transcription factors via transient cooperative interactions in RSV-infected lungs and airway epithelial cells. Other base specific DNA repair proteins had no effects. Collectively, this study identifies unprecedented roles of ROS-generated DNA base lesion(s) and cognate repair protein as a determinant of RSV-induced exuberant inflammation. Pharmaceutical inhibition of OGG1 interaction with its DNA substrate may represent a novel strategy in prevention/intervention of respiratory viral infections.
The potential role of mass spectrometry for the identification and monitoring of patients with plasma cell disorders: Where are we now and which questions remain unanswered?

Mass spectrometry (MS) techniques provide a highly sensitive methodology for the assessment and monitoring of paraproteins compared to standard electrophoretic techniques. The International Myeloma Working Group (IMWG) recently approved the use of intact light chain matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry (MALDI‐TOF MS) in lieu of immunofixation in the clinical assessment of patients and the assessment of patients enrolled on clinical trials. The increased sensitivity of these assays may help to detect and monitor monoclonal proteins (MP) in many patients with previously non‐measurable disease, will reduce complete response (CR) rates and increase detection of low‐level MP. The ability to track the unique mass or amino acid sequence of the MP also eliminates interference from therapeutic monoclonal antibodies (tmAbs) in most patients with IgG kappa myeloma. The intact light chain assays also provide structural information about the monoclonal light chain, including the presence of N‐linked glycosylation, which has been shown to be commoner on amyloidogenic light chains and may have prognostic significance in monoclonal gammopathy of undetermined significance (MGUS). In this review, we discuss these issues alongside differences in the analytical and practical aspects related to the different MS assays under development and the challenges for MS.
Monocarboxylate transporter 1 is a novel target for breast cancer stem like‐cell inhibition by diallyl trisulfide

Diallyl trisulfide (DATS) is a promising small molecule phytochemical that exhibits in vitro and in vivo activity in multiple preclinical solid tumor models including breast cancer, but the underlying mechanism is not fully understood. We have shown previously that forkhead box Q1 (FoxQ1) transcription factor is a novel target for breast cancer stem‐like cells (bCSC) inhibition by DATS. Analysis of the breast TCGA (The Cancer Genome Atlas) data revealed that FoxQ1 expression was positively associated with that of SLC16A1/monocarboxylate transporter 1 (MCT1). Western blot analysis confirmed increased expression of MCT1 protein in SUM159 (basal‐like) and MCF‐7 cells (luminal‐type) stably transfected to overexpress FoxQ1. Furthermore, FoxQ1 was recruited to the promoter of SLC16A1/MCT1. Treatment of SUM159 and MCF‐7 cell lines with DATS resulted in suppression of MCT1 protein level that was accompanied by a decrease in intracellular and secreted levels of lactate. Overexpression or knockdown of MCT1 protein failed to alter DATS‐mediated inhibition of colony formation or cell migration when compared to corresponding control cells. On the other hand, overexpression of MCT1 protein conferred partial but statistically significant protection against DATS‐mediated inhibition of bCSC fraction (CD49fhigh/CD44high and aldehyde dehydrogenase 1 activity). The size of the mammospheres was relatively smaller in the DATS‐treated group compared to control group. Inhibition of bCSC upon DATS treatment was augmented by knockdown of the MCT1 protein. In conclusion, the present study reveals that MCT1 is a novel target for bCSC inhibition by DATS treatment.
68Ga-PSMA-11 PET/MRI in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Adenocarcinoma: PET Findings Correlate with Outcomes After Definitive Treatment

Visual Abstract Prostate-specific membrane antigen (PSMA) PET offers an accuracy superior to other imaging modalities in initial staging of prostate cancer and is more likely to affect management. We examined the prognostic value of 68Ga-PSMA-11 uptake in the primary lesion and presence of metastatic disease on PET in newly diagnosed prostate cancer patients before initial therapy. Methods: In a prospective study from April 2016 to December 2020, 68Ga-PSMA-11 PET/MRI was performed in men with a new diagnosis of intermediate- or high-grade prostate cancer who were candidates for prostatectomy. Patients were followed up after initial therapy for up to 5 y. We examined the Kendall correlation between PET (intense uptake in the primary lesion and presence of metastatic disease) and clinical and pathologic findings (grade group, extraprostatic extension, nodal involvement) relevant for risk stratification, and examined the relationship between PET findings and outcome using Kaplan–Meier analysis. Results: Seventy-three men (age, 64.0 ± 6.3 y) were imaged. Seventy-two had focal uptake in the prostate, and in 20 (27%) PSMA-avid metastatic disease was identified. Uptake correlated with grade group and prostate-specific antigen (PSA). Presence of PSMA metastasis correlated with grade group and pathologic nodal stage. PSMA PET had higher per-patient positivity than nodal dissection in patients with only 5–15 nodes removed (8/41 vs. 3/41) but lower positivity if more than 15 nodes were removed (13/21 vs. 10/21). High uptake in the primary lesion (SUVmax > 12.5, P = 0.008) and presence of PSMA metastasis (P = 0.013) were associated with biochemical failure, and corresponding hazard ratios for recurrence within 2 y (4.93 and 3.95, respectively) were similar to or higher than other clinicopathologic prognostic factors. Conclusion: 68Ga-PSMA-11 PET can risk-stratify patients with intermediate- or high-grade prostate cancer before prostatectomy based on degree of uptake in the prostate and presence of metastatic disease.
Phosphatidylcholine:diacylglycerol cholinephosphotransferase’s unique regulation of castor bean oil quality

Abstract Castor bean (Ricinus communis) seed oil (triacylglycerol [TAG]) is composed of ∼90% of the industrially important ricinoleoyl (12-hydroxy-9-octadecenoyl) groups. Here, phosphatidylcholine (PC):diacylglycerol (DAG) cholinephosphotransferase (PDCT) from castor bean was biochemically characterized and compared with camelina (Camelina sativa) PDCT. DAGs with ricinoleoyl groups were poorly used by Camelina PDCT, and their presence inhibited the utilization of DAG with “common” acyl groups. In contrast, castor PDCT utilized DAG with ricinoleoyl groups similarly to DAG with common acyl groups and showed a 10-fold selectivity for DAG with one ricinoleoyl group over DAG with two ricinoleoyl groups. Castor DAG acyltransferase2 specificities and selectivities toward different DAG and acyl-CoA species were assessed and shown to not acylate DAG without ricinoleoyl groups in the presence of ricinoleoyl-containing DAG. Eighty-five percent of the DAG species in microsomal membranes prepared from developing castor endosperm lacked ricinoleoyl groups. Most of these species were predicted to be derived from PC, which had been formed by PDCT in exchange with DAG with one ricinoleoyl group. A scheme of the function of PDCT in castor endosperm is proposed where one ricinoleoyl group from de novo-synthesized DAG is selectivity transferred to PC. Nonricinoleate DAG is formed and ricinoleoyl groups entering PC are re-used either in de novo synthesis of DAG with two ricinoleoyl groups or in direct synthesis of triricinoleoyl TAG by PDAT. The PC-derived DAG is not used in TAG synthesis but is proposed to serve as a substrate in membrane lipid biosynthesis during oil deposition.
Single Cell RNA Sequencing in Silent Corticotroph Tumors Confirms Impaired POMC Processing and Provides New Insights into Their Invasive Behavior.

OBJECTIVE Provide insights into the defective POMC processing and invasive behavior in silent pituitary corticotroph tumors. DESIGN AND METHODS Single cell RNAseq was used to compare the cellular makeup and transcriptome of silent and active corticotroph tumors. RESULTS A series of transcripts related to hormone processing peptidases and genes involved in the structural organization of secretory vesicles were reduced in silent compared to active corticotroph tumors. Most relevant to their invasive behavior, silent corticotroph tumors exhibited several features of epithelial-to-mesenchymal transition (EMT), with increased expression of mesenchymal genes along with the loss of transcripts which regulate hormonal biogenesis and secretion. Silent corticotroph tumor vascular smooth muscle cell and pericyte stromal cell populations also exhibited plasticity in their mesenchymal features. CONCLUSIONS Our findings provide novel insights into the mechanisms of impaired POMC processing and invasion in silent corticotroph tumors and suggest that a common transcriptional reprogramming mechanism simultaneously impairs POMC processing and activates tumor invasion.
Low risk of SARS-CoV-2 transmission by fomites - a clinical observational study in highly infectious COVID-19 patients.

BACKGROUND The contribution of droplet-contaminated surfaces for virus transmission has been discussed controversially in the context of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic. Importantly, the risk of fomite-based transmission has not been systematically addressed. Therefore, the aim of this study was to evaluate if confirmed hospitalized COVID-19 patients can contaminate stainless steel carriers by coughing or intensive moistening with saliva and to assess the risk of SARS-CoV-2 transmission upon detection of viral loads and infectious virus in cell culture. METHODS We initiated a single-center observational study including fifteen COVID-19 patients with a high baseline viral load (CT value ≤ 25). We documented clinical and laboratory parameters and used patient samples to perform virus culture, quantitative PCR and virus sequencing. RESULTS Nasopharyngeal and oropharyngeal swabs of all patients were positive for viral RNA on the day of the study. Infectious SARS-CoV-2 could be isolated from 6 patient swabs (46.2 %). While after coughing, no infectious virus could be recovered, intensive moistening with saliva resulted in successful viral recovery from steel carriers of 5 patients (38.5 %). CONCLUSIONS Transmission of infectious SARS-CoV-2 via fomites is possible upon extensive moistening, but unlikely to occur in real-life scenarios and from droplet-contaminated fomites.
The memories that people would save or erase differ from their most positive and negative memories on function, emotion and correspondence with the life script

ABSTRACT Autobiographical remembering is a dynamic process in which narrators construct their life story from single memories. What is included in or deleted from the life story depends on many factors. Here, we examined the functions, emotions and correspondence with the life script for the memories that people desire to save or erase from their past. We asked people to generate either the two memories they were most likely to save and erase or the two memories they regarded as their most positive and negative memories. Then everyone rated those memories on function, emotion and correspondence with the life script. Overall, we found save and erase memories corresponded less with the life script relative to most positive and most negative memories though they were similarly emotionally intense. Additionally, erase memories were more associated with shame and less with social functions than most negative memories, whereas most negative memories to a higher degree involved the death of significant others, albeit being similarly traumatic. These findings have important implications for theory about autobiographical memory, and possible clinical relevance.
Effect of inhaled corticosteroids on microbiome and microbial correlations in asthma over a 9‐month period

The effect of inhaled corticosteroids (ICS) on the airway microbiome requires longitudinal research for corroboration. Asthma patients, not undergoing ICS treatment (baseline), were enrolled and prescribed ICS; all these patients were followed up with regular visits at 3 months (visit 1) and 9 months (visit 2). Induced sputum was collected, and fungal microbiota (mycobiome) and bacterial microbiota (bacteriome) were estimated using 16S rRNA and internal transcribed spacer (ITS) sequencing. Bacterial α diversity indices were not significantly different between baseline, visit 1, and visit 2. Visit 1 showed lower fungal evenness than the baseline, and visit 2 showed lower fungal diversity and evenness than the baseline. Fungal, but not bacterial, community compositions differed significantly between the baseline, visit 1, and visit 2. The most abundant bacterial phyla and genera did not differ significantly between the baseline, visit 1, and visit 2. Compared with the baseline, visit 1 showed significantly increased frequency of the fungal phylum Ascomycota and lower frequency of Basidiomycota. We found sharply decreased fungal genera Wallemia, Cladosporium, Penicillium, and Alternaria at visit 1 and visit 2 compared with the baseline, although the differences were not statistically significant. We also found the proportion of Basidiomycota was positively correlated with percentages of sputum eosinophils and neutrophils. The proportions of Saccharomyces, Wallemia, and Aplosporella were positively correlated with percentage of sputum eosinophils. Moreover, we identified distinct inter‐ and intra‐kingdom interactions in baseline, visit 1, and visit 2. Therefore, ICS use altered the airway microbial diversity, evenness, community composition, and microbial connections.
Molecular typing and prevalence of antibiotic resistance and virulence genes in Streptococcus agalactiae isolated from Chinese dairy cows with clinical mastitis

Bovine mastitis is a common disease occurring in dairy farms and can be caused by more than 150 species of pathogenic bacteria. One of the most common causative organisms is Streptococcus agalactiae, which is also potentially harmful to humans and aquatic animals. At present, research on S. agalactiae in China is mostly concentrated in the northern region, with limited research in the southeastern and southwestern regions. In this study, a total of 313 clinical mastitis samples from large-scale dairy farms in five regions of Sichuan were collected for isolation of S. agalactiae. The epidemiological distribution of S. agalactiae was inferred by serotyping isolates with multiplex polymerase chain reaction. Susceptibility testing and drug resistance genes were detected to guide the clinical use of antibiotics. Virulence genes were also detected to deduce the pathogenicity of S. agalactiae in Sichuan Province. One hundred and five strains of S. agalactiae (33.6%) were isolated according to phenotypic features, biochemical characteristics, and 16S rRNA sequencing. Serotype multiplex polymerase chain reaction analysis showed that all isolates were of type Ia. The isolates were up to 100% sensitive to aminoglycosides (kanamycin, gentamicin, neomycin, and tobramycin), and the resistance rate to β-lactams (penicillin, amoxicillin, ceftazidime, and piperacillin) was up to 98.1%. The TEM gene (β-lactam-resistant) was detected in all isolates, which was in accordance with a drug-resistant phenotype. Analysis of virulence genes showed that all isolates harbored the cfb, cylE, fbsA, fbsB, hylB, and α-enolase genes and none harbored bac or lmb. These data could aid in the prevention and control of mastitis and improve our understanding of epidemiological trends in dairy cows infected with S. agalactiae in Sichuan Province.
Natural history and burden of Huntington's disease in the UK: A population‐based cohort study

Huntington's disease (HD) is a rare neurodegenerative disease that presents with progressive psychological, cognitive and motor impairment. These diverse symptoms place a high burden on the patient, families and the healthcare systems they rely on. This study aimed to describe the epidemiology and clinical burden in individuals with HD compared with controls from the general population.