Miracle-dz/UniFAR-FTUs huggingface dataset:
Noise reduction with cross-tracer and cross-protocol deep transfer learning for low-dose PET

Previous studies have demonstrated the feasibility of reducing noise with deep learning-based methods for low-dose fluorodeoxyglucose (FDG) positron emission tomography (PET). This work aimed to investigate the feasibility of noise reduction for tracers without sufficient training datasets using a deep transfer learning approach, which can utilize existing networks trained by the widely available FDG datasets. In this study, the deep transfer learning strategy based on a fully 3D patch-based U-Net was investigated on a 18F-fluoromisonidazole (18F-FMISO) dataset using single-bed scanning and a 68Ga-DOTATATE dataset using whole-body scanning. The datasets of 18F-FDG by single-bed scanning and whole-body scanning were used to obtain pre-trained U-Nets separately for subsequent cross-tracer and cross-protocol transfer learning. The full-dose PET images were used as the labels while low-dose PET images from 10% counts were used as the inputs. Three types of U-Nets were obtained: a U-Net trained by FDG dataset, a pre-trained FDG U-Net fine-tuned by another less-available tracer (FMISO/DOATATE), and a U-Net completely trained by a large number of less-available tracer datasets (FMISO/DOATATE), used as the reference U-Net. The denoising performance of the three types of U-Nets was evaluated on single-bed 18F-FMISO and whole-body 68Ga-DOTATATE separately and compared using normalized root-mean-square error (NRMSE), signal-to-noise ratio (SNR), and relative bias of region of interest (ROI). For cross-tracer transfer learning, all the U-Nets provided denoised images with similar quality for both tracers. There was no significant difference in terms of NRMSE and SNR when comparing the former two U-Nets with the reference U-Net. The ROI biases for these U-Nets were similar. For cross-tracer and cross-protocol transfer learning, the pre-trained single-bed FDG U-Net fine-tuned by whole-body DOTATATE data provided the most consistent images with the reference U-Net. Fine-tuning significantly reduced the NRMSE and the ROI bias and improved the SNR when comparing the fine-tuned U-Net with the U-Net trained by single-bed FDG only (NRMSE: 96.3% ± 21.1% versus 120.6% ± 18.5%, ROI bias: −10.5% ± 13.0% versus −14.7% ± 6.4%, SNR: 4.2 ± 1.4 versus 3.9 ± 1.6, for fine-tuned U-Net and the U-Net trained by single-bed FDG, respectively, with p < 0.01 in all cases). This work demonstrated that it is feasible to utilize existing networks well-trained by FDG datasets to reduce the noise for other less-available tracers and other scanning protocols by using the fine-tuning strategy.
Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries

Background Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD. Methods Clinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Gene, analysis was performed using TopHat, R and MSigDB. Cluster analysis was performed using GoElite and Pathway analysis performed using PANTHERdb Overrepresentation Test. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups. Results Placental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi, and increased fibrin deposition in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Need to include RNA and IHC. Conclusions Despite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the
Yield and agronomic traits of winter rapeseed cultivars registered in China from 2001 to 2010

To understand the relationship between yield and agronomic traits of registered rapeseed in China,205 cultivars from 2001 to 2010 were investigated and compared using correlation and path analysis.Results showed that average yield increased from 2 388.78kg/hm2(during 2001 to 2005) to 2 670.13kg/hm2(during 2006 to 2010) with 11.12% increase.Effective siliquae per plant,seed per siliqua and thousand-seed weight increased 4.03%,0.36% and 7.10% respectively.Yield had significant or highly significant correlations to seed per siliqua,branch number,yield stability and growth duration in 2001-2005 and 2006-2010.Moreover,yield also had highly significant correlation(r=0.38) to effective siliquae per plant in 2006-2010.Thus the effective siliquae per plant and thousand-seed weight were the main factors contributing to yield improvement.Other traits were also important to yield.The order of direct strong effect of traits on yield was incidence of Sclerotinia stem rot,index of Sclerotinia stem rot,index of viral disease,incidence of viral disease,seed per silique and effective siliquae per plant in 2001-2005.The order of direct strong effect of traits on yield was seed per siliqua,incidence of Sclerotinia stem rot,plant height,growth duration,effective siliquae per plant and thousand-seed weight in 2006
Managing Positive Margins After Oncoplastic Surgery

Oncoplastic surgery (OPS) is a type of breast conservation surgery that involves a partial mastectomy and simultaneous reconstruction of the breast using volume displacement or volume replacement techniques. 1 Level 2 volume displacement oncoplastic surgery (LVOS), using oncoplastic reduc-tion designs, is defined as the removal of 20% to 50% of the breast as part of the cancer resection. 1 Although uncommon, positive margins in LVOS may be treated with re- excision rather than completion mastectomy. 2 To date, there is scarce literature describing techniques for re- excision of a positive margin after LVOS. We present 2 patients with positive margins after 2 different LVOS procedures who underwent suc cessful re- excision surgeries. Our cases demonstrate that a positive margin in LVOS should not necessarily mandate a completion mastectomy and that re- excision is possible in appropriately selected patients.
Impact of Fast-Acting Insulin Aspart on Glycemic Control in Patients with Type 1 Diabetes Using Intermittent-Scanning Continuous Glucose Monitoring Within a Real-World Setting: The GoBolus Study

Background: The GoBolus study investigated the real-world effectiveness of faster aspart in patients with type 1 diabetes (T1D) using intermittent-scanning continuous glucose monitoring (iscCGM) systems. Methods: This 24-week, multicenter, single-arm, noninterventional study investigated adults with T1D (HbA1c, 7.5%–9.5%) receiving multiple daily injections (MDI) of insulin and using iscCGM within local healthcare settings for ≥6 months before switching to faster aspart at study start (week 0; baseline). Primary endpoint was HbA1c change from baseline to week 24. Exploratory endpoint was change in iscCGM metrics from baseline to week 24. Results: Overall, 243 patients were included (55.6% male), with mean age/diabetes duration, 49.9/18.8 years; mean HbA1c, 8.1%. By week 24, HbA1c had decreased by 0.19% (−2.1 mmol/mol, P < 0.0001) with no mean change in insulin doses or basal/bolus insulin ratios. For patients with sufficient available iscCGM data (n = 92): “time in range” (TIR; 3.9–10.0 mmol/L) increased from 46.9% to 50.1% (P = 0.01), corresponding to an increase of 46.1 min/day; time in hyperglycemia decreased from 49.1% to 46.1% (>10.0 mmol/L, P = 0.026) and 20.4% to 17.9% (>13.9 mmol/L, P = 0.013), corresponding to 43.5 (P = 0.024) and 35.6 (P = 0.015) fewer minutes per day on average spent in these ranges, respectively; no change for time in hypoglycemia (<3.9 and <3.0 mmol/L). Mean interstitial and postprandial glucose improved from 10.4 to 10.1 mmol/L (P = 0.035) and 11.9 to 11.0 mmol/L (P = 0.002), respectively. Conclusion: Real-world switching to faster aspart in adults with T1D on MDI improved HbA1c, increased TIR, and decreased time in hyperglycemia without affecting time in hypoglycemia. The GoBolus study: NCT03450863.
Effect of COVID-19 on computed tomography usage and critical test results in the emergency department: an observational study.

BACKGROUND The effect of the coronavirus disease 2019 (COVID-19) pandemic on new or unexpected radiologic findings in the emergency department (ED) is unclear. The aim of this study was to determine the effect of the COVID-19 pandemic on the number of computed tomography (CT) critical test results in the ED. METHODS We performed a retrospective observational study of ED CT usage at 4 Ontario hospitals (1 urban academic, 1 northern academic, 1 urban community and 1 rural community) over 1 month during the COVID-19 pandemic (April 2020) and over the same month 1 year earlier (April 2019; before the pandemic). The CT findings from 1 of the 4 hospitals, Hamilton Health Sciences, were reviewed to determine the number of critical test results by body region. Total CT numbers were compared using Poisson regression and CT yields were compared using the χ2 test. RESULTS The median number of ED CT examinations per day was markedly lower during the COVID-19 pandemic than before the pandemic (82 v. 133, p < 0.01), with variation across hospitals (p = 0.001). On review of 1717 CT reports from Hamilton Health Sciences, fewer critical test results were demonstrated on CT pulmonary angiograms (43 v. 88, p < 0.001) and CT examinations of the head (82 v. 112, p < 0.03) during the pandemic than before the pandemic; however, the yield of these examinations did not change. Although the absolute number of all CT examinations with critical test results decreased, the number of CT examinations without critical results decreased more, resulting in a higher yield of CT for critical test results during the pandemic (46% [322/696] v. 37% [379/1021], p < 0.01). INTERPRETATION Emergency department CT volumes markedly decreased during the COVID-19 pandemic, predominantly because there were fewer examinations with new or unexpected findings. This suggests that COVID-19 public information campaigns influenced the behaviours of patients presenting to the ED.
Cross‐scale quality assessment of a mechanistic cation exchange chromatography model

Cation exchange chromatography (CEX) is an essential part of most monoclonal antibody (mAb) purification platforms. Process characterization and root cause investigation of chromatographic unit operations are performed using scale down models (SDM). SDM chromatography columns typically have the identical bed height as the respective manufacturing‐scale, but a significantly reduced inner diameter. While SDMs enable process development demanding less material and time, their comparability to manufacturing‐scale can be affected by variability in feed composition, mobile phase and resin properties, or dispersion effects depending on the chromatography system at hand. Mechanistic models can help to close gaps between scales and reduce experimental efforts compared to experimental SDM applications. In this study, a multicomponent steric mass‐action (SMA) adsorption model was applied to the scale‐up of a CEX polishing step. Based on chromatograms and elution pool data ranging from laboratory‐ to manufacturing‐scale, the proposed modeling workflow enabled early identification of differences between scales, for example, system dispersion effects or ionic capacity variability. A multistage model qualification approach was introduced to measure the model quality and to understand the model's limitations across scales. The experimental SDM and the in silico model were qualified against large‐scale data using the identical state of the art equivalence testing procedure. The mechanistic chromatography model avoided limitations of the SDM by capturing effects of bed height, loading density, feed composition, and mobile phase properties. The results demonstrate the applicability of mechanistic chromatography models as a possible alternative to conventional SDM approaches.
Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: outcomes from a specialist clinic in the UK

Objectives Cognitive behavioural therapy is commonly used to treat chronic fatigue syndrome and has been shown to be effective for reducing fatigue and improving physical functioning. Most of the evidence on the effectiveness of cognitive behavioural therapy for chronic fatigue syndrome is from randomised control trials, but there are only a few studies in naturalistic treatment settings. Our aim was to examine the effectiveness of cognitive behavioural therapy for chronic fatigue syndrome in a naturalistic setting and examine what factors, if any, predicted outcome. Design Using linear mixed effects analysis, we analysed patients' self-reported symptomology over the course of treatment and at three-month follow-up. Furthermore, we explored what baseline factors were associated with improvement at follow-up. Setting Data were available for 995 patients receiving cognitive behavioural therapy for chronic fatigue syndrome at an outpatient clinic in the UK. Participants Participants were referred consecutively to a specialist unit for chronic fatigue or chronic fatigue syndrome. Main outcome measures Patients were assessed throughout their treatment using self-report measures including the Chalder Fatigue Scale, 36-item Short Form Health Survey, Hospital Anxiety and Depression Scale and Global Improvement and Satisfaction. Results Patients’ fatigue, physical functioning and social adjustment scores significantly improved over the duration of treatment with medium to large effect sizes (|d| = 0.45–0.91). Furthermore, 85% of patients self-reported that they felt an improvement in their fatigue at follow-up and 90% were satisfied with their treatment. None of the regression models convincingly predicted improvement in outcomes with the best model being (R2 = 0.137). Conclusions Patients’ fatigue, physical functioning and social adjustment all significantly improved following cognitive behavioural therapy for chronic fatigue syndrome in a naturalistic outpatient setting. These findings support the growing evidence from previous randomised control trials and suggest that cognitive behavioural therapy could be an effective treatment in routine treatment settings.
The Molecular Machinery of Gametogenesis in Geodia Demosponges (Porifera): Evolutionary Origins of a Conserved Toolkit across Animals

Abstract All animals are capable of undergoing gametogenesis. The ability of forming haploid cells from diploid cells through meiosis and recombination appeared early in eukaryotes, whereas further gamete differentiation is mostly a metazoan signature. Morphologically, the gametogenic process presents many similarities across animal taxa, but little is known about its conservation at the molecular level. Porifera are the earliest divergent animals and therefore are an ideal phylum to understand evolution of the gametogenic toolkits. Although sponge gametogenesis is well known at the histological level, the molecular toolkits for gamete production are largely unknown. Our goal was to identify the genes and their expression levels which regulate oogenesis and spermatogenesis in five gonochoristic and oviparous species of the genus Geodia, using both RNAseq and proteomic analyses. In the early stages of both female and male gametogenesis, genes involved in germ cell fate and cell-renewal were upregulated. Then, molecular signals involved in retinoic acid pathway could trigger the meiotic processes. During later stages of oogenesis, female sponges expressed genes involved in cell growth, vitellogenesis, and extracellular matrix reassembly, which are conserved elements of oocyte maturation in Metazoa. Likewise, in spermatogenesis, genes regulating the whole meiotic cycle, chromatin compaction, and flagellum axoneme formation, that are common across Metazoa were overexpressed in the sponges. Finally, molecular signals possibly related to sperm capacitation were identified during late stages of spermatogenesis for the first time in Porifera. In conclusion, the activated molecular toolkit during gametogenesis in sponges was remarkably similar to that deployed during gametogenesis in vertebrates.
Drug utilization study on immediate release Fentanyl in Spain. Prevalence, incidence, and indication

We aimed to characterize the trends of immediate release fentanyl (IRF) use in Spain between 2012 and 2017 and indication for its use. IRF drugs are rapid‐acting opioids approved to treat breakthrough cancer pain (BTCP) in patients already receiving maintenance opioid therapy for chronic cancer pain. A substantial increase in consumption of IRF has been observed with emerging cases of abuse and dependence, most of them in noncancer patients.
Discovery of Roblitinib (FGF401) as a Reversible-Covalent Inhibitor of the Kinase Activity of Fibroblast Growth Factor Receptor 4.

FGF19 signaling through the FGFR4/β-klotho receptor complex has been shown to be a key driver of growth and survival in a subset of hepatocellular carcinomas making selective FGFR4 inhibition an attractive treatment opportunity. A kinome-wide sequence alignment highlighted a poorly-conserved cysteine residue within the FGFR4 ATP-binding site at position 552, two positions beyond the gate-keeper residue. Several strategies for targeting this cysteine to identify FGFR4 selective inhibitor starting points are summarised which made use of both rationale and unbiased screening approaches. The optimisation of a 2-formylquinoline amide hit series is described in which the aldehyde makes a hemithioacetal reversible-covalent interaction with cysteine 552. Key challenges addressed during the optimisation are improving the FGFR4 potency, metabolic stability and solubility leading ultimately to the highly-selective first-in-class clinical candidate roblitinib.
Effects of bactrian camel milk on histology and cell apoptosis of kidney in type 2 diabetes mellitus rats

To investigate the protective effects of bactrian camel milk on histology and cell apoptosis of kidney in type 2diabetes mellitus(T2DM)rats.T2 DM rat model was established by feeding high-calorie forage and intraperitoneal injection of streptozotocin.Sixty adult male rats with similar month of age and body condition were randomly divided into the diabetes model group(DMC)and three treatment groups,including low concentration camel milk(LCM)group,high concentration camel milk(HCM)group and metformin hydrochloride(MTH)group,12 in each group.12 healthy rats were taken as control.After 4weeks treatment,the blood were collected for determining fasting plasma glucose(FPG)concentration.Pathological changes of kidney tissue were observed by HE staining;the expressions of Bax(Bcl2-associated X protein,Bax),Bcl-2(B cell lymphoma/lewkmia-2,Bcl-2),Caspase 3(cysteinyl aspartate specific proteinase 3,Caspase 3)and NF-κB(nuclear factor-kappa B)mRNA were detected by RT-qPCR;the expressions of Bax and Bcl-2protein were detected by immunohistochemical and western blotting methods.Compared with DMC group,FPG in LCM,HCM and MTH group was significantly decreased(P0.01),insulin sensitivity index(ISI)in LCM group was significantly increased(P0.01). HE staining showed that larger renal glomerulus,smaller renal capsule and renal glomerulus bleeding in DMC group,while the structure of kidney tissue was alleviated in LCM,HCM and MTH group.The expressions of Bax mRNA and NF-κB mRNA were the highest in DMC group,Bcl-2mRNA and Caspase 3mRNA were the highest in LCM group and HCM group,respectively.To compare with DMC group,the expression of Bax protein was decreased in LCM,HCM and MTH group,on the contrary,Bcl-2was increased.The results reveal that bactrian camel milk can reduce kidney injury and suppress cell apoptosis of T2 DM rats,which provides an effective treatment for diabetes mellitus.
Comparisons of the Sensitivity and Reliability of Multiple Measures of Listening Effort.

OBJECTIVES The objective of this study was to evaluate the sensitivity and reliability of one subjective (rating scale) and three objective (dual-task paradigm, pupillometry, and skin conductance response amplitude) measures of listening effort across multiple signal to noise ratios (SNRs). DESIGN Twenty adults with normal hearing attended two sessions and listened to sentences presented in quiet and in stationary noise at three different SNRs: 0, -3, and -5 dB. Listening effort was assessed by examining change in reaction time (dual-task paradigm), change in peak to peak pupil diameter (pupillometry), and change in mean skin conductance response amplitude; self-reported listening effort on a scale from 0 to 100 was also evaluated. Responses were averaged within each SNR and based on three word recognition ability categories (≤50%, 51% to 71%, and >71%) across all SNRs. Measures were considered reliable if there were no significant changes between sessions, and intraclass correlation coefficients were a minimum of 0.40. Effect sizes were calculated to compare the sensitivity of the measures. RESULTS Intraclass correlation coefficient values indicated fair-to-moderate reliability for all measures while individual measurement sensitivity was variable. Self-reports were sensitive to listening effort but were less reliable, given that subjective effort was greater during the dual task than either of the physiologic measures. The dual task was sensitive to a narrow range of word recognition abilities but was less reliable as it exhibited a global decrease in reaction time across sessions. Pupillometry was consistently sensitive and reliable to changes in listening effort. Skin conductance response amplitude was not sensitive or reliable while the participants listened to the sentences. Skin conductance response amplitude during the verbal response was sensitive to poor (≤50%) speech recognition abilities; however, it was less reliable as there was a significant change in amplitude across sessions. CONCLUSIONS In this study, pupillometry was the most sensitive and reliable objective measure of listening effort. Intersession variability significantly influenced the other objective measures of listening effort, which suggests challenges for cross-study comparability. Therefore, intraclass correlation coefficients combined with other statistical tests more fully describe the reliability of measures of listening effort across multiple difficulties. Minimizing intersession variability will increase measurement sensitivity. Further work toward standardized methods and analysis will strengthen our understanding of the reliability and sensitivity of measures of listening effort and better facilitate cross-modal and cross-study comparisons.