Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting Gene Expression Divergence between Single-Copy Orthologs in Two Species

Abstract Predicting gene expression divergence is integral to understanding the emergence of new biological functions and associated traits. Whereas several sophisticated methods have been developed for this task, their applications are either limited to duplicate genes or require expression data from more than two species. Thus, here we present PredIcting eXpression dIvergence (PiXi), the first machine learning framework for predicting gene expression divergence between single-copy orthologs in two species. PiXi models gene expression evolution as an Ornstein-Uhlenbeck process, and overlays this model with multi-layer neural network (NN), random forest, and support vector machine architectures for making predictions. It outputs the predicted class “conserved” or “diverged” for each pair of orthologs, as well as their predicted expression optima in the two species. We show that PiXi has high power and accuracy in predicting gene expression divergence between single-copy orthologs, as well as high accuracy and precision in estimating their expression optima in the two species, across a wide range of evolutionary scenarios, with the globally best performance achieved by a multi-layer NN. Moreover, application of our best-performing PiXi predictor to empirical gene expression data from single-copy orthologs residing at different loci in two species of Drosophila reveals that approximately 23% underwent expression divergence after positional relocation. Further analysis shows that several of these “diverged” genes are involved in the electron transport chain of the mitochondrial membrane, suggesting that new chromatin environments may impact energy production in Drosophila. Thus, by providing a toolkit for predicting gene expression divergence between single-copy orthologs in two species, PiXi can shed light on the origins of novel phenotypes across diverse biological processes and study systems.
Generation of focused, nonspherically decaying pulses of electromagnetic radiation

Periodic pulses of polarized electromagnetic radiation can be generated whose intensity diminishes with the distance ${R}_{P}$ from their source like ${R}_{P}^{\ensuremath{-}1}$ instead of ${R}_{P}^{\ensuremath{-}2}. $ The source required is an extended charge with a rotating distribution pattern whose outer parts move with linear phase speeds exceeding the speed of light in vacuo. The coherence and beaming of the radiation in question stem from constructive interference of the emitted waves and formation of caustics. These processes take place at different distances from the source for different sets of waves, so that the propagating wave packets embodying the pulses are constantly dispersed and reconstructed out of other waves.
Structural study of wild-type and phospho-mimic XRCC4 dimer and multimer proteins using circular dichroism spectroscopy

Abstract Purpose To investigate the structural features of wild-type and phospho-mimicking mutated XRCC4 protein, a protein involved in DNA double-strand break repair. Materials and methods XRCC4 with a HisTag were expressed by E. coli harboring plasmid DNA and purified. Phospho-mimicking mutants in which one phosphorylation site was replaced with aspartic acid were also prepared in order to reproduce the negative charge resulting from phosphorylation. The proteins were separated into dimers and multimers by gel filtration chromatography. Circular dichroism (CD) spectroscopy was performed in the region from ultraviolet to vacuum-ultraviolet. The CD spectra were analyzed with two analysis programs to evaluate the secondary structures of the wild-type and phospho-mimicked dimers and multimers. Result and Discussion The proportion of β-strand in the wild-type dimers was very low, particularly in their C-terminal region, including the five phosphorylation sites. The secondary structure of the phospho-mimic hardly changed in the dimeric form. In contrast, the β-strand content increased and the α-helix content decreased upon multimerization of the wild-type protein. The structural change of multimers slightly depended on the phospho-mimic site. These results suggest that the β-strand structure stabilizes the multimerization of XRCC4 and it is regulated by phosphorylation at the C-terminal site in living cells. Conclusion An increase in the β-strand content in XRCC4 is essential for stabilization of the multimeric form through C-terminal phosphorylation, allowing the formation of the large double-strand break repair machinery.
Predicting the Risk of Posttraumatic Osteoarthritis After Primary Anterior Cruciate Ligament Reconstruction: A Machine Learning Time-to-Event Analysis

Background: There is a significant long-term risk of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament reconstruction (ACLR). Elucidating the risk factors and successfully identifying at-risk patients is challenging. Purpose/Hypothesis: The purpose of this study was to produce machine learning survival models that can identify (1) patients at risk of symptomatic PTOA and (2) patients who are at risk of undergoing total knee arthroplasty (TKA) after ACLR. It was hypothesized that these models would outperform traditional Kaplan-Meier estimators. Study Design: Case-control study; Level of evidence, 3. Methods: A geographic database was used to identify patients undergoing ACLR between 1990 and 2016 with a minimum 7.5-year follow-up. Models were used to analyze various factors to predict the rate and time to (1) symptomatic osteoarthritis and (2) TKA using random survival forest (RSF) algorithms. Performance was measured using out-of-bag (OOB) c-statistic, calibration, and Brier score. The predictive performances of the RSF models were compared with Kaplan-Meier estimators. Model interpretability was enhanced utilizing global variable importance and partial dependence curves. Results: A total of 974 patients with ACLR and a minimum follow-up of 7.5 years were included; among these, 215 (22.1%) developed symptomatic osteoarthritis, and 25 (2.6%) progressed to TKA. The RSF algorithms achieved acceptable good to excellent predictive performance for symptomatic arthritis (OOB c-statistic, 0.75; Brier score, 0.128) and progression to TKA (OOB c-statistic, 0.89; Brier score, 0.026), respectively. Significant predictors of symptomatic PTOA included increased pain scores, older age, increased body mass index, increased time to ACLR, total number of arthroscopic surgeries before the diagnosis of arthritis, positive pivot-shift test after reconstruction, concomitant chondral injury, secondary meniscal tear, early (<250 days) or delayed (>500 days) return to sports or activity, and use of allograft. Significant predictors for TKA included older age, increased pain scores, total number of arthroscopic surgeries, high-demand activity/occupation, hypermobility, higher body mass index, systemic inflammatory disease, increased time to surgery, early (<250 days) or delayed (>500 days) return to sports or activity, and midsubstance tears. The Brier score over time revealed that RSF models outperformed traditional Kaplan-Meier estimators. Conclusion: Machine learning survival models were used to reliably identify patients at risk of developing symptomatic PTOA, and these models consistently outperformed traditional Kaplan-Meier estimators. Strong predictors for the development of PTOA after ACLR included increased pain scores at injury and postoperative visit, older age at injury, total number of arthroscopic procedures, positive postoperative pivot-shift test, and secondary meniscal tear.
Hip survival after periacetabular osteotomy in patients with acetabular dysplasia, acetabular retroversion, congenital dislocation of the hip, or Legg-Calvé-Perthes disease: a cohort study on 1,501 hips

Background and purpose Previous studies on hip survival following periacetabular osteotomy (PAO) have reported isolated data for the treatment of 1 underlying condition, making comparison between patient groups difficult. We report the hip survival after PAO in patients with acetabular dysplasia (AD), acetabular retroversion (AR), congenital dislocation of the hip (CDH), and Legg-Calvé-Perthes disease (LCPD) with total hip arthroplasty (THA) as primary endpoint and secondarily the risk of subsequent hip-related operations other than THA. Patients and methods From 1997 to December 2021, 1,501 hips (1,203 patients) underwent PAO in a single center (Odense University Hospital). We identified conversions to THA and other subsequent hip-related operations through patient files and the Danish National Patient Registry (DNPR). Results 123 (8.2%) of the total cohort of 1,501 hips were converted to THA within the study period. The overall Kaplan–Meier hip survival rate was 71% (95% confidence interval [CI] 61–79) at 24 years with a mean follow-up of 7.6 years (range 0.02–25). The individual Kaplan–Meier hip survival rates at 15 years were 81% (CI 76–86) for AD, 94% (CI 91–96) for AR, 84% (CI 66–93) for CDH, and 66% (CI 49–79) for LCPD. In total, the overall risk of additional hip-related operations was 48% (of which 92% were screw removal). Conclusion Encouragingly, 71% of hips were preserved 24 years after PAO. We found that AR patients had the highest (94%) PAO survivorship at 15 years compared with the other underlying hip conditions. Almost half of PAO patients may undergo later additional surgery, of which screw removal is the primary intervention. Overall long-term survival, risk factors for conversion to THA, and risk of additional surgery are relevant information for shared decision-making.
Garlic supplementation attenuates cycling exercise-induced oxidative inflammation but fails to improve time trial performance in healthy adults

ABSTRACT BACKGROUND Garlic extract has been shown to enhance antioxidant and anti-inflammation activities in humans. The present study investigated the effects of garlic supplementation on 40-km cycling time trial performance, exercise-induced oxidative stress, and inflammatory responses in healthy adults. METHODS Eleven healthy males were recruited to perform this single-blind crossover study. Participants were randomly assigned to either garlic (garlic extracts 1000 mg/d for 4 weeks) or placebo trials. Following 4-wks of supplementation, participants performed a 40-km cycling challenge. Total cycling performance time and respiratory exchange ratio (RER) were recorded. Blood samples were collected every 10 km to determine exercise-induced oxidative stress, inflammation, and muscle damage. RESULTS The 40-km cycling time trial performance was not improved following 4 weeks of garlic supplementation. However, 4-wk garlic supplementation significantly increased whole-body antioxidant capacity (total antioxidant capacity, TAC), and subsequently attenuated MDA, TNF-α, and LDH during the 40-km cycling exercise period (p < 0.05). There were no significant differences among the blood biomarkers glucose, NEFA, IL-6, UA, and CK respectively. The respiratory exchange ratio was similar between garlic and placebo trials. CONCLUSION Four-week oral garlic supplementation attenuates exercise-induced oxidative inflammation and muscle damage during a 40-km bout of cycling. However, it appeared that 4-wk oral garlic had no ergogenic effect on cycling performance in healthy males.
Inverse spin Hall effect in Cr: Independence of antiferromagnetic ordering

Chromium is a 3d spin density wave antiferromagnetic (AF) metal with a Néel temperature of 311 K. By using the thermal spin injection method, we have observed large inverse spin Hall voltage in Cr. With negligible magnetic proximity effect and a large spin Hall angle, Cr is a superior intrinsic pure spin current detector than many 5d metals. Even more strikingly, the temperature dependent thermal spin injection measurements show that the large spin Hall angle in Cr is independent of the AF ordering and indicating that the inverse spin Hall effect is unrelated to AF ordering in Cr.
Repeated poisonings in Denmark – a nationwide study

Abstract Objective Poisonings contribute significantly to morbidity and mortality of patients. Some patients have numerous contacts to a poison information center, indicating repeated poisoning exposures. Information on the involved substances is necessary to explore methods to prevent self-harm and reduce mortality. The objective of this study was to characterize the patient population with repeated poison exposures in Denmark and identify the substances involved. Methods This study was a retrospective cohort study of enquiries to the nationwide Danish Poison Information Centre and the Danish National Patient Registry. The databases were used to identify patients with more than five individual poisoning episodes within a 12-month-period between 1 January 2013, and 31 December 2017. Results One hundred and thirty-seven patients and 995 patients met the inclusion criteria in the Danish Poison Information Centre and the Danish National Patient Registry, respectively. The majority were women (82.5% and 66.3% for the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively). The mean age was 24.7 and 29.5 years. Psychiatric comorbidities were frequent with 74.5% and 67.0% suffering from personality disorders and 70.1% and 54.5% from affective disorders in the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively. One thousand seven hundred and fifty-two poisoning episodes were identified in the Danish Poison Information Centre database, and the most common types of substance were ‘pharmaceuticals’ (1,420 episodes). The most common medications ingested were quetiapine, paracetamol and cyclizine. Median number of contacts to the Danish Poison Information Centre was 10. Patients with one or more poisoning episodes involving cyclizine had on average 11.4 poisoning episodes involving cyclizine. In the Danish National Patient Registry cohort 80.9% were alive after 10 years compared to 97.7% in the background population. Conclusion and Implications Most poisonings were intentional and occurred among younger women. Psychiatric comorbidity was frequent. Most often, pharmaceuticals were the toxic substance, mainly quetiapine, paracetamol and cyclizine. Changing the status of cyclizine from over the counter to prescription only medication, and implementing stricter rules for prescribing quetiapine, could limit future poisoning incidences.
Postoperative wound dehiscence in mandibular fractures

Abstract Objective To clarify the occurrence and causes of non-infection-related surgical wound dehiscence (SWD) in intraorally treated mandibular fractures. Material and Methods Patients with one or two fractures of the dentate part of the mandible treated surgically via an intraoral approach were included in this retrospective study. The primary outcome variable was SWD. Associations between patient-, fracture- and surgery-related variables and SWD were evaluated. Results Altogether 232 patients with 270 mandibular angle, body, symphysis and/or parasymphysis fractures were included in the analysis. In all, 22 SWDs were detected. These occurred in 9.5% of patients and in 8.1% of fractures. Surgery performed at night-time showed a significantly higher SWD rate than daytime surgeries (p = .012). Additionally, a significantly greater SWD rate was found among smokers (p = .041). Other studied variables remained statistically non-significant for SWD. In a multivariate analysis, night-time was the only significant independent variable with an odds ratio of 3.297 (95% CI 1.238 − 8.780, p = .017) for SWD. Conclusion The approach or closure technique used and the fracture type had only a minor effect on non-infection-related SWD in patients with mandibular fractures. To avoid SWDs, mandibular fracture surgeries should be conducted during the daytime with adequate support from an experienced surgeon.
Vibrotactile Thresholds on the Wrist for Vibrations Normal to the Skin

In order to facilitate the development of wrist-worn vibrotactile devices, detailed knowledge about how vibrations are perceived by the users is needed. In particular, perceptual thresholds in amplitude are really important. Thresholds have been measured in the literature for other areas of the body, but given the variability reported between areas (shape of the threshold curve, position of maximum sensitivity), thresholds on the wrist can not be inferred from previous measurements and must be measured. The amplitude thresholds for vibrations normal to the skin surface were evaluated on 28 participants, with a three interval forced choice method. They were measured for 7 frequencies that are classical in the literature about vibrotactile perception (25, 40, 80, 160, 250, 320, and 640 Hz). The classical U-shape of the amplitude-threshold curve is observed, with a maximum sensitivity at around 160 Hz, which differs from other body areas, but confirms recent results obtained for vibrations parallel to the skin surface of the same body area. The sensitivity thresholds of vibrotactile signals appear to be in the micrometer range.
Radiomics and dosiomics-based prediction of radiotherapy-induced xerostomia in head and neck cancer patients

Abstract Background and aim Dose-response modeling for radiotherapy-induced xerostomia in head and neck cancer (HN) patients is a promising frontier for personalized therapy. Feature extraction from diagnostic and therapeutic images (radiomics and dosiomics features) can be used for data-driven response modeling. The aim of this study is to develop xerostomia predictive models based on radiomics-dosiomics features. Methods Data from the cancer imaging archive (TCIA) for 31 HN cancer patients were employed. For all patients, parotid CT radiomics features were extracted, utilizing Lasso regression for feature selection and multivariate modeling. The models were developed by selected features from pretreatment (CT1), mid-treatment (CT2), post-treatment (CT3), and delta features (ΔCT2-1, ΔCT3-1, ΔCT3-2). We also considered dosiomics features extracted from the parotid dose distribution images (Dose model). Thus, combination models of radio-dosiomics (CT + dose & ΔCT + dose) were developed. Moreover, clinical, and dose-volume histogram (DVH) models were built. Nested 10-fold cross-validation was used to assess the predictive classification of patients into those with and without xerostomia, and the area under the receiver operative characteristic curve (AUC) was used to compare the predictive power of the models. The sensitivity and accuracy of models also were obtained. Results In total, 59 parotids were assessed, and 13 models were developed. Our results showed three models with AUC of 0.89 as most predictive, namely ΔCT2-1 + Dose (Sensitivity 0.99, Accuracy 0.94 & Specificity 0.86), CT3 model (Sensitivity 0.96, Accuracy 0.94 & Specificity 0.86) and DVH (Sensitivity 0.93, Accuracy 0.89 & Specificity 0.84). These models were followed by Clinical (AUC 0.89, Sensitivity 0.81, Accuracy 0.97 & Specificity 0.89) and CT2 & Dose (AUC 0.86, Sensitivity 0.97, Accuracy 0.87 & Specificity 0.82). The Dose model (developed by dosiomics features only) had AUC, Sensitivity, Specificity, and Accuracy of 0.72, 0.98, 0.33, and 0.79 respectively. Conclusion Quantitative features extracted from diagnostic imaging during and after radiotherapy alone or in combination with dosiomics markers obtained from dose distribution images can be used for radiotherapy response modeling, opening up prospects for personalization of therapies toward improved therapeutic outcomes.
Epitaxial growth and characterization of SnSe phases on Au(111)

Two-dimensional (2D) layered group IV–VI semiconductors attract great interest due to their potential applications in nanoelectronics. Depending on the dimensionality, different phases of the same material can present completely different electronic and optical properties, expanding its applications. Here, we present a combined experimental and theoretical study of the atomic structure and electronic properties of epitaxial SnSe structures grown on a metallic Au(111) substrate, forming almost defect-free 2D layers. We describe a coverage-dependent transition from a metallic β-SnSe to a semiconducting α-SnSe phase. The combination of scanning tunneling microscopy/spectroscopy, non-contact atomic force microscopy, x-ray photoelectron spectroscopy/diffraction and angle-resolved photoemission spectroscopy, complemented by density functional theory, provides a comprehensive study of the geometric and electronic structure of both phases. Our work demonstrates the possibility to grow two distinct SnSe phases on Au(111) with high quality and on a large scale. The strong interaction with the substrate allows the stabilization of the previously experimentally unreported β-SnSe, while the ultra-thin films of orthorhombic α-SnSe are structurally and electronically equivalent to bulk SnSe.
An Investigation of Lesion Detection Accuracy for Artificial Intelligence–Based Denoising of Low-Dose 64Cu-DOTATATE PET Imaging in Patients with Neuroendocrine Neoplasms

Visual Abstract Frequent somatostatin receptor PET, for example, 64Cu-DOTATATE PET, is part of the diagnostic work-up of patients with neuroendocrine neoplasms (NENs), resulting in high accumulated radiation doses. Scan-related radiation exposure should be minimized in accordance with the as-low-as-reasonably achievable principle, for example, by reducing injected radiotracer activity. Previous investigations found that reducing 64Cu-DOTATATE activity to below 50 MBq results in inadequate image quality and lesion detection. We therefore investigated whether image quality and lesion detection of less than 50 MBq of 64Cu-DOTATATE PET could be restored using artificial intelligence (AI). Methods: We implemented a parameter-transferred Wasserstein generative adversarial network for patients with NENs on simulated low-dose 64Cu-DOTATATE PET images corresponding to 25% (PET25%), or about 48 MBq, of the injected activity of the reference full dose (PET100%), or about 191 MBq, to generate denoised PET images (PETAI). We included 38 patients in the training sets for network optimization. We analyzed PET intensity correlation, peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean-square error (MSE) of PETAI/PET100% versus PET25%/PET100%. Two readers assessed Likert scale–defined image quality (1, very poor; 2, poor; 3, moderate; 4, good; 5, excellent) and identified lesion-suspicious foci on PETAI and PET100% in a subset of the patients with no more than 20 lesions per organ (n = 33) to allow comparison of all foci on a 1:1 basis. Detected foci were scored (C1, definite lesion; C0, lesion-suspicious focus) and matched with PET100% as the reference. True-positive (TP), false-positive (FP), and false-negative (FN) lesions were assessed. Results: For PETAI/PET100% versus PET25%/PET100%, PET intensity correlation had a goodness-of-fit value of 0.94 versus 0.81, PSNR was 58.1 versus 53.0, SSIM was 0.908 versus 0.899, and MSE was 2.6 versus 4.7. Likert scale–defined image quality was rated good or excellent in 33 of 33 and 32 of 33 patients on PET100% and PETAI, respectively. Total number of detected lesions was 118 on PET100% and 115 on PETAI. Only 78 PETAI lesions were TP, 40 were FN, and 37 were FP, yielding detection sensitivity (TP/(TP+FN)) and a false discovery rate (FP/(TP+FP)) of 66% (78/118) and 32% (37/115), respectively. In 62% (23/37) of cases, the FP lesion was scored C1, suggesting a definite lesion. Conclusion: PETAI improved visual similarity with PET100% compared with PET25%, and PETAI and PET100% had similar Likert scale–defined image quality. However, lesion detection analysis performed by physicians showed high proportions of FP and FN lesions on PETAI, highlighting the need for clinical validation of AI algorithms.