Miracle-dz/UniFAR-FTUs huggingface dataset:
Transperineal Multiparametric Magnetic Resonance Imaging–Ultrasound Fusion Targeted Prostate Biopsy Combined with Standard Template Improves Prostate Cancer Detection

Purpose: Transperineal (TP) prostate biopsy provides an effective approach to prostate cancer (PCa) detection. Although transrectal targeted biopsy has been well described, the specific advantage of the standard TP template or TP targeted biopsy using multiparametric (mp) magnetic resonance imaging (MRI)-ultrasound (US) fusion remains less understood and without consensus. Materials and Methods: We identified all men who underwent a transperineal standard 20-core template in addition to a targeted biopsy with mpMRI-US fusion-guided software from September 2019 to February 2021. We assessed and compared clinical, MRI and biopsy characteristics between standard TP template and fusion targeted biopsies. Results: A total of 301 men underwent TP fusion biopsy during the study period. Target lesions on MRI were sampled with 3 targeted cores per patient (IQR 3–4). The overall cancer detection rate was 74.1% and 63.5% by standard template and targeted biopsy, respectively, of which 52.5% and 59.7% were clinically significant (cs) PCa. Combined csPCa detection rate was 62.2%. Of 176 cases with a cancer diagnosis by both biopsy methods, 18.8% were upgraded with targeted biopsies while 18.2% were upgraded with template biopsies. Conclusions: In men with suspicious lesions on mpMRI, TP MRI fusion-guided biopsies combined with standard template provide a higher overall cancer detection rate and higher detection rate of csPCa than the standard template or targeted biopsy alone. In the setting of a suspicious mpMRI prostate lesion, targeted plus standard template should be included as part of the TP biopsy procedure.
Impact of Liver Transplantation on Carbon Monoxide Production as Measured by Arterial Carboxyhemoglobin Levels in Cirrhotic Patients with and without Hepatopulmonary Syndrome

Background Hepatic dysfunction is associated with increased production of carbon monoxide. End-stage liver disease patients with hepatopulmonary syndrome (HPS) have been shown to have higher blood carbon monoxide levels than those without HPS. The impact of liver transplantation on blood carbon monoxide levels is currently unknown. We assessed the impact of liver transplantation on blood carbon monoxide and whether this is affected by HPS. Material/Methods Eligible liver transplant recipients had room air arterial blood gas testing performed before and after liver transplantation. The carboxyhemoglobin fraction was obtained from arterial co-oximetry and used as a surrogate for carboxyhemoglobin production. Mean arterial carboxyhemoglobin fraction before transplantation was compared to that after transplantation. Mean absolute and median relative pre- to post-transplant within-patient change in carboxyhemoglobin fraction was compared between those with and without HPS. Results Thirty-nine transplanted cirrhotic patients were analyzed, of whom 14 (36%) met criteria for hepatopulmonary syndrome. The mean pre-transplant carboxyhemoglobin fraction was higher than the post-transplant fraction (2.6 vs 1.8, difference 0.8 [95% CI 0.4–1.2]; P value 0.0002). Of the 14 patients with HPS, 11 (79%) experienced a decrease in their carboxyhemoglobin fraction after liver transplantation; among the 25 patients without HPS, 16 (64%) experienced such a decrease (P=0.48). Neither the absolute nor relative within-patient pre- to post-transplant change in carboxyhemoglobin fraction was significantly different between patients with and without HPS. Conclusions Blood carbon monoxide levels decreased significantly in cirrhotic patients following liver transplantation, but HPS did not affect the magnitude of this change.
The LpoA activator is required to stimulate the peptidoglycan polymerase activity of its cognate cell wall synthase PBP1a

Significance Class A penicillin-binding proteins (aPBPs) assemble the bacterial cell wall and are the targets of penicillin and related β-lactam antibiotics. In gram-negative bacteria, the aPBPs require outer membrane lipoproteins to function. However, little is known about how these proteins promote the activity of their cognate synthases in cells. Here, we show that one of these lipoproteins, called LpoA, has a much more pronounced effect on aPBP activity in cells than anticipated from biochemical studies. It not only modulates the cross-linking of cell wall polymers but is also required for the aPBP to make the polymers in the first place. Our findings therefore provide insights into the regulation of an important class of antibiotic targets in their native cellular context. A cell wall made of the heteropolymer peptidoglycan (PG) surrounds most bacterial cells. This essential surface layer is required to prevent lysis from internal osmotic pressure. The class A penicillin-binding proteins (aPBPs) play key roles in building the PG network. These bifunctional enzymes possess both PG glycosyltransferase (PGT) and transpeptidase (TP) activity to polymerize the wall glycans and cross-link them, respectively. In Escherichia coli and other gram-negative bacteria, aPBP function is dependent on outer membrane lipoproteins. The lipoprotein LpoA activates PBP1a and LpoB promotes PBP1b activity. In a purified system, the major effect of LpoA on PBP1a is TP stimulation. However, the relevance of this activation to the cellular function of LpoA has remained unclear. To better understand why PBP1a requires LpoA for its activity in cells, we identified variants of PBP1a from E. coli and Pseudomonas aeruginosa that function in the absence of the lipoprotein. The changes resulting in LpoA bypass map to the PGT domain and the linker region between the two catalytic domains. Purification of the E. coli variants showed that they are hyperactivated for PGT but not TP activity. Furthermore, in vivo analysis found that LpoA is necessary for the glycan synthesis activity of PBP1a in cells. Thus, our results reveal that LpoA exerts a much greater control over the cellular activity of PBP1a than previously appreciated. It not only modulates PG cross-linking but is also required for its cognate synthase to make PG glycans in the first place.
Indoor exposure levels of radon in dwellings, schools, and offices in China from 2000 to 2020: A systematic review.

After decades of development, the indoor environment in China has changed. A systematic review was conducted from peer-reviewed scientific papers with field test data of indoor radon in China from 2000 to 2020 for three types of buildings. The mean concentrations of indoor radon for dwellings, school buildings, and office buildings are 54.6, 56.1, and 54.9 Bq/m3 . The indoor radon concentration was related to seasons, climate regions, ventilation, decoration, and other factors such as soil and outdoor air. Colder seasons, especially in severe colder areas of China, newer decorated buildings, closed windows, and doors were all associated with higher indoor radon concentrations. Variables like climate region and ventilation showed statistical significance in the correlation analysis. Regarding the increasing trend of indoor radon concentration in China during the last two decades, further study of indoor radon is necessary especially for school buildings and office buildings, and will help access its environmental burden of disease in China more accurately.
Anti–contactin-1 Antibodies Affect Surface Expression and Sodium Currents in Dorsal Root Ganglia

Background and Objectives As autoantibodies to contactin-1 from patients with chronic inflammatory demyelinating polyradiculoneuropathy not only bind to the paranodes where they are supposed to cause conduction failure but also bind to other neuronal cell types, we aimed to investigate the effect of anti–contactin-1 autoantibodies on contactin-1 surface expression in cerebellar granule neurons, dorsal root ganglion neurons, and contactin-1–transfected human embryonic kidney 293 cells. Methods Immunocytochemistry including structured illumination microscopy and immunoblotting was used to determine expression levels of contactin-1 and/or sodium channels after long-term exposure to autoantibodies from 3 seropositive patients. For functional analysis of sodium channels, whole-cell recordings of sodium currents were performed on dorsal root ganglion neurons incubated with anti–contactin-1 autoantibodies. Results We found a reduction in contactin-1 expression levels on dorsal root ganglion neurons, cerebellar granule neurons, and contactin-1–transfected human embryonic kidney 293 cells and decreased dorsal root ganglion sodium currents after long-term exposure to anti–contactin-1 autoantibodies. Sodium channel density did not decrease. Discussion Our results demonstrate a direct effect of anti–contactin-1 autoantibodies on the surface expression of contactin-1 and sodium currents in dorsal root ganglion neurons. This may be the pathophysiologic correlate of sensory ataxia reported in these patients.
An Analysis of the Influence of Noneffective Instructions in Linear Genetic Programming

Abstract Linear Genetic Programming (LGP) represents programs as sequences of instructions and has a Directed Acyclic Graph (DAG) dataflow. The results of instructions are stored in registers that can be used as arguments by other instructions. Instructions that are disconnected from the main part of the program are called noneffective instructions, or structural introns. They also appear in other DAG-based GP approaches like Cartesian Genetic Programming (CGP). This article studies four hypotheses on the role of structural introns: noneffective instructions (1) serve as evolutionary memory, where evolved information is stored and later used in search, (2) preserve population diversity, (3) allow neutral search, where structural introns increase the number of neutral mutations and improve performance, and (4) serve as genetic material to enable program growth. We study different variants of LGP controlling the influence of introns for symbolic regression, classification, and digital circuits problems. We find that there is (1) evolved information in the noneffective instructions that can be reactivated and that (2) structural introns can promote programs with higher effective diversity. However, both effects have no influence on LGP search performance. On the other hand, allowing mutations to not only be applied to effective but also to noneffective instructions (3) increases the rate of neutral mutations and (4) contributes to program growth by making use of the genetic material available as structural introns. This comes along with a significant increase of LGP performance, which makes structural introns important for LGP.
Type 2 Diabetes: Vitamin D Status in Newly Diagnosed Patients, Dinajpur, Bangladesh

Original Research Article Introduction: Vitamin D deficiency is common in patients with type 2 diabetes mellitus (T2DM). Vitamin D status may have a causal role in the onset of T2DM and may influence glycemic control in these patients. The present crosssectional study was done among newly diagnosed 110 T2DM patients. Serum 25(OH) D was measured in all and classified as normal (≥30ng/mL), insufficient (>20 to 29.9ng/mL), and deficient (≤20ng/mL). The mean serum 25(OH) D level was 27.91±2.58ng/mL (mean±SEM). Aim of the Study: Aim of the study was to find out the vitamin D status in newly diagnosed type 2 diabetes patients in. Material & Methods: This cross-sectional study comprising of 110 newly detected subjects with T2DM was conducted in the outpatient department of M Abdur Rahim Medical College, Dinajpur, Bangladesh during the period from January 2019 to December 2019. One hundred and ten (110) participants were selected maintaining an inclusion criteria. Obesity status was determined by body mass index (BMI) categories applicable for the Asian Indians. The relevant Data were analyzed by using Statistical Packages for Social Sciences (SPSS), version 23.0 software (SPSS Inc; Chicago, IL, USA). Results: Among the study subjects, 30% were Vit-D deficient, 36% were Vit-D insufficient and 34% had normal 25(OH) D. There was no statistical difference of 25(OH)D level between the younger (age <40 years) and older (≥40 years) patients (28.31±4.3 vs. 27.44±2.6ng/mL, mean±SEM; p=0.869); males and females (26.79±2.1 vs. 31.09±8.2ng/mL, mean±SEM; p=0.470); among smokers, non-smokers and ex-smokers (26.86±4.31, 27.10±2.49 and 42.62±1.71ng/mL respectively, mean±SEM; p=0.363); among normal weight, overweight and obese (30.61±6.16, 35.61±9.52 and 24.27±1.71ng/mL respectively, mean±SEM; p=0.191); and among normotensive, borderline hypertensive and hypertensive (25.29±2.46, 32.57±5.32 and 20.84±3.66ng/mL respectively, mean±SEM; p=0.277) patients. 25(OH) D level showed significant negative correlation with body mass index (r= -0.391, p=0.017) and positive correlation (r=0.334, p=0.044) with fasting plasma glucose in male subjects. Conclusion: Age, sex, smoking status, BMI, systolic BP, diastolic BP, family history of DM, and smoking status were not found to influence vitamin D level independently. Our study found a high frequency of subnormal vitamin D in newly diagnosed T2DM patients. Screening for vitamin D status may be beneficial in T2DM patients.
Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing

DNA methylation is an epigenetic process that controls DNA accessibility and serves as a transcriptomic switch when deposited at regulatory regions. The adequate functioning of this process is indispensable for tissue homeostasis and cell fate determination. Conversely, altered DNA methylation patterns result in abnormal gene transcription profiles that contribute to tumor initiation and progression. However, whether the consequence of DNA methylation on gene expression and cell fate is uniform regardless of the cell type or state could so far not been tested due to the lack of technologies to target DNA methylation in-situ. Here, we have taken advantage of CRISPR/dCas9 technology adapted for epigenetic editing through site-specific targeting of DNA methylation to characterize the transcriptional changes of the candidate gene and the functional effects on cell fate in different tumor settings. As a proof-of-concept, we were able to induce de-novo site-specific methylation of the gene promoter of IGFBP2 up to 90% with long-term and bona-fide inheritance by daughter cells. Strikingly, this modification led to opposing expression profiles of the target gene in different cancer cell models and affected the expression of mesenchymal genes CDH1, VIM1, TGFB1 and apoptotic marker BCL2. Moreover, methylation-induced changes in expression profiles was also accompanied by a phenotypic switch in cell migration and cell morphology. We conclude that in different cell types the consequence of DNA methylation on gene expression and cell fate can be completely different.
Radiological–pathological signatures of patients with COVID-19-related pneumomediastinum: is there a role for the Sonic hedgehog and Wnt5a pathways?

Pneumomediastinum is a rare complication of acute respiratory distress syndrome (ARDS), when air leaks into the mediastinum. An increased pneumomediastinum incidence, of up to 5–13%, was reported during the coronavirus disease 2019 (COVID-19) pandemic [1, 2] and even occurred spontaneously without a history of mechanical ventilation [3], similarly to the previous severe acute respiratory syndrome (SARS)-1 [4]. Almost half of the 30 consecutive COVID-19 patients who had prolonged invasive mechanical ventilation had full-thickness tracheal lesions and pneumomediastinum [5]. Although pronation and high positive end-expiratory pressure levels were presumed to be the putative causes of pneumomediastinum [5], the mechanism of this COVID-19 complication remains unknown. We hypothesise that sonic hedgehog (SHH) and Wnt5a signalling, crucial pathways in tracheal morphogenesis, and repair/regeneration of cartilage lesions in adulthood [6, 7], could play a role in pneumomediastinum-related COVID-19 tracheal lesions. Pneumomediastinum is a rare complication of ARDS but is more common during #COVID19. The fibrous hyaline degeneration of the tracheal rings seen in this autoptic series is an original observation that has not been previously described in COVID-19 patients. https://bit.ly/3vxTQde
External and Internal Load Measures During Preseason Training in Men Collegiate Soccer Athletes

Abstract Fields, JB, Merigan, JM, Gallo, S, White, JB, and Jones, MT. External and internal load measures during preseason training in men collegiate soccer athletes. J Strength Cond Res 35(9): 2572–2578, 2021—Collegiate athletes are exposed to high volume loads during preseason training. Monitoring training load can inform training and recovery periods. Therefore, the purpose was to examine changes in and bidirectional relationship between external and internal load metrics in men collegiate soccer athletes (n = 20; age, 20 ± 1 year). Internal load measures of heart rate variability (HRV), salivary testosterone (T) and cortisol (C), and self-assessment wellness and ratings of perceived exertion scales were collected daily. External load measures of total distance, player load, high-speed distance, high inertial movement analysis, and repeated high-intensity efforts were collected in each training session using global positioning system/global navigation satellite system technology. A 1-way analysis of variance determined weekly changes in external load, physiological, hormonal, and subjective self-assessment measures of internal load. Bidirectional prediction of external load markers and self-assessment measures on physiological and hormonal markers of internal load were assessed by hierarchical linear regression models (p < 0.05). External load measures, C, energy, sleep, and rate of perceived exertion (RPE) decreased (p < 0.01), whereas T, T:C ratio, anger, depression, and vigor increased (p < 0.01) from week 1 to week 2. Morning C positively predicted afternoon external load and post-training RPE (p < 0.05); T:C ratio negatively predicted afternoon external load and post-training RPE (p < 0.05); and morning HRV negatively predicted post-training RPE (p = 0.031). Despite reduced hormonal stress and external load across weeks, negative perceptions of fatigue increased, suggesting fatigue patterns may have a delayed response. Load may have a more belated, chronic effect on perceptions of fatigue, whereas hormonal changes may be more immediate and sensitive to change. Practitioners may wish to use a variety of external and internal load measures to understand athletes' stress responses to training.
Skyrmion Stabilization at the Domain Morphology Transition in Ferromagnet/Heavy Metal Heterostructures with Low Exchange Stiffness

Herein, the experimental observation of micrometer‐scale magnetic skyrmions at room temperature in several Pt/Co‐based thin film heterostructures designed to possess low exchange stiffness, perpendicular magnetic anisotropy, and a modest interfacial Dzyaloshinskii–Moriya interaction (iDMI) is reported. It is found both experimentally and by micromagnetic and analytic modeling that a low exchange stiffness and modest iDMI eliminates the energetic penalty associated with forming domain walls in thin films. When the domain wall energy density approaches negative values, the remanent morphology transitions from a uniform state to labyrinthine stripes. A low exchange stiffness, indicated by a sub‐400 K Curie temperature, is achieved in Pt/Co, Pt/Co/Ni, and Pt/Co/Ni/Re structures by reducing the Co thickness to the ultrathin limit (<0.3 nm). Similar effects occur in thicker Pt/Co/NixCu1−x structures when the Ni layer is alloyed with Cu. At this transition in domain morphology, skyrmion phases are stabilized by small (<1 mT), perpendicular magnetic fields, and skyrmion motion in response to spin–orbit torque is observed. While the temperature and thickness‐induced morphological phase transitions observed are similar to the well‐studied spin reorientation transition that occurs in the ultrathin limit, the underlying energy balances are substantially modified by the presence of an iDMI.
TXNRD2 (rs35934224) CT genotype as possible protective marker for primary open-angle glaucoma in a Brazilian population.

PURPOSE To investigate the association of the single-nucleotide polymorphism rs35934224 in the TXNRD2 gene with primary open-angle glaucoma in a Brazilian population. METHODS This was a cross-sectional study conducted to verify the association between the rs35934224 TXNRD2 (thioredoxin reductase 2) and primary open-angle glaucoma in a population from the Northeast region of Brazil. A total of 184 individuals were enrolled, including 94 with primary open-angle glaucoma (45 men and 49 women) and 94 controls (40 men and 54 women) from the Recife Eye Institute. RESULTS The mean age was 68.85 years for the patients with glaucoma and 68.55 years for the controls. Genomic DNA was isolated using commercially available kits, and single-nucleotide polymorphism was detected with real-time polymerase chain reaction using TaqMan probes. The studied population was in Hardy-Weinberg equilibrium. The CT genotype was associated with protection against primary open-angle glaucoma (p=0.022). CONCLUSION Our data suggest an association between TXNRD2 gene polymorphism (rs35934224) with primary open-angle glaucoma in an admixed Brazilian po pulation. This is the first study to investigate this single-nucleo tide polymorphism in Latin American individuals with primary open-angle glaucoma.
Improved Measurements of Molecular Cloud Distances Based on Global Search

The principle of the background-eliminated extinction-parallax (BEEP) method is examining the extinction difference between on- and off-cloud regions to reveal the extinction jump caused by molecular clouds, thereby revealing the distance in complex dust environments. The BEEP method requires high-quality images of molecular clouds and high-precision stellar parallaxes and extinction data, which can be provided by the Milky Way Imaging Scroll Painting (MWISP) CO survey and the Gaia DR2 catalog, as well as supplementary A V extinction data. In this work, the BEEP method is further improved (BEEP-II) to measure molecular cloud distances in a global search manner. Applying the BEEP-II method to three regions mapped by the MWISP CO survey, we collectively measured 238 distances for 234 molecular clouds. Compared with previous BEEP results, the BEEP-II method measures distances efficiently, particularly for those molecular clouds with large angular size or in complicated environments, making it suitable for distance measurements of molecular clouds in large samples.
Robustness Evaluation of Entity Disambiguation Using Prior Probes: the Case of Entity Overshadowing

Entity disambiguation (ED) is the last step of entity linking (EL), when candidate entities are reranked according to the context they appear in. All datasets for training and evaluating models for EL consist of convenience samples, such as news articles and tweets, that propagate the prior probability bias of the entity distribution towards more frequently occurring entities. It was shown that the performance of the EL systems on such datasets is overestimated since it is possible to obtain higher accuracy scores by merely learning the prior. To provide a more adequate evaluation benchmark, we introduce the ShadowLink dataset, which includes 16K short text snippets annotated with entity mentions. We evaluate and report the performance of popular EL systems on the ShadowLink benchmark. The results show a considerable difference in accuracy between more and less common entities for all of the EL systems under evaluation, demonstrating the effect of prior probability bias and entity overshadowing.