Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct Comparison of the Tau PET Tracers 18F-Flortaucipir and 18F-MK-6240 in Human Subjects

Visual Abstract Tau PET tracers exhibit varying levels of specific signal and distinct off-target binding patterns that are more diverse than amyloid PET tracers. This study compared 2 frequently used tau PET tracers, 18F-flortaucipir and 18F-MK-6240, in the same subjects. Methods: 18F-flortaucipir and 18F-MK-6240 scans were collected within 2 mo in 15 elderly subjects varying in clinical diagnosis and cognition. FreeSurfer, version 5.3, was applied to 3-T MR images to segment Braak pathologic regions (I–VI) for PET analyses. Off-target binding was assessed in the choroid plexus, meninges, and striatum. SUV ratio (SUVR) outcomes were determined over 80–100 min (18F-flortaucipir) or 70–90 min (18F-MK-6240) normalized to cerebellar gray matter. Masked visual interpretation of images was performed by 5 raters for both the medial temporal lobe and the neocortex, and an overall (majority) rating was determined. Results: Overall visual ratings showed complete concordance between radiotracers for both the medial temporal lobe and the neocortex. SUVR outcomes were highly correlated (r2 > 0.92; P ≪ 0.001) for all Braak regions except Braak II. The dynamic range of SUVRs in target regions was approximately 2-fold higher for 18F-MK-6240 than for 18F-flortaucipir. Cerebellar SUVs were similar for 18F-MK-6240 and 18F-flortaucipir, suggesting that differences in SUVRs are driven by specific signals. Apparent off-target binding was observed often in the striatum and choroid plexus with 18F-flortaucipir and most often in the meninges with 18F-MK-6240. Conclusion: Both 18F-MK-6240 and 18F-flortaucipir are capable of quantifying signal in a common set of brain regions that develop tau pathology in Alzheimer disease; these tracers perform equally well in visual interpretations. Each also shows distinct patterns of apparent off-target binding. 18F-MK-6240 showed a greater dynamic range in SUVR estimates, which may be an advantage in detecting early tau pathology or in performing longitudinal studies to detect small interval changes.
Metabolic imaging detects elevated glucose flux through the pentose phosphate pathway associated with TERT expression in low-grade gliomas.

BACKGROUND Telomerase reverse transcriptase (TERT) is essential for tumor proliferation, including in low-grade oligodendrogliomas (LGOGs). Since TERT is silenced in normal cells, it is also a therapeutic target. Therefore, non-invasive methods of imaging TERT are needed. Here, we examined the link between TERT expression and metabolism in LGOGs, with the goal of leveraging this information for non-invasive magnetic resonance spectroscopy (MRS)-based metabolic imaging of LGOGs. METHODS Immortalized normal human astrocytes with doxycycline-inducible TERT silencing, patient-derived LGOG cells, orthotopic tumors and LGOG patient biopsies were studied to determine the mechanistic link between TERT expression and glucose metabolism. The ability of hyperpolarized [U- 13C, U- 2H]-glucose to non-invasively assess TERT expression was tested in live cells and orthotopic tumors. RESULTS TERT expression was associated with elevated glucose flux through the pentose phosphate pathway (PPP), elevated NADPH, which is a major product of the PPP, and elevated GSH, which is maintained in a reduced state by NADPH. Importantly, hyperpolarized [U- 13C, U- 2H]-glucose metabolism via the PPP non-invasively reported on TERT expression and response to TERT inhibition in patient-derived LGOG cells and orthotopic tumors. Mechanistically, TERT acted via the sirtuin SIRT2 to upregulate the glucose transporter GLUT1 and the rate-limiting PPP enzyme glucose-6-phosphate dehydrogenase. CONCLUSIONS We have, for the first time, leveraged a mechanistic understanding of TERT-associated metabolic reprogramming for non-invasive imaging of LGOGs using hyperpolarized [U- 13C, U- 2H]-glucose. Our findings provide a novel way of imaging a hallmark of tumor immortality and have the potential to improve diagnosis and treatment response assessment for LGOG patients.
Continuation Multiple Instance Learning for Weakly and Fully Supervised Object Detection

Weakly supervised object detection (WSOD) is a challenging task that requires simultaneously learning object detectors and estimating object locations under the supervision of image category labels. Many WSOD methods that adopt multiple instance learning (MIL) have nonconvex objective functions and, therefore, are prone to get stuck in local minima (falsely localize object parts) while missing full object extent during training. In this article, we introduce classical continuation optimization into MIL, thereby creating continuation MIL (C-MIL) with the aim to alleviate the nonconvexity problem in a systematic way. To fulfill this purpose, we partition instances into class-related and spatially related subsets and approximate MIL’s objective function with a series of smoothed objective functions defined within the subsets. We further propose a parametric strategy to implement continuation smooth functions, which enables C-MIL to be applied to instance selection tasks in a uniform manner. Optimizing smoothed loss functions prevents the training procedure from falling prematurely into local minima and facilities learning full object extent. Extensive experiments demonstrate the superiority of CMIL over conventional MIL methods. As a general instance selection method, C-MIL is also applied to supervised object detection to optimize anchors/features, improving the detection performance with a significant margin.
At home or in hospital: Home treatment and mental health stigma

Background: Stigmatized attitudes towards people with mental illness may influence treatment choice for oneself and others. Aim: To gauge the attitudes of the UK general public towards treatment at home for mental illness and to assess the extent to which non-acceptability was related to stigmatized attitudes. Methods: Two hundred and two (101 female) people living in the UK completed an online (vignette) questionnaire in which we asked demographic details and personal experience of mental illness. To measure stigma, we used an adapted version of the Attitudes to Mental Illness Questionnaire (AMIQ) with vignettes asking about treatment at home and using scales for social distance and poor expectations; participants also filled in the Mental Health Knowledge Schedule (MAKS). Results: Participants did not evidence overall agreement with treatment at home for mental illness (i.e. >0; range = −16-to-+16, Mean (M) = 0.86, 95% confidence interval (CI) = −0.08, 1.80, p = . 073), although they showed significant agreement with treatment at home should they experience mental illness themselves (range = −8-to-+8, M = 1.36, CI = 0.82, 1.89, p < .001). Acceptability for treatment at home differed according to specific mental illness considered (range = −4-to-+4); depression (M = 0.47, CI = 0.13, 0.81, p = .006) and alcohol abuse (M = 1.46, CI = 1.14,1.77, p < .001) were considered suitable for being treated at home but schizophrenia was not (M = −0.78, CI = −1.13,−0.43, p < .001). Multivariate analyses revealed that older age and attitudes indicating comfort with less social distance from people with mental illness were independently associated with treatment at home agreeability. Conclusions: Public acceptability of home treatment for mental illness remains ambivalent in the UK, most obviously when considering treatment approaches for individuals other than themselves and for people with schizophrenia. Disagreement with home treatment is particularly evident in younger people and those who prefer less social contact with people with mental illness.
Surface-confinement assisted synthesis of nitrogen-rich single atom Fe−N/C electrocatalyst with dual nitrogen sources for enhanced oxygen reduction reaction

The utilization of earth abundant iron and nitrogen doped carbon as a precious-metal-free electrocatalyst for oxygen reduction reaction (ORR) significantly depends on the rational design and construction of desired Fe−N x moieties on carbon substrates, which however remains an enormous challenge. Herein a typical nanoporous nitrogen-rich single atom Fe−N/C electrocatalyst on carbon nanotube (NR-CNT@FeN-PC) was successfully prepared by using CNT as carbon substrate, polyaniline (PANI) and dicyandiamine (DCD) as binary nitrogen sources and silica-confinement-assisted pyrolysis, which not only facilitate rich N-doping for the inhibition of the Fe agglomeration and the formation of single atom Fe−N x sites in carbon matrix, but also generate more micropores for enlarging BET specific surface area (up to 1500 m2·g−1). Benefiting from the advanced composition, nanoporous structure and surface hydrophilicity to guarantee the sufficient accessible active sites for ORR, the NR-CNT@FeN-PC catalyst under optimized conditions delivers prominent ORR performance with a half-wave potential (0.88 V versus RHE) surpass commercial Pt/C catalyst by 20 mV in alkaline electrolyte. When assembled in a home-made Zn−air battery device as cathodic catalyst, it achieved a maximum output power density of 246 mW·cm−2 and a specific capacity of 719 mA·h·g−1 Zn outperformed commercial Pt/C catalyst, holding encouraging promise for the application in metal-air batteries.
Intrapulmonary bronchopulmonary anastomoses in COVID-19 respiratory failure

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a devastating and worldwide pandemic disease known as coronavirus disease 2019 (COVID-19). COVID-19 causes acute hypoxic respiratory failure (COVID-ARF), a major cause of mortality and morbidity, with an incompletely understood pathophysiological mechanism. Gattinoni et al. [1] noted that COVID-19 patients with acute hypoxic respiratory failure have lung disease that is often characterised by a remarkable dissociation between relatively well-preserved lung mechanics, including lung compliance, and severe hypoxaemia. These findings are consistent with the concept that profound hypoxaemia occurring in ventilated patients with highly compliant lungs could be due to the loss of regulation of lung perfusion and impaired hypoxic pulmonary vasoconstriction. Early autopsy studies suggest that the lung circulation is a major target of coronavirus infection, which leads to striking pulmonary vascular disease due to variable degrees of thrombosis, apoptosis, oedema, inflammation and angiogenesis [2–4]. These changes contribute to dysregulation of the pulmonary vasculature, which induces perfusion abnormalities and contributes to the physiological phenotypes reported in COVID-19 pneumonia. Further, computed tomography suggests a unique “tree in bud” appearance of small pulmonary arteries [3] and transcranial agitated saline microbubble doppler studies of COVID-19 patients with hypoxaemia have demonstrated intrapulmonary shunting of these bubbles, and that the presence and degree of transpulmonary bubble transit correlates with the degree of hypoxaemia [5]. Despite these studies, histopathological correlates of severe hypoxaemia and shunt in the setting of relatively normal lung compliance in COVID-19 patients are largely lacking. Open intrapulmonary bronchopulmonary anastomoses (IBA) were identified in COVID-19 patients who died of respiratory failure. IBA may be the microanatomical basis of intrapulmonary right to left shunt leading to severe hypoxaemia in COVID-19. https://bit.ly/3e2GajO
Construction of liver hepatocellular carcinoma-specific lncRNA-miRNA-mRNA network based on bioinformatics analysis

Liver hepatocellular carcinoma (LIHC) is one of the major causes of cancer-related death worldwide with increasing incidences, however there are very few studies about the underlying mechanisms and pathways in the development of LIHC. We obtained LIHC samples from The Cancer Genome Atlas (TCGA) to screen differentially expressed mRNAs, lncRNAs, miRNAs and driver mutations. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses and protein–protein interaction (PPI) network were performed. Moreover, we constructed a competing endogenous lncRNAs-miRNAs-mRNAs network. Finally, cox proportional hazards regression analysis was used to identify important prognostic differentially expressed genes. Total of 1284 mRNAs, 123 lncRNAs, 47 miRNAs were identified within different tissues of LIHC patients. GO analysis indicated that upregulated and downregulated differentially expressed mRNAs (DEmRNAs) were mainly associated with cell division, DNA replication, mitotic sister chromatid segregation and complement activation respectively. Meanwhile, KEGG terms revealed that upregulated and downregulated DEmRNAs were primarily involved in DNA replication, Metabolic pathways, cell cycle and Metabolic pathways, chemical carcinogenesis, retinol metabolism pathway respectively. Among the DERNAs, 542 lncRNAs-miRNAs-mRNAs pairs were predicted to construct a ceRNA regulatory network including 35 DElncRNAs, 26 DEmiRNAs and 112 DEmRNAs. In the Kaplan‐Meier analysis, total of 43 mRNAs, 14 lncRNAs and 3 miRNAs were screened out to be significantly correlated with overall survival of LIHC. The mutation signatures were analyzed and its correlation with immune infiltrates were evaluated using the TIMER in LIHC. Among the mutation genes, TTN mutation is often associated with poor immune infiltration and a worse prognosis in LIHC. This work conducted a novel lncRNAs-miRNAs-mRNAs network and mutation signatures for finding potential molecular mechanisms underlying the development of LIHC. The biomarkers also can be used for predicting prognosis of LIHC.
The short-term impact of combining pain neuroscience education with exercise for chronic musculoskeletal pain: a systematic review and meta-analysis.

ABSTRACT Exercise and pain neuroscience education (PNE) have both been used as standalone treatments for chronic musculoskeletal pain. The evidence supporting PNE as an adjunct to exercise therapy is growing but remains unclear. The aim of this systematic review and meta-analysis was to evaluate the effect of combining PNE and exercise for patients with chronic musculoskeletal pain, when compared to exercise alone. A systematic search of electronic databases was conducted from inception to November 6, 2020. A quality effects model was used to meta-analyze outcomes where possible. Five high quality randomized controlled studies (n=460) were included in this review. The PEDro scale was used to assess the quality of individual studies and GRADE analysis was conducted to determine the quality of evidence for each outcome. Meta-analyses were performed for pain intensity, disability, kinesiophobia and pain catastrophizing using data reported between 0 and 12 weeks post-intervention. Long-term outcomes (>12 weeks) were only available for two studies and therefore were not suitable for meta-analysis. Meta-analysis revealed a significant difference in pain (WMD, -2.09/10; 95% CI, -3.38 to -0.80; low certainty), disability (SMD, -0.68; 95% CI, -1.17 to -0.20; low certainty), kinesiophobia (SMD, -1.20; CI, -1.84 to -0.57; moderate certainty) and pain catastrophizing (WMD, -7.72; 95% CI, -12.26 to -3.18; very low certainty) that favoured the combination of PNE and exercise. These findings suggest that combining PNE and exercise in the management of chronic musculoskeletal pain results in greater short-term improvements in pain, disability, kinesiophobia and pain catastrophizing relative to exercise alone.
Treatment of renal lower pole stones: an update

The prevalence of urinary lithiasis ranges from 8% to 19% in males and 3% to 5% in females in Western countries and varies greatly worldwide (1). These numbers are rising particularly due to changes in lifestyle including a higher intake of animal protein and carbohydrates and less physical activity, leading to an increased prevalence of obesity and diabetes (1-3). These changes also reflect in the gender gap and stone composition (4). Clinical symptoms, mainly renal pain, develop in approximately 50% of urinary stone patients and require intervention (5). Additionally, 50% of the affected patients will experience a recurrence during their lifetime (6). Lower pole stones (LPS) account for approximately 35% of renal calculi and may remain asymptomatic in many patients. On the other hand, treatment of such stones is challenging due to the difficulty in eliminating fragments and anatomical access to the inferior renal calyx (7). A great debate has arisen regarding the best management of LPS and many controversies still exist since large randomized studies are scarce in the literature. Some reviews and metanalysis have been published and made a significant contribution for a better understanding of this issue but, unfortunately, many of these reviews are based in heterogeneous and low-quality studies. Currently, the management of lower pole stones includes watchful waiting, extracorporeal lithotripsy (SWL), flexible ureterorenoscopy (FURS) and percutaneous nephrolithotripsy (PCNL) with its variations including mini, ultramini, micro and supermini PCNL. The success rates for each of these treatment modalities is related to stone burden and composition, patient’s body habitus and anatomy as well as the surgeon’s experience. The main differences among these modalities is related to their different degrees of invasiveness, anesthetic requirement, stone clearance, complications and costs (8). The aim of this article is to review the results of each of these treatment modalities according to the stone burden and patient’s characteristics in order to help urologists decide what is the optimal approach to manage lower pole stones in each patient.
Epigenetics drive the evolution of sex chromosomes in animals and plants

We review how epigenetics affect sex chromosome evolution in animals and plants. In a few species, sex is determined epigenetically through the action of Y-encoded small RNAs. Epigenetics is also responsible for changing the sex of individuals through time, even in species that carry sex chromosomes, and could favour species adaptation through breeding system plasticity. The Y chromosome accumulates repeats that become epigenetically silenced which leads to an epigenetic conflict with the expression of Y genes and could accelerate Y degeneration. Y heterochromatin can be lost through ageing, which activates transposable elements and lowers male longevity. Y chromosome degeneration has led to the evolution of meiotic sex chromosome inactivation in eutherians (placentals) and marsupials, and dosage compensation mechanisms in animals and plants. X-inactivation convergently evolved in eutherians and marsupials via two independently evolved non-coding RNAs. In Drosophila, male X upregulation by the male specific lethal (MSL) complex can spread to neo-X chromosomes through the transposition of transposable elements that carry an MSL-binding motif. We discuss similarities and possible differences between plants and animals and suggest future directions for this dynamic field of research. This article is part of the theme issue ‘How does epigenetics influence the course of evolution? ’
The impact of epigenetic information on genome evolution

Epigenetic information affects gene function by interacting with chromatin, while not changing the DNA sequence itself. However, it has become apparent that the interactions between epigenetic information and chromatin can, in fact, indirectly lead to DNA mutations and ultimately influence genome evolution. This review evaluates the ways in which epigenetic information affects genome sequence and evolution. We discuss how DNA methylation has strong and pervasive effects on DNA sequence evolution in eukaryotic organisms. We also review how the physical interactions arising from the connections between histone proteins and DNA affect DNA mutation and repair. We then discuss how a variety of epigenetic mechanisms exert substantial effects on genome evolution by suppressing the movement of transposable elements. Finally, we examine how genome expansion through gene duplication is also partially controlled by epigenetic information. Overall, we conclude that epigenetic information has widespread indirect effects on DNA sequences in eukaryotes and represents a potent cause and constraint of genome evolution. This article is part of the theme issue ‘How does epigenetics influence the course of evolution? ’
Maternal achievement-oriented psychological control: Implications for adolescent academic contingent self-esteem and mathematics anxiety

Using random intercept cross-lagged panel analysis, this study examined the longitudinal relations of mathematics anxiety to maternal achievement-oriented psychological control and academic contingent self-esteem in 336 Chinese adolescents from the age of 13 to 17. Results showed that, at the between-person level, adolescents who perceived their mothers as more psychologically controlling in achievement domains over time were also the ones with higher levels of academic contingent self-esteem and mathematics anxiety, compared with other adolescents. Our within-person analyses are in line with the within-person hypotheses that underline self-determination theory: adolescents’ perceptions of maternal achievement-oriented psychological control were linked to mathematics anxiety through academic contingent self-esteem. We also found that the association between maternal achievement-oriented psychological control and mathematics anxiety was bidirectional, which supports the transactional perspective of parental influence. This study contributes to the literature by elucidating potential processes and reciprocal associations involved in parental psychological control, academic contingent self-esteem, and mathematics anxiety.
METAPHOR OF MODALITY IN “EIGHTY DAYS YELLOW” NOVEL BY VINA JACKSON

The purpose of the study to analyze the types of metaphor of modality, describe the realization metaphor of modality and explain the context of metaphor of modality in novel. The research was conducted by applying descriptive qualitative design. The data for this study were the sentences in novel. The data analyzed using Halliday’s Theory. The findings of the study showed that there were three types of the metaphor of modality used in novel such as probability was 50,65% with 109 occurences, usuality was 31,10% with 84 occurences, and obligation 18,25% with 70 occurences, the realization of metaphor of modality in novel were think, will, probably, usually, want, should, expected, usual, and supposed. and the context of metaphor of modality was the social context. We interacted with other people in the social context. Further, the interaction in our surroundings like friends and family. What you speak or how you act to everyone influences how you interprate.
Recovery of some valuable components from industrial waste

ABSTRACT The present work studied several ways for wastewater treatment for the waste from the pulp and paper industries including the recovery of some valuable components from this waste and reaching the acceptable environmental limits for the treatment of waste. The acidification technique showed high efficiency for the removal of solids from the black liquor. A proper treatment for the effluent produced from the pulp and paper industry that used rice straw as raw material. The dose of the alum as a coagulant has an effect on the solid process and is due to the high percentage of solids in the black liquor. Hydrochloric acid is used to control the pH of the solution and separating most of the solids from the black liquor. Sodium hydroxide can be used to remove silica from the other solids by forming sodium silicate. The amount of solids precipitated increased by increasing the stirring time, temperature, rpm of the agitator, and decreasing pH. IR spectroscopy was carried out on the solid to assign the functional groups. Thermal analysis and EDX analysis were done to study the thermal properties of the solids. A proper design of the mixer and drier is accomplished to provide high efficiency of the silica removal process.