Miracle-dz/UniFAR-FTUs huggingface dataset:
Strangers to ourselves: a Nietzschean challenge to the badness of suffering

Is suffering really bad? The late Derek Parfit argued that we all have reasons to want to avoid future agony and that suffering is in itself bad both for the one who suffers and impersonally. Nietzsche denied that suffering was intrinsically bad and that its value could even be impersonal. This paper has two aims. It argues against what I call ‘Realism about the Value of Suffering’ by drawing from a broadly Nietzschean debunking of our evaluative attitudes, showing that a recently influential response to the debunking challenge (the appeal to phenomenal introspection) fails. It also argues that a Nietzschean approach is well suited to support the challenge and is bolstered by the empirical literature. As strangers to ourselves, we cannot know whether suffering is really intrinsically bad for us.
Omnidirectional Monolithic Marker for Intra-Operative MR-Based Positional Sensing in Closed MRI

We present a design of an inductively coupled radio frequency (ICRF) marker for magnetic resonance (MR)-based positional tracking, enabling the robust increase of tracking signal at all scanning orientations in quadrature-excited closed MR imaging (MRI). The marker employs three curved resonant circuits fully covering a cylindrical surface that encloses the signal source. Each resonant circuit is a planar spiral inductor with parallel plate capacitors fabricated monolithically on flexible printed circuit board (FPC) and bent to achieve the curved structure. Size of the constructed marker is Ø3-mm $\times5$ -mm with quality factor > 22, and its tracking performance was validated with 1.5 T MRI scanner. As result, the marker remains as a high positive contrast spot under 360° rotations in 3 axes. The marker can be accurately localized with a maximum error of 0.56 mm under a displacement of 56 mm from the isocenter, along with an inherent standard deviation of 0.1-mm. Accrediting to the high image contrast, the presented marker enables automatic and real-time tracking in 3D without dependency on its orientation with respect to the MRI scanner receive coil. In combination with its small form-factor, the presented marker would facilitate robust and wireless MR-based tracking for intervention and clinical diagnosis. This method targets applications that can involve rotational changes in all axes (X-Y-Z).
Saffron stigma extract and crocin play an important neuroprotective role in therapeutic measures against benzo[a]pyrene-induced behavioral alterations in zebrafish

Abstract Saffron is a well-known expensive spice, which has many pharmacological properties against a variety of ailments. Saffron stigma and leaf contain apocarotenoids and bioactive phytochemicals having therapeutic potential against human disorders. Polycyclic aromatic hydrocarbons (PAHs) are one of the most common toxins in today’s aquatic environment. Benzo[a]pyrene (B[a]P), a high molecular weight PAHs prototype, and reported as a potent neurotoxicant, which is profoundly contaminating the environment. The present study investigated the therapeutic efficacy of Saffron stigma extracts and crocin, on B[a]P-induced behavioral changes, altered antioxidant activities, and neurodegeneration in zebrafish. The behavioral responses monitored through the light-dark preference test and novel tank diving test suggested that B[a]P treated zebrafish group showed alteration in anxiolytic-like behavior. Animals exhibited their native behavior when treated alone with Saffron Stigma Extract (SSE) and crocin, an apocarotenoid which also reduced the altered behavior induced by B[a]P. The SSE and crocin stimulated the antioxidant activities with an accumulation of reduced glutathione and catalase enzymes, indicating a protective role against B[a]P-induced oxidative stress and behavioral deficits. The histopathological studies showed the percentage change of pyknotic cell counts in the Periventricular Gray Zone region of the Optic Tectum was 1.74 folds high in B[a]P treated animals as compared to control. Furthermore, the treatment of SSE and crocin reduced the pyknosis process induced by B[a]P-mediated neurodegeneration, possibly due to a better protective mechanism. Future studies may reveal the detailed mechanisms of action of potent SSE and crocin like bioactive compounds having neuroprotective potentials against neurodegenerative diseases. Graphical Abstract
Clinical, epidemiological, and virological features of Mpox in Beijing, China – May 31–June 21, 2023

ABSTRACT The first locally acquired case in the Chinese mainland was reported on May 31, 2023, lagging behind other countries. In this study, we aimed to examine the early clinical and epidemiological characteristics of the earliest cases of Mpox in Beijing, China. Additionally, we investigated the sequence and transmission patterns of the Mpox virus (MPXV). We analyzed 37 reported cases of Mpox in Beijing from May 31, 2023 to June 21, 2023. The age range of the subjects was 24–51 years. Thirty-six cases (97.3%) were identified in men who have sex with men (MSM), and 19 cases (51.4%) tested positive for the human immunodeficiency virus. Thirty-three cases were symptomatic, while four were asymptomatic. Skin lesions were observed in 32 cases (97.0%), fever in 26 (78.8%), and swollen lymph nodes in 17 (51.5%). Rash typically appeared in the genital or perianal area 1–3 days before fever onset, with a minimum incubation period of 2 days. For individuals with skin rashes, the skin lesion samples showed 100% positivity and low Ct values. There were high oropharyngeal swab (75.8%) and blood (84.6%) positivity rates. All MPXV strains belonged to the B.1. 3 branch of the West African lineage. These strains carried 76–86 nucleotide substitutions compared with the reference human MPXV genome, and genetic diversity was observed. Our findings provide the first insights into the landscape of early transmission of Mpox in Beijing and help inform policy formulation in the Chinese mainland.
B2C-AFM: Bi-Directional Co-Temporal and Cross-Spatial Attention Fusion Model for Human Action Recognition

Human Action Recognition plays a driving engine of many human-computer interaction applications. Most current researches focus on improving the model generalization by integrating multiple homogeneous modalities, including RGB images, human poses, and optical flows. Furthermore, contextual interactions and out-of-context sign languages have been validated to depend on scene category and human per se. Those attempts to integrate appearance features and human poses have shown positive results. However, with human poses’ spatial errors and temporal ambiguities, existing methods are subject to poor scalability, limited robustness, and sub-optimal models. In this paper, inspired by the assumption that different modalities may maintain temporal consistency and spatial complementarity, we present a novel Bi-directional Co-temporal and Cross-spatial Attention Fusion Model (B2C-AFM). Our model is characterized by the asynchronous fusion strategy of multi-modal features along temporal and spatial dimensions. Besides, the novel explicit motion-oriented pose representations called Limb Flow Fields (Lff) are explored to alleviate the temporal ambiguity regarding human poses. Experiments on publicly available datasets validate our contributions. Abundant ablation studies experimentally show that B2C-AFM achieves robust performance across seen and unseen human actions. The codes are available at https://github.com/gftww/B2C.git.
Atl (atlastin) regulates mTor signaling and autophagy in Drosophila muscle through alteration of the lysosomal network

ABSTRACT The hereditary spastic paraplegias (HSPs) represent a family of genetic disorders comprising at least 72 different genes with the common pathology of progressive locomotor deficits and spasticity. ATL1/SPG3A (atlastin GTPase 1) encodes an ER fusion protein that controls ER morphology, which implicates ER structure as a causal factor in HSP. Here we use Drosophila to study effects of decreased atl (atlastin) on properties of the larval body wall muscle. We found that muscle atl loss causes accumulation of aggregates containing polyubiquitin (polyUB), mostly bound to the autophagy receptor ref(2)P/SQSTM1/p62. Muscle atl loss also decreased volume and complexity of the endolysosomal network and decreased lysosome number. To determine effects of these lysosomal deficits on progression through the basal autophagy pathway, we expressed Atg8a tagged with both GFP and mCherry in a wild-type and atl mutant background. We found numerous structures containing mCherry but not GFP fluorescence in wild type, indicating that Atg8a was found mostly in mature autolysosomes. In contrast, muscles lacking atl exhibited significant amounts of GFP signal, indicating failure of autophagosome maturation with acidic lysosomes. Many of these GFP-positive puncta contained the late-endosome marker Rab7 but not Lamp1, indicating that some autophagy cargo was accumulating within amphisomes. We also found that this autophagy block was accompanied by an inability to activate the mTor kinase. Our results provide mechanistic insights into the role of atl in maintaining proper function of the autophagy pathway and suggests that certain pathologies in patients with mutations in ATL1/SPG3A might result from altered MTOR signaling. Abbreviations atl atlastin; ALR autophagic lysosome reformation; ER endoplasmic reticulum; GFP green fluorescent protein; HSP hereditary spastic paraplegia; Lamp1 lysosomal associated membrane protein 1 PolyUB polyubiquitin; RFP red fluorescent protein; spin spinster; mTor mechanistic Target of rapamycin; VCP valosin containing protein
Should there be a definite place for grades in the next TNM staging system for (major) salivary gland malignancies?

We would like to congratulate Ho et al. for their article on reinforcing the importance of grade for salivary gland malignancies and also for showning that it is the primary determinant of prognosis in these malignancies. We are in agreement with the authors for the inclusion of grade in the TNM staging system for salivary gland malignancies not just based on the work of the authors but also based on our work on similar lines published a year ago. The authors in the introduction cited only one study and mentioned that few studies have been published that have looked into the comparative risk of mortality between salivary cancer variants. We would like to bring to everyone's attention about our work on the inclusion of grades in the TNM staging system. We in our article have attempted to integrate the grade into the TNM staging by generating four candidate primary tumor staging systems comparing along with the existing TNM staging system. All four models were tested in SEER data patients treated between 2004 and 2015 (n = 16 270) for discriminative performance by Akaike Information Criterion (AIC), Calibration plot, the Harrel concordance index (C-index), and Visual inspection. We validated the four models further in patients treated in our hospital (n = 269) treated between 2012 and 2019. In our article, incorporation of the tumor histology and grade resulted in a better hazard discrimination, and model 4 had the best results. Though we agree with the authors that there is a need to integrate the grade into the TNM staging as also shown in our study we would like to highlight a few concerns in their article. The authors have included both the major and minor salivary glands in this analysis. We are aware that the staging system for major and minor salivary gland malignancies is not the same. The staging for the minor salivary gland is dictated by the site of its origin, hence the inclusion of grade for the minor salivary gland may not be feasible. Second, there is less clarity about the cases where the grades were not mentioned/missing (n = 8405, 32.9%). A mention of whether such cases were excluded or included in the final analysis is important, as this may have a bearing on the results. Finally, we were also concerned whether the patients included were all operated patients or only biopsied, as there is a mention of sizable data missing without clarity on what was its magnitude in terms of its number as this would help the readers interpret the results better. However, the answer to the question regarding the inclusion of the grade in the next TNM staging system is a big “yes” for the major salivary gland malignancy based on the findings of our study and also in light of the study by Ho et al.
The cluster correlation-network support vector machine for high-dimensional binary classification

ABSTRACT Identifying homogeneous subsets of predictors in classification can be challenging in the presence of high-dimensional data with highly correlated variables. We propose a new method called cluster correlation-network support vector machine (CCNSVM) that simultaneously estimates clusters of predictors that are relevant for classification and coefficients of penalized SVM. The new CCN penalty is a function of the well-known Topological Overlap Matrix whose entries measure the strength of connectivity between predictors. CCNSVM implements an efficient algorithm that alternates between searching for predictors’ clusters and optimizing a penalized SVM loss function using Majorization–Minimization tricks and a coordinate descent algorithm. This combining of clustering and sparsity into a single procedure provides additional insights into the power of exploring dimension reduction structure in high-dimensional binary classification. Simulation studies are considered to compare the performance of our procedure to its competitors. A practical application of CCNSVM on DNA methylation data illustrates its good behaviour.
Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction

Abstract Although elevated blood ketone body levels reduce major adverse cardiac and cerebrovascular events (MACCEs) risk in chronic heart failure, their relationship with acute myocardial infarction remains unknown. We investigated this relationship in patients with acute myocardial infarction. This single-institution retrospective observational study analyzed data from 114 patients with acute myocardial infarction at Nihon University Hospital from May 1, 2018, to November 1, 2022. The cut-off value of acetoacetate for the incidence of in-hospital MACCE was determined by drawing a receiver operating characteristic curve (ROC) and defining patients with acetoacetate above and below the optimal cut-off point value as ROC and low-acetoacetate (LA) groups, respectively. Propensity score matching was performed between the LA and high-acetoacetate (HA) groups. Sex, peak creatine kinase, lactate, and blood glucose were defined as confounding factors between in-hospital MACCEs and acetoacetate, and 1:1 propensity score matching between the LA and HA groups was used, resulting in 40 patients from both groups enrolled in the analysis. There was a significantly lower incidence of in-hospital MACCEs in the HA group (LA group: 9 [22%] vs HA group: 1 [3%], P = 0.014). In conclusion, in acute myocardial infarction, elevated blood acetoacetate levels reduce the risk of MACCE.
Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS‐CoV‐2: Possible molecular mechanisms

The SARS‐CoV‐2 pandemic prompted the development and use of next‐generation vaccines. Among these, mRNA‐based vaccines consist of injectable solutions of mRNA encoding for a recombinant Spike, which is distinguishable from the wild‐type protein due to specific amino acid variations introduced to maintain the protein in a prefused state. This work presents a proteomic approach to reveal the presence of recombinant Spike protein in vaccinated subjects regardless of antibody titer.
Classical stimulants in Dallas County: A retrospective review of toxicological, seized drug, and demographical data from 2017 to 2022

Cocaine and methamphetamine remain highly abused drugs in the United States due to their euphoric effects. This study examines classical stimulant casework, defined as cases positive for methamphetamine and/or cocaine, received by the Toxicology Laboratory and the Drug Analysis Laboratory at the Dallas County Southwestern Institute of Forensic Sciences from local law enforcement agencies and/or the Office of the Medical Examiner (OME) between January 1, 2017, and December 31, 2022. Methamphetamine positivity increased from 10.4% to 20.3% in the Toxicology Laboratory over the 6 years, whereas cocaine positivity remained relatively stable at approximately 17%. Similarly, in the Drug Analysis Laboratory, the methamphetamine positivity rate changed from 24.8% to 33.2%, whereas cocaine identification remained stable at approximately 20%. Blood concentrations of methamphetamine in OME cases ranged from 10.1–42,740.0 ng/mL while they were lower in DWI casework ranging from 10.2–2385.0 ng/mL. The blood concentration trends of cocaine were similar to methamphetamine, with OME casework ranging higher (10.0–24,501.0 ng/mL) than DWI casework (10.2–371.6 ng/mL). Polydrug use was evident for both methamphetamine and cocaine in postmortem cases, and the top three most frequently co‐occurring drug/drug class were opioids/opiates, cannabinoids, and ethanol. The results from this study aid in the understanding of historical usage trends of cocaine and methamphetamine in Dallas County and how those trends have changed over time as newer stimulant drugs have emerged.
Fascial plane blocks in children—Scientifically supported or not?

Since the introduction of Fascial Plane Blocks in 2007 there has been an enormous interest and application of Fascial Plane Blocks, evidenced by substantially more than 1000 PubMed items. Despite this gigantic number of publications, also including randomized controlled trials and meta‐analyses in children, there is still no clear‐cut insight into how much of the purported effect is in fact due to the blockade of nerve structures and how much is merely adding the well‐known analgesic and anti‐inflammatory effects of the plasma levels of local anesthetics that are achieved with these techniques. Furthermore, Fascial Plane Blocks appear useful only if compared to conventional multi‐modal analgesia (no block or placebo) and Fascial Plane Blocks lack the potency to provide surgical anesthesia on their own and appear only to be of value when used for minor‐moderate surgery. Despite the huge literature, there has so far not emerged any clinical situations where Fascial Plane Blocks have definitively been shown to be the block of choice, being decisively more effective than other established regional blocks. Lastly, Fascial Plane Blocks may appear as virtually free of complications, but case reports are emerging that point to a real risk for causing local anesthetic systemic toxicity when using Fascial Plane Blocks. This text aims to synthesize the current knowledge base regarding the Fascial Plane Blocks that are relevant to use in the pediatric context. In summary, there does currently not exist any convincing scientific evidence for the continued support for the use of Fascial Plane Blocks in children, except for the rectus sheath block and possibly also the transmuscular quadratus lumborum block.
Temporal changes in childhood cancer incidence and survival by stage at diagnosis in Australia, 2000–2017

Abstract Background The Toronto Paediatric Cancer Stage Guidelines are a compendium of staging systems developed to facilitate collection of consistent and comparable data on stage at diagnosis for childhood cancers by cancer registries. Material and Methods This retrospective, observational cohort study investigated changes in stage-specific incidence and survival for children diagnosed between 2000-2008 compared to 2009-2017 using the population-based Australian Childhood Cancer Registry. Information on mortality for each patient was available to 31st December 2020. Shifts in incidence by stage were evaluated using chi-square tests, and differences in stage-specific five-year observed survival for all causes of death over time were assessed using flexible parametric models. Results Stage was assigned according to the Toronto Guidelines for 96% (n = 7944) of the total study cohort (n = 8292). Changes in the distribution of incidence by stage between the two diagnosis periods were observed for retinoblastoma, with stage 0 increasing from 26% to 37% of cases (p = 0.02), and hepatoblastoma, with metastatic disease increasing from 22% to 39% of cases (p = 0.04). There were large gains in stage-specific survival over time for stage IV rhabdomyosarcoma (five-year adjusted mortality hazard ratio for 2009–2017 compared to 2000–2008 of 0.38, 95% CI 0.19–0.77; p = 0.01), stage M3 for medulloblastoma (HR = 0.41, 95% CI 0.21–0.79; p = 0.01) and metastatic neuroblastoma excluding stage MS (HR = 0.61, 95% CI 0.44-0.84; p < 0.01). Conclusion These results indicate that improvements in childhood cancer survival in Australia are most likely due to refined management rather than changes in stage at diagnosis, particularly for metastatic solid tumours. Wide international uptake of the Toronto Guidelines will allow comprehensive evaluation of differences in survival between countries.
Developing tree improvement strategies for challenging environmental stresses under global climate change: a review from traditional tree breeding to genomics of adaptive traits for the quaking aspen

Quaking or trembling aspen in North America and Euro-Asia (Populus tremuloides and P. tremula, respectively) are both widely distributed species with a long history of scientific research and tree improvement work in areas such as carbon sequestration, biomass, bioenergy, wood, and fiber, as well as studies evaluating the social, economic, and ecological benefits of the species. This chapter reviews the ecological genetics and genomics of quaking aspen’s adaptive traits with a broad perspective of the relationship between phenotypic variation and genetic (G) and environmental (E) effects as well as their interactions (GxE). Based on recent studies, several adaptive traits are discussed, including spring and fall phenology and stress tolerance to environmental factors such as frost, salinity, drought, heat, UV radiation, etc. We also conducted a meta-analysis of empirical studies on adaptive traits of P. tremuloides and its sister species, as research using P. tremuloides as a true “model species” is currently limited. However, molecular tools and experimental designs in the form of different common gardens constitute an integrated pathway for the development of traits and varieties/populations to promote reforestation under changing climatic conditions.
Differential cross-reactivity to the influenza B virus haemagglutinin underpins lineage-specific susceptibility between birth cohorts

Influenza exposures early in life are believed to shape future susceptibility to influenza infections by imprinting immunological biases that engender differential cross-reactivity to future influenza viruses, but direct serological evidence linked to susceptibility is limited. We analysed hemagglutination-inhibition titres in 1451 cross-sectional samples collected between 1992-2020, from individuals born between 1917-2008, against influenza B virus (IBV) isolates from 1940-2021, including ‘future’ isolates that circulated after sample collection. We demonstrate that immunological biases are conferred by early life IBV infection and result in lineage-specific cross-reactivity of a birth cohort towards future IBV isolates. This translates into differential estimates of susceptibility between birth cohorts towards the two IBV antigenic lineages, explaining lineage-specific age distributions of observed medically attended IBV infections. Our data bridge a critical gap between early life exposure, cross-reactivity, and influenza epidemiology and identify a plausible model to further dissect the interplay between host immunity, viral evolution and epidemiology.