Miracle-dz/UniFAR-FTUs huggingface dataset:
Long term exposure to low level air pollution and mortality in eight European cohorts within the ELAPSE project: pooled analysis

Abstract Objective To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Design Pooled analysis of eight cohorts. Setting Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. Participants 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. Main outcome measures Deaths due to natural causes and cause specific mortality. Results Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Conclusions Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.
Favorable Early Outcomes With Thyroid Lobectomy for Low-Risk Papillary Thyroid Cancer: The Mayo Clinic Experience

Background Until 2015, standard of care for low-risk papillary thyroid cancer (PTC) >1 cm was a total or near-total thyroidectomy. Despite changes in guidelines and surgical management of low-risk PTC since 2015, little data are available regarding the effect on the need for additional surgery or risk for development of lymph node metastases. Our aim was to determine outcomes in patients who underwent initial thyroid lobectomy for low-risk PTC at a high-volume tertiary care institution. Methods Retrospective review of patients ≥18 years old with biopsy proven low-risk PTC 1-4 cm who underwent partial thyroidectomy (eg, lobectomy/isthmusectomy) at Mayo Clinic, Rochester, MN, between March 2016 and June 30, 2019. Results From 1481 thyroidectomies performed during study period, 940 contained PTC on final pathology. Of these, 87 (of 123) patients who had an initial thyroid lobectomy met inclusion criteria. Five (6%) of these patients proceeded to completion thyroidectomy (CT), with 3 requiring CT and radioactive iodine in the first postoperative year and 2 undergoing only CT in the second postoperative year. No postoperative complications were reported. No patient in this cohort required additional surgery or treatment for newly discovered lymph node metastases during the follow-up period. 43 (of 72, 60%) patients not on thyroxine therapy preoperatively were started on thyroxine therapy postoperatively. Conclusions Early outcomes for those undergoing thyroid lobectomy for low-risk PTC at our institution have been favorable. These results support the 2015 American Thyroid Association guidelines to offer lobectomy for those with low-risk PTC 1-4 cm.
Exploiting flow cytometry for the unbiased quantification of protein inclusions in Caenorhabditis elegans

The aggregation of proteins into inclusions or plaques is a prominent hallmark of a diverse range of pathologies including neurodegenerative diseases. The quantification of such inclusions in Caenorhabditis elegans models of aggregation is usually achieved by fluorescence microscopy or other techniques involving biochemical fractionation of worm lysates. Here, we describe a simple and rapid flow cytometry-based approach that allows fluorescently-tagged inclusions to be enumerated in whole worm lysate in a quantitative and unbiased fashion. We demonstrate that this technique is applicable to multiple C. elegans models of aggregation and importantly, can be used to monitor the dynamics of inclusion formation in response to heat shock and during aging. This includes the characterisation of physicochemical properties of inclusions, such as their size, which may reveal how aggregate formation is distinct in different tissues or at different stages of pathology or aging. This new method can be used as a powerful technique for the medium- to high-throughput quantification of inclusions in future studies of genetic or chemical modulators of aggregation in C. elegans.
Red‐Blood‐Cell‐Membrane‐Coated Metal‐Drug Nanoparticles for Enhanced Chemotherapy

To overcome high toxicity, low bioavailability and poor water solubility of chemotherapeutics, a variety of drug carriers have been designed. However, most carriers are severely limited by low drug loading capacity and adverse side eﬀects. Here, a new type of metal‐drug nanoparticles (MDNs) was designed and synthesized. The MDNs self‐assembled with Fe(III) ions and drug molecules through coordination, resulting in nanoparticles with high drug loading. To assist systemic delivery and prolong circulation time, the obtained MDNs were camouflaged with red blood cell (RBCs) membranes (RBCs@Fe‐DOX MDNs) to improve their stability and dispersity. The RBCs@Fe‐DOX MDNs presented pH‐responsive release functionalities, resulting in drug release accelerated in acidic tumor microenvironments. The outstanding in vitro and in vivo antitumor therapeutic outcome was realized by RBCs@Fe‐DOX MDNs. This study provides an innovative design guideline for chemotherapy and demonstrates the great capacity of nanomaterials in anticancer treatments.
A Control Plane for WireGuard

WireGuard is a VPN protocol that has gained significant interest recently. Its main advantages are: (i) simple configuration (via pre-shared SSH-like public keys), (ii) mobility support, (iii) reduced codebase to ease auditing, and (iv) Linux kernel implementation that yields high performance. However, WireGuard (intentionally) lacks a control plane. This means that each peer in a WireGuard network has to be manually configured with the other peers’ public key and IP addresses, or by other means. In this paper we present an architecture based on a centralized server to automatically distribute this information. In a nutshell, first we manually establish a WireGuard tunnel to the centralized server, and ask all the peers to store their public keys and IP addresses in it. Then, WireGuard peers use this secure channel to retrieve on-demand the information for the peers they want to communicate to. Our design strives to: (i) offer a key distribution scheme simpler than PKI-based ones, (ii) limit the number of public keys sent to the peers, and (iii) reduce tunnel establishment latency by means of an UDP-based protocol. We argue that such automation can help the deployment in enterprise or ISP scenarios. We also describe in detail our implementation and analyze several performance metrics. Finally, we discuss possible improvements regarding several shortcomings we found during implementation.
Reviewing the Role of Vultures at the Human-Wildlife-Livestock Disease Interface: An African Perspective

Abstract. Vultures are a key component of an effective scavenger guild and have evolved a number of adaptations that allow them to locate and dispose of carcasses quickly and efficiently. The continuing decline of African vultures is threatening the stability of the African scavenger guild, which may result in increased carcass decomposition times and thus, more rapid development of pathogenic bacteria. The absence of competitive regulation by these apex scavengers may also result in changes in the composition of the vertebrate scavenger guild, with an increase in mammalian scavengers giving rise to increased contact rates at carcasses, which may increase the risk of viral disease transmission to humans, livestock, and other wildlife. Although the economic value of vultures in terms of the sanitation services they provide has been evaluated, their contribution to the economics of human health and veterinary care remains to be quantified. Efforts to do so are hampered by lack of data, as well as a number of confounding factors that may mask causality, such as improved disease prevention and surveillance systems. However, the circumstantial nature of the link between vultures and disease prevention should not deter efforts to conserve them, as their regulation of mammalian scavengers and the sanitation services they provide place them firmly within the sphere of One Health, thereby warranting their urgent protection. The restoration of vulture populations and the ecosystem services they provide will benefit the welfare of all humans, but particularly those who are most vulnerable to economic instability and the spillover of disease at the human-wildlife-livestock interface.
Cooperative amyloid fibre binding and disassembly by the Hsp70 disaggregase

Although amyloid fibres are highly stable protein aggregates, a specific combination of human Hsp70 system chaperones can disassemble them, including fibres formed of α-synuclein, huntingtin or Tau. Disaggregation requires the ATPase activity of the constitutively expressed Hsp70, Hsc70, together with the J domain protein DNAJB1 and the nucleotide exchange factor Apg2. Recruitment and clustering of Hsc70 on the fibrils appear to be necessary for disassembly. Here we use atomic force microscopy (AFM) to show that segments of in vitro assembled α-synuclein fibrils are first coated with chaperones and then undergo bursts of rapid, unidirectional disassembly. Cryo-electron tomography reveals fibrils with regions of densely bound chaperones extending from the fibre surface, preferentially at one end of the fibre. Sub-stoichiometric amounts of Apg2 relative to Hsc70 dramatically increase recruitment of Hsc70 to the fibres, creating localised active zones that then undergo rapid disassembly at a rate of ∼4 subunits per second.
MS-SincResNet: Joint Learning of 1D and 2D Kernels Using Multi-scale SincNet and ResNet for Music Genre Classification

In this study, we proposed a new end-to-end convolutional neural network, called MS-SincResNet, for music genre classification. MS-SincResNet appends 1D multi-scale SincNet (MS-SincNet) to 2D ResNet as the first convolutional layer in an attempt to jointly learn 1D kernels and 2D kernels during the training stage. First, an input music signal is divided into a number of fixed-duration (3 seconds in this study) music clips, and the raw waveform of each music clip is fed into 1D MS-SincNet filter learning module to obtain three-channel 2D representations. The learned representations carry rich timbral, harmonic, and percussive characteristics comparing with spectrograms, harmonic spectrograms, percussive spectrograms and Mel-spectrograms. ResNet is then used to extract discriminative embeddings from these 2D representations. The spatial pyramid pooling (SPP) module is further used to enhance the feature discriminability, in terms of both time and frequency aspects, to obtain the classification label of each music clip. Finally, the voting strategy is applied to summarize the classification results from all 3-second music clips. In our experimental results, we demonstrate that the proposed MS-SincResNet outperforms the baseline SincNet and many well-known hand-crafted features. Considering individual 2D representation, MS-SincResNet also yields competitive results with the state-of-the-art methods on the GTZAN dataset and the ISMIR2004 dataset. The code is available at https://github.com/PeiChunChang/MS-SincResNet.
Polygenic Risk Score Improves Risk Stratification and Prediction of Subsequent Thyroid Cancer after Childhood Cancer

Background: Subsequent thyroid cancer (STC) is one of the most common malignancies in childhood cancer survivors. We aimed to evaluate the polygenic contributions to STC risk and potential utility in improving risk prediction. Methods: A polygenic risk score (PRS) was calculated from 12 independent SNPs associated with thyroid cancer risk in the general population. Associations between PRS and STC risk were evaluated among survivors from St. Jude Lifetime Cohort (SJLIFE) and were replicated in survivors from Childhood Cancer Survivor Study (CCSS). A risk prediction model integrating the PRS and clinical factors, initially developed in SJLIFE, and its performance were validated in CCSS. Results: Among 2,370 SJLIFE survivors with a median follow-up of 28.8 [interquartile range (IQR) = 21.9–36.1] years, 65 (2.7%) developed STC. Among them, the standardized PRS was associated with an increased rate of STC [relative rate (RR) = 1.57; 95% confidence interval (CI) = 1.24–1.98; P < 0.001]. Similar associations were replicated in 6,416 CCSS survivors, among whom 121 (1.9%) developed STC during median follow-up of 28.9 (IQR = 22.6–34.6) years (RR = 1.52; 95% CI = 1.25–1.83; P < 0.001). A risk prediction model integrating the PRS with clinical factors showed better performance than the model considering only clinical factors in SJLIFE (P = 0.004, AUC = 83.2% vs. 82.1%, at age 40), which was further validated in CCSS (P = 0.010, AUC = 72.9% vs. 70.6%). Conclusions: Integration of the PRS with clinical factors provided a statistically significant improvement in risk prediction of STC, although the magnitude of improvement was modest. Impact: PRS improves risk stratification and prediction of STC, suggesting its potential utility for optimizing screening strategies in survivorship care.
Robot Multimodal Anomaly Diagnosis by Learning Time-lagged Complex Dynamics

Robots are prone to making anomalies when performing manipulation tasks in unstructured environments, it is often desirable that robots can detect, diagnose them, and then effectively provides prior experiences for rapidly adapting the robot anomalous behaviors. The traditional methods on anomaly diagnosis are to focus on univariate time series and ignore the modality correlation and time-dependent, which can't be applied in a Human-robot collaborative (HRC) system that is integrated with multiple sensors for improving autonomy and safety. The variability and temporal consistency of multimodal sensory data exacerbate anomaly diagnosis still an open problem in robotics. Here we propose a novel method of multimodal anomaly diagnosis by learning the time-lagged dynamics of anomalies detected during an HRC task. Specifically, a time-lagged variational auto-encoder model ($tlVAE$) is first proposed to compress complex multivariate dynamics into simpler manifolds, and the manifolds are used to fitting a dynamic time warping-based K-nearest neighbors model for anomaly diagnosis in a multi-classes classification scheme. A real-robot anomaly dataset is presented to evaluate the significance and effectiveness in extracting underlying time-dependent patterns, results indicate that the efficiency and precision of diagnosis can be improved by introducing a sparse representation of the multivariate sample. Meanwhile, we compare the accuracy of anomaly diagnosis with several commonly used sparse representation methods, including Principal Component Analysis (PCA), Time-lagged Independent Component Analysis (TICA), Autoencoder (AE) as well as Variational Autoencoder (VAE). The resulting anomaly diagnosis accuracy of 97.6% across 7 kinds of anomalies, which outperformed all the baselines.
Cortisol awakening response in bipolar patients with comorbid type 2 diabetes mellitus

Abstract Objectives Bipolar disorder (BD) is frequently associated with type 2 diabetes mellitus (T2DM). The functioning of the hypothalamic-pituitary-adrenal (HPA) axis has been never investigated in BD with respect to the glucose metabolic status. Therefore, we assessed the cortisol awakening response (CAR) in bipolar patients with or without comorbid T2DM. Methods Twenty euglycemic bipolar patients [12 males and eight females; mean age (±SD): 47.4 ± 14.4 years; mean (±SD) duration of illness: 18.3 ± 12.1 years], 16 BD patients with T2DM [11 males and five females; mean age (±SD): 63.6 ± 12.8 years; mean (±SD) duration of bipolar illness: 17.1 ± 10.8 years; mean (±SD) duration of T2DM: 5.2 ± 5.3 years], 18 healthy subjects [seven males and 11 females; mean age (±SD): 45.0 ± 12.1 years] and 12 non-psychiatric subjects with T2DM [eight males and four females; mean age (±SD): 56.7 ± 11.2 years; mean (±SD) duration of T2DM: 5.2 ± 3.5 years] were recruited. Saliva cortisol was measured at awakening and after 15, 30, and 60 min. Results With respect to both healthy controls and controls with T2DM, euglycemic and diabetic BD patients exhibited a CAR occurring at significantly lower levels. No significant difference emerged in the CAR between the two groups of bipolar patients. Controls with T2DM had an overall post-awakening cortisol production significantly higher than healthy controls. Conclusions Our results show that the CAR of patients with BD is reduced in terms of overall cortisol production but normal in terms of cortisol reactivity independently from the occurrence of comorbid T2DM. The dampened CAR points to a tuning down of the functioning of the HPA axis. in both euglycemic and diabetic BD patients, which may be a factor of vulnerability, since a preserved HPA axis functioning is essential to deal with stressors, which may precipitate affective episodes.
Renal Function Improves After the Discontinuation of Androgen Deprivation Therapy in Japanese Patients With Prostate Cancer

Background: Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued. Patients and Methods: Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed. Results: A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p<0.0001). The eGFR decreased with the duration of ADT treatment. At 12 months, renal function had started to recover in group 1, while it had continued to decrease in group 2. Conclusion: Discontinuation of ADT tended to result in improvements in renal function. Furthermore, this study indicated that renal dysfunction caused by 6 months of ADT is transient. Normalization of the serum testosterone level seen after the discontinuation of ADT may be associated with improvements in renal function. Thus, intermittent ADT may be a useful treatment for PCa, as it would help to preserve renal function.
WiLD: Wireless Passive Moisture Sensing Under Moving Conditions for Smart Manufacturing

The automotive industry still performs the rain isolation quality tests manually, being a bottleneck in the production process, poorly scalable, and prone to human errors. Smart sensors that provide online monitoring and diagnosis are key for smart manufacturing transformation in this industry. In this work, we present WiLD, a RFID-based solution to detect moisture based on standard COTS Ultra High Frequency tags, aimed to improve the rain isolation quality test efficiency through industrial intelligent sensing. The developed moisture sensor solution is largely evaluated considering realistic conditions with non-stationary vehicles which adheres to a typical automotive scenario of an assembling and quality assurance line. WiLD shows a False Negative Rate of 100% when detecting water leakages above 1.5 ml in the evaluated conditions.
Mass of genes rather than master genes underlie the genomic architecture of amphibian speciation

Significance Reproductive isolation is instrumental to the formation of new species (speciation), but it remains largely enigmatic how many incompatibilities are required to prevent hybridization and where they lie across the genome. By studying patterns of admixture in amphibian hybrid zones, we found that reproductive isolation is initiated by numerous small-effect incompatibilities scattered across the genome rather than concentrated in a few important genes. Unlike mammals and birds, in which Y/W degeneracy is a major cause of hybrid dysfunctions, the undifferentiated sex chromosomes of amphibians do not always host more genetic incompatibilities than other chromosomes. These combined results might explain why amphibian speciation is relatively slow, and its clock-like dynamics offer practical perspectives to categorize evolutionary lineages into species or subspecies. The genetic architecture of speciation, i.e., how intrinsic genomic incompatibilities promote reproductive isolation (RI) between diverging lineages, is one of the best-kept secrets of evolution. To directly assess whether incompatibilities arise in a limited set of large-effect speciation genes, or in a multitude of loci, we examined the geographic and genomic landscapes of introgression across the hybrid zones of 41 pairs of frog and toad lineages in the Western Palearctic region. As the divergence between lineages increases, phylogeographic transitions progressively become narrower, and larger parts of the genome resist introgression. This suggests that anuran speciation proceeds through a gradual accumulation of multiple barrier loci scattered across the genome, which ultimately deplete hybrid fitness by intrinsic postzygotic isolation, with behavioral isolation being achieved only at later stages. Moreover, these loci were disproportionately sex linked in one group (Hyla) but not in others (Rana and Bufotes), implying that large X-effects are not necessarily a rule of speciation with undifferentiated sex chromosomes. The highly polygenic nature of RI and the lack of hemizygous X/Z chromosomes could explain why the speciation clock ticks slower in amphibians compared to other vertebrates. The clock-like dynamics of speciation combined with the analytical focus on hybrid zones offer perspectives for more standardized practices of species delimitation.