Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing Load Forecast Uncertainty using Extreme Value Theory

Daily and hourly load forecasting often have to deal with extreme events which are rare but may have sig- nificant consequences. While the climate of the UK might be moving to warmer and wetter winters, and hotter and drier summers, this could lead to significant changes in the shape of the demand profile. Some notable extreme weather events have occurred in the past, e.g. unusually hot summer tem- peratures in 1995 and 2003 that created a surge in regional electricity demand when compared with the long-term av- erage. Such events can pose a challenge to energy forecast- ers who must provide accurate predictions to utility decision makers. This paper thus outlines the use of generalized ex- treme value (GEV) theory and block maxima approach to estimate the maximum load forecast errors (residuals) up to several decades ahead to assess risk in long-term electricity demand projection when climate change effects become im- portant. The maximum residuals are expressed in terms of return level and return period that would occur within a fi- nite time series corresponding to accepted levels of risk so that appropriate risk measures can be taken. The maximum residual is then added to the predicted demand to give the expected demand with a given level of risk.
Tolerability of long‐term cannabidiol supplementation to healthy adult dogs

Abstract Background Cannabidiol (CBD) has therapeutic potential in companion animals. Shorter‐term studies have determined that CBD is well tolerated in dogs with mild adverse effects and an increase in alkaline phosphatase (ALP) activity. There is need to assess CBD's long‐term tolerability. Hypothesis Determine the long‐term tolerability of CBD administered PO to healthy dogs for 36 weeks at dosages of 5 and 10 mg/kg body weight (BW)/day. Our hypothesis was that CBD would be well tolerated by dogs. Methods Eighteen healthy adult beagle dogs were randomly assigned to 3 groups of 6 each that received 0, 5, or 10 mg/kg BW/day CBD PO. Dogs were adapted to their housing for 3 weeks and received treatment for 36 weeks once daily with food. Adverse events (AEs) were recorded daily. Blood biochemistry profiles were monitored every 4 weeks. Data were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05. Results The 0 and 5 mg/kg treatment groups had similar fecal scores, and the 10 mg/kg treatment group had higher frequency of soft feces. No other significant AEs were noted. An increase (P < .0001) in ALP activity occurred in groups that received CBD. Remaining blood variables were within reference range. Conclusions and Clinical Importance Chronic administration of CBD in healthy dogs at 5 mg/kg was better tolerated than 10 mg/kg, and both dosages caused an increase in ALP activity. Although our data does not indicate hepatic damage, it is recommended to monitor liver function in dogs receiving CBD chronically.
Internal RNA 2′-O-methylation on the HIV-1 genome impairs reverse transcription

Abstract Viral RNA genomes are modified by epitranscriptomic marks, including 2′-O-methylation that is added by cellular or viral methyltransferases. 2′-O-Methylation modulates RNA structure, function and discrimination between self- and non-self-RNA by innate immune sensors such as RIG-I-like receptors. This is illustrated by human immunodeficiency virus type-1 (HIV-1) that decorates its RNA genome through hijacking the cellular FTSJ3 2′-O-methyltransferase, thereby limiting immune sensing and interferon production. However, the impact of such an RNA modification during viral genome replication is poorly understood. Here we show by performing endogenous reverse transcription on methylated or hypomethylated HIV-1 particles, that 2′-O-methylation negatively affects HIV-1 reverse transcriptase activity. Biochemical assays confirm that RNA 2′-O-methylation impedes reverse transcriptase activity, especially at low dNTP concentrations reflecting those in quiescent cells, by reducing nucleotide incorporation efficiency and impairing translocation. Mutagenesis highlights K70 as a critical amino acid for the reverse transcriptase to bypass 2′-O-methylation. Hence, the observed antiviral effect due to viral RNA 2′-O-methylation antagonizes the FTSJ3-mediated proviral effects, suggesting the fine-tuning of RNA methylation during viral replication.
Neurologic morbidity and functional independence in adult survivors of childhood cancer

Abstract Objective To examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)‐directed therapies. Methods A total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS‐treated]; median age [range] = 25.5 years [18–48]; time since diagnosis = 17.7 years [6.8–30.2]) and 8039 without CNS‐directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal care needs, ability to work/attend school, attainment of driver's license, marital/partner status). Multivariable regression models, adjusted for age, sex, race/ethnicity, and chronic health conditions, estimated odds ratios (OR) or relative risks (RR) for associations between neurologic morbidity, functional independence, and emotional distress. Results Among CNS‐treated survivors, three classes of independence were identified: (1) moderately independent, never married, and non‐independent living (78.7%); (2) moderately independent, unable to drive (15.6%); and (3) non‐independent (5.7%). In contrast to 50% of non‐CNS‐treated survivors and 60% of siblings, a fourth fully independent class of CNS‐treated survivors was not identified. History of stroke (OR = 2.50, 95% CI: 1.70–3.68), seizure (OR = 9.70, 95% CI: 7.37–12.8), neurosensory deficits (OR = 2.67, 95% CI: 2.16–3.31), and focal neurologic dysfunction (OR = 3.05, 95% CI: 2.40–3.88) were associated with non‐independence among CNS‐treated survivors. Non‐independence was associated with emotional distress symptoms. Interpretation CNS‐treated survivors do not attain full independence comparable to non‐CNS‐treated survivors or siblings. Interventions to promote independence may be beneficial for survivors with treatment‐related neurological sequalae.
The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae

ABSTRACT Gut microbiota plays a crucial role in providing colonization resistance against multi-drug resistant organisms including carbapenem-resistant Klebsiella pneumoniae (CRKP). However, the impact of different carbapenems on intestinal colonization resistance against CRKP remains poorly understood. In this study, we aimed to investigate the effects of three commonly used carbapenems (meropenem, imipenem, and ertapenem) administered at single-day doses, which are typically employed in emergency departments for managing infected patients, on CRKP gut colonization. We conducted experiments in mice by intravenously administering each carbapenem using human-simulated one-day regimens. The composition of the gut microbiota was analyzed using 16S rRNA amplicon sequencing before and after carbapenem administration. Our results revealed that all three carbapenems, when administered at a single-day dose significantly altered the abundance and diversity of the gut microbiota, leading to compromised colonization resistance against CRKP. Notably, the ertapenem and imipenem groups showed an increase in Allobaculum, Bifidobacterium, Enterobacteriaceae, while the meropenem and imipenem groups exhibited a decrease in Ruminococcaceae, S24-7, and Akkermania. Additionally, the Shannon index exhibited a negative correlation with both the number of days of CRKP colonization CFUs and the duration of bacteria shedding. Furthermore, the count of CRKP in mice after ertapenem administration on the first day and the duration of CRKP shedding were significantly lower compared to meropenem and imipenem. Predictive metabolic pathway analysis demonstrated that the three carbapenems similarly affected a range of metabolic pathways of gut microflora, including carbohydrate metabolism and vitamin B. Our findings emphasize that ertapenem, with its relatively narrow spectrum, minimizes perturbations of the gut microbiota and has a relatively less impact on gut colonization resistance against CRKP. IMPORTANCE The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem. The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.
Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver.

INTRODUCTION High-fructose, high-fat diet consumption (HFHF) is one of the primary causes of non-alcoholic fatty liver disease (NAFLD), which is due to impaired beta-oxidation or apolipoprotein secretion by hepatocytes. Activation of autophagy in hepatocytes could be a therapeutic method against hepatic complications. This study was designed to compare effects of rapamycin and intermittent fasting-inducing autophagy in rats with experimentally induced nonalcoholic fatty liver. MATERIAL AND METHODS Male rats were divided into five groups: C (control, n = 6), the experimental group (EX) subdivided, EXIa (HFHF, n = 6), EXIb (recovery, n = 6), EXII (rapamycin, n = 6) and EXIII (intermittent fasting, n = 6). All rats in the experimental group received HFHF diet for 8 weeks to induce nonalcoholic-fatty liver and obesity. Then, for the next 8 weeks the animals received either a daily oral dose of rapamycin (EXII group) or to intermittent fasting (IF) for 16 hours daily (EXIII group). Blood samples were drawn, and serum TG concentration as well as ALT and AST activities were determined. Hepatic sections were examined by light and electron microscopy. LC3B immunohistochemical staining, morphometric and statistical studies were performed. RESULTS Subgroups EXIa (HFHF subgroup) and EXIb (Recovery subgroup) showed marked increase in TG, ALT, and AST levels associated with loss of normal hepatic architecture, cytoplasmic vacuolations and faint LC3B immunoreactivity. Ultrathin sections exhibited many autophagosomes in hepatocytes. On the other hand, rapamycin (EXII) and IF (EXIII) showed significant improvement to a variable extent in comparison to EXI. CONCLUSIONS It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes.
Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume

ABSTRACT Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to traditional SC delivery systems are therefore needed to support higher-volume biologic formulations and to reduce development time and other risks associated with high-concentration biologic formulations. Here, we outline key considerations for SC biologic drug formulations and delivery and explore a paradigm shift: the flexibility afforded by low-to-moderate-concentration drugs in high-volume formulations as an alternative to the traditionally difficult approach of high-concentration, low-volume SC formulation delivery.
Genomic analysis of Streptococcus pneumoniae serogroup 20 isolates in Alberta, Canada from 1993–2019

In the province of Alberta, Canada, invasive disease caused by Streptococcus pneumoniae serogroup 20 (serotypes 20A/20B) has been increasing in incidence. Here, we characterize provincial invasive serogroup 20 isolates collected from 1993 to 2019 alongside invasive and non-invasive serogroup 20 isolates from the Global Pneumococcal Sequencing (GPS) Project collected from 1998 to 2015. Trends in clinical metadata and geographic location were evaluated, and serogroup 20 isolate genomes were subjected to molecular sequence typing, virulence and antimicrobial resistance factor mining, phylogenetic analysis and pangenome calculation. Two hundred and seventy-four serogroup 20 isolates from Alberta were sequenced, and analysed along with 95 GPS Project genomes. The majority of invasive Alberta serogroup 20 isolates were identified after 2007 in primarily middle-aged adults and typed predominantly as ST235, a sequence type that was rare among GPS Project isolates. Most Alberta isolates carried a full-length whaF capsular gene, suggestive of serotype 20B. All Alberta and GPS Project genomes carried molecular resistance determinants implicated in fluoroquinolone and macrolide resistance, with a few Alberta isolates exhibiting phenotypic resistance to azithromycin, clindamycin, erythromycin, tetracycline and trimethoprim-sulfamethoxazole, as well as non-susceptibility to tigecycline. All isolates carried multiple virulence factors including those involved in adherence, immune modulation and nutrient uptake, as well as exotoxins and exoenzymes. Phylogenetically, Alberta serogroup 20 isolates clustered with predominantly invasive GPS Project isolates from the USA, Israel, Brazil and Nepal. Overall, this study highlights the increasing incidence of invasive S. pneumoniae serogroup 20 disease in Alberta, Canada, and provides insights into the genetic and clinical characteristics of these isolates within a global context.
COMPARISON OF METHODS FOR ESTIMATING REFERENCE EVAPOTRANSPIRATION IN SOUTHERN CALIFORNIA

A significant part of precipitation returns back to the atmosphere by evapotranspiration. Developing formulations aimed at accurately quantifying evapotranspiration over a given region can aid a wide variety of audiences, including water managers and hydrologists. In this study, the accuracy of four existing evapotranspiration methods (Thornthwaite, BlaneyCriddle, Turc and Makkink) for southern California is investigated. The end results are compared with those of the FAO Penman-Monteith method, which is taken as the benchmark solution for comparison purposes. The meteorological data from a California Irrigation Management Information System (CIMIS) station in southern California has been used. The comparison is first made by using the original constant coefficients in the above four methods and subsequently using recalibrated constant values. Based on statistical analysis, the methods that performed best in estimating daily and monthly evapotranspiration are recommended with their recalibrated constants for potential use in Southern California.
Noise-Factorized Disentangled Representation Learning for Generalizable Motor Imagery EEG Classification

Motor Imagery (MI) Electroencephalography (EEG) is one of the most common Brain-Computer Interface (BCI) paradigms that has been widely used in neural rehabilitation and gaming. Although considerable research efforts have been dedicated to developing MI EEG classification algorithms, they are mostly limited in handling scenarios where the training and testing data are not from the same subject or session. Such poor generalization capability significantly limits the realization of BCI in real-world applications. In this paper, we proposed a novel framework to disentangle the representation of raw EEG data into three components, subject/session-specific, MI-task-specific, and random noises, so that the subject/session-specific feature extends the generalization capability of the system. This is realized by a joint discriminative and generative framework, supported by a series of fundamental training losses and training strategies. We evaluated our framework on three public MI EEG datasets, and detailed experimental results show that our method can achieve superior performance by a large margin compared to current state-of-the-art benchmark algorithms.
Efficacy of 3-day versus 5-day aprepitant regimens for long-delayed chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy

ABSTRACT Background Chemotherapy-induced nausea and vomiting (CINV) is an ongoing problem. While effectiveness of triplet antiemetic regimens in the delayed CINV phase (24–120 hours after administration of chemotherapy) has been studied, their effectiveness in the long-delayed phase (120–168 hours post-administration) is unknown. We compared the efficacy of 3- and 5-day courses of a triplet antiemetic prophylaxis containing aprepitant (APR) in controlling long-delayed CINV after cisplatin (CDDP)-based chemotherapy. Research design and methods We obtained patient-level data from a nationwide, multicenter, prospective observational study in Japan. The incidence and timing of CINV after 3- and 5-day APR-containing regimens were compared using inverse probability treatment weighting. Results: The analysis included 380 patients. The incidence rates of long-delayed nausea and vomiting were significantly reduced for the 5-day compared with the 3-day regimen (29.1% vs. 22.2%, p = 0.0042; 6.7% vs. 0%, p < 0.0001, respectively). Among those without CINV, vomiting was not reported after day 2 in the 5-day APR group but increased after day 4 in the 3-day APR group. Conclusion A 5-day regimen triplet antiemetic prophylaxis with APR decreased long-delayed vomiting compared with a 3-day regimen in patients receiving CDDP-based chemotherapy. However, the 5-day regimen showed no advantage over the 3-day regimen against long-delayed nausea.
The First Hundred Years of the Ipswich Thistle Pipe Band: A 'Community of Discovery' Approach to Participatory Action Research

The Caledonian Society and Burns Club of Ipswich formed a uniformed pipe and drums band in 1909 that eventually became known as the Ipswich Thistle Pipe Band. As the second-oldest pipe band in Queensland, the members of the Ipswich Thistle Pipe Band have remarkable stories to tell about their hundred year history. I received a commission from Arts Queensland and the Ipswich City Council to help the band research and write a music history book for their centennial celebrations in 2009. This article is about my critical reflection on the participatory action research processes that we used to help band members and supporters to engage with their music heritage and culture. In discussing how I facilitated this practice-led research project, I also describe some of the inter-cultural relationships between the band and the First Australians in order to place the significance of this research within the broader socio-ecological context.
Regulation of pDC fate determination by histone deacetylase 3

Dendritic cells (DCs), the key antigen-presenting cells, are primary regulators of immune responses. Transcriptional regulation of DC development had been one of the major research interests in DC biology, however, the epigenetic regulatory mechanisms during DC development remains unclear. Here, we report that Histone deacetylase 3 (Hdac3), an important epigenetic regulator, is highly expressed in pDCs, and its deficiency profoundly impaired the development of pDCs. Significant disturbance of homeostasis of hematopoietic progenitors was also observed in HDAC3-deficient mice, manifested by altered cell numbers of these progenitors and defective differentiation potentials for pDCs. Using the in vitro Flt3L supplemented DC culture system, we further demonstrated that HDAC3 was required for the differentiation of pDCs from progenitors at all developmental stages. Mechanistically, HDAC3 deficiency resulted in enhanced expression of cDC1-associated genes, owing to markedly elevated H3K27 acetylation (H3K27ac) at these gene sites in BM pDCs. In contrast, the expression of pDC-associated genes was significantly downregulated, leading to defective pDC differentiation. Summary This work reveals for the first time that HDAC3 is required for the development of pDCs and maintenance of homeostasis of hematopoietic progenitors with DC differentiation potential. Mechanistically, HDAC3 promotes pDC development by repressing the expression of cDC1 associated genes in a deacetylase dependent manner.
The SKMT Algorithm: A method for assessing and comparing underlying protein entanglement

We present fast and simple-to-implement measures of the entanglement of protein tertiary structures which are appropriate for highly flexible structure comparison. These are performed using the SKMT algorithm, a novel method of smoothing the Cα backbone to achieve a minimal complexity curve representation of the manner in which the protein’s secondary structure elements fold to form its tertiary structure. Its subsequent complexity is characterised using measures based on the writhe and crossing number quantities heavily utilised in DNA topology studies, and which have shown promising results when applied to proteins recently. The SKMT smoothing is used to derive empirical bounds on a protein’s entanglement relative to its number of secondary structure elements. We show that large scale helical geometries dominantly account for the maximum growth in entanglement of protein monomers, and further that this large scale helical geometry is present in a large array of proteins, consistent across a number of different protein structure types and sequences. We also show how these bounds can be used to constrain the search space of protein structure prediction from small angle x-ray scattering experiments, a method highly suited to determining the likely structure of proteins in solution where crystal structure or machine learning based predictions often fail to match experimental data. Finally we develop a structural comparison metric based on the SKMT smoothing which is used in one specific case to demonstrate significant structural similarity between Rossmann fold and TIM Barrel proteins, a link which is potentially significant as attempts to engineer the latter have in the past produced the former. We provide the SWRITHE interactive python notebook to calculate these metrics.