Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic object detection: An improved approach for transposable elements detection and classification using convolutional neural networks

Analysis of eukaryotic genomes requires the detection and classification of transposable elements (TEs), a crucial but complex and time-consuming task. To improve the performance of tools that accomplish these tasks, Machine Learning approaches (ML) that leverage computer resources, such as GPUs (Graphical Processing Unit) and multiple CPU (Central Processing Unit) cores, have been adopted. However, until now, the use of ML techniques has mostly been limited to classification of TEs. Herein, a detection-classification strategy (named YORO) based on convolutional neural networks is adapted from computer vision (YOLO) to genomics. This approach enables the detection of genomic objects through the prediction of the position, length, and classification in large DNA sequences such as fully sequenced genomes. As a proof of concept, the internal protein-coding domains of LTR-retrotransposons are used to train the proposed neural network. Precision, recall, accuracy, F1-score, execution times and time ratios, as well as several graphical representations were used as metrics to measure performance. These promising results open the door for a new generation of Deep Learning tools for genomics. YORO architecture is available at https://github.com/simonorozcoarias/YORO.
Non-gonadal somatic piRNA pathways ensure sexual differentiation, larval growth, and wing development in silkworms

PIWI-interacting RNAs (piRNAs) guide PIWI proteins to target transposons in germline cells, thereby suppressing transposon activity to preserve genome integrity in metazoans’ gonadal tissues. Piwi, one of three Drosophila PIWI proteins, is expressed in the nucleus and suppresses transposon activity by forming heterochromatin in an RNA cleavage-independent manner. Recently, Piwi was reported to control cell metabolism in Drosophila fat body, providing an example of piRNAs acting in non-gonadal somatic tissues. However, mutant flies of the other two PIWI proteins, Aubergine (Aub) and Argonaute3 (Ago3), show no apparent phenotype except for infertility, blurring the importance of the piRNA pathway in non-gonadal somatic tissues. The silkworm, Bombyx mori, possesses two PIWI proteins, Siwi (Aub homolog) and BmAgo3 (Ago3 homolog), whereas B. mori does not have a Piwi homolog. Siwi and BmAgo3 are mainly expressed in gonadal tissues and play a role in repressing transposon activity by cleaving transposon RNA in the cytoplasm. Here, we generated Siwi and BmAgo3 loss-of-function mutants of B. mori and found that they both showed delayed larval growth and failed to become adult moths. They also exhibited defects in wing development and sexual differentiation. Transcriptome analysis revealed that loss of somatic piRNA biogenesis pathways results in abnormal expression of not only transposons but also host genes, presumably causing severe growth defects. Our results highlight the roles of non-gonadal somatic piRNAs in B. mori development.
Nicotine flux as a powerful tool for regulating nicotine delivery from e-cigarettes: Protocol of two complimentary randomized crossover clinical trials

Introduction Electronic cigarette (EC) use has increased rapidly in the last decade, especially among youth. Regulating nicotine delivery from ECs could help curb youth uptake and leverage EC use in harm reduction yet is complicated by varying device and liquid variables that affect nicotine delivery. Nicotine flux, the nicotine emission rate, is a parameter that incorporates these variables and focuses on the performance rather than the design of an EC. Nicotine flux therefore could be a powerful regulatory tool if it is shown empirically to predict nicotine delivery and subjective effects related to dependence. Methods and analysis This project consists of two complementary clinical trials. In Trial I, we will examine the relationship between nicotine flux and the rate and dose of nicotine delivery from ECs, hence, impacting abuse liability. It will also examine the extent to which this relationship is mediated by nicotine form (i.e., freebase versus protonated). At Yale School of Medicine (YSM), study participants will puff EC devices under conditions that differ by flux and form, while arterial blood is sampled in high time resolution. In Trial II, we will assess the relationship between nicotine flux, form, and subjective effects. At the American University of Beirut (AUB), participants will use EC devices with varying nicotine fluxes and forms, while dependency measures, such as the urge to use ECs, nicotine craving, and withdrawal symptoms, will be assessed. We will also monitor puffing intensity and real-time exposure to toxicants. Ethics and dissemination The protocol of Trial I and Trial II was approved by YSM and AUB IRBs, respectively. We will disseminate study results through peer-reviewed publications and conference presentations. Trial registration NCT05706701 for Trial I and NCT05430334 for Trial II.
Application of formula method for bound state problems in Schrödinger equation

By using Formula method for bound state problems, we have obtained the approximate analytical solution of the radial Schrodinger equation for Varshni potential model. The energy eigenvalues and the corresponding eigenfunctions are calculated in closed forms. In the process, eigen values for a = b =1 , a = −1 , b = −2 , and b = −1 , a = −2 for 2p , 3p , 3d , 4p and 4f states with three different values of the potential range were generated using the Varshni potential. Special cases of the potential are equally studied. Some numerical results have been presented which showed a good agreement with previous results obtained from another method. Keywords: Varshni potential, Schrodinger equation, Formula method, Bound state
Temporal properties of the speed-accuracy trade-off for arm-pointing movements in various directions around the body

Human body movements are based on the intrinsic trade-off between speed and accuracy. Fitts’s law (1954) shows that the time required for movement is represented by a simple logarithmic equation and is applicable to a variety of movements. However, few studies have determined the role of the direction in modulating the performance of upper limb movements and the effects of the interactions between direction and distance and between direction and target size. This study examined the variations in temporal properties of the speed-accuracy trade-off in arm-pointing movements that directly manipulate objects according to the direction, distance, and target size. Participants performed pointing movements to the targets with 3 different sizes presented at 15 locations (5 directions and 3 distances) on a horizontal plane. Movement time (MT) for each trial in each condition was obtained. Subsequently, Mackenzie’s model (1992), MT = a + b log2(D/W +1), where D and W represent the distance and width of the target, respectively, was fitted. The slope factor b, a fitted parameter in the equation, was calculated and evaluated according to the changes in the direction, distance, and target size. The results showed that MTs exhibited anisotropy in the hemifield, being the smallest in the right-forward direction. Additionally, the slope factor b, as a function of distance, was smaller in the rightward direction than in the forward and left-forward directions. These results suggest that the degree of difficulty of upper limb movements expands heterogeneously in various directions around the body.
Burden of respiratory syncytial virus in adults in the United Kingdom: A systematic literature review and gap analysis

Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is limited. This systematic literature review (SLR) aimed to identify the disease burden of RSV in UK adults, including certain high‐risk subgroups and existing evidence gaps. Published studies (2011 onwards) reporting epidemiological, economic and clinical burden outcomes in UK adults (≥15 years) with RSV were identified from indexed databases, including MEDLINE, Embase and the Cochrane library. High‐risk groups included elderly (≥65 years), immunocompromised, co‐morbid and co‐infected patients. Outcomes included RSV incidence/prevalence, mortality, clinical presentation and direct/indirect resource use/costs. Twenty‐eight publications on 28 unique studies were identified, mostly in general/respiratory indicator (n = 17), elderly (n = 10) and immunocompromised (n = 6) cohorts. Main outcomes reported in the general/respiratory indicator cohort were RSV infection incidence (seasonal/annual: 0.09–17.9%/6.6–15.1%), mortality (8,482 deaths/season) and direct resource use (including mean general practitioner [GP] episodes/season: 487,247). Seasonal/annual incidence was 14.6–26.5%/0.7–16% in high‐risk cohorts. Attributed to RSV in the elderly were 7,915 deaths/season and 175,070 mean GP episodes/season. Only two studies reported on co‐morbid cohorts. Clinical burden outcomes were only reported in general and immunocompromised patients, and no evidence was found in any cohort on indirect economic burden or RSV complications. Evidence captured suggests that RSV may have a substantial burden in UK adults. However, available data were limited and highly heterogenous, with further studies needed to characterise the burden of RSV in adults and to validate our findings.
A nomogram for predicting the risk of preeclampsia in women with intrahepatic cholestasis of pregnancy based on prenatal monitoring time: a multicenter retrospective cohort study

Background and aims: Intrahepatic cholestasis of pregnancy (ICP) is a special liver disease during pregnancy, characterized by abnormal bile acid metabolism. However, there is no consensus on how to group women with ICP based on the time of diagnosis worldwide. This study aimed to adopt a new grouping model of women with ICP, and the time from diagnosis to delivery was defined as the monitoring period. Methods: This retrospective real-world data study was conducted across multiple centers and included 3172 women with ICP. The study first evaluated the significant difference in medication and nonmedication during different monitoring times. The least absolute shrinkage and selection operator (LASSO) model was then used to screen nine risk factors based on the predictors. The model's discrimination, clinical usefulness, and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve, and calibration analysis. Results: The incidence of preeclampsia risk in ICP patients without drug intervention increased with the extension of the monitoring period. However, the risk of preeclampsia decreased in ICP patients treated with ursodeoxycholic acid. A predictive nomogram and risk score model was developed based on nine risk factors. The area under the ROC curve of the nomogram was 0.765 [95% confidence interval (CI): 0.724–0.807] and 0.812 (95% CI: 0.736–0.889) for the validation cohort. Conclusions: This study found that a longer ICP monitoring period could lead to adverse pregnancy outcomes in the absence of drug intervention, especially preeclampsia. A predictive nomogram and risk score model was developed to better manage ICP patients, maintain pregnancy to term delivery, and minimize the risk of severe adverse maternal and fetal outcomes.
Diagnostic capability of 18F-PSMA PET-MRI and pelvic MRI plus bone scan in treatment-naive prostate cancer: a single-center paired validating confirmatory study

Background: Radical prostatectomy with pelvic lymph node dissection for the treatment of high-risk localized prostate cancer (PCa) results in long-term benefits in selected patients. But insufficient sensitivity of conventional examinations which are pelvic MRI and bone scan, limits the diagnosis of bone and lymph node metastasis of PCa. This affects the surgical management strategy of a large number of patients. The purpose of this study was to investigate whether 18F-prostate-specific membrane antigen (PSMA) PET-MRI could improve the clinical detection of PCa metastases compared with the conventional pelvic MRI plus bone scan. Materials and methods: From April 2020 to April 2023, we prospectively enroled 472 patients with histologically proven PCa in our centre, and 120 patients underwent 18F-PSMA PET-MRI, multiparametric MRI, and bone scan before laparoscopic radical prostatectomy plus lymph node dissection. The accuracy of imaging results in detecting lymph node and bone metastatic lesions was compared between PSMA PET-MRI and MRI plus bone scan. Results: In diagnosing lymph node metastasis, PSMA PET-MRI had an area under the curve (AUC) of 0.844 (95% CI: 0.738–0.949, P < 0.001), sensitivity and specificity of 75% and 96%, which performed apparently better than MRI [AUC=0.615 (95% CI: 0.480–0.750, P=0.073)]. PSMA PET-MRI showed excellent expression in the diagnosis of bone metastases, with an AUC of 0.910 (95% CI: 0.840–0.981, P <0.001) compared to 0.700 (95% CI: 0.577–0.823, P =0.001) in bone scanning. PSMA PET-MRI also had higher sensitivity than bone scanning (90% vs. 43%), while lower specificity (92% vs. 97%). Conclusion: PSMA PET-MRI is superior to conventional imaging at diagnosing metastases in lymph nodes and bones in PCa and can provide a more accurate stagement.
Biotransformation research advances – 2022 year in review

Abstract This annual review is the eighth of its kind since 2016 (Baillie et al. 2016, Khojasteh et al. 2017, Khojasteh et al. 2018, Khojasteh et al. 2019, Khojasteh et al. 2020, Khojasteh et al. 2021, Khojasteh et al. 2022). Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation.
Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22-modified FK520 analog against C. neoformans

ABSTRACT Fungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections by Cryptococcus neoformans are associated with high mortality, emphasizing the need for novel therapeutic options. Calcineurin is a protein phosphatase that mediates fungal stress responses, and calcineurin inhibition by the natural product FK506 blocks C. neoformans growth at 37°C. Calcineurin is also required for pathogenesis. However, because calcineurin is conserved in humans and inhibition with FK506 results in immunosuppression, the use of FK506 as an anti-infective agent is precluded. We previously elucidated the structures of multiple fungal calcineurin-FK506-FKBP12 complexes and implicated the C-22 position on FK506 as a key point for differential modification of ligand inhibition of mammalian versus fungal target proteins. Through in vitro antifungal and immunosuppressive testing of FK520 (a natural analog of FK506) derivatives, we identified JH-FK-08 as a lead candidate for further antifungal development. JH-FK-08 exhibited significantly reduced immunosuppressive activity and both reduced fungal burden and prolonged survival of infected animals. JH-FK-08 exhibited additive activity in combination with fluconazole in vivo. These findings further advance calcineurin inhibition as an antifungal therapeutic approach. IMPORTANCE Fungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited, and the development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human host. With rising resistance to the current antifungal arsenal and an increasing at-risk population, there is an urgent need for the development of new antifungal compounds. The FK520 analogs described in this study display potent antifungal activity as a novel class of antifungals centered on modifying an existing orally active FDA-approved therapy. This research advances the development of much-needed newer antifungal treatment options with novel mechanisms of action. Fungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited, and the development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human host. With rising resistance to the current antifungal arsenal and an increasing at-risk population, there is an urgent need for the development of new antifungal compounds. The FK520 analogs described in this study display potent antifungal activity as a novel class of antifungals centered on modifying an existing orally active FDA-approved therapy. This research advances the development of much-needed newer antifungal treatment options with novel mechanisms of action.
Apples to apples? Discordant definitions still hinder evidence‐based treatments for sarcopenia

Preservation of skeletal muscle strength, size and function is critical to healthy aging. The progressive loss of each with advancing age — sarcopenia — is deleterious on several levels. Exercise is the primary countermeasure for sarcopenia, but ‘ exercise ’ alone is a broad recommendation. In a recent publication in the Journal of Cachexia, Sarcopenia and Muscle , Shen and colleagues 1 aimed to compare the effectiveness of different exercise interventions for improving relevant patient outcomes (e.g., all-cause mortality, quality of life and falls) in older adults with sarcopenia. The authors summarized the effect of 12 interventions from 42 randomized controlled trials using a network meta-analysis (NMA). Resistance training (strength training) was the most effective exercise for improving quality of life, strength and physical performance, with or without additional exercise/nutritional interventions. The authors 1 deserve substantial recognition for their comprehensive work. In our view, their results support and reinforce resistance training as the primary countermeasure to sarcopenia 2 but also exemplify a major issue: disparate de ﬁ nitions impede the diagnosis and evidence-based treatment of sarcopenia.
ER stress elicits non-canonical CASP8 (caspase 8) activation on autophagosomal membranes to induce apoptosis

ABSTRACT The VPS37A gene encodes a subunit of the endosomal sorting complex required for transport (ESCRT)-I complex that is frequently lost in a wide variety of human solid cancers. We have previously demonstrated the role of VPS37A in directing the ESCRT membrane scission machinery to seal the phagophore for autophagosome completion. Here, we report that VPS37A-deficient cells exhibit an accumulation of the apoptotic initiator CASP8 (caspase 8) on the phagophore and are primed to undergo rapid apoptosis through the intracellular death-inducing signaling complex (iDISC)-mediated CASP8 activation upon exposure to endoplasmic reticulum (ER) stress. Using CRISPR-Cas9 gene editing and comparative transcriptome analysis, we identified the ATF4-mediated stress response pathway as a crucial mediator to elicit iDISC-mediated apoptosis following the inhibition of autophagosome closure. Notably, ATF4-mediated iDISC activation occurred independently of the death receptor TNFRSF10B/DR5 upregulation but required the pro-apoptotic transcriptional factor DDIT3/CHOP to enhance the mitochondrial amplification pathway for full-activation of CASP8 in VPS37A-deficient cells stimulated with ER stress inducers. Our analysis also revealed the upregulation of NFKB/NF-kB signaling as a potential mechanism responsible for restraining iDISC activation and promoting cell survival upon VPS37A depletion. These findings have important implications for the future development of new strategies to treat human cancers, especially those with VPS37A loss. Abbreviations: ATG: autophagy related; BMS: BMS-345541; CASP: caspase; CHMP: charged multivesicular body protein; DKO: double knockout; Dox: doxycycline; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; gRNA: guide RNA; GSEA: gene set enrichment analysis; GSK157: GSK2656157; iDISC: intracellular death-inducing signaling complex; IKK: inhibitor of NFKB kinase; IPA: ingenuity pathway analysis; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NFKB/NF-kB: nuclear factor kappa B; OZ: 5Z-7-oxozeaenol; RNA-seq: RNA sequencing; UPR: unfolded protein response; TFT: transcription factor target; THG: thapsigargin; TUN: tunicamycin; VPS: vacuolar protein sorting.
Space, Settlement, and Environment: Detecting Undocumented Maya Archaeological Sites with Remotely Sensed Data

This study utilizes an integrated remote sensing approach to augment settlement pattern research in the Yalahau Region of northern Quintana Roo, Mexico. The region has a long history of human occupation and an environment ranging from coasts, freshwater wetlands, forests, to fields and towns all above a porous karst geology. By utilizing various sensors (LiDAR, GeoEye and Landsat) and collection methods (satellite, aerial) as well as post-processing (band combinations, component analyses and indices) and cross-referencing the data, it is possible to generate a signature, which strongly correlates with evidence of prehistoric occupation. Field verification of a selection of identified signatures was conducted to assess the presence of human cultural material. The results of this investigation are presented together with other regional settlement pattern data in order to assess the status of a number of methodological and archaeological questions and supplement other regional data already available. INDEX WORDS: Maya, Human Ecology, Remote Sensing, Landsat, LiDAR, Archaeology, Settlement Pattern, Survey, GIS SPACE, SETTLEMENT, AND ENVIRONMENT: DETECTING UNDOCUMENTED MAYA ARCHAEOLOGICAL SITES WITH REMOTELY SENSED DATA
The role of quantitative markers in surgical prognostication after stereoelectroencephalography

Stereoelectroencephalography (SEEG) is the reference method in the presurgical exploration of drug‐resistant focal epilepsy. However, prognosticating surgery on an individual level is difficult. A quantified estimation of the most epileptogenic regions by searching for relevant biomarkers can be proposed for this purpose. We investigated the performances of ictal (Epileptogenicity Index, EI; Connectivity EI, cEI), interictal (spikes, high‐frequency oscillations, HFO [80–300 Hz]; Spikes × HFO), and combined (Spikes × EI; Spikes × cEI) biomarkers in predicting surgical outcome and searched for prognostic factors based on SEEG‐signal quantification.