Miracle-dz/UniFAR-FTUs huggingface dataset:
A Rapid, Whole Genome Sequencing Assay for Detection and Characterization of Novel Coronavirus (SARS-CoV-2) Clinical Specimens Using Nanopore Sequencing

A new human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged at the end of 2019 in Wuhan, China that caused a range of disease severities; including fever, shortness of breath, and coughing. This disease, now known as coronavirus disease 2019 (COVID-19), quickly spread throughout the world, and was declared a pandemic by the World Health Organization in March of 2020. As the disease continues to spread, providing rapid characterization has proven crucial to better inform the design and execution of control measures, such as decontamination methods, diagnostic tests, antiviral drugs, and prophylactic vaccines for long-term control. Our work at the United States Army’s Combat Capabilities Development Command Chemical Biological Center (DEVCOM CBC) is focused on engineering workflows to efficiently identify, characterize, and evaluate the threat level of any potential biological threat in the field and more remote, lower resource settings, such as forward operating bases. While we have successfully established untargeted sequencing approaches for detection of pathogens for rapid identification, our current work entails a more in-depth sequencing analysis for use in evolutionary monitoring. We are developing and validating a SARS-CoV-2 nanopore sequencing assay, based on the ARTIC protocol. The standard ARTIC, Illumina, and nanopore sequencing protocols for SARS-CoV-2 are elaborate and time consuming. The new protocol integrates Oxford Nanopore Technology’s Rapid Sequencing Kit following targeted RT-PCR of RNA extracted from human clinical specimens. This approach decreases sample manipulations and preparation times. Our current bioinformatics pipeline utilizes Centrifuge as the classifier for quick identification of SARS-CoV-2 and RAMPART software for verification and mapping of reads to the full SARS-CoV-2 genome. ARTIC rapid sequencing results, of previous RT-PCR confirmed patient samples, showed that the modified protocol produces high quality data, with up to 98.9% genome coverage at >1,000x depth for samples with presumably higher viral loads. Furthermore, whole genome assembly and subsequent mutational analysis of six of these sequences identified existing and unique mutations to this cluster, including three in the Spike protein: V308L, P521R, and D614G. This work suggests that an accessible, portable, and relatively fast sample-to-sequence process to characterize viral outbreaks is feasible and effective.
Forward Electric Stimulation-Induced Interference in Intracochlear Electrocochleography of Acoustic Stimulation in the Cochlea of Guinea Pigs

Electric-acoustic stimulation (EAS) uses amplified sound by a hearing aid to stimulate an apical low-frequency region of the cochlea and electrical current from a cochlear implant (CI) to stimulate the basal high-frequency region. EAS recipients had significantly improved speech perception, music appreciation, and hearing function in noise compared to those relying on CI electrical stimulation (ES) alone. However, the interaction between basal ES and apical acoustic stimulation (AS) in the cochlea potentially affects EAS advantages. To investigate ES-AS interaction, we designed a system that recorded the electrically evoked compound action potential (ECAP) and the auditory evoked potential (AEP). We used an intracochlear electrode array to deliver ES at the basal cochlea and detect intracochlear electrocochleography (iECochG) generated from apical AS. Within iECochG, 3 or 6 dB (double or quadruple intensity of ECAP threshold) electric stimulation, 1 ms-forward ES significantly increased CAP amplitudes of 4 kHz/20 dB AS compared to 0 dB ES. Notably, 1 ms-forward 3 dB ES significantly increased CAP amplitudes of 4 kHz/20 dB AS, while 3 or 5 ms-forward ES did not change the CAP amplitudes. The elevation in CAP amplitude of 40 dB/4 kHz AS induced by 1 ms-forward 3 dB ES was significantly lower than that in 20 dB/4 kHz AS. With 1 ms-forward 3 dB ES, AS frequency and stimulating electrode location have no significant impact on relative CAP amplitudes of 20 dB AS. These results suggest that the basal forward ES and the following apical AS could produce a cumulative effect on the auditory nerve response.
Toward Rapid, Widely Available Autologous CAR-T Cell Therapy – Artificial Intelligence and Automation Enabling the Smart Manufacturing Hospital

CAR-T cell therapy is a promising treatment for acute leukemia and lymphoma. CAR-T cell therapies take a pioneering role in autologous gene therapy with three EMA-approved products. However, the chance of clinical success remains relatively low as the applicability of CAR-T cell therapy suffers from long, labor-intensive manufacturing and a lack of comprehensive insight into the bioprocess. This leads to high manufacturing costs and limited clinical success, preventing the widespread use of CAR-T cell therapies. New manufacturing approaches are needed to lower costs to improve manufacturing capacity and shorten provision times. Semi-automated devices such as the Miltenyi Prodigy® were developed to reduce hands-on production time. However, these devices are not equipped with the process analytical technology necessary to fully characterize and control the process. An automated AI-driven CAR-T cell manufacturing platform in smart manufacturing hospitals (SMH) is being developed to address these challenges. Automation will increase the cost-effectiveness and robustness of manufacturing. Using Artificial Intelligence (AI) to interpret the data collected on the platform will provide valuable process insights and drive decisions for process optimization. The smart integration of automated CAR-T cell manufacturing platforms into hospitals enables the independent manufacture of autologous CAR-T cell products. In this perspective, we will be discussing current challenges and opportunities of the patient-specific but highly automated, AI-enabled CAR-T cell manufacturing. A first automation concept will be shown, including a system architecture based on current Industry 4.0 approaches for AI integration.
The Association Between Visceral Obesity and Postoperative Outcomes in Elderly Patients With Colorectal Cancer

Background The impact of visceral obesity on the postoperative complications of colorectal cancer in elderly patients has not been well studied. This study aims to explore the influence of visceral obesity on surgical outcomes in elderly patients who have accepted a radical surgery for colorectal cancer. Methods Patients aged over 65 year who had undergone colorectal cancer resections from January 2015 to September 2020 were enrolled. Visceral obesity is typically evaluated based on visceral fat area (VFA) which is measured by computed tomography (CT) imaging. Univariate and multivariate analyses were performed to analyze parameters related to short-term outcomes. Results A total of 528 patients participated in this prospective study. Patients with visceral obesity exhibited the higher incidence of total (34.1% vs. 18.0%, P < 0.001), surgical (26.1% vs. 14.6%, P = 0.001) and medical (12.6% vs. 6.7%, P = 0.022) complications. Based on multivariate analysis, visceral obesity and preoperative poorly controlled hypoalbuminemia were considered as independent risk factors for postoperative complications in elderly patients after colorectal cancer surgery. Conclusions Visceral obesity, evaluated by VFA, was a crucial clinical predictor of short-term outcomes after colorectal cancer surgery in elderly patients. More attentions should be paid to these elderly patients before surgery.
Impact of Carbapenem Peri-Transplant Prophylaxis and Risk of Extended-Spectrum Cephalosporin-Resistant Enterobacterales Early Urinary Tract Infection in Kidney Transplant Recipients: A Propensity Score-Matched Analysis

Background Urinary tract infection (UTI) is the most common bacterial infection after kidney transplantation (KT), leading to unfavorable clinical and allograft outcomes. Gram-negative uropathogenic bacteria are frequently encountered especially extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (EB), causing UTI early after KT. Methods A retrospective single transplant study was conducted between January 2016 and December 2019. We performed 1:1 nearest-neighbor propensity score matching without replacement using recipient age, recipient sex, induction, transplant year, human leukocyte antigen, cold ischemia time, and panel-reactive antibody before analyses. Cumulative incidence of ESC-R EB early (within 14 days after KT) UTI was estimated by the Kaplan–Meier method. Risk factors for ESC-R EB early UTI were analyzed by a Cox proportional hazards model. Variables measured after transplantation were considered time-dependent covariates. Results We included 620 KT recipients (37% women; mean age ± SD, 43 ± 11 years). Overall, 64% and 76% received deceased-donor allograft and induction therapy. Sixty-five (10%) and 555 (90%) received carbapenems and cefuroxime peri-transplant prophylaxis, respectively. Early UTI occurred in 183 (30%) patients, 52% caused by ESC-R EB. Propensity score matching produced 65 well-balanced pairs. During a 14-day follow-up, the cumulative incidence of ESC-R EB early UTI was 5 and 28% in the carbapenems and cefuroxime groups, respectively (log-rank test = 0.003). Peri-transplant carbapenems prophylaxis was a protective factor against ESC-R EB after KT (hazard ratio, 0.19; 95% confidence interval, 0.05–0.64; p = 0.008). Clinical and allograft outcomes did not differ significantly between the groups. Conclusions In the setting where ESC-R EB UTI is common among KT recipients, carbapenems peri-transplant prophylaxis could protect against the occurrence of early ESC-R EB UTI after KT. Further prospective studies should focus on this specific infection prevention strategy.
The embedding capacity of 4-dimensional symplectic ellipsoids

This paper calculates the function $c(a)$ whose value at $a$ is the infimum of the size of a ball that contains a symplectic image of the ellipsoid $E(1,a)$. (Here $a \ge 1$ is the ratio of the area of the large axis to that of the smaller axis.) The structure of the graph of $c(a)$ is surprisingly rich. The volume constraint implies that $c(a)$ is always greater than or equal to the square root of $a$, and it is not hard to see that this is equality for large $a$. However, for $a$ less than the fourth power $\tau^4$ of the golden ratio, $c(a)$ is piecewise linear, with graph that alternately lies on a line through the origin and is horizontal. We prove this by showing that there are exceptional curves in blow ups of the complex projective plane whose homology classes are given by the continued fraction expansions of ratios of Fibonacci numbers. On the interval $[\tau^4,7]$ we find $c(a)=(a+1)/3$. For $a \ge 7$, the function $c(a)$ coincides with the square root except on a finite number of intervals where it is again piecewise linear. The embedding constraints coming from embedded contact homology give rise to another capacity function $c_{ECH}$ which may be computed by counting lattice points in appropriate right angled triangles. According to Hutchings and Taubes, the functorial properties of embedded contact homology imply that $c_{ECH}(a) \le c(a)$ for all $a$. We show here that $c_{ECH}(a) \ge c(a)$ for all $a$.
Methods for Measuring and Identifying Sounds in the Intensive Care Unit

Background Despite many studies in the field examining excessive noise in the intensive care unit, this issue remains an ongoing problem. A limiting factor in the progress of the field is the inability to draw conclusions across studies due to the different and poorly reported approaches used. Therefore, the first goal is to present a method for the general measurement of sound pressure levels and sound sources, with precise details and reasoning, such that future studies can use these procedures as a guideline. The two procedures used in the general method will outline how to record sound pressure levels and sound sources, using sound level meters and observers, respectively. The second goal is to present the data collected using the applied method to show the feasibility of the general method and provide results for future reference. Methods The general method proposes the use of two different procedures for measuring sound pressure levels and sound sources in the intensive care unit. The applied method uses the general method to collect data recorded over 24-h, examining two beds in a four-bed room, via four sound level meters and four observers each working one at a time. Results The interrater reliability of the different categories was found to have an estimate of >0.75 representing good and excellent estimates, for 19 and 16 of the 24 categories, for the two beds examined. The equivalent sound pressure levels (LAeq) for the day, evening, and night shift, as an average of the sound level meters in the patient room, were 54.12, 53.37, and 49.05 dBA. In the 24-h measurement period, talking and human generated sounds occurred for a total of 495 (39.29% of the time) and 470 min (37.30% of the time), at the two beds of interest, respectively. Conclusion A general method was described detailing two independent procedures for measuring sound pressure levels and sound sources in the ICU. In a continuous data recording over 24 h, the feasibility of the proposed general method was confirmed. Moreover, good and excellent interrater reliability was achieved in most categories, making them suitable for future studies.
Subjective and Cardiovascular Responses to an Acute Laboratory Gambling Task in Men and Women

Men have previously been overrepresented in gambling for money but in recent years there has been an increase in recognition that women who gamble are “catching up” with their male counterparts. There have been few experimental studies investigating the subjective effects of gambling, and even less have explored the gender differences. As gender differences previously have been reported in the subjective effects of several drugs of abuse such as opioids, amphetamines and alcohol, we sought to investigate if the subjective effects of gambling also differed by gender. The present article analyzes if gender modulates the subjective and physiological effects of an acute laboratory gambling task in healthy men and women. Eighty-two men and women (n = 35 men, n = 47 women) were tested with an online slot machine gambling session and self-report questionnaires of mood and blood pressure were taken before and after gambling. Both men and women showed stimulatory effects of gambling i.e., feelings of high and euphoria and but no differences were found between genders. Findings suggest that both men and women equally experience a pattern of stimulatory effects of gambling from the gambling situation. Gambling therefore seems to have the same abuse potential in both men and women. Although the gap between men and women is narrowing, immediate subjective and physiologic responses do not explain gender differences in the epidemiology of pathological gambling. The contexts and factors that foster or hinder the evolution of gambling addiction in males and females should be further explored. This conclusion is interesting in light of that men are over three times more at risk to experience gambling related problems than women and this risk may depend on other factors involved in the development of addiction.
Effects of Project-Related and Organizational-Related Factors on Five Dimensions of Project Performance: A Study Across the Construction Sectors in Malaysia

Abstract The objective of this research is to analyze the relationships of project-related and organizational-related factors with five dimensions of project performance across different sectors of the construction industry. Data collected from the project managers and directors of 360 construction firms in Malaysia were analyzed using multiple-regression technique with size of the organization as a control variable. The important finding is that the effects of project-related and organizational-related factors differ by sector type and by dimensions of project performance. The findings of this study can help project managers devise and implement appropriate strategies to support project success.
OMICs-Based Strategies to Explore Stress Tolerance Mechanisms of Saccharomyces cerevisiae for Efficient Fuel Ethanol Production

Efficient biotransformation of lignocellulosic biomass to second-generation (2G) bioethanol requires promising strains harboring built-in resistance against limitations imposed by pretreated lignocellulose-derived compounds. Ethanol fermentation and stress tolerance of yeast cells are almost simultaneously exposed to sequence variations and multiple inhibitory factors during the phases of proliferation, metabolism, and productivity. Several studies have extensively concentrated on identification or characterization of genes which confer resistance to various stresses and yeast tolerance enhancement through genetic breeding. However, the investigation of individual genes is inadequate to explain the global molecular mechanism. Herewith, “OMICs-approaches,” including genomics, transcriptomics, proteomics, and metabolomics, which are comprehensively aimed at comparative, functional profiling of the whole metabolic network, have elucidated complex cellular reactions under stressful conditions. This review briefly discusses the research progress in the field of multi-OMICs with a special focus on stress-responsive factors in frequently used S. cerevisiae. It also highlights how to promote metabolic-engineered strains for increased tolerance and higher production yield, which should be deeply exploited to achieve robustness during the lignocellulose-to-ethanol conversion process.
Prediction of Pan-Arctic Sea Ice Using Attention-Based LSTM Neural Networks

Within the rapidly changing Arctic region, accurate sea ice forecasts are of crucial importance for navigation activities, such as the planning of shipping routes. Numerical climate models have been widely used to generate Arctic sea ice forecasts at different time scales, but they are highly dependent on the initial conditions and are computationally expensive. Recently, with the increasing availability of geoscience data and the advances in deep learning algorithms, the use of artificial intelligence (AI)-based sea ice prediction methods has gained significant attention. In this study, we propose a supervised deep learning approach, namely attention-based long short-term memory networks (LSTMs), to forecast pan-Arctic sea ice at monthly time scales. Our method makes use of historical sea ice concentration (SIC) observations during 1979–2020, from passive microwave brightness temperatures. Based on the persistence of SIC anomalies, which is known as one of the dominant sources of sea ice predictability, our approach exploits the temporal relationships of sea ice conditions across different time windows of the training period. We demonstrate that the attention-based LSTM is able to learn the variations of the Arctic sea ice and can skillfully forecast pan-Arctic SIC on monthly time scale. By designing the loss function and utilizing the attention mechanism, our approach generally improves the accuracy of sea ice forecasts compared to traditional LSTM networks. Moreover, it outperforms forecasts with the climatology and persistence based empirical models, as well as two dynamical models from the Copernicus Climate Change Service (C3S) datastore. This approach shows great promise in enhancing forecasts of Arctic sea ice using AI methods.
Considering the Role of Extracellular Matrix Molecules, in Particular Reelin, in Granule Cell Dispersion Related to Temporal Lobe Epilepsy

The extracellular matrix (ECM) of the nervous system can be considered as a dynamically adaptable compartment between neuronal cells, in particular neurons and glial cells, that participates in physiological functions of the nervous system. It is mainly composed of carbohydrates and proteins that are secreted by the different kinds of cell types found in the nervous system, in particular neurons and glial cells, but also other cell types, such as pericytes of capillaries, ependymocytes and meningeal cells. ECM molecules participate in developmental processes, synaptic plasticity, neurodegeneration and regenerative processes. As an example, the ECM of the hippocampal formation is involved in degenerative and adaptive processes related to epilepsy. The role of various components of the ECM has been explored extensively. In particular, the ECM protein reelin, well known for orchestrating the formation of neuronal layer formation in the cerebral cortex, is also considered as a player involved in the occurrence of postnatal granule cell dispersion (GCD), a morphologically peculiar feature frequently observed in hippocampal tissue from epileptic patients. Possible causes and consequences of GCD have been studied in various in vivo and in vitro models. The present review discusses different interpretations of GCD and different views on the role of ECM protein reelin in the formation of this morphological peculiarity.
Maternal Fecal Microbes Contribute to Shaping the Early Life Assembly of the Intestinal Microbiota of Co-inhabiting Yak and Cattle Calves

The Qinghai-Tibetan Plateau offers one of the most extreme environments for yaks (Bos grunniens). Although the genetic adaptability of yak and rumen metagenomes is increasingly understood, the relative contribution of host genetics and maternal symbiotic microbes throughout early intestinal microbial successions in yaks remains elusive. In this study, we assessed the intestinal microbiota succession of co-inhabiting yak and cattle (Bos taurus) calves at different weeks after birth as well as the modes of transmission of maternal symbiotic microbes (i.e., rumen fluid, feces, oral cavity, and breast skin) to their calves’ intestinal microbiota colonization. We found that the fecal microbiota of yak and cattle calves after birth was dominated by members of the families Ruminococcaceae, Bacteroidaceae, and Lachnospiraceae. The Source Tracker model revealed that maternal fecal microbes played an important role (the average contribution was about 80%) in the intestinal microbial colonization of yak and cattle calves at different weeks after birth. Unlike cattle calves, there was no significant difference in the fecal microbiota composition of yak calves between 5 and 9 weeks after birth (Wilcoxon test, P > 0.05), indicating that yak may adapt to its natural extreme environment to stabilize its intestinal microbiota composition. Additionally, our results also find that the intestinal microbial composition of yak and cattle calves, with age, gradually tend to become similar, and the differences between species gradually decrease. The findings of this study are vital for developing strategies to manipulate the intestinal microbiota in grazing yaks and cattle for better growth and performance on the Qinghai-Tibetan Plateau.