Miracle-dz/UniFAR-FTUs huggingface dataset:
An explainable multi-parameter optimization approach for de novo drug design against proteins from central nervous system

Motivation: Aim of a successful drug design and development is to produce a drug which can inhibit the target protein and has a balanced physicochemical and toxicity profile. Traditionally, this is a multi-step process where different parameters such as activity, physicochemical and pharmacokinetic properties are optimized sequentially, which often leads to high attrition rate during later stages of drug design and development. Results: We have developed a deep learning-based de novo drug design method which can design novel small molecules by optimizing target-specificity as well as multiple parameters (including late stage parameters) in a single step. The model predictions were explained in two ways to remediate the black box nature of deep learning models: (1) the contribution of each parameter during multi-parameter optimization was computed using an adaptation of the SHAP algorithm and (2) an explainable predictive model was used to identify functional groups responsible for the property being optimized. The proposed method was validated against the human 5-hydroxy tryptamine receptor 1B (5-HT1B), a protein from the central nervous system (CNS). Various physicochemical properties specific to CNS drugs were considered along with the target specificity and blood-brain barrier (BBB), which acts as an additional challenge for CNS drug delivery. The contribution of each parameter towards molecule design was identified. The optimized generative model was able to design similar and better inhibitors compared to known inhibitors of 5-HT1B. In addition, the functional groups of the generated small molecules that guide the BBB permeability predictive model were identified through feature attribution techniques.
The COVID-19 Pandemic: Exploring Its Future through Rhizomatic Thinking

Abstract Rhizomatic thinking is used to complement mechanistic models or systems thinking in understanding the COVID-19 pandemic. Virus mutations, vaccination rates, human mobility, and variable immune responses are leading to the emergence of complex spatial and temporal patterns of spread. Contributory factors include changing human mobilities, and urban-to-rural migrations. Worsening inequalities in wealth, power, and access to healthcare are social consequences. They have non-hierarchical and circular interconnections, at all levels. These form unbroken and continuous webs that deterritorialize and reterritorialize. The rhizomatic paradigm leads to whole-system models, synergetics, and planetary epidemiology. Its application in epidemiology is novel.
Effect of Process Control Agents on Fe-15at.%Nb powder during Mechanical Alloying

06, 2021; Accepted: December 07, 2021 In this paper, Fe-15at. %Nb alloys were produced from high purity Fe (min. 99.8%) and Nb (min. 99.8%) powders via a mechanical alloying process. The effects of different Process Control Agents (i.e., methanol, hexane, and stearic acid) were investigated with powder morphologies, particle size distribution, and phase formation, and were sampled after up to 80 milling hours at 350 rpm. The powder morphologies and particle sizes were evaluated using scanning electron microscopy and laser diffraction analysis, respectively, and phases were identified via X-ray powder diffractometry. The results demonstrate for all conditions that, in the early stages, there was significant particle agglomeration due to the ductile-ductile feature of Fe and Nb powders, and latter an amorphization trend up to 80 milling hours. Methanol was the most efficient Process Control Agent in terms of avoiding cold welding, reducing of agglomeration, particle size distribution,
Analysis on Factors Impacting Matching between Learning and Application of Higher Vocational School Graduates

The quantitative research method are adopted to analyze the situation of the matching between learning and ap plication of higher vocational school graduates,and the results are that the mismatching degree is higher;the impact of in ternship experience and subject and specialty on the matching between learning and application of graduates is outstand ing;the matching of learning and application,the region and personal characteristics have appreciable impact on the in come of graduates.
The Impact of Short-Term Outdoor Air Pollution on Clinical Status and Prognosis of Hospitalized Patients with Coronary Artery Disease Treated with Percutaneous Coronary Intervention

Background: The aim of this study was to determine the influence of acute exposure to air pollutants on patients’ profile, short- and mid-term outcomes of hospitalized patients with coronary artery disease (CAD) treated with coronary angioplasty. Methods: Out of 19,582 patients of the TERCET Registry, 7521 patients living in the Upper Silesia and Zaglebie Metropolis were included. The study population was divided into two groups according to the diagnosis of chronic (CCS) or acute coronary syndromes (ACS). Data on 24-h average concentrations of particulate matter with aerodynamic diameter <10 μm (PM10), sulfur dioxide (SO2), nitrogen monoxide (NO), nitrogen dioxide (NO2), and ozone (O3) were obtained from eight environmental monitoring stations. Results: No significant association between pollutants’ concentration with baseline characteristic and in-hospital outcomes was observed. In the ACS group at 30 days, exceeding the 3rd quartile of PM10 was associated with almost 2-fold increased risk of adverse events and more than 3-fold increased risk of death. Exceeding the 3rd quartile of SO2 was connected with more than 8-fold increased risk of death at 30 days. In the CCS group, exceeding the 3rd quartile of SO2 was linked to almost 2,5-fold increased risk of 12-month death. Conclusions: The acute increase in air pollutants’ concentrations affect short- and mid-term prognosis in patients with CAD.
Enhancing the In Vitro Biological Activity of Degraded Silk Sericin and Its Analog Metabolites

Two sericins of high and low molecular weight (HS and LS) were prepared from commercial silkworm cocoon silk with a boiling water and Ca(OH)2 solution with ultrasonic treatments, respectively. This study first investigated the release concentration of the two abovementioned sericins in simulated saliva, gastric juice, and intestinal juice (pH 6.8, 2.0, and 7.4, respectively) within 10 h. The results showed that the order of sericin release rate and its amount in the simulated environment was gastric juice > saliva > intestinal juice. Second, the molecular weights of both sericin metabolites formed by in vitro enzymatic degradation were lower than 15 kDa. The α-glucosidase inhibitory activities of both sericins and their analog metabolites were positively correlated with their concentrations. The IC50 values of the HS- and LS-derived metabolites were 1.02 ± 0.12 mg/mL and 0.91 ± 0.15 mg/mL, respectively, which were five to seven times lower than those of both original sericins. The total antioxidant capacities and hydroxyl radical scavenging capacities of both metabolites were enhanced by one- to three-fold compared with HS and LS. These results indicate that both sericins, regardless of molecular size, have significantly enhanced antioxidant, superoxide free radical scavenging, and glycosidase inhibitory activities after simulated metabolism, and that LS is better than HS regardless of simulated digestion. These results confirm that sericin is important in the sustainable development and utilization of silk resources, especially the reduction in environmental pollution, and provides new ideas for the development of adjuvant treatments for diabetes and the development of foods with anti-hyperglycemic functions.
Empirical Analysis of the Global Supply and Demand of Entrepreneurial Finance: A Random Utility Theory Perspective

Considering the globalized nature of international financial markets and the important role of innovative entrepreneurial endeavors for employment and economic development, this paper analyzes the global supply and demand of entrepreneurial finance, in the form of individuals’ savings and borrowings for entrepreneurial ventures in the global economy. To this end, a theoretical treatment of the potential global entrepreneurial finance market (GEFM) dynamics, in response to governments and private sector financial transfers, is first provided. This is followed by the econometric modeling of such dynamics based on intertemporal random utility maximization, using pooled data from the 2014 and 2017 global financial inclusion surveys. The findings reveal, contrary to theoretical predictions, that private sector financial injections (i.e., electronic wage payments), exert an adverse effect on the GEFM; meanwhile, in accordance with theoretical predictions, public sector financial injections (i.e., electronic welfare payments), do positively influence the growth of the GEFM. In addition, compared to their male counterparts, females are found to be 7% more likely to own a formal account, and are 23.4% more likely to save for farming or business entrepreneurship, while also being 18.8% more likely to borrow for entrepreneurial ventures, therefore suggesting a relatively greater growth potential from female entrepreneurship in the global economy.
Teaching the Central Dogma through an Inquiry-Based Project Using GFP

Abstract The Central Dogma is a crucial concept needed to understand biotechnology and molecular biology. High school students often struggle with a meaningful understanding of this abstract concept. This paper presents an inquiry-based approach to increase critical thinking and understanding of the Central Dogma. Commonly used in high school classrooms is Bio-Rad pGLO plasmid containing green fluorescent protein (GFP), because of its accessibility and the fluorescence it emits when exposed to ultraviolet light. We use the expression of GFP in a high school hands-on class project so that students can visualize and understand the abstract concepts of the Central Dogma. Students will also explore protein structure and its importance for a functional protein. During the entire project, students will be guided by the instructor to build hypotheses and design experiments to test those hypotheses, exercising the scientific method.
An Appraisal of the Knowledge, Attitude and Practices of Abattoir Workers and Butchers on Bovine Tuberculosis in Kaduna Central Abattoir, Kaduna State, Nigeria

Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a chronic infectious and contagious zoonotic disease of domestic animals, wild animals and humans. This research involved abattoir workers who are personnel involved in the management of animals before and during the slaughtering process. Three hundred pretested, well-structured and closed-ended questionnaires were self-administered to abattoir workers made up of 13 Veterinarians, 8 Animal Scientists, 37 Para-veterinarians, 197 butchers and 45 unskilled labourers to determine the level of their knowledge, attitude and practices on tuberculosis. The study revealed that the abattoir workers in this study had low knowledge of bTB 32(10.6%). Their knowledge on the transmission pathways, prevention, control measures against bTB and its zoonotic importance were also sought. Detection of tubercle lesions of bTB in slaughtered cattle makes their potential source of infection to human and pose a public health risk. There is the need for enhanced public education and awareness campaigns among meat handlers and abattoir workers especially on the mode of transmission, aetiology and public health importance of bTB in Kaduna State
Bacteremia in patients with liver cirrhosis in the era of increasing antimicrobial resistance: single-center epidemiology.

INTRODUCTION Liver cirrhosis is commonly associated with bacterial infections, which contribute to unfavorable outcome. This study aimed to investigate the epidemiology of bacteremia and patterns of antibiotic resistance in patients with cirrhosis, factors associated with multidrug-resistant infection, and predictors of mortality. METHODOLOGY This retrospective single-center study included patients with cirrhosis treated between January 2016 and December 2018. Data were collected from the patients' medical records. The severity of liver disease was determined using the Child-Pugh, Model for End-Stage Liver Disease-Na, Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure, and Chronic Liver Failure-Consortium Acute Decompensation scores. RESULTS A total of 85 patients with cirrhosis and bacteremia were included (male: 82.4%, mean age 60.3 ± 9.4 years). The etiology of cirrhosis was mainly alcoholism (87.1%). After 30 days, lethal outcome occurred in 44.7% of the patients. The most commonly isolated pathogens were Enterococcus spp. (31.8%), methicillin-sensitive Staphylococcus aureus (15.3%), and Escherichia coli (14.1%), while 37.3% of all isolated microorganisms were multi-drug resistant. Multi-drug resistant infection [odds ratio (OR): 6.198, 95% confidence interval (CI): 2.326-17.540, p = 0.006] and neutrophil-to-lymphocyte ratio (OR = 1.181, 95% CI = 1.043-1.337, p = 0.009) are independent predictors of mortality. The aforementioned scores, which represent the extent of hepatic insufficiency, are significantly higher in patients with multi-drug resistant isolates, while multi-drug resistant bacteremia was more common in patients with more advanced liver disease. CONCLUSIONS Multi-drug resistant bacteremia is more common in patients in whom liver disease is more severe and is a major independent predictor of mortality.
Understanding and Exploiting the Full Potential of SSD Address Remapping

Duplicate writes are prevalent in storage systems, originating from data duplication, journaling, and data relocations, etc. As flash-based solid state drives (SSDs) have been widely deployed, duplicate writes can significantly degrade their performance and lifetime. Prior studies have proposed innovative approaches that exploit the address remapping utility inside an SSD to eliminate duplicate writes. However, remap operations modify the logical-to-physical (L2P) address mapping table while the physical-to-logical (P2L) mappings persisted on flash memory remain unchanged. Such inconsistency between L2P and P2L mappings may cause data corruption and has long been a major obstacle to utilize SSD address remapping. In this article, we propose a novel SSD design, called Remap-SSD-LH, that realizes the full potential of SSD address remapping. It provides a remap primitive, which allows the host software and SSD firmware to perform logical writes of duplicate data at almost zero cost. To ensure mapping consistency as well as fast mapping lookups, Remap-SSD-LH employs a local log scheme based on hybrid storage. A local log is maintained for each flash garbage collection unit to record relevant P2L mapping changes induced by remap operations. The logs are stored in small nonvolatile RAM (NVRAM), e.g., capacitor-protected DRAM, and can be destaged to flash memory if NVRAM is full. We verify Remap-SSD-LH on a software SSD emulator with three case studies: 1) intra-SSD deduplication; 2) SQLite journaling; and 3) F2FS cleaning. The experimental results show that Remap-SSD-LH can maximally and efficiently exploit address remapping to improve SSD performance and lifetime.
Targeting Sensory and Motor Integration for Recovery of Movement After CNS Injury

The central nervous system (CNS) integrates sensory and motor information to acquire skilled movements, known as sensory-motor integration (SMI). The reciprocal interaction of the sensory and motor systems is a prerequisite for learning and performing skilled movement. Injury to various nodes of the sensorimotor network causes impairment in movement execution and learning. Stimulation methods have been developed to directly recruit the sensorimotor system and modulate neural networks to restore movement after CNS injury. Part 1 reviews the main processes and anatomical interactions responsible for SMI in health. Part 2 details the effects of injury on sites critical for SMI, including the spinal cord, cerebellum, and cerebral cortex. Finally, Part 3 reviews the application of activity-dependent plasticity in ways that specifically target integration of sensory and motor systems. Understanding of each of these components is needed to advance strategies targeting SMI to improve rehabilitation in humans after injury.
Lessons Learned: The Multifaceted Field of (Digital) Neighborhood Development

In a cross-national project, 14 neighborhoods from Germany, Austria and Switzerland were accompanied on their way to digitally supported neighborhood work. This paper discusses general requirements, choosing a suitable digital tool, the implementation process as well as the challenges faced by the various stakeholders. The following factors have been found to play a major role in sustainable neighborhood work: good fit with overall development strategy, interplay between online neighborhood work and physical interactions, strong existing neighborhood management structures, strategic planning of digitalization activities, start-up funding for innovation activities, and above all, the presence of a committed person or team as well as interesting content to attract users. Depending on the neighborhood, self-managed and individualistic solutions are preferred to generic and/or commercial solutions. There is no ‘fit-for-all’ path to sustainable digitally supported neighborhoods.
ETF Ownership and Corporate Cash Holdings

Do exchange ‐ traded funds (ETFs) influence corporate cash holding decisions? Consistent with reduced managerial learning from the stock market and increased uncertainty due to higher ETF ownership, we show that firms included in ETF baskets have higher cash holdings as a precautionary response. We address endogeneity concerns through different natural experiments, namely, the reconstitution of the Russell 1000/2000 index and BlackRock's acquisition of iShares. We identify changes in revenue, external financing, share repurchases and net working capital as potential channels through which cash holdings increase due to higher ETF ownership, with cash holdings increases having a positive impact on firm value
Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Progress, Challenges, and Prospects

Non-small cell lung cancer is one of the most common types of malignances worldwide and the main cause of cancer-related deaths. Current treatment for NSCLC is based on surgical resection, chemotherapy, radiotherapy, and targeted therapy, with poor therapeutic effectiveness. In recent years, immune checkpoint inhibitors have applied in NSCLC treatment. A large number of experimental studies have shown that immune checkpoint inhibitors are safer and more effective than traditional therapeutic modalities and have allowed for the development of better guidance in the clinical treatment of advanced NSCLC patients. In this review, we describe clinical trials using ICI immunotherapies for NSCLC treatment, the available data on clinical efficacy, and the emerging evidence regarding biomarkers.
Spurious Late Historical‐Era Warming in CESM2 Driven by Prescribed Biomass Burning Emissions

19 A spurious increase in the interannual variability of prescribed biomass burning (BB) 20 emissions in the CMIP6 forcing database during the satellite era of wildfire monitoring (199721 2014) is found to lead to warming in the northern hemisphere extratropics in simulations with the 22 Community Earth System Model version 2 (CESM2). Using targeted sensitivity experiments 23 with the CESM2 in which prescribed BB emissions are homogenized and variability is removed, 24 we show that the warming is specifically attributable to BB variability from 40oN-70oN and 25 arises from a net thinning of the cloud field and an associated increase in absorbed solar 26 radiation. Our results also demonstrate the potential pitfalls of introducing discontinuities in 27 climate forcing datasets when trying to incorporate novel observations. 28 Plain Language Summary 29 A discontinuity in the variability of prescribed biomass burning emissions between the 30 satellite era of wildfire monitoring (1997-2014) and both the preceding historical and future time 31 periods is found to drive spurious warming in the Community Earth System Model version 2. 32 The warming arises from a net thinning of the cloud field and an associated increase in absorbed 33 solar radiation during periods of high variability in emissions. Evidence suggestive of similar 34 effects in other climate models is also presented. The results highlight the challenges in 35 evaluating models with observations, even in the modern satellite era. 36
Duration of postoperative analgesia with Nalbuphine vs Butorphanol as an adjunct to spinal anesthesia for lower limb orthopedic surgeries: A randomized double-blind active control trial

Background and Aims: Nalbuphine as well as butorphanol as adjuvant to intrathecal bupivacaine have been studied in comparison to bupivacaine alone. Both are kappa receptor agonist and have never been compared for its efficacy in terms of postoperative analgesia. The aim of this study was to evaluate duration of postoperative analgesia as well as intraoperative block characteristics using intrathecal nalbuphine hydrochloride (800 μg) or butorphanol (25 μg) as adjuvant to hyperbaric bupivacaine (12.5 mg) in lower limb fracture femur surgeries as compared to active control, that is, saline and bupivacaine. Material and Methods: This prospective, randomized, double-blind, active control study was conducted on 90 adult patients of either sex belonging to ASA grade I/II, aged 18–70 years, being operated for fracture femur surgeries in tertiary care hospital of North India. Patients were randomly divided into 3 groups (n = 30) Group A: received 0.5% hyperbaric bupivacaine 12.5 mg with 800 μg nalbuphine. Group B: Received 0.5% hyperbaric bupivacaine 12.5 mg with 25 μg butorphanol. Group C: Received 0.5% hyperbaric bupivacaine 12.5 mg with normal saline. Total volume injected was 3.0 ml. Duration of analgesia, mean VAS scores, requirement of rescue analgesia in 24 h along with intraoperative sensory or motor characteristics of block and hemodynamic parameters were studied. Statistical analysis was done using ANOVA with post-hoc Tukey test, Student's t-test and Chi-Square test. Results: Demographic profile was comparable among all the three groups. Mean duration of postoperative analgesia was 348.33 ± 66.96, 156.17 ± 43.9 and 110.36 ± 29.18 min in group A, B, and C, respectively (P = 0.006). Total doses of rescue analgesia were least in group A (32), followed by group B (42) and group C (64), respectively (P = 0.001). Group A had significantly earlier onset of sensory action (P = 0.03) as compared to group B and C. There was significant difference in sensory (P = 0.08) and motor duration (P = 0.04) among all the three groups. However, onset of motor block, haemodynamic profile and side effects were comparable among groups A, B, and C (P > 0.05). Conclusion: Addition of 800 μg nalbuphine and 25 μg butorphanol as adjuvant to intrathecal bupivacaine has better outcome as compared to active placebo group. But intrathecal nalbuphine was more effective compared to intrathecal butorphanol in terms of prolonging postoperative analgesia, reducing rescue analgesic doses and onset of sensory block. However, hemodynamic profile and side effects were comparable among all groups.