Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options

Acetaminophen, also known as N-acetyl-p-aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, N-acetyl-p-benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.
Small and Large Magnetic Resonance Imaging–Visible Perivascular Spaces in the Basal Ganglia of Parkinson's Disease Patients

Although previously thought to be asymptomatic, recent studies have suggested that magnetic resonance imaging–visible perivascular spaces (PVS) in the basal ganglia (BG‐PVS) of patients with Parkinson's disease (PD) may be markers of motor disability and cognitive decline. In addition, a pathogenic and risk profile difference between small (≤3‐mm diameter) and large (>3‐mm diameter) PVS has been suggested.
PENGARUH STATUS PEKERJA DAN LINGKUNGAN KERJA TERHADAP KINERJA KARYAWAN (Studi pada Karyawan Auto 2000 Sukun Malang)

This research aims to examine s tatus of e mployment and w orking e nvironment simultaneous and partial to e mployee p erformance . The result from multiple linear regression analysis indicates that the independent variable, s tatus of e mployment and w orking e nvironment , both simultaneously and partially have positive impact and significant relationship with e mployees’ p erformance . Based on the results , it can be concluded that workers are satisfied and comfortable with status of employment and working environment provided by the company. Furthermore relationship between employees and leader are much better even though the employees are having different status of employment. The performance of permanent employees is better than the performance temporary employees so hopefully companies can increase their status of employment to increase employee performance. Keywords : Status of Workers, Work Environment, Employee Performance ABSTRAK Penelitian yang dilakukan penulis bertujuan untuk mengetahui pengaruh status pekerja dan lingkungan kerja secara bersama-sama dan parsial terhadap kinerja karyawan serta mengetahui kinerja mana yang lebih baik antara pegawai tetap dan pegawai tidak tetap. Hasil analisis regresi linier berganda dalam penelitian ini menunjukkan bahwa variabel-variabel bebas dalam penelitian yaitu status pekerja dan lingkungan kerja secara bersama-sama dan secara parsial mempunyai pengaruh positif dan hubungan yang signifikan terhadap kinerja karyawan. Hasil penelitian menunjukkan bahwa karyawan puas dan nyaman dengan status pekerjaan dan lingkungan kerja karyawan yang telah diberikan oleh perusahaan. Hubungan antar karyawan dan pimpinan membaik walaupun memiliki status pekerja yang berbeda. Kinerja karyawan tetap lebih baik daripada kinerja karyawan tidak tetap sehingga diharapkan perusahaan dapat meningkatkan status pekerja demi menaikkan kinerja karyawan. K ata K unci : S tatus P ekerja , L ingkungan K erja , K inerja K aryawan
Electric Vehicles as Grid Resources

Electric Vehicles as Grid Resources Mushfiqur R. Sarker Chair of the Supervisory Committee: Professor Miguel Ortega-Vazquez Electrical Engineering Electric vehicles (EV) are poised as environmentally-friendly alternatives to conventional combustion vehicles because of the internal battery which uses electricity for transportation. It is estimated the global EV penetration will hit upwards of 20 million on the road by 2020. Even with this technology available today, consumers’ EV adoption is hindered due to the high upfront cost, lack of adequate charging infrastructure, range anxiety, and slow charging times. On the other hand, the potential revolution of the transportation sector will bring forth economic benefits to the operations of the power system. The EV batteries allow flexibility in the amount of power and the specific time of day when they can charge and discharge. Such features enable the extraction of resources from these batteries in order to benefit the power system and EV owner’s themselves. However, the challenge remains on how to reduce the issues of EV ownership while the power system extracts services from EVs that benefit operations. The main motivation behind this dissertation is to develop frameworks that take advantage of EVs as grid resources.
Reply to “Interpretation of Longitudinal Changes of the Inner Nuclear Layer in MS”

We read with great interest the letter by Nij Bijvank et al commenting on our findings and on the work of Sotirchos et al. We agree that careful determination of reproducibility for retinal inner nuclear layer (INL) thickness measurements is crucial to understand whether the measured change exceeds the metric’s variability.We appreciate the confirmation of our findings in an independent cohort, suggesting that people with multiple sclerosis (MS) present with early retinal INL thickening, likely due to previously described cystic changes and edema, followed by later atrophy. Considering the implications of Nij Bijvank’s observation that the annualized change in INL thickness is small in MS for their cohort over a similar follow-up period, it is important to recognize differences in baseline between our cohorts that may explain the observed differences. The cohort we described, from the University of California, San Francisco EPIC cohort, was constituted by 517 patients, 466 with relapsing MS (RMS; Expanded Disability Status Scale [EDSS] score, median = 105, interquartile range [IQR] = 1; age, mean standard deviation [SD] = 44.4 10.8 years; disease duration, median = 9, IQR = 12 years) and 51 with progressive MS (EDSS, median = 4, IQR = 2.5; age, mean SD = 54.2 9.8 years; disease duration, median = 11, IQR = 19 years) at baseline. The cohort described by Nij Bijvank et al (N = 92) was older (54.5 8.9 years), with a far longer mean disease duration (21.1 6.3 years) and significantly more disability than our RMS cohort (EDSS, median = 4.0, IQR = 2.5). It is important to note that in our cohort, INL thickening is evident when inflammation is most active (age 20–30 years), and subsequently, the rate of thickening declines until atrophy supersedes the swelling (age 55 years). Thus, we believe that the analysis by Nij Bijvank et al predominantly captured a period of lower rate of change. We strongly agree with the authors that repeated measures are a good practice for reducing noise in quantifiable assessments. However, it is equally crucial to consider the practicality of repeating optical coherence tomography macular scans one hour after the initial acquisition in evaluating whether this enhancement is warranted and clinically feasible.
Thermodynamics Affecting Glacier‐Released 4‐Nonylphenol Deposition in Alaska, USA

Glaciers have recently been recognized as a secondary source of organic pollutants. As glacier melt rates increase, downstream ecosystems are at increasing risk of exposure to these pollutants. Nonylphenols (NPs) are well‐documented anthropogenic persistent pollutants whose environmental prevalence and ecotoxicity make them of immediate concern to the health of humans and wildlife populations. As glacier melt increases, transport of NPs to downstream environments will also increase. Snow, ice, meltwater, and till for five glaciers in the Chugach National Forest and Kenai Fjords National Park, Alaska, USA, were investigated for the presence of 4‐nonylphenol (4NP). Average concentrations for snow, ice, meltwater, and glacial till were 0.77 ± . 017 µg/L snow water, 0.75 ± . 006 µg/L, 0.26 ± . 053 µg/L, and 0.016 ± . 004 µg/g, respectively. All samples showed the presence of 4NP. Deposition of 4NP downstream from glaciers will depend more on the ionic strength of the water than organic carbon to drive partitioning and deposition. Laboratory studies of partition coefficients showed that ionic strength contributed 59% of the driving force behind partitioning, while organic carbon contributed 36%. Evidence was found for interaction between organic carbon and the aqueous phase. The 4NP Setschenow constants (Ks) were determined for particle types with varying percentages of organic carbon. Values of Ks increased with the percentage of organic carbon. These relationships will shape further studies of 4NP deposition into the environment downstream of glacier outflow. Environ Toxicol Chem 2022;41:1623–1636. © The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
COVID‐19 and hospice community palliative care in New Zealand: A qualitative study

Abstract Within the context of an ageing population and the added challenges posed by COVID‐19, the need to optimise palliative care management in the community – the setting where a significant proportion of people prefer to die – cannot be underestimated. To date, there has been a dearth of research exploring community palliative care delivery during the pandemic. This study aimed to explore the impact of and response to COVID‐19 for hospice community services in Aotearoa/New Zealand. Eighteen structured interviews were conducted (10 February–18 August 2021) with healthcare professionals from sixteen purposively sampled community hospices from New Zealand regions according to the number of COVID‐19‐positive patients per 100,000 inhabitants (low, medium and high) with oversampling of high prevalence areas. Two overarching themes emerged ‘challenges’ and 'adaptations’. Each theme had several subthemes related to service delivery in communication, visiting, allied health team collaboration and volunteer services. Adaptations involved adjusting official health advice to the local context, increased use of telehealth, reducing infection risk during in‐home visits through triaging of cases, division of the workforce into teams and repurposing volunteers' services. Despite these adaptations, challenges remained, including increased workload pressures for staff and an absence of the human touch for patients and families. Implications for hospice practice and recommendations for future research are discussed. Governments must acknowledge the essential contribution of hospice to the COVID‐19 pandemic and ensure that these services are incorporated into the healthcare system response.
Crop year, harvest date and clone effects on fruit characteristics, chemical composition and olive oil stability from an Empeltre clonal selection grown in Aragon

Abstract BACKGROUND In this study, the effects of crop year, harvest date and clone on the fruit characteristics and chemical composition of Empeltre olive oils were evaluated. For this purpose, the weight and oil content of fruit and the fatty acid composition, polyphenol content and oxidative stability of the olive oil was analysed throughout ripening during three successive seasons. RESULTS The weight and moisture in the fruit, as well as the fatty acids and polyphenol content in the olive oil, were mainly affected by crop year. In contrast, the stability was strongly influenced by the harvest date. Both factors had an influence on the fruit's oil content. The clone was not a substantial component in terms of variability, although the interaction with crop year was notable for some of the characteristics. The oil content increased significantly along with the harvest date and reached maximum values in the last period (44.9%). Conversely, stability and polyphenols decreased significantly (depending on the year, by 30–70%) from October to December, reaching the highest mean values between 1 October and 10 November (15.5 h; 500 mg caffeic acid kg−1). Oleic acid and monounsaturated/polyunsaturated fatty acids (MUFA/PUFA) did not show significant differences depending on the harvest date, but between years, with 2018 having the highest percentage of oleic acid (72.72%) and MUFA/PUFA (8.38). CONCLUSION Early harvesting of Empeltre olives would provide considerably more stable olive oils, regardless of the clone selected, with higher phenolic content. It would not affect the MUFA/PUFA ratio, mainly influenced by the crop year. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Efficacy and safety of azathioprine, mycophenolate mofetil, and reduced dose of rituximab in neuromyelitis optica spectrum disorder

Data regarding the efficacy and safety of currently widely available preventive therapies in neuromyelitis optica spectrum disorder (NMOSD) are needed. We compared the efficacy and safety of azathioprine (AZA), mycophenolate mofetil (MMF), and reduced dose of rituximab (RTX) in NMOSD based on a large multicenter retrospective cohort.
Longitudinal episodic memory trajectories in older adults with normal cognition

Abstract Objective To determine the longitudinal trajectories and normative standards of episodic memory in older adults. Methods Participants were drawn from the cognitively normal(CN) subgroup of the population-based HELIAD cohort, a fairly representative cohort of the older Greek population. Verbal and non-verbal memory were assessed using the Greek Verbal Learning Test and Medical College of Georgia-Complex Figure Test. Baseline and longitudinal associations of memory performance with age, sex and formal education were explored with linear regression analysis and generalized estimated equations. Results A total of 1607 predominantly female (60%) individuals (73.82 ± 5.43 years), with a mean educational attainment of 8.17(±4.86) years were CN at baseline. Baseline analysis revealed a continuum of memory decline with aging and lower educational attainment. Women performed better in composite and verbal memory measures, while men performed better in non-verbal memory tasks. A subgroup of 761 participants with available assessments after 3.07(±0.82) years remained CN at follow-up. Composite memory scores yearly diminished by an additional 0.007 of a SD for each additional year of age at baseline. Regarding verbal learning, immediate free verbal recall, delayed free verbal recall and delayed cued verbal recall, an additional yearly decrease of 0.107, 0.043, 0.036 and 0.026 words were respectively recorded at follow-up, for each additional year of age at baseline. Women underwent steeper yearly decreases of 0.227 words in delayed cued verbal recall. No significant longitudinal associations emerged for immediate non-verbal memory, delayed non-verbal memory and immediate cued verbal recall. Conclusions In the present study, aging (but not educational attainment) was consistently associated with steeper verbal memory decline. Supplemental data for this article is available online at https://doi.org/10.1080/13854046.2022. 2059011 .
The future of Parkinson's disease research: A new paradigm of human-specific investigation is necessary… and possible.

Parkinson's disease (PD) is a complex neurodegenerative condition with a multifactorial origin. To date, approaches to drug discovery for PD have resulted in symptomatic therapies for the motor manifestations and signs associated with neurodegeneration but have failed to identify preventive or curative therapies. This failure mainly originates from the persistence of major gaps in our understanding of the specific molecular basis of PD initiation and progression. New approach methodologies (NAMs) hold the potential to advance PD research while facilitating a move away from animal-based research. We report a workshop involving NAM experts in the field of PD and neurodegenerative diseases, who discussed and identified a scientific strategy for successful, human-specific PD research. We outline some of the most important human-specific NAMs, along with their main potentials and limitations, and suggest possible ways to overcome the latter. Key recommendations to advance PD research include integrating NAMs while accounting for multiple levels of complexity, from molecular to population level; learning from recent advances in Alzheimer's disease research; increasing the sharing of data; promoting innovative pilot studies on disease pathogenesis; and accessing philanthropic funding to enable studies using novel approaches. Collaborative efforts between different stakeholders including researchers, clinicians and funding agencies are urgently needed to create a scientific roadmap and support a paradigm change towards effective, human-specific research for neurodegenerative diseases without animals, as is already happening in the field of toxicology.
Vesicular Stomatitis Virus-Based Epstein-Barr Virus Vaccines Elicit Strong Protective Immune Responses

Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. ABSTRACT Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). In vitro studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. IMPORTANCE Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.
Using Personal‐Disclosure Mutual‐Sharing (PDMS) with first‐year undergraduate students transitioning to higher education

Abstract Background Using Personal‐Disclosure Mutual‐Sharing (PDMS) with students transitioning to Higher Education (HE) has yet to be researched in education. Aims In two studies, we aimed to explore the immediate effects of a Coping Oriented Personal‐Disclosure Mutual‐Sharing (COPDMS) intervention on first‐year undergraduate students’ relational and organizational identification, perceived social support availability, and self‐efficacy for learning and performance. In our second study, we also aimed to examine student‐perceptions of participating in a COPDMS intervention. Sample and Methods At the beginning of induction week in both studies, first‐year undergraduate students on the same degree programme at a HE provider in England received an education session where COPDMS was introduced. Students participated in a COPDMS session a few days later. During COPDMS sessions, students mutually‐shared and disclosed personal information and/or stories relating to transitional experiences. Results Across both studies, students’ relational identification with staff and perceived emotional, esteemed, and informational support availability from others on the degree programme significantly increased from pre‐ to post‐COPDMS phases. Findings relating to relational identification with other Year 1 students and perceived availability of tangible support were mixed. No significant changes occurred for organizational identification with the university and self‐efficacy for learning and performance. In Study 2, five higher‐order themes relating to students’ perceptions of COPDMS were found: (1) emotionality; (2) personal development; (3) storytelling; (4) enhanced group processes; and (5) task appropriateness and value. Conclusions Study findings provide evidence that COPDMS is a useful psychological intervention to deliver to students transitioning to HE. Practical considerations, limitations, and future research suggestions are provided.
Phylogenetically diverse Bradyrhizobium genospecies nodulate Bambara groundnut (Vigna subterranea L. Verdc) and soybean (Glycine max L. Merril) in the northern savanna zones of Ghana

Abstract A total of 102 bacterial strains isolated from nodules of three Bambara groundnut and one soybean cultivars grown in nineteen soil samples collected from northern Ghana were characterized using multilocus gene sequence analysis. Based on a concatenated sequence analysis (glnII-rpoB-recA-gyrB-atpD-dnaK), 54 representative strains were distributed in 12 distinct lineages, many of which were placed mainly in the Bradyrhizobium japonicum and Bradyrhizobium elkanii supergroups. Twenty-four of the 54 representative strains belonged to seven putative novel species, while 30 were conspecific with four recognized Bradyrhizobium species. The nodA phylogeny placed all the representative strains in the cosmopolitan nodA clade III. The strains were further separated in seven nodA subclusters with reference strains mainly of African origin. The nifH phylogeny was somewhat congruent with the nodA phylogeny, but both symbiotic genes were mostly incongruent with the core housekeeping gene phylogeny indicating that the strains acquired their symbiotic genes horizontally from distantly related Bradyrhizobium species. Using redundancy analysis, the distribution of genospecies was found to be influenced by the edaphic factors of the respective sampling sites. In general, these results mainly underscore the high genetic diversity of Bambara groundnut-nodulating bradyrhizobia in Ghanaian soils and suggest a possible vast resource of adapted inoculant strains.