Miracle-dz/UniFAR-FTUs huggingface dataset:
Enzymes in the time of COVID‐19: An overview about the effects in the human body, enzyme market, and perspectives for new drugs

The rising pandemic caused by a coronavirus, resulted in a scientific quest to discover some effective treatments against its etiologic agent, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). This research represented a significant scientific landmark and resulted in many medical advances. However, efforts to understand the viral mechanism of action and how the human body machinery is subverted during the infection are still ongoing. Herein, we contributed to this field with this compilation of the roles of both viral and human enzymes in the context of SARS‐CoV‐2 infection. In this sense, this overview reports that proteases are vital for the infection to take place: from SARS‐CoV‐2 perspective, the main protease (Mpro) and papain‐like protease (PLpro) are highlighted; from the human body, angiotensin‐converting enzyme‐2, transmembrane serine protease‐2, and cathepsins (CatB/L) are pointed out. In addition, the influence of the virus on other enzymes is reported as the JAK/STAT pathway and the levels of lipase, enzymes from the cholesterol metabolism pathway, amylase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and glyceraldehyde 3‐phosphate dehydrogenase are also be disturbed in SARS‐CoV‐2 infection. Finally, this paper discusses the importance of detailed enzymatic studies for future treatments against SARS‐CoV‐2, and how some issues related to the syndrome treatment can create opportunities in the biotechnological market of enzymes and the development of new drugs.
Aberrant expansion of spontaneous splenic germinal centers induced by hallmark genetic lesions of aggressive lymphoma.

Unique molecular vulnerabilities have been identified in the aggressive MCD/C5 genetic subclass of diffuse large B cell lymphoma (DLBCL). However, the pre-malignant cell-of-origin exhibiting MCD-like dependencies remains elusive. In this study, we examined animals carrying up to four hallmark genetic lesions found in MCD consisting of gain-of-function mutations in Myd88 and Cd79b, loss of Prdm1 and overexpression of BCL2. We discovered that expression of combinations of these alleles in vivopromoted a cell-intrinsic accumulation of B cells in spontaneous splenic germinal centers (GCs). Like MCD, these pre-malignant B cells were enriched for B-cell receptors (BCRs) with evidence of self-reactivity, showed a de novo dependence on Tlr9 and were more sensitive to inhibition of BTK. Mutant spontaneous splenic GC B cells (GCB) showed increased proliferation and IRF4 expression. Mice carrying all four genetic lesions showed a greater than 50-fold expansion of spontaneous splenic GCs exhibiting aberrant histologic features with a dark zone immunophenotype and went on to develop DLBCL in the spleen with age. Thus, by combining multiple hallmark genetic alterations associated with MCD, our study identifies aberrant spontaneous splenic GCB as a likely cell-of-origin for this aggressive genetic subtype of lymphoma.
TGF‐β1 peptide‐based inhibitor P144 ameliorates renal fibrosis after ischemia–reperfusion injury by modulating alternatively activated macrophages

Ischemia–reperfusion injury (IRI) is a major cause of chronic renal fibrosis. Currently, numerous therapies have shown a minimal effect on the blockade of fibrosis progression. Here, the therapeutic potential of peptide‐based TGF‐β1 inhibitor P144 in IRI‐induced renal fibrosis and the underlying mechanism were analyzed.
Reliability assessment of the South African wind load design formulation

CITATION: Botha, J., Retief, J. V. & Viljoen, C. 2018. Reliability assessment of the South African wind load design formulation. Journal of the South African Institution of Civil Engineering, 60(3):30-40, doi:10.17159/2309-8775/2018/v60n3a3.
Barriers and strategies needed to improve maternal health services among pregnant adolescents in Uganda: a qualitative study

ABSTRACT Background In Uganda, the uptake of maternal health services is very low, with only 41.1% of pregnant adolescent girls attending the eight antenatal visits that are recommended by the World Health Organisation. Uptake of maternal health services is essential in reducing the current level of adolescent pregnancies as well as its adverse effects on adolescent mothers and their babies, such as preterm deliveries, prolonged labour, death during pregnancy, and childbirth. No previous study has described pregnant adolescents’ experiences with maternal health services in Uganda. Objective This study aimed to describe the barriers and strategies needed to improve maternal health services among pregnant adolescents in Uganda. Methods Data were collected in the Naguru Teenage Information and Health Centre in Uganda through individual interviews involving 31 pregnant adolescents. The transcribed interviews were inductively analysed through content analysis. Results The pregnant adolescents described difficulty in reaching, as well as lack of financial support to visit, the Naguru Teenage Information and Health Centre, which is a clinic providing youth friendly services. Feelings of being discriminated against and disrespected by health workers, and lack of privacy when receiving health services was major barriers that hindered their access to maternal health services. Pregnant adolescents’ access to these services can be enhanced by improving health workers’ working conditions, accelerating community and health worker awareness on ways to mitigate these barriers, and developing policies that encourage men’s involvement in maternal health services. Conclusion Adolescents in Uganda face considerable barriers to accessing improved and quality maternal health services. To mitigate these barriers, according to the adolescents, considerable efforts are required to tackle health workers’ working conditions and sensitise the community on the importance of, as well as securing the availability of, maternal health services for pregnant adolescents. Future research should focus on pregnant adolescents who receive family support.
Combat exposure and behavioral health in U.S. Army Special Forces

Although combat has been found to be associated with adverse health outcomes, little is known about the impact of specific combat exposures, particularly among specialized personnel. This study examined the association of different types of combat exposures with behavioral health outcomes, and whether these associations differed by Army occupational specialization: General Purpose Forces infantrymen (n = 5,361), Ranger Qualified infantrymen (n = 308), and Special Forces personnel (n = 593). Multivariable regression models estimated the association of combat severity, type of combat event (fighting, killing, threat to oneself, death/injury of others), and type of killing with mental health disorders, trouble sleeping, and problem drinking. Combat severity, each type of combat event, and killing noncombatants were associated with adverse health outcomes after adjusting for covariates and other combat exposures. Except for trouble sleeping, these associations did not differ by occupational specialization, though the prevalence and odds of outcomes were generally lower for Special Forces personnel.
Guselkumab shows high efficacy and maintenance in the improvement of response until week 48, a real‐life study

Guselkumab is an IL‐23 inhibitor that has been demonstrated to be effective and safe for the treatment of moderate‐to‐severe plaque psoriasis in clinical trials. The data pool relating to the use of guselkumab in a real‐life setting is still lacking. To evaluate the efficacy and safety of guselkumab in a real‐life setting, focusing on predictors of early clinical response, a single‐center prospective study was conducted enrolling patients with moderate‐to‐severe psoriasis. The clinical data relating to the efficacy and safety of the drug were acquired at initiation of treatment and at all subsequent clinical follow‐ups: the primary endpoint was PASI90 and PASI100 response at week 12, 24, and 48. Out of the total cohort of 74 patients, 62 (83.8) reached a 48‐week follow‐up 64 (87.8%) reached a 24‐week follow‐up, while 72 (97.3%) a 12‐week follow‐up. Treatment with guselkumab reduced the mean PASI from the initial 11 ± 6.3 to 2.5 ± 3.1 at 12 weeks, to 1.2 ± 1.8 at 24 weeks, and to 0.8 ± 1.6 at 48 weeks. At week 12, a PASI 90 and PASI 100 response was achieved by 44.4% and 23.6% of patients, respectively. After 24 weeks, 63% of patients reported a PASI 90 while 46.1% achieved PASI 100. Previous treatment with one or more other biologics did not impact significantly on the achievement of the PASI 90 and 100 at any endpoints analyzed. We reported no difference between bio‐naïve and non‐naïve patients in the response to guselkumab, high safety, and efficacy was showed in both populations.
Little Utility of Fungal Blood Cultures in Surgical and Burn Intensive Care Units

This study demonstrates that regular aerobic and anaerobic blood culture sets are sufficient in detecting the most common causes of fungemia, and thus, sending fungal blood cultures for patients in surgical and burn intensive care units is not a good use of resources. ABSTRACT Critically ill patients are at risk for fungal infections, but there is a paucity of data regarding the clinical utility of dedicated fungal blood cultures to detect such infections. A retrospective review was conducted of patients admitted to the surgical and burn intensive care units at Parkland Memorial Hospital between 1 January 2013 and 31 December 2017 for whom blood cultures (aerobic, anaerobic, and/or fungal cultures) were sent. A total of 1,094 aerobic and anaerobic blood culture sets and 523 fungal blood cultures were sent. Of the aerobic and anaerobic culture sets, 42/1,094 (3.8%) were positive for fungal growth. All fungal species cultured were Candida. Of the fungal blood cultures, 4/523 (0.76%) were positive for growth. Fungal species isolated included Candida albicans, Aspergillus fumigatus, and Histoplasma capsulatum. All 4 patients with positive fungal blood cultures were on empirical antifungal therapy prior to results, and the antifungal regimen was changed for 1 patient based on culture data. The average duration to final fungal culture result was 46 days, while the time to preliminary results varied dramatically. Two of the four patients died prior to fungal culture results, thereby rendering the culture data inconsequential in patient care decisions. This study demonstrates that regular aerobic and anaerobic blood cultures sets are sufficient in detecting the most common causes of fungemia and that results from fungal cultures rarely impact treatment management decisions in patients in surgical and burn intensive care units. There is little clinical utility to routine fungal cultures in this patient population. IMPORTANCE This study demonstrates that regular aerobic and anaerobic blood culture sets are sufficient in detecting the most common causes of fungemia, and thus, sending fungal blood cultures for patients in surgical and burn intensive care units is not a good use of resources.
Ambulatory outpatient venous surgery service: An examination of patient satisfaction and experiences

Background This study aimed to ascertain patients’ experience of the out-patient venous service being provided,; identify the level of patient satisfaction with the service and identify areas for further improvement and development. Method A prospective descriptive quantitative study. A questionnaire was distributed to all patients who used the service between June 2017 and March 2018. A total of 195 questionnaires was distributed with 162 valid questionnaires returned; response rate of 83%. Results This study found high satisfaction levels with endovenous ablation procedures, with concomitant phlebectomy, in the ambulatory outpatient setting and patient experiences of the service are overwhelmingly positive. Conclusion Study findings support the management of ambulatory outpatient varicose vein endovenous ablation procedures as a feasible alternative to day surgery theatre settings and is the blueprint for future management of varicose vein surgery in Ireland.
Relationships between Prediction Accuracy, Metacognitive Reflection, and Performance in Introductory Genetics Students

Cognitive scientists have previously shown that students’ perceptions of their learning and performance on assessments often do not match reality. This process of self-assessing performance is a component of metacognition, which also includes the practice of thinking about one’s knowledge and identifying and implementing strategies to improve understanding. We used a mixed-methods approach to investigate the relationship between students’ perceptions of their performance through grade predictions, their metacognitive reflections after receiving their grades, and their actual performance during a semester-long introductory genetics course. We found that, as a group, students do not display better predictive accuracy nor more metacognitive reflections over the semester. However, those who shift from overpredicting to matching or underpredicting also show improved performance. Higher performers are overall more likely to answer reflection questions than lower-performing peers. Although high-performing students are usually more metacognitive in their reflections, an increase in a student’s frequency of metacognitive responses over time does not necessarily predict a grade increase. We illustrate several example trends in student reflections and suggest possible next steps for helping students implement better metacognitive regulation.
Respiratory complex I with charge symmetry in the membrane arm pumps protons

Significance Respiratory complex I is a central enzyme of cellular energy metabolism coupling quinone reduction with proton translocation. Its mechanism, especially concerning proton translocation, remains enigmatic. Three homologous subunits that contain a conserved pattern of charged and polar amino acid residues catalyze proton translocation. Strikingly, the central subunit NuoM contains a conserved glutamate residue at a position where conserved lysine residues are found in the other two subunits, resulting in a charge asymmetry discussed to be essential for proton translocation. We found that the respective glutamate to lysine mutation in Escherichia coli complex I lowers the amount of protons translocated per electron transferred by one-quarter. These data clarify the discussion about possible mechanisms of proton translocation by complex I.
Brain Cell Senescence: A New Therapeutic Target for the Acute Treatment of Ischemic Stroke.

Aging is a major risk factor for cerebral infarction. Since cellular senescence is intrinsic to aging, we postulated that stroke-induced cellular senescence might contribute to neural dysfunction. Adult male Wistar rats underwent 60-minute middle cerebral artery occlusion and were grouped according to 3 reperfusion times: 24 hours, 3, and 7 days. The major biomarkers of senescence: 1) accumulation of the lysosomal pigment, lipofuscin; 2) expression of the cell cycle arrest markers p21, p53, and p16INK4a; and 3) expression of the senescence-associated secretory phenotype cytokines interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were investigated in brain samples. Lipofuscin accumulation was scarce at the initial stage of brain damage (24 hours), but progressively increased until it reached massive distribution at 7 days post-ischemia. Lipofuscin granules (aggresomes) were mainly confined to the infarcted areas, that is parietal cortex and adjacent caudate-putamen, which were equally affected. The expression of p21, p53, and p16INK4a, and that of IL-6, TNF-α, and IL-1β, was significantly higher in the ischemic hemisphere than in the non-ischemic hemisphere. These data indicate that brain cell senescence develops during acute ischemic infarction and suggest that the acute treatment of ischemic stroke might be enhanced using senolytic drugs.
The influence of thin as compared to thick peri‐implant soft tissues on aesthetic outcomes: A systematic review and meta‐analysis

Abstract Objectives In systematically healthy patients with an implant‐supported fixed restoration (P), what is the influence of thin (E) as compared to thick (C) peri‐implant soft tissues on aesthetic outcomes (O)? Methods Following an a priori protocol, a literature search of six databases was conducted up to August 2020 to identify prospective/retrospective clinical studies on healthy patients with an implant‐supported fixed reconstruction. Measurement of the buccal soft tissue thickness and an aesthetic outcome was a prerequisite, and sites presenting with a buccal soft tissue thickness of <2 mm or shimmering of a periodontal probe were categorized as a thin phenotype. After study selection, data extraction, and risk of bias assessment, random‐effects meta‐analysis of Mean Differences (MD) or Odds Ratios (OR) with their corresponding 95% Confidence Intervals (CI) were conducted, followed by sensitivity analyses and assessment of the quality of evidence. Results Thirty‐four unique studies reporting on 1508 patients with 1606 sites were included (9 randomized controlled trials, one controlled trial, 10 prospective cohort studies, 8 cross‐sectional studies, and 6 retrospective cohort studies). The mean difference of the pink aesthetic score (PES) after the follow‐up was not significantly different between thin (<2.0 mm) or thick soft tissues (≥2.0 mm) or phenotypes (12 studies; MD = 0.15; [95% CI = −0.24, 0.53]; p = .46). PES changes during the follow‐up, however, were significantly in favour of thick soft tissues (≥2.0 mm) or phenotypes (p = .05). An increased mean mucosal thickness was associated with an increased papilla index (5 studies; MD = 0.5; [95% CI = 0.1, 0.3]; p = .002) and an increase in papilla presence (5 studies; OR = 1.6; [95% CI = 1.0, 2.3]; p = .03). Thin soft tissues were associated with more recession, −0.62 mm (4 studies; [95% CI = −1.06, −0.18]; p = .006). Patient‐reported outcome measures (patient satisfaction) were in favour of thick soft tissues −2.33 (6 studies; [95% CI = −4.70, 0.04]; p = .05). However, the quality of evidence was very low in all instances due to the inclusion of non‐randomized studies, high risk of bias and residual confounding. Conclusion Within the limitations of the present study (weak study designs and various soft tissue measurements or time‐points), it can be concluded that increased soft tissue thickness at implant sites was associated with more favourable aesthetic outcomes.
Longitudinal Education and Career Outcomes of a Cancer Research Training Program for Underrepresented Students: The Meharry-Vanderbilt-Tennessee State University Cancer Partnership

This study examined longitudinal education and career outcomes of the Meharry-Vanderbilt-Tennessee State University Cancer Partnership, the longest-running National Cancer Institute (NCI) Comprehensive Partnerships in Advancing Cancer Health Equity (CPACHE) program site in the United States. Degree completion rates were calculated and progression along the entire postsecondary “pipeline” was quantified for 204 participants recruited between 2011 and 2020. For participants who had entered the workforce, career outcomes were also analyzed. Relative to comparison data, participants completed degrees and progressed through the higher education “pipeline” to earn advanced degrees at remarkably high rates; the majority entered careers in which they support or conduct cancer research. The latter is important, because most participants identify with demographic categories currently underrepresented in the cancer research workforce. This article makes two contributions to knowledge on research training programs for underrepresented students: 1) it quantifies participants’ progression along the entire postsecondary education pipeline as well as into the workforce, and 2) it identifies points where participants are most prone to exit the pipeline rather than progress. We identify two types of exits—permanent and temporary—and offer empirically supported operational definitions for both. Evaluators may find the quantitative model and/or definitions useful for analyzing similar programs.
Can the Montreal Cognitive Assessment and Mini-Mental State Examination detect cognitive decline in elderly patients with essential tremor?

Abstract Objective Given the association between essential tremor (ET) and higher rates of cognitive decline, assessing this decline is an important element of research and clinical care. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two broad, brief measures that are widely used to monitor cognitive impairment in various neurological disorders. We sought to determine the relative ability of the MoCA and the MMSE to detect cognitive decline in elderly patients with ET. Methods We administered a neuropsychological battery to an ET cohort every 18 months over 4.5 years. We defined the gold standard for change in cognition as the change in neuropsychological test scores over consecutive evaluations and applied the Reliable Change Method to detect meaningful increases/decreases in test scores. We performed receiver operating characteristics (ROC) analysis to quantify the area under the curve (AUC) and compare the ability of the MoCA and the MMSE to detect cognitive decline. Results The AUCs for the MoCA and the MMSE did not differ significantly at any interval or when all intervals were pooled for analysis. Across all intervals, the ability of the MoCA and the MMSE to detect cognitive decline was consistently fair or poor. Conclusions We found that the ability of the MoCA and the MMSE to detect cognitive decline in ET patients over 18-month intervals is inadequate. Unchanged scores on the MoCA and the MMSE in ET over time should be approached with caution. We propose that these screening tools should be supplemented with additional neuropsychological tests.
Ocular Rigidity and Current Therapy

Abstract Purpose: Ocular rigidity (OR) is an important biomechanical parameter of the eye accounting for the material and geometrical properties of the corneoscleral shell. Methods: This study used a literature search to review the role of ocular rigidity and the application of potential therapies targeting this parameter in glaucoma and myopia. Conclusion: Biomechanical modeling and improved understanding of the biochemistry, and molecular arrangement of sclera and its constituents have yielded important insights. Recent developments, including that of a non-invasive and direct OR measurement method and improved ocular imaging techniques are helping to elucidate the role of OR in healthy and diseased eyes by facilitating large scale and longitudinal clinical studies. Improved understanding of OR at the initial stages of disease processes and its alterations with disease progression will undoubtedly propel research in the field. Furthermore, a better understanding of the determinants of OR is helping to refine novel therapeutic approaches which target and alter the biomechanical properties of the sclera in sight-threatening conditions such as glaucoma and myopia.