Miracle-dz/UniFAR-FTUs huggingface dataset:
The Carbonic Anhydrase as a Paragon: Theoretical and Experimental Investigation of Biomimetic Zinc-Catalyzed Activation of Cumulenes

Biomimetics as an interdisciplinary concept involves learning from and imitating of nature using appropriate models. The mimicry of biological models does not only consist of the construction of engineering systems and modern technology, furthermore, it is able to be a guide for designing and architecturing in the complete range of natural sciences. In particular, the actual development of novel and uncommon chemical reactions is aimed to apply high optimized, biochemical processes to laboratory and industrially usable syntheses. Especially enzymes stand in the visual focus as highly efficient and almost extreme specialized catalysts, as nature has had a long time to develop and optimize a wide diversity of life. Nearly every organism owns different tissues, motion types, sensoring functions and surviving instincts and the basis for all of these properties are highly efficient catalyzed chemical reactions. Organisms have not only to synthesize huge biopolymers for growth, but also to provide small molecules for signal transduction, energy transfers or regulation processes. Therefore, it is obvious that the study of those reactions not only gives insights in important biochemical processes, but also suggests new chemical pathways to use in synthesis or other related appliances. The possibilities of biomimetics in chemistry are outlined on the basis of the enzyme carbonic anhydrase. As this enzyme is one of the most efficient catalysts originated by nature, the investigation of such a catalytical active protein enriches not only the knowledge of biological and biochemical mechanisms and their mode of action, but also gives detailed information about the active center inside of the enzyme. In that way, one can fathom out important factors for the growth and development as well as for the investigation of diseases and glitches. In this chapter we describe the enzymatic metal mediated reaction of the cumulene system carbon dioxide with water and its extention to the bio-analogue activation of further isoelectronic cumulenes (carbonyl sulfide, isothiocyanate and allene).
Leptomeningeal Collateral Flow Modifies Endovascular Treatment Efficacy on Large-Vessel Occlusion Strokes

Supplemental Digital Content is available in the text. Background and Purpose: We aim to evaluate if good collateral flow (CF) modifies endovascular therapy (EVT) efficacy on large-vessel stroke. To do that, we used final degree of reperfusion and number of device-passes performed, factors previously associated with better functional outcome, as main outcome measures. Methods: Single-center retrospective study including consecutive stroke patients receiving EVT for anterior circulation large-vessel stroke. CF degree was assessed on CT angiography before EVT using a previously validated 4-grade score. Final degree of reperfusion, using modified Thrombolysis in Cerebral Ischemia (mTICI), and number of device-passes performed were prospectively collected. Multivariable analysis was performed to evaluate the influence of collateral flow degree on final degree of reperfusion and number of device-passes performed. Results: Six hundred twenty-six patients were included in the study; 369 patients (59%) presented good collateral flow on CT angiography. Five hundred twenty-two patients (84%) achieved successful reperfusion (mTICI 2B-3) after EVT, 304 (48%) of them with a final mTICI 2C-3. Median number of device-passes was 2 (interquartile range, 1–3). Good CF was independently associated with better final degree of reperfusion (shift analysis for mTICI0-2A/2B/2C-3%, poor CF 19/38/43 versus good CF 15/32/53, adjusted odds ratio, 1.51 [95% CI, 1.08–2.11]). Poor CF was independently associated with higher number of device-passes performed to achieve successful reperfusion (mTICI2B-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.59, [95% CI, 1.09–2.31]) and complete reperfusion (mTICI2C-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.70 [95% CI, 1.04–2.90]). Conclusions: Patients with good CF treated with EVT experience higher rates of successful reperfusion with lower number of device-passes. CF may facilitate thrombus retrieval and prevent distal embolization of clot fragments, improving device-passes efficacy.
B cell targeting by molecular adjuvants for enhanced immunogenicity

ABSTRACT Introduction Adjuvants are critical components of vaccines to improve the quality and durability of immune responses. Molecular adjuvants are a specific subclass of adjuvants where ligands of known immune-modulatory receptors are directly fused to an antigen. Co-stimulation of the B cell receptor (BCR) and immune-modulatory receptors through this strategy can augment downstream signaling to improve antibody titers and/or potency, and survival in challenge models. Areas covered C3d has been the most extensively studied molecular adjuvant and shown to improve immune responses to a number of antigens. Similarly, tumor necrosis superfamily ligands, such as BAFF and APRIL, as well as CD40, CD180, and immune complex ligands can also improve humoral immunity as molecular adjuvants. Expert opinion However, no single strategy has emerged that improves immune outcomes in all contexts. Thus, systematic exploration of molecular adjuvants that target B cell receptors will be required to realize their full potential as next-generation vaccine technologies.
Ultrasensitive RDX detection with commercial SERS substrates

Surface-enhanced Raman spectroscopy (SERS) measurements on 1,3,5-trinitroperhydro-1,3,5-triazine were performed with a table-top micro-Raman system exciting the analyte with a diode laser emitting at 785nm. The main Raman features of 1,3,5-trinitroperhydro-1,3,5-triazine were clearly identified, and a careful optimization of acquisition parameters was performed in order to increase the overall sensitivity of the apparatus. The amount of the sampled substance was determined through the analysis of high-resolution scanning electron microscope images of the substrate covered with the residual explosive and resulted to be of the order of few tens of picograms. This value demonstrates the applicability of commercial substrates to the ultrasensitive surface-enhanced Raman spectroscopy detection of explosives, allowing for their identification in real time. Copyright © 2013 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher’s web site.
Testosterone Responses to Intensive, Prolonged Endurance Exercise in Women

Objective: To examine the response of testosterone in women to an intensive, prolonged endurance exercise bout that mimicked a competitive event. Methods: Ten healthy eumenorrheic women ran to exhaustion at ~100% of their ventilatory threshold in their follicular menstrual cycle phase. Testosterone measures were assessed pre-exercise, immediately, 30 min, 60 min, 90 min, and 24 h post-exercise. Results: At exhaustion (75.1 ± 7.0 min), total (56%), free (36%), and bioavailable testosterone (50%) were increased from pre-exercise values (p< 0.05). At 24 h post-exercise, these measures were decreased from pre-exercise values (−21%, −31%, −18%, respectively; p < 0.05). Effect sizes for these changes ranged from medium to large in magnitude. Conclusion: Testosterone was elevated in the early recovery period following exhaustive endurance exercise but was reduced by 24 h afterward. These outcomes are comparable to responses seen in men when sex-based concentration differences are considered.
Guidelines for Evaluating the Feasibility of Recruitment in Pilot Studies of Diverse Populations: An Overlooked but Important Component.

Background In health disparities research, studies often fall short of their recruitment goals. Conducting a pilot feasibility study of recruitment in which data are collected systematically on recruitment processes can help investigators refine methods for the larger study. However, there are few guidelines for conducting pilot feasibility studies, and recruitment methods are seldom the focus. Feasibility indicators differ from traditional reports of recruitment results by focusing on the extent to which recruitment goals are met. Methods We present an organizing framework for assessing the feasibility of recruitment that includes eight steps, briefly: 1) specify recruitment goals; 2) specify recruitment processes; 3) establish a tracking system for each individual; 4) establish a tracking database for monitoring processes and results; 5) implement recruitment and track each individual's progress; 6) summarize recruitment results; 7) calculate and interpret feasibility measures - were goals met; and 8) if goals were not met, utilize tracking data to modify methods for the larger study. We describe methods within each step, with added details for steps 2-5 (the specific processes). The framework draws from a small literature on recruitment feasibility with a focus on health disparities populations. The guidelines blend well-known methods of recruitment with additional information on calculating feasibility indicators. Conclusions These guidelines provide a first step in thinking systematically about recruitment feasibility, to advance the field of measuring feasibility. Feasibility indicators also can be used to track the effectiveness of innovative recruitment strategies as part of building the science of recruitment, especially in disparities populations.
Inhibition of microbial growth by silver nanoparticles synthesized from Fraxinus xanthoxyloides leaf extract

Conventional antibiotics have been failed to treat infectious diseases due to emergence of multidrug resistance (MDR) in some common pathogens. The current study aimed to formulate new antimicrobials from greener sources. In the midst of these efforts, nanotechnology is a newly emerged field, in which the synthesis of new nanoparticles through novel and efficient means is on the rise.
Integrating the Study of Personality and Psychopathology in the Context of Gene-Environment Correlations Across Development.

A key principle of individual differences research is that biological and environmental factors jointly influence personality and psychopathology. Genes and environments interact to influence the emergence and stability of both normal and abnormal behavior (i.e., genetic predisposition, X, is exacerbated or buffered under environmental conditions, Y, or vice versa), including by shaping the neural circuits underpinning behavior. The interplay of genes and environments is also reflected in various ways in which they are correlated (i.e., rGE). That is, the same genetic factors that give rise to personality or psychopathology also shape that person's environment. In this review, we outline passive, evocative, and active rGE processes and review the findings of studies that have addressed rGE in relation to understanding individual differences in personality and psychopathology across development. Throughout, we evaluate the question of whether it is possible, not only to differentiate the person from their problems, but to differentiate the person from their problems and their environment. We provide recommendations for future research to model rGE and better inform our ability to study personality and psychopathology, while separating the influence of the environment.
Gender as a predictive factor in cholecystectomy - is it true or false?

INTRODUCTION Cholecystolithiasis is one of the most frequent disorders of the human digestive system in a present population. It is common to point out that male gender is one of strong risk factors for complications during cholecystectomy, however the debate about that seems to be still open. AIM OF THE STUDY The aim of this study was to compare the values related to the course and treatment effects between gender in patients undergoing cholecystectomy, based on own material. MATERIALS AND METHODS The study encompassed 504 patients who were admitted to General Surgery And Polytraumatic Injury Department of University Hospital in Kraków, Poland between 2013 and 2018, with the initial diagnosis of cholecystolithiasis (scheduled cases) and acute cholecystitis (emergency cases). The patients underwent surgical gallbladder removal. In this group there were 326 (64.7%) female and 178 (35.3%) male patients. RESULTS Statistically significant differences between both genders were found containing age, type of admission, numeric rating scale of pain during admission, results in American Society of Anesthesiologists physical status classification system, outcomes in Acute Physiology And Chronic Health Evaluation II severity-of-disease classification system, percentage of conversions, mortality, period of time from admission to surgical procedure, mean duration of the procedure, blood tests and histopathological results. CONCLUSIONS Subgroups of the cases where determining factor is gender are strongly heterogeneous. Although treatment results were different for both subgroups and these differences were partly statistically significant, it cannot be clearly determined on the basis of a study with such selection of patients, that gender is an independent risk factor for surgical gallbladder removal.
Blunted Rest-Activity Rhythms Link to Higher Body Mass Index and Inflammatory Markers in Children.

STUDY OBJECTIVES Disturbances of rest-activity rhythms are associated with higher body mass index (BMI) in adults. Whether such relationship exists in children is unclear. We aimed to examine cross-sectional associations of rest-activity rhythm characteristics with BMI z-score and obesity-related inflammatory markers in school-age children. METHODS Participants included 411 healthy children (mean±SD age 10.1±1.3 years, 50.8% girls) from a Mediterranean area of Spain who worn wrist accelerometers for 7 consecutive days. Metrics of rest-activity rhythm were derived using both parametric and nonparametric approaches. Obesity-related inflammatory markers were measured in saliva (n=121). RESULTS In a multivariable-adjusted model, higher BMI z-score is associated with less robust 24-hour rest-activity rhythms as represented by lower relative amplitude (-0.16 [95%CI -0.29, -0.02] per SD, P=0.02). The association between BMI z-score and relative amplitude persisted with additional adjustment for sleep duration, and attenuated after adjustment for daytime activity level. Less robust rest-activity rhythms were related to increased levels of several salivary pro-inflammatory markers, including C-reactive protein which is inversely associated with relative amplitude (-32.6% [-47.8%, -12.9%] per SD), independently of BMI z-score, sleep duration, and daytime activity level. CONCLUSION Blunted rest-activity rhythms are associated with higher BMI z-score and salivary pro-inflammatory markers already at an early age. The association with BMI z-score seem to be independent of sleep duration, and those with pro-inflammatory markers further independent of BMI z-score and daytime activity. Novel intervention targets at an early age based on improving the strength of rest-activity rhythms may help to prevent childhood obesity and related inflammation.
Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

Purpose Dissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions. Materials and Methods A total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis). Results The cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography. Conclusion The presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277).
Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease

Paul M. Lantos, Jeffrey Rumbaugh, Linda K. Bockenstedt, Yngve T. Falck-Ytter, Maria E. Aguero-Rosenfeld, Paul G. Auwaerter, Kelly Baldwin, Raveendhara R. Bannuru, Kiran K. Belani, William R. Bowie, John A. Branda, David B. Clifford, Francis J. DiMario Jr., John J. Halperin, Peter J. Krause, Valery Lavergne, Matthew H. Liang, H. Cody Meissner, Lise E. Nigrovic, James (Jay) J. Nocton, Mikala C. Osani, Amy A. Pruitt, Jane Rips, Lynda E. Rosenfeld, Margot L. Savoy, Sunil K. Sood, Allen C. Steere, Franc Strle, Robert Sundel, Jean Tsao, Elizaveta E. Vaysbrot, Gary P. Wormser, and Lawrence S. Zemel
Intravitreal Administration of Acetyl Triethyl Citrate and Benzyl Benzoate Is Retinotoxic in Rabbits but Not in Cynomolgus Monkeys

Sustained drug delivery formulations are developed to reduce dose frequency while maintaining efficacy of intravitreal (ITV) administered therapeutics. Available safety data for components novel to the eye’s posterior segment may be limited, requiring preclinical assessments to identify potential toxicities. We evaluated the in vivo and in vitro safety of two solvents, acetyl triethyl citrate (ATEC) and benzyl benzoate (BB), as novel sustained delivery formulations for ITV administration. In vivo tolerability was assessed following ITV administration of ATEC and BB to rabbits and cynomolgus monkeys. In rabbits, ITV solvent administration resulted in moderate to severe retinal toxicity characterized by focal retinal necrosis and/or degeneration, sometimes accompanied by inflammation, with a clear association between the physical presence of the solvent and areas of retinal damage. In contrast, solvent administration in monkeys appeared well tolerated, producing no histologic abnormalities. Toxicity in primary human retinal pigment epithelial cells, characterized by cellular toxicity and mitochondrial injury, corroborated the retinal toxicity in rabbits. In conclusion, ITV solvent depots of ATEC or BB result in chemical and focal retinal toxicity in rabbits, but not monkeys. Additional investigation is needed to demonstrate a sufficient margin of safety prior to use of ATEC or BB in ITV drug products.
Low serum calcium: a new, important indicator of COVID-19 patients from mild/moderate to severe/critical

Abstract Background: Coronavirus disease 2019 (COVID-19) virus is still spreading, finding out the initial hits of viral infection is important to minimize the mild/moderate population, prevent disease aggravation and organs dysfunction. Objective: We investigated COVID-19 patients with different serum calcium levels. Design: We checked the serum calcium level of the patients based on days after symptom onset as well as the severity of COVID-19. We also checked multiorgan injuries and immune cytokines level in their blood. Results: Both mild/moderate and severe critical cases we observed showed low calcium level in the early stage of viral infection, while the severe/critical cases showed significant lower calcium level than mild/moderate cases in the early stage. We also found that low calcium level related to severe/critical multiorgan injuries especially in the mild/moderate population. Proinflammatory cytokine IL-6 also correlated to calcium change in both mild/moderate and severe/critical cases. Conclusions: Our finding indicates that calcium balance is a primal hit of COVID-19 and a biomarker of clinical severity at the beginning of symptom onset. Calcium is closely associated with virus-associated multiple organ injuries and the increase in inflammatory cytokines. Our results provide a new, important indicator of COVID-19 patients from mild/moderate to severe/critical: serum calcium.
The Orthognathic Quality of Life Questionnaire: Translation and Validation into Dutch

Supplemental Digital Content is available in the text Objective: The aim of this study is to translate and validate the Orthognathic Quality of Life Questionnaire (OQLQ) in the Dutch language (OQLQ-NL). Methods: The translation of the OQLQ into the Dutch language was performed following the guidelines for the Process of Cross-Cultural Adaption of Self-Report Measures. Sixty-two patients who received orthognathic surgery in the past 10 years were included for participation. Internal reliabilities of the OQLQ-NL were evaluated for multiple item scales with the use of the Cronbach alpha coefficient. For the establishment of the test–retest reliability, the OQLQ-NL was repeated with a 2-week interval and the intraclass correlation coefficient was calculated. Spearman correlation was used to test the correlation with the OHIP-49NL and the FACE-Q, to be able to evaluate the construct validity of the OQLQ-NL. Results: Thirty-five patients filled in the OQLQ-NL, OHIP49NL, and FACE-Q upon arrival and 22 patients returned the OQLQ-NL after 2 weeks (response rate of 56.6% and 62.9%, respectively). The OQLQ-NL showed excellent results in internal reliability and test–retest reliability. The vast majority of the correlations between the domains of the questionnaires were as expected. Data from this study and previous studies confirm the construct validity of the OQLQ-NL Conclusion: The OQLQ-NL appears to be a valid and reliable instrument to measure quality of life for patients receiving orthognathic surgery in the Netherlands.