Miracle-dz/UniFAR-FTUs huggingface dataset:
Selected Risk Nutritional Factors for Chemotherapy-Induced Polyneuropathy

The present study seeks to identify the nutritional risk factors involved in the development of neuropathies induced by chemotherapeutic treatments. Unlike the gastrointestinal or hematological adverse effects of chemotherapy there is no protective treatment strategy for polyneuropathy. The aim of this study was to find possible deficiencies in nutritional factors, which can be used for supplementation in the future for prevention of chemotherapy-induced neuropathy development. We analyzed 70 patients undergoing paclitaxel chemotherapy and evaluated the risk factors involved in chemotherapy-induced peripheral neuropathy (CIPN). Several risk factors were considered in the development of CIPN, including deficiency of vitamin B1, B6, and D and fatty acids. The occurrence of CIPN complication in 60% cases was observed. We found significant differences in vitamin D and saturated fatty acid concentration. Vitamin D levels in the group without CIPN were estimated to be 38.2 (24.95, 47.63) nmol/L, whereas in the group with CIPN it was determined to be 25.6 (19.7, 32.55) nmol/L, p = 0.008. The level of total saturated fatty acids in the group without CIPN was of 32.613 Area % (31.322; 36.262), whereas in the group with CIPN it was of 34.209 Area % (32.86; 39.386), p = 0.01. The obtained results suggest a diet lower in saturated fatty acid content during chemotherapy. The most significant finding was that supplementation of vitamin D before chemotherapy could be an efficient neuroprotective in CIPN prophylaxis, as significantly lower levels 25OH derivative of vitamin D were observed in the CIPN group throughout the study period.
Physical principles of intracellular organization via active and passive phase transitions

Exciting recent developments suggest that phase transitions represent an important and ubiquitous mechanism underlying intracellular organization. We describe key experimental findings in this area of study, as well as the application of classical theoretical approaches for quantitatively understanding these data. We also discuss the way in which equilibrium thermodynamic driving forces may interface with the fundamentally out-of-equilibrium nature of living cells. In particular, time and/or space-dependent concentration profiles may modulate the phase behavior of biomolecules in living cells. We suggest future directions for both theoretical and experimental work that will shed light on the way in which biological activity modulates the assembly, properties, and function of viscoelastic states of living matter.
Modeling and experimental investigation of induction welding of thermoplastic composites and comparison with other welding processes

A three-dimensional finite element model of the induction welding of carbon fiber/polyphenylene sulfide thermoplastic composites is developed. The model takes into account a stainless steel mesh heating element located at the interface of the two composite adherends to be welded. This heating element serves to localize the heating where it is needed most, i.e. at the weld interface. The magnetic, electrical, and thermal properties of the carbon fiber/polyphenylene sulfide composite and other materials are identified experimentally or estimated and implemented in the model. The model predicts the temperature–time curves during the heating of the composite and is used to define processing parameters leading to high-quality welded joints. The effect of the heating element size and input current on the thermal behavior is investigated, both experimentally and using the developed model. The welds quality is assessed through microscopic observations of the weld interfaces, mechanical testing, and observations of the fracture surfaces. A comparison with two other welding processes, namely resistance welding and ultrasonic welding is finally conducted.
Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors

Most general anesthetics enhance GABA type A (GABAA) receptor activity at clinically relevant concentrations. Sites of action of volatile anesthetics on the GABAA receptor remain unknown, whereas sites of action of many intravenous anesthetics have been identified in GABAA receptors by using photolabeling. Here, we used photoactivatable analogs of isoflurane (AziISO) and sevoflurane (AziSEVO) to locate their sites on α1β3γ2L and α1β3 GABAA receptors. As with isoflurane and sevoflurane, AziISO and AziSEVO enhanced the currents elicited by GABA. AziISO and AziSEVO each labeled 10 residues in α1β3 receptors and 9 and 8 residues, respectively, in α1β3γ2L receptors. Photolabeled residues were concentrated in transmembrane domains and located in either subunit interfaces or in the interface between the extracellular domain and the transmembrane domain. The majority of these transmembrane residues were protected from photolabeling with the addition of excess parent anesthetic, which indicated specificity. Binding sites were primarily located within α+/β — and β+/α— subunit interfaces, but residues in the α+/γ— interface were also identified, which provided a basis for differential receptor subtype sensitivity. Isoflurane and sevoflurane did not always share binding sites, which suggests an unexpected degree of selectivity. —Woll, K. A. , Zhou, X. , Bhanu, N. V. , Garcia, B. A. , Covarrubias, M. , Miller, K. W. , Eckenhoff, R. G. Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors. FASEB J. 32, 4172–4189 (2018). www.fasebj. org
Singlet Oxygen Induced Products of Linoleates, 10- and 12-(Z,E)-Hydroxyoctadecadienoic Acids (HODE), Can Be Potential Biomarkers for Early Detection of Type 2 Diabetes

Current diagnostic tests such as glycemic indicators have limitations for early detection of impaired glucose tolerance (IGT), which leads to diabetes. Oxidative stress induced by various oxidants in a random and destructive manner is considered to play an important role in the pathophysiology of a number of human disorders and diseases such as impaired glucose tolerance. We have developed an improved method for the measurement of in vivo lipid peroxidation, where the presence of 8-iso-prostaglandin F2α (8-iso-PGF2α), hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and 7-hydroxycholesterol (7-OHCh), as well as their parent molecules, linoleic acid (LA) and cholesterol (Ch), was determined by performing LC-MS/MS (for 8-iso-PGF2α, HODE, and HETE) and GC-MS (for 7-OHCh, LA, and Ch) after reduction with triphenyl phosphine and saponification by potassium hydroxide. We then applied this method to volunteers (n = 57), including normal type (n = 43), “high-normal” (fasting plasma glucose, 100–109 mg/dL, n = 7), pre-diabetic type (IGT, n = 5), and diabetic type (n = 2) subjects who are diagnosed by performing oral glucose tolerance tests (OGTTs). Several biomarkers in plasma, such as insulin, leptin, adiponectin, interleukin-6, tumor necrosis factor-α, high sensitivity-C-reactive protein, HbA1c, and glucose levels were measured during OGTT. We found that the fasting levels of (10- and 12-(Z,E)- HODE)/LA increased significantly with increasing levels of HbA1c and glucose during OGTT and with insulin secretion and resistance index. In conclusion, 10- and 12-(Z,E)-HODE may be prominent biomarkers for the early detection of IGT and “high-normal” type without OGTT.
Regionalization of a Landscape-Based Hazard Index of Malaria Transmission: An Example of the State of Amapá, Brazil

Identifying and assessing the relative effects of the numerous determinants of malaria transmission, at different spatial scales and resolutions, is of primary importance in defining control strategies and reaching the goal of the elimination of malaria. In this context, based on a knowledge-based model, a normalized landscape-based hazard index (NLHI) was established at a local scale, using a 10 m spatial resolution forest vs. non-forest map, landscape metrics and a spatial moving window. Such an index evaluates the contribution of landscape to the probability of human-malaria vector encounters, and thus to malaria transmission risk. Since the knowledge-based model is tailored to the entire Amazon region, such an index might be generalized at large scales for establishing a regional view of the landscape contribution to malaria transmission. Thus, this study uses an open large-scale land use and land cover dataset (i.e., the 30 m TerraClass maps) and proposes an automatic data-processing chain for implementing NLHI at large-scale. First, the impact of coarser spatial resolution (i.e., 30 m) on NLHI values was studied. Second, the data-processing chain was established using R language for customizing the spatial moving window and computing the landscape metrics and NLHI at large scale. This paper presents the results in the State of Amapa, Brazil. It offers the possibility of monitoring a significant determinant of malaria transmission at regional scale.
Integration of A Clinical Pharmacy Specialist into A Substance Use Disorder Intensive Outpatient Treatment Program to Improve Prescribing Rates of Alcohol Use Disorder Pharmacotherapy

Background Research has demonstrated that the combination of pharmacotherapy and psychological interventions in alcohol use disorder (AUD) treatment is superior to either alone. Despite this, medications remain highly underutilized in many outpatient treatment facilities. Pharmacists can serve as an excellent resource to aid in improving access to medications. Methods This study was a prospective, longitudinal evaluation of a pharmacist's role in a substance use disorder (SUD) clinic, specifically an intensive outpatient program (IOP). The primary objective was to determine if the addition of a clinical pharmacy specialist (CPS) as a bridge until next available provider appointment would improve access to AUD pharmacotherapy for patients in the IOP. Results A total of 43 patients were enrolled in the IOP during the study. Of these, 27 patients presented with a primary diagnosis of AUD, and only eight were receiving AUD pharmacotherapy at the start of the program. During this intervention, 11 patients expressed interest in initiating a medication for AUD while in the IOP. The average wait time for a medication evaluation appointment with the CPS was 1.4 days. By comparison, the average wait time for an addiction psychiatrist was approximately 44 days. Each patient was seen for an average of two 30-minute visits, including an initial medication evaluation and one follow-up. Upon completion of CPS services, patients were referred almost equally to an established non-addiction recovery services (ARS) mental health provider (36%), an ARS psychiatrist (36%), or a primary care provider (28%). Conclusion Our study highlights the role that pharmacists can play in improving access to evidence-based AUD pharmacotherapy, as well as in providing medication education to patients and providers. Long-term prospective research and pharmacoeconomic analysis are needed to determine the sustainability of this service, both at our facility and in other similar practice settings.
Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review

Propolis is one of the complex, but valuable, bio-sources for discovering therapeutic compounds. Diterpenes are organic compounds composed of four isoprene units and are known for their biological and pharmacological characteristics, such as antibacterial, anticancer, and anti-inflammatory activities. Recently, advancements have been made in the development of antibacterial and anticancer leads from propolis-isolated diterpenes, and scrutiny of these compounds is being pursued. Thus, this review covers the progress in this arena, with a focus on the chemistry and biological activities of propolis diterpenes. It is anticipated that important information, in a comprehensive and concise manner, will be delivered here for better understanding of natural product drug discovery research.
Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer’s Disease-Like Pattern

Abstract Background Late-life depression patients are at a high risk of developing Alzheimer’s disease, and diminished olfactory identification is an indicator in early screening for Alzheimer’s disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer’s disease in late-life depression patients remains unclear. Methods One hundred and twenty-five late-life depression patients, 50 Alzheimer’s disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. Results The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer’s disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer’s disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer’s disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group. Conclusion The patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer’s disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer’s disease.
A functional role for intrinsic disorder in the tau-tubulin complex

Significance Tau is a neuronal microtubule-associated protein linked to numerous neurodegenerative disorders, including Alzheimer’s disease. Several lines of evidence support tau aggregation as well as loss of its native interactions with microtubules as contributing to pathology. Here, we explored the largely overlooked first step of microtubule assembly, namely the interaction of tau with soluble tubulin heterodimers. Using single-molecule Förster Resonance Energy Transfer (smFRET), we determine the topological features of tau in complex with tubulin. Our results contrast differences in tau isoforms and underscore the importance of conformational flexibility in tau function. Tau is an intrinsically disordered protein with an important role in maintaining the dynamic instability of neuronal microtubules. Despite intensive study, a detailed understanding of the functional mechanism of tau is lacking. Here, we address this deficiency by using intramolecular single-molecule Förster Resonance Energy Transfer (smFRET) to characterize the conformational ensemble of tau bound to soluble tubulin heterodimers. Tau adopts an open conformation on binding tubulin, in which the long-range contacts between both termini and the microtubule binding region that characterize its compact solution structure are diminished. Moreover, the individual repeats within the microtubule binding region that directly interface with tubulin expand to accommodate tubulin binding, despite a lack of extension in the overall dimensions of this region. These results suggest that the disordered nature of tau provides the significant flexibility required to allow for local changes in conformation while preserving global features. The tubulin-associated conformational ensemble is distinct from its aggregation-prone one, highlighting differences between functional and dysfunctional states of tau. Using constraints derived from our measurements, we construct a model of tubulin-bound tau, which draws attention to the importance of the role of tau’s conformational plasticity in function.
Association between Socioeconomic Position and Tuberculosis in a Large Population-Based Study in Rural Malawi

Setting There is increasing interest in social structural interventions for tuberculosis. The association between poverty and tuberculosis is well established in many settings, but less clear in rural Africa. In Karonga District, Malawi, we found an association between higher socioeconomic status and tuberculosis from 1986-1996, independent of HIV status and other factors. Objective To investigate the relationship in the same area in 1997-2010. Design All adults in the district with new laboratory-confirmed tuberculosis were included. They were compared with community controls, selected concurrently and frequency-matched for age, sex and area. Results 1707 cases and 2678 controls were interviewed (response rates >95%). The odds of TB were increased in those working in the cash compared to subsistence economy (p<0.001), and with better housing (p-trend=0.006), but decreased with increased asset ownership (p-trend=0.003). The associations with occupation and housing were partly mediated by HIV status, but remained significant. Conclusion Different socioeconomic measures capture different pathways of the association between socioeconomic status and tuberculosis. Subsistence farmers may be relatively unexposed whereas those in the cash economy travel more, and may be more likely to come forward for diagnosis. In this setting “better houses” may be less well ventilated and residents may spend more time indoors.
Does Nocturnality Drive Binocular Vision? Octodontine Rodents as a Case Study

Binocular vision is a visual property that allows fine discrimination of in-depth distance (stereopsis), as well as enhanced light and contrast sensitivity. In mammals enhanced binocular vision is structurally associated with a large degree of frontal binocular overlap, the presence of a corresponding retinal specialization containing a fovea or an area centralis, and well-developed ipsilateral retinal projections to the lateral thalamus (GLd). We compared these visual traits in two visually active species of the genus Octodon that exhibit contrasting visual habits: the diurnal Octodon degus, and the nocturnal Octodon lunatus. The O. lunatus visual field has a prominent 100° frontal binocular overlap, much larger than the 50° of overlap found in O. degus. Cells in the retinal ganglion cell layer were 40% fewer in O. lunatus (180,000) than in O. degus (300,000). O. lunatus has a poorly developed visual streak, but a well developed area centralis, located centrally near the optic disk (peak density of 4,352 cells/mm2). O. degus has a highly developed visual streak, and an area centralis located more temporally (peak density of 6,384 cells/mm2). The volumes of the contralateral GLd and superior colliculus (SC) are 15% larger in O. degus compared to O. lunatus. However, the ipsilateral projections to GLd and SC are 500% larger in O. lunatus than in O. degus. Other retinorecipient structures related to ocular movements and circadian activity showed no statistical differences between species. Our findings strongly suggest that nocturnal visual behavior leads to an enhancement of the structures associated with binocular vision, at least in the case of these rodents. Expansion of the binocular visual field in nocturnal species may have a beneficial effect in light and contrast sensitivity, but not necessarily in stereopsis. We discuss whether these conclusions can be extended to other mammalian and non-mammalian amniotes.
Seasonal Diet and Prey Preference of the African Lion in a Waterhole-Driven Semi-Arid Savanna

Large carnivores inhabiting ecosystems with heterogeneously distributed environmental resources with strong seasonal variations frequently employ opportunistic foraging strategies, often typified by seasonal switches in diet. In semi-arid ecosystems, herbivore distribution is generally more homogeneous in the wet season, when surface water is abundant, than in the dry season when only permanent sources remain. Here, we investigate the seasonal contribution of the different herbivore species, prey preference and distribution of kills (i.e. feeding locations) of African lions in Hwange National Park, Zimbabwe, a semi-arid African savanna structured by artificial waterholes. We used data from 245 kills and 74 faecal samples. Buffalo consistently emerged as the most frequently utilised prey in all seasons by both male (56%) and female (33%) lions, contributing the most to lion dietary biomass. Jacobs’ index also revealed that buffalo was the most intensively selected species throughout the year. For female lions, kudu and to a lesser extent the group “medium Bovidae” are the most important secondary prey. This study revealed seasonal patterns in secondary prey consumption by female lions partly based on prey ecology with browsers, such as giraffe and kudu, mainly consumed in the early dry season, and grazers, such as zebra and suids, contributing more to female diet in the late dry season. Further, it revealed the opportunistic hunting behaviour of lions for prey as diverse as elephants and mice, with elephants taken mostly as juveniles at the end of the dry season during droughts. Jacobs’ index finally revealed a very strong preference for kills within 2 km from a waterhole for all prey species, except small antelopes, in all seasons. This suggested that surface-water resources form passive traps and contribute to the structuring of lion foraging behaviour.
Functional Diversification within a Predatory Species Flock

Ecological speciation is well-known from adaptive radiations in cichlid fishes inhabiting lentic ecosystems throughout the African rift valley and Central America. Here, we investigate the ecological and morphological diversification of a recently discovered lotic predatory Neotropical cichlid species flock in subtropical South America. We document morphological and functional diversification using geometric morphometrics, stable C and N isotopes, stomach contents and character evolution. This species flock displays species-specific diets and skull and pharyngeal jaw morphology. Moreover, this lineage appears to have independently evolved away from piscivory multiple times and derived forms are highly specialized morphologically and functionally relative to ancestral states. Ecological speciation played a fundamental role in this radiation and our data reveal novel conditions of ecological speciation including a species flock that evolved: 1) in a piscivorous lineage, 2) under lotic conditions and 3) with pronounced morphological novelties, including hypertrophied lips that appear to have evolved rapidly.