Miracle-dz/UniFAR-FTUs huggingface dataset:
Artificially Induced Pluripotent Stem Cell-Derived Whole-Brain Organoid for Modelling the Pathophysiology of Metachromatic Leukodystrophy and Drug Repurposing

Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disease that results from a deficiency of the lysosomal enzyme arylsulfatase A (ARSA). Worldwide, there are between one in 40,000 and one in 160,000 people living with the disease. While there are currently no effective treatments for MLD, induced pluripotent stem cell-derived brain organoids have the potential to provide a better understanding of MLD pathogenesis. However, developing brain organoid models is expensive, time consuming and may not accurately reflect disease progression. Using accurate and inexpensive computer simulations of human brain organoids could overcome the current limitations. Artificially induced whole-brain organoids (aiWBO) have the potential to greatly expand our ability to model MLD and guide future wet lab research. In this study, we have upgraded and validated our artificially induced whole-brain organoid platform (NEUBOrg) using our previously validated machine learning platform, DeepNEU (v6.2). Using this upgraded NEUBorg, we have generated aiWBO simulations of MLD and provided a novel approach to evaluate factors associated with MLD pathogenesis, disease progression and new potential therapeutic options.
Wheat Germ Agglutinin-Conjugated Disulfide Cross-Linked Alginate Nanoparticles as a Docetaxel Carrier for Colon Cancer Therapy

Purpose In chemotherapy, oral administration of drug is limited due to lack of drug specificity for localized colon cancer cells. The inability of drugs to differentiate cancer cells from normal cells induces side effects. Colonic targeting with polymeric nanoparticulate drug delivery offers high potential strategies for delivering hydrophobic drugs and fewer side effects to the target site. Disulfide cross-linked polymers have recently acquired high significance due to their potential to degrade in reducing colon conditions while resisting the upper gastrointestinal tract’s hostile environment. The goal of this project is, therefore, to develop pH-sensitive and redox-responsive fluorescein-labeled wheat germ agglutinin (fWGA)-mounted disulfide cross-linked alginate nanoparticles (fDTP2) directly targeting docetaxel (DTX) in colon cancer cells. Methods fDTP2 was prepared by mounting fWGA on DTX-loaded nanoparticles (DTP2) using the two-step carbodiimide method. Morphology of fDTP2 was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) study was carried out to determine the mean diameter, polydispersity index (PDI) and zeta potential of fDTP2. Cellular uptake efficiency was examined using fluorescence microplate reader. Biocompatibility and active internalization of fDTP2 were conducted on HT-29. Results fDTP2 was found to exhibit a DTX loading efficiency of 19.3%. SEM and TEM tests revealed spherical nanoparticles. The in vitro DTX release test showed a cumulative release of 54.7%. From the DLS study, fDTP2 reported a 277.7 nm mean diameter with PDI below 0.35 and −1.0 mV zeta potential. HT-29 which was fDTP2-treated demonstrated lower viability than L929 with a half maximal inhibitory concentration (IC50) of 34.7 µg/mL. HT-29 (33.4%) internalized fDTP2 efficiently at 2 h incubation. The study on HT-29 active internalization of nanoparticles through fluorescence and confocal imaging indicated such. Conclusion In short, fDTP2 demonstrated promise as a colonic drug delivery DTX transporter.
Design and Implementation of Postgraduate Programs in Health in a Resource-Limited Setting in Mozambique (The Lúrio University)

Purpose To describe the strategies used to design and implement three postgraduate programs at Lúrio University (UniLúrio), a resource-limited setting, in northern Mozambique. Methods We conducted a longitudinal, descriptive case study from 2011 to 2018 in two phases: 1) needs assessment (2011–2012), 2) implementation strategies (2013–2018), taking into account innovations whenever necessary. Results Several obstacles and barriers to the establishment of postgraduate programs were identified. These included a lack of a core curricula aimed at postgraduate programs, shortage of human resources for teaching and mentorship, limited teaching and research infrastructures, limited financial resources, and lack of administrative capacity. With the support of the Medical Education Partnership Initiative (MEPI), three Master degree programs were designed and implemented. During the period of 2013–2018, UniLúrio enrolled 202 students, distributed as follows: Master degree in Tropical Medicine and Global Health (55), Master degree in Health Professional Education (99), and Master degree in Nutrition and Food Security (48). Of those, 152 (75.2%) obtained a Postgraduate Diploma as they did not present a master dissertation, 89 (44.0%) obtained their Master degree, 30 (14.8%) dropped out, and 20 (9.9%) are awaiting decision. UniLurio’s staff trained a Master’s degree or a Postgraduate Diploma in 34 (16.8%) and 15 (7.4%), respectively. Our strategies allowed us to improve research capacity building, and set the basis for long-term sustainability by allowing for the establishment of other postgraduate programs, and offered UniLurio a strong role in its internationalization. Conclusion By sharing multiple resources, long-lasting partnerships were established with multiple institutions, and competency-based training and postgraduate studies management were developed. Research and eLearning were leveraged, retention and faculty development was enhanced, and some inequalities within the country were reduced. These strategies and innovations can be applied to other resource-limited settings, allowing the scaleup of health professional’s training and research capacity building.
Clinical Characteristics and Management of Cerebral Venous Sinus Thrombosis in Patients with Essential Thrombocythemia

Background and Objective Essential thrombocythemia (ET) is a rare cause of cerebral venous sinus thrombosis (CVST). Analysis of the risk factors and treatment therapies of CVST in ET has yielded controversial findings. Subjects and Methods We retrospectively investigated the clinical characteristics of CVST events in ET and compared baseline characteristics, causative factors, hematological effects, and treatments between ET patients with and without CVST. Results Overall, 91 of 115 patients who met the ET diagnosis were included in this study. Among them, 23 (25.27%) patients met the diagnostic criteria of ET with CVST for inclusion, 14 (60.87%) of whom were females, with a median age of 34 (range 25–50). CVST diagnosis was made concomitantly to ET in 19 patients (82.61%). The most common symptom and sites of thrombosis of CVST was an acute or subacute headache and sigmoid sinuses, respectively. Compared with ET patients without CVST, ET patients with CVST were significantly younger (37.65±14.45 vs 60.93±13.46, P<0.001) and had lower prevalence of hypertension (4.34 vs 32.35%, P=0.003) and coronary artery disease (0 vs 14.71%, P = 0.045). Patients with CVST presented with signiﬁcant lower platelet count (510.39±176.71 vs 750.82±249.10, P< 0.001) and higher score of IPSET-thrombosis (P=0.017). Multivariate logistic regression analysis indicated that age (P=0.002, OR 1.096, 95% CI 1.035–1.161), at least one CVRF (P = 0.024, OR 0.037, 95% CI 0.002–0.649), platelet count (P=0.045, OR 0.994, 95% CI 0.989–1.001), and lower percentage of antiplatelet therapy (P=0.035, OR 0.307, 95% CI 0.001-1.280) significantly contributed to the risk of CVST in ET. Conclusion Most patients (95.65%) had a favorable outcome without recurrence after standard anticoagulant and cytoreductive treatment at last follow-up. These findings indicate that CVST may be the initial presentation of ET, with its detection crucial for early diagnosis and appropriate management. Anticoagulant and cytoreductive therapies should be recommended for preventing ET-related CVST with JAK2 V617F mutation.
Evaluation of the Expression Profile of Irinotecan-Induced Diarrhea in Patients with Colorectal Cancer

Irinotecan (CPT-11) is widely used for the treatment of unresectable colorectal cancer in combination with fluoropyrimidines, such as 5-fluorouracil and S-1. Diarrhea is one of the adverse effects associated with CPT-11 and frequently reported by patients treated with CPT-11-containing regimens combined with oral fluoropyrimidines. However, the mechanisms involved in this process, as well as whether fluctuations in the frequency and differences in the onset time of diarrhea with each CPT-11-containing regimen are caused by drug interactions remain unclear. Therefore, we examined the incidence of diarrhea caused by each CPT-11-containing regimen in patients with colorectal cancer using data from the large voluntary reporting Japanese Adverse Drug Event Report (JADER) database. Firstly, we searched for suspected drugs related to the occurrence of diarrhea using reported odds ratio and calculated the signal score to assess drug–drug interactions. Subsequently, we conducted a time-to-onset analysis using Weibull distribution. The results showed that the combination of CPT-11 with S-1 increased the frequency of diarrhea due to a pharmacological interaction but delayed its onset. The present results may contribute to the appropriate management of drug-induced adverse effects by healthcare professionals.
3D PCL/Gelatin/Genipin Nanofiber Sponge as Scaffold for Regenerative Medicine

Recent advancements in tissue engineering and material science have radically improved in vitro culturing platforms to more accurately replicate human tissue. However, the transition to clinical relevance has been slow in part due to the lack of biologically compatible/relevant materials. In the present study, we marry the commonly used two-dimensional (2D) technique of electrospinning and a self-assembly process to construct easily reproducible, highly porous, three-dimensional (3D) nanofiber scaffolds for various tissue engineering applications. Specimens from biologically relevant polymers polycaprolactone (PCL) and gelatin were chemically cross-linked using the naturally occurring cross-linker genipin. Potential cytotoxic effects of the scaffolds were analyzed by culturing human dermal fibroblasts (HDF) up to 23 days. The 3D PCL/gelatin/genipin scaffolds produced here resemble the complex nanofibrous architecture found in naturally occurring extracellular matrix (ECM) and exhibit physiologically relevant mechanical properties as well as excellent cell cytocompatibility. Samples cross-linked with 0.5% genipin demonstrated the highest metabolic activity and proliferation rates for HDF. Scanning electron microscopy (SEM) images indicated excellent cell adhesion and the characteristic morphological features of fibroblasts in all tested samples. The three-dimensional (3D) PCL/gelatin/genipin scaffolds produced here show great potential for various 3D tissue-engineering applications such as ex vivo cell culturing platforms, wound healing, or tissue replacement.
Impact of the Type of Crosslinking Agents on the Properties of Modified Sodium Alginate/Poly(vinyl Alcohol) Hydrogels

Here, we report on studies on the influence of different crosslinking methods (ionic and chemical) on the physicochemical (swelling ability and degradation in simulated body fluids), structural (FT-IR spectra analysis) and morphological (SEM analysis) properties of SA/PVA hydrogels containing active substances of natural origin. First, an aqueous extract of Echinacea purpurea was prepared using a Soxhlet apparatus. Next, a series of modified SA/PVA-based hydrogels were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate (PEGDA, Mn = 700 g/mol) as a crosslinking agent and, additionally, the ionic reaction in the presence of a 5% w/v calcium chloride solution. The compositions of SA/PVA/E. purpurea-based hydrogels contained a polymer of natural origin—sodium alginate (SA, 1.5% solution)—and a synthetic polymer—poly(vinyl alcohol) (PVA, Mn = 72,000 g/mol, 10% solution)—in the ratio 2:1, and different amounts of the aqueous extract of E. purpurea—5, 10, 15 or 20% (v/v). Additionally, the release behavior of echinacoside from the polymeric matrix was evaluated in phosphate-buffered saline (PBS) at 37 °C. The results indicate that the type of the crosslinking method has a direct impact on the release profile. Consequently, it is possible to design a system that delivers an active substance in a way that depends on the application.
Heat Acclimation Following Heat Acclimatization Elicits Additional Physiological Improvements in Male Endurance Athletes

The purpose of this study was to assess the effectiveness of heat acclimatization (HAz) followed by heat acclimation (HA) on physiological adaptations. 25 male endurance athletes (age 36 ± 12 y, height 178.8 ± 6.39 cm, body mass 73.03 ± 8.97 kg, and VO2peak 57.5 ± 7.0 mL·kg−1·min−1) completed HAz and HA. HAz was 3 months of self-directed summer training. In the laboratory, a 5-day HA prescribed exercise to target a hyperthermic zone (HZHA) of Trec between 38.50 and 39.75 °C for 60 min. Exercise trials were 60 min of running (59% ± 2% VO2peak) in an environmental chamber (wet bulb globe temperature 29.53 ± 0.63 °C) and administered at: baseline, post-HAz, and post-HAz+HA. Measured variables included internal body temperature (Trec), heart rate (HR), and sweat rate (SR). Repeated measure ANOVAs and post hoc comparisons were used to assess statistically significant (p < 0.05) differences. Trec was lower post-HAz+HA (38.03 ± 0.39 °C) than post-HAz (38.25 ± 0.42 °C, p = 0.009) and baseline (38.29 ± 0.37 °C, p = 0.005). There were no differences between baseline and post-HAz (p = 0.479) in Trec. HR was lower post-HAz (143 ± 12 bpm, p = 0.002) and post-HAz+HA (134 ± 11 bpm, p < 0.001) than baseline (138 ± 14 bpm). HR was lower post-HAz+HA than post-HAz (p = 0.013). SR was higher post-HAz+HA (1.93 ± 0.47 L·h−1) than post-HAz (1.76 ± 0.43 L·h−1, p = 0.027). Combination HAz and HA increased physiological outcomes above HAz. This method can be used to improve performance and safety in addition to HAz alone.
COR/LEA Proteins as Indicators of Frost Tolerance in Triticeae: A Comparison of Controlled versus Field Conditions

Low temperatures in the autumn induce enhanced expression/relative accumulation of several cold-inducible transcripts/proteins with protective functions from Late-embryogenesis-abundant (LEA) superfamily including dehydrins. Several studies dealing with plants grown under controlled conditions revealed a correlation (significant quantitative relationship) between dehydrin transcript/protein relative accumulation and plant frost tolerance. However, to apply these results in breeding, field experiments are necessary. The aim of the review is to provide a summary of the studies dealing with the relationships between plant acquired frost tolerance and COR/LEA transcripts/proteins relative accumulation in cereals grown in controlled and field conditions. The impacts of cold acclimation and vernalisation processes on the ability of winter-type Triticeae to accumulate COR/LEA proteins are discussed. The factors determining dehydrin relative accumulation under controlled cold acclimation treatments versus field trials during winter seasons are discussed. In conclusion, it can be stated that dehydrins could be used as suitable indicators of winter survival in field-grown winter cereals but only in plant prior to the fulfilment of vernalisation requirement.
Database of Sabethes and Haemagogus (Diptera: Culicidae) in Argentina: Sylvatic Vectors of the Yellow Fever Virus

Abstract Yellow fever is an endemic disease in America caused by an arbovirus that circulates in the sylvatic cycle between nonhuman primates and mosquitoes of the genera Sabethes Robineau-Desvoidy and Haemagogus Williston.The main goal of this work is to report the distribution patterns of these genera in Argentina through an updated database built from published records as well as from own sample collections. These genera are represented in Argentina by a total of 18 species distributed in 14 provinces and 10 ecoregions. The ecoregions with greatest biodiversity were Paranense Forest, Yungas, Campos and Malezales. This database will also allow generating distribution maps for these mosquito genera, and their respective species in Argentina, to establish areas with high probability of viral circulation that are an essential input for vector surveillance, as a tool for public health decision-makers.
Performance evaluation of a staggered three-layer DOI PET detector using a 1 mm LYSO pitch with PETsys TOFPET2 ASIC: comparison of HAMAMATSU and KETEK SiPMs

In this study, we propose a staggered three-layer depth-of-interaction (DOI) detector with a 1 mm crystal pitch and 19.8 mm total crystal thickness for a high-resolution and high-sensitivity small animal in-beam PET scanner. A three-layered stacked LYSO scintillation array (0.9 × 0.9 × 6.6 mm3 crystals, 23 × 22 mm2 surface area) read out by a SiPM array (8 × 8 channels, 3 × 3 mm2 active area/channel and 50 μm microcell size) with data acquisition, signal processing and digitization performed using the PETsys Electronics Evaluations kit (based on the TOFPET v2c ASIC) builds a DOI LYSO detector block. The performance of the DOI detector was evaluated in terms of crystal resolvability, energy resolution, and coincidence resolving time (CRT). A comparative performance evaluation of the staggered three-layer LYSO block was conducted with two different SiPM arrays from KETEK and HAMAMATSU. 100% (KETEK) and 99.8% (HAMAMATSU) of the crystals were identified, by using a flood irradiation the front- and back-side. The average energy resolutions for the 1st, 2nd, and 3rd layers were 16.5 (±2.3)%, 20.9(±4.0)%, and 32.7 (±21.0)% (KETEK) and 19.3 (±3.5)%, 21.2 (±4.1)%, and 26.6 (±10.3)% (HAMAMATSU) for the used SiPM arrays. The measured CRTs (FWHM) for the 1st, 2nd, and 3rd layers were 532 (±111) ps, 463 (±108) ps, and 447 (±111) ps (KETEK) and 402 (±46) ps, 392 (±54) ps, and 408 (±196) ps (HAMAMATSU). In conclusion, the performance of the staggered three-layer DOI detector with 1 mm LYSO pitch and 19.8 mm total crystal thickness was fully characterized. The feasibility of a highly performing readout of a high resolution DOI PET detector via SiPM arrays from KETEK and HAMAMATSU employing the PETsys TOFPET v2c ASIC could be demonstrated.
Characteristics of people on long-acting injectable antipsychotics in Australia: Data from the 2010 National Survey of High Impact Psychosis

Objective: This study investigates (1) the proportion of people with psychosis who are on long-acting injectable antipsychotics; (2) the difference in the demographic, clinical, substance use and adverse drug reaction profiles of people taking long-acting injectables compared to oral antipsychotics; and (3) the differences in the same profiles of those on first-generation antipsychotic versus second-generation antipsychotic long-acting injectables. Methods: Data were collected as part of the Survey of High Impact Psychosis. For this study, participants with diagnoses of schizophrenia or schizoaffective disorder who were on any antipsychotic medication were included (N = 1049). Results: Nearly a third (31.5%) of people with psychosis were on long-acting injectables, of whom 49.7% were on first-generation antipsychotic long-acting injectables and 47.9% were on second-generation antipsychotic long-acting injectables. This contrasts with oral antipsychotics where there was a higher utilisation of second-generation antipsychotics (86.3%). Of note, compared to those on the oral formulation, people on long-acting injectables were almost four times more likely to be under a community treatment order. Furthermore, people on long-acting injectables were more likely to have a longer duration of illness, reduced degree of insight, increased cognitive impairment as well as poor personal and social functioning. They also reported more adverse drug reactions. Compared to those on first-generation antipsychotic long-acting injectables, people on SGA long-acting injectables were younger and had had a shorter duration of illness. They were also more likely to experience dizziness and increased weight, but less likely to experience muscle stiffness or tenseness. Conclusion: Long-acting injectable use in Australia is associated with higher rates of community treatment order use, as well as poorer insight, personal and social performance, and greater cognitive impairment. While long-acting injectables may have the potential to improve the prognosis of people with psychosis, a better understanding of the choices behind the utilisation of long-acting injectable treatment in Australia is urgently needed.
Is serum PSA a predictor of male hypogonadism?

Objective To evaluate the association between some indicators of adiposity and markers of metabolic disorder, evaluate their performance in predicting metabolic syndrome (MetS), and identify their cutoff values among older adults, both in the overall sample and according to sex. Methods Cross-sectional study in 159 older men and women. MetS was defined according to the harmonized criteria. The assessments included waist circumference (WC), waist-to-height ratio (WHtR), conicity index (C index), lipid accumulation product (LAP), visceral adiposity index (VAI), body mass index (BMI), A body shape index (ABSI), area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results LAP and WHtR resulted in the largest AUC values (>0.80). In both sexes, the best indicators were LAP, WC, and WHtR. Both LAP and WHtR presented the highest Youden's index values in the overall sample, with cutoff values of approximately 46.9 (sensitivity 75.0%, specificity 76.7%) and 0.56 (sensitivity 79.3%, specificity 69.8%), respectively. When analyzed by sex, BMI, WC, WHtR, and LAP yielded the highest Youden's index values for the prediction of MetS in older women. Conclusion The indicators LAP, WC, and WHtR performed well in identifying the presence of MetS in older women and could be used to individually or collectively assess and monitor MetS.
Impact of Key Assumptions About the Population Biology of Soil-Transmitted Helminths on the Sustainable Control of Morbidity

Abstract The design and evaluation of control programs for soil-transmitted helminths (STHs) is based on surveillance data recording measurements of egg counts in the stool of infected individuals, which underpin estimates of the prevalence and average intensity of infection. There is considerable uncertainty around these measurements and their interpretation. The uncertainty is composed of several sources of measurement error and the limit of detection of fecal smear tests on the one hand, and key assumptions on STH biology on the other hand, including assumptions on the aggregation of worms within hosts and on the impact of density-dependent influences on worm reproduction. Using 2 independently developed models of STH transmission we show how different aspects of STH biology and human behavior impact on STH surveillance and control programs and how accounting for uncertainty can help to develop optimal and sustainable control strategies to meet the World Health Organization (WHO) morbidity target for STHs.