Miracle-dz/UniFAR-FTUs huggingface dataset:
The technologies used for developing orally disintegrating tablets: A review

The technologies used for developing orally disintegrating tablets: A review Orally disintegrating tablets (ODTs), also known as fast melts, quick melts, fast disintegrating and orodispersible systems, have the unique property of disintegrating in the mouth in seconds without chewing and the need of water and are thus assumed to improve patient compliance. Conventional methods like direct compression, wet granulation, moulding, spray-drying, freeze-drying and sublimation were used to prepare ODTs. New advanced technologies like Orasolv®, Durasolv®, Wowtab®, Flashtab®, Zydis®, Flashdose®, Oraquick®, Lyoc®, Advatab®, Frosta®, Quick-Disc® and Nanomelt® have been introduced by some pharmaceutical companies for the production of ODTs. The main objective of this review is to give a comprehensive insight into conventional and recent technologies used for the preparation of ODTs. Pregled tehnologija priprave oralno raspadljivih tableta Oralno raspadljive tablete (ODT), poznate i kao lako topljive tablete, brzo raspadljive i kao orodisperzibilni sustavi, imaju jedinstveno svojstvo trenutnog raspadanja u ustima, bez žvakanja i bez potrebe uzimanja vode, što poboljšava pacijentovu suradljivost. U pripravi ODT koriste se uobičajene metode kao što su izravna kompresija, vlažna granulacija, kalupljenje, sušenje sprejanjem, sušenje smrzavanjem i sublimacija, a u njihovoj proizvodnji napredne tehnologije kao što su Orasolv®, Durasolv®, Wowtab®, Flashtab®, Zydis®, Flashdose®, Oraquick®, Lyoc®, Advatab®, Frosta®, Quick-Disc® i Nanomelt®. Cilj ovog rada je dati uvid u uobičajene i novije tehnologije u pripravi ODT.
Ambulatory care-sensitive emergency visits among patients with medical home access.

OBJECTIVES To characterize patterns of emergency department (ED) utilization for ambulatory care-sensitive conditions (ACSCs) among patients with established care within a patient-centered medical home. STUDY DESIGN Retrospective chart review using Michigan Medicine's (formerly University of Michigan Health System) electronic health record. METHODS Ten general medicine (GM) physicians reviewed 256 ambulatory care-sensitive ED encounters that occurred between January 1, 2014, and December 31, 2014, among patients of a GM medical home. Physician reviewers abstracted from the medical record the day and time of ED presentation and the source of ED referral (eg, patient self-referral vs physician referral). Physicians assessed the appropriateness of the care location (eg, ED vs primary care). Interrater reliability was assessed using the kappa statistic, and the χ2 test was used to assess differences in the appropriateness of the care location according to ED referral source. RESULTS Compared with all other days of the week, the fewest number of ED visits occurred on weekend days, and nearly half of patients (48%) presented to the ED after daytime hours, which were defined as 8 am to 3:59 pm. The majority (n = 185; 72%) of patients were self-referred to the ED. The ED was considered the appropriate care location in more than half (53%) of the reviewed cases. Among the 119 cases considered appropriate for GM management, the majority (86%) were self-referred to the ED. CONCLUSIONS Patients with ACSCs often presented to the ED without contacting their medical home. Frequently, the ED is the most appropriate location given symptoms at presentation.
Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation

Significance We have long known that thyroid hormone (TH) stimulates formation of red blood cells and patients with thyroid diseases are often anemic, but the underlying molecular mechanisms are unclear. This study uses pharmacologic and genetic approaches in primary cells and animal models to demonstrate essential roles of nuclear receptor coactivator 4 (NCOA4) and TH in late erythropoiesis. We show that TH is essential for the last steps in formation of red cells in culture, and that treatment of cells with drugs that activate a particular nuclear TH receptor, TRβ, stimulates erythroid differentiation and alleviates anemic symptoms in a chronic anemia mouse model, indicating potential clinical applications. Further, we show that TRβ functions together with NCOA4 to regulate red cell formation. An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression. To identify factors that cooperate with TRβ during human erythroid terminal differentiation, we conducted RNA-seq in human reticulocytes and identified nuclear receptor coactivator 4 (NCOA4) as a critical regulator of terminal differentiation. Furthermore, Ncoa4−/− mice are anemic in perinatal periods and fail to respond to TH by enhanced erythropoiesis. Genome-wide analysis suggests that TH promotes NCOA4 recruitment to chromatin regions that are in proximity to Pol II and are highly associated with transcripts abundant during terminal differentiation. Collectively, our results reveal the molecular mechanism by which TH functions during red blood cell formation, results that are potentially useful to treat certain anemias.
Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children

Iron deficiency is the most common micronutrient deficiency in the world. Women of reproductive age and young children are particularly vulnerable. Iron deficiency in late prenatal and early postnatal periods can lead to long-term neurobehavioral deficits, despite iron treatment. This may occur because screening and treatment of iron deficiency in children is currently focused on detection of anemia and not neurodevelopment. Anemia is the end-stage state of iron deficiency. The brain becomes iron deficient before the onset of anemia due to prioritization of the available iron to the red blood cells (RBCs) over other organs. Brain iron deficiency, independent of anemia, is responsible for the adverse neurological effects. Early diagnosis and treatment of impending brain dysfunction in the pre-anemic stage is necessary to prevent neurological deficits. The currently available hematological indices are not sensitive biomarkers of brain iron deficiency and dysfunction. Studies in non-human primate models suggest that serum proteomic and metabolomic analyses may be superior for this purpose. Maternal iron supplementation, delayed clamping or milking of the umbilical cord, and early iron supplementation improve the iron status of at-risk infants. Whether these strategies prevent iron deficiency-induced brain dysfunction has yet to be determined. The potential for oxidant stress, altered gastrointestinal microbiome and other adverse effects associated with iron supplementation cautions against indiscriminate iron supplementation of children in malaria-endemic regions and iron-sufficient populations.
A Comprehensive Study of Mass Murder Precipitants and Motivations of Offenders

Much speculation has been made in the media as to the causes of mass murder in the United States, yet little empirical research exists to verify factors leading to violence. Prior research primarily relies on case study methodologies or small data sets, but none have focused on the underlying issues observed in a comprehensive national sample. Data for the current study include 152 mass murders reported through the FBI’s Supplementary Homicide Reports and USA Today from 2007 to 2011, which were then matched with media reports for each event. The current study shows that mass murders typically occur following a triggering event, are committed by non-strangers, and are rarely committed by persons with mental illnesses. A more realistic image of these incidents is critical, as misperceptions of offenders and case characteristics can improperly shape public policies.
Accounting for the Varying Supply of Solar Energy When Designing Wireless Access Networks

Traditionally, we rely highly upon fossil fuels for our energy provisioning, but there are drawbacks to using these fossil fuels: the risk for depletion in the future; the increased cost as already observed during the last few years, and the high impact on climate change. One virtually carbon-neutral alternative to fossil fuels are renewable energy sources, like solar energy. In this paper, we investigate the energy and network performance of a wireless access network powered by the traditional electricity grid and a photovoltaic panel system. An energy-aware management system for the future wireless access networks is proposed. This system consists of the management of the energy provisioning and storage system and the application of the proposed energy-saving strategies which aim to reduce the energy footprint through the traditional grid in case a renewable energy shortage occurs. To evaluate the network’s performance, this paper proposes a deployment tool with the above described energy-aware management system. The results show that it is promising to further investigate a more evolved and complex energy-aware management system.
Denosumab: non-surgical treatment option for selective arterial embolization resistant aneurysmal bone cyst of the spine and sacrum. Case report.

OBJECTIVE Aneurysmal Bone Cyst (ABC) is a cystic lesion of bone, occurring in 70% of cases as a primary lesion. Even if the metaphyseal region of long bones is more frequently involved, vertebral localization is not rare: ABC represents 15% of all primary spine and sacral tumours. Selective arterial embolization (SAE) represents the first treatment option for vertebral ABC. However, in few cases, multiple SAEs are not possible. The aim of this work is to report two cases of vertebral ABC unresponsive to SAE positively treated with Denosumab. PATIENTS AND METHODS Two patients affected by ABC of the lumbar spine were treated by SAE without any response. Thus, the patients were submitted to an off-label treatment with Denosumab, following the same protocol already used in case of Giant Cell Tumour (GCT): 120 mg once a week for 4 weeks consecutively, then once every 40 days. RESULTS In both cases, patients resulted to be pain-free after 11-13 Denosumab administrations and CT scan showed almost complete ossification of the lesions. CONCLUSIONS The two cases reported here are not conclusive but they may support the project of a prospective study to confirm the effectiveness of Denosumab in ABC treatment as an alternative to SAE.
A Zero-Knowledge Version of vSQL

Zero-knowledge arguments of knowledge are powerful cryptographic primitives that allow a computationally strong prover to convince a weaker verifier for the validity of an NP statement, without revealing anything about the corresponding witness (beyond its existence). Most state-of-the art implementations of such arguments that achieve succinct communication and verification cost follow the quadratic arithmetic program paradigm. One notable exception to this is the vSQL system of [Zhang et al. IEEE S&P 2017] which takes an entirely different approach resulting is significantly fewer cryptographic operations. However, it has the notable downside that is not zero-knowledge (i.e., it does not hide the witness from the verifier), a property that has proven to be of utmost importance in many application (e.g., in cryptocurrencies). In this work, we present a zero-knowledge version of the argument upon which vSQL is based. Our construction utilizes two separate techniques: (i) a novel zero-knowledge verifiable polynomial delegation protocol, and (ii) running parts of the argument of vSQL over homomorphic commitments, thus hiding the committed values.
Avian thermoregulation in the heat: phylogenetic variation among avian orders in evaporative cooling capacity and heat tolerance

ABSTRACT Little is known about the phylogenetic variation of avian evaporative cooling efficiency and heat tolerance in hot environments. We quantified thermoregulatory responses to high air temperature (Ta) in ∼100-g representatives of three orders, namely, the African cuckoo (Cuculus gularis, Cuculiformes), lilac-breasted roller (Coracias caudatus, Coraciiformes) and Burchell's starling (Lamprotornis australis, Passeriformes). All three species initiated respiratory mechanisms to increase evaporative heat dissipation when body temperature (Tb) approached 41.5°C in response to increasing Ta, with gular flutter observed in cuckoos and panting in rollers and starlings. Resting metabolic rate and evaporative water loss increased by quantitatively similar magnitudes in all three species, although maximum rates of evaporative water loss were proportionately lower in starlings. Evaporative cooling efficiency [defined as the ratio of evaporative heat loss (EHL) to metabolic heat production (MHP)] generally remained below 2.0 in cuckoos and starlings, but reached a maximum of ∼3.5 in rollers. The high value for rollers reveals a very efficient evaporative cooling mechanism, and is similar to EHL/MHP maxima for similarly sized columbids which very effectively dissipate heat via cutaneous evaporation. This unexpected phylogenetic variation among the orders tested in the physiological mechanisms of heat dissipation is an important step toward determining the evolution of heat tolerance traits in desert birds. Summary: Avian evaporative cooling efficiency and heat tolerance display substantial taxonomic variation that are, unexpectedly, not systematically related to the use of panting versus gular flutter processes.
Role of the EZH2/miR-200 axis in STAT3-mediated OSCC invasion

Abnormal activation of signal transducer and activator of transcription 3 (STAT3) serves a pivotal role in oral squamous cell carcinoma (OSCC) tumor cell invasion into normal tissues or distant organs. However the downstream regulatory network of STAT3 signaling remains unclear. The present study aimed to investigate the potential mechanism underlying how STAT3 triggers enhancer of zeste homolog 2 (EZH2) expression and inhibits microRNA (miR)-200a/b/429 expression in SCC25 and SCC15 cells in vitro and in vivo. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect expression, and numerous functional tests were conducted to explore cancer metastasis. The results indicated that when STAT3 signaling activity was attenuated by Stattic or enhanced with a STAT3 plasmid, the EZH2/miR-200 axis was markedly altered, thus resulting in modulation of the invasion and migration of OSCC cell lines. In addition, loss of function of EZH2 compromised the oncogenic role of STAT3 in both cell lines. F-actin morphology and the expression of epithelial-mesenchymal transition markers were also altered following disruption of the STAT3/EZH2/miR-200 axis. An orthotopic tumor model derived from SCC15 cells was used to confirm that targeting STAT3 or EZH2 suppressed OSCC invasion in vivo. In conclusion, the EZH2/miR-200 axis was revealed to mediate antitumor effects by targeting STAT3 signaling; these findings may provide a novel therapeutic strategy for the treatment of OSCC.
Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)‐α‐lipoic acid

Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age‐related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as mea¬sured by the rates of 2,7‐dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not α‐tocopherol. A significant age‐related increase (P = 0.05) in steadystate levels of oxidative DNA damage was observed, as monitored by 8‐oxo‐2′‐deoxyguanosine levels. To inves¬tigate whether dietary supplementation with (R)‐α‐lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN‐93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA‐supplemented rats ex¬hibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial‐induced oxidative stress, which is signif¬icantly attenuated by lipoic acid supplementation. — Suh, J. H. , Shigeno, E. T. , Morrow, J. D. , Cox, B. , Rocha, A. E. , Frei, B. , Hagen, T. M. Oxidative stress in the aging rat heart is reversed by dietary supplementationwith (R)‐α‐lipoic acid. FASEB J. 15, 700‐706 (2001)
Investigating the Influence of Biological Sex on the Behavioral and Neural Basis of Face Recognition

Abstract There is interest in understanding the influence of biological factors, like sex, on the organization of brain function. We investigated the influence of biological sex on the behavioral and neural basis of face recognition in healthy, young adults. In behavior, there were no sex differences on the male Cambridge Face Memory Test (CFMT)+ or the female CFMT+ (that we created) and no own-gender bias (OGB) in either group. We evaluated the functional topography of ventral stream organization by measuring the magnitude and functional neural size of 16 individually defined face-, two object-, and two place-related regions bilaterally. There were no sex differences in any of these measures of neural function in any of the regions of interest (ROIs) or in group level comparisons. These findings reveal that men and women have similar category-selective topographic organization in the ventral visual pathway. Next, in a separate task, we measured activation within the 16 face-processing ROIs specifically during recognition of target male and female faces. There were no sex differences in the magnitude of the neural responses in any face-processing region. Furthermore, there was no OGB in the neural responses of either the male or female participants. Our findings suggest that face recognition behavior, including the OGB, is not inherently sexually dimorphic. Face recognition is an essential skill for navigating human social interactions, which is reflected equally in the behavior and neural architecture of men and women.
Stability and Throughput of Random Access With CS-Based MUD for MTC

Recently, compressive random access has been considered for machine-type communications (MTC) as it has a potential to support massive connectivity by exploiting the sparsity of device activity. However, its performance limitations are not well studied yet compared with other well-known candidates for MTC, e.g., multichannel ALOHA. In this paper, we investigate the stability of compressive random access with a controlled access probability strategy under ideal conditions, and derive the maximum stable throughput, which shows that the maximum stable throughput of compressive random access is higher than that of multichannel ALOHA by a factor of 2. We also carry out simulations to see the performance of compressive random access under more realistic conditions with low-complexity multiuser detection (MUD) algorithms. Based on analysis and simulation results, we can claim that compressive random access can support more devices than conventional multichannel ALOHA and is well-suited for MTC.
Proactive interference and concurrent inhibitory processes do not differentially affect item and associative recognition: Implication for the age-related associative memory deficit

ABSTRACT Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. (2000). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170–1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes.
Antibacterial Properties and Effects of Fruit Chilling and Extract Storage on Antioxidant Activity, Total Phenolic and Anthocyanin Content of Four Date Palm (Phoenix dactylifera) Cultivars

Phoenix dactylifera or date palm fruits are reported to contain natural compounds that exhibit antioxidant and antibacterial properties. This research aimed to study the effect of fruit chilling at 4 °C for 8 weeks, extract storage at −20 °C for 5 weeks, and extraction solvents (methanol or acetone) on total phenolic content (TPC), antioxidant activity and antibacterial properties of Saudi Arabian P. dactylifera cv Mabroom, Safawi and Ajwa, as well as Iranian P. dactylifera cv Mariami. The storage stability of total anthocyanin content (TAC) was also evaluated, before and after storing the extracts at −20 °C and 4 °C respectively, for 5 weeks. Mariami had the highest TAC (3.18 ± 1.40 mg cyd 3-glu/100 g DW) while Mabroom had the lowest TAC (0.54 ± 0.15 mg cyd 3-glu/100 g DW). The TAC of all extracts increased after storage. The chilling of date palm fruits for 8 weeks prior to solvent extraction elevated the TPC of all date fruit extracts, except for methanolic extracts of Mabroom and Mariami. All IC50 values of all cultivars decreased after the fruit chilling treatment. Methanol was a better solvent compared to acetone for the extraction of phenolic compounds in dates. The TPC of all cultivars extracts decreased after 5 weeks of extract storage. IC50 values of all cultivars extracts increased after extract storage except for the methanolic extracts of Safawi and Ajwa. Different cultivars exhibited different antibacterial properties. Only the methanolic extract of Ajwa exhibited antibacterial activity against all four bacteria tested: Staphylococcus aureus, Bacillus cereus, Serratia marcescens and Escherichia coli. These results could be useful to the nutraceutical and pharmaceutical industries in the development of natural compound-based products.