Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and characterization of a human three-dimensional chondrosarcoma culture for in vitro drug testing

It has been suggested that chemoresistance of chondrosarcoma (CHS), the cartilage tumor, is caused by the phenotypic microenvironmental features of the tumor tissue, mainly the chondrogenic extracellular matrix (ECM), and hypoxia. We developed and characterized a multicellular tumor spheroid (MCTS) of human chondrosarcoma HEMC-SS cells to gain insight into tumor cell biology and drug response. At Day 7, HEMC-SS spheroids exhibited a homogeneous distribution of proliferative Ki-67 positive cells, whereas in larger spheroids (Day 14 and Day 20), proliferation was mainly localized in the periphery. In the core of larger spheroids, apoptotic cells were evidenced by TUNEL assay, and hypoxia by pimonidazole staining. Interestingly, VEGF excretion, evidenced by ELISA on culture media, was detectable from Day 14 spheroids, and increased as the spheroids grew in size. HEMC-SS spheroids synthesized a chondrogenic extracellular matrix rich in glycosaminoglycans and type-2 collagen. Finally, we investigated the sensitivity of Day 7 and Day 14 chondrosarcoma MCTS to hypoxia-activated prodrug TH-302 and doxorubicin compared with their 2D counterparts. As expected, TH-302 exhibited higher cytotoxic activity on larger hypoxic spheroids (Day 14) than on non-hypoxic spheroids (Day 7), with multicellular resistance index (MCRI) values of 7.7 and 9.1 respectively. For doxorubicin, the larger-sized spheroids exhibited higher drug resistance (MCRI of 5.0 for Day 7 and 18.3 for Day 14 spheroids), possibly due to impeded drug penetration into the deep layer of spheroids, evidenced by its auto-fluorescence property. We have developed a model of human chondrosarcoma MCTS that combines an ECM rich in glycosaminoglycans with a high hypoxic core associated with VEGF excretion. This model could offer a more predictive in vitro chondrosarcoma system for screening drugs targeting tumor cells and their microenvironment.
Late Larval Development and Onset of Symbiosis in the Scleractinian Coral Fungia scutaria.

Many corals that harbor symbiotic algae (zooxanthellae) produce offspring that initially lack zooxanthellae. This study examined late larval development and the acquisition of zooxanthellae in the scleractinian coral Fungia scutaria, which produces planula larvae that lack zooxanthellae. Larvae reared under laboratory conditions developed the ability to feed 3 days after fertilization; feeding behavior was stimulated by homogenized Artemia. Larvae began to settle and metamorphose 5 days after fertilization. In laboratory experiments, larvae acquired experimentally added zooxanthellae by ingesting them while feeding. Zooxanthellae entered the gastric cavity and were phagocytosed by endodermal cells. As early as 1 h after feeding, zooxanthellae were observed in both endodermal and ectodermal cells. Larvae were able to form an association with three genetically distinct strains of zooxanthellae. Both zooxanthellate and azooxanthellate larvae underwent metamorphosis, and azooxanthellate polyps were able to acquire zooxanthellae from the environment. Preliminary evidence suggests that the onset of symbiosis may influence larval development; in one study symbiotic larvae settled earlier than aposymbiotic larvae. Protein profiles of eggs and larvae throughout development revealed a putative yolk protein doublet that was abundant in eggs and 1-day-old larvae and was absent by day 6. This study is the first to examine the onset of symbiosis between a motile cnidarian host and its algal symbiont.
Optimal Distributed Control of a Nonlocal Cahn-Hilliard/Navier-Stokes System in Two Dimensions

We study a diffuse interface model for incompressible isothermal mixtures of two immiscible fluids coupling the Navier--Stokes system with a convective nonlocal Cahn--Hilliard equation in two dimensions of space. We apply recently proved well-posedness and regularity results in order to establish existence of optimal controls as well as first-order necessary optimality conditions for an associated optimal control problem in which a distributed control is applied to the fluid flow.
The chandelier neuron in schizophrenia

Markers of GABA neurotransmission between chandelier neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons, are altered in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia. For example, immunoreactivity for the GABA membrane transporter (GAT1) is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. These alterations are most marked in cortical layers 2–3. In addition, other determinants of the function of chandelier cell‐pyramidal neuron synapses, such as ankyrin‐G (which regulates the recruitment of sodium channels to the AIS), are also selectively altered in superficial layer pyramidal neurons in subjects with schizophrenia. Each of these components of chandelier cell‐pyramidal neuron connectivity exhibits distinctive developmental trajectories in the primate DLPFC, suggesting that disturbances in these trajectories could contribute to the pathogenesis of schizophrenia. Recent findings that inputs from neocortical chandelier neurons are excitatory provide new ideas about the role of this circuitry in the pathophysiology of cortical dysfunction in schizophrenia. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 118–127, 2011
Comparison of three instruments in predicting accidental falls in selected inpatients in a general teaching hospital.

Accidental patient falls are becoming a major cause of concern for hospitalized inpatients. It is well known that patients who fall once during their hospital stay are more likely to fall again and that fall rates tend to be higher in hospitalized elderly individuals. Concerned health care team personnel recognize that many accidental patient falls may be predicted and, thus, prevented. The best tool to predict falls has not been determined yet. The purpose of this study was to compare the abilities of the Morse Fall Scale (MFS), the Functional Reach (FR) test, and the nurses' clinical judgment in predicting those inpatients on a rehabilitation unit and a geriatric medical ward who were most likely to fall. A total of 98 patients were screened in a 3-month period, with each patient undergoing all three instruments the same day. The results showed that the two objective standardized tests (i.e., MFS, FR) were time consuming and often inconvenient and were no better at prediction than the clinical judgments made by the primary nurses.
Visual acuity and endothelial cell density with respect to the graft thickness in Descemet's stripping automated endothelial keratoplasty: one year results.

AIM To evaluate the visual acuity and endothelial cell density according to the thickness in Descemet's stripping automated endothelial keratoplasty (DSAEK) one year after surgery. METHODS DSAEK patients' data were reviewed. Thirty-seven eyes of 37 patients who underwent DSAEK for pseudophakic bullous keratopathy (PBK) were included in this study. Graft thickness was measured with optical coherence tomography (OCT) 12mo after DSAEK. Eyes were divided into 3 groups based on the graft thickness: thick (>200 µm), medium-thick (150-200 µm) and thin (<150 µm). Best corrected visual acuity (BCVA), endothelial cells density (ECD) and complications were assessed and comparisons were done between groups. RESULTS There was no significant difference in age, sex, preoperative BCVA, or follow-up period between DSAEK groups. At postoperative 12mo, mean BCVA was 0.28±0.10 in thick graft group, 0.52±0.08 in medium-thick graft group, and 0.72±0.06 in thin graft group. Thin grafts showed better postoperative BCVA as compared with the medium-thick and thick grafts (P=0.001). Thick graft group had 1637.44±88.19-mm(2), medium thick graft had 1764.50±34.28-mm(2) and thin graft group had 1845.30±65.62-mm(2) ECD at 12mo after the surgery. Thin graft group had better ECD at 12mo after surgery (P=0.001). CONCLUSION Thin grafts after DSAEK ensure better visual rehabilitation. Eyes with thin grafts had significantly lesser loss of ECD compared to eyes with medium-thick and thick grafts one year after surgery.
Aspects of designing and evaluating seasonal‐to‐interannual Arctic sea‐ice prediction systems

Using lessons from idealised predictability experiments, we discuss some issues and perspectives on the design of operational seasonal to inter‐annual Arctic sea‐ice prediction systems. We first review the opportunities to use a hierarchy of different types of experiment to learn about the predictability of Arctic climate. We also examine key issues for ensemble system design, such as measuring skill, the role of ensemble size and generation of ensemble members. When assessing the potential skill of a set of prediction experiments, using more than one metric is essential as different choices can significantly alter conclusions about the presence or lack of skill. We find that increasing both the number of hindcasts and ensemble size is important for reliably assessing the correlation and expected error in forecasts. For other metrics, such as dispersion, increasing ensemble size is most important. Probabilistic measures of skill can also provide useful information about the reliability of forecasts. In addition, various methods for generating the different ensemble members are tested. The range of techniques can produce surprisingly different ensemble spread characteristics. The lessons learnt should help inform the design of future operational prediction systems.
Prescribing practices of rural primary health care physicians in Uzbekistan

Doctors prescribe medications for therapeutic indications and to meet patient expectations. Understanding the pattern of prescribing is a necessary precursor for any intervention and for improving prescribing practices. Using the WHO standard methodology, we investigated the prescribing practices of doctors in rural primary health care (PHC) clinics in the Ferghana region of Uzbekistan. Doctors in these clinics may have over‐prescribed, prescribing 2.9 drugs per patient per encounter. Fifty‐seven per cent of these were for injectable drugs, and 57% for antibiotics. Most prescriptions were for name brand (62%) rather than generic drugs.
Strengthening and Rehabilitation of Reinforced Concrete Slabs with Carbon‐Fiber Reinforced Polymers Using a Refined Bond Model

Abstract: Slabs are one of the main load‐bearing elements in nearly every structure. Because of additional live loads or modifications of the building structure these slabs often have to be strengthened. Using externally bonded carbon‐fiber reinforced polymer (CFRP) strips to strengthen existing concrete structures has become common practice. One of the main failure modes is the loss of the composite action between the concrete and the CFRP strip making the bond force transfer very important. This bond force transfer depends on many parameters including the concrete strength, the ratio between shear force, and bending moment. A new parameter recently discovered by the Technische Universität München (TUM) is the deflection of the structural elements themselves. Because of this deflection self‐inducted contact pressure occurs. This contact pressure affects a higher bond transfer. The lower effective depth of slabs compared to beams causes higher deflections. In this article, first a few principles on the strengthening with adhesive‐bonded CFRP strips and the characteristics of the bond are explained. Then, the basics of the bond force transfer, at the end anchorage and in the rest of the element, are summarized. Based on these essentials, as well as numerous experiments, the change in the bond force transfer at the structural element caused by the curvature is then derived. With these findings, a complete verification concept is presented, which is ideal for computerized calculations. This verification concept is finally compared to several full‐scale test results presented in pertinent literature.
Biosynthesis of silver nanoparticles using Saccharomyces cerevisiae

The objectives of this study were the biosynthesis of silver nanoparticles (NPs) by biotransformations using Saccharomyces cerevisiae and analysis of the sizes and shapes of the NPs produced. Dried and freshly cultured S. cerevisiae were used as the biocatalyst. Dried yeast synthesized few NPs, but freshly cultured yeast produced a large amount of them. Silver NPs were spherical, 2–20 nm in diameter, and the NPs with the size of 5.4 nm were the most frequent ones. NPs were seen inside the cells, within the cell membrane, attached to the cell membrane during the exocytosis, and outside of the cells.
Alcoholic cerebellar degeneration: A clinicopathological study of six Japanese autopsy cases and proposed potential progression pattern in the cerebellar lesion

Alcoholic cerebellar degeneration (ACD) is one of the most common neurological complications in alcoholics. As far as we know, however, only four Japanese autopsy cases of ACD have been reported, and only limited clinicopathological data on this disease are now available in Japan. The aims of this study were: (i) to examine the clinicopathological correlation of six Japanese autopsy cases of ACD, including three asymptomatic cases; and (ii) to elucidate the pattern of progression of the cerebellar lesion in ACD. All six alcoholics were histopathologically diagnosed as having “pure” ACD without Wernicke’s encephalopathy. The characteristics of the topographical distribution of the cerebellar lesion were as follows. Symptomatic cases (cases 1–3) showed more severe and widespread change than asymptomatic cases (cases 4–6). Even in case 6, which had the mildest lesion, the anterior vermis developed a moderate change (Purkinje cell loss and narrowing of the molecular layer). In cases 4 and 5 with more severe and widespread lesions, the superior and posterior vermis and the adjacent regions of the superior hemisphere, including the anterior lobe and simple lobule, were involved. In all symptomatic cases, the anterior superior hemisphere had severe lesions involving the granular cell layer. In contrast to asymptomatic cases, all symptomatic cases also had severe to moderate lesions in the anterior inferior hemisphere. In cases 1 and 2 with the most severe lesions, the moderate to severe changes were distributed in the posterior and inferior portions of both the vermis and hemisphere. These findings suggest that in ACD, severe lesions successively develop: (i) in the anterior superior vermis; (ii) anterior superior hemisphere; (iii) anterior inferior hemisphere; and (iv) anterior inferior vermis. In addition, cerebellar symptoms may frequently occur if the anterior superior hemisphere and anterior inferior hemisphere, in addition to the anterior superior vermis, are involved.
Porcine endogenous retroviruses inhibit human immune cell function: risk for xenotransplantation?

Transgenic pigs are currently the most favored potential source of organs for xenotransplantation. Like all mammalian species they all harbor endogenous retroviruses in their genome. These porcine endogenous retroviruses (PERVs) are produced from several primary cells and cell lines and are able to infect human cells. Here we demonstrate that different pig strains and different animals of one strain differ in their ability to produce PERVs from normal blood cells. We report that purified PERV particles show a protein pattern typical for type C retroviruses and are antigenically related to mammalian leukemia viruses. Like most retroviruses, purified PERVs and peptides derived from the highly conserved immunosuppressive domain of their transmembrane envelope protein inhibit human immune cell functions. This indicates that high titer replication of PERVs in the transplant recipient could therefore lead to an immunodeficiency disease.
Comparison of Surface Roughness and Bacterial Adhesion Between Cosmetic Contact Lenses and Conventional Contact Lenses

Objective: To compare physical characteristics of cosmetic contact lenses (Cos-CLs) and conventional contact lenses (Con-CLs) that might affect susceptibility to bacterial adhesion on the contact lens (CL) surface. Methods: Surface characteristics of Cos-CLs and Con-CLs made from the same material by the same manufacturer were measured by atomic force microscopy (AFM) and scanning electron microscopy. To determine the extent and rate of bacterial adhesion, Cos-CL and Con-CL were immersed in serum-free Roswell Park Memorial Institute media containing Staphylococcus aureus or Pseudomonas aeruginosa. Additionally, the rate of removal of adherent bacteria was evaluated using hand rubbing or immersion in multipurpose disinfecting solutions (MPDS). Results: The mean surface roughness (root mean square and peak-to-valley value) measured by AFM was significantly higher for Cos-CL than for Con-CL. At each time point, significantly more S. aureus and P. aeruginosa adhered to Cos-CL than to Con-CL, which correlated with the surface roughness of CL. In Cos-CL, bacteria were mainly found on the tinted surface rather than on the noncolored or convex areas. Pseudomonas aeruginosa attached earlier than S. aureus to all types of CL. However, P. aeruginosa was more easily removed from the surface of CL than S. aureus by hand rubbing or MPDS soaking. Conclusions: Increased surface roughness is an important physical factor for bacterial adhesion in Cos-CL, which may explain why rates of bacterial keratitis rates are higher in Cos-CL users in CL physical characteristics.
The Endogenous Cannabinoid System Modulates Nicotine Reward and Dependence

A growing body of evidence suggests that the endogenous cannabinoid system modulates the addictive properties of nicotine, the main component of tobacco that produces rewarding effects. In our study, complementary transgenic and pharmacological approaches were used to test the hypothesis that the endocannabinoid system modulates nicotine reward and dependence. An acute injection of nicotine elicited normal analgesic and hypothermic effects in cannabinoid receptor (CB)1 knockout (KO) mice and mice treated with the CB1 antagonist rimonabant. However, disruption of CB1 receptor signaling blocked nicotine reward, as assessed in the conditioned place preference (CPP) paradigm. In contrast, genetic deletion, or pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for catabolism of the endocannabinoid anandamide, enhanced the expression of nicotine CPP. Although the expression of spontaneous nicotine withdrawal (14 days, 24 mg/kg/day nicotine) was unaffected in CB1 KO mice, acute administration of rimonabant (3 mg/kg) ameliorated somatic withdrawal signs in wild-type mice. Increasing endogenous levels of anandamide through genetic or pharmacological approaches exacerbated the physical somatic signs of spontaneous nicotine withdrawal in a milder withdrawal model (7 days, 24 mg/kg/day nicotine). Moreover, FAAH-compromised mice displayed increased conditioned place aversion in a mecamylamine-precipitated model of nicotine withdrawal. These findings indicate that endocannabinoids play a role in the rewarding properties of nicotine as well as nicotine dependence liability. Specifically, increasing endogenous cannabinoid levels magnifies, although disrupting CB1 receptor signaling, attenuates nicotine reward and withdrawal. Taken together, these results support the hypothesis that cannabinoid receptor antagonists may offer therapeutic advantages to treat tobacco dependence.
Role of the internet in communication between patient and surgeon before rhinoplasty

Abstract Our aim was to assess the use of the internet for patients considering rhinoplasty, to identify the influence of the medical information acquired, and to review favourable and adverse aspects of the acquired knowledge online. A prospective study was conducted on 106 patients listed for post-traumatic or aesthetic rhinoplasty. We surveyed 18 questions to evaluate demographic and sociological data, and the importance of the information acquired from the internet. Respondents searched online for description of operations, contact with other patients, and with the surgeon, and for preoperative and postoperative pictures. Patients who were considering aesthetic rhinoplasty were given medical information by a third party or from the internet, and those who were having post-traumatic corrections were usually referred by their general practitioner. We conclude that the internet is an important source of medical information about rhinoplasty for patients, but it does not contain enough data. It plays an essential part, particularly for those patients having the operation for aesthetic reasons, in contrast to those having post-traumatic correction. Reviewing and certifying the plastic surgical websites would validate certified services. Independent, direct contact with the doctor helps patients to obtain more accurate, personalised knowledge. In addition, surgeons should support patients by giving them a list of verified websites, which would contribute to increased doctor-patient communication.
Monotherapy versus combination antimicrobial therapy for pneumococcal pneumonia

Purpose of review In the past 5 years a number of studies have suggested that combination antibiotic therapy may be superior to monotherapy for pneumococcal pneumonia. This review outlines the major findings for and against combination therapy. Recent findings The evidence for a benefit of multiple antibiotics is strongest in patients with severe, bacteremic pneumococcal disease. All of these studies have limitations due to their retrospective or uncontrolled design. Unfortunately prospective, randomized, double-blind, controlled studies have not been performed in an appropriately severe disease cohort and are therefore urgently needed. Several viable mechanisms for a benefit of combination therapy have been proposed, especially related to non-antibiotic effects of macrolides. There is also some evidence that third-generation cephalosporins may be superior to penicillins as the non-macrolide component of combination therapy. Summary Although based on retrospective and observational data, there is substantial evidence to support combination antibiotic therapy, at least in patients with severe bacteremic pneumococcal pneumonia. What evidence is available supports a cephalosporin/macrolide combination as being associated with the highest survival, but proper prospective studies in patients with severe pneumonia are urgently required to clarify this issue.