Miracle-dz/UniFAR-FTUs huggingface dataset:
Calcium Sulfates: What Is the Evidence?

Calcium sulphate has been used extensively as a bioabsorbable bone substitute for 90 years. Its advantages include its low cost, ready availability and unlimited supply, lack of donor site morbidity, use as a delivery vehicle for other compounds (especially antibiotics), inherent osteoconductive properties (based on a structure similar to bone), and its proven safety record. We sought to determine the evidence-based medical studies (prospective and/or randomized clinical trials) that support the use of calcium sulphate as a bioabsorbable bone substitute. At the present time, the majority of reports are basic science investigations, animal studies, and retrospective clinical reviews of varying degrees of quality. Multiple retrospective reviews reveal that calcium sulphate is an effective void-filler in contained bony defects such as metaphyseal voids after impacted fracture reduction (calcaneus, tibial plateau), simple bone cysts, or posttraumatic defects. Three case series examining the use of calcium sulphate in the treatment of bone nonunions revealed a significant failure rate, suggesting that this material, used in isolation, is not optimal to promote union in that setting. A low but consistent complication rate, specifically serous drainage from the wound as the calcium sulphate absorbs, has been reported. This complication is higher when the material is used in higher volumes (greater than 20 mL) or in subcutaneous bones (tibia, ulna). There is some Level I to II evidence (one randomized trial, one case-control study, one prospective cohort study) that antibiotic-impregnated bioabsorbable calcium sulphate has the potential to reduce the number of procedures and surgical morbidity associated with the surgical treatment of chronic osteomyelitis and infected nonunion while maintaining a high rate of infection eradication. Calcium sulphate remains an inexpensive, safe, reliable bone void filler that can also serve as a absorbable delivery vehicle for antibiotics or other compounds. Further high-quality randomized and prospective clinical trials are required to define the role of calcium sulphate in modern orthopaedics.
Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.

AIMS The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. METHODS AND RESULTS Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. CONCLUSION Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.
In Vitro and In Vivo Photosensitization by Protoporphyrins Possessing Different Lipophilicities and Vertical Localization in the Membrane

Abstract Photodynamic therapy (PDT) is being evaluated in clinical trials for treatment of various oncologic and ophthalmic diseases. The main cause for cell inactivation and retardation of tumor growth after photoactivation of sensitizers is very short-lived singlet oxygen molecules that are produced and have limited diffusion distances. In this paper we show that the extent of biological damage can be modulated by using protoporphyrin, which was modified to increase its lipophilicity, and which also places the tetrapyrrole core deeper within the membrane by the carboxylate groups being anchored at the lipid:water interface. The uptake of the parent molecule (PPIX) and its diheptanoic acid analogue (PPIXC6) by WiDR and CT26 cells was investigated by fluorescence microscopy and by fluorescence intensity from the cells. The uptake of PPIXC6 increased almost linearly with incubation length for over 24 h, whereas for PPIX only 1 h was needed to reach maximal intracellular concentration. Fluorescence microscopy of both cell lines indicated that both drugs were distributed diffusely in the plasma membrane and cytoplasm, but remained outside the nucleus. The efficiency of in vitro inactivation of WiDr and CT26 cells increased with the length of the alkylcarboxylic chain. Tumors in mice that were treated with PPIX-PDT grew more slowly than control tumors. However, tumors that were given PPIXC6 followed by light exposure showed a significant delay in their growth.
Does the crowd matter in refereeing decisions? Evidence from Spanish soccer

This paper analyses referee home bias with data from the First Division of the Spanish Football League between the 2002/03 and 2009/10 seasons. The aim is to assess the behaviour of the referee in relation to two decisions, namely free kicks awarded and players booked. The main contribution of this paper is the way in which it analyses referee bias; free kicks and bookings are not considered independent elements, instead it is presumed that the number of free kicks awarded has an impact on the cards shown. Regarding methodology, two random effects panel-data regression models are estimated. The results obtained do not confirm, at least in the period under analysis, that Spanish soccer referees have been biased in favour of the home team when it comes to awarding free kicks. However, once a free kick has been awarded, there does appear to be a referee home bias in the disciplinary sanctions taken against a player for committing a foul. These findings suggest that when there is a large crowd in the stadium, the referee tends to be more inclined to book away team players than home players. A reasonable hypothesis that could explain this result is that the amount of time the referee has to make a decision affects the final outcome. While referees are not biased when it comes to awarding a free kick, they are when given more time to make a decision, as there are more opportunities for social pressure to work in favour of the home team.
Acute Kidney Injury in the Critically Ill Patient

Purpose: A comprehensive review of the literature to provide a focused and thorough update on the issue of acute kidney injury (AKI) in the surgical patient. Methods: A PubMed and Medline search was performed and keywords included AKI, renal failure, critically ill, and renal replacement therapy (RRT). Principal Findings: A common clinical problem encountered in critically ill patients is AKI. The recent consensus definitions for the diagnosis and classification of AKI (ie, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease/Acute Kidney Injury Network) have enabled us to standardize the severity of AKI and facilitate strategies for prevention. These strategies as well as treatment modalities of AKI are discussed. We provide a concise overview of the issue of renal failure. We describe strategies for prevention including types of fluids used for resuscitation, timing of initiation of RRT, and different treatment modalities currently available for clinical practice. Conclusions: Acute kidney injury is a common problem in the critically ill patient and is associated with worse clinical outcomes. A standardized definition and staging system has led to improved diagnosis and understanding of the pathophysiology of AKI. There are many trials leading to improved prevention and management of the disease.
The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Anti–PD-1 Response in Patients with Renal Cell Carcinoma

Tumor cell–intrinsic metabolic factors, a hallmark of kidney cancer, may contribute to anti–PD-1 treatment resistance. This intersection between cancer immunology and metabolism supports an emerging theme of discovery for tumor type–specific biomarkers for immune checkpoint blocking therapies. Pretreatment tumor PD-L1 expression has been shown to correlate with response to anti–PD-1/PD-L1 therapies. Yet, most patients with PD-L1+ tumors do not respond to treatment. The current study was undertaken to investigate mechanisms underlying the failure of PD-1–targeted therapies in patients with advanced renal cell carcinoma (RCC) whose tumors express PD-L1. Formalin-fixed, paraffin-embedded pretreatment tumor biopsies expressing PD-L1 were derived from 13 RCC patients. RNA was isolated from PD-L1+ regions and subjected to whole genome microarray and multiplex quantitative (q)RT-PCR gene expression analysis. A balance between gene expression profiles reflecting metabolic pathways and immune functions was associated with clinical outcomes following anti–PD-1 therapy. In particular, the expression of genes involved in metabolic and solute transport functions such as UGT1A family members, also found in kidney cancer cell lines, was associated with treatment failure in patients with PD-L1+ RCC. Conversely, tumors from responding patients overexpressed immune markers such as BACH2, a regulator of CD4+ T-cell differentiation, and CCL3 involved in leukocyte migration. These findings suggest that tumor cell–intrinsic metabolic factors may contribute to treatment resistance in RCC, thus serving as predictive markers for treatment outcomes and potential new targets for combination therapy regimens with anti–PD-1. Cancer Immunol Res; 4(9); 726–33. ©2016 AACR. See related Spotlight by Ohashi, p. 719.
Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase

Purpose. Rho-associated coiled coil-forming protein kinase (ROCK) is a downstream target of a small GTPase, Rho. The kinase has been reported to regulate actomyosin-based contractility of smooth muscles by modulation of myosin phosphatase activity. Contractility of ciliary muscle could be implicated in regulation of intraocular pressure while that of ocular vessels could affect blood flow to retina. The present study has been performed to investigate the effect of a ROCK inhibitor on intraocular pressure in rabbits. Methods. An inhibitor of ROCK, Y-27632, was dissolved in an ophthalmic solution and topically administered to the eye of a Japanese white rabbit. Intraocular pressure was measured by pneumatonography (n = 12, 24 eyes). Constriction of ciliary muscle was measured by the Magnus method using 12 eyes. Results. Topical application of 0.1 and 0.03% Y-27632 significantly decreased the intraocular pressure, with maximum decreases of 5.3 and 4.3 mm Hg after 90 minutes compared with the control eye. Y-27632 inhibited the carbachol-induced constriction of rabbit ciliary muscle. Conclusions. The ROCK inhibitor reduced intraocular pressure in rabbits by topical instillation. The inhibitor relaxed the excised ciliary muscle which was previously constricted by carbachol suggesting that the inhibitor acts to increase the uveoscleral outflow. Our results suggest that the ROCK inhibitor is a promising treatment for glaucoma therapy in the next generation.
Impact of the SpeB Protease on Binding of the Complement Regulatory Proteins Factor H and Factor H-Like Protein 1 by Streptococcus pyogenes

ABSTRACT Microbial pathogens often exploit human complement regulatory proteins such as factor H (FH) and factor H-like protein 1 (FHL-1) for immune evasion. Fba is an FH and FHL-1 binding protein expressed on the surface of the human pathogenic bacterium Streptococcus pyogenes, a common agent of pharyngeal, skin, and soft-tissue infections. Fba has been shown to contribute to phagocytosis resistance, intracellular invasion, and virulence in mice. Here, we look at the role of Fba in recruitment of FH and FHL-1 by five serotype M1 isolates of streptococci. Inactivation of fba greatly inhibited binding of FH and FHL-1 by all isolates, indicating that Fba is a major FH and FHL-1 binding factor of serotype M1 streptococci. For three isolates, FH binding was significantly reduced in stationary-phase cultures and correlated with high levels of protease activity and SpeB (an extracellular cysteine protease) protein in culture supernatants. Analysis of a speB mutant confirmed that SpeB accounts for the loss of Fba from the cell surface, suggesting that the protease may modulate FH and FHL-1 recruitment during infection. Comparisons of fba DNA sequences revealed that the FH and FHL-1 binding site in Fba is conserved among the M1 isolates. Although the ligand binding site is not strictly conserved in Fba from a serotype M49 isolate, the M49 Fba protein was found to bind both FH and FHL-1. Collectively, these data indicate that binding of FH and FHL-1 is a conserved function of Fba while modulation of Fba function by SpeB is variable.
Infectious episodes before and after a marathon race

The aim of this study was to investigate the incidence of self‐reported infectious episodes (IE) during 3 weeks before (pre‐IE) and 3 weeks after (post‐IE) a marathon race and relate these figures to training status, running time, socioeconomic and demographic factors. Two questionnaires, including questions about important factors for IE incidence, were given to a representative cohort of 1694 runners (17% of all finishers) in the Stockholm Marathon 2000.
Inhibition of chemotherapy-induced apoptosis of testicular cells by squid ink polysaccharide

The aim of this study was to determine the mechanisms driving the protective effects of squid ink polysaccharide (SIP) against cyclophosphamide (CP)-induced testicular damage, focusing on germ cells. In the testes of mice exposed to CP and/or SIP, the present study examined the levels of reactive oxygen species (ROS) and malondialdehyde, activity of superoxide dismutase levels, protein expression levels of B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax), and total Caspase 3, activation of p-p38 and p-Akt proteins, and tissue morphology. The findings indicated that CP induced ROS production and oxidative stress, resulting in testicular damage. However, under administration of SIP, oxidative stress was impaired and the testicular toxicity induced by CP was weakened, which implied that SIP may have an important role in preventing chemotherapeutic damage to the male reproductive system via promoting antioxidant ability. Furthermore, the altered expression levels, including the upregulation of Bax and Caspase 3, downregulation of Bcl-2 and the increased Bax/Bcl-2 ratio, indicated that apoptosis occurred in CP exposed testes of mice; however, the alterations were reversed in mice treated with SIP. Moreover, in CP-exposed testes, p38 and Akt proteins were significantly phosphorylated (P<0.05), whereas in the testes of mice co-treated with SIP and CP, phosphorylation of the two proteins was inhibited, demonstrating that the two signalling pathways participated in the regulative processes of the deleterious effects caused by CP, and the preventive effects SIP mediated.
Treatment of drooling with sublingual atropine sulfate in children and adolescents with cerebral palsy

ABSTRACT Atropine sulfate blocks the muscarinic receptors in the salivary glands and leads to reduced saliva production. There are no published studies about its use in children with cerebral palsy. Objective To report the effect of sublingual atropine sulfate to treat drooling in children with cerebral palsy by comparing the results of the Drooling Impact Scale in a non-controlled open clinical trial. Results Twenty-five children were assessed. The difference in the mean scores of the pre- and post-treatment scales reached statistical significance. There was a low frequency of side effects compared to studies with other anticholinergics. Conclusion The use of sublingual atropine sulfate seems to be safe and there is a reduction in the Drooling Impact Scale score, which suggests efficacy in the treatment of drooling in children and adolescents with cerebral palsy. Our results should be replicated in randomized, placebo-controlled studies with larger numbers of participants.
Source and route of methicillin-resistant Staphylococcus epidermidis transmitted to the surgical wound during cardio-thoracic surgery. Possibility of preventing wound contamination by use of special scrub suits.

The objective of this study was to trace the source and route of transmission of methicillin-resistant Staphylococcus epidermidis (MRSE) in the surgical wound during cardio-thoracic surgery, and to investigate the possibility of reducing wound contamination by wearing special scrub suits. In total 65 elective operations for coronary artery bypass grafting (CABG) with or without concomitant valve replacement were investigated. All staff present in the operating room wore conventional scrub suits during 33 operations and special scrub suits during 32 operations. Samples were taken from the hands of the scrubbed team after surgical scrub but before putting on sterile gowns and gloves, and from patients' skin (incisional area of sternum and vein harvesting area of legs) after preoperative skin preparation with chlorhexidine gluconate. Air samples were taken during operations. Samples were also taken from the wound just before closure. Total counts of bacteria on sternal skin and from the wound (cfu/cm2) were calculated as well as total counts of bacteria in the air (cfu/m3). Strains of MRSE recovered from the different sampling sites were compared by pulsed field gel electrophoresis (PFGE). It was found that wearing special scrub suits did not reduce the number of air-samples where MRSE was found compared with conventional scrub suits. The risk factor most strongly associated with MRSE in the wound at the end of the operation was preoperative carriage of MRSE on sternal skin; RR 2.42 [95% CI 1.43-4.10], P= 0.021. By use of PFGE, it was possible to identify the probable source for four MRSE isolates recovered from the wound. In three cases the source was the patients own skin. Finding MRSE in air-samples, or on the hands of the scrubbed team, were not risk factors for the recovery of MRSE in the wound at the end of operation. In conclusion, with a total bacterial air count around 20 cfu/m3 and a low proportion of MRSE, the reduction of total air counts by use of tightly woven special scrub suits did not reduce air counts of MRSE or wound contamination with MRSE. The patients' sternal skin was the main source for wound contamination with MRSE
Endotoxin and NO induce MIP-1gamma gene transcription in ANA-1 murine macrophages.

The host response to gram-negative endotoxin is characterized by an influx of inflammatory cells into host tissues, mediated in part by localized production of chemokines. In this study, using subtractive suppression hybridization analysis, we demonstrate that ANA-1 murine macrophages produce the CC chemokine, MIP-1gamma, in response to LPS-mediated NO production. Gene transcription and protein translation are upregulated in the setting of LPS-induced NO synthesis. However, NO alone is a necessary but insufficient cofactor for induction of MIP-1gamma protein expression; an NO-independent LPS signalling pathway is also required. This study suggests a novel mechanism by which NO modulates the host inflammatory response to endotoxin.
ACCUMULATION OF DELETERIOUS MUTATIONS: ADDITIONAL DROSOPHILA MELANOGASTER ESTIMATES AND A SIMULATION OF THE EFFECTS OF SELECTION

Abstract We report an assay of egg-to-adult viability in full-sibling mutation accumulation (MA) lines derived from a completely homozygous population of Drosophila melanogaster and maintained for 210 generations. A simultaneous evaluation was also made of a large population derived from the same origin and maintained as a control for the same period. We also present computer simulations to explore the possible decline in viability of the control population due to mutation accumulation and the possible effect of selection within and between MA lines. For this purpose, we used two mutational models independent from the data analyzed and based on radically different assumptions. The first model implies a large number of mutations of small effect, whereas the second implies a much smaller number of mutations with much larger effects. The observed rate of decline in mean viability was very small but significant (0.077%). The rate of increase in among line variance (0.189 × 10−3) was similar to those obtained previously in the same lines. The simulation results indicated that a model of many mutations of small effect is incompatible with the evolution of the mean viability of the control and MA lines over generations, the distribution of line means after 210 generations of mutation accumulation, and the pattern of line extinction over generations. Basically, this model predicted a large drop in viability, both in the control and particularly the MA lines, that is not observed empirically. It also predicted a rate of line extinction too low in the early generations and too high in the later ones. In contrast, the model based on few mutations of large effect was generally consistent with all the observations.
Some Important Issues Involving Real Options

This paper provides an introduction to real options, as well as highlighting some important issues that are often neglected by real options analysts. While many books and surveys have been written on real options, there are some ubiquitous concepts that are not well-understood by many authors and practitioners. The objective of this paper is to redress this shortfall. The paper discusses organizational issues that impede adoption of real options strategies. It discusses modelling and analytic techniques for real options.
The Statistical Evaluation of Correlations between LRS and HRS Relaxations in RRAM Array

The unique tail bits retention failure behavior is observed in the RRAM array. Unlike the previous reports on single device or the average value''s retention behavior, quick retention loss of tail bits is found for both LRS and HRS. By statistically characterized such relaxation effect of tail bits, physical models are built to quantitatively describe the relaxation behaviors of LRS and HRS. The correlation between LRS and HRS relaxations is explored. Interfacial migration of oxygen ions is clarified to be the possible reason for the relaxation, which can provide the basis of the optimization of retention properties in RRAM array.