Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-Year Outcomes of a Randomized, Double-Blind, Placebo-Controlled Study Assessing Safety and Efficacy of C1 Esterase Inhibitor for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES Delayed graft function is related to ischemia-reperfusion injury and may be complement dependent. We previously reported from a randomized, placebo-controlled trial that treatment with C1 esterase inhibitor was associated with a shorter duration of delayed graft function and higher eGFR at 1 year. Here, we report longer-term outcomes from this trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This is a post hoc analysis of a phase 1/2, randomized, controlled trial enrolling 70 recipients of deceased donor kidney transplants at risk for delayed graft function (NCT02134314). Subjects were randomized to receive C1 esterase inhibitor 50 U/kg (n=35) or placebo (n=35) intraoperatively and at 24 hours. The cumulative incidence functions method was used to compare graft failure and death over 3.5 years. eGFR slopes were compared using a linear mixed effects model. RESULTS Three deaths occurred among C1 esterase inhibitor-treated patients compared with none receiving placebo. Seven graft failures developed in the placebo group compared with one among C1 esterase inhibitor-treated recipients; the cumulative incidence of graft failure was lower over 3.5 years among C1 esterase inhibitor-treated recipients compared with placebo (P=0.03). Although no difference in eGFR slopes was observed between groups (P for group-time interaction =0.12), eGFR declined in placebo-treated recipients (-4 ml/min per 1.73 m2 per year; 95% confidence interval, -8 to -0.1) but was stable in C1 esterase inhibitor-treated patients (eGFR slope: 0.5 ml/min per 1.73 m2 per year; 95% confidence interval, -4 to 5). At 3.5 years, eGFR was 56 ml/min per 1.73 m2 (95% confidence interval, 42 to 70) in the C1 esterase inhibitor group versus 35 ml/min per 1.73 m2 (95% confidence interval, 21 to 48) in the placebo group, with an estimated mean eGFR difference of 21 ml/min per 1.73 m2 (95% confidence interval, 2 to 41 ml/min per 1.73 m2). CONCLUSIONS Treatment of patients at risk for ischemia-reperfusion injury and delayed graft function with C1 esterase inhibitor was associated with a lower incidence of graft failure.
Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell–cell and cell–matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells.
Occurrence and Concentration of Chemical Additives in Consumer Products in Korea

As the variety of chemicals used in consumer products (CPs) has increased, concerns about human health risk have grown accordingly. Even though restrictive guidelines and regulations have taken place to minimize the risks, human exposure to these chemicals and their eco-compatibility has remained a matter of greater scientific concern over the years. A major challenge in understanding the reality of the exposure is the lack of available information on the increasing number of ingredients and additives in the products. Even when ingredients of CPs formulations are identified on the product containers, the concentrations of the chemicals are rarely known to consumers. In the present study, an integrated target/suspect/non-target screening procedure using liquid chromatography-high resolution mass spectrometry (LC-HRMS) with stepwise identification workflow was used for the identification of known, suspect, and unknown chemicals in CPs including cosmetics, personal care products, and washing agents. The target screening was applied to identify and quantify isothiazolinones and phthalates. Among analyzed CPs, isothiazolinones and phthalates were found in 47% and in 24% of the samples, respectively. The highest concentrations were 518 mg/kg for benzisothiazolone, 7.1 mg/kg for methylisothiazolinone, 2.0 mg/kg for diethyl phthalate, and 21 mg/kg for dimethyl phthalate. Suspect and non-target analyses yielded six tentatively identified chemicals across the products including benzophenone, ricinine, iodocarb (IPBC), galaxolidone, triethanolamine, and 2-(2H-Benzotriazol-2-yl)-4, 6-bis (1-methyl-1-phenylethyl) phenol. Our results revealed that selected CPs consistently contain chemicals from multiple classes. Excessive use of these chemicals in daily life can increase the risk for human health and the environment.
Microangiopathy: Is it relevant to wound healing in diabetic foot disease?

Chronic diabetic complications – both microvascular and macrovascular – have become serious health issues with their increasing prevalence paralleling the dramatic rise of the diabetic population worldwide. Of these complications, foot disease is a major cause of morbidity and mortality, consuming more health care resource than all other complications combined. Diabetic polyneuropathy and peripheral vascular disease constitute the two main risk factors, with trauma and foot infection being the most important initiating factors and contributors to delayed healing. Intracellular oxidative stress mediated by hyperglycaemia along with hypertension, dyslipidaemia and smoking constitute the main pathological processes in the aetiology of both macrovascular and microvascular disease. Whilst the former remains the major cause of overall mortality in diabetes, the role of microangiopathy in the pathogenesis of diabetes foot disease and its contribution to delayed wound healing in diabetes has yet to be fully understood and indeed continues to be debated. This article will review the key findings to date on structural and functional microvascular abnormalities in the diabetic foot skin and consider their contribution to impaired would healing.
‘Beyond Cancer’: a study protocol of a multimodal occupational rehabilitation programme to support breast cancer survivors to return work

Introduction With more women working and surviving breast cancer, issues concerning sustainable employment must be addressed. Support to transition back to work is a gap in survivorship care. This paper describes the feasibility trial protocol for ‘Beyond Cancer’, a multimodal occupational rehabilitation programme to support breast cancer survivors’ return to work. Breast cancer survivors are hypothesised to show improved work status, work capacity and perceived support at work at 6 months postintervention relative to baseline and a historical usual care group. Methods and analysis The prospective feasibility design allows determination of change in primary (work status) as well as secondary outcome measures work capacity and perceived support at work. Participants: breast cancer survivors of working age, unable to work in their prediagnosis capacity for >3 months, their employers and a historical usual care group. Key intervention elements: an evidence-based biopsychosocial assessment and health coaching programme, employer education and support, and return to work (RTW) planning and monitoring. Health coaching empowers survivors to return to social function, including work. Employer education and support facilitates communication and improves workplace support. For employers, we predict change in confidence in effectively supporting employees’ RTW. Multilevel regression modelling will provide indications of efficacy for primary and secondary outcomes, and thematic analysis will examine perceived efficacy and acceptability. Ethics and dissemination Ethics approval has been granted by Monash and Curtin University Human Research Ethics Committees (HREC: 13300, HRE2019-0280, respectively). The evaluation of this innovative programme will provide the foundation for an Randomised Controlled Trial (RCT) and national roll-out, thus improving the quality of life of those who have been directly affected by breast cancer across Australia. Results will be published in peer-reviewed journals, presented at relevant conferences and disseminated to survivorship-focused organisations. Trial registration number Registered trial with the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12618001985279); Pre-results.
INFLUENCE OF COMBINED ACTION OF X-RADIATION AND CYCLOOXYGENASE-2 - MELOXIVET INHIBITOR ON VEGF AND PGE-2 CONTENT IN BLOOD OF RAT-TUMOR CARRIERS.

OBJECTIVE The objective of this work was to study the effect of the combined action of X-radiation and the cyclooxygenase-2 (COX-2) inhibitor on the level of vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE-2) in blood serum of rat-tumor carriers at irradiation in different doses. MATERIALS AND METHODS 20 tumor-bearing rats of the Wistar population weighing 160-180 g, with transplanted Guerin carcinoma, fractionated irradiation (5 Gy + 5 Gy) and (0.5 Gy + 0.5 Gy) of the tumor growth zone on the RUM- 17 was carried out, with an interval between sessions of 24 hours. The drug «Meloxivet» - a selective inhibitor of cyclooxygenase-2 was administered 24 hours before irradiation and 2 hours before the second exposure (0.2 mg per 1 kg body weight). Blood sampling was performed by the method of life-time decapitation after 24 hours after the last fraction of irradiation. The content of VEGF in blood serum was determined by the method of enzyme immunoas- say using standardResults. After fractionated irradiation in a total dose of 1 Gy (0.5 Gy + 0.5 Gy), the level of VEGF was increased by 1.5 times compared with intact control, and in animals that were irradiated in a total dose of 10 Gy (5 Gy + 5 Gy ), the VEGF level was reduced by 1.92 times. That is, there was a difference in the content of VEGF in blood serum of rat tumor carriers, depending on the dose of irradiation: in a total dose of 1 Gy - stimulation of angiogenesis, and in the total dose of 10 Gy - a significant slowdown in this process. In the case of combined exposure to radiation (10 Gy) and the COX-2 inhibitor, meloxivet, the potential decrease in VEGF levels was 3.49 times compared to con- trol and 1.8 times with isolated exposure. At the same time, the level of PGE-2 also decreased with respect to iso- lated exposure by 1.5 times, indicating COX-2 inhibition. With a combined low dose (1 Gy) irradiation and COX-2- meloxivet inhibitor, VEGF levels were reduced by 1.1 times compared to control and 1.7 times relative to isolated exposure. At the same time, the level of PGE-2 also decreased in comparison with isolated radiation in 1,1 times. The obtained results indicate the influence of the combined act of irradiation and meloxivet on the level of VEGF and PGE-2, which causes the antiangiogenic effect. Сonclusions. It has been shown that low doses of ionizing radiation (1 Gy) and high doses (10 Gy) have a different effect on VEGF expression, and thus on angiogenesis processes. The combined effect of ionizing radiation and the COX-2 inhibitor (meloxivet) affects the level of PGE-2, VEGF, ie, the slowing of angiogenesis. In the case of large doses of exposure, this effect is even more expressed.
The Reliability of Kager's Triangle in Detecting Acute Achilles Tendon Ruptures.

The Achilles tendon is a common site of anatomical injury among athletes and those participating in recreational sporting activities. Acute Achilles tendon ruptures are often misdiagnosed as a sprained ankle and are more common in the male population. Mechanism of injury is often a noncontact injury, resulting from sudden forced plantar flexion or violent dorsiflexion in a plantar flexed foot. Delays in diagnosis and treatment may complicate the clinical outcome. Because findings may be subtle on history and physical examination, the use of readily available adjunctive studies is important for practitioners. One method is the analysis of Kager's triangle on lateral ankle radiographs. Obscuration of Kager's triangle has been described as a radiographic indicator of Achilles tendon rupture, but the sensitivity and specificity of this finding have been poorly reported. [Orthopedics. 2020; xx(x): xx-xx. ].
Expression, purification, and characterization of N‐acetylglucosaminylphosphatidylinositol de‐N‐acetylase (ScGpi12), the enzyme that catalyses the second step of GPI biosynthesis in S. cerevisiae

ScGpi12 is a 304 amino residue long endoplasmic reticulum membrane protein, which participates in the de‐N‐acetylation of N‐acetylglucosaminyl phosphatidylinositol to produce glucosaminyl phosphatidylinositol in the second step of GPI anchor biosynthesis pathway in Saccharomyces cerevisiae. ScGpi12 was cloned in a pMAL‐c2x vector and expressed heterologously in Rosetta‐gami (DE3) strain of E. coli. Affinity purification of the protein yielded low amounts of the MBP‐tagged enzyme, which was active. To the best of our knowledge, this is the first successful purification of full‐length Gpi12 enzyme, without the accompanying GroEL that was seen in other studies. The presence of the tag did not greatly alter the activity of the enzyme. ScGpi12 was optimally active in the pH range of 6.5–8.5 and at 30 °C. It was not sensitive to treatment with EDTA but was stimulated by multiple divalent cations. The divalent cation did not alter the pH profile of the enzyme, suggesting no role of the divalent metal in creating a nucleophile for catalysis. Divalent cations did, however, enhance the turnover number of the enzyme for its substrate, suggesting that they are probably required for the production of a catalytically competent active site by bringing the active site residues within optimum distance of the substrate for catalysis.
Current state of the art MRI for the longitudinal assessment of cystic fibrosis

Pulmonary MRI can now provide high‐resolution images that are sensitive to early disease and specific to inflammation in cystic fibrosis (CF) lung disease. With specificity and function limited via computed tomography (CT), there are significant advantages to MRI. Many of the modern MRI techniques can be performed throughout life, and can be employed to understand changes over time, in addition to quantification of treatment response. Proton density and T1/T2 contrast images can be obtained within a single breath‐hold, providing depiction of structural abnormalities and active inflammation. Modern radial and/or spiral ultrashort echo‐time (UTE) techniques rival CT in resolution for depiction and quantification of structure, for both airway and parenchymal abnormalities. Contrast perfusion MRI techniques are now utilized routinely to visualize changes in pulmonary and bronchial circulation that routinely occur in CF lung disease, and noncontrast techniques are moving closer to clinical translation. Functional information can be obtained from noncontrast proton images alone, using techniques such as Fourier decomposition. Hyperpolarized‐gas MRI, increasingly using 129Xe, is now becoming more widespread and has been demonstrated to have high sensitivity to early airway obstruction in CF via ventilation MRI. The sensitivity of 129Xe MRI promises future use in personalized medicine, management of early CF lung disease, and in future clinical trials. By combining structural and functional techniques, with or without hyperpolarized gases, regional structure–function relationships can be obtained, giving insight into the pathophysiology of disease and improved clinical management. This article reviews the modern MRI techniques that can routinely be employed for CF lung disease in nearly any large medical center.
Maturation of pyramidal cells in anterior piriform cortex may be sufficient to explain the end of early olfactory learning in rats

Studies have shown that neonate rodents exhibit high ability to learn a preference for novel odors associated with thermo-tactile stimuli that mimics maternal care. Artificial odors paired with vigorous strokes in rat pups younger than 10 postnatal days (P), but not older, rapidly induce an orientation-approximation behavior toward the conditioned odor in a two-choice preference test. The olfactory bulb (OB) and the anterior olfactory cortex (aPC), both modulated by norepinephrine (NE), have been identified as part of a neural circuit supporting this transitory olfactory learning. One possible explanation at the neuronal level for why the odor-stroke pairing induces consistent orientation-approximation behavior in P10, is the coincident activation of prior existent neurons in the aPC mediating this behavior. Specifically, odor-stroke conditioning in P10 pups, promoting orientation-approximation behavior in the former but not in the latter. In order to test this hypothesis, we performed in vitro patch-clamp recordings of the aPC pyramidal neurons from rat pups from two age groups (P5–P8 and P14–P17) and built computational models for the OB-aPC neural circuit based on this physiological data. We conditioned the P5–P8 OB-aPC artificial circuit to an odor associated with NE activation (representing the process of maternal odor learning during mother–infant interactions inside the nest) and then evaluated the response of the OB-aPC circuit to the presentation of the conditioned odor. The results show that the number of responsive aPC neurons to the presentation of the conditioned odor in the P14–P17 OB-aPC circuit was lower than in the P5–P8 circuit, suggesting that at P14–P17, the reduced number of responsive neurons to the conditioned (maternal) odor might not be coincident with the responsive neurons for a second conditioned odor.
Retraction: Brain–Computer Interface–Based Communication in the Completely Locked-In State

During their investigation, committees at both institutions concluded that the authors of the study are at fault with regard to data collection, handling, and analysis. However, they did not comment on the methodology underlying the findings. Adhering to the guidelines provided by the Committee on Publication Ethics, the editors retract this manuscript because the authors were found to have engaged in scientific misconduct by Eberhard Karls Universität Tübingen and Deutsche Forschungsgemeinschaft. The authors have declined to sign this retraction, as they stand by their data, analyses, and conclusions, and state that they intend to take legal proceedings to challenge the findings in the reports, which they claim contain errors.
Moving forward the field of combination treatments: shared responsibility of researchers, reviewers, and readers.

In the last several issues, there has been a number of reports on the efficacy of combination treatments (Guo et al., 2019; Kirac-Unal et al., 2019; Moon and Bae, 2019; Tarameshlu et al., 2019). Typically in these studies, an experimental group receives two active treatments concurrently or closely together, whereas a control group receives one or two active or passive comparator treatments. The ‘conventional/standard treatment’ may also be provided either as an add-on to both groups or as a sole control. Although examining multi-component interventions is both inevitable and generally welcomed trend given the expansion of treatment options, we all, in our respective roles, have to be aware of expectations from us, whether it be researchers, reviewers, or readers.
Microbial chemolithotrophy mediates oxidative weathering of granitic bedrock

Significance We utilized the Luquillo Critical Zone Observatory (LCZO) in Puerto Rico to test the hypothesis that mineral-derived Fe(II) within the granitic bedrock at LCZO is capable of supporting microbial Fe(II)-based chemolithotrophy and that the resultant redox-driven mineralogical transformations contribute to bedrock weathering. While this hypothesis had been postulated based on theoretical calculations of Fe(II) loss and potential chemolithotrophic Fe(II)-oxidizing bacterial growth across the bedrock–saprolite interface, to date it has not been verified experimentally. Our study definitively demonstrates the ability of chemolithotrophic Fe(II)-oxidizing bacteria to accelerate oxidative transformation of Fe(II)-silicate minerals. In addition, our work presents insight into complex microbial community interactions, which must be considered when assessing the role of microorganisms in bedrock weathering. The flux of solutes from the chemical weathering of the continental crust supplies a steady supply of essential nutrients necessary for the maintenance of Earth’s biosphere. Promotion of weathering by microorganisms is a well-documented phenomenon and is most often attributed to heterotrophic microbial metabolism for the purposes of nutrient acquisition. Here, we demonstrate the role of chemolithotrophic ferrous iron [Fe(II)]-oxidizing bacteria in biogeochemical weathering of subsurface Fe(II)-silicate minerals at the Luquillo Critical Zone Observatory in Puerto Rico. Under chemolithotrophic growth conditions, mineral-derived Fe(II) in the Rio Blanco Quartz Diorite served as the primary energy source for microbial growth. An enrichment in homologs to gene clusters involved in extracellular electron transfer was associated with dramatically accelerated rates of mineral oxidation and adenosine triphosphate generation relative to sterile diorite suspensions. Transmission electron microscopy and energy-dispersive spectroscopy revealed the accumulation of nanoparticulate Fe–oxyhydroxides on mineral surfaces only under biotic conditions. Microbially oxidized quartz diorite showed greater susceptibility to proton-promoted dissolution, which has important implications for weathering reactions in situ. Collectively, our results suggest that chemolithotrophic Fe(II)-oxidizing bacteria are likely contributors in the transformation of rock to regolith.