Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug-induced acute kidney injury: diverse mechanisms of tubular injury.

PURPOSE OF REVIEW Medications are a relatively common cause of acute kidney injury (AKI), especially in hospitalized patients who are exposed to numerous agents. Drug-related acute tubular/tubulointerstitial injury is the most common cause of AKI associated with these agents. Toxic effects of drugs and their renal handling often lead to various forms of AKI. RECENT FINDINGS The inherent nephrotoxicity of drugs and their transport and metabolism by the kidneys play an important role in the occurrence of acute tubular injury. Apical transport of the aminoglycosides by endocytosis and apical pinocytosis of filtered hydroxyethyl starch into cells lead to acute tubular dysfunction. Transport of tenofovir and cisplatin by organic anion and cation transporters in the basolateral surface of the proximal tubule, respectively, are associated with intracellular drug accumulation and injury. Intratubular deposition of drug crystals with associated AKI occurs with several drugs, in particular the anticancer agent methotrexate. A potentially new mechanism of drug-induced AKI was described with vancomycin - acute vancomycin-related cast nephropathy. Immune-mediated acute tubulointerstitial injury is another cause of drug-induced AKI, as seen with immune checkpoint inhibitors. SUMMARY Drugs lead to AKI through mechanisms that involve their inherent toxicity as well as their transport and handling by the kidneys.
The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy

To date, our understanding of the Substance P (SP) and neurokinin 1 receptor (NK1R) system shows intricate relations between human physiology and disease occurrence or progression. Within the oncological field, overexpression of NK1R and this SP/NK1R system have been implicated in cancer cell progression and poor overall prognosis. This review focuses on providing an update on the current state of knowledge around the wide spectrum of NK1R ligands and applications of radioligands as radiopharmaceuticals. In this review, data concerning both the chemical and biological aspects of peptide and nonpeptide ligands as agonists or antagonists in classical and nuclear medicine, are presented and discussed. However, the research presented here is primarily focused on NK1R nonpeptide antagonistic ligands and the potential application of SP/NK1R system in targeted radionuclide tumour therapy.
The Impacts of the Hierarchical Medical System on National Health Insurance on the Resident’s Health Seeking Behavior in Taiwan: A Case Study on the Policy to Reduce Hospital Visits

Objective: This study investigated the impacts of the hierarchical medical system under the national health insurance program on residents’ healthcare-seeking behavior in Taiwan. Background: Healthcare authorities in Taiwan initiated an allowance reduction for outpatient visits at regional hospitals and higher hierarchical hospitals in 2018. The ultimate goal is to implement a hierarchical medical system to provide residents accessible as well as consistent medical services. Methods: This research was conducted through a questionnaire survey, and data were collected between August and December 2018 from the records of subjects who had recently sought medical attention. A total of 1340 valid questionnaires were returned. Results: A principal finding was that there were significant differences in the knowledge of new policies by age, marital status, annual income, education level, and occupation (p < 0.001). Regarding the effects on healthcare-seeking behavior, there were significant differences from persons aged 40–49 years (p < 0.1), in junior high school (p < 0.05), not aware of the policy (p < 0.001), and awareness of both the hierarchical medical system and the policy to reduce outpatient visits to large hospitals (p < 0.001). Conclusion: The health administration authorities should devote more effort into promoting knowledge of the policy in order to better inform the public about the hierarchical medical system.
Elemental Metabolomics: Modulation of Egg Metallome with Flavonoids, an Exploratory Study

The basic principles of elemental metabolomics were applied to investigate whether alteration of egg metallome could be achieved after two flavonoids addition, namely hesperidin and naringin in diets of laying hens. A total of 72 hens were divided into six groups: Control (C) (basal diet), E1 (750 mg hesperidin/kg diet), E2 (1500 mg hesperidin/kg diet), N1 (750 mg naringin/kg diet), N2 (1500 mg naringin/kg diet), and VE (200 mg vitamin E/kg diet). The same diet was provided to birds of all treatments, with the exception of added supplements. The diets had the same vitamin and mineral premix; thus, all birds received the same number of elements because no differences on feed intake existed. The egg elemental profile consisted of As, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sb, Se, Sr, V, Zn, and was determined using ICP-MS. Flavonoid supplementation altered the elemental profile. Most notably, in both albumen and yolk, hesperidin increased Ni, Pb, and Sr concentration while it decreased that of Co and Sb. Naringin increased Cd, Cr, Cu, Ni, and V and lowered the concentration of Co and Sb in both yolk and albumen. Vitamin E supplementation, in comparison to the control, decreased Co in both albumen and yolk and also raised Sb in albumen. Flavonoid presence led to the differences in deposition of certain trace minerals in egg compared to that of hens fed a basal diet or a diet with vitamin E supplementation.
Long-Term Culture of Giardia lamblia in Cell Culture Medium Requires Intimate Association with Viable Mammalian Cells

Giardia lamblia is usually cultured axenically in TYI-S-33, a complex medium which does not permit survival and growth of mammalian cells. Likewise, medium commonly used to maintain and grow mammalian cells does not support healthy trophozoite survival for more than a few hours. The inability to coculture trophozoites and epithelial cells under optimal conditions limits studies of their interactions as well as interpretation of results. ABSTRACT Giardia lamblia is usually cultured axenically in TYI-S-33, a complex medium which does not permit survival and growth of mammalian cells. Likewise, medium commonly used to maintain and grow mammalian cells does not support healthy trophozoite survival for more than a few hours. The inability to coculture trophozoites and epithelial cells under optimal conditions limits studies of their interactions as well as interpretation of results. Trophozoites of the WB isolate but not the GS isolate were repeatedly adapted to grow stably in long-term cocultures with Caco2, Cos7, and mouse tumor rectal (RIT) cell lines using hybridoma-screened Dulbecco’s modified Eagle’s medium and 10% fetal calf serum. Giardia did not grow in spent cell culture medium or when separated by a permeable membrane using transwell methodology. Giardia chronically cocultured with specific cell lines became adapted (conditioned). These Giardia cocultures grew better than nonconditioned trophozoites, and the cell lines differed in their ability to support trophozoite growth in the order of RIT > Cos7 > Caco2. Trophozoites conditioned on one cell line and then grown in the presence of a heterologous cell line changed their growth rate to that seen in conditioned Giardia from the heterologous cell line. Trophozoite survival required intimate contact with cells, suggesting that trophozoites obtain an essential nutrient or growth factor from mammalian cells. This may explain why Giardia trophozoites adhere to the small intestinal epithelium during human and animal infections. This coculture system will be useful to understand the complex interactions between the host cells and parasite.
Evaluation of Prognostic Factors for the Parotid Cancer Treated With Surgery and Postoperative Radiotherapy

Objectives To investigate the prognostic factors and treatment outcomes of primary parotid carcinoma treated with surgery and postoperative radiotherapy (PORT). Methods We reviewed retrospectively 57 patients with primary parotid carcinoma who were treated with surgery and PORT between 2005 and 2014. Superficial parotidectomy was performed in 19 patients, total parotidectomy in 10 patients, and total parotidectomy with lymph node dissection in 28 patients PORT on the tumor bed was performed in 41 patients, while PORT on tumor bed and ipsilateral cervical lymph nodes was performed in 16 patients. Results With a median follow-up of 66 months, the 5-year overall survival, disease-free survival, locoregional control, and distant control rates were 77.0%, 60.2%, 77.6%, and 72.8%, respectively. The 5-year overall survival by stage was 100%, 100%, 80.0%, and 46.4% in stage I, II, III, and IV, respectively. Recurrences at primary lesions were found in seven patients, while at cervical nodes in six patients. Distant recurrences were developed in 12 patients. No patient with the low and intermediate histologic grade developed distant failure. As prognostic factors, the histologic grade for overall survival (P=0.005), pathological T-stage (P=0.009) and differentiation grade (P=0.009) for disease-free survival, pathological T-stage for locoregional control (P=0.007), and lympho-vascular invasion (P=0.023) for distant recurrence were significant on multivariate analysis. Conclusion This study revealed that differentiation grade, histologic grade, pathological T-stage, and lympho-vascular invasion were significant independent prognostic factors on clinical outcomes.
The Odds Ratio Product (An Objective Sleep Depth Measure): Normal Values, Repeatability, and Change With CPAP in Patients With OSA.

STUDY OBJECTIVES The Odds Ratio Product (ORP) is an objective measure of sleep depth using the relationships of the powers of different electroencephalogram (EEG) frequencies in a single index. The range of the ORP is 0 (deeply asleep) to 2.5 (fully awake). This investigation seeks to elucidate normal values of non-rapid eye movement ORP (ORPNR) in healthy individuals, repeatability of the measure, and the change in ORPNR following continuous positive airway pressure (CPAP) treatment. METHODS Healthy individuals underwent a home sleep apnea test (HSAT) with EEG followed 1 week later by EEG alone. Another cohort with OSA underwent baseline HSAT with EEG followed by a second EEG study approximately 4 weeks into treatment with CPAP. RESULTS Thirty-eight healthy individuals completed the protocol (mean age of 34.9 ± 7.4 years, Epworth Sleepiness Scale score 3.6 ± 2.4, Insomnia Severity Index score 2.0 ± 1.6 and Functional Outcomes of Sleep Questionnaire - shorter version score 19 ± 1.2). The mean ORPNR for all nights was 0.52 ± 0.13. The difference between the first night and the second night was 0.024 ± 0.17 (not significant). The intraclass correlation coefficient was 0.525, suggesting only moderate agreement between the first and second nights. The normal value for ORPNR in healthy individuals is ≤ 0.78 units using two standard deviations as the cutoff. Forty participants completed the OSA protocol (mean age 49 ± 11 years, body mass index 35 ± 6 kg/m², apnea-hypopnea index 33.5 ± 28.4 events/h). The mean pre-CPAP ORPNR was 0.69 ± 0.24 and the mean post-CPAP ORPNR was 0.57 ± 0.22 (P = .02). CONCLUSIONS The ORPNR proves to have significant variability from night to night in healthy individuals. ORPNR objectively improves following CPAP treatment, providing further evidence that it measures sleep depth. CITATION Penner CG, Gerardy B, Ryan R, Williams M. The odds ratio product (an objective sleep depth measure): normal values, repeatability, and change with CPAP in patients with OSA. J Clin Sleep Med. 2019;15(8):1155-1163.
Epigenetics and Mechanobiology in Heart Development and Congenital Heart Disease

Congenital heart disease (CHD) is the most common birth defect worldwide and the number one killer of live-born infants in the United States. Heart development occurs early in embryogenesis and involves complex interactions between multiple cell populations, limiting the understanding and consequent treatment of CHD. Furthermore, genome sequencing has largely failed to predict or yield therapeutics for CHD. In addition to the underlying genome, epigenetics and mechanobiology both drive heart development. A growing body of evidence implicates the aberrant regulation of these two extra-genomic systems in the pathogenesis of CHD. In this review, we describe the stages of human heart development and the heart defects known to manifest at each stage. Next, we discuss the distinct and overlapping roles of epigenetics and mechanobiology in normal development and in the pathogenesis of CHD. Finally, we highlight recent advances in the identification of novel epigenetic biomarkers and environmental risk factors that may be useful for improved diagnosis and further elucidation of CHD etiology.
Electrochemical Synthesis of Ammonia: Recent Efforts and Future Outlook

Ammonia is a key chemical produced in huge quantities worldwide. Its primary industrial production is via the Haber-Bosch method; a process requiring high temperatures and pressures, and consuming large amounts of energy. In the past two decades, several alternatives to the existing process have been proposed, including the electrochemical synthesis. The present paper reviews literature concerning this approach and the experimental research carried out in aqueous, molten salt, or solid electrolyte cells, over the past three years. The electrochemical systems are grouped, described, and discussed according to the operating temperature, which is determined by the electrolyte used, and their performance is valuated. The problems which need to be addressed further in order to scale-up the electrochemical synthesis of ammonia to the industrial level are examined.
Design Variation of a Dual-Antigen Liposomal Vaccine Carrier System

The enclosed work focuses on the construction variables associated with a dual-antigen liposomal carrier, delivering encapsulated polysaccharides and surface-localized proteins, which served as a vaccine delivery device effective against pneumococcal disease. Here, the goal was to better characterize and compare the carrier across a range of formulation steps and assessment metrics. Specifically, the vaccine carrier was subjected to new methods of liposomal formation, including alterations to the base components used for subsequent macromolecule encapsulation and surface attachment, with characterization spanning polysaccharide encapsulation, liposomal size and charge, and surface protein localization. Results demonstrate variations across the liposomal constructs comprised two means of surface-localizing proteins (either via metal or biological affinity). In general, final liposomal constructs demonstrated a size and zeta potential range of approximately 50 to 600 nm and −4 to −41 mV, respectively, while demonstrating at least 60% polysaccharide encapsulation efficiency and 60% protein surface localization for top-performing liposomal carrier constructs. The results, thus, indicate that multiple formulations could serve in support of vaccination studies, and that the selection of a suitable final delivery system would be dictated by preferences or requirements linked to target antigens and/or regulatory demands.
Who is more violent in extremist groups? A comparison of leaders and followers.

Few prior studies have examined the extent to which the behavior and characteristics of political extremists are related to their position within radical groups. In this paper we concentrate on one of the most fundamental distinctions in groups: That between leaders and followers. Our main goal is to investigate the comparative propensity of leaders and followers to engage in political violence. In a sample of individuals who have committed ideologically motivated political crimes in the United States (N = 1,331). we found that even though leaders were more ideologically committed to the group's goals and ideologies, they were at the same time less likely to engage in violent acts. Moreover, we found that leaders in radical criminal organizations shared many characteristics with leaders in noncriminal organizations. Specifically, in comparison to followers, they were more often male, older, and they were more likely to belong to an ethnic majority. We consider implications for future research and policy of the fundamental conclusion that compared to leaders, followers in terrorist organizations are more likely to engage in violent acts.
Cancer Takes a Toll on Skeletal Muscle by Releasing Heat Shock Proteins—An Emerging Mechanism of Cancer-Induced Cachexia

Cancer-associated cachexia (cancer cachexia) is a major contributor to the modality and mortality of a wide variety of solid tumors. It is estimated that cachexia inflicts approximately ~60% of all cancer patients and is the immediate cause of ~30% of all cancer-related death. However, there is no established treatment of this disorder due to the poor understanding of its underlying etiology. The key manifestations of cancer cachexia are systemic inflammation and progressive loss of skeletal muscle mass and function (muscle wasting). A number of inflammatory cytokines and members of the TGFβ superfamily that promote muscle protein degradation have been implicated as mediators of muscle wasting. However, clinical trials targeting some of the identified mediators have not yielded satisfactory results. Thus, the root cause of the muscle wasting associated with cancer cachexia remains to be identified. This review focuses on recent progress of laboratory studies in the understanding of the molecular mechanisms of cancer cachexia that centers on the role of systemic activation of Toll-like receptor 4 (TLR4) by cancer-released Hsp70 and Hsp90 in the development and progression of muscle wasting, and the downstream signaling pathways that activate muscle protein degradation through the ubiquitin–proteasome and the autophagy–lysosome pathways in response to TLR4 activation. Verification of these findings in humans could lead to etiology-based therapies of cancer cachexia by targeting multiple steps in this signaling cascade.
Non-Cirrhotic Liver is Associated with Poor Prognosis of Hepatocellular Carcinoma: A Literature Review

Primary hepatocellular carcinoma (HCC) is the fifth most frequently reported malignancy, and it is also the second most common cause of cancer-related deaths worldwide. Although most HCC cases have been reported to develop from cirrhosis, accumulating data suggest that HCC is also closely related to non-cirrhotic chronic liver disease. Traditionally, HCC was thought to develop mostly from cirrhosis; however, an increasing number of reports have found that HCC can develop directly from inflammation without cirrhosis. The incidence of HCC in non-cirrhotic liver (HCC-NCL) is high, especially in developed countries. Studies have found that the most common cause of HCC-NCL is neglected fatty liver disease. This type of HCC has unique clinical characteristics and is closely related to metabolic disorders. Unfortunately, the prevention of HCC-NCL has not received enough attention worldwide, and there is also a lack of specific screening methods and clinical guidelines. This article mainly reviews the etiology, incidence, clinical characteristics, and screening markers of HCC-NCL to improve the understanding and prevention of this disease.
Mass Spectrometry‐Based Quantitative Proteomics of Murine‐Derived Polymorphonuclear Neutrophils

Polymorphonuclear cells (PMNs or neutrophils) are the most abundant leukocyte in humans and represent an essential component of the innate immune system. The ability of neutrophils to initiate an immediate and non‐specific host response against invading microbial species is the key to determining the outcome of infection. Neutrophils produce and secrete a plethora of immunomodulatory proteins, including major granule proteins and cytokines, as well as various enzymes, which regulate adherence, phagocytosis, chemotaxis, and cell survival. Historically, characterization of neutrophils and their roles during infection have relied on genetic and phenotypic analyses, as well as biochemical assays. However, recent advances in mass spectrometry‐based proteomic workflows and technological platforms have supported the comprehensive profiling of neutrophil‐associated immune responses in consideration of cellular factors and secreted proteins. Given the critical role of neutrophils in maintaining and regulating innate immune function, comprehensive profiling of their response to infection is imperative to ensuring host survival. Here, we briefly discuss the role of neutrophils in host‐defense and describe methods to purify neutrophils from murine samples and comprehensively profile their proteomes. © 2019 by John Wiley & Sons, Inc.
Predicting Attentional Impairment in Women With Posttraumatic Stress Disorder Using Self-Reported and Objective Measures of Sleep.

STUDY OBJECTIVES There is growing evidence to support sleep impairment as a core feature of posttraumatic stress disorder (PTSD). Sleep impairment in PTSD is associated with severe distress and poorer treatment outcomes. Therefore, specific attention to this symptom of PTSD is warranted and accurate assessment of sleep impairment is critical. The current study investigated the association between self-reported and objective assessment of sleep and sustained attention in women with PTSD. METHODS Study participants include 50 treatment-seeking, female, interpersonal violence survivors who have PTSD. Nocturnal sleep duration was measured with self-report sleep diaries and objective actigraphy assessment over the course of 7 nights. Sustained attention during daytime was measured by the Psychomotor Vigilance Task (PVT). RESULTS Results indicated that self-reported nocturnal sleep duration, but not objective or global sleep quality measures, best predicted attentional deficits as indicated by lapses and inverse reaction time on the PVT. Daily sleep diaries predicted 19% and 14% of the variance in attentional lapses and inverse reaction time, respectively. CONCLUSIONS In a sample of women with PTSD, self-reported nocturnal sleep duration predicted deficits in sustained attention. Conversely, sleep duration as measured by actigraphy and global sleep quality, did not predict sustained attention. Findings suggest that assessing sleep impairment on a daily basis may provide clinically relevant information in evaluating daytime symptoms and provide guidance in targeting this particularly troublesome symptom in the treatment of PTSD.