bluuebunny/crossref_metadata_2025_split huggingface dataset:
An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart
Authors: Ahmed Doaa E. , Rashidi Fatma B. , Abdelhakim Heba K. , Mohamed Amr S. , Arafa Hossam M. M. 
Published: August 2021

Abstract
Background
Glufosfamide (β-d-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the β-d-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma. Therefore, the main objective of the current study is to assess the cytotoxic potential of GLU for the first time in the hepatocellular carcinoma HepG2 cell line model.

Methods
Cytotoxicity was assayed by the MTT method, and half-maximal inhibitory concentration (IC50) was calculated. Flow cytometric analysis of apoptosis frequencies was measured by using Annexin V/PI double stain, an immunocytochemical assay of caspase-9, visualization of caspase-3, and Bcl2 gene expression were undertaken as apoptotic markers. Mitochondrial membrane potential was measured using the potentiometric dye; JC-1, as a clue for early apoptosis as well as ATP production, was measured by the luciferase-chemiluminescence assay.

Results
Glufosfamide induced cytotoxicity in HepG2 cells in a concentration- and time-dependent manner. The IC50 values for glufosfamide were significantly lower compared to ifosfamide. The frequency of apoptosis was much higher for glufosfamide than that of ifosfamide. The contents of caspase-9 and caspase-3 were elevated following exposure to GLU more than IFO. The anti-apoptotic Bcl2 gene expression, the mitochondrial membrane potential, and the cellular ATP levels were significantly decreased than in case of ifosfamide.

Conclusions
The current study reported for the first time cytotoxicity activity of glufosfamide in HepG2 cells in vitro. The obtained results confirmed the higher oncolytic activity of glufosfamide than its aglycone ifosfamide. The generated data warrants further elucidations by in vivo study.
The microbiota-related coinfections in COVID-19 patients: a real challenge
Authors: Mohapatra Ranjan K. , Dhama Kuldeep , Mishra Snehasish , Sarangi Ashish K. , Kandi Venkataramana , Tiwari Ruchi , Pintilie Lucia 
Published: August 2021

AbstractBackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of ongoing global pandemic of coronavirus disease 2019 (COVID-19), has infected millions of people around the world, especially the elderly and immunocompromised individuals. The infection transmission rate is considered more rapid than other deadly pandemics and severe epidemics encountered earlier, such as Ebola, Zika, Influenza, Marburg, SARS, and MERS. The public health situation therefore is really at a challenging crossroads.Main bodyThe internal and external and resident microbiota community is crucial in human health and is essential for immune responses. This community tends to be altered due to pathogenic infections which would lead to severity of the disease as it progresses. Few of these resident microflora become negatively active during infectious diseases leading to coinfection, especially the opportunistic pathogens. Once such a condition sets in, it is difficult to diagnose, treat, and manage COVID-19 in a patient.ConclusionThis review highlights the various reported possible coinfections that arise in COVID-19 patients vis-à-vis other serious pathological conditions. The local immunity in lungs, nasal passages, oral cavity, and salivary glands are involved with different aspects of COVID-19 transmission and pathology. Also, the role of adaptive immune system is discussed at the site of infection to control the infection along with the proinflammatory cytokine therapy.
Antidiabetic effect of aqueous stem bark extract of Parinari macrophylla in alloxan-induced diabetic Wistar rats
Authors: Ibrahim Ahmad Alhassan , Abdussalami Muhammed Sani , Appah Joseph , Umar Abdullahi Hussein , Ibrahim Aminu Alhassan , Dauda Kabiru Dawaki 
Published: August 2021

Abstract
Background
Diabetes is a major public health problem with increasing prevalence globally. Plant-based medicines for diabetes are gaining popularity across the world due to perceptions of efficacy, safety and cost-effectiveness. The plant, Parinari macrophylla, has been widely reported to possess potent ethnomedicinal properties especially in the northern part of Nigeria. However, there has been no scientific documentation of this plant to be used as an antidiabetic agent. The objective of this study was to investigate the antidiabetic effect of aqueous stem bark extract of P. macrophylla in alloxan-induced diabetic Wistar rats. Phytochemical screening and acute toxicity studies were conducted. Wistar rats weighing between 100 and 150 g were used for the study and diabetes was induced using alloxan monohydrate (150 mg/kg) intraperitoneally. The animals were treated with different doses of aqueous stem bark extract of P. macrophylla (1000 mg/kg and 2000 mg/kg) for 2 weeks. Blood glucose levels and body weight were then monitored. Histopathological investigation of pancreatic tissue was also conducted.

Results
The phytochemical analysis revealed the presence of alkaloids, saponins, tannins, cardiac glycosides, carbohydrates, steroids, and triterpenes as secondary metabolites. The acute toxicity test revealed no mortality with a median lethal dose determined to be above 5000 mg/kg. Although the two different doses of aqueous stem bark extract of P. macrophylla decreased blood glucose levels at weeks 1 and 2, a statistically significant difference (P < 0.05) was only observed for the group treated with 2000 mg/kg dose compared to the diabetic control group at week 2. The histological investigation revealed that the two different doses of aqueous stem bark extract of P. macrophylla caused regeneration of pancreatic islet cells, with the 2000 mg/kg dose being more evident.

Conclusion
This study suggests that the stem bark extract of P. macrophylla possesses a potent antidiabetic effect and may potentially be used to treat diabetes and associated complications.

Graphical Abstract
Neuroprotective effects of Clitoria ternatea L. against propionic acid-induced behavior and memory impairment in autistic rat model
Authors: Jiji K. N. , Muralidharan P. 
Published: August 2021

Abstract
Background
Autism spectrum disorder is primarily characterized by complex behavioral and altered memory as a consequence of neuronal development abnormalities. The treatment of autism is highly challenging because of the lack of knowledge about its exact etiopathology. In the Ayurvedic system of medicine, there are group of plants named ‘Medhya drugs' because of their ability to improve brain- and neuron-related activities like learning and memory. Clitoria ternatea L. is one of the listed ‘Medhya drugs’ which have been proved for its memory enhancement effects; in the present study, the ethanolic root extract of Clitoria ternatea L. was evaluated for its neuroprotective ability against propionic acid-induced memory and behavior impairments in an autistic rat model. The variation in behavior and memory were investigated by utilizing different procedures like rat elevated plus maze and novel object recognition test. In vitro assays for the estimations of glutamate and serotonin were also performed in isolated rat brain tissue homogenate.

Results
The object recognition and elevated plus maze test were showed the promising effects of Clitoria ternatea L. ethanolic root extract against the propionic acid-induced autism. In this study, the propionic acid infused rats (Group II) fail to recognize and explore the novel object compared to Group I (infused with phosphate-buffered saline) animals; extract treatment at two different doses (250 mg/kg and 500 mg/kg) (Groups III & IV, respectively) prevented these damage significantly (p < 0.001) so that extract-treated groups showed significant improvement in novel object recognition in a dose-dependent manner. Similarly, the effect of extract treatment on learning and memory of rats was investigated using transfer latency as a parameter for acquisition and retention of memory process on elevated plus maze; this further proved the memory enhancement ability of Clitoria ternatea L. Extract treatment also significantly reduced the concentration of different neurotransmitters like serotonin and glutamate in rat brain homogenate (Groups III &IV) in a dose-dependent manner as compared with the Group II.

Conclusion
The ethanolic root extract of Clitoria ternatea L. proved to be effective against propionic acid-induced memory and behavior impairments in an autistic rat model.
Sphacelation with auto-anastomosis of the intestine: a rare outcome of intussusception in a child—a case report
Authors: Tan Shung Ken , Tan Chee Wei , Hassan Junaidah , Nallusamy Mohan Arunasalam , Boo Jian An , Puspanathan Pavitratha 
Published: August 2021

Abstract
Background
Intussusception is the telescoping of a proximal segment of the bowel into a distal segment. It can be idiopathic or pathological. Children commonly present with colicky abdominal pain, vomiting, a palpable abdominal mass, and bloody stools. Our case describes the unusual presentation of bowel sphacelation with auto-anastomosis in a child with intussusception and its clinical progression.

Case presentation
A 3-year-old boy with underlying stage IV rhabdomyosarcoma of the left orbit presented with high-grade fever and diarrhea for 1 day. He was treated for neutropenic sepsis in view of low absolute neutrophil count and recent history of chemotherapy. During his admission, he developed abdominal distension, high bilious aspirates, and diarrhea with bloody stools. Abdominal X-ray showed dilated bowel loops. Impression was septic ileus with coagulopathy. He was treated with blood transfusion and bowel rest. On the 6th day of illness, he passed out a tubular structure per rectum which was confirmed to be a segment of gangrenous bowel by histopathological examination. A diagnosis of intussusception with bowel sphacelation was made. He was treated conservatively, and his obstruction was resolved. He was discharged well with no abdominal symptoms during follow-up.

Conclusion
Intussusception is a common cause of small bowel obstruction in children. A high index of suspicion of intussusception should be maintained in children presenting with vomiting and bloody stools complemented by ultrasound to avoid missing this diagnosis. Sphacelation of the intussuscepted bowel with auto-anastomosis is a rare presentation of intussusception with a favorable outcome.
Pharyngo-laryngeal histoplasmosis in an immunocompromised child—a case report
Authors: Chakravarti Arunabha , Nair Rohini R. , Mojahid Moazzam , Mandal Piali , Chandra Jagdish , Nangia Anita 
Published: August 2021

Abstract
Background
Histoplasmosis is an endemic granulomatous fungal infection which rarely infects the larynx; less than 100 cases have been reported in medical literature till date.

Case presentation
A 6-year-old female child, a diagnosed case of B cell acute lymphoblastic leukemia since past 2 years and on chemotherapy, presented with hoarseness and dysphagia since past 2 months. Direct laryngoscopy revealed granular appearance of posterior pharyngeal wall and the supra-glottic larynx. Histopathological examination and bone marrow aspiration confirmed the diagnosis of disseminated histoplasmosis.

Conclusions
Pharyngo-laryngeal histoplasmosis should be considered in the differential diagnosis of an immunocompromised patient presenting with persistent hoarseness.
Thrombin Cleaves Prolactin Into a Potent 5.6-kDa Vasoinhibin: Implication for Tissue Repair
Authors: Zamora Magdalena , Robles Juan Pablo , Aguilar Manuel B , Romero-Gómez Sergio de Jesús , Bertsch Thomas , Martínez de la Escalera Gonzalo , Triebel Jakob , Clapp Carmen 
Published: August 2021

Abstract
Vasoinhibin is an endogenous prolactin (PRL) fragment with profibrinolytic, antivasopermeability, and antiangiogenic effects. The fact that blood clotting, vascular permeability, and angiogenesis are functionally linked during the wound-healing process led us to investigate whether thrombin, a major protease in tissue repair, generates vasoinhibin. Here, we have incubated human PRL with thrombin and analyzed the resulting proteolytic products by Western blot, mass spectrometry, high-performance liquid chromatography purification, recombinant production, and bioactivity. We unveil a main thrombin cleavage site at R48-G49 that rapidly (&lt; 10 minutes) generates a 5.6-kDa fragment (residues 1-48) with full vasoinhibin activity, that is, it inhibited the proliferation, invasion, and permeability of cultured endothelial cells and promoted the lysis of a fibrin clot in plasma with a similar potency to that of a conventional 14-kDa vasoinhibin (residues 1-123). The R48-G49 cleavage site is highly conserved throughout evolution and precedes the intramolecular disulfide bond (C58-C174), thereby allowing the 5.6-kDa vasoinhibin to be released without a reduction step. Furthermore, the 5.6-kDa vasoinhibin is produced by endogenous thrombin during the clotting process. These findings uncover the smallest vasoinhibin known, add thrombin to the list of PRL-cleaving proteases generating vasoinhibin, and introduce vasoinhibin as a thrombin-activated mechanism for the regulation of hemostasis, vasopermeability, and angiogenesis in response to tissue injury.
Mixed Corticomedullary Tumor Accompanied by Unilateral Aldosterone-Producing Adrenocortical Micronodules: A Case Report
Authors: Yoshida Sawa , Babaya Naru , Ito Hiroyuki , Hiromine Yoshihisa , Taketomo Yasunori , Niwano Fumimaru , Imamura Shuzo , Yamazaki Yuto , Sasano Hironobu , Kawabata Yumiko , Noso Shinsuke , Ikegami Hiroshi 
Published: August 2021

Abstract
Mixed corticomedullary tumors (MCMTs) are rare and comprise medullary and cortical cells in a single adrenal tumor. The mechanisms underlying their development have not been fully elucidated. Here, we report a case of MCMT in a 42-year-old woman. Based on the preoperative clinical findings, the patient was diagnosed as having a pheochromocytoma with subclinical Cushing syndrome. Postoperative pathological diagnosis revealed that the tumor demonstrated morphologically distinct medullary and cortical components, which produced catecholamines and cortisol, respectively. Hybrid tumor cells producing both catecholamines and cortisol were not detected. Adrenocorticotropin (ACTH)-positive tumor cells were identified to be present in the pheochromocytoma. This ectopic production of ACTH can contribute to an autonomous cortisol production in a paracrine manner. In addition, micronodules producing aldosterone were detected in the adrenal tissue adjacent to the tumor. The simultaneous development of these 2 lesions may not be correlated with each other; however, this case confirms the importance of a detailed histopathological examination of the adrenal lesions harboring complicated hormonal abnormalities by providing pivotal and indispensable information on their pathogenesis and the possible interaction of the hormones produced in the adrenal gland.
Ensayando el despertar: Miradas movilizadoras desde el pluriverso del Teatro del Oprimido, edited by Hjalmar Jorge Joffre-Eichhorn (2019)
Authors: Vivas-Martínez Gabriel 
Published: August 2021

Review of: Ensayando el despertar: Miradas movilizadoras desde el pluriverso del Teatro del Oprimido, edited by Hjalmar Jorge Joffre-Eichhorn (2019)
Hamburg: Hjalmar Jorge Joffre Eichhorn and Kickass Books, 481 pp.,
ISBN 978-3-00-064054-4, €20/$22 (individuals) and €60/$66 (institutions)
Resistance and Identity in The God of Small Things Written by Arundhati Roy
Authors: Dizayi Saman A. 
Published: August 2021

This paper presents an analysis of the novel "The God of the Small Things" written by Arundhati Roy. The primary purpose of this paper is to evaluate the idea of resistance and identity that have been described in the novel by the novelist. It will be demonstrated in this novel that how the resistance against the traditions and norms of post-colonial era is related to the self-realisation. There are different kinds of resistance that have been depicted in the novel at various circumstances. In Postcolonial context identity is a complex concept to be located in just a simple definition or to be investigated throughout a single theoretical approach. Resistance as a concept linked to the identity question. The Novel handles this notion and throughout its plot, besides the burden that is left from the colonial legacy, gender identity comes to the surface. Though women resistance appears as a reaction with identity suppression; yet it is a reflection of self-identification of gender inequality under patriarchal traditions inherited from long dominant masculine power. This paper elaborates on each type of resistance and activism that arises against the feudal and patriarchal forces structured by the economic and politically influential people in the new community as a sample in India after postcolonialism. Consequently, one of the points that the research ends with is that the act of resistance validates the pursuit for self-identity, which is an attempt to renown, reclaim and rename the world.
Reading Posthuman Ethics in Daniel Wilson’s Amped
Authors: Abdullah Omar M. , Kaur Hardev 
Published: August 2021

In 20th century and beyond, humans have witnessed numerous advances in technology which have opened new horizons. Science and technology redesigned human life exponentially and humans always search for a more technological world and hence more comfort and ease. As such, going past human confinement could be accessible through a few changes in human form, but these changes posture a contentious point since people grow into being more reliant on technology in order to execute their desires and needs. What will happen to humanness and humanity? What will happen to their moralities and behaviors? In this manner, technological development could have both promising and discouraging pictures within the human mind. The current study cites Daniel H. Wilson’s Amped (2013) to discuss the clash of views between Transhumanists and Bioconservatives. Transhumanists believe that human improvement advances should be made broadly accessible, where people could adopt these innovations and apply them to themselves to have a better life. In particular, bioconservatives consider human enhancement technologies as ‘dehumanizing’ for these technologies might weaken human dignity and affect something that is profoundly valuable about being human. As such, Posthuman theory is consulted in order to analyze the ethical and moral concerns of human enhancement technology in Wilson’s Amped. The findings are summed in the importance of ethics in any kind of enhancement and conclude that the trustworthy source is a priority to ensure success.
Using Team-Based Learning in Teaching English to EFL Undergraduate Students
Authors: Kareem Najat O. 
Published: August 2021

Team Based Learning (TBL) is a method that has been introduced to provide students with both conceptual and procedural knowledge to foster critical and creative thinking skills while students work in high functioning teams. The study throws some light on the TBL approach in general and the researcher's pilot- experiment on using the TBL in teaching English to EFL (English as a Foreign Language) undergraduate students. The main aim of this pilot experiment is to assess the TBL's effects on student engagement, accountability, and satisfaction and to identify the problems faced in applying it and then, in the light of the findings, to propose suggestions about how to use the approach effectively. Forty (40) second-year undergraduate students of the Department of English/ Faculty of Humanities and Social Sciences of Koya University were involved in this experiment and its evaluation. These students were taught through student learning teams for two successive academic years (2017-2018 & 2018-2019) in the subject of English Reading Comprehension. Both quantitative and qualitative data were collected from the students about their TBL experience using questionnaires. The results of the evaluation revealed that the vast majority of the students preferred TBL to the traditional individual learning and that the TBL has more positive effects on the students' engagement in class activities and assignments. The findings also indicate that despite the positive effects and the students' satisfaction with the approach, there are problems and obstacles on the way of its application in the classroom, but that with the proper use of the approach most of these problems can be overcome. What is important about this evaluation is that it is student-centered as it shows the real opinions of the students who lived the experience.
Workplace Heterogeneity and the Returns to Versatility
Authors: Stijepic Damir 
Published: August 2021

Abstract
In the canonical random on-the-job search model with continuous firm heterogeneity, I show that a mean-preserving spread of the firm-productivity distribution raises the returns to mobility, i.e., the inter-firm mobility of workers as measured by the number of outside contacts per employment spell. Both sorting and rent-share mechanisms play a role. In a further contribution, I distinguish frictional and structural impediments to mobility in order to establish a link between mobility and skills via the concept of versatility. Versatility enhances a person’s mobility since a mismatch between job requirements and the person’s skill set is less likely to occur. I provide some statistics in support of the discussed mechanisms. The findings are particularly intriguing in light of the concurrent rise in the productivity dispersion across firms and in the skill premium in many countries.
Die „Magie des Extrems“ in philosophischen Neuorientierungen. Nietzsches neue extreme Problemstellungen und -lösungen und das alte Beispiel des Sokrates
Authors: Stegmaier Werner 
Published: August 2021

AbstractThe later Nietzsche developed the “magic of the extreme” as a special strategy in order to make his philosophical reorientations successful. He needed this strategy not only to be heard at all; also the problems he faced called for it. The article first gives an overview of the most important problems Nietzsche coped with and the extreme solutions he offered. Then, we show how, according to Nietzsche, even Socrates, who stands for the beginning of the European Enlightenment, used the “magic” of extreme irritation and fascination to get this Enlightenment on its way.
Das Bild eines „europäischen Goethe“ in Nietzsches Götzen-Dämmerung. Einige Bemerkungen
Authors: Venturelli Aldo 
Published: August 2021

Abstract
This article analyses the origin of TI 49–51 on the basis of several posthumous fragments from the autumn of 1887, which had been reworked in 1888. This analysis highlights significant connections that got lost along the way to the final version of these aphorisms, such as Nietzsche’s comparison between Goethe and Spinoza which, in 1887, was the beginning of his updated reflections on Goethe. The origin and context of these aphorisms allow for a better understanding of the long-established image of Goethe expressed in the aphorisms of Twilight of the Idols and their close connection to the new reflections on Goethe as they had already come to the fore in Human, All Too Human when Nietzsche distanced himself from Wagner’s ideas. This also presents the opportunity for a more careful consideration of Nietzsche’s conception of European culture and its intellectual heritage and his relation to Napoleon as well as his characterization of the eighteenth-century and the need for self-overcoming during the nineteenth-century. Nietzsche considered this self-overcoming to be an important aspect of his thinking, and Goethe was an important precursor for Nietzsche’s conception of self-overcoming.