bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ethics of Sourcing a Cadaver Population–A Perspective from South Africa
Authors: Kramer Beverley 
Published: May 2022

We cannot deny the early, turbulent unethical history of the sourcing of human bodies for dissection during the 18th and 19th Centuries, but we most certainly can learn from the past. While the International Federation for the Associations of Anatomists (IFAA) has recommended ethical guidelines for the sourcing of bodies from donors only (IFAA, 2021), many institutions around the world have not been able to fulfil these recommendations. In South Africa, as an ethical imperative, most departments of anatomy have converted from the use of unclaimed bodies (although legal by South African law) to body donor programs which are founded on ethics and informed consent. South Africa has a diverse multicultural population derived from four main population groups (Black, Coloured, White and Indian) with health sciences classes being made up of predominantly Black students. As a consequence of the transformation from the use of unclaimed bodies to donor programs, the population diversity of the more recent cadaver populations has been impacted and White bodies now predominate. This transformation of the cadaver population will in time also impact the large skeletal collections in South Africa which are used for teaching and research by both local and international researchers. The change in the cadaver population with respect to population affinity particularly, may also impact our students and how they view the body they dissect. In South Africa and Africa, a number of factors including religious and cultural practices have a bearing on the diversity of the donors in donor programs. Donor programs are extremely important from the ethical perspective, and so too is the informed consent aligned to registration for these programs. In considering establishing diversity in the cadaver population of our donor programs for the future, some of the questions which should be pondered by South African anatomists and anatomists in general are: Is it important to have a body donor cohort that is representative of the demographics of the student population? How do we overcome the religious and cultural challenges which are prevalent in some of the population in order to maintain a donor program that is based on sound ethical behaviour and which is representative of the population at large? In addition, will anatomists be able to maintain ethical standards of sourcing bodies in the light of unexpected crises such as the recent pandemic? There is no doubt that in South Africa, widespread communication, educational programs and community outreach, particularly through the traditional leaders of each community, would assist with increasing the diversity of the donors.ReferenceIFAA. 2012. International Federation of Anatomical Associations. Federative International Committee on Ethics and Medical Humanities (FICEM). Recommendations of good practice for the donation and study of human bodies and tissues for anatomical examination. Plexus 2012: 4‐5.
IMPROVing Communication about Diversity, Equity, and Inclusion in Health Professions Education
Authors: Muldoon Kathleen M. 
Published: May 2022

There has never been a stronger call for authenticity in health professions education than this moment in time. The health inequities laid bare by the COVID‐19 syndemic (a concept that describes the clustering of SARS‐CoV‐2 infection and disease by political, social and economic factors) compels health professions educators to learn how best to engage in, sustain, and deepen conversations on diversity, equity, and inclusion (DEI) within our learning environments. Health professions curricula should address such concerns through explicit faculty training programs in dialogue models of communication. I propose that medical improv can help refocus health professions training to the humanistic values of empathy for others and respect for multiple viewpoints. Medical improv refers to teaching methods that adapt improvisation principles and exercises to enhance professional competencies in the health professions, such as communication. I describe a training series implemented at one institution to prepare faculty facilitators to engage in conversations about DEI in a discussion‐based core course on the social determinants of health for first year medical students called “Humanity in Medicine”. Key elements of dialogue training, including examinations of identity and positionality, caretaking and team‐making, and conversations with a skeptic, are viewed through the lens of improv exercises as a pedagagy in communication. I report on facilitator and medical students’ positive response to facilitator training and the Humanity in Medicine course. Potential next steps towards a formal evaluation of the method, and outcomes assessments of the use of improv in health professions training are discussed.The IRB at MWU (Glendale, AZ) found that this study did not qualify as human subjects research as defined by 45 CFR 46.102.
Metaplasia‐induced Epithelial Heterogeneity Directs Pancreatic Injury and Tumorigenesis
Authors: DelGiorno Kathleen , Ma Zhibo , Lytle Nikki , Chen Bob , Jyotsana Nidhi , Weiser Novak Sammy , Cho Charles , Caplan Leah , Ben‐Levy Olivia , Neininger Abigail , Burnette Dylan , Trinh Vincent , Tan Marcus , Manor Uri , Mills Jason , Goldenring James , Lau Ken , Wahl Geoffrey 
Published: May 2022

Background and AimsDespite years of research, mechanisms of pancreatic injury and healing remain poorly understood. Acute pancreatitis is a painful and debilitating condition; chronic pancreatitis may be asymptomatic, but greatly enhances the risk of pancreatic ductal adenocarcinoma (PDAC). Acinar to ductal metaplasia (ADM), or the transdifferentiation of digestive enzyme producing acinar cells to ductal cells, is an early event in both conditions. While ADM is thought to function in healing and regeneration, it also represents a first step in tumorigenesis, demonstrating the duplicitous nature of this inherent plasticity. The goal of these studies was to define the populations arising in ADM, associated transcriptional changes, and their role in disease progression.MethodsAcinar cells were lineage traced to follow their fate upon injury. Transcripts of more than 13,000 EYFP+ cells were determined using single cell RNA sequencing (scRNA‐seq). Developmental trajectories were generated using several computational biology approaches that rely on non‐overlapping assumptions. Data were compared to scRNA‐seq studies of gastric metaplasia, oncogenic KrasG12D‐induced ADM, and human pancreatitis. Results were confirmed using immunostaining and electron microscopy. Tuft and enteroendocrine cell (EEC) populations were quantified throughout tumorigenesis. KrasG12D was expressed in injury‐induced ADM populations using several inducible Cre drivers.ResultsscRNA‐seq of ADM from chronically injured pancreata revealed emergence of a mucin/ductal population that resembles gastric pyloric metaplasia. Developmental trajectories suggest that some pyloric metaplasia cells generate tuft or EEC populations as distinct lineages. Comparison to KrasG12D‐induced ADM reveals populations associated with disease progression. Immunostaining demonstrates that tuft and EEC formation is an early event in tumorigenesis. Activation of KrasG12D in ADM populations results in neoplastic transformation and the formation of MUC5AC+ pit cells. Human pancreatitis samples reflect a pyloric metaplasia phenotype as well as the formation of tuft and EEC populations.ConclusionsADM under conditions of chronic injury results in the formation of a pyloric‐type metaplasia which seeds disparate tuft and EEC lineages. This carefully orchestrated plasticity generates myriad epithelial cell types which likely mitigate injury, providing protection from the formation of pancreatitis and PDAC. KrasG12D expression is sufficient to drive neoplasia when targeted to injury‐induced ADM populations offering an alternative origin for tumorigenesis. This program is conserved in human pancreatitis and provides insight into early events in pancreas diseases.
Triple Negative Breast Cancer (TNBC) Cells Growth is Inhibited by High Dose Ascorbic Acid
Authors: Bennett Lunawati L. 
Published: May 2022

ObjectiveAccording to the World Health Organization report, the incidence of breast cancer mortality is very high worldwide with 2.1 million women are being affected each year and death are estimated at 627,000 women. There are several subtypes of breast cancer. One of these subtypes is known as triple‐negative breast cancer (TNBC). TNBC doesn’t have the receptors for the hormone estrogen, nor progesterone, nor express HER2/neu; therefore, TNBC doesn’t respond to hormonal nor targeted therapies which makes TNBC difficult to treat.The desired outcome of the cancer therapies is to decrease the proliferative activity of the cancer cells, to minimize drug resistance, and to decrease the toxicity of the anticancer drugs. Ascorbic acid has gained popularity as preventive agent for cancer due to its minimal cytotoxic to normal cellular tissue; however, the use of ascorbic acid for the treatment of cancer has controversial history. Taking oral ascorbic acid had no or little effect on cancer treatment, but recent discovery that intravenous ascorbic acid can provide 100‐fold higher plasma levels than oral intake has renewed interest on the role of ascorbic acid in the cancer treatment.HypothesisAt high dose (pharmacological concentrations), ascorbic acid may act as a prodrug to deliver extracellular H2O2 that is selectively toxic to cancer cells, but non‐toxic and well tolerated to normal cells. It is postulated that TNBC cells growth will be inhibited by high dose of ascorbic acid.MethodsAscorbic acid was buffered to pH 7 with sodium hydroxide and prepared immediately before use. MDA‐MB‐231 cells was used as TNBC model. MTT assay, Hoechst33342, H2DCFDA, and Rhodamine123 staining using fluorescent microscope were conducted to determine cell viability, chromatin inducing apoptosis, intracellular generation of ROS, and mitochondrial membrane potential, respectively. Western Blot to detect different signaling protein expressions such as Poly (ADP‐Ribose) polymerase (PARP), Casp‐3, Casp‐9, P‐53, Bax, Bcl2, Apaf‐1, MMP2, MMP 9, BRCA1, BRCA2, Bim, Map kinases were conducted to test the hypothesis that ascorbic acid was effective to kill TNBC cells.ConclusionThis finding suggests that high dose ascorbic acid has a potential candidate as effective anti‐cancer for TNBC. At 1.6 mM, ascorbic acid killed MDA‐MB‐231, a TNBC cells by causing increased in caspase 3‐9 activities and by decreasing cell cycle regulatory proteins, Mitogen activated kinase 1‐4, and reactive oxygen species.
Let's Play Games: A comparison of case‐based learning approach with gamification technique
Authors: Zafar Umema , Khattak Madiha , Zafar Hamna , Rehman Huma 
Published: May 2022

Case based learning technique (CBL) has been in practice throughout the world for a few decades now. Our institute adopted it some four years back, when it shifted towards modular system of teaching. It is the main technique being used for conducting small group discussions. We decided to introduce a new technique called the gamification technique of conducting small group discussion. Need was there to know the effectiveness of the new technique as well as to assess the factors for its preference so it could be modified to be more productive. The aim of this research was to assess the effectiveness of gamification teaching technique in comparison to the traditional CBL technique both quantitatively and qualitatively.This is a mixed‐method randomized controlled trial, conducted in Khyber Medical College on First Year Medical Students from June to October 2021. Group based teaching involving both CBL and gamification approach was used in this study in a cross over manner. Addressing the ethical concerns, and after informed consent pre‐ and post‐testing was done to quantify the performance and an open‐ended survey was disseminated after the sessions to check the perception of the students.The study recorded (quantitatively) that post testing mean score of gamification teaching technique was 3.41±0.982, while for CBL the mean was 3.55±1.055, recording an insignificant difference with p‐value of 0.608. In qualitative analysis, about 12 (80%) students preferred the gamification technique, their perception being that it instills competitiveness, increases the involvement of students in class and their motivation level. This research further revealed that the CBL approach had the advantage of quick learning via the facilitator presentation, and due to the handouts, it was easy to follow. Some of the negative points of CBL reported were that; the participants found it a boring and monotonous way of learning. The drawback of gamification reported was, that the students were unsure about the accuracy of the information they prepared initially as it wasn’t being directed by the facilitator. The study concluded an insignificant difference among the two techniques quantitatively; however, qualitatively the students preferred gamification as a better technique for learning.
The Microsomal Triglyceride Transfer Protein Inhibitor, Lomitapide, Improves Vascular Function in Obesity
Authors: Munkhsaikhan Undral , Kwon Young‐In , Sahyoun Amal M. , Ait‐Aissa Karima , Kassan Modar , Kassan Adam 
Published: May 2022

ObjectivesIn this study, we investigate the effect of lomitapide, a microsomal triglyceride transfer protein inhibitor, on cardiovascular function in obesity.HypothesisWe hypothesize that lipid level downregulation by lomitapide is a fundamental mechanism that improves cardiovascular function.MethodsEight‐week‐old C57/b6 mice were fed with a high fat diet (HFD) for 12 weeks in the presence and absence of lomitapide. Lomitapide was administered by gavage (1mg/Kg/Day) for the last 2 weeks of HFD feeding. Bodyweight, blood glucose, body composition, and lipid profile were determined. Vascular function and endothelial function markers were studied in aorta and mesenteric resistance arteries (MRA).ResultsLomitapide treatment reduced the body weight in obese mice. Blood glucose, % of fat mass, total cholesterol, and LDL levels were significantly reduced and the % of lean mass was significantly increased after lomitapide treatment. Aortic and mesenteric arteries vascular response to sodium nitroprusside (SNP) was similar among groups. However, the vascular response to acetylcholine (Ach) was improved in the treated group. This was associated with a decreased level of vascular endoplasmic (ER) reticulum stress, inflammation, and oxidative stress.ConclusionsTreatment with lomitapide attenuated the increase in body weight in obese mice and restored the lipid profile and vascular function. These effects were accompanied by a decrease in inflammation and oxidative stress.
Effect of miRNA: MRE Complementarity for SBP‐1 Gene Silencing in a Caenorhabditis Elegans Apoptosis Model
Authors: Cocquyt Alexander J. , Wee Abigale H. , De Lucas 
Published: May 2022

Small Interfering RNAs (siRNA) are a type of post‐transcriptional gene regulator with perfect complementarity to its target gene/mRNA. microRNAs (miRNA) are a type of post‐transcriptional gene regulator that silences a number of genes based on sequence complementarity to the miRNA Response Element (MREs) on the target mRNA. siRNAs of varying complementarity to their target sequence will be used as a proxy to [investigate/disprove] the existence of a miRNA complementarity level that maximizes gene silencing of SBP‐1 which regulates lipid homeostasis in C. elegans.The lipid homeostasis and fatty acid synthesis pathway in C. elegans is homologous to the human SREBP pathway. Red Nile staining and body size measurements provide proxy measurements for C. elegans lipid homeostasis and fatty acid synthesis in response to glucose feeding and siRNA introduction via soaking. SBP‐1, fat‐2, fat‐5, fat‐6, fat‐7, and elo‐2 mRNA expression in C. elegans is measured via RT‐PCR.In this study, we determine whether higher siRNA:mRNA complementarity increases siRNA silencing of the Bcl‐2 and Sbp‐1 pathways in C. elegans following the introduction of high and low complementarity siRNAs as a proxy for investigating the gene silencing effects of miRNA:MRE complementarity.
Cytotoxic Effect of Synthetic Peptides on Normal and Cancerous Cells
Authors: Nyman Karl , Kerns Hailey , Torres Daniel , Sheehan Hugo , Martin Rachael , Borysov Sergiy I. 
Published: May 2022

This research explores anti‐cancer activities of synthetic peptides that inhibit the CMG helicase, the major DNA replicative helicase. Targeting CMG helicases for cancer treatment provides a unique opportunity to develop a cancer treatment that effectively eradicates cancer cells without affecting normal healthy tissues. This approach exploits a natural difference between activation of CMG helicases in normal and cancer cells. Collective evidence shows that normal cells – compare to cancer cells – possess higher levels of CMG helicase reserves available for activation throughout the S phase. Cancer cells, on the other hand, activate the majority of their helicases at once, thereby exhausting their helicase reserves. Based on this, we hypothesized that our peptides – by targeting the CMG helicase – would lead to the death of cancer cells, while spare corresponding normal cells.In this study, we utilized two types of cancerous and normal cell lines: pancreatic cancerous Hs766T and normal hTERT‐HPNE cell lines, as well as glioma M059J and normal glial SVGp12 cell lines. Cells were plated in 96 well plates at a density of 3,000 cells/well and treated with different concentrations of studied peptides. Viabilities of cells were scored by a colorimetric CCK‐8 assay. According to our IC50 calculations, both cancerous cell lines were much more sensitive to the peptide treatments compare to their normal counterparts. Indeed, we observed that normal cell lines required almost 25 times higher concentrations of peptides to reach the same cytotoxic effect as the cancerous cells. Interestingly, we contrast these results with our studies with Gemcitabine, a therapeutic agent that is currently used for cancer treatment. Unlike our studied peptides, treatments with Gemcitabine led to an equal demise of both cancerous and normal cells.
Quantitative Mass Spectrometry Reveals a Proteome‐wide Role for Cyclin A and Cks1 in Multisite, Non‐Proline Directed Phosphorylation by CDK1
Authors: Ly Tony , Al‐Rawi Aymen , Endicott Jane , Korolchuk Svitlana 
Published: May 2022

Cdk1 is a master kinase of mitotic cell division, phosphorylating thousands of substrates in a highly temporally regulated manner. How Cdk1 phosphorylates the right substrate at the right time remains an open question.Cdk1 activity requires complex formation with a cyclin subunit: cyclin A or cyclin B. Additionally, active Cdk1 is found in complex with a small adaptor protein called Cks1. Cyclin subunits activate Cdk1 and tune Cdk1 substrate choice through interactions with short linear motifs on substrates. While Cks1 is essential in all organisms tested to date, a general function for Cks1 in Cdk1 substrate choice has not been demonstrated.In this study, we investigated the roles of the non‐catalytic subunits of Cdk1 in substrate phosphorylation in human cells. We designed an in vitro assay in which we induced protein phosphorylation in fixed and permeabilized human lymphoblasts using active recombinant Cdk1 either in complex with cyclin A, cyclin B, or cyclin B+Cks1. Global phosphorylation levels were then measured using quantitative mass spectrometry.Our data demonstrate that, contrary to the textbook model of Cdk1 as a proline‐directed kinase, both cyclin A and Cks1 facilitate widespread Cdk1 phosphorylation of sites lacking a +1 proline motif. Our results also suggest a role for Cks1 in multisite phosphorylation. We propose a model whereby cyclin A and Cks1 have indispensable functions in promoting non‐proline directed, multisite phosphorylation of Cdk1 substrates to mediate dynamic, switch‐like changes in protein function required for mitotic entry, proper chromosome segregation and cell division.
miRNA Regulation of α‐2,6‐ Sialylation: Comprehensive Analysis of ST6GAL1 & 2
Authors: Jame Chenarboo Faezeh , Mahal Lara K. 
Published: May 2022

MicroRNAs (miRs) are endogenous non‐coding RNAs that modulate gene expression at either the transcriptional or translational level through interaction with untranslated regions of mRNA. Works from the Mahal Lab and others have shown miRs as major regulators of glycosylation. ST6GAL1 and ST6GAL2 decorate glycoproteins with α‐2,6‐sialic acid, an epitope with important roles in immunology and cancer biology.Herein, we analyze miRs that regulate ST6Gal1 and ST6Gal2 gene expression through interaction with 3′UTR regions of target mRNAs. Using miRFluR, a high throughput fluorescent sensor‐based method recently introduced by the Mahal Lab, we analyzed miR regulation of ST6Gal1 & 2 with miR mimics representing the currently known human miRome (~2700 miRs). Our analysis identified 89 miR regulators of ST6GAL1 and 102 regulators of ST6GAL2. Selected hits were validated by Western blot analysis and RT‐PCR. Finally, we took advantage of SNA staining assay using fluorescence microscopy to validate the sialylation outcome by ST6GAL1 after treatment with specific miR mimics. Our data reveals miRNA regulation of α‐2,6‐sialylation that is associated with pancreatic and other cancers.
Detection of proper Type 3 Secretion System Translocon Assembly using a split Luciferase Assay
Authors: Guo Hanling , Heuck Alejandro P. 
Published: May 2022

Type 3 secretion system (T3SS) is used by many Gram‐negative bacteria to colonize the host and inject effector proteins into target cells. Inhibitors targeting T3SS are important to combat the appearance of multidrug‐resistant pathogens. In Pseudomonas aeruginosa, the T3SS secreted proteins PopB (SctE) and PopD (SctB) are required to inject effector proteins into the host cells. PopB and PopD associate with the target membrane and they are proposed to form a translocon pore by which effectors are translocated. This translocon is a potential target for inhibitors because these molecules do not need to overcome the intrinsic problems associated with cell membrane permeability and the presence of efflux pumps.In previous studies, we have reported that the PopD N‐terminus is exposed to host cell cytosol (J. Biol. Chem. 2018 293 8982–8993). We reasoned that the PopD N‐terminal exposure could be used as a reporter for properly assembled translocons. Using a split form of the small NanoLuc (NLuc) luciferase, we have developed an assay to detect the exposure of this N‐terminus to the host cytosol. HeLa cells producing the large truncated version of NLuc are used as targets. These cells are incubated with a P. aeruginosa ΔpopD PAK strain that produces a PopD variant fused with the missing portion of NLuc at the N‐terminus (Nluc10‐PopD). Assembly of a functional translocon is detected by the maturation of NLuc enzyme in the HeLa cell cytosol and the production of luminescence. Failure to assemble a functional translocon did not produce luminescence. The assay has a typical signal‐to‐background ratio (S/B) of 6 ‐ 10 and a Z factor above 0.5, constituting an excellent tool for the screening and detection of small molecule inhibitors of T3SS translocon assembly.