bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO-118: The tumor immune microenvironment is decisive in the survival of pancreatic ductal adenocarcinoma
Authors: Aziz Hosein M. , Saida Lawlaw , de Koning Willem , Stubbs Andrew , Li Yunlei , van Eijck Casper H. J. , Mustafa Dana A. M.
Published: November 2021

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy associated with a poor prognosis. Only 10% of the patients survive longer than five years. So far, factors underlining long-term survivorship in PDAC are not well understood. Therefore, we aimed to identify the key players in the tumor immune microenvironment (TIME) associated with long-term survivorship in PDAC patients. Methods: The immune-related gene expression profiles of surgically resected PDAC tumors of patients who survived and remained recurrence-free of disease for > 3 years (long-term survivors, n=10) were compared to PDAC tumors of patients who had survived ≤ 6 months (short-term survivors, n=10) due to tumor recurrence. Samples were profiled using the nCounter® PanCancer Immune Profiling Panel of NanoString Technology. Validation was performed by spatial analysis of immune cells using the GeoMx™ Digital Spatial Profiler. Results: Tumor-infiltrating B cells were found to be significantly increased in the TIME of long-term survivors by gene expression profiling (p=0.018). The high tumor infiltration of B cells was confirmed by spatial protein profiling (p=0.049). This increase was accompanied by more T cells and antigen-presenting cell infiltration. Moreover, the activated immune cells were found to infiltrate in between tumor cells as well as in stromal areas in long-term survivors. In contrast, the TIME of short-term survivors was characterized by a high density of immunosuppressive cells like CD25 and regulatory T cells infiltrating in a highly fibrotic vicinity. Conclusion: This is the first comprehensive study that connects the immune landscape of gene expression profiles and protein spatial infiltration with the survivorship of PDAC patients. We found higher infiltration of B cells in TIME of long-term survivors which highlights the importance of targeting B cells and B cell-based therapy for future personalized immunotherapy in PDAC patients.

Citation Format: Hosein M. Aziz, Lawlaw Saida, Willem de Koning, Andrew Stubbs, Yunlei Li, Casper H. J. van Eijck, Dana A. M. Mustafa. The tumor immune microenvironment is decisive in the survival of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-118.
Abstract PO-119: DFMO mediated improvement in survival of an orthotopic model of pancreatic cancer is associated with modulating immune suppression in the tumor microenvironment
Authors: Nakkina Sai Preethi , Gitto Sarah B. , Pandey Veethika , Beardsley Jordan M. , Rohr Michael W. , Parikh Jignesh G. , Phanstiel Otto , Altomare Deborah A.
Published: November 2021

There remains an urgent need to target pancreatic tumor cells using innovative strategies. KRAS and MYC, are important oncogenes in pancreatic ductal adenocarcinoma (PDAC) which pose a challenge to successful treatment of PDAC. Our previous studies have shown that inhibition of ornithine decarboxylase 1 (ODC1) using difluoromethylornithine (DFMO) decreases MYC expression and tumorigenesis. GW5074 can modulate RAF1, a downstream effector of KRAS. Here we test the responsiveness of pancreatic tumor cells treated with DFMO alone and in combination with GW5074. We used an orthotopic animal model of pancreatic tumor using KRas-driven murine pancreatic cancer cells (PanO2) to test the effects of these compounds on tumor microenvironment and overall survival. Cellular and molecular changes in the tumor microenvironment were assessed using immunohistochemistry. The results showed an inhibition of pancreatic cancer cell viability in DFMO and DFMO+GW5074 treatment groups in vitro, with a significant decrease in tumor weight compared to control treatment group in vivo. However, in terms of overall survival, DFMO alone resulted in a dramatic increase in survival compared to control treatment group. Interestingly, GW5074 alone or DFMO in combination with GW5074 did not result in a detectable effect on survival. Further investigation of immune cells in the tumor microenvironment revealed that standalone DFMO treatment was associated with an increase in infiltration of macrophages, T cell costimulatory marker CD86 and T cell markers (CD3, CD4 and CD8) compared to control and GW5074 treated groups. Additionally, DFMO is associated with decreased MYC expression compared to control and GW5074 treated groups. In conclusion, DFMO decreased MYC expression and associated immune suppression in the PDAC microenvironment. In contrast standalone GW5074 treatment resulted in maintenance of MYC expression and worse survival. In conclusion, the present study highlights the success of DFMO in PDAC treatment in part through downregulation of MYC and a decrease in associated immune suppression.

Citation Format: Sai Preethi Nakkina, Sarah B. Gitto, Veethika Pandey, Jordan M. Beardsley, Michael W. Rohr, Jignesh G. Parikh, Otto Phanstiel, Deborah A. Altomare. DFMO mediated improvement in survival of an orthotopic model of pancreatic cancer is associated with modulating immune suppression in the tumor microenvironment [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-119.
Abstract PO-129: Targeting CCR1 reprograms tumor associated macrophages in pancreatic cancer
Authors: Zhang Yaqing , Brown Kristee L. , Yan Wei , Nwosu Zeribe C. , Carpenter Eileen K. , Donahue Katelyn L. , Velez-Delgado Ashley , Yang Sion , Pasca di Magliano Marina
Published: November 2021

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDA) includes abundant fibroblasts and infiltrating immune cells, the latter largely immunosuppressive. We previously showed that targeting regulatory T cell (Treg), a prevalent T cell population in pancreatic cancer, failed to relieve immunosuppression and led to accelerated tumor progression. We discovered that Treg depletion reprogrammed tumor associated fibroblasts and increased immunosuppressive myeloid cell recruitment, an effect that was partially mediated by CCLs/CCR1signaling. Thus, we sought to investigate the potential therapeutic effect of targeting CCR1 in pancreatic cancer. By single cell RNA sequencing, we found CCR1 to be mainly expressed by tumor associated macrophages (TAMs) and neutrophils (or granulocytes) in both human and mouse PDA. We then orthotopically transplanted syngeneic mouse pancreatic cancer cells in CCR1 knockout hosts, and observed reduced tumor growth which was rescued by CD8 T cell depletion. Histological analysis showed elevated Granzyme B expression in infiltrating T cells, as well as an increase in cleaved caspase 3 positive cancer cells in tumors implanted in Ccr1−/− mice. Through cytometry by time of flight (CyTOF) and co-immunofluorescence we also discovered that TAMs in tumors implanted in Ccr1−/− mice expressed less Arginase 1 and CD206 -both markers of immunosuppressive macrophages- compared to TAMs in wild type tumors. Thus, our data is consistent with the notion that tumor associated macrophages lacking CCR1 expression are less immunosuppressive, consequently allowing increased CD8 T cell-mediated anti-tumor immunity. We are currently exploring combination approaches targeting CCR1 in pancreatic cancer.

Citation Format: Yaqing Zhang, Kristee L. Brown, Wei Yan, Zeribe C. Nwosu, Eileen K. Carpenter, Katelyn L. Donahue, Ashley Velez-Delgado, Sion Yang, Marina Pasca di Magliano. Targeting CCR1 reprograms tumor associated macrophages in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-129.
Abstract PR-011: Loss of compensatory feedback mechanism involving splicing factor SRSF1 accelerates KrasG12D-mediated pancreatic cancer initiation
Authors: Wan Ledong , Lin Kuan-Ting , Rahman Mohammad A. , Wang Zhikai , Park Youngkyu , Tuveson David A. , Krainer Adrian R.
Published: November 2021

KRAS is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC), triggering the formation of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). However, the majority of pancreatic cells from KC (LSL-KrasG12D/+; Pdx-1-Cre) mice carrying the KrasG12D mutation remain morphologically normal for a long time, suggesting the existence of compensatory feedback mechanisms that buffer KrasG12D signaling, and that additional steps are required for disrupting cell homeostasis and promoting transformation. Here we found that splicing factor SRSF1, which is associated with cell transformation, is downregulated in the majority of morphologically normal pancreas cells with the KrasG12D mutation as a compensatory feedback mechanism. To assess the role of SRSF1 in PDAC, we generated a transgenic mouse strain (SC) with Dox-inducible pancreatic-specific expression of SRSF1 protein. Elevated SRSF1 alone is sufficient to induce pancreatitis and ADM transformation. By further crossing the SC strain with KrasG12D alone (KSC) or together with Trp53R172H (KPSC), we found that increasing SRSF1 accelerated KrasG12D-mediated tumor initiation and resulted in more aggressive PDAC. To address the underlying mechanisms of SRSF1’s involvement in the homeostatic response to KrasG12D mutation and in PDAC initiation, we generated organoid lines from the above mouse strains. Following Dox induction, elevated SRSF1 with Kras WT or KrasG12D consistently activated MAPK signaling, which is one of the top negatively enriched pathways in response to KrasG12D. Furthermore, SRSF1 promoted the expression of Il1r1—an IL1 receptor associated with the activation of MAPK signaling—by regulating an alternative-splicing event in the 5’UTR to generate a more stable mRNA isoform. We conclude that decreased SRSF1 is a compensatory feedback mechanism in pancreatic cells against the KrasG12D mutation, whose disruption facilitates PDAC initiation.

Citation Format: Ledong Wan, Kuan-Ting Lin, Mohammad A. Rahman, Zhikai Wang, Youngkyu Park, David A. Tuveson, Adrian R. Krainer. Loss of compensatory feedback mechanism involving splicing factor SRSF1 accelerates KrasG12D-mediated pancreatic cancer initiation [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PR-011.
BET Inhibition Enhances TNF-Mediated Antitumor Immunity
Authors: Wellinger Lisa C. , Hogg Simon J. , Newman Dane M. , Friess Thomas , Geiss Daniela , Michie Jessica , Ramsbottom Kelly M. , Bacac Marina , Fauti Tanja , Marbach Daniel , Jarassier Laura , Thienger Phillip , Paehler Axel , Cluse Leonie A. , Kearney Conor J. , Vervoort Stephin J. , Trapani Joseph A. , Oliaro Jane , Shortt Jake , Ruefli-Brasse Astrid , Rohle Daniel , Johnstone Ricky W.
Published: November 2021

Targeting chromatin binding proteins and modifying enzymes can concomitantly affect tumor cell proliferation and survival, as well as enhance antitumor immunity and augment cancer immunotherapies. By screening a small-molecule library of epigenetics-based therapeutics, BET (bromo- and extra-terminal domain) inhibitors (BETi) were identified as agents that sensitize tumor cells to the antitumor activity of CD8+ T cells. BETi modulated tumor cells to be sensitized to the cytotoxic effects of the proinflammatory cytokine TNF. By preventing the recruitment of BRD4 to p65-bound cis-regulatory elements, BETi suppressed the induction of inflammatory gene expression, including the key NF-κB target genes BIRC2 (cIAP1) and BIRC3 (cIAP2). Disruption of prosurvival NF-κB signaling by BETi led to unrestrained TNF-mediated activation of the extrinsic apoptotic cascade and tumor cell death. Administration of BETi in combination with T-cell bispecific antibodies (TCB) or immune-checkpoint blockade increased bystander killing of tumor cells and enhanced tumor growth inhibition in vivo in a TNF-dependent manner. This novel epigenetic mechanism of immunomodulation may guide future use of BETi as adjuvants for immune-oncology agents.
Ferula sommieriana (Apiaceae), a new species from Pelagie Islands (Sicily)
Authors: CAMBRIA SALVATORE , BRULLO CRISTIAN , TAVILLA GIANMARCO , SCIANDRELLO SAVERIO , MINISSALE PIETRO , GIUSSO DEL GALDO GIANPIETRO , BRULLO SALVATORE
Published: November 2021

Ferula sommieriana, a new species occurring in Lampedusa and Linosa, islands of Pelagie Archipelago in the Sicilian Channel, is described and illustrated. Previously it was attributed to F. communis, from which it differs in several features regarding mainly the morphology and anatomy of terminal leaf lobes and mericarps, as well as the shape and size of reproductive structures. Its ecology, conservation status and relationships with other allied Mediterranean species of the sect. Ferula are provided, as well as the analytical keys of the species belonging to the aforesaid section.
Unravelling the Past: World War I in Africa
Authors: Samson Anne
Published: November 2021

Africa’s involvement in World War I presents the researcher with challenges that few researchers of the Western Front are likely to encounter. The centenary years of the War have seen a range of publications on the conflict in Africa: from Marike Sherwood who claims little has been written on Africa’s involvement to others who have tended to rely on online articles that are limited in scope and draw on dated publications, thereby perpetuating myths. A handful of researchers are breaking new ground through their accessing of archival material. Authors such as David Killingray and Joe Lunn, writing on West Africa over two World Wars, unwittingly set the scene for how Africa as a whole has been perceived. However, an outcome of the centenary commemorations of the War has been new and varied insights to Africa’s contributions, not least the different approaches taken by Africans and non-Africans, academic and enthusiast, and those interested in the conflicts of French (West) Africa and the rest of Africa. Engagement with the diaspora and people from the across the continent has reinforced the diversity of Africa in contrast to the published narratives and interpretations of the war which have generally been homogeneous in their approach. This study provides an opportunity to explore recent historiographical developments of the war in Africa. In particular, it aims to show that by treating Africa as a single entity (‘Africa is a country’), misconceptions have been perpetuated and experiences of World War II conflated with those of World War I. In addition, the complexities, challenges and rewards of researching Africa’s involvement in World War I are highlighted in the article.
“Looking After Yourself Is Self-Respect”: The Limits and Possibilities of Men’s Care on a Night Out
Authors: Duncan Tristan , Roberts Steven , Elliott Karla , Ralph Brittany , Savic Michael , Robards Brady
Published: November 2021

Notions of masculinity have played a central role in social and cultural research on men’s drinking events. Within this context, masculinity is regularly called on to explain the problematic disparities that mark men’s alcohol consumption, including men’s disproportionate involvement in drinking and a range of alcohol-related harms. More recently, however, researchers have begun to emphasize men’s drinking events as sites of care and support, leading some to suggest that men’s drinking masculinities are evolving in affirmative and health promoting ways. While unsettling the tendency of scholars to problematize men’s drinking masculinities, foregrounding the possibilities of men’s care potentially obscures its complexities and constraints. In this paper, we are concerned to critically re-examine the relationship between masculinity, care, and events of men’s alcohol consumption. Where some authors have positioned men’s care as an innate or uncomplicated good, we draw on a feminist ethics of care approach to explore its complexities, constraints, and exclusions. Through focus group discussions with 101 men, our analysis describes how ideals of masculine autonomy emerged through men’s accounts of drinking events, fundamentally shaping the constitution, practice, and possibilities of care. For the men in our study, the valorization of autonomy fostered ambivalence and tension around care, hindering their capacity as care givers and receivers. In turn, opportunities and accountability for care were overlooked, avoided, or displaced onto women. By highlighting the complexity of men’s care, our account complicates existing scholarship on men’s drinking while also gesturing toward new avenues for public health practice. We conclude by outlining how a more concerted focus on care may be integrated into public health policy, research, and programming and, in the process, contribute to the promotion of more health affirming and ethical modes of masculinity.
The vibration of thermoelastic silicon nitride Nanobeam based on green-naghdi theorem type-II subjected to mechanical damage and ramp-type heat
Authors: Youssef Hamdy M , Alharthi Hamzah , Kurdi Mohamed
Published: November 2021

In this work, an analysis for thermoelastic homogeneous isotropic nanobeams under damage mechanics consideration was built. Under easily supported boundary conditions with fixed side ratios, the Green-Naghdi model type-II, an extended thermoelasticity theory model, has been utilized. For the governing differential equations, the Laplace transforms technique was used on the time variable. The answers were found in the domain of the Laplace transform. Tzou’s approximation approach based on an iteration formula was used to calculate the Laplace transform inversions numerically. The numerical findings for a rectangular silicon nitride thermoelastic nanobeam have been obtained and validated. As a case study, we assumed that the beam is thermally loaded with ramp-type heat and that its two edges are simply supported. Figures representing different scenarios have been used to display the numerical results. Mechanical damage value, ramp-time heat parameter and beam thickness are all reported to have a substantial influence on all of the examined functions.
Realignment and Recidivism Revisited: A Closer Look at the Effects of California’s Historic Correctional Reform on Recidivism Outcomes
Authors: Bird Mia , Nguyen Viet , Grattet Ryken
Published: November 2021

California’s 2011 Public Safety Realignment has received considerable attention nationally as a watershed moment in the movement to downsize prisons. The present study leverages data collected in 12 California counties to provide the most comprehensive examination to date of how Realignment has impacted recidivism for the key offender groups targeted in the reform. We find small to modest increases in rearrest in three of four groups targeted in the reform. The fourth group experienced moderate decreases in rearrest. Moreover, all groups experienced decreases in reconviction, which gives credence to the idea that a significant reprioritization of who should be in prison can positively affect public safety. These findings point to the complex ways that reforms like Realignment can affect custodial and community-based supervision systems by changing incentives for law enforcement and the people who supervise offenders. Our conclusions discuss the implications for other states and systems considering similar reforms.
Processing Human Milk to Increase Nutrient Density for Preterm Infants
Authors: Ulus Hande Z. , Tekbudak Merve Yasemin , Allen Jonathan C.
Published: November 2021

Background:

Human milk is the optimal food for newborns. Choices to feed preterm infants in neonatal intensive care units are mother’s milk, donor milk, or formula. Preterm infants have better tolerance for human milk, but the lower caloric density of donor milk might not meet preterm infant growth needs. Preterm infants have higher protein and energy requirements with a limited stomach capacity. Therefore, there is a need for human milk with increased nutrient density.

Research Aim:

To concentrate donor milk to have a higher caloric and protein density while avoiding side effects of high osmolality by precipitating lactose at low temperatures.

Methods:

We investigated the results of volume reduction and lactose removal processes on the lactose, protein, osmolality, and viscosity of human milk. Donor milk was obtained from WakeMed Mothers’ Milk Bank. Homogenization and evaporative condensation were applied to samples ( N = 36) before they were stored frozen overnight, followed by refrigerated centrifugation for lactose removal at 0 °C. Supernatants were separated and compared to the composition of controls.

Results:

A significant reduction of lactose ( SW = -262, p < .0001) and osmolality ( SW = -211.5 p < .01) was achieved in the concentrated milk without a significant protein loss from centrifugation ( SW = -44.5, p = .49). A 30%–40% volume reduction is within the American Academy of Pediatrics recommended osmolality for infant feeding.

Conclusion:

Concentrating human milk in a milk bank setting for feeding preterm infants might be a simple and low-cost process to achieve a product with higher nutrient density and no non-human components.
Implementing teacher leadership in Malaysian schools: Exploring secondary principals’ perspectives
Authors: Mohd Tahir Lokman , Samah Narina A. , Mohd Anis Siti Nisrin , Ali Mohd Fadzli
Published: November 2021

Objective: The purpose of this study is to explore principals’ perspectives on the concept of teacher leadership, the strategies that they employed to support teacher leadership practice and the challenges and issues that principals faced while implementing teacher leadership. Methodology: This qualitative case study uses interview sessions with 10 purposely selected principals from various types of secondary schools. All schools are public schools that are administered and funded by the Ministry of Education, Malaysia. Findings: The study reveals that principals had a comprehensive understanding of the concept of teacher leadership; in fact, principals were able to list teacher leaders’ characteristics and provide definitions for the concept of teacher leadership. In exploring principals’ strategies to support teacher leadership practice, five themes emerged: developing future leaders, a mentoring programme, involving more teachers as teacher leaders, practising an ‘open door’ policy and providing more opportunities for teachers to offer mutual assistance. In terms of the challenges for teacher leadership practices, principals shared particular issues such as the unwillingness of teachers to become teacher leaders due to their heavy workloads and challenges in eading senior teachers. Significance: This study supplements the literature that explores teacher leadership within the Malaysian schooling context, which has hitherto been understudied. Thus, the concept of teacher leadership needs more in-depth investigation and evaluation to ascertain its suitability within Malaysia's educational system. For the Ministry of Education, this study notes some practical implications for improving teacher leadership in Malaysian schools.
Analytical derivation of thread profile in internal thread milling process
Authors: Dogrusadik Ahmet
Published: November 2021

Thread milling is a new machining process as compared to thread tapping. As a thread making process in use for a long time, thread tapping did not have any alternative processes except the thread turning for limited cases until computer numerical control (CNC) technology had enabled the three axes synchronized motion. Therefore, investigations about the thread milling process are less as compared to other machining processes. In this work, the thread profile in the internal thread milling process was derived analytically. Experimental work was also performed to verify the performance of the analytical model. It was revealed that the thread profile produced by the cutting edge of the tool is not a straight line but a curve, and the average slope through the thread profile is less than the slope of the cutting edge of the tool. Besides, the effective thread profile enlarges along the vertical axis and constricts laterally as the ratio of thread mill diameter to thread diameter increases.
Innovative Marketing Strategies for Small and Medium Enterprises of Western Madhya Pradesh (India): An Analytical Study
Authors: Keshari Pragya
Published: November 2021

The micro, small and medium enterprises are an essential part of the Indian industrial sector. It plays a decisive role in growth and development of Indian economy. The review of literature on various aspects of small and medium enterprises (SMEs) showed that the SMEs, both in the country and other parts of the world, still rely on conventional marketing practices and, more or less, face the same types of challenges. Therefore, the present study is undertaken to examine the marketing strategies of SMEs in western Madhya Pradesh, India, and to suggest some innovative marketing practices for them to prosper. The sample consists of 439 SMEs drawn on a random basis from Indore and Dhar districts of Madhya Pradesh. The primary data are collected through a self-designed instrument with 40 items/statements, developed thorough a review of literature on the topic and personal interviews of managers of SMEs. The data are analysed using statistical tools like factor analysis and chi-square test applied with the help of Statistical Package for Social Sciences (SPSS) 20 Software. The study findings reveal that SME managers still rely on age-old practices of marketing. The article recommends some innovative marketing practices for SMEs.
Factors That Influence Risk Perceptions and Successful COVID-19 Vaccination Communication Campaigns With American Indians
Authors: Boyd Amanda D. , Buchwald Dedra
Published: November 2021

COVID-19 vaccinations are the primary tool to end the pandemic. However, vaccine hesitancy continues to be a barrier to herd-immunity in the United States. American Indians (AI) often have higher levels of distrust in western medicine and lower levels of satisfaction with health care when compared to non-Hispanic Whites. Yet AIs have high COVID-19 vaccination rates. We discuss factors that influence AI risk perceptions of COVID-19 vaccinations including the impact of COVID-19 on AI Elders, community, and culture. We conclude with future research needs on vaccination communication and how culturally congruent communication campaigns may have contributed to high COVID-19 vaccination rates.
Study of Selected Flavonoid Structures and Their Potential Activity as Breast Anticancer Agents
Authors: Al-Jumaili Mohammed Hadi Ali , Al hdeethi Muqdad Khairi Yahya
Published: November 2021

Flavonoids contain pharmacological effects that help to protect cells from damage. However, the anticancer activity of flavonoids is related to their modulation of signal transduction pathways within cancer cells. Natural substances such as flavonoids have immune-stimulating anti-tumor effect that could lower breast cancer risk. However, various diseases included Alzheimer’s and cancer disease are associated with flavonoids intake due to their ability as antioxidant agent to alter essential cellular enzyme’s function. Therefore, through interaction between flavonoids and Cytochrome P450 (CYP) family enzymes led to make them chemopreventive agents for breast cancer. In this analysis, the chemo-informatics properties of 5 selective flavonoid derivatives and their efficiency as anti-breast cancer drugs were evaluated. Flavonoid ligands were docked with the predicted protein, which is human placental aromatase complexes with exemestane, a breast cancer drug (3S7S). Based on various docking energies, the molecular characteristics and bioactivity score of the following components, C15H12O6 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydro-4H-chromen-4-one and C15H12O5 5,8-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one showed greatest molecular properties and bioactivity docking scores of −8.633117 and −8.633117 kcal/mol respectively. Therefore, both compounds could be considered antitumor agent.
Exempting the state and responsibilizing individuals during pandemic governance: Analyzing the health minister’s responses to the Covid-19 pandemic in Turkey
Authors: Akguloglu G Ezgi , Con Wright Gulcin
Published: November 2021

The COVID-19 pandemic pushed the governments of the world to implement different regulative and protective measures. Although these measures required serious re-considerations of public health strategies, they were still grounded on pre-existing contexts of countries’ health systems, namely the “new public health” paradigm. Turkey’s neoliberal health reforms since 2003 coincide with the principles of this paradigm’s trends toward marketizing services and responsibilizing individuals; yet the Turkish context of the pandemic also stands out due to its mixed and unique form of governance. Utilizing the tweets of the Turkish Health Minister between March 13th and October 1st, 2020, we conducted a thematic qualitative analysis investigating the Turkish state’s response to the COVID-19 pandemic. Our analysis revealed that state responsibility was framed around building new pandemic hospitals, informing the public, and building trust. Conversely, his tweets assigned Turkish individuals an active role in shaping pandemic outcomes through their “informed” and “empowered” agency. Finally, he coined “togetherness,” referring to the sum of individual actions, as an indispensable goal in assuring public compliance with precautions. The Minister’s tweets reflect the unique nature of pandemic governance in Turkey with a relatively imposing and swift response of centralized power but a primary focus on “responsibilized” individuals’ collective actions.
Digital well-being theory and research
Authors: Büchi Moritz
Published: November 2021

Digital well-being concerns individuals’ subjective well-being in a social environment where digital media are omnipresent. A general framework is developed to integrate empirical research toward a cumulative science of the impacts of digital media use on well-being. It describes the nature of and connections between three pivotal constructs: digital practices, harms/benefits, and well-being. Individual’s digital practices arise within and shape socio-technical structural conditions, and lead to often concomitant harms and benefits. These pathways are theoretically plausible causal chains that lead from a specific manifestation of digital practice to an individual well-being-related outcome with some regularity. Future digital well-being studies should prioritize descriptive validity and formal theory development.
What should relational egalitarians believe?
Authors: Hojlund Anne-Sofie Greisen
Published: November 2021

Many find that the objectionable nature of paternalism has something to do with belief. However, since it is commonly held that beliefs are directly governed by epistemic as opposed to moral norms, how could it be objectionable to hold paternalistic beliefs about others if they are supported by the evidence? Drawing on central elements of relational egalitarianism, this paper attempts to bridge this gap. In a first step, it argues that holding paternalistic beliefs about others implies a failure to regard them as equals in terms of their moral agency. In a second step, it shows that the fact that we should regard others as equals in this sense raises the threshold for sufficiency of evidence for paternalistic beliefs to be epistemically justified. That is, moral reasons of relational equality encroach on the epistemic. However, these reasons are not decisive. In cases where others are about to jeopardize critical goods such as their lives, mobility or future autonomy, relational equality sometimes calls for paternalistic action and, by extension, the formation of beliefs that render such action rational. The upshot is that in order to meet demands of relational equality we have a pro tanto reason to not hold paternalistic beliefs about others.
Low-Input RNA-Sequencing in Patients with Cartilage Lesions, Osteoarthritis, and Healthy Cartilage
Authors: Wang Katherine , Esbensen Q.Y. , Karlsen T.A. , Eftang C.N. , Owesen C. , Aroen A. , Jakobsen R.B.
Published: November 2021

Objective

To analyze and compare cartilage samples from 3 groups of patients utilizing low-input RNA-sequencing.

Design

Cartilage biopsies were collected from patients in 3 groups ( n = 48): Cartilage lesion (CL) patients had at least ICRS grade 2, osteoarthritis (OA) samples were taken from patients undergoing knee replacement, and healthy cartilage (HC) was taken from ACL-reconstruction patients without CLs. RNA was isolated using an optimized protocol. RNA samples were assessed for quality and sequenced with a low-input SmartSeq2 protocol.

Results

RNA isolation yielded 48 samples with sufficient quality for sequencing. After quality control, 13 samples in the OA group, 9 in the HC group, and 9 in the CL group were included in the analysis. There was a high degree of co-clustering between the HC and CL groups with only 6 genes significantly up- or downregulated. OA and the combined HC/CL group clustered significantly separate from each other, yielding 659 significantly upregulated and 1,369 downregulated genes. GO-term analysis revealed that genes matched to cartilage and connective tissue development terms.

Conclusion

The gene expression profiles from the 3 groups suggest that there are no major differences in gene expression between cartilage from knees with a cartilage injury and knees without an apparent cartilage injury. OA cartilage, as expected, showed markedly different gene expression from the other 2 groups. The gene expression profiles resulting from this low-input RNA-sequencing study offer opportunities to discover new pathways not previously recognized that may be explored in future studies.
Clothing Aesthetics: Consistent Colour Choices to Match Fair and Tanned Skin Tones
Authors: Perrett David Ian , Sprengelmeyer Reiner
Published: November 2021

Fashion stylists advise clothing colours according to personal categories that depend on skin, hair and eye colour. These categories are not defined scientifically, and advised colours are inconsistent. Such caveats may explain the lack of formal tests of clothing colour aesthetics. We assessed whether observers preferred clothing colours that are linked to variation in melanin levels among White women. For this, we presented 12 women's faces: six with fair skin (relatively lower in melanin) and six with tanned skin (relatively higher in melanin). Across two experiments, observers ( N = 96 and 75) selected the colour (hue and saturation or hue and value) of simulated clothing that most suited the skin tone of each face. Observers showed strong preferences for red and blue hues, and in addition favoured ‘cool’ blue hues to match fair skin and ‘warm’ orange/red hues to match tanned skin. This finding suggests that skin tone can determine colour preferences for clothes.
The association between sleep quality, preoperative risk factors for chronic postoperative pain and postoperative pain intensity 12 months after knee and hip arthroplasty
Authors: Boye Larsen Dennis , Laursen Mogens , Simonsen Ole , Arendt-Nielsen Lars , Petersen Kristian Kjaer
Published: November 2021

Background:

Chronic postoperative pain following total joint replacement (TJA) is a substantial clinical problem, and poor sleep may affect predictive factors for postoperative pain, such as pain catastrophizing. However, the magnitude of these associations is currently unknown. This exploratory study investigated (1) the relationship between preoperative sleep quality, clinical pain intensity, pain catastrophizing, anxiety, and depression and (2) their associations with chronic postoperative pain following TJA.

Methods:

This secondary analysis from a larger randomized controlled trial included rest pain intensity (preoperative and 12 months postoperative; visual analogue scale, VAS), preoperative Pittsburgh Sleep Quality Index (PSQI), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) data from 74 knee and 89 hip osteoarthritis (OA) patients scheduled for TJA. Poor sleepers were identified based on preoperative PSQI scores higher than 5.

Results:

Poor sleepers demonstrated higher preoperative VAS, pain catastrophizing, anxiety, and depression compared with good sleepers (all p < 0.003). Preoperative PSQI (β = 0.23, p = 0.006), PCS (β = 0.44, p < 0.005), and anxiety (β = 0.18, p = 0.036) were independent factors for preoperative VAS. Preoperative VAS (β = 0.32, p < 0.005), but not preoperative sleep quality (β = −0.06, p = 0.5), was an independent factor for postoperative VAS.

Conclusion:

The OA patients reporting poor preoperative sleep quality show higher preoperative pain, pain catastrophizing, anxiety, and depression. High preoperative pain intensity, but not poor sleep quality, was associated with higher chronic postoperative pain intensity. Future studies are encouraged to explore associations between sleep and chronic postoperative pain.
Building Theory From Practice: Mapping Executive Chefs’ Menu Planning Processes Using a Flowchart
Authors: Ho Juei-Ling , Lin Cheng-Fa , Lai Mei-Ying , Tseng Liang-Yi , Chiang Tai-Ying
Published: November 2021

The main purpose of this study is to build from practice to theory by developing a flow chart of menu planning based on the practices of a single successful executive chef and then testing the generality of the flow chart by assessing agreement with flows by 10 other executive chefs working in similar environments. This paper involves deep observation of real-life practices of one 5-star executive chef and his associates using. Observation is based on the 5W2H1E approach. A flowchart of the menu planning process is developed based on data from observing. The research uses degrees-of-freedom analysis of responses from ten chefs in assessing acceptance of the flowchart structure. It is concluded that the flow chart is meaningful in that it is generally acceptable. Ideas from the research contribute to theory and have practical implications. Contributions and practical implications are discussed.
Exploring the Determinants of the China-Pakistan Economic Corridor and Its Impact on Local Communities
Authors: Akhtar Nadeem , Khan Hidayat Ullah , Jan Muhammad Asif , Pratt Cornelius B. , Jianfu Ma
Published: November 2021

The China-Pakistan Economic Corridor (CPEC), a major development project in China’s fast-evolving Belt and Road Initiative (BRI), is arguably the most comprehensive of the six BRI economic and infrastructure corridors on land. For Pakistan, it is perceived “as the harbinger of a new era of connectivity and integration” that will not only transform the region’s economic development but also the well-being of Pakistanis. It investigates the impact of CPEC as perceived by the local communities in its ZoI. It also evaluates CPEC’s potential challenges: public support and local communities’ concerns such as their awareness, acceptance, and ownership of CPEC. To accomplish our research objectives, we analyze original microdata from 1,585 respondents living proximate to propose CPEC route(s) of Khyber Pakhtunkhwa province, in Pakistan. After aggregating the data on the basis of age, education, income, and social status, we conduct descriptive, bivariate, and multivariate analyses in an attempt to answer three research questions. We find significantly high level of awareness of CPEC across the board in the older age group of respondents (i.e., 40 years or older), hereinafter referred to as mature, highly educated, that is, respondents with university education. Older respondents expect more environmental and economic benefits than younger respondents, even as the latter expect lower social change and effect on migration than do the former. However, those in the upper social class expect higher economic and political benefits from CPEC, compared with those in the lower social class—an early indication of possible elite capture.
Predicting Outcomes of Talar Osteochondritis Dissecans Lesions in Children
Authors: Johnson Mitchell A. , Park Kunbo , Talwar Divya , Maguire Kathleen J. , Lawrence J. Todd R.
Published: November 2021

Background:

Reports detailing the rates of radiographic healing after treatment of talar osteochondritis dissecans (TOCD) remain scarce. There is also a paucity of data characterizing treatment outcomes and the risk factors associated with poor outcomes in children with TOCD.

Purpose:

To identify factors associated with healing, assess treatment outcomes, and develop a clinically useful nomogram for predicting healing of TOCD in children.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

This was a retrospective review of all patients ≤18 years of age with TOCD from a single pediatric institution over a 12-year period. Surgical treatment was left to the discretion of the treating surgeon based on standard treatment techniques. Medical records and radiographs were reviewed for patient and clinical data, lesion characteristics, and skeletal maturity. Radiographic healing was evaluated at the 1-year follow-up, and patients with complete versus incomplete healing were compared using multivariable logistic regression models to examine the predictive value of the variables.

Results:

The authors analyzed 92 lesions in 74 patients (mean age, 13.1 ± 2.7 years [range, 7.1-18.0 years]; 61% female). Of these, 58 (63%) lesions were treated surgically (drilling, debridement, microfracture, bone grafting, or loose body removal), and the rest were treated nonoperatively. Complete radiographic healing was seen in 43 (47%) lesions. In bivariate analysis, patients with complete healing were younger ( P = .006), were skeletally immature ( P = .013), and had a lower body mass index (BMI; P < .001) versus those with incomplete healing. In a multivariate regression model, the factors that correlated significantly with the rate of complete healing were age at diagnosis, BMI, and initial surgical treatment. The lesion dimensions were not significantly associated with the likelihood of healing. A nomogram was developed using the independent variables that correlated significantly with the likelihood of complete radiographic healing.

Conclusion:

Complete radiographic healing of TOCD lesions was more likely in younger patients with a lower BMI. The effect of initial surgical treatment on potential healing rate was greater in older patients with a higher BMI.
A Decision Rule for Determining the Optimal Transplant Listing Window for Patients With a Fontan Physiology
Authors: Delaney Laura
Published: November 2021

The Fontan is a complex surgical procedure used as a palliative treatment for children with univentricular hearts. In the past, the mortality rate was high and the associated comorbidities as a result of the Fontan circulation were many. However, as research into the condition developed, better understanding has led to a massive reduction in early mortality and a rapidly increasing population of such patients surviving well into adulthood. This has led to a large surge in patients with congenital heart disease being referred for cardiac transplant assessment. According to research, listing these patients at the optimal time is the key to improving transplant outcomes. However, determining that optimal time is unclear and controversial. In this article, I address this issue by developing an optimal timing rule that accounts for the factors faced by specialist cardiologists in determining when transplant ought to be considered for this cohort of patients.
An evaluation of strategies to achieve greater than 90% coverage of maternal influenza and pertussis vaccines including an economic evaluation
Authors: Giles Michelle L. , Khai Kong , Krishnaswamy Sushena , Bellamy Karen , Angliss Margaret , Smith Christopher , Fay Olivia , Paddle Paul , Vollenhoven Beverley
Published: November 2021

Background

Maternal immunisation is an essential public health intervention aimed at improving the health outcomes for pregnant women and providing protection to the newborn. Despite international recommendations, safety and efficacy data for the intervention, and often a fully funded program, uptake of vaccines in pregnancy remain suboptimal. One possible explanation for this includes limited access to vaccination services at the point of antenatal care. The aim of this study is to evaluate the change in vaccine coverage among pregnant women following implementation of a modified model of delivery aimed at improving access at the point of antenatal care, including an economic evaluation.

Methods

This prospective multi-centre study, using action research design, across six maternity services in Victoria, Australia, evaluated the implementation of a co-designed vaccine delivery model (either a pharmacy led model, midwife led model or primary care led model) supported by provider education. The main outcome measure was influenza and pertussis vaccine uptake during pregnancy and the incremental cost of the new model (compared to existing models) and the cost-effectiveness of the new model at each participating health service.

Results

Influenza vaccine coverage in 2019 increased between 50 and 196% from baseline. All services reduced their average cost per immunisation under the new platforms due to efficiencies achieved in the delivery of maternal immunisations. This cost saving ranged from $9 to $71.

Conclusion

Our study demonstrated that there is no ‘one size fits all’ model of vaccine delivery. Future successful strategies to improve maternal vaccine coverage at other maternity services should be site specific, multifaceted, targeted at the existing barriers to maternal vaccine uptake, and heavily involve local stakeholders in the design and implementation of these strategies. The cost-effectiveness analysis indicates that an increase in maternal influenza immunisation uptake can be achieved at a relatively modest cost through amendment of maternal immunisation platforms.