bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO-049: Inhibiting MNK kinases promotes macrophage immunosuppressive phenotype to limit anti-tumor immunity
Authors: Pham Thao N. D. , Spaulding Christina , Shields Mario A. , Khalafalla Mahmoud G. , Principe Daniel R. , Bentrem David J. , Munshi Hidayatullah G.
Published: November 2021

Background MAPK-interacting serine/threonine-protein kinase 1 and 2 (MNK1 and MNK2) are downstream effectors of the MEK/ERK and p38 MAPK pathways. Increased expression and activity of MNK kinases are linked to tumor growth and therapeutic resistance. Select MNK kinase inhibitors are currently being evaluated in clinical trials for different tumor types. Their immunomodulatory effects in tumors with low infiltrating CD8+ T have not been clearly defined. Methods: In vivo efficacy of MNK kinase inhibitors (CGP57380 and eFT508), either as a single agent or in combination with anti-PD-1 or anti-CSF-1R antibody, was tested in syngeneic mouse models of pancreatic cancer. Tumor-associated macrophages (TAMs) and murine bone marrow-derived macrophages (BMDMs) were evaluated in vitro for modulation of their polarization by MNK kinase inhibitors and their suppression of co-cultured T cells. Markers of M1/M2 polarization were measured by qRT-PCR. The effects of MNK kinase inhibitors on the expression of select M2 markers were also evaluated in ex vivo slice cultures of human pancreatic tumors. Results: We first found an inverse relationship between MNK kinase activity and CD8+ T cell abundance in human pancreatic tumors. In tumor-bearing mice, while pharmacological inhibition of MNK kinase activity increased CD8+ T cell infiltration, the tumor-infiltrating CD8+ T cells lacked effector function and failed to mount anti-tumor responses. Mechanistically, we showed that systemic inhibition of MNK kinases increased the expression of several anti-inflammatory genes in BMDMs and potentiated the ability of BMDMs and TAMs to suppress T cell proliferation. Reversal of T cell exhaustion either by an anti-PD-1 antibody or by TAM depletion with an anti-CSF-1R antibody enhanced the anti-tumor efficacy of MNK inhibitors and prolonged animal survival. Importantly, treating ex vivo human pancreatic cancer slice cultures with MNK inhibitors led to increased expression of known immunosuppressive markers in TAMs. Conclusion: Together, these findings provide new insights into the effects of MNK kinase inhibition on CD8+ T cell infiltration and TAM function and identify combination regimens with MNK kinase inhibitors to achieve effective anti-tumor responses in pancreatic cancer patients whose tumors have a low number of functional CD8+ T cells.

Citation Format: Thao N. D. Pham, Christina Spaulding, Mario A. Shields, Mahmoud G. Khalafalla, Daniel R. Principe, David J. Bentrem, Hidayatullah G. Munshi. Inhibiting MNK kinases promotes macrophage immunosuppressive phenotype to limit anti-tumor immunity [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-049.
Abstract PO-055: Phase II clinical trial of subtype directed neoadjuvant therapy in patients with localized pancreatic cancer
Authors: Tsai Susan , Borazanci Erkut , Gulley Margaret , Rashid Naim , Merker Jason , Khan Abdul H. , Chisholm Phillip , Hunt Bryan , Giorgadze Tamara , Hall William , Kamgar Mandana , Evans Douglas B. , Yeh Jen Jen
Published: November 2021

Background: Preoperative (neoadjuvant) therapy has become the preferred treatment sequencing strategy for patients with localized pancreatic cancer. During neoadjuvant therapy, approximately 30% of patients will experience metastatic disease progression while on treatment. Therefore, tools to aid clinicians to select efficacious first-line chemotherapeutic regimens is a critical unmet need. The most common neoadjuvant chemotherapy regimens used are 5-fluorouracil/irinotecan/oxaliplatin (mFOLFIRINOX) and gemcitabine/nab-paclitaxel (GnP). There is growing data to suggest an association of pancreatic cancer subtype (classical versus basal-like) with treatment response to therapy. Recently, the translation of tumor subtyping to the clinic has been successfully achieved using the Purity Independent Subtyping of Tumors (PurIST) single sample classifier. We aim to assess the clinical response to pancreatic cancer subtype-directed therapy in patients with localized pancreatic cancer. Methods: This is a phase II, multicenter, single-arm clinical trial for previously untreated patients with localized (resectable or borderline resectable) pancreatic cancer. Patients will undergo endoscopic ultrasound guided biopsy of the primary tumor and PurIST classifier to determine classical versus basal-like subtype. Patients with classical subtype will be assigned to mFOLFIRINOX and patients with basal-like tumors will be assigned to GnP. Following two months of therapy, patients will be restaged with a computed tomography scan, carbohydrate antigen (CA19-9) levels, performance status assessment, and a repeat endoscopic ultrasound guided biopsy for research. The primary endpoint is composite clinical response as measured by radiographic response, CA19-9 decline, and performance status following two months of treatment. Correlative endpoints include blood-based biomarkers for association with clinical response and stroma-specific response to therapy. The study has enrolled 4 of the anticipated 41 patients at the time of submission. Clinical Trial information: NCT 04683315.

Citation Format: Susan Tsai, Erkut Borazanci, Margaret Gulley, Naim Rashid, Jason Merker, Abdul H. Khan, Phillip Chisholm, Bryan Hunt, Tamara Giorgadze, William Hall, Mandana Kamgar, Douglas B. Evans, Jen Jen Yeh. Phase II clinical trial of subtype directed neoadjuvant therapy in patients with localized 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-055.
Abstract PO-060: N-terminal RHAMM cooperates with dysfunctional p53 to accelerate the progression of pancreatic cancer
Authors: Lin Anthony , Feng Jennifer , Chen Xiang , Wang Dunrui , Wong Megan , Zhang George , Na Joseph , Zhang Tiantian , Chen Zhengming , Chen Yao-Tseng , Du Yi-Chieh Nancy
Published: November 2021

Pancreatic cancer has the lowest survival rate in all types of cancer. Pancreatic cancer patients are often diagnosed at advanced stages. A better therapeutic development for this devastating disease is urgently needed. Receptor for hyaluronan-mediated motility (RHAMM), not expressed in adult normal pancreas, has been suggested as a prognostic factor and a potential therapeutic target for pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET). In this study, we initially sought to determine whether genetic deletion of RHAMM would slow down pancreatic cancer progression using Rhamm−/− mice. However, we found that Rhamm−/− mice expressed a N-terminal RHAMM protein. While N-terminal RHAMM did not enable malignant progression of pancreatic intraepithelial neoplasia in p48-Cre; LSL-KRASG12D mice, it accelerated the formation of invasive PDAC and shortened the survival of p48-Cre; LSL-KRASG12D mice with heterozygous p53 knockout. KrasG12D PDAC mice with homozygous p53 knockout mice died around 10 weeks, and the effect of N-terminal RHAMM was not apparent in these mice with short life span. In addition, N-terminal RHAMM shortened the survival of PNET-bearing RIP-Tag mice, which had inactivated p53. In our analysis of TCGA dataset, pancreatic cancer patients with mutant TP53 or loss of one copy of TP53 had higher RHAMM expression, which, combined, predicted worse outcomes. Taken together, by collaborating with dysfunctional p53, N-terminal RHAMM that lacks the centrosome targeting domain and degrons for interaction with the Anaphase-Promoting Complex (APC) accelerated pancreatic cancer progression.

Citation Format: Anthony Lin, Jennifer Feng, Xiang Chen, Dunrui Wang, Megan Wong, George Zhang, Joseph Na, Tiantian Zhang, Zhengming Chen, Yao-Tseng Chen, Yi-Chieh Nancy Du. N-terminal RHAMM cooperates with dysfunctional p53 to accelerate the progression of 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-060.
Abstract PO-093: JNK2 suppresses the growth and invasion of pancreatic cancer and is opposed by JNK1
Authors: Shi Jingwei , Tian Xiaodong , Kornmann Marko , Traub Benno
Published: November 2021

Introduction: Pancreatic cancer cells are exposed to multiple stressors with both endogenous (proliferation, metabolism and nutrient deprivation) and exogenous (medical treatment) origins. The c-Jun N-terminal protein kinases (JNKs) JNK1 and JNK2 are important stress-activated kinases, responsible for the cellular response to these stressors. Both were demonstrated to exert both tumor-suppressing and tumor-promoting effects in human cancers Most previous studies rely on nonspecific pharmacological JNK inhibition. In this study, we planned to determine the isoform-specific roles in PDAC. Methods: Specific JNK1- and JNK2-knockdown (KD) clones were established in cultured human pancreatic cancer cell lines MIA PaCa-2 and PANC-1 by using specific shRNA plasmids. Anchorage dependent and independent growth, as well as migration and invasion, were analyzed in JNK-1/2 KD clones and compared to pharmacological JNK inhibition using SP600125. Xenograft growth was assessed using an orthotopic mouse model. Mechanistically, we assessed changes in EMT markers both in vitro and in vivo. Results: JNKs were expressed in both cultured pancreatic cancer cell lines as well as in resected human pancreatic cancer samples. Specific downregulation of JNK2 resulted in an overall increase in cell proliferation, invasion and alterations in cytoskeleton structure, while JNK1-KD revealed opposite effects. Nonspecific JNK-inhibition using SP600125 inhibited cell growth of all cell lines except PANC-1. Conclusion: JNK1 and JNK2 play opposing roles in human pancreatic cancer. Specifically targeting JNK1 with the retained function of JNK2 may provide a potential, individualized approach for targeting pancreatic cancer progression.

Citation Format: Jingwei Shi, Xiaodong Tian, Marko Kornmann, Benno Traub. JNK2 suppresses the growth and invasion of pancreatic cancer and is opposed by JNK1 [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-093.
Abstract PO-125: The role of KDM6A in pancreatic cancer immune microenvironment
Authors: Jin Lin , Yang Jing , Yi Zhujun , Kim Hong S. , Tian Feng , Shi Jiaqi
Published: November 2021

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States, with a 10% 5-year survival rate. Immunosuppressive myeloid cells, including tumor-associated neutrophils (TANs), contribute to tumor development and treatment resistance. Lysine (K)-specific demethylase 6A (KDM6A) is one of the most frequently mutated epigenetic genes and a tumor suppressor in PDAC. However, the molecular mechanisms by which KDM6A contributes to PDAC development and whether KDM6A impacts the tumor immune microenvironment are unknown. This study established a genetically engineered pancreas-specific Kdm6a-knockout Ptf1aCre;LSL-KrasG12D/+;LSL-p53R172H/+ (KPC) PDAC mouse model to investigate the influence of KDM6A loss on PDAC development and tumor immune microenvironment. We found that KDM6A loss accelerated PDAC progression and increased metastases. Pancreata of mice with Kdm6a deficiency developed aggressive undifferentiated PDACs. Additionally, KDM6A loss led to increased infiltration of TANs and neutrophil extracellular traps (NETs) formation. Mechanistically, we used Bru-seq technology to investigate the impact of KDM6A on nascent RNA transcription. We demonstrated that many chemotactic cytokines related to neutrophil recruitment, specifically CXCL1, were upregulated in KDM6A-knockout PDAC cells. We further confirmed increased CXCL1 mRNA and protein levels in KDM6A-deficient human and mouse PDAC cells. In addition, immunohistochemical staining also confirmed the upregulated CXCL1 expression in both human and murine PDAC cells with KDM6A loss. TANs were found to express CXCR2, the receptor of CXCL1, by immunofluorescent analysis. To further confirm that cancer cells with KDM6A loss can attract neutrophils in vitro, we performed chemotaxis assays using both human neutrophils derived from PLB-985 cells and mouse primary neutrophils isolated from bone marrow and conditioned media from KDM6A- knockout or knockdown PDAC cells. We found that PDAC cells with KDM6A loss promoted neutrophil recruitment in vitro compared to KDM6A-retained PDAC cells. Furthermore, the CXCL1 neutralizing antibody reversed the chemotactic property of KDM6A-deficient PDAC cells, confirming that CXCL1 is the primary chemokine mediating the neutrophil recruitment. In summary, these findings shed light on the mechanism by which KDM6A loss promotes PDAC development, regulates tumor immune microenvironment, and suggests that the CXCL1-CXCR2 axis may be a candidate target for the treatment of PDAC, especially those with KDM6A mutations.

Citation Format: Lin Jin, Jing Yang, Zhujun Yi, Hong S. Kim, Feng Tian, Jiaqi Shi. The role of KDM6A in pancreatic cancer immune 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-125.
Abstract PO-130: Macropinocytosis at the nexus of crosstalk in the pancreatic tumor microenvironment
Authors: Zhang Yijuan , Recouvreux M. Victoria , Jung Michael , Galencamp Koen , Li Yunbo , Zagnitko Olga , Scott David , Lowy Andrew , Commisso Cosimo
Published: November 2021

A feature of tumor cells is the acquisition of nutrients via macropinocytosis, an endocytic form of protein scavenging that functions to support metabolism and proliferation in the context of a nutrient-depleted tumor microenvironment. Here, we provide evidence that macropinocytosis is also operational in the tumor stroma. We find that glutamine deficiency triggers macropinocytic uptake in patient-derived cancer-associated fibroblasts (CAFs) from pancreatic ductal adenocarcinoma (PDAC) tumors. Mechanistically, stromal macropinocytosis is dependent on a CaMKK2-AMPK signaling axis that activates Rac1. We find that these signaling events are potentiated via an enhancement of cytosolic Ca2+ caused by glutamine limitation. Interestingly, glucose deprivation, which robustly enhances AMPK activation, does not activate Rac1 and fails to induce uptake in CAFs. We determine that the selectivity of the observed macropinocytic response is mediated by the glutamine depletion-induced upregulation of ARHGEF2, a Rho/Rac guanine nucleotide exchange factor. We elucidate that macropinocytosis has dual function in CAFs – it serves as a source of intracellular amino acids that sustain CAF viability, and it provides extracellular amino acids that promote tumor cell survival. By specifically ablating macropinocytosis in the stroma, we demonstrate that macropinocytosis-deficient CAFs are unable to enhance PDAC tumor growth. Current efforts are focused on how different metabolic inputs in the tumor microenviroment can differentially regulate the CaMKK2-AMPK signaling axis in stromal cells. These results highlight the functional role of macropinocytosis in the tumor stroma and provide a mechanistic understanding of how nutrient deficiency can control stromal protein scavenging.

Citation Format: Yijuan Zhang, M. Victoria Recouvreux, Michael Jung, Koen Galencamp, Yunbo Li, Olga Zagnitko, David Scott, Andrew Lowy, Cosimo Commisso. Macropinocytosis at the nexus of crosstalk in the pancreatic 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-130.
Abstract PR-008: Kdm6 demethylases are critical regulators of pancreatic cancer initiation, progression and subtype specification
Authors: Leonhardt Laura , Li Lucia Y. , Berrios David I. , Ashe Sudipta , Hendley Audrey M. , Kim Grace E. , Hebrok Matthias
Published: November 2021

Aberrant epigenetic regulation is a hallmark of pancreatic cancer. Since changes in histone methylation are potentially reversible, they present an attractive target for therapeutic intervention. Kdm6a and Kdm6b belong to a family of histone demethylases specific for lysine 27 of histone 3 and have been implicated in multiple types of cancer, including pancreatic ductal adenocarcinoma (PDA). We have gathered data from the extensive investigation of a mouse model of PDA in which either Kdm6b or both Kdm6a and Kdm6b have been deleted with concomitant activation of oncogenic KrasG12D restricted to adult acinar cells. While prior work had demonstrated an important role for Kdm6a in PDA formation, our data now show that the closely related Kdm6b is implicated in PDA tumorigenesis as well. Partial or complete loss of Kdm6b results in accelerated acinar-to-ductal metaplasia (ADM) and formation of pancreatic intraepithelial neoplasia (PanIN) with increased inflammation and fibrosis. Accelerated ADM formation was also observed ex vivo upon culturing acinar cells in the absence of oncogenic Kras, indicating that Kdm6b activity is critical for the maintenance of acinar identity and suppresses the early stages of pancreatic neoplasia development. However, only mice heterozygous for Kdm6b continue to exhibit a reduced overall median survival compared to KrasG12D alone, while complete loss of Kdm6b results in a similar overall median survival compared to KrasG12D. This suggests a requirement for oncogenic Kdm6b function during later progression of PanIN to invasive cancer. Conversely, concomitant loss of Kdm6a and Kdm6b protects against ADM and PanIN formation in vivo and ex vivo and double mutants display a trend towards an increased overall median survival compared to mice carrying only the KrasG12D mutation. Strikingly, the resulting tumors of Kdm6a/Kdm6b deficient mice exhibit features of an extremely rare subtype of sarcomatoid pancreatic cancer found in human patients. Taken together, this suggests that Kdm6 demethylase function is required during the initiation and progression of PDA. Furthermore, targeting Kdm6a/Kdm6b with specific inhibitors at distinct stages might provide opportunities for novel treatment avenues for pancreatic cancer.

Citation Format: Laura Leonhardt, Lucia Y. Li, David I. Berrios, Sudipta Ashe, Audrey M. Hendley, Grace E. Kim, Matthias Hebrok. Kdm6 demethylases are critical regulators of pancreatic cancer initiation, progression and subtype specification [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-008.
Sentinel Lymph Node Biopsy May Prevent Unnecessary Axillary Dissection in Patients with Inflammatory Breast Cancer Who Respond to Systemic Treatment
Authors: Karanlik Hasan , Cabioglu Neslihan , Oprea Adela Luciana , Ozgur Ilker , Ak Naziye , Aydiner Adnan , Onder Semen , Bademler Süleyman , Gulluoglu Bahadir M.
Published: November 2021

Background and Objectives: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer treated up-front with systemic treatment. Both breast-conserving surgery and sentinel lymph node biopsy (SLNB) are controversial issues in the management of IBC. In this study, we aimed to assess the feasibility of SLNB in pathologically proven node-positive IBC patients. Methods: All patients with a histopathological diagnosis of IBC and biopsy-proven metastatic axillary lymph nodes underwent systemic treatment. Patients with a complete clinical response in the axilla who underwent SLNB followed by standard axillary dissection were analyzed. Results: The study consisted of 25 female patients. The identification rate (IR) and the false negativity rate (FNR) were 17/25 and 2/10, respectively. Overall, 9/25 and 7/25 of patients had a complete pathological response (pCR) in the breast and axilla after systemic treatment, respectively. Although the pCR in the axilla was 2/4 in nonluminal HER2-positive patients, the highest IR 4/4 and the lowest FNR 0/2 were determined in these patients. In triple-negative patients, however, the IR was 2/4 and the FNR was found to be 0/2. Conclusions: SLNB may be considered in selected axilla-downstaged IBC patients including patients with a pCR with HER2-positive and triple-negative tumors. Axillary dissection may be, therefore, omitted in those with negative SLNs.
An Enduring Covenant: The Past and the Present in Contemporary African Christian Practice
Authors: Nwadialor Kanayo L.
Published: November 2021

The arrival of Christianity in Africa witnessed varieties of African response. Each of the patterns of the response has received attention from scholars of various milieus. Missionary historiographers for instance see African initial resistance as the battle of Satan to keep the gospel from invading his so called kingdom; this led to an alliance between the missionaries and European colonial forces that caused Africans’ acceptance of Christianity through imposition. Many scholars have interpreted this imposition to mean that “pagandom” has been defeated and African primal religion has retreated. However, a series of movements emerged for religious independence, manifesting Africa’s attempts to forge a new identity. This paper adopts evolutionist theory and the culture lag theory to provide insight into the interface of this great encounter that produced a movement for social and religious change; a reflection of the echoes of African religio-cultural heritage and a manifestation of an enduring covenant.
Covid-19 and the Celebration of the Fetu Afahye Festival in Ghana
Authors: Assanful Vincent , Boakye Peter
Published: November 2021

Festivals are important occasions that African societies have used to bring members together to foster unity and forge development of the communities. Traditional leaders also use festival to propitiate the ancestral spirits and deities to help dispel evil in the society. Throughout the year, festivals and durbars are held in various parts of the country for reunions and developmental purposes, and to the strengthen beliefs of the society. Festivals help the community and people to forge a closer bond with their ancestors and to ask for their protection. Festivals are also held in order to purify the whole state so that people can enter the New Year with confidence and hope. This paper, uses newspapers, interviews, major secondary works and articles on the internet as a source of data. It also uses qualitative and phenomenological methods to assess the impact of the Covid-19 pandemic on the celebration of the Fetu Afahye festival among the people of Cape Coast (Oguaa) in Ghana. The advent of the pandemic in Ghana altered the lives of the people in the traditional society since it led to the cancellation of the celebration of their festivals. The paper also examines how the non-observance of such festivals, especially the Fetu Afahye, impacted the ritual lives of the people. The paper concludes that even though a ban was placed on the celebration of festivals, due to its significance the traditional leaders found a way to perform the rituals associated with them in the face of the pandemic. This was done in order to avoid incurring the wrath of the sacred and to give the members in the community a sense of identity.
Cities, Migration and the Historiography of Post-war Europe
Authors: Shaev Brian , Hackett Sarah
Published: November 2021

The role of municipalities in migrant integration in post-war European history has largely slipped below the radar in previous migration research. Our special issue presents case studies on how Bristol, Dortmund, Malmö, Mannheim, Stuttgart and Utrecht managed migrant influxes from the mid-1940s to 1960s. Following interdisciplinary advances in local migration studies, our urban histories take a diversity of approaches, present diverse temporalities, and uncover municipal responses that range from generosity to indifference and to outright hostility. In all six cities, despite such diversity in local attitudes and municipal policies, municipal authorities had significant impacts on migrants’ lives. The introductory article explores how our urban perspectives contribute to scholarship on reconstruction and the post-war boom; welfare; democracy and citizenship; and European integration. Using local migration as a lens into postwar European history, we argue, provides important new insights for the historiography of postwar Europe.
Rats, Rooms and Riots: Usage of Space by Immigrants in the Dutch Town Utrecht 1945–1970
Authors: Schrover Marlou
Published: November 2021

Immigrant access to space depended on the activities of local authorities, claim makers, journalists and firms. Together they shaped policies regarding immigrant housing, and more indirectly community formation. Local actors played a key role in migration governance, although they mostly did not work together. This article focusses on the Dutch town Utrecht, where housing was a major issue and immigrant housing was considered to be the worst in the Netherlands. When the number of immigrants was low, when employers arranged housing, and when the immigrants could be presented as much-needed workers, there were fewer protests. This article shows that immigrants lived where they were housed, where they could afford to, or were allowed to live, and only partly where they chose to live. Authorities attached value to the input of immigrant organisation, but most initiatives were for immigrants, rather than by immigrants.
Club Cell Secretion Protein 16 (CC16) Improve Chronic Obstructive Pulmonary Disease In Vivo Study
Authors: Qiu Zhihong , Yan Li , Xu Juan , Qian Xiaojun
Published: November 2021

Purpose: The purpose of this study was to evaluate CC16 in COPD treatment and relative mechanism by vivo study. Materials and methods: The mice were divided into Normal, Model and CC16 groups. Measuring Pathology and goblet cell number by HE or AB/PAS staining; Evaluating
apoptosis cell number by TUNEL assay; using flow separation to analysis inflammatory cells in difference groups; MAPK and NF-κB(p65) protein expression were evaluated by IHC assay in tissues; Total protein concentration of MUC5AC, CC16, Bax and Bcl-2 were evaluated by Western
Blot (WB) assay. Results: Compared with Normal group, the pathology was deteriorate and goblet cell number were significantly up-regulation in Model group, apoptosis goblet cell number were significantly depressed (P < 0.001), lympbocyte rate and hypertrophic rate were significantly
down-regulation and Eosinophils rate, Macrophage rate and Neutrophils rate were significantly up-regulation (P < 0.001, respectively) in Model group. By IHC assay, MAPK and NF-κB(p65) proteins expression were significantly increased (P < 0.001, respectively)
in Model group; by WB assay, MUC5AC and Bcl-2 protein expression were significantly up-regulation and CC16 and Bax proteins expression were significantly down-regulation (P < 0.001, respectively) in Model group. CC16 supplement, the COPD were significantly improved with relative
inflammatory cells rates significantly improving and relative proteins improving. Conclusion: CC16 could improve COPD by inducing goblet cell apoptosis increasing via regulation MAPK/NF-κB(p65) pathway In Vivo study.
Observed Processes Underlying the Favorable Vortex Repositioning Early in the Development of Hurricane Dorian (2019)
Authors: Alvey George R. , Fischer Michael , Reasor Paul , Zawislak Jonathan , Rogers Robert
Published: November 2021

Dorian’s evolution from a weak, disorganized tropical storm to a rapidly intensifying hurricane is documented through a unique multiplatform synthesis of NOAA’s P-3 tail-Doppler radar, airborne in situ data, and Météo-France’s Martinique and Guadeloupe ground radar network. Dorian initially struggled to intensify with a misaligned vortex in moderate midtropospheric vertical wind shear that also allowed detrimental impacts from dry air near the inner core. Despite vertical wind shear eventually decreasing to less than 5 m s−1 and an increasingly symmetric distribution of stratiform precipitation, the vortex maintained its misalignment with asymmetric convection for 12 h. Then, as the low-level circulation (LLC) approached St. Lucia, deep convection near the LLC center dissipated, the LLC broadened, and precipitation expanded radially outward from the center temporally coinciding with the diurnal cycle. Convection then developed farther downtilt within a more favorable, humid environment and deepened appreciably at least partially due to interaction with Martinique. A distinct repositioning of the LLC toward Martinique was induced by a spinup of a mesovortex into a small, compact LLC. It is hypothesized that this somewhat atypical reformation event and the repositioning of the vortex into a more favorable environment, farther from detrimental dry midtropospheric air, increased its favorability for the rapid intensification that subsequently ensued. Although the repositioning resulted in tilt reducing to less than the scale of the vortex itself, the preexisting broad mid- to upper-level cyclonic envelope remained intact with continued misalignment observed between the midlevel center and repositioned LLC even during the early stages of rapid intensification.
Relationships Are Built on Sunny Days: Uncovering Quiet Weather Communication Strategies
Authors: Liu Brooke Fisher , Seate Anita Atwell , Kim Ji Youn , Hawblitzel Daniel , Lee Saymin , Ma Xin
Published: November 2021

This study proposes the concept of quiet weather communication and offers the first framework of quiet weather communication strategies tied to specific public outcomes (e.g., build and maintain organization–public relationships). Most of the risk communication literature focuses on severe weather communication. We posit that through defining and examining quiet weather strategic communication we can better understand how the weather enterprise can prepare communities for future severe weather. Through four virtual focus groups with 28 NWS and broadcast meteorologists, we operationalize quiet weather communication strategies (humanize the organization, provide weather education, share the love of blue skies, and showcase quiet weather trends). We then report meteorologists’ perceptions of the strengths and weaknesses of each strategy and propose future directions for research on quiet weather communication.
Extended Multivariate Generalizability Theory With Complex Design Structures
Authors: Brennan Robert L. , Kim Stella Y. , Lee Won-Chan
Published: November 2021

This article extends multivariate generalizability theory (MGT) to tests with different random-effects designs for each level of a fixed facet. There are numerous situations in which the design of a test and the resulting data structure are not definable by a single design. One example is mixed-format tests that are composed of multiple-choice and free-response items, with the latter involving variability attributable to both items and raters. In this case, two distinct designs are needed to fully characterize the design and capture potential sources of error associated with each item format. Another example involves tests containing both testlets and one or more stand-alone sets of items. Testlet effects need to be taken into account for the testlet-based items, but not the stand-alone sets of items. This article presents an extension of MGT that faithfully models such complex test designs, along with two real-data examples. Among other things, these examples illustrate that estimates of error variance, error–tolerance ratios, and reliability-like coefficients can be biased if there is a mismatch between the user-specified universe of generalization and the complex nature of the test.
Africa’s Contributions to the Economy of Europe’s Two “World” Wars: De-centering the Dominant Narrative
Authors: Arukwe Nnanna Onuoha
Published: November 2021

Histories and stories of Europe’s two “World” Wars are generally centered on narratives that privilege metropolitan empire perspectives over the perspectives of their satellite countries and their societies. As Spivak correctly observes, European and American academic writing is produced to support the economic interests of these countries. Similarly, knowledge or information is never innocent as it expresses the interests of its producers. It has invariably been in the interest of Eurocentric academic chroniclers of the Europe’s “World” Wars to write Africa’s contributions out of the dominant narratives of those wars. Just like European military regiments containing African soldiers and soldiers of African descent, who fought in Europe’s second “World” War and enabled Allied Powers’ victory over Nazi Germany and its Axis Powers allies, were “bleached” off every post-victory battle photographs of the War, the dominant narratives of the two “World” Wars are “bleached” to rid them of Africa’s economic contributions to the successful prosecution of both wars. This article represents an intervention to de -center such dominant albeit erroneous narratives on both wars. It brings focus on Africa’s economic contributions to the war efforts with the underscoring argument that but for Africa’s economic contributions, Africa’s European colonizers could not have achieved victory over Germany in both wars. The article advocates a de-centering agenda, which stems from postcolonial studies and theoretical framework as a useful tool for such corrective scholarship endeavor. The conclusive argument is that Africa’s economic contribution to the successful prosecution of Europe’s “World Wars” is primarily phenomenal rather than epiphenomenal.
Cotton-containing printing wires based on the two-dimensional braiding method for three-dimensional printing of clothing
Authors: Wu Meng-jie , Zhi Chao , Tu Li , Wang Yong-zhen , Dai Yang , Yu Ling-jie , Meng Jia-guang , He Xiao-yi
Published: November 2021

There is a large somatosensory gap between the three-dimensional (3D) printing of clothing and traditional garments due to the limitations (e.g., air permeability and skin-friendliness) of the printing materials. For this reason, the application of traditional textile materials in 3D printing has become a hot topic in the field of 3D printed clothing. Based on the above, this work prepared four kinds of cotton-containing composite solutions and then impregnated thermoplastic polyurethane core yarns in these solutions to obtain four types of 3D printed cotton-containing composite core yarns (3Dp-C-CYs). Afterward, based on the two-dimensional (2D) braiding method, four kinds of cotton-containing 3D printing wires used for fused deposition molding technology were prepared by wrapping low-melting polyester filaments around the different 3Dp-C-CYs. After comparing the printing performance of the four cotton-containing 3D printing wires, the wire containing cotton powders had the best comprehensive performance and was selected to print the cotton-containing 3D printed fabrics. The results showed that the cotton-containing 3D printed fabric has good flatness and contains a large number of cotton powders; in addition, compared with the traditional polylactic acid and acrylonitrile butadiene styrene copolymer 3D printed fabrics, the 3D printed fabric made up of cotton-containing 3D printing wire can provide a closer wearing experience to that of cotton fabric. The 3D printing wire produced by the 2D braiding method offers a new idea for applying traditional textile materials in 3D printing, showing great application potentials in the field of 3D printing of clothing.
Young People Who Use Drugs Views Toward the Power and Authority of Police Officers
Authors: Greer Alissa , Selfridge Marion , Watson Tara Marie , Macdonald Scott , Pauly Bernie
Published: November 2021

Many young people who use drugs are structurally vulnerable to policing powers given the ongoing criminalization of drug possession. Police authority limits and the expression of that authority may play a significant role in police encounters among young people who use drugs. This qualitative study explores the views of young people who use drugs toward police power and authority in their recent encounters with police officers. Interviews were conducted with 38 young people who recently used illegal drugs in British Columbia, Canada. We found five interrelated themes related to perceptions of police authority: (1) skepticism and distrust toward authority; (2) paternalism and authority over drug use; (3) officer use of force; (4) police as power-hungry; and (5) officers above the law. Participants described police authority as limitless, unpredictable, untethered, easily abused, and lacking accountability. Participants feared holding police officers accountable to power abuses in a criminal justice system that they saw as stacked against them. Moving forward, institutional reforms may consider and account for the expression, limits, and use of police authority among young people who use drugs and other structurally vulnerable communities.
Employment of educated youth in rural Punjab: Amidst Stagnancy and (IM)Mobility
Authors: Narwana Kamlesh , Gill Angrej Singh
Published: November 2021

In the context of larger discussions of how education, employment opportunities and social mobility processes intersect, this article presents micro-evidence to interrogate the role of higher education in accessing avenues for mobility regarding employment opportunities for educated youth in India’s rural Punjab. By presenting their career ambitions and trajectories, this fieldwork-based article maps a plethora of dynamics influencing the individual journeys. The article reflects on how social capital, caste and economic marginality affect the career options and mobility potential of these young males and females. The findings reaffirm that caste, compounded by economic inequality, tends to inhibit paths to upward mobility for young people located at the lower end of traditional hierarchies. However, determined efforts by many disadvantaged young rural people to succeed, partly supported by targeted affirmative action programmes, are also showing some remarkable results that offer hope.
Radial Width of the Lateral Meniscus at the Popliteal Hiatus: Relevance to Saucerization of Discoid Lateral Menisci
Authors: Gamble Jamison G. , Abdalla Abdalla B. , Meadows Molly G. , Rauer Thomas , Chan Charles M. , Ganley Theodore J. , Tompkins Marc , Shea Kevin G. , Gamble James G.
Published: November 2021

Background:

A discoid lateral meniscus (DLM) is a congenital anomaly of the knee in which the lateral meniscus has an “O” shape and contains irregular, abnormal collagenous tissue. A DLM can cause mechanical symptoms and pain. Treatment of a symptomatic DLM is arthroscopic saucerization to reshape the meniscus to a more normal contour. Enough tissue must be removed to eliminate mechanical symptoms but not too much to create instability. The residual width of the meniscus is crucial at the popliteus hiatus because here the peripheral rim is unattached at the capsule. Reports in the literature recommend a residual width of 6 to 8 mm.

Purpose/Hypothesis:

The purpose of this research was to determine the width of the lateral meniscus at the popliteal hiatus in normal specimens. Our null hypothesis was that a residual width of 6 to 8 mm will be sufficient to approximate normal anatomy.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

We made direct measurements of the radial width of the lateral meniscus from the outer rim at the popliteal hiatus to the inner edge in 19 specimens (age, 2-120 months.) We measured one 4-year-old specimen with a bilateral complete DLM. We also measured 39 digital images of specimens (age, 1-132 months) using ImageJ. Finally, we made direct arthroscopic measurements of 8 skeletally mature specimens.

Results:

The average width of specimens <3 years old was 5.5 mm. The average width of the 10-year-old specimens was 12 mm. The average width of the skeletally mature specimens was 16 mm. A 4-year-old DLM specimen measured 19 mm.

Conclusion:

We rejected our null hypothesis. Direct measurements suggest that a residual width of 6 to 8 mm is insufficient for children ≥8 years old. A width of at least a full centimeter approximates the normal for 8-year-olds and at least 15 mm for adolescents.
Gender Gaps in Deceptive Self-Presentation on Social-Media Platforms Vary With Gender Equality: A Multinational Investigation
Authors: Kolesnyk Dasha , de Jong Martijn G. , Pieters Rik
Published: November 2021

Deceptive self-presentation on social-media platforms appears to be common. However, its prevalence and determinants are still largely unknown, partly because admitting such behavior is socially sensitive and hard to study. We investigated deceptive self-presentation from the perspective of mating theories in two key domains: physical attractiveness and personal achievement. A truth-telling technique was used to measure deceptive self-presentation in a survey of 12,257 adults (51% female) across 25 countries. As hypothesized, men and women reported more deceptive self-presentation in the domain traditionally most relevant for their gender in a mating context. However, contrary to lay beliefs ( N = 790), results showed larger gender differences in deceptive self-presentation in countries with higher gender equality because there is less gender-atypical (relative to gender-typical) deceptive self-presentation in these countries. Higher gender equality was also associated with less deceptive self-presentation for men and women worldwide.
GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy
Authors: Walia Harleen Kaur , Singh Navneet , Sharma Siddharth
Published: November 2021

Background

Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy.

Methods

The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02).

Conclusions

Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia
Women Entrepreneurs and Determinants of Their Success: An Empirical Study
Authors: Maity Sudarshan , Sahu Tarak Nath
Published: November 2021

Using a Logistic regression model the present study investigates the important factors that influence on ease of doing business by the women entrepreneurs. The respondents are from the four different backward regions in West Bengal, India. The goodness of fit of the model is checked in terms of the Hosmer–Lemeshow test. Moreover, a large share of the women-owned business is a single person enterprise, generates lower revenues, and is smaller in size. The study shows that most women are engaged in small entrepreneurs to help their families financially. Though, women entrepreneurs are facing challenges of financing and non-cooperation from their family members. Even from non-cooperation from the family, they are engaged in entrepreneurship after managing their households’ work. The level of productivity will be enhanced significantly in case easy access to credit and support received from the family members. The support may be in terms of mental as well by helping in households’ work. Further, the application of the Welch’s t-test shows the non-existence of a significant difference in income level among the two groups, who have faced complexities and who have no complexities into running the entrepreneurship. To improve the socio-economic status of the female counterpart of the society, initiatives from the grassroots level are absolutely essential.
Factors of Small Business Mentoring and Practices
Authors: Kar Brajaballav , Sarangi Subrat
Published: November 2021

Mentoring is essential when we consider the socio-economic profile of small business owners and the considerable rate of business failure. Entrepreneurs are independent as well as innovative by nature, and they may not like to discuss their confidential business issues with a third party. On the other hand, a mentor has to understand, help, support and improve overall aspects of the mentee’s business. Thus, mentoring entrepreneurs seems to be inherently contradictory. The function of the mentor and the mentoring process outcomes are not precisely understood. The argument ‘Mentoring is what a mentor does’ indicates the lack of clarity. This research uses a semi-structured interview and survey method to understand the mentoring process in practice. The perceptions and expectations of mentors and small business owners are analysed.

Findings indicate that mentors are more likely to underestimate the outcomes of the mentoring process compared to mentees. The appropriate experience and expertise of the mentor are considered more important in the mentoring process. There are no significant differences in the perceptions between mentors and business owners regarding mentoring contribution to marketing, finance and people management skills. Factor analysis for the 15 variables used in the scale suggests 6 factors such as capacity building, connect, chronemics, collaboration, concreteness and trust (5Cs and 1T) to be critical mentoring outcomes. The article contributes to small business owners, mentoring practitioners and funding agencies by clarifying the relationship among various factors involved in mentoring. The article also discusses the future agenda for research on small business mentoring.