bluuebunny/crossref_metadata_2025 huggingface dataset:
A Pilot Study of Intralesional Injection of Triamcinolone Acetonide for Desmoid Tumors: Two-Year Outcomes
Authors: Wilke Benjamin K. , Garner Hillary W. , Bestic Joseph M. , Chase Lori A. , Heckman Michael G. , Schoch Jennifer J. , Attia Steven
Published: December 2022

Purpose:

The purpose of this pilot study was to examine the clinical efficacy and safety of serial triamcinolone injections for the treatment of desmoid tumors.

Patients and Methods:

Nine patients were enrolled into this prospective study and underwent three serial ultrasound-guided triamcinolone injections (120 mg) at 6-week intervals. MRI was compared at baseline and every 6 months, out to 24 months. Safety and tolerability were assessed by clinical evaluation and questionnaires, including the 12-item short form survey (SF-12), visual analog scale (VAS), and desmoid patient-reported outcome (PRO) tool.

Results:

At 24 months, 8 (88.9%) patients demonstrated a reduction in the volume of their tumor while 1 (11.1%) enlarged. Median tumor volume change was −26.9% (−81.1% to 34.6%; P = 0.055) All 9 tumors remained stable based on World Health Organization criteria, whereas 2 (22.2%) demonstrated partial response based on RECIST. There was a significant decrease in the tumor:muscle postcontrast mean signal intensity ratio at 6 months (P = 0.008) and 24 months (P = 0.004). There was a similar decrease in the tumor:muscle T2 mean signal intensity ratio at 24 months (P = 0.02). We found no difference in the SF-12 and VAS scores, but there were significant improvements in the desmoid PRO.

Conclusions:

Treatment of desmoid tumors with serial triamcinolone injections appears safe and well tolerated by patients, with a 22% partial response based on RECIST. Further research is needed to confirm our results and determine factors predictive of response.
Abstract IA005: Artificial intelligence for breast pathology: Challenges and opportunities (and more challenges!)
Authors: Drage Michael G.
Published: December 2022

This presentation will review some fundamental aspects of breast pathology, introduce PathAI’s approach to building algorithms for computer vision applications, and highlight some applications where AI has shown capacity to yield clinically-relevant insights from breast cancer specimens. I will also highlight some interesting challenges in breast pathology practice pertinent to intraductal proliferations, and how these challenges are beginning to be addressed in the field of AI.

Citation Format: Michael G. Drage. Artificial intelligence for breast pathology: Challenges and opportunities (and more challenges!) [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA005.
Abstract PR011: DCIS-associated myoepithelial cells drive tumor progressive inflammation through up-regulation of integrin αvβ6
Authors: Allen Michael D. , Roozitalab M. Reza , Murtough Stephen , Maniati Eleni , Jones J. Louise
Published: December 2022

Background: Ductal carcinoma in-situ (DCIS) is a pre-invasive stage of breast cancer, however <50% will progress to invasion. A key component in promoting tumor invasion is inflammation, though its role in DCIS progression is unclear. We previously, showed αvβ6 expression on DCIS myoepithelial cells promotes tumor cell invasion. We hypothesized that altered myoepithelial phenotype in DCIS may modulate periductal inflammation to contribute to disease progression. Methods: The inflammatory infiltrate in DCIS cases (20 αvβ6+ and 20 αvβ6-) was characterized by immunohistochemistry (IHC) and immunofluorescence-IHC, focusing on Tumor Associated Macrophages (TAM) and Regulatory T cell markers. A myoepithelial cell line over-expressing αvβ6 (β6-1089) and a control counterpart (N-1089) were analyzed for cytokine and signaling molecule expression with proteome profilers and western blotting. The monocyte cell line (THP-1) was exposed to conditioned media from β6-1089 or N-1089 followed by qPCR for TAM markers (IL4, IL10 and IL8), MTS proliferation assay and western blotting for NFkB and STAT6 activation (involved in macrophage differentiation). 3D models were used to examine if the in vivo changes to macrophages can be modelled in vitro. Results: IHC analysis revealed a significant association between myoepithelial αvβ6 expression and increased T-reg cell infiltrate (p< 0.0001). Similarly, αvβ6 expression associated with increased presence of TAM (p=0.0026), αvβ6 positive DCIS with exhibited a microenvironment comprising 15% TAMs compared to 3% in αvβ6 negative DCIS cases. This shift in macrophage phenotype was recapitulated in 3D organotypic assays incorporating macrophages and myoepithelial cells. Proteome profiler analysis of THP-1 cells grown with conditioned media from αvβ6 positive myoepithelial cells demonstrated increased expression of CCL5 while all other proteins analyzed where generally suppressed. Nuclear and cytoplasmic western blotting of THP-1s demonstrated NfκB and STAT activation were altered by CM from myoepithelial cells +/- avb6. Conclusion: DCIS myoepithelial cells upregulate αvβ6 and exhibit changes in the periductal inflammatory infiltrate indicating a switch to a tumor promoting phenotype. Further investigation is required to determine the prognostic value and underlying mechanisms of this change.

Citation Format: Michael D. Allen, M. Reza Roozitalab, Stephen Murtough, Eleni Maniati, J. Louise Jones. DCIS-associated myoepithelial cells drive tumor progressive inflammation through up-regulation of integrin αvβ6 [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR011.
Abstract A004: Chemoprevention of head and neck cancers by the combination of epigallocatechin gallate (EGCG) and resveratrol
Authors: Adeluola Adeoluwa , Raji Lukmon , Sigdel Saroj , Anisuzzaman A.S.M. , Amin A. R. M. Ruhul
Published: December 2022

Head and neck cancer (HNC) is a devastating disease and the 6th most common cancer worldwide. Most HNC patients are diagnosed with advanced stage disease for which the 5-year survival is below 50%, stressing the need for chemoprevention. Recently, we have reported that the combination of resveratrol and EGCG induces synergistic apoptosis and inhibits xenografted HNC growth by inhibiting AKT-mTOR pathway. In this study, we have investigated the chemopreventive efficacy of resveratrol, EGCG and their combination using 4NQO-induced oral carcinogenesis model. C57BL/6 mice were exposed to 4-NQO (50 μg/ml) via drinking water for 10 weeks, followed by treatment with vehicle (50% sweetened condense milk), resveratrol (30 mg/kg), EGCG (30 mg/kg) and their combination for 8 weeks, 5 days/week. The mice were sacrificed on week 24 and the number of visible and microscopic lesions were counted. Resveratrol alone and in combination with EGCG significantly inhibited the number of visible lesions whereas the number of microscopic lesions and lesion area were significantly inhibited only in the combination group. Furthermore, RNASeq and qPCR analysis using a HNC cell line identified GDF15, ATF3, p21, p27 and Bim as significantly upregulated genes with GDF15 being the most upregulated one. Expression of GDF15 and ATF3 proteins were confirmed by western blotting. Taken together, our data strongly demonstrate the chemopreventive potential of the combination of EGCG and resveratrol and paves the way for further clinical developments. (Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence)

Citation Format: Adeoluwa Adeluola, Lukmon Raji, Saroj Sigdel, A.S.M. Anisuzzaman, A. R. M. Ruhul Amin. Chemoprevention of head and neck cancers by the combination of epigallocatechin gallate (EGCG) and resveratrol [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A004.
Abstract A020: Exploring the effects of resveratrol on the gut microbiome in high fat diet-fed BRAFV600E mutant mice
Authors: Theofanous Despoina , Cai Hong , Brown Karen
Published: December 2022

The polyphenol resveratrol, widely known for its cancer protective activities has been shown to protect against the pro-tumorigenic effects induced by high-fat diets (HFD) in mouse models of colorectal cancer (CRC). Although, the mechanisms of actions of this compound in humans still remain elusive, recent studies suggest its effects may be mediated partly through its interaction with the gut microbiota. Here we sought to determine the changes induced by HFD on the intestinal microbiome and the impact of resveratrol supplementation on these alterations in a mouse model of BRAFV600E mutant CRC.

BRAFV600E; BRAFWT (wild-type) mice were randomised into 8 groups and fed either a standard diet or HFD supplemented with low or high-dose of resveratrol (0.7mg/kg/day and 14mg/kg/day, respectively) for 6-weeks. The mouse faecal microbial profile was then assessed by targeting the V3-V4 area of the bacterial 16S rRNA gene.

Consumption of HFD was associated with significant alternations in the gut microbiome composition in both BRAFV600E and BRAFWT based on beta-diversity analysis (PADONIS<0.05). HFD increased the Firmicutes and Clostridia abundance in BRAFWT compared to animals on a standard diet (P<0.01, P<0.008 respectively), while in BRAFV600E mice, alterations were observed in lower taxonomic levels including the enrichment of Faecalibaculum (P<0.02) and growth inhibition of Lactobacillus johnsonhii (P<0.05). High-dose resveratrol resulted in significant differences in the microbial composition compared to HFD-treated group in the BRAFV600E mice (PADONIS<0.05) but not in BRAFWT . Resveratrol administration did not counteract the HF-induced taxonomic changes but high-dose resveratrol changed Muribaculum, and UBA181 genera abundances in BRAFV600E mice (P<0.001 and P<0.05 respectively) compared to HF-treated mice. Low dose resveratrol had no significant effects on bacterial abundance in both BRAFV600E and BRAFWT mice. It was also observed that BRAFV600E mutation influenced the gut microbiome independently of diet based on beta and alpha-diversity (PADONIS<0.05, PChao1<0.05 respectively).

Resveratrol administration modified the gut microbiota composition of BRAFV600E mice but did not completely reverse the HFD-induced changes indicating that alternative mechanisms may contribute to the protective effects of resveratrol in this mouse model.

Citation Format: Despoina Theofanous, Hong Cai, Karen Brown. Exploring the effects of resveratrol on the gut microbiome in high fat diet-fed BRAFV600E mutant mice [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A020.
Abstract IA004: Targeting STAT3 with TTI-101, an oral small molecule, to prevent colorectal and hepatocellular cancer
Authors: Robinson Prema , Hamana Leticia , Beretta Laura , Kasembeli Moses , Bharadwaj Uddalak , Chun Yun Shin , Wang Yinghong , Wang Xeumei , Reyes Laura , Solis Luisa , Rashid Asif , Maru Dipen , Vila Eduardo , Tsimberidou Apostolia , Kaseb Ahmed , Kopetz Scott , Tweardy David
Published: December 2022

Persistent STAT3 activation contributes to 10 of 14 hallmarks of cancer, including inflammation; successful targeting of STAT3 has the potential to prevent and/or treat cancer. However, no small molecule that directly targets STAT3 has been FDA approved. The Tweardy lab used computer-based docking of drug-like compounds into the SH2 domain of STAT3, along with hit-to-lead optimization and medicinal chemistry, to identify TTI-101; TTI-101 treatment was safe, hit its target in tumor cells, and resulted in clinical benefit in a Phase I trial of patients with advanced solid tumors.

The incidence of colorectal cancer (CRC) is increased 20-30 fold in patients with inflammatory bowel disease (IBD), while 90% of hepatocellular carcinomas (HCC) arise in the setting of chronic inflammation. To assess the contribution of STAT3 to CRC secondary to IBD and to HCC, we performed immunohistochemistry (IHC) staining and computer-based scoring for activated STAT3 (phosphorylated on Y705, pY-STAT3) of epithelial and stromal cells within colonic endoscopic biopsies and surgically resected CRC from IBD patients, as well as of tumor cells and hepatocytes within surgically resected HCC tumors. Compared to epithelium of normal tissue, levels of pY-STAT3 were increased 1.9-fold in dysplastic epithelium (p=0.05) and 1.8-fold in the stroma of normal tissue (p<0.0001). In surgically resected HCC tumors, lower pY-STAT3 scores in tumor cells, but not hepatocytes, correlated with longer recurrence free survival (RFS; p=0.003).

TTI-101 administration in three AOM-DSS mouse models of IBD resulted in a dose-dependent reduction in polyps, adenomas, and/or adenocarcinomas. TTI-101 administration to the HepPten- mouse model of NASH-induced HCC resulted in a dose-dependent reduction in liver pY-STAT3 levels. Thus, STAT3 may be a valid target for chemoprevention using TTI-101 in CRC arising from IBD and in HCC.

We thank Tvardi Therapeutics for providing TTI-101 for these studies.

Citation Format: Prema Robinson, Leticia Hamana, Laura Beretta, Moses Kasembeli, Uddalak Bharadwaj, Yun Shin Chun, Yinghong Wang, Xeumei Wang, Laura Reyes, Luisa Solis, Asif Rashid, Dipen Maru, Eduardo Vila, Apostolia Tsimberidou, Ahmed Kaseb, Scott Kopetz, David Tweardy. Targeting STAT3 with TTI-101, an oral small molecule, to prevent colorectal and hepatocellular cancer [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA004.
Dermal and Transdermal Macromolecule Delivery Using Enhancer Molecules and Colloidal Carrier Systems – Part 2: Percutaneous Administration of Heparin
Authors: Alyoussef Alkrad Jamal , Almalki Yousif Ali , Dahmash Eman Zmaily , Hassouneh Loay Khaled , Neubert Reinhard H.H.
Published: December 2022

Introduction: Heparin is a commonly used anti-coagulant administered either by intravenous or subcutaneous injection for a systemic effect or topically for the treatment of peripheral vascular disorders. Objective: This study aimed to formulate heparin in non-ionic colloidal carrier systems (CCSs) having enhanced percutaneous absorption for systemic and topical administration. Methods: Five CCSs were developed and characterized for their rheological properties, droplet size, and drug loading. The percutaneous absorption of heparin was evaluated in vitro using Franz diffusion cells with rats’ skin and with the aid of a developed high-pressure chromatography method. Furthermore, the efficacy of two developed heparin CCSs was tested percutaneously in rats by measuring the response against the time in comparison to subcutaneous administration. Results: The rheograms and droplet size measurements showed that the developed drug delivery systems have Newtonian properties with a droplet size between 109 and 460 nm. As much as 500 mg of heparin could be loaded in around 5 mL of CCS. Furthermore, using Franz diffusion cells, a diffusion rate of 19.216 ± 2.01 USP U/cm2.h could be achieved for heparin-loaded CCSs. Moreover, the estimated percutaneous in vivo relative bioavailability in comparison to subcutaneous administration could reflect that at least more than 50% of the drug passed through the skin. Conclusion: The developed novel non-toxic CCSs containing heparin can be good candidates for percutaneous administration as alternative delivery systems for subcutaneous and intravenous invasive administration.
Tropoelastin Improves Post-Infarct Cardiac Function
Authors: Hume Robert D. , Kanagalingam Shaan , Deshmukh Tejas , Chen Siqi , Mithieux Suzanne M. , Rashid Fairooj N. , Roohani Iman , Lu Juntang , Doan Tram , Graham Dinny , Clayton Zoe E. , Slaughter Eugene , Kizana Eddy , Stempien-Otero April S. , Brown Paula , Thomas Liza , Weiss Anthony S. , Chong James J.H.
Published: December 2022

Background:

Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to collagen, the extracellular matrix protein elastin has high elasticity and may have more favorable properties within the cardiac scar. We sought to improve post-MI healing by introducing tropoelastin, the soluble subunit of elastin, to alter scar mechanics early after MI.

METHODS AND RESULTS:

We developed an ultrasound-guided direct intramyocardial injection method to administer tropoelastin directly into the left ventricular anterior wall of rats subjected to induced MI. Experimental groups included shams and infarcted rats injected with either PBS vehicle control or tropoelastin. Compared to vehicle treated controls, echocardiography assessments showed tropoelastin significantly improved left ventricular ejection fraction (64.7±4.4% versus 46.0±3.1% control) and reduced left ventricular dyssynchrony (11.4±3.5 ms versus 31.1±5.8 ms control) 28 days post-MI. Additionally, tropoelastin reduced post-MI scar size (8.9±1.5% versus 20.9±2.7% control) and increased scar elastin (22±5.8% versus 6.2±1.5% control) as determined by histological assessments. RNA sequencing (RNAseq) analyses of rat infarcts showed that tropoelastin injection increased genes associated with elastic fiber formation 7 days post-MI and reduced genes associated with immune response 11 days post-MI. To show translational relevance, we performed immunohistochemical analyses on human ischemic heart disease cardiac samples and showed an increase in tropoelastin within fibrotic areas. Using RNA-seq we also demonstrated the tropoelastin gene
ELN
is upregulated in human ischemic heart disease and during human cardiac fibroblast-myofibroblast differentiation. Furthermore, we showed by immunocytochemistry that human cardiac fibroblast synthesize increased elastin in direct response to tropoelastin treatment.

Conclusions:

We demonstrate for the first time that purified human tropoelastin can significantly repair the infarcted heart in a rodent model of MI and that human cardiac fibroblast synthesize elastin. Since human cardiac fibroblasts are primarily responsible for post-MI scar synthesis, our findings suggest exciting future clinical translation options designed to therapeutically manipulate this synthesis.
Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis
Authors: Theodorou Aikaterini , Palaiodimou Lina , Malhotra Konark , Zompola Christina , Katsanos Aristeidis H. , Shoamanesh Ashkan , Boviatsis Efstathios , Dardiotis Efthimios , Spilioti Martha , Sacco Simona , Werring David J. , Cordonnier Charlotte , Alexandrov Andrei V. , Paraskevas George P. , Tsivgoulis Georgios
Published: December 2022

Background:

There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy–related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri.

Methods:

A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I
2
-statistics.

Results:

We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%–84%]; I
2
=82%), focal neurological deficits 55% ([95% CI, 40%–70%]; I
2
=82%), encephalopathy 54% ([95% CI, 39%–68%]; I
2
=43%), seizures 37% ([95% CI, 27%–49%]; I
2
=65%), headache 31% ([95% CI, 22%–42%]; I
2
=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%–100%]; I
2
=44%), lobar cerebral microbleeds 96% ([95% CI, 92%–99%]; I
2
=25%), gadolinium enhancing lesions 54% ([95% CI, 42%–66%]; I
2
=62%), cortical superficial siderosis 51% ([95% CI, 34%–68%]; I
2
=77%) and lobar macrohemorrhage 40% ([95% CI, 11%–73%]; I
2
=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%–53%]; I
2
=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy.

Conclusions:

Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.
Lexical Frequency Effects on the Acquisition of Syntactic Properties in Heritage Spanish: A Study on Unaccusative and Unergative Predicates
Authors: López Otero Julio César
Published: December 2022

This study investigates the acquisition of subject placement in unergative and unaccusative predicates among heritage speakers of Spanish by addressing two constraints ruling the distribution of subject placement (i.e., verb type and focus) as well as by examining whether lexical frequency impacts their acquisition. Sixty-three heritage speakers and twenty-five Spanish-dominant bilinguals completed an oral elicited production task and an acceptability judgment task. Results show that verb type constraints in the heritage speakers are shaped by their proficiency and self-reported lexical frequency: more proficient heritage speakers rated VS sentences higher than their lower-proficient counterparts, and more instances of VS sentences were produced with more frequent unaccusative verbs. Focus constraints only impact the heritage speakers’ acceptability: in narrow focus contexts, heritage speakers rate SV higher than VS sentences. Lexical frequency effects in unaccusative predicates are argued to be the result of spell-outs favoring compatible linear orders as a way to reduce computational costs.
The Protestant Missions to South-East Asia: Experimental Laboratory of Missionary Concepts and of Human Relations (Circa 1780–1840)
Authors: Laamann Lars Peter
Published: December 2022

The relationship between the Anglo-Scottish Ultra-Ganges Mission and the Dutch missionaries in South East Asia, both missions based at Batavia and at Melaka (Malacca), could be described as “distant but cordial” – even during times of colonial conflict – but the same cannot always be said about the internal conditions of the British mission. This article will attempt to place the relationship between the Anglo-Dutch missionary enterprises into a historical context which includes the complex networks built up by the missionaries with the colonial administrations, as well as with the local Malay and Chinese communities. Ultimately, the success of their mission depended as much on such external factors as on the internal cohesion between the individual missionaries. Much of the historical sources for this article has been derived from the Special Collections archives kept at the School of Oriental and African Studies (SOAS), University of London.
Serving and Sustaining Diasporic Connectivities: Hindu Sindhi Women’s Seva in Hong Kong
Authors: Chakraborty Radhika Mathrani
Published: December 2022

This article highlights the role of Hindu Sindhi women in building and sustaining transnational diasporic connectivities through the discourse and practice of “seva” (loosely translated as “selfless service”). Scholars note how the heterodox and syncretic character of Hindu Sindhi religious and cultural identity stretches the contours of textualized Hinduism. However, an analysis of women’s seva demonstrates how Sindhis also deploy an explicitly Hindu identity to negotiate and perform belonging in the diaspora locale of Hong Kong. Through ethnographic fieldwork in Hong Kong, this article explores how women perform acts of seva (e.g., cooking, serving, and maintaining religious spaces) to sustain diaspora ties. Seva positions the community as performing “local civic virtue” and frames Sindhis’ perceived “ethnic difference” in Hong Kong by presenting a legible Hindu identity. Women are pivotal in sacralizing food offerings and facilitating the religio-spiritual meanings of seva in Hong Kong. During the pandemic, the religious connectivities and spaces of seva women maintained, created, shaped, and expanded global Sindhi diaspora ties. For these women, participating in seva becomes a means of personal spiritual growth, fostering social connections, and negotiating/performing gendered roles and expectations.
Sweden's ‘complicated’ relationship with genocide recognition
Authors: Fittante Daniel
Published: December 2022

Scholars have unpacked the rhetorically nuanced ways political actors alter state narratives in resisting pressure to comply with international norms. But many of these rhetorical strategies apply in other contexts, where there exists sufficient norm ambiguity, too. For example, in response to Turkey's long-standing denialism, many governments have been asked to recognise the Armenian Genocide (or 1915 Genocide of Christians in the Ottoman Empire). But, because there exists no clear international norm about recognising genocides perpetuated by other states, even some of the most unlikely government officials adapt their rhetoric to resist recognition and pursue ulterior foreign policy objectives. Building on Dixon's rhetorical adaptation framework, this article argues that, between 1999 and 2021, Swedish political actors often adapted their rhetoric in ways similar to Turkish officials as a result of the normative ambiguity of states recognising the Armenian Genocide. In explaining why Sweden consistently resisted Genocide recognition efforts, this analysis focuses on its larger foreign policy commitments of spreading democracy in Turkey and managing the Syrian refugee crisis.
Nonsentinel Lymph Node Status after Positive Sentinel Lymph Node Biopsy in Early Breast Cancer
Authors: Saidi Reza F. , Dudrick Paul S. , Remine Stephen G. , Mittal Vijay K.
Published: December 2022

Axillary dissection is the current standard of care for patients with breast cancer who are diagnosed with metastasis to axillary sentinel lymph nodes (SLNs). Recently, that concept has come under increasing scrutiny because not all women with a positive SLN will need further dissection. The purpose of this study was to look at nonsentinel lymph node status in patients with breast cancer and axillary SLN metastasis in an effort to determine tumor variables that can guide further treatment if there are additional axillary nodes involved. A retrospective chart review was performed on patients with breast cancer who underwent SLN biopsy between July 1998 and April 2003. χ2 analysis, Student t test, and multivariate analysis were used to determine the significance of tumor size, grade, location, estrogen receptor (ER) and progestrone receptor (PR) receptor status, angiolymphatic invasion, stage, and number and size of SLNs in predicting the status of nonsentinel lymph nodes. During the study interval, 116 patients were identified who underwent SLN biopsy and 34 (29.3%) had positive SLNs. All of these patients underwent complete axillary node dissection and 11 patients (32.3%) had non-SLN metastasis. The presence of palpable breast mass ( P = 0.03), tumor size ( P = 0.04), angiolymphatic invasion ( P = 0.03), and extracapsular extension of SLN metastasis ( P = 0.001) were the variables that predicted non-SLN involvement. Micrometastasis was inversely related to non-SLN involvement. In patients with breast cancer and SLN metastasis, the presence of a palpable breast mass, tumor size, angiolymphatic invasion, and extracapsular node extension increase the likelihood of identifying additional node metastasis on subsequent axillary dissection.
Mucin Secreting Cystic Lesions of the Pancreas: Treatment by Enucleation
Authors: Madura James A. , Yum Moo-Nahm , Lehman Glen A. , Sherman Stuart , Schmidt C. Max
Published: December 2022

Ninety per cent of pancreatic cysts are inflammatory pseudocysts. The other 10 per cent are congenital or neoplastic and include congenital true cysts, retention cysts, lymphoepithelial cysts, the mucinous cystadenoma, mucinous cystadenocarcinoma, and serous microcystic cystadenomas and the more recently described intraductal papillary mucin-secreting neoplasms. The advent of computerized tomographic scanning, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasonography (EUS) has brought many of these lesions to light when they are minimally symptomatic or are incidentally found while investigating unrelated problems. If there is any suspicion of actual or potentially malignant disease, then total excision of the lesion with part of or the entire pancreas is indicated to achieve a likely cure, as survival is better than for the more common ductal adenocarcinomas. There are few reliable preoperative studies to distinguish accurately the etiology and prognosis of this spectrum of cystic lesions, and usually the actual diagnosis is made only at the time of operation or histopathologic examination after the cystic lesion has been biopsied or excised. If a cyst is confirmed to be totally benign, as in the congenital true cyst, lymphoepithelial cyst, or a benign mucinous cyst, they may lend themselves to nonoperative observation or excision without sacrifice of pancreatic parenchyma. However, many mucin-producing cystic lesions may evolve into a dysplastic or invasive malignant lesion requiring more aggressive resective treatment, and it is important not to miss that diagnosis early when cure is still possible. This report presents four benign mucin-secreting cysts treated by local excision. All four were in the head of the pancreas and communicated with the main pancreatic duct and lacked ovarian-type stroma, thus categorizing them as side-branch intraductal papillary mucinous neoplasms. These lesions were able to be easily dissected out of the pancreas with only one patient developing a transient pancreatic fistula. Intraoperative and final histopathology confirmed the benign status, and these patients have remained disease free 3 to 5 years postoperatively. A review of benign tumors reported to have been treated by cyst enucleation in the literature confirms the rationale of this approach in highly selected lesions.
Inguinal Hernia Recurrence following Preperitoneal Kugel Patch Repair
Authors: Schroder Donn M. , Lloyd Larry R. , Boccaccio John E. , Wesen Cheryl A.
Published: December 2022

Three hundred eighty-six preperitoneal inguinal herniorrhaphies using a polypropylene Kugel patch (Davol) were performed in 355 consecutive patients by six surgeons. Variables for recurrence evaluated included age, gender, hernia type, whether the Kugel patch was placed for a primary or recurrent hernia, and the experience of the surgeon. Of 336 patients with long-term follow-up available (18 months to 63 months, median 42 months) 28 recurrences developed 1 to 48 months (mean 16 months) after 366 Kugel patch repairs (7.7%). Recurrence was highest (27.8%) in the subset of patients who had a Kugel patch placed for recurrent inguinal hernias ( P < 0.05). Patients with direct primary hernias involving the entire floor had a recurrence rate of 22.7 per cent ( P < 0.05). Patient age and gender had no bearing on recurrence. Surgeon experience did play a role, as the recurrence rate was 18.2 per cent during each surgeon's first 36 cases and 2.9 per cent thereafter ( P < 0.0005). Surgeons using a preperitoneal Kugel patch for inguinal herniorraphy had a recurrence rate that was unacceptably high. The technique may not be suitable for repair of recurrent inguinal hernias or primary large direct inguinal hernias. Surgeons in this study saw a learning curve of 36 cases.
Inhibition of Heme Oxygenase-1 in Microvascular Lung Pericytes Diminishes at High Concentrations of an Inflammatory Mediator
Authors: Harvey Elizabeth H. , Tyburski James G. , Steffes Christopher P. , Carlin Arthur M.
Published: December 2022

Post-traumatic inflammation and sepsis induce changes in the lung microvasculature causing increased permeability. Pericytes, contractile cells positioned abluminally to endothelial cells, play a role in regulating this response. An in vitro model of microvascular lung pericytes (MLP) was used to investigate the effect of inhibiting heme oxygenase-1 (HO-1), a stress-induced enzyme, in the presence of varying levels of lipopolysaccharide (LPS), a mediator in the initiation of inflammation, on pericyte contractility. Rat MLP were cultured on collagen gel matrices. Cells were exposed to three concentrations of LPS in the presence of zinc protoporphyrin IX (ZnPP-9), a known inhibitor of HO-1. After 24 hours, the surface area of the collagen disks was quantified, thereby measuring pericyte contraction. ZnPP-9 caused a significant attenuation of the LPS-induced relaxation of the pericytes ( P ≤ 0.003). The effects of ZnPP-9, however, depended on the concentration of LPS to which the pericytes were exposed. Greater concentrations of LPS decrease the attenuating power of ZnPP-9. The inhibition of HO-1 diminished MLP relaxation triggered by LPS. The effect of ZnPP-9, however, is dependent on the concentration of LPS to which the MLP are exposed, indicating its saturation. ZnPP-9 may antagonize the microvascular response to trauma.
Early and Late Complications following Laparoscopic Adjustable Gastric Banding
Authors: Sarker Sharfi , Herold Katherine , Creech Steve , Shayani Vafa
Published: December 2022

There is limited U.S. data on short- and long-term complications of laparoscopic adjustable gastric banding (LAGB) as a treatment option for morbid obesity. Hereafter, we present our experience with the first 154 consecutive LAGBs performed at Loyola University Medical Center. Inpatient and outpatient charts were reviewed retrospectively for all patients undergoing LAGB between November 2001 and February 2003 for perioperative morbidity and mortality and repeat operations. Thirty-seven men (24%) and 117 women (76%) underwent LAGB in a 16-month period. There was one (0.6%) death from postoperative myocardial infarction (MI) and one (0.6%) pulmonary embolism. Six (3.9%) patients required readmission to the hospital for dehydration. During a mean follow-up of 33 weeks (range, 4–69 weeks), 14 (9%) patients required repeat operations. There were five (3.2%) band slippages and one (0.6%) gastric erosion. Three bands were removed laparoscopically. Three slippages were revised laparoscopically. One patient underwent laparoscopic cholecystectomy. Seven patients (4.5%) required port revisions for catheter disconnection (4), leak at port site (2), or flipped port (1). LAGB is a safe operative approach for the management of morbid obesity. The incidence of postoperative complications can be minimal with application of a standardized technique. LAGB should be strongly considered for morbidly obese patients who have failed nonoperative management.
Predictors of Mortality in Patients with Traumatic Diaphragmatic Rupture and Associated Thoracic and/or Abdominal Injuries
Authors: Williams Mallory , Carlin Arthur M. , Tyburski James G. , Blocksom Jason M. , Harvey Elizabeth H. , Steffes Christopher P. , Wilson Robert F.
Published: December 2022

This is a retrospective review of 731 patients sustaining diaphragmatic trauma over a 22 year period (1980–2002) at an urban level I trauma center. Patients had an average injury severity score (ISS) of 22 ± 12. The mortality rate (MR) was 23 per cent (168/731). There were a total of 460 left-sided diaphragmatic injuries (L-TDR), 263 right-sided diaphragmatic injuries (R-TDR), and 8 bilateral diaphragmatic injuries (B-TDR). There were no significant differences in mortality with L-TDR versus R-TDR. Shotgun wounds had the highest MR (42%) ( P = 0.0028). Emergency thoracotomies were performed in 31 per cent (225) with a 62 per cent (140) MR. Bilateral thoracotomies had a significantly higher MR of 85 per cent (33/39) compared to the 58 per cent (107/186) for unilateral thoracotomies ( P = 0.0028). Multivariate analysis revealed the most significant independent predictors of mortality to be the revised trauma score, transfusion of pRBCs > 10 units, and need for thoracotomy (P < 0.0001). The infection rate was 41 per cent. Multivariate analysis revealed blunt trauma, blood transfusions, ISS, and pancreatic injury as the most significant independent predictors of infection ( P < 0.001). The initial physiologic presentation of the patient and the severity of hemorrhagic shock are the primary determinants for survival. Prompt identification of associated injuries with rapid control of bleeding is paramount to survival.
Surgeon-Directed Ultrasound for Trauma is a Predictor of Intra-Abdominal Injury in Children
Authors: Suthers S.E. , Albrecht Roxie , Foley David , Mantor P. Cameron , Puffinbarger Nikola K. , Jones Susan K. , Toggle David W.
Published: December 2022

This study investigated the efficacy of surgeon-directed focused assessment with sonography for trauma (FAST) in conjunction with physical exam (PEx) as a predictor of intra-abdominal injury in children. Injured children (ages ≤17) presenting to a level I trauma center with abdominal trauma were evaluated in the emergency department (ED) by the trauma team of surgical attendings and residents. PEx and FAST were performed immediately upon arrival to the ED and results compared to CT, the standard exam for presence of intra-abdominal injury. Data was collected prospectively from July 1, 2000, until April 30, 2002. One hundred and twenty injured children underwent evaluation of abdominal trauma with PEx, FAST, and abdominal CT. Two patients had false-negative CT scans. Bayesian analysis was applied to the results of the remaining 118 patients. FAST compared with CT findings revealed sensitivity 70 per cent, specificity 100 per cent, positive predictive value 100 per cent, and negative predictive value 92 per cent. FAST results were combined with PEx findings such that either suggestive of intra-abdominal injury was regarded as a “positive exam.” Sensitivity was 100 per cent, specificity 74 per cent, positive predictive value 53 per cent, and negative predictive value 100 per cent. Surgeon-directed FAST with consideration of PEx is a predictor of intra-abdominal injury in children.
Neoadjuvant Therapy and Biliary Decompression Lower Biliary and Pancreatic Juice Vascular Endothelial Growth Factor Levels in Patients with Periampullary Adenocarcinoma
Authors: Berger Adam C. , Watson James C. , Ross Eric A. , Zalatoris Alice , Hoffman John P.
Published: December 2022

Increased expression of vascular endothelial growth factor (VEGF) by pancreatic cancer correlates with poor survival. The significance of VEGF in biliary and pancreatic secretions in periampullary cancers is unknown. Bile and pancreatic juice samples were collected from patients undergoing pancreaticoduodenectomy (PD). All samples were frozen at -70°C until subsequent analysis for VEGF concentration using enzyme-linked immunoabsorbent assay (ELISA). Plasma VEGF levels in pancreatic cancer patients were <10 pg/mL. The biliary VEGF concentration for patients with malignancy was significantly elevated compared to benign disease ( P = 0.05). There was no difference in pancreatic VEGF concentrations between benign and malignant disease. Cancer patients undergoing preoperative chemoradiation (CRT) had lower biliary and pancreatic VEGF concentrations than those who did not. Preoperative biliary drainage (BD) was associated with decreased VEGF concentrations in bile (3500 pg/mL vs 7740 pg/mL, P = 0.027). Patients undergoing both CRT and BD had diminished biliary and pancreatic VEGF concentrations compared to those who had neither. This was statistically significant for pancreatic VEGF concentrations (917 pg/mL vs 4723 pg/mL, P = 0.044). VEGF is highly concentrated in bile and pancreatic juice compared to plasma. Preoperative CRT and BD significantly reduce these levels in patients with periampullary cancers. Antiangiogenic therapy aimed at interrupting the VEGF pathway appears to be a logical target in periampullary cancer.
Comparison of Standard Carotid Endarterectomy with Dacron Patch Angioplasty versus Eversion Carotid Endarterectomy during a 4-Year Period
Authors: Littooy Fred N. , Gagovic Veronika , Sandu Cezar , Mansour Ashraf , Kang Steven , Greisler Howard P.
Published: December 2022

Currently, the two primary approaches to carotid endarterectomy for extracranial carotid stenosis are carotid endarterectomy with patch angioplasty and eversion carotid endarterectomy. In a retrospective study over a 4-year period from 1998 to 2002, we had an opportunity to compare the two approaches as two surgeons utilized carotid endarterectomy with Dacron patch angioplasty and two other surgeons utilized eversion carotid endarterectomy. During the 4-year period, 189 carotid endarterectomies were performed, 125 with Dacron patch angioplasty (CE-P) and 64 with eversion (EE) endarterectomy. There were no significant differences in age of the patients, operative indication, or associated risk factors between the two groups. Perioperative outcome measurement in the CE-P versus EE included stroke or transient ischemic attack, 1.6 per cent versus 1.56 per cent, cranial nerve injury, 2.4 per cent versus 3.13 per cent; death, 0.8 per cent versus 0 per cent; need for operative conversion or revision, 2.4 per cent versus 7.81 per cent, respectively. Only the need for operative conversion or revision reached significant difference ( P < 0.05), although the need decreased to 4 per cent for the last 50 EE cases. Recurrent stenosis of 50 per cent to 79 per cent was 4.88 per cent versus 3.13 per cent and >80 per cent was 0.81 per cent versus 0 per cent in the CE-P versus EE group over a follow up of 16.3 months and 17.0 months, respectively. We conclude that both CE-P and EE are equally efficacious operative approaches to extracranial carotid occlusive disease.
Does Surgeon Experience Correlate with Crowd-Sourced Skill Assessment in Robotic Bariatric Surgery?
Authors: Addison Poppy , Bitner Daniel P. , Addy Jermyn , Dechario Samuel , Husk Gregg , Antonacci Anthony , Talamini Mark , Giangola Gary , Filicori Filippo
Published: December 2022

Background

The Global Evaluative Assessment of Robotic Skills (GEARS) rubric provides a measure of skill in robotic surgery. We hypothesize surgery performed by more experienced operators will be associated with higher GEARS scores.

Method

Patients undergoing sleeve gastrectomy from 2016 to 2020 were analyzed. Three groups were defined by time in practice: less than 5, between 5 and 15, and more than 15 years. Continuous variables were compared with ANOVA and multivariable regression was performed.

Results

Fourteen operators performing 154 cases were included. More experienced surgeons had higher GEARS scores and shorter operative times. On multivariable regression, operative time (P = 0.027), efficiency (P = .022), depth perception (P = 0.033), and bimanual dexterity (P = 0.047) were associated with experience.

Conclusions

In our video-based assessment (VBA) model, operative time and several GEARS subcomponent scores were associated with surgical experience. Further studies should determine the association between these metrics and surgical outcomes.
Rapid and unequal decline in adolescent mental health and well-being 2012–2019: Findings from New Zealand cross-sectional surveys
Authors: Sutcliffe Kylie , Ball Jude , Clark Terryann C , Archer Dan , Peiris-John Roshini , Crengle Sue , Fleming Terry (Theresa)
Published: December 2022

Objective:

To investigate prevalence and trends in key mental health and well-being indicators among New Zealand secondary school students.

Methods:

Representative cross-sectional youth health surveys with 2–4% of the New Zealand secondary school population were conducted in 2001, 2007, 2012 and 2019 (total n = 34,548).

Results:

In 2019, 69.1% reported good well-being (95% confidence interval = [67.6, 70.6]; World Health Organization 5-item), 22.8% reported clinically significant depression symptoms (95% confidence interval = [21.4, 24.1]; Reynolds Adolescent Depression Scale–Short Form) and 41.8% reported possible anxiety symptoms (95% confidence interval = [40.5, 43.2]; Generalized Anxiety Disorder 2, adapted). Past-year prevalence of periods of low mood (38.3%, 95% confidence interval = [36.6, 40.1]), deliberate self-harm (24.1%, 95% confidence interval = [22.8, 25.4]), suicide thoughts (20.8%, 95% confidence interval = [19.2, 22.4]) and suicide attempts (6.3%, 95% confidence interval = [5.5, 7.0]) were observed. After relative stability from 2001 to 2012, there were large declines in mental health to 2019. The proportion reporting good well-being decreased (odds ratio 0.71, 95% confidence interval = [0.65, 0.78], p < 0.001), depression symptoms increased (odds ratio 1.96, 95% confidence interval = [1.75, 2.20], p < 0.001) and past-year suicide thoughts and suicide attempts increased (odds ratio 1.41, 95% confidence interval = [1.25, 1.59], p < 0.001; odds ratio 1.60, 95% confidence interval = [1.32, 1.92], p < 0.001). Past-year deliberate self-harm was largely stable. Declines in mental health were unevenly spread and were generally greater among those with higher need in 2012 (females, Māori and Pacific students and those from higher deprivation neighbourhoods), increasing inequity, and among Asian students.

Conclusion:

Adolescent mental health needs are high in New Zealand and have increased sharply from 2012 among all demographic groups, especially females, Māori, Pacific and Asian students and those from high-deprivation neighbourhoods. Ethnic and socioeconomic disparities have widened.
The Digital Workplace: Navigating in a Jungle of Paradoxical Tensions
Authors: Kokshagina Olga , Schneider Sabrina
Published: December 2022

Digital technologies have become omnipresent in our professional and personal lives. While they provide numerous opportunities, they also cause tensions, many of which are paradoxical. They confront us with conflicting yet synergetic and interdependent alternatives that persist over time—such as benefiting from the increasing availability and access to information at the risk of information overload and technostress. Thus far, we know little about the specific paradoxes caused by digital technologies in the workplace and how managers perceive and cope with them. This article offers a comprehensive perspective on the multiplicity and interrelatedness of paradoxes in the digital white-collar workplace and suggests how managers can develop effective coping mechanisms for convergent change and transforming work practices in paradoxical environments.
Testing the Law of Crime Concentration in Georgetown, Guyana
Authors: Cummings Anthony R. , Arredondo Celina , Piquero Alex R. , Wehenkel Aaran , Markandey Nakul , Das Hannah , Tiemann Brittany L. , Lee Kevin G.
Published: December 2022

A consistent finding in criminology is that crime occurs and is concentrated at micro places within cities. To date, most efforts that revealed crime at micro places were completed for developed world settings. Here we draw on newspaper data to examine whether the law of crime concentration is relevant to the developing world city of Georgetown, Guyana. Our analysis showed that robberies and murders were concentrated on 2.77% and 1.96% of the city’s streets. Group-based trajectory analysis revealed an unstable relationship between street segments and crime occurrence, but two areas of Georgetown emerged as centers for robberies and murders. Despite Georgetown’s low population density relative to other Latin American cities, crime is concentrated to a few streets.