bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration and Collapse
Authors: Hayton Jeff
Published: March 2022

Chapter 8 investigates how, unable to eliminate punk coercively, the communist regime instead sought to dilute its criticisms through integration as the East German state promoted punk to generate support in the last years of its existence. Following a series of violent attacks by Skinheads and internal encouragement by cultural authorities, the state abruptly reversed its condemnations of punk in February 1988 and instead sought to win youth subcultures to the regime. Flooding the socialist market with groups known as “die anderen Bands” (the Other Bands), punks appeared in the media, released records, starred in films, and even played in the West as the state instrumentalized the genre to generate popularity, even if youths used state support to continue undermining the regime. However, state partnership also led to crisis which split the subculture between those taking advantage of the increased opportunities and those who rejected any state collaboration as a betrayal. Thus, accompanying the collapse of the SED regime in 1989, were acrimonious rifts dividing the East German subculture, splits and disagreements which have had long-lasting consequences for punk ever since.
Connected Cities, High-skill Migrants, and the Knowledge Economy: A Commentary
Authors: Mudambi Ram
Published: March 2022

Urbanization and global migration are the two biggest current trends affecting the global economy. This short commentary explores how the two trends are intertwined in the context of the twenty-first-century knowledge economy. First, global cities are disproportionately important as hubs of innovation. Second, high-skill migrants are heavily over-represented in the ranks of linchpin actors in international knowledge networks. The chapter argues that this research nexus is one of the most promising research opportunities for international business scholars today. Coda-Zabetta et al. (2022) and Murphree (2022) address two complementary aspects of these drivers of the global economy. The first is globally focused innovation which, as the authors demonstrate, is crucially dependent on migration. The second is locally focused entrepreneurship which is more of an urbanization issue.
Global Cities’ Cross-border Innovation Networks
Authors: Belderbos René , Benoit Florence , Edet Samuel , Ho Lee Geon , Riccaboni Massimo
Published: March 2022

The world’s premier metropolitan areas (‘global cities’) are key nodes in international business networks and function as important international innovation hubs. They are prominent spaces for knowledge exchange and collaboration on innovation yet their specific and changing role in global innovation networks has not received due attention. This chapter contributes an analysis of the changing role of global cities in global collaborative innovation networks, 2000–2014, by examining co-invention linkages across 125 global cities in forty-six countries. The international linkages of global cities have increased substantially over the period. Growth has been most pronounced in a number of Asian cities that rank among the top cities in the world in the most recent period. The patterns attest to the growing importance of international collaboration for innovation and the premier position of global cities as spaces facilitating such collaboration.
How Cross-border Oriented Is Innovation Policy? A Commentary
Authors: Boekholt Patries
Published: March 2022

The commentary on Pietrobelli (2022) and Fagerberg (2022) discusses the active integration in global value chains and the use of demand-side policies in transnational, national, and regional Research and Innovation (R&I). The prevailing strategy for R&I policy to foster cross-border innovation is to make the national innovation system as attractive as possible for foreign investors, partners, and talent. However, the mismatch between foreign investments and national or regional R&I capabilities hampers the potential for cross-border learning. Cross-border policy instruments are predominantly geared to public-sector research collaboration, much less so to the R&I collaboration between enterprises. The rising importance of global and societal challenges as the key rationale for R&I policy produces an impetus for more cross- border collaboration. The return of a more protective industrial policy, whether national or within a global region (e.g. the European Union) has the opposite effect, aiming to shape the geographical scope of value chains.
Previous Accounts of Polarity Logics for Natural Language
Authors: Ludlow Peter , Živanović Sašo
Published: March 2022

This chapter explores several attempts to utilize logical polarity as a fundamental notion underlying logical inference. Ludlow and Živanović look at accounts of logical polarity in contemporary linguistics, including in semantics (where the idea of directional entailingness is developed) and in some syntactic accounts of inference that rely on explicit polarity marking. The authors suggest that the existing syntactic accounts of polarity marking are a bit ad hoc, and they propose that deeper foundations should be provided.
Conservativity, Restrictedness, and Quantification
Authors: Ludlow Peter , Živanović Sašo
Published: March 2022

This chapter develops the idea that aboutness in natural language has a reflex in semantics in the notion of conservativity (a concept that is familiar from work in generalized quantifier theory). Ludlow and Živanović show that the syntactic counterpart of conservativity is restrictedness, which they define in terms of their notion of p-scope, thus connecting restrictedness and the Dynamic Deductive System. Finally, Ludlow and Živanović show that with a notion of restrictedness in place they can use logical polarity to define away quantificational operators in natural language, and also replace disjunctions and conjunctions with a neutral junction. They treat all quantification as involving quantificational closure over free variables; whether quantificational closure is existential or universal, and whether the neutral junction is to be a conjunction or a disjunction, is determined by polarity and restrictedness. In other words, polarity and restrictedness can “rule it all.”
Linguistic Phenomena Through The Lens Of L**
Authors: Ludlow Peter , Živanović Sašo
Published: March 2022

Ludlow and Živanović argue that their account of the syntax of restrictedness and quantification provides a fresh perspective on topics in linguistic theory, such as puzzles in discourse anaphora or presupposition projection. They show that many alleged problems in discourse anaphora dissolve of their own accord when we have a proper understanding of restrictedness and quantification. They then turn to the topic of negative polarity items, and show how their account can also provide fresh tools for examining the phenomenon, and in particular for investigating semantic properties like additivity, anti-additivity, etc.
L**, LF, and Logical Form
Authors: Ludlow Peter , Živanović Sašo
Published: March 2022

A standard view in the semantics of natural language is that first-order predicate logic is not adequate for giving an account of natural language. This chapter shows that on a reasonable formalization of the proposed formal language, this is not the case. Ludlow and Živanović show that their formal system has sufficient expressive power, is compositional in the relevant sense, and the structures are isomorphic to those of natural language. They then discuss a particular version of generative linguistics—the minimalist program—and show how their approach can be integrated into the Minimalist Program, and how that integration can yield fruitful insights for linguistic theory.
Statistical entrepreneurs: the political work of infrastructuring the SDG indicators
Authors: Bandola-Gill Justyna
Published: March 2022

Governing by indicators has emerged as the predominant mode of global public policy. Consequently, global governance has become a field in which different indicators compete for policymakers’ and public attention. This begs a question—what makes some indicators successful when others become irrelevant? This paper explores this problem through the inquiry into the measurement of multidimensional poverty in Sustainable Development Goal 1 (“End poverty in all its forms everywhere”). In the field historically dominated by the World Bank’s dollar-per-day metric (currently 1.9$), multidimensional poverty measurement gained prominence, becoming one of the key measures of global poverty. By tracking the pathways to success of multidimensional poverty measurement—through qualitative interviews with actors in International Organisations this paper argues that the key quality of successful indicators is their ability to become parts of the broader epistemic infrastructure, linking political institutions, actors (including experts and policymakers), and data and statistics. The paper brings the focus on a specific set of actors—statistical entrepreneurs—who advocate for innovations in measurement and work toward creating such infrastructures, thus indirectly promoting new policy ideas reflected in the metrics.
Brain Pericytes Acquire Stemness via the Nrf2-Dependent Antioxidant System
Authors: Sakuma Rika , Kobayashi Miku , Kobashi Rui , Onishi Mako , Maeda Mitsuyo , Kataoka Yosky , Imaoka Susumu
Published: March 2022

Pericytes (PCs) are a mural support cell population elongated at intervals along the walls of capillaries. Recent studies reported that PCs are multipotent cells that are activated in response to tissue injury and contribute to the regenerative process. Using a C.B-17 mouse model of ischemic stroke, it has been proposed that normal brain pericytes (nPCs) are converted to ischemic pericytes (iPCs), some of which function as multipotent stem cells. Furthermore, oxygen-glucose deprivation (OGD) promoted mesenchymal-epithelial transition in nPCs; however, nestin was not induced under OGD conditions. Therefore, further studies are needed to elucidate the PC reprogramming phenomenon. We herein isolated nPCs from the cortex of C.B-17 mice, and compared the traits of iPCs and nPCs. The results obtained showed that nPCs and iPCs shared common pericytic markers. Furthermore, intercellular levels of reactive oxygen species and the nuclear accumulation of nuclear factor erythroid-2-related factor 2 (Nrf2), a key player in antioxidant defenses, were higher in iPCs than in nPCs. OGD/reoxygenation and a treatment with tBHQ, an Nrf2 inducer, increased nestin levels in nPCs. Moreover, epithelial marker levels, including nestin, Sox2, and CDH1 (E-cadherin) mRNAs, were elevated in Nrf2-overexpressing PCs, which formed neurosphere-like cell clusters that differentiated into Tuj1-positive neurons. The present results demonstrate that oxidative stress and Nrf2 are required for the generation of stem cells after stroke and will contribute to the development of novel therapeutic strategies for ischemic stroke.
Arterial Injury Portends Worse Soft Tissue Outcomes and Delayed Coverage in Open Tibial Fractures
Authors: Bi Andrew S. , Fisher Nina D. , Parola Rown , Ganta Abhishek , Egol Kenneth A. , Konda Sanjit R.
Published: March 2022

Objectives:

To investigate if any injury to the three primary branches of the popliteal artery in open tibia fractures lead to increased soft-tissue complications, particularly in the area of the affected angiosome.

Design:

Retrospective cohort comparative study

Setting:

Two academic level one trauma centers

Patients/Participants:

Sixty-eight adult patients with open tibia fractures with a minimum one-year follow up;

Intervention:

N/A

Main Outcome Measurements:

Soft-tissue outcomes as measured by wound healing (delayed healing, dehiscence, or skin breakdown) and fracture related infection (FRI) at time of final follow-up.

Results:

Eleven (15.1%) tibia fractures had confirmed arterial injuries via CTA (7), direct intraoperative visualization (3), intraoperative angiogram (3). Ten (91.0%) were treated with ligation and 1 (9.1%) was directly repaired by vascular surgery. Ultimately, 6 (54.5%) achieved radiographic union and 4 (36.4%) required amputation performed at a mean of 2.62 ± 2.04 months, with one patient going on to nonunion diagnosed at 10 months. Patients with arterial injury had significantly higher rates of wound healing complications, FRI, nonunion, amputation rates, return to the OR, and increased time to coverage or closure. After multivariate regression, arterial injury was associated with higher odds of wound complications, FRI, and nonunion. Ten (90.9%) patients with arterial injury had open wounds in the region of the compromised angiosome, with 7 (70%) experiencing wound complications, 6 (60%) FRIs, and 3 (30%) undergoing amputation.

Conclusions:

Arterial injuries in open tibia fractures with or without repair, have significantly higher rates of wound healing complications, FRI, delayed time to final closure, and need for amputation. Arterial injuries appear to effect wound healing in the affected angiosome.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Dexmedetomidine disrupts esophagus cancer tumorigenesis by modulating circ_0003340/miR-198/HMGA2 axis
Authors: Che Jianpeng , Liu Mingming , Lv Hongwei
Published: March 2022

More and more studies have focused on the regulatory role of circular RNAs (circRNAs) in various cancers. However, it is not clear how dexmedetomidine (DEX) affects esophagus cancer progression by affecting the expression of circRNAs. This study aimed to investigate the role of DEX in esophagus cancer and its underlying mechanism. Cell Counting Kit-8 assay and 5-ethynyl-2′-deoxyuridine assays were conducted to evaluate cell proliferation. Flow cytometry analysis and transwell assay were performed for cell apoptosis and invasion. The protein levels of cleaved caspase-3, matrix metallopeptidase 9, and high mobility group AT-hook 2 (HMGA2) were assessed by western blot assay. The expression levels of circ_0003340 and microRNA-198 (miR-198) were determined by quantitative real-time PCR. Dual-luciferase reporter assay was performed to verify the interaction between miR-198 and circ_0003340 or HMGA2. Murine xenograft model was established to investigate the role of circ_0003340 and DEX in vivo. DEX exerted antitumor effects in esophagus cancer cells. DEX hindered proliferation and invasion while inducing apoptosis of esophagus cancer cells, which was abolished by circ_0003340 elevation, HMGA2 overexpression, or miR-198 silencing. miR-198 directly interacted with circ_0003340 and HMGA2 in esophagus cancer cells. Moreover, knockdown of circ_0003340 could improve the anticancer role of DEX in vivo. DEX constrained cell carcinogenesis by regulating circ_0003340/miR-198/HMGA2 axis in esophagus cancer, providing an effective clinical implication for preventing the development of the esophagus cancer by the DEX.
CircFOXK2 enhances tumorigenesis and immune evasion in non–small cell lung cancer by miR-485-5p/PD-L1 axis
Authors: Zhang Nan , Fan Jian , Deng Zhiping
Published: March 2022

Background

Circular RNAs (circRNAs) serve a key role in lots of cancers. The outcomes of upregulated circular RNA forkhead box K2 (circFOXK2) on non–small cell lung cancer (NSCLC) persisted uncertainly. In this study, the role of circFOXK2 in NSCLC was inspected.

Methods

The abundances of circFOXK2, microRNA-485-5p (miR-485-5p) and programmed cell death ligand-1 (PD-L1) were confirmed by quantitative real-time PCR and western blot. Cell counting kit-8 (CCK-8) assay and clonogenic assay were accomplished to conclude the proliferation of NSCLC cells. Wound healing and transwell assays were implemented to evaluate cell migration and invasion. Lactate dehydrogenase (LDH) cytotoxicity assay was enforced to quantify the cytotoxicity of CD8+ T cells. Flow cytometry assay was employed to detect apoptosis. Besides, the mice experiments were utilized for in vivo tumorigenesis analysis. Dual-luciferase reporter assay was carried out to reveal the associations between miR-485-5p and circFOXK2 or PD-L1.

Results

CircFOXK2 and PD-L1 levels were augmented in NSCLC. CircFOXK2 targeted miR-485-5p, which could bind to PD-L1. CircFOXK2 served a key role in NSCLC tumorigenesis and cytotoxicity of CD8+ T cells. MiR-485-5p inhibition or PD-L1 overexpression abolished the inhibitory effects of circFOXK2 lack on NSCLC tumorigenesis and cytotoxicity of CD8+ T cells.

Conclusion

CircFOXK2 sponged miR-485-5p to stimulate PD-L1 and expedited NSCLC development.
LncRNA SNHG11 enhances bevacizumab resistance in colorectal cancer by mediating miR-1207-5p/ABCC1 axis
Authors: Huang Weizhen , Zhang Hang , Tian Yunming , Li Yi , Li Jun , Zhong Xiaohua , Yuan Xia
Published: March 2022

Long noncoding RNAs (lncRNAs) have been reported to serve as vital regulators in the chemoresistance of human cancers, including colorectal cancer (CRC). In this study, we aimed to explore the functions of lncRNA small nucleolar RNA host gene 11 (SNHG11) in the resistance of CRC to bevacizumab. Quantitative real-time PCR, western blot assay or immunohistochemistry assay were performed to examine the expression of SNHG11, microRNA-1207-5p (miR-1207-5p), ATP binding cassette subfamily C member 1 (ABCC1) and Ki67. Cell Counting Kit-8 assay was conducted to evaluate bevacizumab resistance and cell viability. 5′-ethynyl-2′-deoxyuridine analysis, flow cytometry analysis and wound-healing assay were conducted for cell proliferation, apoptosis and migration, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to analyze the relations among SNHG11, miR-1207-5p and ABCC1. Murine xenograft model assay was employed to analyze bevacizumab resistance in vivo. The exosomes were observed under transmission electron microscopy. SNHG11 was overexpressed in bevacizumab-resistant CRC tissues and cells. Knockdown of SNHG11 restrained bevacizumab resistance, repressed cell proliferation and migration, and promoted apoptosis in bevacizumab-resistant CRC cells. MiR-1207-5p served as the target of SNHG11 and SNHG11 regulated bevacizumab resistance by targeting miR-1207-5p. ABCC1 was the target gene of miR-1207-5p. Overexpression of miR-1207-5p inhibited bevacizumab resistance and cell progression in bevacizumab-resistant CRC cells, with ABCC1 elevation abrogated the impacts. SNHG11 silencing repressed bevacizumab resistance in vivo. In addition, exosomal SNHG11 was upregulated in bevacizumab-resistant CRC cells. SNHG11 contributes to bevacizumab resistance in CRC depending on the modulation of miR-1207-5p and ABCC1.
In-silico drug-likeness analysis, ADME properties, and molecular docking studies of cyanidin-3-arabinoside, pelargonidin-3-glucoside, and peonidin-3-arabinoside as natural anticancer compounds against acting receptor-like kinase 5 receptor
Authors: Kurter Hasan , Mert-Ozupek Nazli , Ellidokuz Hulya , Calibasi-Kocal Gizem
Published: March 2022

Background

The aim of the study was in-silico drug-likeness analysis, absorption, distribution, metabolism, and excretion (ADME) properties, and molecular docking studies of anthocyanins as natural anticancer compounds against acting receptor-like kinase 5 (ALK5) receptor. Transforming growth factor-β (TGF-β) plays an essential role in various cellular processes. Increased expression of TGF-β and its receptor TGFβR-I (i.e. ALK5) have been associated with poor prognosis in cancer patients.

Methods

The drug-likeness activity of anthocyanins was performed using SwissADME tool. Molecular docking studies were carried out by using the Autodock Vina 1.5.6 tool.

Results

The results revealed that cyanidin-3-arabinoside (C3A), pelargonidin-3-glucoside (P3G), and peonidin-3-arabinoside (P3A) were able to use both Lipinski’s rule of five and Ghose variations. The binding energies of C3A, P3G, and P3A against ALK5 were found as −8.0, −8.3, and −8.4 kcal mol−1, respectively.

Conclusion

These selected anthocyanins have shown higher binding energies than known inhibitors to the ALK5 receptor. Further in-vitro and in-vivo studies were strongly recommended to clarify the whole mechanism.
TRIM72 exerts antitumor effects in breast cancer and modulates lactate production and MCT4 promoter activity by interacting with PPP3CA
Authors: Wang Zheng , Li Haixia , Wang Hongxia , Li Xin , Zhang Qiong , Wang Haifang , Li Kui , Qiu Yurong
Published: March 2022

A hypoxic tumor microenvironment (TME) promotes cancer progression, yet its value as a therapeutic target remains underexploited. Tripartite motif-containing 72 (TRIM72) may protect cells against various stresses including hypoxia. Recently, low TRIM72 expression has been implicated in cancer progression. However, the biological role and molecular mechanism of TRIM72 in breast cancer (BC) remain unclear. Herein, we analyzed the TRIM72 expression in BC tissue and cell lines by western blot (WB) and quantitative reverse transcription-PCR. We established the overexpression of TRIM72 using plasmids and lentiviral-mediated upregulation, as well as downregulation of protein phosphatase 3 catalytic subunit alpha (PPP3CA) by siRNA. The tumor-suppressive roles of TRIM72 were assessed on BT549 and MDA-MB-231 cells by MTS, Transwell, and flow cytometry assays in vitro and in xenografted tumors in vivo. The molecular mechanism of TRIM72 was investigated by luciferase reporter and co-immunoprecipitation (Co-IP) assay. Lactate production was measured by ELISA under hypoxic environments induced by CoCl2. Moreover, the expression of PI3K/Akt/mTOR pathway-associated proteins was detected by WB in BC cells. Results showed that TRIM72 was downregulated in BC. Overexpression of TRIM72 inhibited tumor proliferation and invasion in vitro and in a xenograft tumor model. Mechanistically, PPP3CA altered the inhibitory effects of TRIM72 on hypoxia-induced lactate production and monocarboxylate transporter 4-promoter activity, as well as the effect of the PI3K/Akt/mTOR signaling pathway. Our study suggests that TRIM72 modulates the TME and plays tumor-suppressive roles in BC progression. Therefore, TRIM72 may serve as a potential therapeutic target in BC.
LncRNA BBOX1-AS1 promotes pituitary adenoma progression via sponging miR-361-3p/E2F1 axis
Authors: Wu Haijun , Zhou Shaolong , Zheng Yuqian , Pan Zheng , Chen Yongshun , Wang Xinjun
Published: March 2022

Pituitary adenoma is one of the most common intracranial tumors, more and more studies have shown that long non-coding RNA (lncRNA) plays a very important role in pituitary adenoma. However, there are few reports on the function of lncRNA BBOX1-AS1 in pituitary adenomas, and further exploration is needed. The objective of this research is to figure out what function BBOX1-AS1 plays in pituitary adenoma and how it regulates it. The expression of the E2F1, miR-361-3p and BOX1-AS1 genes was measured using a quantitative real-time PCR method. The functional involvement of BBOX1-AS1 in pituitary adenoma was examined utilizing the Transwell assay, western blot assays and the cell counting kit-8. RNA immunoprecipitation and luciferase reporter assays revealed that miR-361-3p binds to E2F1 or BBOX1-AS1. In addition, in-vivo assays were carried out. The expression of BBOX1-AS1 in pituitary adenoma tissues and cells has been increased, according to our findings. Furthermore, it is also noted that downregulation of BBOX1-AS1causes the inhibition of pituitary adenoma cells which result in invasion, apoptosis and proliferation, as well as boosting tumor development in vivo. In addition, BBOX1-AS1 knockdown inhibited tumor development in vivo. We identify BBOX1-AS1 bind to miR-361-3p and to suppress its expression in a negative way. Moreover, miR-361-3p has been shown to bind with E2F1 and inhibit its expression. E2F1 also corrected miR-361-3p-mediated cell invasion, proliferation and apoptosis in BBOX1-AS1-dysregulated pituitary adenoma cells in rescue tests. BBOX1-AS1 increases pituitary adenoma malignant activity by sponging miR-361-3p to upregulate E2F1 expression, which may lead to a new path in pituitary adenoma therapeutic attempts.
What Do We Know About Shoulder Injury Related to Vaccine Administration? An Updated Systematic Review
Authors: MacMahon Aoife , Nayar Suresh K. , Srikumaran Uma
Published: March 2022

Background

Shoulder injury related to vaccine administration (SIRVA) is postulated to be an immune-mediated inflammatory response to a vaccine antigen injected into or near the subacromial bursae or synovium, leading to shoulder pain and dysfunction. The number of studies on this topic is rapidly increasing. Recent comparative studies have reported conflicting conclusions, which suggests that a systematic review of the best-available evidence may be helpful.

Questions/purposes

In this systematic review, we asked: What are the (1) clinical characteristics, (2) diagnoses, and (3) management approaches and outcomes reported in association with SIRVA?

Methods

A search was performed on October 4, 2021, of the PubMed and Medline databases for studies related to SIRVA. Inclusion criteria were English-language comparative studies, case series, and case reports that involved shoulder pain occurring after vaccination. Studies of exclusively neurologic conditions after vaccination were excluded. Forty-two studies met the eligibility criteria, including three retrospective comparative studies (72 patients and 105 controls), five database case series (2273 patients), and 34 case reports (49 patients). Study quality was assessed for the database case series and retrospective comparative studies using the Methodological Index for Non-randomized Studies tool.

Results

Among patients in the case reports, the median age was 51 years (range 15-90 years), and 73% (36 of 49) were women. BMI was reported for 24% of patients (12 of 49) in case reports, with a median of 23.5 kg/m2 (range 21-37.2 kg/m2). The most common symptoms were shoulder pain and reduced ROM. The most common diagnoses were shoulder bursitis, adhesive capsulitis, and rotator cuff tears. The most frequent management modalities included physical or occupational therapy, NSAIDs, and steroid injections, followed by surgery, which was generally used for patients whose symptoms persisted despite nonsurgical management. Full resolution of symptoms was reported in 2.9% to 56% of patients.

Conclusion

The association between inflammatory conditions of the shoulder (such as bursitis) and vaccination appears to be exceedingly rare, occurring after approximately 1:130,000 vaccination events according to the best-available comparative study. Currently, there is no confirmatory experimental evidence supporting the theory of an immune-mediated inflammatory response to vaccine antigens. Although the clinical evidence is limited, similar to any bursitis, typical treatments appear effective, and surgery should rarely be performed. Additional research is needed to determine the best injection technique or evaluate alternate injection sites such as the anterolateral thigh that do not involve positioning a needle close to the shoulder.
The association of age at natural menopause with pre- to postmenopausal changes in left ventricular structure and function: the Coronary Artery Risk Development in Young Adults (CARDIA) study
Authors: Appiah Duke , Nwabuo Chike C. , Ebong Imo A. , Vasconcellos Henrique D. , Wellons Melissa F. , Lewis Cora E. , Lima Joao A. , Schreiner Pamela J.
Published: March 2022

Objective:

The association between menopause and incident cardiovascular disease (CVD) is controversial. We evaluated the relationships of estrogen deficiency (ovarian reproductive aging) assessed by age at natural menopause (ANM), chronological aging, and antecedent CVD risk factors (biological aging) with left ventricular (LV) structure and function among women transitioning from pre- to postmenopause.

Methods:

We studied 771 premenopausal women (37% Black) from the Coronary Artery Risk Development in Young Adults Study with echocardiographic data in 1990 to 1991 (mean age: 32 y) who later reached natural menopause by 2015 to 2016 and had repeated echocardiographic measurements. Linear regression models were used to evaluate the association of ANM with parameters of LV structure and function.

Results:

Mean ANM was 50 (± 3.8) years and the average time from ANM to the last echocardiograph was 7 years. In cross-sectional analyses, a 1-year increase in ANM was significantly associated with lower postmenopausal LV mass (LVM), LVM indexed to body surface area, LV mass-to-volume ratio, and relative wall thickness. In age-adjusted longitudinal analyses, higher ANM was inversely associated with pre- to postmenopausal changes in LVM (β = –0.97; 95% CI: –1.81 to –0.13, P = 0.024) and LVM indexed (β = –0.48; 95% CI: –0.89 to –0.07, P = 0.021). Controlling for baseline LV structure parameters and traditional CVD risk factors attenuated these associations. Further adjustment for hormone therapy uses did not alter these results.

Conclusion:

In this study, premenopausal CVD risk factors attenuated the association of ANM with changes in LV structure parameters. These data suggest that premenopausal CVD risk factors may predispose women to elevated future CVD risk more than ovarian aging.
Avoidable bilateral salpingo-oophorectomy at hysterectomy: a large retrospective study
Authors: Iancu Ana-Maria , Murji Ally , Chow Ovina , Shapiro Jodi , Cipolla Amanda , Shirreff Lindsay
Published: March 2022

Objectives:

Evaluate the proportion of justified bilateral salpingo-oophorectomy (BSO) at hysterectomy, based on pathologic diagnosis, and determine prevalence of avoidable BSO based on pre- and intraoperative considerations and pathologic diagnosis.

Methods:

Retrospective review of hysterectomies at seven Ontario, Canada hospitals from 2016 to 2019. Surgeries completed by oncologists or for invasive placentation were excluded. Patient, case, and surgeon characteristics were recorded along with pathologic diagnoses. Avoidable BSO criteria were: preoperative diagnosis of cervical dysplasia or benign diagnosis other than endometriosis, gender dysphoria, risk reduction or premenstrual dysphoric disorder; age < 51 years; absence of intraoperative endometriosis and adhesions; unjustified pathology (where “justified” pathology was endometriosis or (pre)malignant diagnosis except for cervical dysplasia). Patients with avoidable BSO were compared to those having at least one criterion for BSO. Binary logistic regression identified factors most strongly associated with avoidable BSO.

Results:

Four thousand one hundred ninety-one hysterectomies were completed with 1,422 (33.9%) patients having concomitant BSO. Pathologic diagnosis justified BSO in most patients (1,035/1,422, 72.8%) with endometrial cancer being most common (439/1,422, 30.9%). When preoperative characteristics, intraoperative findings, and pathologic diagnoses were considered, 79 of 1,422 (5.6%) BSOs were avoidable. Compared to cases with at least one criterion for BSO, avoidable BSOs were more frequently completed by generalists (OR 1.80, 95% CI 1.10-2.99, P 
= 0.021), for preoperative diagnoses of abnormal uterine bleeding/menorrhagia (OR 3.82, 95% CI 2.35-6.30, P 
= 0.001) and fibroids (OR 4.25, 95% CI 2.63-6.92, P 
< 0.001).

Conclusion:

Pathologic diagnosis justified most BSOs at hysterectomy. BSO was avoidable in 5.6% of patients, underscoring the need to standardize practice of BSO.
The Role of Insulin-like Growth Factor-1 and Its Receptor in the Eye: A Review and Implications for IGF-1R Inhibition
Authors: Truong Timothy , Silkiss Rona Z.
Published: March 2022

Purpose:

FDA approval of teprotumumab for thyroid eye disease in January 2020 reinforced interest in the pharmacologic potential of insulin-like growth factor-1 (IGF-1) and its receptor, IGF-1R. Despite recent approval and adaptation for ophthalmic use, IGF-1R inhibitors are not a new therapeutic class. In 1986, Yamashita described aIR3, a monoclonal antibody to IGF-1R (anti-IGF-1R), that inhibited the effect of IGF-1 on growth hormone release. Given the widespread presence of IGF-1R, interrupting this receptor can lead to systemic physiologic effects, some adverse. We aim to review what is known about IGF-1/IGF-1R in the eye and consider the possible local side effects, unintended consequences, and potential uses of this medication class.

Methods:

A PubMed database search utilizing the keywords “insulin-like growth factor-1, eye, inhibitor, antibody, side effect” was performed to identify publications discussing IGF-1 in the human eye from January 2011 to August 2021. Criteria for acceptance included studies discussing human subjects or human tissue specifically related to the eye.

Results:

Out of a total of 230 articles, 47 were organized in 3 subject groups for discussion: thyroid-associated orbitopathy, cornea and the ocular surface, and the retina and neovascularization. Review of the literature demonstrated that IGF-1 affects growth and development of the eye, epithelial proliferation, retinal angiogenesis, inflammation, and is associated with thyroid-associated orbitopathy.

Conclusions:

IGF-1R exists throughout in the human body, including the cornea, retina, and orbit. Research regarding ocular effects of IGF-1/IGF-1R outside thyroid eye disease is limited. Carefully designed studies and clinical assessments of patients undergoing treatment with anti-IGF-1R may identify ocular side effects and foster consideration of the role of anti-IGF-1R in ocular therapeutics. Given the increasing use of anti-IGF-1R antibodies, understanding their ocular effects, side effects, and potential systemic implications for use in disease is critical.
Plexiform Neurofibroma With Activating KRAS Mutation and Segmental Presentation Involving the Unilateral Eyelid
Authors: Stallworth Jeannette Y. , Smith Loreley D. , Vagefi M. Reza , Pekmezci Melike
Published: March 2022

Plexiform neurofibromas are classically thought to be pathognomonic for neurofibromatosis type 1. However, isolated forms may occur, particularly as a manifestation of segmental neurofibromatosis related to postzygotic mosaicism in the NF1 gene. Most cases occur on the head and neck, trunk, and extremities with very few cases reported in the periorbital area. The authors report a case of plexiform neurofibroma with perineuriomatous features of the right upper eyelid in a patient with no other stigmata of neurofibromatosis. While suggestive of segmental neurofibromatosis, genetic analysis revealed activating KRAS mutation and inactivating mutation in PHF6 with no evidence of NF1 mutation in germline or tumor tissue. Neither KRAS nor PHF6 have been previously reported in association with neurofibroma.
Bilateral Dacryoadenitis and Central Nervous System Involvement in a Child With Kimura Disease
Authors: Camacho Maria Belen , Chahud Fernando , Boasquevisques Gustavo , Santos de Oliveira Ricardo , Roxo-Junior Persio , Cruz Antonio Augusto Velasco
Published: March 2022

Kimura’s disease (KD) is a systemic inflammatory condition characterized by lymphadenopathy and subcutaneous nodules in the head and neck region. The lesions have a distinctive histopathological pattern formed by follicular hyperplasia, eosinophilic infiltrates, fibrosis, and vessel proliferation. The disease may occur at all ages but predominates among young males with autoimmune dysfunctions. Visceral and orbital involvement is uncommon. We report a girl with KD who developed bilateral enlargement of the lacrimal glands and a lesion in the left lateral ventricle of the brain indistinguishable from a central nervous system neoplasia. A biopsy of both the lacrimal gland and the lateral ventricle was consistent with KD.
Introduction of Steroid Absorbed Spongostan in Endoscopic Dacryocystorhinostomy Improves Success Rates
Authors: Chen Itay , Ayalon Hadar , Drabkin Elena , Cohen Ohad , Peleg Uri
Published: March 2022

Background:

Endoscopic Dacryocystorhinostomy (DCR) has become an acceptable alternative to the open approach, with considerable data demonstrating comparable success rates and advantages such as avoiding skin incisions. Drug-eluting bio-absorbable materials are relatively new innovation in sinus surgery, the usefulness of such materials in Endoscopic DCR is yet to be described.

Methods:

A retrospective analysis of 253 endoscopic DCR procedures performed by a single surgical team from September 2011 to June 2020 was performed. At the end of 2013, a surgical modification took place with the introduction of steroid-eluting Spongostan to the intranasal surgical bed. As a result, 2 cohorts were compared before and after the modification. The first cohort consisted of 55 patients, and the second consisted of 187 patients, respectively. Patient demographics, clinical features, complications and outcomes were examined.

Results:

A total of 242 procedures were evaluated after exclusion. In the first cohort of 55 patients (48 adults and 7 children), the overall and adult functional success rates were 83.6% and 83.3%, respectively. In the second cohort of 187 patients (167 adults and 20 children), where steroid-eluting Spongostan was used, the overall and adult functional success rates were 92.5% and 93.4%, respectively. These differences were statistically significant.

Conclusion:

This is a unique study presenting a single surgical team’s experience over a 9-year period where a novel technique involving drug-eluted bio-absorbable material (Spongostan) was introduced midway through, creating 2 cohorts to compare. Success rates were significantly higher after applying steroid eluted Spongostan to our endoscopic DCR technique.
Orbital Inflammation Following COVID-19 Vaccination
Authors: Reshef Edith R. , Freitag Suzanne K. , Lee Nahyoung Grace
Published: March 2022

Three patients presented with periorbital swelling, pain with extraocular movements, and binocular diplopia 1–4 days after receiving an mRNA Coronavirus Infectious Disease-19 (COVID-19) vaccine (BNT162b2, Pfizer/BioNTech; mRNA-1273, Moderna). All patients had a normal afferent function, unilateral limitation of extraocular motility, proptosis, and periorbital inflammation. Neuroimaging of the orbits with contrast revealed inflammation and enlargement of extraocular muscles in 2 cases and the lacrimal gland in 1 case. In all 3 cases, an extensive infectious and inflammatory laboratory work-up was unremarkable and signs and symptoms of orbital inflammation rapidly improved to complete resolution after treatment with high-dose oral prednisone. This is the first reported series of orbital inflammation occurring shortly after administration of the COVID-19 vaccine. Clinicians may consider an inflammatory postvaccine etiology as an alternative to presumed idiopathic diagnosis in such cases.
Orbital Teratoma: Case Report and Management Review
Authors: Ming Wendy H. , Terry Jefferson , Zhao LeiDi , Dolman Peter J.
Published: March 2022

Orbital teratoma is a rare, vision-threatening, congenital neoplasm derived from all germ cell layers. The management of orbital teratoma is uncertain because of its rarity and variable severity. We present a case with complete tumor excision with preservation of vision and cosmesis. A 4-day-old female presented with progressive proptosis of the OD. She was born term following an uneventful pregnancy and delivery. MRI of the orbits showed a large right-sided mass centered within the intraconal space with heterogeneous signal intensity characteristics consistent with a teratoma. She underwent a right posterior orbitotomy. The tumor was wrapped around the optic nerve but was gradually separated from it and all other normal structures and delivered intact. Histology was compatible with an immature teratoma without evidence of malignancy. The patient is now 6 months old, visually attentive with no evidence of optic neuropathy, and has essentially normal appearance.
Post-acute sensory neurological sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: the COVID-PN observational cohort study
Authors: Odozor Chioma U. , Kannampallil Thomas , Ben Abdallah Arbi , Roles Kristen , Burk Carrie , Warner Benjamin C. , Alaverdyan Harutyun , Clifford David B. , Piccirillo Jay F. , Haroutounian Simon
Published: March 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause neurological sequelae after the resolution of symptomatic COVID-19 illness, but the occurrence of peripheral neuropathy symptoms and cranial nerve dysfunction is unknown. This study aimed to characterize the occurrence and severity of pain and peripheral neuropathy symptoms in patients with SARS-CoV-2 infection. An observational cohort study included adults tested for a SARS-CoV-2 infection at an academic medical center (assigned as CV+ or control, based on test results). Thirty to 90 days after the index SARS-CoV-2 test, patients completed a web-based questionnaire assessing pain, peripheral neuropathy-related sensory symptoms, and symptoms in the distribution of cranial nerves (current symptoms, symptoms at testing and 2 weeks thereafter). Univariate analyses compared the outcomes between the groups. Multivariable analysis was used to determine the odds for neuropathy symptoms after adjusting for key baseline variables. A total of 1556 participants were included: 542 CV+ patients and 1014 control subjects. CV+ patients reported a higher occurrence of peripheral neuropathy symptoms in the extremities anytime within 90 days postinfection (28.8% vs 12.9%, odds ratio [OR] [95% confidence interval] = 2.72 [2.10-3.54]), as well as such symptoms persisting up to 90 days after infection (6.1% vs 1.9%, OR = 3.39 [1.91-6.03]). The occurrence of pain in the extremities was higher in the CV+ group (24.2% vs 9.8%, OR = 2.95 [2.21-3.91]). SARS-CoV-2 infection was also associated with higher occurrence of peripheral neuropathy symptoms, after adjusting for the history of chronic pain and neuropathy (OR = 3.19 [2.37-4.29]). The results suggest that SARS-CoV-2 infection was independently associated with an increased risk of pain and peripheral neuropathy symptoms.
Effects of aggressive predilatation, sizing, and postdilatation strategy for coronary bioresorbable vascular scaffolds implantation
Authors: Chen Hsiang-Yao , Huang Wei-Chieh , Teng Hsin-I , Tsai Chuan-Tsai , Tsai Yi-Lin , Chuang Ming-Ju , Chen Ying-Ying , Lu Tse-Min
Published: March 2022

Background:

The results of the recent Amsterdam Investigator-Initiated Absorb Strategy All-Comers trial showed that the predilatation, sizing, and postdilatation (PSP) technique did not lower the long-term rates of scaffold thrombosis and adverse events. We evaluated the impact of aggressive PSP bioresorbable vascular scaffold (BRS) implantation on the short- and long-term clinical outcomes.

Methods:

From June 2014 to December 2016, 150 patients with BRS implantation were enrolled and received successful percutaneous coronary intervention (PCI), of whom 104 received aggressive PSP technique (high-pressure predilatation and lesion preparation in addition to the traditional PSP technique). Short- and long-term outcomes were compared.

Results:

All patients underwent successful PCI and BRS implantation with final Thrombolysis in Myocardial Infarction grade 3 flow. The baseline and procedure characteristics were similar in both groups. Debulking techniques were used in 13 (8.7%) patients. Intracoronary imaging modalities were used in 73 (48.7%) patients. After BRS implantation, no adverse events were observed within 30 days in both groups. During the mean follow-up period of 2.98 ± 0.77 years, 12 (8.0%) patients experienced major adverse cardiovascular events (MACEs), including one cardiovascular death (0.6%), three nonfatal myocardial infarction (2.0 %), and 11 target-vessel revascularization (7.3 %). Multivariate Cox regression analysis showed that aggressive PSP remained an independent protective factor for MACEs. Moreover, the use of intracoronary imaging and rotablation atherectomy was associated with better clinical outcomes.

Conclusion:

Lesion preparation by aggressive PSP in BRS implantation was associated with better long-term clinical outcomes.
The Discrepancy Between Subjective and Objective Clinical Endpoints in Gastroesophageal Reflux Disease
Authors: Shibli Fahmi , Sandhu Dalbir S. , Fass Ronnie
Published: March 2022

Therapeutic outcome in gastroesophageal reflux disease (GERD) is commonly determined by both subjective and objective clinical endpoints. Clinicians frequently use symptom improvement as a key benchmark of clinical success, in conjunction with normalization of objective parameters such as esophageal acid exposure and inflammation. However, GERD therapeutic trials have demonstrated that a substantial number of patients rendered asymptomatic, whether through medical, surgical, or endoscopic intervention, continue to have persistent abnormal esophageal acid exposure and erosive esophagitis. The opposite has also been demonstrated in therapeutic trials, where patients remained symptomatic despite normalization of esophageal acid exposure and complete resolution of esophageal inflammation. Moreover, there is no substantive evidence that symptomatic response to antireflux treatment requires complete esophageal mucosal healing or normalization of esophageal acid exposure. Thus, it appears that a certain level of improvement in objective parameters is needed to translate into meaningful changes in symptoms and health-related quality of life of GERD patients. This supports the need to reconsider the commonly used “hard” clinical endpoints to evaluate therapeutic trials in GERD.
2021 Patient Perceptions Regarding Colonoscopy Experience
Authors: Vemulapalli Krishna C. , Lahr Rachel E. , Rex Douglas K.
Published: March 2022

Goal:

We sought to document patient perceptions in 2021 regarding colonoscopy experience and potential deterrents to repeat colonoscopy.

Background and Aim:

Bowel preparation has been previously considered by patients to be the worst part of a colonoscopy.

Materials and Methods:

We conducted a prospective survey of consecutive patients age 18 years and older who had just completed colonoscopy at 2 outpatient endoscopy centers at a tertiary academic hospital. The short survey was conducted in the recovery area. The main outcome measure was patient perceptions of the worst part of their colonoscopy experience and which factor would most deter them from a future colonoscopy.

Results:

Four hundred patients completed the survey of 405 approached. Average patient age was 64 years, and 48% were women. Seventy-five percent of patients used low-volume preparations. Bowel preparation was considered the worst part of colonoscopy by 71% of patients. Women were more likely to choose laxatives as the worst part of a colonoscopy. Bowel preparation was chosen most often (55%) as the most likely deterrent to a future colonoscopy. There were minimal differences in responses between those receiving low-volume versus high-volume (4 L) preparations.

Conclusion:

Bowel preparation remains the worst part of the colonoscopy experience for patients, and the most likely deterrent to future colonoscopy.