bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PR007: A single cysteine in PAX3-FOXO1 is relevant for transactivation and survival of rhabdomyosarcoma cells
Authors: Schäfer Beat W. , Benischke Katharina , Wurth Jakob , Laubscher Dominik , Ngo Quy A. , Danielli Sara , Wachtel Marco
Published: September 2022

The fusion transcription factor PAX3-FOXO1 (P3F) is the major driver of alveolar rhabdomyosarcoma. Since these tumors are characterized by a mostly quiet mutational landscape and a paucity of druggable oncogenes, the fusion protein itself remains the most important drug target. Transcription factors are challenging proteins for drug development since they lack enzymatic activities and are, apart from DNA binding domains, largely intrinsically disordered. Identification of defined and possibly druggable structures in such proteins is therefore of great clinical interest. Towards this aim, we performed a CRISPR/Cas9-based domain screen in P3F-positive rhabdomyosarcoma cells and identified a small, structured and highly important domain within the transactivation domain of P3F. Further, we demonstrate that cysteine C793 located in this region is indispensable for target gene activation by P3F. Its mutation significantly reduced cell proliferation and induced differentiation of RMS cells. Mechanistically, we identified p300/CBP proteins as important co-factors and interactors of C793 that co-regulate a majority of P3F target genes. Their inhibition/degradation by small molecules efficiently reduces rhabdomyosarcoma cell survival. These data suggest that mainly one single amino acid drives oncogenicity of P3F and identify a potentially targetable structure within the fusion protein.

Citation Format: Beat W. Schäfer, Katharina Benischke, Jakob Wurth, Dominik Laubscher, Quy A. Ngo, Sara Danielli, Marco Wachtel. A single cysteine in PAX3-FOXO1 is relevant for transactivation and survival of rhabdomyosarcoma cells [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr PR007.
Abstract PR011: Characterization of the precancerous and cancer microenvironment in a zebrafish sarcoma model
Authors: Shive Heather R. , House John S. , Ferguson Jordan L. , Jima Dereje D. , Selmek Aubrie A. , Lloyd Dillon T.
Published: September 2022

Contributions of the microenvironment to soft tissue sarcoma progression are relatively undefined, representing a major impediment to identifying essential regulatory networks in sarcomagenesis. Furthermore, genetic and molecular characteristics that distinguish precancerous versus cancerous microenvironments are not well known across human cancer types. While animal models have the potential to reveal these complex processes, significant impediments to such inquiries include (1) the difficulty in distinguishing microenvironmental cells from precancerous or cancer cells in tissue specimens; and (2) the challenge in defining a discrete tissue with known cancer predilection that represents a precancerous microenvironment. We developed a unique zebrafish model that allows segregation of microenvironmental, precancerous, and cancerous cell populations by fluorescence-activated cell sorting. This model exhibits high predilection for malignant peripheral nerve sheath tumor (MPNST), a type of soft tissue sarcoma with a particularly poor prognosis due to aggressive growth, limited response to conventional treatment, and ineffective targeted therapy options. Using RNA-seq, we profiled the transcriptomes of microenvironmental cells from our zebrafish MPNST model and determined that the precancerous and cancerous microenvironments exhibit broad activation of inflammatory and immune-associated signaling networks. Markers for both M1 and M2 macrophage polarization were upregulated in precancerous and cancerous microenvironments, suggesting the presence of a mixed macrophage population during sarcomagenesis. Patterns of ligand and receptor expression based on a previously defined human ligand-receptor network identified significant upregulation of multiple tumor-promoting ligands in both precancerous and cancerous microenvironments. We also identified specific ligand-receptor pairs that may mediate key signaling events during sarcoma initiation and progression. Together this work provide new insight into distinguishing characteristics of the cancer-prone cellular microenvironment that may promote MPNST initiation and progression in vertebrates.

Citation Format: Heather R. Shive, John S. House, Jordan L. Ferguson, Dereje D. Jima, Aubrie A. Selmek, Dillon T. Lloyd. Characterization of the precancerous and cancer microenvironment in a zebrafish sarcoma model [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr PR011.
Clinical Predictor of Urinary Protein as Adverse Event Associated with Atezolizumab plus Bevacizumab Treatment for Unresectable Hepatocellular Carcinoma
Authors: Hiraoka Atsushi , Kumada Takashi , Tada Toshifumi , Hirooka Masashi , Kariyama Kazuya , Tani Joji , Atsukawa Masanori , Takaguchi Koichi , Itobayashi Ei , Fukunishi Shinya , Tsuji Kunihiko , Ishikawa Toru , Tajiri Kazuto , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Ogawa Chikara , Nishimura Takashi , Hatanaka Takeshi , Kakizaki Satoru , Shimada Noritomo , Kawata Kazuhito , Naganuma Atsushi , Kosaka Hisashi , Ohama Hideko , Tada Fujimasa , Nouso Kazuhiro , Morishita Asahiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Okubo Tomomi , Arai Taeang , Imai Michitaka , Koizumi Yohei , Nakamura Shinichiro , Iijima Hiroko , Kaibori Masaki , Hiasa Yoichi , Kudo Masatoshi ,   On behalf of the Real-life Practice Experts for HCC (RELPEC) Study Group,   HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)
Published: September 2022

Introduction: Adverse events (AEs) of urinary protein from monoclonal antibodies against vascular endothelial growth factor are factors that often inhibit systemic therapy for unresectable hepatocellular carcinoma (uHCC). This study aimed to elucidate risk factors of urinary protein in the early period (<12 weeks) of atezolizumab plus bevacizumab treatment (Atez/Bev). Methods: From 2020 to June 2022, 193 uHCC patients treated with Atez/Bev at our affiliated hospitals were enrolled (median 73 years, 158 males, 183 Child-Pugh A, BCLC-0:A:B:C = 1:7:73:112). AEs related to urinary protein (≥G2) within 12 weeks were defined as significant, and related clinical features were analyzed retrospectively. Results: In analyses of risk factors of urinary protein-related AEs during the first 12 weeks after starting Atez/Bev using a logistic regression method, univariate analysis showed positive for hypertension (odds ratio [OR] 3.54, 95% CI: 1.28–9.80, p = 0.015) and baseline urinary protein and urine creatinine ratio (UPC: ≥0.16) (OR: 2.52, 95% CI: 1.09–5.83, p = 0.031) as pretreatment clinical factors, while elevation of urinary protein in the early period (baseline to 3 weeks) with delta UPC per 3 weeks (ΔUPC/3W) (≥0.23) (OR: 15.80, 95% CI: 6.15–40.50, p < 0.001) was a clinical factor after starting treatment. Multivariate analysis of only baseline clinical factors revealed positive for history of hypertension as the only predictive factor (OR: 3.20, 95% CI: 1.14–8.95, p = 0.027), while only ΔUPC/3W (≥0.23) (OR: 14.40, 95% CI: 4.91–42.00, p < 0.001) were noted in multivariate analysis including ΔUPC/3W. Predictive factors for ΔUPC/3W (≥0.23) were hypertension (OR: 3.50, 95% CI: 1.23–99.90, p = 0.019) and UPC (≥0.16) (OR: 6.12, 95% CI: 2.61–14.30, p < 0.001) in multiple analysis. Discussion/Conclusion: Urinary protein-related AEs are frequently observed during Atez/Bev treatment in uHCC patients with elevated ΔUPC/3W (≥0.23), and ΔUPC/3W (≥0.23) is often seen in patients with hypertension and/or UPC (≥0.16).
Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer
Authors: Ando Takayuki , Hosokawa Ayumu , Sakumura Miho , Motoo Iori , Kajiura Shinya , Hirano Katsuhisa , Miwa Takeshi , Yokota Tomotaka , Nakada Naokatsu , Ueda Yuko , Ueda Akira , Tsukada Kenichiro , Ogawa Kohei , Nakaya Atsuko , Teramoto Akira , Nanjo Sohachi , Mihara Hiroshi , Fujinami Haruka , Fujii Tsutomu , Yasuda Ichiro
Published: September 2022

Introduction: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. Methods: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. Results: The overall survival (OS) was 16.8 months (95% CI: 14.0–19.6) and 9.3 months (95% CI: 7.8–11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15–3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23–3.22), low albumin concentration (OR 2.24; 95% CI: 1.14–4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05–3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6–27.9), respectively. Conclusions: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.
PROX1 Was Associated with LGR5 and Wnt Signaling and Contributed to Poor Prognosis in Gastric Cancer
Authors: Nakazawa Nobuhiro , Sohda Makoto , Ide Munenori , Shimoda Yuki , Tateno Kohei , Watanabe Takayoshi , Sano Akihiko , Sakai Makoto , Yokobori Takehiko , Ogawa Hiroomi , Oyama Tetsunari , Shirabe Ken , Saeki Hiroshi
Published: September 2022

Introduction: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/β-catenin activity in GC. Methods: A total of 196 patients who underwent potentially curative surgery were collected and reviewed retrospectively. Immunohistochemistry was conducted and evaluated the expression PROX1, LGR5, Wnt3a, and β-catenin expression. And we evaluated the relationship between PROX1 expression and clinicopathological features. Results: The PROX1 low-expression group consisted of 105 patients (53.6%) and the high-expression group consisted of 91 patients (46.4%). For LGR5 expression, 76 patients (38.8%) were classified as low-expression, and 120 patients (61.2%) were classified as high-expression. The PROX1 low-expression group was significantly younger (p = 0.0095), had more intestinal type (p = 0.014), and had smaller tumor size (p = 0.013). The PROX1 high-expression group was significantly correlated with high LGR5 expression (p < 0.0001) and high Wnt3a expression (p = 0.012). In addition, there were significantly more cases of postoperative recurrence in the PROX1 high-expression group (p = 0.013). Conclusion: Our findings demonstrate that PROX1 correlated with the cancer stemness markers LGR5 and Wnt3a signaling in GC and had a poor prognosis including postoperative recurrence.
Revisiting the Evidence for Routine Transcervical Thymectomy for the Prevention of Thymic Carcinoid Tumours in MEN-1 Patients
Authors: De Jong Mechteld Christine , Parameswaran Rajeev
Published: September 2022

Background: Malignant thymic carcinoids are uncommon tumours among patients with multiple endocrine neoplasia type 1 (MEN-1). Current guidelines advise performance of a preventative, routine transcervical thymectomy (TCT) during parathyroidectomy, although data on the yield is scarce. In this review, we aimed to revisit available literature to investigate and summarize the efficacy of routine TCT for the prevention of thymic carcinoid tumours among MEN-1 patients after searching four databases (PubMed, Embase, Medline, and Cochrane Library). Summary: Seven eligible studies were identified: retrospective observational studies: 3 and case reports describing one or more patients: 4. A total of 122 patients were included, 56 males (45.9%) and a pooled mean age of 40 years (±10). All underwent a routine TCT as part of parathyroidectomy; no details on the extent of TCT were available. Overall, only one (0.9%) incidental carcinoid was found. However, although all other patients underwent prophylactic TCT at the time of parathyroidectomy, an additional nine (7.4%) developed a thymic carcinoid during follow-up, after a median time of 36 months (range: 8–226). Key Messages: There is currently not enough evidence to support the efficacy of a routine TCT to prevent the development of thymic carcinoid among MEN-1 patients. As this is a rare but potentially highly aggressive tumour, attention should be shifted towards improving follow-up programs and developing specific imaging-screening protocols. This enables early detection of thymic carcinoids in a timely manner and improves outcomes, even after performance of a routine TCT.
Efficacy of Su Jok Seed Therapy in Migraine: A Randomized Placebo-Controlled Study
Authors: Kahraman Aysegul , Cevik Akyil Rahsan
Published: September 2022

Introduction: Migraine is an important health problem that negatively affects individuals’ activities of daily living. The decrease in the quality of life because of migraine increases the need for the development of new pharmacological and nonpharmacological treatment methods for pain management. Limited studies have reported the application of a traditional therapy, such as Su Jok seed therapy, to prevent or minimize migraine. This study aimed to examine the effect of Su Jok seed therapy on the severity, duration, and frequency of headaches in patients with migraine. Methods: The study was conducted between September 2020 and February 2021 with 47 students diagnosed with migraine. Of these, 24 patients were included in the intervention group and 23 in the placebo control group. Data were collected using a patient information form developed by the researchers, a migraine diary, the Numeric Pain Rating Scale (NPRS), and the Headache Impact Test-6 (HIT-6) questionnaire. Each patient in the intervention and placebo groups received eight sessions of Su Jok seed therapy, twice a week for 4 weeks. Data were evaluated at the 30th, 60th, and 120th min of the therapy using NPRS, before the therapy (pretest), after the therapy (posttest), and 4 weeks after the therapy (follow-up) using a migraine diary and the HIT-6 questionnaire. Results: Descriptive statistics (mean, standard deviation/standard error, and percentages) were used for data analysis. Student’s t, Mann-Whitney U, repeated-measures analysis of variance, Bonferroni, Friedman, Dunn-Bonferroni, and χ2 tests were used in this study. Significance was set at p < 0.05. After the administration of Su Jok seed therapy, the difference in mean NPRS scores between the groups was significant (p < 0.05) from the 60th min of the administration. Furthermore, a significant decrease was observed in the severity, duration, and frequency of headaches; the HIT-6 questionnaire scores; and the amount of painkillers consumed by the patients in the intervention group after the therapy and in the follow-up period compared with the pretest data. Additionally, the level of satisfaction of the patients in the intervention group was significantly higher after the therapy than that of those in the placebo group. Conclusion: Su Jok seed therapy reduced the severity, duration, and frequency of migraines, which in turn reduced the amount of painkillers consumed and the HIT-6 scores of patients with migraines.
The Glasgow Prognostic Score Predicts Outcomes of Pembrolizumab or Atezolizumab Monotherapy in Patients with Pretreated Non-Small Cell Lung Cancer
Authors: Kasajima Masashi , Igawa Satoshi , Manaka Hiroya , Yamada Kaori , Akazawa Yuki , Manabe Hideaki , Yagami Yuri , Yamamoto Hiroki , Ito Hiroki , Kaizuka Nobuki , Nakahara Yoshiro , Sato Takashi , Mitshufuji Hisashi , Yokoba Masanori , Kubota Masaru , Sasaki Jiichiro , Naoki Katsuhiko
Published: September 2022

Introduction: Predictors of the effectiveness of immune checkpoint inhibitor (ICI) monotherapy in previously treated patients with non-small cell lung cancer (NSCLC) remain ill-defined. We investigated whether the Glasgow prognostic score (GPS) could serve as such predictors. Methods: Eighty patients treated with pembrolizumab or atezolizumab monotherapy as second- or subsequent-line therapy for NSCLC were retrospectively reviewed, and the associations between GPS, body mass index (BMI), and each of progression-free survival (PFS) and overall survival (OS) were assessed. Results: The median follow-up period was 11.1 months. Patients with a BMI ≥20.4 kg/m2 had significantly longer PFS and OS (3.7 and 22.2 month, respectively) than did those with a BMI <20.4 kg/m2 (2.2 and 11.5 months, respectively). Patients with a GPS of 0 had a significantly longer PFS (6.6 months) than did those with a GPS of 1 (2.2 months, p = 0.002) and 2 (1.8 months, p = 0.029). Patients with a GPS of 0 also had a significantly longer OS (22.2 month) than did those with a GPS of 1 (9.2 months, p = 0.002) and 2 (4.7 months, p = 0.002). Notably, the GPS, BMI, and clinical stage were independent predictors of PFS, while the GPS and performance status were independent predictors of OS. The response rate of patients with a GPS of 0 was significantly higher than that of patients with a GPS of 1–2 (26.2% vs. 7.9%, p = 0.03). Conclusion: The GPS is an independent predictor of PFS and OS in patients with NSCLC who received second- or subsequent-line pembrolizumab or atezolizumab monotherapy.
SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution
Authors: Drozd-Sokołowska Joanna , Mądry Krzysztof , Barankiewicz Joanna , Kobylińska Katarzyna , Biecek Przemysław , Rytel Jagoda , Karakulska-Prystupiuk Ewa , Skwierawska Kamila , Salomon-Perzyński Aleksander , Stokłosa Tomasz , Basak Grzegorz Władysław
Published: September 2022

Introduction: Venetoclax combined with azacitidine (AZA-VEN) constitutes an option for the treatment of acute myeloid leukemia. There are, however, no data on the COVID-19 incidence and outcome in patients treated with AZA-VEN. Methods: Patients with acute leukemia treated with AZA-VEN at a single institution were included in this prospective observational study. Results: Thirteen patients were enrolled, 46% with treatment-naïve, and 56% with relapsed/refractory disease. Fifty-four percent of patients were males; the median age was 69 years. Six patients (46%) developed COVID-19 during the observation time. The median time to COVID-19 was 24 days from the initiation of AZA-VEN. The 2-month cumulative incidence of COVID-19 was 46.2%. Two patients (33%) succumbed to COVID-19. The 100-day COVID-19-free survival from AZA-VEN initiation was 61%. The median follow-up time was 4.3 months. Discussion/Conclusion: COVID-19 constitutes a frequent complication of AZA-VEN treatment in the era of the COVID-19 pandemic, leading to death in a significant proportion of patients.
Altered Expression of Pulmonary Epithelial Cell Markers in Fetal and Adult Mice Generated by in vitro Embryo Culture and Embryo Transfer
Authors: Doğan Göksel , Öztürk Murat , Karakulak Didar Tuğçe , Karagenç Levent
Published: September 2022

Lung development is impaired in mice generated through transfer of in vitro-derived blastocysts. The main objective of the current study was to determine if the composition of epithelial cells in the fetal and adult lung tissue is altered in mice generated through transfer of in vitro-derived blastocysts. The study comprised two experimental (EGs) and two control (CGs) groups. Fetuses (18.5 d.p.c.) and adult mice (8 weeks old) of the EGs (EGfetus, n = 18; EGadult, n = 15) were produced by the transfer of day 5 F2 blastocysts to pseudo-pregnant females. F2 fetuses and adult mice derived from naturally ovulating females served as the CGs (CGfetus, n = 18; CGadult, n = 15). The expression of Tuba-1a (a marker of ciliated cells), Foxj-1 (a marker of motile ciliated cells), Uch-L1 (a marker of neuroendocrine cells), Cldn-10 (a marker of club cells), Aqp-5 (a marker of type I alveolar cells), and Sp-C (a marker of type II alveolar cells) was determined using Western blot, immunohistochemistry/immunofluorescence, and quantitative RT-PCR analyses. Weight of fetuses as well as adult mice is decreased in mice comprising the EGs. Impaired lung development observed in EGfetus was associated with altered expression of Tuba-1a, Foxj-1, Cldn-10, Uch-L1, Sp-C, and Aqp-5. Morphology of the adult lung tissue was similar between the groups except for a significant increase in the thickness of the epithelia in EGadult. The expression of Cldn-10 and Sp-C was also altered in EGadult. It remains to be determined whether altered expression of these genes has any long-term impact on epithelial cell functions in the adult lung tissue.
Time‐Dependent Risk of Cardiovascular Events Following an Exacerbation in Patients With Chronic Obstructive Pulmonary Disease: Post Hoc Analysis From the IMPACT Trial
Authors: Dransfield Mark T. , Criner Gerard J. , Halpin David M. G. , Han MeiLan K. , Hartley Benjamin , Kalhan Ravi , Lange Peter , Lipson David A. , Martinez Fernando J. , Midwinter Dawn , Singh Dave , Wise Robert , Kunisaki Ken M.
Published: September 2022

Background

The association between chronic obstructive pulmonary disease exacerbations and increased cardiovascular event risk has not been adequately studied in a heterogenous population with both low and high cardiovascular risk.

Methods and Results

This post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (N=10 355 symptomatic patients with chronic obstructive pulmonary disease at risk of exacerbations) evaluated time‐dependent risk of cardiovascular adverse events of special interest (CVAESI) following exacerbations and impact of exacerbation history, cardiovascular risk factors, and study treatment on this association. Risk (time‐to‐first) of CVAESI or CVAESI resulting in hospitalization or death was assessed during and 1 to 30, 31 to 90, and 91 to 365 days after resolution of moderate or severe exacerbations. CVAESI risk was compared between the period before and during/after exacerbation. CVAESI risk increased significantly during a moderate (hazard ratio [HR], 2.63 [95% CI, 2.08–3.32]) or severe (HR, 21.84 [95% CI, 17.71–26.93]) exacerbation and remained elevated for 30 days following an exacerbation (moderate: HR, 1.63 [95% CI, 1.28–2.08]; severe: HR, 1.75 [95% CI, 0.99–3.11; nonsignificant]) and decreased over time, returning to baseline by 90 days. Risk of CVAESI resulting in hospitalization or death also increased during an exacerbation (moderate: HR, 2.46 [95% CI, 1.53–3.97]; severe: HR, 41.29 [95% CI, 30.43–56.03]) and decreased in a similar time‐dependent pattern. Results were consistent regardless of exacerbation history, cardiovascular risk at screening, or study treatment.

Conclusions

Overall risk of cardiovascular events was higher during and in the 30 days following chronic obstructive pulmonary disease exacerbations, even among those with low cardiovascular risk, highlighting the need for exacerbation prevention and vigilance for cardiovascular events following exacerbations.

Registration

URL:
https://clinicaltrials.gov/ct2/show/NCT02164513
; Unique identifier: NCT02164513
Contemporary National Patterns of Eligibility and Use of Novel Lipid‐Lowering Therapies in the United States
Authors: Shen Miles , Aghajani Nargesi Arash , Nasir Khurram , Bhatt Deepak L. , Khera Rohan
Published: September 2022

Background

The emergence of PCSK9i (proprotein convertase subtilisin kexin type 9 inhibitor) and icosapent ethyl (IPE) has expanded the role of lipid‐lowering therapies beyond statins. Despite recommendations by clinical practice guidelines, their national eligibility and use rates remain unclear.

Methods and Results

In the National Health and Nutrition Examination Survey data from 2017 to 2020, we assessed eligibility and the use of statins, PCSK9i, and IPE among US adults according to American College of Cardiology/American Heart Association guideline recommendations. Eligibility for PCSK9i and IPE were determined in the following 2 scenarios: (1) assuming existing lipid‐lowering therapy as the maximum tolerated before assessing eligibility for novel therapies and (2) assessing eligibility after assuming initiation and maximal escalation of preexisting lipid‐lowering therapies and accounting for expected lipid improvements. Of 2729 sampled individuals, representing 149.3 million adults, 1376 had indications for statins, representing 65.8 million or 44.0% (95% CI, 40.9%–47.2%) of adults. Current statin use was 45% of those eligible and was low across demographic groups. A total of 9.7 and 11.6 million adults would benefit from PCSK9i and IPE, respectively, based on lipid profiles and existing therapies. Assuming maximal escalation of statins and addition of ezetimibe, 4.1% (95% CI, 2.8%–5.4%) of adults or 6.1 million would benefit from PCSK9i and 6.8% (95% CI, 5.4%–8.3%) or 10.2 million from IPE.

Conclusions

Six and 10 million individuals have clinical profiles whereby PCSK9i and IPE, respectively, would be expected to improve cardiovascular outcomes even after maximum escalation of statins and ezetimibe use, but remain undertreated with lipid‐lowering therapies. Optimal use of lipid‐targeted agents that include these novel agents is needed to improve population health outcomes.
Health Care Usage Among Adolescents With Congenital Heart Defects at 5 Sites in the United States, 2011 to 2013
Authors: Lui George K. , Sommerhalter Kristin , Xi Yizhao , Botto Lorenzo D. , Crume Tessa , Farr Sherry , Feldkamp Marcia L. , Glidewell Jill , Hsu Daphne , Khanna Amber , Krikov Sergey , Li Jennifer , Raskind‐Hood Cheryl , Sarno Lauren , Van Zutphen Alissa R. , Zaidi Ali , Soim Aida , Book Wendy M.
Published: September 2022

Background

We sought to characterize health care usage for adolescents with congenital heart defects (CHDs) using population‐based multisite surveillance data.

Methods and Results

Adolescents aged 11 to 18 years with ≥1 CHD‐related diagnosis code and residing in 5 US sites were identified in clinical and administrative data sources for the years 2011 to 2013. Sites linked data on all inpatient, emergency department (ED), and outpatient visits. Multivariable log‐binomial regression models including age, sex, unweighted Charlson comorbidity index, CHD severity, cardiology visits, and insurance status, were used to identify associations with inpatient, ED, and outpatient visits. Of 9626 eligible adolescents, 26.4% (n=2543) had severe CHDs and 21.4% had Charlson comorbidity index >0. At least 1 inpatient, ED, or outpatient visit was reported for 21%, 25%, and 96% of cases, respectively. Cardiology visits, cardiac imaging, cardiac procedures, and vascular procedures were reported for 38%, 73%, 10%, and 5% of cases, respectively. Inpatient, ED, and outpatient visits were consistently higher for adolescents with severe CHDs compared with nonsevere CHDs. Adolescents with severe and nonsevere CHDs had higher health care usage compared with the 2011 to 2013 general adolescent US population. Adolescents with severe CHDs versus nonsevere CHDs were twice as likely to have at least 1 inpatient visit when Charlson comorbidity index was low (Charlson comorbidity index =0). Adolescents with CHDs and public insurance, compared with private insurance, were more likely to have inpatient (adjusted prevalence ratio, 1.5 [95% CI, 1.3–1.7]) and ED (adjusted prevalence ratio, 1.6 [95% CI, 1.4–1.7]) visits.

Conclusions

High resource usage by adolescents with CHDs indicates a substantial burden of disease, especially with public insurance, severe CHDs, and more comorbidities.
The Impact of Therapy Dogs on Graduate-Level, Military-Affiliated Students
Authors: Stutey Diane M. , Solis Abigail E. , Notestine Lori , Wehrman Joseph
Published: September 2022

Dogs have been companions on college campuses and with military personnel in a variety of therapeutic ways. Although research has been con-ducted regarding college students’ perceptions of therapy dog programs, research specifically examining military-affiliated students’ experiences with therapy dogs is limited. In this study, a therapy dog, registered with Alliance of Therapy Dogs (ATD), was introduced into a classroom with military-affiliated students over the course of one semester. All participants were Field-Grade Officers in a branch of the United States Military and were also recent graduates of a Department of Defense-approved (DOD) Civilian Institution (CI) graduate educational program. Participants shared that the presence of a therapy dog in the classroom positively impacted their mental health and wellbeing. Four themes emerged from the individual and group interviews with participants: Relational Connections, Emotional and Social Support, Positive Change in Climate, and Basic Needs.
High risk of predation suppresses behavioural differences among bold and shy social prey individuals
Authors: Balaban-Feld Jesse , Vijayan Sundararaj , Mitchell William A. , Kotler Burt P. , Badichi Shamir , Abramsky Zvika
Published: September 2022

Prey animals must attempt to optimize foraging success while reducing the probability of being captured. Within social prey groups, intrinsic differences in bold-shy personality among individuals influence their respective risk-taking tendencies. We examined the foraging and refuge use behaviour of mixed groups of goldfish (Carassius auratus) containing half bold individuals and half shy individuals under variable levels of predation risk from a live avian predator (Egretta garzetta). At the group level, the fish groups significantly decreased their foraging time by spending more time under the refuge when the predator spent more time at the focal pool. As expected, the bold fish tended to be the first to leave the refuge, and foraged outside the refuge more often than shy fish under control conditions and at lower risk levels. However, the behavioural differences between bold and shy fish disappeared under higher risk conditions. In terms of mortality, the predator captured significantly more bold fish than shy fish. Our study illustrates how bold individuals in social groups often take greater risks to achieve foraging success, but demonstrates that innate differences in boldness can be diminished in times of elevated predation risk.
An exploratory study of cooperation: food-sharing behaviour in wild varied white-fronted capuchin monkeys (Cebus versicolor) in Central Colombia
Authors: De Aquino Itzel , González-Santoyo Isaac , Link Andres , Muñoz-Delgado Jairo
Published: September 2022

Food-sharing is a cooperative behaviour related to the transfer of resources between conspecifics, and it is considered a complex prosocial behaviour because of its associated costs. It is more likely that an individual cooperates with closely related kin (e.g., in food sharing), and particularly with close maternal kin. In female philopatric species, such as Cebus spp., mother–offspring bonds likely explain patterns of maternal kin biases. On the other hand, the explanation of the evolution of food-sharing among non-kin is diverse. Capuchin monkeys (genera Cebus and Sapajus) are interesting to study cooperation since this is a critical behaviour to gain and protect ecological and reproductive resources in the wild, including care of their offspring. We performed an experimental protocol to induce behavioural observations with a provisioning technique using chicken eggs in a wild group of white-faced capuchin monkeys (Cebus versicolor). We aimed to test whether this white-faced capuchin monkeys engaged in food-sharing in the wild, describing the pattern of this cooperative behaviour. Furthermore, we also described some conditions that might affect this behaviour. We observed that these capuchins shared the eggs in passive exchanges, meaning that possessors let other individuals to eat from their egg. Our results further suggest that these exchanges may be due to mainly maternal kin biases. This study offers a preliminary observation of a little-studied capuchin species in the wild and adds information about how cooperation works in the wild.
Jihad o rivoluzione? Percorsi martirologici ed escatologia politica nell’Islam cinese
Authors: Previato Tommaso
Published: September 2022

Messianic Islam and socialism are often contrasted as either fighting each other or joining their forces against colonialism. If in late imperial China the Islamic legal duty of jihād (lit. struggle) was a byproduct of anti-dynastic uprisings by means of which reformist movements—linked to alienated offshoots of Naqshbandiyya Sufism—sought to legitimate religiously-based violence against the Qing state, during the country’s transition toward a republican system of government such duty became aligned with the state-driven program of nation-building and Chinese-distinctive brand of socialism. By so doing, the jihad added momentum to the Xinhai Revolution initiated by Sun Yat-sen, and its military ideology amalgamated with Sun’s political philosophy which was eventually remoulded by Muslim progressive circles within the Kuomintang or close to Mao Tse-tung’s Red Army and the soviet-style regime installed in Yan’an. Based on the analysis of hagiographical materials and periodicals of the first half of the 20th century, the paper sheds light on this critical juncture in the history of modern China that saw statesmen, revolutionary leaders, and religious élites validate jihad and discourses of pan-Islamic solidarity in a combined effort to boost national unity among ethnic minorities and armed resistance to foreign aggression.
Ontogenetic instars of Elliptochthonius profundus Norton, 1975 (Acari, Oribatida, Elliptochthoniidae), with remarks on juveniles of the superfamily Parhypochthonioidea
Authors: ERMILOV SERGEY G. , BAYARTOGTOKH BADAMDORJ
Published: September 2022

The morphology of juvenile instars of the mite Elliptochthonius profundus Norton, 1975 (Oribatida, Elliptochthoniidae) is studied. Comparative characteristics of juveniles of the representative genera in the superfamily Parhypochthonioidea is given based on our own data and available literature sources, and the major characteristics of larvae and nymphs are presented. It can be summarized that the juveniles of parhypochthonioides have the following character states: body trichoid, i.e., the postpedal scissure of gastronotum is clearly developed; body colour whitish or pale yellowish, lacking the strong cuticular sclerotization, where the flesh cuticle is sparsely foveolate or weakly microtuberculate; the juveniles of the different genera are generally similar, but differ from one another in the shape of bothridial seta, number of gastronotic setae, setations of gnathosomal, anogenital and epimeral regions and legs, development of the genital and aggenital plates and peranal segment.
Barred: Labor Market Dynamics and Human Capital Development among People on Probation and Parole
Authors: Sykes Bryan L. , Ballard Meghan , Kaiser Daniela , Mata Vicente Celestino , Sharry J. Amanda , Sola Justin
Published: September 2022

Obtaining employment is a major barrier to social reintegration for people on probation or parole. Research on the reentry process identifies several mechanisms that accentuate difficulties in locating work, including human capital development, structural changes in the labor market, and onerous probation and parole conditions. In this article, we review theories that explain low labor market participation rates among people reentering society, and we draw on multiple sources of data to identify the types of jobs that are available to people with low human capital. We find that nearly a quarter of people in America’s state and federal prisons had permanently removed themselves from the formal labor market before their most recent arrest; however, exclusionary hiring practices in the formal labor market often push those carrying the stigma of a criminal record into underground or informal labor markets, where wage rates are markedly higher than the federal minimum wage. Our findings demonstrate that severe and chronic employment struggles often predate and follow incarceration. We provide a detailed discussion of policy reform proposals that could help to remedy this harmful dynamic.
From Prison to Entrepreneurship: Can Entrepreneurship be a Reentry Strategy for Justice-Impacted Individuals?
Authors: Hwang Kylie Jiwon
Published: September 2022

Justice-impacted people face significant obstacles to employment. This article explores an alternative pathway for these individuals to find work and income: entrepreneurship. While anecdotal evidence suggests that entrepreneurship is common among people with criminal histories, it remains both theoretically and empirically underexamined. I conduct a synthesis of recent research to assess the viability of entrepreneurship as a path to reintegration for returning citizens. I highlight findings on the prevalence of entrepreneurial entry, the underlying mechanism behind entrepreneurship, the economic and social consequences of entrepreneurship, and the barriers and challenges that reentering entrepreneurs face. Finally, I draw attention to key policy implications and suggest new initiatives that can help enhance the viability of entrepreneurship as a reentry strategy for justice-involved individuals.
Financial and Inpatient Burden of Adhesion-Related Small Bowel Obstruction: A Systematic Review of the Literature
Authors: Garoufalia Zoe , Gefen Rachel , Emile Sameh Hany , Zhou Peige , Silva-Alvarenga Emanuela , Wexner Steven D.
Published: September 2022

Background

Postoperative adhesions may occur after >90% of laparotomies and is the most common cause of small bowel obstruction (SBO). Despite the high incidence, there is a lack of data related to financial implications of adhesion-related SBO (ASBO). This systematic literature review of in-hospital costs for treatment of ASBO searched PubMed, Scopus and Google Scholar databases according to PRISMA guidelines. Exclusion criteria were reviews, editorials, clinical vignettes, studies of patients <18 years of age, studies with no English full text and studies assessing adhesiolysis for causes other than SBO or that used extrapolations with economic models. Main outcome measures were financial costs per patient and national costs.

Results

Seven studies, published between 1999 and 2016, incorporating a total of 39 573 patients, were identified. Four were undertaken in European countries, one in the USA, 1 in New Zealand and 1 in Nigeria. Overall national costs regarding treatment of patients with ASBO ranged between $3.468 million and $1.77 billion. Median overall cost in the medical management group was $2371.5 ($1814-$2568) vs $12370 ($4914-$25321) in the surgical group. Median length of stay was 4 (3-7) days for patients conservatively treated and 11.5 (8-16.3) days for patients who underwent surgery. Median length of stay of operated patients on was almost triple that of patients conservatively managed.

Conclusions

Given the major financial implications of ASBO, further initiatives are needed to avoid operations for SBO when clinically appropriate and minimize delays taking patients with high suspicion of complete SBO to the operating room.
The Clinical Value of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy Score in Predicting Long-Term Major Adverse Cardiovascular And Cerebrovascular Events and Major Bleeding in Acute Coronary Syndrome Patients Who Underwent Percutaneous Coronary Intervention
Authors: Celik Aykan , Esin Fatma Kayaltı , Emren Sadık Volkan , Kiris Tuncay , Karaca Mustafa
Published: September 2022

The PRECISE-DAPT (predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy) score is recommended for predicting out-of-hospital bleeding after percutaneous coronary intervention (PCI). However, its long-term prediction remains unclear. We investigated the performance of this score in predicting long-term outcomes in patients with the acute coronary syndrome (ACS). We divided retrospectively enrolled patients (n = 1071) into two groups according to their PRECISE-DAPT scores: low < 25 and high ≥ 25. Bleeding was assessed using the Bleeding Academic Research Consortium criteria. The ischemic endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events (MACCE). During follow-up (median 7.3 years), MACCE (55 vs 35%, P<.001) and major bleeding (9 vs 4%, P = .002) rates were greater in the high score group. The PRECISE-DAPT score was an independent predictor of MACCE in multivariate analysis (Hazard ratio [HR]: 1.028, 95% confidence interval [CI]: 1.016–1.039, P < .001). Also, the PRECISE-DAPT score predicted all-cause mortality (HR: 2.115, 95% CI: 1.508–2.965, P < .001) at long-term follow-up. The PRECISE-DAPT score may be useful for predicting MACCE at long-term follow-up in addition to the risk of bleeding.
Arytenoid Abduction: Indications and Limitations
Authors: Woodson Gayle
Published: September 2022

Objectives

I report further experience with arytenoid abduction (AAb), a procedure that enlarges the glottis by external rotation of the arytenoid cartilage and thus moves the vocal process laterally and rostrally, but does not preclude adduction for phonation. Therefore, AAb has the potential to preserve voice in patients with bilateral abductor laryngeal paralysis.

Methods

I performed a retrospective review of AAb in 11 patients with bilateral laryngeal paralysis and 3 patients with other neurologic causes of glottal airway compromise, ie, adductor breathing dystonia, frequent laryngospasm, and progressive laryngeal breathing dysfunction.

Results

Seven of the 11 patients with bilateral paralysis had dramatic airway improvement. One patient required a tracheotomy after AAb, and 3 patients with an existing tracheotomy could not be decannulated. Arytenoid abduction relieved airway obstruction in the patient with recurrent laryngospasm and in the child with progressive laryngeal breathing dysfunction, but the patient with adductor breathing dystonia has persistent stridor. The factors associated with a poor airway outcome included prolonged tracheotomy, electromyographic evidence of inspiratory activity of adductor muscles, chronic obstructive pulmonary disease, sleep apnea, and prior cordotomy or arytenoidectomy.

Conclusions

Arytenoid abduction is most effective in patients with bilateral laryngeal paralysis of less than 1 year's duration who do not have unfavorable laryngeal adductor activity.
“It’s Not Easy, But It Needs to Be Done”: Educators’ Perceptions of Preparedness to Teach Students With Internalizing Mental Health Needs
Authors: Firestone Allison R. , Cruz Rebecca A.
Published: September 2022

This mixed methods study surveyed 209 K-12 special education teachers about their perceptions of preparedness to teach students with mental health needs that manifest internally (e.g., quiet distress, withdrawal, excessive worry). We used a construct-modeling approach to develop the survey instrument and establish evidence of validity, reliability, and fairness, and it included both multiple-choice questions, used for descriptive and regression analyses, and open-ended items, coded to identify key themes. Results indicated that special educators generally had low perceptions of preparedness to support students with internalizing needs. In addition, we found that participants possessed critical misconceptions about research-based practices for supporting students with these needs in the school context, and that differences in perceptions of preparedness were associated with teachers’ race and the grade level at which they taught.
The Near-Death Experience and Self-Determination Theory
Authors: King Robert A.
Published: September 2022

When people experience a near-death or life-threatening incident, they sometimes report an altered state of consciousness in which they have the perception of being out of or away from their physical body. During such an experience these individuals at times have the impression of encountering a spiritual personage who offers them a choice to stay or return to their physical life and/or attempts to motivate them to willingly do so, sometimes conflicting with a simultaneous desire to stay in that altered state of consciousness they perceive as the afterlife. This paper discusses how self-determination theory (SDT) is relevant to this process by meeting the experient’s three basic psychological needs for relatedness, competence, and autonomy, resulting in various degrees of effectiveness. It concludes with a postulation that by doing so it may foster a continuing intrinsic motivation to live life well, resulting in a greater overall condition of psychological wellbeing.
Conspiracy Illusion, Superstitions, and Death Anxiety of Older Adults Who Refused Covid-19 Vaccination in Iran: A Cross-Sectional Study on Their Beliefs
Authors: Jafarnezhad Dehmiani Mazaher , Fanisaberi Laleh , Asadollahi Abdolrahim , Bakht Abnoos Abedin , Abyad Abdulrazak
Published: September 2022

The study was aimed to assess mental health of the older adults who did not participate in the three stages of national vaccination program. As a descriptive-analytical study, about 285 Iranian older people were interviewed in 2022. Data collection tools included demographic characteristics, conspiracy scale, superstitious beliefs instrument, and Templer death anxiety. The convenience sampling method was used and data were analyzed using BIM-SPSS version 28. Death anxiety statistically effect on conspiratory and superstitions with scores 0.190 and 0.320 using adjusted Eta squared, respectively and superstitious beliefs effected 81% of conspiracy as well ( p = 0.001). Using ROC analysis, the cutoff points for conspiracy of men and women and final SEM model were extracted too. Interaction of conspiracy illusion, superstitions with death anxiety during the pandemic time among vulnerable groups i.e ageing community can shape a decision line in health policy making.
Rejection Sensitivity and Reactive Aggression in Early Adults: The Mediating Role of Loneliness and Maladaptive Coping
Authors: Du Xiaoli , Ding Cody , Xiang Guangcan , Li Qingqing , Liu Xinyuan , Xiao Mingyue , Song Shiqing , Chen Hong
Published: September 2022

Reactive aggression is an aggressive response to a perceived threat or provocation. It has detrimental effects on individuals and society. Rejection sensitivity, a disposition that one tends to anxiously expect, readily perceive, and intensely react to social rejection, has been associated with reactive aggression. Considering that the mechanism underlying this link remains unclear, this study explores the mediating role of loneliness and maladaptive coping. Participants included 1104 early adults between the ages of 17–23 ( Mage = 20.35, SD = 1.11, 33.6% men) in China who completed the Chinese version of the Tendency to Expect Rejection Scale, Loneliness Scale, Ways of Coping Questionnaire, and Reactive-Active Aggression Questionnaire. The serial mediation model revealed that loneliness and maladaptive coping independently mediated the association of rejection sensitivity with reactive aggression. More importantly, the chain mediating effect of “loneliness-maladaptive coping” also accounted for this link. The above findings contribute to a deeper understanding of the relationships among these factors and suggested that rejection sensitivity could positively be related to reactive aggression through loneliness and maladaptive coping.