bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-11-30: Breast cancer follow-up. Patients expectations versus reality
Authors: Zaluska-Kusz Joanna , Litwiniuk Maria
Published: March 2022

Background: Breast cancer is the most common malignancy among women. The increased incidence and better treatment results lead to an increased number of breast cancer survivors. Polish and international guidelines clearly specify the rules for the tests performed in the follow-up. The only mandatory test is annual mammography. Our aim was to evaluate patients expectations and knowledge regarding follow-up visits. Methods: 188 patients after breast cancer radical treatment completed anonymous questionnaires about their knowledge and preferences of the follow-ups. Results: Median age of the respondents was 64. Median time from the breast cancer diagnosis was 6 years (2-34). 82% of the patients claimed that they were informed by the oncologist about the rules of follow-up visits, 78% knew recommendations about healthy lifestyle and diet. At the same time - 78% would prefer to have more tests done than it’s recommended (abdominal ultrasound - 58 patients (31%), CA 15-3 level- 27 patients (14%), chest x-ray- 18 patients (10%), PET scan - 5 patients (3%), other tests (bone scyntygraphy, brain scan, liver MRI) - 13 patients (7%). Many patients would like to have multiple tests done. When asked if they would prefer to have follow-up visits with their family doctor or in the oncological centre - 94% would prefer to be controlled in the cancer centre. Conclusions: There is a need to educate both oncologists, family doctors and patients, about the rules of follow-up in breast cancer. Patients feel safer if they have more tests done, even though the guidelines recommend only annual mammography. Patients prefer to be controlled in the cancer centres, where they were treated. Because the recommendations were made many years ago, it seems advisable to conduct new studies on possible modifications to these guidelines, due to tremendous advances in breast cancer treatment and the fact that breast cancer is now divided into a numer od biological subtypes. There is a strong need to perform studies to evaluate the role of liquid biopsy, ctDNA and PET-scan in breast cancer follow-up.

Citation Format: Joanna Zaluska-Kusz, Maria Litwiniuk. Breast cancer follow-up. Patients expectations versus reality [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-30.
Abstract P5-01-10: A panel of murine mammary tumor cell lines to study immune responses to epitopes created by different mutagens including human APOBEC3 enzymes
Authors: Naumann Jordan , Carpenter Michael , Argyris Prokopios , Brown William , Harris Reuben
Published: March 2022

Background: Tumor mutation loads are a strong predictor of immunotherapy benefit. This is evidenced by studies on skin, lung, and colon cancer, where well-defined processes elicit high mutation burdens and checkpoint therapies often provoke strong anti-tumor immune responses. In comparison, only a small number of breast cancer patients have responded to checkpoint therapies such as anti-PD-L1 and anti-PD-1 monoclonal antibodies. Approximately one-fourth of primary breast cancer and one-third of metastatic tumors have a significant APOBEC mutation burden defined as C-to-T and C-to-G mutations in TCA or TCT trinucleotide motifs, and many tumors have >10,000 of these APOBEC signature single base substitution mutations. However, to our knowledge, systematic immunotherapy studies focusing on this unique, hypermutated subset of breast cancers have yet to be done. Methods: To address the potential relationship between different checkpoint therapies and APOBEC mutation burden, we created a panel of >30 mammary tumor cell lines derived from fully immune-proficient C57BL/6 animals. At least 6 of these cell lines are immortalized, readily engineered using standard molecular biology procedures, and capable of re-engraftment and tumor formation in immune proficient C57BL/6 animals. Two lines were engineered to inducibly express human APOBEC3A, subjected to 1- to 20-rounds of sublethal mutagenesis, and tested systematically for checkpoint therapy responsiveness. Results: Two cell lines were engineered to inducibly express APOBEC3A or a catalytic mutant (E72A). Clones were characterized for inducible APOBEC3A expression and associated DNA damage responses. After varying rounds of mutagenesis, clones were engrafted into the subcutaneous flank or mammary fat pad of C57BL/6 animals. Immunohistochemical and flow cytometry analysis revealed a robust intratumoral CD8 T cell population including a subset with PD-1 expression. Additionally, engrafted tumor cells expressed high levels PD-L1. Experiments are ongoing and immunotherapy responses will be presented. Conclusions: We have isolated a panel of C57BL/6 mammary tumor-derived cell lines and demonstrated re-engraftment into immunocompetent animals. These cell lines constitute a platform for studying the relationship between different mutagens including APOBEC and immunotherapy responses.

Citation Format: Jordan Naumann, Michael Carpenter, Prokopios Argyris, William Brown, Reuben Harris. A panel of murine mammary tumor cell lines to study immune responses to epitopes created by different mutagens including human APOBEC3 enzymes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-01-10.
Abstract P5-09-02: Tetrameric and monomeric gain-of-function mutant p53 interacts with chromatin
Authors: Annor George Kwakye
Published: March 2022

In 80% of triple-negative breast cancers (TNBC) the TP53 gene is mutated, with a high occurrence of missense changed in the DNA binding domain. These mutations lead to loss of wild-type p53 (wtp53) function and some also create mutant p53 (mtp53) proteins with novel gain-of-function (GOF) tumor-promoting capabilities. We previously reported that mtp53 R273H interacts with replication-associated proteins including MCM2-7 and poly ADP-ribose polymerase (PARP1). Moreover, mtp53 is found on actively replicating nascent DNA. What remains unclear is which domains of mtp53 R273H are responsible for the protein’s chromatin-based replication activities. In this study, we tested whether the oligomerization state of mtp53 plays a role in oncogenic GOF activities. We destabilized tetramer formation by using site-directed mutagenesis to introduce oligomerization domain (OD) point mutations A347D, R337C, or L344P. The site-directed mutagenesis constructs were transiently transfected into p53-/- mammalian cell lines to evaluate the altered functions. The oligomerization state of mtp53 was assessed via glutaraldehyde crosslinking and western blot analyses. Western blot and qPCR analyses were used to test how OD mutations in plasmids expressing either wtp53 or R273H mtp53 regulated the targets p21, CDC7 and RRM2. We used chromatin fractionation and western blot analyses to compare the chromatin association of the R273H mtp53 (with variable OD mutants), PARP1, and MCM2 to assess how destabilizing tetramer formation influenced chromatin interactions. Compared to the tetrameric versions of wildtype (wt) and mutant (mt) p53, the wtp53-A347D and R273H-A347D were predominantly dimers, while wtp53-R337C, wtp53-L344P, mtp53 R273H-R337C, and mtp53R273H-L344P were predominantly monomers. When wtp53 tetramerization was blocked so was its ability to activate the cyclin-dependent kinase p21/waf. Interestingly, all oligomerization forms of mtp53 localized to the chromatin suggesting GOF does not require tetramer formation for all functions. Strikingly, all oligomerization mutants of R273H mtp53, compared to the tetrameric mtp53, had a stronger interaction with MCM2. When we examined the mtp53 GOF transcriptional target we found that only tetrameric mtp53 R273H activated the target gene RRM2. Our findings suggest that destabilizing tetramer formation reduced certain mtp53 R273H GOF oncogenic activities while activating others. These changes of functions require examination in the context of triple-negative breast cancers.

Citation Format: George Kwakye Annor. Tetrameric and monomeric gain-of-function mutant p53 interacts with chromatin [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-09-02.
Abstract PD9-11: Association of body mass index and inflammatory dietary pattern with breast cancer pathologic and genomic immunophenotype in the nurses’ health study
Authors: Stover Daniel G. , Damicis Adrienne , Heng Yujing J. , Collier Katharine A. , Adams Elizabeth J. , Kensler Kevin H. , Baker Gabrielle M. , Wesolowski Robert , Sardesai Sagar , Gatti-Mays Margaret , Ramaswamy Bhuvaneswari , Eliassen A. Heather , Hankinson Susan E. , Tabung Fred K. , Tamimi Rulla M. , Asad Sarah
Published: March 2022

Purpose: Immune infiltration is associated with better treatment response and outcomes in breast cancer, yet data regarding the role of modifiable patient factors in immune infiltration are limited. Patients and Methods: This population-based, prospective observational study evaluated 882 Nurses’ Health Study (NHS) and NHSII participants diagnosed with invasive breast cancer with detailed exposure and gene expression data. Of these, 262 women (training cohort) had breast tumor immunohistochemistry (IHC) for four canonical immune cell markers: CD8, CD4, CD20, CD163. In this training cohort, 105 published immune cell-specific gene expression signatures were calculated, then lasso regression was used to derive four immune cell-specific scores based on association with IHC. In the remaining 620 patient testing cohort, we evaluated association of each immune-cell specific score as outcomes, with body mass index (BMI) change since age 18, physical activity, and the empirical dietary inflammatory pattern (EDIP) score as predictors, using multivariable-adjusted linear regression. Results: Among women with paired expression/IHC data from breast tumor tissue, we identified robust correlation between novel immune cell-specific expression scores and IHC (Spearman’s rho range 0.42-0.54; all p<0.001). BMI change since age 18 was positively associated with CD4+ (β=0.16; SE=0.06; p=0.009), and CD163+ scores (β=0.14; SE=0.07; p=0.04) in multivariable analyses. Neither physical activity nor EDIP were significantly associated with any immune cell-specific expression score in multivariable analyses. Conclusions: BMI change since age 18 was positively associated with novel CD4+ and CD163+ cell scores in breast cancer, supporting further study of the effect of modifiable factors like weight gain on the immune microenvironment.

Citation Format: Daniel G. Stover, Adrienne Damicis, Yujing J. Heng, Katharine A. Collier, Elizabeth J. Adams, Kevin H. Kensler, Gabrielle M. Baker, Robert Wesolowski, Sagar Sardesai, Margaret Gatti-Mays, Bhuvaneswari Ramaswamy, A. Heather Eliassen, Susan E. Hankinson, Fred K. Tabung, Rulla M. Tamimi, Sarah Asad. Association of body mass index and inflammatory dietary pattern with breast cancer pathologic and genomic immunophenotype in the nurses’ health study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-11.
Abstract TF1-2: ER+ word salad decoded: SERD, SERM, SERCA, CERAN, PROTAC
Authors: Jhaveri K
Published: March 2022

Estrogen receptor (ER) plays an important role in gene transcription and the proliferation of ER positive (ER+) breast cancers. Selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and fulvestrant, a selective estrogen receptor degrader (SERD) are currently approved therapeutic approaches for ER positive breast cancers. While these treatment strategies are highly effective, de novo and secondary resistance remains a challenge. Despite resistance mechanisms including due to mutations in the ligand binding domain of the ERα gene (ESR1 mutations), ER+ breast cancers continue to rely on receptor activity for growth signaling, underscoring the need for more effective treatments. To overcome the limitations of the existing endocrine therapies, there has been a quest to develop more potent and selective ER antagonists by altering aspects of drug binding or induction of proteolytic degradation of the receptor through different mechanisms. These orally bioavailable agents offer the potential for low toxicity and improved activity and are in various phases of clinical development either as monotherapy or in combination with targeted therapies.

Citation Format: K Jhaveri. ER+ word salad decoded: SERD, SERM, SERCA, CERAN, PROTAC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr TF1-2.
Abstract TF2-2: Heterogeneity in treatment outcomes for HER2+ breast cancer - Clinical management strategies
Authors: Tolaney S
Published: March 2022

HER2-positive breast cancers are complex tumors that are clinically and biologically heterogeneous. Even within HER2+ breast cancer, there are different molecular subtypes, mutational profiles, levels of HER2 protein, and immune infiltration. Additionally, HER2 may not be expressed homogeneously among all the cancer cells in the same tumor, some tumors may have low HER2 expression, while other tumors evolve during treatment. These molecular differences help explain why patients do not benefit to the same extent to HER2-directed therapies. We will review data regarding outcomes for tumors with known tumor heterogeneity, hormone receptor positivity, HER2-low positivity, and cases where brain metastases may be present. We will discuss optimal clinical management in the modern era with multiple HER2-directed therapies, including next-generation antibody-drug conjugates. Future strategies to tailor therapy to the individual patient will need to not just factor in anatomic tumor burden, but also key molecular features.

Citation Format: S Tolaney. Heterogeneity in treatment outcomes for HER2+ breast cancer - Clinical management strategies [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr TF2-2.
Abstract TF2-3: Molecular heterogeneity in HER2+ breast cancer - can outcomes be predicted?
Authors: Prat A
Published: March 2022

HER2+ breast cancer is clinically and biologically heterogenous. In the last 10 years, translational research in this disease has deciphered many biological features, which are associated with clinical outcomes both in early and metastatic disease. Among them, RNA-based gene expression has identified 4 main molecular subtypes (HER2-enriched, Basal-like, Luminal A and Luminal B), and HER2-enriched tumors within HER2+ breast cancer show high HER2 activation and response to anti-HER2 therapy. At the same time, ERBB2 mRNA levels by itself have also been linked to a higher response to anti-HER2 therapy, including T-DM1. Whether these 2 biological features will predict response to novel anti-HER2 therapies such as DS8201a is currently unknown. One important aspect is that levels of the target (i.e., HER2/ERBB2) and the activation of the downstream signaling pathway (i.e., HER2-enriched) are related but different at the same time. In other words, higher levels of ERBB2 mRNA are associated with a HER2-enriched phenotype; however, a substantial proportion of HER2+ tumors with low levels of ERBB2 are also HER2-enriched. Thus, they should not be considered the same, and this could have clinical implications. Similarly, hormone receptor negative HER2+ breast cancer has higher levels of ERBB2 and higher proportion of HER2-enriched disease than hormone receptor-positive. The high sensitivity of hormone receptor-negative and HER2-enriched disease to anti-HER2 therapy has been demonstrated in the neoadjuvant setting as well as studies looking at on-treatment biology after short-course of anti-HER2 treatment. Indeed, in advanced HER2+ breast cancer, the major gains in overall survival with new anti-HER2-based therapies are seen in hormone receptor-negative disease. Finally, tumor microenvironment plays a critical role. Indeed, tumor-infiltrating lymphocytes and immune gene expression signatures are associated with treatment response and better survival outcome. Whether this immune-related variables predict response to antiPD1/PDL1 is currently unknown, although translational studies do suggest that there might be a link. To conclude, the biological heterogeneity that exists within HER2+ disease is now well-known, and these variables, together with clinical-pathological features, should allow the design of new biomarkers to help answer critical clinical questions.

Citation Format: A Prat. Molecular heterogeneity in HER2+ breast cancer - can outcomes be predicted? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr TF2-3.
Adjuvant PD-1 Blockade in Resected Melanoma: Is Preventing Recurrence Enough?
Authors: Smithy James W. , Shoushtari Alexander N.
Published: March 2022

Grossmann and colleagues report the results of a large randomized trial demonstrating improved recurrence-free survival with adjuvant pembrolizumab in resected melanoma compared with adjuvant ipilimumab or IFNα2b. However, it remains unclear whether adjuvant immunotherapies extend overall survival as outcomes for patients with advanced melanoma continue to improve.

See related article by Grossmann et al., p. 644 (1).
Direct and Indirect Effects of COVID-19 on Long-Term Care Residents and Their Family Members
Authors: Cohen-Mansfield Jiska , Meschiany Guy
Published: March 2022

Introduction: The first cases of COVID-19 in Israel were reported in February 2020. Family visits were prohibited from March 10, 2020, and then allowed on a limited basis on April 20, 2020. This article examines how COVID-19 impacted long-term care residents and their family members from the perspective of long-term care facility (LTCF) administrative staff. Methods: An online survey was sent to Israeli LTCF administrators between mid-July and mid-October 2020, resulting in 52 completed questionnaires. Quantitative analysis involved descriptive statistics using SPSS, with differences compared via t tests, ANOVA, and χ2 tests. Qualitative analysis involved thematic analysis of responses to open-ended questions. Results: COVID-19 was reported to have multiple types of negative impact on residents, including direct effects on morbidity and mortality as well as indirect effects manifested as negative reactions to measures aimed at limiting infection, including isolation from relatives, decreased activities for residents, and COVID-19 testing. The impact of isolation on LTCF residents was reported as negative or very negative by over three-quarters of the respondents. Behavioral problems among residents increased in 32% of the facilities. The qualitative results suggested that adverse effects on residents and family members were partially mitigated by the use of communication technologies. Discussion/Conclusion: The interplay of multiple factors affected LTCF residents against the backdrop of COVID-19 restrictions. The emergence of mitigating factors which provide solutions to some of the challenges has the potential of improving quality of care for LTCF residents as the pandemic continues and thereafter.
A Study on the Effect of 850 nm Low-Level Diode Laser versus Electrical Stimulation in Facial Nerve Regeneration for Patients with Bell’s Palsy
Authors: Shoman Ahmed , Hassan Ashraf , Kassab Ahmed
Published: March 2022

Introduction: Bell’s palsy is acute facial paralysis with unclear etiology that results in weakness of facial muscles or paralysis on one side of the face. Methods: This prospective, randomized, single-blind, controlled study was conducted on 45 patients with Bell’s palsy who were randomly divided into three equal groups. Two groups received either low-level laser therapy (LLLT) or electrical stimulation (E.S.) both in conjunction to medications, massage, and facial exercise treatment. The third group (control) was treated with medication, massage, and facial exercise. Results: The primary outcome was the improvement of nerve conduction velocity of facial nerve while the secondary outcome was the change of Sunnybrook facial grading system (SBGS). The outcome measures were evaluated pre- and posttreatment. There was statistically significant difference between the three groups in favor of the LLLT group regarding the nerve action potential amplitude and latency, in addition to signs of nerve regeneration and improved SBGS. Conclusion: This short-term investigation revealed that LLLT proved to be more efficient than E.S. in facial nerve regeneration for patients with Bell’s palsy.
Contingent cfDNA Screening Implementation: Increasing Diagnostic Accuracy and Reducing Invasive Testing – 6 Years’ Results in a Single Center
Authors: Cubo Ana María , Huélamo Marta , Martín-Seisdedos María Carmen , Hernández-Hernández Estrella , Lapresa-Alcalde Maria Victoria , Rodríguez-Martín María de la O , Doyague María José , Sayagués José María
Published: March 2022

Objectives: Universal screening for trisomy using cell-free DNA (cfDNA) has proven to be more effective than combined test, but it is not cost efficient currently. Contingent cfDNA screening on the results of the first-trimester combined test can improve the detection rate of the combined test and reduce the number of invasive tests at a lower cost than universal screening. In 2018, a contingent screening program was implemented in the community of Castilla y Leon (Spain). This study aims to compare the results achieved in Salamanca University Hospital during the first 3 years of contingent screening (2018–2020) with those of the previous 3 years (2015–2017) to assess the changes in the trisomy detection rate and the number of invasive tests. Methods: A total of 9,903 singleton pregnancies without malformations nor nuchal translucency >p99 were included. 5,165 patients underwent combined screening and 4,738 had contingent screening based on the combined test risk. In the combined test group, women were offered an invasive test if the risk was ≥1:270, while risks under 1:270 were considered low risks, and no further testing was offered. In the contingent screening group, invasive testing was offered if the risk was ≥1:100 (≥1:50 from 2020 onwards), while cfDNA was offered if the combined test risk was between 1:100 and 1:1,000 (1:50–1:1,000 from 2020 onwards). When risk was <1:1,000, no further testing was offered. Aneuploidies detected by cfDNA were confirmed by invasive diagnostic testing. Results: There were 33 cases of trisomy 21 (T21) throughout the 6 years of study. Four cases had low/intermediate risks and were spotted by cfDNA. Risk >1:1,000 threshold for contingent test detected 100% T21. There was a false-positive result for trisomy 13. There were no false-negative results. “No-call” cfDNA results were minimized by repeating blood collection 2 weeks later, as fetal fraction (FF) was doubled. Invasive testing had a drop rate of 84% after contingent screening implementation. Discussion: The implementation of population-based contingent screening significantly reduces the number of invasive tests without lowering diagnostic accuracy. To achieve the maximum efficiency of the program, it is important to know the best cut-offs according to the population where the program is to be implemented. The number of uninformative results due to low FF can be reduced by repeating the test 2 weeks after the initial extraction: this increases the FF to twice the initial one, achieving informative results and avoiding unnecessary invasive tests.
SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells
Authors: Han Yuling , Zhu Jiajun , Yang Liuliu , Nilsson-Payant Benjamin E. , Hurtado Romulo , Lacko Lauretta A. , Sun Xiaolu , Gade Aravind R. , Higgins Christina A. , Sisso Whitney J. , Dong Xue , Wang Maple , Chen Zhengming , Ho David D. , Pitt Geoffrey S. , Schwartz Robert E. , tenOever Benjamin R. , Evans Todd , Chen Shuibing
Published: March 2022

Background:

Increasing evidence suggests that cardiac arrhythmias are frequent clinical features of coronavirus disease 2019 (COVID-19). Sinus node damage may lead to bradycardia. However, it is challenging to explore human sinoatrial node (SAN) pathophysiology due to difficulty in isolating and culturing human SAN cells. Embryonic stem cells (ESCs) can be a source to derive human SAN-like pacemaker cells for disease modeling.

Methods:

We used both a hamster model and human ESC (hESC)–derived SAN-like pacemaker cells to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pacemaker cells of the heart. In the hamster model, quantitative real-time polymerase chain reaction and immunostaining were used to detect viral RNA and protein, respectively. We then created a dual knock-in
SHOX2:GFP;MYH6:mCherry
hESC reporter line to establish a highly efficient strategy to derive functional human SAN-like pacemaker cells, which was further characterized by single-cell RNA sequencing. Following exposure to SARS-CoV-2, quantitative real-time polymerase chain reaction, immunostaining, and RNA sequencing were used to confirm infection and determine the host response of hESC-SAN–like pacemaker cells. Finally, a high content chemical screen was performed to identify drugs that can inhibit SARS-CoV-2 infection, and block SARS-CoV-2–induced ferroptosis.

Results:

Viral RNA and spike protein were detected in SAN cells in the hearts of infected hamsters. We established an efficient strategy to derive from hESCs functional human SAN-like pacemaker cells, which express pacemaker markers and display SAN-like action potentials. Furthermore, SARS-CoV-2 infection causes dysfunction of human SAN-like pacemaker cells and induces ferroptosis. Two drug candidates, deferoxamine and imatinib, were identified from the high content screen, able to block SARS-CoV-2 infection and infection-associated ferroptosis.

Conclusions:

Using a hamster model, we showed that primary pacemaker cells in the heart can be infected by SARS-CoV-2. Infection of hESC-derived functional SAN-like pacemaker cells demonstrates ferroptosis as a potential mechanism for causing cardiac arrhythmias in patients with COVID-19. Finally, we identified candidate drugs that can protect the SAN cells from SARS-CoV-2 infection.
Prognostic Significance of Ventricular Arrhythmias in 13 444 Patients With Acute Coronary Syndrome: A Retrospective Cohort Study Based on Routine Clinical Data (NIHR Health Informatics Collaborative VA‐ACS Study)
Authors: Sau Arunashis , Kaura Amit , Ahmed Amar , Patel Kiran H. K. , Li Xinyang , Mulla Abdulrahim , Glampson Benjamin , Panoulas Vasileios , Davies Jim , Woods Kerrie , Gautama Sanjay , Shah Anoop D. , Elliott Paul , Hemingway Harry , Williams Bryan , Asselbergs Folkert W. , Melikian Narbeh , Peters Nicholas S. , Shah Ajay M. , Perera Divaka , Kharbanda Rajesh , Patel Riyaz S. , Channon Keith M. , Mayet Jamil , Ng Fu Siong
Published: March 2022

Background

A minority of acute coronary syndrome (ACS) cases are associated with ventricular arrhythmias (VA) and/or cardiac arrest (CA). We investigated the effect of VA/CA at the time of ACS on long‐term outcomes.

Methods and Results

We analyzed routine clinical data from 5 National Health Service trusts in the United Kingdom, collected between 2010 and 2017 by the National Institute for Health Research Health Informatics Collaborative. A total of 13 444 patients with ACS, 376 (2.8%) of whom had concurrent VA, survived to hospital discharge and were followed up for a median of 3.42 years. Patients with VA or CA at index presentation had significantly increased risks of subsequent VA during follow‐up (VA group: adjusted hazard ratio [HR], 4.15 [95% CI, 2.42–7.09]; CA group: adjusted HR, 2.60 [95% CI, 1.23–5.48]). Patients who suffered a CA in the context of ACS and survived to discharge also had a 36% increase in long‐term mortality (adjusted HR, 1.36 [95% CI, 1.04–1.78]), although the concurrent diagnosis of VA alone during ACS did not affect all‐cause mortality (adjusted HR, 1.03 [95% CI, 0.80–1.33]).

Conclusions

Patients who develop VA or CA during ACS who survive to discharge have increased risks of subsequent VA, whereas those who have CA during ACS also have an increase in long‐term mortality. These individuals may represent a subgroup at greater risk of subsequent arrhythmic events as a result of intrinsically lower thresholds for developing VA.
New Insights Into Cerebrovascular Pathophysiology and Hypertension
Authors: Webb Alastair J.S. , Werring David J.
Published: March 2022

Despite advances in acute management and prevention of cerebrovascular disease, stroke and vascular cognitive impairment together remain the world’s leading cause of death and neurological disability. Hypertension and its consequences are associated with over 50% of ischemic and 70% of hemorrhagic strokes but despite good control of blood pressure (BP), there remains a 10% risk of recurrent cerebrovascular events, and there is no proven strategy to prevent vascular cognitive impairment. Hypertension evolves over the lifespan, from predominant sympathetically driven hypertension with elevated mean BP in early and mid-life to a late-life phenotype of increasing systolic and falling diastolic pressures, associated with increased arterial stiffness and aortic pulsatility. This pattern may partially explain both the increasing incidence of stroke in younger adults as well as late-onset, chronic cerebrovascular injury associated with concurrent systolic hypertension and historic mid-life diastolic hypertension. With increasing arterial stiffness and autonomic dysfunction, BP variability increases, independently predicting the risk of ischemic and intracerebral hemorrhage, and is potentially modifiable beyond control of mean BP. However, the interaction between hypertension and control of cerebral blood flow remains poorly understood. Cerebral small vessel disease is associated with increased pulsatility in large cerebral vessels and reduced reactivity to carbon dioxide, both of which are being targeted in early phase clinical trials. Cerebral arterial pulsatility is mainly dependent upon increased transmission of aortic pulsatility via stiff vessels to the brain, while cerebrovascular reactivity reflects endothelial dysfunction. In contrast, although cerebral autoregulation is critical to adapt cerebral tone to BP fluctuations to maintain cerebral blood flow, its role as a modifiable risk factor for cerebrovascular disease is uncertain. New insights into hypertension-associated cerebrovascular pathophysiology may provide key targets to prevent chronic cerebrovascular disease, acute events, and vascular cognitive impairment.
Balancing State and Local Power over School Districts’ Finances
Authors: Bowman Kristine L. , Zuschlag Dirk F.
Published: March 2022

During and for many years after the 2008–10 Great Recession, financial crises in districts across the country triggered varying state involvement in those districts’ finances and governance, up to and including complete takeover. While these actions were most prominent in a handful of states, all states have laws that enable them to intervene in school districts’ finances. These laws shape important governance relationships as well as the allocation of educational resources, yet we know very little about them. Accordingly, this policy brief reports our identification of 449 state statutory provisions across the country, which together contain 1049 potential interventions; our analysis of those provisions included identifying patterns, trends, and potential interactions with other areas of education policy. At a national level and disaggregated by state, we present what potential state interventions into school district finances already exist, which is a necessary foundation to understand which interventions a district could be subject to in the near future, and how states can both contextualize their policy approaches and best address districts’ financial conduct and fiscal challenges going forward.
Credit and Poverty in Early Modern Venice
Authors: Pompermaier Matteo
Published: March 2022

In early modern Venice, wine and money were intrinsically linked through the pawnbroking service that innkeepers and bastioneri, the managers of wine warehouses (bastioni), offered their customers. The loans that they supplied were generally small, officially interest-free, and frequent. Moreover, at least one-third of each was paid in wine, at that time considered a staple. Hence, innkeepers and bastioneri were central figures in Venice’s urban context, especially for the poor. Those individuals, usually considered “voiceless” in history were, in fact, the main actors in what might be termed a “handkerchief” economy, named for one of its most pawned items.
Bible Translation as Contextual Theology
Authors: Hwang Jerry
Published: March 2022

Lamin Sanneh has influentially observed that translating the Bible is always a seminal act of doing contextual theology. While this has been well demonstrated for the African context, it has rarely been explored for the Asian context. This article examines the Chinese Union Version (cuv) Bible of 1919, a venerated translation that is simply ‘the Bible’ for Chinese Christians. As a result of being mainly the work of Western translators, however, the cuv has lexicalised and sacralised a distinctly western and Protestant understanding of sin as ‘crime’ which has become conventional usage among Chinese Christians. Even so, the linguistic potential for defamiliarising the concept of sin and recasting it in a more contextual manner for Chinese readers already lies within the cuv. Greater attention to the cuv’s concreteness in rendering Old Testament sin-idioms, as opposed to the standard Protestant abstractions, would therefore refresh the voice of Chinese Christianity.
Wooden Roofing: Split Shingles versus Sawn Boards
Authors: Grabner Michael , Nemestothy Sebastian , Wächter Elisabeth
Published: March 2022

Wooden shingles have been known in Europe and other regions worldwide for several thousands of years. They are usually split, and according to handicraft rules, as well as historical literature, a split surface has many advantages. It is more flexible, more elastic, stronger, and less exposed to cupping than a sawn surface because no fibers have been cut. It also follows wood rays; it is more durable than a sawn surface because cut fibers absorb more moisture, creating good conditions for fungal growth. However, because sawing is the main procedure for dividing logs into timber, sawn boards are currently used for roofing. The short life span of such roofing has often been discussed by craftsmen. In this study, a 37-year-old roofing was evaluated to determine the important parameters of high-durability sawn boards. Results showed that the presence of juvenile wood, fiber deviations, and knots reduced the durability of these boards. Therefore, sawn boards of the same wood quality as split shingles may have the same durability.
Two new species of Hypoxylon (Hypoxylaceae) from China based on morphological and DNA sequence data analyses
Authors: SONG ZIKUN , PAN XIAOYAN , LI CHANGTIAN , MA HAI-XIA , LI YU
Published: March 2022

Two new species, Hypoxylon larissae and Hypoxylon jianfengense, are described and illustrated on the basis of a combination of morphological and molecular characters from China. Hypoxylon larissae was collected from southwest China (Yunnan province), while H. jianfengense was collected from southern China (Hainan province). Hypoxylon larissae is characterized by effused-pulvinate stromata, Orange (7) and Luteous (12) pigments extracted in 10% KOH and light brown to dark brown ascospores with straight germ slit. It is phylogenetically and morphologically closely related to H. fenderi. Hypoxylon jianfengense is distinguished by tubular to long tubular perithecia, Dark Green (21), Isabelline (65) and Dull Green (70) pigments extracted in 10% KOH and conspicuous coil-like perispore ornamentation. Hypoxylon jianfengense clustered with H. invadens and H. trugodes in a well-supported clade. Phylogenetic analyses of multi-gene sequences (ITS-LSU-RPB2-TUB2) support the recognition of the taxa as distinct.
Dichorisandra rhizantha (Commelinaceae), a new morphologically unusual species from Bahia, Brazil
Authors: AONA LIDYANNE Y. S. , DE SOUZA EVERTON HILO , DE ALMEIDA JÚNIOR RAILSON A. C. , MARINHO LUCAS C. , BITTRICH VOLKER , AMARAL MARIA DO CARMO E. DO
Published: March 2022

We describe, discuss, and illustrate Dichorisandra rhizantha, a new species from a transitional area between the Atlantic Forest and Caatinga domains in eastern Bahia state, Brazil. The species was assessed as Endangered, especially for its distribution restricted to forest fragments. The new species is morphologically similar to D. hirtella, D. radicalis and D. jardimii, but clearly differs from these by the inflorescence arising directly from the rhizome, and a pubescent indument on stem, leaves and sepals. We also present a distribution map of the species and taxonomic comments.
NORA3: A Nonhydrostatic High-Resolution Hindcast of the North Sea, the Norwegian Sea, and the Barents Sea
Authors: Haakenstad Hilde , Breivik Øyvind , Furevik Birgitte R. , Reistad Magnar , Bohlinger Patrik , Aarnes Ole Johan
Published: March 2022

The 3-km Norwegian Reanalysis (NORA3) is a 15-yr mesoscale-permitting atmospheric hindcast of the North Sea, the Norwegian Sea, and the Barents Sea. With a horizontal resolution of 3 km, the nonhydrostatic numerical weather prediction model HARMONIE–AROME runs explicitly resolved deep convection and yields hindcast fields that realistically downscale the ERA5 reanalysis. The wind field is much improved relative to its host analysis, in particular in mountainous areas and along the improved grid-resolving coastlines. NORA3 also performs much better than the earlier hydrostatic 10-km Norwegian Hindcast Archive (NORA10) in complex terrain. NORA3 recreates the detailed structures of mesoscale cyclones with sharp gradients in wind and with clear frontal structures, which are particularly important when modeling polar lows. In extratropical windstorms, NORA3 exhibits significantly higher maximum wind speeds and compares much better to observed maximum wind than do NORA10 and ERA5. The activity of the model is much more realistic than that of NORA10 and ERA5, both over the ocean and in complex terrain.
Comprehensive Meta-Analysis of Functional and Structural Markers of Subclinical Atherosclerosis in Women with Polycystic Ovary Syndrome
Authors: Sun Dandan , Wu Yupeng , Ding Mingyan , Zhu Fang
Published: March 2022

The relationship between polycystic ovary syndrome (PCOS) and subclinical atherosclerosis remains unclear. We performed a comprehensive systematic review and meta-analysis to evaluate the effect of PCOS on functional and structural markers of subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT), flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), pulse wave velocity (PWV), and coronary artery calcium (CAC). Standard mean differences (SMDs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Ninety-six articles involving 5550 PCOS patients and 5974 controls were included. Compared with controls, PCOS patients showed significantly thicker cIMT (SMD (95% CI) = .587 (.398, .776), P < .001), lower FMD (SMD (95% CI) = −.649 (−.946, −.353), P < .001) and NMD (SMD (95% CI) = −.502 (−.686, −.317), P < .001), as well as higher PWV (SMD (95% CI) = .382 (.019, .746), P = .039), and increased CAC incidence (OR (95% CI) = 2.204 (1.687, 2.879), P < .001). When analyzing subgroups by age and body mass index (BMI), results were still significant ( P < .05) except for PWV in the BMI subgroup. There was no significant result on sensitivity analysis, and Begg’ test or Egger’s test. PCOS contributes to subclinical atherosclerosis, resulting in functional and structural changes in cIMT, FMD and NMD, PWV, and CAC incidence.
Spectroscopic Investigation of Catalyst Inks and Thin Films Toward the Development of Ionomer Quality Control
Authors: Jacobsen Derek , Porter Jason , Ulsh Michael , Rupnowski Przemyslaw
Published: March 2022

As the production of polymer electrolyte fuel cells expands, novel quality control methods must be invented or adapted in order to support expected rates of production. Ensuring the quality of deposited catalyst layers is an essential step in the fuel cell manufacturing process, as the efficiency of a fuel cell is reliant on the catalyst layer being uniform at both the target platinum loading and the target ionomer content. Implementing a quality control method that is sensitive to these aspects is imperative, as wasting precious metals and other catalyst materials is expensive, and represents a potential barrier to entry into the field for manufacturers experimenting with novel deposition processes. In this work, we analyzed catalyst inks to determine if their ionomer content could be quantized spectroscopically. Attenuated total reflection (ATR) Fourier transform infrared spectroscopic technique was investigated producing a signal proportional to the ionomer content. ATR spectroscopy was able to quantitatively differentiate samples in which the ionomer to carbon mass ratio (I/C) varied between 0.9 and 3.0. The I/C ratio was correlated to the measured ATR signal near the CF2 vibrational bands located between 1100 cm−1 and 1400 cm−1. The experimental results obtained constitute a step toward the development of novel quality control methodologies for catalyst inks utilized by the fuel cell industry.
Exploring Autism, Culture, and Immigrant Experiences: Lessons from Sri Lankan Tamil Mothers
Authors: Shanmugarajah Kajaani , Rosenbaum Peter , Di Rezze Briano
Published: March 2022

Background: Canada is home to a mosaic of cultures with immigrant communities from a wide range of countries, but there are significant variations in how autism spectrum disorder (ASD) may be understood across different immigrant groups, including Sri Lankan Tamils. Such gaps in knowledge may present challenges for immigrant families that are trying to access appropriate care for their child, including occupational therapy services. Purpose: This descriptive qualitative study aimed to better understand the experiences of immigrant Sri Lankan Tamil parents of children diagnosed with ASD in Southern Ontario, Canada. Method: Interviews were analyzed using an in-depth content analysis. Findings: Results demonstrated parents’ perceived supports and barriers towards ASD intervention planning, and indicated that parents were generally satisfied by the level of cultural competence in current ASD systems. However, families may still experience significant immigrant-related barriers that are not fully addressed. Implications: Recommendations to improve cultural awareness among occupational therapists utilizing ASD interventions are suggested.
Resolving Dimensionality in a Child Assessment Tool: An Application of the Multilevel Bifactor Model
Authors: Akaeze Hope O. , Lawrence Frank R. , Wu Jamie Heng-Chieh
Published: March 2022

Multidimensionality and hierarchical data structure are common in assessment data. These design features, if not accounted for, can threaten the validity of the results and inferences generated from factor analysis, a method frequently employed to assess test dimensionality. In this article, we describe and demonstrate the application of the multilevel bifactor model to address these features in examining test dimensionality. The tool for this exposition is the Child Observation Record Advantage 1.5 (COR-Adv1.5), a child assessment instrument widely used in Head Start programs. Previous studies on this assessment tool reported highly correlated factors and did not account for the nesting of children in classrooms. Results from this study show how the flexibility of the multilevel bifactor model, together with useful model-based statistics, can be harnessed to judge the dimensionality of a test instrument and inform the interpretability of the associated factor scores.
COMMENTARY – FIRE BELL IN THE NIGHT
Authors: Skidmore Max J.
Published: March 2022

Abortion is an issue around the world, varying in intensity by location. In the United States, it generates enormous controversy, especially because Protestant fundamentalists have joined Roman Catholics in strenuous opposition and have essentially captured one of the two major political parties. This extended commentary essay contends that anti‐abortion arguments are flawed and that an effective anti‐abortion policy requires a harsh authoritarian, if not totalitarian, government, fueled by misogyny and disregard for human rights. Such policies force pregnant women into what must be described as a condition of slavery.
Livelihood Anxieties of Communities in Mannar, Sri Lanka
Authors: Nainar Vahida
Published: March 2022

The laws in Sri Lanka mandate the allocation of state resources, including access to land, business, educational and employment opportunities on the basis of the population ratio of different communities in the country’s districts. Minority communities located in the north are therefore seized with a demographic anxiety over their access to and control of land and resources. These anxieties have been further sharpened in the process of return and rehabilitation of communities displaced by the civil war and known officially as internally displaced persons (IDP). The article explores how these anxieties have played out with Muslim and Tamil Christian communities in Mannar district located in the north west of Sri Lanka in the nation’s Northern Province. The article is based on a a case study of the dispute between the Uppukulam and the Joseph Vaz Nagar fishermen over the use of a fishing pier. It also examines the role of the state, the courts and the church in locking these communities in competition over access to a source of livelihood.
The effects of task-oriented mental practice on upper limb function and coordination in chronic stroke patients—Randomized controlled trial design
Authors: Park JuHyung
Published: March 2022

Objective

This study is a randomized experimental design study conducted to investigate the effect of task-oriented mental practice (TOMP) on upper limb function and coordination in chronic stroke patients.

Methods

A total of 34 chronic stroke patients participated in this study and were randomly divided into an experimental group (EG) of 17 patients (TOMP) and a control group (CG) of 17 patients (task-oriented training). To measure the subject’s upper extremity function and coordination, the results of Fugl-Meyer assessment (FMA) of motor function (U/E) and co-coordination ratio (CCR) values calculated from the measurements of the BTS FreeEMG 300 were used.

Results

In the comparison before and after group intervention in terms of FMA, the EG showed significant changes in all items of FMA, but the CG showed significant changes only in the shoulder items ( p < 0.05). In the comparison between groups, significant differences were observed only in the total score of FMA ( p < 0.05). In terms of the CCR value, positive changes were found in the EG in all items except for the shoulder flexion, but negative changes were observed in all items in the CG.

Conclusion

It was confirmed that the TOMP applied in this study can have a positive effect on upper limb function and coordination in chronic stroke patients.