bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of HiTOP Constructs Across the Population: A Commentary on the HiTOP Measure Development Project
Authors: Verona Edelyn
Published: October 2021

The set of articles in this issue demonstrates the promise of the HiTOP collaborative effort in advancing a viable alternative dimensional taxonomy of psychopathology. Besides transcending the limitations of our current taxonomic system and categorical diagnoses, the potential contributions of HiTOP should extend to also critically examining long-standing notions of psychopathology and mental wellness, evaluating the ability of symptom measures to capture the various manifestations of disorder in the population, and questioning the emphasis on predominant Western cultural norms as a basis for our definitions of psychopathology and their measurement. This commentary addresses the extent to which the implementation of the measurement studies featured in the special issue centered these goals, drawing on the work of scholars from within and outside the fields of psychiatry and clinical psychology, some who have taken a critical view of these fields. The hope is that we work to challenge some basic assumptions and increase self-reflection, with an eye toward reducing bias and mental health disparities.
Acoustic emission waveforms for damage monitoring in composite materials: Shifting in spectral density, entropy and wavelet packet transform
Authors: Barile Claudia , Casavola Caterina , Pappalettera Giovanni , Paramsamy Kannan Vimalathithan
Published: October 2021

Signal-based acoustic emission data are analysed in this research work for identifying the damage modes in carbon fibre–reinforced plastic (CFRP) composites. The research work is divided into three parts: analysis of the shifting in the spectral density of acoustic waveforms, use of waveform entropy for selecting the best wavelet and implementation of wavelet packet transform (WPT) for identifying the damage process. The first two methodologies introduced in this research work are novel. Shifting in the spectral density is introduced in analogous to ‘flicker noise’ which is popular in the field of waveform processing. The entropy-based wavelet selection is refined by using quadratic Renyi’s entropy and comparing the spectral energy of the dominating frequency band of the acoustic waveforms. Based on the method, ‘dmey’ wavelet is selected for analysing the waveforms using WPT. The slope values of the shifting in spectral density coincide with the results obtained from WPT in characterising the damage modes. The methodologies introduced in this research work are promising. They serve the purpose of identifying the damage process effectively in the CFRP composites.
The New York City Prescriber Notification Program: Assessing the Feasibility of a Patient Overdose Death Notification Pilot
Authors: LaSane Kendall , Allen Bennett , Liebman Emma , Paone Denise
Published: October 2021

Opioid analgesics and benzodiazepines remain substantial contributors to unintentional drug overdose deaths in the United States. To promote judicious prescribing and improve care for patients with substance use disorders, the New York City Department of Health and Mental Hygiene piloted the Prescriber Notification Program, an educational initiative to deliver targeted public health messaging to providers who had prescribed opioid analgesics and/or benzodiazepines to patients who died from overdose in New York City. This article reports on provider responses to receipt of patient death notifications and program feasibility. Findings demonstrate that a majority of prescribers were not aware of patient deaths prior to receiving notification letters. Public health authorities considering prescriber notification systems should address barriers to implementation and sustainability—in particular, consistent and routine access to and linkage of overdose mortality and prescription monitoring data—as part of planning such programs.
Mortality Increases When Radical Nephrectomy is Delayed More Than 60 Days for T3 Renal Cell Carcinoma
Authors: Zhao Fangzheng , Liu Xiaoxiao , Zhang Chu , Zhu Haitao , Qi Nienie
Published: October 2021

Background: Radical nephrectomy is widely accepted as the default management option for patients with T3 renal cell carcinoma (RCC). However, it may require a certain time before surgery for various reasons. There are concerns that the delay in surgery may affect postoperative outcomes. The present study aimed to evaluate the impact of surgical wait time on survival in patients with T3 RCC. Methods: We retrospectively selected 138 patients with T3 RCC who underwent radical surgery between July 2009 and December 2019. Surgical wait time was defined as the period from initial imaging diagnosis to surgery. Patients were divided into the following 2 groups according to wait time: short-wait group(≤60 days), and long-wait group (>60 days). The clinical and pathological characteristics were evaluated. The overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) of each group were calculated and compared. Age, gender, interval, tumor size, pathological grade, Eastern Cooperative Oncology Group performance status (ECOG PS), surgical approach, year of surgery, and pathological type were included in the multivariable model. Results: This study included 91 male (65.9%) and 47 female (34.1%) patients. The median age of all patients was 60 years (interquartile range [IQR] 52-68 years). The median body mass index is 22.2 kg/m2 (IQR 18.9-24.7  kg/m2). There were 128 patients (92.8%) with pT3a disease and 10 patients (7.3%) with pT3b disease. The median surgical wait time for all patients was 16 days (IQR 10-77 days). The median surgical wait time of the short- and long-wait groups was 12 days (IQR 8-16 days) and 92 days (IQR 79-115 days), respectively. Until the last follow-up, 54 patients died. Among them, 49 patients (90.7%) died of tumor-related causes, and 5 patients (9.3%) died of other causes. There are 1 and 4 cases in the short-wait and long-wait groups, respectively. There were no significant differences in gender, ECOG PS, American society of anesthesiologists score, Charlson comorbidity index, clinical T stage, clinical N stage, and body mass index. And there were no significant differences in tumor size, surgical approach, year of surgery, pathological type, tumor grade, pathological T stage, pathological N stage, and venous involvement between the 2 groups. OS, CSS, and RFS were compared. The 5-year OS of the short- and long-wait time groups were 65.0% and 40.9%, respectively ( P = .030). The 5-year CSS rates of the short- and long-wait time groups were 68.7% and 51.5%, respectively ( P = .012). The 5-year RFS rates of the short- and long-wait time groups were 61.5% and 46.8%, respectively ( P = .119). Multivariable analysis revealed that surgical wait time interval and tumor size were independent risk factors for OS and that wait time was also an independent risk factor for CCS. Conclusion: Delay in radical surgery beyond 60 days can negatively affect OS in patients with T3 RCC.
Treating Adolescent Misophonia With Cognitive Behavioral Therapy: Considerations for Including Exposure
Authors: Cecilione Jennifer L. , Hitti Stephanie A. , Vrana Scott R.
Published: October 2021

Although misophonia is not yet included in the primary diagnostic manuals used by psychologists or psychiatrists, proposed criteria suggest that this condition is characterized by a strong negative reaction to and avoidance of certain trigger sounds. Misophonic trigger sounds are largely human-made (e.g., chewing and slurping) and evoke responses such as disgust, irritation, and/or anger that are out of proportion to the situation and cause distress and/or impairment. Currently, there is no gold standard evidence-based treatment for misophonia. As the misophonia treatment literature grows, several important questions are arising: (1) should exposure to aversive sound triggers be included in treatment for misophonia and (2) how can clinicians best assess misophonia symptoms. This case offers one example of misophonia being successfully treated with a cognitive-behavioral approach to treatment (including exposures) in an adolescent girl. This case also offers an example of how clinicians may conduct a comprehensive assessment of misophonia symptoms. Theoretically and empirically derived recommendations for including exposure in misophonia treatment are presented. Information from this case may be helpful in informing future research, as there is a paucity of evidence-based assessment and treatment protocols for misophonia.
Qualitative Evidence Syntheses Within Cochrane Effective Practice and Organisation of Care: Developing a Template and Guidance
Authors: Glenton Claire , Lewin Simon , Downe Soo , Paulsen Elizabeth , Munabi-Babigumira Susan , Johansen Marit , Agarwal Smisha , Ames Heather , Cooper Sara , Daniels Karen , Houghton Catherine , Karimi‐Shahanjarini Akram , Moloi Hlengiwe , Odendaal Willem , Shakibazadeh Elham , Vasudevan Lavanya , Xyrichis Andreas , Bohren Meghan A.
Published: October 2021

A growing number of researchers are preparing systematic reviews of qualitative evidence, often referred to as ‘qualitative evidence syntheses’. Cochrane published its first qualitative evidence synthesis in 2013 and published 27 such syntheses and protocols by August 2020. Most of these syntheses have explored how people experience or value different health conditions, treatments and outcomes. Several have been used by guideline producers and others to identify the topics that matter to people, consider the acceptability and feasibility of different healthcare options and identify implementation considerations, thereby complementing systematic reviews of intervention effectiveness.Guidance on how to conduct and report qualitative evidence syntheses exists. However, methods are evolving, and we still have more to learn about how to translate and integrate existing methodological guidance into practice. Cochrane’s Effective Practice and Organisation of Care (EPOC) ( www.epoc.org ) has been involved in many of Cochrane’s qualitative evidence syntheses through the provision of editorial guidance and support and through co-authorship. In this article, we describe the development of a template and guidance for EPOC’s qualitative evidence syntheses and reflect on this process.
The relevance analysis of GSTP1 rs1695 and lung cancer in the Chinese Han population
Authors: Xiao Jiang , Wang Yulu , Wang Zhimin , Zhang Yao , Li Yutao , Xu Chang , Xiao Man , Wang Haijian , Guo Shicheng , Jin Li , Wang Jiucun , Bao Yang , Shang Yan , Wu Junjie
Published: October 2021

Background

This study explored the relevance between rs1695 and susceptibility to the lung cancer in the Chinese Han population. Stratification analysis was conducted on the basis of age, gender, smoking status, tumor-related family history, and pathological type to observe relations between rs1695 and susceptibility to lung cancer in the subgroups.

Methods

A case-control study was performed with 974 lung cancer patients who were pathologically diagnosed and 1005 healthy cases based on physical examination to analyze the association between rs1695 and the risk of lung cancer.

Results

The frequencies of the AA, GA, and GG genotypes of rs1695 were 68.4%, 28.7%, and 2.9% in cases and 64.8%, 30.8%, and 4.2% in controls, respectively. After adjustment for age, gender, smoking status, and family history, it appears that the rs1695 G allele decreases the risk of lung cancer (OR = 0.811, 95% CI 0.684–0.961, P = 0.016). Moreover, compared with the AA genotype, the GA + GG genotype decreased lung cancer susceptibility (OR = 0.808, 95% CI 0.663–0.985, P = 0.035) and the GG genotype (OR = 0.591, 95% CI 0.347–0.988, P = 0.048). In a stratified analysis, the risk of lung cancer in the G allele carriers decreased among the males, patients without a tumor-related family history, and patients with lung adenocarcinoma, especially in smokers.

Conclusion

The polymorphism of locus rs1695 is related to the risk of lung cancer and is expected to be a target for the prediction of lung cancer.
Criminalizing Unto Death as Act of Judgment, Act of War: The Suicidal Rationality of the Death Penalty
Authors: Govind Rahul
Published: October 2021

This paper attempts to establish that capital punishment is not rational and cannot be rationalized without suicidally destroying the very ground on which lawful and rational punishment bases itself. It argues that in capital punishment, just as in any lawful punishment, the criminal is both held (humanly) rational and therefore culpable. But, unlike other forms of punishment, in capital punishment, the condemned is at the same time, held as irrational and irredeemable, beyond reform, and therein outside the ambit of rationality and humanity. In this sense a fundamental aporia is reached in rationalizing capital punishment because of the contradiction between the basis of punishment (the human as rational) and its operational logic (the condemned person as beyond reform therein irrational). Expressed another way, the judge proclaims a form of infallibility in their reasoning where the incorrigibility of the judgment is horrifically demonstrated and ironically reflected (and projected) in the incorrigibility of the condemned. This broad argument is pursued in two parts; one part interprets canonical texts such as Hobbes, Hegel and Foucault, while the second part interprets the Supreme Court of India’s jurisprudence around the death penalty. While these are very different discourses it will be shown that they share much common ground in their expressing—and negotiating—the fundamental problem as described above.
Teledental Consultations Using a Messaging Application during the COVID-19 Pandemic: Experience from a Singapore COVID-19 Community Care Facility
Authors: Chong Gabriel Tse Feng
Published: October 2021

Introduction

During the ‘Circuit Breaker’ period of the COVID-19 pandemic in Singapore from April to June 2020, governmental policies restricted the practice of dentistry nationwide to the provision of emergency treatment only, regardless of the patient’s COVID status. As such, teledentistry was used as an alternative means to continue providing some form of dental care to COVID-19–positive patients who were admitted to a COVID-19 Community Care Facility.

Description

The patients were physically triaged by physicians who would send clinical photos to the author via a messaging application, who would in turn triage the patients and assess if they required referral for emergency dental treatment. For patients who did not meet the criteria for referral, the author would advise the physicians on the subsequent management plan which included, but was not limited to, the provision of symptomatic relief.

Conclusions

This article shows the feasibility of undertaking teledental consultations using clinical photos transmitted via a messaging application. The practical implication is a reduced barrier for patients and healthcare professionals to access teledentistry, without having to resort to sophisticated equipment. Hopefully, this will translate into the continued provision of some form of dental care to patients during the ongoing pandemic as opposed to no care at all.
Competencies relevant for gerontological nursing: Focus-group interviews with professionals in the nursing of older people
Authors: Tohmola Anniina , Saarnio Reetta , Mikkonen Kristina , Kyngäs Helvi , Elo Satu
Published: October 2021

Older people are present in a variety of nursing settings and have distinct care needs. Evidence about the competencies required is crucial when developing the profession. The aim of the study was to describe competence areas relevant in gerontological nursing. A qualitative, descriptive study design was used with 27 participants included. Finnish gerontological nursing professionals who worked at several healthcare organizations and in education were interviewed in five focus-group interviews. The interviews were carried out between October 2017 and February 2018 and were analyzed using inductive content analysis. The study is reported according to SRQR guidelines. Analysis indicated four main competence areas for gerontological nursing: clinical nursing competence; competence in promoting health and well-being; interaction competence; and ethical competence. Registered nurses (RNs) must possess multiple competencies when caring for older people which should be taken into account in nursing and education.
Disease activity prediction and prognosis of anti-GBM nephritis based on T lymphocyte subset ratios
Authors: Zhang Dan , Zhang Fan , Liu Meiling , Zhang Mingchao , Zhang Jiong , Wang Jinquan
Published: October 2021

Introduction

Cell-mediated autoimmunity, especially the autoreactivity of T cells, is known to underlie the initiation of anti-glomerular basement membrane disease. However, the T lymphocyte subsets that determine the disease activity, renal fibrosis, and prognosis of anti-GBM disease have not been clearly elucidated.

Methods

The T lymphocyte subsets (CD4+ and CD8+) were examined on peripheral blood and renal biopsy tissues from 65 patients with biopsy proven anti-GBM disease. Patients were divided into the high ratio group and low ratio group according to the cutoff values in the receiver operating characteristic curve analysis. The correlations of T lymphocyte subsets with clinical, pathological data, and renal outcome were analyzed.

Results

By the end of follow-up, 45 patients (69.2%) developed end-stage renal disease (ESRD). In peripheral blood, the CD4+/CD8+ ratio showed a predictive ability with a sensitivity and specificity of 91.3% and 52.9%, respectively, which gave rise to a cutoff value of 0.89. There was a significant difference in the activity index between these two groups (3.91 ± 1.38 vs. 2.89 ± 1.13, p = 0.007). In the renal tissues, the CD4+/CD8+ ratio had the optimal cutoff point of 0.82 with a sensitivity of 57.8% and specificity of 85%. The renal activity index was higher for the renal tissues with high CD4+/CD8+ ratios than that of tissues with low CD4+/CD8+ ratios (4.32 ± 1.55 vs. 3.37 ± 1.41, p = 0.016). Peripheral blood CD4+/CD8+ ratios of ≥0.89 or renal tissue CD4+/CD8+ ratios of < 0.82 positively correlated with poor renal prognosis in patients with anti-GBM nephritis.

Conclusions

The CD4+/CD8+ ratio was associated with renal activity index both in peripheral blood and renal tissue and predicts the renal prognosis of patients with anti-GBM nephritis.
Twin Root Replacement in Congenital Heart Disease: Expert Technique
Authors: Krishnan Prasad , Dearani Joseph A. , Overman David M. , Stephens Elizabeth H. , Pochettino Alberto
Published: October 2021

In adult congenital heart disease, there are situations that require both the aortic and pulmonary roots to be replaced at the time of a reoperation. This commonly involves the replacement of a previously implanted right ventricle-pulmonary artery conduit in a patient with late aortic root dilation and/or neo-aortic valve dysfunction following the Ross procedure. Similar scenarios are encountered in patients having undergone previous repair of conotruncal anomalies such as truncus arteriosus and tetralogy of Fallot with pulmonary atresia. We describe our standardized technique for twin root replacement.
The Detrimental Dialogue Between Indian Women, Beauty Discourse, Patriarchy and Indian Feminism
Authors: Pandian Lydia VK
Published: October 2021

This framework article analyses the established connection of body image and skin tone to the ideology of power and status and the need for Indian women to achieve those beauty standards to be celebrated in their field. Even though women have gained more power, they are still defined by and in the context of men in India. Men have subtly and constructively translated this power discourse over women that has been stretching across centuries through the channels of art, literature and the portrayal of the goddesses. This pressure to continually conform to beauty’s cultural ideals and sculpt oneself to those unattainable standards leads to body dissatisfaction. It affects the image the woman has of herself. The patriarchal structure that dominates the Indian women habitus has translated the ideology of this Western concept of beauty into a ‘common sense’ that has compelled women to impose a ‘self-hegemonic’ stance and the role of Indian feminism in fighting this emerging oppressive structure.
A Pathway to Racial Equity: Student Debt Cancellation Policy Designs
Authors: Charron-Chénier Raphaël , Seamster Louise , Shapiro Thomas M. , Sullivan Laura
Published: October 2021

Student debt in the United States has had a disproportionate negative impact on black and Latinx borrowers. We argue that analyses of plans proposing student debt cancellation should therefore foreground their potential impact on racial equity. To do so, we use data from the 2019 Survey of Consumer Finances and model the impact of debt cancellation on four key policy outcomes (reach, impact on the most vulnerable borrowers, borrower wealth gains, and impact on racial wealth gaps). We examine universal policy designs as well as designs that incorporate an income eligibility threshold as a means of targeting benefits toward less affluent borrowers. We find that cancellation amounts ranging from $50,000 to $75,000 yield the most desirable outcomes, especially when paired with a relatively low household income eligibility cutoff at between $100,000 and $150,000. Such policies would cancel roughly half of all outstanding student debt without substantially expanding the racial wealth gap, while still reaching a large majority of borrowers and leading to substantial wealth gains, especially for black households.
Nationally Representative Evidence on the Association Between Preschool and Executive Function Skills Throughout Elementary School
Authors: Little Michael
Published: October 2021

Executive function skills are a set of cognitive processes that help individuals to engage in goal-directed behavior and have been linked to benefits in academic achievement and other learning-related outcomes. Recently, there has been interest in understanding how attending center-based preschool may relate to the development of executive function skills. This study used the nationally representative Early Childhood Longitudinal Study, Kindergarten Class of 2010–2011 (n ~ 9,270) to examine the association between preschool attendance and executive function skills in each grade of elementary school. The results of the analysis suggest small initial associations of preschool attendance with some subdomains of executive function (working memory) but not others (cognitive flexibility). These associations are heterogenous based on preschool type (i.e., public vs. private). The longitudinal analysis revealed rapid attenuation of initially positive associations, but also some indications of so-called “sleeper effects” emerged in late elementary school for working memory. Implications for research and policy are discussed.
Good in Providing Oral Care, but we Could be Better—Nursing Staff Identification of Improvement Areas in Oral Care
Authors: Andersson Maria , Persenius Mona
Published: October 2021

Introduction

Oral care to older people in short-term care units is a complex and challenging everyday practice for nursing staff. Oral care research and knowledge about prerequisites and obstacles is extensive. However, there is a lack of knowledge about how nursing staff in short-term care units describe their satisfaction about provided oral care in order to maintain older people's oral health.

Objective

The purpose of this study was to describe how nursing staff perceive their satisfaction of oral care provided for older people in short-term care units and to identify oral care improvements.

Methods

This study reports on the results of two open-ended questions that were part of a larger study. Informants ( n = 54) were nursing staff working in the involved short-term care units in municipalities from both densely and sparsely populated regions in central and northern Sweden. The answers to the open-ended questions were analyzed using content analysis.

Results

The analysis yielded one main category; “ Working together to improve satisfaction with older people's oral care” and four subcategories: “ Older people's oral health,” “ Consideration and respect for the older person's autonomy,” “ Having access to adequate products,” and “ Working together in the same direction.”

Conclusion

Identification of older people's oral health problems together with adequate nursing intervention will increase older people's health outcomes and quality of life. However, regardless of work role, the nursing staff might have difficulty changing their behavior or transforming intentions into actions. Oral care is a complicated and proactive practice that requires nursing staff's attention as well as both educational and organizational initiatives. Working in a supportive and collaborative relationship provides prerequisites for optimal oral care in short-term care units.
Racial and Gender Shoulder Arthroplasty Utilization Disparities of High- and Low-Volume Centers in New York State
Authors: Markes Alexander R. , Pareek Ayoosh , Mesfin Addisu , Benjamin Ma C. , Ward Derek
Published: October 2021

Introduction

The literature has consistently demonstrated utilization disparities in joint replacement procedures, though no studies have evaluated disparities in total shoulder arthroplasty with regard to operative volume.

Methods

We queried the New York (NY) Statewide Planning and Research Cooperative System (SPARCS) database for 32 410 total shoulder arthroplasties performed between 2009 and 2017. Patients were identified using Clinical Classifications Software code 154 for Non-Hip/Knee Arthroplasty and All Patient Refined-Diagnosis Related Group code 322 for Shoulder. Racial groups included Hispanic, non-Hispanic white, non-Hispanic black, and Other. High-volume centers were facilities that performed 2 standard deviations above the mean annual procedures. Utilization rates were calculated by dividing total shoulder arthroplasties per group by the 2010 NY Census population of that group. The Fisher exact test was used to determine significance.

Results

Total shoulder arthroplasty utilization increased from 43/100 000 to 73/100 000, two-thirds of which was driven by an increase in white resident utilization. More White residents per 100 000 underwent shoulder arthroplasty than Black, Hispanic, and Other residents per 100 000 residents of their respective race. White residents were 90% more likely than Hispanic residents to undergo total shoulder arthroplasty at high-volume centers ( P = .04). There were no differences in utilization rate regarding operative volume comparing Black or Other residents to White residents. More females underwent total shoulder arthroplasty than males, though there was no difference in utilization rate regarding operative volume.

Conclusion

Though total shoulder arthroplasty utilization nearly doubled, disparities persisted across gender and minority groups particularly in Hispanic utilization as White residents were 90% more likely than Hispanic residents to undergo shoulder arthroplasty at high-volume centers.
The Deception of Mass Effect: Subacute Posterior Cerebral Artery Infarction Presenting as a Mimic of Acute Middle Cerebral Artery Syndrome
Authors: Scalabrino R. , Ngo G , Iliceto Alessandro , Bramwit M. , Mirasol Raymond , Rybinnik Igor , Mehta Deviyani , Roychowdhury S.
Published: October 2021

Clinical data from 3 related cases sheds light on the complex presentation of subacute posterior cerebral artery strokes mimicking acute middle cerebral artery (MCA) syndrome. An expert witness in the field of interventional and diagnostic radiology defended a primary care physician against litigation for an alleged missed diagnosis using multimodality imaging to age a cerebrovascular event. The use of basic computerized tomography and magnetic resonance imaging physics principles are applied to determine whether a patient is outside the treatment window for thrombolytic administration or endovascular intervention. In the defended case, earlier stroke recognition would not have changed the patient’s outcome under question as he was deemed to have a completed infarct prior to presenting to the primary care physician’s (PCP’s) office, making the patient ineligible from acute stroke thrombolytic or endovascular treatment.
Indirect comparison of tisagenlecleucel and blinatumomab in pediatric relapsed/refractory acute lymphoblastic leukemia
Authors: Verneris Michael R. , Ma Qiufei , Zhang Jie , Keating Amy , Tiwari Ranjan , Li Junlong , Yang Hongbo , Agarwal Abhijit , Pacaud Lida
Published: October 2021

In the absence of head-to-head trials, an indirect-treatment comparison can estimate the treatment effect of tisagenlecleucel in comparison with blinatumomab on rates of complete remission (CR) and overall survival (OS) in patients with relapsed or primary refractory (R/R) acute lymphoblastic leukemia (ALL). Patient-level data from two pivotal trials, ELIANA (tisagenlecleucel; n = 79) and MT103-205 (blinatumomab; n = 70), were used in comparisons of CR and OS, controlling for cross-trial difference in available patient characteristics. Five different adjustment approaches were implemented: stabilized inverse probability of treatment weight (sIPTW); trimmed sIPTW; stratification by propensity score quintiles; adjustment for prognostic factors; and adjustment for both prognostic factors and propensity score. Comparative analyses indicate that treatment with tisagenlecleucel was associated with a statistically significant higher likelihood of achieving CR and lower hazard of death than treatment with blinatumomab. The tisagenlecleucel group exhibited a higher likelihood of CR than the blinatumomab group in every analysis regardless of adjustment approach (odds ratios: 6.71-9.76). Tisagenlecleucel was also associated with a lower hazard of death than blinatumomab in every analysis, ranging from 68% to 74% lower hazard of death than with blinatumomab, determined using multiple adjustment approaches (hazard ratios: 0.26-0.32). These findings support the growing body of clinical trials and real-world evidence demonstrating that tisagenlecleucel is an important treatment option for children and young adults with R/R ALL.
Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era
Authors: Yeh Jason , Whited Laura , Saliba Rima M. , Rondon Gabriela , Banchs Jose , Shpall Elizabeth , Champlin Richard , Popat Uday
Published: October 2021

Graft-versus-host disease (GVHD) is one of the leading causes of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). Posttransplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicity, and few studies have evaluated the cardiac toxicities that arise after PTCy. We completed a retrospective analysis of patients who underwent matched-donor allo-HCT at our institution and who received PTCy- or non-PTCy–based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after allo-HCT. We included 585 patients in our analysis and found that 38 (6.5%) experienced cardiac toxicity after allo-HCT. The toxicities included arrhythmias (n = 21), heart failure (n = 14), pericardial effusion (n = 10), and myocardial infarction or ischemia (n = 7). Patients who received PTCy had a 7.4% incidence of cardiac toxicity, whereas non-PTCy recipients had an incidence of 5.8% (P = .4). We found that age >55 years (P = .02) and a history of hypertension (P = .01), arrhythmia (P = .003), diabetes (P = .04), and cardiac comorbidities (P < .001) were significant predictors of cardiac toxicity, whereas none of the preparative and GVHD prophylaxis regimens were predictive. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity after allo-HCT. We found that a higher score correlated with an incidence of cardiac toxicity. Furthermore, the development of cardiac toxicity was associated with worse 1-year overall survival (OS) and NRM. The use of PTCy was associated with improvements in 1-year OS and NRM rates.
Polyphosphate expression by cancer cell extracellular vesicles mediates binding of factor XII and contact activation
Authors: Shim Young Jun , Chatterjee Victor , Swaidani Shadi , Alluri Ravi Kumar , Kundu Suman , Merkulova Alona , Angelini Dana , You Dewen , Whitney Samantha A. , Feener Edward P. , Barnard John , Schmaier Alvin H. , Khorana Alok A. , McCrae Keith R.
Published: October 2021

Extracellular vesicles (EV) have been implicated in diverse biological processes, including intracellular communication, transport of nucleic acids, and regulation of vascular function. Levels of EVs are elevated in cancer, and studies suggest that EV may stimulate thrombosis in patients with cancer through expression of tissue factor. However, limited data also implicate EV in the activation of the contact pathway of coagulation through activation of factor XII (FXII) to FXIIa. To better define the ability of EV to initiate contact activation, we compared the ability of EV derived from different cancer cell lines to activate FXII. EV from all cell lines activated FXII, with those derived from pancreatic and lung cancer cell lines demonstrating the most potent activity. Concordant with the activation of FXII, EV induced the cleavage of high molecular weight kininogen (HK) to cleaved kininogen. We also observed that EVs from patients with cancer stimulated FXII activation and HK cleavage. To define the mechanisms of FXII activation by EV, EV were treated with calf intestinal alkaline phosphatase or Escherichia coli exopolyphosphatase to degrade polyphosphate; this treatment blocked binding of FXII to EVs and the ability of EV to mediate FXII activation. In vivo, EV induced pulmonary thrombosis in wild-type mice, with protection conferred by a deficiency in FXII, HK, or prekallikrein. Moreover, pretreatment of EVs with calf intestinal alkaline phosphatase inhibited their prothrombotic effect. These results indicate that polyphosphate mediates the binding of contact factors to EV and that EV-associated polyphosphate may contribute to the prothrombotic effects of EV in cancer.
“The balloon was just the kick start, I had to do the rest myself”: Adolescents living with severe obesity experiences of an intra-gastric balloon alongside a lifestyle support programme
Authors: Reece Lindsey J. , Bissell Paul , Sachdev Pooja , Wright Neil , Mihrshahi Seema , Copeland Robert J.
Published: October 2021

Background

Few treatments exist for adolescents living with severe obesity. This qualitative study explored the experiences of severely obese adolescents and their families who participated in the BOB study.

Methods

Twelve adolescents (5 males;7 females; mean age 15 years; BMI > 3.5 s.d; puberty stage 4 +) who were engaged with the research study BOB (a non-randomised, pilot novel obesity treatment programme that involved the insertion of an intra-gastric balloon coupled with a family lifestyle behavioural support programme). Adolescents attended weekly lifestyle sessions before, during and post balloon insertion. All participants were interviewed at 3 months, (halfway through intra-gastric balloon insertion) and at 12 months follow-up (6 months post intra-gastric balloon removal, 3 months post lifestyle intervention).

Results

All BOB participants had exhausted all treatment options deeming this study their final option. Many alluded to feelings of desperation and referred to a sense of hope that this intervention would be effective. Family involvement and attendance within the structured sessions differed significantly. Adolescents and parents perceived support from the research study ceased when the intra-gastric balloon was removed at 6-months despite attendance post balloon removal being poor. All participants emphasised a need for further support longer term with the integration of the family a critical factor.

Conclusions

Further research is needed to explore the specific role families play within treatment to optimise health and wellbeing outcomes. Adolescents perspectives should be integrated within treatment to inform and improve the effectiveness of future treatment programmes for severely obese adolescents and their families.
Knowledge of Palestinian women about cervical cancer warning signs: a national cross- sectional study
Authors: Elshami Mohamedraed , Al-Slaibi Ibrahim , Abukmail Hanan , Alser Mohammed , Radaydeh Afnan , Alfuqaha Alaa , Thalji Mariam , Khader Salma , Khatib Lana , Fannoun Nour , Ahmad Bisan , Kassab Lina , Khrishi Hiba , Elhussaini Deniz , Abed Nour , Nammari Aya , Abdallah Tumodir , Alqudwa Zaina , Idais Shahd , Tanbouz Ghaid , Hajajreh Ma’alem , Selmiyh Hala Abu , Abo-Hajouj Zakia , Hebi Haya , Zamel Manar , Skaik Refqa , Hammoud Lama , Rjoub Siba , Ayesh Hadeel , Rjoub Toqa , Zakout Rawan , Alser Amany , Abu-El-Noor Nasser , Bottcher Bettina
Published: October 2021

Background

Timely presentation and diagnosis of cervical cancer (CC) are crucial to decrease its mortality especially in low- and middle-income countries like Palestine. This study aimed to evaluate the knowledge of Palestinian women about CC warning signs and determine the factors associated with good knowledge.

Methods

This was a national cross-sectional study conducted between July 2019 and March 2020 in Palestine. Stratified convenience sampling was used to recruit adult women from hospitals, primary healthcare centers, and public spaces of 11 governorates. A translated-into-Arabic version of the validated CC awareness measure (CeCAM) was used to assess women’s knowledge of 12 CC warning signs.

Results

Of 8086 approached, 7223 participants completed the CeCAM (response rate = 89.3%). A total of 7058 questionnaires were included in the analysis: 2655 from the Gaza Strip and 4403 from the West Bank and Jerusalem (WBJ). The median age [interquartile range] for all participants was 34.0 [24.0, 42.0] years. Participants recruited from the WBJ were older, getting higher monthly income, and having more chronic diseases than those recruited from the Gaza Strip.

The most frequently identified warning sign was ‘vaginal bleeding after menopause’ (n = 5028, 71.2%) followed by ‘extreme generalized fatigue’ (n = 4601, 65.2%) and ‘unexplained weight loss’ (n = 4578, 64.9%). Only 1934 participants (27.4%) demonstrated good knowledge of CC warning signs. Participants from the Gaza Strip were slightly more likely than participants from the WBJ to have a good level of knowledge. Factors associated with having good knowledge included having a bachelor or postgraduate degree, being married, divorced, or widowed as well as knowing someone with cancer.

Conclusion

The overall awareness of CC warning signs was low. Educational interventions are needed to increase Palestinian women’s awareness of CC warning signs.
The cytotoxic effect of Baeckea frustescens extracts in eliminating hypoxic breast cancer cells
Authors: Shahruzaman S. H. , Yusof F. Z. , Maniam S. , Fakurazi S. , Maniam S.
Published: October 2021

Background

Adaptive metabolic response towards a low oxygen environment is essential to maintain rapid tumour proliferation and progression. The vascular network that surrounds the tumour develops an intermittent hypoxic condition and stimulates hypoxia-inducing factors. Baeckea frutescens is used in traditional medicine and known to possess antibacterial and cytoprotective properties. In this study, the cytotoxic effect of B. frutescens leaves and branches extracts against hypoxic human breast cancer (MCF-7) was investigated.

Method

The extracts were prepared using Soxhlet apparatus for ethanol and hexane extracts while the water extracts were freeze-dried. In vitro cytotoxic activities of B. frutescens extracts of various concentrations (20 to 160 μg/mL) at 24, 48, and 72 hours time points were studied using MTT in chemically induced hypoxic condition and in 3-dimensional in vitro cell culture system. An initial characterisation of B. frutescens extracts was carried out using Fourier-transform Infrared- Attenuated Total Reflection (FTIR-ATR) to determine the presence of functional groups.

Results

All leaf extracts except for water showed IC50 values ranging from 23 -158 μg/mL. Hexane extract showed the lowest IC50 value (23 μg/mL), indicating its potent cytotoxic activity. Among the branch extracts, only the 70% ethanolic extract (B70) showed an IC50 value. The hexane leaf extract tested on 3- dimensional cultured cells showed an IC50 value of 17.2 μg/mL. The FTIR-ATR spectroscopy analysis identified various characteristic peak values with different functional groups such as alcohol, alkenes, alkynes, carbonyl, aromatic rings, ethers, ester, and carboxylic acids. Interestingly, the FTIR-ATR spectra report a complex and unique profile of the hexane extract, which warrants further investigation.

Conclusion

Adaptation of tumour cells to hypoxia significantly contributes to the aggressiveness and chemoresistance of different tumours. The identification of B. frutescens and its possible role in eliminating breast cancer cells in hypoxic conditions defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer.
Protocol refinement for a diabetes pragmatic trial using the PRECIS-2 framework
Authors: Glasgow Russell E. , Gurfinkel Dennis , Waxmonsky Jeanette , Rementer Jenny , Ritchie Natalie D. , Dailey-Vail Jennifer , Hosokawa Patrick , Dickinson L. Miriam , Kwan Bethany M.
Published: October 2021

Background

This report describes how we refined a protocol for a pragmatic comparative effectiveness study of two models of an evidence-based diabetes shared medical appointment intervention and used the PRECIS-2 rating system to evaluate these adaptations.

Methods

We report primary data collected between June and August 2019, and protocol refinements completed between 2018 and 2020. Twenty-two members of the study team collaborated in protocol refinement and completed the PRECIS-2 ratings of study pragmatism. We discuss study design refinements made to achieve the desired level of pragmatism vs. experimental control for each of the nine PRECIS-2 dimensions. Study team members received training on PRECIS-2 scoring and were asked to rate the study protocol on the nine PRECIS-2 dimensions. Ratings were compared using descriptive statistics.

Results

In general, the PRECIS-2 ratings revealed high levels of pragmatism, but somewhat less pragmatic ratings on the categories of Delivery and Organization (costs and resources). This variation was purposeful, and we provide the rationale for and steps taken to obtain the targeted level of pragmatism on each PRECIS-2 dimension, as well as detail design changes made to a) make the design more pragmatic and b) address COVID-19 issues. There was general agreement among team members and across different types of stakeholders on PRECIS-2 ratings.

Conclusions

We discuss lessons learned from use of PRECIS-2 and experiences in refining the study to be maximally pragmatic on some dimensions and less so on other dimensions. This paper expands on prior research by describing actions to achieve higher levels of pragmatism and revise our protocol fit to the changed context. We make recommendations for future use of PRECIS-2 to help address changing context and other strategies for the planning of and transparent reporting on pragmatic research and comparative effectiveness research.

Trial registration

Clinicaltrials.gov Registration ID: NCT03590041.
A human iPSC-derived inducible neuronal model of Niemann-Pick disease, type C1
Authors: Prabhu Anika V. , Kang Insung , De Pace Raffaella , Wassif Christopher A. , Fujiwara Hideji , Kell Pamela , Jiang Xuntian , Ory Daniel S. , Bonifacino Juan S. , Ward Michael E. , Porter Forbes D.
Published: October 2021

Background

Niemann-Pick disease, type C (NPC) is a childhood-onset, lethal, neurodegenerative disorder caused by autosomal recessive mutations in the genes NPC1 or NPC2 and characterized by impaired cholesterol homeostasis, a lipid essential for cellular function. Cellular cholesterol levels are tightly regulated, and mutations in either NPC1 or NPC2 lead to deficient transport and accumulation of unesterified cholesterol in the late endosome/lysosome compartment, and progressive neurodegeneration in affected individuals. Previous cell-based studies to understand the NPC cellular pathophysiology and screen for therapeutic agents have mainly used patient fibroblasts. However, these do not allow modeling the neurodegenerative aspect of NPC disease, highlighting the need for an in vitro system that permits understanding the cellular mechanisms underlying neuronal loss and identifying appropriate therapies. This study reports the development of a novel human iPSC-derived, inducible neuronal model of Niemann-Pick disease, type C1 (NPC1).

Results

We generated a null i3Neuron (inducible × integrated × isogenic) (NPC1−/− i3Neuron) iPSC-derived neuron model of NPC1. The NPC1−/− and the corresponding isogenic NPC1+/+ i3Neuron cell lines were used to efficiently generate homogenous, synchronized neurons that can be used in high-throughput screens. NPC1−/− i3Neurons recapitulate cardinal cellular NPC1 pathological features including perinuclear endolysosomal storage of unesterified cholesterol, accumulation of GM2 and GM3 gangliosides, mitochondrial dysfunction, and impaired axonal lysosomal transport. Cholesterol storage, mitochondrial dysfunction, and axonal trafficking defects can be ameliorated by treatment with 2-hydroxypropyl-β-cyclodextrin, a drug that has shown efficacy in NPC1 preclinical models and in a phase 1/2a trial.

Conclusion

Our data demonstrate the utility of this new cell line in high-throughput drug/chemical screens to identify potential therapeutic agents. The NPC1−/− i3Neuron line will also be a valuable tool for the NPC1 research community to explore the pathological mechanisms contributing to neuronal degeneration.

Graphical abstract
Prognostic significance of preoperative serum triglycerides and high-density lipoproteins cholesterol in patients with non-small cell lung cancer: a retrospective study
Authors: Ma Cong , Wang Xiaoyan , Guo Jingjing , Liu Ping
Published: October 2021

Background

Abnormalities in serum lipids and lipoproteins have been documented to link to the risk of cancers in recent years, but its prognostic value for cancer is not known. This study retrospectively evaluated the significance of preoperative serum lipids and lipoproteins for NSCLC’s prognosis.

Methods

A retrospective review was implemented of 551 patients succumbed to NSCLC. A ROC curve was utilized to determine the best cut-off value and area under the ROC curve. Kaplan-Meier and a Cox proportional hazards model were utilized to perform survival analysis.

Results

With a median follow-up of 42 months, the NSCLC patients in the high TG (> 1.21 mmol/L) and low HDL-C (≤ 1.26 mmol/L) two groups exhibited shorter OS and DFS. In multivariable analysis, preoperative HDL-C and TG can work as independent prognosis factors for OS (P<0.001 for both) and DFS (P<0.05 for both) in patients succumbed to NSCLC.

Conclusion

Abnormalities of serum lipids and lipoproteins metabolism linked to the survival outcomes of NSCLC. Preoperative serum HDL-C and TG may be promising biomarkers to predict the NSCLC patients’ prognosis.