bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Outcome Analysis of Pyrotinib in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastasis: A Real-World Study
Authors: Liang Xu , Gui Xinyu , Yan Ying , Di Lijun , Liu Xiaoran , Li Huiping , Song Guohong
Published: August 2023

Background

Pyrotinib is currently approved for the treatment of HER2-positive advanced breast cancer in China. Data on the overall survival (OS) and efficacy in patients with brain metastasis (BM) remain scarce. This study evaluated the effectiveness of pyrotinib in a real-world setting, especially in patients with BM.

Methods

We reviewed patients with metastatic breast cancer treated with pyrotinib-based therapy between June 2018 and June 2022. Progression-free survival (PFS), OS, objective response rate, and safety were analyzed following the administration of pyrotinib.

Results

A total of 239 patients were included. The median PFS in patients who received pyrotinib-based therapy as first-line (15/239), second-line (115/239), or third-or-higher-line (109/239) treatment was 14.00, 9.33, and 8.20 months, respectively, and the median OS was not reached, 29.07 and 22.23 months, respectively. The median PFS in patients who pretreated with trastuzumab (214/239), trastuzumab plus pertuzumab (22/239), lapatinib (68/239), or trastuzumab emtansine (14/239) was 9.33, 6.87, 7.20, and 7.20 months, respectively. In 61 patients with BM, the median PFS was 7.50 months, the median central nervous system (CNS)-PFS was 11.17 months, and the median OS was 21.27 months. Furthermore, 19 patients with concomitant brain radiotherapy tended to achieve a longer OS than 42 patients without radiation (34.17 vs. 20.70 months, P = .112).

Conclusions

Long-term outcomes of pyrotinib-based therapy are promising for patients with HER2-positive metastatic breast cancer in real world and in patients with BM, regardless of the treatment lines and prior anti-HER2 therapies.
Increased KRAS G12C Prevalence, High Tumor Mutational Burden, and Specific Mutational Signatures Are Associated With MUTYH Mutations: A Pan-Cancer Analysis
Authors: Disel Umut , Sivakumar Smruthy , Pham Tim , Fleischmann Zoe , Anu R I , Sokol Ethan S , Kurzrock Razelle
Published: August 2023

The aim of this study was to determine the pan-cancer landscape of MUTYH alterations and the relationship between MUTYH mutations and potentially actionable biomarkers such as specific genomic alterations, tumor mutational burden, and mutational signatures. We used a large pan-cancer comprehensive genomic dataset from patients profiled (tissue next generation sequencing) during routine clinical care. Overall, 2.8% of 229 120 solid tumors had MUTYH alterations, of which 55% were predicted germline. Thirty tumor types had a 2% or greater MUTYH mutation rate. MUTYH-altered versus -WT cancers had significantly higher tumor mutational burden and more frequent alterations in KRAS G12C, but not in KRAS in general; these observations were statistically significant, especially in colorectal cancers. Across cancers, PD-L1 expression levels (immunohistochemistry) were not associated with MUTYH alteration status. In silico computation demonstrated that MUTYH mutational signatures are associated with higher levels of hydrophobicity (which may reflect higher immunogenicity of neoantigens) relative to several other signature types such as microsatellite instability. Survival of patients with MUTYH-altered versus -WT tumors was similar. In conclusion, comprehensive genomic profiling suggests that several features of MUTYH-altered cancers may be pharmacologically targetable. Drugs such as sotorasib (targeting KRAS G12C) and immune checkpoint inhibitors, targeting the increased mutational load and higher neo-antigen hydrophobicity/immunogenicity merit investigation in MUTYH-mutated malignancies.
Patient-Reported Outcomes in KEYNOTE-564: Adjuvant Pembrolizumab Versus Placebo for Renal Cell Carcinoma
Authors: Choueiri Toni K , Tomczak Piotr , Park Se Hoon , Venugopal Balaji , Symeonides Stefan , Hajek Jaroslav , Ferguson Thomas , Chang Yen-Hwa , Lee Jae Lyun , Haas Naomi , Sawrycki Piotr , Sarwar Naveed , Gross-Goupil Marine , Thiery-Vuillemin Antoine , Mahave Mauricio , Kimura Go , Perini Rodolfo F , Saretsky Todd L , Bhattacharya Rituparna , Xu Lei , Powles Thomas
Published: August 2023

Background

In patients with renal cell carcinoma (RCC) enrolled in the phase III KEYNOTE-564 trial (NCT03142334), disease-free survival (DFS) following nephrectomy was prolonged with use of adjuvant pembrolizumab therapy versus placebo. Patient-reported outcomes (PROs) provide an important measure of health-related quality of life (HRQoL) and can complement efficacy and safety results.

Patients and Methods

In KEYNOTE-564, 994 patients were randomly assigned to receive pembrolizumab 200 mg (n = 496) or placebo (n = 498) intravenously every 3 weeks for ≤17 cycles. Patients who received ≥1 dose of treatment and completed ≥1 HRQoL assessment were included in this analysis. HRQoL end points were assessed using the EORTC QLQ-C30, FKSI-DRS, and EQ VAS. Prespecified and exploratory PRO end points were mean change from baseline in EORTC QLQ-C30 GHS/QoL score, EORTC QLQ-C30 physical function subscale score, and FKSI-DRS score.

Results

No clinically meaningful difference in least squares mean scores for pembrolizumab versus placebo were observed at week 52 for EORTC QLQ-C30 GHS/QoL (–2.5; 95% CI –5.2 to 0.1), EORTC QLQ-C30 physical functioning (–0.87; 95% CI –2.7 to 1.0), and FKSI-DRS (–0.7; 95% CI –1.2 to –0.1). Most PRO scores remained stable or improved for the EORTC QLQ-C30 GHS/QoL (pembrolizumab, 54.3%; placebo, 67.5%), EORTC QLQ-C30 physical functioning (pembrolizumab, 64.7%; placebo, 68.8%), and FKSI-DRS (pembrolizumab, 58.2%; placebo, 66.3%).

Conclusions

Adjuvant treatment with pembrolizumab did not result in deterioration of HRQoL. These findings together with the safety and efficacy findings support adjuvant pembrolizumab treatment following nephrectomy.

Trial Registration

Clinicaltrials.gov Identifier: NCT03142334
Delayed Versus Immediate Start of Chemotherapy in Asymptomatic Patients With Advanced Cancer: A Meta-Analysis
Authors: Augustinus Simone , Thurairajah Gajanan , Besselink Marc G , van Laarhoven Hanneke W M , van Oijen Martijn G H , Mackay Tara M , Wilmink Johanna W
Published: August 2023

Background

Due to increased use of imaging, advanced stages of cancer are increasingly being diagnosed in an early, asymptomatic phase. Traditionally, chemotherapy is started immediately in these patients. However, a strategy wherein chemotherapy is withheld until symptoms occur may be beneficial for patients in terms of quality of life (QOL). A systematic review regarding optimal timing of chemotherapy including survival and QOL is lacking.

Methods

We systematically searched PubMed, EMBASE, and Cochrane for studies investigating the timing of start of chemotherapy in asymptomatic patients with advanced cancer. Overall survival (OS) was abstracted as primary, QOL, and toxicity as secondary outcomes. A meta-analysis was performed on OS. QOL was described using the global health status derived from the EORTC-QLQ-C30 questionnaire and toxicity as grade 3-4 adverse events.

Results

Overall, 919 patients from 4 randomized controlled trials and 1 retrospective study were included. The included studies investigated colorectal cancer (n = 3), ovarian cancer (n = 1), and gastric cancer (n = 1). Pooled analysis demonstrated no significant differences in OS between delayed and immediate start of chemotherapy (pooled HR: 1.05, 95% CI, 0.90-1.22, P = .52). QOL, evaluated in 3 studies, suggested a better QOL in the delayed treatment group. Toxicity, evaluated in 2 studies, did not differ significantly between groups.

Conclusion

This meta-analysis confirms the need for prospective studies on timing of start of chemotherapy in asymptomatic patients with advanced cancer. The limited evidence available suggests that delayed start of chemotherapy, once symptoms occur, as compared to immediate start in asymptomatic patients does not worsen OS while it may preserve QOL.
Mitochondria in Early Forebrain Development
Authors: Fame Ryann M. , Lehtinin Maria K.
Published: August 2023

Function of the mature central nervous system (CNS) requires a substantial proportion of the body’s energy consumption. During development, the CNS anlage must maintain its structure and perform stage-specific functions as it proceeds through discrete developmental stages. While key extrinsic signals and internal transcriptional controls over these processes are well appreciated, metabolic and mitochondrial states are also critical to appropriate forebrain development. Specifically, metabolic state, mitochondrial function, and mitochondrial dynamics/localization play critical roles in neurulation and CNS progenitor specification, progenitor proliferation and survival, neurogenesis, neural migration, and neurite outgrowth and synaptogenesis. With the goal of integrating neurodevelopmental biologists and mitochondrial specialists, this chapter synthesizes data from disparate models and processes to compile and highlight key roles of mitochondria in the early development of the CNS with specific focus on forebrain development and corticogenesis.
Performing Difference
Authors: Leske Ben , Bibb Jennifer , McFerran Katrina Skewes
Published: August 2023

This chapter explores the experiences of 10 members of the Melbourne Gay and Lesbian Youth Chorus (the Youth Chorus), Australia’s first community choir for same sex attracted and gender diverse (SSAGD) young people. Using interpretive phenomenological analysis (IPA) and the sociological framework of ‘music asylum’, this research describes how the youth chorus were offered a place of safety within the structure of the choir where being queer was the norm rather than the exception. Drawing on the theoretical focus of community music and community music therapy, this chapter analyses how the choir’s construction of difference was expressed musically and socially through performance. The research concludes that the choir provided its members with musical and extra-musical platforms to rehearse and publicly perform musical and social identities, depicting what it means to be different.
Autonomism
Authors: Stear Nils-Hennes
Published: August 2023

This chapter examines autonomism. Autonomism is roughly the view that an artwork’s ethical properties do not bear on its aesthetic or artistic value. The author sketches some of the view’s history before describing various versions of it defended over the last quarter-century. These are divided into ‘radical’, ‘robust’, and ‘moderate’ forms of autonomism. The author considers the strengths and weaknesses of each. The author also devotes some space to the ‘interactionist’ views against which contemporary autonomism is typically opposed. In doing so, he considers the so-called ‘qua problem’ at some length, as well its bearing on these various autonomist positions.
Election Law and Democratic Theory
Authors: Gardner James A.
Published: August 2023

Election law is the body of law by which a society implements its commitment to democracy. Any meaningful evaluation of the suitability or effectiveness of a society’s election law therefore requires some inquiry into the nature of the society’s democratic commitments—the theory or conception of democracy to which it subscribes. Virtually all such theories are rooted in philosophical liberalism but nevertheless come in many varieties. Reconstructing a society’s democratic commitments can be complicated by its failure to articulate or even to reflect upon them. In the United States, that difficulty is compounded by a long history of evolution in American conceptions of democracy, as well as by the presence of a long-standing, competing strand of illiberal and antidemocratic thought, culminating in the sudden, recent turn to right-wing populism. This populism claims to be motivated by a democratic wish to serve the interests of the people, but its conception of the people is narrow and exclusive, and its conception of elections is decidedly illiberal and undemocratic. The kind of populism now associated with the Republican Party is thus not a plausible alternative to the inherited conceptions of liberal democracy to which the U.S. Constitution is demonstrably committed.
Black Women’s Intellectual Traditions
Authors: Stewart Lindsey
Published: August 2023

For those interested in the historical intellectual contributions of African American women, the written archives often present a significant challenge—as many contemporary Black feminist thinkers (i.e., Alice Walker, Toni Morrison, Patricia Hill Collins, Saidiya Hartman) have pointed out. One way that Black feminists have negotiated this challenge is, as Alice Walker suggests, to turn to “our mothers’ gardens” when attempting to trace these intellectual traditions. This chapter takes up Walker’s suggestion by analyzing the oral archive of rootwork, or conjure, a spiritual tradition that heavily relies upon gardening. My analysis centers on two prominent nineteenth-century conjure women: the famous “voodoo queen” of New Orleans, Marie Laveau, and her lesser-known contemporaries Mary Seacole and Betsy Toledano.
Women under Contract
Authors: Philips Menaka
Published: August 2023

Though the story of the sexual contract emerged through studies of canonical male writers, that approach risks erasing women’s agency from view. It also detaches our understanding of the sexual contract and its regulatory institutions from the lived experiences and political insights of its subjected class. Reading through the perspectives of the contract’s male architects, in other words, renders women silent in a story about their own subordination. This chapter proposes an alternative: working with the extant writings of Harriet Taylor Mill (HTM), it recovers women as complex agents in the story of the sexual contract. Drawing on what I call HTM’s “experiential politics”—a politics derived through critical examinations of the everyday—the argument follows her study of marriage and motherhood in nineteenth-century England. Her observations outline how these institutions constructed women as subjects of the sexual contract, as well as the ways in which women consciously worked against and alongside their regulations. Recovering HTM’s experiential politics as a lens through which to understand the sexual contract can thus recenter women as political actors in the story. In so doing, the argument raises important questions about how the intellectual borders of the history of political thought are defined, and about the diverse range of resources that lies beyond them.
New Guinea and Near Oceania
Authors: Golitko Mark
Published: August 2023

This chapter explores the archaeological landscapes of Near Oceania and New Guinea. Even if questions of linguistic diversification and spread have primarily dominated the archaeology of Near Oceania, the region has much to offer to broader studies of island and coastal archaeology. The morphology and environments of coastal Near Oceania have altered dramatically throughout human occupation. In addition to logistical challenges including working across national boundaries, changes in coastal geomorphology have either erased or deeply buried the early archaeological record of much of the region. The chapter highlights the importance of archaeology in the future and addresses the challenges of anthropogenic climate change and development affecting the ecology and heritage in New Guinea and its surrounding islands.
The Parent-Child Dyad and Other Family Factors Associated with Youth Nonsuicidal Self-Injury
Authors: James Kiera M. , Gibb Brandon E.
Published: August 2023

Nonsuicidal self-injury (NSSI) is a significant public health concern with clear negative consequences for the individual and their families. NSSI is most prevalent during adolescence—a developmental period during which youth navigate normative interpersonal stressors and developmental challenges. Although elevated rates of NSSI during adolescence are likely due to a combination of genetic, environmental, and contextual factors, this chapter focuses specifically on the influence of parents and the parent-child relationship on risk. To this end, we outline relevant theoretical frameworks in the context of developmental trajectories of NSSI. We review risk factors involving parents and the parent-child dyad, including parent-related factors that perpetuate risk in the context of parental awareness or youth disclosure of NSSI. We discuss protective factors within the parent-child dyad that reduce risk for youth NSSI, and provide an overview of interventions for youth NSSI that involve strong parental components, including parent training and parent education programs.
Ways of Caring in Music Education Through the Lens of Classic Confucianism and Classic Daoism
Authors: Fung C. Victor
Published: August 2023

Classic principles of Confucianism and Daoism are ubiquitous and have been intertwined with many people’s lives for two and a half millennia. There are striking parallels between their metaphysical principles and the act of caring in education. This chapter focuses on contemporary ways of cultivating care in music education through the lens of these philosophical schools. Core Confucian principles of sincerity, kindness, benevolence, and being an exemplary person and core Daoist principles of non-egoistic action, observation, equality, and flexibility work side-by-side in a complementary way to uncover these parallels with contemporary ethic of care. Along with the Confucian dao and the Daoist dao, multiple ways of cultivating care in music education are explored.
Sometimes I Just Crawl Under the Covers and Hide
Authors: Evison Fiona
Published: August 2023

Times of crises impact music communities on multiple levels, requiring novel care for members and leaders. Using care ethics as a framework, I draw from twelve community music leaders’ perceptions and experiences of maintaining the “community” in their community music groups during a time of far-reaching disruption. When the empathy, compassion, and love that leaders offer members cannot be enacted or reciprocated due to crisis, care can be offered and received through alternative routes that might involve technology, new learning curves and challenges, shifting goals, and need-based approaches. Crises highlight how community educators can maintain the social and musical benefits of music-making under disruption. To do so, however, leaders need caring support systems embedded in reciprocal care relations.
Compassion During Musical Engagement with Young Children
Authors: Dansereau Diana R.
Published: August 2023

Music educators may accept the idea that students are their equals in a humanitarian sense and likely strive toward compassionate teaching; however, truly embracing that young children (inclusive of those who are infants, toddlers, preschoolers, and of early elementary age) are in fact equivalent participants in musical expression and shaping musical interactions, may necessitate a shift in how adults conceptualize childhood. In this chapter, I discuss three commonly held deficit views of childhood and contrast them with a progressive and compassionate reconceptualization of childhood. This reconceptualization positions infants, toddlers, preschoolers, and young children as rich sources of musical knowledge, and active and equal agents in life, relationships and music-making.
Abuse-Deterrent and Sustained-Release Opioid Formulations
Authors: Luba Rachel R. , Comer Sandra D. , Nunes Edward V.
Published: August 2023

Abuse-deterrent formulations (ADF) of opioids were developed to mitigate nonprescribed opioid use in the context of pain management and medication treatment for opioid use disorder (MOUD). This chapter begins with a case study to illustrate the potential value of ADF formulations before outlining the historical context and rationale for developing ADF opioid medications and the principles of these formulations, including their pharmacokinetic and pharmacodynamic properties. It then reviews the laboratory studies of tamper resistance and discusses the subjective effects of these products, including OxyContin, Xtampza ER, Hysingla ER, MorphaBand ER, and RoxyBand, and how they compare to non-ADF versions of these products. Next, the chapter reviews the utility and efficacy of ADFs as outlined in post-marketing studies, before discussing new formulations for buprenorphine including Sublocade, Brixadi, and Probuphine. It concludes with a discussion about the efficacy and utility of these novel formulations for OUD treatment, before returning to our original case example to highlight the added value an ADF compound could provide.
Methadone
Authors: Buchholz Jonathan R. , Kalmoe Molly , Stamschror Justin , Saxon Andrew J.
Published: August 2023

Methadone, a highly effective but tightly regulated treatment for opioid use disorder, reduces morbidity and mortality in patients with this condition. Methadone has a unique pharmacologic profile and is metabolized variably by patients, resulting in a wide range of maintenance doses. An adequate maintenance dose should eliminate opioid withdrawal symptoms for at least 24 hours and abate opioid cravings, allowing the patient to function unimpaired in daily activities. Furthermore, optimal dosing minimizes side effects, which commonly include sedation, nausea, constipation, and sweating. Clinically significant QTc prolongation is rare, but patients with serious cardiac risk factors should be monitored by EKG. While there are no absolute contraindications to methadone, it is important to consider patient preference, ability to dose regularly in clinic, co-morbid medical conditions, and drug–drug interactions. Finally, clinicians and patients alike must remain cognizant of additive respiratory depression and CNS effects when methadone is combined with alcohol and sedative-hypnotics.
Neonatal Abstinence Syndrome
Authors: Heil Sarah H. , Melbostad Heidi S. , Cioffredi Leigh-Anne
Published: August 2023

Neonatal abstinence syndrome (NAS) is a constellation of signs involving the central and autonomic nervous, respiratory, and gastrointestinal systems, that typically appear in the first few days after delivery in infants exposed to opioids and other substances in utero. This chapter uses a case study to highlight some of the history and evolution in the scientific literature on NAS, including the results of many recent reviews. Changing practices around treatment options for pregnant people with opioid use disorder are examined, including medically supervised withdrawal, agonist treatment with methadone and buprenorphine, and antagonist treatment with naltrexone. Maternal medication dose and other factors associated with NAS outcomes, like breastfeeding and rooming in, are also considered and the involvement of child protective services with these families is discussed. In addition, shifts in how NAS is assessed are examined, including clinical judgment, weighted points-based assessments of NAS signs, and a simplified assessment of neonatal functioning. Pharmacotherapies for treating NAS and the neurodevelopmental outcomes of exposed neonates are also considered.
The Contingencies of an Academic Field
Authors: Paquette Jonathan , Bérubé Julie
Published: August 2023

Disciplines such as biology, physics, sociology, and political science, among others, have a long-standing history and place in academia, and the institutional context in which research is conducted has evolved along these lines. Arts management, however, belongs to a different model; it is not a discipline but a heterogeneous field—which, for researchers, may imply a different context and set of conditions for conducting research. This chapter’s objective is to understand academic fields from an institutional perspective, by focusing on the possibilities available to those who navigate and conduct their career in the field of arts management in Canada. More specifically, this chapter seeks to understand both the dynamics of national institutions practicing research in arts management and the financial and symbolic capital available to and accumulable by researchers in the field who work in Canadian universities. To this end, four parameters are studied in relation to arts management: associations and learned societies, publications and journals, available research funding, and research chairs. This chapter concludes with observations on the conditions of arts management research in Canada, and reflections on the methodological challenges pertaining to its study as a field of research.
Ethnicity and Cultural Dynamics
Authors: Bunce John A. , McElreath Richard
Published: August 2023

Much cultural variation in humans is structured by ethnic identity, which entails perceptions of covariance between easily observable markers, difficult to observe norms, and, often, (potentially mythical) ancestry. The dynamics of ethnic identity involve changes in the distributions of these perceptions in a population over time. This chapter synthesizes work in the fields of anthropology, psychology, sociology, and economics on the relationship between ethnicity and cultural evolution, examining concepts such as ethnic markers and boundaries, cultural norms, essentialism, correlative and complementary coordination, and cross-cultural competence. We explore (i) the scope of ethnicity, and the challenge of how to distinguish it from other identity labels, (ii) the adaptive nature of ethnic psychology, (iii) the dynamics of ethnic perceptions, relating both to changes in the perceptions of an individual’s ethnicity, and changes in the perceptions of what a particular ethnic identity entails, (iv) consequences of ethnicity for other cultural dynamics, and (v) challenges for future research.
Citizensourcing policy advisory systems in a turbulent era
Authors: Moon M. Jae , Lee Seulgi , Park Seunggyu
Published: August 2023

Extending previous works on major changes in policy advisory systems (PASs), such as externalization (locus) and politicization (government control), this study examines whether and how democratization (citizensourcing) of PASs works based on the case of the Kwanghwamun Citizensourcing Policy Platform, which operated for 4 years under the Moon Jae-in administration in South Korea. Analyzing more than 11,000 policy suggestions proposed by ordinary citizens on the digital policy platform, this study investigates how citizensourced policy ideas are discussed, incubated, and finally adopted through interactions among ordinary citizens, policy experts, and government agencies. Based on the belief that the operation of PASs becomes increasingly complicated and often dysfunctional as societies face more “wicked”, cross-cutting, and volatile policy problems than ever, this study argues that citizensourcing policymaking is critical to ensuring policy legitimacy and receptivity. This study suggests that both the quality and features of citizensourced policy ideas are important for advancing policymaking processes. This study also finds that political cycle and active citizen policy entrepreneurs are also critical factors, while it shows noteworthy limits on the quality and features of citizensourced policy ideas, which, in fact, lead to a frustratingly low policy adoption rate. This study suggests that governments need to actively capitalize on the power of ordinary citizens as citizen experts, while the shortcomings and risks of citizensourcing PASs also need to be carefully addressed.
Knowledge–practice gap in healthcare payments: the role of policy capacity
Authors: Bali Azad Singh , Ramesh M
Published: August 2023

Fee-for-service remains a popular mode of paying for healthcare despite widespread knowledge of its ill effects. This has resulted in a gap between policy knowledge (understood as consensus among experts) and policy practice (actual policy measures to implement the consensus) in healthcare. The existing literature attributes such gaps to a range of factors, including the stakeholders’ different interests, incentives, ideas, and values. Our focus on this debate is through the lens of policy capacity, specifically the ability of public actors to utilize policy knowledge and inform policy practice. We show that the observed knowledge–practice gap is rooted in the complexity of healthcare payment reforms. While actors agree on the problematic condition, there is a deep disagreement on what to do about it. Agreeing on and adopting alternate payment arrangements are challenging because reformers need to anticipate and respond to the future while accommodating the interests of the current providers who benefit from the status quo. In such instances, the capacity of public actors to devise reforms and overcome resistance to them is critical. We argue that the knowledge–practice gap in healthcare payments exists because of deficiencies in the analytical abilities of governments to devise workable alternate arrangements and shortcomings in their political capacity to overcome the resistance to proposed reforms. Put differently, we argue that no amount of evidence or consensus among stakeholders is sufficient when the analytical and political capacities to act on the evidence are lacking. The arguments are illustrated with reference to payment reforms in South Korea and Thailand.
Unveiling the Therapeutic Potential of Non-Coding RNAs in Stroke-Induced Tissue Regeneration
Authors: Waseem Arshi , Khan Abdul Quaiyoom , Khan Mohsin Ali , Khan Rehan , Uddin Shahab , Boltze Johannes , Raza Syed Shadab
Published: August 2023

Stroke is a major contributor to mortality and impairment on a global scale, with few effective treatments available. Aberrant expression of various non-coding RNAs (ncRNAs) has been identified after stroke onset, impacting neurogenesis, angiogenesis, apoptosis, and autophagy. The roles and mechanisms of ncRNAs hold great promise for future ischemic stroke treatments, as they could modify stroke impact and course on a well-controllable molecular level. Exploring the functions and underlying mechanisms of ncRNAs after stroke has the potential to unveil novel therapeutic targets for the treatment of stroke and may also pave the way toward novel and more precise diagnostic options for stroke and stroke outcomes. This review emphasizes the importance of ncRNAs in the treatment of stroke and their potential as therapeutic targets.
Investing in their best interests: considerations for trustees from the rise of ESG
Authors: Steen Peter , Rhodes Alexander , Carslaw Emilia , Cornaglia Margherita
Published: August 2023

The debate about whether a trustee’s fiduciary duties preclude or require consideration of environmental, social and governance (ESG) issues when making investments is rapidly evolving. The orthodox approach, that a trustee must pursue maximum profit to the exclusion of all other considerations, continues to face increasing pressure. A new generation of beneficiaries is increasingly pushing for investment strategies which respond to global pressures and trends (such as climate change-driven extreme weather events, biodiversity loss and inequality). Markets are increasingly taking account of the materiality of ESG considerations to financial value. Trustees following the orthodoxy now find themselves in an increasingly uncomfortable position as these pressures compete with their traditional duties and powers. Today, trustees must be cognisant of and regularly assess ESG issues and be seen to be doing so, failing which they may be exposed to business and reputational—and, increasingly, legal—risk.
Different patterns of intrinsic functional connectivity at the default mode and attentional networks predict crystalized and fluid abilities in childhood
Authors: Lombardo Diego , Kaufmann Tobias
Published: August 2023

Crystallized abilities are skills used to solve problems based on experience, while fluid abilities are linked to reasoning without evoke prior knowledge. To what extent crystallized and fluid abilities involve dissociated or overlapping neural systems is debatable. Due to often deployed small sample sizes or different study settings in prior work, the neural basis of crystallized and fluid abilities in childhood remains largely unknown. Here we analyzed within and between network connectivity patterns from resting-state functional MRI of 2707 children between 9 and 10 years from the ABCD study. We hypothesized that differences in functional connectivity at the default mode network (DMN), ventral, and dorsal attentional networks (VAN, DAN) explain differences in fluid and crystallized abilities. We found that stronger between-network connectivity of the DMN and VAN, DMN and DAN, and VAN and DAN predicted crystallized abilities. Within-network connectivity of the DAN predicted both crystallized and fluid abilities. Our findings reveal that crystallized abilities rely on the functional coupling between attentional networks and the DMN, whereas fluid abilities are associated with a focal connectivity configuration at the DAN. Our study provides new evidence into the neural basis of child intelligence and calls for future comparative research in adulthood during neuropsychiatric diseases.
The Perioperative Pain Management Bundle is Feasible
Authors: Stamenkovic Dusica , Baumbach Philipp , Radovanovic Dragana , Novovic Milos , Ladjevic Nebojsa , Dubljanin Raspopovic Emilija , Palibrk Ivan , Unic-Stojanovic Dragana , Jukic Aleksandra , Jankovic Radmilo , Bojic Suzana , Gacic Jasna , Stamer Ulrike M. , Meissner Winfried , Zaslansky Ruth
Published: August 2023

Objectives:

The quality of postoperative pain management is often poor. A ‘bundle’, a small set of evidence-based interventions, is associated with improved outcomes in different settings. We assessed whether staff caring for surgical patients could implement a ‘Perioperative Pain Management Bundle’ and whether this would be associated with improved multi-dimensional pain-related Patient-Reported-Outcomes (PROs).

Methods:

PAIN OUT, a perioperative pain registry, offers tools for auditing pain-related PROs and obtaining information about perioperative pain management during the first 24 hours after surgery. Staff from 10 hospitals in Serbia used this methodology to collect data at baseline. They then implemented the ‘perioperative pain management bundle’ into the clinical routine and collected another round of data. The bundle consists of four treatment elements: (1) a full daily dose of 1-2 non-opioid analgesics (e.g. paracetamol, NSAIDs); (2) at least one type of local/regional anesthesia; (3) pain assessment by staff; (4) offering patients information about pain management. The primary endpoint was a multi-dimensional pain composite score (PCS), evaluating pain intensity, interference and side-effects: It was compared between patients who received the full bundlevs.not.

Results:

Implementation of the complete bundle was associated with a significant reduction in the PCS (P<0.001, small-medium effect size [ES]). When each treatment element was evaluated independently, non-opioid analgesics were associated with a higher PCS (i.e. poorer outcome; negligible ES); the other elements were associated with a lower PCS (all negligible-small ES). Individual PROs were consistently better in patients receiving the full bundle compared to 0-3 elements. The PCS was not associated with surgical discipline.

Discussion:

We report findings from using a bundle approach for perioperative pain management in patients undergoing mixed surgical procedures. Future work will seek strategies to improve the effect.

Trial registration:

ClinicalTrials.gov identified NCT02083835
Discrimination, Reliability, Sensitivity, and Specificity of Robotic Surgical Proficiency Assessment With Global Evaluative Assessment of Robotic Skills and Binary Scoring Metrics: Results From a Randomized Controlled Trial
Authors: De Groote Ruben , Puliatti Stefano , Amato Marco , Mazzone Elio , Larcher Alessandro , Farinha Rui , Paludo Artur , Desender Liesbeth , Hubert Nicolas , Cleynenbreugel Ben Van , Bunting Brendan P. , Mottrie Alexandre , Gallagher Anthony G. ,   On behalf of the Junior ERUS/ YAU working group on robot-assisted surgery of the European Association of Urology and the ERUS Education Working Group. Collaborators:, Rosiello Giuseppe , Uvin Pieter , Decoene Jasper , Tuyten Tom , D’Hondt Mathieu , Chatzopoulos Charles , De Troyer Bart , Turri Filippo , Dell’Oglio Paolo , Liakos Nikolaos , Andrea Bravi Carlo , Lambert Edward , Andras Iulia , Di Maida Fabrizio , Everaerts Wouter
Published: August 2023

Objective:

To compare binary metrics and Global Evaluative Assessment of Robotic Skills (GEARS) evaluations of training outcome assessments for reliability, sensitivity, and specificity.

Background:

GEARS–Likert-scale skills assessment are a widely accepted tool for robotic surgical training outcome evaluations. Proficiency-based progression (PBP) training is another methodology but uses binary performance metrics for evaluations.

Methods:

In a prospective, randomized, and blinded study, we compared conventional with PBP training for a robotic suturing, knot-tying anastomosis task. Thirty-six surgical residents from 16 Belgium residency programs were randomized. In the skills laboratory, the PBP group trained until they demonstrated a quantitatively defined proficiency benchmark. The conventional group were yoked to the same training time but without the proficiency requirement. The final trial was video recorded and assessed with binary metrics and GEARS by robotic surgeons blinded to individual, group, and residency program. Sensitivity and specificity of the two assessment methods were evaluated with area under the curve (AUC) and receiver operating characteristics (ROC) curves.

Results:

The PBP group made 42% fewer objectively assessed performance errors than the conventional group (P < 0.001) and scored 15% better on the GEARS assessment (P = 0.033). The mean interrater reliability for binary metrics and GEARS was 0.87 and 0.38, respectively. Binary total error metrics AUC was 97% and for GEARS 85%. With a sensitivity threshold of 0.8, false positives rates were 3% and 25% for, respectively, the binary and GEARS assessments.

Conclusions:

Binary metrics for scoring a robotic VUA task demonstrated better psychometric properties than the GEARS assessment.
Screening for Caregiver-Reported Feeding Concerns in Children with Autism Spectrum Disorder in a Tertiary-Care Clinic
Authors: Kuschner Emily S. , Sivathasan Shalini , McQueen Emma , Berry Rashelle C. , Pulver Stormi L. , Sharp William G. , Klaiman Cheryl
Published: August 2023

Objective:

Feeding concerns, primarily food selectivity, are commonly observed in children with autism spectrum disorder (ASD). Prevalence rates suggest that at least half of autistic youth have feeding difficulties.

Methods:

A retrospective chart review examining records of a large cohort of autistic children (N = 746) referred for ASD evaluation was conducted. Families completed a survey regarding feeding concerns in their children before a diagnostic evaluation.

Results:

Post hoc analyses based on retrospective chart review revealed approximately 30% of caregivers reported significant difficulty feeding their child. Young age, food selectivity, and concerns about weight were associated with increased likelihood of reported feeding difficulties. There was clear overlap between overall feeding difficulties and specific food selectivity; however, 1 in 5 children whose caregivers did not report feeding difficulties endorsed food selectivity.

Conclusion:

Findings highlight the need for multipronged approaches to screening to facilitate service prioritization by pediatric providers.
Histologic Comparison of the Fascicular Area of Processed Nerve Allograft Versus Cabled Sural Nerve Autograft
Authors: Leversedge Fraser J. , Safa Bauback , Lin Walter C. , Iorio Matthew L. , Merced-O’Neill Orlando , Tajdaran Kasra
Published: August 2023

Background:

The use of multiple cables of sural nerve autograft is common for peripheral nerve reconstruction when injured nerve caliber exceeds the nerve graft caliber. Although the optimal matching of neural to nonneural elements and its association with functional outcomes are unknown, it is reasonable to consider maximizing the neural tissue structure available for nerve regeneration. No prior studies have compared directly the cross-sectional fascicular area between cabled nerve autografts and size-selected nerve allografts. This study evaluated the cross-sectional fascicular area between native nerve stumps and two reconstructive nerve grafting methods: cabled sural nerve autograft (CSNA) and processed nerve allograft (PNA).

Methods:

CSNA from matched cadaveric specimens and PNA were used to reconstruct nerve defects in the median and ulnar nerves of six pairs of cadaveric specimens. Nerve reconstructions were done by fellowship-trained hand surgeons. The total nerve area, fascicular area, and nonfascicular area were measured histologically.

Results:

The CSNA grafts had significantly less fascicular area than PNA and caliber-matched native nerve. The PNA grafts had a significantly higher percent fascicular area compared with the intercalary CNSA graft.

Conclusions:

Fascicular area was significantly greater in PNA versus CSNA. The PNA consistently demonstrated a match in fascicular area closer to the native nerve stumps than CSNA, where CSNA had significantly smaller fascicular area compared with native nerve stumps.
Six Years of Complaints Issued by Patients at a Laser Treatment Center in a Plastic Surgery Hospital
Authors: Ding Bo , Su Xueshang , Zhuang Jun , Cai Na , Ou Yangxue , Jiang Haixia , Jiang Hanyi , Hu Jintian
Published: August 2023

Background:

Patient complaints can provide valuable feedback regarding the objective deficiencies of medical services. There are few studies on the complaints of patients receiving photoelectric therapy, so this study aims to understand the expectations and requirements of patients by analyzing the complaints of patients receiving photoelectric therapy.

Methods:

The complaints of patients who underwent photoelectric therapy were retrospectively examined. Authors plan to analyze treatment items, complaint contents, appeals, time trend regarding the number of complaints, and economic compensation.

Results:

Fifty-four patients were involved in the study in total, and all of them were included. According to the standardized coding classification of complaints by Reader et al., the number of clinical, management and relationship complaints were 36 (59.02%), 14 (22.95%), and 11 (18.03%), respectively. These were divided among the categories of quality (31.15%), safety (27.87%), institutional issues (22.95%), communication (8.20%), and humaneness/caring (9.84%); with the most common subcategories involving treatment (31.15%) and safety incidents (24.59%). The patients' demands involved 20 cases (32.26%) requesting a refund of their medical expenses, 16 (25.81%) issuing a warning, 15 (24.19%) requesting compensation for loss, 10 (16.13%) requiring free repair or consultation, and 1 (1.61%) demanding an apology. Eventually, financial compensation was provided to the patients in eight of the cases. At a significance level of P = 0.05, even if the number of annual complaints increased over time, the increasing trend was not significant.

Conclusions:

Patient complaints in photoelectric therapy were most commonly clinical in nature. Specifically, quality and safety concerns are the main complaints.
Truth or DARE (Digital Anal Rectal Examination): Gynecologist Viewpoints on Anal Cancer Screening
Authors: Gaydos Laura M. , Blemur Danielle , Perry Tahira , Stier Elizabeth A. , Khan Michelle J. , Flowers Lisa
Published: August 2023

Objective

The objective of this study is to assess knowledge and prevention practices for anal cancer among gynecologists.

Methods

We conducted a survey for practicing gynecologists recruited through academic institutions, professional societies, and professional groups on social media resulting in 196 respondents. The survey, fielded between January and June 2022, included questions on knowledge, attitudes, training, and practices regarding anal cancer prevention (ACP). Descriptive statistics and χ2 analysis were completed.

Results

In terms of knowledge regarding ACP, over 80% of respondents identified certain clinical indications for anal cancer screening. However, only 36% respondents selected the 3 correct ACP screening tools. Twenty-seven (13.9%) respondents reported receiving training on ACP in medical school, whereas 50 (25.9%) reported receiving training during residency. Only 21% of respondents reported that they perform anal cytology, and 32% reported that they perform digital anal rectal examinations. One hundred thirty-six respondents (75.56%) affirmed that they needed additional training on ACP to be able to provide this service to their patients, and 95 (53.1%) stated they were extremely likely to participate in ACP training if given the opportunity.

Conclusion

Although a limited proportion of practicing gynecologists with trained in ACP, there is willingness to participate in training if it were made available and to incorporate ACP into their practices.
Risk Factors for the Development of Bilateral Ménière's Disease
Authors: Phillips John , Murdin Louisa , Grant Kelly , Shepstone Lee , Sims Erika , Rea Peter , Harcourt Jonny
Published: August 2023

Objective

To identify key risk factors for the development of bilateral Ménière's disease.

Study Designs

Observational study.

Setting

Four NHS Trusts and four independent hospitals or clinics, within three distinct urban and rural regions within the United Kingdom (Norfolk, Leicestershire, and London).

Methods

Patients with Ménière's disease were identified at ENT or audiovestibular medicine secondary/tertiary care and specialist private clinics. A range of patient-reported data, questionnaire data, and clinical data (audiometric, radiological, and specialist balance testing data) was inputted into a bespoke database. A logistic regression model was used to identify potential risk factors for bilateral Ménière's disease compared with unilateral Ménière's disease.

Results

A total of 411 participants were recruited into this study, 263 from NHS Trusts and 148 from independent hospitals or clinics. In our cohort of patients, 22% of individuals were identified as having bilateral Ménière's disease. Two statistically significant independent variables were identified as risk factors for the development of bilateral Ménière's disease: the presence of psoriasis and a history of ear infections.

Conclusions

Psoriasis and a history of ear infection have been identified as key risk factors for the development of bilateral Ménière's disease. It is anticipated that further work based on this finding will allow a better understanding of the underlying pathophysiological mechanisms that predispose to the development of Ménière's disease symptoms.
Enhanced Mitophagy in Cholesteatoma Epithelial Cells
Authors: Li Quan-Cheng , Wang Shu-Qi , Cao Zai-Zai , Zhou Shui-Hong
Published: August 2023

Hypothesis

Mitophagy may have a potential role in the pathogenesis of acquired cholesteatoma.

Background

Enhanced mitophagy has been proven to be involved in various cancers. However, its role in the pathogenesis of cholesteatoma, which shares some common features with cancer, is controversial. This study investigated mitophagy in cholesteatoma epithelial cells.

Methods

The autophagy protein markers LC3-II and p62 and mitophagy proteins BNIP3, Parkin, and PINK1 were analyzed in cholesteatoma epithelial cells and external auditory canal epithelium cells by immunoblotting. The results were confirmed by immunohistochemistry. Adenovirus Ad-mCherry-GFP-LC3B and Ad-GFP-LC3B were used to evaluate autophagic activity. Transmission electron microscopy was used to observe and analyze autophagosomes.

Results

LC3-II expression was increased in cholesteatoma cells, whereas soluble and insoluble p62 levels were decreased. The expressions of BNIP3, Parkin, and PINK1 were higher in total protein and mitochondrial protein of cholesteatoma cells compared with normal external auditory canal epithelium cells. Autophagic activity was increased in cholesteatoma cells compared with normal external auditory canal epithelium cells.

Conclusion

Mitophagy was enhanced in cholesteatoma epithelial cells and may have a potential role in the pathogenesis of acquired cholesteatoma.