bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Connectome Analyses following Low-Grade Glioma Neurosurgery: Implications for Cognitive Rehabilitation
Authors: Poologaindran Anujan , Hart Mike , Santarius Tom , Price Stephen , Sinha Rohit , Sughrue Mike , Erez Yaara , Romero-Garcia Rafael , Suckling John 
Published: October 2021

Abstract

Aims
Low-grade gliomas (LGG) slowly grow and infiltrate the brain's network architecture (the connectome). Unlike strokes that acutely damage the connectome, LGGs intricately remodel it, leading to varying deficits in executive function (i.e. attention, concentration, working memory). By longitudinally mapping the “mesoscale” architecture of the connectome, we may begin to systematically accelerate domain-general cognitive rehabilitation in LGG patients. In this study, we pursued the following aims: 1) track cognitive and connectome trajectories following LGG surgery, 2) determine optimal time period for cognitive rehabilitation, and 3) distinguish patients with perioperative predictors of long-term cognitive deficits (&gt;1 year).

Method
With MRI and cognitive data from n=629 individuals across the lifespan, we first validated the structural, functional, and topological relevance of the multiple demand (MD) system for higher-order cognition. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectome and cognitive data: pre-surgery, post-surgery Day 1, Month 3, & 12. We assessed how glioma infiltration, surgery, and rehabilitation affected MD system trajectories at the single-subject level. Deploying transcriptomic and graph theoretical analyses, we tested if perioperative connectome modularity can accurately distinguish long-term cognitive trajectories.

Results
Controlling for age and sex, the MD system’s multi-scale architecture in health was positively associated with higher-order cognition (Catell’s fluid intelligence). Pre-operative glioma infiltration into the MD system was negatively associated with the number of long-term cognitive deficits (OCS-Bridge cognitive battery), suggesting its functional reorganisation. Mixed-effects modelling demonstrated the resilience of the MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed perioperative modularity can distinguish patients with long-term cognitive deficits at one-year follow-up. Transcriptomic analyses of inter-module connector hubs revealed increased gene expression for mitochondrial metabolism and synaptic plasticity.

Conclusion
This is the first serial functional mapping of LGG patient trajectories for domain-general cognition. By assessing the mesoscale architecture, we demonstrate how connectomics can help overcome the intrinsic heterogeneity in LGG patients and predict long-term rehabilitation trajectories. We discuss how to identify neurobiologically-grounded personalised targets for 'interventional neurorehabilitation' following LGG surgery.
The use of cannabinoid and non-cannabinoid supplementary therapies in patients undergoing treatment for Glioblastoma reveals an urgent need for guidance
Authors: Vaqas Babar , Dulley Louise , Maniar Ruchi 
Published: October 2021

Abstract

Aims
Glioblastoma (GBM) is currently an incurable malignancy with a very poor prognosis for the majority of patients. Many patients undergo debulking surgery, radiotherapy and chemotherapy however therapeutic options are limited, and this can lead to patients sourcing their own treatments. There is some evidence that cannabinoids have the effect of inhibiting GBM tumour growth through a variety of pathways, some of which include CB2 cannabinoid receptor pathway activation. We undertook a patient questionnaire to understand what alternative therapies patients are accessing and why, with a focus on cannabinoid use.

Method
We undertook a prospective observational questionnaire based qualitative study of 50 … consecutive patients undergoing treatment for glioblastoma at our centre.

Results
43 patients responded to our questionnaire. 33% of patients were taking some kind of supplementary therapy with 25% taking cannabis derivatives, mainly CBD oil. There were no clear discriminators amongst our cohort including age or sex when considering the likelihood of taking cannabis derivatives. 6 out of 11 (55%) patients taking cannabis derivatives reported some positive effects with improved sleep and general wellbeing being most commonly reported. Patients reported spending between £10-£300 per month with an average of £42 per month. Cannabis products were obtained via the internet or from friends.

Conclusion
This small cohort of patients indicates that a significant proportion of glioblastoma patients investigate and use alternative therapies, in particular cannabis oil. NICE guidance for clinicians simply notes there is insufficient evidence to support the use of cannabis oil in the treatment of this disease. Given the publicity and interest in the utility of cannabis oil to treat cancers this leaves patients to research the use of these agents without access to robust clinical data to guide their use or indeed to conclude they are not beneficial. The accessing of these compounds, potentially by a sizeable number of patients, leaves them vulnerable to unregulated perhaps unscrupulous drug sources. This small study has further highlighted the unmet need for information and guidance on supplementary treatments for glioma patients and this poses a challenge to all those treating this group of patients to answer a question our patients are clearly wanting answered.
Temozolomide hypersensitivity – A story of success
Authors: Alagiyawanna Lanka , Prince Stephanie , Wright Debbie , Clarke Enrico , Ching Jeng 
Published: October 2021

Abstract

Aims
Background:
Temozolomide is an oral chemotherapy drug widely used in the treatment of glial tumours. This is generally well tolerated however, immediate and delayed hypersensitivity reactions have been described, necessitating treatment interruption that could significantly impact survival.

Method
Case description:
We report a case of a 39-year-old young woman with WHO grade 2 IDH1mutant diffuse astrocytoma (MGMT promoter methylated) of the left temporal lobe. She had tumour resection in 2012 followed by radical radiotherapy. Afterwards, she had close surveillance with regular brain imaging. The tumour started to progress in early 2020. We agreed to commence on temozolomide to control tumour growth.
She developed an itchy rash with easy bruising towards the end of the first cycle. It responded to a course of prednisolone. We proceeded with the second cycle and she developed a worsening rash on the third day. However she did not have signs or symptoms of anaphylaxis. This episode was again managed by a course of steroids and oral antibiotics. Since Temozolomide was the optimal treatment to control the disease progression at this stage, we agreed to persevere with temozolomide using a rapid desensitisation protocol.

Results
On the first day of third cycle, she was brought to the day chemotherapy unit and given prednisolone 30mg, fexofenadine 180mg and ondansetron 8mg, 30 minutes before the treatment. Our protocol was as follows; 5mg, 10mg, 20mg, 30mg, 50mg and 90mg of temozolomide at an interval of 30 minutes between the doses. She was advised to follow the same regime for the next four days of the third cycle. On days 6 -28, she has been advised to take fexofenadine 180mg once daily. Although there was a minor rash appeared on days 6/7, they subsided gradually. She tolerated the treatment without sinister symptoms or signs. We proceeded with the next 4 chemotherapy cycles adhering to the same protocol. The intensity of the rash gradually improved, and she became almost completely asymptomatic by the 7th cycle. It was also encouraging to see the radiological response of the tumour with the treatment.

Conclusion
Although the published literature is minimal, rapid desensitisation is shown to be a safe and effective method to counteract temozolomide hypersensitivity. In an era where there is still a paucity of systemic treatment options for primary brain tumours, adopting rapid desensitisation to induce tolerability to temozolomide, a drug which has shown to improve survival, would be a valuable addition in managing our patients. Further, our experience suggests that this protocol is safe, effective, and does not necessitate inpatient admission.
Resident physicians physical activity during on-call shifts: smartphone-based assessment
Authors: Ben-David R , Savin Z , Herzberg H , Shulman Y , Bar-Yakkov N , Haham A , Yossepowitch O , Sofer M 
Published: October 2021

Abstract

Background
Physical activity of resident physicians (RPs) during on-call shifts is difficult to objectively evaluate. The integration of smartphones in our daily routines may allow quantitative assessment, employing pedometric assessment.

Aims
To evaluate the number of steps that RPs walk during on-call shifts as a marker of physical activity by using smartphone-based pedometers.

Methods
Step counts were collected from 100 RPs’ smartphones who volunteered to participate in the study between January 2018 and May 2019. The conversion rate was 1400 steps = 1 km (application’s default). A shift was defined as regular morning work followed by an in-house on-call stay, totalling 26 hours. Statistical analyses included univariate and multivariate linear mixed models, and Fisher exact test. A P-value &lt; 0.05 was considered statistically significant.

Results
The average walking distance was 12 118 steps (8.6 km/RP/shift). Paediatric intensive care unit and neurosurgery residents recorded the longest walking distances 16 347 and 15 630 steps (11.67 and 11.16 km/shift), respectively. Radiology residents walked the shortest distances 4718 steps (3.37 km/shift). Physically active RPs walked significantly longer distances during their shifts than non-physically active RPs: 12 527 steps versus 11 384 steps (8.95 versus 8.13 km/shift, P &lt; 0.05), respectively. Distances covered during weekday shifts were longer than weekend shifts: 12 092 steps versus 11 570 steps (8.63 versus 8.26 km/shift, P &lt; 0.05), respectively.

Conclusions
Smartphone-based pedometers can aid in analysing physical activity and workload during on-call shifts; such information can be valuable for human resource department, occupational health authorities and medical students with impaired physical mobility when choosing a speciality.
No Standard Oil
Authors: Gordon Deborah 
Published: October 2021

Abstract
The next decade will be decisive in the fight against climate change. It will be impossible to hold the planet to a 1.5 degrees Celsius temperature rise without controlling methane and carbon dioxide emissions from the oil and gas sector. Contrary to popular belief, the world will not run out of these resources anytime soon. Instead, oil and gas are becoming more climate-intensive to supply using technologies like fracking oil and liquefying gas—even as these abundant resources continue to be used to fuel cars, heat homes, and produce consumer goods like shampoo, pajamas, and paint. Policymakers, financial investors, environmental advocates, and citizens need to understand what oils and fossil fuels are doing to our climate to inform decision-making. In No Standard Oil, Deborah Gordon shows that no two oils or gases are environmentally alike. Each has a distinct, quantifiable climate impact. While all oils and gases pollute, some are much worse for the climate than others. In clear, accessible language, Gordon explains the results of the Oil Climate Index Plus Gas (OCI+), an innovative, open-source model that estimates global oil and gas greenhouse gas emissions. Gordon identifies the oils and gases from every region of the globe—along with the specific production, processing, and refining activities—that are the most damaging to the planet and proposes innovative solutions to reduce their climate footprints. Global climate stabilization cannot afford to wait for oil and gas to run out. No Standard Oil shows how people can take immediate, practical steps to cut greenhouse gas emissions in the crucial oil and gas sector while making sustainable progress in transitioning to a carbon-free energy future.
Evolution of Quantitative Research Methods in Strategic Management
Authors: Shaver J. Myles 
Published: October 2021

Abstract
This chapter discusses general trends in quantitative research methods since the early 1980s. It then highlights five contemporaneous issues with respect to the application of quantitative methods within the field—including the tension of simultaneously seeking causal identification and examining meaningful strategy questions. Taking the perspective that a key goal of quantitative strategy research is to aid decision-makers by providing rigorous evidence-based strategic management insights, the chapter proposes practices that, if embraced, will advance the rigor and impact of future quantitative research. A central consideration is addressing issues of causal identification through a cumulative body of research and the importance that research designs play in this consideration. In concluding, the chapter acknowledges significant advances in quantitative methods in the field while noting directions in which the field should continue to evolve.
Networks from Communication
Authors: Fuhse Jan 
Published: October 2021

Abstract
Social networks form, stabilize, and change in the process of communication. Rather than start from actors, communicative events are conceptualized as the basic units. In the sequence of communication, these events are attributed to actors, together with underlying dispositions. Relational expectations about the behavior of actors toward others ensue, effectively structuring communication and making for the regularities of communication we observe as relationships and networks. Social relationships do not exist either/or, but as particular bundles of expectations that gradually arise, stabilize, and change over time. The approach combines recent developments in relational sociology around Harrison White with the theory of communication by Niklas Luhmann and others. Three areas of application and extension of this model are discussed: (1) intercultural communication, (2) collective and corporate actors, and (3) methods for studying communication in networks.
Meditations on Medical Torts
Authors: Saks Michael J. , Landsman Stephan 
Published: October 2021

Abstract
“Meditations on Medical Torts” ponders larger issues concerning the malpractice litigation system in light of systematic empirical and other evidence. The chapter questions whether the tort system actually is a compensation system; probes the system’s deterrence purpose, promoting efficient investment in injury prevention, including reviewing the empirical research on the tort system’s deterrent effect, both in general and specifically concerning its influence on patient safety; discusses the accuracy of tort litigation in targeting the correct events; compares the system’s impact on organizations versus individuals as potential tortfeasors; examines the healthcare industry’s criticisms of the tort system, as well as the healthcare industry’s seemingly paradoxical affection for the malpractice litigation system; and reviews major malpractice reforms of recent decades and studies of their effects.
Legal Innovations to Promote Patient Safety—An Introduction
Authors: Saks Michael J. , Landsman Stephan 
Published: October 2021

Abstract
“Legal Innovations to Promote Patient Safety—An Introduction” provides an overview of legal innovations that could be adopted to reduce iatrogenic harm and is an invitation to a wider effort to discover more. Healthcare exists within a legal infrastructure that can do more to promote safety. Improvement is possible: some healthcare organizations provide better quality and safety than others. Legal innovations should facilitate patient safety innovations: their discovery, validation, and dissemination. Effective law will be evidence-based. Its guidelines are to be interdisciplinary, intervene at optimal levels of generality, impose no more pressure than necessary, regard legal innovations as provisional, and need to be evaluated (and then retained or replaced as results suggest). The law could in various ways support: innovation registries, research, technological advances, industry efforts to coordinate desired improvements, clinical practice guidelines, standard-setting, regulation and engaged surveillance, systems, and so on. The law must also be prepared to motivate adoption of safety innovations by restructuring incentives.
Regulation and Engaged Surveillance
Authors: Saks Michael J. , Landsman Stephan 
Published: October 2021

Abstract
“Regulation and Engaged Surveillance” focuses on the value in regulating certain aspects of medical treatment through effective government surveillance. Focusing on the example of auto safety regulation, beginning in the 1960s, broad scale proscriptive safety regulation apparently is prone to failure because of industry resistance, lack of government expertise, and absence of effective government oversight. If regulation is to improve medical safety it must be backed by close surveillance. Such an approach cannot succeed with the general run of hospital care as envisioned by proposals calling for hospital report cards. But it has been practical and efficacious in narrowly focused, risky treatment areas. The most successful example is New York’s Cardiac Treatment Registry, which drastically improved coronary artery bypass graft surgery, relying on careful government surveillance and sophisticated risk adjustment mechanisms introduced through the efforts of New York’s innovative Health Commissioner, David Axelrod. Other surveillance programs that should be considered include restrictions on the performance of certain risky procedures by less experienced practitioners (the Volume Pledge) and the use of checklist protocols in the intensive care unit.
Death in Life
Authors: Howard Gary C. 
Published: October 2021

Abstract
Everyone dies, and so we naturally associate death with the end of an individual life. However, life is much more complicated, and death is actually interwoven into biology at many levels. Normal development and life could not exist without the carefully regulated death of certain cells; that type of cellular death also serves as one defense against disease. Other cells wear out and die and must be replaced regularly. On a larger scale, death has influenced the direction of entire species. In fact, death has shaped all life through the cycle of life and death, both throughout time and in normal development. It affects our cells, our development, and our life.
Aging and Senescence
Authors: Howard Gary C. 
Published: October 2021

Abstract
Why do we age? Aging has been an important issue in biology for many decades, and many questions remain unanswered. However, any explanation of aging must agree with Darwin’s theory of natural selection. Genes that benefit fitness early on in an individual’s lifetime will be favored. Ones that hinder fitness early on will be selected against because those individuals will reproduce less successfully. Genes that have an effect later in life (after the reproductive years) are not subject to natural selection. Thus, the force of natural selection is lost later in life. Three key theories have been proposed to explain how aging might have evolved: mutation accumulation theory, antagonistic pleiotrophy, and disposable soma. These three main theories are not mutually exclusive. Finally, is aging simply another disease?
Genetics of Life and Death
Authors: Howard Gary C. 
Published: October 2021

Abstract
Longevity seems to run in families, and very old people are sometimes said to have “good” genes. There might be something to that. If there is a key to immortality, molecular geneticists may be able to find it. They recently began to explore the genes and other factors that cause us to age and eventually die and are finding intriguing hints of ways that death can be deferred, such as through caloric restriction, epigenetic techniques, and manipulation of telomeres and stem cells. Inherent in such studies is the concept that many of the diseases associated with aging, such as heart disease, diabetes, cancer, and neurodegenerative disease—the things that kill most people—may be symptoms of the disease of aging.
Death in Plants
Authors: Howard Gary C. 
Published: October 2021

Abstract
Although some plants live for long times, they are not immortal. Like animals, plants eventually succumb to an insult and die. In addition, programmed cell death of various types is common in plants and is involved in plant growth, development, and response to disease. In abscission, a group of cells at the base of a leaf are programmed to die so that the leaf is released from the branch. A similar process releases fruit. Other forms of cell death are used to contain plant diseases and in wound responses. Because plant cells have a hard cell wall that is lacking in animal cells, some researchers have questioned whether plant cell death really involves apoptosis. Others suggest that in plants the process should be termed vacuolar death.
Bioethics
Authors: Howard Gary C. 
Published: October 2021

Abstract
While most people would be happy with extending life span, the possibility raises significant ethical issues. Some concerns are directed at the issue of extending life itself. Should humans play God? Will the longer life be a healthy one? Others challenge various aspects of the research that is attempting to conquer diseases and conditions that threaten life or diminish its quality. Those experiments are not aimed directly at extending life, but might have the same effect if those diseases are ended. Examples of those experiments involve the uses of human cells, freezing embryos, and genome editing.
Future of Death
Authors: Howard Gary C. 
Published: October 2021

Abstract
The future of death is hard to predict. Humans have certainly made great progress in extending life. Many diseases have been conquered. However, death might be thought of as like the Hydra of Greek mythology—whenever one head was cut off, another grew in its place. Antibiotics, modern sanitation, safer childbirth, reducing the amount of smoking, cleaner air, and more—all represent death’s Hydra heads that have been severed. As life span expanded, new diseases appeared, such as neurodegenerative disease, heart disease, and cancer. Other even more dangerous ones lurk nearby: climate change, overpopulation, nuclear weapons. As the second of his twelve labors, Hercules had to kill the Hydra. He did this by cutting off its one immortal head in the center. If aging is a disease, is there one immortal head or regulatory system that can be controlled to stop aging? Will humans be able to kill death? That is too difficult to predict now.