bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn’s Disease: Results from the Phase 2 Open-Label Extension Study
Authors: Ferrante Marc , Feagan Brian G , Panés Julián , Baert Filip , Louis Edouard , Dewit Olivier , Kaser Arthur , Duan W Rachel , Pang Yinuo , Lee Wan-Ju , Gustafson Dawn , Liao Xiaomei , Wallace Kori , Kalabic Jasmina , D’Haens Geert R 
Published: June 2021

Abstract

Background and Aims
Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study.

Methods
Enrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index &lt;150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks.

Results
Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [&gt;71%] and endoscopic remission [&gt;42%].

Conclusions
Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn’s disease, with no new safety signals.
Clinical trial registration number: NCT02513459
PBP4-mediated β-lactam resistance among clinical strains of Staphylococcus aureus
Authors: Satishkumar Nidhi , Alexander J Andrew N , Poon Raymond , Buggeln Emma , Argudín Maria A , Strynadka Natalie C J , Chatterjee Som S 
Published: June 2021

Abstract

Background
PBP4, a low-molecular-weight PBP in Staphylococcus aureus, is not considered to be a classical mediator of β-lactam resistance. Previous studies carried out by our group with laboratory strains of S. aureus demonstrated the ability of PBP4 to produce β-lactam resistance through mutations associated with the pbp4 promoter and/or gene. Recent studies of β-lactam-resistant clinical isolates of S. aureus have reported similar mutations associated with pbp4.

Objectives
To determine if pbp4-associated mutations reported among clinical strains of S. aureus mediate β-lactam resistance.

Methods
The pbp4 promoters and genes bearing mutations from clinical isolates were cloned into a heterologous host. Reporter, growth and Bocillin assays were performed to assess their role in β-lactam resistance. X-ray crystallography was used to obtain acyl-enzyme intermediate structures of the WT and mutant PBP4 with nafcillin and cefoxitin.

Results
Of the five strains that contained pbp4 promoter mutations, three strains exhibited enhanced expression of PBP4. The R200L mutation in pbp4 resulted in increased survival in the presence of the β-lactams nafcillin and cefoxitin. Further, introduction of either a promoter or a gene mutation into the genome of a WT host increased the ability of the strains to resist the action of β-lactams. The four high-resolution X-ray structures presented demonstrate the binding pose of the β-lactams tested and provide hints for further drug development.

Conclusions
Mutations associated with the pbp4 promoter and pbp4 gene altered protein activity and mediated β-lactam resistance among the clinically isolated strains that were studied.
Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: ten Hoorn Sanne , de Back Tim R , Sommeijer Dirkje W , Vermeulen Louis 
Published: June 2021

Abstract

Background
The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs.

Methods
We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized.

Results
In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients.

Conclusions
The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
Exploiting genotype × management interactions to increase rainfed crop production: a case study from south-eastern Australia
Authors: Hunt James R , Kirkegaard John A , Harris Felicity A , Porker Kenton D , Rattey Allan R , Collins Marisa J , Celestina Corinne , Cann David J , Hochman Zvi , Lilley Julianne M , Flohr Bonnie M 
Published: June 2021

Abstract
Crop yield must increase to keep pace with growing global demand. Past increases in crop production have rarely been attributable to an individual innovation but have occurred when technologies and practices combine to form improved farming systems. Inevitably this has involved synergy between genotypic and management improvements. We argue that research focused on developing synergistic systems that overcome clear production constraints will accelerate increases in yield. This offers the opportunity to better focus and multiply the impact of discipline-focused research. Here we use the rainfed grain production systems of south-eastern Australia as a case study of how transformational change in water productivity can be achieved with research focused on genotype × management synergies. In this region, rainfall is low and variable and has declined since 1990. Despite this, growers have maintained yields by implementing synergistic systems combining innovations in (i) soil water conservation, (ii) crop diversity, (iii) earlier sowing, and (iv) matching nitrogen fertilizer to water-limited demand. Further increases are emerging from synergies between genetic improvements to deliver flowering time stability, adjusted sowing times, and potential dual-purpose use. Collaboration between agronomists, physiologists, and crop breeders has led to development of commercial genotypes with stable flowering time that are in early phases of testing and adoption.
Six Steps to Managing Alzheimer's Disease and Dementia
Authors: Budson Andrew E. , O'Connor Maureen K. 
Published: June 2021

Abstract
Six Steps to Managing Alzheimer’s Disease and Dementia: A Guide for Families explains everything that a family member or other caregiver needs to care for their loved one with Alzheimer’s disease or another dementia, all the way from the mild stage through death—and beyond. It begins by explaining Alzheimer’s and dementia, and how to manage problems with memory, language, vision, emotion, behavior, sleep, and bodily functions. Next discussed are which medications help—and which make things worse. Caring for yourself and building a care team are then covered, as well as how to sustain your relationship. Final chapters discuss the progression of dementia, the eventual death, and how to plan for life afterward. It is written in an easy-to-read style, featuring clinical vignettes and character-based stories that provide real-life examples of how to successfully manage Alzheimer’s disease and dementia.
What is Alzheimer’s disease?
Authors: Budson Andrew E. , O’Connor Maureen K. 
Published: June 2021

Abstract
Alzheimer’s is a disease in which amyloid plaques build up in the brain. The plaques damage brain cells, the cells develop tangles, and the tangles destroy the cells. Alzheimer’s disease begins silently and progresses through very mild, mild, moderate, and severe stages. Age, being a woman, and family history are risk factors for the disease. Tests using a lumbar puncture or PET scan can help to confirm the diagnosis of Alzheimer’s disease, but they are only used in special circumstances. Lastly, you can reduce your risk of developing Alzheimer’s disease by eating a Mediterranean-style diet, engaging in aerobic exercise, and staying socially active.
How to manage memory problems
Authors: Budson Andrew E. , O’Connor Maureen K. 
Published: June 2021

Abstract
There are many way to help manage your loved one’s memory problems. If their dementia is fairly mild, memory strategies and aids can often help. Using a pillbox or another method to ensure that medications are being taken correctly is critical. Pictures are more easily learned than words. Don’t tell a person with dementia what not to do; tell them what they should do. Habits and routines are generally preserved in dementia, and new ones can be learned. Use methods to make sure the stove is not left on and the water is not left running. Work to eliminate wandering and write a plan in case it occurs. Take advantage of technological solutions to memory problems. Use reminders of the past to make your loved one feel more at home. Don’t fight false memories. Lastly, reminding your loved one that they have memory problems is rarely helpful.
How to manage vision problems
Authors: Budson Andrew E. , O’Connor Maureen K. 
Published: June 2021

Abstract
Whether caused by dementia or an eye disease, problems with vision can disrupt your loved one’s function, create hallucinations, and even lead them to think you are an imposter. There are, however, many things you can do to help. Start with an eye examination to make sure their eyeglasses prescription is correct and to look for treatable diseases. Ensure adequate lighting in and around their home and increase visual cues in potentially hazardous areas, such as stairs. Adjust for difficulty seeing or paying attention on one side. Increase visual contrast and size of numbers and letters for their daily activities. Use navigation systems with audible directions. Reduce the impact of hallucinations. Lastly, manage difficulties when your loved one does not recognize you, thinks you are someone else, or believes that you have been replaced by an imposter.
Which medications can worsen thinking, memory, behavior, or function?
Authors: Budson Andrew E. , O’Connor Maureen K. 
Published: June 2021

Abstract
Many medications may cause memory impairment, drowsiness, and confusion. Make sure that you know and keep track of all the medications your loved one is taking, including prescriptions, over-the-counter medications, vitamins, herbs, and supplements. Review these medications with their doctor. When possible, stop or lower the dose of medications that are causing problems. There are a variety of medications that can produce impairments in thinking and memory, including anticholinergic medications; antidepressants; antihistamines; antipsychotics; anxiety medications (benzodiazepines); dizziness and vertigo medications; incontinence medications (antispasmodics); migraine medications; muscle relaxants; narcotics (opioids); nausea, stomach, and bowel medications; seizure medications (anticonvulsants); sleeping medications; tremor medications; and herbal remedies. Consider anesthesia and cancer treatments carefully. Lastly, note that cholesterol-lowering medications do not cause memory problems.
Which medications can improve thinking, memory, behavior, or function?
Authors: Budson Andrew E. , O’Connor Maureen K. 
Published: June 2021

Abstract
Dementia disrupts a number of brain chemicals, and medications may be helpful to restore the balance of these neurotransmitters. When considering a new medication, it is important to set clear, measurable goals; start with a low dose; and track the effects over time. Cholinesterase inhibitors help with memory, mood, behavioral problems, and hallucinations; memantine helps with attention, alertness, mood, and behavioral problems; selective serotonin reuptake inhibitors (SSRIs) help with mood, anxiety, and behavioral problems; dextromethorphan/quinidine helps with inappropriate laughing or crying as well as behavioral problems; melatonin and acetaminophen help with sleep; atypical neuroleptics help with agitation, aggression, delusions, hallucinations, and picking; carbidopa/levodopa helps with walking, movement, and parkinsonian tremors; and beta blockers help with essential tremor. Clinical trials of new medications being developed may be available for those who are looking for better treatments for their loved one and for the next generation.
How to plan for the progression of dementia
Authors: Budson Andrew E. , O’Connor Maureen K. 
Published: June 2021

Abstract
As your loved one begins to experience more problems with thinking and memory, they will need help managing their health care, finances, and other aspects of daily living. They may need to leave their home in order to receive the amount or type of care they require. Preparing legal documents such as a will, power of attorney, and health care proxy is an important step in planning for the future. Having conversations with your loved one early after a diagnosis ensures that they can participate in future planning as much as possible, easing your burden as increased care is required. Even if they don’t want to participate, you can still explore options so you will be ready when a crisis occurs.
The Management of Terror
Authors: Rodin Gary , Hales Sarah 
Published: June 2021

Abstract
This chapter addresses the psychological impact of life-threatening disease of acute onset. Anxiety may be profound in this circumstance, with the severity of symptoms often meeting criteria for acute stress disorder (ASD) or posttraumatic stress disorder (PTSD) in both patients and family caregivers. The nature of traumatic stress and the ways in which it may be alleviated by Managing Cancer and Living Meaningfully (CALM) therapy are described here. Terror management theory (TMT), including the psychological pillars that protect individuals from the fear of death, is introduced as a model to understand how death anxiety is managed when mortality salience is heightened. The influence of TMT in formulating our research and in developing the CALM intervention is described here.
Attachment Security
Authors: Rodin Gary , Hales Sarah 
Published: June 2021

Abstract
This chapter provides an overview of the construct of attachment security and describes the threat to this security that may arise in response to the diagnosis or progression of advanced disease. The heightened mortality salience that occurs in this context activates the attachment system, and increased dependency and caregiving needs frequently require an adjustment or renegotiation of attachment security. Attachment security protects from death anxiety and other forms of distress, and so the renegotiation of attachment relationships is often an urgent task that is needed to maintain or restore emotional equilibrium. This chapter explains the central role of attachment security in the Managing Cancer and Living Meaningfully (CALM) intervention, in which the therapeutic relationship can provide a secure base to process distressing thoughts and feelings and to face the challenges that inevitably occur.
The Pearl in the Oyster
Authors: Rodin Gary , Hales Sarah 
Published: June 2021

Abstract
This chapter considers the phenomenon of posttraumatic growth (PTG) in the context of advanced cancer, drawing upon both theory and empirical research. The concept of PTG refers to improvements that have been postulated to occur in psychological, interpersonal, and spiritual domains as a result of successful coping with trauma. Various theoretical models of PTG are described and compared and the controversy as to whether PTG is a real, observable phenomenon is explored. The chapter specifically considers the unique emergence of PTG in advanced cancer, the measurement tools that have been used, and the methodological challenges of research examining this relationship. Finally, the potential of Managing Cancer and Living Meaningfully (CALM) to promote psychological growth in patients with advanced cancer is explored.
The Context of CALM
Authors: Rodin Gary , Hales Sarah 
Published: June 2021

Abstract
This chapter provides an overview of the range of psychotherapeutic interventions that have been applied to patients with advanced and metastatic cancer and the relationship of Managing Cancer and Living Meaningfully (CALM) to the field. Approaches to alleviate distress at the time of diagnosis of advanced or life-threatening cancer, those for patients near the end of life, and those for patients living with metastatic and advanced cancer are discussed. The latter include supportive-expressive, meaning-centered, cognitive-behavioural, mindfulness-based, and grief therapies tailored for individuals, groups, and families. Interventions tailored for the end of life, including Dignity Therapy, Short-Term Life Review, and narrative interventions, are reviewed. The barriers to the optimal delivery of psychosocial interventions for patients with advanced disease are also explored.
The CALM Domains
Authors: Rodin Gary , Hales Sarah 
Published: June 2021

Abstract
This chapter describes the four domains of Managing Cancer and Living Meaningfully (CALM), which represent the general content themes that patients are given the opportunity to address over the course of CALM therapy. These domains—namely, symptom management and communication with healthcare providers; changes in self and relations with close others; spirituality or sense of meaning and purpose; and thinking about the future, hope, and mortality—are discussed here in detail. The general therapeutic goals of exploration in each domain are outlined, with suggested probes to initiate discussion. Case examples, which include potential therapeutic responses and non-CALM responses, are provided to enhance understanding of therapeutic intent within each domain.
CALM Therapy Cases
Authors: Rodin Gary , Hales Sarah 
Published: June 2021

Abstract
This chapter contains case summaries and brief case examples, based on actual patients treated with Managing Cancer and Living Meaningfully (CALM), to illustrate the process of CALM therapy and the common issues that may arise. The case summaries, which include individual and couples-based cases, elucidate the process of CALM as it unfolds from the initial session to the final meeting. Brief case examples are also presented to highlight potential CALM challenges.
Introduction
Authors: Gross Michael L. 
Published: June 2021

Abstract
“Can military medicine be ethical?” is one question that may puzzle readers whose knowledge of medical ethics since 9/11 is colored by the prisons of Abu Ghraib and Guantanamo Bay. To address these and other challenges, Military Medical Ethics in Contemporary Armed Conflict explores controversial topics that include preferential care for compatriot warfighters, force feeding detainees, weaponizing medicine to wage war, medical experimentation, and neural enhancement for warfighters. Less controversial but no less compelling concerns direct our attention to postwar justice: the duty to rebuild war-torn nations and the obligation to care for war-torn veterans.
Moral Reasoning in Military Medical Ethics
Authors: Gross Michael L. 
Published: June 2021

Abstract
Applied ethics must resolve moral dilemmas, because, at the end of the day, medical personnel and military commanders must act. Reaching a defensible ethical decision requires moral agents to define the military and medical mission clearly and answer the following questions. Is the proposed operation or policy an effective and necessary means to attain the mission’s goals? Are the costs proportionate, keeping in mind that costs include military, medical, and moral costs? Finally, is the deliberative forum appropriate? Military medical ethics entails private (doctor-patient) and public discourse. Public discourse or deliberation engages the political community and its institutions. It requires widespread participation, well-reasoned arguments, reasonable pluralism, and, ultimately, responsive public policy.
Military Medicine in Contemporary Armed Conflict
Authors: Gross Michael L. 
Published: June 2021

Abstract
In the Iraq and Afghanistan wars (2001 and ongoing), military medicine saved more wounded than in any previous conflict. Improvised explosive devices (IEDs) injured tens of thousands of the more than three million warfighters deployed. Prominent wounds included multisystem injuries, traumatic brain injuries, limb loss, and post-traumatic stress (PTSD). To care for wounded service personnel, multinational forces established in-theater facilities for lightly and moderately wounded, while evacuating the critically injured to Europe and the United States. Coalition facilities could not offer comprehensive medical attention to host-nation allies or civilians. As the fighting progressed, multinational forces teamed up with local government agencies to slowly rebuild local medical infrastructures through Medical Civic Action Programs (MEDCAP) and Provincial Reconstruction Teams (PRT). As the conflicts wind down, Coalition nations face their responsibility to rebuild each country and to tend discharged veterans at home. Both tasks prove daunting.
Combat Casualty Care
Authors: Gross Michael L. 
Published: June 2021

Abstract
To deliver combat casualty care to warfighters, multinational forces deploy medical units to provide immediate front-line treatment, transfer the injured to in-theater combat hospitals, and evacuate the critically wounded to Europe and the United States. With bed space limited, Coalition medical facilities developed medical rules of eligibility to regulate the flow of multinational patients, host-nation allies, detainees, and local civilians. While multinational patients received unreserved medical attention, local nationals were, at best, only eligible for emergency care before transfer to poorly equipped local facilities. Despite legal provisions that stipulate impartial care based solely on urgent medical need, medical personnel attended to patients based on national identity and military status. Military necessity sometimes permits treating moderately injured warfighters before the critically ill to return the former to duty. Appealing to associative duties, however, allows military medical providers to deliver preferential care to compatriots despite urgent medical need elsewhere.