bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tralokinumab therapy for moderate‐to‐severe atopic dermatitis: Clinical outcomes with targeted IL‐13 inhibition
Authors: Simpson Eric L. , Guttman‐Yassky Emma , Eichenfield Lawrence F. , Boguniewicz Mark , Bieber Thomas , Schneider Shannon , Guana Adriana , Silverberg Jonathan I. 
Published: July 2023

AbstractAtopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)‐13 is a cytokine that acts as a driver of immune dysregulation, skin‐barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL‐13 with high affinity, thereby inhibiting subsequent downstream IL‐13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate‐to‐severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index‐75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient‐reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL‐13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate‐to‐severe AD.
Crisis temporalities and ongoing capabilities in the lives of young people growing up on the streets of African cities: An ethnographic longitudinal perspective
Authors: van Blerk Lorraine , Hunter Janine , Shand Wayne 
Published: July 2023

AbstractUnderstanding young people's lives through a focus on their micro‐geographies has been central for exercising young people's voices through research. However, such a focus has also neglected the multiple and complex realities of growing up that ripple throughout their lives, resulting in calls for more research to go beyond capturing daily snapshots of experience. This paper acknowledges that decades of research with and for young people living on city streets has underpinned activism and challenged western child rights discourse, helping to ensure that abuses and violations of street young people's rights are confronted. Yet, much of this research draws attention to lives lived in present moments – the difficulties encountered and capabilities displayed. It does not account for the temporal fluidity of how young people's realities are future impacted by slow crises and challenging daily life experiences as they grow towards adulthood. This paper explores the crisis temporalities of young people's street lives through a youth‐led ethnographic longitudinal approach. The paper focuses on 18 youth researchers and over 200 of their peers' experiences of research over three years while living on the streets of three African cities. The paper discusses the challenges of undertaking longitudinal research alongside the temporal affordances of surviving urban informality and the compounding effects of slow crises on present and future‐oriented survival. These affordances emerge as street youth respond to daily trials, experience setbacks, crises, triumphs, and failures, yet show resilience and employ capabilities. The paper concludes by demonstrating the crucial importance of ethnographic longitudinal research for policy and practice to ensure that youth who age on the streets, and their families, are supported in accordance with social justice concerns.
Drug shortages. Part 1. Definitions and harms
Authors: Aronson Jeffrey K. , Heneghan Carl , Ferner Robin E. 
Published: July 2023

AbstractDrug shortages are repeatedly in the news. The earliest drug shortages were reported during the First World War, but the numbers of shortages have increased in recent years. In the first part of this two‐part review, we discuss definitions of drug shortages and so‐called stockouts, which are localized shortages, and the harms that they can cause. Drug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations, but we lack an adequate definition. The problems are too complicated to be encompassed in a brief intensional dictionary‐style definition, and that is reflected in the many different attempts at definition that have been proposed. We therefore propose an extensional operational definition that incorporates the processes by which products are manufactured, the causes of shortages and the contributory factors. A definition of this sort allows one to identify the main causes of a particular drug shortage and therefore the remedies that might prevent, mitigate or manage it. In the second part of the review we discuss the causes and solutions in more detail. Adverse drug reactions and medication errors attributable to shortages occur but are not often reported. Adverse reactions to substitute medicines are possible, and errors can occur because of unfamiliarity or unnecessary treatment with replacement medicines. Other harmful outcomes include withdrawal reactions, undertreatment, treatment delays and cancellations, failure of alternatives and disruption of clinical trials.
Drug shortages. Part 2: Trends, causes and solutions
Authors: Aronson Jeffrey K. , Heneghan Carl , Ferner Robin E. 
Published: July 2023

AbstractDrug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations. In the first part of this review we proposed an operational definition that incorporates the processes by which products are manufactured, the causes of shortages and stock‐outs (local shortages), and the contributory factors. Here we discuss causes and possible solutions. Drug shortages have complex causes, and a single cause cannot always be identified. Reasons include lack or shortage of raw materials, manufacturing difficulties, regulatory and political actions, voluntary recalls, just‐in‐time inventory systems, halts in production for financial or other business reasons, low demand (eg, orphan products, reduced usage), mergers, market shifts (eg, diversion to home markets) and unexpected increases in demand (eg, improved diagnosis, new trial information, epidemics and pandemics, inappropriate use, off‐label use). Potential solutions are as diverse as the potential causes. Prevention is hard, because shortages are not easily predicted. Everyone in the supply chain is involved in anticipating and managing shortages, with responsibilities for preventing them or at least trying to mitigate their effects. This includes manufacturers and suppliers, particularly of generic formulations, pharmacists, prescribers, patients and governments. Solutions can therefore be linked to the causes and classified according to where the responsibility for implementing them lies.
The shame of being undone by illness and the power of support through the body of Christ
Authors: Thompson Deanna A. 
Published: July 2023

AbstractThis paper examines shame that arises from living with a body that has been undone by cancer or other serious illness. It draws on first‐person narratives and social‐scientific studies of cancer patients to explore how bodies undone by illness often cease to conform to cultural standards of health as well as gendered expectations of bodies, and how experiences of shame arise from those shifts in how sick bodies appear and perform. Analysis of narratives by and qualitative data about those who are seriously ill also reveals how the undoing of the body by illness often precipitates an undoing of one's sense of self that leads to experiences of shame over an inability to fill roles and expectations in ways that were possible in life before serious illness. The paper then utilizes biblical and theological resources to explore ways religious communities can make space for those living with serious illness to lament what it's like to be undone by illness, to hold them up amid their experiences of vulnerability through public lament and acts of accompaniment, and to affirm their worth in the eyes of God and in the body of Christ.
Association of prediabetes progression and regression with cognitive decline: Findings from the CHARLS
Authors: Xing Xing , Wang Yining , Shen Ziyuan , Pan Faming , Cai Guoqi 
Published: July 2023

AbstractAimThe aim of the study was to describe the association of prediabetes progression and regression with change in cognitive function.MethodsData from three waves (2011, 2015 and 2018) of the China Health and Retirement Longitudinal Study (CHARLS) were analysed. Diabetic statuses in 2011 and 2015 were ascertained using the American Diabetes Association criteria. Cognitive function was assessed and standardized at all three waves, where a total score and its two components (episodic memory and metal status) were calculated. We evaluated the association of prediabetes progression and regression (from 2011 to 2015) with changes in cognitive function from 2011 to 2015 and from 2015 to 2018.ResultsOf 2590 participants (56% women, mean age 58.6 ± 8.4 years) with prediabetes, 12% progressed to diabetes and 41% regressed to normoglycaemia. Compared with participants who remained as prediabetes, those who progressed to diabetes showed a trend to have accelerated decline in episodic memory (β = −0.11, 95% confidence interval −0.22 to 0.003, p = 0.057). However, participants who regressed to normoglycaemia did not have less cognitive decline. Neither prediabetes progression nor regression predicted change in cognitive function from 2015 to 2018. In a separate group of participants who remained as normoglycaemia (n = 858), changes in cognitive function from 2011 to 2015 and from 2015 to 2018 were similar to those who remained as prediabetes.ConclusionIn people with prediabetes, progression to diabetes may be associated with accelerated cognitive decline but regression to normoglycaemia does not retard cognitive decline. Prediabetes progression and regression may not be predictive of change in cognitive function.
Chimeric antigen receptor T cells for acute myeloid leukemia
Authors: Fetsch Viktor , Zeiser Robert 
Published: July 2023

AbstractThe use of T cells expressing chimeric antigen receptors (CARs) that can target and eliminate cancer cells has revolutionized the treatment of B‐cell malignancies. In contrast, CAR T cells have not yet become a routine treatment for myeloid malignancies such as acute myeloid leukemia (AML) or myeloproliferative neoplasms (MPNs). For these disease entities, allogeneic hematopoietic cell transplantation (allo‐HCT) relying on polyclonal allo‐reactive T cells is still the major cellular immunotherapy used in clinical routine. Here, we discuss major hurdles of CAR T‐cell therapy for myeloid malignancies and novel approaches to enhance their efficacy and reduce toxicity. Heterogeneity of the malignant myeloid clone, CAR T‐cell induced toxicity against normal hematopoietic cells, lack of long‐term CAR T‐cell persistence, and loss or downregulation of targetable antigens on myeloid cells are obstacles for successful CAR T cells therapy against AML and MPNs. Strategies to overcome these hurdles include pharmacological interventions, for example, demethylating therapy to increase target antigen expression, multi‐targeted CAR T cells, and gene‐therapy based approaches that delete the CAR target antigen in the hematopoietic cells of the recipient to protect them from CAR‐induced myelotoxicity. Most of these approaches are still in preclinical testing but may reach the clinic in the coming years. In summary, we report on barriers to CAR T‐cell use against AML and novel therapeutic strategies to overcome these challenges, with the goal of clinical treatment of myeloid malignancies with CAR T cells.
Into the Pedocene—Pedology of a changing world
Authors: Hartemink Alfred E. 
Published: July 2023

AbstractPedology, or the study of soil, is often viewed focusing on soil formation, morphology, mapping and classification. But the study of soil has largely expanded beyond these four areas and now includes quantitative studies using soil legacy data combined with technological advances in data collection, soil sampling and computation. We have global availability of soil information and can retrieve pedological information for any location including some indication of its accuracy. Scientific and technological developments in pedology have been led by the rise of several subdisciplines including pedometrics, digital soil mapping, spectral pedology, digital soil morphometrics, hydropedology, microbial pedology, astropedology and the development of pedotransfer functions. With the expansion of pedology and its relevance for understanding the earth system and tackling global change, it is postulated that soil science has now entered the ‘Pedocene’—a soil epoch equivalent to the Anthropocene. The Pedocene is characterized by the quantitative understanding and evaluation of the global soil system, and the effects of human‐induced changes brought to soil.
Potential for carbon sequestration after biochar‐P fertilizer application: A biological and chemical assessment
Authors: Borges Bernardo M. M. N. , Barreto Matheus Sampaio C. , Pavinato Paulo S. , Franco Henrique C. J. , Carvalho João Luís Nunes , Strauss Mathias , Sohi Saran 
Published: July 2023

AbstractInnovation is required on many fronts in agriculture, not only to improve nutrient use efficiency but also to mitigate the effects of climate change. Our previous studies presented the high agronomic efficiency of an experimental phosphate fertilizer using a biochar‐matrix, called ‘BioFert’. However, the efficiency of BioFert for soil carbon sequestration goals has not yet been evaluated. We incubated BioFert and initial raw sugarcane‐biochar over 56 days in two soils (i.e., Ferralsol and Alisol) and measured the total CO2 and δ13C‐CO2 to quantify the contribution of native soil organic matter, sugarcane‐biochar, or BioFert to carbon mineralization. There was no significant difference in cumulative CO2 release between BioFert and the control (without carbon addition), and BioFert was less mineralized than carbon from sugarcane‐biochar regardless of soil type. In addition, accelerated aging by thermal oxidation of these carbon sources revealed that more than 80% of BioFert‐carbon was prevented from accelerated mineralization, while sugarcane‐biochar achieved ~80% of carbon mineralization. The residual solids after oxidation were analysed by X‐ray photoelectron spectroscopy and indicated aliphatic/aromatic and carboxylic chemical bonds on the BioFert surface, which might offer new cation exchange sites over time. We conclude that BioFert is not only a phosphate fertilizer with high phosphorus use efficiency but also a stable source of carbon for soil carbon sequestration purposes.
Lipid biomarkers recording marine microbial community structure changes through the Frasnian‐Famennian mass extinction event
Authors: Chen Jian , Hogancamp Nicholas , Lu Man , Ikejiri Takehito , Malina Natalia , Ojeda Ann , Sun YongGe , Lu YueHan 
Published: July 2023

AbstractStudying the response and recovery of marine microbial communities during mass extinction events provides an evolutionary window through which to understand the adaptation and resilience of the marine ecosystem in the face of significant environmental disturbances. The goal of this study is to reconstruct changes in the marine microbial community structure through the Late Devonian Frasnian‐Famennian (F‐F) transition. We performed a multiproxy investigation on a drill core of the Upper Devonian New Albany Shale from the Illinois Basin (western Kentucky, USA). Aryl isoprenoids show green sulfur bacteria expansion and associated photic zone euxinia (PZE) enhancement during the F‐F interval. These changes can be attributed to augmented terrigenous influxes, as recorded collectively by the long‐chain/short‐chain normal alkane ratio, carbon preference index, C30 moretane/C30 hopane, and diahopane index. Hopane/sterane ratios reveal a more pronounced dominance of eukaryotic over prokaryotic production during the mass extinction interval. Sterane distributions indicate that the microalgal community was primarily composed of green algae clades, and their dominance became more pronounced during the F‐F interval and continued to rise in the subsequent periods. The 2α‐methylhopane index values do not show an evident shift during the mass extinction interval, whereas the 3β‐methylhopane index values record a greater abundance of methanotrophic bacteria during the extinction interval, suggesting enhanced methane cycling due to intensified oxygen depletion. Overall, the Illinois Basin during the F‐F extinction experienced heightened algal productivity due to intensified terrigenous influxes, exhibiting similarities to contemporary coastal oceans that are currently undergoing globalized cultural eutrophication. The observed microbial community shifts associated with the F‐F environmental disturbances were largely restricted to the extinction interval, which suggests a relatively stable, resilient marine microbial ecosystem during the Late Devonian.
Exploring the association between educational aspirations and intentions to migrate among youth in Central Mexico by gender
Authors: Marsiglia Flavio F. , Campos Ana Paola , Wu Shiyou , Nuño‐Gutiérrez Bertha L. , García‐Pérez Hilda , Glick Jennifer E. 
Published: July 2023

AbstractWe assessed the association between educational aspirations and the intention to migrate among 1446 adolescents aged 11–17 years, living in semi‐urban/rural communities in Jalisco, Mexico. Analyses rely on survey data from the Family Migration and Early Life Outcomes study. The outcome variable was the intention to migrate, a three‐category variable coded as no intention to migrate, intention to migrate within Mexico, and intention to migrate internationally. The main independent variable was the adolescents' educational aspirations, conceptualized as the intention to achieve higher education. Multinomial logistic regression models were used to examine associations. We found an association between educational aspirations and intentions to migrate, and it was moderated by gender. Girls with the highest educational aspirations intended to migrate internationally, while higher educational aspirations were not a driver for boys' migration intentions. The study findings have implications for education and migration policies and future research.
Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions
Authors: Dougan Michael 
Published: July 2023

SummaryImmune checkpoint inhibitor (ICI) therapy has revolutionized the field of oncology over the past decade, leading to durable remissions in some patients but also producing a wide spectrum of treatment‐limiting inflammatory toxicities that are referred to as immune‐related adverse events (irAEs). Although irAEs can involve any organ system in the body, they most commonly affect the barrier tissues, including the gastrointestinal tract with colitis and enterocolitis affecting a significant fraction of patients on ICIs. We are beginning to understand the mechanisms that drive ICI colitis, with early experiments indicating a role for CD8+ resident memory T cells (TRMs) in the gut, which become activated and differentiate into cytotoxic cells in response to ICI therapy. The risk factors that define who will develop ICI colitis are not understood and substantial efforts are underway to identify potential biomarkers for risk of this and other toxicities. Optimal management of ICI colitis is also an area of active investigation. Current standard treatments are based largely on small, retrospective analyses, and while drugs like systemic glucocorticoids or the TNFα inhibitor infliximab do appear to be highly active in ICI colitis, the impact of these therapies on antitumor responses is poorly understood. As discussed in this review, future work will have to define the immune mechanisms driving ICI colitis in more detail and in comparison to antitumor responses in order to identify candidate pathways that can be targeted to improve ICI colitis without interfering in antitumor immunity. Studying these interventions will require randomized, controlled trials with both tumor and colitis endpoints, a goal that will necessitate collaboration across institutions and funding agencies. We are at a point where such collaborative trials are feasible, and have the potential to greatly improve the care of patients with ICI colitis as well as other irAEs.
Bromelain‐based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long‐term outcomes
Authors: Shoham Yaron , Gasteratos Konstantinos , Singer Adam J. , Krieger Yuval , Silberstein Eldad , Goverman Jeremy 
Published: July 2023

AbstractIn 2012 the European Medicines Agency approved a pineapple stem‐derived Bromelain‐based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013–2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta‐Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain‐based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non‐surgical eschar removal treatment modality. The benefits of Bromelain‐based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain‐based debridement are expanding to cover “off‐label” cases with significant benefits to the global healthcare economy.