bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rehabilitation needs screening to identify potential beneficiaries: a scoping review
Authors: De Groote Wouter , Corso Melissa , Murnaghan Kent , Duttine Antony , Sabariego Carla 
Published: April 2024

ObjectivesThe aim is to identify and compare the content of screening tools and needs assessments used to select rehabilitation beneficiaries and to describe the context of their use.DesignScoping review.Data sourcesWe systematically searched five indexed databases for studies published from 1 January 2010 to 3 February 2023.Eligibility criteriaWe searched for papers published in English only. Papers describe a screening tool or needs assessment aiming to prospectively select potential beneficiaries of rehabilitation services based on a cut-off score or classification system.Data extraction and synthesisWe charted the evidence according to the characteristics of the paper, rehabilitation needs screening context, screening tool and content of the screening tool. A descriptive synthesis is provided for screening methodology, settings, target populations, rehabilitation need types and phases of care. The WHO International Classification of Functioning, Disability and Health is used to categorise screening items.ResultsWe identified 24 tools that use a range of screening methodologies, but mostly questionnaires that are used by health workers. Most tools have been proposed for the identification of a rehabilitation beneficiary among people with selected health conditions assessing the need to access a specific rehabilitation intervention, programme or occupational group. The majority of tools screen for current functioning limitations, and this is often the only screening component. When mapping screening items with the WHO International Classification of Functioning, Disability and Health (ICF), almost all ICF chapters for body functions and activities and participation have been included across screening tools, with the following most frequently included ICF categories: emotional functions (b152), acquiring, keeping and terminating a job (d845), sensation of pain (b280) and carrying out daily routine (d230).ConclusionsRehabilitation need screening tools commonly include the screening for current functioning limitations among people with selected health conditions. A screening tool that is applicable across health conditions and settings is not available.
Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors
Authors: Frentzas Sophia , Austria Mislang Anna Rachelle , Lemech Charlotte , Nagrial Adnan , Underhill Craig , Wang Wenjing , Wang Zhongmin Maxwell , Li Baiyong , Xia Yu , Coward Jermaine I G 
Published: April 2024

BackgroundStudies showed that vascular endothelial growth factor (VEGF) inhibitors could improve therapeutic efficacy of PD-1/PD-L1 antibodies by transforming the immunosuppressive tumor microenvironment (TME) into an immunoresponsive TME. Ivonescimab is a first-in-class, humanized tetravalent bispecific antibody targeting PD-1 and VEGF-A simultaneously. Here, we report the first-in-human, phase 1a study of ivonescimab in patients with advanced solid tumors.MethodsPatients with advanced solid tumors were treated with ivonescimab 0.3, 1, 3, 10, 20 or 30 mg/kg intravenously every 2 weeks using a 3+3+3 dose escalation design. Dose expansion occurred at 10 and 20 mg/kg in selected tumor types. The primary objective was to assess the safety and tolerability, and to determine the maximum tolerated dose (MTD). The secondary objectives included pharmacokinetics, pharmacodynamics and preliminary antitumor activity based on Response Evaluation Criteria in Solid Tumors V.1.1.ResultsBetween October 2, 2019 and January 14, 2021, a total of 51 patients were enrolled and received ivonescimab. Two dose-limiting toxicities were reported at 30 mg/kg. The MTD of ivonescimab was 20 mg/kg every 2 weeks. Grade≥3 treatment-related adverse events (TRAEs) occurred in 14 patients (27.5%). The most common TRAEs of any grade were rash (29.4%), arthralgia (19.6%), hypertension (19.6%), fatigue (17.6%), diarrhea (15.7%) and pruritus (11.8%). The most common grade≥3 TRAEs were hypertension (7/51, 13.7%), alanine aminotransferase increased (3/51, 5.2%), aspartate aminotransferase increased (2/51, 3.9%) and colitis (2/51, 3.9%). Of 47 patients who had at least one postbaseline assessment, the confirmed objective response rate was 25.5% (12/47) and disease control rate was 63.8% (30/47). Among 19 patients with platinum-resistant ovarian cancer, 5 patients (26.3%) achieved partial response (PR). Efficacy signals were also observed in patients with mismatch repair proficient (pMMR) colorectal cancer, non-small cell lung cancer, and both MMR deficient and pMMR endometrial cancer.ConclusionsIvonescimab demonstrated manageable safety profiles and promising efficacy signals in multiple solid tumors. Exploration of alternative dosing regimens of ivonescimab monotherapy and combination therapies is warranted.Trial registration numberNCT04047290.
Patient-perspective and feasibility of home finger-prick testing to complement and facilitate large-scale research in rheumatology
Authors: Besten Yaëlle R , Boekel Laura , Steenhuis Maurice , Hooijberg Femke , Atiqi Sadaf , Leeuw Maureen , Vogelzang Erik H , Keijser Jim , Keijzer Sofie , Loeff Floris C , Gerritsen Martijn , Tas Sander W , Nurmohamed Michael T , Rispens Theo , Wolbink Gertjan 
Published: April 2024

BackgroundDuring the COVID-19 pandemic, we developed a digital research platform to longitudinally investigate COVID-19-related outcomes in patients with rheumatic diseases and healthy controls. We used home finger-prick testing in order to collect serum samples remotely and increase the overall efficiency of the platform. The aim of the present study was to evaluate the success rate of the finger prick and patients’ perspective towards the finger prick.MethodsSerum samples were collected up to five times during follow-up, either via a venepuncture at the research institute or a finger prick from participants’ home. Participants were asked to complete a digital evaluation questionnaire of the finger prick after their attempts.ResultsA total of 2135 patients and 899 controls performed at least one finger prick and were included in this study. The first finger prick was successfully done by 92% (95% CI: 90% to 93%) of patients, 94% (95% CI: 92% to 95%) of controls, 93% (95% CI: 92% to 94%) of all participants aged ≤70 years and 89% (95% CI: 86% to 92%) of all participants aged >70 years. Sex did not impact these success rates. Repeated failure occurred in 11/439 (0.8%) patients and 4/712 (0.6%) controls. Both patients and controls were less willing to perform a finger prick for individual healthcare compared with scientific research.ConclusionThe vast majority of participants, among which elderly and patients with rheumatic diseases, were able to successfully draw the required amount of blood for serological analyses. This shows that finger-prick testing is suitable for a high-throughput implementation to monitor patients remotely.
Assessment of Patient-Derived Xenograft Growth and Antitumor Activity: The NCI PDXNet Consensus Recommendations
Authors: Meric-Bernstam Funda , Lloyd Michael W. , Koc Soner , Evrard Yvonne A. , McShane Lisa M. , Lewis Michael T. , Evans Kurt W. , Li Dali , Rubinstein Lawrence , Welm Alana , Dean Dennis A. , Srivastava Anuj , Grover Jeffrey W. , Ha Min J. , Chen Huiqin , Huang Xuelin , Varadarajan Kaushik , Wang Jing , Roth Jack A. , Welm Bryan , Govinden Ramaswamy , Ding Li , Kaochar Salma , Mitsiades Nicholas , Carvajal-Carmona Luis , Herylyn Meenhard , Davies Michael A. , Shapiro Geoffrey I. , Fields Ryan , Trevino Jose G. , Harrell Joshua C. ,   NCI PDXNet Consortium, Doroshow James H. , Chuang Jeffrey H. , Moscow Jeffrey A. 
Published: April 2024

Abstract
Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.
INA03: A Potent Transferrin-Competitive Antibody–Drug Conjugate against CD71 for Safer Acute Leukemia Treatment
Authors: Bratti Manuela , Stubbs Elisa , Kolodych Sergii , Souchet Herve , Kelly Lois , Merlin Johanna , Marchal Michelle , Castellano Remy , Josselin Emmanuelle , Pasquer Hélène , Benajiba Lina , Puissant Alexandre , Koniev Oleksandr , Collette Yves , Belanger Coralie , Hermine Olivier , Monteiro Renato C. , Launay Pierre 
Published: April 2024

Abstract
Innovative strategies for enhancing efficacy and overcoming drug resistance in hematologic cancers, such as using antibody–drug conjugates (ADC), have shifted the paradigm of conventional care by delivering promising outcomes in cancer therapies with a significant reduction in the risk of relapse. Transferrin receptor (TfR1), cluster of differentiation 71 (CD71), is known to be overexpressed in malignant cells and considered a potent antitumor target. Therefore, we developed an anti-CD71 ADC, INA03, a humanized antibody conjugated to monomethyl auristatin E through a 3-arylpropiolonitrile–valine–citrulline linker. In this study, we investigated the potency and safety of INA03, in competition with Transferrin (Tf), the CD71’s natural ligand, as a novel strategy to specifically target highly proliferative cells. The high expression of CD71 was confirmed on different leukemic cell lines, allowing INA03 to bind efficiently. Subsequently, INA03 rapidly internalizes into lysosomal compartments, in which its cytotoxic drug is released following cathepsin B cleavage. Downregulation of CD71 expression using shRNA highlighted that INA03-induced cell death was dependent on CD71 density at the cell surface. INA03 intravenous treatment in acute leukemia mouse models significantly reduced tumor burden, increased mouse survival, and showed no residual disease compared with conventional chemotherapies. Because INA03 competes with human Tf, a double knock-in (human CD71/human Tf) competent mouse model was generated to mimic human pharmacokinetics and pharmacodynamics. INA03 administration in human CD71/hTf mice did not reveal any improper toxicities, even at high doses. Hence, these data demonstrate the promising preclinical efficacy and safety of INA03 and support its development as a novel acute leukemia treatment.
Significance: The Tf receptor is believed to be undruggable because of its ubiquitous expression. By entering into competition with its cognate ligand, the Tf and INA03 ADC can safely achieve potency.
Prevalence of H. pylori and Gastric Intestinal Metaplasia in BRCA1 and BRCA2 Carriers
Authors: Niccum Blake A. , Coughlin Sarah , Clay Daniel , Heiman Jordan , Buckley Kole H. , Dungan Michaela , Daniel Michael G. , Ruiz Jose , Maxwell Kara N. , Domchek Susan M. , Leung Galen , Ahmad Nuzhat A. , Ginsberg Gregory G. , Kochman Michael L. , Katona Bryson W. 
Published: April 2024

Abstract
BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer; however, the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of gastric cancer risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of gastric cancer in this population. A total of 100 unselected BRCA1/2 carriers who underwent endoscopic ultrasound from March 2022 to March 2023 underwent concomitant upper endoscopy with nontargeted gastric antrum and body biopsies. The study population (70% women; mean age 60.1 years) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no gastric cancers were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to that in the general population; however, identification of H. pylori or GIM may help inform future gastric cancer risk management strategies in BRCA1/2 carriers.
Prevention Relevance: Evaluating the burden of H. pylori infection and GIM among BRCA1/2 carriers is warranted to better understand the mechanisms of gastric carcinogenesis and to help inform risk management strategies for gastric cancer among this at-risk population.
Reflections on the Novel, Ecology, and the Laws of Thermodynamics
Authors: Gold Barri J. 
Published: April 2024

Abstract
The intertwined narratives of realistic fiction and the laws of thermodynamics parallel one another in their shaping of anthropocentric perspectives. The novel, with its human-centered storytelling, forward trajectory, concern with the details of daily life, and satisfyingly closed endings, has powerfully influenced our expectations for narratives in both fiction and non-fiction alike. Examining two ecologically problematic aspects of the novel—its anthropocentrism and its apparent closure—in relation to the science of energy, this study suggests that understanding the biases within novelistic storytelling can shed light on inherent biases in scientific narratives, encouraging a reevaluation of energy discourse to foster alternative perspectives and ecologically conscious worldviews.
Bites, Blood, Boundaries: Rats, Mosquitoes, and Domestication across Disciplines
Authors: Reis-Castro Luisa , Lee Jia Hui 
Published: April 2024

Abstract
Domestication is a set of processes that requires active reconfigurations of interspecies relations, environments, and technologies. In this view, both ethnographic and historical sources help us track the exact ways that domestication as a practice actively reveals and conceals relations of power among people and between people and other animals. Two pertinent cases—training rats in Tanzania to detect landmines and releasing mosquitoes to deter the transmission of pathogenic viruses in Brazil—take place in contexts where animals are being modified to achieve certain developmental, medical, or humanitarian goals. These animals, like any in the history of domestication, breach boundaries, crossing wild and domestic categories, in these cases at the moment and experience of being bitten. These moments draw our attention to the stakes involved in thinking about domestication.
“Sentient Beings”: Cephalopods’ Minds and U.K. Law
Authors: Shmuely Shira 
Published: April 2024

Abstract
How and why has invertebrate sentience come to be debated by lawmakers, and what does this development tell us about the relationship between scientific knowledge, animal ethics, and the law? This preliminary analysis of this puzzle examines milestones in the production of knowledges about cephalopods (squids, cuttlefish, nautilus, and octopuses) starting in the 1830s and traces the role this knowledge played in the ideas and debates that led to the inclusion of cephalopods in U.K. animal welfare law. New ideas about mind and consciousness emerged from the interplay between interspecies encounters among people and cephalopods and the gradual revision of ethical obligations toward nonhuman animals more generally.
Immediate Operative Trauma Assessment Score: A Simple and Reliable Predictor of Mortality in Trauma Patients Undergoing Urgent/Emergent Surgery
Authors: Silver Elliot , Nahmias Jeffry , Lekawa Michael , Inaba Kenji , Schellenberg Morgan , De Virgilio Christian , Grigorian Areg 
Published: April 2024

Objective: Many current trauma mortality prediction tools are either too intricate or rely on data not readily available during a trauma patient’s initial evaluation. Moreover, none are tailored to those necessitating urgent or emergent surgery. Our objective was to design a practical, user-friendly scoring tool using immediately available variables, and then compare its efficacy to the widely-known Revised Trauma Score (RTS). Methods: The adult 2017-2021 Trauma Quality Improvement Program (TQIP) database was queried to identify patients ≥18 years old undergoing any urgent/emergent operation (direct from Emergency Department to operating room). Patients were divided into derivation and validation groups. A three-step methodology was used. First, multiple logistic regression models were created to determine risk of death using only variables available upon arrival. Second, the weighted average and relative impact of each independent predictor was used to derive an easily calculated Immediate Operative Trauma Assessment Score (IOTAS). We then validated IOTAS using AUROC and compared it to RTS. Results: From 249 208 patients in the derivation-set, 14 635 (5.9%) died. Age ≥65, Glasgow Coma Scale score <9, hypotension (SBP <90 mmHg), and tachycardia (>120/min) on arrival were identified as independent predictors for mortality. Using these, the IOTAS was structured, offering scores between 0-8. The AUROC for this was .88. A clear escalation in mortality was observed across scores: from 4.4% at score 1 to 60.5% at score 8. For the validation set (250 182 patients; mortality rate 5.8%), the AUROC remained consistent at .87, surpassing RTS’s AUROC of .83. Conclusion: IOTAS is a novel, accurate, and now validated tool that is intuitive and efficient in predicting mortality for trauma patients requiring urgent or emergent surgeries. It outperforms RTS, and thereby may help guide clinicians when determining the best course of action in patient management as well as counseling patients and their families.
Poor Acceptance of the Revised Classification of Premalignant Anal Lesions Following the LAST Standardized Project
Authors: Montero Stefania , Sandigo-Saballos Isabela , Tom Cynthia , Lee Hanjoo 
Published: April 2024

Introduction The Lower Anogenital Squamous Terminology (LAST) Project recommended unified classification for HPV–associated squamous lesions of the lower anogenital tract, using a 2-tiered nomenclature in 2013. Adherence to the new nomenclature worldwide is unknown. This study aims to assess the trend of the use of the two-tiered High Squamous Intraepithelial Lesion and Low Squamous Intraepithelial Lesion (HSIL/LSIL) as opposed to the traditional three-tiered Anal Intraepithelial Neoplasia (AIN I/II/III) classification as suggested by the LAST Project. Methods A literature search on full-text English language studies of premalignant anal lesion was performed on PubMed from 2002-2022. The studies were categorized by continent, and the prevalence of HSIL/LSIL classification vs AIN I/II/III was calculated. Results 546 studies and 251 studies were identified using the AIN I/II/II and the HSIL/LSIL classification respectively. Global trend suggested a statistically significant downward trend in the use of the two-tiered nomenclature system in publications globally. Regional trend including North America, Europe, and other (Asia and Latin America) showed variance in adoption of the two-tiered nomenclature system. Conclusion Despite multidisciplinary collaborative effort, adherence to the recommendations to use the two-tiered system for HPV-associated premalignant anal lesions continues to be suboptimal. Further efforts are needed to identify the cause of poor adherence to be able to create strategies that reinforces unification of terminology and integration of LAST the recommendations.
Exploring the association of Indigeneity, social adversity status and externalizing symptoms in children and adolescents
Authors: Vance Alasdair , McGaw Janet , O’Meara Angel , Gone Joseph P , Eades Sandra 
Published: April 2024

Objective: The relationship between Indigeneity, social adversity status and externalizing symptoms is complex and unclear. This study investigates how Indigeneity, social adversity status and externalizing symptoms are related in young people. Methods: A total of 132 Indigenous and 247 non-Indigenous young people aged 6–16 years were recruited from a hospital mental health outpatient service. Normality plots with statistics for social adversity status and parent-reported externalizing symptoms were completed for the two groups, matched for age, gender, mental disorder symptom severity, symptom-linked distress and impairment. Standard multiple regression was used to examine how Indigeneity moderates the relationship between social adversity status and parent-reported externalizing symptoms. A scatterplot investigated the association between Indigeneity and social adversity status in young people with parent-reported externalizing symptoms. Results: The distributions of the two groups and (1) social adversity status and (2) parent -reported externalizing symptoms were non-normal but acceptable for a moderator analysis. Indigeneity and social adversity status made independent significant positive contributions to externalizing symptoms. In contrast the interaction between Indigeneity and social adversity status made a nonsignificant negative trend to externalizing symptoms. A scatterplot revealed Indigeneity moderated the link between social adversity status and externalizing symptoms. Conclusions: High social adversity status is linked to externalizing symptoms in non-Indigenous young people but despite higher social adversity, Indigenous young people don’t necessarily externalize. Potential protective resilience factors for externalizing symptoms in the Indigenous young people need to be ascertained and nurtured. Future systematic investigations of the contribution of these protective factors to Indigenous referral pathways and management are needed. It is also crucial that increased social adversity status is addressed and managed in all young people, regardless of Indigeneity.
The Impact of Behavioral Lifestyle Intervention on Inflammatory Cytokines in Older Adults Living With Type 2 Diabetes: A Feasibility Study
Authors: Jiwani Rozmin , Serra Monica , Espinoza Sara , Berndt Andrea , Patel Darpan 
Published: April 2024

Objective: This study investigates the effects of a behavioral lifestyle intervention on inflammatory cytokines and frailty in older adults (≥ 65 years) with type 2 diabetes (T2D). Method: We conducted a single-arm, 6-month intervention supplemented with diet and activity self-monitoring technology. We assessed frailty using Fried criteria and quantified inflammatory cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating-factor [GM-CSF], interferon [IFN-γ], tumor necrosis factor [TNF-α]) using a multiplex assay. We used paired t-tests with significance at P < .05. We calculated the Spearman correlation and evaluated the relationship between frailty, BMI, and inflammatory cytokines. Results: Eighteen participants completed the study (mean ± SD: 71.5 ± 5.3 years; BMI: 34 ± 6 kg/m2). At baseline, we had 4 frail, 13 pre-frail, and 1 non-frail participant. At 6 months, we observed the therapeutic effects of the intervention on frailty score, BMI, IL-2, IFN-y, and GM-CSF. Discussion: The study highlights the importance of behavioral lifestyle intervention in improving inflammatory cytokines and frailty in older adults.