bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving detection of undiagnosed HIV through routine screening in a central London emergency department
Authors: Fox Matilda , Pettit Rosie , Mutengesa Ernest , Harper Alice , Nakhoul Maria , Mitra Anu 
Published: December 2022

HIV is a global public health issue. Routine testing for HIV should be performed on all 16–59 years old attending emergency departments (EDs) in high-prevalence areas in the UK.In August 2020, Charing Cross Hospital ED, situated in an ‘extremely high-prevalence’ area, had no formal guidelines on HIV testing. We aimed to increase HIV testing in 16–59 years old attending our ED to 25% by August 2021 through a quality improvement project, based on the Methodology for Improvement Model, performing six Plan–Do–Study–Act cycles over a 12-month period.An initial ED staff survey revealed 55% (n=22/40) of respondents were unsure of national HIV testing guidelines. Barriers to good testing practice included: lack of clarity on protocols for consent and indication, cost and perceived stigmatisation of patient groups. Interventions were employed at regular intervals, including employment of an HIV nurse advocate, inclusion of HIV tests in a blood test careset during ED triage, and updated trust guidelines that reflect national guidelines.Overall, we did achieve our original 12 month aim, with an average testing rate of 28% of our target group between September 2020 and August 2021. Extending the project to January 2022 has resulted in continued improvements in monthly testing rates, reaching 44% in December 2021. Further analysis revealed interventions led to a statistically significant and sustained increase in monthly testing rates on seven occasions.Valuable lessons were learnt in sustaining improvements in a busy department, changing long-held beliefs regarding consent for testing, and education around HIV care in the UK. Project write-up was formatted using the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE) template.
Educational needs assessment identifying opportunities to improve sepsis care
Authors: Davino Tammy , Van Hoof Thomas J , Elwell Joy , DeLayo Michelle 
Published: December 2022

IntroductionIn 2015, the Centers for Medicare and Medicaid Services developed a national quality bundle for the management of patients with severe sepsis and septic shock (SEP-1). Despite performance improvement measures, compliance remains low. This needs assessment is the first stage of a quality improvement initiative to improve SEP-1 compliance. Using a conceptual outcomes framework, this needs assessment analyses SEP-1 compliance data, knowledge, and competence to identify gaps in care and educational opportunities.MethodsThe needs assessment began with a review of national and statewide SEP-1 compliance data to identify a need for improvement. The needs assessment proceeded with a retrospective chart review to evaluate process measures and identify which providers would most likely benefit from educational interventions. A focus group provided perspective on the chart review findings.ResultsDuring the period of 1 April 2017–31 March 2018, national SEP-1 compliance was 51% and compliance at the studied institution was 19%. The chart review included 51 patients (66.7% severe sepsis, 33.3% septic shock). Frequently missed SEP-1 measures included administration of intravenous fluids (0% severe sepsis, 58.8% septic shock), repeat lactate levels (52.6% severe sepsis, 60% septic shock), documentation of volume and tissue perfusion assessment (58.8%), vasopressor administration (73.3%) and administration of broad-spectrum antibiotics (76.5%, severe sepsis). Focus group perceptions identified themes related to gaps in declarative and dispositional knowledge.ConclusionsThis educational needs assessment highlights gaps in SEP-1 clinician performance, competence and knowledge. A multifaceted education programme is the next step for this performance improvement project. Education should include a series of meetings, activities, and workshops that include declarative knowledge, procedural knowledge and dispositional knowledge. Simulation activities can provide an opportunity for providers to demonstrate competence. Point-of-care prompts and performance measurement and feedback of patient care data can support clinician performance. This needs assessment underscores the need for a multifaceted approach to clinician education and performance to improve SEP-1 compliance.
Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer
Authors: Miller Richard A , Luke Jason John , Hu Shenshen , Mahabhashyam Suresh , Jones William B , Marron Thomas , Merchan Jaime R , Hughes Brett G M , Willingham Stephen B 
Published: December 2022

BackgroundCD73 is widely expressed on immune cells playing a critical role in immunomodulatory functions including cell adhesion and migration, as a costimulatory molecule for T cells and in production of adenosine. The function of CD73 expressed on B cells has not been fully characterized. Mupadolimab is an anti-human CD73 antibody that activates B cells. We evaluated the characteristics of this antibody and its effects on immune cells in vitro and in vivo.MethodsMupadolimab binding to CD73, inhibition of CD73 enzymatic activity, and effects on lymphocyte activation were evaluated in vitro by measuring changes in immunophenotype by flow cytometry. Cryogenic-transmission electron microscopy was used to determine epitope binding. Effects on human B cells in vivo were evaluated in immunodeficient NSG-SGM3 mice immunized with SARS-CoV-2 and influenza viral antigens. Safety and immune effects were evaluated in the completed dose escalation portion of a phase 1 trial conducted in patients with cancer.ResultsMupadolimab binds to a unique epitope on CD73POSB cells resulting in their activation and differentiation through B cell receptor signaling pathways. Mupadolimab induces expression of CD69, CD83, CD86 and MHC class II on B cells along with morphological transformation into plasmablasts and expression of CD27, CD38 and CD138. These effects are independent of adenosine. Mupadolimab binds to the N-terminal of CD73 in the closed position and competitively inhibits substrate binding. Mupadolimab enhanced antigen specific antibody response to SARS-CoV-2 spike protein and influenza hemagglutinin in humanized mouse models. Mupadolimab was evaluated as a monotherapy in a phase 1 trial (NCT03454451) in 34 patients with advanced cancer and demonstrated binding to CD73POScirculating cells and transient reduction in the number of B cells, with return of CD73NEGB cells with memory phenotype. No dose-limiting toxicities or changes in serum immunoglobulins were seen.ConclusionsMupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69POSB cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant.Trial registration numberNCT03454451.
Predictors of perceived risk in first-degree relatives of patients with rheumatoid arthritis
Authors: Bunnewell Sarah , Wells Imogen , Zemedikun Dawit , Simons Gwenda , Mallen Christian D , Raza Karim , Falahee Marie 
Published: December 2022

ObjectivesTo define variables associated with perceived risk of developing rheumatoid arthritis (RA) in first-degree relatives (FDRs) of patients with RA.MethodsPatients with RA and their FDRs were invited to complete cross-sectional surveys. FDR and index patient responses were linked. FDRs’ perceived absolute risk, comparative risk, experiential risk and worry about risk were assessed using 5-point Likert scales. FDR predictor variables included demographics, illness perceptions and psychosocial variables. Patient predictors of FDR perceived risk were assessed. Binary logistic regression examined the relationship between FDR characteristics and perceived risk of RA. Generalised estimating equations assessed whether patient variables predicted FDR’s perceived risk.Results396 FDRs returned a survey. 395 FDRs provided sufficient data and were included in analysis. Paired data from 213 patients were available for 291 of these FDRs. All measures of perceived risk were inter-correlated. 65.2% of FDRs perceived themselves to be ‘likely’ or ‘very likely’ to develop RA in their lifetime. Relationship with index patient, high health anxiety, female gender, long perceived RA duration, high perceived concern about RA, negative perceived emotional impact of RA and low perceptions of how well treatment would control RA were all associated with increased FDRs’ perceived risk. Patient characteristics did not associate with FDRs’ risk perceptions.ConclusionsFDRs’ perceived risk of RA was high. Key predictors included being a child of a patient with RA, higher health anxiety and lower perceptions of RA treatment control. An understanding of these predictors will inform the development of tailored risk communication resources and preventive clinical strategies for RA.
Dysphagia is associated with worse clinical outcomes in geriatric trauma patients
Authors: Kregel Heather R , Attia Mina , Pedroza Claudia , Meyer David E , Wandling Michael W , Dodwad Shah-Jahan M , Wade Charles E , Harvin John A , Kao Lillian S , Puzio Thaddeus J 
Published: December 2022

IntroductionDysphagia is associated with increased morbidity, mortality, and resource utilization in hospitalized patients, but studies on outcomes in geriatric trauma patients with dysphagia are limited. We hypothesized that geriatric trauma patients with dysphagia would have worse clinical outcomes compared with those without dysphagia.MethodsPatients with and without dysphagia were compared in a single-center retrospective cohort study of trauma patients aged ≥65 years admitted in 2019. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) length of stay (LOS), hospital LOS, discharge destination, and unplanned ICU admission. Multivariable regression analyses and Bayesian analyses adjusted for age, Injury Severity Score, mechanism of injury, and gender were performed to determine the association between dysphagia and clinical outcomes.ResultsOf 1706 geriatric patients, 69 patients (4%) were diagnosed with dysphagia. Patients with dysphagia were older with a higher Injury Severity Score. Increased odds of mortality did not reach statistical significance (OR 1.6, 95% CI 0.6 to 3.4, p=0.30). Dysphagia was associated with increased odds of unplanned ICU admission (OR 4.6, 95% CI 2.0 to 9.6, p≤0.001) and non-home discharge (OR 5.2, 95% CI 2.4 to 13.9, p≤0.001), as well as increased ICU LOS (OR 4.9, 95% CI 3.1 to 8.1, p≤0.001), and hospital LOS (OR 2.1, 95% CI 1.7 to 2.6, p≤0.001). On Bayesian analysis, dysphagia was associated with an increased probability of longer hospital and ICU LOS, unplanned ICU admission, and non-home discharge.ConclusionsClinically apparent dysphagia is associated with poor outcomes, but it remains unclear if dysphagia represents a modifiable risk factor or a marker of underlying frailty, leading to poor outcomes. This study highlights the importance of screening protocols for dysphagia in geriatric trauma patients to possibly mitigate adverse outcomes.Level of evidenceLevel III.
Generating mobility networks with generative adversarial networks
Authors: Mauro Giovanni , Luca Massimiliano , Longa Antonio , Lepri Bruno , Pappalardo Luca 
Published: December 2022

AbstractThe increasingly crucial role of human displacements in complex societal phenomena, such as traffic congestion, segregation, and the diffusion of epidemics, is attracting the interest of scientists from several disciplines. In this article, we address mobility network generation, i.e., generating a city’s entire mobility network, a weighted directed graph in which nodes are geographic locations and weighted edges represent people’s movements between those locations, thus describing the entire mobility set flows within a city. Our solution is MoGAN, a model based on Generative Adversarial Networks (GANs) to generate realistic mobility networks. We conduct extensive experiments on public datasets of bike and taxi rides to show that MoGAN outperforms the classical Gravity and Radiation models regarding the realism of the generated networks. Our model can be used for data augmentation and performing simulations and what-if analysis.
Location Problems with Cutoff
Authors: Müller Raoul , Schöbel Anita , Schuhmacher Dominic 
Published: December 2022

In this paper, we study a generalized version of the Weber problem of finding a point that minimizes the sum of its distances to a finite number of given points. In our setting, these distances may be cut off at a given value [Formula: see text], and we allow for the option of an empty solution at a fixed cost [Formula: see text]. We analyze under which circumstances these problems can be reduced to the simpler Weber problem, and also when we definitely have to solve the more complex problem with cutoff. We furthermore present adaptions of the algorithm of Drezner, Mehrez and Wesolowsky (1991 [The facility location problem with limited distances. Transportation Science, 25(3), 183–187, INFORMS]) to our setting, which in certain situations are able to substantially reduce computation times as demonstrated in a simulation study. The sensitivity with respect to the cutoff value is also studied, which allows us to provide an algorithm that efficiently solves the problem simultaneously for all [Formula: see text].
The construction of the HADES underground research laboratory and its role in the development of the Belgian concept of a deep geological repository
Authors: Li Xiangling , Neerdael Bernard , Raymaekers Didier , Sillen Xavier 
Published: December 2022

Abstract

When the Belgian Nuclear Research Centre (SCK CEN) launched a research, development and demonstration programme on geological disposal in the 1970s, it was not certain if a deep geological repository could be constructed in poorly indurated clay. This was tested by constructing the HADES underground research laboratory (URL) in Boom Clay, 225 m below SCK CEN's site in Mol. The construction history of the URL reflects how the understanding of the Boom Clay increased and how the excavation techniques and design of the gallery lining improved. It demonstrated that shafts, galleries and crossings between galleries can be constructed using industrial techniques. It also allowed characterization of the hydromechanical response of the clay and the clay disturbances induced by the excavation. This increased understanding is also reflected in the evolution of the geological disposal concept considered in Belgium. The current disposal concept foresees the installation of seals in the shafts and galleries. The HADES URL also offered the opportunity to test possible seal designs and develop a better understanding of the behaviour of bentonite, a possible seal material, owing to its swelling capacity, under
in situ
conditions.
A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma
Authors: Lee Hyun-Sung , Jang Hee-Jin , Ramineni Maheshwari , Wang Daniel Y. , Ramos Daniela , Choi Jong Min , Splawn Taylor , Espinoza Monica , Almarez Michelle , Hosey Leandria , Jo Eunji , Hilsenbeck Susan , Amos Christopher I. , Ripley R. Taylor , Burt Bryan M. 
Published: December 2022

Abstract

Purpose:
We report the results of a phase II, randomized, window-of-opportunity trial of neoadjuvant durvalumab versus durvalumab plus tremelimumab followed by surgery in patients with resectable malignant pleural mesothelioma (MPM; NCT02592551).

Patients and Methods:
The primary objective was alteration of the intratumoral CD8/regulatory T cell (Treg) ratio after combination immune checkpoint blockade (ICB) therapy. Secondary and exploratory objectives included other changes in the tumor microenvironment, survival, safety, tumor pathologic response (PR), and systemic immune responses.

Results:
Nine patients received monotherapy and 11 received combination therapy. Seventeen of the 20 patients (85%) receiving ICB underwent planned thoracotomy. Both ICB regimens induced CD8 T-cell infiltration into MPM tumors but did not alter CD8/Treg ratios. At 34.1 months follow-up, patients receiving combination ICB had longer median overall survival (not reached) compared with those receiving monotherapy (14.0 months). Grade ≥3 immunotoxicity occurred in 8% of patients in the monotherapy group and 27% of patients in the combination group. Tumor PR occurred in 6 of 17 patients receiving ICB and thoracotomy (35.3%), among which major PR (&gt;90% tumor regression) occurred in 2 (11.8%). Single-cell profiling of tumor, blood, and bone marrow revealed that combination ICB remodeled the immune contexture of MPM tumors; mobilized CD57+ effector memory T cells from the bone marrow to the circulation; and increased the formation of tertiary lymphoid structures in MPM tumors that were rich in CD57+ T cells.

Conclusions:
These data indicate that neoadjuvant durvalumab plus tremelimumab orchestrates de novo systemic immune responses that extend to the tumor microenvironment and correlate with favorable clinical outcomes.
A Novel Tumor-Promoting Role for Nuclear Factor IX in Glioblastoma Is Mediated through Transcriptional Activation of GINS1
Authors: Ge Ruixiang , Wang Chenci , Liu Jiangang , Jiang Haibo , Jiang Xiaochun , Liu Zhuohao 
Published: December 2022

AbstractOur previous study illustrated that nuclear factor IX (NFIX) promotes glioblastoma (GBM) progression by inducing migration and proliferation of GBM cells. However, the underlying mechanism of how NFIX regulates GBM cell proliferation remains obscure. In this study, we uncovered that Go-Ichi-Ni-San 1 (GINS1) is upregulated and positively correlated with NFIX in human GBM specimen. NFIX silencing downregulates the expression of GINS1, which is pivotal for cell-cycle progression and proliferation of GBM cells. Replenishment of GINS1 largely rescues the NFIX-null effect on GBM cell proliferation. Mechanistic investigation revealed that NFIX transcriptionally actives GINS1 expression by directly binding to promoter region (-1779 to -1793bp) of the GINS1 gene. Furthermore, knockdown of NFIX sensitizes GBM cells to DNA damage-inducing agents including doxorubicin and temozolomide, in a GINS1-dependent manner.Implications:Our study highlights that targeting NFIX–GINS1 axis could be a novel and potential therapeutic approach for GBM treatment.
Technological Leadership of School Heads and Teachers’ Technology Integration: Basis for the Development of a Training Program
Authors: Maala Elenette B , Lagos Fidelito D. 
Published: December 2022

Covid-19 pandemic saw the transition to online distance learning of the education in the Philippines. This became a challenge to both the teachers and heads of the educational institutions in terms of adapting and utilizing technology for better delivery and effective learning of students. The study aimed to determine the level of technological leadership of school heads. Using surveys and tests of collected data, it was revealed that the level of technological leadership of school heads based on technology innovation, technology assessment, technology forecasting, technology management and technology transfer shows a high overall weighted mean. These results showed that the technological leadership of school heads met the quality requirement of becoming technology leaders. Comparing this on teachers’ technology integration using z and t- test, the study also showed that both groups have similar insights regarding the level of technological leadership. The results and conclusions served as basis for developing a training program necessary to further address the needs of school heads and teachers.
Surviving Vulnerabilities of Isolation among Widowed Empty Nesters
Authors: Ablanque Argonne Robert A. , Singson Deborah Natalia E. 
Published: December 2022

A sufficient number of empty nesters living in isolation had been increasing in population, thus it is encouraged to provide a plethora of research data and studies on gerontology and isolation that could contribute to their wellbeing. This study utilized the descriptive phenomenological analysis and purposive sampling method to determine the five participants. Inclusion criteria were established to narrow down participants with common conditions. Data were gathered through online interviews and analyzed using Lichtman’s 3 C’s comprised of codes, categories, and concepts. The following themes emerged: economic vulnerability, physical vulnerability, social vulnerability, emotional vulnerability, coping with isolation vulnerabilities, and hopeful aspirations. In conclusion, empty nesters may experience multiple challenges that made them vulnerable in many aspects, but they were also able to develop coping strategies to manage these vulnerabilities. The limitations encountered in this study may be improved by exploring the experiences of empty nesters from other socio-economic categories and conducting a mixed-method study that would generate a broad range of data. The result of the study exposes various vulnerabilities that contribute to challenges encountered by empty nesters. Since the results are limited from generalizing the entire senior citizen population, it could be noted that the resiliency to survive challenging situations promote a holistic approach for aging and positive psychology as results provided varied sources for coping which ranges from both the internal and external sources. Survival elements of connectedness and transcending difficult situations affirm the practicality of promoting life meaning especially during difficult situations.
Estratégias comunicativas nos processos de parcerias para implementação da Agenda 2030 da ONU
Authors: Kunsch Margarida M. Krohling 
Published: December 2022

Este artigo trata de uma temática mundial na atualidade: a Agenda 2030 da Organização das Nações Unidas (ONU) e os 17 Objetivos de Desenvolvimento Sustentável (ODS), com foco no último – Fortalecer os mecanismos de implementação e revitalizar a parceria global para o desenvolvimento sustentável e o papel da comunicação neste contexto. Situar o papel estratégico da comunicação na promoção da sustentabilidade, mediante um trabalho integrado entre os atores e o poder público, a sociedade civil e as organizações, constitui o propósito básico deste texto reflexivo.