bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery in colorectal carcinoma at high risk of peritoneal carcinomatosis: short-term and long-term outcomes from the CHECK study – protocol for a randomised, multicentre, phase 3 trial
Authors: Pacelli Fabio , Gerardi Chiara , Rulli Eliana , Abatini Carlo , Rotolo Stefano , Garattini Silvio , Melotti Gianluigi , Torri Valter , Galli Fabio , Rulli Erica , Di Giorgio Andrea 
Published: August 2022

IntroductionUp to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts’ involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking.Methods and analysisThis is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method.Ethics and disseminationThis trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark/certification.The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings.Trial registration numberNCT03914820.
Budget impact analysis of providing hospital inpatient care at home virtually, starting with two specific surgical patient groups
Authors: Peters Guido M , Doggen Carine J M , van Harten Wim H 
Published: August 2022

ObjectiveTo determine the budget impact of virtual care.MethodsWe conducted a budget impact analysis of virtual care from the perspective of a large teaching hospital in the Netherlands. Virtual care included remote monitoring of vital signs and three daily remote contacts. Net budget impact over 5 years and net costs per patient per day (costs/patient/day) were calculated for different scenarios: implementation in one ward, in two different wards, in the entire hospital, and in multiple hospitals. Sensitivity analyses included best-case and worst-case scenarios, and reducing the frequency of daily remote contacts.ResultsNet budget impact over 5 years was €2 090 000 for implementation in one ward, €410 000 for two wards and €−6 206 000 for the entire hospital. Costs/patient/day in the first year were €303 for implementation in one ward, €94 for two wards and €11 for the entire hospital, decreasing in subsequent years to a mean of €259 (SD=€72), €17 (SD=€10) and €−55 (SD=€44), respectively. Projecting implementation in every Dutch hospital resulted in a net budget impact over 5 years of €−445 698 500. For this scenario, costs/patient/day decreased to €−37 in the first year, and to €54 in subsequent years in the base case.ConclusionsWith present cost levels, virtual care only saves money if it is deployed at sufficient scale or if it can be designed such that the active involvement of health professionals is minimised. Taking a greenfield approach, involving larger numbers of hospitals, further decreases costs compared with implementing virtual care in one hospital alone.
Effectiveness and implementation of SHared decision-making supported by OUTcome information among patients with breast cancer, stroke and advanced kidney disease: SHOUT study protocol of multiple interrupted time series
Authors: Hackert Mariska Quirina Nikita , Ankersmid Jet W , Engels Noel , Prick Janine C M , Teerenstra Steven , Siesling Sabine , Drossaert Constance H C , Strobbe Luc J A , van Riet Yvonne E A , van den Dorpel René M A , Bos Willem Jan W , van der Nat Paul B , van den Berg-Vos Renske M , van Schaik Sander M , Garvelink Mirjam M , van der Wees Philip J , van Uden-Kraan Cornelia F 
Published: August 2022

IntroductionWithin the value-based healthcare framework, outcome data can be used to inform patients about (treatment) options, and empower them to make shared decisions with their health care professional. To facilitate shared decision-making (SDM) supported by outcome data, a multicomponent intervention has been designed, including patient decision aids on the organisation of post-treatment surveillance (breast cancer); discharge location (stroke) and treatment modality (advanced kidney disease), and training on SDM for health care professionals. The SHared decision-making supported by OUTcome information (SHOUT) study will examine the effectiveness of the intervention and its implementation in clinical practice.Methods and analysisMultiple interrupted time series will be used to stepwise implement the intervention. Patients diagnosed with either breast cancer (N=630), stroke (N=630) or advanced kidney disease (N=473) will be included. Measurements will be performed at baseline, three (stroke), six and twelve (breast cancer and advanced kidney disease) months. Trends on outcomes will be measured over a period of 20 months. The primary outcome will be patients’ perceived level of involvement in decision-making. Secondary outcomes regarding effectiveness will include patient-reported SDM, decisional conflict, role in decision-making, knowledge, quality of life, preferred and chosen care, satisfaction with the intervention, healthcare utilisation and health outcomes. Outcomes regarding implementation will include the implementation rate and a questionnaire on the health care professionals’ perspective on the implementation process.Ethics and disseminationThe Medical research Ethics Committees United in Nieuwegein, the Netherlands, has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. Bureau Onderzoek & Innovatie of Santeon, the Netherlands, approved this study. The results will contribute to insight in and knowledge on the use of outcome data for SDM, and can stimulate sustainable implementation of SDM.Trial registration numberNL8374, NL8375 and NL8376.
Creation of objective performance criteria among medical devices
Authors: Gressler Laura Elisabeth , Marinac-Dabic Danica , dosReis Susan , Goodney Philip , Mullins C. Daniel , Shaya Fadia 
Published: August 2022

ObjectivesObjective performance criteria (OPC) may serve as a tool to expedite the approval process and continue active surveillance of class III medical devices. Thus far, published guidance on the creation of OPC has been clinical area-specific. This study aimed to capture reflections from key stakeholders on the creation of OPC that may serve as a precursor for a formalized conceptual framework within the USA.DesignReflections from key stakeholders and guidance from an advisory committee were captured to gain an understanding of the elements that are crucial to the generation of OPC.SettingA non-probability sampling method using the purposive sampling strategy was employed to identify relevant stakeholders for engagement in semi-structured, open-ended, concept elicitation discussions.ParticipantsStakeholders involved in the generation of OPC.Main outcome measuresElements and themes regarding the priorities of, experiences with, roles within and perceived challenges associated with OPC creation captured through a phenomenological approach.ResultsA total of 27 participants were engaged to represent the following contributors: representatives of registries, health systems, health technology assessment bodies, clinicians, device application reviewers, payers, patients, patient representatives, patient caregivers, device manufacturers, data coordinators, data analysts and data informaticians. Consensus was achieved on the five core elements: (1) identification of medical devices, (2) engagement of key stakeholders, (3) selection of data source, (4) performance of appropriate statistical analyses and (5) reporting of findings. The engagement of key stakeholders (38%) was cited most frequently as the most important core element. Access to meaningful and high-quality data sources (47%) was the most frequently mentioned challenge.ConclusionsThe reflections from the participants identified five elements to be considered when generating an OPC within class III medical devices and may provide the needed foundation for the development of official guidance on OPC generation.
Stretching–buoyancy interplay in the magma-poor rifting process
Authors: Sinha Sudipta Tapan , Nemčok Michal 
Published: August 2022

Abstract
The Cauvery Basin in East India represents a failed rift zone in the west and transform-related termination in the east. The deformation associated with a westward-propagating rift zone involves stretching and necking-related deformation from west to east. The rift axis and the flanks exhibit maximum and minimum deformation.
In this study, we document the increasing role of buoyancy-driven processes and the development of the rift asymmetry during the advanced stages of rifting in a magma-poor setting. We use a series of reflection seismic profiles intersecting the failed rift zone maturing eastward.
The onset of buoyancy-controlled extension correlates with the localized extension. It creates a relatively symmetrical axial dome, and exhibits rift flank rotations and central up-warping. This permanent uplift is associated with lower crustal ductile flow. Notably, the deep-seated syn-rift buoyancy forces progressively operate eastward. We deduce the associated transient dome uplift and its subsequent dissipation using a seismic flattening technique. The axial dome formation is associated with an upwelling asthenosphere and lower lithospheric mantle. This correlates with localized contraction within flat-lying fault blocks at its flanks, concurrently forming the typical hanging-wall and footwall geometry. The multiple shallow- to deep-seated mechanisms promote strain acceleration in the uplifted regions along the rift zone.
HSPB8 Overexpression Ameliorates Cognitive Impairment in Diabetic Mice via Inhibiting NLRP3 Inflammation Activation
Authors: Chang Yanmin , Wu Yanqing , Jiang Xingjun , Zhu Jiahui , Wang Cailin , Ma Rong , Li Gang 
Published: August 2022

Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cognitive impairment. And the underlying mechanism remains unillustrated. HSPB8 is a member of the small heat shock protein family. In this study, we found that the expression of HSPB8 was upregulated in the hippocampus of

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and N2a cells exposed to high glucose. Overexpression of HSPB8 relieved cognitive decline in DM mice. Mechanically, HSPB8 overexpression in the hippocampus of diabetic mice inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation via dephosphorylating mitochondrial fission-associated protein dynamin-related protein 1 (DRP1) at the phosphorylated site Ser616 (p-Drp1S616). Furthermore, HSPB8 overexpression increased mitochondrial membrane potential (MMP) and reduced oxidative stress. These results indicate a protective effect of HSPB8 in the hippocampus of diabetic mice and N2a cells exposed to high glucose. Overexpression of HSPB8 might be a useful strategy for treating T2DM-related cognitive decline.
Na+/H+-exchanger 1 Enhances Antitumor Activity of Engineered NK-92 Natural Killer Cells
Authors: Gong Yao-Yu , Shao Hongguang , Li Yu , Brafford Patricia , Stine Zachary E. , Sun Jing , Felsher Dean W. , Orange Jordan S. , Albelda Steven M. , Dang Chi V. 
Published: August 2022

Adoptive cell transfer (ACT) immunotherapy has remarkable efficacy against some hematologic malignancies. However, its efficacy in solid tumors is limited by the adverse tumor microenvironment (TME) conditions, most notably that acidity inhibits T and natural killer (NK) cell mTOR complex 1 (mTORC1) activity and impairs cytotoxicity. In several reported studies, systemic buffering of tumor acidity enhanced the efficacy of immune checkpoint inhibitors. Paradoxically, we found in a MYC–driven hepatocellular carcinoma model that systemic buffering increased tumor mTORC1 activity, negating inhibition of tumor growth by anti-PD1 treatment. Therefore, in this proof-of-concept study, we tested the metabolic engineering of immune effector cells to mitigate the inhibitory effect of tumor acidity while avoiding side effects associated with systemic buffering. We first overexpressed an activated RHEB in the human NK cell line NK-92, thereby rescuing acid-blunted mTORC1 activity and enhancing cytolytic activity. Then, to directly mitigate the effect of acidity, we ectopically expressed acid extruder proteins. Whereas ectopic expression of carbonic anhydrase IX (CA9) moderately increased mTORC1 activity, it did not enhance effector function. In contrast, overexpressing a constitutively active Na+/H+-exchanger 1 (NHE1; SLC9A1) in NK-92 did not elevate mTORC1 but enhanced degranulation, target engagement, in vitro cytotoxicity, and in vivo antitumor activity. Our findings suggest the feasibility of overcoming the inhibitory effect of the TME by metabolically engineering immune effector cells, which can enhance ACT for better efficacy against solid tumors.Significance:This study demonstrates the feasibility of metabolic engineering immune effector cells to overcome inhibition in the TME, an approach that could enhance the efficacy of adoptive transfer immunotherapy.
Developmental State in Africa
Authors: Temesgen Kidanu A. 
Published: August 2022

Abstract
As various studies have uncovered, a significant number of states in Africa remain in abject poverty and are underdeveloped, long after the end of colonialism. These degrading economic conditions are further reinforced by authoritarian political cultures, unending instability and civil wars. The few exceptions include Botswana, South Africa and Mauritius. To stimulate national economic and social progress, African countries have experimented with different development models. In this paper, we compare the developmental state experiences of Ethiopia and Mauritius. A qualitative research approach was used, and the study is based entirely on an analysis of secondary data sources. The analysis proceeds by using comparative techniques. The findings of the study reveal that though the employment of the developmental state model resulted in growth in both Ethiopia and Mauritius, the way in which they instituted key policies and institutions of the developmental state has been quite different.
Monitoring the use of a canopy bridge and underpasses by arboreal mammals on a Brazilian coastal road
Authors: Franceschi Ingridi Camboim , Dasoler Bibiana Terra , Menger Talita , Kindel Andreas , Almeida da Silva Franciane , Gonçalves Leonardo Júlio Cezar , Braga Ricardo Miranda , Zimmermann Teixeira Fernanda 
Published: August 2022

Abstract
Roads disrupt the canopy and can affect arboreal animals in different ways, such as reducing canopy connectivity, generating habitat loss and degradation, and increasing direct mortality. Since arboreal animals mainly use the canopy for movement, mitigation measures for these species usually focus on maintaining or restoring canopy connectivity to guarantee safe crossings. Here we present a case study of a Brazilian coastal road (ES-060) for which we described the use of a canopy bridge and multiple underpasses by three arboreal mammal species and compared these data with roadkill records of the same species in the vicinity of the crossing structures. Our study includes a 75 m long steel cable canopy bridge, monitored for 3 years, and clusters of different types of underpasses, monitored for 16 years. The use of the crossing structures was monitored with sand track beds installed at entrances on both sides, and roadkill surveys were conducted daily for 16 years. We considered a crossing to be successful if tracks of the same species were recorded on either side of a structure and showed opposite movement trajectories. The canopy bridge survey resulted in an observed rate of 0.16 crossings/month for Callithrix geoffroyi, 7.79 for Coendou insidiosus, and 0.46 for Didelphis aurita, and all types of underpasses combined demonstrated a rate of 0.33, 1.94, and 8.43 crossings/month for each species, respectively. The roadkill surveys resulted in an observed rate of 1.41, 0.78, 2.94 roadkills/month for Callithrix geoffroyi, Coendou insidiosus, and Didelphis aurita, respectively. Even with mitigation structures confirmed to be used by these three species, roadkill hotspots occurred in the road sections with the crossing structures. Our study demonstrated the use of a canopy bridge and different types of underpasses by arboreal mammal species. The canopy bridge was mostly used by Coendou insidiosus, while the underpasses were mainly used by Didelphis aurita. As roadkill hotspots occurred red in the same segments where mitigation crossing structures were installed, our results indicate that some important improvements are needed to mitigate roadkills of arboreal mammals in this area, mainly preventing that these species access the road. We present recommendations for a research agenda to support mitigation planning for arboreal mammals, namely: (1) testing the efficiency of different canopy bridge designs for multispecies mitigation, (2) testing the use of connecting structures, such as ropes that connect to the surrounding forest, to encourage underpass use by arboreal species, and (3) testing fence adaptations to block the access of arboreal mammals to roads.
Refashioning Chinese búshì (不是) rhetoricals
Authors: Chuang Andrew H.C. 
Published: August 2022

Abstract
Two communication types of the Chinese [búshì … ma] patterning can be found in earlier studies in which Type 1 is understood as a yes-no question (default form) and Type 2 a rhetorical question carrying a negative semantic prosody, both types taking place in a “2-party” dialogue. This research has further identified an emergent “construction” (Croft, 2001) that figures also as a rhetorical question (Type 3) except in a “3-party” conversation setting. This Type 3 is found to serve a primary communicative purpose, that is, for “positive interpersonal bonding.” Other findings discussed include: (a) that [búshì … ma] has defaulted from Type 1 to Type 2 in today’s Mandarin Chinese, (b) that there exist subjectivity-based variations in interpreting the thematic agents of a Type 2 expression, (c) that Type 3 expressions have emerged on the grounds of “intersubjectivity,” and (d) that while both Types 2 and 3 are rhetorical questions, they indeed require very different sets of pragmatic competence for implementing an intended illocutionary force. The study looks particularly at how Type 2 and Type 3 [búshì … ma] constructions differentiate themselves from each other and how the [búshì … ma] patterning reflects linguistic economy and efficiency in real-life language use through grammaticalization (grammatical constructionalization).
Does Degeneration of the Patellofemoral Joint After Medial Open-Wedge High Tibial Osteotomy Affect Clinical Outcomes?
Authors: Yoon Wan-Keun , Kim Kang-Il , Kim Jun-Ho , Lee Sang Hak , Jo Myeong-Guk 
Published: August 2022

Background: Although biomechanical and clinical studies have reported adverse effects on the patellofemoral joint after medial open-wedge high tibial osteotomy (MOWHTO), there is a paucity of literature that describes outcomes longer than midterm follow-up. Purpose: We aimed to evaluate the mid- to long-term radiologic and clinical outcomes of the patellofemoral joint after MOWHTO and to assess whether radiologic deterioration of the patellofemoral joint affected clinical outcomes or survivorship after MOWHTO. Study Design: Case series; Level of evidence, 4. Methods: We retrospectively reviewed 170 knees that underwent MOWHTO and had a minimum 5-year follow-up. In radiologic evaluation, serial postoperative changes in the patellofemoral joint compared with the preoperative status were evaluated on the Merchant view according to the Kellgren-Lawrence grade. The American Knee Society (AKS) score, Knee injury and Osteoarthritis Outcome Score (KOOS), Kujala score, incidence of anterior knee pain, and survivorship were used to assess clinical outcomes. Using radiologic assessment of the patellofemoral joint, we divided the patients into a radiologic progression group and a radiologic nonprogression group to evaluate whether radiologic progression of patellofemoral arthritis affected long-term clinical outcomes and survivorship after MOWHTO. Results: The mean follow-up period was 96.3 months (range, 60-163 months). Arthritic progression of the patellofemoral joint on the Merchant view was observed in 44.9%, 56.3%, 66.0%, and 84.0% of the cases at 5, 7, 9, and 11 years, respectively. Clinical outcomes such as AKS scores and KOOS significantly improved after MOWHTO ( P < .001) at the latest follow-up. The incidence of anterior knee pain was 5.3% (9/170 knees). One knee (0.6%) underwent conversion to TKA due to progressive medial osteoarthritis, so the survival rate was 99.4% at a mean follow-up of 96.3 months. Despite patellofemoral degeneration over time, there were no significant differences in clinical outcomes or survivorship between patients with and without radiologic progression at the latest follow-up. Conclusion: Although degeneration of the patellofemoral joint was observed with time after MOWHTO, the related symptoms were minimal and arthritic changes in the patellofemoral joint did not affect the clinical outcomes or survivorship after MOWHTO over a mid- to long-term follow-up.
Are Children with Cleft Palate at Increased Risk for Laryngeal Pathology?
Authors: Fujiki Robert Brinton , Thibeault Susan L. 
Published: August 2022

To determine the prevalence of laryngeal pathology in children presenting with cleft palate with or without cleft lip (CP ± L) who underwent nasoendoscopy to assess palatal function. A secondary aim was to determine the relationship between patient demographics, resonance, articulation, and prevalence of laryngeal pathology in this population. Retrospective, observational cohort study Outpatient pediatric cranio-facial anomalies clinic Children ≤18 years of age presenting with CP ± L (N = 215) who underwent nasoendoscopy, speech language pathology, plastic surgery, and otolaryngological evaluations between 2009 and 2020. Laryngeal diagnosis by pediatric otolaryngologists. 21.9% of children presented with laryngeal pathology. Diagnoses included benign vocal fold lesions and laryngeal edema sufficiently severe to alter vocal fold edge contour. Likelihood of laryngeal pathology increased by approximately 12% with every increase of 1 year in age ( P = .001, OR = 1.12). Children with laryngeal pathology were 50% more likely to have undergone palatal repair ( P < .001, OR = 1.50). In addition, children with severely hypernasal resonance were 78% less likely to present with laryngeal pathology ( P =.046, OR = 0.22). This population is at increased risk for laryngeal pathologies as determined by nasoendoscopy. This finding underscores the importance of careful laryngeal imaging in assessing these children. Additional research is warranted to identify the mechanisms underlying the increased risk for morphological vocal fold changes.