bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bintrafusp Alfa, an Anti-PD-L1:TGFβ Trap Fusion Protein, in Patients with ctDNA-positive, Liver-limited Metastatic Colorectal Cancer
Authors: Morris Van K. , Overman Michael J. , Lam Michael , Parseghian Christine M. , Johnson Benny , Dasari Arvind , Raghav Kanwal , Kee Bryan K. , Huey Ryan , Wolff Robert A. , Shen John Paul , Li June , Zorrilla Isabel , Tzeng Ching-Wei D. , Tran Cao Hop S. , Chun Yun Shin , Newhook Timothy E. , Vauthey Nicolas , Duose Dzifa , Luthra Raja , Haymaker Cara , Kopetz Scott 
Published: August 2022

Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) colorectal cancer, increased TGFβ signaling results in exclusion of antitumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGFβRII receptor (“TGFβ trap”) and anti-PD-L1 antibody. Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1,200 mg of BA intravenously every 14 days for six doses. The primary endpoint was ctDNA clearance. Radiographic characteristics at recurrence were compared using independent t tests to historical data from a similar cohort of patients with liver-limited mCRC who underwent observation. Only 4 of 15 planned patients received BA before the study was stopped early for loss of equipoise. There was no grade ≥3 adverse event. None of the patients cleared ctDNA. All patients developed radiographic recurrence by the first planned restaging. Although not detectable at prior to treatment, TGFβ3 was found in circulation in all patients at cycle 2 day 1. Compared with a historical cohort, patients administered BA developed more metastases (15 vs. 2, P = 0.005) and greater tumor volumes (9 cm vs. 2 cm, P = 0.05). Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific complexity of dual TGFβ and PD-L1 inhibition.Significance:Use of ctDNA to identify patients with micrometastatic disease for therapeutic intervention is feasible. Treatment with BA in patients with liver-limited mCRC and with detectable ctDNA after resection generated rapid progression. Approaches targeting TGFβ signaling must consider its pathway complexity in future immunotherapy combination strategies.
THE ANTIBACTERIAL ACTIVITY OF BETEL (Piper battle L.) AND BASIL (Ocimum sanctum L.) LEAVES INFUSION AS ANTISEPTIC PREPARATIONS AGAINST SOME BACTERIA IN VITRO
Authors: Fatimah Riesy Nor , Budiarti Lia Yulia , Medika Ghea 
Published: August 2022

Betel leaves (Piper battle L.) and basil leaves (Ocimum sanctum L.) are parts of the plant that can be made as antiseptic preparations because they contain antibacterial compounds such as flavonoids, tannins, and saponins. Antiseptic activity can be observed based on its effect in inhibiting the colonization of standard test bacteria of the laboratory, namely Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi as well as the magnitude of the phenol coefficient value. The study aimed to analyze the infusion activity of betel and basil leaves as antiseptic preparations against some test bacteria. This study in vitro used a posttest-only control group design. The infusion treatment of betel and basil leaves is tested in the form of a single preparation and a combination with concentrations of 50%, 75%, and 100% (w/v). The results showed there was a difference in the infusion activity of betel leaves and basil leaves in a single stock and a combination of the number of bacterial colonies tested; the effect of the treatment produces a small number of bacterial colonies in Gram-positive bacteria; 100% combination treatment (b/v) provides an inhibitory effect that is not significantly different from 70% alcohol control against all test bacteria except S.typhi: and obtained the phenol coefficient value from the combination treatment of betel and basil leaves infusion higher against Gram-positive bacteria. The conclusion of this study, the combination of betel and basil leaves infusion has antibacterial activity as an antiseptic preparation that can inhibit the growth of some test bacteria.

Keywords: antiseptic preparations, infusion leaves, Piper battle L, Ocimum sanctum L, number of colonies, phenol coefficient
Maintaining a National Acute Kidney Injury Risk Prediction Model to Support Local Quality Benchmarking
Authors: Davis Sharon E. , Brown Jeremiah R. , Dorn Chad , Westerman Dax , Solomon Richard J. , Matheny Michael E. 
Published: August 2022

Background:
The utility of quality dashboards to inform decision-making and improve clinical outcomes is tightly linked to the accuracy of the information they provide and, in turn, accuracy of underlying prediction models. Despite recognition of the need to update prediction models to maintain accuracy over time, there is limited guidance on updating strategies. We compare predefined and surveillance-based updating strategies applied to a model supporting quality evaluations among US veterans.

Methods:
We evaluated the performance of a US Department of Veterans Affairs–specific model for postcardiac catheterization acute kidney injury using routinely collected observational data over the 6 years following model development (n=90 295 procedures in 2013–2019). Predicted probabilities were generated from the original model, an annually retrained model, and a surveillance-based approach that monitored performance to inform the timing and method of updates. We evaluated how updating the national model impacted regional quality profiles. We compared observed-to-expected outcome ratios, where values above and below 1 indicated more and fewer adverse outcomes than expected, respectively.

Results:
The original model overpredicted risk at the national level (observed-to-expected outcome ratio, 0.75 [0.74–0.77]). Annual retraining updated the model 5×; surveillance-based updating retrained once and recalibrated twice. While both strategies improved performance, the surveillance-based approach provided superior calibration (observed-to-expected outcome ratio, 1.01 [0.99–1.03] versus 0.94 [0.92–0.96]). Overprediction by the original model led to optimistic quality assessments, incorrectly indicating most of the US Department of Veterans Affairs’ 18 regions observed fewer acute kidney injury events than predicted. Both updating strategies revealed 16 regions performed as expected and 2 regions increasingly underperformed, having more acute kidney injury events than predicted.

Conclusions:
Miscalibrated clinical prediction models provide inaccurate pictures of performance across clinical units, and degrading calibration further complicates our understanding of quality. Updating strategies tailored to health system needs and capacity should be incorporated into model implementation plans to promote the utility and longevity of quality reporting tools.
Afghanistan’s Forgotten Boys: Legal Pluralism and Impunity
Authors: Henderson Stacey , Muller Leonie 
Published: August 2022

Abstract
This article critically examines the pluralistic legal environment of Afghanistan, security sector reform processes engaged in by the international community, and the dismissal of the practice of bacha bazi as a cultural issue, which combined to allow the sexual abuse and exploitation of young boys to continue with impunity. The article calls for the United Nations and the international community to show strong, ethical, and transparent leadership on child protection within future mission mandates as a practical implementation of the secondary duty under the responsibility to protect (R2P).
What Controls the Interannual Variability of the Boreal Winter Atmospheric River Activities over the Northern Hemisphere?
Authors: Ma Weiming , Chen Gang 
Published: August 2022

Abstract
Interannual variability of the winter atmospheric river (AR) activities over the Northern Hemisphere is investigated. The leading modes of AR variability over the North Pacific and North Atlantic are first identified and characterized. Over the Pacific, the first mode is characterized by a dipole structure with enhanced AR frequency along the AR peak region at about 30°N and reduced AR frequency farther north. The second mode exhibits a tripole structure with a narrow band of positive AR anomalies at about 30°N and sandwiched by negative anomalies. Over the Atlantic, the first mode exhibits an equatorward shift of the ARs with positive anomalies and negative anomalies located on the equatorward and poleward side of the AR peak region at about 40°N, respectively. The second mode is associated with the strengthening and eastward extension of the AR peak region, which is sandwiched by negative anomalies. A large ensemble of atmospheric global climate models from phase 6 of the Coupled Model Intercomparison Project (CMIP6), which shows high skill in simulating these modes, is then used to quantify the roles of sea surface temperature (SST) forcing versus internal atmospheric variability in driving the formation of these modes. Results show that SST forcing explains about half of the variance for the Pacific leading modes, while that number drops to about a quarter for the Atlantic leading modes, suggesting higher predictability for the Pacific AR variability. An additional ensemble driven only by observed tropical SST is further utilized to demonstrate the more important role that tropical SST plays in controlling the Pacific AR variability while both tropical and extratropical SST exert comparable influences on the Atlantic AR variability.
Depression, anxiety and worry in young Pacific adults in New Zealand during the COVID-19 pandemic
Authors: Siegert Richard J , Narayanan Ajit , Dipnall Joanna , Gossage Lisa , Wrapson Wendy , Sumich Alexander , Merien Fabrice , Berk Michael , Paterson Janis , Tautolo El-Shadan 
Published: August 2022

Objective: To measure symptoms of anxiety, depression and hopelessness in a sample of young Pacific adults living in Auckland, New Zealand during the 2020/2021 COVID-19 pandemic and identify protective factors. Methods: Participants were 267 Pacific adults (58% female) who completed a survey online. Analyses included descriptive statistics, correlations, linear regression and symptom network analysis. Results: Around 25% of the sample scored in the range for moderate to severe anxiety and 10% for moderate to severe depression on standard measures. Almost 40% indicated that they found the first lockdown very stressful and 55% noted that some members of their family found it stressful. Only 16% worried about COVID-19 and their future quite a bit or constantly, while another 25% worried sometimes. Self-compassion and Pacific Identity had moderate, negative correlations, and Worry about COVID-19 had weak positive correlations, with anxiety, depression, hopelessness and perceived stress. Conclusion: These results suggest that, while the prevalence of depression and anxiety are quite high among this population, fostering ethnic identity and self-compassion in Pacific children and adolescents might protect against developing depression and anxiety.
Experience of Disgust and Symptom Severity in Contamination Subtype of Obsessive-Compulsive Disorder: Role of Experiential Avoidance
Authors: D’Mello Raina Jane , Kumar Ajay 
Published: August 2022

Background: The emotion of disgust has been linked with the underlying nature of the contamination subtype of obsessive-compulsive disorder (C-OCD). Prior studies show that disgust contributes to the development of C-OCD by reinforcing avoidance strategies. Therefore, experiential avoidance (EA) may influence the effect between disgust sensitivity (DS) and C-OCD symptom severity. This study aimed to investigate the mediational role of EA between DS and C-OCD severity. Methods: A cross-sectional design was adopted with 45 patients of OCD and 45 healthy controls. Both the groups were assessed on the Obsessive-Compulsive Inventory, the Disgust Scale (Revised), and Acceptance and Action Questionnaire–II. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) checklist and symptom severity scale were additionally administered to the patients with OCD. Independent t-tests, Pearson’s product–moment correlation, regression analysis, and mediation analysis were used. Results: DS and EA were positively associated with contamination-washing symptoms and symptom severity. Regression analysis indicated that DS and EA were highly associated with contamination/washing severity scores among both the patients with C-OCD and the healthy controls. Conclusion: The study implicates that disgust is a central emotion underlying the presentation of obsessions and compulsions, which are of contamination concerns. Further, EA has a role in the maintenance of OCD through avoidance learning; however, it may not be interacting with DS to cause OCD.
Stakeholder perspectives of a pilot multicomponent delirium prevention intervention for adult patients with advanced cancer in palliative care units: A behaviour change theory-based qualitative study
Authors: Green Anna , Hosie Annmarie , Phillips Jane L , Kochovska Slavica , Noble Beverly , Brassil Meg , Cumming Anne , Lawlor Peter G , Bush Shirley H , Davis Jan Maree , Edwards Layla , Hunt Jane , Wilcock Julie , Phillipson Carl , Wesley Ely Eugene , Parr Cynthia , Lovell Melanie , Agar Meera 
Published: August 2022

Background: Theory-based and qualitative evaluations in pilot trials of complex clinical interventions help to understand quantitative results, as well as inform the feasibility and design of subsequent effectiveness and implementation trials. Aim: To explore patient, family, clinician and volunteer (‘stakeholder’) perspectives of the feasibility and acceptability of a multicomponent non-pharmacological delirium prevention intervention for adult patients with advanced cancer in four Australian palliative care units that participated in a phase II trial, the ‘PRESERVE pilot study’. Design: A trial-embedded qualitative study via semi-structured interviews and directed content analysis using Michie’s Behaviour Change Wheel and the Theoretical Domains Framework. Setting/participants: Thirty-nine people involved in the trial: nurses ( n = 17), physicians ( n = 6), patients ( n = 6), family caregivers ( n = 4), physiotherapists ( n = 3), a social worker, a pastoral care worker and a volunteer. Results: Participants’ perspectives aligned with the ‘capability’, ‘opportunity’ and ‘motivation’ domains of the applied frameworks. Of seven themes, three were around the alignment of the delirium prevention intervention with palliative care (intervention was considered routine care; intervention aligned with the compassionate and collaborative culture of palliative care; and differing views of palliative care priorities influenced perspectives of the intervention) and four were about study processes more directly related to adherence to the intervention (shared knowledge increased engagement with the intervention; impact of the intervention checklist on attention, delivery and documentation of the delirium prevention strategies; clinical roles and responsibilities; and addressing environmental barriers to delirium prevention). Conclusion: This theory-informed qualitative study identified multiple influences on the delivery and documentation of a pilot multicomponent non-pharmacological delirium prevention intervention in four palliative care units. Findings inform future definitive studies of delirium prevention in palliative care. Australian New Zealand Clinical Trials Registry, ACTRN12617001070325; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373168
Development of a national strategy with recommendations for the care of seriously ill and dying people and their relatives in pandemics: A modified Delphi study
Authors: Gauder Sonja , Pralong Anne , Rémi Constanze , Hodiamont Farina , Klinger Isabell , Heckel Maria , Simon Steffen T , Bausewein Claudia 
Published: August 2022

Background: The SARS-CoV-2 pandemic is a constant challenge for health care systems, also in Germany. Care of seriously ill and dying people and their relatives is often neglected and suffering increased due to sub-optimal symptom management, visiting restrictions and lonely dying. The project “Palliative Care in Pandemics (PallPan)” intended to develop a national strategy including evidence- and consensus-based recommendations for the care of seriously ill and dying people and their relatives during pandemic times in Germany. Aim: To reach consensus on evidence-based recommendations for the care of seriously ill and dying people and their relatives in pandemics. Methods: Three-step consensus process comprising two online Delphi rounds and an expert workshop conducted from April to June 2021. One hundred twenty experts from various areas of healthcare, administration, and politics in Germany were included. Results: During the consensus-process, pre-formulated evidence-based recommendations were refined step-by-step. This resulted in consensus on 33 recommendations on the topics of “supporting patients and their relatives,” “supporting staff,” and “supporting and maintaining structures and provision of palliative care.” The recommendations address professional carers and various responsibilities on a governmental, federal state and municipal level, and in healthcare facilities. Conclusion: We provide evidence and consensus-based recommendations for the care of seriously ill and dying people and their relatives in pandemics in Germany. This is an important step towards a pandemic preparedness and hopefully improves the future palliative care response to pandemics.
Ideal Eye, Nasal Tip, Cheek, and Forehead Structures Related to Vertical, Oblique Relationships and the Facial Oval Shape
Authors: Young Philip , Young Chloe 
Published: August 2022

Introduction: The Circles of Prominence is a new theory on facial beauty based on what viewers spend the most time observing when they see a face. Here, we test the influence the iris, nasal tip, and lower lip have on the ideal forehead, mouth, and cheek shapes and how they ideally relate to the general oval facial shape. Materials and Methods: This is a subjective survey where 245 participants ranked 5 sets of 20 total line drawings based on attractiveness. The survey was conducted with an online service (SurveyMonkey®). The data underwent statistical analysis. The goal was to test the ideal forehead, mouth and cheek shadowing, ideal forehead height and ideal positioning of the eyes and nasal tip. Results: Vertical shadowing of the forehead, mouth and cheek were most ideal when they aligned with the iris. The upper border of cheek shadowing was most ideal when aligned with the top of the ears and center of the lower lip. The iris and nasal tip were ideally related in the same way the 2 diameters of the facial oval relate to each other. Forehead height is likely most ideal when it is related to the iris to center of the lower lip distance. Discussion: The shape of the forehead, mouth, and cheek are influenced by the vertical position of the iris. The upper border of the cheek is ideally defined by an oblique relationship established by the top of the ears and center of the lower lip which supports the hypothesis that the face is ideally organized in part by parallel, oblique relationships that are established by the iris and nasal tip. The iris and lower lip appears to have an influence on forehead height. The iris and nasal tip orient the eye and nose units and their positioning is influenced by the vertical and horizontal diameters of the oval shape of the face. Conclusion: Facial beauty can be explained by simple mathematics within the face. The iris width and shape ideally dictates all shapes that are close to its size, this is progressively followed by the horizontal aperture of the eye, and the iris-to-iris distance. Here, we find that the iris-to-iris distance or just the absolute position of the iris itself exerts more influence on the forehead, cheek, and mouth shapes, and the iris and nasal tip together ideally organizes the face into parallel oblique relationships and harmonizes with the face by relating to the face’s oval dimensions.
The Chronological Demographics of Ventricular-Arterial Decoupling in Patients with Sepsis and Septic Shock: A Prospective Observational Study
Authors: Nasu Michitaka , Sato Ryota , Takahashi Kuniko , Nakaizumi Takayuki , Maruyama Akiyoshi , Ueda Shinichiro 
Published: August 2022

Background Ventricular-arterial coupling (V-A coupling) recently gathers attention from clinicians to evaluate the interaction between afterload and left ventricular systolic function. We aimed to describe the chronological demographics of V-A decoupling in patients with sepsis and septic shock through the clinical course. Method We conducted a single-center prospective observational study comprising adult patients with sepsis and septic shock admitted to the tertiary care hospital between 04/2017 and 03/2019. Patients’ characteristics, lab data on admission, and echocardiographic parameters including Ea and Ees on the day- 1, 2, 3, 7, and 14–28 were collected. V-A decoupling was defined as Ea/Ees ≥ 1.36. Results Seventy-one patients with sepsis or septic shock were enrolled. The prevalence of V-A decoupling was as follows; day-1: 25.4%, day-2: 23.8%, day-3: 13.3%, day-7: 18.5%, day-14–28: 30.3%, respectively. Ea was higher in patients with V-A decoupling than those without throughout the clinical course (day1; 2.8 vs. 1.8, p < 0.01, day2; 2.7 vs. 1.9, p < 0.01, day3; 2.8 vs. 2.1, p = 0.06, day7; 2.7 vs. 1.9, p = 0.02, day14-28; 2.4 vs. 1.8, p = 0.08). This increase in Ea was mainly induced by reduced stroke volume (SV) as well as high systolic blood pressure (SBP) in the earlier course of sepsis but only by increased SBP in the later course of sepsis. Ees was lower in patients with V-A decoupling than those without throughout the clinical course (day1; 1.3 vs. 2.1, p < 0.01, day2; 1.5 vs. 2.3, p < 0.01, day3; 1.6 vs. 2.3, p = 0.02, day7; 1.8 vs. 2.3, p = 0.01, day14-28; 1.2 vs. 1.9, p = 0.07). Conclusion We reported that V-A decoupling was commonly seen in patients with sepsis and septic shock. In patients with V-A decoupling, both Ea and Ees were significantly altered, but the causes of these alterations appeared to be changing over the clinical course of sepsis.