bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial
Authors: Tong T. M. L. , van der Kooij M. K. , Speetjens F. M. , van Erkel A. R. , van der Meer R. W. , Lutjeboer J. , van Persijn van Meerten E. L. , Martini C. H. , Zoethout R. W. M. , Tijl F. G. J. , Blank C. U. , Burgmans M. C. , Kapiteijn E. 
Published: February 2022

Abstract
Background
While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease.

Methods
Open-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics (t-test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves.

Discussion
This is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver.

Trial Registration
This trial was registered in the US National Library of Medicine with identifier NCT04283890. Registered as per February 2020 - Retrospectively registered.
EudraCT registration number: 2018-004248-49.
Local MREC registration number: NL60508.058.19.
ICONIC study—conservative versus conventional oxygenation targets in intensive care patients: study protocol for a randomized clinical trial
Authors: Grim C. C. A. , van der Wal L. I. , Helmerhorst H. J. F. , van Westerloo D. J. , Pelosi P. , Schultz M. J. , de Jonge E. ,   for the ICONIC Investigators and PROVE Network, del Prado M. R. , Wigbers J. , Sigtermans M. J. , Dawson L. , van der Heijden P. L. J. , den Berg E. Y. Schriel-van , Loef B. G. , Reidinga A. C. , de Vreede E. , Qualm J. , Boerma E. C. , Rijnhart-de Jong H. , Koopmans M. , Cornet A. D. , Krol T. , Rinket M. , Vermeijden J. W. , Beishuizen A. , Schoonderbeek F. J. , van Holten J. , Tsonas A. M. , Botta M. , Winters T. , Horn J. , Paulus F. , Loconte M. , Battaglini D. , Ball L. , Brunetti I. 
Published: February 2022

AbstractBackgroundOxygen therapy is a widely used intervention in acutely ill patients in the intensive care unit (ICU). It is established that not only hypoxia, but also prolonged hyperoxia is associated with poor patient-centered outcomes. Nevertheless, a fundamental knowledge gap remains regarding optimal oxygenation for critically ill patients. In this randomized clinical trial, we aim to compare ventilation that uses conservative oxygenation targets with ventilation that uses conventional oxygen targets with respect to mortality in ICU patients.MethodsThe “ConservatIve versusCONventional oxygenation targets inIntensiveCare patients” trial (ICONIC) is an investigator-initiated, international, multicenter, randomized clinical two-arm trial in ventilated adult ICU patients. The ICONIC trial will run in multiple ICUs in The Netherlands and Italy to enroll 1512 ventilated patients. ICU patients with an expected mechanical ventilation time of more than 24 h are randomized to a ventilation strategy that uses conservative (PaO255–80 mmHg (7.3–10.7 kPa)) or conventional (PaO2110–150 mmHg (14.7–20 kPa)) oxygenation targets. The primary endpoint is 28-day mortality. Secondary endpoints are ventilator-free days at day 28, ICU mortality, in-hospital mortality, 90-day mortality, ICU- and hospital length of stay, ischemic events, quality of life, and patient opinion of research and consent in the emergency setting.DiscussionThe ICONIC trial is expected to provide evidence on the effects of conservative versus conventional oxygenation targets in the ICU population. This study may guide targeted oxygen therapy in the future.Trial registrationTrialregister.nlNTR7376. Registered on 20 July, 2018.
Child food insecurity in the wake of the COVID-19 pandemic: urgent need for policy evaluation and reform in Israel’s school feeding programs
Authors: Azarieva Janetta , Berry Elliot M. , Troen Aron M. 
Published: February 2022

AbstractEven in high-income countries like Israel, children have been particularly vulnerable to the surge in food insecurity driven by quarantines, unemployment, and economic hardships of the COVID-19 pandemic. Under normal circumstances, School Feeding Programs (SFPs) can help to ensure child food security. In the wake of the pandemic, policy makers worldwide have been challenged to adapt national SFPs to provide nutritional support to children (and indirectly to their families) during extended school closures. Most national SFPs implemented contingency plans to ensure continued nutritional support for children. In Israel, where SFPs were largely suspended during long periods of mandated school closing, there was a loss of 30–50% of feeding days for the ~ 454,000 children enrolled in the program. The lack of emergency contingency planning and failure to maintain Israeli SFPs during school closures reveals longstanding structural policy flaws that hindered coordination between relevant ministries and authorities and impeded the mobilization of funds and existing programs to meet the emergent need. The school feeding law does not identify child food security as an explicit aim, there are no benchmarks for monitoring and evaluating the program to ensure that the food aid reaches the children most in need, even routinely, and the Ministry of Education had no obligation to maintain the program and to marshal data on the participants that could be acted upon in the emergency. Moreover, because Israeli SFPs are “selective”, in other words, implemented according to community risk (low-income, high poverty rate) and geographical factors, attendant stigma and financial burdens can make participation in the program less attractive to families and communities that need them the most. We argue that Israel should make urgent, long-term improvements to the SFPs as follows: First, eliminating childhood food insecurity should be made an explicit goal of legislation in the broader context of national social, health, and nutritional goals, and this includes ensuring SFPs are maintained during emergencies. Second, the government should assume responsibility for the routine assessment and data collection on food insecurity among Israeli children. Third, SFPs should be subjected to rigorous independent program evaluation. Finally, a “universal” SFP providing nutritious diets would likely improve the health of all Israeli children, across all socioeconomic backgrounds. These steps to guarantee that Israeli children have food to realize their full physical and cognitive potential would emphasize Israel’s firm commitment to support multiple dimensions of health, educational achievement, and societal values, to combat the complex and long-term consequences of the pandemic, and to prepare for the next one.
Psychometric properties of patient-reported outcome measures for dysphagia in head and neck cancer: a systematic review protocol using COSMIN methodology
Authors: Manduchi Beatrice , Che Zhiyao , Fitch Margaret I. , Ringash Jolie , Howell Doris , Martino Rosemary 
Published: February 2022

Abstract
Background
Dysphagia (swallowing difficulty) is one of the most common and debilitating sequelae of head and neck cancer (HNC). Patient-reported outcome measures (PROMs) are a fundamental component of dysphagia outcomes evaluation, as they inform treatment consequences that cannot be captured by objective clinician measures. Many PROMs for dysphagia in HNC are available, but their validity is unclear. As a consequence, the selection of the most appropriate PROM for dysphagia in HNC is complex and often based on the clinician’s personal preferences, rather than on valid psychometric properties. This protocol describes a systematic review aiming at (1) identifying PROMs specific to dysphagia symptoms, swallowing functional status, swallowing-related health status, and swallowing-related quality of life in HNC, (2) mapping them to our conceptual framework of dysphagia-related PROs, and (3) appraising their psychometric properties using the Consensus Based Standards for the Selection of Health Measurement Instrument (COSMIN) methodology.

Methods
Six electronic databases will be searched from inception to December 2020 for all primary studies in any language and design detailing PROM development, reliability, validity, feasibility, interpretability, and/or cross-cultural adaptation. Eligibility criteria will target PROMs for patients with HNC (≥ 90% of the study sample) with ≥ 20% of their items pertaining to swallowing. Two independent raters will screen abstract and full texts and a third rater will resolve discrepancies. Data will be extracted on study, sample and PROM characteristics, and results of psychometric testing. PROMs will be mapped to our conceptual framework. The methodological quality of included PROMs and their psychometric properties will be appraised using the COSMIN risk of bias checklist and evidence will be summarized using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Discussion
This systematic review will provide a summary of existing dysphagia-related PROMs for people with HNC and a comprehensive account of their psychometric properties. We will provide recommendations on PROMs selection which will aid healthcare professionals to the most appropriate PROM based on its validity, reliability, feasibility, interpretability and suitability for clinical and research settings. Further recommendations will be made on areas of measurement property requiring further testing.

Systematic review registration
PROSPERO registration ID: CRD42021237877
Antenatal care follow-up decreases the likelihood of cultural malpractice during childbirth and postpartum among women who gave birth in the last one-year in Gozamen district, Ethiopia: a community-based cross-sectional study
Authors: Ambaw Yeshinat Lakew , Yirdaw Birhanu Wubale , Biwota Mulunesh Abuhay , Mekuryaw Abebayehu Melesew , Taye Birhan Tsegaw 
Published: February 2022

AbstractBackgroundRecent evidence has found widespread reports of women experiencing cultural malpractice during childbirth in Asia and sub-Saharan African countries. Despite an endeavor made to drop maternal and neonatal mortality, Ethiopia remains amongst the highest mortality rate. Thus, strengthening antenatal care (ANC) follow-up is the midst of cultural malpractice reduction during childbirth. This study was aimed to assess the magnitude of cultural malpractice and associated factors during childbirth and postpartum among women who gave birth within one year in Gozamen district, Ethiopia.MethodsA community-based cross-sectional study was conducted from November 1st to December 30th, 2019. A two-stage sampling technique was used to get a total of 600 women who gave birth within the last one year. Data were collected by using a semi-structured and pretested questionnaire. Then, data were entered into Epi info version 7.0 and exported to SPSS version 25 for analysis. Both bivariate analysis and a multivariable logistic regression model were fitted. The level of significance was declared based on the adjusted odds ratio (AOR) with its 95% confidence interval (CI) and a p-value of ≤0.05.ResultThe Overall magnitude of cultural malpractices during childbirth and postpartum was found to be 31.2% (95%CI: 27.8, 34.7). Out of 600 women, 203(33.9%) were delivered at home, 67(11.2%) practiced abdominal massage, 31(16.6%) avoided colostrum, 24(12.8%) practiced pre-lacteal feeding and 138 (23%) washed their baby before 24 h after delivery. Mothers who have antenatal follow-up (AOR=0.52 95%CI 0.28, 0.94), married marital relation (AOR=0.24, 95%CI:0.07, 0.89), being farmer husband occupation (AOR=6.25 (95%CI: 1.22, 30.30), parity ≥5 (AOR=5, 95%CI: 2.44, 9.52), had significant association with cultural malpractice during childbirth and postpartum.ConclusionsThis study showed there is an improvement in the magnitude of cultural malpractices during childbirth and postpartum, but still it’s high as compared to the country’s maternal health service utilization aim. A well-enforced health education program by well-trained healthcare personnel besides sufficient number of ANC visits are needed to overcome these cultural practices. Further, intervention modalities health education communication outreach programs would be very important to reduce the prevalence of cultural malpractices in the community.
Performance evaluation of furrow irrigation water management practice under Wonji Shoa Sugar Estate condition, in Central Ethiopia
Authors: Yadeta Belay , Ayana Mekonen , Yitayew Muluneh , Hordofa Tilahun 
Published: February 2022

AbstractWonji Shoa Sugar Estate (WSSE) is one of the large-scale irrigation schemes in Ethiopia which was established in 1951. The aim of this study was to evaluate the performance of current furrow irrigation water management practices of WSSE. Performance evaluation of the current furrow irrigation was evaluated based on field experiment and the WinSRFR model. For this purpose, ten fields were selected from commonly used furrow lengths (32, 48, and 64 m). Application efficiency, distribution uniformity, and deep percolation performance indicators were used for evaluation. The performance of furrow irrigation showed poor performance, and as an improvement option, inflow rate and cutoff time were altered keeping furrow geometry constant. Advance and recession times for all furrow lengths were recorded and simulated using the WinSRFR model to obtain an accurate cutoff time of irrigation. The result obtained showed that the time allocated for all furrow lengths was not accurately determined. As an improvement option, both inflow rate and cutoff time changed and the performance of furrow irrigation significantly improved. By changing those decision variables, application efficacy and deep percolation performance indicators were significantly improved but distribution uniformity was not changed. In almost all statistical indices used, predicted performances by model were better than computed values in the existing situation. From the current result, it can be concluded that the inflow rate and cutoff time should be changed to attain good performance and increase furrow irrigation efficiency.
Deep learning identifies robust gender differences in functional brain organization and their dissociable links to clinical symptoms in autism
Authors: Supekar Kaustubh , de los Angeles Carlo , Ryali Srikanth , Cao Kaidi , Ma Tengyu , Menon Vinod 
Published: February 2022

BackgroundAutism spectrum disorder (ASD) is a highly heterogeneous disorder that affects nearly 1 in 189 females and 1 in 42 males. However, the neurobiological basis of gender differences in ASD is poorly understood, as most studies have neglected females and used methods ill-suited to capture such differences.AimsTo identify robust functional brain organisation markers that distinguish between females and males with ASD and predict symptom severity.MethodWe leveraged multiple neuroimaging cohorts (ASD n = 773) and developed a novel spatiotemporal deep neural network (stDNN), which uses spatiotemporal convolution on functional magnetic resonance imaging data to distinguish between groups.ResultsstDNN achieved consistently high classification accuracy in distinguishing between females and males with ASD. Notably, stDNN trained to distinguish between females and males with ASD could not distinguish between neurotypical females and males, suggesting that there are gender differences in the functional brain organisation in ASD that differ from normative gender differences. Brain features associated with motor, language and visuospatial attentional systems reliably distinguished between females and males with ASD. Crucially, these results were observed in a large multisite cohort and replicated in a fully independent cohort. Furthermore, brain features associated with the motor network's primary motor cortex node predicted the severity of restricted/repetitive behaviours in females but not in males with ASD.ConclusionsOur replicable findings reveal that the brains of females and males with ASD are functionally organised differently, contributing to their clinical symptoms in distinct ways. They inform the development of gender-specific diagnoses and treatment strategies for ASD, and ultimately advance precision psychiatry.
Introduction
Authors: Bou Ali Nadia 
Published: February 2022

Abstract
This roundtable revolves around the translation of selections from Amel's book Is the Heart for the East and Reason for the West? On Edward Said's Marx in “Orientalism,” published in Arabic in 1986. The importance of bringing this Arabic text to an English and global readership is twofold: it sheds light on the work of an influential and widely read Arabic critical social theorist and philosopher; and the translation of this critical theoretical work from “the margin” opens up central epistemological and conceptual problems in Marxist theory and its relation to postcolonialism in the present. The work of translation here does not simply involve introducing a marginal novelty into mainstream critical theory; rather it is a process of exhuming the elements that are untranslatable in the text—that is, the conceptual problems that have universal implications from within the particular site of their articulation.
In silico screening of chloroquine analogues for compounds with more affinity for the Plasmodium falciparum chloroquine transporter as potential antimalarial drugs
Authors: Otieno Filex , Walekhwa Michael 
Published: February 2022

Background: Malaria is an acute febrile illness affecting over 229 million people worldwide. Children aged five years and below are affected the most, with the highest prevalence in Sub-Saharan Africa. Chloroquine was previously used as the first-line treatment for malaria due to its affordability and high efficacy, but resistance has developed. Resistance to chloroquine is due to a mutation in the protein Plasmodium falciparum Chloroquine Transporter (pfCRT) which effluxes the drug from the parasitic digestive vacuole, decreasing the drug concentration. Resistance has however been shown to be reversible by compounds that can bind to the protein. Methods: In silico screening for chloroquine analogues was done using SwissSimilarity, SWISSADME, SwissTargetPrediction, Pubchem sketcher, Chimera and Avogadro tools to predict pharmacodynamics and pharmacokinetic profiles of the selected analogues. Results: About 20 compounds with a similarity index of > 95% were obtained from the ZINC database. In total, 12 of the 20 compounds showed a higher binding affinity to the mutant pfCRT protein. Overall, four of the 12 had a binding affinity less than -8.0 compared to -7.0 for chloroquine. Compound ZINC01596768 had the greatest binding strength at -8.3. The other analogues were ZINC38050614, ZINC38050617, and ZINC38050615 with binding interaction strengths of -8.0, -8.2 and -8.2 respectively. Pharmacokinetic profile prediction showed all 12 compounds inhibited the enzymes CYP1A2 and CYP2D6, followed the Lipinski rules, had a high GI absorption, were permeant to the blood brain barrier, had no alerts on the PAINS criteria and had violated the rule of XLOGP3 > 3.5 in lead likeness. Compounds ZINC38050614, ZINC38050617, and ZINC38050615 were predicted to be substrates of P-glycoprotein. The synthetic accessibility score for the twelve compounds were below 3.07. Conclusions: Results demonstrated that the compounds ZINC01596768, ZINC38050614, ZINC38050617, and ZINC38050615 were potential candidates that could be tested and developed as co-formulations of chloroquine.
Comparative study of the effects on the EEG of drinking monotherapy with Naftussya water and therapy supplemented with “Myroslava” and “Khrystyna” mineral waters
Authors: Hrytsak Myroslava , Popovych Dariya , Badiuk Nataliya , Hrytsan Ivanna , Zukow Xawery 
Published: February 2022

Background. Earlier we showed that the newly created sulfate-chloride sodium-magnesium drinking mineral waters of Truskavets’ spa have favorable effects on metabolism and neuroendocrine-immune complex of patients with their dysfunction. This report analyzes the effect of balneotherapy on the parameters of the electroencephalogram of the same contingent of patients. Materials and Methods. The object of clinical-physiological observation were 34 men aged 23-70 years, who underwent rehabilitation treatment of chronic cholecystitis and pyelonephritis in remission in the Truskavets’ spa. The examination was performed twice, before and after a 7-10-day course of balneotherapy. All patients received bioactive water Naftussya, however, 11 men additionally drank water "Khrystyna", and the other 11 men - water "Myroslava". The subject of the study were the parameters of the electroencephalogram. Results. The complex balneotherapy by interval use of sulfate-chloride sodium-magnesium mineral waters with Naftussya water causes significant changes in the constellation of EEG parameters, which are different from the effects of Naftussya water monotherapy. Own effects of mineral waters are estimated by modeling. Two patterns of neurotropic effects have been identified - activating and inhibitory. In general, the neuromodulating effects are physiologically favorable. Conclusion. The newly created sulfate-chloride sodium-magnesium drinking mineral waters of Truskavets’ spa have favorable neuromodulating effects on patients with chronic cholecystitis and pyelonephritis.
Does Industry Employment of Active Regulators Weaken Oversight?
Authors: Heese Jonas 
Published: February 2022

I study whether industry employment of active regulators weakens oversight. To examine this question, I exploit that the Financial Reporting Enforcement Panel (FREP), the German capital-market regulator responsible for enforcing public firms’ compliance with accounting standards, allows its senior regulators to serve on boards of public firms during their FREP tenure. I find that firms are less likely to face enforcement actions after they appoint active regulators to their board. After such an appointment, firms are more likely to receive a qualified audit opinion, more likely to have an above-normal risk of accounting manipulation, as measured by an F-score greater than one, and exhibit higher income-increasing abnormal accruals. These findings suggest that directorships of active regulators can result in conflicts of interest that weaken oversight. This paper was accepted by Brian Bushee, accounting. Supplemental Material: Data are available at https://doi.org/10.1287/mnsc.2022.4326 .