bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioethics in Community Health
Authors: Berlinger Nancy 
Published: August 2022

AbstractWhat keeps community health providers up at night? And how should bioethics evolve to meet the needs of these providers? Hastings Center research scholar Nancy Berlinger introduces a new project and line of research and public‐facing work at The Hastings Center to explore ethical challenges that arise in primary and preventative health care for medically underserved communities, where ethical challenges often reflect the health consequences of social inequalities.
Mask Mandates and Dilemmas of Disability Difference
Authors: Mintz Kevin , Francis Leslie 
Published: August 2022

AbstractA number of recent legal cases in the United States have considered both disability‐based exceptions to Covid‐19‐related mask mandates and disability‐based claims to stronger masking rules in states restricting the abilities of local governments to enforce mask mandates. We argue that a proper legal and ethical analysis of such cases requires understanding the distinction between disability accommodations and disability modifications. Disability accommodations are individualized adjustments that enable qualified individuals to perform jobs or achieve access on terms comparable to those experienced by others. Disability modifications are programmatic changes to structures or policies that increase accessibility. We contend that in the context of mask mandates, modifications rather than accommodations are ethically desirable because modification‐oriented policies promote disability access in a way that treats all individuals fairly, avoiding the risk of promoting misinformation and uncertainty about the health benefits of masking.
Real‐world evidence in health technology assessment of high‐risk medical devices: Fit for purpose?
Authors: Klein Philip , Blommestein Hedwig , Al Maiwenn , Pongiglione Benedetta , Torbica Aleksandra , Groot Saskia de 
Published: August 2022

AbstractHealth technology assessment (HTA) of medical devices (MDs) increasingly rely on real‐world evidence (RWE). The aim of this study was to evaluate the type and the quality of the evidence used to assess the (cost‐)effectiveness of high risk MDs (Class III) by HTA agencies in Europe (four European HTA agencies and EUnetHTA), with particular focus on RWE. Data were extracted from HTA reports on the type of evidence demonstrating (cost‐)effectiveness, and the quality of observational studies of comparative effectiveness using the Good Research for Comparative Effectiveness principles. 25 HTA reports were included that incorporated 28 observational studies of comparative effectiveness. Half of the studies (46%) took important confounding and/or effect modifying variables into account in the design and/or analyses. The most common way of including confounders and/or effect modifiers was through multivariable regression analysis. Other methods, such as propensity score matching, were rarely employed. Furthermore, meaningful analyses to test key assumptions were largely omitted. Resulting recommendations from HTA agencies on MDs is therefore (partially) based on evidence which is riddled with uncertainty. Considering the increasing importance of RWE it is important that the quality of observational studies of comparative effectiveness are systematically assessed when used in decision‐making.
AIF1+CSF1R+ MSCs, induced by TNF‐α, act to generate an inflammatory microenvironment and promote hepatocarcinogenesis
Authors: Zong Chen , Meng Yan , Ye Fei , Yang Xue , Li Rong , Jiang Jinghua , Zhao Qiudong , Gao Lu , Han Zhipeng , Wei Lixin 
Published: August 2022

Background and Aims:
Increasing evidence suggests that mesenchymal stem cells (MSCs) home to injured local tissues and the tumor microenvironment in the liver. Chronic inflammation is regarded as the major trait of primary liver cancer. However, the characteristics of endogenous MSCs in the inflammatory environment and their role in the occurrence of liver cancer remain obscure.

Approach and Results:
Using single‐cell RNA sequencing, we identified a distinct inflammation‐associated subset of MSCs, namely AIF1+CSF1R+ MSCs, which existed in the microenvironment before the occurrence of liver cancer. Furthermore, we found that this MSC subgroup is likely to be induced by TNF‐α stimulation through the TNFR1/SIRT1 (sirtuin 1) pathway. In a rat primary liver cancer model, we showed that MSCs with high SIRT1 expression (Ad‐Sirt1‐MSCs) promoted macrophage recruitment and synergistically facilitated liver cancer occurrence by secreting C‐C motif chemokine ligand (CCL) 5. Interestingly, depletion of macrophages or knockdown of CCL5 expression in Ad‐Sirt1‐MSCs attenuated the promotive effect of Ad‐Sirt1‐MSCs on liver inflammation and hepatocarcinogenesis (HCG). Finally, we demonstrated that SIRT1 up‐regulated CCL5 expression through activation of the AKT/HIF1α signaling axis in MSCs.

Conclusions:
Together, our results show that MSCs, which are mobilized to the injured site, can be educated by macrophages. In turn, the educated MSCs are involved in generating a chronic inflammatory microenvironment and promoting HCG.
Fibroblast growth factor receptor 1/Klothoβ agonist BFKB8488A improves lipids and liver health markers in patients with diabetes or NAFLD: A phase 1b randomized trial
Authors: Wong Chin , Dash Ajit , Fredrickson Jill , Lewin‐Koh Nicholas , Chen Shan , Yoshida Kenta , Liu Yanqiu , Gutierrez Johnny , Kunder Rebecca 
Published: August 2022

Background and Aims:
BFKB8488A is a bispecific antibody targeting fibroblast growth factor receptor 1c and Klothoβ. This phase 1b study assessed safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of BFKB8488A in patients with type 2 diabetes mellitus (T2DM) or NAFLD.

Approach and Results:
Patients were randomized to receive multiple doses of BFKB8488A at various dose levels and dosing intervals (weekly, every 2 weeks, or every 4 weeks) or placebo for 12 weeks. The primary outcome was the safety of BFKB8488A. Overall, 153 patients (T2DM: 91; NAFLD: 62) were enrolled and received at least one dose of treatment. Of these, 102 patients (62.7%) reported at least one adverse event (BFKB8488A: 83 [68.6%]; placebo: 19 [59.4%]). BFKB8488A exhibited nonlinear pharmacokinetics, with greater than dose‐proportional increases in exposure. The treatment‐emergent antidrug antibody incidence was 22.7%. Overall, trends in exposure‐dependent increases in high‐density lipoprotein (HDL) and decreases in triglyceride levels were observed. Decreases in alanine aminotransferase and aspartate aminotransferase were 0.7% and 9.2% for medium exposure and 7.3% and 11.2% for high‐exposure tertiles, compared with increases of 7.5% and 17% in the placebo group, respectively, at Day 85. In patients with NAFLD, the mean decrease from baseline liver fat was 13.0%, 34.5%, and 49.0% in the low‐, medium‐, and high‐exposure tertiles, respectively, compared with 0.1% with placebo at Day 85.

Conclusions:
BFKB8488A was adequately tolerated in patients with T2DM or NAFLD, leading to triglyceride reduction, HDL improvements, and trends in improvement in markers of liver health for both populations and marked liver fat reduction in patients with NAFLD. (ClinicalTrials.gov: NCT03060538).
Cyclohexane and Beyond: Tangled Hexagons and Octahedra
Authors: O'Keeffe Michael , Treacy Michael M. J. 
Published: August 2022

AbstractInspired by Dunitz’s treatment of the geometry and flexibility of cyclohexane, we describe some ways in which hexagons and octahedra can become self‐entangled and linked. Connections to topics such as flexibility of frameworks, tensegrity structures, and Borromean rings are indicated.
Distance and health facility choice: Evidence from a health micro insurance program in Punjab, Pakistan
Authors: Latif Dareen , Ahmed Hamna 
Published: August 2022

AbstractHealth micro insurance offers a promising mechanism to protect the poor against risk and vulnerability arising from catastrophic healthcare expenditures. In light of this, we study the relationship between physical distance to hospitals and the choice of healthcare services in the context of a health micro insurance program in Punjab, Pakistan. We address three main research questions; first, how does physical distance affect choice of health facility? Second, is the burden of physical distance greater for women? Third, can the diffusion of information in social networks be a potential mechanism for reducing the burden of distance? We employ a Probit model with administrative data on hospitalisation claims made between 2014 and 2017. Our findings show that distance impedes individuals from making panel (cashless) claims and thus increases the likelihood of out‐of‐pocket expenditures at nearby non‐panel hospitals. This adverse effect is more pronounced for women as compared to men. Dissemination of information in social networks increases the usage of panel facilities, especially by women. Hence, this can be an effective mechanism in reducing the role that distance plays in the choice of health facility.
Development of a multicriteria model for crises in urban water supply and its application to the case of Brasilia, Brazil
Authors: da Silva Welitom T. P. , de Souza Marco A. A. 
Published: August 2022

Abstract
The expansion of urban water supply crisis (UWC) cases, a context characterized by an inadequate ratio between water consumption and supply capacity, has motivated researchers to search for tools to solve the problem. The objective of this study is to develop a multicriteria tool to help select the solution alternative for UWC cases. The tool (called UWC-MCDA) is based on obtaining consensus on various multicriteria methods for selecting alternatives to solve UWC cases. The proposed methodology consists of the following steps: (1) defining the criteria, (2) defining weights, (3) defining the alternative, (4) defining multicriterial decision support methods, (5) coding the UWC solution alternative selection model, (6) evaluation of the model coding, (7) application of the model coding, and (8) sensitivity analysis. The methods PROMETHEE II, TOPSIS, ELECTRE III, and Consensus ranking are used. The case study considered was the Administrative Region of Brasilia, in the Federal District of Brazil. A multicriteria tool to help select the solution alternative for UWC cases was developed in an easy-to-use environment (Visual Basic for Applications, MS Excel). The UWC-MCDA is able to identify and prioritize, among a set of possible alternatives, the most appropriate solution for the case in question. For the case study, the UWC-MCDA indicated the best alternatives for regulating water consumption, strengthening sanitation service operators and good water conservation practices. Integr Environ Assess Manag 2023;19:99–113. © 2022 SETAC
The presence of vessels encapsulating tumor clusters is associated with an immunosuppressive tumor microenvironment in hepatocellular carcinoma
Authors: Zhang Peiyi , Ono Atsushi , Fujii Yasutoshi , Hayes Clair Nelson , Tamura Yosuke , Miura Ryoichi , Shirane Yuki , Nakahara Hikaru , Yamauchi Masami , Uchikawa Shinsuke , Uchida Takuro , Teraoka Yuji , Fujino Hatsue , Nakahara Takashi , Murakami Eisuke , Miki Daiki , Kawaoka Tomokazu , Okamoto Wataru , Makokha Grace Naswa , Imamura Michio , Arihiro Koji , Kobayashi Tsuyoshi , Ohdan Hideki , Fujita Masashi , Nakagawa Hidewaki , Chayama Kazuaki , Aikata Hiroshi 
Published: August 2022

AbstractRecently, a distinct vascular pattern in hepatocellular carcinoma (HCC) called vessels encapsulating tumor‐forming clusters (VETC) has received attention because of its association with poor prognosis. However, little is known about the mechanism by which VETC promotes an aggressive phenotype at the molecular level. In our study, the association between differences in stepwise signal intensity in the HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment were investigated using the International Cancer Genome Consortium (ICGC) cohort (66 patients). To our knowledge, this is the first study to analyze the molecular patterns of VETC using RNA‐Seq data. The VETC+ HCC group showed significantly lower overall survival and higher cumulative incidence of extrahepatic metastasis after curative hepatic resection than the VETC− HCC group. The VETC+ group exhibited molecular features indicative of lower immune activation than the VETC− group, suggesting that tumor cells in the VETC+ group were more likely to escape from the immune response, which could lead to the shorter OS (Overall survival) and higher risk of metastasis. On the other hand, gene expression levels of fibroblast growth factor receptors were upregulated in VETC+ HCC, suggesting that VETC+ HCC might benefit from lenvatinib treatment. Our results demonstrate that VETC+ HCC was associated with the suppression of tumor immune responses at the molecular level.
Do food safety regulations impede agrifood exports of China?
Authors: Ishaq Muhammad , Haq Zahoor ul , Qing Ping , Li Chongguang 
Published: August 2022

AbstractThis study uses the gravity model to estimate the effects of food safety regulations implemented by the partner countries on agri‐food exports of China. Annual bilateral trade data are compiled for major agrifood export items of China like apples, kidney beans, garlic, mandarins and orange, meat of swine, and tea. The panel data are estimated using both the fixed‐ and random‐effect models. Results of the study show that all the standard gravity‐type variables carry signs according to prior expectations and economic theory. The study concludes that food safety regulations have no effect on exports of all the selected commodities except meat of swine.
Epigallocatechin-3-gallate reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis
Authors: Li Hongxuan , Qiao Cong , Zhao Lingyu , Jing Qingxu , Xue Dongbo , Zhang Yingmei 
Published: August 2022

AbstractNeutrophil extracellular traps (NETs) promote intra-acinar trypsin activation and tissue damage. Therefore, reducing NET formation can reduce tissue damage in severe acute pancreatitis (SAP). However, NET formation pathways may differ among disease models. In this study, we evaluated the role of the myeloperoxidase–neutrophil elastase (NE) pathway in NET formation in SAP. SAP was induced by intraperitoneal injection of cerulein and LPSs in mice, and NE activity was inhibited by GW311616. Pancreatic tissues were collected for multiplex immunofluorescence, scanning electron microscopy, and western blotting to detect NET formation and the effect of NE on citrullinated histone H3, followed by analyses of serum amylase and cytokine levels. Pretreatment with GW311616 significantly reduced NET formation, pancreatic tissue damage, and systemic inflammatory responses in SAP. Network pharmacology analyses using NE as the target revealed the monomeric compound epigallocatechin-3-gallate (EGCG). Binding between EGCG and NE was validated using molecular docking, and the ability of EGCG to inhibit NE activity was verified experimentally. NET formation by PMA-stimulated neutrophils was significantly reduced in vitro when the cells were pretreated with 40 μM EGCG. Pretreatment with EGCG significantly reduced NET formation, pancreatic tissue damage, and systemic inflammatory responses in vivo. These results reveal that NET formation requires the myeloperoxidase-NE pathway, and citrullination of histone H3 is affected by NE activity in SAP. EGCG shows therapeutic potential for affecting NE activity, NET formation, and systemic inflammation in SAP.
Comparative analysis of the clinical and epidemiological characteristics of human influenza virus versus human respiratory syncytial virus versus human metapneumovirus infection in nine provinces of China during 2009−2021
Authors: Cui Aili , Xie Zhibo , Xu Jing , Hu Kongxin , Zhu Runan , Li Zhong , Li Yan , Sun Liwei , Xiang Xingyu , Xu Baoping , Zhang Rongbo , Gao Zhenguo , Zhang Yan , Xu Wenbo 
Published: August 2022

AbstractA comparative analysis of confirmed cases of human influenza virus (HIFV), human respiratory syncytial virus (HRSV), and human metapneumovirus (HMPV) was conducted to describe their clinical and epidemiological characteristics. During 2009−2021, active surveillance of acute respiratory infections (ARIs) was performed in nine provinces of China. Clinical and epidemiological information and laboratory testing results of HIFV, HRSV, and HMPV were analyzed. Among 11591 ARI patients, the single‐infection rates of HIFV, HRSV, and HMPV were 15.00%, 9.59%, and 2.24%, respectively; the coinfection rate of these three viruses was 0.64%. HIFV infection was mainly in adults aged 15−59 years, accounting for 39.10%. HRSV and HMPV infections were mainly in children under 5 years old, accounting for 87.13% and 83.46%, respectively. Patients with HRSV infection were younger than HMPV. HRSV and HMPV had high similarities in clinical manifestations, presenting with lower respiratory symptoms. HIFV mainly presented with an upper respiratory infection. The epidemic peak of HRSV was earlier than that of HIFV, and that of HMPV was later than those of HRSV and HFIV. A total of 85.14% of coinfection cases were children under 5 years old. Coinfection might increase the risk of pneumonia in HIFV cases. During 2020−2021, the positive rates and seasonal patterns of these three viruses changed due to the impact of the COVID‐19 pandemic. Certain clinical and epidemiological features were observed in HIFV, HRSV, and HMPV infections, which could be beneficial for guiding clinical diagnosis, treatment, and prevention of these three viruses in China.
An outbreak of acute respiratory disease caused by HAdV‐55 in Beijing, China, 2020
Authors: Liu HongBo , Li Qingfeng , Xiang Ying , Li Hong , Liu Kangkang , Du Xinying , Yang Chaojie , Liu Hongbo , Shi Mengjing , Hu Xueqian , Wang Hui , Zhang Xiaohong , Li Xiangda , Tian Sai , Bao Renlong , Wang Ligui , Qiu Shaofu , Song Hongbin 
Published: August 2022

AbstractHuman adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV‐55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV‐55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID‐19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real‐time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV‐55 isolate was selected and submitted for whole‐genome sequencing using a MiSeq system and the whole‐genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV‐55 infection in the laboratory using real‐time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ‐446, with 34 761 nucleotides in length. HAdV‐55 isolate BJ‐446 was 99.85% identical to strain QS‐DLL, which was the first HAdV‐55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV‐55 infection associated with the ARD outbreak in Beijing since the emergence of COVID‐19. The study suggests that improved surveillance of HAdV is needed, although COVID‐19 is still prevalent in the world.
Do voluntary environmental programs matter? Evidence from the EPA SmartWay program
Authors: Scott Alex , Li Ming , Cantor David E. , Corsi Thomas M. 
Published: August 2022

AbstractThere is mixed evidence on the effectiveness of voluntary environmental programs. We evaluate a voluntary program aimed at reducing transportation emissions, that is, the U.S. EPA SmartWay Program. We construct a novel database of the physical assets used by firms before and after they joined SmartWay and compare changes in the age of their assets with that of firms that did not join SmartWay. Our results show that firms that participated in SmartWay operate substantially newer (i.e., cleaner) trucks compared with non‐SmartWay participants, indicating that SmartWay participation is a credible signal of a firm's reduced emissions footprint emanating from truck operations. After the start of SmartWay, firms that joined invested in newer trucks relative to firms that did not, with about a year reduction in average truck age several years after the program began. SmartWay had a larger effect on firms that own their trucks compared with firms that outsource ownership, and sustained participation increased the program's effectiveness. We estimate that the SmartWay Program has reduced commercial transportation emissions from operations by 25.2 million metric tons of CO2 by increasing the incentive to invest in newer, cleaner trucks. Our study provides insight into factors that make voluntary environmental programs effective.
The presence of superoxide ions and related dioxygen species in zinc oxide—A structural characterization by in situ Raman spectroscopy
Authors: Fischer Dieter , Zagorac Dejan , Schön J. Christian 
Published: August 2022

AbstractZinc oxide exhibits unique properties that are reflected in a wide variety of applications, particularly in the field of transparent, conductive films. However, less attention has been paid to their color. Here, we present the synthesis of yellow‐gray ZnO films at room temperature by femtosecond pulsed laser deposition. In situ Raman investigations of these polycrystalline ZnO films reveal the existence of superoxide ions, O2−, in zinc oxide, which are responsible for the yellow color, and are also detected in ZnO powder and single crystals. In addition, further dioxygen species are identified in the samples, including the O2‐molecule. The negative charge excess caused by the dioxygen species creates metallic zinc as a byproduct. Structural analysis reveals an unforced realization of the dioxygen species in the ZnO lattice. Density functional theory (DFT) calculations support the assumed structural displacements as well as the observed, unexpected Raman bands. These results open up completely new insights into the behavior of ZnO.