bluuebunny/crossref_metadata_2025_split huggingface dataset:
History and Bioethics
Authors: Fins Joseph J. 
Published: April 2021

AbstractCultural historians and historians of medicine are a rarity in bioethics. Even those who write histories of bioethics are philosophers, sociologists, or theologians. Where have all the historians gone? If bioethics is to contribute to the urgent work of addressing social justice, structural racism, and health inequity, we bioethicists need to embrace history as a fully constituent part of our field. Historians can help us apprehend the ideas that shaped bioethics, and health policy more broadly, and discover the dissenting arguments that might inspire us now. Given our annus horribilis, history has become an instrumental necessity. It is only through the study of history that we can understand the past so as to reimagine how bioethics can influence health policy and work toward health equity.
Coming to Terms with the Black Box Problem: How to Justify AI Systems in Health Care
Authors: Felder Ryan Marshall 
Published: April 2021

AbstractThe use of opaque, uninterpretable artificial intelligence systems in health care can be medically beneficial, but it is often viewed as potentially morally problematic on account of this opacity—because the systems are black boxes. Alex John London has recently argued that opacity is not generally problematic, given that many standard therapies are explanatorily opaque and that we can rely on statistical validation of the systems in deciding whether to implement them. But is statistical validation sufficient to justify implementation of these AI systems in health care, or is it merely one of the necessary criteria? I argue that accountability, which holds an important role in preserving the patient‐physician trust that allows the institution of medicine to function, contributes further to an account of AI system justification. Hence, I endorse the vanishing accountability principle: accountability in medicine, in addition to statistical validation, must be preserved. AI systems that introduce problematic gaps in accountability should not be implemented.
Molecular Characterization of Biliary Tract Cancer Predicts Chemotherapy and Programmed Death 1/Programmed Death‐Ligand 1 Blockade Responses
Authors: Yoon Jihoon G. , Kim Min Hwan , Jang Mi , Kim Hoguen , Hwang Ho Kyoung , Kang Chang Moo , Lee Woo Jung , Kang Beodeul , Lee Choong‐kun , Lee Min Goo , Chung Hyun Cheol , Choi Hye Jin , Park Young Nyun 
Published: April 2021

Background and Aims
Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs.

Approach and Results
We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first‐line palliative chemotherapy; 48 patients underwent programmed death 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response‐associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small‐duct type compared with the large‐duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1‐associated protein‐1/isocitrate dehydrogenase 1/2 and KRAS proto‐oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway‐altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD‐1/PD‐L1 blockade‐treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD‐1/PD‐L1 blockade and low tumor mutational burdens. Low tumor‐infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune‐suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response.

Conclusions
This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors’ molecular features.
Antioxidant‐modulated cytotoxicity of silver nanoparticles
Authors: Barbasz Anna , Oćwieja Magdalena , Piergies Natalia , Duraczyńska Dorota , Nowak Anna 
Published: April 2021

AbstractThe properties of silver nanoparticles (AgNPs) synthesized using compounds exhibiting biological activity seem to constitute an interesting issue worthy of examination. In these studies, two types of AgNPs were synthesized by a chemical reduction method using well‐known antioxidants: gallic acid (GA) and ascorbic acid (AA). Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that the AgNPs were spherical. The average size was equal to 26 ± 6 nm and 20 ± 7 nm in the case of ascorbic acid‐silver nanoparticles (AAgNPs) and gallic acid‐silver nanoparticles (GAAgNPs), respectively. Surface‐enhanced Raman spectroscopy (SERS) confirmed that the AgNPs were not stabilized by pure forms of applied antioxidants. Changes in mitochondrial activity and secretion of inflammatory and apoptosis mediators after the exposure of human promyelocytic (HL‐60) and histiocytic lymphoma (U‐937) cells to the AgNPs were studied to determine the impact of stabilizing layers on nanoparticle toxicity. The GAAgNPs were found to be more toxic for the cells than the AAgNPs. Their toxicity was manifested by a strong reduction in mitochondrial activity and induction of the secretion of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and caspase‐9. The addition of pure antioxidants to the AgNP suspensions was found to influence their toxicity. There was a significant positive effect in the case of the mixture of AA with AAgNPs and GA with GAAgNPs. The results obtained suggest that the presence of stabilizing agents adsorbed on the surface of AgNPs is the main factor in shaping their toxicity. Nevertheless, the toxic effect can be also tuned by the introduction of free antioxidant molecules to the AgNP suspensions.
Working around the border: Shared experiences of art therapists working with families impacted by immigration and political realities in Mexico and the United States
Authors: Metzl Einat S. , Treviño Ana Laura 
Published: April 2021

AbstractThis art‐based, participatory action research sought to foster dialog between art therapists working on both sides of the US (Southern California)–Mexico (Tijuana) border in 2019. The paper summarizes the narratives from three initial focus groups, highlighting main findings arising from systematic analyses of verbal, creative and reflective writing input of participants. Identified themes include therapists' need to respond to immigration crisis; the realities of being a part of a border town; observing differences between communities; learning from the art of art therapists working with immigrants and refugees; and identifying challenges as a therapist. These themes inspired the creation of preliminary guidelines and are discussed within the context of mental health services around the border at this time.
Long non‐coding DANCR targets miR‐185‐5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3β/snail pathway
Authors: Sun Wendong , Zu Shulu , Shao Guangfeng , Wang Wenzhen , Gong Fangxin 
Published: April 2021

AbstractBackgroundLong non‐coding RNA differentiation antagonizing non‐protein coding RNA (DANCR) acts as an oncogene in different cancers, although its roles in prostate cancer are not fully reported. We aimed to explore its mechanism in facilitating the malignancy of prostate cancer.MethodsThe expression of DANCR, microRNA (miR)‐185‐5p and LIM and SH3 protein 1 (LASP1) in 40 pairs of prostate cancer tissues and normal tissues, five prostate cancer cell lines and one epithelial cell line was assessed by a quantitative real‐time polymerase chain reaction, western blotting and immunohistochemistry, respectively. In transfected PC3 and C4‐2 cells, cell proliferation, migration, invasion, cell cycle distribution and epithelial–mesenchymal transition (EMT) protein expression were tested via cell counting kit‐8, wound healing, transwell, flow cytometry and western blot assays, respectively. The interactions between DANCR, miR‐185‐5p and LASP1 were verified by a dual‐luciferase reporter assay. Rescue experiments were conducted to determine the roles of DANCR on the malignant properties of PC3 and C4‐2 cells. The involvement of the signaling pathway was examined using a p‐FAK inhibitor.ResultsDANCR and LASP1 expression was enhanced, whereas miR‐185‐5p expression was diminished in prostate cancer tissues and cell lines. Knockdown of DANCR suppressed cell proliferation, migration, invasion, G1‐S transition and expression of EMT proteins of the transfected PC3 and C4‐2 cells. DANCR sponged miR‐185‐5p to upregulate LASP1 expression. DANCR‐miR‐185‐5p‐LASP1 axis activates the FAK/PI3K/AKT/GSK3β/Snail pathway to promote the malignant properties of PC3 and C4‐2 cells.ConclusionsThese findings suggest that DANCR exerts oncogenic roles in prostate cancer via the miR‐185‐5p/LASP1 axis activating the FAK/PI3K/AKT/GSK3β/Snail pathway. It can be a potential biomarker in the diagnosis and monitoring of prostate cancer.
Safety analysis ofex vivo-expanded canine natural killer cells in a xenogeneic mouse model of graft-versus-host disease
Authors: Kim Cheol-Jung , Park Se-Cheol , Lee Soo-Hyeon , Lim Yu-Jin , Yoon Meesun , Park Jun-Gyu , Baek Yeong-Bin , Cho Kyoung-Oh , Hong Jeong Won , Shin Dong-Jun , Kim Sang-Ki 
Published: April 2021

AbstractCanine natural killer (NK) cells are large, granular lymphocytes that are neither B lymphocytes nor T lymphocytes. However, it has been reported that canine NK cells share some of the phenotypic characteristics of T lymphocytes, such as CD3 and CD5. Studies are needed to assess the safety of canine NK cells for immunotherapy, especially because the safety of using allogeneic NK cells as an immunotherapy for dogs has yet to be shown. In this study, the safety of cultured canine NK cells was assessed using a xenogeneic mouse model of graft-versus-host disease (GVHD). Mice were injected with either canine peripheral blood mononuclear cells (PBMCs) or cultured NK cells for 2 or 3 weeks. Data were then collected on changes in mice body weights, disease severity scores, and survival rates. Histopathological and immunohistochemical evaluations were also performed. All mice injected with canine PBMCs died within 45 days after injection. Severe clinical signs were caused by GVHD. The histopathological and immunohistochemical evaluations showed that mice injected with canine PBMCs had multiple lesions, including necrosis in their lungs, livers, kidneys, and stomachs, and the injected cells were present around the lesions. By contrast, no mice injected with cultured NK cells without removing the CD3+TCR– cells exhibited any clinical abnormalities. Moreover, they all survived the 90-day experimental period without exhibiting any histopathological changes. Accordingly, the results of this study suggest that canine NK cells do not cause significant side effects such as GVHD and allogeneic NK cells can safely be used for cancer immunotherapy in dogs.
Revisiting cell and gene therapies in Huntington’s disease
Authors: Beatriz Margarida , Lopes Carla , Ribeiro Ana Cláudia S. , Rego Ana Cristina Carvalho 
Published: April 2021

AbstractNeurodegenerative movement disorders, such as Huntington's disease (HD), share a progressive and relentless course with increasing motor disability, linked with neuropsychiatric impairment. These diseases exhibit diverse pathophysiological processes and are a topic of intense experimental and clinical research due to the lack of therapeutic options. Restorative therapies are promising approaches with the potential to restore brain circuits. However, there were less compelling results in the few clinical trials. In this review, we discuss cell replacement therapies applied to animal models and HD patients. We thoroughly describe the initial trials using fetal neural tissue transplantation and recent approaches based on alternative cell sources tested in several animal models. Stem cells were shown to generate the desired neuron phenotype and/or provide growth factors to the degenerating host cells. Besides, genetic approaches such as RNA interference and the CRISPR/Cas9 system have been studied in animal models and human‐derived cells. New genetic manipulations have revealed the capability to control or counteract the effect of human gene mutations as described by the use of antisense oligonucleotides in a clinical trial. In HD, innovative strategies are at forefront of human testing and thus other brain genetic diseases may follow similar therapeutic strategies.
Changes in March to May rainfall over Tanzania during 1978–2017
Authors: Makula Exavery Kisesa , Zhou Botao 
Published: April 2021

AbstractThis study assessed the change in March to May (MAM) rainfall over Tanzania during 1978–2017. It is revealed that the MAM rainfall experienced more years of negative (positive) anomalies after (before) the late 1990s. The atmospheric and oceanic background underlying such a change in MAM rainfall was addressed. The results show that the recent decrease in MAM rainfall is associated with the reduction of water vapour transport from the Indian Ocean to Tanzania, the enhancement of tropospheric moisture divergence, and the decrease of convective activities over Tanzania. Changes of sea surface temperature (SST) in the 1990s from a cold phase to a warm phase over the southwestern Indian Ocean and western tropical Pacific Ocean and that from a warm phase to a cold phase over the southern Atlantic Ocean also have a significant contribution. Associated with the SST warming over the southwestern Indian Ocean, an anomalous cyclonic circulation prevails over the tropical Indian Ocean in the upper level, favourable for the increase of subsidence in Tanzania. Concurrently, the Mascarene High shifts eastward, which may weaken the water vapour transport from the southern Indian Ocean toward Tanzania. The warming of SST over the western tropical Pacific Ocean is linked to a Walker‐like circulation with the descending limb over the western Indian Ocean and Tanzania, conducive to the subsidence over Tanzania. Related to the SST cooling over the southern Atlantic Ocean, anomalous atmospheric convergence in the upper level is dominant over Tanzania, concurrent with the easterly outflow toward the Congo basin and the westerly and northerly outflow toward the western Indian Ocean from Tanzania in the low level, favouring the decrease of MAM rainfall.
Early enteral feeding is beneficial for patients after pelvic exenteration surgery: A randomized controlled trial
Authors: Hogan Sophie , Reece Lauren , Solomon Michael , Rangan Anna , Carey Sharon 
Published: April 2021

AbstractBackgroundPostoperative feeding practices vary after pelvic exenteration surgery because of the lack of nutrition research in this specific surgical area. Postoperative ileus (POI) is common after pelvic exenteration surgery, and early enteral feeding is often avoided because of the lack of evidence and the belief that this may induce POI in this patient cohort. The aim of this study was to determine the effects of early enteral feeding after pelvic exenteration surgery on return of bowel movement and POI.MethodsA randomized controlled trial was conducted with patients undergoing pelvic exenteration surgery from November 2018 to June 2020. Forty participants received standard nutrition care (parenteral nutrition) and 47 participants received trophic enteral feeding (20 ml/h) via a nasogastric tube, in addition to standard care, until participants were upgraded to free fluids. Time to first bowel movement and rates of POI were the main outcome measures.ResultsThere was no significant difference between arms for time to first bowel movement; however, POI rates were significantly less in participants who were enterally fed (P = .036) in the per‐protocol analysis. Regressions showed that the longer patients were restricted from an oral diet after surgery, the greater the time was to first bowel movement and the greater the postoperative complication rates (P < .0005).ConclusionsEarly enteral feeding can be commenced safely to improve gastrointestinal function after pelvic exenteration surgery.
Effect paths of environmental factors and community attributes on aboveground net primary productivity of a temperate grassland
Authors: Peng Zhaoyu , Liu Hongyan , Jiang Lubing , Liu Xu , Dai Jingyu , Xu Chongyang , Chen Zhiting , Wu Lu , Liu Feng , Liang Boyi 
Published: April 2021

AbstractAboveground net primary productivity (ANPP) of grassland influenced by both environmental factors and structural plant community attributes indicates its growth situation and ability to provide ecosystem services. However, previous works have focused on the effects of either environmental factors or plant community attributes on ANPP, which makes it difficult to quantify the effect pathways of environmental factors and plant community attributes on ANPP. In our study, we took a temperate grassland in the agropastoral ecotone of northern China as the research area and quantified the effects of environmental factors and plant community attributes on grassland ANPP with a structural equation model, together with correlation and partial correlation analyses. We found that growing season precipitation is the most critical factor for grassland ANPP, and its direct effect (standardized direct positive effect, SDE = 0.401, p < 0.05) on ANPP was the main path. Temperature affected ANPP directly (SDE = 0.230, p < 0.05) and indirectly (standardized indirect positive effect SIE = 0.110, p < 0.05) mainly through community attributes in the area, such as tiller number and cover. The increase in soil sand content reduced tiller number and further affected ANPP (SIE = 0.011, p < 0.05). Human population influenced ANPP through species diversity (SIE = −0.059, p < 0.05), and the increase in livestock number worked on ANPP by degrading the soil. Our results imply that improving grassland community attributes, such as maintaining species diversity and increasing vegetation coverage, will effectively mitigate the negative effects of climate change.
The profunda artery perforator free flap for lower extremity reconstruction
Authors: Ciudad Pedro , Kaciulyte Juste , Torto Federico Lo , Vargas Maria Ines , Bustamante Atenas , Chen Hung‐Chi , Maruccia Michele , Zulueta Jaroslav , Trignano Emilio , Bolletta Alberto 
Published: April 2021

AbstractBackgroundThe profunda artery perforator (PAP) flap has been reported in several types of reconstructions. This report aims to evaluate the usefulness and the clinical outcome of patients who underwent the PAP free flap for lower limb reconstruction.MethodsBetween February 2018 and February 2020, nine patients with injury at lower third of the leg, foot dorsum or foot plant (eight acute injuries and one chronic ulcer) were selected. Mean wound size was 12.5 × 6.3 cm (9 × 5–14.5 × 6.5). Inclusion criteria consisted in patient's request to hide the donor site scar and the absence of previous traumas or surgery in the donor site. Patients considered unable to bear prolonged surgery were excluded. Patients underwent preoperative CT angiography and peri‐operative Doopler, for perforator selection. All flaps were designed with pinch test, in elliptical shape. Microvascular anastomosis was performed to the tibialis anterior/posterior or medial plantar vessels. Outcomes were evaluated in terms of wound coverage success and patient's quality of life through Lower Extremity Functional Scale (LEFS) questionnaire.ResultsThe mean size of the harvested skin paddle was 13.5 × 7.4 cm (9 × 6–15 × 8) and mean pedicle length was 8.5 cm. Mean flap harvest time was 43.5 min (35–55). Flap survival rate was 100%, with one re‐exploration with minimal partial flap loss. Mean follow‐up was 13.5 months . Reconstructive results were successful in wound coverage and function. All patients reported satisfaction with their result by LEFS questionnaire (score:64.7).ConclusionWith proper patient selection, there was 100% flap survival rate with no major complication. According to our data, the PAP free flap could be a valuable option for lower extremity reconstruction.
Tunable multiwavelength optical comb enabledRoF‐OFDM‐PONwith wavelength multiplex
Authors: Ding Qingan , Zhang Lijun , Wang Xiaojuan , Liang Anhui , Zheng Li , Liu Changqing , Nie Bowen , Liu Huixin 
Published: April 2021

AbstractWe propose a hybrid full duplex passive optical network with fusion of wavelength‐division‐multiplexing and orthogonal frequency‐division multiplexing (WDM‐OFDM) for a radio‐over‐fiber (RoF) system application. The key of the system is a tunable optical frequency comb (OFC) embedded cascading modulators and a parameter mixer. Moreover, 23 frequency components with 0.6 dB flatness generated by the OFC are used as light sources for each WDM channel. We utilize a 7.5 GHz OFDM wired signal and a 12.5 GHz OFDM wireless signal for downstream transmission and 10 Gb/s OOK (on–off keyed) signals for upstream traffic. Using polarization multiplexing technique, we extract a central optical carrier to bear the upstream signal so that no excess optical source is introduced into the ONU. Thus, the intricacy and costs of system are diminished. Moreover, successful transmission has been demonstrated since the bit error rates of the downstream and upstream signals are always under the adopted forward error correction limit. Furthermore, the proposed system can enhance power budget and reduce cost, which has a promising prospect for future wireless communication.
Bismuth‐doped fiber Q‐switcher in erbium‐doped fiber laser cavity
Authors: Zhang Pei , Dimyati Kaharuddin , Najm Mustafa Mohammed , Nizamani Bilal , Paul Mukul Chandran , Das Shyamal , Dhar Anirban , Pal Mrinmay , Yasin Moh , Harun Sulaiman Wadi 
Published: April 2021

AbstractWe propose a simple design of all‐fiber Q‐switched erbium‐doped fiber laser (EDFL). The laser is passively Q‐switched by splicing bismuth‐doped fiber into a ring cavity. The design has been experimentally demonstrated at the emission wavelength of 1560.48 nm. A single‐mode Q‐switched pulse with pulse duration of 1.18 μs and pulse energy of 15.6 nJ was obtained with 980 nm pump power of 178 mW. Stable and typical Q‐switched pulses were achieved at the repetition rate changing from 63.3 to 94.6 kHz. To the best of our knowledge, it is the first time to demonstrate bismuth‐doped fiber as an effective saturable absorber for erbium‐doped fiber laser.