bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabidiol converts NF-κB into a tumor suppressor in glioblastoma with defined antioxidative properties
Authors: Volmar Marie N M , Cheng Jiying , Alenezi Haitham , Richter Sven , Haug Alisha , Hassan Zonera , Goldberg Maria , Li Yuping , Hou Mengzhuo , Herold-Mende Christel , Maire Cecile L , Lamszus Katrin , Flüh Charlotte , Held-Feindt Janka , Gargiulo Gaetano , Topping Geoffrey J , Schilling Franz , Saur Dieter , Schneider Günter , Synowitz Michael , Schick Joel A , Kälin Roland E , Glass Rainer
Published: April 2021

Background

The transcription factor NF-κB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma [GBM]). Precise therapeutic modulation of NF-κB activity can suppress central oncogenic signaling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive.

Methods

In a pharmacogenomics study with a panel of transgenic glioma cells, we observed that NF-κB can be converted into a tumor suppressor by the non-psychotropic cannabinoid cannabidiol (CBD). Subsequently, we investigated the anti-tumor effects of CBD, which is used as an anticonvulsive drug (Epidiolex) in pediatric neurology, in a larger set of human primary GBM stem-like cells (hGSC). For this study, we performed pharmacological assays, gene expression profiling, biochemical, and cell-biological experiments. We validated our findings using orthotopic in vivo models and bioinformatics analysis of human GBM datasets.

Results

We found that CBD promotes DNA binding of the NF-κB subunit RELA and simultaneously prevents RELA phosphorylation on serine-311, a key residue that permits genetic transactivation. Strikingly, sustained DNA binding by RELA-lacking phospho-serine 311 was found to mediate hGSC cytotoxicity. Widespread sensitivity to CBD was observed in a cohort of hGSC defined by low levels of reactive oxygen species (ROS), while high ROS content in other tumors blocked CBD-induced hGSC death. Consequently, ROS levels served as a predictive biomarker for CBD-sensitive tumors.

Conclusions

This evidence demonstrates how a clinically approved drug can convert NF-κB into a tumor suppressor and suggests a promising repurposing option for GBM therapy.
Assessing the effectiveness of a forest Habitat Conservation Plan for a threatened seabird, the Marbled Murrelet
Authors: Brunk Kristin , Chinnici Sal , Pidgeon Anna , Peery M Zachariah
Published: April 2021

Habitat Conservation Plans (HCPs) commonly facilitate habitat conservation on private land in the United States, yet the effectiveness of individual HCPs is rarely evaluated. Here, we assess the effectiveness of a high-profile HCP created by a lumber company to protect old-growth forests used for breeding by Marbled Murrelets (Brachyramphus marmoratus) on private land. We used 17 years of HCP-monitoring data to compare trends in murrelet occupancy and inland counts between private HCP areas and public reference areas over time. Based on occupancy models applied to audio-visual survey data, average occupancy was higher in public reference areas (0.85; 85% confidence intervals [CI]: 0.79–0.90) than in private HCP areas (0.46; 85% CI: 0.38–0.54). Numerically, trends in occupancy were slightly positive in public areas ( = 1.01; 85% CI: 0.94–1.08) and slightly negative in private areas ( = 0.97; 85% CI: 0.87–1.06), but CI did not preclude stable occupancy on both ownerships. Based on generalized linear mixed models applied to inland radar survey data, murrelet counts in private HCP areas (least-squares [LS] mean = 8.7; 85% CI: 6.2–12.2) were lower than those in public reference areas (LS mean = 14.8; 85% CI: 10.1–21.7), but CI overlapped. Murrelet counts declined by 12–17% annually on both ownerships over the study period based on the top model, but a closely competing interactive model suggested more rapid declines in public reference (14–20%) than in private HCP (10–15%) areas. Both models indicated that murrelet counts were negatively related to sea surface temperature, suggesting that warm ocean conditions negatively affect murrelet breeding effort. Collectively, these results suggest that while HCP habitat may be lower quality than public reference areas, the HCP has likely not exacerbated ongoing declines of murrelets in the region. This work highlights the importance of including reference areas when evaluating conservation policies.
Stone-Walled Fish traps of Australia and New Guinea as Expressions of Enhanced Sociality
Authors: McNiven Ian J. , Lambrides Ariana B. J.
Published: April 2021

Fishing was and remains an important subsistence activity of many coastal and inland Indigenous peoples of Australia and New Guinea. The range of ethnographically known fishing methods used to obtain freshwater and marine fishes is similar across the two regions. This ethnographic picture of diversity and complexity is not matched archaeologically, where stone-walled fish traps dominate. Archaeological research on stone-walled fish traps has focused on technical dimensions (e.g., mapping, classification, and dating) and social dimensions (e.g., gender, social complexity, and social organization). Stone-walled fish traps can transform the social and ecological landscape and, in an archaeological context, provide an opportunity to explore decision making and the sociocultural changes associated with the installation of these fixed-in-place facilities. Relevant social organizational changes with potential material correlates amenable to archaeological research include the restructuring of residential sites; interregional gatherings and exchange relationships; aquatic resource enhancement and regularization; and ownership and control of facilities and resources, including territorial partitioning of land- and seascapes.
“Study, practice, and a reasonable working method”
Authors: Aschauer Mario
Published: April 2021

This article presents the first step toward a hitherto unwritten history of creative process pedagogy in the territories of the Holy Roman Empire between 1500 and 1850. In answering the question of how musical creativity was taught and learned beyond the obvious theoretical aspects of composition such as counterpoint, harmony, and instrumentation, it analyzes a plethora of treatises, composer’s sketches, and study manuscripts to identify and describe important pedagogical trends and methodologies. These include, for example, the use of principles from classical Latin rhetoric and, as a derivative technique, the study and use of loci or musical commonplaces. Musical “shorthand” notation such as partimento and figured bass are investigated as basis for the sketches and drafts by composers of the Classical period which, in 19th-century treatises, became the foundation for creative process pedagogy themselves.
Young People’s Lived Experience of Music in Everyday Life
Authors: Herbert Ruth
Published: April 2021

Over the last decade, there has been growing psychological interest in studying everyday experiences with and of music in ways that bypass a selective focus on musical function, mood, emotion, or the perception of musical attributes. Ecological perspectives on music listening—where experience is understood as the multimodal sum of a systemic interaction between perceiver, environment, and musical attributes—have also been influential. This has been reflected in an increase in the number of empirical studies exhibiting a phenomenological approach. However, little research has explicitly addressed children’s and adolescents’ holistic interactions with music. Drawing on findings from a mixed-method empirical inquiry into UK ten-to-eighteen-year-olds’ involvement with music (employing interpretative phenomenological analysis), this chapter explores the phenomenology of children’s and adolescents’ unfolding, lived experiences of music in everyday scenarios. It discusses ways in which the experience of music across this time span changes in terms of psychological characteristics, kinds of consciousness, and meanings attached to music. Key themes are related to topics within phenomenology’s philosophical tradition, and the relationship between philosophical and psychological understandings of phenomenology is considered.
Intergenerational Ethics and Individual Duties
Authors: Cripps Elizabeth
Published: April 2021

This chapter defends a cooperative promotional model of individual intergenerational moral duties. The individual can feel powerless and detached in the face of intergenerational moral challenges, which generally result from the combined actions of billions of people and require global-level solutions. Two individual duties are commonly debated: to promote effective collective action and to minimize one’s own contribution to the problem, for example, by cutting one’s carbon footprint. The cooperative promotional model incorporates both possibilities, including in many cases a duty to have a small family. The argument starts by assuming a shared or “weakly collective” duty requiring the global affluent to organize to avoid severe intergenerational injustice, a claim widely defended on positive and negative grounds. On the cooperative promotional model, each individual must cooperate with motivated others as far as reasonably possible to promote fair, effective, efficient collective-level progress toward this collective end. In determining how to act, individuals must consider collective or reliably coordinated action as well as the chance of triggering significant change through adding to aggregated individual actions. The account does not automatically require “taking up the slack” for obstructive individuals and institutions—it will often mandate cooperating to increase compliance—but is complicated by the need to adjust for unwilling duty bearers.
The Strategic Value of the Mono-Brand Store for European Luxury Fashion Brands
Authors: Moore Christopher M. , Doyle Stephen A.
Published: April 2021

Mono-brand stores have traditionally served as the pre-eminent sales and distribution channel for luxury fashion goods. Although the emergence of digital sales channels platforms has certainly challenged the sales channel dominance of mono-brand stores, the consequential impact of digitalisation of luxury-brand selling has been to recast and intensify the strategic value of mono-brand stores, principally as a means of reinforcing, protecting, and communicating the luxury brand’s proposition across international markets. By drawing from and applying agency theory and institutional theory to an understanding of the role of the mono-brand store, we can gain insight into the evolution of the most traditional of luxury-brand distribution methods in the twenty-first century.
Transnational Arbitration Law
Authors: Grisel Florian
Published: April 2021

This chapter suggests how transnational legal theory provides a relevant analytical frame to capture the norms, actors and processes of international arbitration. The chapter first examines the long-standing academic debates over lex mercatoria before turning to the dominant sociolegal analysis of international arbitration. Both examples illustrate the extent to which the analytical frames furnished by legal scholars are grounded in representations that ought to be transcended for a better understanding of the global world. The notion of transnational law provides a useful analytical frame to reconsider these debates under a new light and to open new avenues for future research.
Religion
Authors: Vettori Alessandro
Published: April 2021

This chapter explores the way in which Dante forges an original form of religiosity in his work by embracing Franciscan and apocalyptic ideas. It focuses on three aspects: the prophetic spirit that animates Dante’s critique of the Church and his call for spiritual renewal; his emphasis on the transformative power of prayer and its role in the poet’s construction of his spiritual authority; and the celebration of the female role in salvation through the figures of Lady Poverty and Beatrice. Franciscan thought on Poverty, from Joachim of Flora to radicals such as Ubertino da Casale and Peter John Olivi, informs Dante’s theological (but also political and spiritual) reflections on religion. Moreover, Dante’s personal exile becomes a metaphor for Christian peregrinations on earth, a figura of homo viator’s pilgrimage toward the final destination in the afterlife.
Literary Evidence
Authors: Urbainczyk Theresa
Published: April 2021

Information about slaveries in Greek and Roman antiquity appears in almost all genres of non-fiction: histories, biographies, political and philosophical treatises, speeches, letters, agricultural manuals, and works on estate management. The amount of surviving evidence, however, is comparatively small and unrepresentative, produced by slave owners with typically little interest in slaves for their own sake. There are no surviving non-fiction literary accounts by slaves. Even when slavery is discussed, it is often only ancillary to other issues. The evidence therefore leaves serious gaps in our knowledge. Ancient accounts also often fail to mention slaves who were almost certainly present, or mention them only in passing. One compensation is that non-fiction works do shed light on how writers view slaves in contexts in which they are not trying to prove anything, in contrast to accounts in which slavery and slaves form the direct focus, accounts probably subject to more distortion.
Determining the effects of manganese source and level on growth performance and carcass characteristics of growing–finishing pigs
Authors: Kerkaert Hayden R , Woodworth Jason C , DeRouchey Joel M , Dritz Steve S , Tokach Mike D , Goodband Robert D , Manzke Naiana E
Published: April 2021

Two experiments were conducted to determine the effects of Mn source and level on finishing pig growth performance and carcass characteristics. Dietary treatments were arranged in a 2 × 3 factorial with main effects of Mn source (MnSO4; Eurochem, Veracruz, Mexico, or Mn hydroxychloride (IBM); Micronutrients, Indianapolis, IN) and increasing added Mn (8, 16, and 32 mg/kg of complete diet). The trace mineral premix was formulated without added Mn. Copper was added to all diets at 10 and 150 mg/kg in Exp. 1 and 2, respectively. In both experiments, 1,994 pigs (PIC; 337 × 1050; initially 34.5 ± 0.50 and 40.0 ± 0.77 kg) were used with 27 pigs per pen and 12 replicates per treatment. Diets were corn-soybean meal-distillers dried grains with solubles-based and were fed in four phases. In Exp. 1, there was a marginal Mn source × level interaction (quadratic, Ρ = 0.057) for overall feed efficiency (G:F), with a decrease then increase in pigs fed IBM, but G:F increased with increasing Mn from MnSO4. There was no evidence for Mn source differences for average daily gain (ADG), average daily feed intake (ADFI), or body weight (BW), but pigs fed 16 mg/kg Mn, regardless of source, tended to have decreased (quadratic, Ρ < 0.05) ADG and final BW compared with other levels. For carcass yield, there was a tendency for Mn source × level interaction (quadratic, Ρ = 0.075), where carcass yield did not change by increasing MnSO4 but was greatest for 16 mg/kg Mn from IBM. Loin depth increased (source × level, Ρ = 0.041) for pigs fed increasing Mn from MnSO4 but decreased when Mn was increased from IBM. Pigs fed the intermediate level of Mn tended to have the lightest HCW (quadratic, Ρ = 0.071) and decreased loin depth (quadratic, Ρ = 0.044). Liver Mn concentration increased (linear, Ρ = 0.015) as added Mn increased and tended to be greater (P = 0.075) when supplied by MnSO4 compared with IBM. In Exp. 2, there was no (P > 0.10) Mn source × level interaction observed for ADG, ADFI, and G:F. Pigs fed IBM had increased (P < 0.05) final BW, ADG, and ADFI compared with pigs fed MnSO4. Pigs fed 16 mg/kg of Mn tended (P = 0.088) to have reduced ADFI when compared with pigs fed 8 and 32 mg/kg of Mn. In conclusion, there appears to be little benefit in growth performance by feeding more than 8 mg/kg of added Mn. When high levels of Cu were fed in Exp. 2, pigs fed IBM had improved growth performance when compared with those fed MnSO4. Further research is needed to understand the potential benefits of Mn hydroxychloride fed in conjunction with high levels of Cu on pig growth performance.
Smallholder Cassava Planting Material Movement and Grower Behavior in Zambia: Implications for the Management of Cassava Virus Diseases
Authors: Szyniszewska Anna Maria , Chikoti Patrick Chiza , Tembo Mathias , Mulenga Rabson , Gilligan Christopher Aidan , van den Bosch Frank , McQuaid Christopher Finn
Published: April 2021

Cassava (Manihot esculenta) is an important food crop across sub-Saharan Africa, where production is severely inhibited by two viral diseases, cassava mosaic disease (CMD) and cassava brown streak disease (CBSD), both propagated by a whitefly vector and via human-mediated movement of infected cassava stems. There is limited information on growers’ behavior related to movement of planting material, as well as growers’ perception and awareness of cassava diseases, despite the importance of these factors for disease control. This study surveyed a total of 96 cassava subsistence growers and their fields across five provinces in Zambia between 2015 and 2017 to address these knowledge gaps. CMD symptoms were observed in 81.6% of the fields, with an average incidence of 52% across the infected fields. No CBSD symptoms were observed. Most growers used planting materials from their own (94%) or nearby (<10 km) fields of family and friends, although several large transactions over longer distances (10 to 350 km) occurred with friends (15 transactions), markets (1), middlemen (5), and nongovernmental organizations (6). Information related to cassava diseases and certified clean (disease-free) seed reached only 48% of growers. The most frequent sources of information related to cassava diseases included nearby friends, family, and neighbors, while extension workers were the most highly preferred source of information. These data provide a benchmark on which to plan management approaches to controlling CMD and CBSD, which should include clean propagation material, increasing growers’ awareness of the diseases, and increasing information provided to farmers (specifically disease symptom recognition and disease management options).

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Vascular Ehlers-Danlos Syndrome: Treatment of a Complex Abdominal Wound with Vitamin C and Mesenchymal Stromal Cells
Authors: Prentice David Andrew , Pearson Wendy Ann , Fogarty Janice
Published: April 2021

Vascular Ehlers-Danlos syndrome (EDSv) can present with life-threatening surgical complications. The article describes the case of a patient with EDSv who developed total abdominal wound dehiscence and multiple enterocutaneous fistulas. Treatment with IV allogeneic mesenchymal stromal cells (MSCs) and high-dose vitamin C was trialed with success. Near-complete wound healing of the abdominal dehiscence with a 94% reduction in the size of the wound bed occurred. Maturation of the enterocutaneous fistulas also ensued.

There is no current consensus on the management of large cutaneous wounds in EDSv. This article discusses the pathophysiology of wound healing with regard to nutrition requirements and growth factors with special reference to collagen deficits in EDSv. A potential therapy with IV vitamin C supplementation and MSCs is proposed following the patient’s positive outcome. Medium-dose MSCs and high-dose IV vitamin C may offer significant benefits to complex and problematic wounds.
Exposure Provided by the Gibson Versus the Kocher–Langenbeck Approaches With and Without Trochanteric Osteotomy: A Cadaveric Mapping Study
Authors: Mitchell Phillip M. , Labrum Joseph T. , Beltran Michael J. , Collinge Cory A.
Published: April 2021

Objective:

To determine if prevalent approaches in acetabular fracture surgery provide enhanced anterior and cranial exposure in a cadaveric model.

Methods:

A Kocher–Langenbeck (K-L) approach (followed by a Gibson approach on the contralateral hip) was performed in the lateral position on 8 cadavers. A Steinmann pin was used to create holes outlining the bony surfaces available for instrumentation before and after a trochanteric osteotomy. All soft tissue was then removed from the pelvis, and a calibrated digital picture was taken. The surface area of the pelvis visualized through each approach was calculated and compared with the contralateral side to assess for a difference in exposure between the Gibson approach and the K–L approach. An increase in exposure of greater than 10% was considered significant. The extent of anterior exposure (with and without a trochanteric osteotomy) was then measured from the greater sciatic notch.

Results:

In 2 of 8 cadavers (25%), the Gibson approach yielded an increase in exposure when compared with a K-L approach. The addition of a trochanteric osteotomy yielded on average 1.6 cm (range, 0.7–2.6 cm) of increased anterior exposure in the K-L approaches and 1.5 cm (range 0.9–3.1 cm) in the Gibson approaches.

Conclusion:

The Gibson approach did not reliably provide increased anterior exposure compared with a K-L approach in a cadaver model. A trochanteric osteotomy can be expected to add 1–2 cm of increased anterior exposure in both approaches.
Staged Knee Arthrodesis Using Unilateral Locked Compression Plating: A Treatment for Recurrent Chronic Knee Infection
Authors: Friedman Lisa G.M. , Rothberg David , Horwitz Daniel S.
Published: April 2021

Background:

The treatment following massive infection of the knee remains a difficult problem with above knee amputation and knee fusion being available treatment options when revision arthroplasty is no longer possible. We present a series of 12 patients who underwent fusion using a staged protocol.

Methods:

The patients underwent a first stage involving removal of implants, debridement, and placement of an antibiotic space over a tibial nail. Stage II involved removal of the spacer and nail by fragmenting the cement, and re-debridement. A laterally based locked compression plate was used to achieve fusion.

Results:

There were no intraoperative complications. All patients achieved radiographic fusion. The average limb length discrepancy was 2.6 cm. Five patients required further surgery: 1 for drainage of a postoperative hematoma, 3 for persistent infectious symptoms, and 2 for implant irritation. At final follow-up 1 patient had persistent infection and was unable to ambulate. All other patients returned to ambulation with 4 utilizing assistive devices at final follow-up.

Conclusion:

Failed, infected total knee arthroplasty is a challenging problem without an easy solution. A variety of techniques for knee arthrodesis, including intramedullary nailing and external fixation have been described with a wide success rate ranging from 20% to 100%. Few studies have examined compression plating to achieve knee arthrodesis. The use a 2-stage, single locked compression plate technique to achieve arthrodesis for the treatment of chronic infection after failed revision total knee arthroplasty can be a highly successful approach to a very challenging problem.
Efficacy and safety of abdominal acupuncture for knee osteoarthritis
Authors: Liu Min , Liu Meinian , Zhang Haitao , Peng Guanrong , Sun Xiaobo , Zhu Xingyang , Zeng Yirong
Published: April 2021

Background:

Knee osteoarthritis (KOA) is a disease based on degenerative pathological changes. Most commonly seen in the elderly and is one of Kenn's leading causes, its symptoms include swollen knees, pain in walking up and downstairs. If left untreated, it can lead to joint deformity and disability. Many clinical studies have reported that abdominal acupuncture has a good effect on KOA treatment, but there is no relevant systematic review. So the purpose of this study is to evaluate the effectiveness and safety of abdominal acupuncture in treating KOA.

Methods:

The following 8 electronic databases will be searched, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Web of Science, Chinese Scientific Journal Database (VIP), Wanfang Database, and Chinese Biomedical Literatures Database (CBM) from their inception to November 1, 2020 without any restrictions. Researchers retrieve the literature and extracted the data, evaluation of research methods, quality of literature. The outcomes will include a Visual Analogue Scale. The Western Ontario and McMaster Universities Osteoarthritis Index, total effective rate, incidence of any adverse events. We use the Cochrane Risk of a bias assessment tool to evaluate methodological qualities. Data synthesis will be completed by RevMan 5.3.0.

Results:

We will show the results of this study in a peer-reviewed journal.

Conclusions:

This meta-analysis will provide reliable evidence for abdominal acupuncture treatment of KOA.

INPLASY registration number:

INPLASY2020110020.
Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis
Authors: Asano Tomoyuki , Saito Yuzuka , Matsuoka Naoki , Temmoku Jumpei , Fujita Yuya , Hattori Kasumi , Kobayashi Shunsuke , Ojima Akira , Takahashi Toshiyuki , Matsumoto Haruki , Yashiro-Furuya Makiko , Sato Shuzo , Kobayashi Hiroko , Watanabe Hiroshi , Yano Kiori , Sasajima Tomomi , Fujihara Kazuo , Migita Kiyoshi
Published: April 2021

Rationale:

Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD.

Patient concerns:

We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient's serum and cerebrospinal fluid.

Diagnosis:

A diagnosis of MOGAD complicated with MPA was made.

Interventions:

The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy.

Outcomes:

Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period.

Conclusion:

To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.
Use of Shenhuang paste on Shenque point improves chemotherapy induced gastrointestinal toxicity in breast cancer
Authors: Wang Rongyun , Shi Yanan , Xie Xiaohong , Ge Qinling , Xu Jingming , Sun Qiuhua , Xu Xiaohong
Published: April 2021

Background:

Breast cancer, a malignant disorder, occurs in the epithelial tissue of the breast gland. Chemotherapy is the standard treatment for breast cancer, however, the side effect, especially gastrointestinal dysfunction, due to chemotherapy still remain major problems. Traditional Chinese Medicine has been proven therapeutically effective on reducing adverse effects caused by chemotherapy. Shenhuang Plaster

Methods:

The study is a randomized, placebo-controlled, blind trial. A total of 160 Chinese breast cancer patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed Shenhuang plaster application on shenque point (CV8) plus chemotherapy treatment. Patients in the control group will be prescribed placebo plaster application on CV8 plus chemotherapy treatment. The acupoint application will last 3 days. The primary outcome will be the form of faces every day, and the secondary outcomes the symptom score of traditional Chinese medicine, the changes of fecal bacteria and metabolites, serum motilin, gastrin and ghrelin levels.

Discussion:

This study is to observe therapeutic effects with Shenhuang plaster application on CV8 to regulate chemotherapy-induced gastrointestinal toxicity in breast cancer patients.

Trial registration:

Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=55262) No. ChiCTR2000034313. Registered on July 2, 2020.
Chronic kidney disease as a potential risk factor for retinal vascular disease
Authors: Lin Chun-Ju , Tien Peng-Tai , Lai Chun-Ting , Hsia Ning-Yi , Chang Cheng-Hsien , Yang Yu-Cih , Bair Henry , Chen Huan-Sheng , Wu Wen-Chuan , Tsai Yi-Yu
Published: April 2021

We investigate whether patients with chronic kidney disease (CKD) are at increased risk of retinal vascular disease (RVD). Data was collected from the Taiwan National Health Insurance system and included patients newly diagnosed with CKD between 2000 and 2012. The endpoint of interest was a diagnosis of RVD. Follow-up data of 85,596 patients with CKD and 85,596 matched comparisons (non-CKD) from 2000 to 2012 were analyzed. Patients with CKD were found to have a significantly higher cumulative incidence of RVD (Kaplan–Meier analysis, log-rank test P < .0001). Through multivariate Cox regression analysis, the CKD group was found to have higher risk of developing RVD (adjusted hazard ratio (HR) [95% confidence interval (CI)]: 2.30 [2.16–2.44]) when compared to the control cohort. When comparison of CKD group and non-CKD group was stratified by gender, age and comorbidities (hypertension, diabetes, and hyperlipidemia), the higher risk of RVD in patients with CKD remained significant in all subgroups. Patients with CKD were found to have higher risk of developing RVD in this cohort study. In addition, CKD imposed the same risk for RVD development in all age groups and in patients with or without hypertension or diabetes. Thus, patients with CKD should be vigilant for symptoms of RVD. Understanding the link between CKD and RVD could lead to the development of new treatment and screening strategies for both diseases.
Clinicopathological characteristics and survival outcomes in neuroendocrine prostate cancer
Authors: Zhu Jiamin , Liang Xiao , Wu Dan , Chen Shusen , Yang Baixia , Mao Weidong , Shen Dong
Published: April 2021

Objective:

This study aimed to investigate the clinicopathological features and the survival outcomes of neuroendocrine prostate cancer (NEPC).

Methods:

Within the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, we identified a total of 510 patients with NEPC between 2006 and 2015. Age-adjusted incidence rates were evaluated in the study by the SEER∗Stat Software version 8.3.6. Kaplan–Meier analysed assessed overall survival (OS) after stratification according to marital status, age, histologic subtype, metastatic status, and treatment. The significant differences were assessed in a log-rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS.

Results:

From a total of 560,124 patients with prostate cancer diagnosed between 2006 and 2015, we identified 510 cases of de novo NEPC. Regarding histology, among all the NEPC, 329 (64.5%) patients were diagnosed as small cell carcinoma, 181 (39.8%) were nonsmall cell carcinoma. The overall age-adjusted incidence of NEPC statistically significantly increased from 0.321/1,000,000 person-years in 2006 to 0.587/1,000,000 person-years in 2015. The median OS in our study cohort was 9 months (95% CI, 8–10 months). Multivariate cox regression analysis showed that age, histologic subtype, and stage were independent prognostic factors for NEPC patients. The majority of NEPC (78.2%) were metastatic at diagnosis. In terms of treatment, for metastatic tumor patients, chemotherapy was the most effective therapy. Chemotherapy increased the OS of patients with regional (distant) metastases from 8 months (5 months) to 13.5 months (9 months).

Conclusion:

NEPC is extremely rare but the incidence of NEPC has been increasing in the past years. The prognosis of NEPC is poor because most cases are diagnosed at metastatic stage. The patients with metastases are typically treated with chemotherapy and chemotherapy shows survival benefits in both regional and distant metastatic tumor patients.
Global research status of gastroenterology and hepatology
Authors: Yang Huai-Yu , Wang Dan , Chen Cui , Liu Yu , Han Chao , Gao Ye , Li Zhao-Shen , Liao Zhuan , Hu Liang-Hao
Published: April 2021

Background:

There are no reports on global research status of gastroenterology and hepatology (GI). This study was conducted to reveal the current global research status and trends in GI.

Methods:

Articles published during 2009 to 2018 in international GI journals were retrieved from the PubMed database. The top 20 countries by output were determined. The gross domestic product (GDP) of each country was also retrieved to figure out the correlation between outputs in GI and economy. The 5 highest-ranking countries were compared in the number of total articles, articles per capita, articles published in top journals, the accumulated impact factor (IF), and average IF. Total articles and articles per capita of the 5 countries were conducted time-trend analysis. The frequently-used terms in titles and abstracts of articles published in 2009 and 2018 were retrieved to conduct co-occurrence analysis to figure out the change of research highlights in GI.

Results:

A total of 120,267 articles were included, of which 116,485 articles were from 20 highest-output countries. There was a positive correlation between output and GDP (r = 0.921, P < .001). The USA, Japan, China, Italy, and the UK were the 5 highest-ranking countries. The USA was the largest contributor with 26,215 articles, accounting for 17.4% of the total, but with no significant increasing trend (P = .122). Other 4 countries all showed increasing trends (all P < .001). For articles per capita, Italy ranked 1st among the 5 countries with 1591.0 articles per 10 million. The USA showed a decreasing trend (P = .026), other 4 countries all showed increasing trends (all P < .001). The UK had the highest average IF (6.685). For change of research highlights, it is more inclined to research of endoscopy, inflammatory bowel diseases, and nonalcoholic fatty liver disease.

Conclusion:

It is delightful that the global research output in GI field would be continuingly increased as the major highest-output countries showed increasing trends. However, the developing countries fell behind both in quantity and quality when compared with developed countries.
A systematic review and meta-analysis of the effects of early mobilization therapy in patients after cardiac surgery
Authors: Chen Bin , Xie Guanli , Lin Yuan , Chen Lianghua , Lin Zhichen , You Xiaofang , Xie Xuemin , Dong Danyu , Zheng Xinyi , Li Dong , Lin Wanqing
Published: April 2021

Background:

Prolonged hospitalization and immobility of critical care patients elevate the risk of long-term physical and cognitive impairments. However, the therapeutic effects of early mobilization have been difficult to interpret due to variations in study populations, interventions, and outcome measures. We conducted a meta-analysis to assess the effects of early mobilization therapy on cardiac surgery patients in the intensive care unit (ICU).

Methods:

PubMed, Excerpta Medica database (EMBASE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), and the Cochrane Library were comprehensively searched from their inception to September 2018. Randomized controlled trials were included if patients were adults (≥18 years) admitted to any ICU for cardiac surgery due to cardiovascular disease and who were treated with experimental physiotherapy initiated in the ICU (pre, post, or peri-operative). Data were extracted by 2 reviewers independently using a pre-constructed data extraction form. Length of ICU and hospital stay was evaluated as the primary outcomes. Physical function and adverse events were assessed as the secondary outcomes. Review Manager 5.3 (RevMan 5.3) was used for statistical analysis. For all dichotomous variables, relative risks or odds ratios with 95% confidence intervals (CI) were presented. For all continuous variables, mean differences (MDs) or standard MDs with 95% CIs were calculated.

Results:

The 5 studies with a total of 652 patients were included in the data synthesis final meta-analysis. While a slight favorable effect was detected in 3 out of the 5 studies, the overall effects were not significant, even after adjusting for heterogeneity.

Conclusions:

This population-specific evaluation of the efficacy of early mobilization to reduce hospitalization duration suggests that intervention may not universally justify the labor barriers and resource costs in patients undergoing non-emergency cardiac surgery.

PROSPERO Research registration identifying number:

CRD42019135338.
A meta-analysis on the relationship of exosomes and the prognosis of lung cancer
Authors: Xiang Hui , Li Fan , Luo Jingying , Long Wenting , Hong Liuyan , Hu Yuzhui , Du Hongying , Yuan Yunxiao , Luo Miao
Published: April 2021

Background:

A lot of research evidence shows that exosomes play an indelible role in the prognosis of lung cancer, but there are many disputes. Therefore, we conduct a meta-analysis to further demonstrate.

Methods:

A literature retrieval was performed through a search of PubMed, Embase, Web of Science, Cochrane, CKNI, Wanfang, and other databases to locate documents from the literature that satisfied the inclusion criteria. There were four outcome indicators: overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Subgroup analysis was conducted according to sample size, country, detection method, analysis method, and pathological type. Stata 14.0 software was used to evaluate the prognostic value of exosomes in lung cancer.

Results:

A total of 2456 patients with lung cancer from 29 studies in 16 articles were included. The expression level of exosomes was closely associated with the OS and DFS of patients, although no statistical difference was observed between exosomes and DSS or PFS. Eighteen studies with 2,110 patients were evaluated to examine the prognostic value of exosomes in lung cancer by exploring the association between exosomes and OS. The results showed that exosomes were strongly associated with worse OS, and the combined hazard ratio (HR) was 2.01 (95% confidence interval [CI]: 1.70–2.39, P = .000). Six studies investigated the association between exosomes and DFS, and showed a pooled HR of 2.48 (95% CI: 1.75–3.53, P = .000).

Conclusion:

Our analysis indicated that the expression level of exosomes was closely associated with the OS and DFS of patients with lung cancer, suggesting that exosomes are associated with poor prognosis of lung cancer. Exosomes may be a new biomarker for the prognosis of lung cancer, although a large number of prospective studies are still needed to support this.
The meta-analysis of the effect of 68Ga-PSMA-PET/CT diagnosis of prostatic cancer compared with bone scan
Authors: Zhao Ruining , Li Yajie , Nie Lihong , Qin Kaiyue , Zhang Hang , Shi Hongbin
Published: April 2021

Background:

68Ga-PSMA-PET/CT (positron emission tomography/computed tomography) is a promising method for prostate cancer (PC) detection. However, the ability of 68Ga-PSMA-PET/CT to detect malignant bone lesions, and whether this method is superior to the existing bone imaging methods are still lack of systematic analysis.

Purpose:

To evaluate the value of 68Ga-PSMA-PET/CT and bone scan in clinical diagnosis of prostatic cancer from the perspective of evidence-based medicine.

Methods:

PubMed, The Cochrane Library, EMBASE, Springer Link, Sinomed, CNKI, Wanfang database, and CQVIP database were searched to find the satisfactory studies that needed systematic review of trials and compared the value of 68Ga-PSMA-PET/CT and bone scan. All studies published from inception to March 31, 2020. According to the inclusion and exclusion criteria, 2 reviewers independently evaluated and extracted the literature. Review Manager 5.3 was applied to evaluate the included literature quality. The heterogeneity of the included literature was tested by Meta Disc 1.4, and the effect model was selected according to the heterogeneity test results, and the sensitivity (SEN), specificity (SPE), PLR, NLR and diagnostic odds ratio (DOR) were analyzed. After testing the heterogeneity results of literature by using the 95% confidence interval and the forest map.

Results:

A total of 4 studies were eligible for inclusion in the meta-analysis, which included 318 patients, 120 cases with bone metastasis and 198 cases without bone metastasis. The results of summary evaluation for 68Ga-PSMA-PET/CT and bone scan in diagnosis of prostatic cancer as follow respectively: The SEN were 0.97 and 0.86; the SPE were 1.00 and 0.87; the DOR were 1468.33 and 36.23; PLR were 88.45 and 6.67; NLR were 0.05 and 0.19; and the area under curve (AUC) and 95% CI were 0.9973 (1.0000–0.9927) and 0.8838 (0.9584–0.8092).

Conclusion:

By comparing the diagnostic results of 68Ga-PSMA-PET/CT and bone scan imaging diagnosis methods, the 68Ga-PSMA-PET/CT has a higher SEN and SPE than bone scan, and it has a higher diagnostic efficiency for prostate cancer bone metastasis, which is worthy of clinical application.
Spontaneous rupture of pyogenic liver abscess with subcapsular hemorrhage mimicking ruptured hepatocellular carcinoma
Authors: Kim Nan Seol , Chun Hea Rim , Jung Hae Il , Kang Jin Ku , Park Sul Ki , Bae Sang Ho
Published: April 2021

Rationale:

Spontaneous rupture of PLA (pyogenic liver abscess) is an extremely rare and life-threatening event. Ruptured PLA is very difficult to distinguish from malignant HCC (hepatocellular cancer) rupture or cholangiocarcinoma rupture on CT (computed tomography) scan.

Patient concerns:

We describe the case of a 71-year-old man with fever, right upper abdominal pain, nausea with intermittent vomiting, and general fatigue. He had no medical or surgical history.

Diagnosis:

CT scan showed a hypodense mass in right hepatic lobe and MRI (magnetic resonance imaging) revealed a heterogenous mass of ∼6 cm in segment VI of the liver and heterogenous fluid in the subcapsular region. We made a tentative diagnosis of HCC rupture with subcapsular hemorrhage based on these findings.

Intervention:

After improving the patient's condition by administering empirical therapy consisting of intravenous antibiotics and fluids, we performed surgical exploration. Gross examination of the abdomen showed that almost the entire right hepatic lobe was hemorrhagic and affected by peritonitis. Therefore, we performed right hepatectomy. The intraoperative frozen biopsy revealed suspicious PLA with marked necrosis, neutrophil infiltration, and hemorrhagic rupture, although no malignant tissue or fungus was observed. The postoperative secondary pathology report confirmed the diagnosis of PLA with hemorrhagic rupture.

Outcomes:

The patient was discharged 13 days after the operation. Follow-up CT was performed 5 months after discharge and revealed no abnormal findings.

Lessons:

A high index of suspicion is key to preventing misdiagnosis of ruptured PLA and improving prognosis. Furthermore, even if rupture of the PLA is initially localized, delayed peritonitis may occur during medical treatment. Therefore, vigilant monitoring is essential.
Efficacy and safety of high-flow oxygen therapy application for chronic obstructive pulmonary disease with acute hypercapnic respiratory failure
Authors: Zheng Mingxu , Dong Liangliang , Hao Zerui , Wang Shuyun
Published: April 2021

Background:

Presently, there are no reviews or meta-analyses comparing the efficacy and safety of high-flow oxygen therapy (HFOT) and noninvasive ventilation (NIV) as first-line treatment in exacerbated chronic obstructive pulmonary disease (COPD) patients. The present protocol is conceived to evaluate whether HFOT is noninferior to NIV in treatment of patients with COPD and acute hypercapnic respiratory failure.

Methods:

We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and the recommendations of the Cochrane Collaboration to conduct this meta-analysis. Reviewers will search the PubMed, Cochrane Library, Web of Science, and EMBASE online databases using the key phrases “high-flow oxygen therapy,” “chronic obstructive pulmonary disease,” and “acute hypercapnic respiratory failure” for all English-language cohort studies published up to April, 2021. The cohort studies focusing on assess the efficacy and safety of HFOT and NIV in the treatment of patients with COPD and acute hypercapnic respiratory failure will be included in our meta-analysis. The primary outcome is treatment failure, whereas the secondary outcomes included arterial blood gas analysis, dyspnea score, comfort score, mortality, and total ICU and hospital lengths of stay.

Results:

The trial is conducted to test the hypothesis that HFOT, administered immediately after extubation, is not inferior to the NIV in reducing the rate of treatment failure in patients with COPD who were previously intubated due to hypercapniac respiratory failure.

Registration number:

10.17605/OSF.IO/Z2PEJ.
A pilot study on EORTC or PERCIST for the prediction of progression-free survival with nivolumab therapy in advanced or metastatic gastric cancers
Authors: Nakajo Masatoyo , Kitajima Kazuhiro , Toriihara Akira , Arigami Takaaki , Daisaki Hiromitsu , Nakamura Akira , Ohtsuka Takao , Miwa Hiroto , Yoshiura Takashi
Published: April 2021

Recent breakthrough results from immune checkpoint inhibitors (ICIs) have paved the way to a new era of cancer immunotherapy, and have thus led to a paradigm shift of cancer treatment. In particular, inhibition of the antiprogrammed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with ICI, including nivolumab and pembrolizumab, has been emerging as a novel treatment strategy for advanced gastric cancers. An accurate noninvasive assessment of the response to ICI is important for the management of patients with advanced or metastatic gastric cancer.

To examine whether the European Organization for Research and Treatment of Cancer (EORTC) and PET Response Criteria in Solid Tumors (PERCIST) are valuable for predicting progression-free survival (PFS) in patients with advanced or metastatic gastric cancers treated with nivolumab.

Six patients with advanced or metastatic gastric cancers who underwent 18F-FDG-PET/computed tomography (CT) scans before, and from 2 to 6 months after initiation of nivolumab therapy between September 2017 and August 2019, were evaluated retrospectively. The correlation between tumor progression and EORTC or PERCIST was assessed with the Fisher's exact test. The PFS was assessed with the Kaplan–Meier method.

Two patients were alive without progression, and the remaining 4 patients exhibited tumor progression. Two patients without progression were classified as partial metabolic response (PMR) patients based on EORTC or PERCIST, while the other 4 patients with progression were classified as progressive metabolic disease (PMD) patients based on EORTC (P = .067), or stable metabolic disease (SMD) patients, or PMD patients based on PERCIST (P = .067).

The mean and median PFS of all patients was 12.7 months (95% confidence interval [CI], 4.9–20.4 months) and 5 months (95%CI, 4.0–11.0 months). Two EORTC or PERCIST PMR patients showed significantly longer median PFS compared with 4 non-PMR patients (not reached vs 4.0 months, P = .044). Three PERCIST PMR or SMD patients also showed significantly longer median PFS compared with 3 PMD patients (not reached vs 4.0 months, P = .022). These results suggest that EORTC or PERCIST has the potential to predict PFS of patients with advanced or metastatic gastric cancers treated by nivolumab and further studies are needed to determine its value in larger study populations.