bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexually Dimorphic Relationships Among Saa3 (Serum Amyloid A3), Inflammation, and Cholesterol Metabolism Modulate Atherosclerosis in Mice
Authors: Chait Alan , Wang Shari , Goodspeed Leela , Gomes Diego , Turk Katherine E. , Wietecha Tomasz , Tang Jingjing , Storey Carl , O’Brien Kevin D. , Rubinow Katya B. , Tang Chongren , Vaisar Tomas , Gharib Sina A. , Lusis Aldons J. , Den Hartigh Laura J. 
Published: March 2021

Objective:

Expression of the extrahepatic acute-phase protein Saa3 (serum amyloid A3) increases in response to acute and chronic inflammatory stimuli and is elevated in adipose tissue and macrophages in obese mice. A recent report suggested that Saa3 is proatherogenic in male
ApoE
−/−
mice. Because of our previous observation that female but not male Saa3-deficient mice are protected from obesity, adipose inflammation, and hyperlipidemia, we sought to determine whether Saa3 differentially modulates atherosclerosis in mice of both sexes.

Approach and Results:

To promote atherosclerosis,
Saa3
+/+
and
Saa3
−/−
male and female mice were crossed with
Ldlr
−/−
mice. All mice consumed a diet high in saturated fat and sucrose with 0.15% added cholesterol for 16 weeks. Plasma lipids and atherosclerosis levels were assessed. Female
Saa3
−/−
Ldlr
−/−
mice exhibited elevated cholesterol levels relative to
Saa3
+/+
Ldlr
−/−
controls and exhibited increased atherosclerosis, while male
Saa3
−/−
Ldlr
−/−
mice were protected from atherosclerosis. Data from the hybrid mouse diversity panel revealed that Saa3 associates strongly with inflammatory, Trem2-associated, and tissue remodeling genes and pathways in males but not females, an effect confirmed in liver tissue, atherosclerotic lesions, and cultured macrophages. Macrophages isolated from male and female mice showed differential inflammatory effects of Saa3 deficiency, an effect linked with sex steroid signaling. Cholesterol efflux capacity was increased in
Saa3
−/−
males only.

Conclusions:
Saa3 is proatherogenic in male but atheroprotective in female mice, effects that may be related to sex-specific relationships between Saa3, cholesterol metabolism, inflammatory genes, and Trem2 macrophages.
Race- and Sex-Specific Population Attributable Fractions of Incident Heart Failure
Authors: Sinha Arjun , Ning Hongyan , Carnethon Mercedes R. , Allen Norrina B. , Wilkins John T. , Lloyd-Jones Donald M. , Khan Sadiya S. 
Published: March 2021

Background:
Race- and sex-specific differences in heart failure (HF) risk may be related to differential burden and effect of risk factors. We estimated the population attributable fraction (PAF), which incorporates both prevalence and excess risk of HF associated with each risk factor (obesity, hypertension, diabetes, current smoking, and hyperlipidemia), in specific race-sex groups.

Methods:
A pooled cohort was created using harmonized data from 6 US longitudinal population-based cohorts. Baseline measurements of risk factors were used to determine prevalence. Relative risk of incident HF was assessed using a piecewise constant hazards model adjusted for age, education, other modifiable risk factors, and the competing risk of death from non-HF causes. Within each race-sex group, PAF of HF was estimated for each risk factor individually and for all risk factors simultaneously.

Results:
Of 38 028 participants, 55% were female and 22% Black. Hypertension had the highest PAF among Black men (28.3% [95% CI, 18.7%–36.7%]) and women (25.8% [95% CI, 16.3%–34.2%]). In contrast, PAF associated with obesity was the highest in White men (21.0% [95% CI, 14.6%–27.0%]) and women (17.9% [95% CI, 12.8%–22.6%]). Diabetes disproportionately contributed to HF in Black women (PAF, 16.4% [95% CI, 12.7%–19.9%]). The cumulative PAF of all 5 risk factors was the highest in Black women (51.9% [95% CI, 39.3%–61.8%]).

Conclusions:
The observed differences in contribution of risk factors across race-sex groups can inform tailored prevention strategies to mitigate disparities in HF burden. This novel competing risk analysis suggests that a sizeable proportion of HF risk may not be associated with modifiable risk factors.
Discrimination against LGBTI Persons on the Basis of Scripture: What Did Ancient Church Scholarship Really Say?
Authors: Bantekas Ilias 
Published: March 2021

Abstract
This article seeks to examine homosexuality from the lens of two particular ancient Christian writers, namely Paul the Apostle and Maximus the Confessor. Both were fervent missionaries and did not perceive their writings as doctrinal or philosophical, but merely practical and a defence against other heretical teachings. Even so, contemporary scholars recognise a great profoundness and innovation in their theology. Paul’s references to homosexuality consist of only three or four sentences, whereas Maximus does not discuss the issue directly, given his preoccupation with matters pertaining to the nature of Christ, which at the time were fiercely contested among various Christian groups. The purpose of the article is to examine scriptural references to homosexuality from the perspective of the spiritual context in which they are made, rather than the canonical, ethical or social perspectives to which most scholars and civil society—whether in favour or against—refer to. Homosexuality in the sense of sexual orientation is unknown at the time and even so it is not specifically singled out. Paul seems to be specifically chastising exploitative sexual actions and relationships, whether homosexual or heterosexual.
Between Club Diplomacy and Network Diplomacy: Exploring the Diplomatic Role of Cities in China since 2012
Authors: Wei Chen 
Published: March 2021

Summary
This article addresses the question of whether the emerging role of cities in diplomacy is a reflection of the diplomatic transformation in China, and what the distinctive features are of the diplomatic roles of cities within China’s context. It argues that city diplomacy in China falls between club diplomacy and network diplomacy by exploring five aspects: the number of players, structures, forms, transparency and main purposes. Cities have developed their representation by serving as important agents in managing domestic and international situations, developed their communication channels by contributing in shaping China’s neighbouring diplomacy and global partnerships, and developed their negotiation techniques by participating in reform of global governance system. The article concludes that the diplomatic role of cities in China is to consolidate the social foundation of relations between nations, promote the establishment of a new type of international relations, and promote a community of a shared future for mankind.
Reconsidering Sinophone Studies: The Chinese Cold War, Multiple Sinocentrisms, and Theoretical Generalisation
Authors: Shi Flair Donglai 
Published: March 2021

Abstract
Sinophone studies has improved the visibility of a range of Chinese-language cultural products and is expanding into a transnational and multilingual academic enterprise. With firm acknowledgement of the pragmatic benefits the Sinophone has brought (particularly to Anglophone and Taiwanese academia), this paper reflects on some of the problems embedded in the underlying premises and ideological mechanisms of the concept of the Sinophone that have so far been under-discussed. As a first step towards a more self-reflective meta-discourse about Sinophone studies, it highlights three areas that warrant more clarification and debate before the concept is applied to specific analyses: the significance of the Chinese Cold War; the matrix of multiple Sinocentrisms; and the double-edged sword of theoretical generalisation. In this process, I emphasise the institutional formation of the ‘Sinophone’ both as a cultural field and as an academic discourse, and highlight the significant role that Taiwan has been playing in this.
Accuracy of half-way mucosa-supported implant guides for edentulous jaws: a retrospective study with a median follow-up of 2 years
Authors: Tang Weiwei , Liu Qilong , Zeng Xianshang , Yu Jiali , Shu Dalong , Shen Guorong , Yu Weiguang , Liu Xiangzhen , Xu Guixing 
Published: March 2021

Objective To assess the accuracy of half-way digital mucosa-supported implant guides (HDMIGs) for edentulous jaws. Methods Ninety-five consecutive patients (859 implants) with edentulous jaws who underwent implant placement using an HDMIG from July 2012 to June 2018 were retrospectively identified. The primary endpoint was implant-related complications (nerve injury and unexpected perforation), and the secondary endpoints were the faciolingual distance, mesiodistal distance, buccolingual angle, and mesiodistal angle. Follow-ups occurred at 1 month, 2 months, and then every 2 months following implant placement. Results Twenty-seven (28.4%) patients met the exclusion criteria, leaving 68 eligible patients (636 implants) for the final analysis. The median follow-up was 24 months (range, 18–27 months). No patients developed nerve injury, revision, or unexpected perforation. At the final follow-up, the mean faciolingual distance was 0.65 ± 0.16 mm, the mean mesiodistal distance was 1.16 ± 0.61 mm, the mean buccolingual angle was 4.04° ± 2.26°, and the mean mesiodistal angle was 3.75° ± 2.56°. In the comparison of the first month after surgery and the last follow-up, no significant differences were detected in any of the four measured variables. Conclusion Use of an HDMIG may be a convenient and safe method to ensure correct implantation.
Laparoscopic surgery experience does not influence oncological and functional results of robotic-assisted laparoscopic prostatectomy
Authors: Cetin Taha , Yalcin Mehmet Yigit , Karaca Erkin , Ozbilen Mert Hamza , Ergani Batuhan , Koc Gokhan , Boyacioglu Hayal , Ilbey Yusuf Ozlem 
Published: March 2021

Introduction: Surgery is one of the treatment alternatives for prostate cancer, and robotic-assisted laparoscopic prostatectomy (RALP) has become the new trend in the past decade. There is no consensus yet for surgeons who will perform RALP whether they need to be trained or experienced in laparoscopy. In this study, it was aimed to investigate the effectiveness of the surgeon’s laparoscopy experience in the perioperative and postoperative results of RALP patients. Material and method: Patients who underwent RALP were retrospectively screened. The first 20 cases done by surgeons in both groups and 40 cases in total were included in the study. Surgeons with laparoscopy training were designated as group 1, and surgeons without laparoscopy training were designated as group 2. Patient’s age, preoperative prostate-specific antigen (PSA) value, prostate biopsy pathology, radical prostatectomy pathology, surgical margin positivity, extracapsular extension, and seminal vesicle invasion status, blood transfusion rate, operation time, length of hospital stay, and 1-year follow-up potency and urinary incontinence rates were compared. Results: There was no difference between the two groups in terms of age, preoperative PSA, preoperative biopsy results, blood transfusion rates, operation times, and the length of hospital stay of the patients. When the postoperative oncological and functional results of the patients were examined, there was no difference between the two groups in the prostatectomy pathology ( p = 0.895), extracapsular extension (pT3a) ( p = 0.519), positive surgical margin (pSM) ( p = 0.723), and seminal vesicle invasion (pT3b) ( p = 0.756). Potency and urinary incontinence rates were similar in both groups at the end of one year follow-up ( p = 0.327, 0.500 respectively). Conclusions: Based on our study, it is clearly seen that regardless of the surgeon’s experience of laparoscopy, it can be safely preferred when looking at the oncological and functional results of RALP.
A Qualitative Study Describing Pediatric Palliative Care in Non-Metropolitan Areas of Illinois
Authors: Murday Patrick , Downing Kimberly , Gaab Erin , Misasi Jennifer , Michelson Kelly N. 
Published: March 2021

Background: There is little information about providing pediatric palliative care (PPC) in non-metropolitan areas. Objective: Describe the strengths of and challenges to delivering PPC in non-metropolitan communities and identify opportunities to improve care delivery. Design: A qualitative study involving focus groups (FGs) with PPC stakeholders. Setting/Participants: From 4 non-metropolitan areas in Illinois, we recruited 3 stakeholder groups: healthcare providers (HPs); bereaved parents; and parents caring for a seriously ill child (SIC). Measurements: At each site, we held an FG with people of the same stakeholder group and then an FG involving all stakeholders. Discussion topics included: availability and strengths of local PPC services, barriers to local PPC, opportunities for improving local PPC access and quality, and clinician educational needs. We analyzed data using phenomenology and directed content analysis. Results: Thirty people, 12 parents and 18 HPs, participated in FGs. Identified themes related to: PPC perceptions; availability and use of local resources; and challenges associated with travel, care coordination, and finances. Participants described benefits of and limits to local PPC including pediatric-specific issues such as attending to siblings, creating child peer-support activities, providing school guidance, and financing for PPC. Recommendations included suggestions to enhance care coordination, use existing resources, improve community and provider education, develop community networks, and minimize financial challenges. Conclusion: Unique PPC challenges exist in non-metropolitan areas. PPC in non-metropolitan areas would benefit from enhancing local resource utilization and quality. Future work should address the challenges to providing PPC in non-metropolitan areas with a focus on pediatric-specific issues.
Quality assessment of Diflucan® tablets distributed online: Diflucan® distributed online
Authors: Sanada Tomoko , Ohnishi Myu , Yoshida Naoko , Kimura Kazuko , Tsuboi Hirohito 
Published: March 2021

Background: Falsified medical products have been reported worldwide. Falsified medicines with poor quality are a potential health hazard. Some Internet sites advertise fluconazole (Diflucan®), an antifungal medicine used to treat deep mycoses, as “female Viagra®.” Aim: The aim of this study was to investigate the authenticity and quality of Diflucan® tablets distributed on the Internet. Methods: We ordered Diflucan® tablets via the Internet and evaluated them by visual observation, authenticity investigation, quality evaluation (quantity of the active pharmaceutical ingredient, content uniformity, and dissolution), and near-infrared and Raman scattering spectroscopy. Results: We obtained 11 samples of Diflucan® tablets from all 11 Japanese Internet sites identified in our search. Of 11 sites, 7 advertised fluconazole as having effects on female sexual function. Ten of the Diflucan® samples were confirmed as genuine and one sample was falsified. The genuine Diflucan® samples met the specifications of all quality evaluations. The packaging, size, and color of the falsified Diflucan® sample obtained in this study differed from the authentic Diflucan® tablet. The falsified Diflucan® sample obtained in this study did not contain fluconazole and instead contained what appeared to be sildenafil citrate. The spectra of the falsified Diflucan® tablet obtained in this study differed from the authentic Diflucan® tablet in near-infrared and Raman scattering spectroscopy. Conclusion: We confirmed that one falsified Diflucan® tablet was distributed online. Thus, continued measures against falsified medicines are required.
Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma
Authors: Facon Thierry , Venner Christopher P. , Bahlis Nizar J. , Offner Fritz , White Darrell J. , Karlin Lionel , Benboubker Lotfi , Rigaudeau Sophie , Rodon Philippe , Voog Eric , Yoon Sung-Soo , Suzuki Kenshi , Shibayama Hirohiko , Zhang Xiaoquan , Twumasi-Ankrah Philip , Yung Godwin , Rifkin Robert M. , Moreau Philippe , Lonial Sagar , Kumar Shaji K. , Richardson Paul G. , Rajkumar S. Vincent 
Published: March 2021

Abstract
Continuous lenalidomide-dexamethasone (Rd)-based regimens are among the standards of care in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. The oral proteasome inhibitor ixazomib is suitable for continuous dosing, with predictable, manageable toxicities. In the double-blind, placebo-controlled TOURMALINE-MM2 trial, transplant-ineligible NDMM patients were randomized to ixazomib 4 mg (n = 351) or placebo (n = 354) plus Rd. After 18 cycles, dexamethasone was discontinued and treatment was continued using reduced-dose ixazomib (3 mg) and lenalidomide (10 mg) until progression/toxicity. The primary endpoint was progression-free survival (PFS). Median PFS was 35.3 vs 21.8 months with ixazomib-Rd vs placebo-Rd, respectively (hazard ratio [HR], 0.830; 95% confidence interval, 0.676-1.018; P = .073; median follow-up, 53.3 and 55.8 months). Complete (26% vs 14%; odds ratio [OR], 2.10; P &lt; .001) and ≥ very good partial response (63% vs 48%; OR, 1.87; P &lt; .001) rates were higher with ixazomib-Rd vs placebo-Rd. In a prespecified high-risk cytogenetics subgroup, median PFS was 23.8 vs 18.0 months (HR, 0.690; P = .019). Overall, treatment-emergent adverse events (TEAEs) were mostly grade 1/2. With ixazomib-Rd vs placebo-Rd, 88% vs 81% of patients experienced grade ≥3 TEAEs, 66% vs 62% serious TEAEs, and 35% vs 27% TEAEs resulting in regimen discontinuation; 8% vs 6% died on study. Addition of ixazomib to Rd was tolerable with no new safety signals and led to a clinically meaningful PFS benefit of 13.5 months. Ixazomib-Rd is a feasible option for certain patients who can benefit from an all-oral triplet combination. This trial was registered at www.clinicaltrials.gov as #NCT01850524.
Single-cell transcriptomics dissects hematopoietic cell destruction and T-cell engagement in aplastic anemia
Authors: Zhu Caiying , Lian Yu , Wang Chenchen , Wu Peng , Li Xuan , Gao Yan , Fan Sibin , Ai Lanlan , Fang Liwei , Pan Hong , Cheng Tao , Shi Jun , Zhu Ping 
Published: March 2021

AbstractAplastic anemia (AA) is a T cell–mediated autoimmune disorder of the hematopoietic system manifested by severe depletion of the hematopoietic stem and progenitor cells (HSPCs). Nonetheless, our understanding of the complex relationship between HSPCs and T cells is still obscure, mainly limited by techniques and the sparsity of HSPCs in the context of bone marrow failure. Here we performed single-cell transcriptome analysis of residual HSPCs and T cells to identify the molecular players from patients with AA. We observed that residual HSPCs in AA exhibited lineage-specific alterations in gene expression and transcriptional regulatory networks, indicating a selective disruption of distinct lineage-committed progenitor pools. In particular, HSPCs displayed frequently altered alternative splicing events and skewed patterns of polyadenylation in transcripts related to DNA damage and repair, suggesting a likely role in AA progression to myelodysplastic syndromes. We further identified cell type–specific ligand-receptor interactions as potential mediators for ongoing HSPCs destruction by T cells. By tracking patients after immunosuppressive therapy (IST), we showed that hematopoiesis remission was incomplete accompanied by IST insensitive interactions between HSPCs and T cells as well as sustained abnormal transcription state. These data collectively constitute the transcriptomic landscape of disrupted hematopoiesis in AA at single-cell resolution, providing new insights into the molecular interactions of engaged T cells with residual HSPCs and render novel therapeutic opportunities for AA.
Nanocell-mediated delivery of miR-34a counteracts temozolomide resistance in glioblastoma
Authors: Khan Muhammad Babar , Ruggieri Rosamaria , Jamil Eesha , Tran Nhan L. , Gonzalez Camila , Mugridge Nancy , Gao Steven , MacDiarmid Jennifer , Brahmbhatt Himanshu , Sarkaria Jann N. , Boockvar John , Symons Marc 
Published: March 2021

Abstract
Background
Glioblastoma is the most common primary brain tumor and remains uniformly fatal, highlighting the dire need for developing effective therapeutics. Significant intra- and inter-tumor heterogeneity and inadequate delivery of therapeutics across blood–brain barrier continue to be significant impediments towards developing therapies which can significantly enhance survival. We hypothesize that microRNAs have the potential to serve as effective therapeutics for glioblastoma as they modulate the activity of multiple signaling pathways, and hence can counteract heterogeneity if successfully delivered.

Methods
Using a computational approach, we identified microRNA-34a as a microRNA that maximally reduces the activation status of the three core signaling networks (the receptor tyrosine kinase, p53 and Rb networks) that have been found to be deregulated in most glioblastoma tumors. Glioblastoma cultures were transfected with microRNA-34a or control microRNA to assess biological function and therapeutic potential in vitro. Nanocells were derived from genetically modified bacteria and loaded with microRNA-34a for intravenous administration to orthotopic patient-derived glioblastoma xenografts in mice.

Results
Overexpression of microRNA-34a strongly reduced the activation status of the three core signaling networks. microRNA-34a transfection also inhibited the survival of multiple established glioblastoma cell lines, as well as primary patient-derived xenograft cultures representing the proneural, mesenchymal and classical subtypes. Transfection of microRNA-34a enhanced temozolomide (TMZ) response in in vitro cultures of glioblastoma cells with primary TMZ sensitivity, primary TMZ resistance and acquired TMZ resistance. Mechanistically, microRNA-34a downregulated multiple therapeutic resistance genes which are associated with worse survival in glioblastoma patients and are enriched in specific tumor spatial compartments. Importantly, intravenous administration of nanocells carrying miR-34a and targeted to epidermal growth factor receptor (EGFR) strongly enhanced TMZ sensitivity in an orthotopic patient-derived xenograft mouse model of glioblastoma.

Conclusions
Targeted bacterially-derived nanocells are an effective vehicle for the delivery of microRNA-34a to glioblastoma tumors. microRNA-34a inhibits survival and strongly sensitizes a wide range of glioblastoma cell cultures to TMZ, suggesting that combination therapy of TMZ with microRNA-34a loaded nanocells may serve as a novel therapeutic approach for the treatment of glioblastoma tumors.