bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612
Authors: Ge Lite , Xun Chengfeng , Li Wenshui , Jin Shengyu , Liu Zuo , Zhuo Yi , Duan Da , Hu Zhiping , Chen Ping , Lu Ming 
Published: November 2021

AbstractMesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration, such as the induction of angiogenesis, particularly under hypoxic conditions. However, the molecular mechanisms underlying hypoxic MSC activation remain largely unknown. MSC-derived extracellular vesicles (EVs) are vital mediators of cell-to-cell communication and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of EVs from human hypoxic olfactory mucosa MSCs (OM-MSCs) on angiogenesis and its underlying mechanism. EVs were isolated from normoxic (N) OM-MSCs (N-EVs) and hypoxic (H) OM-MSCs (H-EVs) using differential centrifugation and identified by transmission electron microscopy and flow cytometry. In vitro and in vivo, both types of OM-MSC-EVs promoted the proliferation, migration, and angiogenic activities of human brain microvascular endothelial cells (HBMECs). In addition, angiogenesis-stimulatory activity in the H-EV group was significantly enhanced compared to the N-EV group. MicroRNA profiling revealed a higher abundance of miR-612 in H-EVs than in N-EVs, while miR-612 inactivation abolished the N-EV treatment benefit. To explore the roles of miR-612, overexpression and knock-down experiments were performed using a mimic and inhibitor or agomir and antagomir of miR-612. The miR-612 target genes were confirmed using the luciferase reporter assay. Gain- and loss-of-function studies allowed the validation of miR-612 (enriched in hypoxic OM-MSC-EVs) as a functional messenger that stimulates angiogenesis and represses the expression of TP53 by targeting its 3′-untranslated region. Further functional assays showed that hypoxic OM-MSC-EVs promote paracrine Hypoxia-inducible factor 1-alpha (HIF-1α)-Vascular endothelial growth factor (VEGF) signaling in HBMECs via the exosomal miR-612-TP53-HIF-1α-VEGF axis. These findings suggest that hypoxic OM-MSC-EVs may represent a promising strategy for ischemic disease by promoting angiogenesis via miR-612 transfer.
Graphical Abstract
Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics
Authors: Zhu Menglu , Shi Yi , Shan Yifan , Guo Junyan , Song Xuelong , Wu Yuhua , Wu Miaolian , Lu Yan , Chen Wei , Xu Xiaoling , Tang Longguang 
Published: November 2021

AbstractPolydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.Graphical Abstract
Quality of life in patients with stable coronary artery disease submitted to percutaneous, surgical, and medical therapies: a cohort study
Authors: da Silveira Lucas Molinari Veloso , Almeida Adriana Silveira , Fuchs Felipe C. , Silva Aline Gonçalves , Lucca Marcelo Balbinot , Scopel Samuel , Fuchs Sandra C. , Fuchs Flávio D. 
Published: November 2021

Abstract
Background
Clinical, surgical, and percutaneous strategies similarly prevent major cardiovascular events in patients with stable coronary artery disease (CAD). The possibility that these strategies have differential effects on health-related quality of life (HRQoL) has been debated, particularly in patients treated outside clinical trials.

Methods
We assigned 454 patients diagnosed with CAD during an elective diagnostic coronary angiography to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical treatment (OMT), and followed them for an average of 5.2 ± 1.5 years. HRQoL was assessed using a validated Brazilian version of the 12-Item Short-Form Health Survey questionnaire. The association between therapeutic strategies and quality of life scores was tested using variance analysis and adjusted for confounders in a general linear model.

Results
There were no differences in the mental component summary scores in the follow-up evaluation by therapeutic strategies: 51.4, 53.7, and 52.3 for OMT, PCI, and CABG, respectively. Physical component summary scores were higher in the PCI group than the CABG and OMT groups (46.4 vs. 42.9 and 43.8, respectively); however, these differences were no longer different after adjustment for confounding variables.

Conclusion
In a long-term follow-up of patients with stable CAD, HRQoL did not differ in patients treated by medical, percutaneous, or surgical treatments.
Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group’s analysis
Authors: Graziosi Luigina , Marino Elisabetta , Bencivenga Maria , D’Ignazio Alessia , Solaini Leonardo , Ministrini Silvia , Caprioli Michela , Sacco Michele , Marrelli Daniele , Mura Gianni , Degiuli Maurizio , Morgagni Paolo , Tiberio Guido Alberto Massimo , De Manzoni Giovanni , Roviello Franco , Donini Annibale 
Published: November 2021

Abstract
Background
The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery.

Methods
It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences.

Results
Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment.

Conclusion
The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with “radical oncological intent”, that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.
Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review
Authors: Li Hong-Bo , Yang Zi-Han , Guo Qing-Qu 
Published: November 2021

AbstractPancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting.
High efficiency closed-system gene transfer using automated spinoculation
Authors: Remley Victoria Ann , Jin Jianjian , Sarkar Sarmila , Moses Larry , Prochazkova Michaela , Cai Yihua , Shao Lipei , Liu Hui , Fuksenko Tatyana , Jin Ping , Stroncek David F. , Highfill Steven L. 
Published: November 2021

Abstract
Background
Gene transfer is an important tool for cellular therapies. Lentiviral vectors are most effectively transferred into lymphocytes or hematopoietic progenitor cells using spinoculation. To enable cGMP (current Good Manufacturing Practice)-compliant cell therapy production, we developed and compared a closed-system spinoculation method that uses cell culture bags, and an automated closed system spinoculation method to decrease technician hands on time and reduce the likelihood for microbial contamination.

Methods
Sepax spinoculation, bag spinoculation, and static bag transduction without spinoculation were compared for lentiviral gene transfer in lymphocytes collected by apheresis. The lymphocytes were transduced once and cultured for 9 days. The lentiviral vectors tested encoded a CD19/CD22 Bispecific Chimeric Antigen Receptor (CAR), a FGFR4-CAR, or a CD22-CAR. Sepax spinoculation times were evaluated by testing against bag spinoculation and static transduction to optimize the Sepax spin time. The Sepax spinoculation was then used to test the transduction of different CAR vectors. The performance of the process using healthy donor and a patient sample was evaluated. Functional assessment was performed of the CD19/22 and CD22 CAR T-cells using killing assays against the NALM6 tumor cell line and cytokine secretion analysis. Finally, gene expression of the transduced T-cells was examined to determine if there were any major changes that may have occurred as a result of the spinoculation process.

Results
The process of spinoculation lead to significant enhancement in gene transfer. Sepax spinoculation using a 1-h spin time showed comparable transduction efficiency to the bag spinoculation, and much greater than the static bag transduction method (83.4%, 72.8%, 35.7% n = 3). The performance of three different methods were consistent for all lentiviral vectors tested and no significant difference was observed when using starting cells from healthy donor versus a patient sample. Sepax spinoculation does not affect the function of the CAR T-cells against tumor cells, as these cells appeared to kill target cells equally well. Spinoculation also does not appear to affect gene expression patterns that are necessary for imparting function on the cell.

Conclusions
Closed system-bag spinoculation resulted in more efficient lymphocyte gene transfer than standard bag transductions without spinoculation. This method is effective for both retroviral and lentiviral vector gene transfer in lymphocytes and may be a feasible approach for gene transfer into other cell types including hematopoietic and myeloid progenitors. Sepax spinoculation further improved upon the process by offering an automated, closed system approach that significantly decreased hands-on time while also decreasing the risk of culture bag tears and microbial contamination.
Going digital: added value of electronic data collection in 2018 Afghanistan Health Survey
Authors: Mergenthaler Christina , Yadav Rajpal Singh , Safi Sohrab , Rood Ente , Alba Sandra 
Published: November 2021

Abstract
Background
Through a nationally representative household survey in Afghanistan, we conducted an operational study in two relatively secure provinces comparing effectiveness of computer-aided personal interviewing (CAPI) with paper-and-pencil interviewing (PAPI).

Methods
In Panjshir and Parwan provinces, household survey data were collected using paper questionnaires in 15 clusters, and OpenDataKit (ODK) software on electronic tablets in 15 other clusters. Added value was evaluated from three perspectives: efficient implementation, data quality, and acceptability. Efficiency was measured through financial expenditures and time stamped data. Data quality was measured by examining completeness. Acceptability was studied through focus group discussions with survey staff.

Results
Survey costs were 68% more expensive in CAPI clusters compared to PAPI clusters, due primarily to the upfront one-time investment for survey programming. Enumerators spent significantly less time administering surveys in CAPI cluster households (248 min survey time) compared to PAPI (289 min), for an average savings of 41 min per household (95% CI 25–55). CAPI offered a savings of 87 days for data management over PAPI.
Among 49 tracer variables (meaning responses were required from all respondents), small differences were observed between PAPI and CAPI. 2.2% of the cleaned dataset’s tracer data points were missing in CAPI surveys (1216/ 56,073 data points), compared to 3.2% in PAPI surveys (1953/ 60,675 data points). In pre-cleaned datasets, 3.9% of tracer data points were missing in CAPI surveys (2151/ 55,092 data points) compared to 3.2% in PAPI surveys (1924/ 60,113 data points).
Enumerators from Panjsher and Parwan preferred CAPI over PAPI due to time savings, user-friendliness, improved data security, and less conspicuity when traveling; however approximately half of enumerators trained from all 34 provinces reported feeling unsafe due to Taliban presence. Community and household respondent skepticism could be resolved by enumerator reassurance. Enumerators shared that in the future, they prefer collecting data using CAPI when possible.

Conclusions
CAPI offers clear gains in efficiency over PAPI for data collection and management time, although costs are relatively comparable even without the programming investment. However, serious field staff concerns around Taliban threats and general insecurity mean that CAPI should only be conducted in relatively secure areas.
Massive hemorrhage from the posterior intercostal artery following lower partial sternotomy
Authors: Hattori Masashi , Matsumura Yu , Yamaki Fumitaka 
Published: November 2021

Abstract
Background
Median sternotomy remains the most common approach in cardiovascular surgery. Recently, minimally invasive procedures, such as minimally invasive cardiac surgery, robot surgery, and catheter therapy have been developed in cardiovascular surgery. However, all these surgeries cannot be performed by minimally invasive approaches. Several complications associated with median sternotomy have been reported, although post-sternotomy hemorrhage from the posterior intercostal artery is extremely rare.

Case presentation
We present a case of posterior intercostal artery bleeding following lower partial sternotomy. A 79-year-old man underwent aortic valve replacement using lower partial median inverted L-shaped sternotomy that cut into the right second intercostal space. A postoperative chest radiograph indicated a hematoma in the right upper chest wall and pleural effusion. Hence, we inserted a drainage tube immediately. Approximately 2 hours after the surgery, his blood pressure gradually decreased. Blood drainage was observed from the tube, and the amount of blood drainage was not large. Contrast-enhanced computed tomography revealed a huge hematoma and hemorrhage from the fourth right posterior intercostal artery. Immediately, we performed emergency surgery. The lower partial sternotomy was repeated. We detected the origin of the bleeding that was identified in the right fourth posterior intercostal artery, and the bleeding was stopped. The postoperative course was uneventful.

Conclusions
This case highlights the possibility of intraoperative bleeding from the intercostal artery, even in the absence of clearly rib fracture. In our case, we did not identify the cause of bleeding, although we suggest the inhomogeneous stress on the posterior ribs upon attaching the sternal retractor for lower partial sternotomy may have affected the posterior intercostal artery.
Giant left anterior descending artery aneurysm in a patient with active systemic lupus erythematosus: a case report
Authors: Yao Zipeng , Long Yanhong , Zong Zheng , Wang Lin 
Published: November 2021

Abstract
Background
Although not common, coronary artery aneurysms (CAAs) can develop to over 8 mm in diameter to become giant CAAs. In the context of systemic lupus erythematosus (SLE), autoantibody- and immune complex-mediated atherosclerosis is believed to be the most prevalent cause of aneurysm.

Case presentation
We report the case of a 53-year-old female SLE patient who presented to our hospital with radiating chest pain. Coronary angiography revealed a giant aneurysm in the middle segment of the left anterior descending artery (LAD) and distal subtotal occlusion in the left circumflex artery (LCX). Laboratory testing also identified risk factors such as an abnormal pulmonary enzyme profile, dyslipidemia, and nephritis parameters.To prevent thromboembolism, anticoagulation and antiplatelet therapy were administered. In addition, one stent was implanted at the distal end of the LCX and repeated coronary angiography verified restoration of TIMI grade III flow.The patient was discharged with resolved chest pain. During 6 months of follow-up, the patient is in good health.

Conclusions
Our case study, together with 16 recent comparable reports, emphasizes the need for coronary aneurysm screening in SLE patients. It is necessary that thromboembolism, anticoagulation and antiplatelet therapy were administered for CAA.
Development and content validation of a symptom assessment for eosinophilic gastritis and eosinophilic gastroenteritis in adults and adolescents
Authors: Ho Calvin N. , O’Quinn Sean , Bailey Julie , Meyers Oren , Slagle Ashley F. , Dellon Evan S. , Datto Catherine 
Published: November 2021

Abstract
Background
A patient reported outcome (PRO) instrument with evidence of validity and reliability for assessing symptoms of eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) is needed to measure treatment benefit in clinical trials. The aim of this research is to develop an EG/EGE symptom PRO instrument for patients aged 12 and above.

Methods
The Symptom Assessment for Gastrointestinal Eosinophilic Diseases (SAGED) was developed through a literature review, discussions with expert clinicians, and concept elicitation and cognitive debriefing interviews with patients. Patients (n = 28) were recruited based on confirmed diagnosis and self-reported symptoms. The final instrument was translated and linguistically validated with additional cognitive debriefing interviews (n = 105).

Results
SAGED is a 24-h recall questionnaire consisting of eight items evaluating the core symptoms of EG and EGE (abdominal pain, nausea, bloating, early satiety, loss of appetite, vomiting, and diarrhea). Seven of the eight items are evaluated on an 11-point numerical rating scale ranging from ‘none’ to ‘worst imaginable’. Cognitive debriefing interviews showed that adults and adolescents understand the content and are able to select a response that reflects their experience. The linguistic validation process produced 21 translations that are understandable to patients and conceptually equivalent to the source version.

Conclusions
SAGED is suitable for measuring symptom improvement in adult and adolescent patients with EG and/or EGE. The content validity of SAGED has been established through best practices in qualitative research for PRO instrument development. The psychometric properties of SAGED will be evaluated in a future study.
Effect of interventions to reduce malaria incidence among military personnel on active duty: study protocol for a cluster randomised controlled trial of the impact of etofenprox-treated uniforms, permethrin-treated uniforms and DEET insect repellent
Authors: Msellemu Daniel , Ross Amanda , Temu Lucky , Moshi Irene , Hofer Lorenz , Mwanziva Charles , Kohi Yadon M. , Moore Sarah J. 
Published: November 2021

Abstract
Background
While there is strong evidence that bite protection methods such as permethrin-treated clothing and topical insect repellents are protective against insect bites, there are few studies assessing the impact on malaria infection. This study will estimate the protective efficacy of treated uniforms and DEET insect repellent on the incidence of malaria infection among military personnel in an operational setting. Permethrin-treated uniforms used with DEET lotion will be compared to etofenprox-treated uniforms with DEET lotion. The effect of DEET lotion will be estimated by comparing permethrin-treated uniforms with DEET or placebo lotion.

Method
A cluster randomised double-blind placebo-controlled trial is planned to evaluate the effectiveness of the interventions on preventing malaria infections in soldiers on active duty at Mgambo National Service Camp in Tanga, Tanzania. The arms are (1) permethrin-treated uniform with 30% DEET liposome formula; (2) permethrin-treated uniform with placebo lotion; (3) candidate insect repellent system, i.e. etofenprox-treated uniform with 30% DEET liposome formula; and (4) placebo, i.e. untreated uniforms with placebo lotion. The primary outcome is the incidence of Plasmodium falciparum malaria infection detected by polymerase chain reaction (PCR) by active case detection using surveys every 2 weeks for 12 months. Rapid diagnostic tests will be used for the diagnosis of participants with symptoms.
The unit of randomisation will be combania: companies formed by recruits aged 18 to 25 years; combania do activities together and sleep in the same dormitory. Unequal randomisation will be used to optimise statistical power for the primary comparison between permethrin-treated uniforms with DEET and etofenprox-treated uniforms with DEET.

Discussion
This trial will provide the estimate of the effects of permethrin with DEET compared to those of the new fabric treatment etofenprox with DEET and any additional effect of using DEET. The results will inform strategies to protect military personnel and civilians who have more outdoor or occupational malaria exposure than the general public.

Trial registration
ClinicalTrials.govNCT02938975.