bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rebuilding child health in South Kivu, Democratic Republic of Congo (DRC): evaluating the Asili social enterprise program
Authors: Behl Rasika , Ali Sofia , Altamirano Jonathan , Leno Abraham , Maldonado Yvonne , Sarnquist Clea 
Published: May 2022

Abstract
Background
The Democratic Republic of Congo (DRC) has a long history of conflict and ongoing local instability; the eastern provinces, including South Kivu, have been especially affected. Health systems and livelihoods have been undermined, contributing to massive inequities in access to health services and high rates of internal displacement. Asili, an innovative social enterprise program, aimed to provide essential community services and improve the health of under-five children in two South Kivu communities, Mudaka and Panzi, via provision of small-format, franchisable health clinics and clean water services.

Methods
We evaluated utilization and acceptance of Asili services in two study sites, Mudaka and Panzi. Data collected included questions on housing conditions, food security, and at follow up, Asili membership and use, satisfaction with services, and recommendations for improvement. Structured pre- and post-interviews with primary caregivers of families with under-five children were the primary source of data with additional community input collected through focus group discussions.

Results
At baseline, we enrolled 843 households in Mudaka and 890 in Panzi. Market segmentation analysis illuminated service usage patterns, showing Asili services were well received overall in both Mudaka and Panzi. Families reporting higher levels of proxy measures of socioeconomic status (SES), such as electricity, land ownership, and education, were more likely to use Asili services, findings that were further supported by focus group discussions among community members.

Conclusions
Rebuilding health infrastructure in post-conflict settings, especially those that continue to be conflict-affected and very low SES, is a challenging prospect. Focus group results for this study highlighted the positive community response to Asili, while also underscoring challenges related to cost of services. Programs may need, in particular, to have different levels of costs for different SES groups. Additionally, longer follow-up periods and increased stability may be needed to assess the potential of social enterprise interventions such as Asili to improve health outcomes, especially in children.

Trial registration

Institutional Review Board approval for this study was obtained at Stanford University (IRB 35216) and the University of Kinshasa, DRC. Further, this study has been registered on Clinicaltrials.gov (record NCT03536286), retrospectively registered as of 4/23/2018.
Antiallodynic effects of KDS2010, a novel MAO-B inhibitor, via ROS-GABA inhibitory transmission in a paclitaxel-induced tactile hypersensitivity model
Authors: Park Su Eun , Neupane Chiranjivi , Noh Chan , Sharma Ramesh , Shin Hyun Jin , Pham Thuy Linh , Lee Gyu-Seung , Park Ki Duk , Lee C. Justin , Kang Dong-Wook , Lee So Yeong , Kim Hyun-Woo , Park Jin Bong 
Published: May 2022

AbstractMonoamine oxidase (MAO) inhibitors have been investigated for the treatment of neuropathic pain. Here, we assessed the antiallodynic effects of a novel MAO-B inhibitor, KDS2010, on paclitaxel (PTX)-induced mechanical hypersensitivity. Oral administration of KDS2010 effectively relieved PTX-induced mechanical hypersensitivity in a dose-dependent manner. KDS2010 (25 mg/Kg) significantly prevented and suppressed PTX-induced pain responses with minimal effects on the body weight, motor activity, and working memory. KDS2010 significantly reduced reactive astrocytosis and reactive oxygen species (ROS) level in the L4–L6 spinal cord of PTX-treated mice. Furthermore, KDS2010 reversed the attenuation of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency in spinal dorsal horn neurons, although it failed to restore the reduced tonic GABAA inhibition nor the increased GABA transporter 1 (GAT1) expression in PTX-treated mice. In addition, bath application of a reactive oxygen species (ROS) scavenger (PBN) restored the sIPSC frequency in PTX-treated mice but not in control and PTX + KDS2010-treated mice. These results indicated that the antiallodynic effect of KDS2010 is not due to a MAO-B-dependent GABA production. Finally, PBN alone also exerted a similar analgesic effect as KDS2010, but a co-treatment of PBN with KDS2010 showed no additive effect, suggesting that inhibition of MAO-B-dependent ROS production is responsible for the analgesic effect by KDS2010 on PTX-induced allodynia. Overall, KDS2010 attenuated PTX-induced pain behaviors by restoring the altered ROS level and GABAergic inhibitory signaling in the spinal cord, suggesting that KDS2010 is a promising therapeutic strategy for chemotherapy-induced peripheral neuropathy.
The dual role of autophagy in acute myeloid leukemia
Authors: Seo Wonhyoung , Silwal Prashanta , Song Ik-Chan , Jo Eun-Kyeong 
Published: May 2022

AbstractAcute myeloid leukemia (AML) is a severe hematologic malignancy prevalent in older patients, and the identification of potential therapeutic targets for AML is problematic. Autophagy is a lysosome-dependent catabolic pathway involved in the tumorigenesis and/or treatment of various cancers. Mounting evidence has suggested that autophagy plays a critical role in the initiation and progression of AML and anticancer responses. In this review, we describe recent updates on the multifaceted functions of autophagy linking to genetic alterations of AML. We also summarize the latest evidence for autophagy-related genes as potential prognostic predictors and drivers of AML tumorigenesis. We then discuss the crosstalk between autophagy and tumor cell metabolism into the impact on both AML progression and anti-leukemic treatment. Moreover, a series of autophagy regulators, i.e., the inhibitors and activators, are described as potential therapeutics for AML. Finally, we describe the translation of autophagy-modulating therapeutics into clinical practice. Autophagy in AML is a double-edged sword, necessitating a deeper understanding of how autophagy influences dual functions in AML tumorigenesis and anti-leukemic responses.
A novel role of lysophosphatidic acid (LPA) in human myeloma resistance to proteasome inhibitors
Authors: Su Pan , Xiao Liuling , Ye Lingqun , Wang Zhuo , Xiong Wei , Wang Qiang , Ma Xingzhe , Xian Miao , Yang Maojie , Zu Youli , Pingali Sai Ravi , Qian Jianfei , Yi Qing 
Published: May 2022

AbstractLysophosphatidic acid (LPA) is a naturally occurring phospholipid that regulates cell proliferation, survival, and migration. However, its role on human multiple myeloma (MM) cells is largely unknown. In this study, we show that LPA, which is highly elevated in MM patients, plays an important role in protecting human MM cells against proteasome inhibitor (PI)-induced apoptosis. LPA bound to its receptor LPAR2 activated its downstream MEK1/2-ERK1/2 signaling pathway and enhanced oxidative phosphorylation (OXPHOS) in mitochondria in MM cells. Increased OXPHOS activity produced more NAD+ and ATP, reduced proteasome activity, and enhanced protein folding and refolding in endoplasmic reticulum (ER), leading to induction of MM resistance to PIs. Importantly, inhibiting LPAR2 activity or knocking out LPAR2 in MM cells significantly enhanced MM sensitivity to PI-induced apoptosis in vitro and in vivo. Interestingly, primary MM cells from LPA-high patients were more resistant to PI-induced apoptosis than MM cells from LPA-low patients. Thus, our study indicates that LPA-LPAR2-mediated signaling pathways play an important role in MM sensitivity to PIs and targeting LPA or LPAR2 may potentially be used to (re)sensitize patients to PI-based therapy.
A novel tRNA-derived fragment AS-tDR-007333 promotes the malignancy of NSCLC via the HSPB1/MED29 and ELK4/MED29 axes
Authors: Yang Wenhan , Gao Kaiping , Qian Youhui , Huang Yongyi , Xiang Qin , Chen Cheng , Chen Qianqian , Wang Yiling , Fang Fuyuan , He Qihan , Chen Siqi , Xiong Juan , Chen Yangchao , Xie Ni , Zheng Duo , Zhai Rihong 
Published: May 2022

Abstract
Background
Transfer RNA-derived fragments (tRFs) are a new class of small non-coding RNAs. Recent studies suggest that tRFs participate in some pathological processes. However, the biological functions and mechanisms of tRFs in non-small cell lung cancer (NSCLC) are largely unknown.

Methods
Differentially expressed tRFs were identified by tRF and tiRNA sequencing using 9 pairs of pre- and post-operation plasma from patients with NSCLC. Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to determine the levels of tRF in tissues, plasma, and cells. Gain- and loss-of-function experiments were implemented to investigate the oncogenic effects of tRF on NSCLC cells in vitro and in vivo. Chromatin immunoprecipitation (ChIP), luciferase reporter, RNA pulldown, mass spectrum, RNA immunoprecipitation (RIP), Western blot, co-immunoprecipitation (Co-IP) assays, and rescue experiments were performed to explore the regulatory mechanisms of tRF in NSCLC.

Results
AS-tDR-007333 was an uncharacterized tRF and significantly up-regulated in NSCLC tissues, plasma, and cells. Clinically, AS-tDR-007333 overexpression could distinguish NSCLC patients from healthy controls and associated with poorer prognosis of NSCLC patients. Functionally, overexpression of AS-tDR-007333 enhanced proliferation and migration of NSCLC cells, whereas knockdown of AS-tDR-007333 resulted in opposite effects. Mechanistically, AS-tDR-007333 promoted the malignancy of NSCLC cells by activating MED29 through two distinct mechanisms. First, AS-tDR-007333 bound to and interacted with HSPB1, which activated MED29 expression by enhancing H3K4me1 and H3K27ac in MED29 promoter. Second, AS-tDR-007333 stimulated the expression of transcription factor ELK4, which bound to MED29 promoter and increased its transcription. Therapeutically, inhibition of AS-tDR-007333 suppressed NSCLC cell growth in vivo.

Conclusions
Our study identifies a new oncogenic tRF and uncovers a novel mechanism that AS-tDR-007333 promotes NSCLC malignancy through the HSPB1-MED29 and ELK4-MED29 axes. AS-tDR-007333 is a potential diagnostic or prognostic marker and therapeutic target for NSCLC.
LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma
Authors: Liu Yihao , Shi Minmin , He Xingfeng , Cao Yizhi , Liu Pengyi , Li Fanlu , Zou Siyi , Wen Chenlei , Zhan Qian , Xu Zhiwei , Wang Jiancheng , Sun Baofa , Shen Baiyong 
Published: May 2022

Abstract
Background
LncRNA-PACERR plays critical role in the polarization of tissue-associated macrophages (TAMs). In this study, we found the function and molecular mechanism of PACERR in TAMs to regulate pancreatic ductal adenocarcinoma (PDAC) progression.

Methods
We used qPCR to analyse the expression of PACERR in TAMs and M1-tissue-resident macrophages (M1-NTRMs) which were isolated from 46 PDAC tissues. The function of PACERR on macrophages polarization and PDAC proliferation, migration and invasion were confirmed through in vivo and in vitro assays. The molecular mechanism of PACERR was discussed via fluorescence in situ hybridization (FISH), RNA pull-down, ChIP-qPCR, RIP-qPCR and luciferase assays.

Results
LncRNA-PACERR was high expression in TAMs and associated with poor prognosis in PDAC patients. Our finding validated that LncRNA-PACERR increased the number of M2-polarized cells and facilized cell proliferation, invasion and migration in vitro and in vivo. Mechanistically, LncRNA-PACERR activate KLF12/p-AKT/c-myc pathway by binding to miR-671-3p. And LncRNA-PACERR which bound to IGF2BP2 acts as an m6A-dependent manner to enhance the stability of KLF12 and c-myc in cytoplasm. In addition, the promoter of LncRNA-PACERR was a target of KLF12 and LncRNA-PACERR recruited EP300 to increase the acetylation of histone by interacting with KLF12 in nucleus.

Conclusions
This study found that LncRNA-PACERR functions as key regulator of TAMs in PDAC microenvironment and revealed the novel mechanisms in cytoplasm and in nucleus.
SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders
Authors: Piñana José Luis , López-Corral Lucia , Martino Rodrigo , Vazquez Lourdes , Pérez Ariadna , Martin-Martin Gabriel , Gago Beatriz , Sanz-Linares Gabriela , Sanchez-Salinas Andrés , Villalon Lucia , Conesa-Garcia Venancio , Olave María T. , Corona Magdalena , Marcos-Corrales Sara , Tormo Mar , Hernández-Rivas José Ángel , Montoro Juan , Rodriguez-Fernandez Alicia , Risco-Gálvez Irene , Rodríguez-Belenguer Pablo , Hernandez-Boluda Juan Carlos , García-Cadenas Irene , Ruiz-García Montserrat , Muñoz-Bellido Juan Luis , Solano Carlos , Cedillo Ángel , Sureda Anna , Navarro David ,   the Infectious Complications Subcommittee of the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH-TC)
Published: May 2022

Abstract
Background
The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established.

Patients and methods
A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3–6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders.

Results
At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7–195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3–6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2–4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0–4854.93) vs 730.81 BAU/mL (range 0–56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower.

Conclusions
Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants.
Kinesin family member 23, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/β-catenin pathway
Authors: Li Zhi , Yang Hai-Yan , Zhang Xiao-Lan , Zhang Xu , Huang Yu-Zhou , Dai Xin-Yuan , Shi Liang , Zhou Guo-Ren , Wei Ji-Fu , Ding Qiang 
Published: May 2022

Abstract
Background
Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. KIF23 plays a crucial role in the tumorigenesis and cancer progression. However, the role of KIF23 in development of TNBC and the underlying mechanism remain unknown. The study aimed to elucidate the biological function and regulatory mechanism of KIF23 in TNBC.

Methods
Quantitative real-time PCR and Western blot were used to determine the KIF23 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of KIF23 on tumor growth and metastasis in TNBC. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of KIF23 in TNBC.

Results
We found that KIF23 was significantly up-regulated and associated with poor prognosis in TNBC. KIF23 could promote TNBC proliferation, migration and invasion in vitro and in vivo. KIF23 could activate Wnt/β-catenin pathway and promote EMT progression in TNBC. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of KIF23 gene to promote its transcription and accelerated TNBC progression via Wnt/β-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression.

Conclusions
Our findings elucidate WDR5/FOXM1/KIF23/Wnt/β-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.
Survival of primary ankle replacements: data from global joint registries
Authors: Perry Thomas A. , Silman Alan , Culliford David , Gates Lucy , Arden Nigel , Bowen Catherine ,   the International Ankle Arthroplasty Registry Consortium
Published: May 2022

AbstractBackgroundAnkle arthroplasty, commonly known as ankle replacement, is a surgical procedure for treating end‐stage ankle osteoarthritis. Whilst evidence shows good clinical results after surgery, little is known of the long‐term survival of ankle replacements and the need for ankle revision. Using more recent implant data and long‐term data, there is now opportunity to examine at a population‐level the survival rate for ankle implants, to examine between‐country differences in ankle revision surgery, and to compare temporal trends in revision rates between countries.MethodsFour national joint registries from Australia, New Zealand, Norway and Sweden provided the necessary data on revision outcome following primary ankle replacement, for various periods of observation – the earliest starting in 1993 up to the end of 2019. Data were either acquired from published, online annual reports or were provided from direct contact with the joint registries. The key information extracted were Kaplan‐Meier estimates to plot survival probability curves following primary ankle replacement.ResultsThe survival rates varied between countries. At 2 years, across all registries, survival rates all exceeded 0.9 (range 0.91 to 0.97). The variation widened at 5 years (range 0.80 to 0.91), at 10 years (range 0.66 to 0.84) and further at 15‐years follow‐up (0.56 to 0.78). At each time point, implant survival was greater in Australia and New Zealand with lower rates in Sweden and Norway.ConclusionsWe observed variation in primary ankle replacement survival rates across these national registries, although even after 5 years, these population derived data show an 80% revision free survival. These data raise a number of hypotheses concerning the reasons for between‐country differences in revision‐free survival which will require access to primary data for analysis.
Helicopter inter-hospital transfer for patients undergoing extracorporeal membrane oxygenation: a retrospective 12-year analysis of a service system
Authors: Fuchs Alexander , Schmucki Renate , Meuli Lorenz , Wendel-Garcia Pedro David , Albrecht Roland , Greif Robert , Pietsch Urs 
Published: May 2022

Abstract
Background
Patients undergoing extracorporeal membrane oxygenation (ECMO) are critically ill and show high mortality. Inter-hospital transfer of these patients has to be safe, with high survival rates during transport without potentially serious and life-threatening adverse events. The Swiss Air-Rescue provides 24-h/7-days per week inter-hospital helicopter transfers that include on-site ECMO cannulation if needed. This retrospective observational study describes adverse events of patients on ECMO transported by helicopter, and their associated survival.

Methods
All patients on ECMO with inter-hospital transfer by helicopter from start of service in February 2009 until May 2021 were included. Patients not transported by helicopter or with missing medical records were excluded. Patient demographics (age, sex) and medical history (type of and reason for ECMO), mission details (flight distance, times, primary or secondary transport), adverse events during the inter-hospital transfer, and survival of transferred patients were recorded. The primary endpoint was patient survival during transfer. Secondary endpoints were adverse events during transfer and 28-day survival.

Results
We screened 214 ECMO-related missions and included 191 in this analysis. Median age was 54.6 [IQR 46.1–62.0] years, 70.7% were male, and most patients had veno-arterial ECMO (56.5%). The main reasons for ECMO were pulmonary (46.1%) or cardiac (44.0%) failure. Most were daytime (69.8%) and primary missions (n = 100), median total mission time was 182.0 [143.0–254.0] min, and median transfer distance was 52.7 [33.2–71.1] km. All patients survived the transfer. Forty-four adverse events were recorded during 37 missions (19.4%), where 31 (70.5%) were medical and none resulted in patient harm. Adverse events occurred more frequently during night-time missions (59.9%, p = 0.047). Data for 28-day survival were available for 157 patients, of which 86 (54.8%) were alive.

Conclusion
All patients under ECMO survived the helicopter transport. Adverse events were observed for about 20% of the flight missions, with a tendency during the night-time flights, none harmed the patients. Inter-hospital transfer for patients undergoing ECMO provided by 24-h/7-d per week helicopter emergency medical service teams can be considered as feasible and safe. The majority of the patients (54.8%) were still alive after 28 days.
Epidemiology and antimicrobial susceptibility of Staphylococcus aureus in children in a tertiary care pediatric hospital in Milan, Italy, 2017—2021
Authors: La Vecchia Adriano , Ippolito Giulio , Taccani Vittoria , Gatti Elisabetta , Bono Patrizia , Bettocchi Silvia , Pinzani Raffaella , Tagliabue Claudia , Bosis Samantha , Marchisio Paola , Agostoni Carlo 
Published: May 2022

Abstract
Background
Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent worldwide and can cause severe diseases. MRSA is associated with other antibiotic resistance. COVID-19 pandemic increased antimicrobial resistance in adult patients. Only a few data report the antimicrobial susceptibility of S. aureus in the Italian pediatric population, before and during the COVID-19 pandemic.

Methods
We included all the S. aureus positive samples with an available antibiogram isolated from pediatric patients (< 18 years old) in a tertiary care hospital in Milan, Italy, from January 2017 to December 2021. We collected data on demographics, antimicrobial susceptibility, and clinical history. We compared methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA strains. We calculated the frequency of isolation by year. The incidence of isolates during 2020 was compared with the average year isolation frequency using the univariate Poisson test. We compared the proportion of MRSA isolates during 2020 to the average proportion of other years with the Chi-squared test.

Results
Our dataset included a total of 255 S. aureus isolated from 226 patients, 120 (53%) males, and 106 (47%) females, with a median age of 3.4 years (IQR 0.8 – 10.5). The mean isolation frequency per year was 51. We observed a significant decrease of isolations during 2020 (p = 0.02), but after adjusting for the total number of hospitalization per year there was no evidence that the incidence changed. Seventy-six (30%) S. aureus were MRSA. Twenty (26%) MRSA vs 23 (13%) MSSA (p = 0.02) were hospital-acquired. MRSA strains showed higher resistance to cotrimoxazole, clindamycin, macrolides, levofloxacin, gentamicin, and tetracyclin than MSSA strains. None of MRSA were resistant to linezolid and vancomycin, one was resistant to daptomycin. The proportion of MRSA did not change during the COVID-19 pandemic. The overall clindamycin resistance was high (17%). Recent antibiotic therapy was related to MRSA infection.

Conclusion
The proportion of MRSA did not change during the COVID-19 pandemic and remained high. Clindamycin should not be used as an empirical MRSA treatment due to its high resistance.