bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inefficiency of public hospitals: a multistage data envelopment analysis in an Italian region
Authors: Piubello Orsini Luca , Leardini Chiara , Vernizzi Silvia , Campedelli Bettina 
Published: November 2021

Abstract
Background
The objective of this study was to assess public hospital efficiency, including quality outputs, inefficiency determinants, and changes to efficiency over time, in an Italian region. To achieve this aim, the study used secondary data from the Veneto region for the years 2018 and 2019.

Methods
A nonparametric approach—that is, multistage data envelopment analysis (DEA)—was applied to a sample of 43 hospitals. We identified three categories of input: capital investments (Beds), labor (FTE), operating expenses. We selected five efficiency outputs (outpatient visits, inpatients, outpatient visit revenue, inpatient revenue, bed occupancy rate) and two quality outputs (mortality rate and inappropriate admission rate). Efficiency scores were estimated and decomposed into two components. Slack analysis was then conducted. Further, DEA efficiency scores were regressed on internal and external variables using a Tobit model. Finally, the Malmquist Productivity Index was applied.

Results
On average, the hospitals in the Veneto region operated at more than 95% efficiency. Technical and scale inefficiencies often occurred jointly, with 77% of inefficient hospitals needing a downsizing strategy to gain efficiency. The inputs identified as needing significant reductions were full-time employee (FTE) administrative staff and technicians. The size of the hospital in relation to the size of the population served and the length of patient stay were important factors for the efficiency score. The major cause of decreased efficiency over time was technical change (0.908) rather than efficiency change (0.974).

Conclusions
The study reveals improvements that should be made from both the policy and managerial perspectives. Hospital size is an important feature of inefficiency. On average, the results show that it is advisable for hospitals to reorganize nonmedical staff to enhance efficiency. Further, increasing technology investment could enable higher efficiency levels.
Adult retrospective report of child abuse and prospective indicators of childhood harm: a population birth cohort study
Authors: Pinto Pereira Snehal M. , Rogers Nina T. , Power Christine 
Published: November 2021

Abstract
Background
We aim to determine whether adult retrospective report of child abuse is associated with greater risk of prospectively assessed harmful environments in childhood. We assessed possible recall basis by adult depression status.

Methods
At 45 years, participants of the 1958 British birth cohort (N = 9308) reported a range of abuse types (by 16 years). Prospective data, ages 7–16 years, were obtained for impoverished upbringing, hazardous conditions, anti-social behaviours and 16 years poor parent-child relationships. We estimated associations between retrospective report of child abuse and prospectively measured harm using (i) odds ratios (ORs, 95% confidence intervals) and (ii) positive predictive values (PPVs). PPVs were calculated stratified by adult depression status.

Results
Prevalence of retrospectively reported abuse ranged from 10.7% (psychological) to 1.60% (sexual) and 14.8% reported ≥ 1 type; prospectively recorded harm ranged from 10% (hazardous conditions/poor parent-child relationships) to 20% (anti-social behaviours). Adults retrospectively reporting abuse were more likely to have had harmful childhood environments: 52.4% had ≥ 1 indicator of harm (vs. 35.6% among others); ORsex-adjusted for poor relationships with parents was 2.98 (2.50, 3.54). For retrospectively reported (vs. none) abuse, there was a trend of increasing relative risk ratio with number of harms, from 1.75 (1.50, 2.03) for 1 to 4.68 (3.39, 6.45) for 3/4 childhood harms. The PPV of ≥ 1 prospectively recorded harm did not differ between depressed (0.58 (0.52, 0.64)) and non-depressed (0.58 (0.55, 0.61)) groups.

Conclusions
In a population cohort, adult retrospective report of child abuse was associated with several harms, prospectively measured from childhood to adolescence, providing support for the validity of retrospective report-based research. Findings suggest retrospectively reported child abuse is not biased by depression in adulthood.
Molecular prevalence and risk factors associated with tick-borne pathogens in cattle in western Kenya
Authors: Chiuya Tatenda , Villinger Jandouwe , Masiga Daniel K. , Ondifu Dickens O. , Murungi Maurice K. , Wambua Lillian , Bastos Armanda D. S. , Fèvre Eric M. , Falzon Laura C. 
Published: November 2021

Abstract
Background
Tick-borne pathogens (TBPs) are of global importance, especially in sub-Saharan Africa where they represent a major constraint to livestock production. Their association with human disease is also increasingly recognized, signalling their zoonotic importance. It is therefore crucial to investigate TBPs prevalence in livestock populations and the factors associated with their presence. We set out to identify TBPs present in cattle and to determine associated risk factors in western Kenya, where smallholder livestock production is important for subsistence and market-driven income.

Results
Tick-borne pathogen infections in blood samples collected from cattle at livestock markets and slaughterhouses between May 2017 and January 2019 were identified by high-resolution melting analysis and sequencing of PCR products of genus-specific primers. Of the 422 cattle sampled, 30.1% (127/422) were infected with at least one TBP, while 8.8% (37/422) had dual infections. Anaplasma spp. (19.7%) were the most prevalent, followed by Theileria (12.3%), Ehrlichia (6.6%), and Babesia (0.2%) spp. Sequence analysis of the TBPs revealed them to be Anaplasma platys-like organisms (13.5%), Theileria velifera (7.4%), Anaplasma marginale (4.9%), Theileria mutans (3.1%), Theileria parva (1.6%), and Babesia bigemina (0.2%). Ehrlichia ruminantium, Rickettsia spp., and arboviruses were not detected. Exotic breeds of cattle were more likely to be infected with A. marginale compared to local breeds (OR: 7.99, 95% CI: 3.04–22.02, p <  0.001). Presence of ticks was a significant predictor for Anaplasma spp. (OR: 2.18, 95% CI: 1.32–3.69, p = 0.003) and Ehrlichia spp. (OR: 2.79, 95% CI: 1.22–7.23, p = 0.022) infection. Cattle sampled at slaughterhouses were more likely to be positive for Anaplasma spp. (OR: 1.64, 95% CI: 1.01–2.70, p = 0.048) and A. marginale (OR: 3.84, 95% CI: 1.43–12.21, p = 0.012), compared to those sampled at livestock markets.

Conclusion
This study reports TBP prevalence and associated risk factors in western Kenya, factors which are key to informing surveillance and control measures.
Safety of delivering bronchial thermoplasty in two treatment sessions
Authors: Koshy Kavya , Sha Joy , Bennetts Kim , Langton David 
Published: November 2021

Abstract
Background
Bronchial thermoplasty (BT) is a novel endoscopic therapy for severe asthma. Traditionally it is performed in three separate treatment sessions, targeting different portions of the lung, and each requires an anaesthetic and hospital admission. Compression of treatment into 2 sessions would present a more convenient alternative for patients. In this prospective observational study, the safety of compressing BT into two treatment sessions was compared with the traditional 3 treatment approach.

Methods
Sixteen patients meeting ERS/ATS criteria for severe asthma consented to participate in an accelerated treatment schedule (ABT), which treated the whole left lung followed by the right lung four weeks later. The short-term outcomes of these patients were compared with 37 patients treated with conventional BT scheduling (CBT). The outcome measures used to assess safety were (1) the requirement to remain in hospital beyond the electively planned 24-h admission and (2) the need for re-admission for any cause within of 30 days of treatment.

Results
The total number of radiofrequency activations delivered in the ABT group was similar to CBT (187 ± 21 vs 176 ± 40, p = 0.326). With ABT, 11 in 31 admissions (37.9%) required prolonged admission due to wheezing, compared to 5.4% with CBT (p = 0.0025). The mean hospital length of stay with ABT was 1.8 ± 1.3 days, compared to 1.1 ± 0.4 days (p < 0.001). ICU monitoring was required on 5 occasions with ABT (16.1%), compared to 0.9% with CBT (p = 0.002). Subgroup analysis demonstrated that females were more likely to require prolonged admission (OR 11.6, p = 0.0025). The 30-day hospital readmission rate was similar for both groups (6.4% vs 5.4%, p = 0.67). All patients made a complete recovery after treatment with similar outcomes at the 6-month follow-up reassessment.

Conclusion
This study demonstrates that ABT results in greater short-term deterioration in lung function associated with a greater risk of prolonged hospital and ICU stay, predominantly affecting females. Therefore, in females, these risks need to be balanced against the convenience of fewer treatment sessions. In males, it may be an advantage to compress treatment.
Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
Authors: Xie Kairu , Xiong Hairong , Xiao Wen , Xiong Zhiyong , Hu Wenjun , Ye Jiaxin , Xu Ning , Shi Jian , Yuan Changfei , Chen Zhixian , Miao Daojia , Zhang Xiaoping , Yang Hongmei 
Published: November 2021

Abstract
Background
Cancer cachexia is a wasting disorder characterized by significant weight loss, and is attributed to skeletal muscle weakness. In the process of cancer development, microRNAs act as oncogenes or tumor suppressors. Moreover, they are implicated in muscle development and wasting. This study sought to explore the mechanisms and correlation between miR-29c and muscle wasting in lung cancer cachexia.

Methods
Data for expression analysis were retrieved from the Cancer Genome Atlas (TCGA) database. qRT-PCR analyses were performed to explore the expression levels of miR-29c and Leukemia Inhibitory Factor (LIF). Lewis lung carcinoma (LLC) cell line was used to establish a cachexia model to explore the functions of miR-29c and LIF in lung cancer cachexia. Furthermore, in vitro (in C2C12 myotubes) and in vivo (in LLC tumor-bearing mice) experiments were performed to explore the mechanisms of miR-29c and LIF in lung cachexia.

Results
Analysis of the lung cancer cachexia model showed that miR-29c was down-regulated, and its expression was negatively correlated with muscle catabolic activity. Overexpression of miR-29c mitigated the cachectic phenotype. Mechanistic studies showed that LIF was a direct target gene of miR-29c, and LIF was upregulated in vitro and in vivo. Analysis showed that LIF promoted muscle wasting through the JAK/STAT and MAP-kinase pathways.

Conclusions
The findings indicated that miR-29c was negatively correlated with the cachectic phenotype, and the miR-29c-LIF axis is a potential therapeutic target for cancer cachexia.
The circular RNA circSLC7A11 functions as a mir-330-3p sponge to accelerate hepatocellular carcinoma progression by regulating cyclin-dependent kinase 1 expression
Authors: Huang Yu , Ge Wenhao , Ding Yuan , Zhang Lufei , Zhou Jiarong , Kong Yang , Cui Bijun , Gao Bingqiang , Qian Xiaohui , Wang Weilin 
Published: November 2021

Abstract
Background
Circular RNAs (circRNAs), which are endogenous non-coding RNAs, are associated with various biological processes including development, homeostatic maintenance, and pathological responses. Accumulating evidence has implicated non-coding RNAs in cancer progression, and the role of circRNAs in particular has drawn wide attention. However, circRNA expression patterns and functions in hepatocellular carcinoma (HCC) remain poorly understood.

Methods
CircRNA sequencing was performed to screen differentially expressed circRNAs in HCC. Northern blotting, quantitative real-time polymerase chain reaction, nucleocytoplasmic fractionation, and fluorescence in situ hybridization analyses were conducted to evaluate the expression and localization of circSLC7A11 in HCC tissues and cells. CircSLC7A11 expression levels were modified in cultured HCC cell lines to explore the association between the expression of circSLC7A11 and the malignant behavior of these cells using several cell-based assays. The modified cells were implanted into immunocompetent nude mice to assess tumor growth and metastasis in vivo. We applied bioinformatics methods, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays to explore the mechanisms of circSLC7A11 in HCC.

Results
CircSLC7A11 (hsa_circ_0070975) was conserved and dramatically overexpressed in HCC tissues and cells. HCC patients showing high circSLC7A11 expression had worse prognoses. Our in vitro and in vivo experiments showed that circSLC7A11 markedly accelerated HCC progression and metastasis through the circSLC7A11/miR-330-3p/CDK1 axis.

Conclusions
The acceleration of HCC progression and metastasis by circSLC7A11 through the circSLC7A11/miR-330-3p/CDK1 axis suggests that circSLC7A11 is a potential novel diagnostic and therapeutic target for HCC treatment.
Automated landmarking of bends in vascular structures: a comparative study with application to the internal carotid artery
Authors: Kjeldsberg Henrik A , Bergersen Aslak W , Valen-Sendstad Kristian 
Published: November 2021

AbstractAutomated tools for landmarking the internal carotid artery (ICA) bends have the potential for efficient and objective medical image-based morphometric analysis. The two existing algorithms rely on numerical approximations of curvature and torsion of the centerline. However, input parameters, original source code, comparability, and robustness of the algorithms remain unknown. To address the former two, we have re-implemented the algorithms, followed by sensitivity analyses. Of the input parameters, the centerline smoothing had the least impact resulting in 6–7 bends, which is anatomically realistic. In contrast, centerline resolution showed to completely over- and underestimated the number of bends varying from 3 to 33. Applying the algorithms to the same cohort revealed a variability that makes comparison of results between previous studies questionable. Assessment of robustness revealed how one algorithm is vulnerable to model smoothness and noise, but conceptually independent of application. In contrast, the other algorithm is robust and consistent, but with limited general applicability. In conclusion, both algorithms are equally valid albeit they produce vastly different results. We have provided a well-documented open-source implementation of the algorithms. Finally, we have successfully performed this study on the ICA, but application to other vascular regions should be performed with caution.
15-Lipoxygenase and its metabolites in the pathogenesis of breast cancer: A double-edged sword
Authors: Vaezi Mohammad Amin , Safizadeh Banafsheh , Eghtedari Amir Reza , Ghorbanhosseini Seyedeh Sara , Rastegar Mostafa , Salimi Vahid , Tavakoli-Yaraki Masoumeh 
Published: November 2021

Abstract15-lipoxygenase is one of the key enzymes for the metabolism of unsaturated fatty acids that its manipulation has been proposed recently as a new molecular target for regulating cancer cell growth. Aberrant expression of 15-lipoxygenase enzyme seems to play an indicative role in the pathology of different cancer types, tumor progression, metastasis, or apoptosis. Based on the fact that breast cancer is one of the most common cancers that imposes a burden of mortality in women also, on the other hand, evidence in experimental models and human studies indicate the emerging role of the 15-lipoxygenase pathway in breast cancer pathogenesis, we present a review of recent findings related to the role of 15- lipoxygenase enzyme and metabolites in breast cancer growth, apoptosis, metastasis, and invasion as well as their local and circulating expression pattern in patients with breast cancer. Our review supports the emerging role of 15- lipoxygenase in molecular and cellular processes regulating breast tumor cell fate with both positive and negative effects.
Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer
Authors: Pan Xiang , Qi Yuchen , Du Zhen , He Jian , Yao Sheng , Lu Wei , Ding Kefeng , Zhou Min 
Published: November 2021

Abstract
Background
Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy.

Methods
Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer.

Results
Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model.

Conclusions
We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise.

Graphic abstract
Bone morphogenetic protein 2 inhibits growth differentiation factor 8-induced cell signaling via upregulation of gremlin2 expression in human granulosa-lutein cells
Authors: Luo Xiaoyan , Chang Hsun-Ming , Yi Yuyin , Sun Yingpu , Leung Peter C. K. 
Published: November 2021

Abstract
Background
Bone morphogenetic protein 2 (BMP2), growth differentiation factor 8 (GDF8) and their functional receptors are expressed in human ovarian follicles, and these two intrafollicular factors play essential roles in regulating follicle development and luteal function. As BMP antagonists, gremlin1 (GREM1) and gremlin2 (GREM2) suppress BMP signaling through blockage of ligand-receptor binding. However, whether BMP2 regulates the expression of GREM1 and GREM2 in follicular development remains to be determined.

Methods
In the present study, we investigated the effect of BMP2 on the expression of GREM1 and GREM2 and the underlying mechanisms in human granulosa-lutein (hGL) cells. An established immortalized human granulosa cell line (SVOG) and primary hGL cells were used as study models. The expression of GREM1 and GREM2 were examined following cell incubation with BMP2 at different concentrations and time courses. The TGF-β type I inhibitors (dorsomorphin, DMH-1 and SB431542) and small interfering RNAs targeting ALK2, ALK3, SMAD2/3, SMAD1/5/8 and SMAD4 were used to investigate the involvement of the SMAD-dependent pathway.

Results
Our results showed that BMP2 significantly increased the expression of GREM2 (but not GREM1) in a dose- and time-dependent manner. Using a dual inhibition approach combining kinase inhibitors and siRNA-mediated knockdown, we found that the BMP2-induced upregulation of GREM2 expression was mediated by the ALK2/3-SMAD1/5-SMAD4 signaling pathway. Moreover, we demonstrated that BMP2 pretreatment significantly attenuated the GDF8-induced phosphorylation of SMAD2 and SMAD3, and this suppressive effect was reversed by knocking down GREM2 expression.

Conclusions
Our findings provide new insight into the molecular mechanisms by which BMP2 modulates the cellular activity induced by GDF8 through the upregulated expression of their antagonist (GREM2).
A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
Authors: Naderi Elnaz , Crijns Anne Petra Gerarda , Steenbakkers Roel Johannes Henricus Marinus , van den Hoek Johanna Geertruida Maria , Boezen Hendrika Marike , Alizadeh Behrooz Ziad , Langendijk Johannes Albertus 
Published: November 2021

Abstract
Background
Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort.

Methods
A two-stage GWAS was performed in 1279 HNC patients treated with RT and prospectively scored for mucositis, xerostomia, sticky saliva, and dysphagia. The area under the curve (AUC) was used to estimate the average load of toxicity during RT. At the discovery study, multivariate linear regression was used in 957 patients, and the top-ranking SNPs were tested in 322 independent replication cohort. Next, the discovery and the replication studies were meta-analyzed.

Results
A region on 5q21.3 containing 16 SNPs showed genome-wide (GW) significance association at P-value < 5.0 × 10–8 with patient-rated acute xerostomia in the discovery study. The top signal was rs35542 with an adjusted effect size of 0.17*A (95% CI 0.12 to 0.23; P-value <  = 3.78 × 10–9). The genome wide significant SNPs were located within three genes (EFNA5, FBXL17, and FER). In-silico functional analysis showed these genes may be involved in DNA damage response and co-expressed in minor salivary glands. We found 428 suggestive SNPs (P-value < 1.0 × 10–5) for other toxicities, taken to the replication study. Eleven of them showed a nominal association (P-value < 0.05).

Conclusions
This GWAS suggested novel SNPs for patient-rated acute xerostomia in HNC patients. If validated, these SNPs and their related functional pathways could lead to a predictive assay to identify sensitive patients to radiation, which may eventually allow a more individualized RT treatment.