bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal therapies and trials for lysosomal storage diseases: a survey of attitudes of parents and patients
Authors: Schwab Marisa E. , Brown Julia E. H. , Lianoglou Billie , Jin Chengshi , Conroy Patricia C. , Gallagher Renata C. , Harmatz Paul , MacKenzie Tippi C. 
Published: January 2022

Abstract
Background
Lysosomal storage diseases (LSDs) are inherited metabolic disorders that may lead to severe multi-organ disease. Current ERTs are limited by anti-drug antibodies, the blood–brain barrier, and early disease onset and progression before ERT is started. We have opened a phase I clinical trial of enzyme replacement therapy (ERT) for fetuses with LSDs (NCT04532047). We evaluated the attitudes of parents and patients with LSDs towards fetal clinical trials and therapies.

Methods
A multidisciplinary team designed a survey which was distributed by five international patient advocacy groups. We collected patients’ demographic, diagnostic, and treatment information. Associations between respondent characteristics and attitudes towards fetal therapies/trials were analyzed using multivariate ordinal logistic regression.

Results
The survey was completed by 181 adults from 19 countries. The majority of respondents were mothers from the United States. The most common diseases were MPS1 (26%), MPS3 (19%), and infantile-onset Pompe (14%). Most patients (88%) were diagnosed after birth, at a median of 21 months. Altogether, 65% of participating patients and children of participants had received ERT, 27% a stem cell transplant, and 4% gene therapy. We found that half (49%) of respondents were unlikely to terminate a future affected pregnancy, 55% would enroll in a phase I clinical trial for fetal ERT, and 46% would enroll in a fetal gene therapy trial. Respondents who received postnatal ERT were significantly more likely enroll in a trial for fetal ERT or gene therapy (ERT OR 4.48, 95% CI 2.13–9.44, p < 0.0001; gene therapy OR 3.03, 95% CI 1.43–6.43, p = 0.0038). Respondents who used clinicaltrials.gov as a main source of information were more likely to choose to participate in a fetal trial (ERT OR 2.43, 95% CI 1.18–5.01, p = 0.016; gene therapy OR 2.86, 95% CI 1.27–6.46, p = 0.011).

Conclusions
Familiarity with postnatal ERT increased respondents’ likelihood of pursuing fetal therapies. Families who use clinicaltrials.gov may be more receptive to innovative fetal treatments. The patient community has a favorable attitude towards fetal therapy; over half of respondents would enroll in a phase I clinical trial to assess the safety and efficacy of fetal ERT.
Progress of HOTAIR-microRNA in hepatocellular carcinoma
Authors: Wang Bing-rong , Chu Dong-xia , Cheng Mei-yu , Jin Yu , Luo Hao-ge , Li Na 
Published: January 2022

AbstractThe Hox transcript antisense intergenic RNA (HOTAIR) has been identified as a tumor gene, and its expression in HCC is significantly increased. HOTAIR is associated with the proliferation, invasion, metastasis and poor prognosis of HCC. In addition, HOTAIR can also regulate the expression and function of microRNA by recruiting the polycomb repressive complex 2 (PRC2) and competitive adsorption, thus promoting the occurrence and development of HCC. In this review, we discussed the two mechanisms of HOTAIR regulating miRNA through direct binding miRNA and indirect regulation, and emphasized the role of HOTAIR in HCC through miRNA, explained the regulatory pathway of HOTAIR-miRNA-mRNA and introduced the role of this pathway in HCC proliferation, drug resistance, invasion and metastasis.
Identification of parameters and formulation of a statistical and machine learning model to identify Babesia canis infections in dogs using available ADVIA hematology analyzer data
Authors: Pijnacker Tera , Bartels Richard , van Leeuwen Martin , Teske Erik 
Published: January 2022

Abstract
Background
Canine babesiosis is an important tick-borne disease in endemic regions. One of the relevant subspecies in Europe is Babesia canis, and it can cause severe clinical signs such as hemolytic anemia. Apart from acute clinical symptoms dogs can also have a more chronic disease development or be asymptomatic carriers. Our objective was to identify readily available ADVIA hematology analyzer parameters suggestive of B. canis parasitemia in dogs and to formulate a predictive model.

Methods
A historical dataset of complete blood count data from an ADVIA hematology system with blood smear or PCR confirmed parasitemia cases was used to obtain a model by conventional statistics (CS) methods and machine learning (ML) using logistical regression and tree methods.

Results
Both methods identified that important parameters were platelet count, mean platelet volume and percentage large unstained cells. We were able to formulate a CS model and ML model to screen for Babesia parasitemia in dogs with a sensitivity of 84.6% (CS) and 100% (ML), a specificity of 97.7% (CS) and 95.7% (ML) and a positive likelihood ratio (LR+) of 36.78 (CS) and 23.2 (ML).

Conclusions
This study introduces two methods of screening for B. canis parasitemia on readily available data from ADVIA hematology systems. The algorithms can easily be introduced in laboratories that use these analyzers. When the algorithm marks a sample as ‘suggestive’ for Babesia parasitemia, the sample is approximately 37 times more likely to show Babesia merozoites on blood smear analysis.

Graphical Abstract
Plasma 1,5-anhydro-d-glucitol is associated with peripheral nerve function and diabetic peripheral neuropathy in patients with type 2 diabetes and mild-to-moderate hyperglycemia
Authors: Xu Feng , Zhao Li-hua , Wang Xiao-hua , Wang Chun-hua , Yu Chao , Zhang Xiu-lin , Ning Li-yan , Huang Hai-yan , Su Jian-bin , Wang Xue-qin 
Published: January 2022

Abstract
Background
Plasma 1,5-anhydro-d-glucitol (1,5-AG) may be a easily accessible marker for glycemic variability under mild-to-moderate hyperglycemia. The present study was to investigate the association of 1,5-AG with peripheral nerve function and diabetic peripheral neuropathy (DPN) in patients with T2D and mild-to-moderate hyperglycemia.

Methods
We recruited 574 T2D patients with mild-to-moderate hyperglycemia (HbA1c  < 8.0%) for this cross-sectional study, with plasma 1,5-AG synchronously detected. All patients were questioned for neurologic symptoms, examined for neurologic signs and screened for peripheral nerve function. Nerve function included the latency, amplitude and nerve conduction velocity (NCV) of limbs nerves (median, ulnar nerve, common peroneal, superficial peroneal, tibial and sural nerve). Besides, composite Z-score of latency, amplitude and NCV were calculated. DPN was identified as both at least a neurologic symptom/sign and an abnormality of peripheral nerve function.

Results
Among the recruited patients, 23.9% (n  = 137) were identified to be with DPN, and the prevalence of DPN decreased from 36.6%, 24.5%, 21.2%, 13.3% from first (Q1), second (Q2), and third (Q3) to fourth quartile (Q4) of 1,5-AG. Moreover, multivariable linear regression analysis showed 1,5-AG was associated with composite Z-score of nerve latency (β  = − 0.18, t  = − 3.84, p  < 0.001), amplitude(β  =  0.26, t  = 5.35, p  < 0.001) and NCV (β  = 0.24, t  = 5.61, p  < 0.001), respectively. Furthermore, compared to Q4 of 1,5-AG as reference, the adjusted odds ratios and 95% CIs for DPN of Q3, Q2, and Q1 were 1.29(0.59–2.81), 1.85(0.87–3.97), and 2.72(1.16–6.34), respectively. Additionally, receiver operating characteristic analysis revealed that optimal cutoff value of 1,5-AG to indicate DPN was  ≤ 30.8 μmol/L, with sensitivity of 56.20% and specificity of 66.36%.

Conclusions
Low plasma 1,5-AG is closely associated with impaired peripheral nerve function and DPN in T2D patients under mild-to-moderate hyperglycemia.
Single-cell RNA sequencing to track novel perspectives in HSC heterogeneity
Authors: Zhang Pan , Li Xiang , Pan Chengwei , Zheng Xinmin , Hu Bohan , Xie Ruiheng , Hu Jialu , Shang Xuequn , Yang Hui 
Published: January 2022

AbstractAs the importance of cell heterogeneity has begun to be emphasized, single-cell sequencing approaches are rapidly adopted to study cell heterogeneity and cellular evolutionary relationships of various cells, including stem cell populations. The hematopoietic stem and progenitor cell (HSPC) compartment contains HSC hematopoietic stem cells (HSCs) and distinct hematopoietic cells with different abilities to self-renew. These cells perform their own functions to maintain different hematopoietic lineages. Undeniably, single-cell sequencing approaches, including single-cell RNA sequencing (scRNA-seq) technologies, empower more opportunities to study the heterogeneity of normal and pathological HSCs. In this review, we discuss how these scRNA-seq technologies contribute to tracing origin and lineage commitment of HSCs, profiling the bone marrow microenvironment and providing high-resolution dissection of malignant hematopoiesis, leading to exciting new findings in HSC biology.
Advancing universal health coverage in the COVID-19 era: an assessment of public health services technical efficiency and applied cost allocation in Cambodia
Authors: Kolesar Robert John , Bogetoft Peter , Chea Vanara , Erreygers Guido , Pheakdey Sambo 
Published: January 2022

Abstract
Background
Achieving universal health coverage (UHC) is a global priority and a keystone element of the 2030 Sustainable Development Goals. However, COVID-19 is causing serious impacts on tax revenue and many countries are facing constraints to new investment in health. To advance UHC progress, countries can also focus on improving health system technical efficiency to maximize the service outputs given the current health financing levels.

Methods
This study assesses Cambodia’s public health services technical efficiency, unit costs, and utilization rates to quantify the extent to which current health financing can accommodate the expansion of social health protection coverage. This study employs Data Envelopment Analysis (DEA), truncated regression, and pioneers the application of DEA Aumann-Shapley applied cost allocation to the health sector, enabling unit cost estimation for the major social health insurance payment categories.

Results
Overall, for the public health system to be fully efficient output would need to increase by 34 and 73% for hospitals and health centers, respectively. We find public sector service quality, private sector providers, and non-discretionary financing to be statistically significant factors affecting technical efficiency. We estimate there is potential supply-side ‘service space’ to expand population coverage to an additional 4.69 million social health insurance beneficiaries with existing financing if the public health system were fully efficient.

Conclusions
Public health service efficiency in Cambodia can be improved by increasing utilization of cost-effective services. This can be achieved by enrolling more beneficiaries into the social health insurance schemes with current supply-side financing levels. Other factors that can lead to increased efficiency are improving health service quality, regulating private sector providers, focusing on discretionary health financing, and incentivizing a referral system.
L-carnitine does not improve valproic acid poisoning management: a cohort study with toxicokinetics and concentration/effect relationships
Authors: Nguyen Philippe , Chevillard Lucie , Gouda Ahmed S. , Gourlain Hervé , Labat Laurence , Malissin Isabelle , Deye Nicolas , Voicu Sebastian , Mégarbane Bruno 
Published: January 2022

AbstractBackgroundValproic acid (VPA) poisoning is responsible for life-threatening neurological and metabolic impairments. Despite only low-level evidence of effectiveness, L-carnitine has been used for years to prevent or reverse VPA-related toxicity. We aimed to evaluate the effects of L-carnitine used to treat acute VPA poisoning on the time-course of plasma VPA concentrations and VPA-related toxicity. We designed a single-center cohort study including all VPA-poisoned patients admitted to the intensive care unit. We studied VPA toxicokinetics using a nonlinear mixed-effects model-based population approach and modeled individual plasma VPA/blood lactate concentration relationships. Then, we evaluated L-carnitine-attributed effects by comparing VPA elimination half-lives and time-courses of blood lactate levels and organ dysfunction [assessed by the Sequential Organ Failure Assessment (SOFA) score] between matched L-carnitine-treated and non-treated patients using a multivariate analysis including a propensity score.ResultsSixty-nine VPA-poisoned patients (40F/29 M; age, 41 years [32–47]) (median [25th–75th percentiles]; SOFA score, 4 [1–6]) were included. The presumed VPA ingested dose was 15 g [10–32]. Plasma VPA concentration on admission was 231 mg/L [147–415]. The most common manifestations were coma (70%), hyperlactatemia (3.9 mmol/L [2.7–4.9]) and hyperammonemia (127 mmol/L [92–159]). VPA toxicokinetics well fitted a one-compartment linear model with a mean elimination half-life of 22.9 h (coefficient of variation, 28.1%). Plasma VPA (C)/blood lactate concentration (E) relationships were well described by an exponential growth equation [$$E={E}_{0}\times {e}^{k\cdot C}$$E=E0×ek·C; with baselineE0 = 1.3 mmol/L (43.9%) and rate constant of the effect,k = 0.003 L/mg (59.5%)]. Based on a multivariate analysis, peak blood lactate concentration was the only factor independently associated with L-carnitine administration (odds ratio, 1.9, 95% confidence interval, 1.2–2.8;P = 0.004). We found no significant contribution of L-carnitine to enhancing VPA elimination, accelerating blood lactate level normalization and/or preventing organ dysfunction.ConclusionsVPA poisoning results in severe toxicity. While L-carnitine does not contribute to enhancing VPA clearance, its impact on accelerating blood lactate level normalization and/or preventing organ dysfunction remains uncertain. Investigating VPA toxicokinetics and concentration/effect relationships may help understanding how to improve VPA-poisoned patient management.
Quantization-aware sampling set selection for bandlimited graph signals
Authors: Kim Yoon Hak 
Published: January 2022

AbstractWe consider a scenario in which nodes of a graph are sampled for bandlimited graph signals which are uniformly quantized with optimal rate and original signals are reconstructed from the quantized signal values residing on the nodes in the sampling set. We seek to construct the best sampling set in a greedy manner that minimizes the average reconstruction error. We manipulate the reconstruction error by using the QR factorization and derive an analytic result stating that the next minimizing node can be iteratively selected by finding the one that minimizes the geometric mean of the row vectors of the inverse upper triangular matrix $$\mathbf {R}^{-1}$$

R

-
1

in the QR factorization. We also compare the complexity of the proposed algorithm with different sampling methods and evaluate the performance of the proposed algorithm by experiments for various graphs, showing the superiority to the existing sampling methods when quantization is involved.
A delayed plant disease model with Caputo fractional derivatives
Authors: Kumar Pushpendra , Baleanu Dumitru , Erturk Vedat Suat , Inc Mustafa , Govindaraj V. 
Published: January 2022

AbstractWe analyze a time-delay Caputo-type fractional mathematical model containing the infection rate of Beddington–DeAngelis functional response to study the structure of a vector-borne plant epidemic. We prove the unique global solution existence for the given delay mathematical model by using fixed point results. We use the Adams–Bashforth–Moulton P-C algorithm for solving the given dynamical model. We give a number of graphical interpretations of the proposed solution. A number of novel results are demonstrated from the given practical and theoretical observations. By using 3-D plots we observe the variations in the flatness of our plots when the fractional order varies. The role of time delay on the proposed plant disease dynamics and the effects of infection rate in the population of susceptible and infectious classes are investigated. The main motivation of this research study is examining the dynamics of the vector-borne epidemic in the sense of fractional derivatives under memory effects. This study is an example of how the fractional derivatives are useful in plant epidemiology. The application of Caputo derivative with equal dimensionality includes the memory in the model, which is the main novelty of this study.
COVID-19 cases, hospitalizations and deaths in Belgian nursing homes: results of a surveillance conducted between April and December 2020
Authors: Vandael Eline , Latour Katrien , Islamaj Esma , Panis Laura Int , Callies Milena , Haarhuis Freek , Proesmans Kristiaan , Devleesschauwer Brecht , Rebolledo Gonzalez Javiera , Hannecart Alice , Mahieu Romain , de Viron Louise , De Clercq Etienne , Kongs Anne , Hammami Naïma , François Jean-Marc , Dubourg Dominique , Henz Sarah , Catry Boudewijn , Dequeker Sara 
Published: January 2022

Abstract
Background
In Belgium, the first COVID-19 death was reported on 10 March 2020. Nursing home (NH) residents are particularly vulnerable for COVID-19, making it essential to follow-up the spread of COVID-19 in this setting. This manuscript describes the methodology of surveillance and epidemiology of COVID-19 cases, hospitalizations and deaths in Belgian NHs.

Methods
A COVID-19 surveillance in all Belgian NHs (n = 1542) was set up by the regional health authorities and Sciensano. Aggregated data on possible/confirmed COVID-19 cases and hospitalizations and case-based data on deaths were reported by NHs at least once a week. The study period covered April–December 2020. Weekly incidence/prevalence data were calculated per 1000 residents or staff members.

Results
This surveillance has been launched within 14 days after the first COVID-19 death in Belgium. Automatic data cleaning was installed using different validation rules. More than 99% of NHs participated at least once, with a median weekly participation rate of 95%. The cumulative incidence of possible/confirmed COVID-19 cases among residents was 206/1000 in the first wave and 367/1000 in the second wave. Most NHs (82%) reported cases in both waves and 74% registered ≥10 possible/confirmed cases among residents at one point in time. In 51% of NHs, at least 10% of staff was absent due to COVID-19 at one point. Between 11 March 2020 and 3 January 2021, 11,329 COVID-19 deaths among NH residents were reported, comprising 57% of all COVID-19 deaths in Belgium in that period.

Conclusions
This surveillance was crucial in mapping COVID-19 in this vulnerable setting and guiding public health interventions, despite limitations of aggregated data and necessary changes in protocol over time. Belgian NHs were severely hit by COVID-19 with many fatal cases. The measure of not allowing visitors, implemented in the beginning of the pandemic, could not avoid the spread of SARS-CoV-2 in the NHs during the first wave. The virus was probably often introduced by staff. Once the virus was introduced, it was difficult to prevent healthcare-associated outbreaks. Although, in contrast to the first wave, personal protective equipment was available in the second wave, again a high number of cases were reported.
Communication and innovation in the performance of weaving and pottery crafts in Gojjam, Ethiopia
Authors: Dessie Wondifraw Mihret , Mengistu Gojjam Ademe , Mulualem Tigist Abera 
Published: January 2022

AbstractCompetitive organizations harness information and knowledge sharing undertakings to take risks and break customary routines. This study investigates craftspeople’s communication practices and innovation implementation towards improving business performance. Cross-sectional survey research design was employed to describe and see the association of communication and innovation with business performance. Data were collected from a sample of 326 craftspeople through structured questionnaire and field observation. Both descriptive and Structural Equation Modeling (SEM) statistics were mainly used to analyze data. Findings revealed that communication practices vital for craftspeople to be innovative and integrate them with clients were negligible. The communication flaws in turn resulted in stagnant and in-house limited trifling inventiveness in craft industries. Moreover, reflexivity, frequency of communication on creativity, product and market innovation were significantly associated with craftspeople’s performance. Hence, it is recommended to arrange training and experience sharing schemes for craftspeople to enhance their communication and innovation skills thereby improve performance.
Long-read metagenomic sequencing reveals shifts in associations of antibiotic resistance genes with mobile genetic elements from sewage to activated sludge
Authors: Dai Dongjuan , Brown Connor , Bürgmann Helmut , Larsson D. G. Joakim , Nambi Indumathi , Zhang Tong , Flach Carl-Fredrik , Pruden Amy , Vikesland Peter J. 
Published: January 2022

Abstract
Background
There is concern that the microbially rich activated sludge environment of wastewater treatment plants (WWTPs) may contribute to the dissemination of antibiotic resistance genes (ARGs). We applied long-read (nanopore) sequencing to profile ARGs and their neighboring genes to illuminate their fate in the activated sludge treatment by comparing their abundance, genetic locations, mobility potential, and bacterial hosts within activated sludge relative to those in influent sewage across five WWTPs from three continents.

Results
The abundances (gene copies per Gb of reads, aka gc/Gb) of all ARGs and those carried by putative pathogens decreased 75–90% from influent sewage (192-605 gc/Gb) to activated sludge (31-62 gc/Gb) at all five WWTPs. Long reads enabled quantification of the percent abundance of ARGs with mobility potential (i.e., located on plasmids or co-located with other mobile genetic elements (MGEs)). The abundance of plasmid-associated ARGs decreased at four of five WWTPs (from 40–73 to 31–68%), and ARGs co-located with transposable, integrative, and conjugative element hallmark genes showed similar trends. Most ARG-associated elements decreased 0.35–13.52% while integrative and transposable elements displayed slight increases at two WWTPs (1.4–2.4%). While resistome and taxonomic compositions both shifted significantly, host phyla for chromosomal ARG classes remained relatively consistent, indicating vertical gene transfer via active biomass growth in activated sludge as the key pathway of chromosomal ARG dissemination.

Conclusions
Overall, our results suggest that the activated sludge process acted as a barrier against the proliferation of most ARGs, while those that persisted or increased warrant further attention.