bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoglycemia with lactic acidosis caused by a new MRPS2 gene mutation in a Chinese girl: a case report
Authors: Liu ChangZhi , Zhou WeiRan , Liu QuanE , Peng ZaiXin 
Published: January 2022

Abstract
Background
Mitochondrial ribosomal protein S2 (MRPS2) gene mutation, which is related to severe hypoglycemia and lactic acidosis, is rarely reported globally.

Case presentation
We report a case of a new MRPS2 gene mutation in a Chinese girl who presented with hypoglycemia and lactic acidosis. A homozygous C.412C > G variant that could cause complex oxidative phosphorylation deficiency and had not been reported before was identified. The clinical manifestations included recurrent vomiting, hypoglycemia, lactic acidosis, sensorineural hearing loss, and gall bladder calculi. Hypoglycemia and lactic acidosis improved after the administration of sugary liquid and supportive treatments.

Conclusions
Recurrent hypoglycemia with lactic acidosis and sensorineural hearing loss should lead to suspicion of mitochondrial defects and the early refinement of genetic tests.
Vitamin D deficiency associations with metabolic, bone turnover and adverse general health markers in community free living adults
Authors: Gariballa Salah , Yasin Javed , Abluwi Ghada , Al Essa Awad 
Published: January 2022

Abstract
Background
Although there is some evidence that vitamin D deficiency is highly prevalent in the Middle East, however its health impact is still not clear. The aim of this study was to assess the prevalence, causes and health implications of vitamin D deficiency in local United Arab Emirates (UAE) citizens.

Methods
A cross-sectional study was conducted on community free living adults living in the city of Al Ain, UAE. Following informed written consent eligible subject’s blood and urine samples were taken for measurements of vitamin D [25(OH)D], metabolic and bone turnover markers. Clinical assessment that includes general and self-rated health, muscle health, and physical activity were also performed.

Results
A total of 648 subjects (491 female) were included in this analysis. Their mean (SD) age was 38 (12) years. Mean 25(OH)D was 24 ng/ml (range: 4–67) with 286 (44%) subjects found to have vitamin D deficiency (< 20 ng/ml), 234 (36%) subjects have insufficiency (20-32 ng/ml) and 128 (20%) subjects have optimal concentrations (> 32 ng/ml). 25(OH)D concentrations were significantly higher in local indigenous UAE subjects compared to other Arab expatriates (p = 0.071). Although there were no statistically significant differences in clinical markers between groups, however, utra-sensitive C-reactive protein (us-CRP), parathyroid hormone (PTH), body mass index (BMI) and the bone markers U-PYD and PYD/CR were higher in vitamin D deficient older subjects aged ≥50 years and female subjects younger than 50 years respectively compared to those with insufficiency or optimal concentrations (p value < 0.05. Multiple logistic regression analysis revealed significant and independent association between 25(OH)D status and age and sex (p < 0.05).

Conclusion
Older subjects with vitamin D deficiency have increased BMI, inflammation and PTH compared with those with insufficiency or optimal concentrations. Co-existence of obesity and vitamin D deficiency may have increased adverse health effects.
Preference for initiation of end-of-life care discussion in Indonesia: a quantitative study
Authors: Eng Venita , Hewitt Victoria , Kekalih Aria 
Published: January 2022

Abstract
Background
Initiating discussion about death and dying is often considered a difficult topic for healthcare providers, thus there is a need for further research to understand this area, particularly in developing countries. The aim of this study was to describe preferences for the initiation of end-of-life care discussions in Indonesia, comparing the general population and health care professionals.

Methods
This cross-sectional, descriptive study analysed quantitative data from 368 respondents to an online questionnaire (255 general population (69%); 113 healthcare professionals (31%)) utilizing consecutive sampling and snowball sampling methods.

Results
Overall, most respondents (80%) stated that they would like to discuss end-of-life issues with a healthcare professional in the case of terminal illness. This was more marked amongst healthcare professionals compared with the general population (94% vs. 75%, respectively, p < 0,001). The preferred time for discussion was at first diagnosis (68% general population, 52% healthcare professionals, p = 0.017) and the preferred person to start the discussion was the doctor (59% general population, 71% healthcare professionals, p = 0.036). Fewer respondents wanted to know about prognosis compared to diagnosis (overall 76% v 93% respectively).

Conclusion
Doctors have vital role in end-of-life care discussion, and attempts should be made to encourage physicians to initiate these conversations and respond to patient’s requests when needed. These findings contribute to the existing body of knowledge in this area of practice, with focus on a developing country. The role of socio-cultural influences on these conversations warrants further research, in order to develop practical resources to support clinicians to appropriately conduct end-of-life care discussions with their patients and to provide data for policymakers to develop services.
Priority and age specific vaccination algorithm for the pandemic diseases: a comprehensive parametric prediction model
Authors: Tutsoy Onder , Tanrikulu Mahmud Yusuf 
Published: January 2022

Abstract
Background
There have been several destructive pandemic diseases in the human history. Since these pandemic diseases spread through human-to-human infection, a number of non-pharmacological policies has been enforced until an effective vaccine has been developed. In addition, even though a vaccine has been developed, due to the challenges in the production and distribution of the vaccine, the authorities have to optimize the vaccination policies based on the priorities. Considering all these facts, a comprehensive but simple parametric model enriched with the pharmacological and non-pharmacological policies has been proposed in this study to analyse and predict the future pandemic casualties.

Method
This paper develops a priority and age specific vaccination policy and modifies the non-pharmacological policies including the curfews, lockdowns, and restrictions. These policies are incorporated with the susceptible, suspicious, infected, hospitalized, intensive care, intubated, recovered, and death sub-models. The resulting model is parameterizable by the available data where a recursive least squares algorithm with the inequality constraints optimizes the unknown parameters. The inequality constraints ensure that the structural requirements are satisfied and the parameter weights are distributed proportionally.

Results
The results exhibit a distinctive third peak in the casualties occurring in 40 days and confirm that the intensive care, intubated, and death casualties converge to zero faster than the susceptible, suspicious, and infected casualties with the priority and age specific vaccination policy. The model also estimates that removing the curfews on the weekends and holidays cause more casualties than lifting the restrictions on the people with the chronic diseases and age over 65.

Conclusion
Sophisticated parametric models equipped with the pharmacological and non-pharmacological policies can predict the future pandemic casualties for various cases.
Elevated levels of interleukin-12/23p40 may serve as a potential indicator of dysfunctional heart rate variability in type 2 diabetes
Authors: Wegeberg A. M. , Okdahl T. , Riahi S. , Ejskjaer N. , Pociot F. , Størling J. , Brock B. , Brock C. 
Published: January 2022

AbstractBackgroundSystemic inflammatory processes plausibly contribute to the development of cardiovascular complications, causing increased morbidity and mortality in type 2 diabetes. Circulating inflammatory markers, i.e., interleukin (IL)-6 and tumour necrosis factor-α, are associated with neurocardiac measures. We examined a broad panel of various inflammatory and inflammation-related serum markers to obtain more detailed insight into the possible neuro-immune interaction between cardiovascular regulation and systemic level of inflammation.MethodsSerum samples from 100 participants with type 2 diabetes were analysed. Heart rate variability, cardiovascular autonomic reflex tests, and cardiac vagal tone tests were performed based on electrocardiographic readings. Data regarding covariates (demographic-, diabetes-, and cardiovascular risk factors) were registered.ResultsIncreased serum levels of IL-12/IL-23p40 (p  < 0.01) and intercellular adhesion molecule (ICAM)-1 (p  < 0.007) were associated with diminished heart rate variability measures. After all adjustments, the associations between IL-12/23p40, SDANN and VLF persisted (p  = 0.001). Additionally, serum levels of vascular endothelial growth factor (VEGF)-C were associated with response to standing (p  = 0.005).DiscussionThe few but robust associations between neurocardiac regulation and serum markers found in this study suggest systemic changes in proinflammatory, endothelial, and lymphatic function, which collectively impacts the systemic cardiovascular function. Our results warrant further exploration of IL-12/IL-23p40, ICAM-1, and VEGF-C as possible cardiovascular biomarkers in T2D that may support future decisions regarding treatment strategies for improved patient care.
Evaluation of the long-term prognostic ability of triglyceride-glucose index for elderly acute coronary syndrome patients: a cohort study
Authors: Jiao Yang , Su Yongkang , Shen Jian , Hou Xiaoling , Li Ying , Wang Jihang , Liu Bing , Qiu Dongfeng , Sun Zhijun , Chen Yundai , Xi Qing , Shen Mingzhi , Fu Zhenhong 
Published: January 2022

Abstract
Background
With the advancement of the world population aging, more attention should be paid to the prognosis of elderly patients with acute coronary syndrome (ACS). Triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance (IR) and is closely related to traditional risk factors of cardiovascular disease (CVD). However, the effect of TyG index on the prognosis of long-term adverse events in elderly ACS patients has not been reported. This study evaluated the prognostic power of TyG index in predicting adverse events in elderly ACS patients.

Methods
In this study, 662 ACS patients > 80 years old who were hospitalized from January 2006 to December 2012 were enrolled consecutively and the general clinical data and baseline blood biochemical indicators were collected. The follow-up time after discharge was 40–120 months (median, 63 months; interquartile range, 51‒74 months). In addition, the following formula was used to calculate the TyG index: Ln [fasting TG (mg/dL) × FBG (mg/dL)/2], and patients were divided into three groups according to the tertile of the TyG index.

Results
The mean age of the subjects was 81.87 ± 2.14 years, the proportion of females was 28.10%, and the mean TyG index was 8.76 ± 0.72. The TyG index was closely associated with the traditional risk factors of CVD. In the fully-adjusted Cox regression model, the Hazard ratio (95% CI) of all-cause mortality (in tertile 3) was 1.64 (1.06, 2.54) and major adverse cardiac event (MACE) (in tertile 3) was 1.36 (1.05, 1.95) for each SD increase in the TyG index. The subgroup analyses also confirmed the significant association of the TyG index and long-term prognosis.

Conclusion
The TyG index is an independent predictor of long-term all-cause mortality and MACE in elderly ACS patients.
Light-induced production of isobutanol and 3-methyl-1-butanol by metabolically engineered cyanobacteria
Authors: Kobayashi Shunichi , Atsumi Shota , Ikebukuro Kazunori , Sode Koji , Asano Ryutaro 
Published: January 2022

Abstract
Background
Cyanobacteria are engineered via heterologous biosynthetic pathways to produce value-added chemicals via photosynthesis. Various chemicals have been successfully produced in engineered cyanobacteria. Chemical inducer-dependent promoters are used to induce the expression of target biosynthetic pathway genes. A chemical inducer is not ideal for large-scale reactions owing to its high cost; therefore, it is important to develop scaling-up methods to avoid their use. In this study, we designed a green light-inducible alcohol production system using the CcaS/CcaR green light gene expression system in the cyanobacterium Synechocystis sp. PCC 6803 (PCC 6803).

Results
To establish the green light-inducible production of isobutanol and 3-methyl-1-butanol (3MB) in PCC 6803, keto-acid decarboxylase (kdc) and alcohol dehydrogenase (adh) were expressed under the control of the CcaS/CcaR system. Increases in the transcription level were induced by irradiation with red and green light without severe effects on host cell growth. We found that the production of isobutanol and 3MB from carbon dioxide (CO2) was induced under red and green light illumination and was substantially repressed under red light illumination alone. Finally, production titers of isobutanol and 3MB reached 238 mg L−1 and 75 mg L−1, respectively, in 5 days under red and green light illumination, and these values are comparable to those reported in previous studies using chemical inducers.

Conclusion
A green light-induced alcohol production system was successfully integrated into cyanobacteria to produce value-added chemicals without using expensive chemical inducers. The green light-regulated production of isobutanol and 3MB from CO2 is eco-friendly and cost-effective. This study demonstrates that light regulation is a potential tool for producing chemicals and increases the feasibility of cyanobacterial bioprocesses.

Graphical Abstract
Functional characterization of 5′ UTR cis-acting sequence elements that modulate translational efficiency in Plasmodium falciparum and humans
Authors: Garcia Valentina E. , Dial Rebekah , DeRisi Joseph L. 
Published: January 2022

Abstract
Background
The eukaryotic parasite Plasmodium falciparum causes millions of malarial infections annually while drug resistance to common anti-malarials is further confounding eradication efforts. Translation is an attractive therapeutic target that will benefit from a deeper mechanistic understanding. As the rate limiting step of translation, initiation is a primary driver of translational efficiency. It is a complex process regulated by both cis and trans acting factors, providing numerous potential targets. Relative to model organisms and humans, P. falciparum mRNAs feature unusual 5′ untranslated regions suggesting cis-acting sequence complexity in this parasite may act to tune levels of protein synthesis through their effects on translational efficiency.

Methods
Here, in vitro translation is deployed to compare the role of cis-acting regulatory sequences in P. falciparum and humans. Using parasite mRNAs with high or low translational efficiency, the presence, position, and termination status of upstream “AUG”s, in addition to the base composition of the 5′ untranslated regions, were characterized.

Results
The density of upstream “AUG”s differed significantly among the most and least efficiently translated genes in P. falciparum, as did the average “GC” content of the 5′ untranslated regions. Using exemplars from highly translated and poorly translated mRNAs, multiple putative upstream elements were interrogated for impact on translational efficiency. Upstream “AUG”s were found to repress translation to varying degrees, depending on their position and context, while combinations of upstream “AUG”s had non-additive effects. The base composition of the 5′ untranslated regions also impacted translation, but to a lesser degree. Surprisingly, the effects of cis-acting sequences were remarkably conserved between P. falciparum and humans.

Conclusions
While translational regulation is inherently complex, this work contributes toward a more comprehensive understanding of parasite and human translational regulation by examining the impact of discrete cis-acting features, acting alone or in context.
Evaluating performance of multiplex real time PCR for the diagnosis of malaria at elimination targeted low transmission settings of Ethiopia
Authors: Belachew Mahlet , Wolde Mistire , Nega Desalegn , Gidey Bokretsion , Negash Legessie , Assefa Ashenafi , Tasew Geremew , Woyessa Adugna , Abera Adugna 
Published: January 2022

Abstract
Background
Malaria incidence has declined in Ethiopia in the past 10 years. Current malaria diagnostic tests, including light microscopy and rapid antigen-detecting diagnostic tests (RDTs) cannot reliably detect low-density infections. Studies have shown that nucleic acid amplification tests are highly sensitive and specific in detecting malaria infection. This study took place with the aim of evaluating the performance of multiplex real time PCR for the diagnosis of malaria using patient samples collected from health facilities located at malaria elimination targeted low transmission settings in Ethiopia.

Methods
A health facility-based, cross-sectional survey was conducted in selected malaria sentinel sites. Malaria-suspected febrile outpatients referred to laboratory for malaria testing between December 2019 and March 2020 was enrolled into this study. Sociodemographic information and capillary blood samples were collected from the study participants and tested at spot with RDTs. Additionally, five circles of dry blood spot (DBS) samples on Whatman filter paper and thick and thin smear were prepared for molecular testing and microscopic examination, respectively. Multiplex real time PCR assay was performed at Ethiopian Public Health Institute (EPHI) malaria laboratory. The performance of multiplex real time PCR assay, microscopy and RDT for the diagnosis of malaria was compared and evaluated against each other.

Results
Out of 271 blood samples, multiplex real time PCR identified 69 malaria cases as Plasmodium falciparum infection, 16 as Plasmodium vivax and 3 as mixed infections. Of the total samples, light microscopy detected 33 as P. falciparum, 18 as P. vivax, and RDT detected 43 as P. falciparum, 17 as P. vivax, and one mixed infection. Using light microscopy as reference test, the sensitivity and specificity of multiplex real time PCR were 100% (95% CI (93–100)) and 83.2% (95% CI (77.6–87.9)), respectively. Using multiplex real time PCR as a reference, light microscopy and RDT had sensitivity of 58% (95% CI 46.9–68.4) and 67% (95% CI 56.2–76.7); and 100% (95% CI 98–100) and 98.9% (95% CI 96–99.9), respectively. Substantial level of agreement was reported between microscopy and multiplex real time PCR results with kappa value of 0.65.

Conclusions
Multiplex real-time PCR had an advanced performance in parasite detection and species identification on febrile patients’ samples than did microscopy and RDT in low malaria transmission settings. It is highly sensitive malaria diagnostic method that can be used in malaria elimination programme, particularly for community based epidemiological samples. Although microscopy and RDT had reduced performance when compared to multiplex real time PCR, still had an acceptable performance in diagnosis of malaria cases on patient samples at clinical facilities.
Ultrasensitive dynamic light scattering immunosensing platform for NT-proBNP detection using boronate affinity amplification
Authors: Hu Jiaqi , Ding Lu , Chen Jing , Fu Jinhua , Zhu Kang , Guo Qian , Huang Xiaolin , Xiong Yonghua 
Published: January 2022

AbstractHerein, we reported a new dynamic light scattering (DLS) immunosensing technology for the rapid and sensitive detection of glycoprotein N-terminal pro-brain natriuretic peptide (NT-proBNP). In this design, the boronate affinity recognition based on the interaction of boronic acid ligands and cis-diols was introduced to amplify the nanoparticle aggregation to enable highly sensitive DLS transduction, thereby lowering the limit of detection (LOD) of the methodology. After covalently coupling with antibodies, magnetic nanoparticles (MNPs) were employed as the nanoprobes to selectively capture trace amount of NT-proBNP from complex samples and facilitate DLS signal transduction. Meanwhile, silica nanoparticles modified with phenylboronic acid (SiO2@PBA) were designed as the crosslinking agent to bridge the aggregation of MNPs in the presence of target NT-proBNP. Owing to the multivalent and fast affinity recognition between NT-proBNP containing cis-diols and SiO2@PBA, the developed DLS immunosensor exhibited charming advantages over traditional immunoassays, including ultrahigh sensitivity with an LOD of 7.4 fg mL−1, fast response time (< 20 min), and small sample consumption (1 μL). The DLS immunosensor was further characterized with good selectivity, accuracy, precision, reproducibility, and practicability. Collectively, this work demonstrated the promising application of the designed boronate affinity amplified-DLS immunosensor for field or point-of-care testing of cis-diol-containing molecules.
Graphical Abstract
Extracellular matrix-degrading STING nanoagonists for mild NIR-II photothermal-augmented chemodynamic-immunotherapy
Authors: Zhan Meixiao , Yu Xiangrong , Zhao Wei , Peng Yongjun , Peng Shaojun , Li Jingchao , Lu Ligong 
Published: January 2022

AbstractRegulation of stimulator of interferon genes (STING) pathway using agonists can boost antitumor immunity for cancer treatment, while the rapid plasma clearance, limited membrane permeability, and inefficient cytosolic transport of STING agonists greatly compromise their therapeutic efficacy. In this study, we describe an extracellular matrix (ECM)-degrading nanoagonist (dNAc) with second near-infrared (NIR-II) light controlled activation of intracellular STING pathway for mild photothermal-augmented chemodynamic-immunotherapy of breast cancer. The dNAc consists of a thermal-responsive liposome inside loading with ferrous sulfide (FeS2) nanoparticles as both NIR-II photothermal converters and Fenton catalysts, 2′3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) as the STING agonist, and an ECM-degrading enzyme (bromelain) on the liposome surface. Mild heat generated by dNAc upon NIR-II photoirradiation improves Fenton reaction efficacy to kill tumor cells and cause immunogenic cell death (ICD). Meanwhile, the generated heat triggers a controlled release of cGAMP from thermal-responsive liposomes to active STING pathway. The mild photothermal activation of STING pathway combined with ICD promotes anti-tumor immune responses, which leads to improved infiltration of effector T cells into tumor tissues after bromelain-mediated ECM degradation. As a result, after treatment with dNAc upon NIR-II photoactivation, both primary and distant tumors in a murine mouse model are inhibited and the liver and lung metastasis are effectively suppressed. This work presents a photoactivatable system for STING pathway and combinational immunotherapy with improved therapeutic outcome.
Graphical Abstract