bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repression of the expression of proinflammatory genes by mitochondrial transcription factor A is linked to its alternative splicing regulation in human lung epithelial cells
Authors: Luo Jinsong , Liu Hong , Li Daniel K. Jun , Song Bin , Zhang Yi 
Published: December 2021

Abstract
Background
Mitochondrial transcription factor A (TFAM) is associated with a number of neurodegenerative diseases and also with asthma. TFAM deficiency-induced mitochondrial DNA stress primes the antiviral innate immune response in mouse embryonic fibroblasts. However, the role of TFAM in asthma related inflammation remains obscure. The purpose of this study was to investigate the regulatory mechanism of TFAM in asthma.

Results
In this study, we overexpressed TFAM in human lung epithelial cells (A549), then obtained the TFAM-regulated transcriptome by Illumina sequencing technology. Transcriptome analysis revealed that TFAM overexpression down-regulated and up-regulated the expression of 642 and 169 differentially expressed genes (DEGs), respectively. The TFAM-repressed genes were strongly enriched in cytokine-mediated signaling pathway, type I interferon- and INF-γ-mediated signaling pathways, and viral response pathways. We also revealed that 2563 alternative splicing events in 1796 alternative splicing genes (ASGs) were de-regulated upon TFAM overexpression. These TFAM-responding ASGs were enriched in DNA repair, nerve growth factor receptor signaling pathway, and also transcription regulation. Further analysis revealed that the promoters of TFAM-repressed DEGs were enriched by DNA binding motifs of transcription factors whose alternative splicing was regulated by TFAM.

Conclusions
These findings suggest that TFAM regulates not only immune response gene expression in human lung epithelial cells, but also pre-mRNA alternative splicing which may mediate transcriptional regulation; this TFAM-centered gene regulation network could be targeted in developing therapies against various diseases.
Saccharomyces boulardii improves the behaviour and emotions of spastic cerebral palsy rats through the gut-brain axis pathway
Authors: Tao Deshuang , Zhong Tangwu , Pang Wei , li Xiaojie 
Published: December 2021

AbstractBackgroundCerebral palsy (CP) is a kind of disability that influences motion, and children with CP also exhibit depression-like behaviour. Inflammation has been recognized as a contributor to CP and depression, and some studies suggest that the gut-brain axis may be a contributing factor. Our team observed that Saccharomyces boulardii (S. boulardii) could reduce the inflammatory level of rats with hyperbilirubinemia and improve abnormal behaviour. Both CP and depression are related to inflammation, and probiotics can improve depression by reducing inflammation. Therefore, we hypothesize that S. boulardii may improve the behaviour and emotions of spastic CP rats through the gut-brain axis pathway.MethodsOur new rat model was produced by resecting the cortex and subcortical white matter. Seventeen-day-old CP rats were exposed to S. boulardii or vehicle control by gastric gavage for 9 days, and different behavioural domains and general conditions were tested. Inflammation was assessed by measuring the inflammatory markers IL-6 and TNF-α. Hypothalamic–pituitary–adrenal (HPA) axis activity was assessed by measuring adrenocorticotropic hormone and corticosterone in the serum. Changes in the gut microbiome were detected by 16S rRNA.ResultsThe hemiplegic spastic CP rats we made with typical spastic paralysis exhibited depression-like behaviour. S. boulardii treatment of hemiplegic spastic CP rats improves behaviour and general conditions and significantly reduces the level of inflammation, decreases HPA axis activity, and increases gut microbiota diversity.ConclusionsThe model developed in this study mimics a hemiplegic spastic cerebral palsy. Damage to the cortex and subcortical white matter of 17-day-old Sprague–Dawley (SD) rats led to spastic CP-like behaviour, and the rats exhibited symptoms of depression-like behaviour. Our results indicate that S. boulardii might have potential in treating hemiplegic spastic CP rat models or as an add-on therapy via the gut-brain axis pathway.
Comparative transcriptome analysis reveals compatible and recalcitrant genotypic response of barley microspore-derived embryogenic callus toward Agrobacterium infection
Authors: Li Yingbo , Guo Guimei , Xu Hongwei , He Ting , Zong Yingjie , Zhang Shuwei , Faheem Muhammad , Lu Ruiju , Zhou Longhua , Liu Chenghong 
Published: December 2021

AbstractBackgroundTheAgrobacteriummediated transformation has been routinely used in lots of plant species as a powerful tool to deliver genes of interest into a host plant. However, the transformation of elite and commercially valuable cultivar is still limited by the genotype-dependency, and the efficiency ofAgrobacteriuminfection efficiency is crucial for the success of transformation.ResultsIn this study, the microspore-derived embryogenic calli (MDEC) of barley elite cultivars and breeding lines were employed as unique subjects to characterize the genotypic response duringAgrobacteriuminfection process. Our results identified compatible barley genotypes (GanPi 6 and L07, assigned as GP6-L07 group) and one recalcitrant genotype (Hong 99, assigned as H99) for theAgrobacteriumstrain LBA4404 infection using GUS assay. The accumulation trend of reactive oxygen species (ROS) was similar among genotypes across the time course. The results of RNA-seq depicted that the average expressional intensity of whole genomic genes was similar among barley genotypes duringAgrobacteriuminfection. However, the numbers of differentially expressed genes (DEGs) exhibited significant expressional variation between GP6-L07 and H99 groups from 6 to 12 h post-inoculation (hpi). Gene ontology (GO) enrichment analysis revealed different regulation patterns for the predicted biological processes between the early (up-regulated DEGs overrepresented at 2 hpi) and late stages (down-regulated DEGs overrepresented from 6 to 24 hpi) of infection. KEGG analysis predicted 12 pathways duringAgrobacteriuminfection. Among which one pathway related to pyruvate metabolism was enriched in GP6 and L07 at 6 hpi. Two pathways related to plant hormone signal transduction and DNA replication showed expressional variation between GP6-L07 and H99 at 24 hpi. It was further validated by qRT-PCR assay for seven candidate genes (Aldehyde dehydrogenase,SAUR,SAUR50,ARG7,Replication protein A,DNA helicaseandDNA replication licensing factor) involved in the three pathways, which are all up-regulated in compatible while down-regulated in recalcitrant genotypes, suggesting the potential compatibility achieved at later stage for the growth ofAgrobacteriuminfected cells.ConclusionsOur findings demonstrated the similarity and difference between compatible and recalcitrant genotypes of barley MDEC uponAgrobacteriuminfection. Seven candidate genes involved in pyruvate metabolism, hormonal signal transduction and DNA replication were identified, which advocates the genotypic dependency duringAgrobacteriuminfection process.
Prognostic scores and early management of septic patients in the emergency department of a secondary hospital: results of a retrospective study
Authors: Colussi GianLuca , Perrotta Giacomo , Pillinini Pierpaolo , Dibenedetto Alessia G. , Da Porto Andrea , Catena Cristiana , Sechi Leonardo A. 
Published: December 2021

Abstract
Background
Sequential Organ Failure Assessment (SOFA) and other illness prognostic scores predict adverse outcomes in critical patients. Their validation as a decision-making tool in the emergency department (ED) of secondary hospitals is not well established. The aim of this study was to compare SOFA, NEWS2, APACHE II, and SAPS II scores as predictors of adverse outcomes and decision-making tool in ED.

Methods
Data of 121 patients (age 73 ± 10 years, 58% males, Charlson Comorbidity Index 5.7 ± 2.1) with a confirmed sepsis were included in a retrospective study between January 2017 and February 2020. Scores were computed within the first 24 h after admission. Primary outcome was the occurrence of either in-hospital death or mechanical ventilation within 7 days. Secondary outcome was 30-day all-cause mortality.

Results
Patients older than 64 years (elderly) represent 82% of sample. Primary and secondary outcomes occurred in 40 and 44%, respectively. Median 30-day survival time of dead patients was 4 days (interquartile range 1–11). The best predictive score based on the area under the receiver operating curve (AUROC) was SAPS II (0.823, 95% confidence interval, CI, 0.744–0.902), followed by APACHE II (0.762, 95% CI 0.673–0.850), NEWS2 (0.708, 95% CI 0.616–0.800), and SOFA (0.650, 95% CI 0.548–0.751). SAPS II cut-off of 49 showed the lowest false-positive rate (12, 95% CI 5–20) and the highest positive predictive value (80, 95% CI 68–92), whereas NEWS2 cut-off of 7 showed the lowest false-negative rate (10, 95% CI 2–19) and the highest negative predictive value (86, 95% CI 74–97). By combining NEWS2 and SAPS II cut-offs, we accurately classified 64% of patients. In survival analysis, SAPS II cut-off showed the highest difference in 30-day mortality (Hazards Ratio, HR, 5.24, 95% CI 2.99–9.21, P < 0.001). Best independent negative predictors of 30-day mortality were body temperature, mean arterial pressure, arterial oxygen saturation, and hematocrit levels. Positive predictors were male sex, heart rate and serum sodium concentration.

Conclusions
SAPS II is a good prognostic tool for discriminating high-risk patient suitable for sub-intensive/intensive care units, whereas NEWS2 for discriminating low-risk patients for low-intensive units. Our results should be limited to cohorts with a high prevalence of elderly or comorbidities.
Mechanisms of impact and contextual aspects of a dementia special care unit in long-term care: a process evaluation
Authors: Adlbrecht Laura , Bartholomeyczik Sabine , Mayer Hanna 
Published: December 2021

AbstractBackgroundIn long-term care, persons with dementia are often cared for in specialised facilities, which are rather heterogeneous in regard to care concepts. Little information is available on how these facilities and care concepts bring about changes in the targeted outcomes. Such knowledge is needed to understand the effects of care concepts and to consciously shape further developments. This study aimed to explore the mechanisms of impact of a specific care concept from a dementia special care unit and the contextual aspects that influence its implementation or outcomes.MethodsUsing a qualitative approach to process evaluation of complex interventions, we conducted participating observations and focus groups with nurses and single interviews with ward and nursing home managers. Data were collected from two identical dementia special care units to enhance the contrasts in the analysis of two non-specialised nursing homes. We analysed the data thematically. We conducted 16 observations, three group interviews and eleven individual interviews.ResultsWe identified seven themes in three domains related to mechanisms that lead to outcomes regarding residents’ and nurses’ behaviour and well-being. The themes include the development of nurses’ skills and knowledge, the promotion of a positive work climate, adjusted spatial structures, adjusted personnel deployment strategy “dedicated time for activities”, promotion of relaxation, of engagement in activities and of engagement in social interaction of residents. The implementation and outcomes of the care concept are influenced by contextual aspects relating to the (target) population and cultural, organisational and financial features.ConclusionsThe study found expected and unexpected mechanisms of impact and contextual aspects. The care concept of the dementia special care unit results in higher levels of relaxation, activities, and social interaction of residents. Its implementation highly depends on the shared understanding of nursing and the skills of the nursing team. Changes in residents’ characteristics result in altered effects of the concept.Trial registrationDRKS00011513.
Factors associated with insomnia in older adult outpatients vary by gender: a cross-sectional study
Authors: Peng Yu-Ting , Hsu Ying-Hsin , Chou Ming-Yueh , Chu Che-Sheng , Su Chen-San , Liang Chih-Kuang , Wang Yu-Chun , Yang Tsan , Chen Liang-Kung , Lin Yu-Te 
Published: December 2021

Abstract
Background
Insomnia is a common sleep disturbance in older adults and is associated with many poor health outcomes. This study aimed to explore factors associated with insomnia in older adult outpatient clinics, and to further analyze the influence of gender on factors associated with insomnia.

Methods
This cross-sectional study was conducted in the outpatient clinics of a tertiary hospital in Southern Taiwan from July to September 2018. A total of 400 consecutive subjects aged 60 years or older were recruited. Insomnia was defined as a score of ≥6 points on the Athens Insomnia Scale (AIS). Socio-demographics, health behaviors and clinical data were collected by face-to-face interview. Multivariable logistic regression was adopted for statistical analysis of the entire sample and stratified by gender.

Results
Participants’ mean age was 74.74 ± 8.54 years, and the majority (93%) had more than one chronic disease. The prevalence of insomnia accounted for 30% (120/400) of all subjects, with males 22.9% (46/201) and females 37.2% (74/199). Gender, appetite, exercise, depressive symptoms, and sleep-related conditions such as short sleep duration, sleeping pills usage, medium-high risk of obstructive sleep apnea (OSA) and restless leg syndrome (RLS) were factors associated with insomnia in older adults. Exercise, sleeping pills usage, and RLS were independently associated with insomnia only in men, while appetite and medium-high risk of OSA were associated with insomnia in women only. In addition, after further adjusting for covariates, prevalence of the insomnia-related symptoms such as sleep induction, total sleep duration, sleep quality and sleepiness during the day was significantly higher in females than in males.

Conclusions
Insomnia symptoms are highly prevalent among older adults, predominantly females. Significant differences are found between genders in factors associated with insomnia and insomnia-related symptoms. Understanding gender differences may help clinicians to modify associated factors when managing older adults with insomnia.
Antimicrobial resistance among GLASS priority pathogens from Pakistan: 2006–2018
Authors: Saeed Dania Khalid , Farooqi Joveria , Shakoor Sadia , Hasan Rumina 
Published: December 2021

Abstract
Background
In 2018 Pakistan initiated its national antimicrobial resistance (AMR) surveillance aligned with Global Antimicrobial Surveillance System (GLASS). To complement this surveillance, we conducted a situational analysis of AMR rates among GLASS organisms in the country. Data from published studies and from antibiograms was compared and role of antibiograms as potential contributors to national AMR surveillance explored.

Methods
AMR rates for GLASS specified pathogen/antimicrobials combination from Pakistan were reviewed. Data sources included published studies (2006–2018) providing AMR rates from Pakistan (n = 54) as well as antibiograms (2011–2018) available on the Pakistan Antimicrobial Resistance Network (PARN) website. Resistance rates were categorized as follows: Very low: 0–10%, Low: 11–30%, Moderate: 30–50% and High: > 50%.

Results
Published data from hospital and community/laboratory-based studies report resistance rates of > 50% and 30–50% respectively to 3rd generation cephalosporins, fluoroquinolones and cotrimoxazole amongst Klebsiella pneumoniae and Escherichia coli. Carbapenem resistance rates amongst these organisms remained below 30%. High (> 50%) resistance was reported in Acinetobacter species to aminoglycosides and carbapenems among hospitalized patients. The evolution of ceftriaxone resistant Salmonella Typhi and Shigella species is reported. The data showed > 50% to fluoroquinolones amongst Neisseria gonorrhoeae and the spread of methicillin resistant Staphylococcus aureus (< 30%; 2008) to (> 50%; 2010) in hospital settings. Resistance reported in published studies aligned well with antibiogram data. The latter also captured a clear picture of evolution of resistance over the study period.

Conclusion
Both published studies as well antibiograms suggest high rates of AMR in Pakistan. Antibiogram data demonstrating steady increase in AMR highlight its potential role towards supplementing national AMR surveillance efforts particularly in settings where reach of national surveillance may be limited.
Disseminated Nocardia farcinica involves the spinal cord: a case report and review of the literature
Authors: Wu Jing , Li Xiaoran , Zhang Tao , Lin Xin , Chen Yu-Chen 
Published: December 2021

Abstract
Background
Nocardia is a relatively rare opportunistic pathogenic bacteria group, commonly seen in patients with immunocompromised or defective immune system. It can affect multiple organs of the body and cause disseminated infection, among which most occurs in the lung, secondly in the nervous system, soft tissues, rare in the spinal cord and pituitary. No case has been reported involving lung, spinal cord, skin and pituitary gland at the same time.

Case presentation
We report a 55-year-old female with Nocardia infection involving the lung, skin, spinal cord, and pituitary gland. The patient underwent a full set of imaging examinations and showed typical imaging findings. Chest computed tomography (CT) showed multiple nodules with cavities in the lungs. The magnetic resonance imaging (MRI) of the vertebral body showed abnormal signal of the entire spinal cord with cavity formation and ring enhancement. The subcutaneous nodules of the abdomen were punctured under ultrasound. Through the etiological tissue culture of subcutaneous nodules and the second generation sequencing of cerebrospinal fluid, the diagnosis was finally confirmed.

Conclusion
Disseminated Nocardiosis is an uncommon disease. This article will report a rare case of disseminated Nocardiosis simultaneously involving the lung, spinal cord, subcutaneous soft tissue and pituitary gland, especially with neuropathy as the initial symptom. Imaging is helpful for the early diagnosis of the disease and pathological and microbiological examinations are helpful for its confirming.
β-Thalassemia minor & renal tubular dysfunction: is there any association?
Authors: Sadeghi Mohsen Vakili , Mirghorbani Maryam , Akbari Roghayeh 
Published: December 2021

AbstractObjectiveBeta(β)-thalassemia is one of the most common hereditary hematologic disorders. Patients with thalassemia minor (TM) are often asymptomatic and the rate of renal dysfunction is unknown in these patients. Due to the high prevalence of renal dysfunction in Iran, the current study aimed to determine renal tubular dysfunction in patients with beta-TM.MethodsIn this case-control study, 40 patients with TM and 20 healthy subjects were enrolled and urinary and blood biochemical analysis was done on their samples. Renal tubular function indices were determined and compared in both groups. Data was analyzed by SPSS software, version 20.0.ResultsThe fraction excretion (FE) of uric acid was 8.31 ± 3.98% in the case and 6.2 ± 34.71% in the control group (p = 0.048). Also, FE of potassium was significantly higher in patients with TM (3.22 ± 3.13 vs. 1.91 ± 0.81;p = 0.036). The mean Plasma NGAL level was 133.78 ± 120.28 ng/mL in patients with thalassemia and 84.55 ± 45.50 ng/mL in the control group (p = 0.083). At least one parameter of tubular dysfunction was found in 45% of patients with thalassemia.ConclusionBased on the results of this study, the prevalence of tubular dysfunction in beta-thalassemia minor patients is high. Due to the lack of knowledge of patients about this disorder, periodic evaluation of renal function in TM patients can prevent renal failure by early diagnosis.
Tacrolimus trough levels in kidney transplant recipients
Authors: Hwang Young Hui , Kim Hyunjung , Min Kyungok , Yang Jaeseok 
Published: December 2021

Abstract
Background
It is very important that kidney transplant recipients (KTRs) take immunosuppressive drugs to prevent graft rejection. This study aimed to identify the tacrolimus trough levels (TTL)-mean, TTL-standard deviation (SD), and TTL- coefficient of variation (CV) as well as factors affecting these values over a 2-year period in clinically stable patients > 5 years after kidney transplantation (KT).

Methods
This retrospective study analyzed data from 248 adult outpatients > 5 years after KT. Medical chart data, including TTL, graft rejection, and tacrolimus dose change during a 2-year period, between January 2017 and December 2018, were collected. Multivariable regression analyses were conducted to determine the factors influencing the TTL-mean, TTL-SD, and TTL-CV.

Results
The TTL-mean, TTL-SD, and TTL-CV were 6.00 ± 1.07 ng/mL, 1.51 ± 1.09 ng/mL, and 0.25 ± 0.14, respectively. The TTL-mean, TTL-SD, and TTL-CV did not differ according to sex, type of donor, retransplant, pretransplant kidney disease, body mass index, or posttransplant time; hence, they are stable in kidney transplant recipients > 5 years after KT. The higher the TTL-mean, the higher the TTL-SD. Age and the TTL-SD significantly predicted the TTL-mean (p < .001). Tacrolimus dose change and the TTL-mean significantly predicted the TTL-SD (p < .001). Tacrolimus dose change significantly predicted the TTL-CV (p = .008).

Conclusion
In clinically stable KTRs, TTL-SD and TTL-CV change sensitively in relation to tacrolimus dose changes. Therefore, changes in TTL-SD and TTL-CV in stable KTRs with no tacrolimus dose change require medical interest and attention.
Carboplatin versus cisplatin in combination with etoposide in the first-line treatment of small cell lung cancer: a pooled analysis
Authors: Jiang Shiyu , Huang Liling , Zhen Hongnan , Jin Peijie , Wang Jing , Hu Zhihuang 
Published: December 2021

Abstract
Background
Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive disease with poor survival, and platinum-etoposide chemotherapy is indicated as the mainstay of treatment. In this study, we compared the efficacy and safety between the cisplatin plus etoposide (EP) and carboplatin plus etoposide (EC) regimens.

Methods
A total of 1305 patients with previously untreated ES-SCLC were included in this study. Data from five trials were collected from the public database Project Data Sphere. Survival analysis and adverse events (AEs) analysis were conducted.

Results
Of the 1305 patients, 800 received the EC regimen whereas 505 received the EP regimen as their front-line treatment. Overall, the median progression-free survival (PFS) and the median overall survival (OS) were 172 and 289 days, respectively. The EP and EC treatment groups did not have significantly different PFS or OS. After adjusting for age, sex, body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) performance status (PS), the EP regimen was independently associated with better PFS (hazard ratio [HR] = 0.76, 95% CI = 0.63–0.92, p = 0.0041) and OS (HR = 0.79, 95% CI = 0.64–0.97, p = 0.0220) among patients who were overweight and obese (BMI ≥ 25 kg/m2). In the safety analysis, patients who received the EC treatment experienced significantly more grade ≥ 3 AEs (n = 599, 74.9%) than those who received the EP treatment (n = 337, 66.7%; p = 0.002). Furthermore, the EC regimen was associated with a higher risk of grade 3–4 neutropaenia (p = 0.001), thrombocytopaenia (p < 0.001) and hyponatraemia (p = 0.036), whereas the EP regimen was associated with a higher risk of grade 3–4 vomiting (p = 0.021).

Conclusions
In summary, this study presented the efficacy and safety of the EC and EP regimens in patients with ES-SCLC in the first-line setting. Patients who are overweight and obese benefit more from the EP regimen than EC regimen. Approaches to define the optimal chemotherapy regimen in different BMI subgroups are needed.