bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment and Fractionation of Metastatic Axillary Lymph Node Cell Suspension for Determination of Protein Expression Levels of Nuclear cFOS and Cytosolic TGFβ1 from Breast Cancer Patients
Authors: Ivanović Vesna , Dedović-Tanić Nasta , Milovanović Zorka , Stojiljković Bratislav , Demajo Miroslav , Mandušić Vesna 
Published: June 2022

Abstract
Background
Metastatic Axillary Lymph Node (mALN) status is currently the most important prognostic factor in the management of primary breast cancer (BC). Thus, development of specimens which enable identification of new mALN markers, involved in the progression of the disease, are of considerable interest. The specific aim of this work was to describe the method of establishment of Metastatic Axillary Nodal Cell Suspension and its fractionation, termed Fractionated Nodal Cell Suspension (FNCS), into nuclear and cytosolic extracts to enable determination of protein expression levels of nuclear cFOS and cytosolic Transforming Growth Factor β1 (TGFβ1) in BC patients.

Results
To standardize the procedure, HeLa cells were successfully fractionated into nuclear/cytosolic extracts with confirmed presence of nuclear cFOS and cytosolic TGFβ1 proteins. Subsequently, the ALN Cell Suspension specimens were obtained and further fractionated from a pilot sample of six ALN tissue pairs, mALN versus autologous normal ALN (nALN), dissected from invasive BC patients. The mALN/nALN results revealed overexpression of both nuclear cFOS and cytosolic TGFβ1 protein levels. However, only the TGFβ1 data exhibited statistically significant overexpression, which was proportional to the respective values of mALN diameter of tumor deposits.

Conclusions
Detailed protocol for establishment and fractionation of mALN cell suspension specimens, termed FNCS, into nuclear and cytosolic extracts is here described for the first time. This approach might be a convenient ex vivo model for simultaneous analysis of protein, RNA and DNA biomarkers from nuclear/cytosolic extracts of the same mALN tissue sample. It might have potential to enable, in the age of genomics and personalized medicine, an identification of novel mALN biomarkers and thus improve the screening, diagnosis and prognosis of invasive BC.
Antagonistic regulatory effects of a single cis-acting expression quantitative trait locus between transcription and translation of the MRPL43 gene
Authors: Han Jooyeon , Lee Chaeyoung 
Published: June 2022

Abstract
Background
Heterogeneity of expression quantitative trait locus (eQTL) effects have been shown across gene expression processes. Knowledge on how to produce the heterogeneity is quite limited. This study aims to examine fluctuations in differential gene expression by alleles of sequence variants across expression processes.

Results
Genome-wide eQTL analyses with transcriptome-wide gene expression data revealed 20 cis-acting eQTLs associated simultaneously with mRNA expression, ribosome occupancy, and protein abundance. A 97 kb-long eQTL signal for mitochondrial ribosomal protein L43 (MRPL43) covered the gene, showing a heterogeneous effect size on gene products across expression stages. One allele of the eQTL was associated with increased mRNA expression and ribosome occupancy but decreased protein abundance. We examined the heterogeneity and found that the eQTL can be attributed to the independent functions of three nucleotide variants, with a strong linkage. NC_000010.11:g.100987606G > T, upstream of MRPL43, may regulate the binding affinity of transcription factors. NC_000010.11:g.100986746C > G, 3 bp from an MRPL43 splice donor site, may alter the splice site. NC_000010.11:g.100978794A > G, in the isoform with a long 3′-UTR, may strengthen the binding affinity of the microRNA. Individuals with the TGG haplotype at these three variants had higher levels of mRNA expression and ribosome occupancy than individuals with the GCA haplotype but lower protein levels, producing the flipped effect throughout the expression process.

Conclusions
These findings suggest that multiple functional variants in a linkage exert their regulatory functions at different points in the gene expression process, producing a complexity of single eQTLs.
Temperature regulation of carotenoid accumulation in the petals of sweet osmanthus via modulating expression of carotenoid biosynthesis and degradation genes
Authors: Wang Yiguang , Zhang Chao , Xu Bin , Fu Jianxin , Du Yanxia , Fang Qiu , Dong Bin , Zhao Hongbo 
Published: June 2022

Abstract
Background
Temperature is involved in the regulation of carotenoid accumulation in many plants. The floral color of sweet osmanthus (Osmanthus fragrans Lour.) which is mainly contributed by carotenoid content, is affected by temperature in autumn. However, the mechanism remains unknown. Here, to reveal how temperature regulates the floral color of sweet osmanthus, potted sweet osmanthus ‘Jinqiu Gui’ were treated by different temperatures (15 °C, 19 °C or 32 °C). The floral color, carotenoid content, and the expression level of carotenoid-related genes in petals of sweet osmanthus ‘Jinqiu Gui’ under different temperature treatments were investigated.

Results
Compared to the control (19 °C), high temperature (32 °C) changed the floral color from yellow to yellowish-white with higher lightness (L*) value and lower redness (a*) value, while low temperature (15 °C) turned the floral color from yellow to pale orange with decreased L* value and increased a* value. Total carotenoid content and the content of individual carotenoids (α-carotene, β-carotene, α-cryptoxanthin, β-cryptoxanthin, lutein and zeaxanthin) were inhibited by high temperature, but were enhanced by low temperature. Lower carotenoid accumulation under high temperature was probably attributed to transcriptional down-regulation of the biosynthesis gene OfPSY1, OfZ-ISO1 and OfLCYB1, and up-regulation of degradation genes OfNCED3, OfCCD1-1, OfCCD1-2, and OfCCD4-1. Up-regulation of OfLCYB1, and down-regulation of OfNCED3 and OfCCD4-1 were predicted to be involved in low-temperature-regulated carotenoid accumulation. Luciferase assays showed that the promoter activity of OfLCYB1 was activated by low temperature, and repressed by high temperature. However, the promoter activity of OfCCD4-1 was repressed by low temperature, and activated by high temperature.

Conclusions
Our study revealed that high temperature suppressed the floral coloration by repressing the expression of carotenoid biosynthesis genes, and activating the expression of carotenoid degradation genes. However, the relative low temperature had opposite effects on floral coloration and carotenoid biosynthesis in sweet osmanthus. These results will help reveal the regulatory mechanism of temperature on carotenoid accumulation in the petals of sweet osmanthus.
Transcriptomic analysis provides insights into molecular mechanisms of thermal physiology
Authors: Drown Melissa K. , Crawford Douglas L. , Oleksiak Marjorie F. 
Published: June 2022

AbstractPhysiological trait variation underlies health, responses to global climate change, and ecological performance. Yet, most physiological traits are complex, and we have little understanding of the genes and genomic architectures that define their variation. To provide insight into the genetic architecture of physiological processes, we related physiological traits to heart and brain mRNA expression using a weighted gene co-expression network analysis. mRNA expression was used to explain variation in six physiological traits (whole animal metabolism (WAM), critical thermal maximum (CTmax), and four substrate specific cardiac metabolic rates (CaM)) under 12 °C and 28 °C acclimation conditions. Notably, the physiological trait variations among the three geographically close (within 15 km) and genetically similarF. heteroclituspopulations are similar to those found among 77 aquatic species spanning 15–20° of latitude (~ 2,000 km). These large physiological trait variations among genetically similar individuals provide a powerful approach to determine the relationship between mRNA expression and heritable fitness related traits unconfounded by interspecific differences. Expression patterns explained up to 82% of metabolic trait variation and were enriched for multiple signaling pathways known to impact metabolic and thermal tolerance (e.g., AMPK, PPAR, mTOR, FoxO, and MAPK) but also contained several unexpected pathways (e.g., apoptosis, cellular senescence), suggesting that physiological trait variation is affected by many diverse genes.
The Kandelia obovata transcription factor KoWRKY40 enhances cold tolerance in transgenic Arabidopsis
Authors: Fei Jiao , Wang You-Shao , Cheng Hao , Su Yu-Bin , Zhong Yong-Jia , Zheng Lei 
Published: June 2022

Abstract
Background
WRKY transcription factors play key roles in plant development processes and stress response. Kandelia obovata is the most cold-resistant species of mangrove plants, which are the important contributors to coastal marine environment. However, there is little known about the WRKY genes in K. obovata.

Results
In this study, a WRKY transcription factor gene, named KoWRKY40, was identified from mangrove plant K. obovata. The full-length cDNA of KoWRKY40 gene was 1420 nucleotide bases, which encoded 318 amino acids. The KoWRKY40 protein contained a typical WRKY domain and a C2H2 zinc-finger motif, which were common signatures to group II of WRKY family. The three-dimensional (3D) model of KoWRKY40 was formed by one α-helix and five β-strands. Evolutionary analysis revealed that KoWRKY40 has the closest homology with a WRKY protein from another mangrove plant Bruguiera gymnorhiza. The KoWRKY40 protein was verified to be exclusively located in nucleus of tobacco epidermis cells. Gene expression analysis demonstrated that KoWRKY40 was induced highly in the roots and leaves, but lowly in stems in K. obovata under cold stress. Overexpression of KoWRKY40 in Arabidopsis significantly enhanced the fresh weight, root length, and lateral root number of the transgenic lines under cold stress. KoWRKY40 transgenic Arabidopsis exhibited higher proline content, SOD, POD, and CAT activities, and lower MDA content, and H2O2 content than wild-type Arabidopsis under cold stress condition. Cold stress affected the expression of genes related to proline biosynthesis, antioxidant system, and the ICE-CBF-COR signaling pathway, including AtP5CS1, AtPRODH1, AtMnSOD, AtPOD, AtCAT1, AtCBF1, AtCBF2, AtICE1, AtCOR47 in KoWRKY40 transgenic Arabidopsis plants.

Conclusion
These results demonstrated that KoWRKY40 conferred cold tolerance in transgenic Arabidopsis by regulating plant growth, osmotic balance, the antioxidant system, and ICE-CBF-COR signaling pathway. The study indicates that KoWRKY40 is an important regulator involved in the cold stress response in plants.
Effects of structured involvement of the primary care team versus standard care after a cancer diagnosis on patient satisfaction and healthcare use: the GRIP randomised controlled trial
Authors: Perfors I. A. A. , Helsper C. W. , Noteboom E. A. , Visserman E. A. , van Dorst E. B. L. , van Dalen T. , Verhagen M. A. M. T. , Witkamp A. J. , Koelemij R. , Flinterman A. E. , Pruissen-Peeters K. A. B. M. , Schramel F. M. N. H. , van Rens M. T. M. , Ernst M. F. , Moons L. M. G. , van der Wall E. , de Wit N. J. , May A. M. 
Published: June 2022

Abstract
Background
The growing number of cancer survivors and treatment possibilities call for more personalised and integrated cancer care. Primary care seems well positioned to support this. We aimed to assess the effects of structured follow-up of a primary care team after a cancer diagnosis.

Methods
We performed a multicentre randomised controlled trial enrolling patients curatively treated for breast, lung, colorectal, gynaecologic cancer or melanoma. In addition to usual cancer care in the control group, patients randomized to intervention were offered a “Time Out consultation” (TOC) with the general practitioner (GP) after diagnosis, and subsequent follow-up during and after treatment by a home care oncology nurse (HON). Primary outcomes were patient satisfaction with care (questionnaire: EORTC-INPATSAT-32) and healthcare utilisation. Intention-to-treat linear mixed regression analyses were used for satisfaction with care and other continuous outcome variables. The difference in healthcare utilisation for categorical data was calculated with a Pearson Chi-Square or a Fisher exact test and count data (none versus any) with a log-binomial regression.

Results
We included 154 patients (control n = 77, intervention n = 77) who were mostly female (75%), mainly diagnosed with breast cancer (51%), and had a mean age of 61 (SD ± 11.9) years. 81% of the intervention patients had a TOC and 68% had HON contact. Satisfaction with care was high (8 out of 10) in both study groups. At 3 months after treatment, GP satisfaction was significantly lower in the intervention group on 3 of 6 subscales, i.e., quality (− 14.2 (95%CI -27.0;-1.3)), availability (− 15,9 (− 29.1;-2.6)) and information provision (− 15.2 (− 29.1;-1.4)). Patients in the intervention group visited the GP practice and the emergency department more often ((RR 1.3 (1.0;1.7) and 1.70 (1.0;2.8)), respectively).

Conclusions
In conclusion, the GRIP intervention, which was designed to involve the primary care team during and after cancer treatment, increased the number of primary healthcare contacts. However, it did not improve patient satisfaction with care and it increased emergency department visits. As the high uptake of the intervention suggests a need of patients, future research should focus on optimizing the design and implementation of the intervention.

Trial registration
GRIP is retrospectively (21/06/2016) registered in the ‘Netherlands Trial Register’ (NTR5909).
Is multimorbidity associated with higher risk of falls among older adults in India?
Authors: Barik Manish , Panda Sushree Nibedita , Tripathy Sweta Sulagna , Sinha Abhinav , Ghosal Shishirendu , Acharya Ardhendhu Sekhar , Kanungo Srikanta , Pati Sanghamitra 
Published: June 2022

AbstractBackgroundFall, a multifaceted health condition, is one of the major causes of mortality among older adults. Rapid ageing and increased multimorbidity in low-and middle-income countries (LMICs), including India, might elevate the risk of fall. Although, fall is associated with significant healthcare utilization, it still remains an under-recognized public health issue. This accentuates a need for evidence on fall to integrate it into existing healthcare programs, a gap in geriatric care. The present study aimed to assess the association of fall with multimorbidity among older adults in India.MethodsWe included 28,567 participants aged ≥ 60 years from Longitudinal Ageing Study in India (LASI), wave-1 conducted during 2017–19. Descriptive statistics were used to compute the prevalence of self-reported falls along with 95% confidence interval as a measure of uncertainty. The association between falls and multimorbidity was assessed by multivariable logistic regression and presented as an adjusted odds ratio (AOR).ResultsThe prevalence of falls was 12.5%, being higher among women (13.6% vs. 11.4%) than men. The major determinants of fall were females, rural residents and smokeless tobacco use. We observed multimorbidity [AOR: 1.29 (1.14–1.46)] to be significantly associated with falls.ConclusionFalls are commonly prevalent among older adults having multimorbidity as its important predictor. Existing health programs should incorporate falls as an important part of geriatric care. Additionally, primary health care facilities should be strengthened to provide comprehensive care for injuries sustained due to falls.
A case of recurrent acute cholecystitis caused by Actinomyces odontolyticus, rare actinomycosis
Authors: Furuya Kento , Ito Kenta , Sugiyama Kyohei , Fujita Akitsugu , Kanemoto Hideyuki , Shimada Toshio 
Published: June 2022

Abstract
Backgrounds
Actinomyces species are gram-positive, obligate anaerobic rods and are rare causes of cholecystitis. Because Actinomyces species are anaerobic bacteria, it is difficult for Actinomyces to survive in bile apart from A. naeslundii. We experienced a case of recurrent acute cholecystitis caused by A. odontolyticus.

Case presentation
A patient had been diagnosed with acute cholecystitis and treated one month before and after that, admitted to our hospital because of recurrent cholecystitis. Gram stain of the bile revealed gram-positive rods and gram-positive cocci. We found A. odontolyticus and MRSA in bile culture and MRSA in blood culture. We administered piperacillin-tazobactam and then changed it to ampicillin-sulbactam and vancomycin. The patient underwent laparoscopic cholecystectomy and was discharged safely.

Conclusions
To our knowledge, this is the first case of cholecystitis caused by A. odontolyticus. Cholecystitis caused by Actinomyces species is rare. In addition, we may overlook it with the low positivity of bile cultures of Actinomyces. Whenever the cholecystitis recurs without any obstruction of the biliary tract, we should search for the gram-positive rods hidden in the bile, such as A. odontolyticus, as the causative organism, even if the bile culture is negative.
Catheter-related bloodstream Mycobacterium wolinskyi infection in an umbilical cord blood transplant recipient: a case report
Authors: Muranaka Emiri , Hase Ryota , Utsu Yoshikazu , Watari Tomohisa , Otsuka Yoshihito , Hosokawa Naoto 
Published: June 2022

Abstract
Background
Catheter-related bloodstream infection (CRBSI), caused by rapidly growing mycobacteria (RGM), is a rare infectious complication in hematopoietic stem cell transplant (HSCT) recipients and can often be misdiagnosed as Gram-positive rod (GPR) bacteremia.

Case presentation
We present a case of CRBSI caused by Mycobacterium wolinskyi, a rare RGM, in a 44-year-old female patient who received an umbilical cord blood transplant.

Conclusions
Rapidly growing mycobacteria can stain as GPRs and may grow in routine blood culture media after 3–4 days of incubation. These features are not widely known to clinicians, and acid-fast staining is therefore recommended when unidentifiable GPRs are detected in blood cultures, especially in immunocompromised patients, such as those with hematologic malignancies or intravascular devices.
Impact of COVID-19 pandemic on the epidemiology of STDs in China: based on the GM (1,1) model
Authors: Yan Jingmin , Li Yanbo , Zhou Pingyu 
Published: June 2022

AbstractBackgroundCOVID-19 and Sexually Transmitted Diseases (STDs) are two very important diseases. However, relevant researches about how COVID-19 pandemic has impacted on the epidemiological trend of STDs are limited in China. This study aimed to analyze the impact of COVID-19 on STDs in China and proposed relevant recommendations to be used in bettering health.MethodsThe incidence of HIV infection, syphilis and gonorrhea in China from 2008 to 2020 were collected. Grey Model (1,1) were established to predict the incidence of STDs with the incidence data of these three STDs from 2013 to 2018 considering the impact of policies in China, respectively. We then calculated the predictive incidence of each STD in 2019, 2020 and 2021 by the established Model. And we estimated the extent of the impact of COVID-19 on the epidemiological changes of STDs by analyzing the difference between the absolute percentage error (APE) of the predictive incidence and actual rate in 2019 and 2020.ResultsThe incidence of HIV infection and syphilis showed a trend of increase from 2008 to 2019 in China, but that for gonorrhea was fluctuant. Of note, the incidence of these three STDs decreased significantly in 2020 compared with that in 2019. The APE of HIV infection, syphilis and gonorrhea in 2020 (20.54%, 15.45% and 60.88%) were about 7 times, 4 times and 2 times of that in 2019 (2.94%, 4.07% and 30.41%). The incidence of HIV infection, syphilis and gonorrhea would be 5.77/100,000, 39.64/100,000 and 13.19/100,000 in 2021 based on our model.ConclusionsThe epidemiological trend of STDs in China was significant influenced by COVID-19 pandemic. It is important to balance the control of COVID-19 and timely management of STDs during the COVID-19 epidemic to prevent or reduce the poor outcome among COVID-19 patients with STDs. New management strategies on STDs, such as leveraging social media, online medical care, rapid self-testing, timely diagnosis and treatment guarantee and balance of medical resources for STDs management should be adapted in the context of the long-term effects of COVID-19.
Impact of delayed processing of positive blood cultures on organism detection: a prospective multi-centre study
Authors: Roberts Tamalee , Chandna Arjun , Watthanaworawit Wanitda , Thaiprakong Areerat , Soeng Sona , Simmalavong Manivone , Phoumin Phonelavanh , Saengchun Weerawut , Khatta Nongyao , Hinfonthong Pattaraporn , Kaewpundoem Napaporn , Lee Sue J. , Perrone Carlo , Amos Ben , Turner Paul , Ashley Elizabeth A. , Ling Clare L. 
Published: June 2022

Abstract
Background
Blood cultures remain the gold standard investigation for the diagnosis of bloodstream infections. In many locations, quality-assured processing of positive blood cultures is not possible. One solution is to incubate blood cultures locally, and then transport bottles that flag positive to a central reference laboratory for organism identification and antimicrobial susceptibility testing. However, the impact of delay between the bottle flagging positive and subsequent sub-culture on the viability of the isolate has received little attention.

Methods
This study evaluated the impact of delays to sub-culture (22 h to seven days) in three different temperature conditions (2–8 °C, 22–27 °C and 35 ± 2 °C) for bottles that had flagged positive in automated detection systems using a mixture of spiked and routine clinical specimens. Ninety spiked samples for five common bacterial causes of sepsis (Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae) and 125 consecutive positive clinical blood cultures were evaluated at four laboratories located in Cambodia, Lao PDR and Thailand. In addition, the utility of transport swabs for preserving organism viability was investigated.

Results
All organisms were recoverable from all sub-cultures in all temperature conditions with the exception of S. pneumoniae, which was less likely to be recoverable after longer delays (> 46–50 h), when stored in hotter temperatures (35 °C), and from BacT/ALERT when compared with BACTEC blood culture bottles. Storage of positive blood culture bottles in cooler temperatures (22–27 °C or below) and the use of Amies bacterial transport swabs helped preserve viability of S. pneumoniae.

Conclusions
These results have practical implications for the optimal workflow for blood culture bottles that have flagged positive in automated detection systems located remotely from a central processing laboratory, particularly in tropical resource-constrained contexts.