bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in sepsis diagnosis and management: a paradigm shift towards nanotechnology
Authors: Pant Amit , Mackraj Irene , Govender Thirumala 
Published: January 2021

AbstractSepsis, a dysregulated immune response due to life-threatening organ dysfunction, caused by drug-resistant pathogens, is a major global health threat contributing to high disease burden. Clinical outcomes in sepsis depend on timely diagnosis and appropriate early therapeutic intervention. There is a growing interest in the evaluation of nanotechnology-based solutions for sepsis management due to the inherent and unique properties of these nano-sized systems. This review presents recent advancements in nanotechnology-based solutions for sepsis diagnosis and management. Development of nanosensors based on electrochemical, immunological or magnetic principals provide highly sensitive, selective and rapid detection of sepsis biomarkers such as procalcitonin and C-reactive protein and are reviewed extensively. Nanoparticle-based drug delivery of antibiotics in sepsis models have shown promising results in combating drug resistance. Surface functionalization with antimicrobial peptides further enhances efficacy by targeting pathogens or specific microenvironments. Various strategies in nanoformulations have demonstrated the ability to deliver antibiotics and anti-inflammatory agents, simultaneously, have been reviewed. The critical role of nanoformulations of other adjuvant therapies including antioxidant, antitoxins and extracorporeal blood purification in sepsis management are also highlighted. Nanodiagnostics and nanotherapeutics in sepsis have enormous potential and provide new perspectives in sepsis management, supported by promising future biomedical applications included in the review.
Translation and validation of the Traditional Chinese version of the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (Version 2)
Authors: Chan Dorothy N. S. , Choi Kai Chow , Ng Marques S. N. , Xing Weijie , Law Bernard M. H. , Ho Pui Shan , Au Cecilia , Chan Mandy , Tong Man , Ling Wai Man , Chan Maggie , Mak Suzanne S. S. , Chan Raymond J. , So Winnie K. W. 
Published: January 2021

Abstract
Background
Cancer patients often experience severe financial distress due to the high cost of their treatment, and strategies are needed to objectively measure this financial distress. The COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) is one instrument used to measure such financial distress. This study aimed to translate the COST-FACIT (Version 2) [COST-FACIT-v2] instrument into traditional Chinese (COST-FACIT-v2 [TC]) and evaluate its psychometric properties.

Methods
The Functional Assessment of Chronic Illness Therapy (FACIT) translation method was adopted. The translated version was reviewed by an expert panel and by 20 cancer patients for content validity and face validity, respectively, and 640 cancer patients, recruited from three oncology departments, completed the translated scale. Its reliability was evaluated in terms of internal consistency and test–retest reliability. Confirmatory factor analysis has been used to evaluate the one- and two-factor structures of the instrument reported in the literature. The convergent validity was examined by the correlation with health-related quality of life (HRQoL) and psychological distress. Known-group validity was examined by the difference in the COST-FACIT-v2 (TC) total mean score between groups with different income levels and frequency of health care service use.

Results
The COST-FACIT-v2 (TC) showed good content and face validity and demonstrated high internal consistency (Cronbach’s alpha, 0.86) and acceptable test–retest reliability (intraclass correlation coefficient, 0.71). Confirmatory factor analysis showed that the one- and two-factor structures of the instrument that have been reported in the literature could not be satisfactorily fitted to the data. Psychological distress correlated significantly with the COST-FACIT-v2 (TC) score (r = 0.47; p < 0.001). HRQOL showed a weak to moderate negative correlation with the COST-FACIT-v2 (TC) score (r = − 0.23 to − 0.46; p < 0.001). Significant differences were seen among the COST-FACIT-v2 (TC) scores obtained in groups of different income level and frequency of health care service use.

Conclusions
The COST-FACIT-v2 (TC) showed some desirable psychometric properties to support its validity and reliability for assessing cancer patients’ level of financial toxicity.
Hypoxia and its possible relationship with endometrial receptivity in adenomyosis: a preliminary study
Authors: Guo Song , Zhang Di , Lu Xiaowei , Zhang Qian , Gu Ruihuan , Sun Binghui , Sun Yijuan 
Published: January 2021

Abstract
Background
Adenomyosis (AM) is an important cause of female infertility. However, the underlying mechanism remains unclear. This report describes a preliminary study of hypoxia and its possible association with endometrial receptivity in AM.

Methods
The study was divided into in vitro and in vivo experiments. In vitro, expression levels of the endometrial receptivity markers HOXA10 and HOXA11 in the implantation period were examined using real-time PCR and western blotting. Endometrial expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, and HIF-3α was determined using immunohistochemistry. In vivo, using an AM mouse model established by oral administration of tamoxifen, we inhibited expression of HIF-2α using an HIF-2α antagonist (PT2399; 30 mg/kg body weight, twice daily by oral gavage for 2 days) and then examined expression levels of Hoxa10 and Hoxa11 using real-time PCR and western blotting.

Results
Endometrial mRNA and protein expression levels of HOXA10 and HOXA11 were significantly lower in patients with AM than in control patients. Expression of HIF-2α was significantly higher in the AM group than in the control group, whereas that of HIF-1α and HIF-3α was equivalent in both groups. In vivo analysis showed that administration of the HIF-2α antagonist resulted in increased expression of Hoxa10 and Hoxa11 at both the mRNA and protein levels in AM model mice.

Conclusions
HIF-2α overexpression may be one reason for decreased endometrial receptivity in AM. The current findings provide insight into HIF-2α-mediated AM-related infertility and suggest that PT2399 has potential as a treatment for AM.

Trial registration
This trial was retrospectively registered.
Effects of spinal manipulative therapy on inflammatory mediators in patients with non-specific low back pain: a non-randomized controlled clinical trial
Authors: Teodorczyk-Injeyan Julita A. , Triano John J. , Gringmuth Robert , DeGraauw Christopher , Chow Adrian , Injeyan H. Stephen 
Published: January 2021

AbstractBackgroundThe inflammatory profiles of patients with acute and chronic nonspecific low back pain (LBP) patients are distinct. Spinal manipulative therapy (SMT) has been shown to modulate the production of nociceptive chemokines differently in these patient cohorts. The present study further investigates the effect(s) of SMT on other inflammatory mediators in the same LBP patient cohorts.MethodsAcute (n = 22) and chronic (n = 25) LBP patients with minimum pain scores of 3 on a 10-point numeric scale, and asymptomatic controls (n = 24) were recruited according to stringent exclusion criteria. Blood samples were obtained at baseline and after 2 weeks during which patients received 6 SMTs in the lumbar or lumbosacral region. The in vitro production of tumor necrosis factor (TNFα), interleukin-1 β (IL-1β), IL-6, IL-2, interferon ɣ (IFNɣ), IL-1 receptor antagonist (IL-1RA), TNF soluble receptor type 2 (sTNFR2) and IL-10 was determined by specific immunoassays. Parametric as well as non-parametric statistics (PAST 3.18 beta software) was used to determine significance of differences between and within study groups prior and post-SMT. Effect size (ES) estimates were obtained using Cohen’sd.ResultsCompared with asymptomatic controls, SMT-related change scores were significant (P = 0.03–0.01) in reducing the production levels of TNFα in both patient cohorts and those of IL-6, IFNɣ and sTNFR2 (P = 0.001–0.02) in patients with chronic LBP. Above-moderate to large ES (d > 0.6–1.4) was observed for these mediators. Compared with respective baselines, a significant post-SMT reduction (P = 0.01) of IL-6 production was detected only in patients with chronic LBP while a significant increase of IL-2 production (P = 0.001 vs. control, andP = 0.004 vs. chronic LBP group) and a large ES (d = 0.87) were observed in patients with acute LBP. Pain and disability scores declined significantly (P < 0.001) in all LBP patients, and were positively correlated (P = 0.03) with IFNɣ and IL-2 levels in the acute LBP cohort.ConclusionThe short course of SMT treatments of non-specific LBP patients resulted in significant albeit limited and diverse alterations in the production of several of the mediators investigated in this study. This exploratory study highlights the potential of SMT to modulate the production of inflammatory components in acute and chronic non-specific LBP patients and suggests a need for further, randomized controlled clinical trials in this area.Trial registrationThis study was prospectively registered April 2012 with Clinical Trials.gov (#NCT01766141).https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0003ZIL&selectaction=Edit&uid=U0001V74&ts=2&cx=-axvqtg
miR-145 inhibits mitochondrial function of ovarian cancer by targeting ARL5B
Authors: Zhao Shuo , Zhang Yun , Pei Meili , Wu Lei , Li Jie 
Published: January 2021

AbstractMetabolic reprogramming refers to the transformation of the whole metabolic network including glycolysis and mitochondrial metabolism, mainly manifested in Warburg effect and mitochondrial metabolic reprogramming. The roles of miR-145 in glycolysis have been established in ovarian cancer cells. Howerer, its roles in mitochondrial metabolic reprogramming are still unclear. This study aims to identify whether miR-145 regulates mitochondrial metabolic reprogramming in ovarian cancer cells. First, functional experiment showed that overexpression of miR-145 inhibited mitochondrial function in ovarian cancer cells, evident by the decreased mtDNA copy numbers, ATP level, mitochondrial membrane potential, and the expression levels of mitochondrial markers. Mechanistically, miR-145 inhibited mitochondrial function by targeting ARL5B directly. Futhermore, miR-145 overexpression decreased ARL5B expression in ovarian cancer tissue subcutaneous tumors of nude mice. In conclusion, we have highlighted that miR-145 inhibits mitochondrial function and achieves this by targeting ARL5B directly for the first time. The results provides a more adequate theoretical basis for understanding the molecular pathology of ovarian cancer, and provides the necessary basic data for miR-145 as a potential diagnosis and treatment target for ovarian cancer.
Evolution of regulatory networks associated with traits under selection in cichlids
Authors: Mehta Tarang K. , Koch Christopher , Nash Will , Knaack Sara A. , Sudhakar Padhmanand , Olbei Marton , Bastkowski Sarah , Penso-Dolfin Luca , Korcsmaros Tamas , Haerty Wilfried , Roy Sushmita , Di-Palma Federica 
Published: January 2021

AbstractBackgroundSeminal studies of vertebrate protein evolution speculated that gene regulatory changes can drive anatomical innovations. However, very little is known about gene regulatory network (GRN) evolution associated with phenotypic effect across ecologically diverse species. Here we use a novel approach for comparative GRN analysis in vertebrate species to study GRN evolution in representative species of the most striking examples of adaptive radiations, the East African cichlids. We previously demonstrated how the explosive phenotypic diversification of East African cichlids can be attributed to diverse molecular mechanisms, including accelerated regulatory sequence evolution and gene expression divergence.ResultsTo investigate these mechanisms across species at a genome-wide scale, we develop a novel computational pipeline that predicts regulators for co-extant and ancestral co-expression modules along a phylogeny, and candidate regulatory regions associated with traits under selection in cichlids. As a case study, we apply our approach to a well-studied adaptive trait—the visual system—for which we report striking cases of network rewiring for visual opsin genes, identify discrete regulatory variants, and investigate their association with cichlid visual system evolution. In regulatory regions of visual opsin genes, in vitro assays confirm that transcription factor binding site mutations disrupt regulatory edges across species and segregate according to lake species phylogeny and ecology, suggesting GRN rewiring in radiating cichlids.ConclusionsOur approach reveals numerous novel potential candidate regulators and regulatory regions across cichlid genomes, including some novel and some previously reported associations to known adaptive evolutionary traits.
Homology-mediated inter-chromosomal interactions in hexaploid wheat lead to specific subgenome territories following polyploidization and introgression
Authors: Jia Jizeng , Xie Yilin , Cheng Jingfei , Kong Chuizheng , Wang Meiyue , Gao Lifeng , Zhao Fei , Guo Jingyu , Wang Kai , Li Guangwei , Cui Dangqun , Hu Tiezhu , Zhao Guangyao , Wang Daowen , Ru Zhengang , Zhang Yijing 
Published: January 2021

Abstract
Background
Polyploidization and introgression are major events driving plant genome evolution and influencing crop breeding. However, the mechanisms underlying the higher-order chromatin organization of subgenomes and alien chromosomes are largely unknown.

Results
We probe the three-dimensional chromatin architecture of Aikang 58 (AK58), a widely cultivated allohexaploid wheat variety in China carrying the 1RS/1BL translocation chromosome. The regions involved in inter-chromosomal interactions, both within and between subgenomes, have highly similar sequences. Subgenome-specific territories tend to be connected by subgenome-dominant homologous transposable elements (TEs). The alien 1RS chromosomal arm, which was introgressed from rye and differs from its wheat counterpart, has relatively few inter-chromosome interactions with wheat chromosomes. An analysis of local chromatin structures reveals topologically associating domain (TAD)-like regions covering 52% of the AK58 genome, the boundaries of which are enriched with active genes, zinc-finger factor-binding motifs, CHH methylation, and 24-nt small RNAs. The chromatin loops are mostly localized around TAD boundaries, and the number of gene loops is positively associated with gene activity.

Conclusions
The present study reveals the impact of the genetic sequence context on the higher-order chromatin structure and subgenome stability in hexaploid wheat. Specifically, we characterized the sequence homology-mediated inter-chromosome interactions and the non-canonical role of subgenome-biased TEs. Our findings may have profound implications for future investigations of the interplay between genetic sequences and higher-order structures and their consequences on polyploid genome evolution and introgression-based breeding of crop plants.
Evaluation of robotic versus open partial pancreatoduodenectomy—study protocol for a randomised controlled pilot trial (EUROPA, DRKS00020407)
Authors: Klotz Rosa , Dörr-Harim Colette , Bruckner Thomas , Knebel Philipp , Diener Markus K. , Hackert Thilo , Mihaljevic André L. 
Published: January 2021

Abstract
Background
Partial pancreatoduodenectomy (PD) is the indicated surgical procedure for a wide range of benign and malignant diseases of the pancreatic head and distal bile duct and offers the only potential cure for pancreatic head cancer. The current gold standard, open PD (OPD) performed via laparotomy, is associated with morbidity in around 40% of cases, even at specialised centres. Robotic PD (RPD) might offer a viable alternative to OPD and has been shown to be feasible. Encouraging perioperative results have been reported for RPD in a number of small, non-randomised studies. However, since those studies showed a considerable risk of bias, a thorough comparison of RPD with OPD is warranted.

Methods
The EUROPA (EvalUation of RObotic partial PAncreatoduodenectomy) trial is designed as a randomised controlled unblinded exploratory surgical trial with two parallel study groups. A total of 80 patients scheduled for elective PD will be randomised after giving written informed consent. Patients with borderline or non-resectable carcinoma of the pancreatic head as defined by the National Comprehensive Cancer Network guidelines, distant metastases or an American Society of Anaesthesiologists (ASA) score > III will be excluded. The experimental intervention, RPD, will be compared with the control intervention, OPD. An intraoperative dropout of approximately eight patients per group is expected because they may receive another type of surgical procedure than planned. Overall, 64 patients need to be analysed. The primary endpoint of the trial is overall postoperative morbidity within 90 days after index operation, measured using the Comprehensive Complication Index (CCI). The secondary endpoints include the feasibility of recruitment and assessment of clinical, oncological and safety parameters and quality of life and cost-effectiveness.

Discussion
The EUROPA trial is the first randomised controlled trial comparing RPD with OPD. Differences in postoperative morbidity will be evaluated to design a future multicentre confirmatory efficacy trial.

Trial registration
German Clinical Trial Register DRKS00020407. Registered on 9 March 2020
Process optimization for mass production of 2,3-butanediol by Bacillus subtilis CS13
Authors: Wang Dexin , Oh Baek-Rock , Lee Sungbeom , Kim Dae-Hyuk , Joe Min-Ho 
Published: January 2021

Abstract
Background
Bacillus subtilis CS13 was previously isolated for 2,3-butanediol (2,3-BD) and poly-γ-glutamic acid (γ-PGA) co-production. When culturing this strain without L-glutamic acid in the medium, 2,3-BD is the main metabolic product. 2,3-BD is an important substance and fuel with applications in the chemical, food, and pharmaceutical industries. However, the yield and productivity for the B. subtilis strain should be improved for more efficient production of 2,3-BD.

Results
The medium composition, which contained 281.1 g/L sucrose, 21.9 g/L ammonium citrate, and 3.6 g/L MgSO4·7H2O, was optimized by response surface methodology for 2,3-BD production using B. subtilis CS13. The maximum amount of 2,3-BD (125.5 ± 3.1 g/L) was obtained from the optimized medium after 96 h. The highest concentration and productivity of 2,3-BD were achieved simultaneously at an agitation speed of 500 rpm and aeration rate of 2 L/min in the batch cultures. A total of 132.4 ± 4.4 g/L 2,3-BD was obtained with a productivity of 2.45 ± 0.08 g/L/h and yield of 0.45 g2,3-BD/gsucrose by fed-batch fermentation. The meso-2,3-BD/2,3-BD ratio of the 2,3-BD produced by B. subtilis CS13 was 92.1%. Furthermore, 89.6 ± 2.8 g/L 2,3-BD with a productivity of 2.13 ± 0.07 g/L/h and yield of 0.42 g2,3-BD/gsugar was achieved using molasses as a carbon source.

Conclusions
The production of 2,3-BD by B. subtilis CS13 showed a higher concentration, productivity, and yield compared to the reported generally recognized as safe 2,3-BD producers. These results suggest that B. subtilis CS13 is a promising strain for industrial-scale production of 2,3-BD.
Familial chylomicronemia syndrome: a case report
Authors: Susheela Ammu Thampi , Vadakapet Padmesh , Pillai Lekshmi , Thampi Susheela 
Published: January 2021

Abstract
Background
Familial chylomicronemia is an extremely rare disease. Lipoprotein lipase deficiency, lipoprotein defect or lipoprotein receptor defect are the main genetic causes of familial chylomicronemia.

Case presentation
We report a rare case of hypertriglyceridemia which was diagnosed at 24 days after birth. A newborn south east Asian baby born for G3P2A1 mother was presented with hematuria at 24 days at the hospital. The patient's family history is significant for pink blood in an elder sibling who died within a few months of birth without a proper diagnosis. Physical examination was not significant for any findings. Urinalysis revealed numerous RBC in the urine. Blood draw to perform renal function test revealed a characteristic pink blood. Baby’s blood was normal and red in color at the time of birth. During the present visit, although most of the blood test were not able to be carried out by the regular laboratory instruments, the patient’s lipid profile was alarmingly high with triglyceride levels over 4000 mg/dL. Due to a very high triglyceride level in a neonate and a significant familial history, a genetic cause of hypertriglyceridemia is suspected. Upon diagnosis, baby was discontinued of breast feeding completely and was given a special diet devoid of triglyceride and containing medium chain fatty acid diet and was also started with fenofibrate. After a month and a half, follow up tests were conducted which showed the triglyceride level was reduced to 1300 and a reversal of the blood color from pink to red. Since the imported diet was extremely expensive for the family, the patient was put on skimmed milk with medium-chain triglyceride (MCT) oil. With 6 weeks of treatment, baby’s condition has improved and is thriving well.

Conclusions
Our case reports an extremely rare and fatal condition and illustrated the significance of timely diagnosis and intervention for saving the life of the baby.
The impact of savings on economic growth in a developing country (the case of Kosovo)
Authors: Ribaj Artur , Mexhuani Fitim 
Published: January 2021

AbstractThe correlation between savings and economic growth has been the subject of research for some well-known economists. This study provides further insight on such correlation by examining the case of Kosovo from both a qualitative and quantitative research methodology. The data used was from 2010 to 2017 and has been analyzed using the augmented Dickey-Fuller tests, Johansen cointegration tests, and Ganger causality test. The test of the unit root confirms stationarity, and the regression results showed that deposits have a significant positive impact on Kosovo’s economic growth, because savings stimulate investment, production, and employment and consequently generate greater sustainable economic growth. Furthermore, loans and remittances also help boost the economy of Kosovo through their direct impact on investment. This paper confirms that countries whose national savings rate is high are not dependent on foreign direct investment; consequently, the risk arising from volatile foreign direct investment decreases significantly.
Bilateral severe heterotopic ossification following primary total knee arthroplasty: a case report in Pakistan
Authors: Iqbal Faizan , Memon Nouman , Noor Syed Shahid , Ahmed Nasir , Sozera Muhammad Farhan , Abro Arsalan 
Published: January 2021

AbstractThe incidence of unilateral minor heterotopic ossification after primary total knee arthroplasty is still unknown, but bilateral severe heterotopic ossification is rare and has not been reported before. Presented in this report is a 60-year-old female patient who developed bilateral knee pain and stiffness 2 weeks after primary total knee arthroplasty. Her weight was 70 kg and body mass index was 32.2. Preoperatively, she had bilateral varus deformity of both knees. X-rays taken 3 months after surgery revealed bilateral severe heterotopic ossification. The patient had been on non-operative treatment (including anti-inflammatory drugs and physiotherapy). There was a marked improvement 6 months after surgery. This case report showed the non-operative treatment may produce acceptable results for patients with severe bilateral heterotopic ossification after primary total knee arthroplasty, and exerted no influence on the final clinical outcome.