bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic risk for coronary artery disease in the Scottish and English population
Authors: Yang Chuhua , Starnecker Fabian , Pang Shichao , Chen Zhifen , Güldener Ulrich , Li Ling , Heinig Matthias , Schunkert Heribert
Published: December 2021

Background

Epidemiological studies have repeatedly observed a markedly higher risk for coronary artery disease (CAD) in Scotland as compared to England. Up to now, it is unclear whether environmental or genetic factors might explain this phenomenon.

Methods

Using UK Biobank (UKB) data, we assessed CAD risk, based on the Framingham risk score (FRS) and common genetic variants, to explore the respective contribution to CAD prevalence in Scotland (n = 31,963) and England (n = 317,889). We calculated FRS based on sex, age, body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), antihypertensive medication, smoking status, and diabetes. We determined the allele frequency of published genome-wide significant risk CAD alleles and a weighted genetic risk score (wGRS) for quantifying genetic CAD risk.

Results

Prevalence of CAD was 16% higher in Scotland as compared to England (8.98% vs. 7.68%, P < 0.001). However, the FRS only predicted a marginally higher CAD risk (less than 1%) in Scotland (12.5 ± 10.5 vs.12.6 ± 10.6, P = 0.03). Likewise, the overall number of genome-wide significant variants affecting CAD risk (157.6 ± 7.7 and 157.5 ± 7.7; P = 0.12) and a wGRS for CAD (2.49 ± 0.25 in both populations, P = 0.14) were remarkably similar in the English and Scottish population. Interestingly, we observed substantial differences in the allele frequencies of individual risk variants. Of the previously described 163 genome-wide significant variants studied here, 35 variants had higher frequencies in Scotland, whereas 37 had higher frequencies in England (P < 0.001 each).

Conclusions

Neither the traditional risk factors included in the FRS nor a genetic risk score (GRS) based on established common risk alleles explained the higher CAD prevalence in Scotland. However, we observed marked differences in the distribution of individual risk alleles, which emphasizes that even geographically and ethnically closely related populations may display relevant differences in the genetic architecture of a common disease.
Evaluating the transitions in care for children presenting with acute asthma to emergency departments: a retrospective cohort study
Authors: Kroetch Kimberly R. , Rowe Brian H. , Rosychuk Rhonda J.
Published: December 2021

Background

Acute asthma is a common presentation to emergency departments (EDs) worldwide and, due to overcrowding, delays in treatment often occur. This study deconstructs the total ED length of stay into stages and estimates covariate effects on transition times for children presenting with asthma.

Methods

We extracted ED presentations in 2019 made by children in Alberta, Canada for acute asthma. We used multivariable Cox regressions in a multistate model to model transition times among the stages of start, physician initial assessment (PIA), disposition decision, and ED departure.

Results

Data from 6598 patients on 8270 ED presentations were extracted. The individual PIA time was longer (i.e., HR < 1) when time to the crowding metric (hourly PIA) was above 1 h (HR = 0.32; 95% CI:0.30,0.34), for tertiary (HR = 0.65; 95% CI:0.61,0.70) and urban EDs (HR = 0.77; 95% CI:0.70,0.84), for younger patients (HR = 0.99 per year; 95% CI:0.99,1.00), and for patients triaged less urgent/non-urgent (HR = 0.89; 95% CI:0.84,0.95). It was shorter for patients arriving by ambulance (HR = 1.22; 95% CI:1.04,1.42). Times from PIA to disposition decision were longer for tertiary (HR = 0.47; 95% CI:0.44,0.51) and urban (HR = 0.69; 95% CI:0.63,0.75) EDs, for patients triaged as resuscitation/emergent (HR = 0.51; 95% CI:0.48,0.54), and for patients arriving by ambulance (HR = 0.78; 95% CI:0.70,0.87). Times from disposition decision to ED departure were longer for patients who were admitted (HR = 0.16; 95% CI:0.13,0.20) or transferred (HR = 0.42; 95% CI:0.35,0.50), and for tertiary EDs (HR = 0.93; 95% CI:0.92,0.94).

Conclusions

All transition times were impacted by ED presentation characteristics. The sole key patient characteristic was age and it only impacted time to PIA. ED crowding demonstrated strong effects of time to PIA but not for the transition times involving disposition decision and ED departure stages.
Clinical impact of multidrug-resistant bacteria in older hospitalized patients with community-acquired urinary tract infection
Authors: Madrazo Manuel , Esparcia Ana , López-Cruz Ian , Alberola Juan , Piles Laura , Viana Alba , Eiros José María , Artero Arturo
Published: December 2021

Introduction

Previous studies have described some risk factors for multidrug-resistant (MDR) bacteria in urinary tract infection (UTI). However, the clinical impact of MDR bacteria on older hospitalized patients with community-acquired UTI has not been broadly analyzed. We conducted a study in older adults with community-acquired UTI in order to identify risk factors for MDR bacteria and to know their clinical impact.

Methods

Cohort prospective observational study of patients of 65 years or older, consecutively admitted to a university hospital, diagnosed with community-acquired UTI. We compared epidemiological and clinical variables and outcomes, from UTI due to MDR and non-MDR bacteria. Independent risk factors for MDR bacteria were analyzed using logistic regression.

Results

348 patients were included, 41.4% of them with UTI due to MDR bacteria. Median age was 81 years. Hospital mortality was 8.6%, with no difference between the MDR and non-MDR bacteria groups. Median length of stay was 5 [4–8] days, with a longer stay in the MDR group (6 [4–8] vs. 5 [4–7] days, p = 0.029). Inadequate empirical antimicrobial therapy (IEAT) was 23.3%, with statistically significant differences between groups (33.3% vs. 16.2%, p < 0.001). Healthcare-associated UTI variables, in particular previous antimicrobial therapy and residence in a nursing home, were found to be independent risk factors for MDR bacteria.

Conclusions

The clinical impact of MDR bacteria was moderate. MDR bacteria cases had higher IEAT and longer hospital stay, although mortality was not higher. Previous antimicrobial therapy and residence in a nursing home were independent risk factors for MDR bacteria.
Laparoscopic pancreatectomy for benign or low-grade malignant pancreatic tumors: outcomes in a single high-volume institution
Authors: Cai He , Feng Lu , Peng Bing
Published: December 2021

Objective

To investigate the perioperative and long-term outcomes of laparoscopic pancreatectomy for benign and low-grade malignant pancreatic tumors, and further compare the outcomes between different surgical techniques.

Methods

We retrospectively collected clinical data of consecutive patients with benign or low-grade malignant pancreatic tumors underwent surgery from February 2014 to February 2019. Patients were grouped and compared according to different surgical operations they accepted.

Results

Totally 164 patients were reviewed and 83 patients underwent laparoscopic pylorus-preserving pancreaticoduodenectomy (LPPPD), 41 patients underwent laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and 20 patients underwent laparoscopic central pancreatectomy (LCP) were included in this study, the rest 20 patients underwent laparoscopic enucleation were excluded. There were 53 male patients and 91 female patients. The median age of these patients was 53.0 years (IQR 39.3–63.0 years). The median BMI was 21.5 kg/m2 (IQR 19.7–24.0 kg/m2). The postoperative severe complication was 4.2% and the 90-days mortality was 0. Compare with LCP group, the LPPPD and LSPDP group had longer operation time (300.4 ± 89.7 vs. 197.5 ± 30.5 min, P < 0.001) while LSPDP group had shorter operation time (174.8 ± 46.4 vs. 197.5 ± 30.5 min, P = 0.027), more blood loss [140.0 (50.0–1000.0) vs. 50.0 (20.0–200.0) ml P < 0.001 and 100.0 (20.0–300.0) vs. 50.0 (20.0–200.0 ml, P = 0.039, respectively), lower rate of clinically relevant postoperative pancreatic fistula [3 (3.6%) vs. 8 (40.0%), P < 0.001 and 3 (7.3%) vs. 8 (40.0%), P = 0.006, respectively], lower rate of postpancreatectomy hemorrhage [0 (0%) vs. 2 (10.0%), P = 0.036 and (0%) vs. 2 (10.0%) P = 0.104, respectively] and lower rate of postoperative severe complications [2 (2.4%) vs.4 (20.0%), P = 0.012 and 0 (0%) vs. 4 (20.0%), P = 0.009, respectively], higher proportion of postoperative pancreatin and insulin treatment (pancreatin: 39.8% vs., 15% P = 0.037 and 24.4%vs. 15%, P = 0.390; insulin: 0 vs. 18.1%, P = 0.040 and 0 vs. 12.2%, P = 0.041).

Conclusions

Overall, laparoscopic pancreatectomy could be safely performed for benign and low-grade malignant pancreatic tumors while the decision to perform laparoscopic central pancreatectomy should be made carefully for fit patients who can sustain a significant postoperative morbidity and could benefit from the excellent long-term results even in a high-volume center.
Transparency in public pharmaceutical sector: the key informants’ perceptions from a developing country
Authors: Esfandiari Atefeh , Yazdi-Feyzabadi Vahid , Zarei Leila , Rashidian Arash , Salari Hedayat
Published: December 2021

Background

Policymaking in the pharmaceutical sector plays a pivotal role in achieving the health systems’ goals. Transparency in the pharmaceutical policy could increase confidence in decision-making processes. This study aims to assess transparency in the public pharmaceutical sector of Iran.

Methods

This qualitative study with a content analysis approach was conducted in 2017 using the World Health Organization tool to explore pharmaceutical transparency. The perceptions of the various stakeholders of the health system through semi-structured interviews with a maximum variation of stakeholders were obtained in eight functions, including registration, licensing, inspection, promotion, clinical trials, selection, procurement, and distribution of medicines.

Results

There are some problems in two main categories: (1) General problems, including lack of transparency, conflict of interest, centralization, and monopoly. (2) Ethical problems include illegal payments, gifts, bribes, conflicts of interest, hidden power, hoarding, relationship-oriented behavior, medicine trafficking, and counterfeit medicine. Suggested solutions include evidence-based decision-making, the use of transparent and accountable processes, standardization, needs assessment, declaring a conflict of interest, skilled human resources, and tracking prescription.

Conclusion

Despite the development of effective pharmaceutical policy in the health care system and government interventions for the control of the market, in some functions, reviewing the pharmaceutical policy is essential. Additionally, declaring a conflict of interest statement must be at the core of policy development to provide greater transparency.
Cupriavidus in the intestinal microbiota of Tibet endemic fish Glyptosternum maculatum can help it adapt to habitat of the Qinghai Tibet Plateau
Authors: Pan Yingzi , Li Zhichao , Zhou Jianshe , Wang Qielu , Xu Huifen , Mou Zhenbo
Published: December 2021

Background

Gut microbes play an important role in the growth and development of fish. The Tibetan Plateau fish Glyptosternum maculatum is a unique species of sisorid catfish living in the river up to 4200 m altitude.

Results

To understand the mechanisms underlying the ability of G. maculatum to adapt to the high-altitude habitat, the intestinal microbiota of G. maculatum was studied. We used high-throughput sequencing of the 16S ribosomal RNA gene of intestinal microorganisms of wild and cultured G. maculatum to explore the characteristics of intestinal microorganisms and compared the gut microbial community of wild and cultured G. maculatum. The results showed that the α-diversity and richness of the intestinal microbiome were higher in wild G. maculatum than in cultured fish. The most abundant phylum in both G. maculatum were Fusobacteria, Proteobacteria, Firmicutes, and Bacteroidetes; Cetobacterium and Cupriavidus are the most dominant genus. The membership and structure of intestinal bacterial communities in wild G. maculatum are similar to the cultured fish, suggesting that a core microbiota is present in both G. maculatum intestinal bacterial communities. Metastats analysis showed that six genera were differentially represented between the wild and cultured G. maculatum.

Conclusions

The most interesting characteristic of the intestinal microbial communities of G. maculatum is that there were large numbers of Cupriavidus, which may play an important role in the adaptation of G. maculatum to the water of the Yarlung Zangbo River with a high Cu content. This result, in turn, can guide us on breeding G. maculatum.
Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors
Authors: Ba Sai , Gao Guangpeng , Li Tianhu , Zhang Hao
Published: December 2021

Most activity-based molecular probes are designed to target enzymes that catalyze the breaking of chemical bonds and the conversion of a unimolecular substrate into bimolecular products. However, DNA topoisomerases are a class of enzymes that alter DNA topology without producing any molecular segments during catalysis, which hinders the development of practical methods for diagnosing these key biomarkers in living cells. Here, we established a new strategy for the effective sensing of the expression levels and catalytic activities of topoisomerases in cell-free systems and human cells. Using our newly designed biosensors, we tricked DNA topoisomerases within their catalytic cycles to switch on fluorescence and resume new rounds of catalysis. Considering that human topoisomerases have been widely recognized as biomarkers for multiple cancers and identified as promising targets for several anticancer drugs, we believe that these DNA-based biosensors and our design strategy would greatly benefit the future development of clinical tools for cancer diagnosis and treatment.

Graphical Abstract
A core-shell Au@Cu2-xSe heterogeneous metal nanocomposite for photoacoustic and computed tomography dual-imaging-guided photothermal boosted chemodynamic therapy
Authors: Zhang Le , Jiang Chunjuan , Li Bing , Liu Zhengwang , Gu Bingxin , He Simin , Li Panli , Sun Yun , Song Shaoli
Published: December 2021

Chemodynamic therapy (CDT) has aroused extensive attention for conquering cancers because of its high specificity and low invasiveness. Quick generation of hydroxyl radicals (·OH) during CDT could induce more irreparable damage to cancer cells. The generation rate of ·OH could be magnified via the selection of suitable nanocatalysts or under the assistance of exogenous thermal energy from photothermal therapy (PTT). Here, we construct a kind of monodisperse core-shell Au@Cu2-xSe heterogeneous metal nanoparticles (NPs) for PTT boosted CDT synergistic therapy. Due to the localized surface plasmon resonance (LSPR) coupling effect in the core-shell structure, the photothermal conversion efficiency of Au@Cu2-xSe NPs is up to 56.6%. The in situ generated heat from photothermal can then accelerate the Fenton-like reaction at Cu+ sites to produce abundant ·OH, which will induce apoptotic cell death by attacking DNA, contributing to a heat-boosted CDT. Both in vitro and in vivo results showed that after this synergistic therapy, tumors could be remarkably suppressed. Guided by photoacoustic (PA) and computed tomography (CT) imaging, the therapeutic effects were more specified. Our results revealed that PA and CT dual-imaging-guided PTT boosted CDT synergistic therapy based on core-shell Au@Cu2-xSe NPs is an effective cancer treatment strategy.

Graphical Abstract
Rhamnolipid-coated W/O/W double emulsion nanoparticles for efficient delivery of doxorubicin/erlotinib and combination chemotherapy
Authors: Lee Yeeun , Lee Donghyun , Park Eunyoung , Jang Seok-young , Cheon Seo Young , Han Seongryeong , Koo Heebeom
Published: December 2021

Background

Combination therapy using more than one drug can result in a synergetic effect in clinical treatment of cancer. For this, it is important to develop an efficient drug delivery system that can contain multiple drugs and provide high accumulation in tumor tissue. In particular, simultaneous and stable loading of drugs with different chemical properties into a single nanoparticle carrier is a difficult problem.

Results

We developed rhamnolipid-coated double emulsion nanoparticles containing doxorubicin and erlotinib (RL-NP-DOX-ERL) for efficient drug delivery to tumor tissue and combination chemotherapy. The double emulsion method enabled simultaneous loading of hydrophilic DOX and hydrophobic ERL in the NPs, and biosurfactant RL provided stable surface coating. The resulting NPs showed fast cellular uptake and synergetic tumor cell killing in SCC7 cells. In real-time imaging, they showed high accumulation in SCC7 tumor tissue in mice after intravenous injection. Furthermore, enhanced tumor suppression was observed by RL-NP-DOX-ERL in the same mouse model compared to control groups using free drugs and NPs containing a single drug.

Conclusions

The developed RL-NP-DOX-ERL provided efficient delivery of DOX and ERL to tumor tissue and successful tumor therapy with a synergetic effect. Importantly, this study demonstrated the promising potential of double-emulsion NPs and RL coating for combination therapy.

Graphical Abstract
Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration
Authors: Hellenbrand Daniel J. , Quinn Charles M. , Piper Zachariah J. , Morehouse Carolyn N. , Fixel Jordyn A. , Hanna Amgad S.
Published: December 2021

Traumatic spinal cord injury (SCI) is a devastating neurological condition that results in a loss of motor and sensory function. Although extensive research to develop treatments for SCI has been performed, to date, none of these treatments have produced a meaningful amount of functional recovery after injury. The primary injury is caused by the initial trauma to the spinal cord and results in ischemia, oxidative damage, edema, and glutamate excitotoxicity. This process initiates a secondary injury cascade, which starts just a few hours post-injury and may continue for more than 6 months, leading to additional cell death and spinal cord damage. Inflammation after SCI is complex and driven by a diverse set of cells and signaling molecules. In this review, we utilize an extensive literature survey to develop the timeline of local immune cell and cytokine behavior after SCI in rodent models. We discuss the precise functional roles of several key cytokines and their effects on a variety of cell types involved in the secondary injury cascade. Furthermore, variations in the inflammatory response between rats and mice are highlighted. Since current SCI treatment options do not successfully initiate functional recovery or axonal regeneration, identifying the specific mechanisms attributed to secondary injury is critical. With a more thorough understanding of the complex SCI pathophysiology, effective therapeutic targets with realistic timelines for intervention may be established to successfully attenuate secondary damage.
What does early initiation and duration of breastfeeding have to do with childhood mortality? Analysis of pooled population-based data in 35 sub-Saharan African countries
Authors: Ekholuenetale Michael , Barrow Amadou
Published: December 2021

Background

Breastfeeding practices and their impact on infant health and survival are unquestionably of global interest. The aim of this study was to examine the link between breastfeeding initiation within one hour of birth, breastfeeding duration and childhood mortality in sub-Saharan Africa.

Methods

This study used data from the Demographic and Health Survey, which was conducted in 35 Sub-Saharan African countries between 2008 and 2017. Early initiation and duration of breastfeeding, food consumption indices, and infant mortality were all important variables. Analysis used percentage, median/interquartile range, and regression models (logistic, linear, Cox).

Results

Early initiation of breastfeeding within one hour after birth was lowest in Chad (23.0%) and highest in Burundi (85.0%). The pooled median duration of breastfeeding was 12 months. Female children had 3% significant lower odds of consuming tinned, powdered or fresh milk, compared with male children (OR 0.97; 95% CI 0.94, 0.99). Conversely, female children were more likely to be put to breast within one hour after birth, compared with male children (OR 1.03; 95% CI 1.01, 1.05). Results from the pooled sample showed approximately 20% (HR 0.80; 95% CI 0.67, 0.96) and 21% (HR 0.79; 95% CI 0.77, 0.80) reduction in infant mortality for children breastfed within one hour after birth and for every unit increase in the months of breastfeeding respectively. In addition, countries with the leading infant mortality rate include; Sierra Leone (92 deaths per 1000 live births), Chad (72 deaths per 1000 live births), Nigeria (69 deaths per 1000 live births), Cote d’ Ivoire (68 deaths per 1000 live births), Guinea (67 deaths per 1000 live births), Burkina-Faso (65 deaths per 1000 live births) and Mozambique (64 deaths per 1000 live births) respectively.

Conclusions

The findings from this study underscores the need for early breastfeeding initiation and prolong breastfeeding to be considered in programmes on improving childhood survival. Efforts should be made to improve optimal breastfeeding practices as only about half of children in the pooled sample had best practices of breastfeeding.
RiboPlotR: a visualization tool for periodic Ribo-seq reads
Authors: Wu Hsin-Yen Larry , Hsu Polly Yingshan
Published: December 2021

Background

Ribo-seq has revolutionized the study of genome-wide mRNA translation. High-quality Ribo-seq data display strong 3-nucleotide (nt) periodicity, which corresponds to translating ribosomes deciphering three nts at a time. While 3-nt periodicity has been widely used to study novel translation events such as upstream ORFs in 5′ untranslated regions and small ORFs in presumed non-coding RNAs, tools that allow the visualization of these events remain underdeveloped.

Results

RiboPlotR is a visualization package written in R that presents both RNA-seq coverage and Ribo-seq reads in genomic coordinates for all annotated transcript isoforms of a gene. Specifically, for individual isoform models, RiboPlotR plots Ribo-seq data in the context of gene structures, including 5′ and 3′ untranslated regions and introns, and it presents the reads for all three reading frames in three different colors. The inclusion of gene structures and color-coding the reading frames facilitate observing new translation events and identifying potential regulatory mechanisms.

Conclusions

RiboPlotR is freely available (https://github.com/hsinyenwu/RiboPlotR and https://sourceforge.net/projects/riboplotr/) and allows the visualization of translated features identified in Ribo-seq data.
Return to play after treating acute muscle injuries in elite football players with radial extracorporeal shock wave therapy
Authors: Morgan James P. M. , Hamm Mario , Schmitz Christoph , Brem Matthias H.
Published: December 2021

Background

To compare lay-off times achieved by treating acute muscle injuries in elite football players with a multimodal therapy approach that includes a specific protocol of almost daily radial extracorporeal shock wave therapy (rESWT) with corresponding data reported in the literature.

Methods

We performed a retrospective analysis of treatments and recovery times of muscle injuries suffered by the players of an elite football team competing in the first/second German Bundesliga during one of the previous seasons.

Results

A total of 20 acute muscle injuries were diagnosed and treated in the aforementioned season, of which eight (40%) were diagnosed as Type 1a/muscular tightness injuries, five (25%) as Type 2b/muscle strain injuries, four (20%) as Type 3a/partial muscle tear injuries and three (15%) as contusions. All injuries were treated with the previously mentioned multimodal therapy approach. Compared with data reported by Ekstrand et al. (Br J Sports Med 47:769–774, 2013), lay-off times (median/mean) were shortened by 54% and 58%, respectively, in the case of Type 1a injuries, by 50% and 55%, respectively, in the case of Type 2b injuries as well as by 8% and 21%, respectively, in the case of Type 3a injuries. No adverse reactions were observed.

Conclusions

Overall, the multimodal therapy approach investigated in this study is a safe and effective treatment approach for treating Type 1a and 2b acute muscle injuries amongst elite football players and may help to prevent more severe, structural muscle injuries.
Trapeziectomy for basal thumb osteoarthritis does not increase the risk of developing wrist osteoarthritis in the long term
Authors: Brogren Elisabeth , Besjakov Jack , Åkesson Anna , Atroshi Isam
Published: December 2021

Background

Symptomatic osteoarthritis of the basal joint of the thumb (trapeziometacarpal joint) is a common disabling condition mainly affecting women. It is frequently treated with complete removal of the trapezium with or without soft-tissue interposition. There is limited evidence about whether removal of the trapezium affects stability of the wrist joint and increases the risk of developing wrist osteoarthritis. The aim of this study was to evaluate the long-term prevalence of OA in wrists with previous trapeziectomy compared to wrists with intact trapezium.

Methods

Patients treated with surgery for trapeziometacarpal osteoarthritis at one orthopedic department were invited 10–29 (mean 17) years postoperatively for bilateral radiographic examination. We included radiographs from 114 hands with trapeziectomy and 46 hands with intact trapezium; 38 patients had unilateral trapeziectomy and intact contralateral trapezium. The radiographs were blinded so that the intact trapezium or the trapezial space after trapeziectomy was not visible. The radiographs were then evaluated for radiocarpal/midcarpal osteoarthritis independently by two assessors using three different osteoarthritis grading systems, including the Kellgren–Lawrence classification. The patients rated their satisfaction with the function of each of their hands on a visual analog scale (VAS) from 0 to 100 (higher score better).

Results

The prevalence of osteoarthritis ranged from 20 to 26%, mostly mild (Kellgren–Lawrence grade 1). The prevalence of osteoarthritis did not differ between wrists with previous trapeziectomy and those with intact trapezium, both in the whole cohort and in the subgroup of patients with unilateral trapeziectomy and intact contralateral trapezium. There was no significant difference in hand function VAS scores between hands with previous trapeziectomy and hands with intact trapezium in the whole cohort or in the subgroup.

Conclusions

Removal of the trapezium as treatment for basal thumb osteoarthritis does not increase the risk of developing wrist osteoarthritis in the long term.
GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma
Authors: Xie Chaofan , Xiang Wei , Shen Huiyong , Shen Jingnan
Published: December 2021

Background

G2 and S phase-expressed-1 (GTSE1) negatively regulates the tumor-suppressive protein p53 and is potentially correlated with chemoresistance of cancer cells. This study aims to explore the effect of GTSE1 on the DNA damage repair and cisplatin (CDDP) resistance in osteosarcoma (OS).

Materials and methods

Expression of GTSE1 in OS was predicted in bioinformatics system GEPIA and then validated in clinically obtained tissues and acquired cell lines using RT-qPCR, immunohistochemical staining, and western blot assays. Gain- and loss-of-function studies of GTSE1 were performed in MG-63 and 143B cells to examine its function in cell cycle progression, DNA replication, and CDDP resistance. Stably transfected MG-63 cells were administrated into mice, followed by CDDP treatment to detect the role of GTSE1 in CDDP resistance in vivo.

Results

GTSE1 was highly expressed in patients with OS and correlated with poor survival according to the bioinformatics predictions. Elevated GTSE1 expression was detected in OS tissues and cell lines. GTSE1 silencing reduced S/G2 transition and DNA replication, and it increased the CDDP sensitivity and decreased the expression of DNA repair-related biomarkers in MG-63 cells. GTSE1 overexpression in 143B cells led to inverse trends. In vivo, downregulation of GTSE1 strengthened the treating effect of CDDP and significantly repressed growth of xenograft tumors in nude mice. However, overexpression of GTSE1 blocked the anti-tumor effect of CDDP.

Conclusion

This study demonstrates that GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in OS.
Outcomes of surgically treated infective endocarditis in a Western Australian population
Authors: Eranki Aditya , Wilson-Smith Ashley R. , Ali Umar , Saxena Akshat , Slimani Eric
Published: December 2021

Background

Infective endocarditis is a disease that carries high morbidity and mortality. The primary endpoint of this study is to assess factors associated with in-hospital mortality in patients undergoing valvular surgery for infective endocarditis. The secondary endpoint of this study is to assess the incidence of post-operative stroke, renal failure, complete heart block and recurrence.

Methods

Between the years of 2015 to 2019, a total of 89 patients underwent surgery for infective endocarditis at Fiona Stanley Hospital, Western Australia. Data was collected from the Australia and New Zealand Cardiac Surgery Database from 2015 to 2019 as well as patients electronic medical record. A number of preoperative and perioperative factors were assessed in relation to patient mortality and morbidity. Univariate and multivariate logistical regression analysis was done to assess for the association between factors and in-hospital morbidity and mortality.

Results

A total of 89 patients underwent surgery for infective endocarditis from 2015 to 2019, affecting a total of 101 valves. The mean age of patients was 53.7 ± 16.5. A total of 79 patients had a positive blood culture pre-operatively, with Staphylococcus Aureus being the most frequently cultured organism (39%). Fourteen patients (16%) were deemed emergent and underwent surgery within 24 h of review. A total of five patients died within their hospital stay postoperatively. Variables significantly associated with mortality on univariate analysis were intravenous drug use, emergent surgery, perioperative dialysis, perioperative inotropes, cardiopulmonary bypass time and cross clamp time. Only CBP time was significantly associated with mortality on multivariate analysis. A total of 19 patients (21%) required hemodialysis after surgery, 10 patients sustained a postoperative stroke (11%), 11 patients developed a complete heart block post operatively (12%) and endocarditis recurred in 10 patients (11%).

Conclusion

Prolonged cardiopulmonary bypass times were significantly associated with mortality. This study is novel to report a lower mortality rate than previously quoted in the literature. We also report our findings of organisms, preoperative embolic phenomena and surgery in a Western Australian population. We recommend that all patients with endocarditis are discussed in multidisciplinary forum.
Ascending aorta graft pseudoaneurysm and aortobronchial fistula caused by a fractured sternal wire: a case report
Authors: Amirghofran Ahmad Ali , Nirooei Elahe , Ostovan Mohammad Ali
Published: December 2021

Background

Pseudoaneurysm of ascending aorta is a rare but serious complication of cardiovascular surgeries and it infrequently occurs in the normal prosthetic graft materials. We share our experience with an unusual case of ascending aorta Dacron graft pseudoaneurysm caused by a fractured sternal wire.

Case presentation

A 34-year-old man, known case of Marfan syndrome, with history of two prior aortic surgeries for aneurysm of ascending aorta, arch and thoracoabdominal aorta, presented with hemoptysis. The hemoptysis originated from an aortobronchial fistula secondary to a huge ascending aorta Dacron graft pseudoaneurysm. The graft erosion and subsequent pseudoaneurysm was caused by a fractured sternal wire. Surgical repair of the pseudoaneurysm was performed successfully and a Gore-tex patch was placed behind the sternum over the graft to prevent further direct contact of the wire and the graft.

Conclusion

Sternal wires can damage the adjacent vascular grafts and lead to fatal complications such as pseudoaneurysm formation. Thus, preventive measures such as using sternal bands and placing a covering layer between the sternal wires and aortic grafts are recommended in patients with dilated or replaced ascending aorta.
Beta blocker use in traumatic brain injury based on the high-sensitive troponin status (BBTBBT): methodology and protocol implementation of a double-blind randomized controlled clinical trial
Authors: El-Menyar Ayman , Asim Mohammad , Bahey Ahmed Abdel-Aziz , Chughtai Talat , Alyafai Abdulnasser , Abdelrahman Husham , Rizoli Sandro , Peralta Ruben , Al-Thani Hassan
Published: December 2021

Background

Beta-adrenergic receptor blockers (BB) play an important role in the protection of organs that are susceptible for secondary injury due to stress-induced adrenergic surge. However, the use of BB in traumatic brain injury (TBI) patients is not yet the standard of care which necessitates clear scientific evidence to be used. The BBTBBT study aims to determine whether early administration of propranolol based on the high-sensitive troponin T(HsTnT) status will improve the outcome of TBI patients. We hypothesized that early propranolol use is effective in reducing 10- and 30-day mortality in TBI patients. Secondary outcomes will include correlation between serum biomarkers (troponin, epinephrine, cytokines, enolase, S100 calcium binding protein B) and the severity of injury and the impact of BB use on the duration of hospital stay and functional status at a 3-month period.

Methods

The BBTBBT study is a prospective, randomized, double-blinded, placebo-controlled three-arm trial of BB use in mild-to-severe TBI patients based on the HsTnT status. All enrolled patients will be tested for HsTnT at the first 4 and 6 h post-injury. Patients with positive HsTnT will receive BB if there is no contraindication (group 1). Patients with negative HsTnT will be randomized to receive either propranolol (group 2) or placebo (group 3). The time widow for receiving the study treatment is the first 24 h post-injury.

Discussion

Early BB use may reduce the catecholamine storm and subsequently the cascade of immune and inflammatory changes associated with TBI. HsTnT could be a useful fast diagnostic and prognostic tool in TBI patients. This study will be of great clinical interest to improve survival and functional outcomes of TBI patients.

Trial registration

ClinicalTrials.gov NCT04508244. Registered on 7 August 2020. Recruitment started on 29 December 2020 and is ongoing.
The advanced performance of microbial consortium for simultaneous utilization of glucose and xylose to produce lactic acid directly from dilute sulfuric acid pretreated corn stover
Authors: Sun Yaqin , Li Xiaoying , Wu Lida , Li Yi , Li Fan , Xiu Zhilong , Tong Yi
Published: December 2021

Background

Lignocellulosic feedstocks have attracted much attention as a potential carbon source for lactic acid (LA) production because of their ready availability, sustainability, and renewability. However, there are at least two major technical challenges to producing LA from lignocellulose. Inhibitors derived from lignocellulose pretreatment have a negative impact on the growth of cells producing LA. Furthermore, pentose sugars produced from the pretreatment are difficultly utilized by most LA producers, which is known as the carbon catabolite repression (CCR) effect. This complex feedstock can be utilized by a robust microbial consortium with high bioconversion efficiency.

Results

In this study, a thermophilic consortium DUT50 producing LA was enriched and employed to improve corn stover (CS) utilization. Enterococcus was the dominant family in the consortium DUT50, accounting for 93.66% of the total abundance, with Lactobacillus, Bacillus, Lactococcus, and Trichococcus accounted for the remaining 2.68%. This consortium could be resistant to inhibitors concentration up to 9.74 g/L (2.88 g/L acetic acid, 2.46 g/L furfural, 2.20 g/L 5-HMF, and 2.20 g/L vanillin derived from pretreatment of CS), and simultaneously metabolizes hexose and pentose without CCR effect. Based on the promising consortium features, an efficient process of simultaneous saccharification and co-fermentation (SSCF) was developed to produce LA from acid pretreated corn stover, in which solid–liquid separation and detoxification were avoided. The key influencing factors were investigated and optimized, including dry biomass and cellulase loading, corn steep liquor powder concentration, and the pre-hydrolysis time. The highest LA titer of 71.04 g/L with a yield of 0.49 g/g-CS was achieved at a dry biomass loading of 20% (w/v), which is the highest LA production from non-detoxified acid pretreated corn stover via the SSCF process without wastewater generation reported to date. The simultaneous metabolism of hexose and pentose revealed collaboration between Enterococcus in the consortium, whereas xylose may be efficiently metabolized by Lactobacillus and Bacillus with low abundance via the pentose phosphate pathway.

Conclusions

The experimental results demonstrated the potential advantage of symbiosis in microbial consortia used for LA production from lignocellulosic biomass.
The inertial relaxed algorithm with Armijo-type line search for solving multiple-sets split feasibility problem
Authors: Chen Wenting , Li Meixia
Published: December 2021

The multiple-sets split feasibility problem is the generalization of split feasibility problem, which has been widely used in fuzzy image reconstruction and sparse signal processing systems. In this paper, we present an inertial relaxed algorithm to solve the multiple-sets split feasibility problem by using an alternating inertial step. The advantage of this algorithm is that the choice of stepsize is determined by Armijo-type line search, which avoids calculating the norms of operators. The weak convergence of the sequence obtained by our algorithm is proved under mild conditions. In addition, the numerical experiments are given to verify the convergence and validity of the algorithm.
Machine learning techniques to predict daily rainfall amount
Authors: Liyew Chalachew Muluken , Melese Haileyesus Amsaya
Published: December 2021

Predicting the amount of daily rainfall improves agricultural productivity and secures food and water supply to keep citizens healthy. To predict rainfall, several types of research have been conducted using data mining and machine learning techniques of different countries’ environmental datasets. An erratic rainfall distribution in the country affects the agriculture on which the economy of the country depends on. Wise use of rainfall water should be planned and practiced in the country to minimize the problem of the drought and flood occurred in the country. The main objective of this study is to identify the relevant atmospheric features that cause rainfall and predict the intensity of daily rainfall using machine learning techniques. The Pearson correlation technique was used to select relevant environmental variables which were used as an input for the machine learning model. The dataset was collected from the local meteorological office at Bahir Dar City, Ethiopia to measure the performance of three machine learning techniques (Multivariate Linear Regression, Random Forest, and Extreme Gradient Boost). Root mean squared error and Mean absolute Error methods were used to measure the performance of the machine learning model. The result of the study revealed that the Extreme Gradient Boosting machine learning algorithm performed better than others.
A study on ER stress-induced apoptosis pathway in cervical cancer HeLa cells treated with biosynthesized gold nanoparticles
Authors: Kamala Priya M. R. , Iyer Priya R.
Published: December 2021

Background

The expression of apoptotic family of protein plays a major role in induction of programmed cell death. There are six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl1. All these proteins have crucial role in the regulation of apoptosis through mitochondrial degradation, DNA damage, nuclear condensation and eventually cell death of the cancerous cells. It was observed that the apoptotic pathway has been initiated in the cancer cells from the expression of the apoptotic proteins. The results emphasized that the apoptotic cell death has been induced by the nanomaterials against cervical cancer HeLa cell line.

Methods

Initially, the nanomaterials were individually checked for potential anticancer activities through MTT assay. The cervical cancer HeLa cell line was treated with nanoparticles, nanoconjugates, nano-dox conjugate and chitosan–nano-dox conjugates. The cell lysates were processed for SDS–PAGE followed by Western blotting. The apoptotic expression has been studied for six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl 1.

Results

In the present study, the biosynthesized gold nanoparticles, nanoconjugates, nano-dox conjugate, chitosan–nano-dox conjugate were treated against cervical cancer HeLa cell line. The results demonstrated anticancer effects of the nanocompounds implying nanoparticles induced apoptotic pathway in the cancer cells. Further apoptotic expression was studied for six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl 1. The present study was focussed on anticancer efficiency of biosynthesized nanomaterials.

Conclusions

The in vitro anticancer study showed that the nanomaterials induced cell death over the treated cervical cancer cells. In the process of apoptotic cell death, the caspase cascade pathway was activated. The gene expression was checked in line with some of the genes involved in apoptosis, cell death. The expression was checked for Caspase 12, BAX, Bcl2, cyt c, PARP3 and Mcl 1. The expression of apoptotic proteins suggested that the cancer cell death was mediated through ER stress-induced pathway involving the major apoptotic proteins.
Purification and characterization of actinidin from Actinidia deliciosa and its utilization in inactivation of α-amylase
Authors: Dhiman Vivek Kumar , Chauhan Vivek , Kanwar Shamsher Singh , Singh Devendra , Pandey Himanshu
Published: December 2021

Background

Actinidin is an anionic thiol-proteinase predominant and unique to Chinese gooseberry or kiwifruit, whose strong digestibility enables proteins or enzymes vulnerable to digestion. The arrangement of active cysteine–thiol residues (Cys22-Cys65, Cys56-Cys98, and Cys156-Cys206) stabilizes the catalytic unit, thus allowing an effective Inhibition of α-amylase protein on exposure to the highest concentrations of actinidin under optimum conditions. When starch-rich foods are consumed with kiwifruit, starch digestion may be slowed by the inactivation of α-amylase (digestive enzyme), specifically reducing the blood sugar levels by hindering starch digestion that is helpful in diabetes mellitus. Thus, the study aimed at actinidin purification, optimization for maximal activity, and its demonstration as a potential to degrade α-amylase.

Results

Protease showed a molecular mass of 27 kDa on SDS-PAGE analysis. One factor at a time method was applied for process optimization, increasing the actinidin yield up to 176.03 U/mg. The enzyme was stable at a wide pH range; however, it was most active and stable at pH 7.5. The enzyme possessed half‐life at 35 °C of 5.5 h, at 40 °C of 4.5 h, at 45 °C of 2.5 h, and at 50 °C of 1 h. Lineweaver–Burk plot showed Michaelis–Menten constant (Km: 3.14 mg/ml) and maximal velocity (Vmax: 1.428 mmol/ml/min) using casein. The actinidin activity was enhanced with Ca2+ while it was inhibited by Cd2+ and Hg2+ ions. The α-amylase protein was successfully inactivated upon incubation with actinidin for 30 min; around ~ 85% of the α-amylase activity diminished. IC50 for inhibition of α-amylase was 2.54 mg/ml for crude actinidin and 1.86 mg/ml for purified actinidin.

Conclusions

Purified Actinidin showed a 1.28-fold increase in proteolytic activity. The proteinase showed an active pH range of 3.5–8.5 under varied buffer conditions and thermostability up to 50 °C. The results revealed a significant potential utility of actinidin to retard amylase as it effectively degraded the amylolytic enzyme under in vitro conditions and could be beneficial for lowering glycemic response to ingested starch. However, further in vitro as well as in vivo studies need to be conducted under gastrointestinal conditions to establish the hypothesis.
A bolder One Health: expanding the moral circle to optimize health for all
Authors: Coghlan Simon , Coghlan Benjamin John , Capon Anthony , Singer Peter
Published: December 2021

One Health is a ground-breaking philosophy for improving health. It imaginatively challenges centuries-old assumptions about wellbeing and is now widely regarded as the ‘best solution’ for mitigating human health problems, including pandemic zoonotic diseases. One Health’s success is imperative because without big changes to the status quo, great suffering and ill-health will follow. However, even in its more ambitious guises, One Health is not radical enough. For example, it has not embraced the emerging philosophical view that historical anthropocentrism is an unfounded ethical prejudice against other animals. This paper argues that One Health should be more imaginative and adventurous in its core philosophy and ultimately in its recommendations and activities. It must expand the circle of moral concern beyond a narrow focus on human interests to include nonhuman beings and the environment. On this bolder agenda, progressive ethical and practical thinking converge for the benefit of the planet and its diverse inhabitants—human and nonhuman.
The effect of cytokine leukemia-inhibitory factor (LIF) and interleukin-11 (IL-11) gene expression on the primary infertility related to polycystic ovary syndrome, Tubal factor, and Unexplained infertility in Turkish women
Authors: Alzaidi Zahraa , Yildiz Şule Menziletoğlu , Saatçi Çetin , Akalin Hilal Ünlü , Muderris Iptisam Ipek , Aynekin Buşra , Şahin Izem Olcay , Dündar Munis
Published: December 2021

Background

Successful implantation of blastocysts is indeed an important path in mammalian reproduction that is governed by a complicated web of cytokines interactions. Leukemia inhibitory factor (LIF) and interleukin-11 (IL-11) part of the interleukin (IL)-6 groups are cytokines that are needed for effective implantation and prevent infertility symptoms. This study aimed to determine the expression level (LIF, IL-11) genes in patients with primary infertility related to polycystic ovary syndrome (PCOS), tubal factor infertility (TFI), and unexplained infertility (UI).

Results

In this study, 75 infertility women and 40 controls were involved. The expressions of LIF and IL-11 genes were evaluated by quantitative real-time polymerase chain reaction qRT–PCR Light Cycler in patients and healthy controls. PCOS, TFI, and UI groups showed promising results regarding LIF gene, which appeared at very small levels compared to the control (p < 0.0001). Regarding IL-11, the two groups TFI and UI were significantly linked to the lower level of gene expression, while the PCOS group has no significant difference when it is compared to the control group (p < 0.0001, < 0.05, 0.19), respectively.

Conclusion

The current findings show that low levels of LIF and IL-11 gene expression are linked to various primary infertility conditions, including PCOS, tubal factor, and unexplained infertility since they play a fundamental role in embryo implantation.