bluuebunny/crossref_metadata_2025_split huggingface dataset:
Holistic description of new deep sea megafauna (Cephalopoda: Cirrata) using a minimally invasive approach
Authors: Ziegler Alexander , Sagorny Christina 
Published: April 2021

Abstract
Background
In zoology, species descriptions conventionally rely on invasive morphological techniques, frequently leading to damage of the specimens and thus only a partial understanding of their structural complexity. More recently, non-destructive imaging techniques have successfully been used to describe smaller fauna, but this approach has so far not been applied to identify or describe larger animal species. Here, we present a combination of entirely non-invasive as well as minimally invasive methods that permit taxonomic descriptions of large zoological specimens in a more comprehensive manner.

Results
Using the single available representative of an allegedly novel species of deep-sea cephalopod (Mollusca: Cephalopoda), digital photography, standardized external measurements, high-field magnetic resonance imaging, micro-computed tomography, and DNA barcoding were combined to gather all morphological and molecular characters relevant for a full species description. The results show that this specimen belongs to the cirrate octopod (Octopoda: Cirrata) genus Grimpoteuthis Robson, 1932. Based on the number of suckers, position of web nodules, cirrus length, presence of a radula, and various shell characters, the specimen is designated as the holotype of a new species of dumbo octopus, G. imperator sp. nov. The digital nature of the acquired data permits a seamless online deposition of raw as well as derived morphological and molecular datasets in publicly accessible repositories.

Conclusions
Using high-resolution, non-invasive imaging systems intended for the analysis of larger biological objects, all external as well as internal morphological character states relevant for the identification of a new megafaunal species were obtained. Potentially harmful effects on this unique deep-sea cephalopod specimen were avoided by scanning the fixed animal without admixture of a contrast agent. Additional support for the taxonomic placement of the new dumbo octopus species was obtained through DNA barcoding, further underlining the importance of combining morphological and molecular datasets for a holistic description of zoological specimens.
A cornucopia of research resources for the fourth rodent malaria parasite species
Authors: Carlton Jane M. 
Published: April 2021

AbstractThe study of human malaria caused by species of Plasmodium has undoubtedly been enriched by the use of model systems, such as the rodent malaria parasites originally isolated from African thicket rats. A significant gap in the arsenal of resources of the species that make up the rodent malaria parasites has been the lack of any such tools for the fourth of the species, Plasmodium vinckei. This has recently been rectified by Abhinay Ramaprasad and colleagues, whose pivotal paper published in BMC Biology describes a cornucopia of new P. vinckei ‘omics datasets, mosquito transmission experiments, transfection protocols, and virulence phenotypes, to propel this species firmly into the twenty-first century.
Proteomics-based identification of TMED9 is linked to vascular invasion and poor prognoses in patients with hepatocellular carcinoma
Authors: Yang Yi-Chieh , Chien Ming-Hsien , Lai Tsung-Ching , Tung Min-Che , Jan Yi-Hua , Chang Wei-Ming , Jung Shih-Ming , Chen Ming-Huang , Yeh Chun-Nan , Hsiao Michael 
Published: April 2021

AbstractBackgroundDue to the difficulties in early diagnosing and treating hepatocellular carcinoma (HCC), prognoses for patients remained poor in the past decade. In this study, we established a screening model to discover novel prognostic biomarkers in HCC patients.MethodsCandidate biomarkers were screened by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analyses of five HCC normal (N)/tumor (T) paired tissues and preliminarily verified them through several in silico database analyses. Expression levels and functional roles of candidate biomarkers were respectively evaluated by immunohistochemical staining in N/T paired tissue (n = 120) and MTS, colony formation, and transwell migration/invasion assays in HCC cell lines. Associations of clinicopathological features and prognoses with candidate biomarkers in HCC patients were analyzed from GEO and TCGA datasets and our recruited cohort.ResultsWe found that the transmembrane P24 trafficking protein 9 (TMED9) protein was elevated in HCC tissues according to a global proteomic analysis. Higher messenger (m)RNA and protein levels of TMED9 were observed in HCC tissues compared to normal liver tissues or pre-neoplastic lesions. The TMED9 mRNA expression level was significantly associated with an advanced stage and a poor prognosis of overall survival (OS,p = 0.00084) in HCC patients. Moreover, the TMED9 protein expression level was positively correlated with vascular invasion (p = 0.026), OS (p = 0.044), and disease-free survival (p = 0.015) in our recruited Taiwanese cohort. In vitro, manipulation of TMED9 expression in HCC cells significantly affected cell migratory, invasive, proliferative, and colony-forming abilities.ConclusionsOurs is the first work to identify an oncogenic role of TMED9 in HCC cells and may provide insights into the application of TMED9 as a novel predictor of clinical outcomes and a potential therapeutic target in patients with HCC.
Effects of sodium‐glucose cotransporter type 2 inhibitors on cardiovascular, renal, and safety outcomes in patients with cardiovascular disease: a meta‐analysis of randomized controlled trials
Authors: Zheng Caiyun , Lin Meimei , Chen Yan , Xu Haiting , Yan Lingqun , Dai Hengfen 
Published: April 2021

AbstractBackgroundControlled studies and observational studies have shown that sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) are beneficial for the survival of patients with heart failure (HF). However, it is unclear whether SGLT-2i can provide benefit in patients with other cardiovascular diseases. Here, we conducted a systematic review and meta-analysis to determine the outcomes of cardiovascular, renal, and safety outcomes of SGLT-2i administration in patients with cardiovascular diseases.MethodsWe searched PubMed, EMBASE, Cochrane Library, Web of Science databases, and ClinicalTrials.gov databases for randomised controlled trials written in English from inception until November 1, 2020. Two reviewers independently identified randomised controlled trials comparing the effects of SGLT-2i in patients with cardiovascular disease with or without diabetes. Primary outcomes were cardiovascular outcomes and renal outcomes. Secondary outcomes were safety outcomes, including adverse endocrine outcomes and adverse infection outcomes. The effects of SGLT-2i were evaluated using RevMan5.3 software. The Cochrane risk of bias tool was used to assess study quality.ResultsWe identified 10 randomised controlled trials (25,108 patients in the SGLT-2i group and 18,574 patients in the placebo group). Meta-analysis revealed that SGLT-2i treatment significantly reduced all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure (HHF) in patients with cardiovascular disease (all-cause mortality relative risk [RR]: 0.86; 95% confidence interval [CI] 0.81–0.91;P < 0.00001;I2 = 0%; cardiovascular mortality RR: 0.85; 95% CI 0.79–0.92;P < 0.0001;I2 = 26%; HHF RR: 0.69; 95% CI 0.64–0.81;P < 0.00001;I2 = 0%). In patients with HF, mortality and HHF after SGLT-2i treatment for HF with reduced ejection fraction were significantly reduced, whereas HF with preserved ejection fraction did not differ compared with placebo treatment. Moreover, SGLT-2i induced a lower incidence of renal damage and myocardial infarction than the placebo group; however, the risk of infection, amputation, volume depletion, and diabetic ketoacidosis was higher.ConclusionsSGLT-2i had significant clinical effects on cardiovascular outcomes and significantly influenced acute kidney injury. The effects of SGLT-2i on cardiovascular disease were independent of diabetic status. Sotagliflozin could have advantages over other SGLT-2i in lowering HHF.
Association of mushroom consumption with all-cause and cause-specific mortality among American adults: prospective cohort study findings from NHANES III
Authors: Ba Djibril M. , Gao Xiang , Muscat Joshua , Al-Shaar Laila , Chinchilli Vernon , Zhang Xinyuan , Ssentongo Paddy , Beelman Robert B. , Richie John P. 
Published: April 2021

Abstract
Background
Whether mushroom consumption, which is rich in several bioactive compounds, including the crucial antioxidants ergothioneine and glutathione, is inversely associated with low all-cause and cause-specific mortality remains uncertain. This study aimed to prospectively investigate the association between mushroom consumption and all-cause and cause-specific mortality risk.

Methods
Longitudinal analyses of participants from the Third National Health and Nutrition Examination Survey (NHANES III) extant data (1988–1994). Mushroom intake was assessed by a single 24-h dietary recall using the US Department of Agriculture food codes for recipe foods. All-cause and cause-specific mortality were assessed in all participants linked to the National Death Index mortality data (1988–2015). We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cause-specific mortality.

Results
Among 15,546 participants included in the current analysis, the mean (SE) age was 44.3 (0.5) years. During a mean (SD) follow-up duration of 19.5 (7.4) years , a total of 5826 deaths were documented. Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.73–0.98) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors including total energy. When cause-specific mortality was examined, we did not observe any statistically significant associations with mushroom consumption. Consuming 1-serving of mushrooms per day instead of 1-serving of processed or red meats was associated with lower risk of all-cause mortality (adjusted HR = 0.65; 95% CI: 0.50–0.84). We also observed a dose-response relationship between higher mushroom consumption and lower risk of all-cause mortality (P-trend = 0.03).

Conclusion
Mushroom consumption was associated with a lower risk of total mortality in this nationally representative sample of US adults.
Comparative proteomics analysis reveals differentially accumulated proteins associated with male and female A. chinensis var. chinensis bud development
Authors: Zhang Yu , Wang Yuexing , Zhou Wanying , Zheng Shimao , Zhang Wenhui 
Published: April 2021

Abstract
Background
Kiwifruit (Actinidia chinensis var. Chinensis) is abundant with vitamin C and is a rapidly developing crop in China, New Zealand, and other countries. It has been widely used as a raw material for food and kiwifruit wine. Among these, A. chinensis var. chinensis and A. chinensis var. deliciosa are the most valuable kiwifruit in production. Kiwifruit is a typical dioecious plant and its female and male plants have different economic values. Therefore, sex identification, especially at the seedling stage, has important implications for the scientific planning of its production and economic benefits. However, the kiwifruit sex regulation mechanism is very complex and molecular studies are in the initial stages. Currently, there is not a universal and effective sex identification method for A. chinensis.

Methods
In this study, we used a label-free quantitative proteomics approach to investigate differentially accumulated proteins, including their presence/absence and significantly different levels of abundances during A. chinensis var. chinensis male and female flower bud development.

Results
A total of 6485 proteins were identified, among which, 203 were identified in male buds, which were mainly associated with phenylalanine metabolism, tyrosine metabolism, and plant hormone signal transduction. In female buds, 241 were identified, which were mainly associated with the ErbB signaling pathway, growth hormone synthesis, secretion and action, and mRNA surveillance pathway. A total of 373 proteins were significantly differentially accumulated proteins (fold change > 2; P < 0.05), of which, 168 were upregulated and 205 were downregulated. Significant differences between proteins involved 13 signaling pathways, most of which were involved in flavonoid biosynthesis, phenylpropanoid biosynthesis, and starch and sucrose metabolism. Protein interaction analysis showed that enriched protein nodes included cell division cycle 5-like protein, 40S ribosomal protein S8, ribosomal protein, and 40S ribosomal protein like, which interact with 35, 25, 22, and 22 proteins, respectively.

Conclusions
This study provide valuable information for cloning key genes that control sex traits and functionally analyze their roles, which lay a foundation to the development of molecular markers for male and female kiwifruit identification.
Diet-induced prediabetes: effects of exercise treatment on risk factors for cardiovascular complications
Authors: Luvuno Mluleki , Khathi Andile , Mabandla Musa V. 
Published: April 2021

AbstractBackgroundAn animal model of prediabetes that has been developed in our laboratory using a high fat high carbohydrate diet and lack of physical activity displays risk factors for cardiovascular complications. The effect of exercise against these risk factors in this animal model remains unknown. Therefore, we evaluated the effect of intermittent and regular exercise treatment on the risk factors for cardiovascular complications in this animal model of prediabetes.MethodsFollowing prediabetes induction, animals were randomly assigned to the following groups (n = 6): non-diabetic, prediabetic, intermittently exercising prediabetic and regularly exercising prediabetic. Exercise exposure was 7 weeks long. Body weight changes, caloric intake, blood glucose, total cholesterol, and triglyceride concentration was measured after 20 and 29 weeks while blood pressure was only measured after 29 weeks. Plasma endothelial nitric oxide synthase, malonaldehyde, glutathione peroxidase, tumour necrosis factor-alpha and C-reactive protein concentration from the heart were measured 2 weeks post-exercise termination (week 30).ResultsWe found increased body weight, caloric intake and mean arterial pressure in the prediabetic group by comparison to the non-prediabetic group. The same trend was observed in blood glucose and triglyceride concentrations. However, all of these parameters were reduced in the intermittently exercising prediabetic and regularly exercising prediabetic groups. This reduction was further accompanied by a decrease in the endothelial nitric oxide synthase, tumour necrosis factor-alpha and C-reactive protein concentration with improved oxidative stress biomarkers.ConclusionsThe progression of pre-diabetes to diabetes is slowed or possibly stopped by exercise (regular or intermittent). Additionally, biomarker profiles indicative of cardiovascular disease in pre-diabetics are improved by exercise.
Effects of estrogen deficiency during puberty on maxillary and mandibular growth and associated gene expression – an μCT study on rats
Authors: Küchler Erika Calvano , de Lara Rafaela Mariana , Omori Marjorie Ayumi , Marañón-Vásquez Guido , Baratto-Filho Flares , Nelson-Filho Paulo , Stuani Maria Bernadete Sasso , Blanck-Lubarsch Moritz , Schroeder Agnes , Proff Peter , Kirschneck Christian 
Published: April 2021

AbstractBackgroundEstrogen is a well-known and important hormone involved in skeletal homeostasis, which regulates genes involved in bone biology. Some studies support that estrogen is important for craniofacial growth and development. Therefore this in vivo animal study aimed to investigate, whether and in which way low estrogen levels in the prepubertal period affect craniofacial development in the postpubertal stage and to quantify the gene expression of RANK, RANKL and OPG in cranial growth sites in ovariectomized estrogen-deficient rats during puberty.MethodsControl (sham-operated,n = 18) and ovariectomy (OVX, n = 18) surgeries were performed on 21-days-old female Wistar rats. Animals euthanized at an age of 45 days (pubertal stage) were used for gene expression analyses (n = 6 per group) and immunohistochemistry of RANK, RANKL and OPG. Animals euthanized at 63 days of age (post-pubertal stage) were used for craniofacial two-dimensional and three-dimensional craniofacial measurements using μCT imaging (n = 12 per group).ResultsIn the μCT analysis of the mandible and maxilla many statistically significant differences between sham-operated and OVX groups were observed, such as increased maxillary and mandibular bone length in OVX animals (p < 0.05). Condylar volume was also significantly different between groups (p < 0.05). The sham-operated group showed a higher level of RANK expression in the midpalatal suture (p = 0.036) and the RANKL:OPG ratio levels were higher in the OVX group (p = 0.015).ConclusionsOur results suggest that estrogen deficiency during the prepubertal period is associated with alterations in the maxillary and mandibular bone length and condylar growth.
Bedside voluntary and evoked forces evaluation in intensive care unit patients: a narrative review
Authors: Kennouche Djahid , Luneau Eric , Lapole Thomas , Morel Jérome , Millet Guillaume Y. , Gondin Julien 
Published: April 2021

AbstractAround one third of intensive care unit (ICU) patients will develop severe neuromuscular alterations, known as intensive care unit-acquired weakness (ICUAW), during their stay. The diagnosis of ICUAW is difficult and often delayed as a result of sedation or delirium. Indeed, the clinical evaluation of both Medical Research Council score and maximal voluntary force (e.g., using handgrip and/or handheld dynamometers), two independent predictors of mortality, can be performed only in awake and cooperative patients. Transcutaneous electrical/magnetic stimulation applied over motor nerves combined with the development of dedicated ergometer have recently been introduced in ICU patients in order to propose an early and non-invasive measurement of evoked force. The aim of this narrative review is to summarize the different tools allowing bedside force evaluation in ICU patients and the related experimental protocols. We suggest that non-invasive electrical and/or magnetic evoked force measurements could be a relevant strategy to characterize muscle weakness in the early phase of ICU and diagnose ICUAW.
Ceftolozane-tazobactam versus meropenem for definitive treatment of bloodstream infection due to extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales (“MERINO-3”): study protocol for a multicentre, open-label randomised non-inferiority trial
Authors: Stewart Adam G. , Harris Patrick N. A. , Chatfield Mark D. , Littleford Roberta , Paterson David L. 
Published: April 2021

Abstract
Background
Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli.

Methods
This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected.

Discussion
Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024.

Trial registration
The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390. Registered on 23 January 2020.
Complete pathological response to olaparib and bevacizumab in advanced cervical cancer following chemoradiation in a BRCA1 mutation carrier: a case report
Authors: Montero-Macias Rosa , Koual Meriem , Crespel Céline , Le Frére-Belda Marie Aude , Hélène Hélène Blons , Nguyen-Xuan Huyen-Thu , Garinet Simon , Perkins Géraldine , Balay Vincent , Durdux Catherine , Florin Marie , Péré Hélène , Bats Anne-Sophie 
Published: April 2021

Abstract
Background
Homologous recombination deficiency is a marker of response to poly(ADP-ribose) polymerase inhibitors in different cancer types including ovary, prostate, and pancreatic cancer. To date, no report about poly(ADP-ribose) polymerase inhibitors has been published on cervical cancer.

Case presentation
Here we present the case of a patient with cervical cancer treated in this setting. A 49-year-old woman diagnosed with International Federation of Obstetricians and Gynecologists stage 2018 IIIC2 locally advanced undifferentiated cervical cancer received first-line chemoradiotherapy followed by carboplatin, paclitaxel, and bevacizumab with partial response. Because of a family history of cancers, the patient was tested and found positive for a pathogenic BRCA1 germline and somatic mutation, which motivated bevacizumab plus olaparib maintenance treatment. A simple hysterectomy was performed after 2 years stable disease; pathological report showed complete pathological response, and 12 months follow-up showed no recurrence.

Conclusion
Poly(ADP-ribose) polymerase inhibitors could be an alternative maintenance treatment for patients with persistent advanced cervical cancer previously treated with platinum, especially when familial history of cancers is reported. Clinical trials using poly(ADP-ribose) polymerase inhibitors for advanced cervical cancer are warranted.