bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood cultures and blood microbiota analysis as surrogates for bronchoalveolar lavage fluid analysis in dogs with bacterial pneumonia
Authors: Vientós-Plotts A. I. , Ericsson A. C. , Rindt H. , Reinero C. R. 
Published: March 2021

AbstractBackgroundDiagnosis of canine bacterial pneumonia relies on airway lavage to confirm septic, suppurative inflammation, and a positive bacterial culture. Considering risks of bronchoalveolar lavage fluid (BALF) collection, minimally invasive methods like culture or next generation sequencing of blood would be appealing. In dogs with bacterial pneumonia, our study aims included (1): determining proportion of agreement between cultivable bacteria in BALF and blood (2); characterizing BALF, blood, and oropharyngeal (OP) microbiota and determining if bacteria cultured from BALF were present in these communities; and (3) comparing relatedness of microbial community composition at all three sites. Bacterial cultures were performed on BALF and blood. After DNA extraction of BALF, blood and OP, 16S rRNA amplicon libraries were generated, sequenced, and compared to a bacterial gene sequence database.ResultsDisregarding one false positive, blood cultures were positive in 2/9 dogs (5 total isolates), all 5 isolates were present in BALF cultures (16 total isolates). Based on sequencing data, all sites had rich and diverse microbial communities. Comparing cultured BALF bacterial genera with sequenced taxa, all dogs had ≥1 cultured isolate present in their microbiota: cultured BALF isolates were found in microbiota of BALF (12/16), blood (7/16), and OP (6/11; only 7 dogs had OP swabs). Of 394 distinct taxa detected in BALF, these were present in 75% OP and 45% blood samples. BALF community composition was significantly different than OP (p = 0.0059) and blood (p = 0.0009).ConclusionsBlood cultures are insensitive but specific for cultured BALF bacteria in canine bacterial pneumonia. Cultivable BALF bacteria were present in BALF, blood and OP microbiota to differing degrees.
Bioprocess performance analysis of novel methanol-independent promoters for recombinant protein production with Pichia pastoris
Authors: Garrigós-Martínez Javier , Vuoristo Kiira , Nieto-Taype Miguel Angel , Tähtiharju Juha , Uusitalo Jaana , Tukiainen Pauliina , Schmid Christian , Tolstorukov Ilya , Madden Knut , Penttilä Merja , Montesinos-Seguí José Luis , Valero Francisco , Glieder Anton , Garcia-Ortega Xavier 
Published: March 2021

Abstract
Background
Pichia pastoris is a powerful and broadly used host for recombinant protein production (RPP), where past bioprocess performance has often been directed with the methanol regulated AOX1 promoter (PAOX1), and the constitutive GAP promoter (PGAP). Since promoters play a crucial role in an expression system and the bioprocess efficiency, innovative alternatives are constantly developed and implemented. Here, a thorough comparative kinetic characterization of two expression systems based on the commercial PDF and UPP promoters (PPDF, PUPP) was first conducted in chemostat cultures. Most promising conditions were subsequently tested in fed-batch cultivations. These new alternatives were compared with the classical strong promoter PGAP, using the Candida antarctica lipase B (CalB) as model protein for expression system performance.

Results
Both the PPDF and PUPP-based expression systems outperformed similar PGAP-based expression in chemostat cultivations, reaching ninefold higher specific production rates (qp). CALB transcription levels were drastically higher when employing the novel expression systems. This higher expression was also correlated with a marked upregulation of unfolded protein response (UPR) related genes, likely from an increased protein burden in the endoplasmic reticulum (ER). Based on the chemostat results obtained, best culture strategies for both PPDF and PUPP expression systems were also successfully implemented in 15 L fed-batch cultivations where qp and product to biomass yield (YP/X*) values were similar than those obtained in chemostat cultivations.

Conclusions
As an outcome of the macrokinetic characterization presented, the novel PPDF and PUPP were observed to offer much higher efficiency for CalB production than the widely used PGAP-based methanol-free alternative. Thus, both systems arise as highly productive alternatives for P. pastoris-based RPP bioprocesses. Furthermore, the different expression regulation patterns observed indicate the level of gene expression can be adjusted, or tuned, which is interesting when using Pichia pastoris as a cell factory for different products of interest.
Performance of liver stiffness measurements obtained with FibroScan is affected by glucose metabolism in patients with nonalcoholic fatty liver disease
Authors: Yang Xinyu , Chang Xinxia , Wu Shengdi , Sun Xiaoyang , Zhu Xiaopeng , Wang Liu , Xu Yushan , Yao Xiuzhong , Rao Shengxiang , Hu Xiqi , Xia Mingfeng , Bian Hua , Yan Hongmei , Gao Xin 
Published: March 2021

Abstract
Background
The performance of liver stiffness measurements (LSMs) obtained using FibroScan can be affected by several factors, and cut-off values are different for fibrosis caused by various aetiologies. The study aims to evaluate the diagnostic accuracy of LSM in nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism and investigate whether the LSM value would be affected by metabolic indicators.

Methods
The study involved 91 NAFLD patients with abnormal glucose metabolism who underwent liver biopsy. The diagnostic accuracy of LSM value was evaluated by the receiver operator characteristic (ROC) curves, with the biopsy results taken as the gold standard. Multivariate linear regression and subgroup analysis were performed to determine the correlated indicators.

Results
The areas under the ROC curves (AUROCs) of LSM values for detecting fibrosis stage ≥1, 2, 3 and 4 were 0.793 (95% confidence interval [CI]: 0.695–0.871), 0.764 (95% CI: 0.663–0.846), 0.837 (95% CI: 0.744–0.906) and 0.902 (95% CI: 0.822–0.955), with cut-off values of 6.3, 7.6, 8.3 and 13.8 kPa, respectively. Multivariate linear regression demonstrated that haemoglobin A1c (HbA1c, β = 0.205, P = 0.026) and alanine aminotransferase (ALT, β = 0.192, P = 0.047) were independently associated with the LSM value after adjustment for fibrosis stage, ballooning and inflammation grade from liver biopsy. Subgroup analysis demonstrated that LSM values were slightly higher in patients with HbA1c ≥7% than in those with HbA1c < 7% and in patients with body mass index (BMI) ≥30 kg/m2 than in those with BMI < 30 kg/m2.

Conclusions
FibroScan was valuable for the evaluation of liver fibrosis in NAFLD patients with abnormal glucose metabolism. FibroScan is recommended to evaluate severe fibrosis, especially to exclude advanced fibrosis. Glucose metabolism state may affect LSM values.
Active clearance vs conventional management of chest tubes after cardiac surgery: a randomized controlled study
Authors: St-Onge Samuel , Chauvette Vincent , Hamad Raphael , Bouchard Denis , Jeanmart Hugues , Lamarche Yoan , Perrault Louis P. , Demers Philippe 
Published: March 2021

Abstract
Background
Chest tubes are routinely used after cardiac surgery to evacuate shed mediastinal blood. Incomplete chest drainage due to chest tube clogging can lead to retained blood after cardiac surgery. This can include cardiac tamponade, hemothorax, bloody effusions and postoperative atrial fibrillation (POAF). Prior published non randomized studies have demonstrated that active tube clearance (ATC) of chest tubes can reduce retained blood complications prompting the ERAS Cardiac Society guidelines to recommend this modality.

Objective
A randomized prospective trial to evaluate whether an ATC protocol aimed at improving chest tube patency without breaking the sterile field could efficiently reduce complications related to retained blood after cardiac surgery.

Methods
This was a pragmatic, single-blinded, parallel randomized control trial held from November 2015 to June 2017 including a 30-day post index surgery follow-up. The setting was two academic centers affiliated with the Université de Montréal School of Medicine; the Montreal Heart Institute and the Hôpital du Sacré-Coeur de Montréal. Adult patients admitted for non-emergent coronary bypass grafting and/or valvular heart surgery through median sternotomy, in sinus rhythm for a minimum of 30 days prior to the surgical intervention were eligible for inclusion.
In the active tube clearance group (ATC), a 28F PleuraFlow device was positioned within the mediastinum. In the standard drainage group, a conventional chest tube (Teleflex Inc.) was used. Other chest tubes were left at the discretion of the operating surgeon.

Results
A total of 520 adult patients undergoing cardiac surgery were randomized to receive either ATC (n = 257) or standard drainage (n = 263). ATC was associated with a 72% reduction in re-exploration for bleeding (5.7% vs 1.6%, p = .01) and an 89% reduction in complete chest tube occlusion (2% vs 19%, p = .01). There was an 18% reduction in POAF between the ATC and control group that was not statistically significant (31% vs 38%, p = .08).

Conclusions and relevance
In this RCT, the implementation of active clearance of chest tubes reduced re-exploration and chest tube clogging in patients after cardiac surgery further supporting recommendations to consider this modality postoperatively.

Trial registration
Clinical Trials NCT02808897. Retrospectively registered 22 June 2016.
Association of body mass index with in-hospital major adverse outcomes in acute type A aortic dissection patients in Fujian Province, China: a retrospective study
Authors: Lin Lingyu , Lin Yanjuan , Chen Qiong , Peng Yanchun , Li Sailan , Chen Liangwan , Huang Xizhen 
Published: March 2021

Abstract
Background
Abnormal body mass index (BMI) has been related to a higher risk of adverse outcomes in patients undergoing cardiac surgery. However, the effects of BMI in patients with acute type A aortic dissection (AAAD) on postoperative outcomes remain unclear. This study aimed to explore the relationships between BMI and in-hospital major adverse outcomes (MAO) in AAAD patients.

Methods
Patients who underwent AAAD surgery at Cardiac Medical Center of Fujian Province from June 2013 to March 2020 were retrospectively evaluated. They were divided into three groups on the basis of Chinese BMI classification established by the World Health Organization: normal weight group (BMI 18.5–23.9 kg/m2), overweight group (BMI 24–27.9 kg/m2), and obese group (BMI >28 kg/m2). Patients’ baseline characteristics, preoperative, operative, and postoperative data were collected. A multivariable logistic regression analysis model was performed to identify the association between BMI and MAO in AAAD patients.

Results
Of 777 cases, 31.9% were normal weight, 52.5% were overweight, and 15.6% were obese. A total of 160(20.6%) patients died in-hospital. There was a significant difference between the three groups for MAO (62.9% vs 72.1% vs 77.7%, respectively, P = 0.006). The incidence of postoperative complications did not differ among the three groups, except for postoperative bleeding, and prolonged mechanical ventilation, the proportion of which were higher in the overweight and obese groups. Besides, multivariable logistic regression analysis demonstrated that a higher risk of MAO in the overweight [odds ratios (ORs):1.475, 95%CI:1.006–2.162], and obese patients (ORs:2.147, 95%CI:1.219–3.782) with reference to the normal weight patients, and age, white blood cell, prior stroke and cardiopulmonary bypass time were also associated with in-hospital MAO (P<0.05).

Conclusions
BMI is independently associated with higher in-hospital MAO in patients who underwent AAAD surgery.
Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression
Authors: Zhang Shouhua , Li Nuoya , Sheng Yanling , Chen Wen , Ma Qiangliang , Yu Xin , Lian Jianping , Zeng Junquan , Yang Yipeng , Yan Jinlong 
Published: March 2021

Abstract
Background
HBV promotes cell survival by upregulating the expression of the cellular inhibitor of apoptosis protein 2 (cIAP2), however whether it is involved in HBV-induced sorafenib resistance in liver cancer remains unclear.

Methods
cIAP2 overexpression and knockdown was adopted to assess the involvement of cIAP2 in HBV-induced sorafenib resistance. Anti-HBV drug lamivudine and Akt inhibitor were used to investigate the impact of HBV replication on cIAP2 expression and sorafenib resistance. Xenotransplantation mouse model was used to confirm the data on cell lines in vitro.

Results
Liver cancer cell line HepG2.215 showed increased cIAP2 expression and enhanced resistance to sorafenib. Upon sorafenib treatment, overexpression of cIAP2 in HepG2 lead to decreased cleaved caspase 3 level and increased cell viability, while knockdown of cIAP2 in HepG2.215 resulted in increased level of cleaved caspase 3 and decreased cell viability, suggesting the involvement of cIAP2 in HBV-induced sorafenib resistance. Furthermore, anti-HBV treatment reduced cIAP2 expression and partially restored sorafenib sensitivity in HepG2.215 cells. Xenotransplantation mouse model further confirmed that co-treatment with lamivudine and sorafenib could reduce sorafenib-resistant HepG2.215 tumor cell growth.

Conclusion
cIAP2 is involved in HBV-induced sorafenib resistance in liver cancer and anti-HBV treatments reduce cIAP2 expression and partially restore sorafenib sensibility.
Occurrence of faecal endoparasites in reindeer (Rangifer tarandus) in two grazing areas in northern Norway
Authors: Idland Lene , Juul Amalie Moen , Solevåg Ellen Karin , Tysnes Kristoffer Relling , Robertson Lucy Jane , Utaaker Kjersti Selstad 
Published: March 2021

Abstract
Background
Semi-domesticated reindeer represent an important livestock industry and livelihood for a proportion of the human population in northern Fennoscandia. Reindeer husbandry is considered an extensive animal husbandry, where the animals are kept mostly on natural pastures, although sometimes kept in fenced areas for shorter periods. These reindeer may harbour a variety of parasites that may affect animal health and production. The relatively limited close contact between herds and owners gives limited opportunities for diagnosis and treatment of diseases in general. Furthermore, the effects of subclinical parasitism in livestock are commonly expressed as a reduction in productivity rather than clinical disease and mortality. Thus, specific knowledge of endoparasites and parasitic infections in these herds is scarce. This study investigated the occurrence of various endoparasites in reindeer by analysis of a total of 114 faecal samples from winter-slaughtered reindeer from two different grazing areas in Troms and Finnmark, Norway.

Results
Using a McMaster method, a Baermann technique, and a direct immunofluorescent antibody test, the following parasites were identified in the faecal samples with the occurrence data given as percentages: Strongylid eggs (62%), Nematodirinae spp. eggs (24%), Capillaria sp. eggs (42%) and Moniezia spp. eggs (17%), Dictyocaulus spp. larvae (14%) protostrongylid larvae (40%), Eimera spp. oocysts (23%), and Giardia duodenalis cysts (5%). Cryptosporidium oocysts were not detected. Parasite eggs, oocysts, and cysts were quantified.
Molecular analysis revealed G. duodenalis sub-assemblage AI, a potentially zoonotic genotype not previously reported in reindeer from this region. Morphological analyses of Eimeria oocysts identified two species, Eimeria mayeri and Eimeria rangiferis, and molecular analyses of the cytochrome C oxidase I (coi) gene and 18 s rRNA (18SSU) gene of Eimeria confirmed the presence of Eimeria species that are specific to reindeer.

Conclusions
A high prevalence, but low burden, of endoparasites was detected in samples from these semi-domesticated reindeer. The samples were collected during winter, when adult gastrointestinal parasites usually produce only low numbers of transmission stages. Therefore, together with the low number of samples, detailed and definitive conclusions regarding parasite status of semi-domesticated reindeer are avoided. Nevertheless, these data provide a snapshot overview of parasite occurrence in a semi-domesticated animal group vulnerable to the various environmental changes to which they are exposed.
First report of polymorphisms in MTRR, GATA4, VEGF, and ISL1 genes in Pakistani children with isolated ventricular septal defects (VSD)
Authors: Sarwar Sumbal , Ehsan Farah , Shabana  , Tahir Amna , Jamil Mahrukh , Shahid Saleem Ullah , Khan Asim , Hasnain Shahida 
Published: March 2021

Abstract
Background
Ventricular septal defects (VSDs) are malformations in the septum separating the heart’s ventricles. VSDs may present as a single anomaly (isolated/nonsyndromic VSD) or as part of a group of phenotypes (syndromic VSD). The exact location of the defect is crucial in linking the defect to the underlying genetic cause. The number of children visiting cardiac surgery units is constantly increasing. However, there are no representative data available on the genetics of VSDs in Pakistani children.

Methods
Two hundred forty-two subjects (121 VSD children and 121 healthy controls) were recruited from pediatric cardiac units of Lahore. The clinical and demographic data of the subjects were collected. A total of four SNPs, one each from MTRR, GATA4, VEGF, and ISL1 genes were genotyped by PCR-RFLP.

Results
The results showed that the minor allele (T) frequency (MAFs) for the MTRR gene variant rs1532268 (c.524C > T) was 0.20 and 0.41 in the controls and the cases, respectively, with the genotype frequencies 3, 35, 62% in the controls and 12, 59 and 29% in the cases for TT, CT, CC genotypes, respectively (allelic OR: 5.73, CI: 3.82–8.61, p-value: 5.11 × 10− 7). For the GATA4 variant rs104894073 (c.886G > A), the MAF for the controls and the cases was 0.16 and 0.37, respectively, the frequencies of AA, GA and GG genotypes were 2, 28, and 70% in the controls and 5, 64 and 31% of the cases (allelic OR: 3.08, CI: 2.00–4.74, p-value: 8.36 × 10− 8). The rs699947 (c.-2578C > A) of VEGF gene showed MAF 0.36 and 0.53 for the controls and cases, respectively, with the genotype frequencies 13, 42, and 45% in the controls and 22, 15, and 63% in the cases for the AA, CA, CC (allelic OR: 2.03, CI: 1.41–2.92, p-value: 0.0001). The ISL1 gene variant rs6867206 (g.51356860 T > C), the MAFs were 0.26 and 0.31 in the controls and cases, respectively. The genotype frequencies were 48, 52, 0% in the controls and 39, 61, 0% in the cases for TT, TC, CC genotypes (allelic OR: 0.27, CI: 0.85–1.89, p-value: 0.227). The MTRR, GATA4 and VEGF variants showed association while ISL1 variant did not appear to be associated with the VSD in the recruited cohort.

Conclusion
This first report in Pakistani children demonstrates that single nucleotide polymorphisms in genes encoding transcription factors, signaling molecules and structural heart genes involved in fetal heart development are associated with developmental heart defects., however further work is needed to validate the results of the current investigation.
Per-protocol analysis of the ZINC trial for HIV disease among alcohol users
Authors: Lodi Sara , Freiberg Matthew , Gnatienko Natalia , Blokhina Elena , Yaroslavtseva Tatiana , Krupitsky Evgeny , Murray Eleanor , Samet Jeffrey H. , Cheng Debbie M. 
Published: March 2021

Abstract
Background
The Zinc for INflammation and Chronic disease in HIV (ZINC) trial randomized person who live with HIV (PLWH) who engage in heavy drinking to either daily zinc supplementation or placebo. The primary outcome was change in the Veterans Aging Cohort Study (VACS) index, a predictor of mortality, between baseline and 18 months. Because adherence and follow-up were suboptimal, the intention-to-treat analysis, which was not statistically significant, may have underestimated the effect of the zinc supplementation.

Objective
We estimated the per-protocol effect of zinc versus placebo in the ZINC trial (i.e., the effect that would have been observed if all participants had had high adherence and none was lost to follow-up).

Methods
Adherence was measured as the self-reported percentage of pills taken in the previous 6 weeks and assessed at all post-baseline visits. We used inverse probability weighting to estimate and compare the change in the VACS index at 18 months in the zinc and placebo groups, had all the trial participants had high adherence (i.e., cumulative adherence ≥80% at 18 months). To examine trends by level of adherence, we rerun the analyses using thresholds for high adherence of 70% and 90% of average self-reported pill coverage.

Results
The estimated (95% confidence interval) change in the VACS index was − 2.16 (− 8.07, 3.59) and 5.84 (0.73, 11.80) under high adherence and no loss to follow-up in the zinc and placebo groups, respectively. The per-protocol effect estimate of the mean difference in the change between the zinc and placebo groups was − 8.01 (− 16.42, 0.01), somewhat larger than the intention-to-treat effect difference in change (− 4.68 (− 9.62, 0.25)), but it was still not statistically significant. The mean difference in the change between individuals in the zinc and placebo groups was − 4.07 (− 11.5, 2.75) and −12.34 (− 20.14, −4.14) for high adherence defined as 70% and 90% of pill coverage, respectively.

Conclusions
Overall, high adherence to zinc was associated with a lower VACS score, but confidence intervals were wide and crossed 0. Further studies with a larger sample size are needed to quantify the benefits of zinc supplementation in this population.

Trial registration
ClinicalTrials.gov NCT01934803. Registered on August 30, 2013
Phylogenetic analysis of HIV-1 archived DNA in blood and gut-associated lymphoid tissue in two patients under antiretroviral therapy
Authors: Recordon-Pinson Patricia , Gosselin Annie , Ancuta Petronela , Routy Jean-Pierre , Fleury Hervé 
Published: March 2021

AbstractOne of the approaches to cure human immunodeficiency virus (HIV) is the use of therapeutic vaccination. We have launched the Provir/Latitude 45 study to identify conserved CTL epitopes in archived HIV-1 DNA according to the HLA class I alleles in aviremic patients under antiretroviral therapy (ART). A HIV-1 polypeptidic therapeutic vaccine based on viral sequence data obtained from circulating blood was proposed; here, our aim was to compare the proviral DNA in blood and gut-associated lymphoid tissue (GALT). Peripheral blood mononuclear cells and gut biopsies were obtained from two HIV-1 infected patients under successful antiretroviral therapy. Total DNA was extracted including the proviral DNA. The HIV-1 reverse transcriptase was sequenced in both compartments using next generation sequencing followed by single genome sequencing; phylogenetic trees were established and compared. The proviral sequences of both compartments intra-patient exhibited a very low genetic divergence while it was possible to differentiate the sequences inter-patients; single genome sequencing analysis of two couples of samples confirmed that there was no compartmentalization of the sequences intra-patient. We conclude that, considering these two cases, the proviral DNA sequences in blood and GALT are similar and that the epitope analysis of HIV-1 provirus in blood should be considered as relevant to that observed in the GALT, a hard-to-reach major compartment, and can therefore be used for therapeutic vaccine approaches.