bluuebunny/crossref_metadata_2025_split huggingface dataset:
The utility of fibrinogen level as a predictor of complications after laparoscopic gynecologic surgery: a prospective observational study
Authors: Macciò Antonio , Chiappe Giacomo , Kotsonis Paraskevas , Lavra Fabrizio , Nieddu Romualdo , Onnis Paolo , Sanna Elisabetta , Mais Valerio , Madeddu Clelia 
Published: November 2019

AbstractBackgroundComplications after laparoscopic gynecological surgery may increase patients’ morbidity and mortality; therefore, their timely diagnosis and early treatment would help clinicians to avoid life-threatening situations. We aimed to evaluate the predictive role of fibrinogen for diagnosing complications after laparoscopic gynecologic surgery for benign and malignant conditions.Patients and methodsAll patients who underwent elective laparoscopic gynecologic surgery between June 2013 and December 2017 at the Department of Gynecologic Oncology, Azienda Ospedaliera Brotzu, Cagliari, were prospectively included. Post-operative complications were assessed and graded according to the Clavien-Dindo classification. Fibrinogen and white blood cell level were determined preoperatively, on the first post-operative day and at the appearance of symptoms indicative of an irregular post-operative course or at the time of re-hospitalization for persistent symptoms. The postoperative changes (calculated from the first postoperative day) were correlated with the occurrence and severity of complications and their predictive role was assessed.ResultsWe enrolled 1016 patients: 36% underwent surgery for benign pathologies (mainly voluminous fibromatous uteri and severe deep endometriosis) and 64% for gynecologic malignancies. The overall complication rate was of 3.45%, the rate of major postoperative complications was 2.85%. A postoperative fibrinogen increase ≥ 20% had a high diagnostic accuracy to identify postoperative complications early (AUC 0.931, sensitivity 89%, and specificity 99%). The magnitude of postoperative fibrinogen change was associated with complication severity.ConclusionsOur findings demonstrated that fibrinogen increase can enable the early detection of postoperative complications after laparoscopic gynecological surgery. Further prospective and multi-center studies are warranted to confirm these results.
Accuracy of genomic selection for grain yield and agronomic traits in soft red winter wheat
Authors: Lozada Dennis N. , Mason R. Esten , Sarinelli Jose Martin , Brown-Guedira Gina 
Published: November 2019

AbstractBackgroundGenomic selection has the potential to increase genetic gains by using molecular markers as predictors of breeding values of individuals. This study evaluated the accuracy of predictions for grain yield, heading date, plant height, and yield components in soft red winter wheat under different prediction scenarios. Response to selection for grain yield was also compared across different selection strategies- phenotypic, marker-based, genomic, combination of phenotypic and genomic, and random selections.ResultsGenomic selection was implemented through a ridge regression best linear unbiased prediction model in two scenarios- cross-validations and independent predictions. Accuracy for cross-validations was assessed using a diverse panel under different marker number, training population size, relatedness between training and validation populations, and inclusion of fixed effect in the model. The population in the first scenario was then trained and used to predict grain yield of biparental populations for independent validations. Using subsets of significant markers from association mapping increased accuracy by 64–70% for grain yield but resulted in lower accuracy for traits with high heritability such as plant height. Increasing size of training population resulted in an increase in accuracy,with maximum values reached when ~ 60% of the lines were used as a training panel. Predictions using related subpopulations also resulted in higher accuracies. Inclusion of major growth habit genes as fixed effect in the model caused increase in grain yield accuracy under a cross-validation procedure. Independent predictions resulted in accuracy ranging between − 0.14 and 0.43, dependent on the grouping of site-year data for the training and validation populations. Genomic selection was “superior” to marker-based selection in terms of response to selection for yield. Supplementing phenotypic with genomic selection resulted in approximately 10% gain in response compared to using phenotypic selection alone.ConclusionsOur results showed the effects of different factors on accuracy for yield and agronomic traits. Among the factors studied, training population size and relatedness between training and validation population had the greatest impact on accuracy. Ultimately, combining phenotypic with genomic selection would be relevant for accelerating genetic gains for yield in winter wheat.
Antimicrobial susceptibility testing of Enterobacteriaceae: determination of disk content and Kirby-Bauer breakpoint for ceftazidime/avibactam
Authors: Yang Xianggui , Wang Dan , Zhou Qin , Nie Fang , Du Hongfei , Pang Xueli , Fan Yingzi , Bai Tingting , Xu Ying 
Published: November 2019

AbstractBackgroundDetection of ceftazidime/avibactam (CAZ/AVI) antibacterial activity is absolutely vital with the rapid growth of carbapenem resistantEnterobacteriaceae(CRE). But now, there is no available automated antimicrobial susceptibility testing card for CAZ/AVI, so Kirby-Bauer has become an economical and practical method for detecting CAZ/AVI antibacterial activity againstEnterobacteriaceae.ResultIn this study, antimicrobial susceptibility testing of CAZ/AVI against 386Enterobacteriaceae(188Klebsiella pneumoniae, 122Escherichia coli, 76Enterobacter cloacae) isolated from clinical patients was performed by broth microdilution. Of the 386 strains, 54 extended spectrum β lactamases negative (ESBL(−)), 104 extended spectrum β lactamases positive (ESBL(+)), 228 CRE. 287 isolates were susceptible to CAZ/AVI and 99 isolates were resistant to CAZ/AVI. At the same time, to obtain optimal content avibactam (AVI) disk containing ceftazidime (30 μg), inhibition zone diameter of four kinds of ceftazidime (30 μg) disk containing different AVI content (0 μg, 10 μg, 25 μg, 50 μg) were tested by Kirby-Bauer method. The microdilution broth method interpretation was used as the standard to estimate susceptible or resistance and then coherence analysis was carried out between Kirby-Bauer and broth microdilution. The result shows the inhibition zone diameter of 30 μg/50 μg disk, susceptible isolates: 20.5 mm–31.5 mm, resistance isolates: 8.25 mm–21.5 mm. The inhibition zone diameter of 30 μg/25 μg disk, susceptible isolates: 19.7 mm–31.3 mm, resistance isolates: 6.5 mm–19.2 mm. The inhibition zone diameter of 30 μg/10 μg disk, susceptible isolates: 19.5 mm–31 mm, resistance isolates: 6.5 mm–11 mm. The inhibition zone diameter of ceftazidime (30 μg), susceptible isolates: 6.5 mm–27.5 mm, resistance isolates 6.5 mm.ConclusionOur results show that 30 μg/50 μg, 30 μg/25 μg, 30 μg/10 μg CAZ/AVI disk have significant statistical differences to determinate CAZ/AVI antibacterial activity, but for 30 μg/50 μg disk, there has a cross section between susceptible isolates (minimum 20.5 mm) and resistance isolates (maximum 21.5 mm). For 30 μg/25 μg disk, it is hard to distinguish the difference between susceptible isolates (minimum 19.7 mm) and resistance isolates (maximum 19.2 mm), so 30 μg/10 μg CAZ/AVI disk is more conducive to determinate antibacterial activity.
Optimizing microbiome sequencing for small intestinal aspirates: validation of novel techniques through the REIMAGINE study
Authors: Leite Gabriela Guimaraes Sousa , Morales Walter , Weitsman Stacy , Celly Shreya , Parodi Gonzalo , Mathur Ruchi , Sedighi Rashin , Barlow Gillian M. , Rezaie Ali , Pimentel Mark 
Published: November 2019

AbstractBackgroundThe human small intestine plays a central role in the processes of digestion and nutrient absorption. However, characterizations of the human gut microbiome have largely relied on stool samples, and the associated methodologies are ill-suited for the viscosity and low microbial biomass of small intestine samples. As part of the REIMAGINE study to examine the specific roles of the small bowel microbiome in human health and disease, this study aimed to develop and validate methodologies to optimize microbial analysis of the small intestine.ResultsSubjects undergoing esophagogastroduodenoscopy without colon preparation for standard of care were prospectively recruited, and ~ 2 ml samples of luminal fluid were obtained from the duodenum using a custom sterile aspiration catheter. Samples of duodenal aspirates were either untreated (DA-U,N = 127) or pretreated with dithiothreitol (DA-DTT,N = 101), then cultured on MacConkey agar for quantitation of aerobic gram-negative bacteria, typically from the class Gammaproteobacteria, and on blood agar for quantitation of anaerobic microorganisms. DA-DTT exhibited 2.86-fold greater anaerobic bacterial counts compared to DA-U (P = 0.0101), but were not statistically different on MacConkey agar.DNA isolation from DA-U (N = 112) and DA-DTT (N = 43) samples and library preparation for 16S rRNA gene sequencing were also performed using modified protocols. DA-DTT samples exhibited 3.81-fold higher DNA concentrations (P = 0.0014) and 4.18-fold higher 16S library concentrations (P < 0.0001) then DA-U samples. 16S rRNA gene sequencing revealed increases in the detected relative abundances of obligate and facultative anaerobes in DA-DTT samples, including increases in the generaClostridium(false discovery rate (FDR)P = 4.38E-6),Enterococcus(FDRP = 2.57E-8),Fusobacterium(FDRP = 0.02) andBacteroides(FDRP = 5.43E-9). Detected levels of Gram-negative enteropathogens from the phylumProteobacteria, such asKlebsiella(FDRP = 2.73E-6) andProvidencia(FDRP < 0.0001) (familyEnterobacteriaceae) andPseudomonas (familyPseudomonadaceae) (FDRP = 0.04), were also increased in DA-DTT samples.ConclusionsThis study validates novel DTT-based methodology which optimizes microbial culture and 16S rRNA gene sequencing for the study of the small bowel microbiome. The microbial analyses indicate increased isolation of facultative and obligate anaerobes from the mucus layer using these novel techniques.
A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer
Authors: Strickler John H. , Rushing Christel N. , Niedzwiecki Donna , McLeod Abigail , Altomare Ivy , Uronis Hope E. , Hsu S. David , Zafar S. Yousuf , Morse Michael A. , Chang David Z. , Wells James L. , Blackwell Kimberly L. , Marcom P. Kelly , Arrowood Christy , Bolch Emily , Haley Sherri , Rangwala Fatima A. , Hatch Ace J. , Nixon Andrew B. , Hurwitz Herbert I. 
Published: November 2019

Abstract

Background
Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC.

Methods
All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS).

Results
A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1–14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60–84%). Median PFS and OS were 3.9 months (95% CI, 2.3–4.5) and 7.1 months (95% CI: 5.8–10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes.

Conclusion
The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study.

Trial registration
This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
Dietary-phytochemical mediated reversion of cancer-specific splicing inhibits Warburg effect in head and neck cancer
Authors: Yadav Sandhya , Bhagat Somnath D. , Gupta Amit , Samaiya Atul , Srivastava Aasheesh , Shukla Sanjeev 
Published: November 2019

Abstract

Background
The deregulated alternative splicing of key glycolytic enzyme, Pyruvate Kinase muscle isoenzyme (PKM) is implicated in metabolic adaptation of cancer cells. The splicing switch from normal PKM1 to cancer-specific PKM2 isoform allows the cancer cells to meet their energy and biosynthetic demands, thereby facilitating the cancer cells growth. We have investigated the largely unexplored epigenetic mechanism of PKM splicing switch in head and neck cancer (HNC) cells. Considering the reversible nature of epigenetic marks, we have also examined the utility of dietary-phytochemical in reverting the splicing switch from PKM2 to PKM1 isoform and thereby inhibition of HNC tumorigenesis.

Methods
We present HNC-patients samples, showing the splicing-switch from PKM1-isoform to PKM2-isoform analyzed via immunoblotting and qRT-PCR. We performed methylated-DNA-immunoprecipitation to examine the DNA methylation level and chromatin-immunoprecipitation to assess the BORIS (Brother of Regulator of Imprinted Sites) recruitment and polII enrichment. The effect of dietary-phytochemical on the activity of denovo-DNA-methyltransferase-3b (DNMT3B) was detected by DNA-methyltransferase-activity assay. We also analyzed the Warburg effect and growth inhibition using lactate, glucose uptake assay, invasion assay, cell proliferation, and apoptosis assay. The global change in transcriptome upon dietary-phytochemical treatment was assayed using Human Transcriptome Array 2.0 (HTA2.0).

Results
Here, we report the role of DNA-methylation mediated recruitment of the BORIS at exon-10 of PKM-gene regulating the alternative-splicing to generate the PKM2-splice-isoform in HNC. Notably, the reversal of Warburg effect was achieved by employing a dietary-phytochemical, which inhibits the DNMT3B, resulting in the reduced DNA-methylation at exon-10 and hence, PKM-splicing switch from cancer-specific PKM2 to normal PKM1. Global-transcriptome-analysis of dietary-phytochemical-treated cells revealed its effect on alternative splicing of various genes involved in HNC.

Conclusion
This study identifies the epigenetic mechanism of PKM-splicing switch in HNC and reports the role of dietary-phytochemical in reverting the splicing switch from cancer-specific PKM2 to normal PKM1-isoform and hence the reduced Warburg effect and growth inhibition of HNC. We envisage that this approach can provide an effective way to modulate cancer-specific-splicing and thereby aid in the treatment of HNC.
Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy
Authors: Trotsyuk Iryna , Sparschuh Halina , Müller Alice Josephine , Neumann Konrad , Kruschewski Martin , Horst David , Elezkurtaj Sefer 
Published: November 2019

AbstractBackgroundBudding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy.MethodsA total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining.ResultsA budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15–6.44,p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62–16.61,p = 0.006).ConclusionBudding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance.
Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer
Authors: Martin Steve Z. , Wagner Daniel C. , Hörner Nina , Horst David , Lang Hauke , Tagscherer Katrin E. , Roth Wilfried 
Published: November 2019

Abstract

Background
The lack of predictive biomarkers or test systems contributes to high failure rates of systemic therapy in metastasized colorectal carcinoma, accounting for a still unfavorable prognosis. Here, we present an ex vivo functional assay to measure drug-response based on a tissue slice culture approach.

Methods
Tumor tissue slices of hepatic metastases of nine patients suffering from colorectal carcinoma were cultivated for 72 h and treated with different concentrations of the clinically relevant drugs Oxaliplatin, Cetuximab and Pembrolizumab. Easy to use, objective and automated analysis routines based on the Halo platform were developed to measure changes in proliferative activity and the morphometric make-up of the tumor. Apoptotic indices were assessed semiquantitatively.

Results
Untreated tumor tissue slices showed high morphological comparability with the original “in vivo”-tumor, preserving proliferation and stromal-tumor interactions. All but one patients showed a dosage dependent susceptibility to treatment with Oxaliplatin, whereas only two patients showed responses to Cetuximab and Pembrolizumab, respectively. Furthermore, we identified possible non-responders to Cetuximab therapy in absence of RAS-mutations.

Conclusions
This is the first time to demonstrate feasibility of the tissue slice culture approach for metastatic tissue of colorectal carcinoma. An automated readout of proliferation and tumor-morphometry allows for quantification of drug susceptibility. This strongly indicates a potential value of this technique as a patient-specific test-system of targeted therapy in metastatic colorectal cancer. Co-clinical trials are needed to customize for clinical application and to define adequate read-out cut-off values.
Associations of sociodemographic and clinical factors with perinatal depression among Israeli women: a cross-sectional study
Authors: Adler Limor , Tsamir Judith , Katz Rachel , Koren Gideon , Yehoshua Ilan 
Published: November 2019

Abstract

Background
Perinatal depression is a common problem that affects about 18% of women worldwide, though the heterogeneity between countries is great. The aims of this study were to assess the prevalence of perinatal depressive symptoms in a national sample of women in Israel, and to investigate associations of these symptoms with demographic, medical and lifestyle factors.

Methods
The study included all members of Maccabi Health Services, the second largest health maintenance organization in Israel, who filled the Edinburgh Postnatal Depression Scale (EPDS) during 2015–2016. Crude odds ratios (ORs) and adjusted ORs (aORs) are presented for associations of sociodemographic, medical and lifestyle factors with perinatal depressive symptoms, according to a score ≥ 10 on the EPDS.

Results
Of 27,520 women who filled the EPDS, 1346 (4.9%) met the criteria for perinatal depression. In a logistic regression analysis we found the following factors associated with perinatal depression: the use of antidepressant medications (aOR = 2.34, 95% CI 1.94–2.82, P < 0.001 and aOR = 3.44; 95% CI 2.99–3.97, P < 0.001 for ≤3 months and > 3 months respectively), a diagnosis of chronic diabetes mellitus (aOR = 2.04; 95% CI 1.22–3.43, P = 0.007), Arab background (aOR = 2.28; 95% CI 1.82–2.86, P < 0.001), current and past smoking (aOR = 1.62; 95% CI 1.35–1.94, P < 0.001 and aOR = 1.36; 95% CI 1.05–1.76, P = 0.021, respectively), and anaemia (aOR = 1.17; 95% CI 1.04–1.32, P = 0.011). Orthodox Jewish affiliation and residence in the periphery of the country were associated with lower perinatal depression (aOR = 0.48; 95% CI 0.36–0.63, P < 0.001 and aOR = 0.72; 95% CI 0.57–0.92, P = 0.007, respectively).

Conclusions
The prevalence of perinatal depression in this study was 4.9%. Perinatal depression was associated with a number of demographic, medical and lifestyle factors, including the use of antidepressant medication, chronic diabetes mellitus, Arab background, current or past smoking, and anaemia. These risk factors may help identify women at risk of perinatal depression.
Sense it and use it: interoceptive accuracy and sensibility in suicide ideators
Authors: Forkmann Thomas , Volz-Sidiropoulou Eftychia , Helbing Trientje , Drüke Barbara , Mainz Verena , Rath Dajana , Gauggel Siegfried , Teismann Tobias 
Published: November 2019

Abstract

Background
Interoceptive deficits have been found to be associated with suicidal ideation and behavior. However, an objective measure of interoceptive accuracy has not been investigated in participants with suicide ideation, by now. This study aimed at investigating interoceptive accuracy and sensibility in persons with and without suicide ideation (SI) while controlling for severity of depressive symptoms.

Method
Ninety-five participants (age: M = 34.8, SD = 11.6, n = 56 female [58.9%]; n = 51 patients with a Major Depressive Disorder and n = 44 healthy participants) were assessed for interoceptive accuracy and sensibility, depression and SI.

Results
Twenty-five participants (26%) reported SI. They showed interoceptive accuracy comparable to persons without SI (t = −.81, p = .422), but significantly lower interoceptive sensibility. After controlling for severity of depressive symptoms in a hierarchical linear regression analysis, most associations between interoceptive sensibility and SI disappeared.

Conclusion
Results suggest that suicide ideators do not lack the ability to perceive their own bodily signals but they feel less able to use them in a way that is advantageous for them. Differences between suicide ideators and non-ideators appear to be largely driven by depressive symptoms (depression bias).