bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excessive unilateral proliferation of spermatogonia in a patient with non-obstructive azoospermia – adverse effect of clomiphene citrate pre-treatment?
Authors: Fietz Daniela , Pilatz Adrian , Diemer Thorsten , Wagenlehner Florian , Bergmann Martin , Schuppe Hans-Christian 
Published: August 2020

Abstract
Background
Clomiphene citrate has been proposed as pre-treatment for infertile men with non-obstructive, testicular azoospermia (NOA) before surgery for testicular sperm extraction (TESE), especially when serum testosterone is low.

Case presentation
Here, we report on a 33-year old azoospermic patient with a previous history of repeated “fresh” TESE and clomiphene citrate therapy (50 mg/day over 6 months) before undergoing microscopically assisted, bilateral testicular biopsy. Comprehensive histological and immunohistochemical work-up revealed a heterogeneous spermatogenic arrest at the level of spermatogonia or primary spermatocytes, with focally preserved spermatogenesis up to elongated spermatids in the right testis. In the left testis, the majority of tubules (> 70%) showed no tubular lumen or regular seminiferous epithelium but a great number of spermatogonia-like cells. These cells proved to be normally differentiated spermatogonia (positive for melanoma associated antigen 4 (MAGEA4), negative for placental alkaline phosphatase (PlAP)) with increased proliferative activity (positive for proliferating cell nuclear antigen (PCNA)) and a slightly higher rate of apoptotic cells. When compared to a tissue control with normal spermatogenesis, expression of sex hormone receptors androgen receptor (AR), estrogen receptor (ER) alpha, and G-protein coupled estrogen receptor 1 (GPER1) was not altered in patient samples. Sertoli cells appeared to be mature (positive for vimentin, negative for cytokeratin 18), whereas the expression of zona occludens protein 1 (ZO-1), claudin 11, and connexin 43 was absent or dislocated in the tubules with abundance of spermatogonia.

Conclusion
This result suggests that formation of the blood-testis barrier is disturbed in affected tubules. To our knowledge this is the first observation of excessive, non-malignant proliferation of spermatogonia in a NOA patient. Although underlying molecular mechanisms remain to be elucidated, we hypothesize that the unusual pathology was triggered by the high-dose clomiphene citrate treatment preceding testicular biopsy.
Common bean resistance to Xanthomonas is associated with upregulation of the salicylic acid pathway and downregulation of photosynthesis
Authors: Foucher Justine , Ruh Mylène , Préveaux Anne , Carrère Sébastien , Pelletier Sandra , Briand Martial , Serre Rémy-Félix , Jacques Marie-Agnès , Chen Nicolas W. G. 
Published: August 2020

Abstract
Background
Common bacterial blight (CBB) caused by Xanthomonas phaseoli pv. phaseoli and Xanthomonas citri pv. fuscans is one of the major threats to common bean crops (Phaseolus vulgaris L.). Resistance to CBB is particularly complex as 26 quantitative resistance loci to CBB have been described so far. To date, transcriptomic studies after CBB infection have been very scarce and the molecular mechanisms underlying susceptibility or resistance are largely unknown.

Results
We sequenced and annotated the genomes of two common bean genotypes being either resistant (BAT93) or susceptible (JaloEEP558) to CBB. Reciprocal BLASTp analysis led to a list of 20,787 homologs between these genotypes and the common bean reference genome (G19833), which provides a solid dataset for further comparative analyses. RNA-Seq after inoculation with X. phaseoli pv. phaseoli showed that the susceptible genotype initiated a more intense and diverse biological response than the resistant genotype. Resistance was linked to upregulation of the salicylic acid pathway and downregulation of photosynthesis and sugar metabolism, while susceptibility was linked to downregulation of resistance genes and upregulation of the ethylene pathway and of genes involved in cell wall modification.

Conclusions
This study helps better understanding the mechanisms occurring during the early colonization phase of common bean by Xanthomonas and unveils new actors potentially important for resistance and susceptibility to CBB. We discuss the potential link between the pathways induced during bean colonization and genes induced by transcription activator-like effectors (TALEs), as illustrated in other Xanthomonas pathovars.
Conditionally essential genes for survival during starvation in Enterococcus faecium E745
Authors: de Maat Vincent , Arredondo-Alonso Sergio , Willems Rob J. L. , van Schaik Willem 
Published: August 2020

Abstract
Background
The nosocomial pathogen Enterococcus faecium can survive for prolonged periods of time on surfaces in the absence of nutrients. This trait is thought to contribute to the ability of E. faecium to spread among patients in hospitals. There is currently a lack of data on the mechanisms that are responsible for the ability of E. faecium to survive in the absence of nutrients.

Results
We performed a high-throughput transposon mutant library screening (Tn-seq) to identify genes that have a role in long-term survival during incubation in phosphate-buffered saline (PBS) at 20 °C. A total of 24 genes were identified by Tn-seq to contribute to survival in PBS, with functions associated with the general stress response, DNA repair, metabolism, and membrane homeostasis. The gene which was quantitatively most important for survival in PBS was usp (locus tag: EfmE745_02439), which is predicted to encode a 17.4 kDa universal stress protein. After generating a targeted deletion mutant in usp, we were able to confirm that usp significantly contributes to survival in PBS and this defect was restored by in trans complementation. The usp gene is present in 99% of a set of 1644 E. faecium genomes that collectively span the diversity of the species.

Conclusions
We postulate that usp is a key determinant for the remarkable environmental robustness of E. faecium. Further mechanistic studies into usp and other genes identified in this study may shed further light on the mechanisms by which E. faecium can survive in the absence of nutrients for prolonged periods of time.
Ertapenem and Faropenem against Mycobacterium tuberculosis: in vitro testing and comparison by macro and microdilution
Authors: Gonzalo Ximena , Satta Giovanni , Ortiz Canseco Julio , McHugh Timothy D. , Drobniewski Francis 
Published: August 2020

Abstract
Background
Interest in carbapenems has been rising in the last few years due to the emergence of drug resistant tuberculosis. Ertapenem (ETP), given once a day parenteral, and faropenem (FAR), oral, have a better administration profile than meropenem (MEM), imipenem (IPM) and doripenem (DOR). The addition of amoxicillin-clavulanate (AMC) inhibits the hydrolysis by the carbapenemase present in Mycobacterium tuberculosis (MTB).
The aim of this study was to determine the in vitro activity of ETP and FAR against susceptible and resistant clinical MTB strains by two widely use methodologies, the BACTEC960 MGIT and microdilution.

Results
19 clinical isolates with different susceptibility profiles and H37Rv were included. Minimal inhibitory concentration (MIC) testing was performed using two methods of different concentrations of ETP and FAR with and without AMC.
MIC50 was 2 and 8 for FAR with and without AMC by both methods. MIC90 was > 16 and > 8 by microdilution and MGIT respectively and did not change after AMC addition.
18/20 samples were resistant to the highest concentration of ETP, with and without AMC. Half of the samples had some susceptibility to FAR; addition of AMC further reduced the MIC level in seven isolates.
10/20 isolates showed susceptibility to FAR and the addition of AMC further reduced the MIC in 7 isolates. However, most of the MICs were near the limit of effectiveness (8 μg/mL).
Resistance to FAR was associated with resistance to MEM (p = 0.04) but not to resistance profiles of other drugs, including M/XDR status.

Conclusions
The lack of ETP activity may be associated with its degradation, independent of carbapenemase, during incubation.
No susceptibility pattern to traditional drugs can predict susceptibility to FAR and susceptibility testing is not routinely available. PK/PD studies are needed as reaching the concentrations tested in these experiments may be challenging.
This work highlighted some of the limitations of carbapenem use. More evidence is needed to clarify their true impact in TB treatment and outcome, considering the financial burden, complications and microbiota changes associated with their use.
Identification of SNPs and InDels associated with berry size in table grapes integrating genetic and transcriptomic approaches
Authors: Muñoz-Espinoza Claudia , Di Genova Alex , Sánchez Alicia , Correa José , Espinoza Alonso , Meneses Claudio , Maass Alejandro , Orellana Ariel , Hinrichsen Patricio 
Published: August 2020

AbstractBackgroundBerry size is considered as one of the main selection criteria in table grapes breeding programs, due to the consumer preferences. However, berry size is a complex quantitive trait under polygenic control, and its genetic determination of berry weight is not yet fully understood. The aim of this work was to perform marker discovery using a transcriptomic approach, in order to identify and characterize SNP and InDel markers associated with berry size in table grapes. We used an integrative analysis based on RNA-Seq, SNP/InDel search and validation on table grape segregants and varieties with different genetic backgrounds.ResultsThirty SNPs and eight InDels were identified using a transcriptomic approach (RNA-Seq). These markers were selected from SNP/InDel found among segregants from a Ruby x Sultanina population with contrasting phenotypes for berry size. The set of 38 SNP and InDel markers was distributed in eight chromosomes. Genotype-phenotype association analyses were performed using a set of 13 RxS segregants and 41 table grapes varieties with different genetic backgrounds during three seasons. The results showed several degrees of association of these markers with berry size (10.2 to 30.7%) as other berry-related traits such as length and width. The co-localization of SNP and /or InDel markers and previously reported QTLs and candidate genes associated with berry size were analysed.ConclusionsWe identified a set of informative and transferable SNP and InDel markers associated with berry size. Our results suggest the suitability of SNPs and InDels as candidate markers for berry weight in seedless table grape breeding. The identification of genomic regions associated with berry weight in chromosomes 8, 15 and 17 was achieved with supporting evidence derived from a transcriptome experiment focused on SNP/InDel search, as well as from a QTL-linkage mapping approach. New regions possibly associated with berry weight in chromosomes 3, 6, 9 and 14 were identified.
A prediction model of contrast-associated acute kidney injury in patients with hypoalbuminemia undergoing coronary angiography
Authors: Liu Liwei , Liu Jin , Lei Li , Wang Bo , Sun Guoli , Guo Zhaodong , He Yibo , Song Feier , Lun Zhubin , Liu Bowen , Chen Guanzhong , Chen Shiqun , Yang Yongquan , Liu Yong , Chen Jiyan 
Published: August 2020

AbstractBackgroundRisk stratification is recommended as the key step to prevent contrast-associated acute kidney injury (CA-AKI) among at-risk patients following coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). Patients with hypoalbuminemia are prone to CA-AKI and do not have their own risk stratification tool. Therefore, this study developed and validated a new model for predicting CA-AKI among hypoalbuminemia patients CAG/PCI.Methods1272 patients with hypoalbuminemia receiving CAG/PCI were enrolled and randomly allocated (2:1 ratio) into the development cohort (n = 848) and the validation cohort (n = 424). CA-AKI was defined as an increase of ≥0.3 mg/dL or 50% in serum creatinine (SCr) compared to baseline in the 48 to 72 h after CAG/PCI. A prediction model was established with independent predictors according to stepwise logistic regression, showing as a nomogram. The discrimination of the new model was evaluated by the area under the curve (AUC) and was compared to the classic Mehran CA-AKI model. The Hosmer-Lemeshow test was conducted to assess the calibration of our model.ResultsOverall, 8.4% (71/848) patients of the development group and 11.2% (48/424) patients of the validation group experienced CA-AKI. A new nomogram included estimated glomerular filtration rate (eGFR), serum albumin (ALB), age and the use of intra-aortic balloon pump (IABP); showed better predictive ability than the Mehran score (C-index 0.756 vs. 0.693,p = 0.02); and had good calibration (Hosmer–Lemeshow testp = 0.187).ConclusionsWe developed a simple model for predicting CA-AKI among patients with hypoalbuminemia undergoing CAG/PCI, but our findings need validating externally.Trial registrationhttp://www.ClinicalTrials.govNCT01400295, retrospectively registered 21 July 2011.
99mTc-sodium phytate is a valid alternative to the gold-standard 99mTc-sulfur colloid in the measurement of gastric emptying among healthy multi-ethnic Asian population: results of a randomized cross-over trial
Authors: Mat Nawi Norazlina , Tagiling Nashrulhaq , Mohd Rohani Mohd Fazrin , Wan Zainon Wan Mohd Nazlee , Zanial Muhammad Saifuddin , Wong Mung Seong , Lee Yeong Yeh 
Published: August 2020

Abstract
Background
It is unclear if the 99mTc-sodium phytate (99mTc-SP) is as reliable as the gold-standard 99mTc-sulfur colloid (99mTc-SC) for gastric emptying scintigraphy (GES). This study is aimed to compare the emptying rates of both radiotracers in a prospective, randomized cross-over trial and to determine the normative data of a healthy multi-ethnic Asian population.

Methods
Out of the 44 healthy individuals screened, 31 (14 females; mean age: 28.4 ± 7.0 years) were enrolled and underwent GES using the standardized egg-white meal. All participants were randomly assigned to either 99mTc-SP or 99mTc-SC on the first GES session before crossed over to the other formulation after 2 weeks.

Results
Both kits achieved the radiochemical purities of > 95%. The median rate (95th upper normative limit) of gastric emptying, reported as total gastric meal retention between 99mTc-SP and 99mTc-SC, was found to be comparable at all measured time points: 0.5 h [85.0% (96.6%) vs. 82.0% (94.0%)], 1 h [70.0% (86.4%) vs. 65.0% (86.6%)], 2 h [31.0% (55.8%) vs. 25.0% (64.4%)], 3 h [7.0% (26.3%) vs. 5.0% (29.9%)], and 4 h [3.0% (10.3%) vs. 2.0% (9.9%)]; P > 0.05. In addition, both radiotracers correlated well (Kendall’s Tau (τ) coefficient = 0.498, P < 0.001) and presented with a good agreement at the 4th-hour time frame based on the Bland-Altman plot analysis.

Conclusions
99mTc-SP is a valid radiotracer alternative to 99mTc-SC for routine GES examination. The normative values for both radiotracers have also been determined for the healthy multi-ethnic Asian population.

Trial registration
This trial was registered retrospectively in the Thai Clinical Trials Registry on May 23rd, 2020 (Identifier: TCTR20200526004; http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=6296).
Seropositivity to dengue and associated risk factors among non-malarias acute febrile patients in Arba Minch districts, southern Ethiopia
Authors: Eshetu Daniel , Shimelis Techalew , Nigussie Eshetu , Shumie Girma , Chali Wakwoya , Yeshitela Biruck , Assefa Abraham , Gadisa Endalamaw 
Published: August 2020

Abstract
Background
Dengue fever is an arthropod vector-borne disease transmitted to humans by infected Aedes mosquitoes. Ethiopia has a favorable ecology for arthropods and report high burden of acute febrile illnesses. However, the contribution of arboviral infections to the burden of acute febrile illnesses is barely known. In this study the seropositivity to dengue virus infection and associated risk factors were assessed in Arba Minch districts, southern Ethiopia.

Methods
An institution based cross-sectional study was conducted in a consecutive group of 529 acute febrile patients between May to August 2016. Socio-demographic data, residence place and clinical signs and symptoms were collected using structured questionnaires. Sera were tested for anti-dengue IgG and IgM using Euroimmune indirect immunofluorescent assay. Data analysis was done using SPSS V-20 (IBM Corp, 2012). P-value < 0.05 was taken as statistically significant.

Result
Seropositivity was 25.1% (133/529) and 8.1% (43/529) for anti- IgG and IgM respectively.

Conclusion
The high IgM prevalence detected indicate the probability of active transmission with a potential of public health significance that calls for a proactive follow up of the communities in the study area to forecast and avert the risk.
Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: systematic review and meta-analysis
Authors: Xie Yewei , Wang Zaisheng , Liao Huipeng , Marley Gifty , Wu Dan , Tang Weiming 
Published: August 2020

Abstract
Background
The COVID-19 pandemic has affected the world deeply, with more than 14,000,000 people infected and nearly 600,000 deaths. This review aimed to summarize the epidemiologic traits, clinical spectrum, CT results and laboratory findings of the COVID-19 pandemic.

Methods
We scoped for relevant literatures published during 1st December 2019 to 16th July 2020 based on three databases using English and Chinese languages. We reviewed and analyzed the relevant outcomes.

Results
The COVID-19 pandemic was found to have a higher transmission rate compared to SARS and MERS and involved 4 stages of evolution. The basic reproduction number (R0) is 3.32 (95% CI:3.24–3.39), the incubation period was 5.24 days (95% CI:3.97–6.50, 5 studies) on average, and the average time for symptoms onset varied by countries. Common clinical spectrums identified included fever (38.1–39.0 °C), cough and fatigue, with Acute Respiratory Distress Syndrome (ARDS) being the most common complication reported. Body temperatures above 39.0 °C, dyspnea, and anorexia were more common symptoms in severe patients. Aged over 65 years old, having co-morbidities, and developing complications were the commonest high-risk factors associated with severe conditions. Leucopenia and lymphopenia were the most common signs of infection while liver and kidney damage were rare but may cause bad outcomes for patients. The bilateral, multifocal Ground-Glass Opacification (GGO) on peripheral, and the consolidative pulmonary opacity were the most frequent CT results and the tendency of mortality rates differed by region.

Conclusions
We provided a bird’s-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease’s future research, control and prevention.
Phase II study on first-line treatment of NIVolumab in combination with folfoxiri/bevacizumab in patients with Advanced COloRectal cancer RAS or BRAF mutated – NIVACOR trial (GOIRC-03-2018)
Authors: Damato Angela , Iachetta Francesco , Antonuzzo Lorenzo , Nasti Guglielmo , Bergamo Francesca , Bordonaro Roberto , Maiello Evaristo , Zaniboni Alberto , Tonini Giuseppe , Romagnani Alessandra , Berselli Annalisa , Normanno Nicola , Pinto Carmine 
Published: August 2020

AbstractBackgroundFOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab has shown to be one of the therapeutic regimens in first line with the highest activity in patients (pts.) with metastatic colorectal cancer (mCRC) unselected for biomolecular alterations. Generally, tumors co-opt the programmed death-1/ligand 1 (PD-1/PD-L1) signaling pathway as one key mechanism to evade immune surveillance. As today, anti-PD-1 monoclonal antibodies are FDA approved only for DNA mismatch repair deficient/microsatellite instability-high (MMRd/MSI-H), which represent only about 5% among all mCRC. Nowadays, there are no data demonstrating anti PD-1 activity in proficient and stable disease (MMRp/MSS). A different target in mCRC is also the Vascular Endothelial Growth Factor A (VEGF-A), which acts on endothelial cells to stimulate angiogenesis. VEGF-A inhibition with bevacizumab has shown to increase the immune cell infiltration, providing a solid rationale for combining VEGF targeted agents with immune checkpoint inhibitors. Based on these evidences, we explore the combination of triplet chemotherapy (FOLFOXIRI) with bevacizumab and nivolumab in pts. with mCRCRAS/BRAFmutant regardless of microsatellite status.Methods/designThis is a prospective, open-label, multicentric phase II trial where pts. with mCRCRAS/BRAFmutated, in first line will receive nivolumab in combination with FOLFOXIRI/bevacizumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks. Bevacizumab will be administered intravenously at dose of 5 mg/kg every 2 weeks and nivolumab intravenously as a flat dose of 240 mg every 2 weeks. The primary endpoint is the overall response rate (ORR). This study hypothesis is that the treatment is able to improve the ORR from 66 to 80%. Secondary endpoints include OS, safety, time to progression, duration of response. Collateral translational studies evaluate the i) tumor mutational burden, and ii) genetic alterations by circulating free DNA (cfDNA) obtained from plasma samples. The trial is open to enrollment, 9 of planned 70 pts. have been enrolled.Trial registrationNIVACOR is registered at ClinicalTrials.gov:NCT04072198, August 28, 2019.
UBR-box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target
Authors: Saurabh Kumar , Shah Parag P. , Doll Mark A. , Siskind Leah J. , Beverly Levi J. 
Published: August 2020

Abstract
Background
N-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer.

Methods
We determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples. Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays and in vivo xenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA for in vitro studies and Wilcoxon paired t-test for in vivo tumor volumes.

Results
We show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples. To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Data indicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated that shRNA-mediated loss of UBR5 decreases cell viability and clonogenic potential of lung adenocarcinoma cell lines. In addition, we found decreased levels of activated AKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice.

Conclusions
These findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.