bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stat5 and Stat3 Differentially Regulate Early and Late Stages of Primary Embryonic Erythroid Cell Maturation
Authors: Murphy Zachary C. , Kingsley Paul D. , McGrath Kathleen E. , Palis James 
Published: November 2019

Erythropoietin is the critical regulator of adult (definitive) red cell production, acting through its cognate receptor (EpoR) and downstream Janus kinase (Jak)2 and signal transducer and activator of transcription (Stat)5 signaling. Mutant JAK2 activation causes hyperproliferation of erythroid precursors in polycythemia vera, highlighting the importance of Jak2-STAT signaling in pathologic states in addition to normal development. EpoR-null mouse embryos die at midgestation of profound anemia and we have recently determined that EpoR signaling is also specifically required for the survival and terminal maturation of primitive erythroblasts. Unlike definitive erythropoiesis, Stat3 is significantly expressed in primitive erythroblasts but its function in erythropoiesis remains poorly understood. We find that Stat3, in addition to Stat5, is phosphorylated downstream of EpoR in primitive erythroblasts. Interestingly, phospho-Stat5 intensity decreases during primitive erythroblast maturation while phospho-Stat3 levels remain constant, resulting in an increase in relative phospho-Stat3 in late-stage primitive erythroblasts. Knockdown of Jak2 and Stat5 each results in accelerated maturation, decreased cell size, and increased apoptosis of primary primitive erythroblasts. In contrast, Stat3 knockdown results in delayed maturation and increased cell size of late-stage primary primitive erythroblasts, consistent with an increased role of phospho-Stat3 once phospho-Stat5 signal intensity has diminished. Stat3 knockdown, both in vitro and in vivo, also increased apoptosis of late-stage primitive erythroblasts. While Stat3 and Stat5 bind many apoptosis-related genes in common, Stat3 specifically binds several caspase genes and their regulators. We find that activated caspase3 levels increase in late-stage primitive erythroblasts, and that knockdown of Stat3 results in decreased levels of caspases and their regulators. In addition, caspase inhibition, like Stat3 knockdown, results in delayed maturation of late-stage primitive erythroblasts. Taken together, our data support a model where Stat3 and Stat5 differentially regulate erythroid maturation and Stat3 preferentially regulates terminal stages of primitive erythropoiesis through its activation and regulation of apoptotic machinery.

Disclosures
No relevant conflicts of interest to declare.
The associations of self-rated health with cardiovascular risk proteins: a proteomics approach
Authors: Bao Xue , Borné Yan , Yin Songjiang , Niu Kaijun , Orho-Melander Marju , Nilsson Jan , Melander Olle , Engström Gunnar 
Published: November 2019

AbstractBackgroundThough subjective, poor self-rated health (SRH) has consistently been shown to predict cardiovascular disease (CVD). The underlying mechanism is unclear. This study evaluates the associations of SRH with biomarkers for CVD, aiming to explore potential pathways between poor SRH and CVD.MethodsBased on the Malmö Diet and Cancer Cardiovascular Cohort study, a targeted proteomics approach was used to assess the associations of SRH with 88 cardiovascular risk proteins, measured in plasma from 4521 participants without CVD. The false discovery rate (FDR) was controlled using the Benjamini and Hochberg method. Covariates taken into consideration were age, sex, traditional CVD risk factors (low-density lipoprotein cholesterol, systolic blood pressure, anti-hypertensive medication, diabetes, body mass index, smoking), comorbidity, life-style and psycho-social factors (education level, living alone, alcohol consumption, low physical activity, psychiatric medication, sleep duration, and unemployment).ResultsAge and sex-adjusted associations with SRH was found for 34 plasma proteins. Nine of them remained significant after adjustments for traditional CVD risk factors. After further adjustment for comorbidity, life-style and psycho-social factors, only leptin (β = − 0.035, correctedp = 0.016) and C–C motif chemokine 20 (CCL20; β = − 0.054, correctedp = 0.016) were significantly associated with SRH.ConclusionsPoor SRH was associated with raised concentrations of many plasma proteins. However, the relationships were largely attenuated by adjustments for CVD risk factors, comorbidity and psycho-social factors. Leptin and CCL20 were associated with poor SRH in the present study and could potentially be involved in the SRH–CVD link.
A multi-chamber tissue culture device for load-dependent parallel evaluation of tendon explants
Authors: Soreide Endre , Denbeigh Janet M. , Lewallen Eric A. , Thaler Roman , Samsonraj Rebekah M. , Jones Dakota L. , Xu Wei , Larson Dirk , Nordsletten Lars , Kakar Sanjeev , van Wijnen Andre J. 
Published: November 2019

AbstractBackgroundInjuries in the musculoskeletal system, such as tendon and ligament ruptures, are challenging to manage and often require surgical reconstructions with limited long-term success. Thus, characterizations of these tissues are urgently needed to better understand cellular mechanisms that regulate tissue homeostasis and healing. Explant culturing systems allow for ex vivo analysis of tissues in an environment that mimics the native microenvironment in vivo.MethodsCollaborative efforts within our institution facilitated the establishment of a novel explant culturing system. Tissue specimens cultured in single wells, with individual applied loading and/or biological environment, allowed characterization of tissue cultured under a variety of biological loading conditions. Quantitative PCR analysis for selected gene markers was our primary outcome.ResultsData were stratified for analysis by either culture environment or loading condition. Our gene expression results show that specimens clustered by culture condition may differ in molecular markers related to ECM production (e.g., Col1a1, Adamts4) and/or organization (e.g., Tnc, Dnc). In contrast, loading condition did significantly alter the median gene expression levels of tissues in comparison to unloaded control samples, although gene expression values related to ECM degradation (e.g., Mmp1, Mmp10) were altered in tendons cultured under tension in the device.ConclusionOur study demonstrates promising utility of a novel explant culturing system for further characterization of musculoskeletal tissues such as native tendons and ligaments, as well as pathologic fibrotic tissues resulting from arthrofibrosis or Dupuytren’s disease.
Genomic adaptations to chemosymbiosis in the deep-sea seep-dwelling tubeworm Lamellibrachia luymesi
Authors: Li Yuanning , Tassia Michael G. , Waits Damien S. , Bogantes Viktoria E. , David Kyle T. , Halanych Kenneth M. 
Published: November 2019

Abstract
Background
Symbiotic relationships between microbes and their hosts are widespread and diverse, often providing protection or nutrients, and may be either obligate or facultative. However, the genetic mechanisms allowing organisms to maintain host-symbiont associations at the molecular level are still mostly unknown, and in the case of bacterial-animal associations, most genetic studies have focused on adaptations and mechanisms of the bacterial partner. The gutless tubeworms (Siboglinidae, Annelida) are obligate hosts of chemoautotrophic endosymbionts (except for Osedax which houses heterotrophic Oceanospirillales), which rely on the sulfide-oxidizing symbionts for nutrition and growth. Whereas several siboglinid endosymbiont genomes have been characterized, genomes of hosts and their adaptations to this symbiosis remain unexplored.

Results
Here, we present and characterize adaptations of the cold seep-dwelling tubeworm Lamellibrachia luymesi, one of the longest-lived solitary invertebrates. We sequenced the worm’s ~ 688-Mb haploid genome with an overall completeness of ~ 95% and discovered that L. luymesi lacks many genes essential in amino acid biosynthesis, obligating them to products provided by symbionts. Interestingly, the host is known to carry hydrogen sulfide to thiotrophic endosymbionts using hemoglobin. We also found an expansion of hemoglobin B1 genes, many of which possess a free cysteine residue which is hypothesized to function in sulfide binding. Contrary to previous analyses, the sulfide binding mediated by zinc ions is not conserved across tubeworms. Thus, the sulfide-binding mechanisms in sibgolinids need to be further explored, and B1 globins might play a more important role than previously thought. Our comparative analyses also suggest the Toll-like receptor pathway may be essential for tolerance/sensitivity to symbionts and pathogens. Several genes related to the worm’s unique life history which are known to play important roles in apoptosis, cell proliferation, and aging were also identified. Last, molecular clock analyses based on phylogenomic data suggest modern siboglinid diversity originated in 267 mya (± 70 my) support previous hypotheses indicating a Late Mesozoic or Cenozoic origins of approximately 50–126 mya for vestimentiferans.

Conclusions
Here, we elucidate several specific adaptations along various molecular pathways that link phenome to genome to improve understanding of holobiont evolution. Our findings of adaptation in genomic mechanisms to reducing environments likely extend to other chemosynthetic symbiotic systems.
Modified score based on revised Tokuhashi score is needed for the determination of surgical intervention in patients with lung cancer metastases to the spine
Authors: Cai Zhenyu , Tang Xiaodong , Yang Rongli , Yan Taiqiang , Guo Wei 
Published: November 2019

Abstract
Background
Revised Tokuhashi score (RTS) is no longer accurate to predict the survival of patients with lung cancer metastases to the spine. This study is to identify additional prognostic factors in those patients, develop a modified prognostic score based on RTS, and verify the accuracy of the score in prediction.

Methods
Our study included patients with lung cancer metastases to the spine who underwent surgery for spine metastasis. Potential prognostic factors were analyzed. Points were allocated for prognostic factors obtained from survival analyses. A modified score was developed by including prognostic factors and their points to RTS. Accuracy of the modified score was evaluated by comparing the coincidence between predicted and observed survival. Kaplan–Meier analysis and Cox regression models were used. Predictive values of scores for 6-month survival were measured via receiver operating characteristic (ROC) curves.

Results
Targeted therapy and tumor markers were additional independent prognostic factors. In the modified score, 2 and 1 points were allocated to the new evaluation factors. The points for factors based on RTS remained the same, and two prognostic groups were redefined. For group A patients who were predicted to live for less than 6 months, conservative procedures would be recommended. For group B patients who were predicted to live for 6 months or more, palliative surgery would be recommended. When comparing the modified score to RTS, the area under the receiver operating characteristic curve (AUCROC) and accuracy of score were improved.

Conclusions
The modified RTS has improved prognostic accuracy in patients with lung cancer metastases to the spine.
Root phenotypic detection of different vigorous maize seeds based on Progressive Corrosion Joining algorithm of image
Authors: Lu Wei , Li Ye , Deng Yiming 
Published: November 2019

Abstract
Background
The root phenotypes of different vigorous maize seeds vary a lot. Imaging roots of growing maize is a non-invasive, affordable and high throughput approach. However, it’s difficult to get integral root images because of the block of the soil. The paper proposed an algorithm to repair incomplete root images for maize root fast non-invasive phenotyping detection.

Results
A two-layer transparent stress growth device with two concentric cylinders was developed as mesocosms and the maize seeds were planted in the annulus of it. The maize roots grow in soil against two acrylic plastic surfaces due to the press of the small growing area to acquire more root details during roots visualization and imaging. Even though, parts of the roots are occluded which means that it’s tough to extract the information of root general physical construction. For recovering gaps from disconnected root segments, Progressive Corrosion Joining (PCJ) algorithm was proposed based on the physiological characteristics of hydrotropism, geostrophic and continuity with three steps which are root image thinning, progressive corrosion and joining processing respectively. The experiments indicate that maize phenotyping parameters are negative correlation with seed aging days. And specifically, Root Number (RTN), Root Length (RTL), Root Width (RTW) and Root Extension Length (REL) of unaged and 14-day-aged maize seeds are decreased from 15.40, 82.40 mm, 1.53 mm and 82.20 mm to 4.58, 38.6 mm, 1.35 mm and 55.20 mm, and the growing speed of them are changed from 1.68 per day, 8.80 mm/d, 0.06 mm/d, 9.0 mm/d to 0.70 per day, 4.3 mm/d, 0.05 mm/d and 5.70 mm/d respectively. Whereas Root Extension Angle (REA) is basically irrelevant with the level of maize seed aging.

Conclusion
The developed double-layer Annular Root Phenotyping Container (ARPC) can satisfy the general physical construction of maize as well as push each root growing along the inner wall of the container which help to acquire more root information. The presented novel PCJ algorithm can recover the missing parts, even for big gaps, of maize roots effectively according to root morphological properties. The experiments show that the proposed method can be applied to evaluate the vigor of maize seeds which has vast application prospect in high throughput root phenotyping area.
Combining gene expression programming and genetic algorithm as a powerful hybrid modeling approach for pear rootstocks tissue culture media formulation
Authors: Jamshidi Saeid , Yadollahi Abbas , Arab Mohammad Mehdi , Soltani Mohammad , Eftekhari Maliheh , Sabzalipoor Hamed , Sheikhi Abdollatif , Shiri Jalal 
Published: November 2019

AbstractBackgroundPredicting impact of plant tissue culture media components on explant proliferation is important especially in commercial scale for optimizing efficient culture media. Previous studies have focused on predicting the impact of media components on explant growth via conventional multi-layer perceptron neural networks (MLPNN) and Multiple Linear Regression (MLR) methods. So, there is an opportunity to find more efficient algorithms such as Radial Basis Function Neural Network (RBFNN) and Gene Expression Programming (GEP). Here, a novel algorithm, i.e. GEP which has not been previously applied in plant tissue culture researches was compared to RBFNN and MLR for the first time. Pear rootstocks (Pyrodwarf and OHF) were used as case studies on predicting the effect of minerals and some hormones in the culture medium on proliferation indices.ResultsGenerally, RBFNN and GEP showed extremely higher performance accuracy than the MLR. Moreover, GEP models as the most accurate models were optimized using genetic algorithm (GA). The improvement was mainly due to the RBFNN and GEP strong estimation capability and their superior tolerance to experimental noises or improbability.ConclusionsGEP as the most robust and accurate prospecting procedure to achieve the highest proliferation quality and quantity has also the benefit of being easy to use.
An improved method of constructing degradome library suitable for sequencing using Illumina platform
Authors: Li Yong-Fang , Zhao Miao , Wang Menglei , Guo Junqiang , Wang Li , Ji Jie , Qiu Zongbo , Zheng Yun , Sunkar Ramanjulu 
Published: November 2019

Abstract
Background
Post-transcriptional gene regulation is one of the critical layers of overall gene expression programs and microRNAs (miRNAs) play an indispensable role in this process by guiding cleavage on the messenger RNA targets. The transcriptome-wide cleavages on the target transcripts can be identified by analyzing the degradome or PARE or GMUCT libraries. However, high-throughput sequencing of PARE or degradome libraries using Illumina platform, a widely used platform, is not so straightforward. Moreover, the currently used degradome or PARE methods utilize MmeI restriction site in the 5′ RNA adapter and the resulting fragments are only 20-nt long, which often poses difficulty in distinguishing between the members of the same target gene family or distinguishing miRNA biogenesis intermediates from the primary miRNA transcripts belonging to the same miRNA family. Consequently, developing a method which can generate longer fragments from the PARE or degradome libraries which can also be sequenced easily using Illumina platform is ideal.

Results
In this protocol, 3′ end of the 5′RNA adaptor of TruSeq small RNA library is modified by introducing EcoP15I recognition site. Correspondingly, the double-strand DNA (dsDNA) adaptor sequence is also modified to suit with the ends generated by the restriction enzyme EcoP15I. These modifications allow amplification of the degradome library by primer pairs used for small RNA library preparation, thus amenable for sequencing using Illumina platform, like small RNA library.

Conclusions
Degradome library generated using this improved protocol can be sequenced easily using Illumina platform, and the resulting tag length is ~ 27-nt, which is longer than the MmeI generated fragment (20-nt) that can facilitate better accuracy in validating target transcripts belonging to the same gene family or distinguishing miRNA biogenesis intermediates of the same miRNA family. Furthermore, this improved method allows pooling and sequencing degradome libraries and small RNA libraries simultaneously using Illumina platform.
Mechanisms and evolution of resistance to environmental extremes in animals
Authors: Boothby Thomas C. 
Published: November 2019

AbstractWhen animals are exposed to an extreme environmental stress, one of three possible outcomes takes place: the animal dies, the animal avoids the environmental stress and survives, or the animal tolerates the environmental stress and survives. This review is concerned with the third possibility, and will look at mechanisms that rare animals use to survive extreme environmental stresses including freezing, desiccation, intense heat, irradiation, and low-oxygen conditions (hypoxia). In addition, an increasing understanding of the molecular mechanisms involved in environmental stress tolerance allows us to speculate on how these tolerances arose. Uncovering the mechanisms of extreme environmental stress tolerance and how they evolve has broad implications for our understanding of the evolution of early life on this planet, colonization of new environments, and the search for novel forms of life both on Earth and elsewhere, as well as a number of agricultural and health-related applications.
A radiologic review of hoarse voice from anatomic and neurologic perspectives
Authors: Montoya Simone , Portanova Anthony , Bhatt Alok A. 
Published: November 2019

AbstractThe differential diagnosis for hoarseness is extensive and includes a multitude of etiologies that span a large geographic area from the brainstem to the mediastinum. Therefore, localizing a causative lesion can be extremely difficult for clinicians and radiologists alike. In this review, we will first discuss the normal anatomy of the larynx and its innervation via the vagus and recurrent laryngeal nerves. We will then proceed with a guided tour of the various infectious/inflammatory, neoplastic, congenital, and traumatic/iatrogenic causes of hoarseness subdivided by anatomic location (brainstem, skull base, carotid sheath, thyroid, larynx, and superior mediastinum). Along the way, we will discuss the various cross-sectional imaging modalities best suited to detect the often subtle signs of recurrent laryngeal nerve injury. With thorough knowledge of these entities, radiologists can impact patient care by suggesting the appropriate imaging test and tailoring their search patterns to detect the subtle findings of laryngeal dysfunction.
The role of cardiac rehabilitation using exercise to decrease natriuretic peptide levels in non-surgical patients: a systematic review
Authors: Alphonsus Christella S. , Govender Pooveshni , Rodseth Reitze N. , Biccard Bruce M. 
Published: November 2019

AbstractExercise is recommended in patients with cardiac failure. In the perioperative patient, exercise is also gaining popularity as a form of prehabilitation. In this meta-analysis, we examine if exercise is able to reduce natriuretic peptide levels. Natriuretic peptide (NP) has strong prognostic ability in identifying patients who will develop adverse postoperative cardiovascular outcomes. The protocol was registered with PROSPERO (CRD42017051468). The database search included MEDLINE (PubMed), CINAHL (EBSCO host), EMBASE (EBSCO host), ProQuest, Web of Science, and Cochrane database. The primary outcomes were to determine whether exercise therapy was effective in reducing NP levels as compared to control group, the shortest time period required to reduce NP levels after exercise therapy, and whether reducing NP levels decreased morbidity and mortality. Full texts of 16 trials were retrieved for this review. Exercise therapy showed a significant reduction in natriuretic peptide levels between the intervention and control groups (SMD − 0.45, 95% CI − 0.88 to − 0.03) with significant heterogeneity between the included trials. This was also shown in the within a 12-week period.
Rethinking the combination treatment of fulvestrant and anastrozole for metastatic breast cancer: an integrated reanalysis of aromatase–estrogen receptor axis
Authors: Huang Xing 
Published: November 2019

AbstractAberrant expression or hyperactivation of aromatase (CYP19A1)–estrogen receptor (ESR) axis is well identified as one of the major causes of breast cancer. Lots of drugs have been developed for targeting CYP19A1 or ESR respectively, such as anastrozole and fulvestrant. Recently, Mehta et al. reported in NEJM that the combined treatment of anastrozole and fulvestrant increased long‐term survival of patients with metastatic breast cancer, especially for those without receiving endocrine therapy. However, the integrated prognostic analyses of CYP19A1 and ESR1/ESR2 indicated some contradictory outcomes to the recent clinical trial. Moreover, immunological investigation further revealed that targeting the whole CYP19A1–ESR axis might cause the inactivation of anti‐tumor immune response, which largely attenuated its application prospects in breast cancer. Considered the pathophysiologic functions of CYP19A1 and ESR1/ESR2‐mediated signaling pathway in breast cancer seem as more complicated than what we have already known, more precise evaluation will be needed in urgent.