bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Sensitivity Detection of Malignant-Specific M-Proteins Using Mass Spectrometry
Authors: Murray David L , Mills John R , Katzmann Jerry A. , Kyle Robert , Rajkumar Vincent , Dispenzieri Angela , Barnidge David R 
Published: November 2019

Abstract
Detection of an M-protein (monoclonal immunoglobulin) has been used to diagnose and monitor multiple myeloma (MM). As therapies for MM have improved, more sensitive methods have been used to define response: immunofixation electrophoresis (IFX) of serum and urine, normalization of the serum immunoglobulin free light chain (FLC) ratio, and high sensitivity flow cytometry to detect clonal plasma bone marrow cells. It is hoped that these more sensitive approaches will differentiate those patients with minimal residual disease (MRD) versus no residual disease (NRD), that later which could mean a cure. Flow cytometry of plasma cells requires bone marrow aspiration, which is inconvenient and expensive and is potentially limited by sampling bias. More sensitive methods to differentiate MRD from NRD using serum would be advantageous.
We have developed a sensitive test for the presence of the monoclonal antibody produced by the plasma cells which may serve as a substitute for invasive bone marrow biopsy. Briefly, patient serum is enriched for immunoglobulins (Ig) and the Ig light chains are decoupled from the heavy chain by reduction with DTT. The mass distribution of the light chains is resolved using a micro LC-ESI-Q-TOF mass spectrometry and the presence of the M-protein is detected as a spike in the mass distribution. In addition to the detection, the accurate mass measurement of the light chain serves as a unique individualized marker which can aid in detection in subsequent patient monitoring. We have termed this method: monoclonal-immunoglobulin-Rapid-Accurate-Mass-Measurement (miRAMM). By spiking monoclonal immunoglobulins into human serum, we have demonstrated that miRAMM is approximately 1000x more sensitive than SPEP at detecting M-proteins. Initial results on 21 patients in stringent complete response (sCR) demonstrated that 67% (n=14) had detectable malignant specific clones by miRAMM. Given these promising results we have extended the method to a larger series of myeloma patients for whom we had long term follow-up and serum samples prior to treatment and at 6-12 months status post stem cell treatment. The results of this data will be correlated to the clinical outcomes for these patients. Early results demonstrate the potential of miRAMM to be a more sensitive, cost effective approach to detect MRD compared with current methods.

Disclosures
Murray: Mayo Clinic: Patent Application filed Patents & Royalties. Barnidge:Mayo Clinic: Patent filed Patents & Royalties.
Male circumcision and global HIV/AIDS epidemic challenges
Authors: Olapade-Olaopa Emiola Oluwabunmi , Salami Mudasiru Adebayo , Lawal Taiwo Akeem 
Published: November 2019

AbstractBackgroundGiven the devastating mortality and morbidity associated with HIV/AIDS, many potential prevention measures against HIV infection continue to be explored. Most prevention methods are in the realm of sexual behavior change. However, of all aspects of human behavior, it is sexual behavior that is least amenable to change. Newer and simpler interventions are therefore required. Male circumcision, the surgical removal of some or all of the foreskin (or prepuce) from the penis, is one of the ways being promoted as a preventive measure. This paper reviews the scientific basis and evidence for the efficacy of male circumcision within the context of the global challenges involved.Main bodyWe reviewed articles with emphasis on male circumcision and HIV/AIDS transmission. Published abstracts of presentations at international scientific meetings were also reviewed.ConclusionsCurrent epidemiological evidence supports the promotion of male circumcision for HIV prevention, especially in populations with high HIV prevalence and low circumcision rates. Three notable randomized control trials strengthen the case for applied research studies to demonstrate that safe male circumcision is protective at the population level, particularly as ideal and well-resourced conditions of a randomized trial are often not replicated in other service delivery settings. Ethically and culturally responsive strategies in promoting circumcision in a culturally heterogenous world need to be developed, too. Male circumcision should also be viewed as a complementary measure along with other proven approaches to turn the HIV/AIDS epidemic around.
Study protocol: a single-blind, multi-center, randomized controlled trial comparing dynamic intraligamentary stabilization, internal brace ligament augmentation and reconstruction in individuals with an acute anterior cruciate ligament rupture: LIBRƎ study
Authors: Heusdens Christiaan H. W. , Zazulia Katja , Roelant Ella , Dossche Lieven , van Tiggelen Damien , Roeykens Johan , Smits Elke , Vanlauwe Johan , Van Dyck Pieter 
Published: November 2019

AbstractBackgroundThe current gold standard for the treatment of an anterior cruciate ligament (ACL) rupture is reconstruction with tendon graft. Recently, two surgical ACL repair techniques have been developed for treating an acute ACL rupture: Dynamic Intraligamentary Stabilization (DIS, Ligamys®) and Internal Brace Ligament Augmentation (IBLA,InternalBrace™). We will conduct a single-blind, multi-center, randomized controlled trial which compares DIS, IBLA and reconstruction for relative clinical efficacy and economic benefit.MethodsSubjects, aged 18–50 years, with a proximal, primary and repairable ACL rupture will be included. DIS is preferably performed within 4 weeks post-rupture, IBLA within 12 weeks and reconstruction after 4 weeks post-rupture. Patients are included in study 1 if they present within 0–4 weeks post-rupture and surgery is feasible within 4 weeks post-rupture. Patients of study 1 will be randomized to either DIS or IBLA. Patients are included in study 2 if they present after 4 weeks post-rupture and surgery is feasible between 5 and 12 weeks post-rupture. Patients of study 2 will be randomized to either IBLA or reconstruction. A total of 96 patients will be included, with 48 patients per study and 24 patients per study arm. Patients will be followed-up for 2 years. The primary outcome is change from baseline (pre-rupture) in International Knee Documentation Committee score to 6 months post-operatively. The main secondary outcomes are the EQ-5D-5 L, Tegner score, Lysholm score, Lachman test, isokinetic and proprioceptive measurements, magnetic resonance imaging outcome, return to work and sports, and re-rupture/failure rates. The statistical analysis will be based on the intention-to-treat principle. The economic impact of the surgery techniques will be evaluated by the cost-utility analysis. The LIBRƎ study is to be conducted between 2018 and 2022.DiscussionThis LIBRƎ study protocol is the first study to compare DIS, IBLA and ACL reconstruction for relative clinical efficacy and economic benefit. The outcomes of this study will provide data which could aid orthopaedic surgeons to choose between the different treatment options for the surgical treatment of an acute ACL rupture.Trial registrationThis study is registered at ClinicalTrials.gov;NCT03441295. Date registered 13.02.2018.
YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma
Authors: Hou Jiajie , Zhang He , Liu Jun , Zhao Zhenjun , Wang Jianye , Lu Zhike , Hu Bian , Zhou Jiankui , Zhao Zhicong , Feng Mingxuan , Zhang Haiyan , Shen Bin , Huang Xingxu , Sun Beicheng , He Chuan , Xia Qiang 
Published: November 2019

Abstract
Background
Dynamic N6-methyladenosine (m6A) modification was previously identified as a ubiquitous post-transcriptional regulation that affected mRNA homeostasis. However, the m6A-related epitranscriptomic alterations and functions remain elusive in human cancer. Here we aim to identify the profile and outcome of m6A-methylation in hepatocellular carcinoma (HCC).

Results
Using liquid chromatography-tandem mass spectrometry and m6A-immunoprecipitation in combination with high-throughput sequencing, we determined the m6A-mRNA levels in human HCC. Human HCC exhibited a characteristic gain of m6A modification in tandem with an increase of mRNA expression, owing to YTH domain family 2 (YTHDF2) reduction. The latter predicted poor classification and prognosis of HCC patients, and highly correlated with HCC m6A landscape. YTHDF2 silenced in human HCC cells or ablated in mouse hepatocytes provoked inflammation, vascular reconstruction and metastatic progression. Mechanistically, YTHDF2 processed the decay of m6A-containing interleukin 11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs, which were responsible for the inflammation-mediated malignancy and disruption of vascular normalization. Reciprocally, YTHDF2 transcription succumbed to hypoxia-inducible factor-2α (HIF-2α). Administration of a HIF-2α antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer.

Conclusion
Our results have characterized the m6A-mRNA landscape in human HCC and revealed YTHDF2 as a molecular ‘rheostat’ in epitranscriptome and cancer progression.
Uterine lesions with sex cord-like architectures: a systematic review
Authors: Jia Meng , Sun Ping-Li , Gao Hongwen 
Published: November 2019

Abstract
Background
Sex cord-like elements are rarely observed in uterine lesions, but these morphological patterns could appear in a variety of uterine tumors and non-tumorous lesions. In this review, we collected the literatures regarding the uterine tumorous and non-tumorous lesions containing sex cord-like elements and summarized these lesions in terms of clinicopathological, immunohistochemical, and molecular features in order to further understand these lesions and provide some new ideas for differential diagnosis.

Main body
This section provides a comprehensive overview of the clinicopathological, immunohistochemical, and molecular features of uterine lesions with sex cord-like architectures including uterine tumors resembling ovarian sex cord tumors, endometrial stromal tumors, adenomyosis, endometrial polyps, leiomyoma, epithelioid leiomyosarcoma, adenosarcoma, sertoliform endometrioid carcinoma, corded and hyalinized endometrioid carcinoma, mesonephric adenocarcinoma, and mesonephric-like adenocarcinoma. The differential diagnosis based on morphology, immunohistochemistry, and molecular alterations has also been discussed.

Conclusion
The sex cord-like areas in these lesions show heterogeneous but similar morphological features. Additionally, immunohistochemical staining plays a limited role in differential diagnosis. Furthermore, it is of significance for pathologists to better understand these lesions in order to avoid confusion and mistakes during pathological diagnosis, especially in a biopsy/curettage specimen.
Proteomics: a powerful tool to study plant responses to biotic stress
Authors: Liu Yahui , Lu Song , Liu Kefu , Wang Sheng , Huang Luqi , Guo Lanping 
Published: November 2019

AbstractIn recent years, mass spectrometry-based proteomics has provided scientists with the tremendous capability to study plants more precisely than previously possible. Currently, proteomics has been transformed from an isolated field into a comprehensive tool for biological research that can be used to explain biological functions. Several studies have successfully used the power of proteomics as a discovery tool to uncover plant resistance mechanisms. There is growing evidence that indicates that the spatial proteome and post-translational modifications (PTMs) of proteins directly participate in the plant immune response. Therefore, understanding the subcellular localization and PTMs of proteins is crucial for a comprehensive understanding of plant responses to biotic stress. In this review, we discuss current approaches to plant proteomics that use mass spectrometry, with particular emphasis on the application of spatial proteomics and PTMs. The purpose of this paper is to investigate the current status of the field, discuss recent research challenges, and encourage the application of proteomics techniques to further research.
Machine learning driven non-invasive approach of water content estimation in living plant leaves using terahertz waves
Authors: Zahid Adnan , Abbas Hasan T. , Ren Aifeng , Zoha Ahmed , Heidari Hadi , Shah Syed A. , Imran Muhammad A. , Alomainy Akram , Abbasi Qammer H. 
Published: November 2019

AbstractBackgroundThe demand for effective use of water resources has increased because of ongoing global climate transformations in the agriculture science sector. Cost-effective and timely distributions of the appropriate amount of water are vital not only to maintain a healthy status of plants leaves but to drive the productivity of the crops and achieve economic benefits. In this regard, employing a terahertz (THz) technology can be more reliable and progressive technique due to its distinctive features. This paper presents a novel, and non-invasive machine learning (ML) driven approach using terahertz waves with a swissto12 material characterization kit (MCK) in the frequency range of 0.75 to 1.1 THz in real-life digital agriculture interventions, aiming to develop a feasible and viable technique for the precise estimation of water content (WC) in plants leaves for 4 days. For this purpose, using measurements observations data, multi-domain features are extracted from frequency, time, time–frequency domains to incorporate three different machine learning algorithms such as support vector machine (SVM), K-nearest neighbour (KNN) and decision-tree (D-Tree).ResultsThe results demonstrated SVM outperformed other classifiers using tenfold and leave-one-observations-out cross-validation for different days classification with an overall accuracy of 98.8%, 97.15%, and 96.82% for Coffee, pea shoot, and baby spinach leaves respectively. In addition, using SFS technique, coffee leaf showed a significant improvement of 15%, 11.9%, 6.5% in computational time for SVM, KNN and D-tree. For pea-shoot, 21.28%, 10.01%, and 8.53% of improvement was noticed in operating time for SVM, KNN and D-Tree classifiers, respectively. Lastly, baby spinach leaf exhibited a further improvement of 21.28% in SVM, 10.01% in KNN, and 8.53% in D-tree in overall operating time for classifiers. These improvements in classifiers produced significant advancements in classification accuracy, indicating a more precise quantification of WC in leaves.ConclusionThus, the proposed method incorporating ML using terahertz waves can be beneficial for precise estimation of WC in leaves and can provide prolific recommendations and insights for growers to take proactive actions in relations to plants health monitoring.
TMRS: an algorithm for computing the time to the most recent substitution event from a multiple alignment column
Authors: Kiryu Hisanori , Ichikawa Yuto , Kojima Yasuhiro 
Published: November 2019

Abstract
Background
As the number of sequenced genomes grows, researchers have access to an increasingly rich source for discovering detailed evolutionary information. However, the computational technologies for inferring biologically important evolutionary events are not sufficiently developed.

Results
We present algorithms to estimate the evolutionary time ($$t_{\text {MRS}}$$tMRS) to the most recent substitution event from a multiple alignment column by using a probabilistic model of sequence evolution. As the confidence in estimated $$t_{\text {MRS}}$$tMRS values varies depending on gap fractions and nucleotide patterns of alignment columns, we also compute the standard deviation $$\sigma$$σ of $$t_{\text {MRS}}$$tMRS by using a dynamic programming algorithm. We identified a number of human genomic sites at which the last substitutions occurred between two speciation events in the human lineage with confidence. A large fraction of such sites have substitutions that occurred between the concestor nodes of Hominoidea and Euarchontoglires. We investigated the correlation between tissue-specific transcribed enhancers and the distribution of the sites with specific substitution time intervals, and found that brain-specific transcribed enhancers are threefold enriched in the density of substitutions in the human lineage relative to expectations.

Conclusions
We have presented algorithms to estimate the evolutionary time ($$t_{\text {MRS}}$$tMRS) to the most recent substitution event from a multiple alignment column by using a probabilistic model of sequence evolution. Our algorithms will be useful for Evo-Devo studies, as they facilitate screening potential genomic sites that have played an important role in the acquisition of unique biological features by target species.
Looking into the crystal ball: quality of life, delinquency, and problems experienced by young male adults after discharge from a secure residential care setting in the Netherlands
Authors: Janssen-de Ruijter E. A. W. , Mulder E. A. , Bongers I. L. , Omlo L. , van Nieuwenhuizen Ch. 
Published: November 2019

Abstract
Background
Adolescents in residential care are a vulnerable population with many problems in several life areas. For most of these adolescents, these problems persist after discharge and into adulthood. Since an accumulation of risk factors in multiple domains increases the likelihood of future adverse outcomes, it would be valuable to investigate whether there are differences in life after residential care between subgroups based on multiple co-occurring risk factors.

Aims and hypothesis
The aim of this exploratory follow-up study is to explore differences between young adults—classified in four risk profiles—in relation to life after discharge from a secure residential care setting. It is hypothesised that young adults with a profile with many risks in multiple domains will experience more problems after discharge, such as (persistent) delinquency, compared to young adults with a profile with lower risks.

Methods
Follow-up data were collected from 46 former patients of a hospital for youth forensic psychiatry and orthopsychiatry in the Netherlands. In order to illustrate these young adults’ life after discharge, self-reported outcome measures divided into five domains (i.e., quality of life, daily life, social life, problems, and delinquency) were used. Differences between four classes based on pre-admission risk factors, which were identified in a previous study by latent class analysis, were explored by three (non-)parametric statistical tests.

Results
Life after discharge for most young adults was characterised by close friends and a high quality of life, but also by substance abuse, professional support, debts, and delinquency. Only a few significant differences between the classes were found, primarily between young adults with risk factors in the individual, family, school, and peer domains and young adults in the other three classes.

Conclusions
Young adults experience a high quality of life after discharge from secure residential care, despite the presence of persistent problems. Some indications have been found that young adults with risk factors in four domains are at greatest risk for persistent problems in young adulthood. Because of the high amount of persistent problems, residential treatment and aftercare should focus more on patients’ long-term needs.
Polyphenolic compounds as electron shuttles for sustainable energy utilization
Authors: Hsueh Chung-Chuan , Wu Chia-Chyi , Chen Bor-Yann 
Published: November 2019

AbstractFor renewable and sustainable bioenergy utilization with cost-effectiveness, electron-shuttles (ESs) (or redox mediators (RMs)) act as electrochemical “catalysts” to enhance rates of redox reactions, catalytically accelerating electron transport efficiency for abiotic and biotic electrochemical reactions. ESs are popularly used in cellular respiratory systems, metabolisms in organisms, and widely applied to support global lives. Apparently, they are applicable to increase power-generating capabilities for energy utilization and/or fuel storage (i.e., dye-sensitized solar cell, batteries, and microbial fuel cells (MFCs)). This first-attempt review specifically deciphers the chemical structure association with characteristics of ESs, and discloses redox-mediating potentials of polyphenolics-abundant ESs via MFC modules. Moreover, to effectively convert electron-shuttling capabilities from non-sustainable antioxidant activities, environmental conditions to induce electrochemical mediation apparently play critical roles of great significance for bioenergy stimulation. For example, pH levels would significantly affect electrochemical potentials to be exhibited (e.g., alkaline pHs are electrochemically favorable for expression of such electron-shuttling characteristics). Regarding chemical structure effect, chemicals withortho- andpara-dihydroxyl substituents-bearing aromatics own convertible characteristics of non-renewable antioxidants and electrochemically catalytic ESs; however, ES capabilities ofmeta-dihydroxyl substituents can be evidently repressed due to lack of resonance effect in the structure for intermediate radical(s) during redox reaction. Moreover, this review provides conclusive remarks to elucidate the promising feasibility to identify whether such characteristics are non-renewable antioxidants or reversible ESs from natural polyphenols via cyclic voltammetry and MFC evaluation. Evidently, considering sustainable development, such electrochemically convertible polyphenolic species in plant extracts can be reversibly expressed for bioenergy-stimulating capabilities in MFCs under electrochemically favorable conditions.
Horizontal jumping biomechanics among elite female handball players with and without anterior cruciate ligament reconstruction: an ISU based study
Authors: Setuain Igor , Bikandi Eder , Amú Ruiz Francisco Antonio , Urtasun Fernando , Izquierdo Mikel 
Published: November 2019

Abstract
Background
Handball is a strenuous body-contact team sport that places high loads on the knee joint. Anterior cruciate ligament (ACL) tear is one of the most devastating injuries that any handball player can suffer, and female athletes are at particular risk due to their intrinsic anatomical, hormonal, neuromuscular and biomechanical characteristics. The purpose of this study was to analyze the horizontal jumping biomechanics of female elite handball players with or without previous ACL reconstruction.

Methods
Twenty-one female participants (6 with previous ACL reconstruction and 15 uninjured controls) were recruited. Two horizontal hopping tasks were evaluated using inertial sensor unit (ISU)-based technology to assess jumping biomechanics through a direct mechanics-based approach.

Results
The athletes with previous ACL reconstruction demonstrated a significant (P < 0.05) reduction in the unilateral triple hop for distance compared with the healthy controls. Furthermore, during the initial propulsive phase of the unilateral cross-over hop, the control participants generated significantly (P < 0.05) higher force values in the mediolateral direction (the X axis) with their dominant limb compared with the ACL-reconstructed (ACL-R) limb of previously injured participants.

Conclusions
Three-dimensional horizontal jumping biomechanics analyses using ISU-based technologies could provide clinicians with more accurate information regarding the horizontal jumping biomechanical patterns among elite handball female athletes. Furthermore, several mechanical alterations could still be observed among those players who had undergone previous ACL reconstruction, even when several years have passed since the original ACL injury.