bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe anemia in patients with Propionic acidemia is associated with branched-chain amino acid imbalance
Authors: Stanescu Sinziana , Belanger-Quintana Amaya , Fernandez-Felix Borja Manuel , Arrieta Francisco , Quintero Victor , Maldonado Maria Soledad , Alcaide Patricia , Martínez-Pardo Mercedes 
Published: May 2021

Abstract
Background
Propionic acidemia (PA), an inborn error of metabolism, is caused by a deficiency in propionyl-CoA carboxylase. Patients have to follow a diet restricted in the propiogenic amino acids isoleucine (Ile), valine (Val), methionine (Met) and threonine (Thr); proper adherence can prevent and treat acute decompensation and increase life expectancy. However, chronic complications occur in several organs even though metabolic control may be largely maintained. Bone marrow aplasia and anemia are among the more common.

Materials and methods
In this retrospective study, data for patients with PA being monitored at the Hospital Ramón y Cajal (Madrid, Spain) (n = 10) in the past 10 years were examined to statistically detect relationships between persistent severe anemia outside of metabolic decompensation episodes and dietary practices such as natural protein intake and medical food consumption (special mixture of precursor-free amino acids) along with plasma levels of branched-chain amino acids (BCAA). High ferritin levels were deemed to indicate that a patient had received repeated transfusions for persistent anemia since data on hemoglobin levels at the moment of transfusion were not always passed on by the attending centers.

Results
Three patients had severe, persistent anemia that required repeated blood transfusions. Higher medical food consumption and plasma Leu levels were associated with iron overload. Notably, natural protein intake and plasma Val were negatively correlated with ferritin levels. We also observed an inverse relationship between plasma Val/Leu and Ile/Leu ratios and ferritin.

Conclusion
The present results suggest that severe anemia in patients with PA might be associated with low natural protein intake and BCAA imbalance.
Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment
Authors: Ye Di , Xu Huanji , Xia Hongwei , Zhang Chenliang , Tang Qiulin , Bi Feng 
Published: May 2021

Abstract
Background
Serotonin signaling has been associated with tumorigenesis and tumor progression. Targeting the serotonin transporter to block serotonin cellular uptake confers antineoplastic effects in various tumors, including colon cancer. However, the antineoplastic mechanism of serotonin transporter inhibition and serotonin metabolism alterations in the absence of serotonin transporter have not been elucidated, especially in colon cancer, which might limit anti-tumor effects associating with targeting serotonin transporter.

Methods
The promotion in the uptake and catabolism of extracellular tryptophan and targeting serotonin transporter was detected by using quantitative reverse-transcription polymerase chain reaction, western blotting and liquid chromatography tandem mass spectrometry. Western blotting Immunoprecipitation and immunofluorescence was utilized to research the serotonylation of mTOR by serotonin and serotonin transporter inhibition. The primary mouse model, homograft model and tissue microarry was used to explore the tryptophan pathway in colon cancer. The cell viability assay, western blotting, xenograft and primary colon cancer mouse model were used to identify whether the combination of sertraline and tryptophan restriction had a synergistic effect.

Results
Targeting serotonin transporter through genetic ablation or pharmacological inhibition in vitro and in vivo induced a compensatory effect by promoting the uptake and catabolism of extracellular tryptophan in colon cancer. Mechanistically, targeting serotonin transporter suppressed mTOR serotonylation, leading to mTOR inactivation and increased tryptophan uptake. In turn, this process promoted serotonin biosynthesis and oncogenic metabolite kynurenine production through enhanced tryptophan catabolism. Tryptophan deprivation, or blocking its uptake by using trametinib, a MEK inhibitor, can sensitize colon cancer to selective serotonin reuptake inhibitors.

Conclusions
The present study elucidated a novel feedback mechanism involved in the regulation of serotonin homeostasis and suggested innovative strategies for selective serotonin reuptake inhibitors-based treatment of colon cancer.
VISTA regulates microglia homeostasis and myelin phagocytosis, and is associated with MS lesion pathology
Authors: Borggrewe Malte , Kooistra Susanne M. , Wesseling Evelyn M. , Gierschek Fenja L. , Brummer Maaike L. , Nowak Elizabeth C. , Medeiros-Furquim Tiago , Otto Tegan A. , Lee Sam W. , Noelle Randolph J. , Eggen Bart J. L. , Laman Jon D. 
Published: May 2021

AbstractV-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) is a negative checkpoint regulator (NCR) that is involved in T-cell quiescence, inhibition of T-cell activation, and in myeloid cells regulates cytokine production, chemotaxis, phagocytosis, and tolerance induction. In the central nervous system (CNS), VISTA is expressed by microglia, the resident macrophage of the parenchyma, and expression is decreased during neuroinflammation; however, the function of VISTA in microglia is unknown. Here, we extensively analyzed VISTA expression in different MS lesion stages and characterized the function of VISTA in the CNS by deleting VISTA in microglia. VISTA is differentially expressed in distinct MS lesion stages. In mice, VISTA deletion in Cx3Cr1-expressing cells induced a more amoeboid microglia morphology, indicating an immune-activated phenotype. Expression of genes associated with cell cycle and immune-activation was increased in VISTA KO microglia. In response to LPS and during experimental autoimmune encephalomyelitis (EAE), VISTA KO and WT microglia shared similar transcriptional profiles and VISTA deletion did not affect EAE disease progression or microglia responses. VISTA KO in microglia in vitro decreased the uptake of myelin. This study demonstrates that VISTA is involved in microglia function, which likely affects healthy CNS homeostasis and neuroinflammation.
Agricultural management practices influence the soil enzyme activity and bacterial community structure in tea plantations
Authors: Chen Yu-Pei , Tsai Chia-Fang , Rekha P. D. , Ghate Sudeep D. , Huang Hsi-Yuan , Hsu Yi-Han , Liaw Li-Ling , Young Chiu-Chung 
Published: May 2021

Abstract
Background
The soil quality and health of the tea plantations are dependent on agriculture management practices, and long-term chemical fertilizer use is implicated in soil decline. Hence, several sustainable practices are used to improve and maintain the soil quality. Here, in this study, changes in soil properties, enzymatic activity, and dysbiosis in bacterial community composition were compared using three agricultural management practices, namely conventional (CA), sustainable (SA), and transformational agriculture (TA) in the tea plantation during 2016 and 2017 period. Soil samples at two-months intervals were collected and analyzed.

Results
The results of the enzyme activities revealed that acid phosphatase, arylsulfatase, β-glucosidase, and urease activities differed considerably among the soils representing the three management practices. Combining the redundancy and multiple regression analysis, the change in the arylsulfatase activity was explained by soil pH as a significant predictor in the SA soils. The soil bacterial community was predominated by the phyla Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, and Bacteroidetes in the soil throughout the sampling period. Higher Alpha diversity scores indicated increased bacterial abundance and diversity in the SA soils. A significant relationship between bacterial richness indices (SOBS, Chao and ACE) and soil pH, K and, P was observed in the SA soils. The diversity indices namely Shannon and Simpson also showed variations, suggesting the shift in the diversity of less abundant and more common species. Furthermore, the agricultural management practices, soil pH fluctuation, and the extractable elements had a greater influence on bacterial structure than that of temporal change.

Conclusions
Based on the cross-over analysis of the bacterial composition, enzymatic activity, and soil properties, the relationship between bacterial composition and biologically-driven ecological processes can be identified as indicators of sustainability for the tea plantation.
Nasal sill augmentation: an overlooked concept in rhinoplasty—a technical note and review of the literatures
Authors: Adham Gholamhossein , Keyhan Seied Omid , Fallahi Hamid Reza , Ziaei Heliya , Thomas Mohan 
Published: May 2021

Abstract
Background
Nasal sill is one of the components of the alar ring, affecting the esthetic outcomes of rhinoplasty; accordingly, we developed a novel technique to adjust defects in this area and compared it with the available techniques.

Methods
Our technique was based on creating a tunnel access to the nasal sill area through an incision made in the lower third of the columella using the open approach or through a nostril base incision in patients, who underwent alar base reduction, followed by insertion of a cartilaginous graft into the marked defect area.

Results
A total number of 54 patients with a defect in the nasal sill area were included in this study. Thirty-one patients underwent open rhinoplasty with the sill approach from the lower third of the columella, while 23 patients underwent rhinoplasty with a nostril base approach for nasal sill augmentation procedure. There were no reports of patient dissatisfaction, infection, bleeding, sensory dysfunction, or remaining asymmetry of the sill area.

Conclusion
Based on the findings of the present study, this technique can be successfully used in reconstructing the nasal sill area with minimal complications and morbidity.
Application of Machine Learning in Translational Medicine: Current Status and Future Opportunities
Authors: Terranova Nadia , Venkatakrishnan Karthik , Benincosa Lisa J. 
Published: May 2021

AbstractThe exponential increase in our ability to harness multi-dimensional biological and clinical data from experimental to real-world settings has transformed pharmaceutical research and development in recent years, with increasing applications of artificial intelligence (AI) and machine learning (ML). Patient-centered iterative forward and reverse translation is at the heart of precision medicine discovery and development across the continuum from target validation to optimization of pharmacotherapy. Integration of advanced analytics into the practice of Translational Medicine is now a fundamental enabler to fully exploit information contained in diverse sources of big data sets such as “omics” data, as illustrated by deep characterizations of the genome, transcriptome, proteome, metabolome, microbiome, and exposome. In this commentary, we provide an overview of ML applications in drug discovery and development, aligned with the three strategic pillars of Translational Medicine (target, patient, dose) and offer perspectives on their potential to transform the science and practice of the discipline. Opportunities for integrating ML approaches into the discipline of Pharmacometrics are discussed and will revolutionize the practice of model-informed drug discovery and development. Finally, we posit that joint efforts of Clinical Pharmacology, Bioinformatics, and Biomarker Technology experts are vital in cross-functional team settings to realize the promise of AI/ML-enabled Translational and Precision Medicine.
Associations of Osteocalcin Forms With Metabolic Syndrome and Its Individual Components in Older Men: The Health In Men Study
Authors: Liu Xiaoying , Yeap Bu B , Brock Kaye E , Levinger Itamar , Golledge Jonathan , Flicker Leon , Brennan-Speranza Tara C 
Published: May 2021

Abstract

Context
The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies have indicated the undercarboxylated form of OC (ucOC) drives its association with metabolic outcomes.

Objective
We compared associations of ucOC and carboxylated OC (cOC) with MetS and its components in older men.

Methods
A cross-sectional analysis of 2575 men aged ≥70 years and older resident in Perth, Western Australia. ucOC was assayed using a hydroxyapatite-binding method, and cOC calculated by subtracting ucOC from total OC. Main outcome measures were MetS and its components.

Results
Both lower serum ucOC and cOC levels, and the proportion of cOC (%cOC) were associated with less favorable metabolic parameters (higher waist circumference, triglyceride, glucose, blood pressure, and lower high-density lipoprotein cholesterol), whereas inverse associations were found with %ucOC. Men in the lowest quintile of ucOC had higher risk of MetS compared to men in the highest quintile (Q1 ≤ 7.7 vs Q5 &gt; 13.8 ng/mL; OR = 2.4; 95% CI, 1.8-3.2). Men in the lowest quintile of cOC had higher risk of MetS compared to those in the highest quintile (≤ 5.8 vs &gt; 13.0 ng/mL; OR = 2.4; 95% CI, 1.8-3.2).

Conclusion
Lower concentrations of serum ucOC or cOC were associated with less favorable metabolic parameters and a higher risk of MetS. In contrast, a lower proportion of ucOC was associated with better metabolic parameters and lower MetS risk. Further research is warranted to determine whether ucOC and cOC are suitable biomarkers for cardiometabolic risk in men.
Rab11 is required for lysosome exocytosis through the interaction with Rab3a, Sec15 and GRAB
Authors: Escrevente Cristina , Bento-Lopes Liliana , Ramalho José S. , Barral Duarte C. 
Published: May 2021

ABSTRACT
Lysosomes are dynamic organelles, capable of undergoing exocytosis. This process is crucial for several cellular functions, namely plasma membrane repair. Nevertheless, the molecular machinery involved in this process is poorly understood. Here, we identify Rab11a and Rab11b as regulators of Ca2+-induced lysosome exocytosis. Interestingly, Rab11-positive vesicles transiently interact with lysosomes at the cell periphery, indicating that this interaction is required for the last steps of lysosome exocytosis. Additionally, we found that the silencing of the exocyst subunit Sec15, a Rab11 effector, impairs lysosome exocytosis, suggesting that Sec15 acts together with Rab11 in the regulation of lysosome exocytosis. Furthermore, we show that Rab11 binds the guanine nucleotide exchange factor for Rab3a (GRAB) as well as Rab3a, which we have previously described to be a regulator of the positioning and exocytosis of lysosomes. Thus, our study identifies new players required for lysosome exocytosis and suggest the existence of a Rab11–Rab3a cascade involved in this process.
Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
Authors: Andersson Stefanie , Romero Antonia , Rodrigues Joana Isabel , Hua Sansan , Hao Xinxin , Jacobson Therese , Karl Vivien , Becker Nathalie , Ashouri Arghavan , Rauch Sebastien , Nyström Thomas , Liu Beidong , Tamás Markus J. 
Published: May 2021

ABSTRACT
The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis.
This article has an associated First Person interview with the first authors of the paper.
Amyloid-β oligomers block lysosomal targeting of miRNPs to prevent miRNP recycling and target repression in glial cells
Authors: De Dipayan , Bhattacharyya Suvendra N. 
Published: May 2021

ABSTRACT
Upon exposure to amyloid-β oligomers (Aβ1–42), glial cells start expressing proinflammatory cytokines, despite an increase in levels of repressive microRNAs (miRNAs). Exploring the mechanism of this potential immunity of target cytokine mRNAs against repressive miRNAs in amyloid-β-exposed glial cells, we have identified differential compartmentalization of repressive miRNAs in glial cells that explains this aberrant miRNA function. In Aβ1–42-treated cells, whereas target mRNAs were found to be associated with polysomes attached to endoplasmic reticulum (ER), the miRNA ribonucleoprotein complexes (miRNPs) were found to be present predominantly with endosomes that failed to recycle to ER-attached polysomes, preventing repression of mRNA targets. Aβ1–42 oligomers, by masking Rab7a proteins on endosomal surfaces, affected Rab7a interaction with Rab-interacting lysosomal protein (RILP), restricting the lysosomal targeting and recycling of miRNPs. RNA-processing body (P-body) localization of the miRNPs was found to be enhanced in amyloid-β-treated cells as a consequence of enhanced endosomal retention of miRNPs. Interestingly, depletion of P-body components partly rescued the miRNA function in glial cells exposed to amyloid-β and restricted the excess cytokine expression.
This article has an associated First Person interview with the first author of the paper.
Metal pollutants have additive negative effects on honey bee cognition
Authors: Monchanin Coline , Drujont Erwann , Devaud Jean-Marc , Lihoreau Mathieu , Barron Andrew B. 
Published: May 2021

ABSTRACT
Environmental pollutants can exert sublethal deleterious effects on animals. These include disruption of cognitive functions underlying crucial behaviours. While agrochemicals have been identified as a major threat to pollinators, metal pollutants, which are often found in complex mixtures, have so far been overlooked. Here, we assessed the impact of acute exposure to field-realistic concentrations of three common metal pollutants, lead, copper and arsenic, and their combinations, on honey bee appetitive learning and memory. All treatments involving single metals slowed down learning and disrupted memory retrieval at 24 h. Combinations of these metals had additive negative effects on both processes, suggesting common pathways of toxicity. Our results highlight the need to further assess the risks of metal pollution on invertebrates.
Morbidity and mortality in patients undergoing lower limb arthroplasty surgery during the initial surge of the COVID-19 pandemic in the UK at a single-speciality orthopaedic hospital
Authors: Agrawal Yuvraj , Vasudev Ashish , Sharma Akash , Cooper George , Stevenson Jonathan , Parry Michael C. , Dunlop David 
Published: May 2021

Aims The COVID-19 pandemic posed significant challenges to healthcare systems across the globe in 2020. There were concerns surrounding early reports of increased mortality among patients undergoing emergency or non-urgent surgery. We report the morbidity and mortality in patients who underwent arthroplasty procedures during the UK first stage of the pandemic. Methods Institutional review board approval was obtained for a review of prospectively collected data on consecutive patients who underwent arthroplasty procedures between March and May 2020 at a specialist orthopaedic centre in the UK. Data included diagnoses, comorbidities, BMI, American Society of Anesthesiologists grade, length of stay, and complications. The primary outcome was 30-day mortality and secondary outcomes were prevalence of SARS-CoV-2 infection, medical and surgical complications, and readmission within 30 days of discharge. The data collated were compared with series from the preceding three months. Results There were 167 elective procedures performed in the first three weeks of the study period, prior to the first national lockdown, and 57 emergency procedures thereafter. Three patients (1.3%) were readmitted within 30 days of discharge. There was one death (0.45%) due to SARS-CoV-2 infection after an emergency procedure. None of the patients developed complications of SARS-CoV-2 infection after elective arthroplasty. There was no observed spike in complications during in-hospital stay or in the early postoperative period. There was no statistically significant difference in survival between pre-COVID-19 and peri-COVID-19 groups (p = 0.624). We observed a higher number of emergency procedures performed during the pandemic within our institute. Conclusion An international cohort has reported 30-day mortality as 28.8% following orthopaedic procedures during the pandemic. There are currently no reports on clinical outcomes of patients treated with lower limb reconstructive surgery during the same period. While an effective vaccine is developed and widely accepted, it is very likely that SARS-CoV2 infection remains endemic. We believe that this report will help guide future restoration planning here in the UK and abroad. Cite this article: Bone Jt Open 2021;2(5):323–329.
Design and analysis of a compact subwavelength-grating-assisted 1.55/2  µm wavelength demultiplexer
Authors: Liao Jianfei , Xie Yuan , Huang Tianye , Cheng Zhuo 
Published: May 2021

The wavelength demultiplexer (deWMUX) is an indispensable component for the wavelength diversity system. In this paper, we propose a subwavelength-grating-assisted

1

×

2

deWMUX based on the principle of multimode interference, which aims to output 1.55 and 2 µm wavelengths from two different channels. The simulation results show that the contrast of the designed deWMUX at both wavelengths is greater than 24 dB, the insertion loss is less than 0.5 dB, and the 1 dB bandwidth is wider than 100 nm. In addition, the manufacturing tolerances of the device are also studied.
Design of a Littrow-type diode laser with independent control of cavity length and grating rotation
Authors: Duca Lucia , Perego Elia , Berto Federico , Sias Carlo 
Published: May 2021

We present a novel, to the best of our knowledge, extended-cavity diode laser based on a modified Littrow configuration. The coarse wavelength adjustment via the rotation of a diffraction grating is decoupled from the fine tuning of the external cavity modes by positioning a piezo transducer behind the diode laser, making the laser robust against misalignment and hysteresis even with long external cavities. Two laser prototypes with external cavities of different lengths were tested with a 780 nm laser diode, and locked to an atomic reference. We observed a mode-hop-free frequency tunability broader than the free spectral range of the external cavity upon changes in its length. The design is well suited to atomic and molecular experiments demanding a high level of stability over time.