bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics of casein genes
Authors: Madende Moses , Osthoff Gernot 
Published: July 2019

AbstractThis research paper addresses the hypothesis that comparative genomics can give a new insight into the functionality of casein genes with respect to the casein micelle. Comparative genomics is a rapidly emerging field in computational biology whereby two or more genomes are compared in order to obtain a global view on genomes as well as assigning previously unknown functions for genes. Casein genes are among the most rapidly evolving mammalian genes, with the gene products mainly grouped into four types (αs1-, αs2-, β- and κ-casein). Functionally, casein genes are central to the casein micelle, the exact structure of which is still a subject of intense debate. Moreover, and adding to this complexity, some mammals lack some of the casein genes, although casein micelles have been observed in their milk. This observation has prompted an investigation into the distribution of casein genes across a host of mammalian species. It was apparent from this study that casein gene sequences are very diverse from each other and we confirmed that many mammalian species lack one or more of the casein genes. The genes encoding β- and κ-caseins are present in most mammals whereas α-casein encoding genes are less represented. This suggests different mechanisms for casein micelle formation in different species as well as the functions that are assigned to each individual casein.
Four reasons why early detection centers for psychosis should be renamed and their treatment targets reconsidered: we should not catastrophize a future we can neither reliably predict nor change
Authors: Moritz Steffen , Gawęda Łukasz , Heinz Andreas , Gallinat Jürgen 
Published: July 2019

AbstractSince the 1990s, facilities for individuals at putative risk for psychosis have mushroomed and within a very short time have become part of the standard psychiatric infrastructure in many countries. The idea of preventing a severe mental disorder before its exacerbation is laudable, and early data indeed strongly suggested that the sooner the intervention, the better the outcome. In this paper, the authors provide four reasons why they think that early detection or prodromal facilities should be renamed and their treatment targets reconsidered. First, the association between the duration of untreated psychosis and outcome is empirically established but has become increasingly weak over the years. Moreover, its applicability to those who are considered at risk remains elusive. Second, instruments designed to identify future psychosis are prone to many biases that are not yet sufficiently controlled. None of these instruments allows an even remotely precise prognosis. Third, the rate of transition to psychosis in at-risk patients is likely lower than initially thought, and evidence for the success of early intervention in preventing future psychosis is promising but still equivocal. Perhaps most importantly, the treatment is not hope-oriented. Patients are more or less told that schizophrenia is looming over them, which may stigmatize individuals who will never, in fact, develop psychosis. In addition self-stigma has been associated with suicidality and depression. The authors recommend that treatment of help-seeking individuals with mental problems but no established diagnosis should be need-based, and the risk of psychosis should be de-emphasized as it is only one of many possible outcomes, including full remission. Prodromal clinics should not be abolished but should be renamed and restructured. Such clinics exist, but the transformation process needs to be facilitated.
Autophagy flux in critical illness, a translational approach
Authors: Tardif Nicolas , Polia Franck , Tjäder Inga , Gustafsson Thomas , Rooyackers Olav 
Published: July 2019

AbstractRecent clinical trials suggest that early nutritional support might block the induction of autophagy in critically ill patients leading to the development of organ failure. However, the regulation of autophagy, especially by nutrients, in critical illness is largely unclear. The autophagy flux (AF) in relation to critical illness and nutrition was investigated by using an in vitro model of human primary myotubes incubated with serum from critically ill patients (ICU). AF was calculated as the difference of p62 expression in the presence and absence of chloroquine (50 µM, 6 h), in primary myotubes incubated for 24 h with serum from healthy volunteers (n = 10) and ICU patients (n = 93). We observed 3 different phenotypes in AF, non-altered (ICU non-responder group), increased (ICU inducer group) or blocked (ICU blocker group). This block was not associate with a change in amino acids serum levels and was located at the accumulation of autophagosomes. The increase in the AF was associated with lower serum levels of non-essential amino acids. Thus, early nutrition during critical illness might not block autophagy but could attenuate the beneficial effect of starvation on reactivation of the autophagy process. This could be of clinical importance in the individual patients in whom this process is inhibited by the critical illness insult.
Accuracy of standard clinical 3T prostate MRI for pelvic lymph node staging: Comparison to 68Ga-PSMA PET-CT
Authors: Meißner Sebastian , Janssen Jan-Carlo , Prasad Vikas , Diederichs Gerd , Hamm Bernd , Brenner Winfried , Makowski Marcus R. 
Published: July 2019

AbstractThe aim was to assess the performance of prostate 3T MRI for pelvic lymph node (LN) staging in prostate cancer (PCa), in comparison to 68Gallium-prostate specific membrane antigen PET-CT (68Ga-PSMA PET-CT) as reference standard for LN detection. 130 patients with PCa underwent non-contrast-enhanced multiparametric prostate 3T MRI and 68Ga-PSMA-PET-CT within 180 days at our institution. Overall, 187 LN metastases (n = 43 patients) detected by 68Ga-PSMA-PET-CT were characterized by calculating maximum standardized uptake value (SUVmax), area, diameter and anatomical location including iliac, obturator, presacral and inguinal region. MRI achieved an overall sensitivity, specificity, positive and negative predictive value of 81.6% (CI 71.1–88.9%), 98.6% (CI 97.6–99.2%), 73.5% (CI 52.1–87.6%) and 99.5% (CI 98.8–99.8%), respectively. On a region-based analysis, detection rates differed non-significantly (ps > 0.12) in the anatomical regions. On a size-dependent analysis, detection of LN > 10 mm did not differ significantly (ps > 0.09) from LN ≤ 10 mm. In comparison to single T1 sequence evaluation, additional use of the T2 weighted sequences did not improve the overall performance significantly (p > 0.05). 3T prostate MRI represented an accurate tool for the detection of LN compared to 68Ga-PSMA-PET-CT. Especially for LN metastases smaller than 10 mm, MRI was less accurate compared to 68Ga-PSMA-PET-CT.
The effect of asymmetric reproductive ability on the evolution of cooperation on interdependent networks
Authors: Du Chunpeng , Geng Yini , Yin Xiaoxiao , Ma Yongjuan , Li Xiaogang , Shi Lei 
Published: July 2019

AbstractIn this paper, we consider an asymmetric reproductive ability on interdependent networks and investigate how this setting affects the evolution of cooperation. In detail, players decide to update their strategies at each step on main network (network B), while for sub network (network A), players update their strategies with a fixed probability p. Obviously, the system restores the traditional case when p = 1, where cooperation can survive by interdependent network reciprocity. And our asymmetric set-up comes into play when p < 1. Numerical simulation results show that our asymmetric coupling will hinder the overall cooperation level for small p. In detail, the introduction of asymmetric reproductive ability urges the formation of symmetry breaking and further weakens the positive impact by location synchronous effect. And the root cause is entirely distinct situation of utility differences on two networks. These observations further demonstrate a class of phenomena on interdependent networks that it would have catastrophic consequences on one network even if a unrelated change only occurs seemingly on another network.
Molecular complexity of the major urinary protein system of the Norway rat, Rattus norvegicus
Authors: Gómez-Baena Guadalupe , Armstrong Stuart D. , Halstead Josiah O. , Prescott Mark , Roberts Sarah A. , McLean Lynn , Mudge Jonathan M. , Hurst Jane L. , Beynon Robert J. 
Published: July 2019

AbstractMajor urinary proteins (MUP) are the major component of the urinary protein fraction in house mice (Mus spp.) and rats (Rattus spp.). The structure, polymorphism and functions of these lipocalins have been well described in the western European house mouse (Mus musculus domesticus), clarifying their role in semiochemical communication. The complexity of these roles in the mouse raises the question of similar functions in other rodents, including the Norway rat, Rattus norvegicus. Norway rats express MUPs in urine but information about specific MUP isoform sequences and functions is limited. In this study, we present a detailed molecular characterization of the MUP proteoforms expressed in the urine of two laboratory strains, Wistar Han and Brown Norway, and wild caught animals, using a combination of manual gene annotation, intact protein mass spectrometry and bottom-up mass spectrometry-based proteomic approaches. Cluster analysis shows the existence of only 10 predicted mup genes. Further, detailed sequencing of the urinary MUP isoforms reveals a less complex pattern of primary sequence polymorphism in the rat than the mouse. However, unlike the mouse, rat MUPs exhibit added complexity in the form of post-translational modifications, including the phosphorylation of Ser4 in some isoforms, and exoproteolytic trimming of specific isoforms. Our results raise the possibility that urinary MUPs may have different roles in rat chemical communication than those they play in the house mouse. Shotgun proteomics data are available via ProteomExchange with identifier PXD013986.
Evaluation of reference genes for real-time quantitative PCR analysis in southern corn rootworm, Diabrotica undecimpunctata howardi (Barber)
Authors: Basu Saumik , Pereira Adriano E. , Pinheiro Daniele H. , Wang Haichuan , Valencia-Jiménez Arnubio , Siegfried Blair D. , Louis Joe , Zhou Xuguo ‘Joe’ , Vélez Ana Maria 
Published: July 2019

AbstractQuantitative reverse transcription PCR (RT-qPCR) is one of the most efficient, reliable and widely used techniques to quantify gene expression. In this study, we evaluated the performance of six southern corn rootworm, Diabrotica undecimpunctata howardi (Barber), housekeeping genes (HKG), β-actin (Actin), β-tubulin (Tubulin), elongation factor 1 alpha (EF1α), glyceraldehyde-3 phosphate dehydrogenase (GAPDH), 40 S ribosomal protein S9 (RpS9) and ubiquitin-conjugating protein (Ubi), under different experimental conditions such as developmental stage, exposure of neonate and adults to dsRNA, exposure of adults to different temperatures, different 3rd instar larva tissues, and neonate starvation. The HKGs were analyzed with four algorithms, including geNorm, NormFinder, BestKeeper, and delta-CT. Although the six HKGs showed a relatively stable expression pattern among different treatments, some variability was observed. Among the six genes, EF1α exhibited the lowest Ct values for all treatments while Ubi exhibited the highest. Among life stages and across treatments, Ubi exhibited the least stable expression pattern. GAPDH, Actin, and EF1α were among the most stable HKGs in the majority of the treatments. This research provides HKG for accurate normalization of RT-qPCR data in the southern corn rootworm. Furthermore, this information can contribute to future genomic and functional genomic research in Diabrotica species.
Optimization of Molecules via Deep Reinforcement Learning
Authors: Zhou Zhenpeng , Kearnes Steven , Li Li , Zare Richard N. , Riley Patrick 
Published: July 2019

AbstractWe present a framework, which we call Molecule Deep Q-Networks (MolDQN), for molecule optimization by combining domain knowledge of chemistry and state-of-the-art reinforcement learning techniques (double Q-learning and randomized value functions). We directly define modifications on molecules, thereby ensuring 100% chemical validity. Further, we operate without pre-training on any dataset to avoid possible bias from the choice of that set. MolDQN achieves comparable or better performance against several other recently published algorithms for benchmark molecular optimization tasks. However, we also argue that many of these tasks are not representative of real optimization problems in drug discovery. Inspired by problems faced during medicinal chemistry lead optimization, we extend our model with multi-objective reinforcement learning, which maximizes drug-likeness while maintaining similarity to the original molecule. We further show the path through chemical space to achieve optimization for a molecule to understand how the model works.
Modeling the Amplification of Immunoglobulins through Machine Learning on Sequence-Specific Features
Authors: Döring Matthias , Kreer Christoph , Lehnen Nathalie , Klein Florian , Pfeifer Nico 
Published: July 2019

AbstractSuccessful primer design for polymerase chain reaction (PCR) hinges on the ability to identify primers that efficiently amplify template sequences. Here, we generated a novel Taq PCR data set that reports the amplification status for pairs of primers and templates from a reference set of 47 immunoglobulin heavy chain variable sequences and 20 primers. Using logistic regression, we developed TMM, a model for predicting whether a primer amplifies a template given their nucleotide sequences. The model suggests that the free energy of annealing, ΔG, is the key driver of amplification (p = 7.35e-12) and that 3′ mismatches should be considered in dependence on ΔG and the mismatch closest to the 3′ terminus (p = 1.67e-05). We validated TMM by comparing its estimates with those from the thermodynamic model of DECIPHER (DE) and a model based solely on the free energy of annealing (FE). TMM outperformed the other approaches in terms of the area under the receiver operating characteristic curve (TMM: 0.953, FE: 0.941, DE: 0.896). TMM can improve primer design and is freely available via openPrimeR (http://openPrimeR.mpi-inf.mpg.de).
Plasticity of patient-matched normal mammary epithelial cells is dependent on autologous adipose-derived stem cells
Authors: Kengelbach-Weigand Annika , Tasbihi Kereshmeh , Strissel Pamela L. , Schmid Rafael , Marques Jasmin Monteiro , Beier Justus P. , Beckmann Matthias W. , Strick Reiner , Horch Raymund E. , Boos Anja M. 
Published: July 2019

AbstractDue to the increasing clinical application of adipose-derived stem cells (ADSC), e.g. lipotransfer for breast reconstruction, this study aimed to gain novel insights regarding ADSC influence on breast tissue remodeling and determine patient-dependent factors affecting lipotransfer as well as begin to address its oncological risks. The ADSC secretome was analyzed from five normal breast reduction patients and contained elevated levels of growth factors, cytokines and proteins mediating invasion. ADSC/ADSC secretomes were tested for their influence on the function of primary mammary epithelial cells, and tumor epithelial cells using cell culture assays. ADSC/ADSC secretomes significantly stimulated proliferation, transmigration and 3D-invasion of primary normal and tumor epithelial cells. IL-6 significantly induced an EMT and invasion. The ADSC secretome significantly upregulated normal epithelial cell gene expression including MMPs and ECM receptors. Our study supports that ADSC and its secretome promote favorable conditions for normal breast tissue remodeling by changing the microenvironment. and may also be important regarding residual breast cancer cells following surgery.
Study of mitochondrial swelling, membrane fluidity and ROS production induced by nano-TiO2 and prevented by Fe incorporation
Authors: Barkhade Tejal , Mahapatra Santosh Kumar , Banerjee Indrani 
Published: July 2019

Abstract
The potential impact of TiO2 and Fe incorporated TiO2 nanoparticles at the organelle level has been reported. The toxicity of the samples on mitochondria isolated from chicken liver tissue has been examined through mitochondrial swelling, membrane fluidity, ROS generation capacity, and activity of complex II. The toxic effect of TiO2 was prevented by incorporating Fe into the TiO2 matrix at different concentrations. The activity of the succinate dehydrogenase enzyme complex was affected and permeabilization of the mitochondrial inner membrane to H+ and K+ and its alteration in membrane fluidity at 100 μg mL−1 of nano-TiO2 dosage were investigated, which showed significant changes in the anisotropy of DPH-labeled mitochondria. Fe incorporation into the TiO2 matrix makes it more biocompatible by changing its structure and morphology.
The role of Activin A in fibrodysplasia ossificans progressiva: a prominent mediator
Authors: Lin Hui , Shi Fuli , Gao Jiayu , Hua Ping 
Published: July 2019

AbstractHeterotopic ossification (HO) is the aberrant formation of mature, lamellar bone in nonosseous tissue. Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disorder that causes progressive HO in the ligaments, tendons, and muscles throughout the body. FOP is attributed to an autosomal mutation in activin receptor-like kinase 2 (ALK2), a bone morphogenetic protein (BMP) type I receptor. Initial studies show that mutant ALK2 drives HO by constitutively activating the BMP signaling pathway. Recently, mutant ALK2 has been shown to transduce Smad1/5 signaling and enhance chondrogenesis, calcification in response to Activin A, which normally signals through Smad2/3 and inhibits BMP signaling pathway. Furthermore, Activin A induces heterotopic bone formation via mutant ALK2, while inhibition of Activin A blocks spontaneous and trauma-induced HO. In this manuscript, we describe the molecular mechanism of the causative gene ALK2 in FOP, mainly focusing on the prominent role of Activin A in HO. It reveals a potential strategy for prevention and treatment of FOP by inhibition of Activin A. Further studies are needed to explore the cellular and molecular mechanisms of Activin A in FOP in more detail.
Patient Safety in Microvascular Plastic Surgery
Authors: Colakoglu Salih , Tebockhorst Seth , Chong Tae W. , Mathes David W. 
Published: July 2019

Patient safety is defined as freedom from accidental or preventable harm produced by medical care. The identification of patient- and procedure-related risk factors enables the surgical team to carry out prophylactic measures to reduce the rate of complications and adverse events.The purpose of this review is to identify the characteristics of patients, practitioners, and microvascular surgical procedures that place patients at risk for preventable harm, and to discuss evidence-based prevention practices that can potentially help to generate a culture of patient safety.
Systematic Review of Diagnosis of Clinically Suspected Scaphoid Fractures
Authors: Bäcker Henrik Constantin , Wu Chia H. , Strauch Robert J. 
Published: July 2019

Background Scaphoid fracture accounts for approximately 15% of acute wrist fractures. Clinical examination and plain X-rays are commonly used to diagnose the fracture, but this approach may miss up to 16% of fractures in the absence of clear-cut lucent lines on plain radiographs. As such, additional imaging may be required. It is not clear which imaging modality is the best. The goal of this study is to summarize the current literature on scaphoid fractures to evaluate the sensitivity, specificity, and accuracy of four different imaging modalities.
Case Description A systematic-review and meta-analysis was performed. The search term “scaphoid fracture” was used and all prospective articles investigating magnetic resonance imaging (MRI), computed tomography (CT), bone scintigraphy, and ultrasound were included. In total, 2,808 abstracts were reviewed. Of these, 42 articles investigating 51 different diagnostic tools in 2,507 patients were included.
Literature Review The mean age was 34.1 ± 5.7 years, and the overall incidence of scaphoid fractures missed on X-ray and diagnosed on advanced imaging was 21.8%. MRI had the highest sensitivity and specificity for diagnosing scaphoid fractures, which were 94.2 and 97.7%, respectively, followed by CT scan with a sensitivity and specificity at 81.5 and 96.0%, respectively. The sensitivity and specificity of ultrasound were 81.5 and 77.4%, respectively. Significant differences between MRI, bone scintigraphy, CT, and ultrasound were identified.
Clinical Relevance MRI has higher sensitivity and specificity than CT scan, bone scintigraphy, or ultrasound.
Level of Evidence This is a Level II systematic review.
Inpatient Flap Monitoring after Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction: How Long Is Long Enough?
Authors: Carruthers Katherine H. , Tiwari Pankaj , Yoshida Shunsuke , Kocak Ergun 
Published: July 2019

Background There is a growing trend across health care to perform increasingly complex procedures in less acute settings. This shift has been fueled, in part, by enhanced recovery protocols, which have shortened hospital stays after major surgeries. We set out to determine the timing of microvascular complications after deep inferior epigastric artery perforator (DIEP) free flap breast reconstruction in a high-volume practice using continuous flap monitoring technologies.
Methods The medical charts of all patients who underwent breast reconstruction with DIEP flaps over 24 consecutive months were reviewed. Postoperatively, all flaps were monitored according to a protocol that included continuous tissue oximetry with near-infrared spectroscopy. The primary end points evaluated included any unplanned return to the operating room, time to takeback, and flap loss rate.
Results A total of 196 patients underwent breast reconstruction with a total of 301 DIEP flaps. Five of the flaps (1.7%) were taken back to the operating room for microvascular issues, and nine (3.0%) were taken back for nonvascular issues. Of patients who were brought back for microvascular issues, all five (100.0%) were initially identified by continuous noninvasive monitoring and taken back to the operating room within the first 14 hours (range: 1.2–13.6 hours). In the series, the flap failure rate was 0.66% (n = 2).
Conclusion All of the microvascular issues were detected in the initial 23 hours after surgery, leading to prompt flap salvage. The results of this study bring into question the need for lengthy flap monitoring protocols and suggest that shorter inpatient, or even observation admissions, may be reasonable, particularly when flap monitoring protocols incorporating continuous noninvasive flap monitoring are used.