bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model
Authors: Zhuo Qian , Yu Bohai , Zhou Jing , Zhang Jingyun , Zhang Runling , Xie Jingyan , Wang Qingling , Zhao Shuli 
Published: December 2019

AbstractPrevious reports have suggested that many gut microbiomes were associated with the development of colorectal cancer (CRC), and could modulate response to numerous forms of cancer therapy, including checkpoint blockade immunotherapy. Here we evaluated the protective efficacy of Lactobacillus acidophilus (L. acidophilus) cell lysates combined with an anti-CTL antigen-4 blocking antibody (CTLA-4 mAb) in syngeneic BALB/c mice CRC models induce by a single intraperitoneal injection of 10 mg/kg azoxymethane (AOM), followed by three cycles of 2% dextran sulfate sodium (DSS) in drinking water. In contrast to CTLA-4 mAb monotherapy, L. acidophilus lysates could attenuate the loss of body weight and the combined administration significantly protected mice against CRC development, which suggested that the lysates enhanced antitumor activity of CTLA-4 mAb in model mice. The enhanced efficacy was associated with the increased CD8 + T cell, increased effector memory T cells (CD44 + CD8 + CD62L+), decreased Treg (CD4 + CD25 + Foxp3+) and M2 macrophages (F4/80 + CD206+) in the tumor microenvironment. In addition, our results revealed that L. acidophilus lysates had an immunomodulatory effect through inhibition the M2 polarization and the IL-10 expressed levels of LPS-activated Raw264.7 macrophages. Finally, the 16S rRNA gene sequencing of fecal microbiota demonstrated that the combined administration significantly inhibited the abnormal increase in the relative abundance of proteobacteria and partly counterbalance CRC-induced dysbiosis in model mice. Overall, these data support promising clinical possibilities of L. acidophilus lysates with CTLA-4 mAb in cancer patients and the hypothesis that probiotics help shape the anticancer immune response.
Yeast R2TP Interacts with Extended Termini of Client Protein Nop58p
Authors: Yu Ge , Zhao Yu , Tian Shaoxiong , Rai Jay , He Huan , Spear John , Sousa Duncan , Fan Jinbo , Yu Hong-Guo , Stagg Scott M. , Li Hong 
Published: December 2019

AbstractThe AAA + ATPase R2TP complex facilitates assembly of a number of ribonucleoprotein particles (RNPs). Although the architecture of R2TP is known, its molecular basis for acting upon multiple RNPs remains unknown. In yeast, the core subunit of the box C/D small nucleolar RNPs, Nop58p, is the target for R2TP function. In the recently observed U3 box C/D snoRNP as part of the 90 S small subunit processome, the unfolded regions of Nop58p are observed to form extensive interactions, suggesting a possible role of R2TP in stabilizing the unfolded region of Nop58p prior to its assembly. Here, we analyze the interaction between R2TP and a Maltose Binding Protein (MBP)-fused Nop58p by biophysical and yeast genetics methods. We present evidence that R2TP interacts largely with the unfolded termini of Nop58p. Our results suggest a general mechanism for R2TP to impart specificity by recognizing unfolded regions in its clients.
Hepatic Mitochondrial Oxidative Metabolism and Lipogenesis Synergistically Adapt to Mediate Healthy Embryonic-to-Neonatal Transition in Chicken
Authors: Surugihalli Chaitra , Porter Tom E. , Chan Angela , Farley Linda S. , Maguire Meghan , Zhang Christine , Kattapuram Nathan , Muyyarikkandy Muhammed S. , Liu Hsiao-Ching , Sunny Nishanth E. 
Published: December 2019

AbstractDuring the normal embryonic-to-neonatal development, the chicken liver is subjected to intense lipid burden from high rates of yolk-lipid oxidation and also from the accumulation of the yolk-derived and newly synthesized lipids from carbohydrates. High rates of hepatic lipid oxidation and lipogenesis are also central features of non-alcoholic fatty liver disease (NAFLD) in both rodents and humans, but is associated with impaired insulin signaling, dysfunctional mitochondrial energetics and oxidative stress. However, these adverse effects are not apparent in the liver of embryonic and neonatal chicken, despite lipid burden. Utilizing comprehensive metabolic profiling, we identify that steady induction of hepatic mitochondrial tricarboxylic acid (TCA) cycle and lipogenesis are central features of embryonic-to-neonatal transition. More importantly, the induction of TCA cycle and lipogenesis occurred together with the downregulation of hepatic β-oxidation and ketogenesis in the neonatal chicken. This synergistic remodeling of hepatic metabolic networks blunted inflammatory onset, prevented accumulation of lipotoxic intermediates (ceramides and diacylglycerols) and reduced reactive oxygen species production during embryonic-to-neonatal development. This dynamic remodeling of hepatic mitochondrial oxidative flux and lipogenesis aids in the healthy embryonic-to-neonatal transition in chicken. This natural physiological system could help identify mechanisms regulating mitochondrial function and lipogenesis, with potential implications towards treatment of NAFLD.
A microfluidics-based wound-healing assay for studying the effects of shear stresses, wound widths, and chemicals on the wound-healing process
Authors: Lin Jin-Young , Lo Kai-Yin , Sun Yung-Shin 
Published: December 2019

AbstractCollective cell migration plays important roles in various physiological processes. To investigate this collective cellular movement, various wound-healing assays have been developed. In these assays, a “wound” is created mechanically, chemically, optically, or electrically out of a cellular monolayer. Most of these assays are subject to drawbacks of run-to-run variations in wound size/shape and damages to cells/substrate. Moreover, in all these assays, cells are cultured in open, static (non-circulating) environments. In this study, we reported a microfluidics-based wound-healing assay by using the trypsin flow-focusing technique. Fibroblasts were first cultured inside this chip to a cellular monolayer. Then three parallel fluidic flows (containing normal medium and trypsin solution) were introduced into the channels, and cells exposed to protease trypsin were enzymatically detached from the surface. Wounds of three different widths were generated, and subsequent wound-healing processes were observed. This assay is capable of creating three or more wounds of different widths for investigating the effects of various physical and chemical stimuli on wound-healing speeds. The effects of shear stresses, wound widths, and β-lapachone (a wound healing-promoting chemical) on wound-healing speeds were studied. It was found that the wound-healing speed (total area healed per unit time) increased with increasing shear stress and wound width, but under a shear stress of 0.174 mPa the linear healing speed (percent area healed per unit time) was independent of the wound width. Also, the addition of β-lapachone up to 0.5 μM did not accelerate wound healing. This microfluidics-based assay can definitely help in understanding the mechanisms of the wound-healing process and developing new wound-healing therapies.
Bidirectional Selector Utilizing Hybrid Diodes for PCRAM Applications
Authors: Shuang Yi , Hatayama Shogo , An Junseop , Hong Jinpyo , Ando Daisuke , Song Yunheub , Sutou Yuji 
Published: December 2019

AbstractThree-dimensional crossbar technology has been of great significance for realizing high density and multiple terabytes of data storage in memory devices. However, to further scale down the size of memory devices, a selector exhibiting nonlinear electrical properties should be in series with a memory layer in case of unwanted sneak current disturbance. Conventional selectors usually utilize a complicated multilayer structure to realize the high nonlinearity of current, which might be incompatible with certain manufacturing processes or limit the scalability of memory. Herein, we propose a simple heterojunction diode using an n-type oxide semiconductor, specifically, InGaZnO4(IGZO), and a p-type phase change material (PCM), specifically, N-doped Cr2Ge2Te6(NCrGT), to realize self-selective performance. The electrode/IGZO/NCrGT/plug-electrode structure with an IGZO/NCrGT pn diode and NCrGT/plug-electrode Schottky diode can realize bidirectional, self-selective phase change random access memory (PCRAM) for either amorphous or crystalline NCrGT. The approximate equilibrium energy band diagrams for the IGZO/NCrGT pn junction and the IGZO/NCrGT/W hybrid junction were proposed to explain the possible conduction mechanism. We demonstrated that hybrid diode-type PCM memory exhibits both selectivity and resistive switching characteristics. The present findings offer new insight into selector technology for PCM.
Real-world safety evaluation of musculoskeletal adverse events associated with Korean pediatric fluoroquinolone use: a nationwide longitudinal retrospective cohort study
Authors: Kim Yoonhye , Paik Minwoo , Khan Chanjoo , Kim Yae-Jean , Kim EunYoung 
Published: December 2019

AbstractThough the pediatric use of fluoroquinolones (FQs) is limited for musculoskeletal safety concerns, the clinical usefulness still exists. This study examined the association between FQs and musculoskeletal adverse events (AEs) as well as the possible risk factors associated with the pediatric FQs uses. This population-based, longitudinal, retrospective study was conducted using Korean National Sample Cohort database originating between 2002 and 2015. An FQ-treated pediatric cohort (<18 years old) was compared to a control treated with amoxicillin. Propensity score matching (PSM) and a Cox proportional hazard model was used to estimate the hazard ratio (HR) for a diagnosis of musculoskeletal AEs within 60 days of the first prescription. Among one million participants, total of 15,706 and 147,840 children were eligible for the FQ and amoxicillin cohorts, respectively. The PSM cohorts showed a slightly increased risk of musculoskeletal AEs after FQ treatment (HR, 1.19; 95% confidence interval, 1.01–1.40; p = 0.042). This association was stronger in males, older patients, and some FQs users. This study indicates that pediatric FQ use is associated with a risk of musculoskeletal AEs and that FQ use should be carefully monitored in groups with certain risk factors. Well-designed pragmatic trials could be expected to clarify these issues.
Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling
Authors: Park Sung-Soo , Lee Yeon-Joo , Kang Hyuno , Yang Garam , Hong Eun Jeong , Lim Jin Yeong , Oh Sejong , Kim Eungseok 
Published: December 2019

AbstractBrowning of white adipose tissue (WAT) is currently considered a potential therapeutic strategy to treat diet-induced obesity. While some probiotics have protective effects against diet-induced obesity, the role of probiotics in adipose browning has not been explored. Here, we show that administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function, as well as the thermogenic gene program (increased Ucp1, PPARγ, and PGC-1α expression and decreased RIP140 expression), in subcutaneous inguinal WAT and also increased body temperature. Furthermore, LKU4 administration increased the interaction between PPARγ and PGC-1α through release of RIP140 to stimulate Ucp1 expression, thereby promoting browning of white adipocytes. In addition, lactate, the levels of which are elevated in plasma of HFD-fed mice following LKU4 administration, elicited the same effect on the interaction between PPARγ and PGC-1α in 3T3-L1 adipocytes, leading to a brown-like adipocyte phenotype that included enhanced Ucp1 expression, mitochondrial levels and function, and oxygen consumption rate. Together, these data reveal that LKU4 facilitates browning of white adipocytes through the PPARγ-PGC-1α transcriptional complex, at least in part by increasing lactate levels, leading to inhibition of diet-induced obesity.
Multi-Factor Regulation of the Master Modulator LeuO for the Cyclic-(Phe-Pro) Signaling Pathway in Vibrio vulnificus
Authors: Park Na-Young , Kim In Hwang , Wen Yancheng , Lee Keun-Woo , Lee Sora , Kim Jeong-A , Jung Kwang-Hwan , Lee Kyu-Ho , Kim Kun-Soo 
Published: December 2019

AbstractLeuO plays the role of a master regulator in the cyclic-L-phenylalanine-L-proline (cFP)-dependent signaling pathway in Vibrio vulnificus. cFP, as shown through isothermal titration calorimetry analysis, binds specifically to the periplasmic domain of ToxR. Binding of cFP triggers a change in the cytoplasmic domain of ToxR, which then activates transcription of leuO encoding a LysR-type regulator. LeuO binds to the region upstream of its own coding sequence, inhibiting its own transcription and maintaining a controlled level of expression. A five-bp deletion in this region abolished expression of LeuO, but a ten-bp deletion did not, suggesting that a DNA bending mechanism is involved in the regulation. Furthermore, binding of RNA polymerase was significantly lower both in the deletion of the ToxR binding site and in the five-bp deletion, but not in the ten-bp deletion, as shown in pull-down assays using an antibody against RNA polymerase subunit α. In summary, multiple factors are involved in control of the expression of LeuO, a master regulator that orchestrates downstream regulators to modulate factors required for survival and pathogenicity of the pathogen.
Fluctuation analysis in the dynamic characteristics of continental glacier based on Full-Stokes model
Authors: Wu Zhen , Zhang Huiwen , Liu Shiyin , Ren Dong , Bai Xuejian , Xun Zhaojie , Ma Zhentao 
Published: December 2019

AbstractIce thickness has a great influence on glacial movement and ablation. Over the course of the change in thickness, area and external climate, the dynamic process of how glaciers change and whether a glacier’s changes in melting tend to be stable or irregular is a problem that needs to be studied in depth. In our study, the changes in the dynamic process of the No. 8 Glacier in Hei Valley (H8) under the conditions of different thicknesses in 1969 and 2009 were simulated based on the Full-Stokes code Elmer/Ice (http://www.csc.fi/elmer/). The results were as follows: (1) The thickness reduction in glaciers would lead to a decrease in ice surface tension and basal pressure and friction at the bottom, and the resulting extensional and compressional flow played an important role in the variations in glacial velocity. (2) The force at the bottom of the glacier was key to maintaining the overall stress balance, and the glaciers that often melted and collapsed in bedrock were more easily destroyed by the overall force balance and increased change rate of glacial thaw. (3) Temperature changes at different altitudes affected the ice viscous force. The closer the ice surface temperature was to the melting point, the greater the influence of temperature changes on the ice viscous force and ice surface velocity. Finally, we used the RCP 4.8 and 8.5 climate models to simulate the changes in H8 over the next 40 years. The results showed that with some decreases in ice surface compression and tension, the gravity component changes caused by local topography begin to control the ice flow movement on the surface of glacier, and melting of the glacial surface will appear as an irregular change. The simulation results further confirmed that the fluctuation in glacial dynamic characteristics could be attributed to the change in the gravity component caused by ablation.
Historical Perspective of “How Did We Get Here and Where Are We Going” in the Rehabilitation of Patients With Vestibular Hypofunction
Authors: Herdman Susan J. 
Published: December 2019

PurposeVestibular rehabilitation for patients with vestibular hypofunction is a relatively new clinical specialty, with effective therapies developing over the last 40 years for the most common peripheral vestibular disorders. This chapter illustrates the evolution of treatments used for the wide variety of vestibular disorders that we now recognize and takes us back to the origins of some of the assessment tools that we use to make a diagnosis. The chapter will also explore the current status of this field and the potential areas into which vestibular rehabilitation may grow.ConclusionsIn reality, the origins of various treatments date back almost 100 years, and the development of assessment tools dates back several hundred years. Today, as physical and occupational therapists who specialize in the management of people with dizziness and vestibular disorders and audiologists who test and analyze the function of the vestibular system, we do so with the confidence that our efforts will be beneficial to the patient. This is largely because of the availability of clinical research—systematic analyses of published research and clinical practice guidelines that support the decisions that we make about diagnoses and treatment. It is important to remember, however, that the skills now used in vestibular rehabilitation are based on generations of observation, deduction, and opinion that gradually evolved into the body of knowledge that we have today.
Vestibular Rehabilitation
Authors: Shepard Neil T. 
Published: December 2019

Purpose
In this introduction, the author introduces the reader to two articles that cover the basic area of vestibular and balance rehabilitation therapy (VBRT). The articles explain some of the uses of VBRT but not the techniques of how to establish such a program for a patient with dizziness and balance disorders.

Conclusion
The audiologist needs to be familiar with the various uses of VBRT and the techniques for identification and treatment of benign paroxysmal positional vertigo. However, without the audiologist undergoing further specific musculoskeletal training, the remainder of VBRT should occur in the physical therapy arena.
Thoracodorsal Artery Perforator and Superior Epigastric Artery Perforator Flaps for Volume Replacement Oncoplastic Breast Surgery
Authors: Jaiswal Dushyant , Yadav Prabha Subhash , Shankhdhar Vinay Kant , Belgaumwala Tasneem Jaffer 
Published: December 2019

Abstract
Introduction Breast conservation therapy (BCT) and oncoplastic breast surgery (OBS) are now established modalities of treatment for breast cancer, with proven oncological safety. Traditionally, latissimus dorsi (LD) flaps have been the one-stop solution workhorse when volume replacement is needed. We present our experience with thoracodorsal artery perforator (TDAP) and superior epigastric artery perforator (SEAP) flaps. These flaps allow the preservation of muscle structure and function.
Material and Methods Data were collected prospectively of patients in whom pedicled perforator flaps after BCT were used. A handheld 8-MHz audio Doppler was used to locate the perforators. TDAP flaps were used in four patients, whereas SEAP flaps were used in two patients. Skin paddle sizes ranged from 10 × 3 cm to 21 × 7 cm.
Results TDAP flaps were used in four patients, whereas SEAP flaps were used in two patients All flaps survived. No flap had partial necrosis or fat necrosis. All donor sites were closed primarily and healed uneventfully, and none had a seroma requiring aspiration.
Conclusion TDAP flaps can be selectively employed when the LD muscle function needs to be preserved. SEAP flaps can also be employed as a rare option in case of lower inner quadrant defects. Pedicled perforator flaps are a useful and reliable option for volume replacement OBS in select patients for reconstructing partial mastectomy defects.
“Door-In to Door-Out” Delay in Patients with Acute ST-Segment Elevation Myocardial Infarction Transferred for Primary Percutaneous Coronary Intervention in a Metropolitan STEMI Network of a Developing Country
Authors: Dakota Iwan , Dharma Surya , Andriantoro Hananto , Firdaus Isman , Danny Siska Suridanda , Zamroni Dian , Radi Basuni 
Published: December 2019

AbstractRoutine performance measures of primary percutaneous coronary intervention (PCI) within an ST-segment elevation myocardial infarction (STEMI) network are needed to improve care.We evaluated the door-in to door-out (DI–DO) delays at the initial hospitals in STEMI patients as a routine performance measure of the metropolitan STEMI network.We retrospectively analyzed the DI–DO time from 1,076 patients with acute STEMI who were transferred by ground ambulance to a primary PCI center for primary PCI between 4 October 2014 and 1 April 2019. Correlation analysis between DI–DO times and total ischemia time was performed using Spearman's test. Logistic regression analyses were used to find variables associated with a longer DI–DO time.Median DI–DO time was 180 minutes (25th percentile to 75th percentile: 120–252 minutes). DI–DO time showed a positive correlation with total ischemia time (r = 0.4, p < 0.001). The median door-to-device time at the PCI center was 70 minutes (25th percentile to 75th percentile: 58–88 minutes). Multivariate analysis showed that women patients were independently associated with DI–DO time > 120 minutes (odds ratio 1.55, 95% confidence interval 1.03 to 2.33, p = 0.03).The DI–DO time reported in this study has not reached the guideline recommendation. To improve the overall performance of primary PCI in the region, interventions aimed at improving the DI–DO time at the initial hospitals and specific threat for women patients with STEMI are possibly the best efforts in improving the total ischemia time.
Indian Subcontinent’s First Bilateral Supracondylar Level Upper Limb Transplantation
Authors: Sharma Mohit , Iyer Subramania , P. Kishore , Mathew Jimmy , R. Janarthanan , Maharaja Nirav , Dhake Swapnil , Omkumar Akshay , Joe Thomas , Sharma Dimpy , Kapathia Radhika , Harijee Ankita , Reddy Srilekha , Paul Jerry , Rajan Sunil , Kurian George , Paul Zacharia , Shaji Druvan , Babu Balu C. , Sharma Anubhav 
Published: December 2019

Abstract
Introduction This is the first case of supracondylar level transplant from the Indian subcontinent, performed for a bilateral below elbow amputee. It has a completely different set of challenges for the transplant team, with a relatively shorter ischemia time window.The technical considerations for the same have been discussed in detail in this article.
Materials and Methods The patient was a 19-year-old female who lost her both upper limbs at proximal forearm level due to severe crush injury following a road traffic accident. Insufficient bone length on either side necessitated a supracondylar level transplant. The preoperative workup included detailed clinical evaluation, biochemical, and psychological evaluation.The donor was a young brain-dead, male patient from a hospital, 30 minutes away. The donor and recipient preparations in this case were unique. The recipient’s own elbow flexors and extensors were used while the elbow joint was from the donor. The specific challenges we faced during this procedure have been described in detail.
Results The transplantation has been a complete technical success, with the patient rehabilitated back to her independent life style. This article describes only the technical considerations. The functional recovery aspect is part of an another soon to be published manuscript.
Conclusion Supracondylar level arm-transplant requires a highly coordinated team effort with precise preoperative planning, along with meticulous attention to detail to achieve a successful outcome. In properly selected patients, it could be a life-changing procedure, worth all the effort.