bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of kinesthetic motor imagery and effector specificity on the long-latency stretch response
Authors: Forgaard Christopher J. , Franks Ian M. , Maslovat Dana , Chua Romeo 
Published: September 2019

The long-latency “reflexive” response (LLR) following an upper limb mechanical perturbation is generated by neural circuitry shared with voluntary control. This feedback response supports many task-dependent behaviors and permits the expression of goal-directed corrections at latencies shorter than voluntary reaction time. An extensive body of literature has demonstrated that the LLR shows flexibility akin to voluntary control, but it has not yet been tested whether instruction-dependent LLR changes can also occur in the absence of an overt voluntary response. The present study used kinesthetic motor imagery ( experiment 1) and instructed participants to execute movement with the unperturbed contralateral limb ( experiment 2) to explore the relationship between the overt production of a voluntary response and LLR facilitation. Activity in stretched right wrist flexors were compared with standard “do not-intervene” and “compensate” conditions. Our findings revealed that on ~40% of imagery and ~50% of contralateral trials, a response occurred during the voluntary epoch in the stretched right wrist flexors. On these “leaked” trials, the early portion of the LLR (R2) was facilitated and displayed a similar increase to compensate trials. The latter half of the LLR (R3) showed further modulation, mirroring the patterns of voluntary epoch activity. By contrast, the LLR on “non-leaked” imagery and contralateral trials did not modulate. We suggest that even though a hastened voluntary response cannot account for all instruction-dependent LLR modulation, the overt execution of a response during the voluntary epoch in the same muscle(s) as the LLR is a prerequisite for instruction-dependent facilitation of this feedback response. NEW & NOTEWORTHY Using motor imagery and contralateral responses, we provide novel evidence that facilitation of the long-latency reflex (LLR) requires the execution of a response during the voluntary epoch. A high proportion of overt response “leaks” were found where the mentally simulated or mirrored response appeared in stretched muscle. The first half of the LLR was categorically sensitive to the appearance of leaks, whereas the latter half displayed characteristics closely resembling activity in the ensuing voluntary period.
Preferential activation of spinal sensorimotor networks via lateralized transcutaneous spinal stimulation in neurologically intact humans
Authors: Calvert Jonathan S. , Manson Gerome A. , Grahn Peter J. , Sayenko Dimitry G. 
Published: September 2019

Transcutaneous spinal stimulation (TSS), a noninvasive technique to modulate sensorimotor circuitry within the spinal cord, has been shown to enable a wide range of functions that were thought to be permanently impaired in humans with spinal cord injury. However, the extent to which TSS can be used to target specific mediolateral spinal cord circuitry remains undefined. We tested the hypothesis that TSS applied unilaterally to the skin ~2 cm lateral to the midline of the lumbosacral spine selectively activates ipsilateral spinal sensorimotor circuitry, resulting in ipsilateral activation of downstream lower extremity neuromusculature. TSS cathodes and anodes were positioned lateral from the midline of the spine in 15 healthy subjects while supine, and the timing of TSS pulses was synchronized to recordings of lower extremity muscle activity and force. At motor threshold, left and right TSS-evoked muscle activity was significantly higher in the ipsilateral leg compared with contralateral recordings from the same muscles. Similarly, we observed a significant increase in force production in the ipsilateral leg compared with the contralateral leg. Delivery of paired TSS pulses, during which an initial stimulus was applied to one side of the spinal cord and 50 ms later a second stimulus was applied to the contralateral side, revealed that ipsilateral leg muscle responses decreased following the initial stimulus, whereas contralateral muscle responses did not decrease, indicating side-specific activation of lateral spinal sensorimotor circuitry. Our results indicate TSS can selectively engage ipsilateral neuromusculature via lumbosacral sensorimotor networks responsible for lower extremity function in healthy humans. NEW & NOTEWORTHY We demonstrate the selectivity of transcutaneous spinal stimulation (TSS), which has been shown to enable function in humans with chronic paralysis. Specifically, we demonstrate that TSS applied to locations lateral to the spinal cord can selectively activate ipsilateral spinal sensorimotor networks. We quantified lumbosacral spinal network activity by recording lower extremity muscle electromyography and force. Our results suggest lumbosacral TSS engages side-specific spinal sensorimotor networks associated with ipsilateral lower extremity function in humans.
Scutellarin Suppresses Patient-Derived Xenograft Tumor Growth by Directly Targeting AKT in Esophageal Squamous Cell Carcinoma
Authors: Liu Feifei , Zu Xueyin , Xie Xiaomeng , Zhang Yuanyuan , Liu Kangdong , Chen Hanyong , Wang Ting , Bode Ann M. , Dong Zigang , Kim Dong Joon 
Published: September 2019

Abstract
Scutellarin is a flavonoid compound that is found in Scutellaria barbata. It has been reported to exhibit anticancer and anti-inflammation activities. However, the anticancer properties of scutellarin and its molecular targets have not been investigated in esophageal squamous cell carcinoma (ESCC). In the current study, we report that scutellarin is a potential AKT inhibitor that suppresses patient-derived xenograft ESCC tumor growth. To identify possible molecular targets of scutellarin, potential candidate proteins were screened by an in vitro kinase assay and Western blotting. We found that scutellarin directly binds to the AKT1/2 proteins and inhibits activities of AKT1/2 in vitro. The AKT protein is activated in ESCC tissues and knockdown of AKT significantly suppresses growth of ESCC cells. Scutellarin significantly inhibits anchorage-dependent and independent cell growth and induces G2 phase cell-cycle arrest in ESCC cells. The inhibition of cell growth by scutellarin is dependent on the expression of the AKT protein. Notably, scutellarin strongly suppresses patient-derived xenograft ESCC tumor growth in an in vivo mouse model. Taken together, our data suggest that scutellarin is a novel AKT inhibitor that may prevent progression of ESCC.
Comparison of Systemic Exposure to Toxic and/or Carcinogenic Volatile Organic Compounds (VOC) during Vaping, Smoking, and Abstention
Authors: St. Helen Gideon , Liakoni Evangelia , Nardone Natalie , Addo Newton , Jacob Peyton , Benowitz Neal L. 
Published: September 2019

Abstract
Comparisons of systemic exposure to toxicants during monitored cigarette smoking, electronic cigarette (e-cigarette) use, and abstention are needed to enhance our understanding of the risks of e-cigarette use (vaping). In a cross-over study, we measured 10 mercapturic acid metabolites of volatile organic compounds (VOCs) in 24-hour urine samples collected from 36 dual users (8 women) of e-cigarettes and cigarettes during 2 days of ad libitum vaping or cigarette-only use, and 2 days of enforced abstention. Concentrations of VOC metabolites were higher during smoking compared with vaping, except for the methylating agents' metabolite. The fold-difference in concentrations when smoking relative to vaping ranged from 1.31 (1.06–1.61; geometric mean, 95% confidence interval; 1,3-butadiene) to 7.09 (5.88–8.54; acrylonitrile). Metabolites of acrylamide [fold difference of 1.21 (1.03–1.43)] and benzene [1.46 (1.13–1.90)] were higher during vaping compared with abstention. The 1,3-butadiene and propylene oxide metabolites were higher in variable-power tank users compared with users of cig-a-likes. E-cigarettes expose users to lower levels of toxic VOCs compared with cigarette smoking, supporting their harm reduction potential among smokers. However, some e-cigarettes expose users to VOCs such as acrylamide, benzene, and propylene oxide, and may pose health risks to nonsmoking users. The results of our study will inform regulators in assessing e-cigarettes with respect to the balance between its potential harm reduction for adult smokers and risk to nonsmoking users.
Radiotherapy and Immunotherapy Promote Tumoral Lipid Oxidation and Ferroptosis via Synergistic Repression of SLC7A11
Authors: Lang Xueting , Green Michael D. , Wang Weimin , Yu Jiali , Choi Jae Eun , Jiang Long , Liao Peng , Zhou Jiajia , Zhang Qiang , Dow Ania , Saripalli Anjali L. , Kryczek Ilona , Wei Shuang , Szeliga Wojciech , Vatan Linda , Stone Everett M. , Georgiou George , Cieslik Marcin , Wahl Daniel R. , Morgan Meredith A. , Chinnaiyan Arul M. , Lawrence Theodore S. , Zou Weiping 
Published: September 2019

Abstract

A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor-cell ferroptosis. Mechanistically, IFNγ derived from immunotherapy-activated CD8+ T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate–cystine antiporter xc−, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy.

Significance:
This article describes ferroptosis as a previously unappreciated mechanism of action for radiotherapy. Further, it shows that ferroptosis is a novel point of synergy between immunotherapy and radiotherapy. Finally, it nominates SLC7A11, a critical regulator of ferroptosis, as a mechanistic determinant of synergy between radiotherapy and immunotherapy.
This article is highlighted in the In This Issue feature, p. 1631
Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men
Authors: Ascher Simon B. , Scherzer Rebecca , Estrella Michelle M. , Shlipak Michael G. , Ng Derek K. , Palella Frank J. , Witt Mallory D. , Ho Ken , Bennett Michael R , Parikh Chirag R. , Ix Joachim H. , Jotwani Vasantha 
Published: September 2019

<b><i>Background:</i></b> HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. <b><i>Methods:</i></b> In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. <b><i>Results:</i></b> Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m<sup>2</sup>/year in HIV+ men and 1.22 mL/min/1.73 m<sup>2</sup>/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m<sup>2</sup>/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m<sup>2</sup>/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m<sup>2</sup>/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. <b><i>Conclusions:</i></b> Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.
Loss of Orai2-Mediated Capacitative Ca
2+
Entry Is Neuroprotective in Acute Ischemic Stroke
Authors: Stegner David , Hofmann Sebastian , Schuhmann Michael K. , Kraft Peter , Herrmann Alexander M. , Popp Sandy , Höhn Marlen , Popp Michael , Klaus Vanessa , Post Antonia , Kleinschnitz Christoph , Braun Attila , Meuth Sven G. , Lesch Klaus-Peter , Stoll Guido , Kraft Robert , Nieswandt Bernhard 
Published: September 2019

Background and Purpose—

Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed. Calcium overload is one of the major triggers of neuronal cell death. We have previously shown that capacitative Ca
2+
entry, which is triggered by the depletion of intracellular calcium stores, contributes to ischemia-induced calcium influx in neurons, but the responsible Ca
2+
channel is not known.

Methods—
Here, we have generated mice lacking the calcium channel subunit Orai2 and analyzed them in experimental stroke.

Results—

Orai2-deficient mice were protected from ischemic neuronal death both during acute ischemia under vessel occlusion and during ischemia/reperfusion upon successful recanalization. Calcium signals induced by calcium store depletion or oxygen/glucose deprivation were significantly diminished in Orai2-deficient neurons demonstrating that Orai2 is a central mediator of neuronal capacitative Ca
2+
entry and is involved in calcium overload during ischemia.

Conclusions—
Our experimental data identify Orai2 as an attractive target for pharmaceutical intervention in acute stroke.
Long-Term Outcomes of Indirect Bypass for 629 Children With Moyamoya Disease
Authors: Ha Eun Jin , Kim Kyung Hyun , Wang Kyu-Chang , Phi Ji Hoon , Lee Ji Yeoun , Choi Jung Won , Cho Byung-Kyu , Yang Jeyul , Byun Yoon Hwan , Kim Seung-Ki 
Published: September 2019

Background and Purpose—
In pediatric moyamoya disease, there are few reports on the efficacy of surgical intervention for stroke prevention. We evaluated the long-term outcomes of indirect bypass surgery on a relatively large number of children with moyamoya disease in a single center.

Methods—
From August 1988 to December 2012, 772 children underwent indirect bypass surgery. This study included 629 patients who were followed up for >5 years, excluding patients with moyamoya syndrome. The mean clinical follow-up duration was 12 years (range, 5–29 years). Cross-sectional analysis was performed based on either Karnofsky Performance Scale or Lansky Play Performance Scale to evaluate overall clinical outcomes and factors associated with unfavorable outcomes. To analyze the longitudinal effect of surgery, the annual risk of symptomatic infarction or hemorrhage on the operated hemisphere after indirect bypass surgery was calculated with a person-year method, and the event-free survival rate was evaluated using the Kaplan-Meier method.

Results—
The overall clinical outcome was favorable in 95% of the patients. The annual risks of symptomatic infarction and hemorrhage on the operated hemispheres were 0.08% and 0.04%, respectively. Furthermore, the 10-year event-free survival rates for symptomatic infarction and hemorrhage were 99.2% and 99.8%.

Conclusions—
Indirect bypass surgery could provide satisfactory long-term improvement in overall clinical outcome and prevention of recurrent stroke in children with moyamoya disease.
From Signaling and Expression to Conversation and Fiction
Authors: S. Green Mitchell 
Published: September 2019

This essay ties together some main strands of the author’s research spanning the last quarter-century. Because of its broad scope and space limitations, he prescinds from detailed arguments and instead intuitively motivates the general points which are supported more fully in other publications to which he provides references. After an initial delineation of several distinct notions of meaning (Section 1), the author considers (Section 2) such a notion deriving from the evolutionary biology of communication that he terms ‘organic meaning’, and places it in the context of evolutionary game theory. That provides a framework for a special type of organic meaning found in the phenomenon of expression (3), of which the author here offers an updated characterization while highlighting its wide philosophical interest. Expression in turn generalizes to a paradigmatic form of human communication—conversation—and section 4 provides a taxonomy of conversation-types while arguing that attention to such types helps to sharpen predictions of what speakers say rather than conversationally implicate. We close (5) with a view of fictional discourse on which authors of fictional works are engaged in conversation with their readers, and can provide them with knowledge in spite of the fictional character of their conversation. Such knowledge includes knowledge of how an emotion feels and is thus a route to empathy.
A New Instrument For Rhinoplasty: The Osteotom With Lighting Guide Transilluminating Osteotomy
Authors: Ersözlü Tolga 
Published: September 2019

Rhinoplasty remains one of the most commonly performed aesthetic surgical procedure that demands a meticulous intraoperative precision as well as maximum precaution and control. Nasal osteotomy is a key component to shape the bony vault in aesthetic rhinoplasty, but it is also the so versatile, dangerous, and difficult to learn. The present study aims to evaluate the usefulness of our locator instrument for beginners which is called transilluminating osteotome. The use of transilluminating osteotome instead of guided lateral nasal osteotome is a reliable instrument since it facilitates the localization of osteotome and osteotomy line beneath the soft tissue with a limited damage to the surrounding soft tissues. Level of Evidence: III
Comparison between use of single lightwand and video laryngoscope-guided lightwand for tracheal intubation in simulated cervical spine-immobilized patients: a single-blind randomized study
Authors: Kim Ha Yeon , Kim Eun Jung , Yoon Hei Jin , Ko Byungwoong , Choi Seung Yeon , Koo Bon-Nyeo 
Published: September 2019

Objective This study was performed to compare the use of a video laryngoscope-guided lightwand versus a single lightwand for tracheal intubation performed by non-experts in cervical spine-immobilized patients. Methods In total, 318 patients under general anesthesia were assigned either to the single lightwand group (Group L) or the video laryngoscope-guided lightwand group (Group VL) at a 1:1 ratio. First- or second-grade residents performed tracheal intubation with the assigned device after applying semi-hard fitted cervical collars to the patients. Outcomes, including the success rate and airway complications, were compared between the two groups. Results There were no significant differences in demographics or airway-related characteristics between the two groups. The success rate of intubation on the first attempt was significantly higher in Group VL than in Group L (90% vs. 64%, respectively). Postoperative complications, including oral mucosal bleeding, hoarseness, and sore throat scores at 1 and 24 hours after surgery, were significantly lower in Group VL than in Group L. Conclusions The use of a video laryngoscope-guided lightwand for tracheal intubation can be useful for non-experts who encounter difficult airway situations.
Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study
Authors: Williet Nicolas , Saint Angélique , Pointet Anne-Laure , Tougeron David , Pernot Simon , Pozet Astrid , Bechade Dominique , Trouilloud Isabelle , Lourenco Nelson , Hautefeuille Vincent , Locher Christophe , Desrame Jérome , Artru Pascal , Thirot Bidault Anne , Le Roy Bertrand , Pezet Denis , Phelip Jean-Marc , Taieb Julien 
Published: September 2019

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.
Incidence and prevalence of common respiratory pathogens before and after implementation of the Cystic Fibrosis Foundation Infection Prevention and Control Guideline
Authors: Kim Christy , delaRiva-Velasco Elizabeth , Budhram Arvind , Farri Folashade , Krich Daniel , Nolan Sheila S , Gjonaj Suzette , Paul Lisa , Dozor Allen J , Welter John J 
Published: September 2019

Background: The 2013 Cystic Fibrosis Foundation’s Infection Prevention and Control Guideline (CFF IP&C) was developed to reduce the risk of acquisition and transmission of respiratory pathogens in patients with cystic fibrosis (CF). Objective: We hypothesised that the incidence of common CF respiratory pathogens would decrease at our centre after implementation of the guideline. Methods: All patients with CF seen at our centre from August 2012 through August 2017 who had respiratory cultures were included. Patients were excluded from incidence analysis if they did not have at least one culture per year. Quarterly data were collected for one year before and three years after implementation of the guidelines to determine the incidence and prevalence of seven organisms commonly found in respiratory cultures of patients with CF. Results: Quarterly and annual incidence and prevalence rates of common organisms did not change during the study period. Discussion: There were no significant differences in the incidence or prevalence of common respiratory organisms in the first three years after implementation of the CF IP&C guideline. Long-term follow-up is needed to determine if changes occur over time.