bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70
T293
and destabilization of the signalosome
Authors: Giardino Torchia Maria Letizia , Dutta Debjani , Mittelstadt Paul R. , Guha June , Gaida Matthias M. , Fish Kamonwan , Barr Valarie A. , Akpan Itoro O. , Samelson Lawrence E. , Tagad Harichandra D. , Debnath Subrata , Miller Jenkins Lisa M. , Appella Ettore , Ashwell Jonathan D. 
Published: February 2018

Significance
Activation of T cells via their antigen receptor (TCR) and the formation of a multimolecular signaling complex in or near the plasma membrane is a key initial event in the generation of an immune response. Here we find that p38, a serine/threonine kinase activated by TCR signaling, in turn phosphorylates its upstream tyrosine kinase ZAP-70. This results in a decrease in the size and longevity of the TCR signaling complex, limiting T cell effector responses. Therefore, cross-talk between an upstream and downstream kinase in the signaling complex itself generates a negative feedback loop that may limit excessive T cell responses.
Cryo-EM structure of the bacterial actin AlfA reveals unique assembly and ATP-binding interactions and the absence of a conserved subdomain
Authors: Usluer Gülsima D. , DiMaio Frank , Yang Shun Kai , Hansen Jesse M. , Polka Jessica K. , Mullins R. Dyche , Kollman Justin M. 
Published: February 2018

Significance
Actin filaments are dynamic cytoskeletal elements that assemble upon ATP binding. Actin homologs are present in all domains of life, and all share a similar 3D structure of the assembling subunit, but evolutionary changes to the subunit have generated many different actin filament structures. The filament structure of the bacterial actin AlfA, which positions plasmids—small, circular DNA molecules that encode important genes—ensures that each daughter cell receives at least one copy at cell division. AlfA is different from all other actins in two critical ways: it binds to ATP in a unique way and it is missing a quarter of the conserved structural core. These differences explain unusual AlfA assembly dynamics that underlie its ability to move plasmids.
hMENA is a key regulator in endothelin-1/β-arrestin1–induced invadopodial function and metastatic process
Authors: Di Modugno Francesca , Caprara Valentina , Chellini Lidia , Tocci Piera , Spadaro Francesca , Ferrandina Gabriella , Sacconi Andrea , Blandino Giovanni , Nisticò Paola , Bagnato Anna , Rosanò Laura 
Published: February 2018

Significance
Discovering new targets and novel determinants of metastatic spread is an unmet need in ovarian cancer, which is plagued by high rates of recurrence. Endothelin-1 receptors (ET-1R), belonging to the G-protein–coupled receptor family, represent important targets critically involved in malignant progression. Here we identify a mechanistic link between ET-1R and the actin regulatory protein hMENA/hMENAΔv6 through the specific interaction with the multifunctional protein β-arrestin1 (β-arr1), which initiates signaling cascades as part of the molecular complex crucial for invadopodial maturation and malignant dissemination. Targeting ET-1R by using macitentan, a Food and Drug Administration-approved antipulmonary arterial hypertension drug, can impair the β-arr1–mediated signaling network controlling ovarian cancer progression and therefore represents a therapeutic option for ovarian cancer patients.
STING-dependent translation inhibition restricts RNA virus replication
Authors: Franz Kate M. , Neidermyer William J. , Tan Yee-Joo , Whelan Sean P. J. , Kagan Jonathan C. 
Published: February 2018

Significance
In mammalian cells, a protein called STING (stimulator of IFN genes) is typically viewed as a factor dedicated to defense strategies induced by DNA viruses. The antiviral activities of STING are linked to its ability to induce the expression of genes that combat viral replication cycles. In our study, we have discovered a transcription-independent function for STING in the restriction of viruses that contain RNA genomes. We found that cells lacking STING are sensitive to RNA virus infections and that during these infections, STING inhibits the translation machinery to prevent viral protein synthesis. This study therefore establishes that STING has dual functions in host defense, regulating antiviral gene expression or interfering with translation, to restrict replication of distinct classes of viruses.
Flexible usage and social function in primate vocalizations
Authors: Cheney Dorothy L. , Seyfarth Robert M. 
Published: February 2018

SignificanceWhen compared with humans, nonhuman primates have small vocal repertoires that show little acoustic modification during development. These limitations pose a dilemma for those interested in the evolution of language. Recent research, however, suggests that monkeys and apes show an extensive ability to modify their use of calls in different social contexts. Many vocalizations function to facilitate social interaction by reducing the uncertainty about the signaler’s intentions and likely behavior. Such interactions help to establish and maintain the social bonds that increase reproductive success. For scientists interested in the evolutionary transition from nonlinguistic communication to language, a logical starting point should be social interactions between long-lived individuals who interact repeatedly and for whom long-term social bonds are of paramount importance.
Poldip2 is an oxygen-sensitive protein that controls PDH and αKGDH lipoylation and activation to support metabolic adaptation in hypoxia and cancer
Authors: Paredes Felipe , Sheldon Kely , Lassègue Bernard , Williams Holly C. , Faidley Elizabeth A. , Benavides Gloria A. , Torres Gloria , Sanhueza-Olivares Fernanda , Yeligar Samantha M. , Griendling Kathy K. , Darley-Usmar Victor , San Martin Alejandra 
Published: February 2018

Significance
The present work establishes that the addition of the prosthetic group lipoic acid to catabolic enzymes is a dynamically regulated posttranslational modification that increases metabolic plasticity under hypoxia and in cancer cells. We show that that the polymerase-δ interacting protein 2 (Poldip2) is an oxygen-sensitive protein that regulates the lipoylation and activation of the pyruvate and α-ketoglutarate dehydrogenase complexes. Additionally, our work reveals that mitochondrial peptidases participate in an integrated response needed for metabolic adaptation. This study positions Poldip2 as a key regulator of mitochondrial function and cell metabolism.
Payments for watershed ecosystem services: mechanism, progress and challenges
Authors: Feng Danyang , Wu Wenliang , Liang Long , Li Li , Zhao Guishen 
Published: February 2018

ABSTRACT

Introduction:
Payment for watershed ecosystem services (PWES), a policy instrument for compensating for the externality of watershed ecosystem/environmental services, has gained in policy importance in China over the past two decades. Many scholars and researchers have contributed to the conceptualization of this policy framework by developing operational mechanisms as well as compensation standards for PWES.

Outcomes:
This article reviews 27 PWES schemes piloted in China and in 10 other countries, with a particular emphasis on successful cases of land-use conversion programs, such as the Paddy Land to Dry Land Program and Sloping Land Conversion Program that have been implemented in China.

Discussion:
By comparing different cases, the authors attempt to answer the following questions: what were the ecological and institutional contexts in which these schemes were established and how did they work? What were the actual efficiencies and impacts of these piloted schemes? Which scheme worked better in certain ecological, socio- economic, and institutional contexts?

Conclusion:
Based on case studies, the authors draw the following conclusions about Chinese PWES: (1) to establish an acceptable standard for a PWES program, it is necessary to estimate the economic and social costs regarding the livelihoods of households; (2) multi-stakeholder negotiation mechanism for PWES, including intermediaries, such as the local government, NGO/NPOs, village committees, and user associations, should be used; (3) ES, non-market services, should acquire positive externalities to accomplish an optimal win–win pattern concerning both environmental goals and the livelihoods of local resource users.
Obese Hypertensive Men Have Lower Circulating Proatrial Natriuretic Peptide Concentrations Despite Greater Left Atrial Size
Authors: Asferg Camilla L , Andersen Ulrik B , Linneberg Allan , Goetze Jens P , Jeppesen Jørgen L 
Published: February 2018

Abstract

BACKGROUND
Obese persons have lower circulating natriuretic peptide (NP) concentrations. It has been proposed that this natriuretic handicap plays a role in obesity-related hypertension. In contrast, hypertensive patients with left atrial enlargement have higher circulating NP concentrations. On this background, we investigated whether obese hypertensive men could have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size.

METHODS
We examined 98 obese men (body mass index [BMI] ≥ 30.0 kg/m2) and 27 lean normotensive men (BMI 20.0–24.9 kg/m2). All men were healthy, medication free, with normal left ventricular ejection fraction. We measured blood pressure using 24-hour ambulatory blood pressure (ABP) recordings. Hypertension was defined as 24-hour ABP ≥ 130/80 mm Hg, and normotension was defined as 24-hour ABP &lt; 130/80 mm Hg. We determined left atrial size using echocardiography, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP).

RESULTS
Of the 98 obese men, 62 had hypertension and 36 were normotensive. The obese hypertensive men had greater left atrial size (mean ± SD: 28.7 ± 6.0 ml/m2) compared with the lean normotensive men (23.5 ± 4.5 ml/m2) and the obese normotensive men (22.7 ± 5.1 ml/m2), P &lt; 0.01. Nevertheless, despite evidence of pressure-induced greater left atrial size, the obese hypertensive men had lower serum MR-proANP concentrations (median [interquartile range]: 48.5 [37.0–64.7] pmol/l) compared with the lean normotensive men (69.3 [54.3–82.9] pmol/l), P &lt; 0.01, whereas the obese normotensive men had serum MR-proANP concentrations in between the 2 other groups (54.1 [43.6–62.9] pmol/l).

CONCLUSIONS
Despite greater left atrial size, obese hypertensive men have lower circulating MR-proANP concentrations compared with lean normotensive men.
Techniques to Ensure Accurate Targeting for Delivery of Awake Laser Interstitial Thermotherapy
Authors: Laurent Dimitri , Oliveria Seth F , Shang Michael , Bova Frank , Freedman Rachel , Rahman Maryam 
Published: February 2018

Abstract

BACKGROUND
Magnetic resonance imaging (MRI) guided laser interstitial thermal therapy (LITT) is an emerging neurosurgical treatment modality that is typically performed under general anesthesia. We describe a novel workflow developed at the University of Florida to deliver LITT in conscious patients without the use of general anesthesia.

OBJECTIVE
To describe a novel workflow for LITT implementation in the awake patient with equivalent treatment results when compared to procedures performed under general anesthesia.

METHODS
For trajectories near a post of the Cosman-Roberts-Wells (CRW) frame (Integra LifeSciences, Plainsboro, New Jersey), we used preoperative MRI imaging to 3-dimensional-print a patient-specific mask with a trajectory guide to indicate the planned entry point during headframe placement. Otherwise, routine headframe placement and stereotactic registration were performed. Stereotactic biopsy and placement of the cranial bolt were performed in a standard neurosurgical operating room. The patient was transferred to a diagnostic MRI suite and positioned in the MRI scanner using beanbags and a custom molded thermoplastic mask. LITT was delivered with the patient conscious in the MRI scanner according to the manufacturer's recommendations. We collected patient demographics, treatment time, length of stay, and calculated preoperative tumor volume and postoperative ablation volumes.

RESULTS
Ten sequential patients were treated with LITT from January 2016 until March 2017. The average preoperative tumor volume was 6.9 cm3. The average tissue volume ablated was 18.3 cm3. The mean operative time was 31 min (standard deviation [SD] 10 min) and mean time with laser delivery in MRI was 79 min (SD 27 min). The mean length of stay was 1.4 d (SD 0.9). There were no major complications.

CONCLUSION
Using trajectory preplanning, customized face masks, and noninvasive head immobilization, LITT can be delivered to patients safely and accurately without general anesthesia.
Clinical Criteria of Central Sensitization in Chronic Pelvic and Perineal Pain (Convergences PP Criteria): Elaboration of a Clinical Evaluation Tool Based on Formal Expert Consensus
Authors: Levesque Amélie , Riant Thibault , Ploteau Stéphane , Rigaud Jérôme , Labat Jean-Jacques ,   Convergences PP Network, Amarenco Gérard , Attal Nadine , Bautrant Eric , Marc Beer Gabel , Cervigni Mauro , Chelimsky Thomas , Farmer Melissa , Adela Giamberardino Maria , Greenslade Gareth , Hughes John , Lord Marie Josée , Marchand Serge , Messelink Bert , Moyal Barracco Micheline , Tu Franck F , Usandizaga Elio Ràmon , Vancaillie Thierry , Vincent Katy , Watier Alain 
Published: February 2018

AbstractBackgroundThe evaluation of chronic pelvic and perineal pain (CPP) is often complex. The patient’s description of the pain often appears to be disproportionate to the limited findings on physical examination and/or complementary investigations. The concept of central sensitization may allow better understanding and management of patients with CPP.ObjectiveThe aim of this study was to elaborate a clinical evaluation tool designed to simply identify sensitization in pelvic pain.MethodsA list of 63 items was submitted to 22 international CPP experts according to the Delphi method.ResultsTen clinical criteria were adopted for the creation of a clinical evaluation tool: 1) pain influenced by bladder filling and/or urination, 2) pain influenced by rectal distension and/or defecation, 3) pain during sexual activity, 4) perineal and/or vulvar pain in response to normally nonpainful stimulation, 5) pelvic trigger points (e.g., in the piriformis, obturator internus, and/or levator ani muscles), 6) pain after urination, 7) pain after defecation, 8) pain after sexual activity, 9) variable (fluctuating) pain intensity and/or variable pain distribution, 10) migraine or tension headaches and/or fibromyalgia and/or chronic fatigue syndrome and/or post-traumatic stress disorder and/or restless legs syndrome and/or temporomandibular joint dysfunction and/or multiple chemical sensitivity.Conclusions This process resulted in the elaboration of a clinical evaluation tool designed to identify and appropriately manage patients with CPP comprising a sensitization component.
Long-term Scar Quality after Treatment of Standardized Partial-Thickness Skin Graft Donor Sites
Authors: Schulz Alexandra , Rothermund Irene , Lefering Rolf , Fuchs Paul Christian , Schiefer Jennifer 
Published: February 2018

ABSTRACT

BACKGROUND:
The long-term aesthetic appearance of scars is of great importance to patients. Biobrane (Smith and Nephew, Fort Worth, Texas), a biosynthetic skin dressing, is a successfully established dressing for the treatment of superficial wounds. A new silk barrier dressing (Dressilk; Prevor, Moulin de Verville, France) has also shown good results in wound healing. This study evaluated the long-term scar quality of superficial wounds treated with these dressings.

METHODS:
From February 2012 to May 2013, 11 patients with burns in need of skin grafting received donor site treatment. Study authors dressed 2 adjacent, standardized, partial-thickness skin graft donor sites on each participant with Biobrane or Dressilk. Scar formation on both treated areas was compared 24 months after initial application using subjective and objective assessment methods.

RESULTS:
Independent of treatment, the majority of the patients described scar quality similar to normal skin using subjective and objective evaluation tools. However, for scar perfusion, significantly lower oxygen saturation was shown in both treated areas compared with untreated skin.

CONCLUSIONS:
Comparatively, the 2 wound dressings showed similar results, making silk dressings an interesting alternative to biosynthetic ones.
Anxiety Sensitivity Physical and Cognitive Concerns in Relation to Smoking-oriented Cognition: An Examination Among Treatment-seeking Adults Who Smoke
Authors: Langdon Kirsten J. , Bakhshaie Jafar , Lopez Alicia , Tavakoli Niloofar , Garey Lorra , Raines Amanda M. , Kauffman Brooke Y. , Schmidt Norman B. , Zvolensky Michael J. 
Published: February 2018

Objectives:
Elevated levels of anxiety sensitivity (AS; fear of anxiety and internal sensations) is highly common among adults who smoke, and contributes to several maladaptive smoking beliefs and behaviors. AS is comprised of 3 empirically established factors, relating to fears of social concerns, fears of physical symptoms, and fears of cognitive dyscontrol. Relatively few studies have examined how these 3 subscales pertain to smoking processes. The aim of the present investigation was to examine, among treatment-seeking adults who smoke, the interactive effects of AS-physical and cognitive concerns in relation to: perceived barriers to smoking cessation; smoking-related negative reinforcement expectancies; and smoking-related avoidance and inflexibility.

Methods:
Participants included 470 adults who smoke (47.8% female; mean age 37.2, SD 13.5), who were recruited to participate in a smoking-cessation treatment study. At the baseline assessment, participants completed self-report measures, including the Anxiety Sensitivity Index-3, Barriers to Cessation Scale, Smoking Consequences Questionnaire, and Avoidance and Inflexibility Scale.

Results:
Results indicated that after controlling for the effects of sex, cigarette dependence, alcohol problems, tobacco-related medical illness, current axis 1 disorder, and AS-social concerns, a significant interaction emerged, such that the association between AS-cognitive concerns and the studied smoking-based cognitions were stronger among lower levels of AS-physical concerns (but not higher physical concerns).

Conclusions:
The current findings suggest that it may be beneficial to provide specialized smoking-cessation interventions for certain subgroups of adults who smoke, such as those with different AS profiles, to promote healthier beliefs about quitting.
Management of Behçet's disease
Authors: Alibaz-Oner Fatma , Sawalha Amr H. , Direskeneli Haner 
Published: February 2018

Purpose of review
Current treatment modalities in Behçet's disease will be summarized in light of new studies published within the last 2 years.

Recent findings
There is an increasing interest in the treatment of refractory mucocutaneous symptoms of Behçet's disease, and results were quite promising with apremilast, anakinra, and ustekinumab. Data from large case series confirmed both the efficacy and safety of tumor necrosis factor-α inhibitors for the treatment of refractory major organ manifestations such as ocular, neurologic, vascular, and gastrointestinal involvement. In refractory ocular disease, long-term results also confirmed the efficacy and safety of interferon-α. Interleukin-1 inhibitors and tocilizumab seem to be alternative options in patients with refractory ocular involvement.

Summary
Prospective and controlled studies for the management of major organ involvement in Behçet's disease are still limited. Data from primarily retrospective studies confirmed better outcomes of major organ involvement with tumor necrosis factor-α inhibitors and interferon-α. There were also acceptable results with interleukin-1 inhibitors for the management of refractory ocular disease, and with apremilast, anakinra, and ustekinumab for refractory mucocutaneous involvement.
Evaluation of Intramedullary Fixation for Pediatric Femoral Shaft Fractures in Developing Countries
Authors: Chen Andrew T. , Morris William Z. , Zirkle Lewis G. , Liu Raymond W. 
Published: February 2018

Objectives:
To report the clinical results after treatment of pediatric femoral shaft fractures with the SIGN Fracture Care International (SIGN) pediatric and standard fin nails.

Design:
Retrospective review of prospectively collected data.

Setting:
Sixteen global SIGN centers from 2003 to 2013.

Patients/Participants:
One hundred twelve pediatric patients who sustained a diaphyseal pediatric femoral shaft fracture.

Intervention:
Intramedullary fixation with the standard or pediatric SIGN nail.

Main Outcome Measurements:
Main outcome measurements include clinical and radiographic healing and postoperative complications.

Results:
The mean age of the pediatric fin patients was 9.4 years (4–15) and 11.2 years (4–18) for the standard fin patients. Painless weight bearing was achieved in 94.7% and 94.5% of the patients at the last follow-up. In total, 23 patients had repeat surgery for the removal of implant. Failure of implant with bending of the nail and/or a valgus or varus deformity (>10 degrees) was noted in 7/57 (12.3%) of the patients treated with the pediatric fin nail, of which 6/7 were >10 years old. Five of these 7 patients were classified as technical errors attributed to inadequate nail diameter, length, or initial malreduction. No complications were noted at any age in the standard fin nail group.

Conclusions:
In resource-poor settings, SIGN pediatric fin and standard fin nails seem to be an effective treatment option for femoral shaft fractures. In patients with larger canals, the surgeon should consider using the standard fin nail for improved stability and to minimize potential complications.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Outcomes of Early Surgical Intervention in Geriatric Proximal Femur Fractures Among Patients Receiving Direct Oral Anticoagulation
Authors: Franklin Nathan A. , Ali Ashley H. , Hurley Richard K. , Mir Hassan R. , Beltran Michael J. 
Published: February 2018

Objective:
To evaluate the prehospital use of direct oral anticoagulant (DOAC) agents on the outcomes of early surgical fixation of a geriatric hip fracture.

Design:
Case control study.

Setting:
Two academic Level 1 trauma centers.

Intervention:
Early (<48 h) surgical fixation of a geriatric proximal femur fracture.

Patients:
Nineteen patients receiving Pradaxa (dabigatran), Eliquis (apixaban), or Xarelto (rivaroxaban) who underwent surgery between 2010 and 2015 and 74 control patients.

Main Outcome Measurements:
Time to surgery, transfusion rates, changes in hemoglobin levels, postoperative complications, readmission rates, and survival out to 1 year.

Results:
There were no differences in transfusions, changes in hemoglobin levels, wound complications, or survival at any time point. Patients on DOAC had a longer delay to reach the operating room (28.9 h v 21.4 h P = 0.03) and were more likely to undergo readmission within 30 days (21% vs. 5.3% P = 0.05). No readmissions occurred for a complication of the surgical site, bleeding, or a venous thromboembolic event.

Conclusions:
Geriatric patients with hip fractures receiving DOAC before admission did not demonstrate worse outcomes with early surgical intervention. The increased readmission rate in this population seems attributable to the underlying cardiac conditions for which the patients were receiving anticoagulation. These results suggest that the delay recommended for patients using a DOAC before elective procedures may be unwarranted in the surgically urgent setting of a hip fracture. Additional studies will be necessary for appropriate meta-analysis.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.