bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coxiella burnetii (Q fever) prevalence in associated populations of humans and small ruminants in The Gambia
Authors: Bok Jeroen , Hogerwerf Lenny , Germeraad Eveline A. , Roest Hendrik I. J. , Faye‐Joof Tisbeh , Jeng Momodou , Nwakanma Davis , Secka Arss , Stegeman Arjan , Goossens Bart , Wegmüller Rita , van der Sande Marianne A. B. , van der Hoek Wim , Secka Ousman 
Published: December 2016

AbstractObjectivesTo simultaneously estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among adults and small ruminants, and C. burnetii shedding prevalence among small ruminants in households in the Kiang West district of The Gambia, and to assess associated risk factors.MethodsSera of 599 adults and 615 small ruminants from 125 compounds within 12 villages were tested for antibodies against C. burnetii using ELISA. Vaginal swabs and milk samples of 155 small ruminants were tested using PCR to investigate shedding of C. burnetii.ResultsA total of 3.8–9.7% of adults, depending on ELISA test cut‐off, and 24.9% of small ruminants in Kiang West were seropositive. Having at least one seropositive animal in one's compound was a risk factor for human seropositivity (OR: 3.35, 95% CI: 1.09–14.44). A grazing area within a village was a risk factor for seropositivity in small ruminants (OR: 2.07, 95% CI: 1.26–3.50); others were having lambed (OR: 2.75, 95% CI: 1.37–5.76) and older age of the animals (OR: 2.75, 95% CI: 1.37–5.76 for 1–3 years and OR 5.84, 95% CI: 3.10–11.64 for >3 years); 57.4% of sampled small ruminants were shedding C. burnetii.ConclusionCoxiella burnetii infection is endemic among both humans and small ruminants in this area of The Gambia. Human and animal exposure to C. burnetii were related at compound level. Further research into the clinical relevance of C. burnetii infection in West Africa is needed.
Poor stem cell harvest may not always be related to poor mobilization: lessons gained from a mobilization study in patients with β‐thalassemia major
Authors: Constantinou Varnavas C. , Bouinta Asimina , Karponi Garyfalia , Zervou Fani , Papayanni Penelope‐Georgia , Stamatoyannopoulos George , Anagnostopoulos Achilles , Yannaki Evangelia 
Published: December 2016

BACKGROUNDHematopoietic stem cell mobilization and leukapheresis in adult patients with β‐thalassemia have recently been optimized in the context of clinical trials for obtaining hematopoietic stem cells for thalassemia gene therapy. In some patients, however, the yield of cluster of differentiation 34‐positive (CD34+) cells was poor despite successful mobilization, and a modification of apheresis settings was mandatory for harvest rescue.STUDY DESIGN AND METHODSData were analyzed from 20 adult patients with β‐thalassemia who were enrolled in a clinical trial of optimizing mobilization strategies for stem cell gene therapy. The aim of this post‐hoc analysis was to assess how certain hematological and/or clinical parameters may correlate with low collection efficiency in the presence of adequate numbers of circulating stem cells after pharmacological mobilization and standard leukapheresis procedures.RESULTSAmong 19 patients who achieved optimal mobilization with Plerixafor, four who underwent splenectomy demonstrated disproportionately poor CD34+ cell harvests, as determined by their circulating CD34+ cell counts after mobilization. All four patients who underwent splenectomy presented at baseline and before first apheresis with lymphocytosis resulting in lymphocyte/neutrophil ratios well above 1 and marked reticulocytosis compared with patients who achieved optimal mobilization/CD34+ cell harvest. Such unexpected expansion of specific cell populations disrupted the normal cell layer separation and necessitated modification of the apheresis settings to rescue the harvests.CONCLUSIONSBy close examination of certain hematological and/or clinical parameters before leukapheresis, patients who, despite adequate mobilization, are at risk for poor CD34+ cell harvests may be identified, and harvest failure can be prevented by adjusting the apheresis settings.
Customizing anticoagulation strategies during leukapheresis to limit citrate exposure
Authors: McMannes J. L. , Hershberger J. , Parker D. M. , De Reys S. , Loos T. , Hematti P. 
Published: December 2016

Background and ObjectivesLeukapheresis has become a standard practice to collect CD34+ haematopoietic progenitor cells (HPC) from peripheral blood. Hypocalcemic toxicity (hypocalcaemia) is the most common complication during leukapheresis associated with citrate‐based anticoagulation (AC) infusion. This report describes a new approach to limit citrate exposure by increasing the inlet:AC ratio while maintaining original inlet flow rates on the device in order to decrease the AC infusion rate.Materials and MethodsA retrospective analysis was performed on 63 autologous and 29 allogeneic HPC collections. Procedures were started at a conservative inlet:AC ratio of 12:1 with gradual ratio ramping (RR) during the procedure, or at an inlet:AC ratio of 13:1 or higher (HIR), with constant inlet flow rates. The clinical decision to change the ratio was based on platelet counts and concomitant medications, such as systemic anticoagulants. Symptoms of citrate toxicity were treated by calcium supplementation.ResultsCustomization of AC management with RR or HIR was performed in 91 of 92 procedures with a final inlet:AC ratio of 13:1–20:1, under careful supervision for platelet clumping episodes. Notably, 33 procedures were completed in individuals chronically treated with aspirin and/or warfarin. Citrate infusion gradually decreased with higher inlet:AC ratios, without affecting procedure time. The HIR strategy resulted in significantly smaller AC infusion volumes compared to RR, and lower frequency of calcium administration. CD34+ collection efficiency was not influenced by increasing inlet:AC ratios.ConclusionCustomization of the inlet:AC ratio while maintaining a constant, stable inlet flow rate is effective in limiting citrate exposure during leukapheresis.
Activation of protease‐activated receptor 2 mediates cutaneous vasodilatation but not sweating: roles of nitric oxide synthase and cyclo‐oxygenase
Authors: Fujii Naoto , McNeely Brendan D. , Zhang Sarah Y. , Abdellaoui Yasmine C. , Danquah Mercy O. , Kenny Glen P. 
Published: December 2016

New Findings
What is the central question of this study?
Protease‐activated receptor 2 (PAR2) is located in the endothelial cells of skin vessels and eccrine sweat glands. However, a functional role of PAR2 in the control of cutaneous blood flow and sweating remains to be assessed in humans in vivo.

What is the main finding and its importance?
Our results demonstrate that in normothermic resting humans in vivo, activation of PAR2 elicits cutaneous vasodilatation partly through nitric oxide synthase‐dependent mechanisms, but does not mediate sweating. These results provide important new insights into the physiological significance of PAR2 in human skin.

Protease‐activated receptor 2 (PAR2) is present in human skin, including keratinocytes, endothelial cells of skin microvessels and eccrine sweat glands. However, whether PAR2 contributes functionally to the regulation of cutaneous blood flow and sweating remains entirely unclear in humans in vivo. We hypothesized that activation of PAR2 directly stimulates cutaneous vasodilatation and sweating via actions of nitric oxide synthase (NOS) and cyclo‐oxygenase (COX). In 12 physically active young men (29 ± 5 years old), cutaneous vascular conductance (CVC) and sweat rate were measured at four intradermal microdialysis forearm skin sites that were treated with the following: (i) lactated Ringer's solution (control); (ii) 10 mm NG‐nitro‐l‐arginine (NOS inhibitor); (iii) 10 mm ketorolac (COX inhibitor); or (iv) a combination of both inhibitors. At all sites, a PAR2 agonist (SLIGKV‐NH2) was co‐administered in a dose‐dependent fashion (0.06, 0.18, 0.55, 1.66 and 5 mm, each for 25 min). The highest dose of SLIGKV‐NH2 (5 mm) increased CVC from baseline at the control site (P ≤ 0.05). This increase in CVC associated with PAR2 activation was attenuated by NOS inhibition regardless of the presence or absence of simultaneous COX inhibition (both P ≤ 0.05). However, COX inhibition alone did not affect the PAR2‐mediated increase in CVC (P > 0.05). No increase in sweat rate was measured at any administered dose of SLIGKV‐NH2 (all P > 0.05). We show that in normothermic resting humans in vivo, PAR2 activation does not increase sweat rate, whereas it does modulate cutaneous vasodilatation through NOS‐dependent mechanisms.
High‐fat diet induces protein kinase A and G‐protein receptor kinase phosphorylation of β2‐adrenergic receptor and impairs cardiac adrenergic reserve in animal hearts
Authors: Fu Qin , Hu Yuting , Wang Qingtong , Liu Yongming , Li Ning , Xu Bing , Kim Sungjin , Chiamvimonvat Nipavan , Xiang Yang K. 
Published: December 2016

Key points
Patients with diabetes show a blunted cardiac inotropic response to β‐adrenergic stimulation despite normal cardiac contractile reserve.
Acute insulin stimulation impairs β‐adrenergically induced contractile function in isolated cardiomyocytes and Langendorff‐perfused hearts.
In this study, we aimed to examine the potential effects of hyperinsulinaemia associated with high‐fat diet (HFD) feeding on the cardiac β2‐adrenergic receptor signalling and the impacts on cardiac contractile function.
We showed that 8 weeks of HFD feeding leads to reductions in cardiac functional reserve in response to β‐adrenergic stimulation without significant alteration of cardiac structure and function, which is associated with significant changes in β2‐adrenergic receptor phosphorylation at protein kinase A and G‐protein receptor kinase sites in the myocardium.
The results suggest that clinical intervention might be applied to subjects in early diabetes without cardiac symptoms to prevent further cardiac complications.
AbstractPatients with diabetes display reduced exercise capability and impaired cardiac contractile reserve in response to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. The aim of this study was to understand the impacts of high‐fat diet (HFD) on the insulin–adrenergic receptor signal network in hearts. After 8 weeks of HFD feeding, mice exhibited diabetes, with elevated insulin and glucose concentrations associated with body weight gain. Mice fed an HFD had normal cardiac structure and function. However, the HFD‐fed mice displayed a significant elevation of phosphorylation of the β2‐adrenergic receptor (β2AR) at both the protein kinase A site serine 261/262 and the G‐protein‐coupled receptor kinase site serine 355/356 and impaired adrenergic reserve when compared with mice fed on normal chow. Isolated myocytes from HFD‐fed mice also displayed a reduced contractile response to adrenergic stimulation when compared with those of control mice fed normal chow. Genetic deletion of the β2AR led to a normalized adrenergic response and preserved cardiac contractile reserve in HFD‐fed mice. Together, these data indicate that HFD promotes phosphorylation of the β2AR, contributing to impairment of cardiac contractile reserve before cardiac structural and functional remodelling, suggesting that early intervention in the insulin–adrenergic signalling network might be effective in prevention of cardiac complications in diabetes.
The quantal catecholamine release from mouse chromaffin cells challenged with repeated ACh pulses is regulated by the mitochondrial Na+/Ca2+ exchanger
Authors: López‐Gil Angela , Nanclares Carmen , Méndez‐López Iago , Martínez‐Ramírez Carmen , de los Rios Cristóbal , Padín‐Nogueira J. Fernando , Montero Mayte , Gandía Luis , García Antonio G. 
Published: December 2016

Key points
Upon repeated application of short ACh pulses to C57BL6J mouse chromaffin cells, the amperometrically monitored secretory responses promptly decayed to a steady‐state level of around 25% of the initial response. A subsequent K+ pulse, however, overcame such decay. These data suggest that mouse chromaffin cells have a ready release‐vesicle pool that is selectively recruited by the physiological neurotransmitter ACh.
The ACh‐sensitive vesicle pool is refilled and maintained by the rate of Ca2+ delivery from mitochondria to the cytosol, through the mitochondrial Na+/Ca2+ exchanger (mNCX). ITH12662, a novel blocker of the mNCX, prevented the decay of secretion elicited by ACh pulses and delayed the rate of [Ca2+]c clearance.
This regulatory pathway may be physiologically relevant in situations of prolonged stressful conflicts where a sustained catecholamine release is regulated by mitochondrial Ca2+ circulation through the mNCX, which couples respiration and ATP synthesis to long‐term stimulation of chromaffin cells by endogenously released ACh.
AbstractUsing caged‐Ca2+ photorelease or paired depolarising pulses in voltage‐clamped chromaffin cells (CCs), various pools of secretory vesicles with different readiness to undergo exocytosis have been identified. Whether these pools are present in unclamped CCs challenged with ACh, the physiological neurotransmitter at the splanchnic nerve‐CC synapse, is unknown. We have explored here whether an ACh‐sensitive ready‐release vesicle pool (ASP) is present in C57BL6J mouse chromaffin cells (MCCs). Single cells were fast perfused with a Tyrode solution at 37°C, and challenged with 12 sequential ACh pulses (100 μm, 2 s, every 30 s) plus a K+ pulse given at the end (75 mm K+). After the first 2–3 ACh pulses the amperometrically monitored secretory responses promptly decayed to a steady‐state level of around 25% of the initial response. The last K+ pulse, however, overcame such decay. Repeated ACh pulses to voltage‐clamped cells elicited non‐desensitising nicotinic currents. Also, the [Ca2+]c transients elicited by repeated ACh pulses that were superimposed on a stable baseline elevation did not undergo decay. The novel blocker of the mitochondrial Na+/Ca2+ exchanger (mNCX) ITH12662 prevented the decay of secretion elicited by ACh pulses and delayed the rate of [Ca2+]c clearance. The experiments are compatible with the idea that C57BL6J MCCs have an ASP vesicle pool that is selectively recruited by the physiological neurotransmitter ACh and is regulated by the rate of Ca2+ delivery from mitochondria to the cytosol, through the mNCX.
The How Project: understanding contextual challenges to global surgical care provision in low-resource settings
Authors: Raykar Nakul P , Yorlets Rachel R , Liu Charles , Goldman Roberta , Greenberg Sarah L M , Kotagal Meera , Farmer Paul E , Meara John G , Roy Nobhojit , Gillies Rowan D 
Published: December 2016

Introduction5 billion people around the world do not have access to safe, affordable, timely surgical care. This series of qualitative interviews was launched by TheLancetCommission on Global Surgery (LCoGS) with the aim of understanding the contextual challenges—the specific circumstances—faced by surgical care providers in low-resource settings who care for impoverished patients, and how those providers overcome these challenges.MethodsFrom January 2014 to February 2015, 20 LCoGS collaborators conducted semistructured interviews with 148 surgical providers in low-resource settings in 21 countries. Stratified purposive sampling was used to include both rural and urban providers, and reputational case selection identified individuals. Interviewers were trained with an implementation manual. Following immersion into de-identified texts from completed interviews, topical coding and further analysis of coded texts was completed by an independent analyst with periodic validation from a second analyst.ResultsProviders described substantial financial, geographic and cultural barriers to patient access. Rural surgical teams reported a lack of a trained workforce and insufficient infrastructure, equipment, supplies and banked blood. Urban providers face overcrowding, exacerbated by minimal clinical and administrative support, and limited interhospital care coordination. Many providers across contexts identified national health policies that do not reflect the realities of resource-poor settings. Some findings were region-specific, such as weak patient–provider relationships and unreliable supply chains. In all settings, surgical teams have created workarounds to deliver care despite the challenges.DiscussionWhile some differences exist between countries, the barriers to safe surgery and anaesthesia are overall consistent and resource-dependent. Efforts to advance and expand global surgery must address these commonalities, while local policymakers can tailor responses to key contextual differences.
How did rapid scale-up of HIV services impact on workplace and interpersonal trust in Zambian primary health centres: a case-based health systems analysis
Authors: Topp Stephanie M , Chipukuma Julien M 
Published: December 2016

BackgroundIn sub-Saharan Africa, large amounts of funding continue to be directed towards HIV-specific care and treatment, often with claims of ‘health system strengthening’ effect. Such claims rarely account for the impact on human relationships and decisions that are core to functional health systems. This research examined how establishment of externally funded HIV services influenced trusting relationships in Zambian health centres.MethodsAn in-depth, multicase study included four health centres selected for urban, peri-urban and rural characteristics. Case data included healthcare worker (HCW) interviews (60); patient interviews (180); direct observation of facility operations (2 weeks/centre) and key informant interviews (14) which were recorded and transcribed verbatim. Thematic analysis adopted inductive and deductive coding guided by a framework incorporating concepts of workplace trust, patient–provider trust, intrinsic and extrinsic motivation.ResultsHIV service scale-up impacted trust in positive and negative ways. Investment in HIV-specific infrastructure, supplies and quality assurance mechanisms strengthened workplace trust, HCW motivation and patient–provider trust in HIV departments in the short-term. In the health centres more broadly and over time, however, non-governmental organisation-led investment and support of HIV departments reinforced HCW's perceptions of the government as uninterested or unable to provide a quality work environment. Exacerbating existing perceptions of systemic workplace inequity and nepotism, uneven distribution of personal and professional opportunities related to HIV service establishment contributed to interdepartmental antagonism and reinforced workplace practices designed to protect individual HCW's interests.ConclusionsFindings illustrate long-term negative effects of the vertical HIV resourcing and support structures which failed to address and sometimes exacerbated HCW (dis)trust with their own government and supervisors. The short-term and long-term effects of weakened workplace trust on HCWs' motivation and performance signal the importance of understanding how such relationships play a role in generating virtuous or perverse cycles of actor interactions, with implications for service outcomes.
Influence of oxygen partial pressure on the metastable copper oxide thin films
Authors: Geçici Birol , Korkmaz Şadan , Özen Soner , Şenay Volkan , Pat Suat 
Published: December 2016

Paramelaconite (Cu4O3) is a metastable copper oxide. Metastable copper oxide thin films were deposited on glass substrates by reactive RF magnetron sputtering in argon (Ar) and oxygen (O2) gas mixture atmospheres. Ar/O2 gas ratios in the sputtering ambient were chosen as 1/1 and 1/9. The surface and optical properties were determined by X-ray diffractometer (XRD), atomic force microscope (AFM) and UV-Vis spectrophotometer. The XRD patterns of the samples exhibited single strong diffraction peaks at 35.39[Formula: see text] and 35.49[Formula: see text], corresponding to the (202) peak of Cu4O3. The mean thickness values were measured as 100 nm and 80 nm for the films deposited at 1/1 and 1/9 Ar/O2 gas ratios, respectively. The samples showed low transmittance and high absorbance in the high frequency region.
Human Papillomavirus Regulates HER3 Expression in Head and Neck Cancer: Implications for Targeted HER3 Therapy in HPV+ Patients
Authors: Brand Toni M. , Hartmann Stefan , Bhola Neil E. , Peyser Noah D. , Li Hua , Zeng Yan , Isaacson Wechsler Erin , Ranall Max V. , Bandyopadhyay Sourav , Duvvuri Umamaheswar , LaVallee Theresa M. , Jordan Richard C.K. , Johnson Daniel E. , Grandis Jennifer R. 
Published: December 2016

Abstract

Purpose:
Human papillomavirus (HPV) 16 plays an etiologic role in a growing subset of head and neck squamous cell carcinomas (HNSCC), where viral expression of the E6 and E7 oncoproteins is necessary for tumor growth and maintenance. Although patients with HPV+ tumors have a more favorable prognosis, there are currently no HPV-selective therapies. Recent studies identified differential receptor tyrosine kinase (RTK) profiles in HPV+ versus HPV− tumors. One such RTK, HER3, is overexpressed and interacts with phosphoinositide-3-kinase (PI3K) in HPV+ tumors. Therefore, we investigated the role of HPV oncoproteins in regulating HER3-mediated signaling and determined whether HER3 could be a molecular target in HPV+ HNSCC.

Experimental Design:
HER3 was investigated as a molecular target in HPV+ HNSCC using established cell lines, patient-derived xenografts (PDX), and human tumor specimens. A mechanistic link between HPV and HER3 was examined by augmenting E6 and E7 expression levels in HNSCC cell lines. The dependency of HPV+ and HPV− HNSCC models on HER3 was evaluated with anti-HER3 siRNAs and the clinical stage anti-HER3 monoclonal antibody KTN3379.

Results:
HER3 was overexpressed in HPV+ HNSCC, where it was associated with worse overall survival in patients with pharyngeal cancer. Further investigation indicated that E6 and E7 regulated HER3 protein expression and downstream PI3K pathway signaling. Targeting HER3 with siRNAs or KTN3379 significantly inhibited the growth of HPV+ cell lines and PDXs.

Conclusions:
This study uncovers a direct relationship between HPV infection and HER3 in HNSCC and provides a rationale for the clinical evaluation of targeted HER3 therapy for the treatment of HPV+ patients. Clin Cancer Res; 23(12); 3072–83. ©2016 AACR.