bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety: a cross-sectional survey in the private sector in Uganda
Authors: Mbonye Anthony K , Buregyeya Esther , Rutebemberwa Elizeus , Clarke Siân E , Lal Sham , Hansen Kristian S , Magnussen Pascal , LaRussa Philip 
Published: March 2016

ObjectivesThe main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety in the private health sector in Uganda.MethodsA survey was conducted within 57 parishes from August to October 2014 in Mukono District, Uganda. Data was captured on the following variables: drug shop characteristics, training of staff in management of pneumonia, availability of guidelines and basic equipment, available antibiotics, knowledge on treatment of pneumonia in children aged <5 years. The main study outcome was the proportion of private health facilities prescribing an antibiotic.ResultsA total of 170 registered drug shops were surveyed between August and October 2014. The majority of drug shops, 93.5% were prescribing antibiotics, especially amoxicillin and trimethoprim-sulfamethoxazole (septrin). The professional qualification of a provider was significantly associated with this practice, p=0.04; where lower cadre staff (nursing assistants and enrolled nurses) overprescribed antibiotics. A third, 29.4% of drug shop providers reported that antibiotics were the first-line treatment for children with diarrhoea; yet the standard guideline is to give oral rehydration salts and zinc tablets. Only few providers, 8.2%, had training on antibiotics, with 10.6% on pneumonia case management. Further to this, 7.1% drug shops had WHO-Integrated Management of Childhood Illness guidelines, and a negligible proportion (<1%) had respiratory timers and baby weighing scales. Although the majority of providers, 82.4%, knew severe signs and symptoms of pneumonia, few, 17.6%, knew that amoxicillin was the first-line drug for treatment of pneumonia in children according to the guidelines.ConclusionsThere is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets.
Enhanced Histone Deacetylase Activity in Malignant Melanoma Provokes RAD51 and FANCD2-Triggered Drug Resistance
Authors: Krumm Andrea , Barckhausen Christina , Kücük Pelin , Tomaszowski Karl-Heinz , Loquai Carmen , Fahrer Jörg , Krämer Oliver Holger , Kaina Bernd , Roos Wynand Paul 
Published: March 2016

Abstract
DNA-damaging anticancer drugs remain a part of metastatic melanoma therapy. Epigenetic reprogramming caused by increased histone deacetylase (HDAC) activity arising during tumor formation may contribute to resistance of melanomas to the alkylating drugs temozolomide, dacarbazine, and fotemustine. Here, we report on the impact of class I HDACs on the response of malignant melanoma cells treated with alkylating agents. The data show that malignant melanomas in situ contain a high level of HDAC1/2 and malignant melanoma cells overexpress HDAC1/2/3 compared with noncancer cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes malignant melanoma cells to apoptosis following exposure to alkylating agents, while not affecting primary melanocytes. Inhibition of HDAC1/2/3 caused sensitization of melanoma cells to temozolomide in vitro and in melanoma xenografts in vivo. HDAC1/2/3 inhibition resulted in suppression of DNA double-strand break (DSB) repair by homologous recombination because of downregulation of RAD51 and FANCD2. This sensitized cells to the cytotoxic DNA lesion O6-methylguanine and caused a synthetic lethal interaction with the PARP-1 inhibitor olaparib. Furthermore, knockdown experiments identified HDAC2 as being responsible for the regulation of RAD51. The influence of class I HDACs on DSB repair by homologous recombination and the possible clinical implication on malignant melanoma therapy with temozolomide and other alkylating drugs suggests a combination approach where class I HDAC inhibitors such as valproic acid or MS-275 (entinostat) appear to counteract HDAC- and RAD51/FANCD2-mediated melanoma cell resistance. Cancer Res; 76(10); 3067–77. ©2016 AACR.
CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation
Authors: Liu Yuan , Amin Elianna B. , Mayo Marty W. , Chudgar Neel P. , Bucciarelli Peter R. , Kadota Kyuichi , Adusumilli Prasad S. , Jones David R. 
Published: March 2016

Abstract
Breast cancer metastasis suppressor 1 (BRMS1) is decreased in non–small cell lung cancer (NSCLC) and other solid tumors, and its loss correlates with increased metastases. We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ϵ–mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome–induced BRMS1 degradation. Using our in vivo orthotopic mouse model of lung cancer metastases, we found that mutation of S30 in BRMS1 or the use of the CK2-specific small-molecule inhibitor CX4945 abrogates CK2α'-induced cell migration and invasion and decreases NSCLC metastasis by 60-fold. Analysis of 160 human NSCLC specimens confirmed that tumor CK2α' and cytoplasmic BRMS1 expression levels are associated with increased tumor recurrence, metastatic foci, and reduced disease-free survival. Collectively, we identify a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. Cancer Res; 76(9); 2675–86. ©2016 AACR.
Effectiveness of Prophylactic Surgeries inBRCA1orBRCA2Mutation Carriers: A Meta-analysis and Systematic Review
Authors: Li Xiao , You Ran , Wang Xinwei , Liu Congxin , Xu Zicheng , Zhou Jin , Yu Bin , Xu Ting , Cai Hongzhou , Zou Qing 
Published: March 2016

AbstractPurpose: To systematically investigate the effectiveness of prophylactic surgeries (PS) implemented in women carrying BRCA1/2 mutations.Experimental Design: The PubMed database was searched till August 2014 and 15 studies met the inclusion criteria. Fixed- or random-effects models were conducted according to study heterogeneity. We calculated the pooled relative risks (RR) for cancer risk or mortality along with 95% confidence intervals (CI).Results: Prophylactic bilateral salpingo-oophorectomy (PBSO) and bilateral prophylactic mastectomy (BPM) were both associated with a decreased breast cancer risk in BRCA1/2 mutation carriers (RR, 0.552; 95% CI, 0.448–0.682; RR, 0.114; 95% CI, 0.041–0.317, respectively). Similar findings were observed in BRCA1 and BRCA2 mutation carriers separately. Moreover, contralateral prophylactic mastectomy (CPM) significantly decreased contralateral breast cancer incidence in BRCA1/2 mutation carriers (RR, 0.072; 95% CI, 0.035–0.148). Of note, PBSO was associated with significantly lower all-cause mortality in BRCA1/2 mutation carriers without breast cancer (HR, 0.349; 95% CI, 0.190–0.639) and those with breast cancer (HR, 0.432; 95% CI, 0.318–0.588). In addition, all-cause mortality was significantly lower for patients with CPM than those without (HR, 0.512; 95% CI, 0.368–0.714). However, BPM was not significantly associated with reduced all-cause mortality. Data were insufficient to obtain separate estimates of survival benefit with PS in BRCA1 or BRCA2 mutation carriers.Conclusions: BRCA1/2 mutation carriers who have been treated with PS have a substantially reduced breast cancer incidence and mortality. Clin Cancer Res; 22(15); 3971–81. ©2016 AACR.
Chemotherapy-Induced Inflammatory Gene Signature and Protumorigenic Phenotype in Pancreatic CAFs via Stress-Associated MAPK
Authors: Toste Paul A. , Nguyen Andrew H. , Kadera Brian E. , Duong Mindy , Wu Nanping , Gawlas Irmina , Tran Linh M. , Bikhchandani Mihir , Li Luyi , Patel Sanjeet G. , Dawson David W. , Donahue Timothy R. 
Published: March 2016

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer-associated fibroblasts (CAF). CAFs promote tumor growth, metastasis, and treatment resistance. This study aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAF) were generated by continuous incubation in gemcitabine. Gene expression differences between treatment-naïve CAFs (N-CAF) and R-CAFs were compared by array analysis. Functionally, tumor cells (TC) were exposed to N-CAF– or R-CAF–conditioned media and assayed for migration, invasion, and viability in vitro. Furthermore, a coinjection (TC and CAF) model was used to compare tumor growth in vivo. R-CAFs increased TC viability, migration, and invasion compared with N-CAFs. In vivo, TCs coinjected with R-CAFs grew larger than those accompanied by N-CAFs. Genomic analysis demonstrated that R-CAFs had increased expression of various inflammatory mediators, similar to the previously described senescence-associated secretory phenotype (SASP). In addition, SASP mediators were found to be upregulated in response to short duration treatment with gemcitabine in both immortalized and primary CAFs. Inhibition of stress-associated MAPK signaling (P38 MAPK or JNK) attenuated SASP induction as well as the tumor-supportive functions of chemotherapy-treated CAFs in vitro and in vivo. These results identify a negative consequence of chemotherapy on the PDAC microenvironment that could be targeted to improve the efficacy of current therapeutic regimens.
Implications: Chemotherapy treatment of pancreatic cancer–associated fibroblasts results in a proinflammatory response driven by stress-associated MAPK signaling that enhances tumor cell growth and invasiveness. Mol Cancer Res; 14(5); 437–47. ©2016 AACR.
Genetic Risk Scores Predict Recurrence of Acute Coronary Syndrome
Authors: Vaara Satu , Tikkanen Emmi , Parkkonen Olavi , Lokki Marja-Liisa , Ripatti Samuli , Perola Markus , Nieminen Markku S. , Sinisalo Juha 
Published: March 2016

Background—
Several clinical risk estimation tools have established their role in the prediction of recurrence of acute coronary syndrome (ACS), but the value of genetic risk scores (GRSs) remains unclear. We examined how well 2 different GRSs estimate recurrent ACS and whether clinical factors are associated with GRSs.

Methods and Results—

A cohort of 2090 consecutive patients with ACS who underwent coronary angiography between July 2006 and March 2008 in a single tertiary center was genotyped and prospectively followed up for a median of 5.5 years. We formed 2 partially overlapping GRSs: GRS47 of 47 single-nucleotide polymorphisms with previously reported significant association with coronary artery disease and GRS153 of 153 single-nucleotide polymorphisms with significant or suggestive association with coronary artery disease. GRS47 showed association with recurrent ACS independent of clinical factors (
P
=0.037; hazard ratio, 1.17; 95% confidence interval, 1.01–1.36). GRS153 had no association with either recurrent ACS or composite of recurrent ACS or death. Also, GRS47 was associated inversely with smoking and ST-segment–elevation myocardial infarction (
P
=0.004; odds ratio, 0.22; 95% confidence interval, 0.08–0.62 and
P
=0.041; odds ratio, 0.36; 95% confidence interval, 0.13–0.96, respectively).

Conclusions—
GRSs combined of 47 known coronary artery disease risk single-nucleotide polymorphisms were associated with recurrent ACS after multivariable adjustments in a heterogenic ACS population for the first time. Smoking and ST-segment–elevation myocardial infarction had an inverse association with the GRSs. The significance of smoking in relation to genetic coronary artery disease predisposition may merit further evaluation in patients with ACS.
Retinal Microvascular Calibers Are Associated With Enlarged Perivascular Spaces in the Brain
Authors: Mutlu Unal , Adams Hieab H.H. , Hofman Albert , Lugt Aad van der , Klaver Caroline C.W. , Vernooij Meike W. , Ikram M. Kamran , Ikram M. Arfan 
Published: March 2016

Background and Purpose—
Perivascular enlargement in the brain is a putative imaging marker for microvascular brain damage, but this link has not yet been confirmed using direct in vivo visualization of small vessels. We investigated the relation between microvascular calibers on retinal imaging and enlarged perivascular spaces (ePVSs) on brain magnetic resonance imaging.

Methods—
We included 704 participants from the Rotterdam study. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. ePVSs were counted in the centrum semiovale, basal ganglia, hippocampus, and mesencephalon, using a standardized rating method. We determined the association between retinal microvascular calibers and ePVSs with negative binomial regression models, adjusting for age, sex, the other vascular caliber, structural brain magnetic resonance imaging markers, and cardiovascular risk factors.

Results—
Both narrower arteriolar and wider venular calibers were associated with more ePVSs in the centrum semiovale and hippocampal region. Rate ratios (95% confidence interval) for arterioles in the centrum semiovale and hippocampus were 1.07 (1.01–1.14) and 1.13 (1.04–1.22), respectively, and for venules 1.08 (1.01–1.16) and 1.09 (1.00–1.18), respectively. These associations were independent from other brain magnetic resonance imaging markers and cardiovascular risk factors.

Conclusions—
Retinal microvascular calibers are related to ePVSs, confirming the putative link between microvascular damage and ePVSs.
Does Diffusion Lesion Volume Above 70 mL Preclude Favorable Outcome Despite Post-Thrombolysis Recanalization?
Authors: Tisserand Marie , Turc Guillaume , Charron Sylvain , Legrand Laurence , Edjlali Myriam , Seners Pierre , Roca Pauline , Lion Stéphanie , Naggara Olivier , Mas Jean-Louis , Méder Jean-François , Baron Jean-Claude , Oppenheim Catherine 
Published: March 2016

Background and Purpose—
Whether to withhold recanalization treatment when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is unsettled. Our aim was to assess the impact of recanalization on outcome in patients with baseline DWI lesion ≥70 mL (DWI≥70 mL) treated ≤4.5 hours from onset. We hypothesized that recanalization is beneficial in a sizeable fraction of these patients and that this is associated with a larger DWI lesion reversal.

Methods—
We analyzed 267 consecutive patients treated with intravenous recombinant tissue-type plasminogen activator for middle cerebral artery territory stroke in whom an occlusion was present on magnetic resonance angiography and 24-hour recanalization and 90-day clinical outcome could be assessed. After stratification relative to the 70-mL DWI lesion cut point, we calculated the odds ratio for recanalization of the primary arterial occlusive lesion (AOL score ≥2) to predict favorable outcome (modified Rankin scale score ≤2). DWI lesion reversal was compared between recanalizers with DWI≥70 mL with favorable and unfavorable outcomes.

Results—

Median (interquartile range) DWI lesion volume was 22 mL (10–60), and median onset time to imaging was 116 minutes (86–151). Twelve (22%) of the 54 patients with DWI≥70 mL experienced favorable outcome, of which 9 had recanalized. In patients with DWI≥70 mL, recanalization was significantly associated with favorable outcome after adjustment for age and National Institutes of Health Stroke Scale (odds ratio =4.72 [1.09–20.32];
P
=0.0375). Among recanalizers with DWI≥70 mL, absolute and relative DWI reversal volumes were larger in those with favorable as compared with unfavorable outcome (18.8 mL [12.2–47.6] versus 8.5 mL [4.3–31.1];
P
=0.17; and 19.6% [10.9–62.8] versus 8.7% [3.9–16.5], respectively;
P
=0.049).

Conclusions—
Patients with DWI lesion volume ≥70 mL can benefit from recanalization after intravenous recombinant tissue-type plasminogen activator. This may partly reflect a larger amount of DWI lesion reversal.
THE HONG KONG CANTONESE SPEECH COMMUNITY
Authors: Bauer Robert S. 
Published: March 2016

Paroe qu'il est parlé par plus de 90 % de la population de Hong Kong qui compte 5 millions 300 000 personnes, le cantonais est le dialecte chinois le plus important après le mandarin. Nul doute que cette situation changera lorsque le statut politique de Hong Kong sera modifié en 1997.
Cet article retrace l'évolution historique et linguistique de Hong Kong et analyse les facteurs de développement du cantonais dans l'île avant de caractériser dans le détail la situation socio-linguistique de Hong Kong par un examen attentif des données statistiques dont on dispose sur la population de Hong Kong.
DEVELOPMENT OF A MANDARIN-SPEAKING CHILD'S COMPREHENSION OF WH-QUESTIONS
Authors: Thomas LEE Hun-tak 
Published: March 2016

On s'attache ici à décrire le développement de la compréhension des interrogatifs chez un enfant entre l'âge de 17;0 à 24;0 parlant le mandarin. Les données se composent d'enregistrements au magnétophone et de notes personnelles. Les questions posées sont les suivantes : Quand et comment l'enfant apprend-il à distinguer entre les interrogatifs et les autres parties du discours ? Quelles stratégies de réponse adopte-t-il face aux interrogatifs employés par les adultes ? Quelles sont les évolutions dans sa compréhension des questions avec shenme "quoi ?", nali "où ?" et shei "qui ?" ?On apporte des éléments qui permettent de répondre que l'enfant, face aux questions qu'il ne comprend pas, s'appuie sur la répétition d'éléments se trouvant dans la question et sur des réponses stéréotypées.
Les informations recueillies indiquent que la compréhension des interrogatifs peuvent suivre plusieurs phases de développement. Enfin, on compare les niveaux de compréhension et de production de phrases avec des interrogatifs chez l'enfant.
Wood anatomy and acoustic properties of selected tropical hardwoods
Authors: Baar Jan , Tippner Jan , Gryc Vladimir 
Published: March 2016

Selected anatomical features and ground tissue composition were studied in four tropical hardwoods (Afzelia sp. [Doussié], Intsia sp. [Merbau], Astronium sp. [Muiracatiara] and Millettia sp. [Wengé]). These woods can be applied in musical instrument production, especially for xylophone bars. The measured density, 1st bending natural frequency and the logarithmic decrement of damping were used to calculate other acoustic properties such as dynamic young modulus of elasticity (Erf), specific modulus of elasticity (E´/ρ), internal friction (tan δ), and acoustic conversion efficiency (ACE).
The correlations between anatomy and acoustic properties were determined. Despite difficulties in specifying general characteristics of hardwoods due to their complicated and variable structure, correlations valid between species were found for specific modulus of elasticity. Specific modulus of elasticity was negatively correlated with ray tissue volume and positively with ray height to width ratio and fiber length. The diversity in ground tissue composition was the main criterion for the species choice and probably should condition diverse correlations of anatomical features found for individual species. It seems that better acoustic properties (higher stiffness, ACE or specific modulus of elasticity) are performed by wood with longer fibers and slender rays, causing minimal deflection of adjoining fibers.
Reconstruction of Lateral Skull Base Defects
Authors: Howard Brittany E. , Nagel Thomas H. , Barrs David M. , Donald Carrlene B. , Hayden Richard E. 
Published: March 2016

ObjectivesTo compare reconstructive techniques, operative times, duration of hospitalization, and need for subsequent flap revisions between reconstructive approaches to lateral skull base defects.Study DesignCase series with chart review.SettingTertiary academic referral center.SubjectsPatients (n = 31) undergoing reconstruction of composite lateral skull base defects from 2002 to 2014.MethodsData were analyzed for demographics, tumor characteristics, reconstructive technique, operative time, duration of hospitalization, complications, and outcomes.ResultsThirty‐one patients were identified for inclusion. Lateral temporal bone defects resulted from resection of malignant lesions, including squamous cell carcinoma (n = 25), basal cell carcinoma (n = 2), and other carcinoma (n = 4). Defects were reconstructed with submental flaps (n = 16), pedicled latissimus dorsi flaps (n = 6), and free anterolateral thigh flaps (n = 9). All cases involved neurosurgery, neurotology, and head and neck surgery services. Although time of surgical resection was similar, time saving was noticed with submental reconstruction. Compared with free flaps, submental flap reconstruction was associated with significantly reduced total operative time (mean, 544 vs 683 min; P =. 00817) and duration of hospitalization (4.9 vs 9.8 days; P =. 02067). Submental flaps were significantly less likely to require revision debulking procedures (mean = 0.6) compared with latissimus dorsi flaps (mean, 1.3; P <. 00001) and free flaps (mean, 1.6; P <. 00001). There was 100% flap survival.ConclusionThe musculocutaneous submental flap provides an excellent option for reconstruction of lateral skull base defects given its proximity, reliability, ease of harvest, and exceptional color match. Submental flap reconstruction was associated with reduced operative time, hospitalization duration, and flap revisions.
Upper Airway Stimulation for OSA
Authors: Kent David T. , Lee Jake J. , Strollo Patrick J. , Soose Ryan J. 
Published: March 2016

ObjectiveTo review outcome measures and objective adherence data for patients treated with hypoglossal nerve stimulation (HNS) therapy for moderate to severe obstructive sleep apnea (OSA).Study DesignCase series with chart review.SettingAcademic sleep medicine center.Subjects and MethodsThe first 20 implanted patients to complete postoperative sleep laboratory testing were assessed. All patients had moderate to severe OSA, were unable to adhere to positive pressure therapy, and met previously published inclusion criteria for the commercially available implantable HNS system. Data included demographics, body mass index (BMI), apnea‐hypopnea index (AHI), Epworth Sleepiness Score (ESS), nightly hours of device usage, and procedure‐ and therapy‐related complications.ResultsMean age was 64.8 ± 12.0 years, with 50% female. Mean BMI was unchanged postoperatively (26.5 ± 4.2 to 26.8 ± 4.5 kg/m2; P >. 05). Mean AHI (33.3 ± 13.0 to 5.1 ± 4.3; P <. 0001) and mean ESS (10.3 ± 5.2 to 6.0 ± 4.4; P <. 01) decreased significantly. Seventy percent (14/20) of patients achieved a treatment AHI <5, 85% (17/20) an AHI <10, and 95% (19/20) an AHI <15. Average stimulation amplitude was 1.89 ± 0.50 V after titration. Adherence monitoring via device interrogation showed high rates of voluntary device use (mean 7.0 ± 2.2 h/night).ConclusionFor a clinical and anatomical subset of patients with OSA, HNS therapy is associated with good objective adherence, low morbidity, and improved OSA outcome measures. Early results at one institution suggest that HNS therapy can be implemented successfully into routine clinical practice, outside of a trial setting.