bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Sandwich ELISA for Tartrate-Resistant Acid Phosphatase 5a and 5b Protein Reveals that Both Isoforms are Secreted by Differentiating Osteoclasts and Correlate to the Type I Collagen Degradation Marker CTX-I In Vivo and In Vitro
Authors: Mira-Pascual Laia , Patlaka Christina , Desai Suchita , Paulie Staffan , Näreoja Tuomas , Lång Pernilla , Andersson Göran 
Published: October 2019

AbstractTartrate-resistant acid phosphatase type 5 (TRAP) exists as two isoforms, 5a and 5b. 5b is a marker of osteoclast number and 5a of chronic inflammation; however, its association with bone resorption is unknown. In this study, a double-TRAP 5a/5b sandwich ELISA measuring 5a and 5b protein in the same sample was developed. TRAP 5a and 5b protein levels were evaluated as osteoclast differentiation/activity markers in serum and in culture, and their correlation to the resorption marker CTX-I was examined. Serum TRAP 5a and 5b concentrations in healthy men were 4.4 ± 0.6 ng/ml and 1.3 ± 0.2 ng/ml, respectively, and they correlated moderately to each other suggesting that their secretion is coupled under healthy conditions. A correlation was also observed between serum TRAP 5a and 5b with CTX-I, suggesting that both TRAP isoforms associate with osteoclast number. During osteoclast differentiation on plastic/bone, predominantly 5b increased in media/lysate from M-CSF/RANKL-stimulated CD14+ PBMCs. However, substantial levels of 5a were detected at later stages suggesting that both isoforms are secreted from differentiating OCs. More TRAP 5b was released on bone indicating a connection to osteoclast resorptive activity, and a peak in TRAP 5b/5a-ratio coincided with rapid CTX-I release. At the end of the culture period of M-CSF + RANKL-stimulated CD14+ PBMCs, there was a correlation between the secretion of TRAP 5a and 5b proteins with CTX-I. The correlation of not only 5b but also 5a with collagen degradation, both in serum and osteoclast cultures indicates that a considerable proportion of the TRAP 5a originates from osteoclasts and may reflect a hitherto undisclosed regulatory mechanism during bone resorption and bone remodeling.
Curative Surgery Improves Survival for Colorectal Cancer in Rural Kenya
Authors: Parker Robert K. , Mwachiro Michael M. , Ranketi Sinkeet S. , Mogambi Faith C. , Topazian Hillary M. , White Russell E. 
Published: October 2019

AbstractBackground/aimsColorectal cancer (CRC) is increasing in low‐ and middle‐income countries. Surgical care is essential for the treatment. Many patients do not have access to curative surgery for colorectal cancer in rural Kenya. To better understand the impact of surgical care on colorectal cancer in a resource‐limited setting, we compared the experience of patients undergoing operations to those who did not.MethodsAll patients with histologically confirmed CRC at Tenwek Hospital from January 1, 1999, to December 31, 2017, were reviewed. Demographic and clinical data were extracted from records when available. The exposure was either curative operation, palliative operation, or no operation. The primary outcome was survival at 5 years, assessed with Cox proportional hazard analysis after propensity‐score matching for age, sex, tumor site, time period, and stage.ResultsOne hundred and sixty‐five patients were identified on chart review. Survival information was available for 150 patients with a median follow‐up of 319 days. Fifty‐two percent had colon cancer and 48% had rectal cancer. At diagnosis, the mean age was 55.4 years (SD: 16.7) and the male to female ratio was 1.1:1. Thirty‐nine percent underwent curative operations, 25% palliative operations, and 36% no operations. One‐year survival was estimated to be 98% for curative surgery, 73% for palliative surgery, and 83% for no surgery (p = 0.0005). On crude analysis, 5‐year survival improved with curative operation in comparison to no operation with a hazard ratio of 0.30 (CI: 0.14–0.64) (p = 0.002). After propensity matching, the hazard ratio for curative operation versus no operation remained significant, 0.34 (CI: 0.14–0.80) (p = 0.01).ConclusionsCurative surgery improves survival in our resource‐limited environment. Although various factors contribute to the use of surgical treatment, the survival advantage persists after adjusted analysis. Barriers exist for access to prompt surgical evaluation and treatment. Surgical care should be a priority to address the increasing burden of CRC in resource‐limited settings.
The Efficacy of Coil Embolization to Obtain Intrahepatic Redistribution in Radioembolization: Qualitative and Quantitative Analyses
Authors: Alsultan Ahmed A. , van Roekel Caren , Barentsz Maarten W. , Braat Arthur J. A. T. , van Doormaal Pieter Jan , Lam Marnix G. E. H. , Smits Maarten L. J. 
Published: October 2019

Abstract

Purpose
To evaluate the efficacy of coil embolization to obtain intrahepatic redistribution in patients undergoing radioembolization.

Materials and Method
All patients treated with radioembolization at our institute were retrospectively analyzed, and all cases in which a tumor-feeding vessel was coil-embolized were selected. Two nuclear medicine physicians visually assessed the effect of redistribution. Furthermore, the redistribution of microspheres was measured by quantifying the activity distributed to the coil-embolized (dependent) segment relative to the other (non-dependent) segments and to the tumor(s) in that segment. Quantitative analysis was performed on post-treatment 90Y-PET and 166Ho-SPECT using Simplicit90Y software. Lesion response was measured according to RECIST 1.1 criteria at 3 months post-treatment.

Results
Out of 37 cases, 32 were suitable for quantitative analysis and 37 for qualitative analysis. In the qualitative analysis, redistribution was deemed successful in 69% of cases. The quantitative analysis showed that the median ratio of the activity to the dependent embolized segments and the non-dependent segments was 0.88 (range 0.26–2.05) and 0.80 (range 0.19–1.62) for tumors in dependent segments compared with tumors in non-dependent segments. Using a cutoff ratio of 0.7 (30% lower activity concentration in comparison with the rest of the liver), 57% of cases were successful. At 3 months post-treatment, 6% of dependent tumors had partial response, 20% progressive disease, and 74% stable disease. In non-dependent tumors, this was, respectively, 16%, 20%, and 64%.

Conclusion
Coil embolization of hepatic arteries to induce redistribution of microspheres has a limited success rate. Qualitative assessment tends to overrate redistribution.
Investigating the risk of breast cancer among women exposed to chemicals: a nested case–control study using improved exposure estimates
Authors: Videnros Cecilia , Selander Jenny , Wiebert Pernilla , Albin Maria , Plato Nils , Borgquist Signe , Manjer Jonas , Gustavsson Per 
Published: October 2019

Abstract

Purpose
The aim of this study was to examine if exposures to chemicals at the workplace were associated with an increased risk of postmenopausal breast cancer, using improved exposure estimates.

Methods
The design is a case–control study, nested within a cohort of women from the Malmö Diet and Cancer Study. The study comprised 2400 women, 731 cases and 1669 matched controls, born 1923–1950 and living in Malmö, Sweden between 1991 and 1996. An occupational hygienist reclassified the probability for exposure given by a job-exposure matrix, using individual data on work tasks. First-time diagnoses of invasive breast cancer were identified through the Swedish Cancer Registry.

Results
Women exposed to chemicals in their occupational environment had a statistically significantly increased risk (OR 1.59, 95% CI 1.11–2.29) of breast cancer, and the risk correlated positively with duration of exposure but not with exposure intensity. Women exposed to chlorinated hydrocarbon solvents for more than 10 years had a significant higher risk of breast cancer (OR 3.06, 95% CI 1.18–7.96) as well as women exposed to oil mist for more than 10 years (OR 3.08, 95% CI 1.12–8.49).

Conclusions
This study gives some support to the hypothesis that exposure to organic solvents as well as oil mist is associated with increased risk of breast cancer.
Evaluation of preoperative risk factors for postpancreatectomy hemorrhage
Authors: Izumo Wataru , Higuchi Ryota , Yazawa Takehisa , Uemura Shuichiro , Shiihara Masahiro , Yamamoto Masakazu 
Published: October 2019

Abstract

Purpose
To investigate the risk factors for post-pancreatectomy hemorrhage (PPH).

Methods
The incidence, outcome, and risk factors for PPH were evaluated in 1169 patients who underwent pancreatectomy.

Results
The incidence and mortality rates of PPH were 3% and 11% in all pancreatectomies, 4% and 11% in pancreatoduodenectomy, 1% and 20% in distal pancreatectomy, and 3% and 0% in total pancreatectomy, respectively. Male sex [odds ratio (OR) 2.32], body mass index (BMI) ≥ 25 kg/m2 (OR 3.70), absence of diabetes mellitus (DM; HbA1c ≤ 6.2%; OR 3.62), and pancreatoduodenectomy (OR 3.06) were risk factors for PPH after all pancreatectomies. The PPH incidence was 0%, 1%, 2%, 6%, and 20% in patients with risk scores of 0 (n = 65), 1 (n = 325), 2 (n = 455), 3 (n = 299), and 4 (n = 25), respectively. The differences between risk-score groups 0–2 (2%) and 3–4 (7%) were significant (P < 0.05, OR 4.7). In patients who had undergone pancreatoduodenectomy, postoperative pancreatic fistula (POPF; OR 31.7) and absence of DM (OR 3.45) were risk factors for PPH. There was no significant association between POPF and PPH after distal pancreatectomy (P = 0.28). The incidence of POPF post-pancreatoduodenectomy was 20%. BMI ≥ 25 kg/m2 (OR 3.17), serum albumin < 3.5 g/dl (OR 1.77), absence of DM (OR 1.75), distal extrahepatic bile duct carcinoma (OR 4.05), and carcinoma of the papilla of Vater (OR 5.19) were risk factors for POPF post-pancreatoduodenectomy.

Conclusion
Our study clarified the preoperative risk factors for PPH and recommends using a risk scoring system that includes “absence of DM” for predicting PPH.
Dose-dependent green tea effect on decrease of inflammation in human oral gingival epithelial keratinocytes: in vitro study
Authors: Hagiu Ana , Attin Thomas , Schmidlin Patrick R. , Ramenzoni Liza L. 
Published: October 2019

Abstract

Objectives
This in vitro study aimed to analyze the anti-inflammatory and wound healing potential of green tea extract (GTE) in human gingival epithelial keratinocytes (HGEK) treated with lipopolysaccharides (LPS).

Materials and methods
A cell viability assay was conducted using MTT to determine nontoxic levels of GTE on immortalized HGEK. Cells were concomitantly treated with LPS (1 μg/ml) and GTE (1 mg/ml, 2.5 mg/ml, 5 mg/ml, and 10 mg/ml) to assess inflammation. Gene expression levels of inflammatory markers IL-β1, IL-6, and TNFα were measured by RT-PCR and their protein production was assessed by ELISA. The scratch wound healing assay was used to investigate the effects of different concentrations of GTE on cell migration. We also explored the effect of GTE on the induction of the Nrf2/HO-1 pathway in the cells with or without LPS.

Results
GTE at concentrations of 2.5 mg/ml, 5 mg/ml, and 10 mg/ml significantly enhanced cell viability (p < 0.05). And IL-β1, IL-6, and TNFα gene expression presented up to 10-fold decrease compared with LPS-treated cells, which was also similarly found on the protein levels. At the same concentrations, cell migration increased.

Conclusions
The mechanism results showed that GTE produced the anti-inflammatory response by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and increasing the level of anti-oxidant protein heme oxygenase-1 (HO-1).

Clinical relevance
GTE may be potentially used as oral rinse anti-inflammatory drug for treatment and prevention of oral inflammatory diseases, which is shown here by the ability to reduce the inflammation and increase in cell migration in a dose-dependent manner.
Micro-mechanical investigation of railway ballast behavior under cyclic loading in a box test using DEM: effects of elastic layers and ballast types
Authors: Kumar Nishant , Suhr Bettina , Marschnig Stefan , Dietmaier Peter , Marte Christof , Six Klaus 
Published: October 2019

Abstract
Ballasted tracks are the commonly used railway track systems with constant demands for reducing maintenance cost and improved performance.
Elastic layers are increasingly used for improving ballasted tracks. In order to better understand the effects of elastic layers, physical understanding at the ballast particle level is crucial. Here, discrete element method (DEM) is used to investigate the effects of elastic layers – under sleeper pad ($$\text {USP}$$USP) at the sleeper/ballast interface and under ballast mat ($$\text {UBM}$$UBM) at the ballast/bottom interface – on micro-mechanical behavior of railway ballast. In the DEM model, the Conical Damage Model (CDM) is used for contact modelling. This model was calibrated in Suhr et al. (Granul Matter 20(4):70, 2018) for the simulation of two different types of ballast. The CDM model accounts for particle edge breakage, which is an important phenomenon especially at the early stage of a tamping cycle, and thus essential, when investigating the impact of elastic layers in the ballast bed. DEM results confirm that during cyclic loading, $$\text {USP}$$USP reduces the edge breakage at the sleeper/ballast interface. On the other hand, $$\text {UBM}$$UBM shows higher particle movement throughout the ballast bed. Both the edge breakage and particle movement in the ballast bed are found to influence the sleeper settlement. Micro-mechanical investigations show that the force chain in deeper regions of the ballast bed is less affected by $$\text {USP}$$USP for the two types of ballast. Conversely, dense lateral forces near to the box bottom were seen with $$\text {UBM}$$UBM. The findings are in good (qualitative) agreement with the experimental observations. Thus, DEM simulations can aid to better understand the micro-macro phenomena for railway ballast. This can help to improve the track components and track design based on simulation models taking into account the physical behavior of ballast.

Graphical Abstract
Si cycling in transition zones: a study of Si isotopes and biogenic silica accumulation in the Chesapeake Bay through the Holocene
Authors: Nantke Carla K. M. , Frings Patrick J. , Stadmark Johanna , Czymzik Markus , Conley Daniel J. 
Published: October 2019

AbstractSi fluxes from the continents to the ocean are a key element of the global Si cycle. Due to the ability of coastal ecosystems to process and retain Si, the ‘coastal filter’ has the potential to alter Si fluxes at a global scale. Coastal zones are diverse systems, sensitive to local environmental changes, where Si cycling is currently poorly understood. Here, we present the first palaeoenvironmental study of estuarine biogenic silica (BSi) fluxes and silicon isotope ratios in diatoms (δ30Sidiatom) using hand-picked diatom frustules in two sediment cores (CBdist and CBprox) from the Chesapeake Bay covering the last 12000 and 8000 years, respectively. Constrained by the well-understood Holocene evolution of the Chesapeake Bay, we interpret variations in Si cycling in the context of local climate, vegetation and land use changes. δ30Sidiatom varies between + 0.8 and + 1.7‰ in both sediment cores. A Si mass balance for the Chesapeake Bay suggests much higher rates of Si retention (~ 90%) within the system than seen in other coastal systems. BSi fluxes for both sediment cores co-vary with periods of sea level rise (between 9500 and 7500 a BP) and enhanced erosion due to deforestation (between 250 and 50 a BP). However, differences in δ30Sidiatom and BSi flux between the sites emphasize the importance of the seawater/freshwater mixing ratios and locally variable Si inputs from the catchment. Further, we interpret variations in δ30Sidiatom and the increase in BSi fluxes observed since European settlement (~ 250 a BP) to reflect a growing human influence on the Si cycle in the Chesapeake Bay. Thereby, land use change, especially deforestation, in the catchment is likely the major mechanism.
Real-life experience of using brinzolamide/brimonidine fixed drop combination in a tertiary glaucoma centre
Authors: Kóthy Péter , Holló Gábor 
Published: October 2019

Abstract

Purpose
To investigate the intraocular pressure (IOP)-lowering efficacy and tolerance of brinzolamide/brimonidine fixed combination (BBFC) under real-life conditions in a tertiary glaucoma centre.

Methods
Medical records of all ocular hypertensive and open-angle glaucoma patients (n = 52) treated with BBFC were retrospectively analysed.

Results
Thirty-nine patients had primary open-angle, 6 exfoliative, 2 pigment, 1 normal tension and 1 juvenile open-angle glaucoma and 3 ocular hypertension. The prior therapy was a prostaglandin analogue (PG) (n = 4), PG/timolol (n = 20), PG/timolol and topical carbonic anhydrase inhibitor (CAI; n = 19), timolol/CAI (n = 1), PG and CAI (n = 4), timolol/pilocarpine and PG (n = 1), timolol/brimonidine and PG (n = 1) and timolol/brimonidine, PG and CAI (n = 2). These were simplified to PG/timolol and BBFC (n = 41), PG and BBFC (n = 9), timolol and BBFC (n = 1) and timolol/pilocarpine, PG and BBFC (n = 1). The IOP on the study eyes was 21.2 ± 3.7 mmHg before and 16.9 ± 2.6, 16.0 ± 2.2, 17.6 ± 3.1 and 18.0 ± 3.1 mmHg after the introduction of BBFC at month 1, 3, 6 and 12, respectively (p < 0.0003 for all time points compared to baseline, p = 1.0 for all other comparisons). Thirty-one patients (59.6%) experienced no adverse event, 17 (32.7%) reported ocular and 6 (11.5%) systemic adverse events. BBFC therapy was terminated on 27 patients (51.9%): on 19 (36.5%) due to adverse events and on 8 (15.4%) due to insufficient IOP reduction.

Conclusion
In real-life practice, the introduction of BBCF allows significant and clinically meaningful IOP reduction and therapy simplification in glaucoma patients requiring complex medication, but in more than one third of the patients it is not tolerated due to adverse events.
Electrostatic-field and surface-shape similarity for virtual screening and pose prediction
Authors: Cleves Ann E. , Johnson Stephen R. , Jain Ajay N. 
Published: October 2019

Abstract
We introduce a new method for rapid computation of 3D molecular similarity that combines electrostatic field comparison with comparison of molecular surface-shape and directional hydrogen-bonding preferences (called “eSim”). Rather than employing heuristic “colors” or user-defined molecular feature types to represent conformation-dependent molecular electrostatics, eSim calculates the similarity of the electrostatic fields of two molecules (in addition to shape and hydrogen-bonding). We present detailed virtual screening performance data on the standard 102 target DUD-E set. In its moderately fast screening mode, eSim running on a single computing core is capable of processing over 60 molecules per second. In this mode, eSim performed significantly better than all alternate methods for which full DUD-E data were available (mean ROC area of 0.74, p $$< 10^{-9}$$<10-9, by paired t-test, compared with the best performing alternate method). In addition, for 92 targets of the DUD-E set where multiple ligand-bound crystal structures were available, screening performance was assessed using alternate ligands or sets thereof (in their bound poses) as similarity targets. Using the joint alignment of five ligands for each protein target, mean ROC area exceeded 0.82 for the 92 targets. Design-focused application of ligand similarity methods depends on accurate predictions of geometric molecular relationships. We comprehensively assessed pose prediction accuracy by curating nearly 400,000 bound ligand pose pairs across the DUD-E targets. Overall, beginning from agnostic initial poses, we observed an 80% success rate for RMSD $$\le 2.0$$≤2.0 Å among the top 20 predicted eSim poses. These examples were split roughly 50/50 into cases with high direct atomic overlap (where a shared scaffold exists between a pair) and low direct atomic overlap (where where a ligand pair has dissimilar scaffolds but largely occupies the same space). Within the high direct atomic overlap subset, the pose prediction success rate was 93%. For the more challenging subset (where dissimilar scaffolds are to be aligned), the success rate was 70%. The eSim approach enables both large-scale screening and rational design of ligands and is rooted in physically meaningful, non-heuristic, molecular comparisons.
Identification and resolution of drug-related problems in a tertiary hospital respiratory unit in China
Authors: Zhu Yulin , Liu Cheng , Zhang Yong , Shi Qingping , Kong Yiqiu , Wang Muqun , Xia Xuemei , Zhang Feng 
Published: October 2019

Abstract
Background The prevalence of drug-related problems in patients hospitalized at respiratory care units is unknown in mainland China. Objective To identify and categorize drug-related problems in a respiratory care unit in China. Setting Respiratory care unit in a tertiary university hospital in China. Methods Clinical pharmacy services were introduced and documented during an 18-months study period. The problems were categorized using the Pharmaceutical Care Network Europe DRP classification tool V8.02. Main outcome measures Problems and causes of drug-related problems, interventions proposed, and outcome of pharmacy recommendations. Results A total of 474 patients were reviewed, 164 patients had DRPs (34.6%). Total 410 problems were identified, an average of 2.5 per patient. Treatment effectiveness was the major type of problem detected (219; 53.4%) followed by treatment safety (140; 34.1%). The most common causes of the problems were patient-related (25.8%), drug selection (24.0%), and drug use process (23.4%). Pharmacist made 773 interventions; average 1.9 per drug-related problem. A total of 96.2% of these interventions were accepted leading to solving 81.9% of the identified problems. Conclusion There is a high prevalence of drug-related problems in patients hospitalized at the respiratory unit of this clinic. Clinical pharmacists should focus on improving prescribing practice and patient counseling.