bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of an in situ simulation-based training adapted from Morbidity and Mortality conference cases: effect on the occurrence of adverse events—study protocol of a cluster randomised controlled trial
Authors: Michel Nicolas , Bui-Xuan Bernard , Bapteste Lionel , Rimmele Thomas , Lilot Marc , Chollet François , Favre Hélène , Duclos Antoine , Michel Philippe 
Published: February 2022

Abstract
Background
Morbidity and Mortality conference provides the necessary improvement measures for patient safety. However, they are an underused resource mainly because the conclusions to be drawn from the discussion and their implications for practice are not always well integrated by inpatient care teams. We therefore propose in this study two interventions to optimise their effectiveness: a passive feedback with wide dissemination by e-mail and/or on paper of the results of the Morbidity and Mortality conference to inpatient care teams and an active feedback with in situ inter-professional simulation-training programme in which scenarios will be based on cases studied in Morbidity and Mortality conference. In the present study, we hypothesise that the greatest reduction the occurrence of adverse event will be in the active feedback arm.

Methods
A cluster randomised controlled study will be performed at four study sites. The unit of randomisation is wards within the study sites. Fifteen wards will be randomly assigned to passive feedback, active feedback, or a standard MMC (control arm). Passive feedback and active feedback arms will be compared to standard arm in terms of occurrence of adverse events. The trigger tool methodology used to identify adverse events is a retrospective review of inpatient records using “triggers”: an adverse event is defined as a patient’s stay with at least one positive trigger.

Discussion
The in situ simulation training based on cases processed in Morbidity and Mortality conference is built according to the main topics identified for the successful implementation of healthcare simulation in patient safety programmes: technical skills, nontechnical skills, assessment, effectiveness, and system probing. The in situ simulation-training programme conducted as part of the study has the potential to improve patient safety during hospitalisation. We therefore expect the greatest reduction in the occurrence of adverse events in patients hospitalised in the active feedback arm. This expected result would have a direct impact on patient safety and would place in situ simulation at the highest level of the Kirkpatrick model.

Trial registration
Clinicaltrials.gov NCT02771613. Registered on May 12, 2016. All items from the WHO Trial Registration Data Set can be found within the protocol.
Dietary calcium requirements of broilers fed a conventional corn-soybean meal diet from 1 to 21 days of age
Authors: Bai Shiping , Yang Yunfeng , Ma Xuelian , Liao Xiudong , Wang Runlian , Zhang Liyang , Li Sufen , Luo Xugang , Lu Lin 
Published: February 2022

Abstract
Background
The current calcium (Ca) recommendation for broilers is primarily based on studies conducted more than 30 years ago with birds of markedly different productive potentials from those which exist today. And the response indicators in these studies are mainly growth performance and bone ash percentage. Therefore, the present study was carried out to investigate the effect of dietary Ca level on growth performance, serum parameters, bone characteristics and Ca metabolism-related gene expressions, so as to estimate dietary Ca requirements of broilers fed a conventional corn-soybean meal diet from 1 to 21 days of age.

Methods
A total of 420 1-day-old Arbor Acres male broilers were randomly assigned to 1 of 7 treatments with 6 replicates (10 birds per cage) and fed the corn-soybean meal diets containing 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, 1.10% or 1.20% Ca for 21 days. Each diet contained the constant non-phytate phosphorus content of about 0.39%.

Results
The average daily gain decreased linearly (P < 0.001) as dietary Ca level increased. The serum and tibia alkaline phosphatase (ALP) activities, tibia bone mineral density (BMD), middle toe BMD, tibia ash percentage, tibia breaking strength, and tibia ALP protein expression level were affected (P < 0.05) by dietary Ca level, and showed significant quadratic responses (P < 0.02) to dietary Ca levels. The estimates of dietary Ca requirements were 0.80 to 1.00% based on the best fitted broken-line or quadratic models (P < 0.03) of the above serum and bone parameters, respectively.

Conclusions
The results from the present study indicate that the Ca requirements would be about 0.60% to obtain the best growth rate, and 1.00% to meet all of the Ca metabolisms and bone development of broilers fed a conventional corn-soybean meal diet from 1 to 21 days of age.
Novel approach for treating challenging implant-borne maxillary dental rehabilitation cases of cleft lip and palate: a retrospective study
Authors: Rahlf Björn , Korn Philippe , Zeller Alexander-Nicolai , Spalthoff Simon , Jehn Philipp , Lentge Fritjof , Gellrich Nils-Claudius 
Published: February 2022

Abstract
Purpose
Dental restoration in cleft lip and palate (CLP) patients is demanding and often results in bone loss and dental implant failure. Furthermore, unfavorable conditions of hard and soft tissues as well as skeletal deformities aggravate surgical and dental treatment. Therefore, this study was designed to assess the feasibility of using a new type of patient-specific implant (IPS-preprosthetic®) in CLP patients.

Methods
Of the 63 patients who received a IPS-preprosthetic® implant in the Department of Oral and Maxillofacial Surgery at the Hannover Medical School, Germany, six patients were treated for a CLP deformity with significant soft and hard tissue impairment. Two patients were partially edentulous, whereas four patients were edentulous for the maxilla. All implants were inserted in a single-step outpatient surgery and were followed up for up to 40 months.

Results
Within the observation period, no implant failed and no screw loosening or change in stability of the implant to recipient site occurred (mean number of screws: 21). This study demonstrates, for the first time, the efficient use of a one-piece multivector screw primarily retained a stable patient-specific implant for implant-borne prosthodontic rehabilitation of CLP patients with deformities and challenging initial situations.

Conclusions
IPS-preprosthetic® implants offer a novel approach to implant dentistry treatment protocols, especially in difficult cases of unusual anatomy, even when previous conventional treatment fails.
Risk factors for interstitial lung disease induced by gemcitabine plus albumin-bound paclitaxel therapy in pancreatic ductal adenocarcinoma patients
Authors: Ueda Rikako , Yamamoto Naho , Hori Yuki , Yoshida Kouji , Ohtsubo Koushiro , Terashima Takeshi , Shimada Tsutomu , Sai Yoshimichi 
Published: February 2022

Abstract
Background
Gemcitabine plus nab-paclitaxel (GnP) therapy is used for unresectable pancreatic ductal adenocarcinoma, but may cause interstitial lung disease (ILD) as a serious side effect. However, the risk factors for ILD in patients receiving GnP therapy are not well established. Here, we retrospectively investigated the incidence of GnP-induced ILD in pancreatic ductal adenocarcinoma patients, and the risk factors.

Methods
We investigated the patients’ background, laboratory data, previous treatment history, concomitant medications, number of doses of GnP, cumulative dosage and administration period, and occurrence of side effects.

Results
Of the 105 patients included in this study, ILD occurred in 10 (9.5%). Patients with ILD had a significantly higher frequency of concomitant treatment with Kampo medicines, especially goshajinkigan, which is considered to help prevent chemotherapy-induced peripheral neuropathy (CIPN) (odds ratio: 11.5, 95% confidence interval: 2.67–49.38). No significant differences were observed in other clinical characteristics. Notably, the severity of CIPN in patients who used goshajinkigan for prevention was not significantly different from that in patients who did not use goshajinkigan in this study.

Conclusions
These results suggest that administration of goshajinkigan to patients receiving GnP therapy for prevention of CIPN may need to be reconsidered.
Anti-inflammatory and analgesic activities of black cumin (BC, Nigella sativa L.) extracts in in vivo model systems
Authors: Shaheen Nazma , Azam Afiatul , Ganguly Amlan , Anwar Saeed , Parvez Md. Sorwer Alam , Punyamurtula Ujwal , Hasan Md. Kamrul 
Published: February 2022

Abstract
Background
Black cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including analgesic, bronchial asthma, anti-inflammatory properties, and others. We sought to evaluate BC extracts' efficacy for the anti-inflammatory and analgesic properties using a comprehensive in vivo and in silico experimental setup. To investigate whether BC extract has anti-inflammatory and analgesic therapeutic potentials in vivo anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test and ingenuity analysis of the BC extracts in inflammation control.

Results
The acetic acid-induced writhing test had shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test showed the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation.

Conclusions
This study suggests that bioactive compounds in BC extract act as an anti-inflammatory and analgesic agent by regulating several downstream and upstream inflammation pathways.
High Plasma Oxytocin Levels in Men With Hypersexual Disorder
Authors: Flanagan John , Chatzittofis Andreas , Boström Adrian Desai E , Hallberg Jonas , Öberg Katarina Görts , Arver Stefan , Jokinen Jussi 
Published: February 2022

Abstract

Context
Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior.

Objective
We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol.

Design
Longitudinal.

Setting
ANOVA clinic (Karolinska University Hospital).

Patients or other participants
64 males with HD and 38 age-matched healthy volunteers.

Main Outcome Measures
Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms.

Interventions
A patient subgroup (n = 30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured.

Results
Hypersexual men (n = 64) exhibited significantly higher oxytocin plasma levels (mean ± SD: 31.0 ± 9.9 pM) compared with healthy volunteers (16.9 ± 3.9 pM; P &lt; 0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n = 30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5 ± 10.1 pM) to posttreatment (20.2 ± 8.0 pM; P &lt; 0.001).

Conclusions
The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress.
Safety, Efficacy, and Pharmacokinetics of HP501 in Healthy Volunteers and Hyperuricemic Patients: A Phase I/IIa Study
Authors: Wang Zhenlei , Li Xinghai , Jin Ying , Liu Runhan , Di Xiangjie , Zhou Yi , Wang Ying , Fan Lei , Chen Yuanwei , Wang Yongsheng , Zheng Li 
Published: February 2022

Abstract

Context
Uricosuric agents are the typical approach to the control of hyperuricemia; however, their use has been eclipsed by adverse reactions, and a safer uricosuric drug is badly needed.

Objective
HP501 is a novel renal urate transporter 1 inhibitor for the treatment of hyperuricemia. In this first-in-human study, we investigated the safety, efficacy, and pharmacokinetics of HP501 in healthy volunteers and hyperuricemic patients.

Methods
The placebo-controlled, double-blind, randomized, 3-part, phase I/IIa study consists of a single ascending dose (SAD) part with 32 participants, a multiple ascending dose part with 48 participants, and a drug-drug interaction part with 20 participants. Effects of food in healthy volunteers administered 45 mg HP501 in the fed state were also assessed in the SAD part.

Results
A total of 68 healthy volunteers and 32 hyperuricemic patients were enrolled. HP501 appeared to be safe and well tolerated in both groups. In hyperuricemic patients dosed with 45 mg HP501 over 10 days, 2/10 and 3/10 patients had elevated AST (&lt; 2 times upper limit of normal [ULN]) and ALT (&lt; 2.5 times ULN), respectively. No dose-limiting adverse events were observed. Across doses of HP501 from 5 to 60 mg, the concentrations of serum uric acid (sUA) are reduced by a maximum of about 50%. HP501 exhibited predictable pharmacokinetics across different dose levels in healthy volunteers or hyperuricemic patients. HP501 and febuxostat have obvious synergistic sUA-lowering effects with no apparent pharmacokinetics interaction.

Conclusion
HP501 was effective at reducing sUA in healthy volunteers and hyperuricemic patients with a tolerable safety profile, warranting further development.
Population-based Assessment of Cardiometabolic-related Diagnoses in Youth With Klinefelter Syndrome: A PEDSnet Study
Authors: Davis Shanlee M , Nokoff Natalie J , Furniss Anna , Pyle Laura , Valentine Anna , Fechner Patricia , Ikomi Chijioke , Magnusen Brianna , Nahata Leena , Vogiatzi Maria G , Dempsey Amanda 
Published: February 2022

AbstractContextDiabetes and cardiovascular diseases are common among men with Klinefelter syndrome (KS) and contribute to high morbidity and mortality.ObjectiveTo determine if cardiometabolic-related diagnoses are more prevalent among youth with KS than matched controls in a large population-based cohort.MethodsSecondary data analysis of electronic health records from 6 pediatric institutions in the United States (PEDSnet). Patients included all youth with KS in the database (n = 1080) and 4497 youth without KS matched for sex, age (mean 13 years at last encounter), year of birth, race, ethnicity, insurance, site, and duration of care (mean 7 years). The main outcome measures were prevalence of 5 cardiometabolic-related outcomes: overweight/obesity, dyslipidemia, dysglycemia, hypertension, and liver dysfunction.ResultsThe odds of overweight/obesity (OR 1.6; 95% CI 1.4-1.8), dyslipidemia (3.0; 2.2-3.9), and liver dysfunction (2.0; 1.6-2.5) were all higher in KS than in controls. Adjusting for covariates (obesity, testosterone treatment, and antipsychotic use) attenuated the effect of KS on these outcomes; however, boys with KS still had 45% greater odds of overweight/obesity (95% CI 1.2-1.7) and 70% greater odds of liver dysfunction (95% CI 1.3-2.2) than controls, and both dyslipidemia (1.6; 1.1-2.4) and dysglycemia (1.8; 1.1-3.2) were higher in KS but of borderline statistical significance when accounting for multiple comparisons. The odds of hypertension were not different between groups.ConclusionThis large, population-based cohort of youth with KS had a higher odds of most cardiometabolic-related diagnoses than matched controls.
Association of Antithyroid Antibodies in Checkpoint Inhibitor–Associated Thyroid Immune–Related Adverse Events
Authors: Muir Christopher A , Wood Cameron C G , Clifton-Bligh Roderick J , Long Georgina V , Scolyer Richard A , Carlino Matteo S , Menzies Alexander M , Tsang Venessa H M 
Published: February 2022

Abstract

Context
The significance of thyroid peroxidase (TPOAb) and thyroglobulin antibody (TgAb) in the pathogenesis of thyroid immune-related adverse events (irAEs) is unknown.

Objective
To characterize the association of anti-thyroid antibodies with the development of thyroid immune related adverse events.

Methods
A retrospective cohort study was conducted of patients with melanoma receiving immune checkpoint inhibitor (ICI) treatment. TPOAb, TgAb, and interleukin-6 (IL-6) were measured retrospectively using tumor-banked samples at baseline and at time of diagnosis of a thyroid irAE. In euthyroid patients (without thyroid irAEs) measures were repeated 30 to 60 days after ICI commencement, which was similar to the median time to onset of thyroid irAEs in other patients.

Results
A total of 122 patients were included—31 remained euthyroid, 47 developed subclinical thyrotoxicosis, 37 developed overt thyrotoxicosis, and 7 developed overt hypothyroidism without preceding thyrotoxicosis. Baseline elevation of TPOAb or TgAb was present in 19 (16%) and 28 (23%) patients, respectively. Positive TPOAb or TgAb at baseline was 97% and 100% specific for eventual development of a thyroid irAE, respectively. During ICI treatment, overt thyrotoxicosis, but not other subtypes of thyroid irAE, was associated with statistically significant increases in the titer of TgAb and TPOAb. Baseline IL-6 levels were not associated with thyroid irAE onset but statistically significantly increased during treatment in patients who developed overt hypothyroidism.

Conclusions
TPOAb and TgAb positivity at baseline was more prevalent in patients who developed thyroid irAEs. Statistically significant increases or new antibody positivity was observed in association with overt thyrotoxicosis. TPOAb and TgAb positivity or increases during ICI treatment may be a useful biomarker to identify patients at increased risk of thyroid irAEs, particularly overt thyrotoxicosis.
Single-cell imaging of ERK and Akt activation dynamics and heterogeneity induced by G-protein-coupled receptors
Authors: Chavez-Abiega Sergei , Grönloh Max L. B. , Gadella Theodorus W. J. , Bruggeman Frank J. , Goedhart Joachim 
Published: February 2022

ABSTRACT
Kinases play key roles in signaling networks that are activated by G-protein-coupled receptors (GPCRs). Kinase activities are generally inferred from cell lysates, hiding cell-to-cell variability. To study the dynamics and heterogeneity of ERK and Akt proteins, we employed high-content biosensor imaging with kinase translocation reporters. The kinases were activated with GPCR ligands. We observed ligand concentration-dependent response kinetics to histamine, α2-adrenergic and S1P receptor stimulation. By using G-protein inhibitors, we observed that Gq mediated the ERK and Akt responses to histamine. In contrast, Gi was necessary for ERK and Akt activation in response to α2-adrenergic receptor activation. ERK and Akt were also strongly activated by S1P, showing high heterogeneity at the single-cell level, especially for ERK. Cluster analysis of time series derived from 68,000 cells obtained under the different conditions revealed several distinct populations of cells that display similar response dynamics. ERK response dynamics to S1P showed high heterogeneity, which was reduced by the inhibition of Gi. To conclude, we have set up an imaging and analysis strategy that reveals substantial cell-to-cell heterogeneity in kinase activity driven by GPCRs.
Do Sunk Costs Affect Prices in the Housing Market?
Authors: Ratnadiwakara Dimuthu , Yerramilli Vijay 
Published: February 2022

We use a unique feature of California’s property tax system to empirically identify the causal effect of selling homeowners’ past property tax payments on their choice of listing price. Although past property taxes are sunk costs, we find that they have a significant positive effect on the sellers’ choice of listing price, which is inconsistent with rational models of decision making. This effect is stronger when sellers expect to sell at a loss relative to their purchase price and for properties whose value is harder to assess. The effect of property taxes on listing price is mostly transmitted to the selling price, which is consistent with the idea that buyers use listing prices as anchors to assess property values. Overall, our results suggest that sunk costs affect prices in the housing market. This paper was accepted by Tomasz Piskorski, finance. Supplemental Material: Data files are available at https://doi.org/10.1287/mnsc.2021.4285 .
Millijoule 265 fs Tm:YAP regenerative amplifier for driving ultrabroad band collinear mid-infrared optical parametric amplifiers
Authors: Rezvani Seyed Ali , Fuji Takao 
Published: February 2022

Generation of 265-fs millijoule pulses at 1940 nm from a solid-state regenerative amplifier has been demonstrated. The amplification chain consists of a thulium-doped fluoride (Tm:ZBLAN) fiber oscillator, a two stage Tm:ZBLAN fiber preamplifier, and a regenerative amplifier with a thermoelectrically cooled thulium-doped yttrium aluminium perovskite crystal. The newly developed light source is used for pumping an ultra broadband mid-infrared optical parametric amplifier based on a gallium selenide crystal. The 2.5–4 µm range of a multioctave supercontinuum, generated in a polarization-maintaining ZBALN fiber, is used as the MIR seed. The amplified signal in combination with the corresponding idler pulses spread from 2.5 to 10 µm in a collinear geometry.