bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technicians’ perception of pharmacist leadership behaviors on their own commitment and turnover intention
Authors: Desselle Shane P , Wasem Valerie , Hosseini Sina , Hohmeier Kenneth C , Woodyard Ashley , McKeirnan Kimberly C 
Published: September 2022

AbstractPurposeTo evaluate technicians’ perceptions of how they are supported and supervised by pharmacists through assessment of various components of pharmacists’ leadership behaviors in developing the technician workforce. Additional objectives included evaluating levels of pharmacy technician uncertainty about their future, job commitment, and turnover intention in relation to perceived pharmacist leadership behaviors.MethodsThis study employed a cross-sectional design involving administration of an online questionnaire survey. The target population was technicians certified through the National Healthcareer Association. The questionnaire was disseminated to a random, nationwide sample of 3,000 technicians. It solicited responses to an adapted version of the Multifactorial Leadership Questionnaire (MLQ), a 29-item instrument for measuring the frequency of observed pharmacist supervisory behaviors, which are categorized as transactional, transformative, or both. The questionnaire also inquired as to respondents’ levels of future uncertainty, profession commitment, organization commitment, and turnover intentions.ResultsResponses were acquired from 882 certified pharmacy technicians, who reported their observance of pharmacy supervisory behaviors, as measured by the adapted MLQ, with moderate frequency. Higher technician-reported levels of transformative leadership behavior by pharmacists were associated with lower levels of future uncertainty, greater profession and organization commitment, and diminished turnover intentions.ConclusionPharmacists’ supervisory behaviors, namely transformative leadership behaviors, may be impactful to pharmacy technicians’ attitudes and work-related outcomes. The pharmacy profession’s leaders and educators might consider these results in educating current and future pharmacists so as to improve the workplace and, potentially, organizational and profession-wide outcomes in the delivery of care.
A Well-Outfitted Militia: German–American Translations of the Second Amendment and Original Public Meaning
Authors: Kinney Brandon 
Published: September 2022

Abstract
This article seeks to uncover the original public meaning of the Second Amendment by scrutinizing unusual and previously unexamined sources: German–American translations of the Bill of Rights during the Founding Era. Translations offer a unique perspective of political culture, because they served as thoughtful analysis and contextual commentary on the source text. Using six German–American translations in the Founding Era, this article argues that the public understanding of the Second Amendment during the Founding Era was one that recognized the individual right to own firearms for individual use unconnected to militia service as well as a constitutional endorsement of an armed population as the best bulwark to preserve the liberty of the national people. Though the exact text of the translations differ across publishers and states, they retain thematic and syntactic similarities that suggest a public consensus over the meaning of the text. The notion that the Second Amendment protects an individual right rather than a collective one is borne out by additional translations well into the mid-nineteenth century. Printers adjusted their translations of the amendment after the militia as a military institution had fallen into disuse but preserved or strengthened the clause protecting the individual right to arms rather than letting it ‘fall silent’.
A Placebo-Controlled Randomized Trial of Vigabatrin in the Management of Acute Alcohol Withdrawal
Authors: Williams James , Collins Lisa , Norman Amanda , O’Neill Helen , Lloyd-Jones Martyn , Ogden Edward , Bonomo Yvonne , Pastor Adam 
Published: September 2022

Abstract

Objective
To undertake a double blinded randomised placebo-controlled trial to assess the efficacy of vigabatrin, a GABA-transaminase inhibitor, as a benzodiazepine sparing agent in the management of acute alcohol withdrawal syndrome in a residential setting.

Methods
We enrolled 120 patients with alcohol use disorder who were randomly assigned to either treatment with vigabatrin (2g/day for 4 days) or placebo. The primary outcome was defined as the number of participants in each treatment arm needing diazepam for withdrawal management. A secondary outcome prespecified was the total dose of diazepam received by participants in each treatment arm. Participants were recruited on admission to a residential withdrawal unit at St Vincent’s Hospital Melbourne from December 2014 to April 2019.

Results
No significant difference was observed in the number of participants requiring benzodiazepines during their residential withdrawal stay with 44 participants (78.6%) in placebo arm requiring at least one dose of diazepam compared to 38 (66.7%) in vigabatrin arm (p = .156). An 18.1% difference was observed between the proportion of participants who received a total dose of &gt;100mg of diazepam during their residential withdrawal stay in placebo arm (32.1%), compared to vigabatrin arm (14.0%, p = .022). There were higher rates of reported adverse events in placebo arm with nine (15.0%) participants reporting adverse events compared with two (3.3%) participants in vigabatrin arm (p = .027).

Conclusion
Vigabatrin significantly reduced the number of participants requiring &gt;100mg diazepam over the course of their alcohol withdrawal and was associated with a reduction in adverse effects when compared to placebo.
TOSCA: an automated Tumor Only Somatic CAlling workflow for somatic mutation detection without matched normal samples
Authors: Del Corvo Marcello , Mazzara Saveria , Pileri Stefano A 
Published: September 2022

Abstract

Motivation
Accurate classification of somatic variants in a tumor sample is often accomplished by utilizing a paired normal tissue sample from the same patient to enable the separation of private germline mutations from somatic variants. However, a paired normal sample is not always available, making a reliable somatic variant calling more challenging. In silico screening of variants against public or private databases and other filtering approaches are often used in absence of a paired normal sample. Nevertheless, difficulties in performing a tumor-only calling with sufficient accuracy and lack of open-source software have limited their applications in clinical research.

Results
To address these limitations, we developed TOSCA, the first automated tumor-only somatic calling workflow in whole-exome sequencing and targeted panel sequencing data which performs an end-to-end analysis from raw read files, via quality checks, alignment and variant calling to functional annotation, databases filtering, tumor purity and ploidy estimation and variant classification. Application of our workflow to tumor-only data provides estimates of somatic and germline variants that are consistent with results from paired analyses.

Availability and implementation
TOSCA is a Snakemake-based workflow and freely available at https://github.com/mdelcorvo/TOSCA.

Supplementary information
Supplementary data are available at Bioinformatics Advances online.
149. LOCAL INFLAMMATORY RESPONSE TO GASTROESOPHAGEAL REFLUX: ASSOCIATION OF GENE EXPRESSION OF INFLAMMATORY CYTOKINES WITH MULTICHANNEL INTRALUMINAL PH-IMPEDANCE DATA
Authors: Morozov Sergey , Sentsova Tatyana 
Published: September 2022

Abstract
Expression of inflammatory cytokines’ genes may take part in pathophysiology of different forms of gastroesophageal reflux disease (GERD).
Aim: to explore the expression of inflammatory cytokines’ genes in esophageal mucosa in patients with erosive esophagitis and non-erosive forms of gastroesophageal reflux disease and its association with data of esophageal multichannel intraluminal pH-impedance measurements.
This was a single-center prospective study. Esophageal mucosa samples were taken from lower part of the esophagus during endoscopy. Expression of IL-1β, IL-10, IL-18, TNFA, TLR4, GATA3, CD68, beta-2 macroglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays. Multichannel intraluminal esophageal pH-impedance (MII-pH) studies performed to all the participants. Diagnosis of GERD was confirmed by the results of MII-pH data. Patients were allocated to erosive esophagitis (EE) or non-erosive GERD groups (NERD). Non-symptomatic subjects with normal endoscopy and MII-pH results served as a control. Spearman rank correlation was used to asses association of genes expression and results of MII-pH.
Data of 60 patients with GERD and 10 subjects of the control group were available for the analysis. Higher expression of IL-18 (5.89 ± 0.4 vs 5.28 ± 1.1, p = 0.04) and GATA3 (2.92 ± 0.86 vs 2.23 ± 0.96, p = 0.03) genes was found in EE group compared to NERD. Expression of IL-1β, IL-18, TNFA, and TLR4 genes was lower (P &lt; 0.05) in the control group compared to EE and NERD. Esophageal acid exposure correlated with the expression of IL-1β (R = 0.29), IL-18 (R = 0.31), TNFA (R = 0.35), GATA3 (R = 0.34), TLR4 (R = 0.29), CD68 (R = 0.37) genes. Mean esophageal рН correlated inversely with the expressions of IL-18, TNFA, GATA3, TLR4, CD68 genes.
In patients with erosive esophagitis, local expression of interleukin 18 and GATA3 transcription factor genes was higher compared to subjects with non-erosive form of gastroesophageal reflux disease. Esophageal acid exposure correlated directly with expression of IL-1β, IL-18, TNFA, TLR4, CD68 and B2M genes. Inverse correlation revealed between expression of IL-18, TNFA, GATA3, TLR4 CD68 genes and mean esophageal pH.
152. CLINICAL OUTCOME OF NIVOLUMAB COMBINATION THERAPY AS 1ST LINE TREATMENT FOR ESOPHAGEAL CANCER IN A JAPANESE HOSPITAL (CHECKMATE 648)
Authors: Makino Tomoki , Tanaka Koji , Yamashita Kotaro , Eguchi Hidetoshi , Doki Yuchiro 
Published: September 2022

Abstract
Currently, immuno-checkpoint inhibitor (ICI) has been widely used for unresectable advanced/recurrent esophageal squamous cell carcinoma (ESCC) as 2nd or later line treatment, however clinical evidence regarding efficacy or safety of the 1st line ICI treatment for ESCC remains limited. The global phase 3 CheckMate 648 (ONO-4538-50) demonstrated significant overall survival (OS) benefit of nivolumab + chemotherapy and nivolumab+ ipilimumab versus chemotherapy (5FU/CDDP) in previously untreated patients with advanced ESCC with an acceptable safety profile.
A total 970 ESCC patients with unresectable advanced/recurrent disease were randomized globally and this post-hoc exploratory subgroup analysis presented here includes only the 34 patients randomized and treated at this hospital during Dec, 2017-Dec, 2019. Treatment efficacy and adverse events were assessed among the three groups; nivolumab (3 mg/kg every 2 weeks) + ipilimumab (1 mg/kg every 6 weeks) (Group A, n = 11), nivolumab (240 mg every 2 weeks) + 5FU/CDDP (5FU800 mg/m2 day1–5/CDDP80 mg/m2 day 1、every 4 weeks) (Group B, n = 13) and 5FU/CDDP (5FU800 mg/m2 day1–5/CDDP80 mg/m2 day 1、every 4 weeks) (Group C, n = 10).
Patient characteristics of the group A/B/C were as follows; age = 69 (52–82)/70 (52–85)/70 (55–75), gender (male/female) = 11:0/10:3/9:1. Regarding survival analysis (median follow-up time; 19.5 months) of Jan 24th, 2022, median OS were not reached in the group A, 15 months (95%CI = 5–28) in the group B and 12 (95%CI = 2–25) months in the group C. The most common treatment-related adverse events (≥ grade3) were pruritus in 2 cases, rash in 2 (Group A), neutropenia in 5 cases, leukopenia in 3, and anorexia in 3 (Group B) and no cases (Group C). No treatment-related death was identified in any groups.
The results from this Japanese single-center exploratory subgroup analysis are consistent with the global study results, and support nivolumab + ipilimumab and nivolumab + chemotherapy as promising first-line treatments for patients with unresectable advanced/recurrent ESCC. Also, establishment of useful biomarker in distinguishing use of nivolumab + chemotherapy and nivolumab+ ipilimumab would be urgent.
153. APPLICATION OF RAMAN SPECTROSCOPY AND MACHINE LEARNING IN THE CLASSIFICATION OF ESOPHAGEAL SQUAMOUS CARCINOMA
Authors: Chen Long-Qi , Huang Wenhua 
Published: September 2022

Abstract
Esophageal squamous cell carcinoma (ESCC) is a common disease among all malignant tumors. Advanced detect technologies of the esophageal cancer, Raman spectroscopy have then been developed with the aim of improving diagnosis sensitivity and specificity and accuracy. The aim of this study was to demonstrate an effective and noninvasive technique, Raman spectroscopy, which was able to differentiate and classify ESCC cell lines (esophageal cancer tissue types).
5 ESCC cell lines and tissues of ESCC patient with staging of T3N1M0 (n = 4) and T3N2M0 (n = 4) in low and high differentiation were examined through Raman spectroscopy. Raman spectra data analysis with four machine learning algorithms: PCA-LDA, PCA-XGB, PCA-SVM and PCA- (LDA, XGB, SVM)-stacked GBM were applied. The Student’s t test was used to analyze the differences between the two groups.
PCA-LDA model achieved predictive sensitivity greater than 89%, specificity greater than 96% and the overall accuracy rate greater than 90% for the classification of ESCC cells. PCA-XGM and PCA-SVM models showed overall predictive accuracies of 85% and 87.7%, respectively. The overall accuracy reached to 94.7% in classifying the ESCC cells and normal esophageal cells. In ESCC tissue, Raman intensity of DNA/RNA (780 cm − 1) and lipids (1440 cm − 1) were higher in ESCC tissues compared with that in adjacent tissues. We used PCA-XGB model to classify ESCC tissues and adjacent tissues, which showed the overall predictive accuracy of 85%.
This study illustrates Raman spectral traits of ESCC cell lines and esophageal tissues related to clinical pathological diagnosis, and one more possible detection method has been added in the field of esophageal cancer detection. Future studies to determine the role of different Raman spectral features altered in ESCC pathogenesis are warranted.
155. CAN ANAEROBIC THRESHOLD (AT) PREDICT LENGTH OF STAY IN PATIENTS UNDERGOING IVOR LEWIS OESOPHAGECTOMY
Authors: Joel Abraham , Samuel Maria , Quake Sharmaine , Bailey Haydn , Zeyuan Chew , Ahmed Salman , Viswanath YKS , Dresner Samuel , Davis Peter 
Published: September 2022

Abstract
Variables from cardiopulmonary exercise testing (CPET) has been used to predict negative prognostic markers in oesophagectomy. We investigate the predictive value of anaerobic threshold (AT) ≥11 mL/kg/min in predicting length of stay (LOS) in patients having Ivor Lewis oesophagectomy (ILO). We also correlate AT with pulmonary complications (pneumonia), anastomotic leak rate and survival in our outcome analysis.
A retrospective analysis of a prospectively maintained database was carried out at a regional centre in the UK, evaluating patients undergoing ILO for oesophageal cancer (OC) between May 2016 and December 2019. Data was collected using the hospitals electronic system containing clinic letters, anaesthetic assessment including CPET, pathology reports and information regarding death of the patient. Patients were divided into AT &lt;11 mg/kg/min (LAT) and those with AT ≥11 mg/kg/min (HAT). χ2 test of association were used for categorical variables and Mann–Whitney test to compare two sets of non-parametric data. A p &lt; 0.05 was considered significant. Kaplan–Meier curve was used for survival analysis.
153 patients underwent ILO (median age 67, 86% males). 70 from this cohort underwent CPET testing. Median AT was 10.5 (7.4–11.7). There was a statistically significant negative correlation between AT and LOS (p = 0.03). Median LOS for patients with LAT was 15.5 days (11–225) and HAT was 13.5 days (10–19.75) with no significant differences in LOS when comparing LOS between LAT and HAT (p = 0.09). There was no difference in anastomotic leaks between LAT and HAT (χ2 test) (p = 0.15). Overall survival estimated using Kaplan–Meier curves failed to demonstrate a statistical difference between LAT and HAT (median 28.5 vs 30.5) (p = 0.71).
Our analysis shows a negative correlation between AT and LOS. Although LOS, anastomotic leaks, and survival were quantitatively better in the HAT group, it failed to reach statistical significance. This suggests that CPET variables are more beneficial as adjuncts to help shared decision making but not to predict post-operative outcomes. AT does not predict LOS in patients undergoing ILO.
159. NEW ENDOSCOPIC TREATMENT TECHNIQUE TO PREVENT REFRACTORY CORROSIVE ESOPHAGEAL STRICTURES
Authors: Tharavej Chadin , Chobarporn Thitiporn 
Published: September 2022

Abstract
Refractory esophageal stricture is an undesired complication after caustic ingestion associated with increased morbidity and mortality. Prevention rather than treatment of the stricture is a desirable goal. The objective of this study was to report the safety and outcome of our novel endoscopic technique using Repeated endoscopy with Intraluminal Fibrinous adhesioLysis of the Esophagus (RIFLE) during the first 2 weeks of caustic ingestion aiming to prevent the development of refractory esophageal stricture and bypass surgery.
Patients with Zagar’s grade IIb-IIIa corrosive esophageal injury were included. Patients undergoing emergent surgery were excluded. Since 2018, upper endoscopy with lysis of intraluminal fibrinous adhesion by advancing endoscopic tip through the lesions has been gently performed initially at the third day and then repeated twice a week during the first 2 weeks of the ingestion in 15 patients of the study group. Before 2018, a standard ‘wait and see’ treatment with early dilation at 4–6 weeks after injury had been applied only patients with evidence of esophageal stricture. Patients in the standard were 1:1 matched to the study group.
A median number of endoscopic RIFLE session was 4, and there was no treatment-related complication in all 15 patients in the study group. Fifteen out of the 102 patients with grade IIb-IIIa esophageal injury in our database with standard treatment were well matched to the study group. At the median follow-up of 30 months, the frequency of esophageal stricture, refractory esophageal stricture, esophageal replacement procedure, and a median number of dilation session between the study and standard treatment group were 4/15 (27%) vs 10/15 (67%), p = 0.02, 1/15(7%) vs 7/15(47%), p = 0.01, 1/15(7%) vs 6/15(40%), p = 0.03, and 4 vs 11, p &lt; 0.001, respectively.
In patients with severe non-transmural caustic esophageal injury, repeated endoscopy with intraluminal fibrinous adhesiolysis of the esophagus during the first 2 weeks of the ingestion is safe and associated with decreasing proportion of patients with refractory esophageal stricture and requiring esophageal replacement procedure.
166. A STUDY OF THE LEARNING CURVE FOR LAPAROSCOPIC-ASSISTED SINGLE-PORT MEDIASTINOSCOPIC ESOPHAGECTOMY
Authors: Cao Qingdong , Wu Xiangwen , Li Wenhao , Gan Xiangfeng 
Published: September 2022

Abstract
Laparoscopic-assisted single-port mediastinoscopic esophagectomy is a safe and effective emerging minimally invasive esophagectomy. However, nothing has been reported about the learning curve for this technique. The goal of this study was to analyze the learning curve of this technique and to determine the number of procedures performed to achieve different levels of proficiency to improve surgeons’ understanding of the learning process of this new technique.
This study retrospectively collected clinical data on consecutive laparoscopic-assisted single-port mediastinoscopic esophagectomies performed by the same surgeon at our center from October 2016 to August 2021. A simple scatter plot of the number of procedures versus procedure time and its trend line were plotted, using procedure time as an indicator of efficiency. Learning curves were quantitatively assessed by unadjusted cumulative sum values using the cumulative summation method, different segments were derived using joint point linear regression analysis, and variables were compared between subgroups using trend analysis. The survival analysis was performed using the Kaplan–Meier method.

The learning curve could be divided into 3 different stages: the 1st–91st, 91st-125th, and 125th-182nd procedures comprised the preliminary, transition, and proficient stages, respectively. Compared with the preliminary stage, the procedure time, bleeding volume, postoperative hospital stays, and the incidence of anastomotic fistula were significantly lower in the proficiency stage, whereas the number of harvested lymph nodes and the rate of recurrent laryngeal nerve lymph node harvest was significantly higher. Additionally, there were no significant differences in overall survival and disease-free survival at different stages for patients with all, different T stages, and different N stages within 1 year postoperatively.
In this study, there may be 3 stages of varying proficiency in the learning curve of laparoscopic-assisted single-port mediastinoscopic esophagectomy. Approximately 91 consecutive procedures were required to overcome the preliminary stage, whereas proficiency in this technique required approximately 125 consecutive procedures. Moreover, as the learning curve reached the proficiency stage, the perioperative indicators tended to stabilize. Furthermore, the short-term survival of patients might not be influenced by technical proficiency.
167. LYMPHATIC INVASION CAN PREDICT POSTOPERATIVE LYMPH NODE RECURRENCE IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Ma Yu , Wang Hongtao , Zhu Jianfei 
Published: September 2022

Abstract
Lymph node metastasis is an important pathological feature of esophageal squamous cell carcinoma (ESCC), and previous studies have confirmed that patients with lymphatic invasion (LI) have poor prognosis. However, the correlation between LI and pathological N stage and its impact on patient prognosis are less studied.
Patients with ESCC who underwent radical esophagectomy in our center were included in a retrospective analysis, and LI was assessed using hematoxylin and eosin (H&E) staining and D2–40 immunohistochemistry (IHC). Correlations between PI and clinicopathological features and clinical outcomes were also analyzed.
Totally, LI presented in ESCC were 22.5% (86 of 383). LI was closely related to the pN stage, with the pN stage from N0 to N1, then to N2, and finally to N3, the incidence of LI gradually increased from 1% to 40%. Furthermore, PNI-positive patients had poorer disease-free survival (DFS) than PNI-negative patients (21.0 months vs 41.4 months, P &lt; 0.001), the same result was obtained in OS (26.4 months vs 56.4 months, P &lt; 0.001). Finally, the probability of postoperative lymph node recurrence in LI-positive patients was significantly higher than that in LI-negative patients (20.9% vs 18.5%, P = 0.026).
LI is related to pN stage of ESCC patients. It is also an important predictor of postoperative lymph node recurrence in patients with ESCC.