bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Lean Healthcare Implementation Self-Assessment Instrument (LHISI) in the finnish healthcare context
Authors: Reponen Elina , Jokela Ritva , Blodgett Janet C. , Rundall Thomas G. , Shortell Stephen M. , Nuutinen Mikko , Skants Noora , Mäkijärvi Markku , Torkki Paulus 
Published: December 2021

Abstract
Background
Lean management is growing in popularity in the healthcare sector worldwide, yet healthcare organizations are struggling with assessing the maturity of their Lean implementation and monitoring its change over time. Most existing methods for such assessments are time consuming, require site visits by external consultants, and lack frontline involvement. The original Lean Healthcare Implementation Self-Assessment Instrument (LHISI) was developed by the Center for Lean Engagement and Research (CLEAR), University of California, Berkeley as a Lean principles-based survey instrument that avoids the above problems. We validated the original LHISI in the context of Finnish healthcare.

Methods
The original HISI survey was sent over a secure organizational email system to the over 26,000 employees of the Hospital District of Helsinki and Uusimaa in March 2020. The data were randomly split with one part used to carry out an exploratory factor analysis (EFA), and the other for testing the resulting model using confirmatory factor analysis (CFA).

Results
A total of 6073 employees responded to the LHISI survey, for an overall response rate of 23%. The results indicated that the 43 items used in the original LHISI can be reduced to 25 items, and these items measure a five-dimensional model of the progress of Lean implementation: leadership, commitment, standard work, communication, and daily management system. In comparison with a single-factor model, the fit measures for the 5-factor model were better: smaller X2, larger comparative fit index (CFI), smaller root mean square error of approximation (RMSEA), and smaller standardized root mean square residual (SRMR).

Conclusions
The 25 item LHISI is valid and feasible to use in the context of Finnish healthcare. The LHISI allows the organization to self-monitor the progress of its Lean implementation and provides the leadership with actionable knowledge to guide the path towards Lean maturity across the organization. Our findings encourage further studies on the adoption and validation of the LHISI in healthcare organizations worldwide.
Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
Authors: De Filippi Rosaria , Morabito Fortunato , Santoro Armando , Tripepi Giovanni , D’Alò Francesco , Rigacci Luigi , Ricci Francesca , Morelli Emanuela , Zinzani Pier Luigi , Pinto Antonio 
Published: December 2021

Abstract
Background
Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade.

Methods
Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions.

Results
Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI.

Conclusions
In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic ‘equalizers’ counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.
Baseline [18F]GTP1 tau PET imaging is associated with subsequent cognitive decline in Alzheimer’s disease
Authors: Teng Edmond , Manser Paul T. , Sanabria Bohorquez Sandra , Wildsmith Kristin R. , Pickthorn Karen , Baker Suzanne L. , Ward Michael , Kerchner Geoffrey A. , Weimer Robby M. 
Published: December 2021

Abstract
Background
The role and implementation of tau PET imaging for predicting subsequent cognitive decline in Alzheimer’s disease (AD) remains uncertain. This study was designed to evaluate the relationship between baseline [18F]GTP1 tau PET and subsequent longitudinal change across multiple cognitive measures over 18 months.

Methods
Our analyses incorporated data from 67 participants, including cognitively normal controls (n = 10) and β-amyloid (Aβ)-positive individuals ([18F] florbetapir Aβ PET) with prodromal (n = 26), mild (n = 16), or moderate (n = 15) AD. Baseline measurements included cortical volume (MRI), tau burden ([18F]GTP1 tau PET), and cognitive assessments [Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), 13-item version of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)]. Cognitive assessments were repeated at 6-month intervals over an 18-month period. Associations between baseline [18F]GTP1 tau PET indices and longitudinal cognitive performance were assessed via univariate (Spearman correlations) and multivariate (linear mixed effects models) approaches. The utility of potential prognostic tau PET cut points was assessed with ROC curves.

Results
Univariate analyses indicated that greater baseline [18F]GTP1 tau PET signal was associated with faster rates of subsequent decline on the MMSE, CDR, and ADAS-Cog13 across regions of interest (ROIs). In multivariate analyses adjusted for baseline age, cognitive performance, cortical volume, and Aβ PET SUVR, the prognostic performance of [18F]GTP1 SUVR was most robust in the whole cortical gray ROI. When AD participants were dichotomized into low versus high tau subgroups based on baseline [18F]GTP1 PET standardized uptake value ratios (SUVR) in the temporal (cutoff = 1.325) or whole cortical gray (cutoff = 1.245) ROIs, high tau subgroups demonstrated significantly more decline on the MMSE, CDR, and ADAS-Cog13.

Conclusions
Our results suggest that [18F]GTP1 tau PET represents a prognostic biomarker in AD and are consistent with data from other tau PET tracers. Tau PET imaging may have utility for identifying AD patients at risk for more rapid cognitive decline and for stratification and/or enrichment of participant selection in AD clinical trials.
Trial registration
ClinicalTrials.gov NCT02640092. Registered on December 28, 2015
Rabies is still a fatal but neglected disease: a case report
Authors: Amoako Y. A. , El-Duah P. , Sylverken A. A. , Owusu M. , Yeboah R. , Gorman R. , Adade T. , Bonney J. , Tasiame W. , Nyarko-Jectey K. , Binger T. , Corman V. M. , Drosten C. , Phillips R. O. 
Published: December 2021

Abstract
Background
Rabies, caused by a lyssavirus, is a viral zoonosis that affects people in many parts of the world, especially those in low income countries. Contact with domestic animals, especially dogs, is the main source of human infections. Humans may present with the disease only after a long period of exposure. Nearly half of rabies cases occur in children <15 years old. We report on a fatal case of rabies in a Ghanaian school child 5 years after the exposure incident, and the vital role of molecular tools in the confirmation of the diagnosis.

Case presentation
The patient, an 11-year-old junior high school Ghanaian student from the Obuasi Municipality in Ghana, presented with aggressive behavior, which rapidly progressed to confusion and loss of consciousness within a day of onset. Her parents reported that the patient had experienced a bite from a stray dog on her right leg 5 years prior to presentation, for which no antirabies prophylaxis was given. The patient died within minutes of arrival in hospital (within 24 hours of symptom onset). Real-time polymerase chain reaction testing of cerebrospinal fluid obtained after her death confirmed the diagnosis of rabies. Subsequent phylogenetic analysis showed the virus to belong to the Africa 2 lineage of rabies viruses, which is one of the predominant circulating lineages in Ghana.

Conclusion
The incubation period of rabies is highly variable so patients may only present with symptoms long after the exposure incident. Appropriate molecular testing tools, when available as part of rabies control programmes, are vital in confirming cases of rabies.
Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
Authors: Sun Na , Trajkovic-Arsic Marija , Li Fengxia , Wu Yin , Münch Corinna , Kunzke Thomas , Feuchtinger Annette , Steiger Katja , Schlitter Anna Melissa , Weichert Wilko , Esposito Irene , Siveke Jens T. , Walch Axel 
Published: December 2021

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies to date. The impressively developed stroma that surrounds and modulates the behavior of cancer cells is one of the main factors regulating the PDAC growth, metastasis and therapy resistance. Here, we postulate that stromal and cancer cell compartments differentiate in protein/lipid glycosylation patterns and analyze differences in glycan fragments in those compartments with clinicopathologic correlates.

Results
We analyzed native glycan fragments in 109 human FFPE PDAC samples using high mass resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometric imaging (MALDI-FT-ICR-MSI). Our method allows detection of native glycan fragments without previous digestion with PNGase or any other biochemical reaction. With this method, 8 and 18 native glycans were identified as uniquely expressed in only stromal or only cancer cell compartment, respectively. Kaplan–Meier survival model identified glycan fragments that are expressed in cancer cell or stromal compartment and significantly associated with patient outcome. Among cancer cell region-specific glycans, 10 predicted better and 6 worse patient survival. In the stroma, 1 glycan predicted good and 4 poor patient survival. Using factor analysis as a dimension reduction method, we were able to group the identified glycans in 2 factors. Multivariate analysis revealed that these factors can be used as independent survival prognostic elements with regard to the established Union for International Cancer Control (UICC) classification both in tumor and stroma regions.

Conclusion
Our method allows in situ detection of naturally occurring glycans in FFPE samples of human PDAC tissue and highlights the differences among glycans found in stromal and cancer cell compartment offering a basis for further exploration on the role of specific glycans in cancer–stroma communication.
More crime in cities? On the scaling laws of crime and the inadequacy of per capita rankings—a cross-country study
Authors: Oliveira Marcos 
Published: December 2021

AbstractCrime rates per capita are used virtually everywhere to rank and compare cities. However, their usage relies on a strong linear assumption that crime increases at the same pace as the number of people in a region. In this paper, we demonstrate that using per capita rates to rank cities can produce substantially different rankings from rankings adjusted for population size. We analyze the population–crime relationship in cities across 12 countries and assess the impact of per capita measurements on crime analyses, depending on the type of offense. In most countries, we find that theft increases superlinearly with population size, whereas burglary increases linearly. Our results reveal that per capita rankings can differ from population-adjusted rankings such that they disagree in approximately half of the top 10 most dangerous cities in the data analyzed here. Hence, we advise caution when using crime rates per capita to rank cities and recommend evaluating the linear plausibility before doing so.
A case of complete atrioventricular block with extremely high blood concentration of azelnidipine
Authors: Ide Naohito , Mochizuki Ayaka , Kagawa Yoshiyuki , Ito Masaharu 
Published: December 2021

Abstract
Background
Azelnidipine, a dihydropyridine calcium channel blocker (CCB), has less adverse effects (e.g. hot flushes and reflex tachycardia) compared to other dihydropyridine CCBs. Azelnidipine has been reported to reduce heart rate as opposed to inducing tachycardia. No evidence of bradycardia or complete atrioventricular block (CAVB) with azelnidipine treatment has been reported.

Case presentation
In the present study, a 92-year-old woman was diagnosed with CAVB while taking azelnidipine and simvastatin for an extended period of time, and referred to our medical center. It was thought that the CAVB may have been an adverse effect of azelnidipine treatment. Specifically, it was considered that in this patient, one of the causes might be the concomitant use of simvastatin inhibiting the metabolism of azelnidipine by cytochrome P450 enzyme 3A4. Consequently, it was suggested to the patient’s physician that the patient’s serum azelnidipine levels be measured and treatment with azelnidipine and simvastatin be discontinued. The patient’s serum concentration of azelnidipine at the time of her visit to our center was 63.4 ng/mL, higher than the normal acceptable level. There was no occurrence of CAVB for 4 weeks, to present, following discontinuation of azelnidipine and simvastatin treatment.

Conclusions
Azelnidipine has a different mechanism of action that other CCBs. In very rare cases, it may cause CAVB when combined with CYP3A4 inhibitors. If a patient taking azelnidipine is diagnosed with CAVB, physicians should suspect that the condition may be an adverse effect of azelnidipine and should consider discontinuing azelnidipine. And, in the elderly, it is necessary to avoid concomitant use of CYP3A4 inhibitors.
Associations between measurements of central blood pressure and target organ damage in high-risk patients
Authors: Jeon Ki-Hyun , Kim Hack-Lyoung , Lim Woo-Hyun , Seo Jae-Bin , Kim Sang-Hyun , Zo Joo-Hee , Kim Myung-A 
Published: December 2021

Abstract
Background
It is not well-known which components of central blood pressure (CBP) are more influential to target organ damage (TOD). This study aimed to determine the relationship between CBP measurements and various types of TOD in high-risk patients.

Methods
A total of 148 patients who had documented atherosclerotic cardiovascular disease or its multiple risk factors were prospectively enrolled. CBP was measured by using applanation tonometry of the radial artery. The following nine TOD parameters were evaluated: left ventricular mass index, relative wall thickness, septal e′ velocity, septal E/e′, brachial-ankle pulse wave velocity, ankle-brachial index, estimated glomerular filtration rate, urine protein and obstructive coronary artery disease.

Results
The mean age of the study population was 67.1 ± 9.0 years and 108 (73 %) were male. Among four CBP measurements (systolic, diastolic, mean, and pulse pressures), central pulse pressure (CPP) was associated with the largest number of TOD parameters. As CPP increased, the number of TOD increased (P = 0.010), but this association was not observed in other CBP measurements (P > 0.05 for each).

Conclusions
CPP had a stronger correlation with TOD than other CBP measurements. Non-invasive CPP could be a useful indicator for predicting TOD in patients at high coronary risk.
Medico-legal evidence collection in child sexual assault cases: a forensic significance
Authors: Kaur Suminder , Kaur Simarpreet , Rawat Banita 
Published: December 2021

Abstract
Background
Every year, millions of children face sexual exploitation worldwide. In India, 109 children (National Crime Records Bureau2018) were sexually abused everyday (22% jump from the previous year). Even with advanced DNA techniques, the conviction rate remains low. The methods used for forensic DNA evidence analysis vary around the world, but the primary step of biological evidence collection plays the most vital role. Proper and timely evidence collection from the victim by a trained medical professional is important.

Main body
Dynamics of child sexual assault being massively different from an adult rape demands altogether different approach of evidence collection. A standard sexual kit employed for evidence collection needs urgent modifications considering genital development of pre- and post-pubertal victims. In the present study, parameters including systemic collection and evaluation of forensic evidences, medico-legal examination, and developmental consequences of sexual assault on pre-pubertal victims were assessed. Further suggestions for separate evidence collection kit during medico-legal examination were given for pre-pubertal victims and alleged accused in sexual assault cases in order to streamline and for better evaluation of DNA analysis in forensic laboratories.

Conclusion
The importance of expert medical practitioners plays a significant role in collection of appropriate information and evidences from the victim of sexual assault. General guidelines for evidence collection in sexual assault cases are not well suited for pre-pubertal victims. Appropriate reforms pertaining to the age and genital development of victims are required. Securing clothing as forensic evidence is essential in most cases as it turned out to be the exclusive evidence bearing material. The purpose of this article is to bring awareness about the thorough medical examination and modified sexual assault kit for pre-pubertal victims and alleged accused for a better approach in evidence collection and conviction rate.
Functional outcome in operated patients of multilevel lumbar canal stenosis and use of HRQoL role in depicting the anxiety and its correlation with the pain
Authors: Singh Ajay Kumar , Singh Prashant Raj , Pandey Tarun Kumar , Kumar Ankur , Agarwal Abhay Kumar 
Published: December 2021

Abstract
Background
Lumbar canal stenosis (LCS) is a degenerative spinal disease of elderly people, and it not only impairs the mechanical activity but also alters the economic and mental status of the patients indirectly.
This is single-center observational prospective study conducted for 2 years and included 30 consecutive operated patients of multilevel LCS patients and excluded the patients with single-level LCS, with primary LCS or with grade II subluxation. We analyzed the various measurement indices used for the surgical outcome assessment as ED-5D 5L and OLBPDI (Oswestry low back pain disability index). Statistical analysis was done using SPSS (Statistical Package for Social Sciences) Version 21.0 statistical Analysis Software. The independent t test, post hoc analysis, Wilcoxon signed rank statistic test and RM-ANOVA test were also applied.

Result
Most patients have improvement in pain and all the components of HRQoL (health-related quality of life) after surgery, which was further improved in mean follow-up of 1 year. Our study also suggested that the patients with higher anxiety/depression have higher pain intensity and low HRQoL, which was persistent in postoperative period (p < .001).

Conclusion
ED-5D 5L and OLBPD are good indices to assess all the components of quality of life and give valuable information overall. Anxiety has shown important correlation with the pain component in both preoperative and postoperative phase.
Privacy preserving divisible double auction with a hybridized TEE-blockchain system
Authors: Liu Bingyu , Xie Shangyu , Yang Yuanzhou , Wang Rujia , Hong Yuan 
Published: December 2021

AbstractDouble auction mechanisms have been designed to trade a variety of divisible resources (e.g., electricity, mobile data, and cloud resources) among distributed agents. In such divisible double auction, all the agents (both buyers and sellers) are expected to submit their bid profiles, and dynamically achieve the best responses. In practice, these agents may not trust each other without a market mediator. Fortunately, smart contract is extensively used to ensure digital agreement among mutually distrustful agents. The consensus protocol helps the smart contract execution on the blockchain to ensure strong integrity and availability. However, severe privacy risks would emerge in the divisible double auction since all the agents should disclose their sensitive data such as the bid profiles (i.e., bid amount and prices in different iterations) to other agents for resource allocation and such data are replicated on all the nodes in the network. Furthermore, the consensus requirements will bring a huge burden for the blockchain, which impacts the overall performance. To address these concerns, we propose a hybridized TEE-Blockchain system (system and auction mechanism co-design) to privately execute the divisible double auction. The designed hybridized system ensures privacy, honesty and high efficiency among distributed agents. The bid profiles are sealed for optimally allocating divisible resources while ensuring truthfulness with a Nash Equilibrium. Finally, we conduct experiments and empirical studies to validate the system and auction performance using two real-world applications.
‘Clear explanation’ in mental capacity assessment
Authors: Owen Gareth , Kane Nuala , Keene Alex Ruck 
Published: December 2021

SUMMARYWe comment on Martin Curtice's article on expert and professional reports for the Court of Protection, which highlights the importance of ‘clear explanation’ in mental capacity assessment. We put the Court in a broader context of the Mental Capacity Act and summarise recent research and education that aims to help give clinicians working in England and Wales capacity assessment guidance that is clinically grounded, multi-perspectival and legally defensible.
Orbital selectivity in the normal state of KFe(2)Se(2) superconductor
Authors: Craco Luis , Leoni Stefano 
Published: December 2021

Abstract
Using density functional dynamical mean-ﬁeld theory, we show how correlation eﬀects lead to pseudogap and Kondo-quasiparticle features in the electronic structure of pure and doped KFe2Se2 superconductor. Therein, correlation- and doping-induced orbital diﬀerentiation are linked to the emergence of an incoherent-coherent crossover in the normal state of KFe2Se2 superconductor. This crossover explains the puzzling temperature and doping dependent evolution of resistivity and Hall coeﬃcient, seen in experiments of alkali-metal intercalated iron-selenide superconductors. Our microscopic description emphasises the role of incoherent and coherent electronic excitations towards unconventional transport responses of strange, bad-metals.