bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation and characterizations of glyceryl oleate ufasomes of terbinafine hydrochloride: a novel approach to trigger Candida albicans fungal infection
Authors: Bhattacharya Sankha 
Published: January 2021

Abstract
Background
Worldwide fungal infection cases are increasing by leaps and bounds. The patients who are immunocompromised, i.e., cancer and AIDS, are more susceptible to different types of fungal infections like cutaneous candidiasis and its associate infections. The available treatment for such a disease is creams, gels, etc. However, due to the lack of penetrability and higher systematic absorption, these formulations have reported many side effects. To overcome such challenges, various novel drug delivery systems were introduced. The present research focused on the preparation of glyceryl oleate ufasomes of terbinafine hydrochloride using the film hydration method.

Result
The prepared formulations were characterized for globular size (nm), zeta potential (mV), PDI, morphological characteristics, thermal behavior, in vitro drug release, in vitro antifungal activity, and in vitro skin permeation retention studies. After suitable formulation optimization using thin-film hydration method, 3:7 drug to glyceryl oleate ratio, UF3 formulation was found to produce higher drug entrapment efficacy (52.45 ± 0.56%), stable anionic zeta potential (− 33.37 ± 0.231 mV), desired globular size (376.5 ± 0.42 nm), and decent polydispersity index (0.348 ± 0.0345). Diffusion-controlled and zero-order sustained release profile was observed in the optimized UF3 batch. From the 5 days in vitro antifungal activity studies, it confirmed that UF3 ufasomes possessed good applicability in more prolonged therapy.

Conclusion
From the current investigation, it can be concluded that glyceryl oleate ufasomes of terbinafine hydrochloride could be an excellent approach to treat topical fungal infections.
Analysing Joker: an attempt to establish diagnosis for a film icon
Authors: Skryabin Valentin Yurievich 
Published: January 2021

SummaryTodd Phillips's film Joker, a 2019 psychological thriller, has stirred up strong reactions to the portrayal of the lead character's mental disorder, which is never specified. I used DSM-5 criteria to study whether Joker/Arthur Fleck showed signs of a real mental disorder. The psychopathology Arthur exhibits is unclear, preventing diagnosis of psychotic disorder or schizophrenia; the unusual combination of symptoms suggests a complex mix of features of certain personality traits, namely psychopathy and narcissism (he meets DSM-5 criteria for narcissistic personality disorder). He also shows the symptoms of pseudobulbar affect due to traumatic brain injury. This apparent co-occurrence of both mental disorder and a neurological condition may be confusing for audiences trying to understand mental illness.
Prehabilitation during a pandemic: preoperative exercise to improve fitness in patients undergoing complex surgery for cancer of the lung or oesophagus, the PRE-HIIT trial: an updated study protocol
Authors: Sheill Grainne , Guinan Emer , O'Neill Linda , Smyth Emily , Normand Charles , L. Doyle Suzanne , Moore Sarah , Newell John , McDermott Grainne , Ryan Ronan , V. Reynolds John , Hussey Juliette 
Published: January 2021

Background: Pre-operative fitness is an established predictor of postoperative outcome; accordingly, targeting pre-operative fitness through exercise prehabilitation has logical appeal. Exercise prehabilitation for patients with cancer of the lung or oesophagus is challenging to implement due to the short opportunity for intervention between diagnosis and surgery. In addition, there are now additional challenges to providing prehabilitation during the coronavirus disease 2019 (COVID-19) pandemic due to concerns about social distancing and minimising patient contact. The PRE-HIIT project will examine the influence of virtually delivered exercise prehabilitation on physiological outcomes and postoperative recovery. Methods: The PRE-HIIT randomised controlled trial (RCT) will compare a 2-week high intensity interval training programme to standard preoperative care in a cohort of patients with thoracic and oesophageal cancers. A protocol for this study has been published previously. As a result of the COVID-19 pandemic, changes to the study assessment battery and the mode of intervention delivery have been made. The PRE-HIIT programme will now be a home-based intervention. Both the exercise intervention and standard care will be delivered via telehealth. The recruitment target for the study remains 78 participants. There is no change to the primary outcome of the study; cardiorespiratory fitness. Secondary outcomes include measures of pulmonary and physical function, quality of life and post-operative morbidity. Outcomes will be measured at baseline and post-intervention. The impact of PRE-HIIT on well-being will be examined qualitatively with interviews post-intervention (T1). This revised protocol will also explore participant’s satisfaction with delivery of prehabilitation via telehealth. The healthcare costs associated with the PRE-HITT programme will also be examined. Discussion: The overall aim of this RCT is to examine the effect of tailored, individually prescribed high intensity interval training on pre-operative fitness and postoperative recovery for patients undergoing complex surgical resections. Trial registration: ClinicalTrials.Gov NCT03978325 07/06/2019
Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers
Authors: Ruzhanskaya Anna , Ichihara Kiyoshi , Evgina Svetlana , Skibo Irina , Vybornova Nina , Vasiliev Anton , Agarkova Galina , Emanuel Vladimir 
Published: January 2021

Objectives
A multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 22 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population.

Methods
According to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 758 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 17 hormones and related tests by Beckman Coulter’s UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age.

Results
SDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5% males and 11.3% females); for insulin, those with BMI≥28 kg/m2 (31%); for the thyroid panel, those with anti-thyroid antibodies (10.3% males; 24.5% females), for CEA those with smoking habit (30% males and 16% females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for alpha-fetoprotein, CEA, all sex-hormones for females, FSH and progesterone for both sexes. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol for females in postmenopause, and progesterone for females in premenopause, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit.

Conclusion
RIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.
A study of evaluating specific tissue oxygen saturation values of gastrointestinal tumors by removing adherent substances in oxygen saturation imaging
Authors: Nishihara Keiichiro , Hori Keisuke , Saito Takaaki , Omori Toshihiko , Sunakawa Hironori , Minamide Tatsunori , Suyama Masayuki , Yamamoto Yoichi , Yoda Yusuke , Shinmura Kensuke , Ikematsu Hiroaki , Yano Tomonori 
Published: January 2021

Objectives
Oxygen saturation (OS) imaging is a new method of endoscopic imaging that has clinical applications in oncology which can directly measure tissue oxygen saturation (Sto2) of the surface of gastrointestinal tract without any additional drugs or devices. This imaging technology is expected to contribute to research into cancer biology which leads to clinical benefit such as prediction to efficacy of chemotherapy or radiotherapy. However, adherent substances on tumors such as blood and white coating, pose a challenge for accurate measurements of the StO2 values in tumors. The aim of this study was to develop algorithms for discriminating between the tumors and their adherent substances, and to investigate whether it is possible to evaluate the tumor specific StO2 values excluding adherent substances during OS imaging.

Methods
We plotted areas of tumors and their adherent substances using white-light images of 50 upper digestive tumors: blood (68 plots); reddish tumor (83 plots); white coating (89 plots); and whitish tumor (79 plots). Scatter diagrams and discriminating algorithms using spectrum signal intensity values were constructed and verified using validation datasets. StO2 values were compared between the tumors and tumor adherent substances using OS images of gastrointestinal tumors.

Results
The discriminating algorithms and their accuracy rates (AR) were as follows: blood vs. reddish tumor: Y> - 4.90X+7.13 (AR: 95.9%) and white coating vs. whitish tumor: Y< -0.52X+0.17 (AR: 96.0%). The StO2 values (median, [range]) were as follows: blood, 79.3% [37.8%–100.0%]; reddish tumor, 74.5% [62.0%–86.9%]; white coating, 73.8% [42.1%–100.0%]; and whitish tumor, 65.7% [53.0%–76.3%].

Conclusions
OS imaging is strongly influenced by adherent substances for evaluating the specific StO2 value of tumors; therefore, it is important to eliminate the information of adherent substances for clinical application of OS imaging.
What could prevent chronic condition admissions assessed as preventable in rural and metropolitan contexts? An analysis of clinicians’ perspectives from the DaPPHne study
Authors: Longman Jo , Johnston Jennifer , Ewald Dan , Gilliland Adrian , Burke Michael , Mutonga Tabeth , Passey Megan 
Published: January 2021

Introduction
Reducing potentially preventable hospitalisations (PPH) is a priority for health services. This paper describes the factors that clinicians perceived contributed to preventable admissions for angina, diabetes, congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD), and what they considered might have been done in the three months leading up to an admission to prevent it.

Methods
The study was conducted in a rural and a metropolitan health district in NSW, Australia. Expert Panels reviewed detailed case reports to assess preventability. For those admissions identified as preventable, comments from clinicians indicating what they perceived could have made a difference and/or been done differently to prevent each of the preventable admissions were analysed qualitatively.

Results
148 (46%) of 323 admissions were assessed as preventable. Across the two districts, the most commonly identified groups of contributing factors to preventable admissions were: ‘Systems issues: Community based services missing or inadequate or not referred to’; ‘Patient issues: Problems with adherence/self-management’; and ‘Clinician issues: GP care inadequate’. In some instances, important differences drove these groups of factors. For example, in the rural district ‘Systems issues: Community based services missing or inadequate or not referred to’ was largely driven by social and welfare support services missing/inadequate/not referred to, whereas in the metropolitan district it was largely driven by community nursing, allied health, care coordination or integrated care services missing/inadequate/not referred to. Analyses revealed the complexity of system, clinician and patient factors contributing to each admission. Admissions for COPD (rural) and CHF (metropolitan) admissions showed greatest complexity.

Discussion and conclusion
These findings suggest preventability of individual admissions is complex and context specific. There is no single, simple solution likely to reduce PPH. Rather, an approach addressing multiple factors is required. This need for comprehensiveness may explain why many programs seeking to reduce PPH have been unsuccessful.
Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: A prospective observational Brazilian study
Authors: Brandão Neto Rodrigo A. , Marchini Julio F. , Marino Lucas O. , Alencar Julio C. G. , Lazar Neto Felippe , Ribeiro Sabrina , Salvetti Fernando V. , Rahhal Hassan , Gomez Gomez Luz Marina , Bueno Caue G. , Faria Carine C. , da Cunha Victor P. , Padrão Eduardo , Velasco Irineu T. , de Souza Heraldo Possolo ,   Emergencia USP Covid group
Published: January 2021

BackgroundThe first cases of coronavirus disease (COVID-19) in Brazil were diagnosed in February 2020. Our Emergency Department (ED) was designated as a COVID-19 exclusive service. We report our first 500 confirmed COVID-19 pneumonia patients.MethodsFrom 14 March to 16 May 2020, we enrolled all patients admitted to our ED that had a diagnosis of COVID-19 pneumonia. Infection was confirmed via nasopharyngeal swabs or tracheal aspirate PCR. The outcomes included hospital discharge, invasive mechanical ventilation, and in-hospital death, among others.ResultsFrom 2219 patients received in the ED, we included 506 with confirmed COVID-19 pneumonia. We found that 333 patients were discharged home (65.9%), 153 died (30.2%), and 20 (3.9%) remained in the hospital. A total of 300 patients (59.3%) required ICU admission, and 227 (44.9%) needed invasive ventilation. The multivariate analysis found age, number of comorbidities, extension of ground glass opacities on chest CT and troponin with a direct relationship with all-cause mortality, whereas dysgeusia, use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker and number of lymphocytes with an inverse relationship with all-cause mortalityConclusionsThis was a sample of severe patients with COVID-19, with 59.2% admitted to the ICU and 41.5% requiring mechanical ventilator support. We were able to ascertain the outcome in majority (96%) of patients. While the overall mortality was 30.2%, mortality for intubated patients was 55.9%. Multivariate analysis agreed with data found in other studies although the use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker as a protective factor could be promising but would need further studies.Trial registrationThe study was registered in the Brazilian registry of clinical trials:RBR-5d4dj5.
(TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study
Authors: Waskowski Jan , Pfortmueller Carmen A. , Schenk Noelle , Buehlmann Roman , Schmidli Juerg , Erdoes Gabor , Schefold Joerg C. 
Published: January 2021

Objective
Postoperative acute kidney injury (po-AKI) is frequently observed after major vascular surgery and impacts on mortality rates. Early identification of po-AKI patients using the novel urinary biomarkers insulin-like growth factor-binding-protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) might help in early identification of individuals at risk of AKI and enable timely introduction of preventative or therapeutic interventions with the aim of reducing the incidence of po-AKI. We investigated whether biomarker-based monitoring would allow for early detection of po-AKI in patients undergoing abdominal aortic interventions.

Methods
In an investigator-initiated prospective single-center observational study in a tertiary care academic center, adult patients with emergency/ elective abdominal aortic repair were included. Patients were tested for concentrations of urinary (TIMP-2) x (IGFBP7) at baseline, after surgical interventions (PO), and in the mornings of the first postoperative day (POD1). The primary endpoint was a difference in urinary (TIMP-2) x (IGFBP7) levels at POD1 in patients with/ without po-AKI (all KDIGO stages, po-AKI until seven days after surgery). Secondary endpoints included sensitivity/ specificity analyses of previously proposed cut-off levels and clinical outcome measures (e.g. need for renal replacement therapy).

Results
93 patients (n = 71 open surgery) were included. Po-AKI was observed in 33% (31/93) of patients. Urinary (TIMP-2) x (IGFBP7) levels at POD1 did not differ between patients with/ without AKI (median 0.39, interquartile range [IQR] 0.13–1.05 and median 0.23, IQR 0.14–0.53, p = .11, respectively) and PO (median 0.2, IQR 0.08–0.42, 0.18, IQR 0.09–0.46; p = .79). Higher median (TIMP-2) x (IGFBP7) levels were noted in KDIGO stage 3 pAKI patients at POD1 (3.75, IQR 1.97–6.92; p = .003). Previously proposed cutoff levels (0.3, 2) showed moderate sensitivity/ specificity (0.58/0.58 and 0.16/0.98, respectively).

Conclusion
In a prospective monocentric observational study in patients after abdominal aortic repair, early assessment of urinary (TIMP-2) x (IGFBP7) did not appear to have adequate sensitivity/ specificity to identify patients that later developed postoperative AKI.

Clinicaltrials.gov
NCT03469765, registered March 19, 2018.
The complex interplay of climate, TBEV vector dynamics and TBEV infection rates in ticks—Monitoring a natural TBEV focus in Germany, 2009–2018
Authors: Borde Johannes P. , Kaier Klaus , Hehn Philip , Matzarakis Andreas , Frey Stefan , Bestehorn Malena , Dobler Gerhard , Chitimia-Dobler Lidia 
Published: January 2021

Background
Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia and causes disease in humans and in a number of animals, among them dogs and horses. There is still no good correlation between tick numbers, weather conditions and human cases. There is the hypothesis that co-feeding due to simultaneous occurrence of larvae and nymphs may be a factor for the increased transmission of the virus in nature and for human disease. Based on long-term data from a natural TBEV focus, phylogenetic results and meteorological data we sought to challenge this hypothesis.

Methods
Ticks from an identified TBE natural focus were sampled monthly from 04/2009 to 12/2018. Ticks were identified and pooled. Pools were tested by RT-qPCR. Positive pools were confirmed by virus isolation and/or sequencing of additional genes (E gene, NS2 gene). Temperature data such as the decadal (10-day) mean daily maximum air temperature (DMDMAT) were obtained from a nearby weather station and statistical correlations between tick occurrence and minimal infection rates (MIR) were calculated.

Results
In the study period from 04/2009 to 12/2018 a total of 15,530 ticks (2,226 females, 2,268 males, 11,036 nymphs) were collected. The overall MIR in nymphs over the whole period was 77/15,530 (0.49%), ranging from 0.09% (2009) to 1.36% (2015). The overall MIR of female ticks was 0.76% (17/2,226 ticks), range 0.14% (2013) to 3.59% (2016). The overall MIR of males was 0.57% (13/2,268 ticks), range from 0.26% (2009) to 0.97% (2015). The number of nymphs was statistically associated with a later start of spring/vegetation period, indicated by the onset of forsythia flowering.

Conclusion
There was no particular correlation between DMDMAT dynamics in spring and/or autumn and the MIR of nymphs or adult ticks detected. However, there was a positive correlation between the number of nymphs and the number of reported human TBE cases in the following months, but not in the following year. The hypothesis of the importance of co-feeding of larvae and nymphs for the maintenance of transmission cycle of TBEV in nature is not supported by our findings.
Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations
Authors: Taylor Sarah A. , Chen Shang-Yang , Gadhvi Gaurav , Feng Liang , Gromer Kyle D. , Abdala-Valencia Hiam , Nam Kiwon , Dominguez Salina T. , Montgomery Anna B. , Reyfman Paul A. , Ostilla Lorena , Wechsler Joshua B. , Cuda Carla M. , Green Richard M. , Perlman Harris , Winter Deborah R. 
Published: January 2021

Background & aims
Limited understanding of the role for specific macrophage subsets in the pathogenesis of cholestatic liver injury is a barrier to advancing medical therapy. Macrophages have previously been implicated in both the mal-adaptive and protective responses in obstructive cholestasis. Recently two macrophage subsets were identified in non-diseased human liver; however, no studies to date fully define the heterogeneous macrophage subsets during the pathogenesis of cholestasis. Here, we aim to further characterize the transcriptional profile of macrophages in pediatric cholestatic liver disease.

Methods
We isolated live hepatic immune cells from patients with biliary atresia (BA), Alagille syndrome (ALGS), and non-cholestatic pediatric liver by fluorescence activated cell sorting. Through single-cell RNA sequencing analysis and immunofluorescence, we characterized cholestatic macrophages. We next compared the transcriptional profile of pediatric cholestatic and non-cholestatic macrophage populations to previously published data on normal adult hepatic macrophages.

Results
We identified 3 distinct macrophage populations across cholestatic liver samples and annotated them as lipid-associated macrophages, monocyte-like macrophages, and adaptive macrophages based on their transcriptional profile. Immunofluorescence of liver tissue using markers for each subset confirmed their presence across BA (n = 6) and ALGS (n = 6) patients. Cholestatic macrophages demonstrated reduced expression of immune regulatory genes as compared to normal hepatic macrophages and were distinct from macrophage populations defined in either healthy adult or pediatric non-cholestatic liver.

Conclusions
We are the first to perform single-cell RNA sequencing on human pediatric cholestatic liver and identified three macrophage subsets with distinct transcriptional signatures from healthy liver macrophages. Further analyses will identify similarities and differences in these macrophage sub-populations across etiologies of cholestatic liver disease. Taken together, these findings may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.