bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and factors associated with post‐anesthesia care unit complications in resource‐limited settings: An observational study
Authors: Abebe Bisrat , Kifle Natnael , Gunta Muluken , Tantu Temesgen , Wondwosen Mekete , Zewdu Dereje
Published: May 2022

Background and aims

Postoperative complications are frequent encounters in the patients admitted to postanesthesia care units (PACU). The main aim of this study was to assess the incidence of complications and associated factors among surgical patients admitted in limited‐resource settings of the PACU.

Methods

This is an observational study of 396 surgical patients admitted to PACU. This study was conducted from February 1 to March 30, 2021, in Ethiopia. Study participants' demographics, anesthesia, and surgery‐related parameters, PACU complications, and length of stay in PACU were documented. Multivariate and bivariate logistic regression analyses, the odds ratio (OR), and 95% confidence interval (CI) were calculated. p‐value < 0.05 was considered as statistically significant.

Results

The incidence of complications among surgical patients admitted to PACU was 54.8%. Of these, respiratory‐related complications and postoperative nausea/vomiting were the most common types of PACU complications. Being a female (adjusted odds ratio [AOR] = 2.928; 95% CI: 1.899–4.512) was significantly associated with an increased risk of developing PACU complications. Duration of anesthesia >4 h (AOR = 5.406; 95% CI: 2.418–12.088) revealed an increased risk of association with PACU complications. The occurrences of intraoperative complications (AOR = 2.238; 95% CI: 0.991–5.056) during surgery were also associated with PACU complications. Patients who develop PACU complications were strongly associated with length of PACU stay for >4 h (AOR = 2.177; 95% CI: 0.741–6.401).

Conclusion

The identified risk factors for complications in surgical patients admitted to PACU are female sex, longer duration of anesthesia, and intraoperative complications occurrences. Patients who developed complications had a long time of stay in PACU. Based on our findings, we recommend the PACU team needs to develop area‐specific institutional guidelines and protocols to improve the patients' quality of care and outcomes in PACU.
‎Factors associated with coronavirus disease 2019 infection severity among a sample of Lebanese adults: Data from a cross‐sectional study
Authors: El‐Hayek Elissar , Kahwagi Georges‐Junior , Issy Nour , Tawil Christina , Younis Nabil , Abou‐Khalil Rony , Matar Madonna , Hallit Souheil
Published: May 2022

Background and Aims

Identification of factors responsible for severe illness related to coronavirus disease 2019 (COVID‐19) could help in the early management of patients with high risk, especially in developing countries with poor medical care systems. To date, no data have been published concerning the factors associated with COVID‐19 severity in Lebanon. In this study, we aimed at investigating the relation between sociodemographic variables, health status, and the clinical outcomes of COVID‐19 in a sample of Lebanese adults.

Methods

In our cross‐sectional study, 1052 patients (563 male and 489 female, with the median age of 42.83 ± 17.88 years), tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) between January and March 2021, were recruited from a hospital in Byblos, Lebanon. Basic demographic data, medical history, clinical data, and selfreported symptoms related to COVID‐19 were collected. Clinical classification of COVID‐19 severity was carried out according to the WHO interim guidance on May 27, 2020. Multi and bivariate regression analysis were performed.

Results

When comparing patients with moderate symptoms versus mild, the results showed that older age (aOR = 1.05; 95% CI: 1.03–1.06) and having dyslipidemia (aOR = 1.89; 95% CI: 1.01–3.49) were significantly associated with higher odds of having moderate symptoms. When comparing patients with severe symptoms versus mild, older age (aOR = 1.08; 95% CI: 1.06–1.10), higher body mass index (aOR = 1.09; 95% CI: 1.04–1.15) and having respiratory diseases (aOR = 2.57; 95% CI: 1.03–6.36) were significantly associated with higher odds of having severe symptoms, whereas female gender (aOR = 0.56; 95% CI: 0.32–0.98) was significantly associated with lower odds of having severe symptoms compared to males. Finally, when comparing patients with severe symptoms versus moderate, older age (aOR = 1.03; 95% CI: 1.01–1.05) was found to be significantly associated with higher odds of having severe symptoms.

Conclusion

Identification of risk factors may contribute to a better understanding of the COVID‐19 pathogenesis and provide clinical reference for early prognosis and management of patients.
Investigation of predictors of bleeding complications in COVID‐19 using rotational thromboelastometry (ROTEMⓇ): A retrospective study
Authors: Matsuoka Ayaka , Koami Hiroyuki , Shinada Kota , Sasaki Akira , Yamazaki Hirotaka , Mori Kosuke , Nakayama Kento , Asahi Miho , Yoshitake Kunimasa , Narumi Shogo , Koba Mayuko , Kawaguchi Atsushi , Sakamoto Yuichiro
Published: May 2022

Background

Hemorrhagic complications in patients with coronavirus 19 disease (COVID‐19) are infrequent but associated with a prognosis. This study aimed to elucidate the risk factors for bleeding complications in patients with COVID‐19 using rotational thromboelastometry (ROTEM) parameters and blood tests performed at admission.

Methods

In total, 31 patients with severe COVID‐19 treated intensively at Saga University Hospital were included in this study. Patients were divided into two groups according to the presence or absence of hemorrhagic complications. Results from the blood tests performed at admission and during hospitalization, and ROTEM values acquired upon admission, were compared between the two groups.

Results

There were significant differences in ROTEM values upon admission between the bleeding and non‐bleeding groups. Receiver operating curve analysis showed that the area under the curve for prothrombin time international normalized ratio (PT‐INR) and extrinsically‐activated test with tissue factor (EXTEM) amplitude at 10 min (A10) were 0.82 (0.52–0.92) and 0.81 (0.58–0.93), respectively. Logistic regression analysis with PT‐INR and EXTEM A10 as factors calculated an odds ratio of 1.94 (1.04–3.62) and EXTEM A10 0.86 (0.71–1.05) for bleeding complications occurrence.

Conclusion

ROTEM may be a sensitive predictor for bleeding complications in patients with COVID‐19.
Prevalence of hepatitis B virus and associated risk factors among adults patients at Dessie referral and Kemise general hospitals in northeastern Ethiopia
Authors: Mohammed Hussein , Eshetie Aragaw , Melese Dessie
Published: May 2022

Background and Aims

Hepatitis is an inflammation of the liver that can reason a variety of health problems and can be fatal. According to the most recent estimates of the Global Burden of Disease study and WHO, viral hepatitis is accountable for around 1.34 million deaths yearly, which is comparable to the yearly number of deaths from HIV/AIDS (1.3 million), malaria (0.9 million), and tuberculosis (1.3 million). This study aimed to assess the prevalence of the Hepatitis B virus and associated risk factors among adults patients at Dessie Referral and Kemise General Hospitals.

Methods

The source for the data on Hepatitis B virus (HBV) was all adults aged≥18 years that were admitted and tested for HBV from September 2020 to February 2021 were included in the study. A total of 1283 adults were admitted out of which, 1080 adults have completed measurements and had been taken into consideration for this examination, and others had been excluded from the examination because of exclusion criteria. To meet our objective descriptive statistics, the χ2 test and multiple logistic regression statistical models were used for data analysis.

Results

In this study, a total of 1080 adults were included out of which 631 (58.4%) female and 449 (41.6%) were male with a mean age of 34(SD ± 12.56) years. The overall prevalence of HBV among adults was 27.4% (95% confidence interval [CI];24.8–30.2). The results of this study showed that age 25–34(odds ratio [OR] = 3.6, p‐value = 0.005), 35–44 (OR = 6.67, p‐value <0.001), ≥45 (OR = 3.85, p‐value = 0.005), male (OR = 4.36, p‐value < 0.001), history of hospitalization (OR = 0.644, p‐value = 0.04), family history of HBV (OR = 1.96, p‐value = 0.005), and jaundice (OR = 2.50, p‐value = 0.005) were significant risk factors of HBV.

Conclusion

The prevalence of HBV in this study is 27.4%. The results of this study showed that age, male, history of hospitalization, family history of HBV, and jaundice were significant risk factors for Hepatitis B virus.
Thermal uniformity enhancement of the motorcycle exhaust thermoelectric generator—Part 2: Muffler outlet optimization
Authors: Hong Thong Duc , Nghiem Quan Thien Phan , Hua Phuc Bao , Vo Tan Viet
Published: May 2022

Following the development of the muffler with the optimal guide fins (MOGF) in the companion paper (Part 1), this study optimizes the muffler outlet in terms of structure and geometry to further improve the thermal uniformity of the hot‐side heat exchanger (HHE). Two outlet structures and two outlet geometry parameters (i.e., outlet angle φ and outlet position y) are proposed. The exhaust flow uniformity of HHE serves as an assessment criterion in numerous computational fluid dynamics simulations to determine the optimal outlet structure and optimal values of φ and y. The outlet of the MOGF is then modified based on the simulation results to create the muffler with the optimal guide fins and outlet (MOGFO). Various experiments on the MOGFO are conducted to verify the simulation results and evaluate the improvement of the HHE's thermal uniformity. The simulation results prove that the optimal outlet improves the exhaust flow uniformity by 1.78% on average compared with the original outlet. In experiments, the combination of optimal muffler's outlet and optimal muffler's guide fins on the MOGFO raises the thermal uniformity of HHE by an average of 22.71% and 50% compared with the MOGF and the muffler model with nonoptimal guide fins and outlet in Part 1, respectively. The remarkable outcomes of this paper, together with Part 1, are expected to enhance the efficiency and lifespan of the thermoelectric generator unit.
Cabozantinib‐nivolumab sequence in metastatic renal cell carcinoma: The CABIR study
Authors: Vano Yann‐Alexandre , Phan Letuan , Gravis Gwenaelle , Korakis Iphigénie , Schlürmann Friederike , Maillet Denis , Bennamoun Mostefa , Houede Nadine , Topart Delphine , Borchiellini Delphine , Barthelemy Philippe , Ratta Raffaele , Ryckewaert Thomas , Hasbini Ali , Hans Sophie , Emambux Sheik , Cournier Sandra , Braychenko Elena , Elaidi Réza‐Thierry , Oudard Stéphane
Published: May 2022

Nivolumab and cabozantinib are approved agents in mRCC patients after sunitinib/pazopanib (TKI) failure. However, the optimal sequence, cabozantinib then nivolumab (CN) or nivolumab then cabozantinib (NC), is still unknown. The CABIR study aimed to identify the optimal sequence between CN and NC after frontline VEGFR‐TKI. In this multicenter retrospective study, we collected data from mRCC pts receiving CN or NC, after frontline VEGFR‐TKI. A propensity score (PrS) was calculated to manage bias selection, and sequence comparisons were carried out with a cox model on a matched sample 1:1. The primary endpoint was progression‐free survival (PFS) from the start of second line to progression in third line (PFS2‐3). Key secondary endpoints included overall survival from second line (OS2). Out of 139 included mRCC patients, 38 (27%) and 101 (73%) received CN and NC, respectively. Overlap in PrS allowed 1:1 matching for each CN pts, with characteristics well balanced. For both PFS2‐3 and OS2, NC sequence was superior to CN (PFS2‐3: HR = 0.58 [0.34‐0.98], P = .043; OS2: 0.66 [0.42‐1.05], P = .080). Superior PFS2‐3 was in patients treated between 6 and 18 months with prior VEGFR‐TKI (P = .019) and was driven by a higher PFSL3 with cabozantinib when given after nivolumab (P < .001). The CABIR study shows a prolonged PFS of the NC sequence compared to CN in mRCC after first line VEGFR‐TKI failure. The data suggest that cabozantinib may be more effective than nivolumab in the third‐line setting, possibly related to an ability of cabozantinib to overcome resistance to PD‐1 blockade.
Inflammatory myofibroblastic tumor: Amulti‐institutionalstudy from the Pediatric Surgical Oncology Research Collaborative
Authors: Rich Barrie S. , Fishbein Joanna , Lautz Timothy , Rubalcava Nathan S. , Kartal Tanvi , Newman Erika , Wok Pei En , Romao Rodrigo L. P. , Whitlock Richard , Naik‐Mathuria Bindi , Polites Stephanie F. , Løfberg Katrine , Lascano Danny , Kim Eugene , Davidson Jacob , Bütter Andreana , Kastenberg Zachary J. , Short Scott S. , Meyers Rebecka L. , Mastropolo Rosemarie , Malek Marcus M. , Weller Jennine , Irfan Ahmer , Rhee Daniel S. , Utria Alan F. , Rothstein David H. , Riehle Kimberly , Commander Sarah Jane , Tracy Elisabeth , Becktell Kerri , Hallis Brian , Lal Dave , Li Orville , Dal‐Soglio Dorothé B. , Piché Nelson , Quevedo Oswaldo Gomez , Murphy Andrew J. , Davidoff Andrew M. , Barber Jo Cooke , Watters Erin , Dasgupta Roshni , Glick Richard D.
Published: May 2022

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi‐institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty‐two patients were identified with median age of 11 years. Thirty‐three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety‐one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty‐six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow‐up time was 36 months. Overall 5‐year survival was 95% and 5‐year event‐free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.
Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease
Authors: Pu Jing
Published: May 2022

The multiple functions of the lysosome, including degradation, nutrient sensing, signaling, and gene regulation, enable the lysosome to regulate lipid metabolism at different levels. In this review, I summarize the recent studies on lysosomal regulation of lipid metabolism and the alterations of the lysosome functions in the livers affected by nonalcoholic fatty liver disease (NAFLD). NAFLD is a highly prevalent lipid metabolic disorder. The progression of NAFLD leads to nonalcoholic steatohepatitis (NASH) and other severe liver diseases, and thus the prevention and treatments of NAFLD progression are critically needed. Targeting the lysosome is a promising strategy. I also discuss the current manipulations of the lysosome functions in the preclinical studies of NAFLD and propose my perspectives on potential future directions.
The modified COVID‐19 Yorkshire Rehabilitation Scale (C19‐YRSm) patient‐reported outcome measure for Long Covid or Post‐COVID‐19 syndrome
Authors: Sivan Manoj , Preston Nick , Parkin Amy , Makower Sophie , Gee Jeremy , Ross Denise , Tarrant Rachel , Davison Jennifer , Halpin Stephen , O'Connor Rory J. , Horton Mike
Published: May 2022

Background

The C19‐YRS is the literature's first condition‐specific, validated scale for patient assessment and monitoring in Post‐COVID‐19 syndrome (PCS). The 22‐item scale's subscales (scores) are symptom severity (0–100), functional disability (0–50), additional symptoms (0–60), and overall health (0–10).

Objectives

This study aimed to test the scale's psychometric properties using Rasch analysis and modify the scale based on analysis findings, emerging information on essential PCS symptoms, and feedback from a working group of patients and professionals.

Methods

Data from 370 PCS patients were assessed using a Rasch Measurement Theory framework to test model fit, local dependency, response category functioning, differential item functioning, targeting, reliability, and unidimensionality. The working group undertook iterative changes to the scale based on the psychometric results and including essential symptoms.

Results

Symptom severity and functional disability subscales showed good targeting and reliability. Post hoc rescoring suggested that a 4‐point response category structure would be more appropriate than an 11‐point response for both subscales. Symptoms with binary responses were placed in the other symptoms subscale. The overall health single‐item subscale remained unchanged.

Conclusion

A 17‐item C19‐YRSm was developed with subscales (scores): symptom severity (0–30), functional disability (0–15), other symptoms (0–25), and overall health (0–10).
Designing technology for on‐demand delivery: The effect of customer tipping on crowdsourced driver behavior and last mile performance
Authors: Castillo Vincent E. , Mollenkopf Diane A. , Bell John E. , Esper Terry L.
Published: May 2022

Crowdsourcing technology platforms specializing in on‐demand last mile delivery face a novel problem—heightened agent independence increases uncertainty in last mile delivery and has the potential to undermine operational performance. Uncertainty emanates from drivers' competing interests, or opportunity costs. Rather than increase remuneration, some platforms have designed the technology to allow customers to tip, but the subsequent effects on driver behavior and last mile performance have not yet been studied. We explore this feature of on‐demand delivery technology design—customer tipping—and its implications for crowdsourced delivery performance. Using netnography and secondary data sources, we empirically ground an adaptive, multi‐agent hybrid simulation to propose how customer tipping impacts service performance through context‐contingent driver behavior. Our results generally indicate that tipping as a technology design feature mitigates uncertainty in the crowdsourced delivery fleet and reduces fulfillment times and unit delivery costs. We also find evidence suggesting that the impact of tipping on driver behavior is geography‐contingent, with tipping having unexpectedly detrimental effects in high population density areas relative to low‐density areas. We conclude by making a series of theoretical propositions and managerial implications about designing technology to facilitate crowdsourced delivery.
Senior and technology entrepreneurship: An analysis forOECDcountries
Authors: Fernández‐López Sara , Rodeiro‐Pazos David , Zapata‐Huamaní Guillermo Andrés , Rodríguez‐Gulías María Jesús
Published: May 2022

Aging of the population has created a direct effect on economies and tension on social security systems. Policymakers have been senior entrepreneurship as an option to reduce unemployment and delay the age of retirement. The positive effects, of creating a firm increase when is operating in technology‐based sectors. This paper explores the technological and senior entrepreneurship relations, analyzing if age influences technological entrepreneurship and if determining factors for senior and non‐senior groups are different. By using a sample of 8637 entrepreneurs in 22 OECD countries based onGlobal Entrepreneurial Monitor2018 data, the results firstly show a negative effect of being a senior entrepreneur, understood as an entrepreneur aged 50+ years, on technological entrepreneurship. Secondly, it has been detected that in some way senior entrepreneurship follows a different pattern of the probability of entrepreneurship in technology sectors than the sample of the non‐senior entrepreneurs.
Classification of Thyroid Nodules by Using Deep Learning Radiomics Based on Ultrasound Dynamic Video
Authors: Zhang Chunquan , Liu Dan , Huang Long , Zhao Yu , Chen Lili , Guo Youmin
Published: May 2022

Objectives

We aimed to design a radiomics model for differential diagnosis of thyroid carcinoma based on dynamic ultrasound video, and compare its diagnostic performance with that of radiomics model based on static ultrasound images.

Methods

Between January 2019 and May 2021, 890 patients with 1015 thyroid nodules (775 for training, 240 for validation) were prospectively enrolled. In total 890 patients underwent thyroidectomy within 1 month, and ultrasound dynamic video and static images were both acquired. Two deep learning (DL) models, namely DL‐video and DL‐image models, were proposed to diagnose thyroid nodules by analyzing ultrasound video and static images respectively. The performance of models was assessed by areas under the receiver operating characteristic curve (AUC). The DL model on ultrasound cines was re‐visualized to help radiologists understand its potential working mechanism.

Results

The AUC of DL‐video were 0.947 (95% CI: 0.931–0.963) and 0.923 (95% CI: 0.892–0.955) in training and validation cohorts, respectively. For DL‐image model, the AUC were 0.928 (95% CI: 0.910–0.945) and 0.864 (95% CI: 0.819–0.910), respectively. The diagnosis performance of the DL‐video was superior to that of DL‐image, and there was significant difference between the AUC of DL‐video and DL‐image model in validation cohort (P = .028). The visualization demonstrated certain important ultrasound features that could be recognized by human eyes.

Conclusions

The proposed DL radiomics model based on dynamic ultrasound video can accurately and individually classified thyroid nodules. The constructed DL‐video model combining ultrasound video holds good potential for benefiting the management of patients with thyroid nodules.
A low seepage threshold and super‐toughness of polybutylene succinate‐based composites with double percolation structure: Synergy of multi‐wall carbon nanotubes and polyvinyl butyral
Authors: Jia Shikui , Zhang Xiangyang , Zhu Yan , Yan Zongying , Zhang Guizhen , Zhao Zhongguo , Ding Liu
Published: May 2022

To obtain a super‐toughness and low seepage threshold for the conductivity of biodegradable soft polymer material, biodegradable polybutylene succinate (PBS)‐based composites with different contents of polyvinyl butyral (PVB) and multi‐wall carbon nanotubes (MWCNTs) were prepared by melt‐blending method. Synergy effects of different modified MWCNTs and PVB on the morphology, crystallization, and electrical and mechanical properties of MWCNTs/PVB/PBS composites were examined by Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscope (SEM), transmission electron microscopy (TEM), wide angle X‐ray diffraction (WAXD), differential scanning calorimetry (DSC), polarizing microscope (POM), resistance tester, and universal testing machine. Compared with pure PBS, with increasing MWCNT content, the electrical conductivity of the MWCNTs/PBS composites showed an upward trend, and the percolation threshold for electrical conductivity of the MWCNTs/PBS composites reached 0.47%. The electrical conductivity of the PBS composite mixed with 1.0 wt% of surface modified MWCNTs slightly increased by one order of magnitude compared with that of pure PBS. By adding 20 wt% of the PVB and 1 wt% of the unmodified MWCNTs, the electrical conductivity of the MWCNTs/PVB/PBS composite increased by seven orders of magnitude compared with that of pure PBS. The percolation threshold for electrical conductivity of the MWCNTs/PVB/PBS composites decreased to 0.049% owing to the formation of double percolation structure. Furthermore, compared with pure PBS, when the PVB content was 20 wt%, and the MWCNTs was 1 wt%, the elongation at break and V‐notch impact strength of PBS‐based composite dramatically increased by approximately 300% and 12‐fold, respectively.
In situ modulated photoluminescence study of the hydrogenation processes of tunnel oxide passivating contacts during plasma processes
Authors: Desthieux Anatole , Gaillard Sophie , Posada Jorge , Roca i Cabarrocas Pere
Published: May 2022

Compared to current c‐Si solar cell technologies, fired passivating contacts (FPCs) can reduce the thermal budget of the solar cell fabrication process. In this study, a simplified process flow for the fabrication of these contacts is investigated along with the use of two hole transport materials: p‐type nanocrystalline silicon ((p) nc‐Si:H) and nanocrystalline silicon oxide ((p) nc‐SiOx:H). More specifically, the passivation properties provided by the FPC stack are assessed at different stages of the manufacturing. The hydrogenation process is studied using in situ modulated photoluminescence (MPL) which allows to measure in real time the effective minority carrier lifetime in the sample during a process step. The increase of passivation observed during the deposition of the capping silicon‐nitride (a‐SiNx:H) layer by plasma‐enhanced chemical vapor deposition is shown to be due to both annealing of the sample and the deposition in presence of silane in the plasma, while the exposure to an NH3 and H2 plasma is mostly detrimental for the passivation properties. The in situ MPL measurements additionally allow us to show that the improvement of the passivation properties happens during the first few minutes of a‐SiNx:H deposition.
Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
Authors: dela Peña Ike C. , Figueroa Johnny D. , Shi Wei‐Xing
Published: May 2022

The prolonged exposure to obesogenic diets disrupts the mesocortical dopaminergic input to the prefrontal cortex (PFC). This leads to suboptimal dopamine levels in this brain region, which affects cognition and control of food intake. Treatments that restore mesocortical dopaminergic neurotransmission may improve obesity‐associated cognitive dysfunction and modulate food intake to induce weight loss. Given the complexity and multifactorial nature of obesity, combination treatments would likely achieve sizeable and sustained body weight loss and improve obesity‐linked outcomes, such as cognitive dysfunction. Given this background, we hypothesize that concomitant activation of serotonin 5‐HT2C and histamine H1 receptors, coupled with antagonism of histamine H3 receptors, synergistically modulates mesocortical dopamine neurotransmission and ameliorates obesity‐induced cognitive dysfunction. We propose to test the hypothesis in a diet‐induced obesity (DIO) rat model by treating animals with the 5‐HT2C agonist lorcaserin and the H1 agonist and H3 antagonist betahistine. Consistent with our hypothesis, both lorcaserin and betahistine have been shown to reduce body weight in humans with obesity and animals. Both drugs have been demonstrated to improve cognitive functions by influencing dopaminergic signaling in the PFC. The proposed combination treatment addresses the paucity of studies on obesity treatments that improve cognitive function. This research may also help identify a potential targetable mechanism connecting obesity and neurocognitive outcomes.
Inhibition of acyl‐ACP thioesterase as site of action of the commercial herbicides cumyluron, oxaziclomefone, bromobutide, methyldymron and tebutam
Authors: Johnen Philipp , Zimmermann Sophie , Betz Michael , Hendriks Janneke , Zimmermann Alexandra , Marnet Martina , De Inessa , Zimmermann Gunther , Kibat Christine , Cornaciu Irina , Mariaule Vincent , Pica Andrea , Clavel Damien , Márquez José Antonio , Witschel Matthias
Published: May 2022

BACKGROUND

Understanding the mode and site of action of a herbicide is key for its efficient development, the evaluation of its toxicological risk, efficient weed control and resistance management. Recently, the mode of action (MoA) of the herbicide cinmethylin was identified in lipid biosynthesis with acyl‐ACP thioesterase (FAT) as the site of action (SoA). Cinmethylin was registered for selective use in cereal crops for the control of grass weeds in 2020.

RESULTS

Here, we present a high‐resolution co‐crystal structure of FAT in complex with cumyluron identified by a high throughput crystallization screen. We show binding to and inhibition of FAT by cumyluron. Furthermore, in an array of experiments consisting of FAT binding assays, FAT inhibition assays, physiological and metabolic profiling, we tested compounds that are structurally related to cumyluron and identified the commercial herbicides oxaziclomefone, methyldymron, tebutam and bromobutide, with so far unknown sites of action, as FAT inhibitors. Additionally, we show that the previously described FAT inhibitors cinmethylin and methiozolin bind to FAT in a nanomolar range, inhibit FAT enzymatic activity and lead to similar metabolic changes.

CONCLUSION

Based on presented data, we corroborate cinmethylin and methiozolin as potent FAT inhibitors and identify FAT as the SoA of the herbicides cumyluron, oxaziclomefone, bromobutide, methyldymron and tebutam. © 2022 Society of Chemical Industry.
Machine learning algorithms to estimate everolimus exposure trained on simulated and patient pharmacokinetic profiles
Authors: Labriffe Marc , Woillard Jean‐Baptiste , Debord Jean , Marquet Pierre
Published: May 2022

Everolimus is an immunosuppressant with a small therapeutic index and large between‐patient variability. The area under the concentration versus time curve (AUC) is the best marker of exposure but measuring it requires collecting many blood samples. The objective of this study was to train machine learning (ML) algorithms using pharmacokinetic (PK) profiles from kidney transplant recipients, simulated profiles, or both types, and compare their performance for everolimus AUC0‐12h estimation using a limited number of predictors, as compared to an independent set of full PK profiles from patients, as well as to the corresponding maximum a posteriori Bayesian estimates (MAP‐BE). XGBoost was first trained on 508 patient interdose AUCs estimated using MAP‐BE, and then on 500–10,000 rich interdose PK profiles simulated using previously published population PK parameters. The predictors used were: predose, ~1 h, and ~2 h whole blood concentrations, differences between these concentrations, relative deviations from theoretical sampling times, morning dose, patient age, and time elapsed since transplantation. The best results were obtained with XGBoost trained on 5016 simulated profiles. AUC estimation achieved in an external dataset of 114 full‐PK profiles was excellent (root mean squared error [RMSE] = 10.8 μg*h/L) and slightly better than MAP‐BE (RMSE = 11.9 μg*h/L). Using more profiles (n = 10,035) did not improve the ML algorithm performance. The contribution of mixing patient and simulated profiles was significant only when they were in balanced numbers, with ~500 for each (RMSE = 12.5 μg*h/L), compared with patient data alone (RMSE = 18.0 μg*h/L).
Optimal unplanned design modification in adaptive two‐stage trials
Authors: Pilz Maximilian , Herrmann Carolin , Rauch Geraldine , Kieser Meinhard
Published: May 2022

Adaptive planning of clinical trials allows modifying the entire trial design at any time point mid‐course. In this paper, we consider the case when a trial‐external update of the planning assumptions during the ongoing trial makes an unforeseen design adaptation necessary. We take up the idea to construct adaptive designs with defined features by solving an optimization problem and apply it to the situation of unplanned design reassessment. By using the conditional error principle, we present an approach on how to optimally modify the trial design at an unplanned interim analysis while at the same time strictly protecting the type I error rate. This linking of optimal design planning and the conditional error principle allows sound reactions to unforeseen events that make a design reassessment necessary.
Statistical methodology for highly variable compounds: A novel design approach for the ofatumumab Phase 2 bioequivalence study
Authors: Jones Byron , Li Bingbing , Bagger Morten , Goodyear Alex , Ludwig Inga
Published: May 2022

This article describes a novel mixed‐scaling testing strategy, in combination with an adaptive parallel‐groups bioequivalence trial, to test pharmacokinetic equivalence of two formulations of a drug with highly variable pharmacokinetics. The methodology was applied to the Phase 2 APLIOS study in relapsing multiple sclerosis patients, where the bioequivalence of subcutaneous ofatumumab 20 mg administered via an autoinjector pen (test formulation) versus prefilled syringe (reference formulation) in the abdomen has been studied. Due to a high coefficient of variation (CV) of the relevant pharmacokinetic metrics (AUCtau and Cmax) for the reference formulation (>30%), a reference‐Scaled bioequivalence (RSABE) approach was applied but modified for a parallel‐groups design. In the absence of regulatory guidance for applying RSABE in parallel‐group designs, and in contrast to the available regulatory guidance for RSABE in cross‐over trials, the suggested testing strategy uses the between‐subject variability of the reference drug instead of the corresponding within‐subject variability that would be available if a standard cross‐over bioequivalence trial had been possible. Moreover, due to high uncertainty in the initial CV estimate for the sample size determination, a two‐stage adaptive design was used, allowing for a sample size adjustment based on the pharmacokinetic variability observed at an interim analysis. The interim analysis timing was pre‐specified based on simulations which included re‐estimation of the final sample size at the end of the first stage to ensure sufficient power of the RSABE test at the end of the second stage. Using this approach, bioequivalence was shown between the test and reference formulations.

The APLIOS trial is registered at ClinicalTrials.gov: NCT03560739.
Apolipoprotein A1 is associated with pulmonary vascular resistance and adverse clinical outcomes in patients with pulmonary hypertension secondary to heart failure
Authors: Yu Wande , Dujiang Xie , Yi Wang , Guanwen Ding , Mengyu Zhang , Chang Pan , Aikai Zhang , Juan Zhang , Linlin Zhu , Hang Zhang
Published: May 2022

Pulmonary hypertension secondary to heart failure (HF‐PH) combined with pulmonary vascular remodeling has a high mortality rate. Apolipoprotein A1 (ApoA1) has been shown to adversely affect outcomes in patients with HF. A prospective follow‐up study was performed on 239 consecutive patients with HF‐PH who underwent right heart catheterization. Proteomics technology was used to analyze different proteins in plasma between post‐ and precapillary pulmonary hypertension (CpcPH) and isolated postcapillary pulmonary hypertension (IpcPH) filtered by propensity score matching. Ultimately, 175 patients were enrolled and followed for an average of 4.4 years. Lipoprotein components in plasma were measured, and the following clinical events were tracked. Proteomics data showed that lipid metabolism and inflammation were different between CpcPH and IpcPH. ApoA1 levels in HF‐PH patients with CpcPH were lower than those in HF‐PH patients with IpcPH. The patients with lower ApoA1 levels (≤1.025 g/L) were in a higher New York Heart Association class and had high levels of NT‐proBNP, mean pulmonary artery pressure, PVR, and diastolic pressure gradient. Besides, HF‐PH patients with lower ApoA1 levels had a 2.836‐fold higher relative risk of comorbid CpcPH compared with patients with higher ApoA1 levels. Moreover, patients with lower ApoA1 levels had a lower survival rate after adjusting for CpcPH. In conclusion, ApoA1 levels were negatively correlated with PVR levels. Lower ApoA1 levels were an independent risk factor for pulmonary vascular remodeling in HF‐PH patients. The survival of HF‐PH patients with lower ApoA1 levels was reduced.
Environmental drivers of cyanobacterial abundance and cyanotoxin production in backwaters of the Upper Mississippi River
Authors: Giblin Shawn M. , Larson James H. , King Jeremy D.
Published: May 2022

High densities of cyanobacteria in aquatic ecosystems can cause impacts to ecosystem services because they serve as a poor‐quality food resource, produce toxins and can indirectly cause a variety of other negative impacts to water quality. There are many hypotheses about the potential environmental drivers of variation in cyanobacterial abundance and toxicity, but these hypotheses have rarely been considered in combination and rarely been examined in large river ecosystems. Here, we use monthly data from backwater habitats of the Upper Mississippi River (UMR) to evaluate associations between environmental conditions and cyanobacterial abundance and toxicity (microcystin and anatoxin‐a) that would be expected based on several hypotheses. Backwaters in the Mississippi River vary in flushing rate, temperature, turbidity, nutrient availability, water depth, and vegetative cover. We find support for hypotheses that suggest physical conditions in backwaters (flushing rate, temperature, turbidity, rooted vegetation cover, and water depth) and nutrient availability influence cyanobacterial abundance and toxicity. We then used structural equation modeling to incorporate several hypotheses into a causal modeling framework, which indicated that backwater connectivity (flushing) strongly influences cyanobacterial abundance via the regulation of water temperature, and that nutrient availability strongly influences the presence of microcystin concentrations above our detection limit. Our data suggest that management of backwater connectivity could influence cyanobacterial abundance and toxicity in UMR backwaters. Reconnecting backwaters (via alteration of levees) could serve as a local adaptation to minimize the effects of climate change and excessive nutrient loading.
Rapid Approach for Pharmaceutical Quality Evaluation and Comparison
Authors: Pettinau Francesca , Manca Ilaria , Manca Ilaria , Pittau Barbara
Published: May 2022

A rapid approach, with the association of Fourier‐transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR), is proposed in order to provide a fast quality evaluation of pharmaceutical products. It offers an analytical screening tool also useful to compare drug products including generics. The approach requires a minimal amount of solvents and little sample preparation. In this paper characterization of pharmaceutical product samples containing telmisartan, allopurinol, anastrozole, metformin hydrochloride and lamivudine, active pharmaceutical ingredients (APIs) in solid dosage forms, are reported. The results show how this approach can provide useful data for a rapid screening of pharmaceutical composition and comparison of drugs with useful information also in terms of equivalence risk analysis.
A Naphthalimides‐Based Probe for Sequential Detection of Cu2+ and PPi and Its Application in Cells Imaging
Authors: Wang Wei , Wang Baihui , Liu Huimin , Liu Qinglei , Li Shanshan , Zhao Bing , Gao Yan
Published: May 2022

A novel naphthalimides‐based fluorescent probe (NPHD) selectively detected Cu2+ and PPi through “strong yellow‐weak green‐strong yellow” photonic response in a sequential manner. The formation of NPHD‐Cu2+ resulted in obvious fluorescence decreased and wavelength shift from 595 nm to 525 nm by adding Cu2+ to NPHD solution. The mechanism could be attributed to d→π* electron transfer (ET) from Cu2+ to NPHD. Furthermore, the NPHD‐Cu2+ complex exhibited high selectivity toward PPi through via emission recovery of chemosensor NPHD. The detection limits of NPHD to Cu2+ and NPHD‐Cu2+ to PPi were estimated to be 5.72×108M and 2.39×108M. In addition, NPHD could be employed to detect exogenous Cu2+ and PPi in Hep G2 cells.
Sulfur‐Doped Hydrogen‐Bonded Organic Framework for Improved Oxygen Evolution Reaction
Authors: Wang Jiaji , Zhang Ling , Lin Shiwei
Published: May 2022

Developing the efficient electrocatalysts for oxygen evolution reaction (OER) is highly required but still challenging, especially for hydrogen‐bonded organic framework (HOF) materials. Herein, we report a sulfur‐doped HOF material (S@HOF‐H2BDC) for improved OER performance for the first time. The prepared S@HOF‐H2BDC shows a greatly enhanced OER activity, lowing the overpotential of 48 mV at a current density of 10 mA cm−2relative to the undoped one, and even comparable to the benchmark IrO2. Results have shown that doping S atoms can induce more active sites, and accelerate the charge transfer kinetics. Moreover, the OOH*adsorption energy of S@HOF‐H2BDC can be remarkably modulated after introducing S atoms, thus increasing its catalyst performance.
Beyond the Paradox of Trust and Digital Platforms: Populism and the Reshaping of Internet Regulations
Authors: Flew Terry
Published: May 2022

One of the paradoxes of the misinformation and ‘fake news’ debates are that they require a greater degree of trust in media, digital platforms and governments in order to combat conspiracy theories, when in fact distrust of media, digital platforms and governments is part of a wider crisis of trust in institutions and expertise. This suggests that we need a more sophisticated analysis of the politics of expertise and how they intersect with both policies towards digital platforms and shifts in the political sphere. Drawing upon the work of Thomas Piketty on shifts in electoral politics, and Pippa Norris on the rise of populism, it is argued that debates about tech policy are largely played out between educated elites from ‘liberal’ and ‘cosmopolitan’ perspectives, which leaves them open to populist critique. One of the reasons why there are greater calls to regulate digital platforms is the rise of political populism, which can leave digital activists in a political bind: they favour measures to rein in the power of ‘Big Tech’ in principle, but are very wary of any measures perceived to increase the power of nation states with regards to the Internet.
Altwerden zwischen Speckgürtel und Peripherie – ein Blick auf das Land Brandenburg
Authors: Stellmacher Thorsten , Wolter Birgit
Published: May 2022

Gute Rahmenbedingungen für das Leben im Alter zu bieten, stellt insbesondere im ländlichen Raum die Kommunen vor große Herausforderungen. Der Anteil älterer Menschen an der Bevölkerung ist in den ländlichen Regionen meist höher als in den städtischen Ballungsräumen.
Steigende Wohnkosten im Alter – (k)ein Problem?
Authors: Vogel Claudia , Lozano Alcántara Alberto , Romeu Gordo Laura
Published: May 2022

Die Wohnkosten sind in den letzten Jahren stärker gestiegen als die Alterseinkommen. Die Wohnkostenbelastung müsste somit bei den älteren Haushalten gestiegen sein. Auf Basis des Sozio-oekonomischen Panels (1996–2018) gehen wir den Fragen nach, wie sich die relative Wohnkostenbelastung seit Mitte der 1990er Jahre bei älteren Menschen entwickelt hat, und für welche Gruppen älterer Haushalte die hohen Wohnkosten zu einer finanziellen Überbelastung führen können. Die Ergebnisse zeigen, dass die relative Wohnkostenbelastung für ältere Menschen seit 1996 angestiegen ist, und zwar insbesondere für Mieterhaushalte. Zu den Gruppen, die durch Wohnkosten besonders überbelastet sind, gehören vor allem Mieterhaushalte und ältere Alleinlebende mit niedrigen Einkommen.
Wohnbedingungen und Pflegebedarf – Analysen von Erstbegutachtungen des Medizinischen Dienstes der Krankenversicherung
Authors: Stein Thomas , Schilling Ralph
Published: May 2022

Bei aktueller Lebenszeitprävalenz muss ein Großteil der Bevölkerung in Deutschland damit rechnen, im Laufe des Lebens pflegebedürftig zu werden. Etwa 75 % der im Jahr 2017 verstorbenen Frauen und 60 % der verstorbenen Männer waren zuvor pflegebedürftig.
Bauernhöfe als Orte für Menschen mit Demenz – Ergebnisse einer explorativen Studie aus Schleswig–Holstein
Authors: Schmidt Annika , Wolf-Ostermann Karin
Published: May 2022

Aufgrund der Bevölkerungsalterung, der Zunahme von altersspezifischen Erkrankungen und dem damit einhergehenden Anstieg der Pflegebedürftigkeit ist die Frage nach Versorgungserfordernissen und -bedarfen zunehmend von Bedeutung. Alternative und integrative Unterstützungsangebote gewinnen an Zuspruch. Als eine alternative Betreuungsform, auch für MmD leben, hat sich in vergangenen Jahren das Konzept der Green Care Farms international entwickelt. Der Beitrag thematisiert das in Deutschland angesiedelte Projekt „Bauernhöfe als Orte für MmD in Schleswig–Holstein“ vor und zeigt die Ressourcen und Barrieren des Angebotes auf.
Classic Theories of Distance Education
Authors: Evans Terry , Jakupec Viktor
Published: May 2022

This chapter explores the influence of three of distance education’s classic theorists—Otto Peters, Börje Holmberg, and Michael Moore—on its subsequent conceptualization and practice. The classic theorists’ understanding of theory and theorizing is discussed critically in the context of the articulation of each’s particular theory. This is then contextualized in terms of the history of the development of distance education and its institutions, from Pitman’s correspondence courses on shorthand, through correspondence schooling and higher education external studies, to the rise of the United Kingdom Open University in the 1960s. The latter’s subsequent powerful influence on the theory and practice of open and distance education internationally is described as stimulating a fertile context for the classic theorists’ endeavors. Finally, consideration is given to more recent scholars’ interpretations and adaptations of the classic theories of distance education. This leads to a concluding reflection on the authors’ engagement with distance education theorizing and the prospects for the future of distance education’s theorizing and practice.
Analyse steigender Behandlungskosten bei erhöhtem BMI von Patienten mit proximaler Femurfraktur
Authors: Gutwerk Alexander , Müller Michael , Crönlein Moritz , Kirchhoff Chlodwig , Biberthaler Peter , Pförringer Dominik , Braun Karl
Published: May 2022

Die proximale Femurfraktur ist eine Frakturentität mit ansteigender Prävalenz, ein Effekt, welcher durch die zunehmende Alterung der Allgemeinbevölkerung noch zusätzlich verstärkt werden wird. In der Summe stellt sie sowohl die Operateure als auch das deutsche Gesundheitssystem als Ganzes vor Herausforderungen. Zudem führt ein stetiges Ansteigen des BMI in der Bevölkerung zu immer mehr adipösen Patienten mit proximaler Femurfraktur, was dann durch komplexere Operationen, längere Liegezeiten und eine wachsende Zahl postoperativer Komplikationen wiederum zu Herausforderungen führt.

Ziel der vorliegenden Arbeit ist es, den monetären Aspekt dieser Entwicklung zu beleuchten. Hierzu wurden retrospektiv 950 Patientenfälle mit proximaler Femurfraktur analysiert. Hierbei konnte gezeigt werden, dass mit steigendem BMI höhere Kosten pro Fall entstanden (10.452 €, 11.505 €, 12.085 € bzw. 13.681 € für BMI < 18,5 kg/m2, BMI = 18,5–24,9 kg/m2, BMI = 25,0–29,9 kg/m2 bzw. BMI ≥ 30,0 kg/m2), da sowohl die Operationszeit als auch die Zeit des stationären Aufenthalts relevant verlängert waren.