bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosing Regimen Prediction and Confirmation With Rivaroxaban for Thromboprophylaxis in Children After the Fontan Procedure: Insights From the Phase III UNIVERSE Study
Authors: Zhu Peijuan , Willmann Stefan , Zhou Wangda , Yang Haitao , Michelson Alan D. , McCrindle Brian W. , Li Jennifer S. , Harris Kevin C. , Pina Liza Miriam , Weber Traci , Nessel Kimberly , Lesko Lawrence J. , Kubitza Dagmar , Zannikos Peter
Published: September 2021

Thrombosis remains an important complication for children with single‐ventricle physiology following the Fontan procedure, and effective thromboprophylaxis is an important unmet medical need. To obviate conventional dose‐finding studies and expedite clinical development, a rivaroxaban dose regimen for this indication was determined using a model‐informed drug development approach. A physiologically based pharmacokinetic rivaroxaban model was used to predict a pediatric dosing regimen that would produce drug exposures similar to that of 10 mg once daily in adults. This regimen was used in an open‐label, multicenter phase III study, which investigated the use of rivaroxaban for thromboprophylaxis in post‐Fontan patients 2 to 8 years of age. The pharmacokinetics (PK) of rivaroxaban was assessed in part A (n = 12) and in part B (n = 64) of the UNIVERSE study. The safety and efficacy in the rivaroxaban group were compared to those in the acetylsalicylic acid group for 12 months. Pharmacodynamic end points were assessed in both parts of the study. Rivaroxaban exposures achieved in parts A and B were similar to the adult reference exposures. Prothrombin time also showed similarity to the adult reference. Exposure‐response analysis did not identify a quantitative relationship between rivaroxaban exposures and efficacy/safety outcomes within the observed exposure ranges. A body weight–based dose regimen selected by physiologically based pharmacokinetic modeling was shown in the UNIVERSE study to be appropriate for thromboprophylaxis in the post‐Fontan pediatric population. Model‐based dose selection can support pediatric drug development and bridge adult dose data to pediatrics, thereby obviating the need for dose‐finding studies in pediatric programs.
Muscle strength and muscle mass as predictors of hospital length of stay in patients with moderate to severe COVID‐19: a prospective observational study
Authors: Gil Saulo , Jacob Filho Wilson , Shinjo Samuel Katsuyuki , Ferriolli Eduardo , Busse Alexandre Leopold , Avelino‐Silva Thiago Junqueira , Longobardi Igor , de Oliveira Júnior Gersiel Nascimento , Swinton Paul , Gualano Bruno , Roschel Hamilton ,   The HCFMUSP COVID‐19 Study Group
Published: September 2021

Background

Strength and muscle mass are predictors of relevant clinical outcomes in critically ill patients, but in hospitalized patients with COVID‐19, it remains to be determined. In this prospective observational study, we investigated whether muscle strength or muscle mass are predictive of hospital length of stay (LOS) in patients with moderate to severe COVID‐19 patients.

Methods

We evaluated prospectively 196 patients at hospital admission for muscle mass and strength. Ten patients did not test positive for SARS‐CoV‐2 during hospitalization and were excluded from the analyses.

Results

The sample comprised patients of both sexes (50% male) with a mean age (SD) of 59 (±15) years, body mass index of 29.5 (±6.9) kg/m2. The prevalence of current smoking patients was 24.7%, and more prevalent coexisting conditions were hypertension (67.7%), obesity (40.9%), and type 2 diabetes (36.0%). Mean (SD) LOS was 8.6 days (7.7); 17.0% of the patients required intensive care; 3.8% used invasive mechanical ventilation; and 6.6% died during the hospitalization period. The crude hazard ratio (HR) for LOS was greatest for handgrip strength comparing the strongest versus other patients (1.47 [95% CI: 1.07–2.03; P = 0.019]). Evidence of an association between increased handgrip strength and shorter hospital stay was also identified when handgrip strength was standardized according to the sex‐specific mean and standard deviation (1.23 [95% CI: 1.06–1.43; P = 0.007]). Mean LOS was shorter for the strongest patients (7.5 ± 6.1 days) versus others (9.2 ± 8.4 days). Evidence of associations were also present for vastus lateralis cross‐sectional area. The crude HR identified shorter hospital stay for patients with greater sex‐specific standardized values (1.20 [95% CI: 1.03–1.39; P = 0.016]). Evidence was also obtained associating longer hospital stays for patients with the lowest values for vastus lateralis cross‐sectional area (0.63 [95% CI: 0.46–0.88; P = 0.006). Mean LOS for the patients with the lowest muscle cross‐sectional area was longer (10.8 ± 8.8 days) versus others (7.7 ± 7.2 days). The magnitude of associations for handgrip strength and vastus lateralis cross‐sectional area remained consistent and statistically significant after adjusting for other covariates.

Conclusions

Muscle strength and mass assessed upon hospital admission are predictors of LOS in patients with moderate to severe COVID‐19, which stresses the value of muscle health in prognosis of this disease.
Kinetic analysis of the methanization of the byproducts from OFMSW fermentation
Authors: Jojoa‐Unigarro German D , González‐Martínez Simón
Published: September 2021

BACKGROUND

During anaerobic digestion of wastes, volatile fatty acid (VFA) production has been studied, but little attention has been paid to alcohols and lactic acid. Thermodynamically, lactic acid and alcohols are better substrates to produce methane than other VFA. This research identified the metabolites produced during the fermentation of the organic fraction of municipal solid waste and studied their methanization in a second stage. Analysis of the methane production curves is provided and explained according to Gibbʼs free energy of acetogenesis and methanogenesis. Based on the Michaelis–Menten model, a kinetic analysis is presented.

RESULTS

The specific methane production of the identified acids and alcohols are acetic acid, 343 NL/kgCOD; ethanol, 296; methanol, 181; butyric acid, 108; lactic acid, 64. Lactic and butyric acids present a long adaptation phase followed by a fast and short methane production. Acetic acid and ethanol finished the reaction in less than 16 h. The highest methane production rates (Vmax) were for butyric acid, methanol, and ethanol with 2136, 1934, and 1928 NmL L–1, respectively. The best affinity (lowest Km) values were for acetic and lactic acids and ethanol with 1.2, 1.9, and 2.0 gCOD L–1.

CONCLUSION

Together, acetic acid and ethanol represent 92% of all fermentation products. No endogenous methane production was observed during the methanization from acetic acid and ethanol. The highest specific methane production belongs to acetic acid (98% of the theoretical) and the lowest corresponds to lactic acid. Except for propionic acid, the methanization of the selected substrates follows the Michaelis and Menten model. © 2021 Society of Chemical Industry (SCI).
Analysis of the reported use of practice‐based competencies by North American genetic counselors during the COVID‐19 pandemic
Authors: Wagner Naomi E. , Witherington Sarah , Waldman Larissa , Ryan Lauren , Hardy Melanie W.
Published: September 2021

Genetic counseling services changed due to the COVID‐19 pandemic. Many genetic counselors (GCs) moved from in‐person to telehealth services. Others were redeployed by choice or necessity, using their expertise to provide COVID‐19 care and education. For some, their employment status changed due to budgetary constraints or decreasing referrals. This study surveyed North American GCs to assess the relative use of genetic counseling Practice‐Based Competencies (PBCs) as a proxy for the skills used during the first wave of the pandemic, whether GCs were in their current role or in new or adjusted roles. A secondary aim was to determine whether GCs believe their training should be refocused in view of the workforce shifts posed by the pandemic. The survey comprised closed‐ and open‐ended questions and was completed in full by 97 respondents. The study population was representative of the general genetic counseling workforce in terms of gender, race/ethnicity, age, and practice area when compared to the National Society of Genetic Counselors 2020 Professional Status Survey. Most participants (97.9%) indicated that the COVID‐19 pandemic resulted in a change to their work, and 89.7% used at least one PBC at a different frequency than before the pandemic. The most significant change was the adaptation of genetic counseling skills for varied service delivery models: 83.5% of respondents indicated that their roles and responsibilities moved to a remote setting and/or utilized telehealth. The majority of participants felt competent using the PBCs during the pandemic. Major themes that emerged from the qualitative data were as follows: (a) adaptation of service delivery, (b) translation of genetic counseling skills, and (c) provision of psychosocial support. This study highlights practice changes for GCs due to the COVID‐19 pandemic as well as the increased use of, and need for focused training in, varied service delivery models.
Should the world collaborate imminently to develop neglected live‐attenuated vaccines for COVID‐19?
Authors: Chen Ji‐Ming
Published: September 2021

The rapid spread of the Delta variant suggests that SARS‐CoV‐2 will likely be rampant for months or years and could claim millions of more lives. All the known vaccines cannot well defeat SARS‐CoV‐2 due to their limited efficacy and production efficiency, except for the neglected live‐attenuated vaccines (LAVs), which could have a much higher efficacy and much higher production efficiency than other vaccines. LAVs, like messiahs, have defeated far more pathogenic viruses than other vaccines in history, and most current human vaccines for viral diseases are safe LAVs. LAVs can block completely infection and transmission of relevant viruses and their variants. They can hence inhibit the emergence of vaccine‐escape and virulence‐enhancing variants and protect immunologically abnormal individuals better in general. The safety of COVID‐19 LAVs, which could save millions of more lives, can be solidly guaranteed through animal experiments and clinical trials. The safety of COVID‐19 LAVs could be greatly enhanced with intramuscular or oral administration, or administration along with humanized neutralizing monoclonal antibodies. Together, extensive global collaboration, which can greatly accelerate the development of safe COVID‐19 LAVs, is imminently needed.
Evaluation of the correlation between the access SARS‐CoV‐2 IgM and IgG II antibody tests with the SARS‐CoV‐2 surrogate virus neutralization test
Authors: Kitagawa Yutaro , Imai Kazuo , Matsuoka Masaru , Fukada Ai , Kubota Katsumi , Sato Momoko , Takada Tomohito , Noguchi Sakiko , Tarumoto Norihito , Maesaki Shigefumi , Takeuchi Shinichi , Maeda Takuya
Published: September 2021

Fully automated immunoassays for detecting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies that are strongly correlated with neutralization antibodies (nAbs) are clinically important because they enable the assessment of humoral immunity after infection and vaccination. Access SARS‐CoV‐2 immunoglobulin M (IgM) and immunoglobulin G (IgG) II antibody tests are semi‐quantitative, fully automated immunoassays that detect anti‐receptor‐binding domain (RBD) antibodies and might reflect nAb levels in coronavirus disease 2019 (COVID‐19). However, no studies have investigated the clinical utility of these tests in association with nAbs to date.

To evaluate the clinical utility of Access SARS‐CoV‐2 IgM and IgG II antibody tests and their correlation with the SARS‐CoV‐2 surrogate virus neutralization test (sVNT) that measures nAbs in patients with COVID‐19, we analyzed 54 convalescent serum samples from COVID‐19 patients and 89 serum samples from non‐COVID‐19 patients. The presence of anti‐RBD antibodies was detected using Access SARS‐CoV‐2 IgM and IgG II antibody tests, while nAbs were measured by sVNT.

The sensitivity and specificity of sVNT were 94.4% and 98.9%, respectively. There were strong positive correlations between the inhibition values of sVNT and the results of the Access SARS‐CoV‐2 IgM (R = 0.95, R2 = 0.90, p < 0.001) and IgG II antibody tests (R = 0.96, R2 = 0.92, p < 0.001). In terms of the presence of nAbs, the sensitivity and specificity were 98.1% and 98.9% in the IgM assay and 100.0% and 100.0% in the IgG II assay, respectively.

The Access SARS‐CoV‐2 IgM and IgG II antibody tests showed high sensitivity and specificity for the detection of nAbs in COVID‐19 patients and might be alternatives for measuring nAbs.
Paraspinal muscle pathophysiology associated with low back pain and spine degenerative disorders
Authors: Noonan Alex M. , Brown Stephen H. M.
Published: September 2021

Low back pain disorders affect more than 80% of adults in their lifetime and are the leading cause of global disability. The muscles attaching to the spine (ie, paraspinal muscles) are critical for proper spine health and play a crucial role in the functioning of the spine and whole body; however, reports of muscle dysfunction and insufficiency in chronic LBP (CLBP) patients are common. This article presents a review of the current understanding of the relationship between paraspinal muscle pathophysiology and spine‐related disorders. Human literature demonstrates a clear association between altered muscle structure/function, most notably fatty infiltration and fibrosis, and low back pain disorders; other associations, including muscle cell atrophy and fiber type changes, are less clear. Animal literature then provides some mechanistic insight into the complex relationships, including initiating factors and time courses, between the spine and spine muscles under pathological conditions. It is apparent that spine pathology can directly lead to changes in the paraspinal muscle structure, function, and biology. It also appears that changes to the muscle structure and function can directly lead to changes in the spine (eg, deformity); however, this relationship is less well studied. Future work must focus on providing insight into possible mechanisms that regulate spine and paraspinal muscle health, as well as probing how muscle degeneration/dysfunction might be an initiating factor in the progression of spine pathology.
Strategies to circumvent the solvent strength mismatch problem in online comprehensive two‐dimensional liquid chromatography
Authors: Chapel Soraya , Heinisch Sabine
Published: September 2021

On‐line comprehensive two‐dimensional liquid chromatography is a powerful technique for the separation of highly complex samples. Due to the addition of the second dimension of separation, impressive peak capacities can be obtained within a reasonable analysis time compared to one‐dimensional liquid chromatography. In online comprehensive two‐dimensional liquid chromatography, the separation power is maximized by selecting two separation dimensions as orthogonal as possible, which most often requires the combination of different mobile phases and stationary phases. The online transfer of a given solvent from the first dimension to the second dimension may cause severe injection effects in the second dimension, mostly due to solvent strength mismatch. Those injection effects may include peak broadening, peak distortion, peak splitting or breakthrough phenomenon. They are often found to reduce significantly the peak capacity and the peak intensity. To overcome such effects, arising specifically in online comprehensive two‐dimensional liquid chromatography, different methods have been developed over the years. In this review, we focused on the most recently reported ones. A critical discussion, supported by a theoretical approach, gives an overview of their advantages and drawbacks.
Early Everolimus‐Facilitated Reduced Tacrolimus in Liver Transplantation: Results From the Randomized HEPHAISTOS Trial
Authors: Nashan Björn , Schemmer Peter , Braun Felix , Schlitt Hans J. , Pascher Andreas , Klein Christian G. , Neumann Ulf P. , Kroeger Irena , Wimmer Peter ,   Hephaistos Study Group
Published: September 2021

Everolimus‐facilitated reduced‐exposure tacrolimus (EVR + rTAC) at 30 days after liver transplantation (LT) has shown advantages in renal preservation. This study evaluated the effects of early initiation of EVR + rTAC in de novo LT recipients (LTRs). In HEPHAISTOS (NCT01551212, EudraCT 2011‐003118‐17), a 12‐month, multicenter, controlled study, LTRs were randomly assigned at 7 to 21 days after LT to receive EVR + rTAC or standard‐exposure tacrolimus (sTAC) with steroids. The primary objective was to demonstrate superior renal function (assessed by estimated glomerular filtration rate [eGFR]) with EVR + rTAC versus sTAC at month 12 in the full analysis set (FAS). Other assessments at month 12 included the evaluation of renal function in compliance set and on‐treatment (OT) patients, efficacy (composite endpoint of graft loss, death, or treated biopsy‐proven acute rejection [tBPAR] and individual components) in FAS, and safety. In total, 333 patients (EVR + rTAC, 169; sTAC, 164) were included in the FAS. A high proportion of patients was nonadherent in maintaining tacrolimus trough levels (EVR + rTAC, 36.1%; sTAC, 34.7%). At month 12, the adjusted least square mean eGFR was numerically higher with EVR + rTAC versus sTAC (76.2 versus 72.1 mL/minute/1.73 m2, difference: 4.1 mL/minute/1.73 m2; P = 0.097). A significant difference of 8.3 mL/minute/1.73 m2 (P = 0.03) favoring EVR + rTAC was noted in the compliance set. Incidence of composite efficacy endpoint (7.7% versus 7.9%) and tBPAR (7.1% versus 5.5%) at month 12 as well as incidence of treatment‐emergent adverse events (AEs) and serious AEs were comparable between groups. A lower proportion of patients discontinued EVR + rTAC than sTAC treatment (27.2% versus 34.1%). Early use of everolimus in combination with rTAC showed comparable efficacy, safety, and well‐preserved renal function versus sTAC therapy at month 12. Of note, renal function was significantly enhanced in the compliance set.
PROVOKE: HOW TO LEAD WITH PURPOSE
Authors: Goldbach Steven , Tuff Geoff
Published: September 2021

The authors contend that “the best leaders have the conviction to act. To just do something.” As they elaborate, “Action creates potential energy. Action allows you to position yourself to see the unfolding future sooner and more clearly than others. Action gives you the power to identify important trends and know if the key question is ‘if’ they will materialize or ‘when’ they will materialize to determine the right response.” Their work with CEOs led to a new book, Provoke: How Leaders Shape the Future By Overcoming Fatal Human Flaws, in which they “identify five moves to enable leaders to recognize patterns and broaden their peripheral vision to move forward with not just progress, but also purpose.” Those moves are Envision, Position, Drive, Adapt, and Activate. They describe three “Provocateurs,” who have used these principles at a high level: Deborah Bial, of the Posse Foundation, Ryan Gravel, creator of the BeltLine in Atlanta, and Valerie Irick Rainford, of Elloree Talent Strategies. The latter and Bial are examples of using the Activate principle, and Gravel used the principle of Envision. The authors conclude that “we genuinely believe that we will all live in a better world if you just go out and do something!”
Catalyst‐Free Vitrimer Cross‐Linked by Biomass‐Derived Compounds with Mechanical Robustness, Reprocessability, and Multishape Memory Effects
Authors: Huang Lingyun , Yang Yinxin , Niu Zhen , Wu Ruiyao , Fan Weifeng , Dai Quanquan , He Jianyun , Bai Chenxi
Published: September 2021

Vitrimerization of thermoset polymers plays an important role in addressing resource recovery and reuse. Vitrimer elastomers with good mechanical properties often require well‐designed crosslinking agents or fillers, but this increases processing complexity or reduces vitrimer dynamic properties. In this report, a simple green strategy to build a strong vitrimer elastomer is designed. Commercially available epoxidized natural rubber (ENR) is cross‐linked with biomass‐derived D‐Fructose 1,6‐bisphosphoric acid to get a vitrimer elastomer cross‐linked by β‐hydroxy phosphate ester bonds and has abundant hydrogen bonds. Hydrogen bonds can preferentially break and dissipate energy under external forces, which makes the sample robust. The topological network can be reformed at high temperatures through the dynamic exchange of β‐hydroxy phosphate ester bonds, which gives the material malleability and recyclability. In addition, through the strategy of combining reprocessing and welding, multiple shape memory effects can be achieved in one postprocessing step. Considering that a variety of commercially available epoxy polymers are easily available, it is believed that this strategy can be a simple and versatile way to enable commercial epoxy polymers to achieve green crosslinking through biomass crosslink agents, which results in robust and recyclable vitrimers based on β‐hydroxy phosphate bonds.
Simple Model for the Spreading of Inks in Bioprinting—Revealing Relevant Scaling Laws—Part I Theory
Authors: Schubert Dirk W.
Published: September 2021

A model taking into consideration viscosity and evaporation is suggested to describe the spreading kinetics of struts in bioprinting. Scenarios resulting by complete and partial wetting are discussed and described. Applicable fit functions and predictive scaling laws are given, relating viscosity of bioinks, process parameters such as print speed and throughput to the strut width. The approach is primarily based on 1D spreading.
Vieta–Fibonacci wavelets: Application in solving fractional pantograph equations
Authors: Azin Hadis , Heydari Mohammad Hossein , Mohammadi Fakhrodin
Published: September 2021

In this paper, the Vieta–Fibonacci wavelets as a new family of orthonormal wavelets are generated. An operational matrix concerning fractional integration of these wavelets is extracted. A numerical scheme is established based on these wavelets and their fractional integral matrix together with the collocation technique to solve fractional pantograph equations. The presented method reduces solving the problem under study into solving a system of algebraic equations. Several examples are provided to show the accuracy of the method.
Industry Advances Shine at Display Week and in the New IDMS Release
Authors: Atwood Stephen P.
Published: September 2021

Optical metrology always has been an important facet of information display research and development. Having tools to characterize the performance of any technology is an obvious requirement, but it's especially important in a field that bridges the boundary between human visual perception and the flow of information. Understanding how the images on a display are rendered and perceived is critical. The perception part is handled by an array of specialists in the visual sciences. The other part is addressed by dedicated researchers in the field of display measurement.
IDMS‐HDR: A Modern Guide to HDR Display Metrology
Authors: Friedrich Florian , Kunkel Timo
Published: September 2021

The International Committee for Display Metrology just released version 1.1 of the Information Display Measurements Standard containing a new high dynamic range (HDR) chapter and HDR tutorial. This article provides background for the new content and describes why these contributions are a must‐read for anyone interested in HDR.
A systematic review and meta‐analytic evaluation of psychosocial interventions in parents of children with cancer with an exploratory focus on minority outcomes
Authors: Eche Ijeoma Julie , Yusufov Miryam , Isibor Docia Akwaboah , Wolfe Joanne
Published: September 2021

Parents of children with cancer are prone to psychosocial distress, yet little is known about intervention response among diverse parents. Our systematic review and meta‐analysis evaluated the efficacy of psychosocial interventions on anxiety and depression among parents of children with cancer and explored race and/or ethnicity differences in the efficacy of these interventions. Twenty articles met inclusion. The aggregate effect size on anxiety (−0.01, 95% CI: −0.95, 0.93, p = .97) and depression (−0.56, 95% CI: −1.65, 0.54, p = .32) showed micro to medium effects, with larger negative effect sizes indicating that anxiety and depression scores after treatment were lower for parents in intervention group as compared to control group. Neither aggregate effect size was statistically significantly different from zero. Due to underrepresentation of minorities, we could not perform subgroup or moderator analyses. Several efficacious psychosocial interventions were found to reduce parental anxiety. Future studies to examine psychosocial interventions in minority parents are warranted.
CFTR gene mutation spectrum among 735 Iranian patients with cystic fibrosis: A comprehensive systematic review
Authors: Alibakhshi Reza , Mohammadi Aboozar , Khamooshian Sahand , Kazeminia Mohsen , Moradi Keivan
Published: September 2021

In this study, the spectrum and frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations previously reported among Iranian cystic fibrosis (CF) patients have been reviewed and discussed. Using the keywords of Cystic Fibrosis, CF, CFTR, and Iran, along with their Persian equivalents, a comprehensive search was performed on the online databases. After applying the inclusion and exclusion criteria, 16 articles with an overall sample of 735 Iranian patients with CF, were included in this systematic review. A total of 101 different CFTR gene variants had been reported. The mutation of p.Phe508del (c.1521_1523delCTT) (21.22%) was the most frequent one among Iranian patients with CF. In conclusion, due to the fact that in many provinces of Iran no specific study has been done so far, it seems that the CFTR gene mutation spectrum in patients with CF from Iran is much wider.
Improvement in overall and cancer‐specific survival in contemporary, metastatic prostate cancer chemotherapy exposed patients
Authors: Hoeh Benedikt , Würnschimmel Christoph , Flammia Rocco S. , Horlemann Benedikt , Sorce Gabriele , Chierigo Francesco , Tian Zhe , Saad Fred , Graefen Markus , Gallucci Michele , Briganti Alberto , Terrone Carlo , Shariat Shahrokh F. , Tilki Derya , Kluth Luis A. , Mandel Philipp , Chun Felix K. H. , Karakiewicz Pierre I.
Published: September 2021

Introduction

Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real‐world data validating this effect within large‐scale epidemiological data sets are scarce. We addressed this void.

Materials and Methods

Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004–2016). Patients were divided between historical (2004–2013) versus contemporary (2014–2016). Chemotherapy rates were plotted over time. Kaplan–Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer‐specific mortality. All tests were repeated in propensity‐matched analyses.

Results

Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy‐exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate‐specific antigen, GGG, cT‐stage, cN‐stage, cM‐stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer‐specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001).

Conclusions

In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.
Using defined daily doses to review antibiotic prescribing
Authors: Motta Marco , Wilcock Mike , Heald Adrian
Published: September 2021

Optimising antibiotic prescribing in the primary care setting is a key component of the UK antimicrobial resistance (AMR) strategy. In this project, the authors worked with eight GP practices in Cornwall that had high levels of antibiotic prescribing to help them find ways to improve their prescribing and reduce antibiotic consumption, using defined daily doses (DDDs) as a measure of consumption.
Anthocyanin oligomers stimulate browning in 3T3‐L1 white adipocytes via activation of the β3‐adrenergic receptor and ERK signaling pathway
Authors: Choi Minji , Mukherjee Sulagna , Yun Jong Won
Published: September 2021

Microbial fermentation of grape‐skin extracts is found to synthesize anthocyanin oligomers (AO), which are more active than the monomeric anthocyanins that are effective for some metabolic diseases such as diabetes and obesity. This study investigated the functional role of AO in 3T3‐L1 white adipocyte metabolism, with a focus on inducing browning. To achieve this, we determined the expressions of core genes and protein markers responsible for browning and lipid metabolism in response to AO treatment of 3T3‐L1 white adipocytes. AO exposure significantly increases the expressions of beige‐specific genes (Cidea, Cited1, Ppargc1α, Prdm16, Tbx1, Tmem26, and Ucp1) and brown‐fat signature proteins (UCP1, PRDM16, and PGC‐1α), and suppresses the expressions of lipogenic marker proteins while enhancing the protein levels of lipolysis in white adipocytes. The mechanistic study revealed stimulation of white fat browning via activation of the β3‐AR/PKA/p38 axis and ERK/CREB signaling pathway subsequent to AO treatment. In conclusion, our current findings indicate the beneficial effects of AO for the treatment of obesity with interesting properties such as regulating the browning of adipocytes and increasing thermogenic activity. Although further research based on animal models or clinical trials remains, AO treatment can bring more insights into the treatment of obesity and metabolic syndrome.
Spatial modeling of epidermal nerve fiber patterns
Authors: Konstantinou Konstantinos , Särkkä Aila
Published: September 2021

Peripheral neuropathy is a condition associated with poor nerve functionality. Epidermal nerve fiber (ENF) counts per epidermal surface are dramatically reduced and the two‐dimensional (2D) spatial structure of ENFs tends to become more clustered as neuropathy progresses. Therefore, studying the spatial structure of ENFs is essential to fully understand the mechanisms that guide those morphological changes. In this article, we compare ENF patterns of healthy controls and subjects suffering from mild diabetic neuropathy by using suction skin blister specimens obtained from the right foot. Previous analysis of these data has focused on the analysis and modeling of the spatial ENF patterns consisting of the points where the nerves enter the epidermis, base points, and the points where the nerve fibers terminate, end points, projected on a 2D plane, regarding the patterns as realizations of spatial point processes. Here, we include the first branching points, the points where the nerve trees branch for the first time, and model the three‐dimensional (3D) patterns consisting of these three types of points. To analyze the patterns, spatial summary statistics are used and a new epidermal active territory that measures the volume in the epidermis that is covered by the individual nerve fibers is constructed. We developed a model for both the 2D and the 3D patterns including the branching points. Also, possible competitive behavior between individual nerves is examined. Our results indicate that changes in the ENFs spatial structure can more easily be detected in the later parts of the ENFs.
Electrochemical Preparation of ZnO/PEDOT‐Type Conducting Polymers Composites for Ultraviolet Photodetector
Authors: Helil Zulpikar , Jamal Ruxangul , Niyaz Mariyam , Sawut Nurbiye , Li Junxia , Liu Yajun , Ali Ahmat , Abdiryim Tursun
Published: September 2021

Generally, the ultraviolet photodetector devices based on ZnO/PEDOT composites were fabricated by spin coating of PEDOT solutions on ZnO nanorods array, which needs the polymer disperesed in solvent. In this paper, an electrochemical deposition method was proposed for the prepparation of ZnO/PEDOT‐type conducting polymers composites for ultraviolet photodetector. The poly(3,4‐proplene‐dioxythiophene) (PProDOT) and poly(3,4‐ethylenedioxy‐thiophene)(PEDOT) were selected as PEDOT‐type conducting polymers. The structure of composite materials was characterized by UV‐vis, XRD, Raman, SEM,EDS and XPS analysis. The effects of different polymers on the UV sensing ability of ZnO nanorods were studied. The structural results showed that the composites were successfully prepared by electrochemical deposition method indicating that the electrochecmial method was an effective way to prepraration of this type composites.The photoelectric performance test showed that the structure of the polymer chain affected the responsiveness of the materials, and the response time of ZnO/PProDOT was 14 s shorter than that of ZnO/PEDOT, and it displayed an excellent long‐term stability. After deposition of PProDOT, the UV responsivity of ZnO nanorods was increased from 2.5 A W−1 to 27.5 A W−1, and the external quantum efficiency and detectivity were significantly improved, implying that the PProDOT can be ideal candidate material for ultraviolet photodetector.
Real‐Time Detection of Fibrinogen via Imprinted Recognition Sites
Authors: Çimen Duygu , Üzek Recep , Günaydın Serdar , Denizli Adil
Published: September 2021

In this study, the fibrinogen imprinted surface plasmon resonance (SPR) biosensor was developed for the monitoring of fibrinogen levels in patient serum samples using a microcontact imprinting method. The fibrinogen imprinted and non‐imprinted polymeric films on the SPR chip surface were prepared by the microcontact imprinting approach and characterized by ellipsometer, contact angle measurements, and Fourier transform infrared spectroscopy. The limit of detection and quantification values of the fibrinogen imprinted SPR biosensors in the linear range of 0.05–9.0 mg/mL were 0.00066 and 0.00219 mg/mL, respectively. In all kinetic analyzes, the response time was 11 min for equilibration, adsorption, and desorption cycles. The selectivity studies of SPR biosensors were performed in the presence of fibrinogen, myoglobin, hemoglobin, and immunoglobulin G in a competitive manner. For the validation studies of the fibrinogen imprinted SPR biosensor, the fibrinogen level of diluted patient serum samples was determined by enzyme‐linked immunosorbent assay (ELISA). The experimental results show that the serum samples of patients in high and low‐risk groups were identified with the recovery of about % 97–99 according to both SPR biosensor and ELISA analysis results.
Highly Diastereo‐ and Enantioselective Aza‐Mannich Addition of Oxazolones toN‐Boc Protected α‐Amido Sulfones Catalyzed by Bifunctional Thiourea‐modified Cinchona Alkaloid
Authors: Zhang Hui , Song Lihua , Yuan Weicheng , Zhang Xiaomei
Published: September 2021

A diastereo‐ and enantioselective aza‐Mannich addition of oxazolones to α‐amino sulfones catalyzed by tertiary amine‐1‐phenylethyl thiourea based on cinchona structure has been developed. The reaction afforded the azlactone adducts bearing quaternary and tertiary stereogenic centers with high yields (up to 98 %) and moderate to excellent diastereo‐ and enantioselectivities (up to >99 : 1 dr and 96 % ee). The absolute configuration of a product was assigned by X‐ray crystal structural analyses and a plausible reaction mechanism was proposed.
Nonplanar Helicene Benzo[4]Helicenium for the Precise Treatment of Renal cell Carcinoma
Authors: He Xiaozhen , Gan Fuwei , Zhou Yan , Zhang Yuanliang , Zhao Peipei , Zhao Bingru , Tang Qianyun , Ye Li , Bu Jun , Mei Junyang , Du Ling , Dai Huili , Qiu Huibin , Liu Peifeng
Published: September 2021

Immune and targeted therapy are becoming the first‐line treatment for renal cell carcinoma (RCC). However, therapeutic outcomes are limited due to the low efficiency and side effect. Here, it is found that helicenes are able to exhibit an anticancer capability through changing the molecular structure from planar to nonplanar. Furthermore, the cytotoxicity in vitro and cancer inhibition ability of nonplanar helicenes increase with its aromatic rings’ number. It is further demonstrated that benzo[4]helicenium shows the specific killing efficiency against the RCC cancer as compared to normal kidney cells. This is majorly originated from a more selective damage of benzo[4]helicenium for mitochondria and DNA in RCC cancer cells, not the normal kidney. The selective killing ability of benzo[4]helicenium makes it have potential to be used as a targeted drug for the precise treatment of RCC.
A Novel Strategy to Overcome the Hurdle for Commercial All‐Solid‐State Batteries via Low‐Cost Synthesis of Sulfide Solid Electrolytes
Authors: Kim Min‐Ju , Choi Ik‐Hyeon , Jo Seong Chan , Kim Byung Gon , Ha Yoon‐Cheol , Lee Sang‐Min , Kang Sung , Baeg Kang‐Jun , Park Jun‐Woo
Published: September 2021

Unlike commercial lithium‐ion batteries, the high cost and low ionic conductivity of solid electrolytes (SEs) continues to be a big hurdle in commercially available all‐solid‐state batteries (ASSBs). Rather than the conventional dry‐process and high‐energy ball milling processes, the productive solution synthesis of bulk‐type SEs is the most crucial issue in the successful application of high‐energy‐density ASSBs. In this study, the way is paved to overcome the hurdle for commercial lithium phosphorus sulfide chloride (LPSCl) SEs via a readily processable bulk‐type solution‐based synthesis without acquiring any high‐energy ball‐milling processes. By incorporating an elemental sulfur additive during the preparation process, Li2S and S form a polysulfide, and P2S5 is induced to react readily to provide LPSCl with excellent ion conductivity as high as 1.8 mS cm−1. Surprisingly, the purity of bulk type precursors does not affect the final composition and ionic conductivity of sulfide electrolytes, which show the same electrochemical characteristics of ASSB cells with a high discharge capacity of 185.6 mA h g−1. The study offers a promising strategy for saving the production cost of sulfide SEs, possibly up to 92%, and their commercial ASSBs are expected to be achieving a competitive cost per energy density of ≈0.46 $ W−1.
A Low‐Temperature Carbon Encapsulation Strategy for Stable and Poisoning‐Tolerant Electrocatalysts
Authors: Hu Yezhou , Zhang Jujia , Shen Tao , Lu Yun , Chen Ke , Tu Zhengkai , Lu Shanfu , Wang Deli
Published: September 2021

Carbon encapsulation is an effective strategy for enhancing the durability of Pt‐based electrocatalysts for the oxygen reduction reaction (ORR). However, high‐temperature treatment is not only energy‐intensive but also unavoidably leads to possible aggregation. Herein, a low‐temperature polymeric carbon encapsulation strategy (≈150 °C) is reported to encase Pt nanoparticles in thin and amorphous carbonaceous layers. Benefiting from the physical confinement effect and enhanced antioxidant property induced by the surface carbon species, significantly improved stabilities can be achieved for polymeric carbon species encapsulated Pt nanoparticles (Pt@C/C). Particularly, a better antipoisoning capability toward CO, SOx, and POx is observed in the case of Pt@C/C. To minimize the thickness of the catalyst layer and reduce the mass transfer resistance, the high mass loading Pt@C/C (40 wt%) is prepared and applied to high‐temperature polymer electrolyte membrane fuel cells (HT‐PEMFCs). At 160 °C, a peak power density of 662 mW cm−2 is achieved with 40% Pt@C/C cathode in H2–O2 HT‐PEMFCs, which is superior to that with 40% Pt/C cathode. The facile strategy provides guidance for the synthesis of highly durable carbon encapsulated noble metal electrocatalysts toward ORR.
Estimation of the average treatment effect on the treated with misclassified binary outcome
Authors: Wei Shaojie , Zhang Zhongzhan , Li Gaorong
Published: September 2021

The estimation of the average treatment effect on the treated (ATT) plays an essential role when the effect of an intervention or a treatment on those participants who actually received it is the focus. However, the validity of conventional estimation methods relies on the precise measurement of variables. Misclassified category outcome variables may cause non‐negligible bias when estimating ATT. In this paper, under the assumption that the misclassification probability is homogeneous, we develop a bias‐corrected estimation method to consistently estimate ATT when internal validation data are available for a subgroup of the study population. We further derive a doubly robust estimator by augmenting the bias‐corrected estimator to provide protection against treatment model misspecification. Through simulation experiments and real data analysis, we demonstrate the satisfactory performance of the proposed estimators.
Developments in the Chemical Synthesis of Heparin and Heparan Sulfate
Authors: Pongener Imlirenla , O'Shea Conor , Wootton Hannah , Watkinson Michael , Miller Gavin J.
Published: September 2021

Heparin and heparan sulfate represent key members of the glycosaminoglycan family of carbohydrates and underpin considerable repertoires of biological importance. As such, their efficiency of synthesis represents a key requirement, to further understand and exploit the H/HS structure‐to‐biological function axis. In this review we focus on chemical approaches to and methodology improvements for the synthesis of these essential sugars (from 2015 onwards). We first consider advances in accessing the heparin‐derived pentasaccharide anticoagulant fondaparinux. This is followed by heparan sulfate targets, including key building block synthesis, oligosaccharide construction and chemical sulfation techniques. We end with a consideration of technological improvements to traditional, solution‐phase synthesis approaches that are increasingly being utilised.
Concept of Sea Power
Authors: Albrecht Torsten , Tsetsos Konstantinos , Grunwald Philipp
Published: September 2021

In this chapter different perspectives on the concept of sea power are considered. On the one hand, sea power is defined accordingly, whereby it must be emphasized that sea power is not only composed of the number of ships or material but also of the degree to which it can influence and compel other countries/actors. The concept of sea power is then examined based on the International Relations theories of Realism and Liberalism. In order to understand the origins and also the development in the twentieth century of the concept of sea power, the most important cornerstones of the leading naval thinkers of the “blue-water school,” Alfred Thayer Mahan and Sir Julian Corbett, are presented. This work ends with a review of the concept of sea power during the Cold War.
A Plant Sociological Procedure for the Ecological Design and Enhancement of Urban Green Infrastructure
Authors: Catalano Chiara , Pasta Salvatore , Guarino Riccardo
Published: September 2021

Urban green infrastructure could represent an important mean for environmental mitigation, if designed according to the principles of restoration ecology. Moreover, if suitably executed, managed and sized, they may be assimilated to meta-populations of natural habitats, deserving to be included in the biodiversity monitoring networks. In this chapter, we combined automatised and expert opinion-based procedures in order to select the vascular plant assemblages to populate different microhabitats (differing in terms of light and moisture) co-occurring on an existing green roof in Zurich (Switzerland). Our results lead to identify three main plant species groups, which prove to be the most suitable for the target roof. These guilds belong to mesoxeric perennial grasslands (Festuco-Brometea), nitrophilous ephemeral communities (Stellarietea mediae) and drought-tolerant pioneer species linked to nutrient-poor soils (Koelerio-Corynephoretea). Some ruderal and stress-tolerant species referred to the class Artemisietea vulgaris appear to fit well with local roof characteristics, too. Inspired by plant sociology, this method also considers conservation issues, analysing whether the plants selected through our procedure were characteristic of habitats of conservation interest according to Swiss and European laws and directives. Selecting plant species with different life cycles and life traits may lead to higher plant species richness, which in turn may improve the functional complexity and the ecosystem services provided by green roofs and green infrastructure in general.
Nutzenbewertung digitaler Gesundheitsanwendungen – Herausforderungen und Möglichkeiten
Authors: Hemkens Lars G.
Published: September 2021

Digitale Gesundheitsanwendungen (DiGA) versprechen, die Gesundheit und medizinische Versorgung von Patienten zu verbessern. Dieser Beitrag gibt eine kurze Übersicht zur evidenzbasierten Nutzenbewertung und den Herausforderungen an die zugrunde liegende Evidenz als Voraussetzungen für eine optimale, patientenorientierte Entscheidungsfindung. Es werden klassische Konzepte des Studiendesigns, aktuelle Entwicklungen und innovative Ansätze beschrieben mit dem Ziel, zukünftige Entwicklungsfelder für innovative Studiendesigns und strategische Evaluationskonzepte für DiGA aufzuzeigen. Ein besonderer Schwerpunkt liegt auf der Anwendung pragmatischer Studiendesigns.

Evidenzbasierte Nutzenbewertung hat fundamentale Anforderungen und Maßstäbe unabhängig von der Art der evaluierten Behandlungen. Zuverlässige Evidenz ist unverzichtbar. Eine schnelle, effiziente, zuverlässige und praxisrelevante Evaluation von DiGA gelingt nicht durch eine Hinwendung zu nichtrandomisierten Studien, sondern vielmehr durch bessere, pragmatische randomisierte Studien. Sie sind machbar und verbinden die Charakteristika von DiGA, klassische methodische Konzepte und neue Ansätze der Studiendurchführung. Routinedaten, kontaktarme Studiendurchführung („virtual trials“, „remote trials“) und digitale Biomarker fördern nützliche randomisierte Real-World-Evidenz als solide Evidenzbasis von DiGA. Eine kontinuierliche, lernende Evaluation im Versorgungsalltag mit in die Routine eingebetteten randomisierten Studiendesigns ist der Schlüssel zur nachhaltigen und effizienten Nutzenbewertung von DiGA und kann entscheidend für eine strategische Verbesserung der Gesundheitsversorgung sein.