bluuebunny/crossref_metadata_2025 huggingface dataset:
Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE‐063): A randomized, open‐label, phase 3 trial in Asian patients
Authors: Chung Hyun Cheol , Kang Yoon‐Koo , Chen Zhendong , Bai Yuxian , Wan Ishak Wan Zamaniah , Shim Byoung Yong , Park Young Lee , Koo Dong‐Hoe , Lu Jianwei , Xu Jianming , Chon Hong Jae , Bai Li‐Yuan , Zeng Shan , Yuan Ying , Chen Yen‐Yang , Gu Kangsheng , Zhong Wen Yan , Kuang Shu , Shih Chie‐Schin , Qin Shu‐Kui
Published: December 2021

Background

KEYNOTE‐063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second‐line therapy in Asian patients with advanced programmed death ligand 1 (PD‐L1)–positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer.

Methods

This randomized, open‐label, phase 3 study was conducted at 36 medical centers in China (mainland), Malaysia, South Korea, and Taiwan. Patients were randomly assigned 1:1 to 200 mg of pembrolizumab intravenously every 3 weeks for ≤2 years or 80 mg/m2 of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression‐free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety.

Results

Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE‐061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval [CI], 4‐10 months) with pembrolizumab versus 8 months (95% CI, 5‐11 months) with paclitaxel (hazard ratio [HR], 0.99; 95% CI, 0.63‐1.54). Median PFS was 2 months (95% CI, 1‐3 months) with pembrolizumab versus 4 months (95% CI, 3‐6 months) with paclitaxel (HR, 1.62; 95% CI, 1.04‐2.52). ORR was 13% for pembrolizumab versus 19% for paclitaxel. Any‐grade treatment‐related adverse events occurred in 28 pembrolizumab‐treated patients (60%) and 42 paclitaxel‐treated patients (96%); grades 3 to 5 events occurred in 5 patients (11%) and 28 patients (64%), respectively.

Conclusions

Definitive conclusions about the efficacy of second‐line pembrolizumab in Asian patients with advanced PD‐L1–positive gastric/GEJ cancer are limited because of insufficient power, but pembrolizumab was well tolerated in this patient population. Efficacy followed a trend similar to that observed in the phase 3 KEYNOTE‐061 trial.
Similar zooplankton responses to lowpHand calcium may impair long‐term recovery from acidification
Authors: Ross Alexander J. , Arnott Shelley E.
Published: December 2021

Throughout much of the 20th century, unprecedented industrial emissions have led to widespread acidification of regions in North America and Europe and, as lake water pH dropped, aquatic ecosystems have experienced dramatic declines in biodiversity. International emission‐control agreements have led to sweeping increases in lake pH, however acid‐structured zooplankton communities still persist in many lakes. Concomitantly, calcium concentrations have been declining as a legacy of acidification and are approaching or have reached concentrations that could represent a barrier to the re‐establishment of zooplankton communities similar to those in non‐acidified or circumneutral reference lakes. To understand how declining calcium may influence the re‐establishment of zooplankton in acid‐damaged lakes we manipulated calcium and pH using a factorial in‐lake mesocosm experiment and assessed their individual and combined effects on a regionally diverse zooplankton assemblage. We found that the impacts of low calcium on zooplankton species were similar to those of acidification and, consequently, may prevent the recovery of acid‐structured communities. Abundance of the larger bodied and acid‐sensitiveDaphnia pulex/pulicariaincreased in high pH treatments, albeit nonsignificantly yet, by the end of our experiment, only two individuals were sampled among our 10 low calcium enclosures. In contrast, small acid‐tolerant cladocerans, such asDaphnia catawba,Daphnia ambigua, and eubosminids maintained significantly higher abundances in low calcium treatments relative to all other treatment combinations. Although we did not detect an effect of calcium on mean body size, the disproportionately high abundance of small cladocerans in low calcium treatments resulted in low calcium communities with higher overall abundance and lower cladoceran evenness. Our results, along with a landscape comparison demonstrating parallel changes in zooplankton relative abundance from 34 historically acidified lakes, suggests that declining calcium will be an important, on‐going factor that may limit the recovery of zooplankton, despite regional improvements in lake pH.
High vulnerability of juvenileNathusius' pipistrelle bats (Pipistrellus nathusii) at wind turbines
Authors: Kruszynski Cecilia , Bailey Liam D. , Bach Lothar , Bach Petra , Fritze Marcus , Lindecke Oliver , Teige Tobias , Voigt Christian C.
Published: December 2021

Large numbers of bats are killed by wind turbines globally, yet the specific demographic consequences of wind turbine mortality are still unclear. In this study, we compared characteristics of Nathusius' pipistrelles (Pipistrellus nathusii) killed at wind turbines (N = 119) to those observed within the live population (N = 524) during the summer migration period in Germany. We used generalized linear mixed‐effects modeling to identify demographic groups most vulnerable to wind turbine mortality, including sex (female or male), age (adult or juvenile), and geographic origin (regional or long‐distance migrant; depicted by fur stable hydrogen isotope ratios). Juveniles contributed with a higher proportion of carcasses at wind turbines than expected given their frequency in the live population suggesting that juvenile bats may be particularly vulnerable to wind turbine mortality. This effect varied with wind turbine density. Specifically, at low wind turbine densities, representing mostly inland areas with water bodies and forests where Nathusius' pipistrelles breed, juveniles were found more often dead beneath turbines than expected based on their abundance in the live population. At high wind turbine densities, representing mostly coastal areas where Nathusius' pipistrelles migrate, adults and juveniles were equally vulnerable. We found no evidence of increased vulnerability to wind turbines in either sex, yet we observed a higher proportion of females than males among both carcasses and the live population, which may reflect a female bias in the live population most likely caused by females migrating from their northeastern breeding areas migrating into Germany. A high mortality of females is conservation concern for this migratory bat species because it affects the annual reproduction rate of populations. A distant origin did not influence the likelihood of getting killed at wind turbines. A disproportionately high vulnerability of juveniles to wind turbine mortality may reduce juvenile recruitment, which may limit the resilience of Nathusius' pipistrelles to environmental stressors such as climate change or habitat loss. Schemes to mitigate wind turbine mortality, such as elevated cut‐in speeds, should be implemented throughout Europe to prevent population declines of Nathusius' pipistrelles and other migratory bats.
Balanced polymorphisms and their divergence in a Heliconius butterfly
Authors: Ogilvie James G. , Van Belleghem Steven , Range Ryan , Papa Riccardo , McMillan Owen W. , Chouteau Mathieu , Counterman Brian A.
Published: December 2021

The evolution of mimicry in similarly defended prey is well described by the Müllerian mimicry theory, which predicts the convergence of warning patterns in order to gain the most protection from predators. However, despite this prediction, we can find great diversity of color patterns among Müllerian mimics such as Heliconius butterflies in the neotropics. Furthermore, some species have evolved the ability to maintain multiple distinct warning patterns in single populations, a phenomenon known as polymorphic mimicry. The adaptive benefit of these polymorphisms is questionable since variation from the most common warning patterns is expected to be disadvantageous as novel signals are punished by predators naive to them. In this study, we use artificial butterfly models throughout Central and South America to characterize the selective pressures maintaining polymorphic mimicry in Heliconius doris. Our results highlight the complexity of positive frequency‐dependent selection, the principal selective pressure driving convergence among Müllerian mimics, and its impacts on interspecific variation of mimetic warning coloration. We further show how this selection regime can both limit and facilitate the diversification of mimetic traits.
Tailoring Mg2+ Solvation Structure in a Facile All‐Inorganic [MgxLiyCl2x+y·nTHF] Complex Electrolyte for High Rate and Long Cycle‐Life Mg Battery
Authors: Fan Haiyan , Zhang Xinxin , Zhao Yuxing , Xiao Jianhua , Yuan Hua , Wang Guang , Lin Yitao , Zhang Jifang , Pan Ludi , Pan Ting , Liu Yang , Zhang Yuegang
Published: December 2021

A high‐performance all‐inorganic magnesium–lithium chloride complex (MLCC) electrolyte is synthesized by a simple room‐temperature reaction of LiCl with MgCl2 in tetrahydrofuran (THF) solvent. Molecular dynamics simulation, density functional theory calculation, Raman spectroscopy, and nuclear magnetic resonance spectroscopy reveal that the formation of [MgxLiyCl2x+y·nTHF] complex solvation structure significantly lowers the coordination number of THF in the first solvation sheath of Mg2+, which significantly enhances its de‐solvation kinetics. The MLCC electrolyte presents a stable electrochemical window up to 3.1 V (vs Mg/Mg2+) and enables reversible cycling of Mg metal deposition/stripping with an outstanding Coulombic efficiency up to 99% at current densities as high as 10 mA cm−2. Utilizing the MLCC electrolyte, a Mg/Mo6S8 full cell can be cycled for over 10 000 cycles with a superior capacity retention of 85 mA h g−1 under an ultrahigh rate of 50 C (1 C = 128.8 mA g−1). The facile synthesis of high‐performance MLCC electrolyte provides a promising solution for future practical magnesium batteries.
Resting and exercise haemodynamic characteristics of patients with advanced heart failure and preserved ejection fraction
Authors: Deis T. , Wolsk E. , Mujkanovic J. , Komtebedde J. , Burkhoff D. , Kaye D. , Hasenfuß G. , Hayward C. , Van der Heyden J. , Petrie M.C. , Shah S.J. , Borlaug B.A. , Kahwash R. , Litwin S. , Hoendermis E. , Hummel S. , Gustafsson F.
Published: December 2021

Aims

This study aimed to describe haemodynamic features of patients with advanced heart failure with preserved ejection fraction (HFpEF) as defined by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Methods and results

We used pooled data from two dedicated HFpEF studies with invasive exercise haemodynamic protocols, the REDUCE LAP‐HF (Reduce Elevated Left Atrial Pressure in Patients with Heart Failure) trial and the REDUCE LAP‐HF I trial, and categorized patients according to advanced heart failure (AdHF) criteria. The well‐characterized HFpEF patients were considered advanced if they had persistent New York Heart Association classification of III–IV and heart failure (HF) hospitalization < 12 months and a 6 min walk test distance < 300 m. Twenty‐four (22%) out of 108 patients met the AdHF criteria. On evaluation, clinical characteristics and resting haemodynamics were not different in the two groups. Patients with AdHF had lower work capacity compared with non‐advanced patients (35 ± 16 vs. 45 ± 18 W, P = 0.021). Workload‐corrected pulmonary capillary wedge pressure normalized to body weight (PCWL) was higher in AdHF patients compared with non‐advanced (112 ± 55 vs. 86 ± 49 mmHg/W/kg, P = 0.04). Further, AdHF patients had a smaller increase in cardiac index during exercise (1.1 ± 0.7 vs. 1.6 ± 0.9 L/min/m2, P = 0.028).

Conclusions

A significantly higher PCWL and lower cardiac index reserve during exercise were observed in AdHF patients compared with non‐advanced. These differences were not apparent at rest. Therapies targeting the haemodynamic compromise associated with advanced HFpEF are needed.
Assessment of the impact of different N terminal pro brain natriuretic peptide thresholds on echocardiography services
Authors: Yii Eric , Fersia Omar , McFadyen Angus , Isles Christopher
Published: December 2021

Aims

N terminal pro brain natriuretic peptide (NT‐proBNP) is considered a rule‐out test for patients with suspected heart failure. The NT‐proBNP thresholds recommended for echocardiography by the European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) are based on small studies of patients with heart failure and left ventricular (LV) systolic dysfunction (LVSD). The purpose of our study was to examine the relation between NT‐proBNP and LVSD in a larger number of patients with symptoms suggestive of heart failure in a non‐acute setting.

Methods and results

One thousand patients with suspected chronic heart failure underwent echocardiography within 6 months of NT‐proBNP measurement. NT‐proBNP was the strongest predictor of any form of LVSD in univariate (OR 2.52, 95% CI 2.19–2.91, P value < 0.001) and multivariate (OR 2.73, 95% CI 2.32–3.21, P value < 0.001) analyses. Negative predictive value (NPV) of NT‐proBNP for impaired LV systolic function (ejection fraction 35–49%) was 98% at 125 pg/mL (the ESC threshold), 93% at 400 pg/mL (the NICE threshold), 91% at 1000 pg/mL and 90% at 2000 pg/mL. Corresponding values for severe LVSD (ejection fraction <35%) were 100%, 99%, 98% and 96%. The number of patients per 1000 with suspected chronic heart failure requiring echocardiography at each threshold was 851, 543, 324, and 182, respectively.

Conclusions

N terminal pro brain natriuretic peptide thresholds recommended by ESC and NICE result in large numbers of patients with suspected chronic heart failure being referred for echocardiography. Raising the NT‐proBNP threshold would improve access to echocardiography with minimal negative impact on the clinical performance of this cardiac biomarker.
Echocardiographic and clinical predictors of cardiac amyloidosis: limitations of apical sparing
Authors: Kyrouac Douglas , Schiffer Walter , Lennep Brandon , Fergestrom Nicole , Zhang Kathleen W. , Gorcsan John , Lenihan Daniel J. , Mitchell Joshua D.
Published: December 2021

Aims

The accuracy of an apical‐sparing strain pattern on transthoracic echocardiography (TTE) for predicting cardiac amyloidosis (CA) has varied in prior studies depending on the underlying cohort. We sought to evaluate the performance of apical sparing and other TTE strain findings to screen for CA in an unselected population and determine the frequency that patients with echocardiographic concern for CA undergo evaluation for amyloidosis in clinical practice.

Methods and results

As strain is routinely performed at our institution on all clinical TTEs, we identified all TTEs performed from 2016 through 2019 with reported concern for CA or apical sparing. We determined the performance characteristics for echocardiographic strain findings in discriminating CA including apical sparing, the ejection fraction to global longitudinal strain ratio (EF/GLS), and the septal apical–septal basal ratio (SA/SB); other clinical predictors of confirmed CA; and predictors of patients who underwent complete evaluation for CA. CA was confirmed by endomyocardial biopsy or diagnostic cardiac imaging. A total of 547 TTEs, representing 451 patients, reported concern for CA and had adequate strain for analysis. A total of 111 patients underwent complete evaluation for amyloidosis with 100 patients undergoing complete cardiac evaluation for CA. In those 100 patients, multivariable predictors of confirmed CA were age [odds ratio (OR) 3.37 per 5 years], a visual apical‐sparing pattern (OR 10.85), and left ventricular ejection fraction (LVEF)/GLS > 4.1 (OR 35.37). CA was less likely in those with coronary artery disease (OR 0.04), hypertension (OR 0.18), and increased systolic blood pressure (OR 0.60 per 5 mm Hg increase). SA/SB [area under the curve (AUC) 0.72, 95% confidence interval (CI) 0.60–0.84] and LVEF/GLS (AUC 0.72, 95% CI 0.60–0.84) both had improved discrimination for CA compared with the apical‐sparing ratio (AUC 0.66, 95% CI 0.54–0.79). Many patients with suggestive TTE findings did not receive an evaluation for amyloidosis. Complete evaluation was more likely with Caucasian race (OR 2.1), increased septal thickness (OR 1.4), increased body mass index (OR 1.2), and if the report specifically stated ‘amyloid’ (OR 1.9). Evaluations were less likely in patients with comorbidities. While hypertension reduced the likelihood of evaluating for CA, 34% of patients with CA had hypertension (>130/80 mm Hg) at time of diagnosis.

Conclusions

In a broad population of patients undergoing TTE, apical sparing on strain imaging increased the likelihood of CA diagnosis but with modest sensitivity and specificity. GLS/EF ratio may be a more reliable tool to screen for CA. The low rate of complete evaluation in patients with concerning TTE findings indicates a strong need for practice improvement and enhanced disease awareness.
The depositional evolution and responses to controlling factors in the Permian Upper Urho Formation, Western Mahu Slope, Junggar Basin, NW China
Authors: Shi Yong , Yu Jingfeng , Xu Heng , Fang Zhibin , Luo Xudong , Wang Zhiqiang , Lu Jing , Tan Dujuan , Wang Jingqi , He Naixiang
Published: December 2021

The abundant petroleum reserves have been found in the Urho Formation in the past few years in western Mahu Slope, Junggar Basin. A great deal of studies has been carried out regarding tectonic evolution, sequence stratigraphy, reservoir prediction, and mechanism in the Urho Formation. However, little is known concerning the depositional evolution and associated controlling factors in the Upper Urho Formation. In this study, thin sections, cores, wireline logs, and seismic volumes are utilized to identify and describe sedimentary facies/microfacies, analyse mineral components and micro characteristics of microfacies, predict facies/microfacies distributions, and reveal depositional evolution and associated controlling factors. The results indicate the identification of eight sedimentary microfacies and the evolution of fan delta systems in Upper Urho Formation. In addition, depositional evolution of fan delta systems from bottom to top in Upper Urho Formation is characterized by retrogradation during lacustrine transgression period. The controlling factors, including tectonic activities along northwestern thrust fold belt and lacustrine fluctuations together exert influences over depositional evolution of regressive fan delta systems in Upper Urho Formation.
Cu–Al2O3/engine oil Williamson hybrid nanofluid flow over a stretching/shrinking Riga plate with viscous dissipation and radiation effect
Authors: Nidhi  , Kumar Lokendra
Published: December 2021

The current effort aims to analyze fluid flow characteristics in engine oil Williamson hybrid nanofluid flow past a Riga‐plate. The employed model is influenced by thermal radiation effect, viscous dissipation, and convective surface boundary conditions. The composed equations are distorted into dimensionless form by an appropriate similarity technique. Dual solutions (a stable and an unstable solution) to the resultant highly nonlinear coupled system are found using the shooting approach. In the restricted situation, the results attained agree with published work. The impact of the necessary controlling parameters on velocity profile, temperature profile, skin friction coefficient, and reduced Nusselt number are illustrated graphically. Numerically calculated values of skin friction coefficients in both and directions and reduced Nusselt numbers are also presented in the tabular form. The notable finding of the problem analyzed is that a sufficient amount of suction is necessary for the shrinking flow to be possible. Biot number, Eckert number, and radiation parameter do not affect boundary layer separation whereas an upsurge in width of electrodes and magnets decreases the range of the first and the second solutions, and modified Hartmann number increases it.
Effects of norepinephrine on microglial neuroinflammation and neuropathic pain
Authors: Zou He‐Lin , Li Juan , Zhou Jun‐Li , Yi Xi , Cao Song
Published: December 2021

Norepinephrine (NE) is an important neurotransmitter in the central nervous system. NE is released from locus coeruleus neurons and is involved in a variety of physiological and pathological processes. Neuroinflammation is a common manifestation of many kinds of neurological diseases. The activation of microglia directly affects the status of neuroinflammation. Several kinds of adrenergic receptors, which anchor on microglia and can be regulated by NE, affect the activation of microglia and neuroinflammation. NE influences chronic pain, anxiety, and depression by regulating the activation of microglia.
Effects of modified multimodal analgesia on postoperative pain, sedation, and prognosis of gynecological patients
Authors: Zhang Fan , Luo Man , Liu De‐Xing , Zhu Yu‐Hang , Zhu Zhao‐Qiong
Published: December 2021

Patient‐controlled intravenous analgesia is one of the most common pain relief methods in  the postoperative period, but its adverse reactions remain high. This study aimed to explore the role of improved combined analgesia methods in pain, sedation, postoperative nausea, and vomiting (PONV) in patients undergoing gynecological surgeries. This study was a prospective, randomized, double‐blind controlled study. A study population of 72 patients undergoing gynecological surgery were randomly assigned to either the TAPB + S group or the TAPB + N group. All patients in both groups underwent a transversus abdominis plane block (TAPB) after induction of anesthesia. The TAPB + S group received a continuous intravenous infusion (2 ml/h) of sufentanil (1 μg/kg) plus metoclopramide (30 mg) through 100 ml elastomeric pumps postoperatively. The TAPB + N group received a continuous intravenous infusion (2 ml/h) of nalbuphine hydrochloride (1 mg/kg) plus metoclopramide (30 mg) postoperatively. The main outcome measures were as follows: postoperative pain intensity, Ramsay sedation score (RSS) after surgery, PONV occurrence rate, and rescue analgesics. The RSS of the TAPB + S group was significantly higher than that of the TAPB + N group at 2, 4, and 6 h after the operation. However, the visual analog scale score of the TAPB + S group was much higher than that of the TAPB + N group. No significant differences were found between the two groups in terms of consumption of opioids and other narcotic drugs at 2, 4, 6, 24, and 48 h after the operation. No statistically significant differences were found with respect to PONV and other adverse events in both groups. Taken together, our data indicate that the TAPB + N program can provide better postoperative analgesia and also reduce the use of strong opioids. The more optimized scheme of perioperative analgesia still needs to be researched further.
Temporal changes in the water quality of urban tropical streams: An approach to daily variation in seasonality
Authors: Bega João Miguel Merces , Zanetoni Filho José Antônio , Albertin Liliane Lazzari , Oliveira Jefferson Nascimento de
Published: December 2021

Using water quality indices (WQIs) is one way to monitor watercourses for water quality. Currently, there is a lack of information about their behavior in the diurnal cycle because sampling is often carried out in the morning. Also, few articles focus on assessing the urban impact on the spatial variability of WQIs in tropical first-order streams. Such streams receive many pollutants varying in intensity according to population habits, justifying the possible diurnal variation in water quality in addition to climatic attributes. This paper aims to evaluate the fluctuations in Brazilian WQIs and their parameters (temperature, turbidity, total solids [TS], hydrogen potential, dissolved oxygen [DO], biochemical oxygen demand [BOD], total phosphorus [TP], total nitrogen [TN], and Escherichia coli) between the morning (8 AM), afternoon (2 PM), and night (7 PM) periods for an urban first-order tropical stream. Overall, the lowest DO concentrations and highest values of TS, turbidity, BOD, TP, TN, and E. coli were obtained in the morning, possibly representing population habits: the greatest generation of pollutants occurs overnight and in the early morning because there are clandestine domestic wastewater inputs into the stream, whose hourly periodicity generates a similar periodicity in the WQI of the evaluated stream. Although there was a significant variation in WQI average values between morning (15.50 ± 1.97) and afternoon (20.83 ± 5.42) only during the dry season (p < 0.05), different results were common throughout the day in all months, and the water quality was often classified in distinct categories: very bad, bad, and regular. Our findings present another dimension to be considered when assessing urban water quality, leading to direct benefits to the management and use of urban waters. Integr Environ Assess Manag 2022;18:1260–1271. © 2021 SETAC

KEY POINTS

This paper presents the variations in the Brazilian water quality index (WQI) and its parameters between three periods of the day (8 AM, 2 PM, and 7 PM). The greatest generation of clandestine domestic effluents occurs overnight and in the early morning, whose hourly periodicity generates a similar periodicity in the WQI. Our findings present another dimension to be considered when assessing urban water quality, leading to direct benefits to the management and use of urban waters. All parameters are equally important for the Brazilian WQI since no parameter can replace other parameters (possible if they would have similar behavior at all periods).
Disclosure obligations of a debtor under the Singapore scheme of arrangement: Lessons from England and the US
Authors: Eu Alfino Zijian
Published: December 2021

The Singapore scheme of arrangement has received considerable attention from the international community in recent years due to the Chapter 11‐inspired reforms enacted in 2017. However, an overlooked, and perhaps underdeveloped, aspect of the Singapore scheme has been the disclosure obligations of the debtor throughout the scheme process. This article seeks to provide a critical evaluation of the disclosure framework under the Singapore scheme and, drawing on features of the English scheme and Chapter 11 in the US, to identify potential avenues for reform. Three, in particular, are highlighted. The first relates to a lack of formal requirements in Singapore prescribing the form and duration of notice which a debtor is required to give to its creditors of its application for leave to convene the creditor's meeting. The second concerns the uncertainty surrounding the precise types of information to be included in the explanatory statement which is circulated to the creditors. This is a particularly important issue given that Singapore schemes often feature retail investors who would generally be reliant on the explanatory statement to make an informed decision. Third, given the significant reforms enacted to the Singapore scheme, namely the availability of a broader moratorium and rescue financing provisions, there is a heightened need for more comprehensive financial disclosures at an earlier stage in the scheme process even before the debtor applies for leave to convene the creditors' meeting.
Nanobioglass enhanced polyurethane/collagen conduit in sciatic nerve regeneration
Authors: Nasab Somayeh Tofighi , Roodbari Nasim Hayati , Goodarzi Vahabodin , Khonakdar Hossein Ali , Nourani Mohammad Reza
Published: December 2021

The main purpose of neural tissue engineering and regenerative medicine is the development of biological substitutions to preserve, improve, and regenerate the damaged functions of tissues and organs. Three novel conduits, including polyurethane (PU), polyurethane/collagen (PU/C), and polyurethane/collagen/nano‐bio glass (PU/C/NBG), were fabricated by the electrospinning technique. After confirming the suitability of conduits in the in‐vitro environment, conduits were surgically sutured in a 10‐mm gap in the sciatic nerve of a rat to evaluate their role in sciatic nerve reconstruction. After 4, 8, and 12 weeks of surgery, nerve regeneration was assessed by the hot plate test, sciatic functional index, electromyography, histology, and immunohistochemistry against S100, NF200, and CD31 antibodies. The results of various examinations revealed that the PU/C/NBG conduit is significantly more suitable than PU and PU/C conduits in terms of nerve regeneration. However, all three groups of conduits had the potential to be used for nerve regeneration. Overall, this study discovered that the PU/C/NBG conduit is a biocompatible neural conduit, which is a favorable candidate for peripheral nerve regeneration and axonal growth.
Malnutrition on admission increases the in‐hospital mortality and length of stay in elder adults with acute ischemic stroke
Authors: Hao Ruixiao , Qi Xuemei , Xia Xiaoshuang , Wang Lin , Li Xin
Published: December 2021

Purpose

Malnutrition, as determined by the Controlling Nutritional Status (CONUT), has an effect on the 3‐month and long‐term prognosis of stroke patients. The association between malnutrition and in‐hospital mortality has not been well established. We aimed to investigate the relationship between the CONUT score on admission and in‐hospital mortality and length of stay (LOS) in elderly patients with acute ischemic stroke (AIS).

Methods

This study analyzed controls and patients with AIS. Malnutrition was determined using the CONUT score. A CONUT score of 5–12 was defined as undernutrition status. Based on the CONUT scores, the patients were divided into the low CONUT (0–4) and high CONUT (5–12) groups.

Results

In total, 1079 participants were recruited, comprising 288 controls and 791 AIS patients. Among the 791 patients, 64 (8.1%) had malnutrition and 63 (7.9%) had an in‐hospital death. Compared to the controls, the AIS patients presented higher CONUT scores, higher proportion of in‐hospital mortality (8.0%), and longer length of stay. Malnutrition was independently associated with in‐hospital mortality in the AIS patients (adjusted odds ratio: 3.77, 95% confidence interval [CI]: 1.55–9.15; p = 0.003). The general linear models showed an association between the CONUT score and LOS (β = 0.574, 95% CI: 0.208–0.934; p = 0.002). Furthermore, the effect of the interaction between infection and nutrition status on in‐hospital mortality showed borderline statistical significance (p = 0.06).

Conclusions

Malnutrition estimated by the CONUT score on admission can be a predictor of in‐hospital mortality and increased LOS in elderly AIS patients.
How the rise of testosterone therapy in men was inspired by lizard research with David Crews
Authors: Morgentaler Abraham
Published: December 2021

A chance encounter in 1975 with David Crews in Harvard Square led to 3 years of research in his lab, investigating the role of testosterone (T) in male sexual behavior of the lizard, Anolis carolinensis. In 1988 when I began my practice as a urologist and specialist in men's health, my research experience with lizards led me to offer testosterone therapy (TTh) to men suffering with symptoms of testosterone deficiency, despite the universal belief that TTh caused prostate cancer (PCa). My investigation of this topic over 30+ years has led to revolutionary changes in the diagnosis and treatment of men with testosterone deficiency and our understanding of the biology of testosterone and PCa. Today, it is routine for men successfully treated for PCa to receive TTh, a remarkable fact given that standard treatment for men with advanced PCa has been androgen deprivation for the last 80 years. Our research showed low T was not protective for PCa; TTh did not appear to worsen PCa for various cancer stages; and provided the theoretical framework for understanding why androgen deprivation shrinks PCa tumors, yet TTh appears to not cause PCa growth under most conditions. This is based on the Saturation Model, which recognizes there is a finite ability of androgens to stimulate PCa growth, which becomes maximal at low T concentrations. David Crews was an outstanding mentor—the lessons I learned from him inspired a lifetime of work, which in turn led to improved quality of life for millions of men.
Evaluation of optical 3D scanning system for radiotherapy use
Authors: Crowe Scott , Luscombe Jenna , Maxwell Sarah , Simpson‐Page Emily , Poroa Tania , Wilks Rachael , Li Weizheng , Cleland Susannah , Chan Philip , Lin Charles , Kairn Tanya
Published: December 2021

Introduction

Optical three‐dimensional scanning devices can produce geometrically accurate, high‐resolution models of patients suitable for clinical use. This article describes the use of a metrology‐grade structured light scanner for the design and production of radiotherapy medical devices and synthetic water‐equivalent computer tomography images.

Methods

Following commissioning of the device by scanning objects of known properties, 173 scans were performed on 26 volunteers, with observations of subjects and operators collected.

Results

The fit of devices produced using these scans was assessed, and a workflow for the design of complex devices using a treatment planning system was identified.

Conclusions

Recommendations are provided on the use of the device within a radiation oncology department.
Modeling and forecasting the total number of cases and deaths due to pandemic
Authors: Khan Nasrullah , Arshad Asma , Azam Muhammad , Al‐marshadi Ali Hussein , Aslam Muhammad
Published: December 2021

The COVID‐19 pandemic has appeared as the predominant disease of the 21st century at the end of 2019 and was a drastic start with thousands of casualties and the COVID‐19 victims in 2020. Due to the drastic effect, COVID‐19 scientists are trying to work on pandemic diseases and Governments are interested in the development of methodologies that will minimize the losses and speed up the process of cure by providing vaccines and treatment for such pandemics. The development of a new vaccine for any pandemic requires long in vitro and in vivo trials to use. Thus the strategies require understanding how the pandemic is spreading in terms of affected cases and casualties occurring from this disease, here we developed a forecasting model that can predict the no of cases and deaths due to pandemic and that can help the researcher, government, and other stakeholders to devise their strategies so that the damages can be minimized. This model can also be used for the judicial distribution of resources as it provides the estimates of the number of casualties and number of deaths with high accuracy, Government and policymakers on the basis of forecasted value can plan in a better way. The model efficiency is discussed on the basis of the available dataset of John Hopkins University repository in the period when the disease was first reported in the six countries till the mid of May 2020, the model was developed on the basis of this data, and then it is tested by forecasting the no of deaths and cases for next 7 days, where the proposed strategy provided excellent forecasting. The forecast models are developed for six countries including Pakistan, India, Afghanistan, Iran, Italy, and China using polynomial regression of degrees 3–5. But the models are analyzed up to the 6th‐degree and the suitable models are selected based on higher adjusted R‐square (R2) and lower root‐mean‐square error and the mean absolute percentage error (MAPE). The values of R2 are greater than 99% for all countries other than China whereas for China this R2 was 97%. The high values of R2 and Low value of MAPE statistics increase the validity of proposed models to forecast the total no cases and total no of deaths in all countries. Iran, Italy, and Afghanistan also show a mild decreasing trend but the number of cases is far higher than the decrease percentage. Although India is expected to have a consistent result, more or less it depicts some other biasing factors which should be figured out in separate research.
Articular contact motion at the knee during daily activities
Authors: Thomeer Lucas T. , Guan Shanyuanye , Gray Hans A. , Pandy Marcus G.
Published: December 2021

We combined mobile biplane X‐ray imaging and magnetic resonance imaging to measure the regions of articular cartilage contact and cartilage thickness at the tibiofemoral and patellofemoral joints during six functional activities: standing, level walking, downhill walking, stair ascent, stair descent, and open‐chain (non‐weight‐bearing) knee flexion. The contact centers traced similar paths on the medial and lateral femoral condyles, femoral trochlea, and patellar facet in all activities while their locations on the tibial plateau were more varied. The translations of the contact centers on the femur and patella were tightly coupled to the tibiofemoral flexion angle in all activities (r2 > 0.95) whereas those on the tibia were only moderately related to the flexion angle (r2 > 0.62). The regions of contacting cartilage were significantly thicker than the regions of non‐contacting cartilage on the patella, femoral trochlea, and the medial and lateral tibial plateaus in all activities (p < 0.001). There were no significant differences in thickness between contacting and non‐contacting cartilage on the medial and lateral femoral condyles in all activities, except open‐chain knee flexion. Our results provide partial support for the proposition that cartilage thickness is adapted to joint load and do not exclude the possibility that other factors, such as joint congruence, also play a role in regulating the structure and organization of healthy cartilage. The data obtained in this study may serve as a guide when evaluating articular contact motion in osteoarthritic and reconstructed knees.
The Cardiac Caval Index: Improving Noninvasive Assessment of Cardiac Preload
Authors: Ermini Leonardo , Seddone Stefano , Policastro Piero , Mesin Luca , Pasquero Paolo , Roatta Silvestro
Published: December 2021

Objectives

Inferior vena cava (IVC) pulsatility quantified by the Caval Index (CI) is characterized by poor reliability, also due to the irregular magnitude of spontaneous respiratory activity generating the major pulsatile component. The aim of this study was to test whether the IVC cardiac oscillatory component could provide a more stable index (Cardiac CI‐CCI) compared to CI or respiratory CI (RCI).

Methods

Nine healthy volunteers underwent long‐term monitoring in supine position of IVC, followed by 3 minutes passive leg raising (PLR). CI, RCI, and CCI were extracted from video recordings by automated edge‐tracking and CCI was averaged over each respiratory cycle (aCCI). Cardiac output (CO), mean arterial pressure (MAP) and heart rate (HR) were also recorded during baseline (1 minutes prior to PLR) and PLR (first minute).

Results

In response to PLR, all IVC indices decreased (P < .01), CO increased by 4 ± 4% (P = .055) while HR and MAP did not vary. The Coefficient of Variation (CoV) of aCCI (13 ± 5%) was lower than that of CI (17 ± 5%, P < .01), RCI (26 ± 7%, P < .001) and CCI (25 ± 7%, P < .001). The mutual correlations in time of the indices were 0.81 (CI‐RCI), 0.49 (CI‐aCCI) and 0.2 (RCI‐aCCI).

Conclusions

Long‐term IVC monitoring by automated edge‐tracking allowed us to evidence that 1) respiratory and averaged cardiac pulsatility components are uncorrelated and thus carry different information and 2) the new index aCCI, exhibiting the lowest CoV while maintaining good sensitivity to blood volume changes, may overcome the poor reliability of CI and RCI.
Block‐wise Exploration of Molecular Descriptors with Multi‐block Orthogonal Component Analysis (MOCA)
Authors: Schmidt Sebastian , Schindler Michael , Eriksson Lennart
Published: December 2021

Data tables for machine learning and structure‐activity relationship modelling (QSAR) are often naturally organized in blocks of data, where multiple molecular representations or sets of descriptors form the blocks. Multi‐block Orthogonal Component Analysis (MOCA), a new analytical tool, can be used to explore such data structures in a single model, identifying principal components that are unique to a single block or joint over multiple blocks. We applied MOCA to two sets of 550 and 300 molecules and up to 9213 molecular descriptors organized in 11 blocks. The MOCA models reveal relationships between the blocks and overarching trends across the whole dataset. Based on the MOCA joint components, we propose a quantitative metric for the redundancy of blocks, useful for a priori block‐wise feature selection or evaluation of new molecular representations. The second data set includes 7 ecotoxicological study endpoints for crop protection chemicals, for which we (re‐)discovered some general trends and linked them to molecular properties. Using a single MOCA model we estimated the predictive potential of each block and the model‐ability of the target block.
A spectrum analyzer system with wide bandwidth and high frequency resolution based on chirp transform
Authors: Ru Peng‐Lei , Liu Meng‐Wei , Gong Jun‐Jie , Wang Wen , Zhu Hao‐Tian
Published: December 2021

With the advantages of low power consumption and high stability, chirp transform spectrometer (CTS) has become a powerful tool widely used in spectrum analysis today. In recent years, compared with other spectrum analyzers, CTS is limited by the lack of bandwidth, which severely restricts its application and development. In this article, a CTS system with a wide bandwidth is proposed. The chirp signal with 2 GHz bandwidth is generated by DAC and multiplier, and its dispersion characteristics are matched with a 1 GHz bandwidth surface acoustic wave (SAW) filter to build a spectrum analyzer with an analysis bandwidth of 1 GHz. Experimental results show that the system frequency resolution can reach up to 102 kHz, which is very close to the theoretical value (100 kHz).
The development and validation of a Patient‐Perceived Methotrexate Intolerance Scale for use in adult rheumatoid arthritis patients
Authors: Salt Elizabeth , Wiggins Amanda , Lohr Kristine , Crofford Leslie , Studts Jamie , Nowell W. Benjamin , Cappelleri Joseph C. , Rayens Mary Kay
Published: December 2021

Introduction/Objective

To develop a scale to measure methotrexate intolerance for use in adult rheumatoid arthritis (RA) patients and to describe its psychometric properties.

Methods

A three‐phase study was conducted. During Phase 1, we conducted individual interviews with RA patients (n = 14) to inform our item development process. During Phase 2, we asked for RA patients' (n = 10) feedback on item readability, clarity and the scale's ability to measure methotrexate intolerance. During Phase 3, we had patients with RA (n = 204) complete the scale to develop a final version and to describe the scale's internal validity (Cronbach’s alpha), test–retest reliability (intra‐class correlation coefficients), construct validity and discriminant validity and the ability of the scale to discriminate between past and present methotrexate users.

Results

The newly developed, weighted scale (Patient‐Perceived Methotrexate Intolerance Scale[PPMIS]) includes four subscales:Methotrexate Benefits, Methotrexate Risks‐Side Effect Considerations, RA RisksandMethotrexate Risks‐Willingness to Take Methotrexate Despite Risks. Cronbach's alpha ranged from 0.79 to 0.94. Test–retest reliability at 2 weeks was 0.73–0.88. Construct validity was supported with significant logical relationships between subscale scores and the existing methotrexate intolerance scale and past/present methotrexate use. The PPMIS was able to correctly classify RA patients as a past versus present methotrexate user 77% of the time. At the cut point of 3.29, the sensitivity of the PPMIS is 74% and specificity is 72% to correctly classify patients into past/present methotrexate use.

Conclusion

This is the first known scale with favourable measurement properties to evaluate methotrexate intolerance using a patient‐centred perspective.
Clinical placements as a challenging opportunity in midwifery education: A qualitative study
Authors: Modarres Maryam , Geranmayeh Mehrnaz , Amini Mitra , Toosi Monireh
Published: December 2021

Aim

The aim of this qualitative study was to explore some of the existing statuses of clinical education and examine the strengths and weaknesses of the clinical faculty programme.

Design

A qualitative study.

Methods

This qualitative study was designed through the directed content analysis approach, which was completed according to the Context, Input, Process, and Product evaluation model. The purposeful sampling method of maximum variation was employed to select 33 participants, and the data were collected through in‐depth individual interviews and focus group discussion.

Results

After the interview transcripts were analysed, the participants' opinions of the clinical faculty programme and the relevant challenges, dimensions and factors were classified into four categories and sixteen subcategories. The categories were compiled in the CIPP evaluation model, including context, input, process and product. Based on the content analysis results, appropriate planning was recommended for teaching effective clinical skills to students.
Formation and reinforcing effect of epitaxial oriented crystallization of polyethylene induced by self‐assembly nucleating agent under stress
Authors: Wu Buyong , Kong Chen , Cai Yudong , Ye Lin , Chen Shangtao , Li Shuanhong , Zhao Xiaowen
Published: December 2021

A rare earth nucleating agent (RENA) was introduced to fabricate polyethylene (PE) pipe resin, which self‐assembled into various structures in PE melt during processing and further induced PE molecules to epitaxially crystallize on its surface to form, among others, a hybrid shish‐kebab crystalline structure due to good crystallographic matching between RENA and PE. Under stress, the shish structure formed by needle‐like RENA assembly arranged preferentially along the drawing direction, which was beneficial for an orderly arrangement of PE chains epitaxially crystallizing on its surface in the process of stress‐induced recrystallization and thus promoted the formation of a dense oriented crystalline structure with a large number of shish structures, resulting in higher degree of crystallinity and orientation, and lower long period and lateral size of lamellae than those of PE sample. By orientation, compared with PE sample at the same draw ratio, PE‐RENA samples showed much higher tensile strength and modulus. Especially, the oriented PE‐RENA pipes showed an approximately 96% and 100% increase in tensile strength along the hoop direction and internal pressure resistance, respectively, compared with unoriented pipe sample. This work provides a facile method for fabricating highly enhanced PE pipes with wide application prospects. © 2021 Society of Industrial Chemistry.
Editor's Letter
Authors: Mick Connie Snyder
Published: December 2021

This letter from the editor provides a brief summary of the articles contained in this issue and invites readers to respond and submit their own articles.