bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic imaging for suspected pulmonary embolism during pregnancy and postpartum: A comparative radiation dose study
Authors: Tester Jodie , Rees Megan , Pascoe Diane , Earl Victoria , Einsiedel Paul , Lim Wen Kwang , Irving Louis , Hammerschlag Gary
Published: May 2022

Introduction

To compare the radiation dose exposure and diagnostic efficiency of computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion imaging (V/Q) for clinically suspected pulmonary embolism (PE) in pregnant and postpartum women in a tertiary hospital setting.

Methods

A retrospective cohort study of 473 pregnant and postpartum women referred for CTPA or V/Q for clinically suspected PE between January 2013 and December 2018 at a tertiary hospital. Maternal effective radiation dose, breast‐absorbed radiation dose and fetal‐absorbed dose estimates were calculated. Diagnostic yield was evaluated from radiological findings.

Results

Computed tomographic pulmonary angiography (CTPA) was more commonly used for the imaging of suspected PE in pregnant and postpartum populations (51.9% vs. 48.1% and 77.1% vs. 22.9%, respectively). CTPA was associated with higher maternal effective and breast‐absorbed doses (maternal effective CTPA 4.7 (±2.9) mSv (millisievert), V/Q 1.7(±0.8) mSv (mean difference 2.93 mSv P < 0.001), and breast‐absorbed CTPA 8.0 (±5.2) mGy (milligray), V/Q 0.3 (±0.1) (mean difference 7.67 mGy P < 0.001), respectively). Fetal radiation dose exposure was low. The incidence of positive PE was 5.5%. Indeterminate rates of CTPA and V/Q were 3.0% and 5.5% (P = 0.176), respectively.

Conclusions

Compared to V/Q, CTPA is associated with higher maternal and breast radiation dose; however, modern CT scanners achieve lower radiation doses than historically described. Fetal radiation dose was comparably low. The diagnostic yield of the imaging modalities in pregnant and postpartum women is similar. Revision of guidelines should occur with the advances in CT technology.
Effect of magnetite addition on transcriptional profiles of syntrophic Bacteria and Archaea during anaerobic digestion of propionate in wastewater sludge
Authors: Dyksma Stefan , Gallert Claudia
Published: May 2022

Anaerobic digestion (AD) is an important technology for the effective conversion of waste and wastewater to methane. Here, syntrophic bacteria transfer molecular hydrogen (H2), formate, or directly supply electrons (direct interspecies electron transfer, DIET) to the methanogens. Evidence is accumulating that the methanation of short‐chain fatty acids can be enhanced by the addition of conductive material to the anaerobic digester, which has often been attributed to the stimulation of DIET. Since little is known about the transcriptional response of a complex AD microbial community to the addition of conductive material, we added magnetite to propionate‐fed laboratory‐scale reactors that were inoculated with wastewater sludge. Compared to the control reactors, the magnetite‐amended reactors showed improved methanation of propionate. A genome‐centric metatranscriptomics approach identified the active SCFA‐oxidizing bacteria that affiliated with Firmicutes, Desulfobacterota and Cloacimonadota. The transcriptional profiles revealed that the syntrophic bacteria transferred acetate, H2 and formate to acetoclastic and hydrogenotrophic methanogens, whereas transcription of potential determinants for DIET such as conductive pili and outer‐membrane cytochromes did not significantly change with magnetite addition. Overall, changes in the transcriptional profiles of syntrophic Bacteria and Archaea in propionate‐fed lab‐scale reactors amended with magnetite refute a major role of DIET in the studied system.
Facial imaging to screen for fetal alcohol spectrum disorder: A scoping review
Authors: Roomaney Imaan , Nyirenda Clement , Chetty Manogari
Published: May 2022

Facial imaging tools have rapidly advanced in recent years and show potential for use in fetal alcohol spectrum disorder (FASD) screening and diagnosis. This scoping review describes the current state of evidence regarding the use of facial imaging being as a screening tool for FASD at a community level. This review follows the guidelines for the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) extension for scoping reviews and is registered with the Open Science Framework (osf.io/e4xw6). An electronic search of five databases was conducted. The time frame was limited to the period 2006 to 2022. The search included any form of imaging of the head, neck, oral cavity, and dentition. Animal and antenatal studies were excluded, as were those using only brain imaging. The search retrieved 730 unique titles. After title, abstract, and full‐text screening, 28 primary studies were included in this review. Most studies were conducted with South African participants. Imaging included 2D photographs, 3D stereophotogrammetry, 3D laser scanning, and radiographs. Various measurements and landmarks were used to discriminate FASD from non‐FASD participants, which included anthropometry, face shape analysis, and facial curvatures. Methods of data processing, analysis, and modeling ranged from manual methods to fully automated systems utilizing artificial intelligence. The use of facial imaging to screen for and diagnose patients with FASD is a rapidly advancing field. Most studies in the field remain exploratory, attempting to find accurate, reliable, and consistent landmarks and measures across different populations. For community screening, none of the tools in this review in their current form completely fulfill all the identified properties of an ideal screening tool. More research and development are needed prior to advocating for the use of any tool listed and the ethical implications are yet to be fully explored.
Predictors of abstinence, no heavy drinking days, and a 2‐level reduction in World Health Organization drinking levels during treatment for alcohol use disorder in the COMBINE study
Authors: Wallach Joshua D. , Gueorguieva Ralitza , Phan Huong , Witkiewitz Katie , Wu Ran , O'Malley Stephanie S.
Published: May 2022

Background

Data from trials of medications for alcohol use disorder (AUD) can be used to identify predictors of drinking outcomes regardless of treatment, which can inform the design of future trials with heterogeneous populations. Here, we identified predictors of abstinence, no heavy drinking days, and a 2‐level reduction in World Health Organization (WHO) drinking levels during treatment for AUD in the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) Study.

Methods

We utilized data from the COMBINE Study, a randomized placebo‐controlled trial evaluating the efficacy of naltrexone and acamprosate, both alone and in combination, for AUD (n = 1168). A tree‐based machine learning algorithm was used to construct classification trees predicting abstinence, no heavy drinking days, and a 2‐level reduction in WHO drinking levels in the last 4 weeks of treatment, based on 89 baseline variables.

Results

The final tree for predicting abstinence had one split based on consecutive days abstinent prior to randomization, with a higher proportion of subjects achieving abstinence among those classified as abstinent for >2 versus ≤2 consecutive weeks prior to randomization (66% vs. 29%). The final tree for predicting no heavy drinking days in the last 4 weeks of treatment had three splits based on consecutive days abstinent, age, and total Alcohol Dependence Scale score at baseline. Seventy‐three percent of the subjects classified as abstinent for >2 consecutive weeks prior to randomization had no heavy drinking days in the last 4 weeks of treatment. Among those classified as abstinent ≤2 consecutive weeks prior, three additional splits showed that younger subjects (age ≤44 years; 37%), and older subjects (age >44) with a total Alcohol Dependence Scale score >13 and complete abstinence (56%) or other drinking goals (35%), were less likely to have no heavy drinking days than older subjects with a total Alcohol Dependence Scale score ≤13 (67%). The final tree for predicting a 2‐level reduction in WHO levels had no splits.

Conclusions

Consecutive days abstinent prior to randomization may predict abstinence and no heavy drinking days and total Alcohol Dependence Scale score and age may predict no heavy drinking days. The 2‐level reduction in WHO levels outcome may be less likely to discriminate based on multiple patient characteristics.
Alternance of alternative stable states influence the functional diversity of microcrustaceans in a shallow subtropical lake
Authors: Martins Karoline Pereira , Albertoni Edélti Faria
Published: May 2022

Shallow lakes in subtropical climate regions may have a clear water state with a predominance of submerged or floating macrophytes and a turbid water state with a predominance of phytoplankton. The relationship between microcrustaceans and these changes in alternative states is still incipient in the literature. And to better understand these relationships, the functional approach is an excellent tool. Thus, the present work seeks to test the hypothesis that changes in alternative stable states over time reflect the variability of composition and functional diversity of microcrustaceans. For this, samples of microcrustaceans collected in a subtropical shallow lake, which underwent alternate state changes in the period to 2000–2014, were used. Our results demonstrate a variation in composition and functional diversity among alternative states, thus supporting our hypothesis. In periods of clear water with a predominance of floating macrophytes, we found a greater functional diversity and richness of genera. This result may be associated with several factors such as greater habitat heterogeneity and lower predation pressure. The lowest values of functional diversity found in periods of turbid waters with predominance of phytoplankton and periods of clear waters with submerged macrophytes are related to the dominance of functional traits, such as scraper feeding type, herbivorous/omnivorous trophic group, littoral habitat and asexual reproduction. These traits are functional features of most Ostracoda genera, a taxonomic group abundant in these two alternative states. The predominance of this group may be related to the environmental characteristics of these periods, such as the high vegetation cover and the availability of niches unoccupied by more sensitive species, since most Ostracoda have high environmental tolerance. We conclude that the functional traits approach combined with taxonomic groups respond to temporal variations of alternative stable states and are important tools to detect environmental changes.
Psarocolius decumanus(Icteridae) acts as a seedling disperser ofGomesa recurva(Orchidaceae) in the Brazilian Atlantic Forest
Authors: do Nascimento Tubarão Felipe , Fajardo Villela Antolin Barberena Felipe
Published: May 2022

Psarocolius decumanus(crested oropendola) (Icteridae) is a neotropical bird whose reproductive biology is well studied. Its nests consist of pendulous bags up to 2‐m long usually made ofTillandsia usneoides(Bromeliaceae) with dry leaves lining up the incubation chamber. Several materials from different botanical families have been reported in the nests of crested oropendolas. However, these other plants have not been recognized at the specific level. In the present study, we report the use of roots and pseudobulbs ofGomesa recurva(Orchidaceae) by crested oropendolas to build nests in strictly protected area in the Brazilian Atlantic Forest. The roots ofG. recurvaare fibrous, eventually intertwined and reach tens of centimetres, constituting a suitable material for building nests. This interaction could also be beneficial for the orchid, because when searching for roots and pulling them out, the birds end up taking with them also small pseudobulbs. When building the nest with these parts ofG. recurva, crested oropendolas promote the dispersal of the orchid throughout the area. Seedlings may occasionally get attached to the lower branches and grow at more basal strata of the phorophytes or as terricolous in the forest understory after nests fall. In addition, as the nests are always built in the upper strata of trees, crested oropendolas may also be improving plant performance since many orchid species need relatively high light environments to bloom. The relationship betweenP. decumanusandG. recurvaand the ecological conditions required by both species need to be better investigated in future studies.
Real‐world staging computed tomography scanning technique and important reporting discrepancies in pancreatic ductal adenocarcinoma
Authors: Grogan Alexander , Loveday Benjamin , Michael Michael , Wong Hui‐Li , Gibbs Peter , Thomson Benjamin , Lee Belinda , Ko Hyun Soo
Published: May 2022

Background

Computed tomography (CT) is the first‐line staging imaging modality for pancreatic ductal adenocarcinoma (PDAC) which determines resectability and treatment pathways.

Methods

Between January 2016 and December 2019, prospectively collated data from two Australian cancer centres was extracted from the PURPLE Pancreatic Cancer registry. Real‐world staging CTs and corresponding reports were blindly reviewed by a sub‐specialist radiologist and compared to initial reports.

Results

Of 131 patients assessed, 117 (89.3%) presented with symptoms, 74 (56.5%) CTs included slices ≤3 mm thickness and CT pancreas protocol was applied in 69 (52.7%) patients. Initial reports lacked synoptic reporting in 131 (100%), tumour identification in 2 (1.6%) and tumour measurement in 13 (9.9%) cases. Tumour‐vascular relationship reporting was missing in 69–109 (52.7–83.2%) for regarding the key arterial and venous structures that is required to assess resectability. Initial reports had no comment on venous thrombus or venous collaterals in 80 (61.1%) and 109 (83.2%) and lacked locoregional lymphadenopathy interpretation in 13 (9.9%) cases. Complete initial staging report was present in 72 (55.0%) patients. Sub‐specialist radiological review resulted in down‐staging in 16 (22.2%) and up‐staging in 1 (1.4%) patient. Staging discrepancies were mainly regarding metastatic disease (12, 70.6%) and tumour‐vascular relationship (5, 29.4%).

Conclusion

Real‐world staging imaging in PDAC patients show low proportion of dedicated CT pancreas protocol, high proportion of incomplete staging reports and no synoptic reporting. The most common discrepancy between initial and sub‐specialist reporting was regarding metastases and tumour‐vascular relationship assessment resulting in sub‐specialist down‐staging in almost every fifth case.
Processes of Peripheralisation: Toehold and Aspirational Urbanisation in theGCR
Authors: Howe Lindsay Blair
Published: May 2022

This article interrogates the term “periphery” by examining the forms of urbanisation unfolding in the Gauteng City‐Region (GCR) of South Africa. Among the urbanisation processes identified, it focuses on two, situating them among debates on informality and defining new vocabularies of urbanisation. Aligned with discussions of peripherality as a social phenomenon, the article first depicts how some marginalised groups of people using transversal means carve out “toeholds” near urban centralities and opportunities. Second, it conveys how peripherality is also a geographical phenomenon, describing “aspirational” mass housing for the lower‐middle class on urban peripheries that can generate unexpected forms of precarity. The article concludes that toehold urbanisation and aspirational urbanisation drive peripheralisation in the GCR, and considers the implications of these concepts for critical geography and urban studies.
Future Eco‐Perfect: Temporal Fixes of Liberal Environmentalism
Authors: Collard Rosemary‐Claire , Dempsey Jessica
Published: May 2022

In the last half century runaway wildlife declines have been simultaneous with the liberal environmental state’s ascent. Despite proliferating legislation to arrest these declines, states have fuelled economic growth at species’ expense. Through what tactics of power does the liberal environmental state manage this contradiction between promising species protection while authorising their obliteration? Manipulations of tense, futurity, temporal pace and scope are central. Responding to the plight of endangered caribou in Canada, the state tinkers and repeatedly resets time (“starting … now!”) while hailing the future eco‐perfect, a time just‐around‐the‐corner when caribou and the economy will flourish.
Impact of expanding hepatitis B treatment guidelines: A modelling and economic impact analysis
Authors: Lim Young‐Suk , Ahn Sang Hoon , Shim Jae‐Jun , Razavi Homie , Razavi‐Shearer Devin , Sinn Dong Hyun
Published: May 2022

Background

Antiviral treatment in patients with chronic hepatitis B (CHB) may decrease the risk of hepatocellular carcinoma (HCC) and death. However, only 2.2% of CHB patients receive antiviral treatment globally. The complexity and strictness of the current clinical practice guidelines may limit expanding the treatment coverage for CHB.

Aims

To examine the impact of expanding treatment criteria on future disease burden in Korea, a hepatitis B virus (HBV) endemic country with high diagnostic rates.

Materials

Dynamic country‐level data were used to estimate the HCC incidence, overall mortality and economic impact of three incremental scenarios compared to the base case in Korea through 2035.

Results

In 2020, 1,409,000 CHB cases were estimated, with the majority born before 1995. All scenarios assumed treating 70% of eligible individuals. The first scenario removed viral load restrictions in cirrhotic patients, which would avert 13,000 cases of HCC and save 11,800 lives. The second scenario, lowering the alanine aminotransferase (ALT) level restriction to the upper limit of the normal in non‐cirrhotic patients, would avert 26,700 cases of HCC and save 23,300 lives. The last scenario removed the restriction by ALT and HBeAg in treating non‐cirrhotic individuals with a viral load of ≥2000 IU/ml, which would avert 43,300 cases of HCC and save 37,000 lives. All scenarios were highly cost‐effective.

Conclusions

Simplifying and expanding treatment eligibility for CHB would save many lives and be highly cost‐effective when combined with high diagnostic rates. These dynamic country‐level data may provide new insights for their global application.
Decrease in species richness and diversity, and shrub encroachment in Cerrado grasslands: A 20 years study
Authors: de Souza Gabriella Ferreira , Ferreira Maxmiller Cardoso , Munhoz Cássia Beatriz Rodrigues
Published: May 2022

Question

The Cerrado is a global biodiversity hotspot, highly threatened by changes in land use. Alterations in species composition and the colonization of Cerrado grasslands by woody species can lead to long‐term changes in these communities. In this study, we investigated changes over 20 years in three grassland areas, in terms of species richness and diversity and growth‐form cover, as well as the effects of shrub and grass encroachment on species richness.

Location

Cerrado Brazilian savanna, moist grassland and dry shrub grassland. Areas under low and high anthropogenic pressure.

Methods

Plant species composition and cover were sampled on seven occasions between the years 2000 and 2020, in permanent line‐transects. We compared plant cover, richness, diversity and growth‐form cover between the periods for each area. Next, we developed mixed‐effect linear models to test whether species richness in grasslands at the latest sampling event was altered by species representing 70% of the species cover at this time.

Results

Grasslands located in areas under higher anthropogenic pressure presented reduced richness and diversity, and cover concentrated on a few species of shrubs and large tussock grasses. Moist grassland undergoing encroachment by the native shrub Trembleya parviflora had lost over 50% of its diversity since encroachment. In the same area, a shrub grassland undergoing encroachment by native shrub Raulinoreitzia tremula, three native grass species and one exotic grass presented significantly reduced species richness. The moist grassland in an area under low anthropogenic pressure showed a reordering of the species cover over time, but a decrease in species richness.

Conclusion

We observed changes in plant richness, diversity, cover, composition and growth‐form cover over a period of 20 years in grassland communities. We found, however, different trajectories in the three grassland areas sampled, mainly due to the encroachment of a few species, leading to floristic homogenization in grasslands located in areas under high anthropogenic pressure.
Scalability of effective adherence interventions for patients using cardiovascular disease medication: A realist synthesis‐inspired systematic review
Authors: Hogervorst Stijn , Vervloet Marcia , Adriaanse Marcel C. , Zamboni Karen , Zullig Leah L. , Schoonmade Linda , Hugtenburg Jacqueline G. , van Dijk Liset
Published: May 2022

Upscaling of medication adherence interventions to routine care is still challenging. This realist theory‐inspired review aimed to assess which intervention aspects are potentially important for the scalability of effective cardiovascular disease (CVD) medication adherence interventions and how they are reported in effectiveness studies. A total of 4097 articles from four databases were screened of which ultimately 31 studies were included. Relevant information on scalability was extracted using a theoretic framework based on the scalability assessment tool used in the QUALIDEC study for the following domains: (i) innovation, (ii) implementers and patients, (iii) adopting organizations and health system, and (iv) socio‐political context. Extracted articles were analysed for themes and chains of inference, which were grouped based on commonality and source of evidence to form new hypotheses. Six different domains relevant for scalability of adherence interventions were identified: (1) Complexity of the intervention; (2) training; (3) customization of the intervention; (4) drivers of the intervention; (5) technical interventions; and (6) stakeholder involvement. These six domains might be useful for the development of more scalable interventions by bridging the gap between research and practice. Data relevant for scalability is not well reported on in effectiveness trials for CVD medication adherence interventions and only limited data on scalability has been published in additional papers. We believe the adoption and reach of effective CVD medication adherence interventions will improve with increased awareness for the necessity of scalability in all phases of intervention development.
Hydroxybenzamide derivatives protect pancreatic β cell by suppressing unfolded protein response activation
Authors: Eeda Venkateswararao , Rawal Komal N. , Matlock H. Greg , Herlea‐Pana Oana , Lim Hui‐Ying , Wang Weidong
Published: May 2022

Endoplasmic reticulum (ER) stress‐induced Pancreatic β‐cell dysfunction and death plays important roles in the development of diabetes. The 1,2,3‐triazole derivative 1 is one of only a few structures that have thus far been identified that protect β cells against ER stress, but it is limited for its narrow activity range. In this study, we designed and synthesized a series of hydroxybenzamide (HBA) derivatives in which the triazole pharmacophore was substituted with an amide linker. Structure–activity relationship studies identified WO3i (3‐hydroxy‐N‐(4‐[trifluoromethyl]benzyl)benzamide) that possesses β‐cell protective activity against ER stress at a 100% maximal activity with EC50 at 0.19 μM). We showed that WO3i suppresses the expression of CHOP, a key mediator of ER stress‐induced apoptosis, and the activation of apoptotic genes. Mechanistically, we further showed that WO3i suppresses the ER stress‐induced activation of all three pathways of unfolded protein response—ATF6, IRE1α, and PERK. Identification of this novel β‐cell‐protective scaffold thus provides a new promising modality for the potential for drug development for the treatment of diabetes.
2, 4, 5‐Trideoxyhexopyranosides derivatives of diphyllin: Synthesis and anticancer activity
Authors: Cai Rui , Li Yu , Zhu Li , Wei Caiyan , Bao Xiaofeng , Zhao Yu
Published: May 2022

Diphyllin and its natural derivatives were identified as potent vacuolar H+‐ATPase (V‐ATPase) inhibitors. In this study, twelve 2, 4, 5‐trideoxyhexopyranosides derivatives of diphyllin were synthesized. Most of these compounds showed potent abilities to inhibit the growth of HT‐29, MCF‐7, HepG2 cancer cells with IC50 values at submicromolar concentration. The compounds 5c3 and 5c4 showed the best inhibitory activity on breast cancer cell lines MCF‐7 with IC50 values of 0.09 and 0.10 μM. Compounds 5c3 and 5c4 showed similar V‐ATPase inhibitory potency to diphyllin. Molecular docking showed that a hydrogen bond was found between the hydroxyl of 5c3 and SerA534 in the pocket of the V‐ATPase receptor.
Retinal neural dysfunction in diabetes revealed with handheld chromatic pupillometry
Authors: Tan Tien‐En , Finkelstein Maxwell T. , Tan Gavin Siew Wei , Tan Anna Cheng Sim , Chan Choi Mun , Mathur Ranjana , Wong Edmund Yick Mun , Cheung Chui Ming Gemmy , Wong Tien Yin , Milea Dan , Najjar Raymond P.
Published: May 2022

Background

To evaluate the ability of handheld chromatic pupillometry to reveal and localise retinal neural dysfunction in diabetic patients with and without diabetic retinopathy (DR).

Methods

This cross‐sectional study included 82 diabetics (DM) and 93 controls (60.4 ± 8.4 years, 44.1% males). DM patients included those without (n = 25, 64.7 ± 6.3 years, 44.0% males) and with DR (n = 57, 60.3 ± 8.5 years, 64.9% males). Changes in horizontal pupil radius in response to blue (469 nm) and red (640 nm) light stimuli were assessed monocularly, in clinics, using a custom‐built handheld pupillometer. Pupillometric parameters (phasic constriction amplitudes [predominantly from the outer retina], maximal constriction amplitudes [from the inner and outer retina] and post‐illumination pupillary responses [PIPRs; predominantly from the inner retina]) were extracted from baseline‐adjusted pupillary light response traces and compared between controls, DM without DR, and DR. Net PIPR was defined as the difference between blue and red PIPRs.

Results

Phasic constriction amplitudes to blue and red lights were decreased in DR compared to controls (p < 0.001; p < 0.001). Maximal constriction amplitudes to blue and red lights were decreased in DR compared to DM without DR (p < 0.001; p = 0.02), and in DM without DR compared to controls (p < 0.001; p = 0.005). Net PIPR was decreased in both DR and DM without DR compared to controls (p = 0.02; p = 0.03), suggesting a wavelength‐dependent (and hence retinal) pupillometric dysfunction in diabetic patients with or without DR.

Conclusions

Handheld chromatic pupillometry can reveal retinal neural dysfunction in diabetes, even without DR. Patients with DM but no DR displayed primarily inner retinal dysfunction, while patients with DR showed both inner and outer retinal dysfunction.
Pharmacokinetics of asciminib in the presence of CYP3A or P‐gp inhibitors, CYP3A inducers, and acid‐reducing agents
Authors: Hoch Matthias , Huth Felix , Sato Masahiko , Sengupta Tirtha , Quinlan Michelle , Dodd Stephanie , Kapoor Shruti , Hourcade‐Potelleret Florence
Published: May 2022

Asciminib is a first‐in‐class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. Asciminib is a substrate of CYP3A4 and P‐glycoprotein (P‐gp) and possesses pH‐dependent solubility in aqueous solution. This report summarizes the results of two phase I studies in healthy subjects aimed at assessing the impact of CYP3A and P‐gp inhibitors, CYP3A inducers and acid‐reducing agents (ARAs) on the pharmacokinetics (PK) of asciminib (single dose of 40 mg). Asciminib exposure (area under the curve [AUC]) unexpectedly decreased by ~40% when administered concomitantly with the strong CYP3A inhibitor itraconazole oral solution, whereas maximum plasma concentration (Cmax) decreased by ~50%. However, asciminib exposure was slightly increased in subjects receiving an itraconazole capsule (~3%) or clarithromycin (~35%), another strong CYP3A inhibitor. Macroflux studies showed that cyclodextrin (present in high quantities as excipient [40‐fold excess to itraconazole] in the oral solution formulation of itraconazole) decreased asciminib flux through a lipid membrane by ~80%. The AUC of asciminib was marginally decreased by concomitant administration with the strong CYP3A inducer rifampicin (by ~13–15%) and the strong P‐gp inhibitor quinidine (by ~13–16%). Concomitant administration of the ARA rabeprazole had little or no effect on asciminib AUC, with a 9% decrease in Cmax. The treatments were generally well tolerated. Taking into account the large therapeutic window of asciminib, the observed changes in asciminib PK following multiple doses of P‐gp, CYP3A inhibitors, CYP3A inducers, or ARAs are not considered to be clinically meaningful. Care should be exercised when administering asciminib concomitantly with cyclodextrin‐containing drug formulations.
Looking is not enough: Multimodal attention supports the real‐time learning of new words
Authors: Schroer Sara E , Yu Chen
Published: May 2022

Most research on early language learning focuses on the objects that infants see and the words they hear in their daily lives, although growing evidence suggests that motor development is also closely tied to language development. To study the real‐time behaviors required for learning new words during free‐flowing toy play, we measured infants’ visual attention and manual actions on to‐be‐learned toys. Parents and 12‐to‐26‐month‐old infants wore wireless head‐mounted eye trackers, allowing them to move freely around a home‐like lab environment. After the play session, infants were tested on their knowledge of object‐label mappings. We found that how often parents named objects during play did not predict learning, but instead, it was infants’ attention during and around a labeling utterance that predicted whether an object‐label mapping was learned. More specifically, we found that infant visual attention alone did not predict word learning. Instead, coordinated, multimodal attention–when infants’ hands and eyes were attending to the same object–predicted word learning. Our results implicate a causal pathway through which infants’ bodily actions play a critical role in early word learning.
Doing aid chains differently: Evaluating the potential ofMulti‐StakeholderPartnerships
Authors: Gerard Kelly
Published: May 2022

Motivation

Donors have increasingly disbursed funds using aid chains, whereby work is subcontracted to organizations socially and geographically closer to recipients. Aid chains reduce scope for opportunism in contracting. They do, however, enable donors to distance themselves from the messy work of engaging the politics of interventions—“ethics dumping”—with negative impacts on project outcomes.

Purpose

How can aid chains—and project outcomes—be improved? This article investigates what can be learned from global value chains (GVCs). In particular, it examines Multi‐Stakeholder Partnerships (MSPs)—currently considered the gold standard for governing GVCs—and evaluates their potential fit for aid chains.

Methods and approach

The article describes aid chains' drivers and challenges, and theoretically links the fragmentation of public‐sector service provision to the fragmentation of global production processes. By reviewing MSP case studies and thematically analysing their scope to transform power asymmetries, it empirically evaluates MSPs' potential by assessing the case of the Australian NGO Cooperation Program.

Findings

While MSPs offer an ambitious framework, their application is weakened by, first, the lack of a consumer role, and second, their central focus on relational practices in transforming power asymmetries. The article's conclusion that MSPs offer limited policy transferability furthers nascent literatures on ethical public‐sector procurement; power asymmetries in MSPs; and how aid chains might be improved.

Policy implications

Aid chains reduce the scope for opportunism in contracting, however their power asymmetries have negative impacts on project outcomes that cannot be ignored. MSPs offer an ambitious but problematic policy option for improving aid chain governance. Their lack of effective measures to address power asymmetries limits their potential, calling into question their status as the gold standard for GVC governance and their policy transferability.
Autologous stem cell transplantation in multiple myeloma patients over 70 years: A GIMEMA Lazio Working Group experience in a retrospective case–control study
Authors: Rago Angela , Annibali Ombretta , Tomarchio Valeria , Coppetelli Ugo , Fazio Francesca , Cupelli Luca , Fiorini Alessia , Piciocchi Alfonso , Tafuri Agostino , Caravita di Toritto Tommaso
Published: May 2022

High‐dose chemotherapy followed by autologous stem cell transplantation (auto‐SCT) is the standard treatment for young patient ≤65 years with multiple myeloma (MM). The role of auto‐SCT in elderly patients older than 70 years remains controversial in the era of novel agents and especially since the recent introduction of monoclonal antibodies (AbMo). In this study, we evaluated 12 patients with MM over 70 years old undergoing auto‐SCT (elderly graft cohort) in seven centers of GIMEMA Working Group Lazio. We compared the baseline characteristics, treatment and outcome with 97 MM elderly patients who did not receive auto‐SCT (nontransplant patients) from the same registry who were ≥ 70 years old, but did not undergo auto‐SCT. The median progression free survival (PFS) for graft versus no‐graft cohort was 56.4 versus 26.1 months, respectively. There was a trend for better PFS among graft compared to nontransplant patient (p = .1). On the other hand, the median overall survival for transplant versus nontransplant cohort was 107.6 versus 49.5 months (p = .02). Despite the small number of patients aged ≥70 years and ≤74 years, it seems that auto‐SCT is well tolerated, safe and effective. Therefore, we propose that it should be considered an important treatment option in the era of new drugs in elderly fit patients with MM.
Disability progression in multiple sclerosis patients using early first‐line treatments
Authors: Lefort Mathilde , Vukusic Sandra , Casey Romain , Edan Gilles , Leray Emmanuelle ,   OFSEP investigators
Published: May 2022

Background and purpose

Therapeutic management of relapsing–remitting multiple sclerosis (RRMS) has evolved towards early treatment. The objective was to assess the impact of early treatment initiation on disability progression amongst RRMS first‐line‐treated patients.

Methods

This study included all incident RRMS cases starting interferon or glatiramer acetate for the first time from 1 January 1996 to 31 December 2012 (N = 5279) from 10 MS expert Observatoire Français de la Sclérose en Plaques centres. The delay from treatment start to attaining an irreversible Expanded Disability Status Scale (EDSS) score of 3.0 was compared between the early group (N = 1882; treated within 12 months following MS clinical onset) and the later group using propensity score weighted Kaplan–Meier methods, overall and stratified by age.

Results

Overall, the restricted mean time before reaching EDSS 3.0 from treatment start was 11 years and 2 months for patients treated within the year following MS clinical onset and 10 years and 7 months for patients treated later. Thus, early treated patients gained 7 months (95% confidence interval [CI] 4–11 months) in the time to reach EDSS 3.0 compared to patients treated later (treatment start delayed by 28 months). The difference in restricted mean time was respectively 6 months (95% CI 1–10 months) and 14 months (95% CI 4–24 months) in the ≤40 years age group and in the >40 years age group, in favour of the early group.

Conclusions

Early treatment initiation resulted in a significant reduction of disability progression amongst patients with RRMS, and also amongst older patients.
Climate change and fishing are pulling the functional diversity of the world's largest marine fisheries to opposite extremes
Authors: Zhao Kangshun , Gaines Steven D. , García Molinos Jorge , Zhang Min , Xu Jun
Published: May 2022

Aim

Marine biodiversity is increasingly threatened by overfishing and climate change, but it is still unclear how these drivers have shaped the functional diversity (FD) of marine fish. Here, we explore how the FD of commercial marine fish communities responds to climate change and fishing pressure.

Major taxa studied

Marine fish.

Location

China Seas.

Time period

1989–2018.

Methods

We used a catch database of four individual species and 12 species groups that were reported continuously in China from 1989 to 2018. Seven traits were selected to calculate FD. We adopted generalized linear mixed models to analyse the complex relationship among climate change, fishing pressure and several metrics of marine fish FD. We identified the percentage change in diversity for communities to assess the relative contribution of each species or species group by removing individual species or a species group from the dataset.

Results

Climate change and fishing pressure exerted statistically significant opposing effects on the functional evenness (FEve) and functional divergence (FDiv) of commercial fish communities. Increasing sea surface temperature had a significant positive effect on FEve but a negative effect on FDiv. In contrast, increasing fishing pressure had the opposite effects on FEve and FDiv. These results were driven by the significantly varying relative contributions of fish species or species groups to the functional space, whereby low‐trophic‐level pelagic fish species or species groups are closer to the boundaries of the functional trait space than high‐trophic‐level demersal fish species or species groups.

Main conclusions

The FD of commercial marine fish communities responds significantly to climate warming and increasing fishing pressure, with opposite effects driven by different response patterns of fish species or species groups. Our results suggest that management actions should address the two issues simultaneously, because considering only one will unleash greater functional changes in the other.
Insights into the endogenous cathepsins on modori of fermented carp (Cyprinus carpio) sausage gels in acid environment
Authors: Zhang Furong , Yongde Zeng , Wu Jiangli , Yang Zhengbin , Zhang Wei , Fan Jin , Zeng Xuefeng
Published: May 2022

This research aims to monitor the modori of fermented fish sausage and determine the effect of endogenous cathepsins. Proteolysis, structure and physico‐chemical properties of carp sausage were determined using texture profile, rheological, SEM, FTIR and SDS‐PAGE, respectively. In the forming stage of gels, the rapid reduction in pH dropped below 5.16 within 36 h of fermentation. Meanwhile, the hardness (g), elasticity, Chewiness (mJ) and gumminess increased. The results of elasticity modulus (G′) exhibited strong correlation with TPA. Gels presented a three‐dimensional network structure at 36 h. In the degradation stage of gels, the increase of TVB‐N, TCA‐soluble peptides and FAAs indicated that muscle proteins were strongly degraded. SDS‐PAGE demonstrated that the degradation of insoluble protein was coincided with the modori of gels. During fermentation, cathepsin B (CPB) and cathepsin L (CPL) exhibited high activity, while cathepsin D (CPD) revealed low activity. β‐ sheet and α‐ helix increased to 1.07 and 1.05 times of the initial value (P > 0.05), while random coil and β‐turn dropped to 10.27% and 21.98%, respectively. PCA suggested that acids played a major role in the formation of gels and that CPB and CPL were closely related to the modori of gels. Moreover, this study provided theoretical guidance for controlling the formation and inhibiting the modori of fish sausage gel.
Properties of beeswax antifungal coatings obtained by high‐pressure homogenisation and their application for preserving bananas during storage
Authors: Agyemang Bridget , Grabulos Joel , Hubert Olivier , Bourlieu Claire , Nigen Michael , Lebrun Marc , Coffigniez Fanny , Guillard Valérie , Brat Pierre
Published: May 2022

Bananas are tropical fruits that are perishable and susceptible to fungal diseases, mainly caused by Colletotrichum musae. Antimicrobial emulsion‐based coating materials have been used extensively to inhibit the growth of these fungi and extend the shelf life of bananas. Targeted emulsion‐based film functionalities offer excellent mechanical, physicochemical and barrier properties and limit fungal growth kinetics. Antifungal compounds, such as essential oils or phenolic compounds, are added to emulsion‐based (wax/biopolymer) coatings to enhance their antimicrobial properties. This study set out to formulate a beeswax‐based emulsion for banana coatings using high‐pressure homogenisation (HPH) and hydrophilic food‐grade/organic coating materials. The particle size distribution, stability and mechanical properties of the film‐forming emulsions, water vapour and the oxygen permeabilities of the resulting coating were investigated. The most promising sucrose emulsions were tested as coatings on banana fruits to assess their efficacy against moisture and firmness loss during storage. Adding thymol (0.5% w/w) to the sucrose emulsions further enhanced the inhibition of Colletotrichum musae growth to its barest minimum of <20%. Emulsion stability was clearly enhanced using HPH while the best inhibition was obtained with a 20% diluted sucrose emulsion containing 0.5% thymol, with or without HPH.
Predicting perioperative outcomes of robot‐assisted radical cystectomy: Data from the Asian Robot‐Assisted Radical Cystectomy Consortium
Authors: Lee Alvin Yuanming , Allen John Carson , Teoh Jeremy Yuen‐Chun , Kang Seok‐Ho , Patel Manish I , Muto Satoru , Yang Cheng‐Kuang , Hatakeyama Shingo , Zhang Ruiyun , Kijvikai Kittinut , Chen Haige , Ohyama Chikara , Horie Shigeo , Chan Eddie Shu‐Yin , Lee Lui‐Shiong
Published: May 2022

Objectives

To report the perioperative outcomes of robot‐assisted radical cystectomy and elucidate their risk factors.

Methods

A review of the Asian Robot‐Assisted Radical Cystectomy Consortium database from 2007 to 2020 was performed. The perioperative outcomes studied included complication rates, time to solid food intake, estimated blood loss, length of hospital stay, and 30‐day readmission rates.

Results

Of 568 patients, the overall complication rate was 49.2%, comprising major complications in 15.6%. Preoperative hydronephrosis was associated with an increased risk of major complications (odds ratio 3.27, 95% confidence interval 1.48–7.26, P = 0.004) while neoadjuvant chemotherapy was protective (odds ratio 0.46, 95% confidence interval 0.25–0.84, P = 0.012). The median time to solid food intake was 4 days (interquartile range 3–7) and smoking was a risk factor (odds ratio 4.28, 95% confidence interval 2.36–7.79, P < 0.001) for prolonged time to solid food intake. Median length of hospital stay was 13 days (interquartile range 9–19), and diabetes mellitus (odds ratio 1.66, 95% confidence interval 1.08–2.56, P = 0.021), neoadjuvant chemotherapy (odds ratio 2.21, 95% confidence interval 1.46–3.33, P < 0.001), and orthotopic bladder substitute creation (odds ratio 2.82, 95% confidence interval 1.90–4.18, P < 0.001) were independent risk factors for prolonged length of hospital stay. The 30‐day readmission rate was 23.4% and higher in those with bilateral hydronephrosis (odds ratio 4.58, 95% confidence interval 1.97–10.65, P < 0.001) and orthotopic bladder substitute creation (odds ratio 1.87, 95% confidence interval 1.16–3.02, P = 0.010).

Conclusions

There are preoperative conditions which are significant risk factors for adverse perioperative outcomes in robot‐assisted radical cystectomy. Most are potentially modifiable and can direct strategies to reduce surgical morbidity related to this major oncological procedure.
Effect of Sb addition on SbxSn1‐xS thin films: The structural, morphological, and linear/nonlinear optical changes for optoelectronic applications
Authors: Parida A. , Alagarasan D. , Ganesan R. , Vardhrajaperumal S. , Naik R.
Published: May 2022

The current paper reports the changes in the structural and optical properties of antimony‐doped tin sulfide ternary (SbxSn1‐xS) (x = 0, 0.05, 0.1, 0.15, 0.2) thin films synthesized by the thermal evaporation technique on a glass substrate. Structural characterization techniques such as X‐ray diffraction and Raman spectroscopy of the prepared sample revealed that the thin films are crystalline in nature. The nanoflake‐like structure was found from the surface morphological analysis performed by field emission scanning electron microscopy. The concentration of the compositional elements was confirmed from the energy dispersive X‐ray analysis. The linear and nonlinear optical parameters were calculated by using the transmission data obtained from UV–vis spectroscopy in the range of 800–1100 nm. The optical measurements showed an increase in transmittance and shifting of the absorption edge. The optical bandgap increased (1.239–1.378 eV) and the refractive index decreased with the increase of Sb concentration, satisfying the Moss rule. The nonlinear susceptibility and the nonlinear refractive index (n2) decreased with Sb content. The changes in both linear and nonlinear parameters by varying the antimony doping concentration could be helpful for controlling the optical properties of SbxSn1‐xS thin films and could be a suitable candidate for many photonics and optoelectronic applications.
Stand‐alone Focal Impulse and Rotor Modulation (FIRM) ablation versus second‐generation cryoballoon pulmonary vein isolation for paroxysmal atrial fibrillation
Authors: Tilz Roland R. , Yalin Kivanc , Lyan Evgeny , Heeger Christian‐Hendrik , Schlüter Michael , Fink Thomas , Sciacca Vanessa , Liosis Spyridon , Kuck Karl‐Heinz , Popescu Sorin Ștefan , Mortensen Kai , Meyer‐Saraei Roza , Eitel Charlotte , Vogler Julia
Published: May 2022

Introduction

Focal Impulse and Rotor Modulation (FIRM) guided catheter ablation aiming at stable rotors has been investigated as a treatment option in patients with atrial fibrillation (AF). The objective of this study was to compare the safety and efficacy of FIRM‐guided ablation with second‐generation cryoballoon pulmonary vein isolation (CB2‐PVI) in paroxysmal AF.

Methods

Consecutive patients (n = 22, mean age 60 ± 11 years, 59.1% of males) who were treated with a stand‐alone FIRM‐guided ablation were included in this retrospective single‐center study. Procedural data and arrhythmia‐free survival at 12 months were compared with n = 86 consecutive patients (mean age 62 ± 13 years, 62.4% of males) who received de‐novo CB2‐PVI.

Results

Median procedure duration was significantly longer in the FIRM group than in the CB2‐PVI group (152 [IQR 120–176] minutes vs. 122 [110–145] minutes; p = .031). One patient (1.2%) in the CB2‐PVI group and five patients (22.7%) in the FIRM group had vascular access complications. Atrial tachyarrhythmias recurred in 15 patients in the FIRM group and 11 in the CB2‐PVI group. Kaplan–Meier estimation of single‐procedure arrhythmia‐free survival at 12 months was 25% (95% confidence interval [CI] 6%–44%) in the FIRM group and 87% (95% CI 78%–96%) in the CB2‐PVI group (p < .001). Repeat ablations were performed in 14/20 (70.0%) patients in the FIRM group and in 12/85 (14.1%) in the CB2‐PVI group (p < .001).

Conclusion

De novo ablation of AF using FIRM‐guided AF ablation results in shorter arrhythmia‐free survival after 12 months compared to CB2‐PVI and a need for repeat ablation in the majority of patients to achieve stable sinus rhythm.