bluuebunny/crossref_metadata_2025 huggingface dataset:
Aripiprazole Lauroxil Dosing Regimens: Understanding Dosage Strengths and Injection Intervals
Authors: Sommi Roger W. , Rege Bhaskar , Wehr Angela , Faldu Sejal , Du Yangchun , Weiden Peter J.
Published: December 2020

Aripiprazole lauroxil (AL) is a long-acting atypical antipsychotic approved for the treatment of schizophrenia in adults. AL has five regimen options that offer three different injection intervals using four different dosage strengths. The relationship between dosage strength (milligram injected), injection interval (time between injection visits), and expected steady-state plasma aripiprazole concentrations may not be readily apparent. This article illustrates the relationship by providing visual scenarios of steady-state plasma aripiprazole concentrations for the five AL regimens. The efficacy of AL was originally demonstrated in a pivotal study of two AL regimens (approved as 441 mg monthly and 882 mg monthly). The three additional regimens (662 mg monthly, 882 mg every 6 weeks, and 1064 mg every 2 months) were approved based on pharmacokinetic bridging studies and population pharmacokinetic models. For this paper, expected steady-state concentrations for each AL regimen were derived from the published population pharmacokinetic models and compared using median values and ranges. The five labeled AL regimens differ in dosage strength and injection interval; however, model-simulated concentrations illustrate that each regimen produces steady-state plasma aripiprazole concentrations within the upper and lower bounds associated with known efficacy for AL 441 mg and 882 mg administered monthly. This visual presentation of the relationship between dosage strength of the AL injection, the interval between successive injections, and steady-state aripiprazole plasma concentrations may demonstrate for clinicians how dosage strength and injection interval can be considered in selecting the AL regimen option that best fits the clinical circumstances of the individual patient.
Stigma and functional neurological disorder: a research agenda targeting the clinical encounter
Authors: MacDuffie Katherine E. , Grubbs Lindsey , Best Tammyjo , LaRoche Suzette , Mildon Bridget , Myers Lorna , Stafford Elizabeth , Rommelfanger Karen S.
Published: December 2020

Stigma against patients with functional neurological disorder (FND) presents obstacles to diagnosis, treatment, and research. The lack of biomarkers and the potential for symptoms to be misunderstood, invalidated, or dismissed can leave patients, families, and healthcare professionals at a loss. Stigma exacerbates suffering and unmet needs of patients and families, and can result in poor clinical management and prolonged, repetitive use of healthcare resources. Our current understanding of stigma in FND comes from surveys documenting frustration experienced by providers and distressing healthcare interactions experienced by patients. However, little is known about the origins of FND stigma, its prevalence across different healthcare contexts, its impact on patient health outcomes, and optimal methods for reduction. In this paper, we set forth a research agenda directed at better understanding the prevalence and context of stigma, clarifying its impact on patients and providers, and promoting best practices for stigma reduction.
Does body mass index predict response to intravenous ketamine treatment in adults with major depressive and bipolar disorder? Results from the Canadian Rapid Treatment Center of Excellence
Authors: Lipsitz Orly , McIntyre Roger S. , Rodrigues Nelson B. , Lee Yena , Gill Hartej , Subramaniapillai Mehala , Kratiuk Kevin , Nasri Flora , Mansur Rodrigo B. , Rosenblat Joshua D.
Published: December 2020

Background

Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).

Methods

Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith–Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).

Results

Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups.

Conclusions

The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.
Treason and Loyalty to the Royal Court: The Kan Narrative in Nineteenth- and Early-Twentieth-Century Khmer Chronicle Manuscripts
Authors: THUN THEARA
Published: December 2020

The Kan narrative presents a series of events that are believed, by many Cambodians today including top leaders, to be the historical contestation for kingship between a commoner named Kan and members of the royal family during the early sixteenth century. Discussing the contents, the formats, the epistemology, and key figures bound up in the Kan narrative, this article provides insights on its contextual origins and reception as well as the texts that recount it. Rather than a proven historical episode, the narrative was effectively re-constructed by two groups of chronicle writers during the early 1900s in order to promote ideas about ‘treason’ and ‘loyalty’ to the throne. Uncovering the contextual origins and reception of the narrative not only allows us to understand the process whereby a long-held body of local scholarship lying outside the scholarly practice of ‘history’ in the present-day sense was used to shape collective knowledge, but also to see its profound impact on colonial and post-independence collective memory and culture.
A SPHERICAL VERSION OF THE KOWALSKI–SŁODKOWSKI THEOREM AND ITS APPLICATIONS
Authors: OI SHIHO
Published: December 2020

Li et al. [‘Weak 2-local isometries on uniform algebras and Lipschitz algebras’, Publ. Mat.63 (2019), 241–264] generalized the Kowalski–Słodkowski theorem by establishing the following spherical variant: let A be a unital complex Banach algebra and let

$\Delta : A \to \mathbb {C}$
be a mapping satisfying the following properties:

(a)

$\Delta $
is 1-homogeneous (that is,

$\Delta (\lambda x)=\lambda \Delta (x)$
for all

$x \in A$
,

$\lambda \in \mathbb C$
);

(b)

$\Delta (x)-\Delta (y) \in \mathbb {T}\sigma (x-y), \quad x,y \in A$
.

Then

$\Delta $
is linear and there exists

$\lambda _{0} \in \mathbb {T}$
such that

$\lambda _{0}\Delta $
is multiplicative. In this note we prove that if (a) is relaxed to

$\Delta (0)=0$
, then

$\Delta $
is complex-linear or conjugate-linear and

$\overline {\Delta (\mathbf {1})}\Delta $
is multiplicative. We extend the Kowalski–Słodkowski theorem as a conclusion. As a corollary, we prove that every 2-local map in the set of all surjective isometries (without assuming linearity) on a certain function space is in fact a surjective isometry. This gives an affirmative answer to a problem on 2-local isometries posed by Molnár [‘On 2-local *-automorphisms and 2-local isometries of B(H)', J. Math. Anal. Appl.479(1) (2019), 569–580] and also in a private communication between Molnár and O. Hatori, 2018.
European Forum for Primary Care: Position Paper for Primary Care Mental Health
Authors: Smit Dineke , Hill Lisa , Walton Ian , Kendall Sally , de Lepeleire Jan
Published: December 2020

There is a need for a paradigm shift across mental health in primary care to improve the lives of millions of Europeans. To contribute to this paradigm shift, the European Forum for Primary Care (EFPC-MH) working group for Mental Health, produced a Position Paper for Primary Care Mental Health outlining 14 themes that needed prioritizing. These themes were developed and discussed interactively during the EFPC conferences between 2012 and 2019. The Position Paper on Mental Health gives direction to the necessary improvements over the next ten years. The themes vary from preferable healthcare model to the social determinants highlighting issues such as inequalities. The Statement of Mental Health in Primary Care will be established in cooperation with fellow organizations.
Empowering families facing end-stage nonmalignant chronic diseases with a holistic, transdisciplinary, community-based intervention: 3 months outcome of the Life Rainbow Program
Authors: Law Man-Chi , Lau Bobo Hi-Po , Kwok Anna Y. Y. , Lee Judy S. H. , Lui Rain N. Y. , Liu K. H. , Leung Pamela P. Y. , Chan Cecilia L. W.
Published: December 2020

Objectives

Families facing end-stage nonmalignant chronic diseases (NMCDs) are presented with similar symptom burdens and need for psycho-social–spiritual support as their counterparts with advanced cancers. However, NMCD patients tend to face more variable disease trajectories, and thus may require different anticipatory supports, delivered in familiar environments. The Life Rainbow Programme (LRP) provides holistic, transdisciplinary, community-based end-of-life care for patients with NMCDs and their caregivers. This paper reports on the 3-month outcomes using a single-group, pre–post comparison.

Method

Patients with end-stage NMCDs were screened for eligibility by a medical team before being referred to the LRP. Patients were assessed at baseline (T0), 1 month (T1), and 3 months (T2) using the Integrated Palliative Outcome Scale (IPOS). Their hospital use in the previous month was also measured by presentations at accident and emergency services, admissions to intensive care units, and number of hospital bed-days. Caregivers were assessed at T0 and T2 using the Chinese version of the Modified Caregiver Strain Index, and self-reported health, psychological, spiritual, and overall well-being. Over-time changes in outcomes for patients, and caregivers, were tested using paired-samplet-tests, Wilcoxon-signed rank tests, and chi-square tests.

Results

Seventy-four patients and 36 caregivers participated in this research study. Patients reported significant improvements in all IPOS domains at both 1 and 3 months [ranging from Cohen'sd= 0.495 (nausea) to 1.793 (depression and information needs fulfilled)]. Average hospital bed-days in the previous month fell from 3.50 to 1.68, comparing baseline and 1 month (p< 0.05). At 3 months, caregiver strain was significantly reduced (r= 0.332), while spiritual well-being was enhanced (r= 0.333).

Significance

After receiving 3 month's LRP services, patients with end-stage NMCDs and their caregivers experienced significant improvements in the quality of life and well-being, and their hospital bed-days were reduced.
Save Our Senior Noncitizens: Extending Old Age Assistance to Immigrants in the United States, 1935–71
Authors: Fox Cybelle
Published: December 2020

When do states grant social rights to noncitizens? I explore this question by examining the extension of Old Age Assistance (OAA) to noncitizens after the passage of the 1935 Social Security Act. While the act contained no alienage-based restrictions, states were permitted to bar noncitizens from means-tested programs. In 1939, 31 states had alienage restrictions for OAA. By 1971, when the Supreme Court declared state-level alienage restrictions unconstitutional, only eight states still did. States with more Mexicans and Asians were slower to repeal restriction, however. Using in-depth case studies of New York, California, and Texas, I demonstrate the importance of federal and state institutional arrangements and immigrant political power for the extension of social rights to noncitizens. I also show that to secure access to OAA, immigrant advocates adapted their strategies to match the institutional and political context.
Remembering John C. Loehlin: ‘Our Field Has Lost a Lion’/Twin Research Reviews: Cognitive Skills and Social Mobility, Risk of Arachnoid Hemorrhage, Heritability of Dental Traits, and Twin-to-Twin Transfusion Syndrome/Media Reports: Identical Twins With Different Health Histories, Twins Born 97 Days Apart, Retiring Twin Tennis Players,TikTokTwins and Twin Reality Stars
Authors: Segal Nancy L.
Published: December 2020

John C. Loehlin, professor of psychology at the University of Texas, at Austin, passed away on August 9, 2020. John was 94 years of age. He will be remembered for his seminal contributions that have furthered the field of twin research in so many ways. An overview of his career is presented, with fond memories from his son and several colleagues. This tribute is followed by reviews of twin research on cognitive skills and social mobility, risk of subarachnoid hemorrhage, heritability of selected dental traits and twin-to-twin transfusion syndrome. Finally, twin-related topics of human interest include identical twins with different health histories, twins born 97 days apart, retiring twin tennis players,TikToktwins and twin reality stars.
Variation and Reactivity of Organic Matter in the Surface Sediments of the Changjiang Estuary and Its Adjacent East China Sea
Authors: Chen Yan , Hu Chun , Yang Gui‐Peng , Gao Xian‐Chi , Zhou Li‐Min
Published: December 2020

The Changjiang Estuary and its adjacent sea make up a highly dynamic ecosystem where the processes influencing the sources and degradation of organic matter (OM) in sediments are still not well understood. In this study, we analyzed the total organic carbon (TOC), total nitrogen (TN), stable carbon isotope (δ13C), and total hydrolysable amino acids (THAA) to investigate the distribution and degradation of sedimentary organic matter (SOM). TOC and TN contents ranged from 0.13% to 0.93% and 0.03% to 0.15%, respectively, with elevated values occurring in the muddy areas near the estuary. The δ13C of SOM became increasingly enriched from inshore (−23.5‰) to offshore (−20.5‰), and the TOC/TN molar ratios (C/N ratios) decreased from 8.16 to 5.84, indicating increasing contributions of marine OM. As the labile fraction of bulk OM, THAA concentrations ranged from 1.36 to 11.76 μmol/g and the distribution of THAA was influenced by terrestrial inputs along with the complex hydrography. The δ13C values and C/N ratios indicated that the SOM in the study area was mainly from marine and terrestrial origins (soil derived). The relatively low degradation index (DI) of SOM (mean: −0.57 ± 0.36) indicated that the OM had already undergone extensive degradation. Consistent with previous findings, our results indicated that the degraded OM was adsorbed by fine‐grained particles and selectively transported southward along the coast. The fresh SOM in the sandy area was mainly from in situ production. Additionally, diatoms appeared to be the primary source of the fresh OM buried in the sediments of the study area.
Does Satellite Chlorophyll‐a Respond to Southernmost Patagonian Dust? A Multi‐year, Event‐Based Approach
Authors: Cosentino N. J. , Ruiz‐Etcheverry L. A. , Bia G. L. , Simonella L. E. , Coppo R. , Torre G. , Saraceno M. , Tur V. M. , Gaiero D. M.
Published: December 2020

Mineral aerosols may affect global climate indirectly by enhancing net primary productivity (NPP) upon deposition to the oceans and associated atmosphere‐to‐ocean CO2 flux. This mechanism is hypothesized to have contributed significantly to the last interglacial‐to‐glacial climatic transition. However, the dust‐NPP connection remains contentious for the present‐day climate system. We analyze the impact of southernmost Patagonian dust emissions on southwestern Atlantic Ocean continental shelf and proximal open ocean satellite chlorophyll‐a concentration. We use the first decadal time series of surface dust mass flux in southern Patagonia, along with in situ visibility data, to model dust emission, transport, and deposition to the ocean. We then perform a dust event‐based analysis of chlorophyll‐a time series, using a novel approach by which time series are corrected for post‐depositional particle advection due to ocean currents. Finally, we performed chemical analysis of iron in dust samples, a key micronutrient limiting phytoplankton biomass in high‐nutrient, low‐chlorophyll oceans such as offshore of the 200‐m isobath off Patagonia. We find no compelling evidence for an influence of dust as an enhancer of phytoplankton biomass either on shelf or proximal open ocean waters of the southwestern Atlantic Ocean. For open ocean waters this is consistent with a lack of source‐inherited bioavailable iron in dust samples. Future case studies addressing similar questions should concentrate on dust sources with identified high contents of bioavailable iron, particularly in the Southern Hemisphere where atmospheric processing of iron is weak.
Rifting of Collapsed Orogens: Successive Incision of Continental Crust in the Proximal Margin Offshore Norway
Authors: Osmundsen Per Terje , Péron‐Pinvidic Gwenn , Bunkholt Halvor
Published: December 2020

Structures related to orogenic “collapse” may provide an important template for reactivation during later rifting. In the proximal rifted margin offshore Norway, the tectono‐sedimentary template related to collapse of the Caledonian mountain belt became widely eroded but inherited metamorphic core complexes and detachment faults evolved further in Late Paleozoic and Earliest Mesozoic time and became associated with very significant crustal thinning. The earliest rifting mode was dominated by structures that mimic the Devonian post‐Caledonian template and comprised a suite of Late Paleozoic to Early Triassic metamorphic core complexes, detachment faults, and supradetachment basins. The deep structure indicates necking of brittle over remnant ductile crust, and we document how the main decoupling level utilized by the earliest rifting structures were cut by a suite of steeper, more deeply incising set of seaward‐ and landward‐dipping Triassic faults. The latter exploited deep shear zones related to the previous intracrustal necking, enabling changes in polarity over short distances. The change from a core complex mode of extension to one involving more deeply incising faults took place prior to deposition of the Late Triassic‐Early Jurassic interrift succession and pre‐dated the main phase of lithospheric‐scale necking associated with Jurassic‐Cretaceous extension. The latter phase of large‐magnitude faulting commenced with reactivation of seaward‐dipping, deeply incised faults inherited from early rifting as well as structures related to the phase of Devonian post‐orogenic transtension. The current study demonstrates that great structural complexity and significant magnitudes of extension may be present in proximal margins, in particular those developed along collapsed orogens.
Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance
Authors: Krook Melanie A. , Reeser Julie W. , Ernst Gabrielle , Barker Hannah , Wilberding Max , Li Gary , Chen Hui-Zi , Roychowdhury Sameek
Published: December 2020

Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity ofFGFRgenomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment ofFGFR3-mutated urothelial carcinoma andFGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.
Meta-analysis of the effects of 1-methylcyclopropene (1-MCP) treatment on climacteric fruit ripening
Authors: Zhang Jing , Ma Yuanchun , Dong Chao , Terry Leon A. , Watkins Christopher B. , Yu Zhifang , Cheng Zong-Ming
Published: December 2020

1-Methylcyclopropene (1-MCP) is an inhibitor of ethylene perception that is widely used to maintain the quality of several climacteric fruits during storage. A large body of literature now exists on the effects of 1-MCP on climacteric fruit ripening for different species and environmental conditions, presenting an opportunity to use meta-analysis to systematically dissect these effects. We classified 44 ripening indicators of climacteric fruits into five categories: physiology and biochemistry, quality, enzyme activity, color, and volatiles. Meta-analysis showed that 1-MCP treatment reduced 20 of the 44 indicators by a minimum of 22% and increased 6 indicators by at least 20%. These effects were associated with positive effects on delaying ripening and maintaining quality. Of the seven moderating variables, species, 1-MCP concentration, storage temperature and time had substantial impacts on the responses of fruit to 1-MCP treatment. Fruits from different species varied in their responses to 1-MCP, with the most pronounced responses observed in rosaceous fruits, especially apple, European pear fruits, and tropical fruits. The effect of gaseous 1-MCP was optimal at 1 μl/l, with a treatment time of 12–24 h, when the storage temperature was 0 °C for temperate fruits or 20 °C for tropical fruits, and when the shelf temperature was 20 °C, reflecting the majority of experimental approaches. These findings will help improve the efficacy of 1-MCP application during the storage of climacteric fruits, reduce fruit quality losses and increase commercial value.
Pathway engineering in yeast for synthesizing the complex polyketide bikaverin
Authors: Zhao Meng , Zhao Yu , Yao Mingdong , Iqbal Hala , Hu Qi , Liu Hong , Qiao Bin , Li Chun , Skovbjerg Christine A. S. , Nielsen Jens Christian , Nielsen Jens , Frandsen Rasmus J. N. , Yuan Yingjin , Boeke Jef D.
Published: December 2020

Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast.
Docking of acetyl-CoA carboxylase to the plastid envelope membrane attenuates fatty acid production in plants
Authors: Ye Yajin , Nikovics Krisztina , To Alexandra , Lepiniec Loïc , Fedosejevs Eric T. , Van Doren Steven R. , Baud Sébastien , Thelen Jay J.
Published: December 2020

In plants, light-dependent activation of de novo fatty acid synthesis (FAS) is partially mediated by acetyl-CoA carboxylase (ACCase), the first committed step for this pathway. However, it is not fully understood how plants control light-dependent FAS regulation to meet the cellular demand for acyl chains. We report here the identification of a gene family encoding for three small plastidial proteins of the envelope membrane that interact with the α-carboxyltransferase (α-CT) subunit of ACCase and participate in an original mechanism restraining FAS in the light. Light enhances the interaction between carboxyltransferase interactors (CTIs) and α-CT, which in turn attenuates carbon flux into FAS. Knockouts for CTI exhibit higher rates of FAS and marked increase in absolute triacylglycerol levels in leaves, more than 4-fold higher than in wild-type plants. Furthermore, WRINKLED1, a master transcriptional regulator of FAS, positively regulates CTI1 expression by direct binding to its promoter. This study reveals that in addition to light-dependent activation, “envelope docking” of ACCase permits fine-tuning of fatty acid supply during the plant life cycle.
Glacial heterogeneity in Southern Ocean carbon storage abated by fast South Indian deglacial carbon release
Authors: Gottschalk Julia , Michel Elisabeth , Thöle Lena M. , Studer Anja S. , Hasenfratz Adam P. , Schmid Nicole , Butzin Martin , Mazaud Alain , Martínez-García Alfredo , Szidat Sönke , Jaccard Samuel L.
Published: December 2020

Past changes in ocean 14C disequilibria have been suggested to reflect the Southern Ocean control on global exogenic carbon cycling. Yet, the volumetric extent of the glacial carbon pool and the deglacial mechanisms contributing to release remineralized carbon, particularly from regions with enhanced mixing today, remain insufficiently constrained. Here, we reconstruct the deglacial ventilation history of the South Indian upwelling hotspot near Kerguelen Island, using high-resolution 14C-dating of smaller-than-conventional foraminiferal samples and multi-proxy deep-ocean oxygen estimates. We find marked regional differences in Southern Ocean overturning with distinct South Indian fingerprints on (early de-)glacial atmospheric CO2 change. The dissipation of this heterogeneity commenced 14.6 kyr ago, signaling the onset of modern-like, strong South Indian Ocean upwelling, likely promoted by rejuvenated Atlantic overturning. Our findings highlight the South Indian Ocean’s capacity to influence atmospheric CO2 levels and amplify the impacts of inter-hemispheric climate variability on global carbon cycling within centuries and millennia.
Author Correction: The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma
Authors: McBride Matthew J. , Mashtalir Nazar , Winter Evan B. , Dao Hai T. , Filipovski Martin , D’Avino Andrew R. , Seo Hyuk-Soo , Umbreit Neil T. , St. Pierre Roodolph , Valencia Alfredo M. , Qian Kristin , Zullow Hayley J. , Jaffe Jacob D. , Dhe-Paganon Sirano , Muir Tom W. , Kadoch Cigall
Published: December 2020

A Correction to this paper has been published: https://doi.org/10.1038/s41594-020-00540-y.
Polycrystalline Ni nanotubes under compression: a molecular dynamics study
Authors: Rojas-Nunez J. , Baltazar S. E. , Gonzalez R. I. , Bringa E. M. , Allende S. , Kiwi M. , Valencia F. J.
Published: December 2020

Mechanical properties of nanomaterials, such as nanowires and nanotubes, are an important feature for the design of novel electromechanical nano-architectures. Since grain boundary structures and surface modifications can be used as a route to modify nanostructured materials, it is of interest to understand how they affect material strength and plasticity. We report large-scale atomistic simulations to determine the mechanical response of nickel nanowires and nanotubes subject to uniaxial compression. Our results suggest that the incorporation of nanocrystalline structure allows completely flexible deformation, in sharp contrast with single crystals. While crystalline structures at high compression are dominated by dislocation pinning and the multiplication of highly localized shear regions, in nanocrystalline systems the dislocation distribution is significantly more homogeneous. Therefore, for large compressions (large strains) coiling instead of bulging is the dominant deformation mode. Additionally, it is observed that nanotubes with only 70% of the nanowire mass but of the same diameter, exhibit similar mechanical behavior up to 0.3 strain. Our results are useful for the design of new flexible and light-weight metamaterials, when highly deformable struts are required.
Early prediction of neoadjuvant chemotherapy response for advanced breast cancer using PET/MRI image deep learning
Authors: Choi Joon Ho , Kim Hyun-Ah , Kim Wook , Lim Ilhan , Lee Inki , Byun Byung Hyun , Noh Woo Chul , Seong Min-Ki , Lee Seung-Sook , Kim Byung Il , Choi Chang Woon , Lim Sang Moo , Woo Sang-Keun
Published: December 2020

This study aimed to investigate the predictive efficacy of positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the pathological response of advanced breast cancer to neoadjuvant chemotherapy (NAC). The breast PET/MRI image deep learning model was introduced and compared with the conventional methods. PET/CT and MRI parameters were evaluated before and after the first NAC cycle in patients with advanced breast cancer [n = 56; all women; median age, 49 (range 26–66) years]. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained with the corresponding baseline values (SUV0, MTV0, and TLG0, respectively) and interim PET images (SUV1, MTV1, and TLG1, respectively). Mean apparent diffusion coefficients were obtained from baseline and interim diffusion MR images (ADC0 and ADC1, respectively). The differences between the baseline and interim parameters were measured (ΔSUV, ΔMTV, ΔTLG, and ΔADC). Subgroup analysis was performed for the HER2-negative and triple-negative groups. Datasets for convolutional neural network (CNN), assigned as training (80%) and test datasets (20%), were cropped from the baseline (PET0, MRI0) and interim (PET1, MRI1) images. Histopathologic responses were assessed using the Miller and Payne system, after three cycles of chemotherapy. Receiver operating characteristic curve analysis was used to assess the performance of the differentiating responders and non-responders. There were six responders (11%) and 50 non-responders (89%). The area under the curve (AUC) was the highest for ΔSUV at 0.805 (95% CI 0.677–0.899). The AUC was the highest for ΔSUV at 0.879 (95% CI 0.722–0.965) for the HER2-negative subtype. AUC improved following CNN application (SUV0:PET0 = 0.652:0.886, SUV1:PET1 = 0.687:0.980, and ADC1:MRI1 = 0.537:0.701), except for ADC0 (ADC0:MRI0 = 0.703:0.602). PET/MRI image deep learning model can predict pathological responses to NAC in patients with advanced breast cancer.
Evaluation of the relationship between glaucomatous disc subtypes and occurrence of disc hemorrhage and glaucoma progression in open angle glaucoma
Authors: Yamagami Akiko , Tomidokoro Astuo , Matsumoto Shun , Yamazaki Yoshio , Yoshikawa Keiji , Yamagami Junkichi , Tomita Goji , Araie Makoto
Published: December 2020

To compare the occurrence of disc hemorrhages (DH) and glaucoma progression in open-angle glaucoma (OAG) patients with different glaucomatous disc types. Prospective, hospital-based, observational cohort study. OAG patients examined between 2000 and 2005, whose discs were classified as typical myopic glaucomatous (MG), generalized enlargement of cup (GE), or focal glaucomatous (FG) disc type were included and followed for 5 years. The first occurrence of DH during follow-up was analyzed using Kaplan–Meier analysis and difference in DH occurrence based on glaucomatous disc type using the Cox proportional-hazards model to adjust for effects of confounding factors. For inter-group comparison of glaucoma progression, the change rate of the mean deviation, Collaborative Initial Glaucoma Treatment Study scores, and fundus photographs were used. Thirty-nine patients with MG-, 18 with FG-, and 17 with GE-disc types were included. No significant inter-group difference was seen in the rate of glaucoma progression. The five-year probability of DH occurrence was much lower with MG- than with FG- or GE-disc types (P < 0.0220). The central corneal thickness (P = 0.0024) and mean intraocular pressure and its variations (P = 0.0450, 0.0219) contributed to DH occurrence. The MG-disc type demonstrated a much lower DH occurrence during follow-up than other disc types.
Serum angiopoietin-like 3 levels are elevated in obese non diabetic men but are unaffected during an oral glucose tolerance test
Authors: Garcés Maria Fernanda , Buell-Acosta Julieth Daniela , Rodríguez-Navarro Haiver Antonio , Pulido-Sánchez Estefania , Rincon-Ramírez Juan José , Moreno-Ordóñez Diana Carolina , Franco-Vega Roberto , Roncancio-Muñoz Jhoan Sebastian , Burgos-Cardenas Alvaro Javier , Lacunza Ezequiel , Castaño Justo P. , Diéguez Carlos , Nogueiras Rubén , Sanchez Elizabeth , Caminos Jorge Eduardo
Published: December 2020

This study aimed to determine ANGPTL3 serum levels in healthy young lean and obese non-diabetic men during an oral glucose tolerance test (OGTT) and correlate them with anthropometric, biochemical and hormonal parameters. A case–control study was carried out and 30 young obese non-diabetic (23.90 ± 3.84 years and BMI 37.92 ± 4.85 kg/m2) and 28 age-matched healthy lean (24.56 ± 3.50 years and BMI of 22.10 ± 1.72 kg/m2) men were included in this study. The primary outcome measures were serum basal ANGPTL3 and ANGPTL3–area under the curve (AUC) levels. The percentage of body fat was measured by dual-energy X-ray absorptiometry and biochemical, hormonal and insulin resistance indices were determined. Basal ANGPTL3 and ANGPTL3–AUC levels were significantly elevated (p < 0.05) in young obese subjects compared with lean subjects and were positively and significantly associated with different anthropometric measurements. Fasting ANGPTL3 serum levels were positively correlated with fasting insulin, leptin, Leptin/Adiponectin index and triglyceride—glucose index. Moreover, ANGPTL3–AUC was negatively correlated with Matsuda index. In this regard, chronically high ANGPTL3 levels in young obese subjects might favor triglyceride-rich lipoprotein clearance to replenish triglyceride stores by white adipose tissue rather than oxidative tissues.
Incisional hernia after surgical correction of abdominal congenital anomalies in infants: a systematic review with meta-analysis
Authors: Eeftinck Schattenkerk Laurens D. , Musters Gijsbert D. , Nijssen David J. , de Jonge Wouter J. , de Vries Ralph , van Heurn L. W. Ernest , Derikx Joep PM.
Published: December 2020

Incisional hernia (IH) in children could result in life-threatening complications, including incarceration and bowel strangulation. The incidence and risk factors of IH in infants are scarcely reported. Since IH-correction may require extensive surgery and a long recovery program, identifying infants and birth defects at risk, may lead to a different approach during the primary surgery. Therefore, the aim of this review is to systematically review the available data on the incidence of IH following surgery for congenital anomalies in infants. All studies describing IH were considered eligible. PubMed and Embase were searched and risk of bias was assessed. Primary outcome was the incidence of IH, secondary outcomes were difference in IH occurrence between disease severity (complex vs simple) and closure method (SILO vs primary closure) in gastroschisis patients. A meta-analysis was performed to pool the reported incidences in total and per congenital anomaly separately. Subgroup analysis within gastroschisis articles was performed. The 50 included studies represent 3140 patients. The pooled proportion of IH was 0.03 (95% CI 0.02–0.05; I2 = 79%, p ≤ 0.01) all anomalies combined. Gastroschisis (GS) reported highest pooled proportion 0.10 (95% CI 0.06–0.17; n = 142/1273; I2 = 86%; p ≤ 0.01). SILO closure (OR 3.09) and simple gastroschisis, i.e. without additional anomalies, (OR 0.18) were of significant influence. This review reports the incidence of IH in infants with different congenital abdominal anomalies, of which gastroschisis reported the highest risk. In GS patients, complex GS and SILO closure are risk factors for IH development.
Quantification and epigenetic evaluation of the residual pool of hepatitis B covalently closed circular DNA in long-term nucleoside analogue-treated patients
Authors: Lebossé Fanny , Inchauspé Aurore , Locatelli Maëlle , Miaglia Clothilde , Diederichs Audrey , Fresquet Judith , Chapus Fleur , Hamed Kamal , Testoni Barbara , Zoulim Fabien
Published: December 2020

Hepatitis B virus (HBV) covalently closed circular (ccc)DNA is the key genomic form responsible for viral persistence and virological relapse after treatment withdrawal. The assessment of residual intrahepatic cccDNA levels and activity after long-term nucleos(t)ide analogues therapy still represents a technical challenge. Quantitative (q)PCR, rolling circle amplification (RCA) and droplet digital (dd)PCR assays were used to quantify residual intrahepatic cccDNA in liver biopsies from 56 chronically HBV infected patients after 3 to 5 years of telbivudine treatment. Activity of residual cccDNA was evaluated by quantifying 3.5 kB HBV RNA (preC/pgRNA) and by assessing cccDNA-associated histone tails post-transcriptional modifications (PTMs) by micro-chromatin immunoprecipitation. Long-term telbivudine treatment resulted in serum HBV DNA suppression, with most of the patients reaching undetectable levels. Despite 38 out of 56 patients had undetectable cccDNA when assessed by qPCR, RCA and ddPCR assays detected cccDNA in all-but-one negative samples. Low preC/pgRNA level in telbivudine-treated samples was associated with enrichment for cccDNA histone PTMs related to repressed transcription. No difference in cccDNA levels was found according to serum viral markers evolution. This panel of cccDNA evaluation techniques should provide an added value for the new proof-of-concept clinical trials aiming at a functional cure of chronic hepatitis B.
On the possibility of using temperature to aid in thyroid nodule investigation
Authors: Damião C. P. , Montero J. R. G. , Moran M. B. H. , da Cruz Filho R. A. , Fontes C. A. P. , Lima G. A. B. , Conci A.
Published: December 2020

Thyroid nodules are common, and their investigation is very important to exclude the possibility of cancer. The increase in blood vessels of malignant tumours may be related to local temperature augmentation detectable on the skin surface. The objective of this paper is to evaluate the feasibility of Infrared Thermography for cancer identification. For this purpose, two studies were performed. One used numerical modelling to simulate regional metabolic temperature propagation to evaluate whether a nodule is perceptible on the skin surface. A second study considered thyroid nodule identification by using convolutional neural networks (CNNs). First, variations in nodular size and fat thickness were investigated, showing that the fat layer has an important role in regional heat transfer. In the second study, the training process achieved accuracy of 96% for in-sample and 95% for validation. In the testing phase, 92% accuracy, 100% precision and 80% recall were achieved. Thus, the presented studies suggest the feasibility of using Infrared Thermography with the CNN Artificial Intelligence technique as additional information in the investigation of thyroid nodules for patients without a very thick subcutaneous fat layer.
Forecasting the long-term trend of COVID-19 epidemic using a dynamic model
Authors: Sun Jichao , Chen Xi , Zhang Ziheng , Lai Shengzhang , Zhao Bo , Liu Hualuo , Wang Shuojia , Huan Wenjing , Zhao Ruihui , Ng Man Tat Alexander , Zheng Yefeng
Published: December 2020

The current outbreak of coronavirus disease 2019 (COVID-19) has recently been declared as a pandemic and spread over 200 countries and territories. Forecasting the long-term trend of the COVID-19 epidemic can help health authorities determine the transmission characteristics of the virus and take appropriate prevention and control strategies beforehand. Previous studies that solely applied traditional epidemic models or machine learning models were subject to underfitting or overfitting problems. We propose a new model named Dynamic-Susceptible-Exposed-Infective-Quarantined (D-SEIQ), by making appropriate modifications of the Susceptible-Exposed-Infective-Recovered (SEIR) model and integrating machine learning based parameter optimization under epidemiological rational constraints. We used the model to predict the long-term reported cumulative numbers of COVID-19 cases in China from January 27, 2020. We evaluated our model on officially reported confirmed cases from three different regions in China, and the results proved the effectiveness of our model in terms of simulating and predicting the trend of the COVID-19 outbreak. In China-Excluding-Hubei area within 7 days after the first public report, our model successfully and accurately predicted the long trend up to 40 days and the exact date of the outbreak peak. The predicted cumulative number (12,506) by March 10, 2020, was only 3·8% different from the actual number (13,005). The parameters obtained by our model proved the effectiveness of prevention and intervention strategies on epidemic control in China. The prediction results for five other countries suggested the external validity of our model. The integrated approach of epidemic and machine learning models could accurately forecast the long-term trend of the COVID-19 outbreak. The model parameters also provided insights into the analysis of COVID-19 transmission and the effectiveness of interventions in China.
Production of a toxic polypeptide as a fusion inside GroEL cavity
Authors: Yurkova Maria S. , Sadykhov Elchin G. , Fedorov Alexey N.
Published: December 2020

The system is developed for efficient biosynthetic production of difficult-to-express polypeptides. A target polypeptide is produced fused into T. thermophilus GroEL chaperonin polypeptide chain in such a way that it is presented inside the GroEL cavity near the substrate binding surface. Such presentation allows alleviating potential problems of instability, toxicity or hydrophobicity of the fused peptide. Thermostability of thermophilic GroEL can be used for its one-step separation from the host cell proteins by heating. The target polypeptide may be released by any of amino acid-specific chemical treatments. In this study, GroEL was adapted for methionine-specific cleavage with cyanogen bromide by total replacement of methionine residues to facilitate further purification of the target polypeptide. The procedure is simple, robust and easy to scale-up. The capacity of this system to produce difficult-to-express polypeptides is demonstrated by production in bacterial system of one of the most potent antibacterial peptides polyphemusin I.
Effects of nickel content on the microstructure, microhardness and corrosion behavior of high-entropy AlCoCrFeNix alloys
Authors: López Ríos M. , Socorro Perdomo P. P. , Voiculescu I. , Geanta V. , Crăciun V. , Boerasu I. , Mirza Rosca J. C.
Published: December 2020

In this study the effect of three different nickel concentration on the microstructure, hardness and corrosion properties of high entropy alloys (HEAs) from AlCrFeCoNi system as an alternative material for medical instruments fabrication was investigated. The analyzed HEAs were AlCrFeCoNix obtained by vacuum arc remelting from high purity raw materials and having nickel atomic ratio x = 1.0, 1.4 and 1.8. The microscopy examination revealed the dendritic morphology for the reference alloy (AlCrFeCoNi) and that the extent of the interdendritic areas increased with the concentration of nickel while Cr was more segregated in the interdendritic areas than in dendrites. Hardness values decreased as the percentage of nickel increased due to the dissolution of the precipitates in a nickel-rich matrix and consequently the formation of continuous solid solutions. The corrosion properties of the synthesized HEAs were evaluated using a potentiodynamic polarization method. The alloys were immersed in Simulated Body Fluid during one week and the corrosion parameters were recorded. The low corrosion rates, low corrosion currents and high polarization resistance attest the good stability of these HEAs in simulated biological environment indicating their possible use for surgical and dental instruments.
Tellurium doped zinc imidazole framework (Te@ZIF-8) for quantitative determination of hydrogen peroxide from serum of pancreatic cancer patients
Authors: Fatima Batool , Hussain Dilshad , Saeed Adeela , Sajid Muhammad Salman , Majeed Saadat , Nawaz Rahat , Ashiq Muhammad Naeem , Najam-ul-Haq Muhammad , Mehmood Rubaida
Published: December 2020

The tellurium doped zinc imidazole framework (Te@ZIF-8) is prepared by a two-step hydrothermal strategy for the electrochemical sensing of hydrogen peroxide. Material is characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The electrochemical characterization of the MOF modified electrode is done by a three-electrode system. Electrochemical sensing of hydrogen peroxide is made by cyclic voltammetry, amperometry, and impedance measurements. Results demonstrate that Te@ZIF-8 shows a detection limit of 60 µM with linearity up to 0.98855. Material is stable to 1000 cycles with no significant change in electrochemical response. Amperometry depicts the recovery of hydrogen peroxide from human serum up to 101%. Impedance curve reveals the surface of Te@ZIF-8-GCE (glassy carbon electrode) as porous and rough and an interface is developed between analyte ions and the sensing material. Finally, the modified electrode is used for the quantitative determination of hydrogen peroxide from serum samples of pancreatic cancer patients, diagnosed with CA 19-9.
Three-dimensional CBCT based evaluation of the inferior part of the maxillary sinus: Retrospective Study
Authors: Lee Jeong-Hyun , Han Won-Jeong , Park Jong-Tae
Published: December 2020

The maxillary sinus is the largest of the four paranasal sinuses in humans, and its close proximity to the teeth means that caution is required during dental treatment. In particular, implant surgeries involving the maxillary posterior teeth should include evaluating the inferior part of the maxillary sinus. The purpose of this study is to evaluate the differences by comparing the inferior part of the maxillary sinus based on the nasal cavity floor (NCF) between patients (male 30, female 30) genders through the use of the three-dimensional (3-D) program that can facilitate 3-D visualizations. The present study results obtained from 3-D visualizations using cone beam computed tomography (CBCT) data showed that the inferior part of the maxillary sinus was mostly larger in males than in females. In addition, the utilization of 3-D visualization data was more likely to assure accuracy than when using data obtained by two-dimensional (2-D) imaging. Therefore, 3-D visualizations of the inferior part of the maxillary sinus will contribute to accurate analyses of its anatomical structure during implant surgery and other operations. Further studies utilizing 3-D visualization will yield useful fundamental data and guidelines for future research.