bluuebunny/crossref_metadata_2025 huggingface dataset:
Dried blood spot as an alternative sample for screening of fatty acid, amino acid, and keto acid metabolism in humans
Authors: Laštovičková Lenka , Kopčil Michal , Kanďár Roman
Published: June 2022

Dried blood spot (DBS) is a simple and noninvasive sample collection technique allowing self‐collection at home. It can be used as an alternative sample for the screening of metabolism in humans because changes in the levels of some fatty acids (FAs), amino acids (AAs), and keto acids (KAs) can be associated with metabolic disorders (e.g., diabetes mellitus). In this study, we optimized three different methods that are sensitive enough for the determination of the aforementioned analytes from a small volume of biological material in DBS. A total of 20 AAs, 5 KAs, and 24 FAs were determined. This sampling technique was applied to prepare samples from 60 individuals by a finger prick. The samples were analyzed using chromatographic methods, and acquired data were statistically evaluated. Even though most analytes were higher in men, only five AAs, three KAs, and eight FAs showed significant gender dependency (α = 0.05). Asparagine, serine, and α‐ and γ‐linolenic acids showed significant age dependency (α = 0.05). Most statistically significant correlations were positive and were found within one category. This work shows that because of many benefits, the DBS sample could be a good alternative to whole blood sample collection for the screening of metabolism in humans, in general, or in individualized medicine. The chromatographic methods can be used in future research, for example, to set the reference range or plasma‐correction factors (various aspects such as age or gender should be considered).
Proton Acid Doped Superior Capacitive Performances of Pseudocapacitance Electrodes for Energy Storage
Authors: Liu Jian , Ma Xiaohang , Zi Zhenfa
Published: June 2022

In this work, three‐dimensional (3D) nanostructures of polyaniline nano‐sheets, nano‐particles, nano‐nets and nano‐flowers were synthesized with valine, sulfuric acid, sodium acetate and L‐phenylalanine as doping acids, respectively. Conductive polyaniline with 3D nanostructure was proven as an excellent energy storage material because of its superior electrical properties and unique structure. The porous structure not only greatly improved the charge transfer efficiency and reduced the resistance, but also improved the cycle stability and energy storage of the electrode material. Polyaniline nano‐flowers doped with L‐phenylalanine (PANI‐NF) showed a maximum specific capacitance of 580 F g−1(I=0.5 A g−1), a maximum energy density of 53.9 Wh kg−1, and excellent cycle stability at high current density.
NiCoP/Mo3Se4 Nano‐Heterojunction as a Promising Bifunctional Catalyst for Full‐Water Splitting under Low Cell Voltage
Authors: Wang Minmin , Song Wenwu , Miao Xu , Zhou Li , Wang Xunyue , Tang Yanfeng
Published: June 2022

The simultaneous manipulation of the catalytic activity and intrinsic electrical conductivity in a unified system is difficult yet meaningful to unravel the possible strategy that can enhance the water splitting performance. In this work, a low cost and highly efficient NiCoP/Mo3Se4 nano‐heterogeneous bifunctional catalyst was reported for full water splitting. Further analysis revealed the abundance interfaces in NiCoP/Mo3Se4 played a great role in optimizing the electronic structure of the nanoheterogeneous to efficient charge transfer. As expected, a low voltage of 1.90 V was needed to drive full water splitting at the high current density of 400 mA cm−2.
Chiral Motifs in Highly Interpenetrated Metal–Organic Frameworks Formed from Achiral Tetrahedral Ligands**
Authors: Wen Qiang , di Gregorio Maria Chiara , Shimon Linda J. W. , Pinkas Iddo , Malik Naveen , Kossoy Anna , Alexandrov Eugeny V. , Proserpio Davide M. , Lahav Michal , van der Boom Milko E.
Published: June 2022

Formation of highly interpenetrated frameworks is demonstrated. An interesting observation is the presence of very large adamantane‐shaped cages in a single network, making these crystals new entries in the collection of diamondoid‐type metal–organic frameworks (MOFs). The frameworks were constructed by assembling tetrahedral pyridine ligands and copper dichloride. Currently, the networks’ degree of interpenetration is among the highest reported and increases when the size of the ligand is increased. Highly interpenetrated frameworks typically have low surface contact areas. In contrast, in our systems, the voids take up to 63 % of the unit cell volume. The MOFs have chiral features but are formed from achiral components. The chirality is manifested by the coordination chemistry around the metal center, the structure of the helicoidal channels, and the motifs of the individual networks. Channels of both handednesses are present within the unit cells. This phenomenon shapes the walls of the channels, which are composed of 10, 16, or 32 chains correlated with the degree of interpenetration 10‐, 16‐, and 32‐fold, respectively. By changing the distance between the center of the ligand and the coordination moieties, we succeeded in tuning the diameter of the channels. Relatively large channels were formed, having diameters up to 31.0 Å×14.8 Å.
Metal‐Mediated Directional Capping of Rod‐Packing Metal–Organic Frameworks
Authors: Hong Anh N. , Luong Diana , Alghamdi Mohammed , Liao Wei‐Cheng , Zhang Weiyi , Kusumoputro Emily , Chen Yichong , Greaney P. Alex , Cui Yongtao , Shi Jing , Bu Xianhui , Fokwa Boniface P. T. , Feng Pingyun
Published: June 2022

Two new rod‐packing metal–organic frameworks (RPMOF) are constructed by regulating the in situ formation of the capping agent. In CPM‐s7, carboxylate linkers extend 1D manganese‐oxide chains in four additional directions, forming 3D RPMOF. The substitution of Mn2+ with a stronger Lewis acidic Co2+, leads to an acceleration of the hydrolysis‐prone sulfonate linker, resulting in presence of sulfate ions to reduce two out of the four carboxylate‐extending directions, and thus forming a new 2D rod‐packing CPM‐s8. Density functional theory calculations and magnetization measurements reveal ferrimagnetic ordering of CPM‐s8, signifying the potential of exploring 2D RPMOF for effective low‐dimensional magnetic materials.
Heterolytic O−O Bond Cleavage Upon Single Electron Transfer to a Nonheme Fe(III)−OOH Complex
Authors: Bohn Antoine , Sénéchal‐David Katell , Rebilly Jean‐Noël , Herrero Christian , Leibl Winfried , Anxolabéhère‐Mallart Elodie , Banse Frédéric
Published: June 2022

The one‐electron reduction of the nonheme iron(III)‐hydroperoxo complex, [FeIII(OOH)(L52)]2+ (L52=N‐methyl‐N,N’,N’‐tris(2‐pyridylmethyl)ethane‐1,2‐diamine), carried out at −70 °C results in the release of dioxygen and in the formation of [FeII(OH)(L52)]+ following a bimolecular process. This reaction can be performed either with cobaltocene as chemical reductant, or electrochemically. These experimental observations are consistent with the disproportionation of the hydroperoxo group in the putative FeII(OOH) intermediate generated upon reduction of the FeIII(OOH) starting complex. One plausible mechanistic scenario is that this disproportionation reaction follows an O−O heterolytic cleavage pathway via a FeIV‐oxo species.
Grazing‐Incidence Texture Tomography and Diffuse Reflectivity Tomography of an Organic Semiconductor Device Array**
Authors: Smilgies Detlef‐M. , Koker Margaret K. A. , Li Ruipeng , Shaw Leo , Bao Zhenan
Published: June 2022

The use of grazing‐incidence scattering methods for the characterization of 2D patterned organic thin films is limited due to the elongated 1D footprint of the X‐ray beam on the sample. However, this characteristic feature can be turned into an advantage, when combined with tomographic reconstruction. In this pilot study we show, how the use of a chosen texture reflection and a diffuse reflectivity signal can each provide 2D images of the deposits, simultaneously revealing the organic film's crystal orientation and the location of the metal electrodes in a field‐effect transistor structure from a single sequence of diffraction images.
Clinical activity of CC‐90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies
Authors: Hollebecque Antoine , Salvagni Stefania , Plummer Ruth , Niccoli Patricia , Capdevila Jaume , Curigliano Giuseppe , Moreno Victor , de Braud Filippo , de Villambrosia Sonia Gonzalez , Martin‐Romano Patricia , Baudin Eric , Arias Marina , de Alvaro Juan , Parra‐Palau Josep L. , Sánchez‐Pérez Tania , Aronchik Ida , Filvaroff Ellen H. , Lamba Manisha , Nikolova Zariana , de Bono Johann S.
Published: June 2022

Background

CC‐90011 is an oral, potent, selective, reversible inhibitor of lysine‐specific demethylase 1 (LSD1) that was well tolerated, with encouraging activity in patients who had advanced solid tumors or relapsed/refractory marginal zone lymphoma. The authors present long‐term safety and efficacy and novel pharmacodynamic and pharmacokinetic data from the first‐in‐human study of CC‐90011.

Methods

CC‐90011‐ST‐001 (ClincalTrials.gov identifier NCT02875223; Eudract number 2015–005243‐13) is a phase 1, multicenter study in which patients received CC‐90011 once per week in 28‐day cycles. The objectives were to determine the safety, maximum tolerated dose, and/or recommended phase 2 dose (primary) and to evaluate preliminary efficacy and pharmacokinetics (secondary).

Results

Sixty‐nine patients were enrolled, including 50 in the dose‐escalation arm and 19 in the dose‐expansion arm. Thrombocytopenia was the most common treatment‐related adverse event and was successfully managed with dose modifications. Clinical activity with prolonged, durable responses were observed, particularly in patients who had neuroendocrine neoplasms. In the dose‐escalation arm, one patient with relapsed/refractory marginal zone lymphoma achieved a complete response (ongoing in cycle 58). In the dose‐expansion arm, three patients with neuroendocrine neoplasms had stable disease after nine or more cycles, including one patient who was in cycle 46 of ongoing treatment. CC‐90011 decreased levels of secreted neuroendocrine peptides chromogranin A, progastrin‐releasing peptide, and RNA expression of the blood pharmacodynamic marker monocyte‐to‐macrophage differentiation–associated.

Conclusions

The safety profile of CC‐90011 suggested that its reversible mechanism of action may provide an advantage over other irreversible LSD1 inhibitors. The favorable tolerability profile, clinical activity, durable responses, and once‐per‐week dosing support further exploration of CC‐90011 as monotherapy and in combination with other treatments for patients with advanced solid tumors and other malignancies.
Comparative Bioavailability of a Single Dose of Trametinib (TMT212) Containing 9% vs 11% Dimethyl Sulfoxide in Randomized Healthy Volunteers to Assess Long‐Term Storage at Room Temperature
Authors: Tan Eugene Y. , Chiparus Ovidiu , Choudhury Somesh , Kim Christina , Lau Mike , Ziltener Christoph , Ilankumaran Palanichamy
Published: June 2022

Storage of trametinib tablets outside of 2‐8°C protected from moisture may lead to loss of dimethyl sulfoxide (DMSO) and adversely impact trametinib bioavailability. In this open‐label, phase 1, single‐dose, randomized, 2‐treatment, 2‐period crossover study in healthy volunteers, bioavailability of a single 2‐mg tablet of trametinib containing 9% DMSO (test formulation), corresponding to the lowest DMSO content in the tablet after storage at 25°C for 36 months, was evaluated vs bioavailability of a 2‐mg tablet containing 11% DMSO (reference formulation). Sixty‐five percent of subjects (n = 39/65) were men, and mean (standard deviation) age was 45.6 (11.17) years. Time to reach maximum plasma concentration occurred at 1.5 hours after dosing. The geometric mean ratio (90%CI) comparing 2‐mg trametinib containing 9% DMSO with 2‐mg trametinib containing 11% DMSO for area under the concentration‐time curve from time 0 to the last measurable plasma concentration sampling time was 0.890 (0.848‐0.935), suggesting the 2 formulations have similar bioavailability. The majority of adverse events were mild, with 1 subject experiencing 1 grade 3 headache. These results indicated that storage of trametinib at room temperatures ≤25°C during the overall shelf life of 36 months would not negatively impact trametinib bioavailability.
Influence of non‐uniform magnetic field on relativistic q‐Gaussian laser pulses propagating in magnetized plasmas
Authors: Daraei Mohammad Esmaeil , Abedi‐Varaki Mehdi
Published: June 2022

In this work, the influence of a non‐uniform magnetic field on the self‐focusing of relativistic q‐Gaussian (QG) laser pulse propagating in magnetized plasma is studied. Utilizing the non‐linear Schrodinger equation with higher‐order paraxial approximation, the higher‐order terms of the dielectric function and the eikonal in the presence of a non‐uniform magnetic field have been obtained. Numerical results reveal that while the non‐uniform magnetized field decreases, the pulse width parameter (g) decreases, and subsequently the spot‐size of the laser declines too. As a consequence, the QG laser pulse will be more focused. Besides, it is shown that increasing the values of q‐parameter leads to a decline in self‐focusing qualities and, at lower values of q‐parameter, sharp self‐focusing of QG laser pulse is observed. Furthermore, it is found that when the QG laser pulse is propagated in the magnetized plasma, the amplitude of the pulse width decreases with decreasing the δ‐parameter, and consequently, the laser pulse becomes more compressed. Moreover, it is observed that the application of a non‐uniform magnetic field improves the self‐focusing of the QG laser pulse propagated through magnetized plasma.
Immunophenotypic characteristics of ZNF384 rearrangement compared with BCR‐ABL1, KMT2A rearrangement, and other adult B‐cell precursor acute lymphoblastic leukemia
Authors: Wang Ya‐Zhe , Qin Ya‐Zhen , Chang Yan , Yuan Xiao‐Ying , Chen Wen‐Min , He Ling‐Ling , Hao Le , Shi Wei‐Hua , Jiang Qian , Jiang Hao , Huang Xiao‐Jun , Liu Yan‐Rong
Published: June 2022

Background

ZNF384 rearrangement has been recently identified as a new subtype of B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). However, comprehensive studies clarifying immunophenotypic features and discriminating them from non‐ZNF384 in adult BCP‐ALL remain scarce to date.

Methods

Flow cytometric assessments were retrospectively performed in 43 patients with ZNF384 rearrangement, 45 with BCR‐ABL1, 29 with KMT2A rearrangement and 44 with other BCP‐ALL in the analysis cohort.

Results

CD33‐ and CD13‐positive frequencies were significantly higher in patients with ZNF384 rearrangement than in those with non‐ZNF384; however, no significant difference was observed in CD10‐ and CD123‐positive frequencies. Analysis of antigen‐positive cell proportion and median fluorescence intensity (MFI) further indicated that patients with ZNF384 rearrangement had significantly lower CD10 and higher CD33, CD13, and CD123 proportion and MFI. However, compared with KMT2A rearrangement, the CD10 expression in patients with ZNF384 rearrangement was higher, with the median percentage and MFI of 36.16 (3.63–94.79)% versus 4.53 (0.03–21.00)%, and 4.50 (0.86–32.26) versus 2.06 (0.87–4.04), respectively (p < 0.0001). Furthermore, compared with BCR‐ABL1 and other BCP‐ALL, ZNF384 rearrangement had significantly higher CD33 and CD13 proportion and MFI (p < 0.0001 and p < 0.05, respectively). In addition, higher CD123 proportion and MFI in ZNF384 rearrangement than those in the other three groups were reported for the first time (p < 0.01). A flow cytometry scoring system, including CD10%, CD33MFI, CD13%, and CD123MFI, was proposed and verified to predict ZNF384 rearrangement with high sensitivity and specificity, that is, 76.74% and 91.53% in the analysis and 87.50% and 91.30% in the validation cohort.

Conclusions

The multiparameter immunophenotypic scoring system could suggest ZNF384 rearrangement.
Limited decadal growth of mountain birch saplings has minor impact on surrounding tundra vegetation
Authors: Scharn Ruud , Negri Isabel S. , Sundqvist Maja K. , Løkken Jørn O. , Bacon Christine D. , Antonelli Alexandre , Hofgaard Annika , Nilsson R. Henrik , Björk Robert G.
Published: June 2022

Temperatures over the Arctic region are increasing at three times the rate of the global average. Consequently, Arctic vegetation is changing and trees are encroaching into the tundra. In this study, we examine the establishment and growth of mountain birch (Betula pubescens ssp. tortuosa), which forms the treeline in subarctic Europe, and its impact on community composition across the treeline ecotone nearby Abisko, Sweden. Birch advancement along elevational gradients was studied by comparing data collected in 2016 with data collected 10 and 15 years previously. Species identity, cover, and phylogenetic relatedness were used to assess the impact of birch encroachment on community composition. Our results show that birch occurrence above the treeline did not affect plant community composition, probably owing to the observed lack of significant growth due to herbivore browsing, nitrogen limitation, or a reduction in snow cover. Independent of birch performance, the tundra community structure shifted toward a novel community dissimilar from the forest plant community found below the treeline. Taken together, our findings are explained by species‐specific responses to climate change, rather than by a linear forest advance. Future treeline advancements are likely more restricted than previously expected.
Standardizing protocols for determining the cause of mortality in wildlife studies
Authors: Cristescu Bogdan , Elbroch L. Mark , Forrester Tavis D. , Allen Maximilian L. , Spitz Derek B. , Wilmers Christopher C. , Wittmer Heiko U.
Published: June 2022

Mortality site investigations of telemetered wildlife are important for cause‐specific survival analyses and understanding underlying causes of observed population dynamics. Yet, eroding ecoliteracy and a lack of quality control in data collection can lead researchers to make incorrect conclusions, which may negatively impact management decisions for wildlife populations. We reviewed a random sample of 50 peer‐reviewed studies published between 2000 and 2019 on survival and cause‐specific mortality of ungulates monitored with telemetry devices. This concise review revealed extensive variation in reporting of field procedures, with many studies omitting critical information for the cause of mortality inference. Field protocols used to investigate mortality sites and ascertain the cause of mortality are often minimally described and frequently fail to address how investigators dealt with uncertainty. We outline a step‐by‐step procedure for mortality site investigations of telemetered ungulates, including evidence that should be documented in the field. Specifically, we highlight data that can be useful to differentiate predation from scavenging and more conclusively identify the predator species that killed the ungulate. We also outline how uncertainty in identifying the cause of mortality could be acknowledged and reported. We demonstrate the importance of rigorous protocols and prompt site investigations using data from our 5‐year study on survival and cause‐specific mortality of telemetered mule deer (Odocoileus hemionus) in northern California. Over the course of our study, we visited mortality sites of neonates (n = 91) and adults (n = 23) to ascertain the cause of mortality. Rapid site visitations significantly improved the successful identification of the cause of mortality and confidence levels for neonates. We discuss the need for rigorous and standardized protocols that include measures of confidence for mortality site investigations. We invite reviewers and journal editors to encourage authors to provide supportive information associated with the identification of causes of mortality, including uncertainty.
“Jack‐of‐all‐trades” is parthenogenetic
Authors: Maraun Mark , Bischof Paul S. P. , Klemp Finn L. , Pollack Jule , Raab Linnea , Schmerbach Jan , Schaefer Ina , Scheu Stefan , Caruso Tancredi
Published: June 2022

Sex is evolutionarily more costly than parthenogenesis, evolutionary ecologists therefore wonder why sex is much more frequent than parthenogenesis in the majority of animal lineages. Intriguingly, parthenogenetic individuals and species are as common as or even more common than sexuals in some major and putative ancient animal lineages such as oribatid mites and rotifers. Here, we analyzed oribatid mites (Acari: Oribatida) as a model group because these mites are ancient (early Paleozoic), widely distributed around the globe, and include a high number of parthenogenetic species, which often co‐exist with sexual oribatid mite species. There is evidence that the reproductive mode is phylogenetically conserved in oribatid mites, which makes them an ideal model to test hypotheses on the relationship between reproductive mode and species' ecological strategies. We used oribatid mites to test the frozen niche variation hypothesis; we hypothesized that parthenogenetic oribatid mites occupy narrow specialized ecological niches. We used the geographic range of species as a proxy for specialization as specialized species typically do have narrower geographic ranges than generalistic species. After correcting for phylogenetic signal in reproductive mode and demonstrating that geographic range size has no phylogenetic signal, we found that parthenogenetic lineages have a higher probability to have broader geographic ranges than sexual species arguing against the frozen niche variation hypothesis. Rather, the results suggest that parthenogenetic oribatid mite species are more generalistic than sexual species supporting the general‐purpose genotype hypothesis. The reason why parthenogenetic oribatid mite species are generalists with wide geographic range sizes might be that they are of ancient origin reflecting that they adapted to varying environmental conditions during evolutionary history. Overall, our findings indicate that parthenogenetic oribatid mite species possess a widely adapted general‐purpose genotype and therefore might be viewed as “Jack‐of‐all‐trades.”
Harnessing the temporal and projective attributes of human agency to promote anticipatory climate change adaptation
Authors: Serrao‐Neumann Silvia , Taygfeld Pazit , Asbridge Emma F. , Mackey Brendan , Rogers Kerrylee , Low Choy Darryl
Published: June 2022

Human agency is seen as a critical component of adaptive capacity concerning environmental change. This capacity may entail social actor's ability to learn from past experience, and create opportunities in the present for dealing with uncertainty and change in the future. However, it also means that actors need to be able to overturn structural barriers that impede anticipatory adaptation to climate change such as lack of political leadership, power imbalances, acceptance of climate risks and willingness to act. While scholarship around questions of structural barriers is common in environmental studies literature, there is less understanding about how future thinking could help to strengthen human agency. Harnessing the temporal and projective attributes of human agency by which social actors can exert influence over the future and create solutions may comprise a promising way forward. This paper investigates how social actors understand past social and environmental change and explores how scenario planning may help actors apply their understanding of changes over time to devise policies for climate change adaptation. The paper applies this exploratory lens to an Australian coastal local government area engaged in scenario planning and adaptation pathways planning. Findings indicate that the temporality aspect of agency applied to solving complex issues and overcoming structural barriers manifests differently from an individual to a collective perspective. This means that while scenario planning and adaptation pathways planning helps with anticipatory identification and experimentation, this may not be sufficient to overturn structural barriers to adaptation in the short‐term.
Dynamic risk stratification using Markov chain modelling in patients with chronic heart failure
Authors: Kazmi Syed , Kambhampati Chandrasekhar , Cleland John G.F. , Cuthbert Joe , Kazmi Khurram Shehzad , Pellicori Pierpaolo , Rigby Alan S. , Clark Andrew L.
Published: June 2022

Aims

Risk changes with the progression of disease and the impact of treatment. We developed a dynamic risk stratification Markov chain model using artificial intelligence in patients with chronic heart failure (CHF).

Methods and results

We described the pattern of behaviour among 7496 consecutive patients assessed for suspected HF. The following mutually exclusive health states were defined and assessed every 4 months: death, hospitalization, outpatient visit, no event, and leaving the service altogether (defined as no event at any point following assessment). The observed figures at the first transition (4 months) weres 427 (6%), 1559 (21%), 2254 (30%), 1414 (19%), and 1842 (25%), respectively. The probabilities derived from the first two transitions (i.e. from baseline to 4 months and from 4 to 8 months) were used to construct the model. An example of the model's prediction is that at cycle 4, the cumulative probability of death was 14%; leaving the system, 37%; being hospitalized between 12 and 16 months, 10%; having an outpatient visit, 8%; and having no event, 31%. The corresponding observed figures were 14%, 41%, 10%, 15%, and 21%, respectively. The model predicted that during the first 2 years, a patient had a probability of dying of 0.19, and the observed value was 0.18.

Conclusions

A model derived from the first 8 months of follow‐up is strongly predictive of future events in a population of patients with chronic heart failure. The course of CHF is more linear than is commonly supposed, and thus more predictable.
Effective therapy of polymyositis in mice via selective inhibition of the immunoproteasome
Authors: del Rio Oliva Marta , Kirk Christopher J , Groettrup Marcus , Basler Michael
Published: June 2022

Polymyositis (PM) is a chronic autoimmune inflammatory myopathy resulting in muscle weakness. The limited approved therapies and their poor efficacy contribute to its comorbidity. We investigated the therapeutic use of ONX 0914 and KZR‐616, selective inhibitors of the immunoproteasome, in C protein‐induced myositis (CIM), a mouse model of PM that closely resembles the human disease. Diseased mice (day 13 postimmunization) were treated with 10 mg/kg ONX 0914, KZR‐616, or vehicle on alternate days until day 28. Endpoints included muscle strength assessed by a grip strength meter, serum creatine kinase activity, histology, and immunohistochemistry analysis. Treatment with ONX 0914 or KZR‐616 prevented the loss of grip strength in mice after CIM induction, while vehicle‐treated animals displayed progressive muscle weakness. Immunoproteasome inhibition lowered PM‐associated leukocyte infiltration of the muscle and prevented increased serum creatine kinase levels. LMP7‐deficient mice were resistant to CIM induction, as they showed no alterations in grip strength or creatine kinase (CK) levels or muscular alterations. In conclusion, selective inhibition of the immunoproteasome displays therapeutic efficacy in a preclinical mouse model of PM with suppression of muscle inflammation and preservation of muscle strength. Positive results from this study support the rationale for using KZR‐616 in clinical studies.
The positivity‐preserving finite volume scheme with fixed stencils for anisotropic diffusion problems on general polyhedral meshes
Authors: Yang Di , Gao Zhiming , Ni Guoxi
Published: June 2022

Two kinds of nonlinear cell‐centered positivity‐preserving finite volume schemes are proposed for the anisotropic diffusion problems on general three‐dimensional polyhedral meshes. Firstly, the one‐sided flux on the cell‐faces is discretized using the fixed stencil of all vertices, then the cell‐centered discretization scheme is obtained using the nonlinear two‐point flux approximation. On this basis, a new explicit weighted second‐order vertex interpolation algorithm for arbitrary polyhedral meshes is designed to eliminate the vertex auxiliary unknowns in the scheme. In addition, an improved Anderson acceleration algorithm is adopted for nonlinear iteration. Finally, some benchmark examples are given to verify the convergence and positivity‐preserving property of the two schemes.
The intersectionality of life course socioeconomic status, race, and cognitive decline: An 18‐year follow‐up
Authors: Zeng Yue , Lum Terry Yat Sang , Chen Yu‐Chih
Published: June 2022

Objectives

Studies have documented the impact of childhood socioeconomic status (SES) on cognition. However, research that simultaneously considers SES in varied life stages, the multidimensional mechanisms, and racial differences is relatively understudied. This study examines the intersectionality across age, SES, and race and its impact on cognitive trajectories.

Methods

Using 8376 respondents aged 65+ from the 1998–2016 Health and Retirement Study, we used latent growth curve modeling to examine the effects of four life course models (latency, pathway, accumulation, and mobility) on 18‐year trajectories of mental status and episodic memory. We further tested for differences in the links between SES and cognitive trajectories between black and white respondents.

Results

Cognitive function declines with age and is interrelated with SES and race. Adulthood has a stronger effect on cognitive performance than childhood. However, linked positive childhood and adulthood SES contributes to positive cognition. Accumulated SES disadvantages were associated with lower cognition. Older adults with downward mobility and low SES throughout their lifespans had the lowest cognition scores. Life course models operated differently on trajectories of cognitive decline, yet the effects were particularly evident among older black respondents. Overall, those with socioeconomic advantages tended to have a slower decline in cognition, while a faster decline occurred for those with accrued disadvantages.

Conclusions

Cognitive performance is a complex, longitudinal process intertwined with socioeconomic conditions and population heterogeneity shaped by life course contexts. Policies that facilitate healthy cognitive performance and address SES inequality could equalize health opportunities and address racial cognitive disparities later in life.
Prediction of childhood maltreatment and subtypes with personalized functional connectome of large‐scale brain networks
Authors: Zhang Jiang , Zhao Tianyu , Zhang Jingyue , Zhang Zhiwei , Li Hongming , Cheng Bochao , Pang Yajing , Wu Huawang , Wang Jiaojian
Published: June 2022

Childhood maltreatment (CM) has a long impact on physical and mental health of children. However, the neural underpinnings of CM are still unclear. In this study, we aimed to establish the associations between functional connectome of large‐scale brain networks and influences of CM evaluated through Childhood Trauma Questionnaire (CTQ) at the individual level based on resting‐state functional magnetic resonance imaging data of 215 adults. A novel individual functional mapping approach was employed to identify subject‐specific functional networks and functional network connectivities (FNCs). A connectome‐based predictive modeling (CPM) was used to estimate CM total and subscale scores using individual FNCs. The CPM established with FNCs can well predict CM total scores and subscale scores including emotion abuse, emotion neglect, physical abuse, physical neglect, and sexual abuse. These FNCs primarily involve default mode network, fronto‐parietal network, visual network, limbic network, motor network, dorsal and ventral attention networks, and different networks have distinct contributions to predicting CM and subtypes. Moreover, we found that CM showed age and sex effects on individual functional connections. Taken together, the present findings revealed that different types of CM are associated with different atypical neural networks which provide new clues to understand the neurobiological consequences of childhood adversity.
Long‐term outcomes of high dose carbon‐ion radiation therapy for unresectable upper cervical (C1‐2) chordoma
Authors: Aoki Shuri , Koto Masashi , Ikawa Hiroaki , Imai Reiko , Tokuhiko Omatsu , Shinoto Makoto , Takiyama Hirotoshi , Yamada Shigeru , Tsuji Hiroshi
Published: June 2022

Background

Chordoma is a rare, locally invasive neoplasm of the axial skeleton. Complete resection is often difficult, especially for the upper‐cervical (C1‐2) spine. We evaluated the efficacy and safety of carbon‐ion radiotherapy (CIRT) for unresectable C1‐2 chordoma.

Methods

Patients with C1‐2 chordoma treated with definitive CIRT (60.8 Gy [RBE] in 16 fractions) were retrospectively analyzed. We evaluated OS, LC, PFS, and toxicity.

Results

Nineteen eligible patients all completed the planned course of CIRT. With the median follow‐up 68 months (range: 29–144), median OS was 126 months (range: 36‐NA). Five‐year OS, LC, and PFS were 68.4% (95% CI, 42.8%–84.4%), 75.2% (46.1%–90.0%), and 64.1% (36.3%–82.3%), respectively. Regarding acute toxicity of grade ≥3, there was only one grade 3 mucositis. Late toxicity included radiation‐induced myelitis (grade 3 in 1 patient; 5.3%), and compression fractures (n = 5; 26.3%).

Conclusions

High‐dose CIRT is a promising treatment option for unresectable upper cervical chordoma.
Permutationally invariant polynomial representation of polarizability tensor surfaces for linear regression analysis
Authors: Omodemi Oluwaseun , Kaledin Martina , Kaledin Alexey L.
Published: June 2022

A linearly parameterized functional form for a Cartesian representation of molecular dipole polarizability tensor surfaces (PTS) is described. The proposed expression for the PTS is a linearization of the recently reported power series ansatz of the original Applequist model, which by construction is non‐linear in parameter space. This new approach possesses (i) a unique solution to the least‐squares fitting problem; (ii) a low level of the computational complexity of the resulting linear regression procedure, comparable to those of the potential energy and dipole moment surfaces; and (iii) a competitive level of accuracy compared to the non‐linear PTS model. Calculations of CH4 PTS, with polarizabilities fitted to 9000 training set points with the energies up to 14,000 cm−1 show an impressive level of accuracy of the linear PTS model obtained with ~1600 parameters: ~1% versus 0.3% RMSE for the non‐linear vs. linear model on a test set of 1000 configurations.
The role of anxiety and gender in anticipation and avoidance of naturalistic anxiety‐provoking experiences during adolescence: An ecological momentary assessment study
Authors: Smith Ashley R. , Jones Emily L. , Subar Anni R. , Do Quyen B. , Kircanski Katharina , Leibenluft Ellen , Brotman Melissa A. , Pine Daniel S. , Silk Jennifer S.
Published: June 2022

Objective

Anxiety symptoms often increase in late childhood/early adolescence, particularly among girls. However, few studies examine anxiety‐relevant gender differences during anticipation and avoidance of naturalistic experiences during adolescence. The current study uses ecological momentary assessment (EMA) to examine associations among clinical anxiety, gender, anticipation, and attempted avoidance of person‐specific anxiety‐provoking experiences in youth ages 8–18.

Method

124 youth (73 girls) completed 7 consecutive days of EMA. Seventy participants (42 girls) met criteria for one or more anxiety disorders, while the remaining 54 were healthy controls (31 girls). Participants reported the experience that they were “most worried about happening that day” and completed ratings about that event including whether they attempted to avoid that experience. Multilevel models examined whether diagnostic group (anxious, healthy), gender (boys, girls), or their interaction predicted anticipatory ratings or avoidance of these experiences.

Results

Analyses revealed significant diagnostic group by gender interactions for anticipatory ratings. Specifically, anxious girls reported greater worry and predicted more negative outcomes related to future experiences. However, only a main effect of diagnostic group emerged for attempted avoidance. Finally, anticipatory worry predicted higher rates of attempted avoidance, but this association did not vary by diagnostic group, gender, or their interaction.

Conclusion

These findings extend the literature on the interplay of anticipation and avoidance to person‐specific naturalistic experiences in pediatric anxiety. They reveal that anxious girls report more anticipatory anxiety and worry, while avoidance of real‐world anxiety‐provoking scenarios is a key concern for anxious youth independent of gender. By using EMA to examine person‐specific anxiety‐inducing experiences we can begin to understand how these processes and experiences unfold in the real world.
A qualitative assessment of dental hygiene educators’ COVID‐19 related burnout
Authors: Arnett Michelle C. , Ramaswamy Vidya , Snay Sarah , Evans Elizabeth , Rulli Danielle
Published: June 2022

Purpose

The purpose of this study was to elicit ideas or concerns influencing dental hygiene educators’ experiences of personal and professional burnout, burnout working with students, and teaching efficacy in an online/hybrid environment as a result of the COVID‐19 pandemic.

Methods

A qualitative, content‐analysis study included a convenience sample of dental hygiene educators emails. An invitation to participate in an August 2021 or October 2021 focus group was sent via Qualtricsxm with informed consent, and focus groups were held over Zoom. Conversations were audio recorded, transcribed, and de‐identified. Consensus on a codebook by two coders achieved an 88% agreement.

Results

Fifty‐three were invited to the August 2021 focus groups for a 26% (n = 14) response rate, and 116 were invited to the October 2021 focus groups for an 11% (n = 13) response rate. Contributing factors to experiences of burnout expressed were: (1) work–life balance (n = 59), including (a) overwork, (b) pressure to be available, and (c) lack of boundaries; (2) change (n = 34) involving (a) developing new protocols, (b) constant uncertainty, (c) COVID‐19 requirements, and (d) new platforms; and (3) negative interactions (n = 32) with (a) students and (b) faculty.

Conclusion

A lack of work–life balance from overwork, pressure to be available at all times, no boundaries with students, and an absence of a sense of connection for workplace vitality were contributors to burnout. Work‐from‐home flexibility, a work environment that supported wellness and mental well‐being, and the ability to leave the workplace for periods of time were reported as helpful solutions to combatting burnout.
A prospective study of sequential hepatic vein embolization after portal vein embolization in patients scheduled for right‐sided major hepatectomy: Results of feasibility and surgical strategy using functional liver assessment
Authors: Araki Kenichiro , Shibuya Kei , Harimoto Norifumi , Watanabe Akira , Tsukagoshi Mariko , Ishii Norihiro , Ikota Hayato , Yokobori Takehiko , Tsushima Yoshito , Shirabe Ken
Published: June 2022

Background

Hepatic vein embolization (HVE) added to portal vein embolization (PVE) can further increase future remnant liver volume (FRLV) compared with PVE alone. This study was aimed to evaluate feasibility of sequential HVE in a prospective trial and to verify surgical strategy using functional FRLV (fFRLV).

Methods

Hepatic vein embolization was prospectively indicated for post‐PVE patients scheduled for right‐sided major hepatectomy if the resection limit of fFRLV using EOB‐magnetic resonance imaging was not satisfied. The resection limit was fFRLV: 615 mL/m2 for predicting post‐hepatectomy liver failure. Patients who underwent sequential PVE‐HVE (n = 12) were compared with those who underwent PVE alone (n = 31).

Results

All patients underwent HVE with no severe complications. Median fFRLV increased from 396 (range: 251‐581) to 634 (range: 422‐740) mL/m2 by sequential PVE‐HVE. From PVE to HVE, both of FRLV (P < .001) and fFRLV (P = .005) significantly increased. The increased width of fFRLV was larger than that of FRLV after performing HVE. Median growth rate was 71.3 (range: 33.3‐80.3) %, which was higher than that of PVE alone (27.0%, range: 6.0‐78.0). All‐cohort resection rate was 88.3%. Strategy of using fFRLV for the resection limit and performing HVE in patients with insufficient functional volume resulted in no liver failure in all patients who underwent hepatectomy.

Conclusions

Sequential HVE after PVE is feasible and safe, and HVE induced possibility of further liver growth and its functional improvement. Our surgical strategy using fFRLV may be justified.
Mycobacterium fortuitum fabG4knockdown studies: Implication as pellicle and biofilm specific drug target
Authors: Sharma Ayushi , Vashistt Jitendraa , Shrivastava Rahul
Published: June 2022

The fatty acid biosynthesis pathway is crucial for the formation of the mycobacterial cell envelope. The fatty acid synthase type‐II (FAS‐II) components are attractive targets for designing anti‐biofilm inhibitors. Literature review, bioinformatics analysis, cloning, and sequencing led to the identification of a novelMycobacterium fortuitumFAS‐II gene MFfabG4which interacts with mycobacterial proteins involved in biofilm formation. A manually curatedM. fortuitumfatty acid biosynthesis pathway has been proposed exploiting functional studies from the Kyoto Encyclopedia of Genes and Genomes and Mycobrowser databases for MFFabG4.M. fortuitumMFfabG4knockdown strain (FA) was constructed and validated by quantitative polymerase chain reaction. The FA strain displayed unstructured smooth colony architecture, correlating with decreased pathogenicity and virulence. MFfabG4knockdown resulted in diminished pellicle and attenuated biofilm formation, along with impaired sliding motility, and reduced cell sedimentation. The FA strain showed lowered cell surface hydrophobicity, indicating attenuation inM. fortuitumintracellular infection‐causing ability. Stress survival studies showed the requirement of MFfabG4for survival in a nutrient‐starved environment. The results indicate that MFfabG4maintains the physiology of the cell envelope and is required for the formation ofM. fortuitumpellicle and biofilm. The study corroborates the role of MFfabG4as a pellicle‐ and biofilm‐specific drug target and a potential diagnostic marker forM. fortuitumand related pathogenic mycobacteria.
How can the positive Indian Ocean Dipole events co‐occur with La Niña?
Authors: Song Ge , Ren Rongcai
Published: June 2022

Positive/negative Indian Ocean Dipole (IOD) tends to co‐occur with El Niño/La Niña. Five positive IODs, however, are observed under La Niña condition in 1961, 1966, 1967, 2007, and 2011. This study uses the monthly ocean temperature and atmospheric reanalysis datasets from ECMWF to investigate how these positive IOD events occurred. It is found that the five positive IODs are consistently accompanied by a moderately strong positive subsurface IOD (Sub‐IOD) event that initiated earlier. The Sub‐IOD‐related oceanic dynamical processes including oceanic Kelvin and Rossby waves help to promote the development of the positive IODs. More specifically, the equatorial easterly anomalies in the Tropical Indian Ocean (TIO) that are crucial for the development of the positive Sub‐IODs and IODs in 1961/2011 are triggered by an anticyclonic curl over South Indian Ocean that is induced by a Southern Hemispheric Indian Ocean Subtropical Dipole mode. The crucial equatorial easterly anomalies in 1967 are triggered by a thermocline warming in the southwestern TIO induced by westward downwelling oceanic Rossby waves, while in 1966/2007, the equatorial easterly anomalies are connected with the anomalous Walker circulation resulting from the certain sea surface temperature anomaly pattern over the equatorial Pacific. On the other hand, the remote effects of La Niña on TIO are relatively weaker, being overwhelmed by the above triggering processes.
Raised bog biodiversity loss: A case‐study of ground beetles (Coleoptera, Carabidae) as indicators of ecosystem degradation after peat mining
Authors: Kędzior Renata , Zarzycki Jan , Zając Ewelina
Published: June 2022

Peatlands are unique ecosystems inhabited by highly specialized biota. Due to extraction and drainage, these valuable ecosystems decline or represent only fragmented habitat patches. The aim of this study was to compare the carabid species composition, diversity, and life history traits between bog habitat types: 20 and 40 year post‐extraction sites and undisturbed one. We tried to determine whether populations of rare carabid bog specialists would persist in the post‐extraction habitats. The study was conducted in the raised bog, where 30 sampling transects with a total of 90 pitfall traps were established. 1616 individuals belonging to 30 carabid species were collected. The results revealed the significance differences in carabid species composition between studied habitat types and increasing the abundance and species richness in post‐extraction sites. According to spontaneous succession in post‐mining sites, the shift in life history traits of carabids towards forest assemblages was observed. We observed decline of the most valuable bog species in post‐mining sites. Agonum ericeti, Pterostichus rhaeticus and Bembidion humerale were present on the reference bog, with large covers of Sphagnum and shrubs, but sporadically at the 20 year post‐extraction site (except for A. ericeti), or not at all at the 40 year post‐extraction site overgrown by trees. Therefore measures should be undertaken in post‐extraction areas to enable the restoration of such specific conditions and a properly functioning raised bog ecosystem. This mainly requires restoration of a suitable hydrological regime, which is the key factor for the preservation of groups of bog specialist plants and animals.
Should the firm or the employee pay for upskilling? A contract theory approach
Authors: Vranceanu Radu , Sutan Angela
Published: June 2022

Upskilling involves costly effort on behalf of existing employees to acquire new skills that are required to execute high value‐added projects. A firm‐financed training scheme allows the screening of applicants but comes with the cost of hidden actions, as some employees might train themselves yet continue working on low‐value projects. A policy relying on worker self‐training and incentive compatible contracts allows attracting more workers to high‐value projects, yet it must grant a positive informational rent to flexible workers. The analysis reveals the optimal contract specific to each of the two training schemes. The profit comparison shows that the training strategy depends on how large is the net value created by upskilling, which is a characteristic of the business or industry.