bluuebunny/crossref_metadata_2025 huggingface dataset:
Hexafluoroisopropyl Carbamates as Selective MAGL and Dual MAGL/FAAH Inhibitors: Biochemical and Physicochemical Properties
Authors: Barth Maximilian , Rudolph Stefan , Kampschulze Jan , Meyer zu Vilsendorf Imke , Hanekamp Walburga , Mulac Dennis , Langer Klaus , Lehr Matthias
Published: January 2022

A series of hexafluoroisopropyl carbamates with indolylalkyl‐ and azaindolylalkyl‐substituents at the carbamate nitrogen was synthesized and evaluated for inhibition of the endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The synthesized derivatives with butyl to heptyl spacers between the heteroaryl and the carbamate moiety were inhibitors of both enzymes. For investigated compounds in which the alkyl chain was partially incorporated into a piperidine ring, different results were obtained. Compounds with a methylene spacer between the piperidine ring and the heteroaromatic system were found to be selective MAGL inhibitors, while an extension of the alkyl spacer to two to four atoms resulted in dual inhibition of FAAH/MAGL. The only small change in enzyme inhibitory activity with variation of the heteroaromatic system indicates that the reactive hexafluoroisopropyl carbamate group is mainly responsible for the strength of the inhibitory effect of the compounds. Selected derivatives were also tested for hydrolytic stability in aqueous solution, liver homogenate and blood plasma as well as for aqueous solubility and for permeability in a Caco‐2 cell model. Some compounds showed a slightly higher MAGL inhibitory effect than the known selective MAGL inhibitor ABX‐1431 and also partly surpassed this substance with regard to certain physicochemical and biochemical properties such as water solubility and cell permeability.
Metal vs. Metal‐Free Catalysts for Oxidation of 5‐Hydroxymethylfurfural and Levoglucosenone to Biosourced Chemicals
Authors: Ayoub Nadim , Toufaily Joumana , Guénin Erwann , Enderlin Gérald
Published: January 2022

Lignocellulosic feedstocks, such as forestry biomass and agricultural crop residues, can be utilized to generate biofuels and biochemicals. Converting these organic waste materials into biochemicals is widely regarded as a remedial approach to develop a sustainable, clean, and green energy source. Nevertheless, are these methods sustainable and clean? Prior studies have shown that most such conversions use metals – including heavy metals or noble metals – as catalysts. In addition to the fact that many metals (e. g., aluminum, cobalt, titanium, platinum) have been listed as critical minerals, these methods suffer from high cost, deactivation, and leakage problems and the release of toxic wastes. This Review summarizes catalytic methods using metal and metal‐free catalysts for the oxidation of the platform molecules 5‐hydroxymethylfurfural and levoglucosenone and demonstrates the potential and effectiveness of metal‐free catalysts.
DROSHA but not DICER is required for human haematopoietic stem cell function
Authors: Gu Karen , Walpole Carina , Gooneratne Shayarana , Liu Xin , Haigh Oscar L , Radford Kristen J , Chong Mark MW
Published: January 2022

Objectives

DROSHA and DICER have central roles in the biogenesis of microRNAs (miRNAs). However, we previously showed that in the murine system, DROSHA has an alternate function where it directly recognises and cleaves protein‐coding messenger (m)RNAs and this is critical for safeguarding the pluripotency of haematopoietic stem cells (HSCs). Maintenance of murine HSC function is dependent on DROSHA‐mediated cleavage of two mRNAs, Myl9 and Todr1. The goal of this study is to determine whether this pathway is conserved in human HSCs.

Methods

DROSHA and DICER were knocked down in human cord blood CD34+ HSCs with short hairpin RNAs. The function of HSCs was analysed in vitro and in humanised mice. Analysis of mRNA cleavage was performed by capture of 5′ phosphorylated RNAs.

Results

Consistent with murine HSCs, DROSHA knockdown impaired the differentiation of human HSCs in vitro and engraftment into humanised mice, whereas DICER knockdown had no impact. DROSHA cleaves the MYL9 mRNA in human HSCs and DROSHA deficiency resulted in the accumulation of the mRNA. However, ectopic expression of MYL9 did not impair human HSC function. We were unable to identify a human homolog of Todr1.

Conclusion

A miRNA‐independent function of DROSHA is critical for the function of human HSCs. DROSHA directly recognises and degrades mRNAs in humans HSCs. However, unlike in murine HSCs, the degradation of the MYL9 mRNA alone is not critical for human HSC function. Therefore, DROSHA must be inhibiting other targets and/or has another miRNA‐independent function that is essential for safeguarding the pluripotency of human HSCs.
Interventional‐ and amputation‐stage muscle proteomes in the chronically threatened ischemic limb
Authors: Ryan Terence E. , Kim Kyoungrae , Scali Salvatore T. , Berceli Scott A. , Thome Trace , Salyers Zachary R. , O'Malley Kerri A. , Green Thomas D. , Karnekar Reema , Fisher‐Wellman Kelsey H. , Yamaguchi Dean J. , McClung Joseph M.
Published: January 2022

Background

Despite improved surgical approaches for chronic limb‐threatening ischemia (CLTI), amputation rates remain high and contributing tissue‐level factors remain unknown. The purpose of this study was twofold: (1) to identify differences between the healthy adult and CLTI limb muscle proteome, and (2) to identify differences in the limb muscle proteome of CLTI patients prior to surgical intervention or at the time of amputation.

Methods and results

Gastrocnemius muscle was collected from non‐ischemic controls (n = 19) and either pre‐interventional surgery (n = 10) or at amputation outcome (n = 29) CLTI patients. All samples were subjected to isobaric tandem‐mass‐tag‐assisted proteomics. The mitochondrion was the primary classification of downregulated proteins (> 70%) in CLTI limb muscles and paralleled robust functional mitochondrial impairment. Upregulated proteins (> 38%) were largely from the extracellular matrix. Across the two independent sites, 39 proteins were downregulated and 12 upregulated uniformly. Pre‐interventional CLTI muscles revealed a robust upregulation of mitochondrial proteins but modest functional impairments in fatty acid oxidation as compared with controls. Comparison of pre‐intervention and amputation CLTI limb muscles revealed mitochondrial proteome and functional deficits similar to that between amputation and non‐ischemic controls. Interestingly, these observed changes occurred despite 62% of the amputation CLTI patients having undergone a prior surgical intervention.

Conclusions

The CLTI proteome supports failing mitochondria as a phenotype that is unique to amputation outcomes. The signature of pre‐intervention CLTI muscle reveals stable mitochondrial protein abundance that is insufficient to uniformly prevent functional impairments. Taken together, these findings support the need for future longitudinal investigations aimed to determine whether mitochondrial failure is causally involved in amputation outcomes from CLTI.
Simulating climate changein situin a tropical rainforest understorey using active air warming and CO2addition
Authors: Bader Maaike Y. , Moureau Elodie , Nikolić Nada , Madena Thomas , Koehn Nils , Zotz Gerhard
Published: January 2022

Future climate‐change effects on plant growth are most effectively studied using microclimate‐manipulation experiments, the design of which has seen much advance in recent years. For tropical forests, however, such experiments are particularly hard to install and have hence not been widely used. We present a system of active heating and CO2fertilization for use in tropical forest understoreys, where passive heating is not possible. The system was run for 2 years to study climate‐change effects on epiphytic bryophytes, but is also deemed suitable to study other understorey plants. Warm air and CO2addition were applied in 1.6‐m‐tall, 1.2‐m‐diameter hexagonal open‐top chambers and the microclimate in the chambers compared to outside air. Warming was regulated with a feedback system while CO2addition was fixed. The setup successfully heated the air by 2.8 K and increased CO2by 250 ppm on average, with +3 K and +300 ppm as the targets. Variation was high, especially due to technical breakdowns, but not biased to times of the day or year. In the warming treatment, absolute humidity slightly increased but relative humidity dropped by between 6% and 15% (and the vapor pressure deficit increased) compared to ambient, depending on the level of warming achieved in each chamber. Compared to other heating systems, the chambers provide a realistic warming and CO2treatment, but moistening the incoming air would be needed to avoid drying as a confounding factor. The method is preferable over infrared heating in the radiation‐poor forest understorey, particularly when combined with CO2fertilization. It is suitable for plant‐level studies, but ecosystem‐level studies in forests may require chamber‐less approaches like infrared heating and free‐air CO2enrichment. By presenting the advantages and limitations of our approach, we aim to facilitate further climate‐change experiments in tropical forests, which are urgently needed to understand the processes determining future element fluxes and biodiversity changes in these ecosystems.
Metabarcoding reveals massive species diversity of Diptera in a subtropical ecosystem
Authors: Huang Junhao , Miao Xiaoqian , Wang Qingyun , Menzel Frank , Tang Pu , Yang Ding , Wu Hong , Vogler Alfried P.
Published: January 2022

Diptera is often considered to be the richest insect group due to its great species diversity and broad ecological versatility. However, data on dipteran diversity from subtropical ecosystems have hitherto been scarce, due to the lack of studies conducted at an appropriate large scale. We investigated the diversity and composition of Diptera communities on Tianmu Mountain, Zhejiang, China, using DNA metabarcoding technology, and evaluated their dynamic responses to the effects of slope aspect, season, and altitudinal zone. A total of 5,092 operational taxonomic units (OTUs) were discovered and tentatively assigned to 72 dipteran families, including 2 family records new for China and 30 family records new for the locality. Cecidomyiidae, Sciaridae, and Phoridae were the predominant families, representing 53.6% of total OTUs, while 52 families include >95% unidentified and presumed undescribed species. We found that the community structure of Diptera was significantly affected by aspect, seasonality (month) and elevation, with richer diversity harbored in north‐facing than south‐facing slopes, and seasonality a more profound driver of community structure and diversity than elevation. Overall, massive species diversity of Diptera communities was discovered in this subtropical ecosystem of east China. The huge diversity of potentially undescribed species only revealed by metabarcoding now requires more detailed taxonomic study, as a step toward an evolutionary integration that accumulates information on species’ geographic ranges, ecological traits, functional roles, and species interactions, and thus places the local communities in the context of the growing knowledge base of global biodiversity and its response to environmental change.
Interannual climate variability has predominant effects on seedling survival in a temperate forest
Authors: Xu Zhichao , Johnson Daniel J. , Zhu Kai , Lin Fei , Ye Ji , Yuan Zuoqiang , Mao Zikun , Fang Shuai , Hao Zhanqing , Wang Xugao
Published: January 2022

Mechanisms such as conspecific negative density dependence (CNDD) and niche partitioning have been proposed to explain species coexistence and community diversity. However, as a potentially important axis of niche partitioning, the role of interannual climate variability in driving local community dynamics remains largely unknown. Here we used a 15‐year monitoring data set of more than 53,000 seedlings in a temperate forest to examine (1) what are the relative effects of interannual climate variability, biotic interactions, and habitat conditions on seedling survival; (2) how the effects of biotic interactions change with interannual climate variability, and habitat conditions; and (3) whether the impacts of interannual climate variability, biotic interactions, and habitat conditions differ with plant traits. Interannual climate variability accounted for the most variation in seedling survival at the community level, followed by biotic interactions, and habitat conditions. Increased snowpack and decreased minimum temperature during the non‐growing season had positive effects on seedling survival. Effects of conspecific neighbor density were weakened in higher snowpack, effective accumulated temperature, elevation, and soil‐resource gradient, but were intensified with increased ultraviolet radiation, maximum precipitation, minimum temperature, and soil moisture. In addition, the relative importance of interannual climate variability versus biotic interactions differed depending on species‐trait groups. Specifically, biotic interactions for gravity‐dispersed species had a larger effect size in affecting seedling survival than other trait groups. Also, gravity‐dispersed species experienced a stronger CNDD than wind‐dispersed, probably because wind‐dispersed seedlings rarely had adult conspecifics nearby. We found that interannual climate variability was most strongly associated with seedling survival, but the magnitude of climatic effects varied among species‐trait groups. Interannual climate variability may act as an inhibitor or accelerator to density‐dependent interactions and should be accounted for in future studies, as both a potential direct and indirect factor in understanding the diversity of forest communities.
Plant community data from a statewide survey of paired serpentine and non‐serpentine soils in California, USA
Authors: Miller Jesse E. D. , Copeland Stella , Davies Kendi , Anacker Brian , Safford Hugh , Harrison Susan
Published: January 2022

Soils derived from ultramafic parent materials (hereafter serpentine) provide habitat for unique plant communities containing species with adaptations to the low nutrient levels, high magnesium : calcium ratios, and high metal content (Ni, Zn) that characterize serpentine. Plants on serpentine have long been studied in evolution and ecology, and plants adapted to serpentine contribute disproportionately to plant diversity in many parts of the world. In 2000–2003, serpentine plant communities were sampled at 107 locations representing the full range of occurrence of serpentine in California, USA, spanning large gradients in climate. In 2009–2010, plant communities were similarly sampled at 97 locations on nonserpentine soil, near to and paired with 97 of the serpentine sampling locations. (Some serpentine locations were revisited in 2009–2010 to assess the degree of change since 2000–2003, which was minimal.) At each serpentine or nonserpentine location, a north‐ and a south‐facing 50 × 10 m plot were sampled. This design produced 97 “sites” each consisting of four “plots” (north‐south exposure, serpentine‐nonserpentine soil). All plots were initially visited three or more times over two years to record plant diversity and cover, and a subset were revisited in 2014 to examine community change after a drought. The original question guiding the study was how plant diversity is shaped by the spatially patchy nature of the serpentine habitat. Subsequently, we investigated how climate drives plant diversity at multiple scales (within locations, between locations on the same and different soil types, and across entire regions) and at different levels of organization (taxonomic, functional, and phylogenetic). There are no copyright restrictions and users should cite this data paper in publications that result from use of the data.
Species‐specific plant‐mediated effects between herbivores converge at high damage intensity
Authors: Wan Jinlong , Yi Jiahui , Tao Zhibin , Ren Zhikun , Otieno Evans O. , Tian Baoliang , Ding Jianqing , Siemann Evan , Erb Matthias , Huang Wei
Published: January 2022

Plants are often exposed to multiple herbivores and densities of these attackers (or corresponding damage intensities) often fluctuate greatly in the field. Plant‐mediated interactions vary among herbivore species and with changing feeding intensity, but little is known about how herbivore identity and density interact to determine plant responses and herbivore fitness. Here, we investigated this question using Triadica sebifera (tallow) and two common and abundant specialist insect herbivores, Bikasha collaris (flea beetle) and Heterapoderopsis bicallosicollis (weevil). By manipulating densities of leaf‐feeding adults of these two herbivore species, we tested how variations in the intensity of leaf damage caused by flea beetle or weevil adults affected the performance of root‐feeding flea beetle larvae and evaluated the potential of induced tallow root traits to predict flea beetle larval performance. We found that weevil adults consistently decreased the survival of flea beetle larvae with increasing leaf damage intensities. In contrast, conspecific flea beetle adults increased their larval survival at low damage then decreased larval survival at high damage, resulting in a unimodal pattern. Chemical analyses showed that increasing leaf damage from weevil adults linearly decreased root carbohydrates and increased root tannin, whereas flea beetle adults had opposite effects as weevil adults at low damage and similar effects as them at high damage. Furthermore, across all feeding treatments, flea beetle larval survival correlated positively with concentrations of carbohydrates and negatively with concentration of tannin, suggesting that root primary and secondary metabolism might underlie the observed effects on flea beetle larvae. Our study demonstrates that herbivore identity and density interact to determine systemic plant responses and plant‐mediated effects on herbivores. In particular, effects are species‐specific at low densities, but converge at high densities. These findings emphasize the importance of considering herbivore identity and density simultaneously when investigating factors driving plant‐mediated interactions between herbivores, which advances our understanding of the structure and composition of herbivore communities and terrestrial food webs.
Electrochemical Investigation of Ruxolitinib: Sensitive Voltammetric Assay in Drug Product and Human Serum by Using Different Solid Electrodes
Authors: Bilge Selva , Karadurmus Leyla , Atici Esen Bellur , Sınağ Ali , Ozkan Sibel A.
Published: January 2022

Ruxolitinib (RUX), a compound of the pyrrolopyrimidines class with activity as a tyrosine kinase inhibitory drug, is used to treat myelofibrosis. This study is reported for the detailed electrochemical behavior of RUX. The effects of supporting electrolyte, pH, and scanning rate on the peak potentials and currents of RUX were investigated by BDDE and GCE using different voltammetric techniques. Under optimum experimental conditions, calibration curves for RUX were obtained as 4 μM–80 μM and 1 μM–80 μM with a limit of detection (LOD) of 0.517 μM and 0.192 μM by the GCE and BDDE, respectively using DPV.
Molecular dynamics simulation‐guided toehold mediated strand displacement probe for single‐nucleotide variants detection
Authors: Zhang Linghao , Chen Jing , He Mengya , Su Xin
Published: January 2022

Single nucleotide variant (SNV) has become an emerging biomarker for various diseases such as cancers and infectious diseases. Toehold‐mediated strand displacement (TMSD), the core reaction of DNA nanotechnology, has been widely leveraged to identify SNVs. However, inappropriate choice of mismatch location results in poor discrimination ability. Here, we comprehensively investigate the effect of mismatch location on TMSD kinetics by molecular dynamic simulation tool oxDNA through umbrella sampling and forward flux sampling disclosing that mismatches at the border of the toehold and branch migration domain yield the lowest TMSD reaction rate. Nine disease‐related SNVs (SARS‐CoV‐2‐D614G, EGFR‐L858R, EGFR‐T790M, KRAS‐G12R, etc.) were tested experimentally showing a good agreement with simulation. The best choice of mismatch location enables high discrimination factor with a median of 124 for SNV and wild type. Coupling with a probe‐sink system, a low variant allele frequency of 0.1% was detected with 3 S/N. We successfully used the probes to detect SNVs with high confidence in the PCR clones of constructed plasmids. This work provides mechanistic insights into TMSD process at the single‐nucleotide level and can be a guidance for the design of TMSD system with fine‐tuning kinetics for various applications in biosensors and nanotechnology.
Iterated discretization error transport equations for laminar and turbulent flows
Authors: Wang Hongyu , Xue Weicheng , Roy Christopher J.
Published: January 2022

The focus of this work is on discretization error estimation for finite‐volume schemes using iterated forms of the linear and nonlinear error transport equations. The accuracy of the discretization error estimates is studied by applying the error estimates as corrections to the primal problem and calculating the observed order of accuracy of the corrected solution. The test cases used in this work include two‐dimensional Cross Term Sinusoidal manufactured solutions for laminar flow and turbulent flow modeled by the Spalart–Allmaras and Menter's Shear Stress Transport model and a boundary layer manufactured solution for the Spalart–Allmaras model. The discretization error estimates of the linearized error transport equations and the nonlinear error transport equations are compared. Higher‐order accurate corrected solutions have been obtained which shows that the discretization error estimates are sufficiently accurate.
Declining disease burden of HCC in the United States, 1992–2017: A population‐based analysis
Authors: Han Jianglong , Wang Bin , Liu Wenmin , Wang Shijie , Chen Ruyan , Chen Mingkai , Fu Zhenming
Published: January 2022

Background and Aims

The incidence of HCC has recently been consistently reported to decline in the United States. However, decreased overall mortality of HCC has just been suggested and needs further examination.

Approach and Results

Using data from the Surveillance, Epidemiology, and End Results databases, we assessed HCC incidence, incidence‐based mortality (IBM), and 1‐year survival rates from 1992 through 2017 in the United States. These secular trends were analyzed using the National Cancer Institute’s Joinpoint Regression Program. Age‐period‐cohort analyses were performed to address underlying reasons for the observed temporal trends. The incidence and mortality of liver cancer in the United States by different etiologies were acquired from the Global Burden of Disease study (1990–2019) as a likely validation set. Joinpoint and age‐period‐cohort analyses were performed by etiologies. The incidence rates of HCC increased during 1992–2011 and sharply decreased thereafter by −2.3% annually (95% CI: −3.5% to −1.1%). IBM peaked in 2013 (age‐standardized mortality rate: 6.98 per 100,000 person‐years) in the US population. IBM started to decrease significantly in 2013 by −3.2%/year (95% CI: −5.4% to −1.1% per year) after a continuous increase of 3.5% annually during 1993–2013. Overall, the 1‐year survival of HCC improved from 21.4% to 56.6% over the study period. However, the highest HCC incidence and mortality risk for patients aged 60–69 and born between 1952–1957 were found.

Conclusions

We found significantly decreased overall HCC‐specific mortality since 2013 in the US population, along with decreased incidence and continuously improved survival. The changing etiologies, advances in screening and diagnosis, and improved treatment modality and allocation might all contribute to the downward trends of the disease burden of HCC in the United States.
Polar Substituents Enable Efficient Catalysis for a Class of Cobalt Polypyridyl Hydrogen Evolving Catalysts
Authors: Müller Peter , Probst Benjamin , Spingler Bernhard , Blacque Olivier , Alberto Roger
Published: January 2022

A series of structurally related, acyclic cobalt tetrapyridyl hydrogen evolving catalysts (HEC) were prepared and characterized. The common motif, di(2,2′‐bipyridin‐6‐yl)‐methane, was derivatized at the bridging methylene to include a carbonyl group (L1), a hydroxy (L2), a methyl and a hydroxy (L3), a 1,1′‐biphenyl‐2,2′‐diyl (L4), a hydroxy and a phenyl (L5) or a hydroxy and a pyrid‐6‐yl group. These catalysts were compared with the known HEC [Co(appy)Br]Br. Photo‐ and electrochemistry showed a distinct influence of the bridging position on rates and stabilities of the hydrogen evolution reaction (HER). Apolar ligands resulted in inferior catalytic performance as compared to HECs with polar substituents. Electrochemically, [Co(L1)Br2] was shown to be converted to [Co(L2)Br2] in catalysis. The best catalyst made more than 10’000 turnovers, albeit at an overpotential of 600 mV. Additional pH dependent mechanistic aspects were elucidated by cyclic voltammetry.
Closed‐incision negative pressure therapy at −125 mmHg significantly reduces surgical site complications following total hip and knee arthroplasties: A stratified meta‐analysis of randomized controlled trials
Authors: Elhage Kareem G. , Awad Mohamed E. , Irfan Furqan B. , Lumbley Joshua , Mostafa Gamal , Saleh Khaled J.
Published: January 2022

Background

Closed‐incision negative pressure wound therapy (ciNPT) has shown promising effects for managing infected wounds. This meta‐analysis explores the current state of knowledge on ciNPT in orthopedics and addresses whether ciNPT at −125 mmHg or −80 mmHg or conventional dressing reduces the incidence of surgical site complications in hip and knee arthroplasty.

Methods

This meta‐analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta‐analysis (PRISMA) guidelines and Cochrane Handbook. Prospective randomized controlled trials (RCTs) with ciNPT use compared to conventional dressings following hip and knee surgeries were considered for inclusion. Non‐stratified and stratified meta‐analyses of six RCTs were conducted to test for confounding and biases. A P value less than .05 was considered statistically significant.

Results

The included six RCTs have 611 patients. Total hip and knee arthroplasties were performed for 51.7% and 48.2% of the included population, respectively. Of 611 patients, conventional dressings were applied in 315 patients and 296 patients received ciNPT. Two ciNPT systems have been used across the six RCTs; PREVENA Incision Management System (−125 mmHg) (63.1%) and PICO dressing (−80 mmHg) (36.8%). The non‐stratified analysis showed that the ciNPT system had a statistically significant, lower risk of persistent wound drainage as compared to conventional dressing following total hip and knee arthroplasties (OR = 0.28; P = .002). There was no difference between ciNPT and conventional dressings in terms of wound hematoma, blistering, seroma, and dehiscence. The stratified meta‐analysis indicated that patients undergoing treatment with high‐pressure ciNPT (120 mmHg) displayed significantly fewer overall complications and persistent wound drainage (P = .00001 and P = .002, respectively) when compared to low‐pressure ciNPT (80 mmHg) and conventional dressings. In addition, ciNPT is associated with shorter hospital stays. (P = .005).

Conclusion

When compared to conventional wound dressing and −80 mmHg ciNPT, the use of −125 mmHg ciNPT is recommended in patients undergoing total joint arthroplasty.
Synergistic‐engineered van der Waals photodiodes with high efficiency
Authors: Liu Baishan , Zhang Xiankun , Du Junli , Xiao Jiankun , Yu Huihui , Hong Mengyu , Gao Li , Ou Yang , Kang Zhuo , Liao Qingliang , Zhang Zheng , Zhang Yue
Published: January 2022

Van der Waals (vdW) heterostructures based on two‐dimensional transition‐metal dichalcogenides have provided unprecedented opportunities for photovoltaic detectors owing to their strong light‐matter interaction and ultrafast interfacial charge transfer. Despite continued advancement, insufficient control of photocarrier behaviors still limits the external quantum efficiency (EQE) and operation speed of such detectors. Here, we propose a synergistic strategy of contact‐configuration design and thickness‐modulation to construct high‐performance vdW photodiodes based on the typical type II heterostructure (MoS2/WSe2). Through integrating three contact architectures into one device to exclude other factors, we solid the superiority of designed 1L‐MoS2/WSe2/graphene heterostructures incorporating efficient photocarrier collection and gate modulation. Together with leveraging the layer‐number‐dependent properties of WSe2, we observe the critical thickness of WSe2 (11 layers) for the highest EQE, which verifies the thickness‐dependent competition between photocarrier generation, dissociation, and collection. Finally, we demonstrate the synergistic‐engineered vdW heterostructure can trigger record‐high EQE (61%) and manifest ultrafast photoresponse (4.1 μs) at the atomically thin limit (8 nm). The proposed strategy enables architecture‐design and thickness‐engineering to unlock the potential to realize high‐performance optoelectronic devices.
Sodium‐rich NASICON‐structured cathodes for boosting the energy density and lifespan of sodium‐free‐anode sodium metal batteries
Authors: Wu Junxiong , Lin Cong , Liang Qinghua , Zhou Guodong , Liu Jiapeng , Liang Gemeng , Wang Man , Li Baohua , Hu Liang , Ciucci Francesco , Liu Qiang , Chen Guohua , Yu Xiaoliang
Published: January 2022

Rechargeable sodium metal batteries (SMBs) have emerged as promising alternatives to commercial Li‐ion batteries because of the natural abundance and low cost of sodium resources. However, the overuse of metallic sodium in conventional SMBs limits their energy densities and leads to severe safety concerns. Herein, we propose a sodium‐free‐anode SMB (SFA‐SMB) configuration consisting of a sodium‐rich Na superionic conductor‐structured cathode and a bare Al/C current collector to address the above challenges. Sodiated Na3V2(PO4)3 in the form of Na5V2(PO4)3 was investigated as a cathode to provide a stable and controllable sodium source in the SFA‐SMB. It provides not only remarkable Coulombic efficiencies of Na plating/stripping cycles but also a highly reversible three‐electron redox reaction within 1.0–3.8 V versus Na/Na+ confirmed by structural/electrochemical measurements. Consequently, an ultrahigh energy density of 400 Wh kg−1 was achieved for the SFA‐SMB with fast Na storage kinetics and impressive capacity retention of 93% after 130 cycles. A narrowed voltage window (3.0–3.8 V vs. Na/Na+) further increased the lifespan to over 300 cycles with a high retained specific energy of 320 Wh kg−1. Therefore, the proposed SFA‐SMB configuration opens a new avenue for fabricating next‐generation batteries with high energy densities and long lifetimes.

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Sensitivity and uncertainty analysis for predicted soil test phosphorus using the Annual Phosphorus Loss Estimator model
Authors: Bolster Carl H. , Wessel Barret M. , Vadas Peter A. , Fiorellino Nicole M.
Published: January 2022

In this study we conducted a sensitivity and uncertainty analysis using the Annual P Loss Estimator (APLE) model focusing on model predictions of soil test phosphorus (STP). We calculated and evaluated the sensitivity coefficients of predicted STP and changes in STP using 1‐ and 10‐yr simulations with and without P application. We also compared two methods for estimating prediction uncertainties: first‐order variance approximation (FOVA) and Monte Carlo simulation (MCS). Finally, we compared uncertainties in APLE‐predicted STP with uncertainties in measured STP collected from multiple sites in Maryland under different manuring and cropping treatments. Results from our sensitivity analysis showed that predicted STP and changes in STP for 1‐yr simulations without P inputs were most sensitive to initial STP, whereas model STP predictions were most sensitive to manure and fertilizer application rates when sensitivity analyses included P inputs. For the 10‐yr simulations without P application inputs, the range in sensitivity coefficients for crop uptake and precipitation were much greater than for the 1‐yr simulations. Prediction uncertainties from FOVA were comparable to those from MCS for model input uncertainties up to 50%. Using FOVA to calculate APLE STP prediction uncertainties using the Maryland data set, the mean measured STP for nearly all site years fell within the 95% confidence intervals of the STP prediction uncertainties. Our results provide users of APLE insight into what model inputs require the most careful measurement when using the model to predict changes in STP under conditions of P drawdown (i.e., no P application) or P buildup.
Similarity and difference between aging and puncture‐induced intervertebral disc degeneration
Authors: He Shuangjun , Zhang Yijian , Zhou Zhangzhe , Shao Xiaofeng , Chen Kangwu , Dai Shouqian , Liang Ting , Qian Zhonglai , Luo Zongping
Published: January 2022

The purpose of our study was to investigate the changes in micromorphology and mechanical properties of intervertebral discs degeneration induced by aging and puncture. Normal group (NG), 2 weeks post‐puncture degeneration group (PDG) and aging degeneration group (ADG) each included 10 rats. Plain film, magnetic resonance imaging, and histological testing were utilized to assess intervertebral disc degeneration. Atomic force microscope was utilized to analyze the microstructure and elastic modulus of the intervertebral disc, while immunohistochemistry was employed to assess alterations in the cell matrix using collagen I, collagen II, matrix metalloproteinase‐3 (MMP‐3), and tumour necrosis factor‐α (TNF‐α). The results showed that the disc height ratio between PDG and ADG decreased. In the PDG and ADG group, histological scores both increased, the gray value of the T2 signal decreased, the proportion of MMP‐3 and TNF‐positive cells in intervertebral disc tissues was higher (p < 0.05) and the IOD values of COL‐2 lower in intervertebral disc tissues (p < 0.05). The elastic modulus of PDG and ADG annulus fibers (AF) increased compared to the NG (p < 0.05); when compared to PDG, the elastic modulus of ADG AF decreased (p < 0.05). The elastic modulus of PDG and ADG collagen increased in the nucleus pulposus (NP, p < 0.05); ADG had a greater AF diameter than NG and PDG (p < 0.05). The results indicated that ADG fiber diameter thickens, and chronic inflammation indicators rise; PDG suffers from severe extracellular matrix loss. The degeneration of the ADG and PDG intervertebral discs is different. The results provide foundation for clinical research.
Restoring subsided coal mined land to farmland using optimized placement of Yellow River sediment to amend soil
Authors: Hu Zhenqi , Wang Xiaotong , McSweeney Kevin , Li Yong
Published: January 2022

Underground coal mining causes land subsidence and large areas of cultivated land are destroyed. The Yellow River interlayer filling reclamation technology is a powerful way to restore cultivated land. Understanding the mechanism of action of interlayers in reconstructed soil filled with Yellow River sediment is essential to achieving sustainable land management in the Yellow River regions. Column experiments and field experiments were conducted to explore optimum interlayer placement in reconstructed soil with Yellow River sediment for restoring subsided land. Our findings show that the inclusion of interlayers in the sediment reduced water leakage and moisture evaporation and improved the water‐holding capacity of the material in comparison to a conventional reconstructed soil profile (CK2). The optimal profile with the highest water‐holding capacity was constructed using two 30 cm thick interlayers (T6). In comparison to CK2, the migration rate of the wetting front decreases by 32.16%, the cumulative evaporation decreases by 16.29%, the volumetric water content of the filling layer (θfl) increases by 121.56%, and the water‐holding coefficient (CWR) increases by 59.47%. The same trend is also demonstrated by field experiments. The wheat and maize yields of T6 improved 45.85% and 60.69%, respectively, as compared with CK2, that more closely resembles undisturbed farmland (CK1). This study provides a valuable framework for subsided land reclamation regarding the method of placing interlayers into Yellow River sediment for enhancing water retention and productivity.
Multifunctional Liquid Crystal Device for Grayscale Pattern Display and Holography with Tunable Spectral‐Response
Authors: Chen Kuixian , Xu Chunting , Zhou Zhou , Li Zile , Chen Peng , Zheng Guoxing , Hu Wei , Lu Yanqing
Published: January 2022

Conventional liquid‐crystal (LC) devices can only realize a single‐manipulation of optical amplitude or phase, which hinders the development of LC devices toward ultracompact multifunctional integration. Herein, it is shown LC devices can be readily extended to multifunctional ones without the cost of complex design and fabrication. Specifically, by combining Pancharatnam–Berry phase with orientation‐degeneracy implied in Malus's law, each operation‐unit of LC devices can manipulate the amplitude and phase of incident light separately, representing a new paradigm for designing innovative LC devices. A multifunctional LC device which can display a grayscale pattern right at the surface of LC, while simultaneously project an independent phase‐only holographic image in the far‐field is experimentally demonstrated. More interestingly, with the LC directors tilted with external applied voltages, a new degree‐of‐freedom is provided to modulate the spectral‐response of LC devices, contributing to the distinct function of optical switch. Owing to these unique characteristics of dual‐manipulations and spectrum‐tunability, the proposed multifunctional LCs have promising prospects in information multiplexing, optical communications, spectral measurements, etc.
Real‐Life Turning Movements Capture Subtle Longitudinal and Preataxic Changes in Cerebellar Ataxia
Authors: Thierfelder Annika , Seemann Jens , John Natalie , Harmuth Florian , Giese Martin , Schüle Rebecca , Schöls Ludger , Timmann Dagmar , Synofzik Matthis , Ilg Winfried
Published: January 2022

Background

Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints that capture change in ataxia severity in patients' real life.

Objectives

This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real‐life turning movements that are sensitive for changes both longitudinally and at the preataxic stage.

Methods

Combined cross‐sectional (n = 30) and longitudinal (n = 14, 1‐year interval) observational study in degenerative cerebellar disease (including eight preataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body‐worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real‐life movements.

Results

Measures that quantified dynamic balance during turning—lateral velocity change (LVC) and outward acceleration—but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life (effect size δ = 0.68), with LVC also differentiating preataxic against healthy subjects (δ = 0.53). LVC was highly correlated with clinical ataxia severity (scale for the assessment and rating of ataxia [SARA] score, effect size ρ = 0.79) and patient reported balance confidence (activity‐specific balance confidence scale [ABC] score, ρ = 0.66). Moreover, LVC in real life—but not general turning measures or the SARA score—allowed detecting significant longitudinal change in 1‐year follow‐up with high effect size (rprb = 0.66).

Conclusions

Measures of turning allow capturing specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers, even in the highly treatment‐relevant early stages of degenerative cerebellar disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Detecting perturbations of a radiation field inside a head‐sized phantom exposed to therapeutic carbon‐ion beams through charged‐fragment tracking
Authors: Ghesquière‐Diérickx Laura , Félix‐Bautista Renato , Schlechter Annika , Kelleter Laurent , Reimold Marvin , Echner Gernot , Soukup Pavel , Jäkel Oliver , Gehrke Tim , Martišíková Maria
Published: January 2022

Purpose

Noninvasive methods to monitor carbon‐ion beams in patients are desired to fully exploit the advantages of carbon‐ion radiotherapy. Prompt secondary ions produced in nuclear fragmentations of carbon ions are of particular interest for monitoring purposes as they can escape the patient and thus be detected and tracked to measure the radiation field in the irradiated object. This study aims to evaluate the performance of secondary‐ion tracking to detect, visualize, and localize an internal air cavity used to mimic inter‐fractional changes in the patient anatomy at different depths along the beam axis.

Methods

In this work, a homogeneous head phantom was irradiated with a realistic carbon‐ion treatment plan with a typical prescribed fraction dose of 3 Gy(RBE). Secondary ions were detected by a mini‐tracker with an active area of 2 cm2, based on the Timepix3 semiconductor pixel detector technology. The mini‐tracker was placed 120 mm behind the center of the target at an angle of 30 degrees with respect to the beam axis. To assess the performance of the developed method, a 2‐mm thick air cavity was inserted in the head phantom at several depths: in front of as well as at the entrance, in the middle, and at the distal end of the target volume. Different reconstruction methods of secondary‐ion emission profile were studied using the FLUKA Monte Carlo simulation package. The perturbations in the emission profiles caused by the air cavity were analyzed to detect the presence of the air cavity and localize its position.

Results

The perturbations in the radiation field mimicked by the 2‐mm thick cavity were found to be significant. A detection significance of at least three standard deviations in terms of spatial distribution of the measured tracks was found for all investigated cavity depths, while the highest significance (six standard deviations) was obtained when the cavity was located upstream of the tumor. For a tracker with an eight‐fold sensitive area, the detection significance rose to at least nine standard deviations and up to 17 standard deviations, respectively. The cavity could be detected at all depths and its position measured within 6.5 ± 1.4 mm, which is sufficient for the targeted clinical performance of 10 mm.

Conclusion

The presented systematic study concerning the detection and localization of small inter‐fractional structure changes in a realistic clinical setting demonstrates that secondary ions carry a large amount of information on the internal structure of the irradiated object and are thus attractive to be further studied for noninvasive monitoring of carbon‐ion treatments.
The establishment of the normal contact force model for a one‐dimensional sphere chain subjected to impact load
Authors: Liu Jun , Zhao Futian , Xiao Zhimin , Wang Yue , Liu Zheng , Zheng Haowen
Published: January 2022

The normal contact force determines the behavior of a particle system. To investigate the normal contact force in a one‐dimensional sphere chain subjected to impact load, by comparing the simulation results of the existing typical normal contact force models embedded in the discrete element program, an improved normal contact force model was proposed in this paper. The improved model consists of two parts: the Cundall model for loading and the Daniel model for unloading. Moreover, a systematic test was designed to verify the accuracy and applicability of the improved model. The results showed that the calculated contact force curves agree well with the experimental results. Furthermore, the improved model is implemented in the solution algorithm without need for complex numerical methods and parameters fitting, leading to more efficient simulations.
Health Disparities and Health Omissions: Pushing Medical Anthropology Forward in the United States
Authors: Carter Chelsey R.
Published: January 2022

Racialized diagnosis of the fatal neurodegenerative disease ALS illustrates the limitations of medical anthropological knowledge that focuses only on “ethnic differences” to explain health disparities at the population level. I argue that a central focus on racism in our analysis of biomedical US spaces, and explicitly anti‐Black racism, will better equip anthropologists to understand how racialized forms of knowledge production in medicine and science have deleterious effects on people’s lives and bodies. The aggregate effects of racial science (the belief that human beings can be separated into biologically distinct groups) in slavery’s afterlife impact how clinicians and researchers see and treat Black people. I elaborate the concept of “health omissions” to equip anthropologists, clinical researchers, and biomedical clinicians with an analytical and truth‐telling lens that can attend to the ways that systemic marginalization in slavery’s afterlife omits Black people’s health problems and care.
Ifenprodil for the treatment of methamphetamine use disorder: An exploratory, randomized, double‐blind, placebo‐controlled trial
Authors: Kotajima‐Murakami Hiroko , Takano Ayumi , Hirakawa Shinya , Ogai Yasukazu , Funada Daisuke , Tanibuchi Yuko , Ban Eriko , Kikuchi Minako , Tachimori Hisateru , Maruo Kazushi , Kawashima Takahiro , Tomo Yui , Sasaki Tsuyoshi , Oi Hideki , Matsumoto Toshihiko , Ikeda Kazutaka
Published: January 2022

Aim

No effective pharmacological interventions have been developed for patients with methamphetamine use disorder. Ifenprodil is a blocker of G protein‐activated inwardly rectifying potassium channels, which play a key role in the mechanism of action of addictive substances. We conducted a randomized, double‑blind, exploratory, dose‐ranging, placebo‐controlled trial to examine the clinical efficacy of ifenprodil for the treatment of methamphetamine use disorder.

Methods

Participants were assigned to three groups: placebo, 60 mg/d ifenprodil, or 120 mg/d ifenprodil. The drug administration period was 84 days. The primary outcome was the use or nonuse of methamphetamine during the drug administration period in the placebo group vs 120 mg/d ifenprodil group. We also assessed drug use status, relapse risk based on the Stimulant Relapse Risk Scale (SRRS), drug craving, and methamphetamine in urine as secondary outcomes. We further evaluated drug use status and SRRS subscale scores in patients who were not taking addiction medications during the study.

Results

Ifenprodil did not affect the primary or secondary outcomes. However, the additional analyses showed that the number of days of methamphetamine use during the follow‐up period and scores on the emotionality problems subscale of the SRRS improved in the 120 mg/d ifenprodil group. The safety of ifenprodil was confirmed in patients with methamphetamine use disorder.

Conclusion

The present findings did not confirm the efficacy of ifenprodil for methamphetamine use disorder treatment based on the primary or secondary outcomes, but we found evidence of its safety and efficacy in reducing emotionality problems.

Clinical trial registration

The study was registered at the University Hospital Medical Information Network Clinical Trial Registry (no. UMIN000030849) and Japan Registry of Clinical Trials (no. jRCTs031180080). The main registration site is jRCT (https://jrct.niph.go.jp/).