bluuebunny/crossref_metadata_2025 huggingface dataset:
Detrital zircon U–Pb ages of Tertiary sequences (Palaeocene‐Miocene): Inner Fold Belt and Belt of Schuppen, Indo‐Myanmar Ranges, India
Authors: Ding Lin , Goswami Tapos K. , Cai Fu Long , Baral Upendra , Sarmah Ranjan K. , Bezbaruah Devojit
Published: April 2022

The along‐strike heterogeneity in the tectonics of Himalaya is well recognized; however, the eastern segment of Himalaya is less studied compared to the other segments. This study combines the comprehensive field data, as well as the U–Pb geochronology of sandstone samples from the Indo‐Burma Range (east India). The study shows that the Lower Disang Formation was deposited in an open marine environment with a steep gradient during the Late Cretaceous to Mid‐Eocene, accommodating the detritus solely from an Indian source. Furthermore, during the Early to Late Eocene interval, the sedimentary basin changed to a shallow marine shelf when the sediments from Himalayan as well as trans‐Himalaya were deposited. The Upper Disang Formation must have been deposited just before or during the collision process between the Indian and Asian plates. After the India‐Asian collision, there was a remnant ocean, in which the sediments of the Barail and Surma groups were deposited in the shallow marine to deltaic environments. The Tethys Ocean completely dried out in the Late Miocene resulting in a change from marine to fluvial environments, which facilitated the deposition of the sandstones of the Tipam Formation. Based on the U–Pb ages, the Palaeogene basin history in the Indo‐Burma Range was unlike the central Himalaya, that is, the detritus were mainly sourced from the Burmese Plate and adjoining magmatic rocks.
Aberrant dynamic structure–function relationship of rich‐club organization in treatment‐naïve newly diagnosed juvenile myoclonic epilepsy
Authors: Liu Guangyao , Zheng Weihao , Liu Hong , Guo Man , Ma Laiyang , Hu Wanjun , Ke Ming , Sun Yu , Zhang Jing , Zhang Zhe
Published: April 2022

Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich‐club organization—a core feature of the brain networks. Moreover, it is unclear how structure–function relationships dynamically change over time in JME. Here, we quantify the anatomical rich‐club organization and dynamic structural and functional connectivity (SC–FC) coupling in 47 treatment‐naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC–FC coupling were also calculated to examine the supporting of structure–function relationship to brain information transfer. The results showed that the anatomical rich‐club organization was disrupted in the patient group, along with decreased connectivity strength among rich‐club hub nodes. Furthermore, reduced SC–FC coupling in rich‐club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor‐cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC–FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The aberrant dynamic SC–FC coupling of rich‐club organization suggests a selective influence of densely interconnected network core in patients with JME at the early phase of the disease, offering new insights and potential biomarkers into the underlying neurodevelopmental basis of behavioral and cognitive impairments observed in JME.
A phase 1b study of OXIRI in pancreatic adenocarcinoma patients and its immunomodulatory effects
Authors: Ng Matthew , Chen Sylvia , Ong Whee Sze , Balachander Akhila , Seet Amanda , Yeong Joe , Sutiman Natalia , Lim Tony Kiat Hon , Lee Bernett , Guo Yu Amanda , Leong Wai Fook , Lee Sze Sing , Lam Justina , Choo Su Pin , Skanderup Anders Jacobsen , Biswas Subhra Kumar , Tai David , Chowbay Balram
Published: April 2022

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and debilitating disease with limited therapeutic options. The aim of this clinical study was to evaluate the safety, efficacy and pharmacokinetics of a novel regimen comprised of metronomic oxaliplatin (O), chronomodulated capecitabine (X) and UGT1A1 genotype‐guided dosing of irinotecan (IRI) [OXIRI] as well as its immunomodulatory effects. Thirty‐six patients were enrolled into either dose‐escalation or expansion cohorts. In the dose escalation phase, capecitabine doses (2000, 2650, 3500 and 4500 mg/day) were administered at midnight on days 1 to 14 while oxaliplatin and irinotecan were intravenously infused at fixed doses of 50 and 75 mg/m2 respectively on days 1, 8 in a 21‐day cycle. The maximum tolerated dose of capecitabine was 2650 mg/day and the most common grade 3 adverse events were neutropenia (30.6%) and diarrhea (13.9%). No grade 4 toxicity was observed. UGT1A1‐genotype directed dosing resulted in similar exposure levels of irinotecan, SN‐38 and SN‐38G in all patients. Objective response rate was 22.2%. Median overall survival and progression‐free survival were 8.1 and 5.2 months, respectively. Exploratory immunoprofiling by flow cytometry and quantitative spatial localization analysis of infiltrated immune cells performed on biopsy and plasma samples revealed significant declines in CCL22, CCL2 and TNFα levels at end of first cycle and an active host immune response. Our study showed that OXIRI was well‐tolerated and exhibited good efficacy, with immunomodulatory effects. It may be considered as an alternative to FOLFIRINOX in patients intolerant to the latter.
The Associations of Dietary Inflammatory Potential With Musculoskeletal Health in Chinese Community-Dwelling Older People: The Mr. OS and Ms. OS (Hong Kong) Cohort Study
Authors: Su Yi , Yeung Suey S.Y. , Chen Yu-Ming , Leung Jason C.S. , Kwok Timothy C.Y.
Published: April 2022

Inflammation, an important contributory factor of muscle and bone aging, is potentially modulated by diet. This study examined the associations of dietary inflammatory index (DII) score with musculoskeletal parameters and related disease outcomes in 3995 community-dwelling Chinese men and women aged ≥65 years in Hong Kong. DII score at baseline was estimated from a food frequency questionnaire. Bone mineral density (BMD) and muscle mass estimated by dual-energy X-ray absorptiometry (DXA), hand grip strength, gait speed, and chair stand test were measured at baseline, year 4, and year 14. The associations of DII score with the longitudinal changes of musculoskeletal parameters, and incidence of osteoporosis, sarcopenia, and fractures were examined by using general linear model, multinomial logistic regression model, and Cox proportional hazards regression model, respectively. After multiple adjustments, each tertile increase in DII score in men was associated with 0.37 (95% confidence interval [CI], 0.10–0.64) kg loss in grip strength and 0.02 (95% CI, 0.01–0.03) m/s loss in gait speed over 4 years. In men, the highest tertile of DII was associated with a higher risk of incident fractures, with adjusted and competing death adjusted hazard ratio (HR) (95% CI) of 1.56 (1.14–2.14) and 1.40 (1.02–1.91), respectively. In women, DII score was not significantly associated with any muscle-related outcomes or incidence of fracture, but a significant association between higher DII score and risk of osteoporosis at year 14 was observed, with the highest tertile of DII score having adjusted odds ratio (OR) (95% CI) of 1.90 (1.03–3.52). In conclusion, pro-inflammatory diet consumption promoted loss of muscle strength and physical function, and increased risk of fractures in older Chinese men. Pro-inflammatory diets had no significant association with muscle related outcomes but increased the long-term risk of osteoporosis in older Chinese women. © 2022 American Society for Bone and Mineral Research (ASBMR).
Audit committee financial expertise, accrual, and real earnings management
Authors: Cheung Kwok Yip , Adelopo Ismail
Published: April 2022

This study examines the effectiveness of audit committee (AC) financial expertise in mitigating accrual and real earnings management (AEM and REM hereafter). Although extant studies have examined the effects of AC expertise on earnings management, findings are inconclusive. Prior studies have also focused mainly on AEM not REM. We used the data for a sample of Hong Kong Hang Seng Composite Index with 1714 firm‐year observations between 2010 and 2015, which was analyzed using panel fixed effect regression models. The results show statistically significant negative relationship between AC financial expertise and AEM but surprisingly, we find that AC financial expertise is associated with increase in REM. We argue that whilst AC members have developed monitoring skills on AEM, REMs are relatively recent and are more complicated to detect. We argue that management may be shifting their opportunistic use of earnings management from AEM to REM. A possible reason could be a steep AC's learning curve on the nature of REM. Our investigation provides evidence on the impact of AC expertise on both AEM and REM from a unique context.
Youth gun carrying and household firearm ownership in 22 US states
Authors: Chavez Leo , Kivisto Aaron J. , Gray Samantha L. , Thomas Kendra J.
Published: April 2022

Youth gun carrying is associated with a range of adverse outcomes, including increased risks for homicide, suicide, school disciplinary problems, and criminal legal involvement. In this study we examined the association between state‐level household firearm ownership rates and the odds of past‐year gun carrying among high‐school‐aged youth. Using survey‐weighted multivariable logistic regression models, results showed that each 1% point increase in state‐level gun ownership was associated with a 2.7% (95% confidence interval [CI] = [1.1%, 4.2%], p = 0.001) increased odds of youth gun carrying, controlling for histories of school‐based victimization, physical fighting, and substance use. Among a subset of weapon‐carrying youth, state‐level firearm availability was a significant factor in determining whether the weapon carried was a gun or a less lethal (i.e., nonfirearm) weapon (odds ratio = 1.021, 95% CI = [1.005, 1.038], p = 0.01). These findings show that firearm availability confers additional risk for youth gun carrying beyond the psychosocial risks emphasized in prior research and efforts to restrict youth access to firearms might be particularly important, especially in communities with high levels of household gun ownership.
Plasma neurofilament light levels associate with muscle mass and strength in middle‐aged and older adults: findings from GenoFit
Authors: Pratt Jedd , De Vito Giuseppe , Segurado Ricardo , Pessanha Ludmilla , Dolan Jackie , Narici Marco , Boreham Colin
Published: April 2022

Background

Efforts to enhance diagnostic measures for sarcopenia have led to an increased focus on the screening utility of blood‐based biomarkers. In this regard, circulating neurofilament light chain (NfL) levels are a potent indicator of axonal damage and have been linked with several neurological disorders. However, despite the strong neurogenic contribution to skeletal muscle health, no studies have explored the relevance of NfL concentrations to sarcopenia. With that in mind, this study aimed to examine the association between plasma NfL concentration and sarcopenic domains.

Methods

Three hundred adults aged between 50 and 83 years participated to this study (male participants, n = 150; mean age: 64.2 ± 8.7 years and female participants, n = 150; mean age: 63.9 ± 8.3 years). Body composition was assessed using dual‐energy X‐ray absorptiometry, and a skeletal muscle index (SMI) was calculated. Muscle strength was assessed with hand dynamometry. Sarcopenia was classified using the European Working Group on Sarcopenia in Older People criteria. Plasma NfL concentration was determined using a highly sensitive, enzyme‐linked immunosorbent assay.

Results

Neurofilament light chain levels were associated with grip strength and SMI (P = 0.005 and P = 0.045, respectively) and were significantly elevated in sarcopenic individuals, compared with non‐sarcopenic participants (P < 0.001). Individuals with pre‐sarcopenia (either low grip strength or low SMI) had significantly higher NfL levels, compared with healthy controls (P = 0.001 and P = 0.006, respectively). Male participants with either low grip strength or low SMI had significantly raised NfL levels (P = 0.006 and P = 0.002, respectively), while in female participants, NfL concentrations were significantly elevated only in those with low grip strength (P = 0.049). NfL concentration displayed acceptable diagnostic accuracy for sarcopenia (area under the curve = 0.726, P < 0.001).

Conclusions

Our study clearly demonstrates the indicative pertinence of circulating NfL levels to sarcopenic domains, supporting its potential use as a biomarker of sarcopenia. More studies are needed, however, to further illuminate the diagnostic value of circulating NfL. Future research should explore whether NfL levels are more powerfully linked with muscle strength than mass and whether sex mediates the relevance of NfL concentrations to sarcopenic phenotypes.
Applications of operant demand to treatment selection III: Consumer behavior analysis of treatment choice
Authors: Gilroy Shawn P. , Picardo Rochelle
Published: April 2022

Behavior analysts and psychologists advocate for the use of therapies and strategies based on credible, scientific evidence. Researchers and clinicians regularly advocate for Evidence‐based Practices (EBPs) over questionable “alternatives” because caregivers seldom choose interventions based on scientific evidence alone. This study applied methods and concepts from Consumer Behavior Analysis to conduct a reinforcer‐based evaluation of the consequences that influence treatment choices. Hypothetical Treatment Purchase Tasks (HTPTs) were designed to evaluate how utilitarian (UR; i.e., the efficacy of treatment) and informational sources of reinforcement (IR; i.e., community support for treatment) jointly influence treatment‐related choices. A total of 104 caregivers were recruited using the Amazon Mechanical Turk (MTurk) framework to complete two HTPTs. Results indicated that caregivers overall favored treatments with greater IR over those with greater UR, suggesting that indirect contingencies for treatment choices exerted greater overall influence than the direct contingencies of treatment choices (i.e., efficacy). This finding extends the literature on treatment choice by providing a reinforcer‐based perspective on why ‘fad’, questionable, and pseudoscientific practices can achieve and maintain high levels of adoption by caregivers. This work concludes with a discussion of Consumer Behavior Analysis and how reinforcer‐based interpretations of choice can be used to improve efforts to support and advocate for evidence‐based child behavior treatments.
Heterogeneity in extracellular vesicle secretion by single human macrophages revealed by super‐resolution microscopy
Authors: Dechantsreiter Susanne , Ambrose Ashley R. , Worboys Jonathan D. , Lim Joey M. E. , Liu Sylvia , Shah Rajesh , Montero M. Angeles , Quinn Anne Marie , Hussell Tracy , Tannahill Gillian M. , Davis Daniel M.
Published: April 2022

The diverse origins, nanometre‐scale and invasive isolation procedures associated with extracellular vesicles (EVs) mean they are usually studied in bulk and disconnected from their parental cell. Here, we used super‐resolution microscopy to directly compare EVs secreted by individual human monocyte‐derived macrophages (MDMs). MDMs were differentiated to be M0‐, M1‐ or M2‐like, with all three secreting EVs at similar densities following activation. However, M0‐like cells secreted larger EVs than M1‐ and M2‐like macrophages. Proteomic analysis revealed variations in the contents of differently sized EVs as well as between EVs secreted by different MDM phenotypes. Super resolution microscopy of single‐cell secretions identified that the class II MHC protein, HLA‐DR, was expressed on ∼40% of EVs secreted from M1‐like MDMs, which was double the frequency observed for M0‐like and M2‐like EVs. Strikingly, human macrophages, isolated from the resected lungs of cancer patients, secreted EVs that expressed HLA‐DR at double the frequency and with greater intensity than M1‐like EVs. Quantitative analysis of single‐cell EV profiles from all four macrophage phenotypes revealed distinct secretion types, five of which were consistent across multiple sample cohorts. A sub‐population of M1‐like MDMs secreted EVs similar to lung macrophages, suggesting an expansion or recruitment of cells with a specific EV secretion profile within the lungs of cancer patients. Thus, quantitative analysis of EV heterogeneity can be used for single cell profiling and to reveal novel macrophage biology.
Laterally biased diffusion of males of the water flea Daphnia magna
Authors: Toyota Kenji , Yasugi Masaki , Tatarazako Norihisa , Iguchi Taisen , Watanabe Eiji
Published: April 2022

The water flea, Daphnia magna, is a representative zooplankton that lives in freshwater environments. It primarily propagates via asexual reproduction in normal and healthy environmental conditions. Unsuitable environmental conditions induce D. magna to change its mode of reproduction from asexual to sexual reproduction. During sexual reproduction, D. magna produces special tough eggs (resting eggs) that can survive severe environmental conditions. Despite an increase in our understanding of their mating behavior, the sex‐specific characteristics of swimming behavior among daphnid species are poorly understood. In this study, we analysed the swimming patterns and dynamics of female and male adult D. magna using computer modeling. Males displayed laterally biased diffusion in contrast to the homogeneous, nondirectional diffusion of females. Computer modeling analysis using a discrete‐time Markov chain simulation, in which the frequencies of turning behavior were evaluated as probability distributions, explained the greater diffusion of males in the horizontal direction. We presumed that high diffusion in the horizontal direction would increase the probability of encountering a distant mate. Our findings suggest that male D. magna increases genotypic heterogeneity by effectively selecting certain motion parameters.
Family with Peutz–Jeghers syndrome in Indonesia
Authors: Parewangi Muhammad Luthfi , Rusman Resha Dermawansyah , Akil Fardah , Daud Nu'man A S , Bachtiar Rini , Kusuma Susanto Hendra , Rifai Amelia , Tahir Akiko Syawalidhany , Miskad Upik , Syarifuddin Erwin
Published: April 2022

Peutz–Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterised by mucocutaneous pigmentation, gastrointestinal polyps and an increased risk of gastrointestinal and other cancers. We report an Indonesian woman, aged 28, with black spots on her lips who had multiple polyps extending from the stomach to the rectum. Her father and a son also had mucocutaneous lesions but they did not undergo gastrointestinal investigations. All three had mutations in the serine/threonine kinase 11 gene (STK11).
Association of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with disease severity in COVID‐19 patients: A pilot study
Authors: Lapić Ivana , Radić Antolic Margareta , Horvat Ivana , Premužić Vedran , Palić Jozefina , Rogić Dunja , Zadro Renata
Published: April 2022

The present study aimed to assess the association of 16 polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with COVID‐19 disease severity: FV G1691A, FV H1299R, FII G20210A, MTHFR C677T, MTHFR A1298, factor XIII V34L, PAI‐1 4G/5G, EPCR haplotypes (A1/A2/A3), eNOS −786 T > C, eNOS G894T, LTA C804A, ACE I/D, ITGB3 PIA1/A2, ITGA2B Baka/b, β‐Fbg −455 G > A and ApoB R3500Q. The study included 30 patients with severe COVID‐19 and 49 non‐severe COVID‐19 patients. All studied polymorphisms except ITGA2B Baka/b were determined using multilocus genotyping assays CVD StripAssays (ViennaLab Diagnostics), while ITGA2B was genotyped using a real‐time PCR method based on TaqMan technology. A higher frequency of carriers of at least one ITGB3 PIA2 allele was found in severe COVID‐19 patients (p = 0.009). The distribution of genotypes was significantly different for ß‐Fbg −455 G > A (p = 0.042), with only three homozygous AA genotypes found among severe COVID‐19 patients. The association with an increased risk for severe COVID‐19 was found for ITGB3, with carriers of at least one ITGB3 PIA2 allele having a 3.5‐fold greater risk of severe COVID‐19 (p = 0.011). Genotype distribution differences were obtained for the combinations of FV H1299R and FXIII V34L (p = 0.026), ITGB3 PIA1/A2 and ITGA2B Baka/b (p = 0.024), and ACE I/D and PAI‐1 4G/5G (p = 0.046). ITGB3 polymorphism emerged as an independent risk factor for severe COVID‐19 and homozygosity for ß‐Fbg −455 G > A mutation could contribute to disease severity. The combined effect of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors could further contribute to disease severity.
Plasma proteomic analysis reveals altered protein abundances in HIV‐infected patients with or without non‐Hodgkin lymphoma
Authors: Zhuang Ke , Zhang Yongxi , Mo Pingzheng , Deng Liping , Jiang Yong , Yu Lei , Mei Fanghua , Huang Shaoxin , Chen Xi , Yan Yajun , Tang Hongbin , Li Xiangdong , Xiong Yong , Wu Shuwen , Ke Hengning , Gui Xien , Lan Ke
Published: April 2022

The identification of circulating proteins associated with acquired immunodeficiency syndrome‐related non‐Hodgkin lymphoma (AIDS‐NHL) may help in the development of promising biomarkers for screening, diagnosis, treatment, and prognosis. Here, we used quantitative liquid chromatography‐tandem mass spectrometry (LC–MS/MS) to identify differentially expressed proteins (DEPs) in plasma collected from patients with AIDS‐NHL and human immunodeficiency virus (HIV)‐infected patients without NHL (HIV+). Proteins with a log2 (fold change) in abundance >0.26 and p < 0.05 were considered differentially abundant. In total, 84 DEPs were identified, among which 20 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. Some of the proteins were further verified in a retrospective analysis of the medical records of patients in a larger cohort. These markedly altered proteins were found to mediate pathophysiological pathways that likely contribute to AIDS‐NHL pathogenesis, such as the humoral immune response, complement activation, and complement and coagulation cascades. Our findings provide a new molecular understanding of AIDS‐NHL pathogenesis and provide new evidence supporting the identification of these proteins as possible biomarkers in AIDS‐NHL.
Microbial properties in tropical montane forest soils developed from contrasting parent material—An incubation experiment
Authors: Kidinda Laurent K. , Olagoke Folasade K. , Vogel Cordula , Bukombe Benjamin , Kalbitz Karsten , Doetterl Sebastian
Published: April 2022

Background

Soil microbes are key drivers of carbon (C) and nutrient cycling in terrestrial ecosystems, and their properties are influenced by the relationship between resource demand and availability.

Aims

Our objective was to investigate patterns of microbial properties and their controls to understand whether they differ between soils derived from geochemically contrasting parent material in tropical montane forests.

Methods

We measured microbial biomass C (MBCSoil), potential extracellular enzyme activity (pEEA), and assessed microbial investments in C and nutrient acquisition at the beginning and end of a 120‐day laboratory incubation experiment using soils developed from three geochemically contrasting parent material (i.e., mafic, mixed sediment, and felsic) and three soil depths (0–70 cm).

Results

We found that MBCSoil and pEEA were highest in soils developed from the mafic parent material. Microbial investment in C acquisition was highest in soils developed from mixed sedimentary rocks and lowest in soils developed from the felsic parent material. We propose that our findings are related to the strength of contrasting mineral‐related C stabilization mechanisms and varying C quality. No predominant microbial investment in nitrogen (N) acquisition was observed, whereas investment in phosphorus (P) acquisition was highest in subsoils. We found lower microbial investment in C acquisition in subsoils indicating relatively high C availability, and that microbes in subsoils can substantially participate in C cycling and limit C storage if moisture and oxygen conditions are suitable. Geochemical soil properties and substrate quality were important controls on MBCSoil per unit soil organic C (MBCSOC), particularly after the exhaustion of labile and fast cycling C, that is, at the end of the incubation.

Conclusion

Although a laboratory incubation experiment cannot reflect real‐world conditions, it allowed us to understand how soil properties affect microbial properties. We conclude that parent material is an important driver of microbial properties in tropical montane forests despite the advanced weathering degree of soils.
Los Aljezares archaeological site (Alicante, Spain) and the MIS 6/5 open‐air settlement in the Iberian Peninsula
Authors: EIXEA ALEIX , CUEVAS‐GONZÁLEZ JAIME , DÍEZ‐CANSECO DAVINIA , BEL MIGUEL ÁNGEL , BONNET ANA , CARRIÓN YOLANDA , MARTÍNEZ‐ALFARO ÁLVARO , MARTÍNEZ‐RUBIO VÍCTOR , MARTÍNEZ‐VAREA CARMEN M. , PARDO RAQUEL , RIOS‐GARAIZAR JOSEBA
Published: April 2022

The record of open‐air Middle Palaeolithic sites in the Iberian Peninsula—specifically in the Mediterranean basin—is scarce, hampering the interpretation of the landscape use strategies developed by Neanderthals in this area. In this work, we present Los Aljezares, a new Middle Palaeolithic site found in Pleistocene fluvio‐lacustrine deposits in the sedimentary basin of the Vinalopó River. A U/Th age (132 ± 10 ka) from associated carbonate deposits allows us to attribute the site to the uppermost part of the Middle Pleistocene to Late Pleistocene (marine isotope stage 6/5). To date, a total of two levels of human occupation have been identified in which the density of lithic remains is low compared with cave and rock shelter sites in the region. The first results of technology and use‐wear, raw material procurement and geological data indicate a settlement in Los Aljezares along a territory characterised by ephemeral channels and their associated palustrine and lacustrine zones. This palaeoenvironmental setting provided biotic and abiotic resources in a transit area between inland and coastal locations.
Is it C4 or ‘C3 in disguise’? Disentangling the ambiguity in palaeovegetation estimation
Authors: SREEMANY ARPITA , BERA MELINDA KUMAR
Published: April 2022

Increasing stable carbon isotopic ratio (δ13C) of sedimentary organic matter (SOM) has traditionally been interpreted to reflect an increase in C4 vegetation abundance, though microbial degradation or increasing δ13C values of C3 plants in response to precipitation change can also cause a similar effect. Therefore, δ13CSOM values alone cannot reveal the true origin of the observed 13C enrichment in SOM. Here, employing a wet‐oxidation method on modern sediment, we have demonstrated that this treatment removes partly degraded and degradation‐prone components of the C3 plant‐derived organic matter (OM). Therefore, it helps to understand the real contribution of C4‐derived organic carbon (OC) in the modern sediment and identify the C3 plant‐derived OC in disguise. As a test case, we extend our inference to Middle to Late Holocene lower Gangetic floodplain records, which were supposed to register a complete switchover from a C3‐dominated to a C4‐dominated system (~10‰ positive shifts in δ13CSOM values). However, the present study showed that ~60% (~6‰) of the observed positive shift in δ13CSOM values actually register a temporal change in the C3 plant end‐member δ13C value in response to reduction in Indian summer monsoon precipitation.
Reassessment of the temperature dependent oxidation of 2‐methyl‐3‐butene‐2‐ol (MBO) by Cl atoms: A kinetic and product study
Authors: Allani Amira , Romanias Manolis N.
Published: April 2022

In the current study, the temperature dependence of the Cl atom rate coefficient with 2‐methyl‐3‐butene‐2‐ol (MBO) is re‐assessed. Relative rate kinetic measurements were performed inside THALAMOS (thermally regulated atmospheric simulation chamber) facility under atmospheric pressure (760 Torr) of zero air in the temperature range of 256–353 K. The rate coefficient of the title reaction was found to be independent of temperature with a value of kMBO = (3.20 ± 0.10) × 10−10 cm3 molecule–1 s–1, where the quoted error corresponds to 2σ standard error of the mean value and includes the overall uncertainty of the measurements. Besides the kinetic study we have also determined the yields of the major products formed, in the temperature range of 273–353 K. Acetone and chloroacetaldehyde were identified as primary oxidation products with almost identical yields, ranging between 60% and 80%. Formaldehyde and methyl vinyl ketone were also observed with yields below 10% and 0.5%, respectively. Our experimental results indicate that the dominant reaction pathway is the addition of Cl atoms to the terminal carbon atom of MBO.
A novel feature space monitoring index of salinisation in the Yellow River Delta based on SENTINEL‐2B MSI images
Authors: Guo Bing , Yang Fei
Published: April 2022

Most of previous studies utilized the surface parameters from LANDSAT images to construct the feature space monitoring index model of salinisation (salinization), and a few studies that have combined the feature space model with SENTINEL‐2B MSI images have been reported. In addition, the red edge index derived from SENTINEL‐2B MSI images can provide more detailed information to indicate the vegetation condition when monitoring salinized land ecosystems. Based on SENTINEL‐2B MSI images, this paper introduces seven typical parameters, namely NDVI, MSAVI, SI, Albedo, NDre1, NDre2, and NDre3 (red edge index) to construct two category features space models (point‐to‐line type and point‐to‐point type), and then, a novel salinisation monitoring index for use in the Yellow River Delta (YRD). Our main conclusions showed that: (1) the monitoring index model based on SENTINEL‐2B MSI images and a feature space model has high applicability for the salinisation monitoring in the YRD, with an average precision of R2 = 0.8499; (2) the point‐to‐point monitoring index of soil salinisation based on the NDre1‐SI feature space model has the best inversion accuracy of R2 = 0.9305 and RMSE = 0.9926; (3) the red edge index can better indicate the state and evolution process of soil salinisation. The salinisation monitoring models that included the red edge indexes have higher inversion accuracy with an average value of R2 = 0.8650; (4) the soil salinisation in the YRD was more serious in its eastern and northeastern regions than other parts. The results provide a new technical and methodological approach for the prevention and treatment of regional salinisation.
Switchable Copolymerization of Maleic Anhydride/Epoxides/Lactide Mixtures: A Straightforward Approach to Block Copolymers with Unsaturated Polyester Sequences
Authors: Wang Yu‐Bo , Wang Ming‐Qian , Shi Yi‐Bo , Chen Xiao‐Lu , Song Dong‐Po , Li Yue‐Sheng , Wang Bin
Published: April 2022

Switchable copolymerization of oxygenated heterocycle mixtures by a single catalytic system has been proved to be a promising approach to sequence‐controlled block copolymers. However, there are still big challenges in one‐step synthesis of multiblock copolymers containing unsaturated polyester blocks from maleic anhydride, epoxides, and lactone mixtures. Herein, a switchable pathway for polylactide‐b‐poly(MAH‐alt‐epoxide)‐b‐polylactide block copolymers is established. The excellent chemoselectivity in multicomponent copolymerization is achieved by bipyridine bisphenolate aluminum complexes that can induce an obvious kinetic differentiation between ring‐opening copolymerization of maleic anhydride/epoxides and ring‐opening polymerization of lactide. The scope of the epoxide for switchable copolymerization is explored and it is found that the steric hindrance of the substituents on epoxide significantly influences the formation of block copolymers. Block copolymers with various sequential and topological structures can be easily prepared by exquisite selection of different initiators. Furthermore, it is demonstrated that the conversion of cis‐maleate units in the block copolyester could be completely converted to trans‐fumarate units by isomerization without chain degradation, cross‐linking, and chain scrambling.
Mefloquine induces ER stress and apoptosis in BRAFi‐resistant A375‐BRAFV600E/NRASQ61K malignant melanoma cells targeting intracranial tumors in a bioluminescent murine model
Authors: Jandova Jana , Park Sophia L. , Corenblum Mandi J. , Madhavan Lalitha , Snell Jeremy A. , Rounds Liliana , Wondrak Georg T.
Published: April 2022

Molecularly targeted therapeutics have revolutionized the treatment of BRAFV600E‐driven malignant melanoma, but the rapid development of resistance to BRAF kinase inhibitors (BRAFi) presents a significant obstacle. The use of clinical antimalarials for the investigational treatment of malignant melanoma has shown only moderate promise, attributed mostly to inhibition of lysosomal‐autophagic adaptations of cancer cells, but identification of specific antimalarials displaying single‐agent antimelanoma activity has remained elusive. Here, we have screened a focused library of clinically used artemisinin‐combination therapeutic (ACT) antimalarials for the apoptotic elimination of cultured malignant melanoma cell lines, also examining feasibility of overcoming BRAFi‐resistance comparing isogenic melanoma cells that differ only by NRAS mutational status (BRAFi‐sensitive A375‐BRAFV600E/NRASQ61 vs. BRAFi‐resistant A375‐BRAFV600E/NRASQ61K). Among ACT antimalarials tested, mefloquine (MQ) was the only apoptogenic agent causing melanoma cell death at low micromolar concentrations. Comparative gene expression‐array analysis (A375‐BRAFV600E/NRASQ61 vs. A375‐BRAFV600E/NRASQ61K) revealed that MQ is a dual inducer of endoplasmic reticulum (ER) and redox stress responses that precede MQ‐induced loss of viability. ER‐trackerTM DPX fluorescence imaging and electron microscopy indicated ER swelling, accompanied by rapid induction of ER stress signaling (phospho‐eIF2α, XBP‐1s, ATF4). Fluo‐4 AM‐fluorescence indicated the occurrence of cytosolic calcium overload observable within seconds of MQ exposure. In a bioluminescent murine model employing intracranial injection of A375‐Luc2 (BRAFV600E/NRASQ61K) cells, an oral MQ regimen efficiently antagonized brain tumor growth. Taken together, these data suggest that the clinical antimalarial MQ may be a valid candidate for drug repurposing aiming at chemotherapeutic elimination of malignant melanoma cells, even if metastasized to the brain and BRAFi‐resistant.
Longitudinal Follow‐Up of Mood in Cervical Dystonia and Influence on Age at Onset
Authors: Moriarty Andrew , Rafee Shameer , Ndukwe Ihedinachi , O'Riordan Sean , Hutchinson Michael
Published: April 2022

Background

Anxiety and depression are highly prevalent conditions in cervical dystonia and considered intrinsic to the disease mechanism. Psychiatric symptoms do not appear to be influenced by botulinum toxin therapy. Studies focusing on changes in mood disorder during the course of the disease are limited in this chronic, lifelong disorder.

Objective

To assess the longitudinal prevalence of mood disorder, pain, and quality of life in patients with cervical dystonia attending a botulinum toxin clinic.

Methods

Patients involved in phase I of our study were invited to be involved in reassessment using the Beck Depression Inventory, Second Revision; Beck Anxiety Index; Cervical Dystonia Impact Profile–58 (CDIP‐58); and the Toronto Western Spasmodic Torticollis Rating Scale–2 Pain Scale (TWSTRS2‐Pain).

Results

A total of 53 participants took part after a mean study interval duration of 24 months. There were no significant differences between the 2 study time points in the prevalence of anxiety (P = 0.2919) and depressive symptoms (P = 0.5). Self‐reported quality of life by CDIP‐58 (P = 0.96) and pain by TWSTRS2‐Pain (P = 0.9321) were unchanged. Men and women with significant symptoms of mood disorder had an earlier age of onset of cervical dystonia (P = 0.008).

Conclusion

Anxiety and depressive symptoms persist in cervical dystonia, seem to be unrelated to pain severity, and need to be specifically targeted to improve quality of life. The relationship between mood disorder and age of onset suggest that mood disorder may be part of the disease pathophysiology.
Advanced‐Stage Parkinson's Disease: From Identification to Characterization Using a Nationwide Database
Authors: Barer Yael , Gurevich Tanya , Chodick Gabriel , Giladi Nir , Gross Ruth , Cohen Raanan , Bergmann Lars , Jalundhwala Yash J. , Shalev Varda , Grabarnik‐John Meital , Thaler Avner
Published: April 2022

Background

As Parkinson's disease (PD) progresses, response to oral medications decreases and motor complications appear. Timely intervention has been demonstrated as effective in reducing symptoms. However, current instruments for the identification of these patients are often complicated and inadequate. It has been suggested that anti‐PD intensified therapy (IT) can serve as a proxy for increased burden of disease.

Objective

To explore whether IT aligns with events reflecting advanced PD (APD) burden.

Methods

This was a retrospective analysis of PD beneficiaries in the second‐largest healthcare provider in Israel. Patients with PD diagnosed between January 2000 and June 2018 and treated with levodopa (l‐dopa) ≥5 times/day and/or ≥1000 mg l‐dopa equivalent daily dose were defined as the IT cohort (n = 2037). Treated patients with PD not fulfilling this criterion were defined as the nonintensified therapy (NIT) cohort (n = 3402). Point prevalence and 5‐ and 10‐year cumulative incidence of IT were assessed. Baseline demographic and comorbidities, 1‐year healthcare resource use, health costs, and time to clinical events were assessed and compared between cohorts.

Results

IT was associated with significantly (P < 0.05) higher healthcare resource use compared with NIT. In turn, IT patients incurred higher healthcare costs (P < 0.001) and were at greater risk for mortality, hospitalization, disability, and device‐aided therapy use (P < 0.001, for all comparisons).

Conclusions

Treatment intensity can serve as an objective and robust indicator of more APD. This readily extractable marker can be easily integrated into electronic medical record alerts to actively target more advanced patients and to guide risk‐appropriate care.
Homogenization problems for the compressible Navier–Stokes system in 2D perforated domains
Authors: Nečasová Šárka , Pan Jiaojiao
Published: April 2022

In this paper, we study the homogenization problems for stationary compressible Navier–Stokes system in a bounded 2D domain, where the domain is perforated with very tiny holes (or obstacles) whose diameters are much smaller than their mutual distances. We obtain that the process of homogenization doesn't change the motion of the fluids. From another point of view, we obtain the same system of equations in asymptotic limit. It is the first result of homogenization problem in 2D compressible case.
A hydrodynamic model for analyzing the closure stresses in the wellbore strengthening problem
Authors: Sarris Ernestos N. , Gravanis Elias
Published: April 2022

The problem of creating unwanted fractures while drilling ultradeep wells is mitigated with the application of wellbore strengthening techniques. Despite the numerous applications, an open question remains about the efficiency of the loss of circulation materials (LCM) and its implications on the closure stress distribution change during plugging. This work investigates the effects on the stress field before and after plugging along the fracture extension axis by introducing a hydrodynamic plug. With the hydrodynamic plug, fluid flow is constrained by pressure conditions at specific locations in the fracture simulating the LCM. Three different scenarios were considered. First, the efficiency of the bridge is simulated by varying the pressure drop. Second, the location of the bridge inside the fracture and finally a nearly packed fracture. The models are fully coupled and were solved with the finite element method in impermeable and permeable hard rocks. We find that for high‐efficiency bridges, narrower fracture profiles are predicted, which causes the induced closure stresses to increase significantly. On the other hand, when the bridge is close and near the wellbore area, the fracture profiles are maintained wide and narrow when it is nearest to the tip. The predicted fracture geometry induces higher closure stresses when the plug is near the well and slightly reduces when it is near the tip. Finally, the pressure profile resulting from the packed fracture significantly affects the fracture dimensions, resulting in narrower fracture, however resulting in a smooth variation of induced closure stresses with high magnitude comparable to the stresses at the state of propagation. The diffusion occurring in the permeable case creates back‐stresses that appear to have an additive contribution to the induced closure stresses. This underlines the significance of diffusion on the induced coupled closure stresses for large fractures while performing wellbore strengthening methodologies.
Lineage tracing in human tissues
Authors: Gabbutt Calum , Wright Nicholas A , Baker Ann‐Marie , Shibata Darryl , Graham Trevor A
Published: April 2022

The dynamical process of cell division that underpins homeostasis in the human body cannot be directly observed in vivo, but instead is measurable from the pattern of somatic genetic or epigenetic mutations that accrue in tissues over an individual's lifetime. Because somatic mutations are heritable, they serve as natural lineage tracing markers that delineate clonal expansions. Mathematical analysis of the distribution of somatic clone sizes gives a quantitative readout of the rates of cell birth, death, and replacement. In this review we explore the broad range of somatic mutation types that have been used for lineage tracing in human tissues, introduce the mathematical concepts used to infer dynamical information from these clone size data, and discuss the insights of this lineage tracing approach for our understanding of homeostasis and cancer development. We use the human colon as a particularly instructive exemplar tissue. There is a rich history of human somatic cell dynamics surreptitiously written into the cell genomes that is being uncovered by advances in sequencing and careful mathematical analysis lineage of tracing data. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Emerging technologies for prenatal diagnosis: The application of whole genome and RNA sequencing
Authors: Liu Pengfei , Vossaert Liesbeth
Published: April 2022

DNA sequencing technologies for clinical genetic testing have been rapidly evolving in recent years, and steadily become more important within the field of prenatal diagnostics. This review aims to give an overview of recent developments and to describe how they have the potential to fill the gaps of the currently clinically implemented methods for prenatal diagnosis of various genetic disorders. It has been shown for postnatal testing that whole genome sequencing provides a set of added benefits compared to exome sequencing, and it is to be expected that this will be the case for prenatal testing as well. RNA‐sequencing, already used postnatally, can provide valuable complementary data to DNA‐based testing, and aid in variant interpretation. While not ready for clinical implementation, emerging technologies such as long‐read and Hi‐C sequencing analyses might add to the toolbox for interpreting the expanding genetic data sets generated by genome‐wide sequencing. Lastly, we also discuss some more practical implications of introducing these emerging technologies, which generate larger and larger genomic data sets, in the prenatal field.
Cost structure and resource efficiency of plasma processes
Authors: Oehr Christian , Hegemann Dirk , Liehr Michael , Wohlfart Peter
Published: April 2022

Total cost‐of‐ownership, operation costs, and resource efficiency of low‐pressure plasma systems and processes must be taken into consideration if new processes for surface treatment are to be introduced. All three aspects will determine the costs of any value increase per component subjected to a plasma process, and they will be the focus of this article. At first glance, coating costs using plasma processes seem to be dominated by high initial investments. However, the following discussion will show that operating costs are at least of the same importance. With the examples of solar cells, hard coatings, organic film deposition, and simple surface activation, it will be illustrated how the different factors above dominate final production cost.
Domain Wall Formation and Magnon Localization in Twisted Chromium Trihalides
Authors: Soriano David
Published: April 2022

The rise of twistronics revolutionizes the field of condensed matter physics, and more specifically the future applications of 2D materials. At small twist angles, the microscopic world becomes strongly correlated, and unexpected physical phenomena such as superconductivity emerge. For magnetic layers, stacking plays a crucial role in the magnetic exchange coupling between the layers leading to nontrivial spin configurations and flat spin‐wave dispersion when twisted. Herein, a short overview of the most recent theoretical and experimental works reporting the effect of twist angles on 2D magnets is given. In addition, the effect of the twist angle and the local antiferromagnetic interlayer exchange coupling on the formation of antiferromagnetic domains in chromium trihalides is discussed. Finally, some preliminary results on the effect of the stacking and the twist angle on the spin‐wave dispersion of bilayer CrI3 are shown.
Unusual Electrical and Magnetic Properties in Layered EuZn2As2
Authors: Blawat Joanna , Marshall Madalynn , Singleton John , Feng Erxi , Cao Huibo , Xie Weiwei , Jin Rongying
Published: April 2022

Eu‐based compounds often exhibit unusual magnetism, which is critical for nontrivial topological properties seen in materials such as EuCd2As2. The authors investigate the structure and physical properties of EuZn2As2 through measurements of the electrical resistivity, Hall effect, magnetization, and neutron diffraction. Their data show that EuZn2As2 orders antiferromagnetically with an A‐type spin configuration belowTN = 19 K. Surprisingly, there is strong evidence for dominant ferromagnetic fluctuations aboveTN, as reflected by positive Curie–Weiss temperature and extremely large negative magnetoresistance (MR) betweenTNandTfl≈200 K. Furthermore, the angle dependence of the MRabindicates field‐induced spin reorientation from theab‐plane to a direction ≈45° from theabplane. Compared to EuCd2As2, the doubledTNandTflmake EuZn2As2 a better platform for exploring nontrivial magnetic and electronic properties in both magnetic fluctuation (TN < T < Tfl) and ordered (T < TN) regimes.