bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality of Seagrass Meadows May Not Kill Their Methane Release
Authors: Smith Derek
Published: April 2022

New research indicates that seagrasses continue to release methane even after they die, complicating blue carbon initiatives.
Revealing the Circulation Pattern Most Conducive to Precipitation Extremes in Henan Province of North China
Authors: Zhang Sihan , Chen Yangruixue , Luo Yali , Liu Bo , Ren Guoyu , Zhou Tianjun , Martinez‐Villalobos Cristian , Chang Meiyu
Published: April 2022

Two catastrophic extreme precipitation events in July 2021 and August 1975 caused tremendous damages and deaths in Henan, one of the most populated provinces in China. Revealing the relationship between large‐scale circulation patterns and precipitation extremes is vital for understanding the physical mechanisms and providing potential value for improving prediction and hence reducing impacts. Here, nine large‐scale circulation patterns are identified for July–August using the self‐organizing map. We find daily precipitation extremes under the fifth pattern (P5), characterized with the strongest easterly wind anomalies in Henan, feature the highest frequency and the largest intensity. Seven out of total 11 days in the two catastrophic extreme precipitation events belong to P5, and the top two maximum hourly precipitation extremes over continental China occurred under P5. The larger intensity of precipitation extremes is attributed to the dynamical contribution, suggesting more‐intense precipitation extremes under P5 are largely dominated by stronger ascending motions.
Left ventricular hypertrophy and incident cognitive decline in older adults with hypertension
Authors: Xu Ying , Bouliotis George , Beckett Nigel S. , Antikainen Riitta L. , Anderson Craig S. , Bulpitt Christopher J. , Peters Ruth
Published: April 2022

The association between raised blood pressure and increased risk of subsequent cognitive decline is well known. Left ventricular hypertrophy (LVH), as a marker of hypertensive target organ damage, may help identify those at risk of cognitive decline. We assessed whether LVH was associated with subsequent cognitive decline or dementia in hypertensive participants aged ≥80 years in the randomized, placebo-controlled Hypertension in the Very Elderly Trial. LVH was assessed using 12-lead electrocardiography (ECG) based on the Cornell Product (CP-LVH), Sokolow-Lyon (SL-LVH), and Cornell Voltage (CV-LVH) criteria. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and annually. A fall in MMSE to <24 or an annual fall of >3 points were defined as cognitive decline and triggered dementia screening (Diagnostic Statistical Manual IV). Death was defined as a competing event. Fine-Gray regression models were used to examine the relationship between baseline LVH and cognitive outcomes. There were 2645 in the analytical sample, including 201 (7.6%) with CP-LVH, 225 (8.5%) SL-LVH and 251 (9.5%) CV-LVH. CP-LVH was associated with increased risk of cognitive decline, subdistribution hazard ratio (sHR)1.3 (95% confidence interval (CI) 1.01–1.67) in multivariate analyses. SL-LVH and CV-LVH were not associated with cognitive decline (sHR1.06 (95% CI 0.82–1.37) and sHR1.13 (95% CI 0.89–1.43), respectively). LVH was not associated with dementia. LVH may be related to subsequent cognitive decline, but evidence was inconsistent depending on ECG criterion and there were no associations with incident dementia. Additional work is needed to understand the relationships between blood pressure, LVH assessment and cognition.
Extremely premature infants born at 23–25 weeks gestation are at substantial risk for pulmonary hypertension
Authors: Sallmon Hannes , Koestenberger Martin , Avian Alexander , Reiterer Friedrich , Schwaberger Bernhard , Meinel Katharina , Cvirn Gerhard , Kurath-Koller Stefan , Gamillscheg Andreas , Hansmann Georg
Published: April 2022

Objective

Extremely low gestational age newborns (ELGANs) represent an especially vulnerable population. Herein, we aimed to determine incidence and severity of pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) in extremely immature ELGANs (gestational age: 230/6–256/7 weeks).

Methods

In this prospective observational cohort study, we assessed BPD-PH by means of several echocardiography markers and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at 3 and 12 months of chronological age. In addition, we analyzed incidence and efficacy of pharmacologic treatment for BPD-PH.

Results

At 3 months 15/34 ELGANs had echocardiographic evidence of BPD-PH, while at 12 months of age 6/34 still had PH. PH-targeted therapy consisted of sildenafil monotherapy in 11 and dual oral combination therapy (sildenafil and macitentan) in four ELGANs at 3 and 12 months.

Conclusion

44% (15/34) of ELGANs developed BPD-PH. All received PH-targeted pharmacotherapy at 3 months, leading to hemodynamic improvements at 12 months in most infants.
Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia
Authors: Bellon Alfredo , Feuillet Vincent , Cortez-Resendiz Alonso , Mouaffak Faycal , Kong Lan , Hong L. Elliot , De Godoy Lilian , Jay Therese M. , Hosmalin Anne , Krebs Marie-Odile
Published: April 2022

The long lapse between the presumptive origin of schizophrenia (SCZ) during early development and its diagnosis in late adolescence has hindered the study of crucial neurodevelopmental processes directly in living patients. Dopamine, a neurotransmitter consistently associated with the pathophysiology of SCZ, participates in several aspects of brain development including pruning of neuronal extensions. Excessive pruning is considered the cause of the most consistent finding in SCZ, namely decreased brain volume. It is therefore possible that patients with SCZ carry an increased susceptibility to dopamine’s pruning effects and that this susceptibility would be more obvious in the early stages of neuronal development when dopamine pruning effects appear to be more prominent. Obtaining developing neurons from living patients is not feasible. Instead, we used Monocyte-Derived-Neuronal-like Cells (MDNCs) as these cells can be generated in only 20 days and deliver reproducible results. In this study, we expanded the number of individuals in whom we tested the reproducibility of MDNCs. We also deepened the characterization of MDNCs by comparing its neurostructure to that of human developing neurons. Moreover, we studied MDNCs from 12 controls and 13 patients with SCZ. Patients’ cells differentiate more efficiently, extend longer secondary neurites and grow more primary neurites. In addition, MDNCs from medicated patients expresses less D1R and prune more primary neurites when exposed to dopamine. Haloperidol did not influence our results but the role of other antipsychotics was not examined and thus, needs to be considered as a confounder.
Efficacy of neurostimulation across mental disorders: systematic review and meta-analysis of 208 randomized controlled trials
Authors: Hyde Joshua , Carr Hannah , Kelley Nicholas , Seneviratne Rose , Reed Claire , Parlatini Valeria , Garner Matthew , Solmi Marco , Rosson Stella , Cortese Samuele , Brandt Valerie
Published: April 2022

Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), is a potentially effective treatment strategy for a number of mental conditions. However, no quantitative evidence synthesis of randomized controlled trials (RCTs) of TMS or tDCS using the same criteria including several mental conditions is available. Based on 208 RCTs identified in a systematic review, we conducted a series of random effects meta-analyses to assess the efficacy of NIBS, compared to sham, for core symptoms and cognitive functioning within a broad range of mental conditions. Outcomes included changes in core symptom severity and cognitive functioning from pre- to post-treatment. We found significant positive effects for several outcomes without significant heterogeneity including TMS for symptoms of generalized anxiety disorder (SMD = −1.8 (95% CI: −2.6 to −1), and tDCS for symptoms of substance use disorder (−0.73, −1.00 to −0.46). There was also significant effects for TMS in obsessive-compulsive disorder (−0.66, −0.91 to −0.41) and unipolar depression symptoms (−0.60, −0.78 to −0.42) but with significant heterogeneity. However, subgroup analyses based on stimulation site and number of treatment sessions revealed evidence of positive effects, without significant heterogeneity, for specific TMS stimulation protocols. For neurocognitive outcomes, there was only significant evidence, without significant heterogeneity, for tDCS for improving attention (−0.3, −0.55 to −0.05) and working memory (−0.38, −0.74 to −0.03) in individuals with schizophrenia. We concluded that TMS and tDCS can benefit individuals with a variety of mental conditions, significantly improving clinical dimensions, including cognitive deficits in schizophrenia which are poorly responsive to pharmacotherapy.
IL-36 signalling enhances a pro-tumorigenic phenotype in colon cancer cells with cancer cell growth restricted by administration of the IL-36R antagonist
Authors: Baker Kevin , O’Donnell Charlotte , Bendix Maura , Keogh Samuel , Byrne James , O’Riordain Michael , Neary Peter , Houston Aileen , Brint Elizabeth
Published: April 2022

The IL-36 cytokines are a recently described subset of the IL-1 family of cytokines, shown to play a role in the pathogenesis of intestinal diseases such as Inflammatory Bowel Disease (IBD). Given the link between IBD and colitis –associated cancer, as well as the involvement of other IL-1 family members in intestinal tumorigenesis, the aim of this work was to investigate whether IL-36 cytokines play a role in the pathogenesis of colon cancer. Whilst research to date has focused on the role of IL-36 family members in augmenting the immune response to induce tumour rejection, very little remains known about IL-36R signalling in tumour cells in this context. In this study we demonstrate that expression of IL-36 family member mRNA and protein are significantly increased in colorectal cancer tissue compared to adjacent non-tumour. In vitro assays showed stimulation of colon cancer cell lines with IL-36R agonists resulted in the activation of the pro-tumorigenic phenotypes of increased cellular migration, invasion and proliferation in both 2D and 3D models. In addition, the IL-36 cytokines induced strong expression of pro-inflammatory chemokines in both human and murine cell lines. Intraperitoneal injection of IL-36Ra significantly reduced tumour burden using the subcutaneous CT26 tumour model in syngeneic Balb/mice, and this was associated with a decrease in Ki-67 expression by tumour cells in the IL-36Ra- treated group relative to untreated, suggesting the inhibition of the pro-proliferative signalling of IL-36 agonists resulted in the decreased tumour size. Moreover, colon cancer cells lacking the IL-36R also showed reduced tumour growth and reduced Ki-67 expression in vivo. Taken together, this data suggests that targeting IL-36R signalling may be a useful targeted therapy for colorectal cancer patients with IL-36R+ tumour cells.
Telomere length and mitochondrial DNA copy number in bipolar disorder: identification of a subgroup of young individuals with accelerated cellular aging
Authors: Spano L. , Etain B. , Meyrel M. , Hennion V. , Gross G. , Laplanche J-L. , Bellivier F. , Marie-Claire C.
Published: April 2022

The 10–15-years decrease in life expectancy observed in individuals with bipolar disorder (BD) has been linked to the concept of accelerated cellular aging. Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) have been proposed as markers of cellular aging and comparisons between individuals with BD and healthy controls (HC) sometimes led to conflicting results. Previous studies had moderate sample sizes and studies combining these two markers into a single analysis are scarce. Using quantitative polymerase chain reaction, we measured both TL and mtDNAcn in DNA (peripheral blood) in a sample of 130 individuals with BD and 78 HC. Regression analyses, receiver operating characteristic (ROC), and clustering analyses were performed. We observed significantly lower TL and mtDNAcn in individuals with BD as compared to HC (respective decrease of 26.5 and 35.8%). ROC analyses showed that TL and mtDNAcn highly discriminated groups (AUC = 0.904 for TL and AUC = 0.931 for mtDNAcn). In the whole population, clustering analyses identified a group of young individuals (age around 36 years), with accelerated cellular aging (both shorter TL and lower mtDNAcn), which consisted mostly of individuals with BD (85.5%). The subgroup of patients with young age but accelerated aging was not characterized by specific clinical variables related to the course of BD or childhood maltreatment. However, patients in this subgroup were more frequently treated with anticonvulsants. Further characterization of this subgroup is required to better understand the molecular mechanisms and the risk factors of accelerated cellular aging in BD.
Ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory myeloma: MUKeight phase II randomised controlled trial results
Authors: Auner Holger W. , Brown Sarah R. , Walker Katrina , Kendall Jessica , Dawkins Bryony , Meads David , Morgan Gareth J. , Kaiser Martin F. , Cook Mark , Roberts Sadie , Parrish Christopher , Cook Gordon
Published: April 2022

The all-oral combination of ixazomib, cyclophosphamide, and dexamethasone (ICD) is well tolerated and effective in newly diagnosed and relapsed multiple myeloma (MM). We carried out MUKeight, a randomised, controlled, open, parallel group, multi-centre phase II trial in patients with relapsed MM after prior treatment with thalidomide, lenalidomide, and a proteasome inhibitor (ISRCTN58227268), with the primary objective to test whether ICD has improved clinical activity compared to cyclophosphamide and dexamethasone (CD) in terms of progression-free survival (PFS). Between January 2016 and December 2018, 112 participants were randomised between ICD (n = 58) and CD (n = 54) in 33 UK centres. Patients had a median age of 70 years and had received a median of four prior lines of therapy. 74% were classed as frail. Median PFS in the ICD arm was 5.6 months, compared to 6.7 months with CD (hazard ratio (HR) = 1.21, 80% CI 0.9–1.6, p = 0.3634). Response rates and overall survival were not significantly different between ICD and CD. Dose modifications or omissions, and serious adverse events (SAEs), occurred more often in the ICD arm. In summary, the addition of ixazomib to cyclophosphamide and dexamethasone did not improve outcomes in the comparatively frail patients enroled in the MUKeight trial.
Hypothesized pathways for the association of vitamin D status and insulin sensitivity with resting energy expenditure: a cross sectional mediation analysis in Australian adults of European ancestry
Authors: Soares Mario J. , Calton Emily K. , Pathak Kaveri , Zhao Yun
Published: April 2022

Background

The role of vitamin D in human energy expenditure requires confirmation. We explored whether insulin sensitivity (IS)/insulin resistance (IR) mediated the association of vitamin D status (25OHD) on resting energy expenditure (REE).

Methods

REE, body composition (by DEXA) and clinical biochemistry of 155 Australian men and women were collated. A hypothesized mediation pathway through IS/IR on the direct association between 25OHD and REE was modeled, using three surrogate indices of IS/IR: McAuley’s insulin sensitivity index (McA), Quantitative insulin sensitivity check index (QUICKI) and triglyceride to glucose ratio (TYG). The modeling was performed on PROCESS SPSS Macro (version 4.0) based on 5000 bootstrapped samples, with and without the adjustment for covariates.

Results

Unadjusted models indicated a sizeable negative mediation by all IS/IR indices but no significant direct effect of 25OHD on REE. On adjustment for covariates, a negative indirect mediation effect of McA [β coefficient (SE) −2.1(0.821); bootstrapped 95% CI:−3.934, −0.703;p < 0.05] and a similar negative mediation of TYG [−1.935 (0.780); bootstrapped 95% CI: (−3.679, −0.622;p < 0.05] was observed. These models also showed a positive direct effect of 25OHD on REE. In contrast, QUICKI made a smaller contribution to the total effect though in the same direction as the other two measures [−0.783 (0.534); bootstrapped 95% CI: (−1.939, 0.134;P > 0.05].

Conclusions

A sizeable, partial, negative mediation of IS/IR on the direct relationship between 25OHD and REE, dampened the total effect of vitamin D on REE. Validation of the proposed causal framework would clarify vitamin D’s role in human energy metabolism.
DNA methylation signature associated with Bohring-Opitz syndrome: a new tool for functional classification of variants in ASXL genes
Authors: Awamleh Zain , Chater-Diehl Eric , Choufani Sanaa , Wei Elizabeth , Kianmahd Rebecca R. , Yu Anna , Chad Lauren , Costain Gregory , Tan Wen-Hann , Scherer Stephen W. , Arboleda Valerie A. , Russell Bianca E. , Weksberg Rosanna
Published: April 2022

The additional sex combs-like (ASXL) gene family—encoded by ASXL1, ASXL2, and ASXL3—is crucial for mammalian development. Pathogenic variants in the ASXL gene family are associated with three phenotypically distinct neurodevelopmental syndromes. Our previous work has shown that syndromic conditions caused by pathogenic variants in epigenetic regulatory genes show consistent patterns of genome-wide DNA methylation (DNAm) alterations, i.e., DNAm signatures in peripheral blood. Given the role of ASXL1 in chromatin modification, we hypothesized that pathogenic ASXL1 variants underlying Bohring-Opitz syndrome (BOS) have a unique DNAm signature. We profiled whole-blood DNAm for 17 ASXL1 variants, and 35 sex- and age-matched typically developing individuals, using Illumina’s Infinium EPIC array. We identified 763 differentially methylated CpG sites in individuals with BOS. Differentially methylated sites overlapped 323 unique genes, including HOXA5 and HOXB4, supporting the functional relevance of DNAm signatures. We used a machine-learning classification model based on the BOS DNAm signature to classify variants of uncertain significance in ASXL1, as well as pathogenic ASXL2 and ASXL3 variants. The DNAm profile of one individual with the ASXL2 variant was BOS-like, whereas the DNAm profiles of three individuals with ASXL3 variants were control-like. We also used Horvath’s epigenetic clock, which showed acceleration in DNAm age in individuals with pathogenic ASXL1 variants, and the individual with the pathogenic ASXL2 variant, but not in individuals with ASXL3 variants. These studies enhance our understanding of the epigenetic dysregulation underpinning ASXL gene family-associated syndromes.
ERN GENTURIS clinical practice guidelines for the diagnosis, treatment, management and surveillance of people with schwannomatosis
Authors: Evans D. Gareth , Mostaccioli Stefania , Pang David , Fadzil O Connor Mary , Pittara Melpo , Champollion Nicolas , Wolkenstein Pierre , Thomas Nick , Ferner Rosalie E. , Kalamarides Michel , Peyre Matthieu , Papi Laura , Legius Eric , Becerra Juan Luis , King Andrew , Duff Chris , Stivaros Stavros , Blanco Ignacio
Published: April 2022

A Guideline Group (GG) was convened from multiple specialties and patients to develop the first comprehensive schwannomatosis guideline. The GG undertook thorough literature review and wrote recommendations for treatment and surveillance. A modified Delphi process was used to gain approval for recommendations which were further altered for maximal consensus. Schwannomatosis is a tumour predisposition syndrome leading to development of multiple benign nerve-sheath non-intra-cutaneous schwannomas that infrequently affect the vestibulocochlear nerves. Two definitive genes (SMARCB1/LZTR1) have been identified on chromosome 22q centromeric to NF2 that cause schwannoma development by a 3-event, 4-hit mechanism leading to complete inactivation of each gene plus NF2. These genes together account for 70–85% of familial schwannomatosis and 30–40% of isolated cases in which there is considerable overlap with mosaic NF2. Craniospinal MRI is generally recommended from symptomatic diagnosis or from age 12–14 if molecularly confirmed in asymptomatic individuals whose relative has schwannomas. Whole-body MRI may also be deployed and can alternate with craniospinal MRI. Ultrasound scans are useful in limbs where typical pain is not associated with palpable lumps. Malignant-Peripheral-Nerve-Sheath-Tumour-MPNST should be suspected in anyone with rapidly growing tumours and/or functional loss especially with SMARCB1-related schwannomatosis. Pain (often intractable to medication) is the most frequent symptom. Surgical removal, the most effective treatment, must be balanced against potential loss of function of adjacent nerves. Assessment of patients’ psychosocial needs should be assessed annually as well as review of pain/pain medication. Genetic diagnosis and counselling should be guided ideally by both blood and tumour molecular testing.
Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer
Authors: Minas Tsion Zewdu , Candia Julián , Dorsey Tiffany H. , Baker Francine , Tang Wei , Kiely Maeve , Smith Cheryl J. , Zhang Amy L. , Jordan Symone V. , Obadi Obadi M. , Ajao Anuoluwapo , Tettey Yao , Biritwum Richard B. , Adjei Andrew A. , Mensah James E. , Hoover Robert N. , Jenkins Frank J. , Kittles Rick , Hsing Ann W. , Wang Xin W. , Loffredo Christopher A. , Yates Clayton , Cook Michael B. , Ambs Stefan
Published: April 2022

There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determine if men of African descent harbor a unique systemic immune-oncological signature and measure 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis are elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associates with metastatic and lethal prostate cancer, pointing to clinical importance. Moreover, two markers, pleiotrophin and TNFRSF9, predict poor disease survival specifically among African American men. These findings indicate that immune-oncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.
Biological invasions facilitate zoonotic disease emergences
Authors: Zhang Lin , Rohr Jason , Cui Ruina , Xin Yusi , Han Lixia , Yang Xiaona , Gu Shimin , Du Yuanbao , Liang Jing , Wang Xuyu , Wu Zhengjun , Hao Qin , Liu Xuan
Published: April 2022

Outbreaks of zoonotic diseases are accelerating at an unprecedented rate in the current era of globalization, with substantial impacts on the global economy, public health, and sustainability. Alien species invasions have been hypothesized to be important to zoonotic diseases by introducing both existing and novel pathogens to invaded ranges. However, few studies have evaluated the generality of alien species facilitating zoonoses across multiple host and parasite taxa worldwide. Here, we simultaneously quantify the role of 795 established alien hosts on the 10,473 zoonosis events across the globe since the 14thcentury. We observe an average of ~5.9 zoonoses per alien zoonotic host. After accounting for species-, disease-, and geographic-level sampling biases, spatial autocorrelation, and the lack of independence of zoonosis events, we find that the number of zoonosis events increase with the richness of alien zoonotic hosts, both across space and through time. We also detect positive associations between the number of zoonosis events per unit space and climate change, land-use change, biodiversity loss, human population density, and PubMed citations. These findings suggest that alien host introductions have likely contributed to zoonosis emergences throughout recent history and that minimizing future zoonotic host species introductions could have global health benefits.
Historically inconsistent productivity and respiration fluxes in the global terrestrial carbon cycle
Authors: Jian Jinshi , Bailey Vanessa , Dorheim Kalyn , Konings Alexandra G. , Hao Dalei , Shiklomanov Alexey N. , Snyder Abigail , Steele Meredith , Teramoto Munemasa , Vargas Rodrigo , Bond-Lamberty Ben
Published: April 2022

The terrestrial carbon cycle is a major source of uncertainty in climate projections. Its dominant fluxes, gross primary productivity (GPP), and respiration (in particular soil respiration, RS), are typically estimated from independent satellite-driven models and upscaled in situ measurements, respectively. We combine carbon-cycle flux estimates and partitioning coefficients to show that historical estimates of global GPP and RS are irreconcilable. When we estimate GPP based on RS measurements and some assumptions about RS:GPP ratios, we found the resulted global GPP values (bootstrap mean $${149}_{-23}^{+29}$$

149

−
23

+
29

Pg C yr−1) are significantly higher than most GPP estimates reported in the literature ($${113}_{-18}^{+18}$$

113

−
18

+
18

Pg C yr−1). Similarly, historical GPP estimates imply a soil respiration flux (RsGPP, bootstrap mean of $${68}_{-8}^{+10}$$

68

−
8

+
10

Pg C yr−1) statistically inconsistent with most published RS values ($${87}_{-8}^{+9}$$

87

−
8

+
9

Pg C yr−1), although recent, higher, GPP estimates are narrowing this gap. Furthermore, global RS:GPP ratios are inconsistent with spatial averages of this ratio calculated from individual sites as well as CMIP6 model results. This discrepancy has implications for our understanding of carbon turnover times and the terrestrial sensitivity to climate change. Future efforts should reconcile the discrepancies associated with calculations for GPP and Rs to improve estimates of the global carbon budget.
Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses
Authors: Rodríguez-Ubreva Javier , Arutyunyan Anna , Bonder Marc Jan , Del Pino-Molina Lucía , Clark Stephen J. , de la Calle-Fabregat Carlos , Garcia-Alonso Luz , Handfield Louis-François , Ciudad Laura , Andrés-León Eduardo , Krueger Felix , Català-Moll Francesc , Rodríguez-Cortez Virginia C. , Polanski Krzysztof , Mamanova Lira , van Dongen Stijn , Kiselev Vladimir Yu. , Martínez-Saavedra María T. , Heyn Holger , Martín Javier , Warnatz Klaus , López-Granados Eduardo , Rodríguez-Gallego Carlos , Stegle Oliver , Kelsey Gavin , Vento-Tormo Roser , Ballestar Esteban
Published: April 2022

Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients.
Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification
Authors: Zi Zhenzhen , Zhang Zhuzhen , Feng Qiang , Kim Chiho , Wang Xu-Dong , Scherer Philipp E. , Gao Jinming , Levine Beth , Yu Yonghao
Published: April 2022

The evolutionarily conserved serine/threonine kinase mTORC1 is a central regulator of cell growth and proliferation. mTORC1 is activated on the lysosome surface. However, once mTORC1 is activated, it is unclear whether mTORC1 phosphorylates local lysosomal proteins to regulate specific aspects of lysosomal biology. Through cross-reference analyses of the lysosome proteome with the mTORC1-regulated phosphoproteome, we identify STK11IP as a lysosome-specific substrate of mTORC1. mTORC1 phosphorylates STK11IP at Ser404. Knockout of STK11IP leads to a robust increase of autophagy flux. Dephosphorylation of STK11IP at Ser404 represses the role of STK11IP as an autophagy inhibitor. Mechanistically, STK11IP binds to V-ATPase, and regulates the activity of V-ATPase. Knockout of STK11IP protects mice from fasting or Methionine/Choline-Deficient Diet (MCD)-induced fatty liver. Thus, our study demonstrates that STK11IP phosphorylation represents a mechanism for mTORC1 to regulate lysosomal acidification and autophagy, and points to STK11IP as a promising therapeutic target for the amelioration of diseases with aberrant autophagy signaling.
Quantifying daily rhythms with non-negative matrix factorization applied to mobile phone data
Authors: Aledavood Talayeh , Kivimäki Ilkka , Lehmann Sune , Saramäki Jari
Published: April 2022

Human activities follow daily, weekly, and seasonal rhythms. The emergence of these rhythms is related to physiology and natural cycles as well as social constructs. The human body and its biological functions undergo near 24-h rhythms (circadian rhythms). While their frequencies are similar across people, their phases differ. In the chronobiology literature, people are categorized into morning-type, evening-type, and intermediate-type groups called chronotypes based on their tendency to sleep at different times of day. Typically, this typology builds on carefully designed questionnaires or manually crafted features of time series data on people’s activity. Here, we introduce a method where time-stamped data from smartphones are decomposed into components using non-negative matrix factorization. The method does not require any predetermined assumptions about the typical times of sleep or activity: the results are fully context-dependent and determined by the most prominent features of the activity data. We demonstrate our method by applying it to a dataset of mobile phone screen usage logs of 400 university students, collected over a year. We find four emergent temporal components: morning activity, night activity, evening activity and activity at noon. Individual behavior can be reduced to weights on these four components. We do not observe any clear categories of people based on the weights, but individuals are rather placed on a continuous spectrum according to the timings of their phone activities. High weights for the morning and night components strongly correlate with sleep and wake-up times. Our work points towards a data-driven way of characterizing people based on their full daily and weekly rhythms of activity and behavior, instead of only focusing on the timing of their sleeping periods.
Bladder cancer cells shift rapidly and spontaneously to cisplatin-resistant oxidative phosphorylation that is trackable in real time
Authors: Xu Tong , Junge Jason A. , Delfarah Alireza , Lu Yi-Tsung , Arnesano Cosimo , Iqbal Maheen , Delijani Kevin , Hsieh Tien-Chan , Hodara Emmanuelle , Mehta Hemal H. , Cohen Pinchas , Graham Nicholas A. , Fraser Scott E. , Goldkorn Amir
Published: April 2022

Genetic mutations have long been recognized as drivers of cancer drug resistance, but recent work has defined additional non-genetic mechanisms of plasticity, wherein cancer cells assume a drug resistant phenotype marked by altered epigenetic and transcriptional states. Currently, little is known about the real-time, dynamic nature of this phenotypic shift. Using a bladder cancer model of nongenetic plasticity, we discovered that rapid transition to drug resistance entails upregulation of mitochondrial gene expression and a corresponding metabolic shift towards the tricarboxylic acid cycle and oxidative phosphorylation. Based on this distinction, we were able to track cancer cell metabolic profiles in real time using fluorescence lifetime microscopy (FLIM). We observed single cells transitioning spontaneously to an oxidative phosphorylation state over hours to days, a trend that intensified with exposure to cisplatin chemotherapy. Conversely, pharmacological inhibition of oxidative phosphorylation significantly reversed the FLIM metabolic signature and reduced cisplatin resistance. These rapid, spontaneous metabolic shifts offer a new means of tracking nongenetic cancer plasticity and forestalling the emergence of drug resistance.
Controlled polymerization of metal complex monomers – fabricating random copolymers comprising different metal species and nano-colloids
Authors: Osawa Shigehito , Kurokawa Sosuke , Otsuka Hidenori
Published: April 2022

Monomers with metal complexes were polymerized and the random co-polymers having different metal species were successfully obtained, further extending to prepare nanoparticles using plasmid DNA as a template and the polymers as lego blocks.
Multiscale molecular modelling: from electronic structure to dynamics of nanosystems and beyond
Authors: Salahub Dennis R.
Published: April 2022

This tutorial review provides an introduction to multiscale modelling of complex chemical, physical and biological processes through case studies, aimed at beginning researchers and more senior colleagues who are changing direction to focus on multiscale aspects of their research.
Nanomaterial-assisted thread-based isotachophoresis with on-thread solute trapping
Authors: Chen Liang , Ghiasvand Alireza , Sanz Rodriguez Estrella , Innis Peter C. , Paull Brett
Published: April 2022

This research describes a nanomaterial-assisted TB-ITP setup for the clean-up, preconcentration, and trapping of alkaloids in biological fluids, followed by their on-thread DESI-MS determination.
Partial induced reorientation of 5CB in a liquid crystal microarray and a signal-on sensing assay for the detection of aflatoxin B1
Authors: Wang Shihong , Huang Ting , Zhou Jun , Chen Qianshan , Wu Zhaoyang , Yu Ruqin
Published: April 2022

A signal-on liquid crystal microarray (LCM) sensor with a micro-spectral optical signal for the detection of AFB1.
Do 2-coordinate iodine(i) and silver(i) complexes form nucleophilic iodonium interactions (NIIs) in solution?
Authors: Wilcox Scott , Sethio Daniel , Ward Jas S. , Frontera Antonio , Lindh Roland , Rissanen Kari , Erdélyi Máté
Published: April 2022

The interaction of a [bis(pyridine)iodine(i)]+ cation with a [bis(pyridine)silver(i)]+ cation, in which an iodonium ion acts as a nucleophile by transferring electron density to the silver(i) cation, is reinvestigated herein.
Correction: Chemical structure modulation in conductive MOFs by adjusting the oxidation state of the ligand and introducing alkali metal ions
Authors: Wu Xiaoyu , Wu Haowei , Wu Sicheng , Sun Yimeng , Zhu Jia , Zou Ye , Xu Wei , Zhu Daoben
Published: April 2022

Correction for ‘Chemical structure modulation in conductive MOFs by adjusting the oxidation state of the ligand and introducing alkali metal ions’ by Xiaoyu Wu et al., Chem. Commun., 2022, 58, 2702–2705, DOI: 10.1039/D1CC06407J.
Facile synthesis of polypyrrole nanoparticles with tunable conductivity for efficient electromagnetic wave absorption and shielding performance
Authors: Dai Yun-Liang , Zhang Xiao-Juan , Wen Bian-Ying , Du Qiu-Yue
Published: April 2022

The tunable σ of PPy nanoparticles can serve as a switch to fabricate efficient EM absorbing and shielding materials. PPy with medium σ is suitable as an absorbent, while PPy with higher σ tends to be used as a shielding filler.
Insight into cold- and melt crystallization phenomena of a smectogenic liquid crystal
Authors: Drzewicz Anna , Juszyńska-Gałązka Ewa , Jasiurkowska-Delaporte Małgorzata , Kula Przemysław
Published: April 2022

This paper describes the insight into the different nature of cold- and melt crystallization kinetics of a smectogenic liquid crystal.
Collision-induced dissociation of homodimeric and heterodimeric radical cations of 9-methylguanine and 9-methyl-8-oxoguanine: correlation between intra-base pair proton transfer originating from the N1–H at a Watson–Crick edge and non-statistical dissociation
Authors: Moe May Myat , Benny Jonathan , Liu Jianbo
Published: April 2022

Non-statistical dissociation in heterodimeric 8-oxoguanine–guanine base-pair radical cation.
Theoretical study of the O(3P) + SiH4 reaction: global potential energy surface, kinetics and dynamics study
Authors: Rangel C. , Espinosa-Garcia J.
Published: April 2022

A global potential energy surface based on high-level ab initio calculations describing the O(3P) + SiH4 → HO + SiH3 reaction helps in understanding kinetics and dynamics discrepancies.
First principles molecular dynamics calculations of the mechanical properties of endofullerenes containing noble gas atoms or small molecules
Authors: Pizzagalli Laurent
Published: April 2022

The mechanical properties of endofullerenes have been investigated by performing compression tests using finite temperature first principles molecular dynamics calculations.
Monothia [22]pentaphyrin(2.0.1.1.0): a core-modified isomer of sapphyrin
Authors: Sahoo Sipra Sucharita , Sahoo Sameeta , Panda Pradeepta K.
Published: April 2022

A novel [22]pentaphyrin(2.0.1.1.0) was designed and synthesized, displaying the attributes of both sapphyrin and porphycene; it is hence named sapphycene and exhibits unique coordination chemistry as a neutral ligand.
Significantly improved radiochemical yields in gaseous tritium reactions by iridium(i)-catalyzed hydrogen isotope exchange
Authors: Morawietz Patrick , Weck Remo , Scholte Andrew A. , Atzrodt Jens , Güssregen Stefan , Derdau Volker
Published: April 2022

Hydrogen isotope exchange reactions with iridium(i) catalyst [(COD)Ir(IMes)(PPh3)]X 2 with significantly increased (up to 7 fold) radiochemical yields (RCY) in tritium gas reactions are reported.
Nitrogen-doped graphene quantum dots coated with molecularly imprinted polymers as a fluorescent sensor for selective determination of warfarin
Authors: Li Peipei , Du Yingxiang , Ma Mingxuan , Zhang Jian
Published: April 2022

The strong photoluminescence of NGQDs and the selectivity of MIPs were combined to construct a fluorescent sensor for rapid determination of warfarin.
Electrochemically reconstructed high-entropy amorphous FeCoNiCrVB as a highly active oxygen evolution catalyst
Authors: Zhong Xu , Zhu Yin’an , Dai Weiji , Yu Jin , Lu Tao , Pan Ye
Published: April 2022

Highly active and robust electrocatalysts for the oxygen evolution reaction by intentional surface reconstruction of high-entropy amorphous alloys.
Mesoporous maltose/calcium oxalate hybrid material with abundant reaction sites and its efficient Pb(ii) removal from diverse water bodies
Authors: Chen Xinxin , Zhang Xia , Li Fei , Yang Xitong , Du Mengmeng , Fan Jing
Published: April 2022

Maltose/calcium oxalate exhibits high capacity and selective adsorption of Pb(ii) due to the synergistic mechanism of ion exchange, electrostatic and complexation.
Radical borylation of vinyl azides with NHC-boranes: divergent synthesis of α-boryl ketones and borylated triazoles
Authors: Zhang Yifei , Liao Yangzhen , Liu Peijun , Ran Yu , Liu Xiaozu
Published: April 2022

A radical borylation of vinyl azides with NHC-boranes in the presence of tBuSH is described, which enables the divergent synthesis of α-boryl ketones and borylated triazoles with excellent functional group tolerance and a broad substrate scope.
Influence of period and surface anchoring strength in liquid crystal optical axis gratings
Authors: Xue Xiangyu , Nys Inge , Neyts Kristiaan , Beeckman Jeroen
Published: April 2022

LC-based geometric phase optics are becoming increasingly promising. Our research provides an in-depth study of the behavior of small-period LC optical axis gratings, leading to the fabrication of higher quality optical components.
An Introduction to Speech Privacy for Early Career Clinicians: General Considerations and the Specific Example of Electrolarynx Users
Authors: Cox Steven R. , Koenig Laura L.
Published: April 2022

Purpose:

This article introduces early career clinicians to speech privacy (SP): its definition, a brief history in the context of the Health Insurance Portability and Accountability Act, and applications in health care settings. General considerations for speech-language pathologists (SLPs) are outlined, along with basic principles for considering what might threaten SP. The example of speakers who use an electrolarynx (EL) is used to call attention to some specific issues that clinicians may encounter in trying to maintain SP.

Conclusions:

This article provided an overview of SP considerations for early career clinicians. In the case of EL users, these include the unique quality of EL speech and the settings in which SLPs may work with these patients. More research is needed to investigate SP concerns for specific clinical populations that seek SLP services and the physical conditions in which clinician–client discussions occur. Recommendations for clinical practice are provided.
Optimal distributed generation penetration considering relay coordination and power quality requirements
Authors: Sadeghi Mohammad Hossein , Dastfan Ali , Damchi Yaser
Published: April 2022

Although the electric energy supply from distributed generation (DG) resources is increasing, these sources also face limitations. Protection and power quality constraints are the most important issues that limit the maximum DG penetration in power systems. Changing the short circuit level due to DGs' presence—especially synchronous‐based (SDG) type—may lead to miscoordination of the protective relays. Also, standard harmonic limits may be violated due to harmonic injection of inverter‐based DGs and non‐linear loads. A protection coordination problem is solved for the basic configuration, and the optimal settings are applied. Then, using a proposed approach and a new objective function, the location, size, and type of DGs are optimized to maximize the DG penetration and the speed of protection system, while reducing power losses. Finally, the protection setting of SDGs is optimized and applied. In these optimizations, the protection coordination constraints and the power quality requirements are considered and met. IEEE 14‐bus system and a real sub‐transmission system are simulated to evaluate the proposed approach and the new objective function. The obtained results show significant power loss reduction and protection speed improvement for different scenarios and case studies.
The morphology of the HD 163296 jet as a window on its planetary system
Authors: Kirwan A. , Murphy A. , Schneider P. C. , Whelan E. T. , Dougados C. , Eislöffel J.
Published: April 2022

Context. HD 163296 is a Herbig Ae star which drives a bipolar knotty jet with a total length of ~6000 au. Strong evidence exists that the disk of HD 163296 harbors planets. Studies have shown that the presence of companions around jet-driving stars could affect the morphology of the jets. This includes a ‘wiggling’ of the jet axis and a periodicity in the positions of the jet knots.

Aims. In this study we investigate the morphology (including the jet width and axis position) and proper motions of the HD 163296 jets, and use our results to better understand the whole system.

Methods. This study is based on optical integral-field spectroscopy observations obtained with VLT/MUSE in 2017. Using spectro-images and position velocity diagrams extracted from the MUSE data cube, we investigated the number and positions of the jet knots. A comparison was made to X-shooter data collected in 2012 and the knot proper motions were estimated. The jet width and jet axis position with distance from the star were studied from the extracted spectro-images. This was done using Gaussian fitting to spatial profiles of the jet emission extracted perpendicular to the position angle of the jet. The centroid of the fit is taken as the position of the jet axis.

Results. We observe the merging of knots and identify two previously undetected knots. We find proper motions that are broadly in agreement with previous studies. The jet width increases with distance from the source and we measure an opening angle of ~5° and 2.5° for the red and blue lobes, respectively. Measurements of the jet axis position, derived from Gaussian centroids of transverse intensity profiles, reveal a similar pattern of deviation in all forbidden emission lines along the first 20 arcsec of the jets. This result is interpreted as being due to asymmetric shocks and not due to a wiggling of the jet axis.

Conclusions. The number of new knots detected and their positions challenge the 16-yr knot ejection periodicity proposed in prior studies, arguing for a more complicated jet system than was previously assumed. We use the non-detection of a jet axis wiggling to rule out companions with a mass >0.1 M⊙ and orbits between 1 au and 35 au. Any object inferred at these distances using other methods must be a brown dwarf or planet, otherwise it would have impacted the jet axis position. Both the precession and orbital motion scenarios are considered. Overall it is concluded that it is difficult to detect planets with orbits >1 au through a study of the jet axis.
H2CS deuteration maps towards the pre-stellar core L1544
Authors: Spezzano S. , Sipilä O. , Caselli P. , Jensen S. S. , Czakli S. , Bizzocchi L. , Chantzos J. , Esplugues G. , Fuente A. , Eisenhauer F.
Published: April 2022

Context. Deuteration is a crucial tool for understanding the complexity of interstellar chemical processes, especially when they involve the interplay of gas-phase and grain-surface chemistry. In the case of multiple deuteration, comparing observation with the results of chemical modelling is particularly effective to study how molecules are inherited in the different stages within the process of star and planet formation.

Aims. We aim to study the D/H ratio in H2CS across the prototypical pre-stellar core L1544. This study allows us to test current gas–dust chemical models involving sulfur in dense cores.

Methods. Here, we present single-dish observations of H2CS, HDCS and D2CS with the IRAM 30 m telescope. We analysed their column densities and distributions and compared these observations with gas–grain chemical models. The deuteration maps of H2CS in L1544 were compared with the deuteration maps of methanol, H2CO, N2H+, and HCO+ towards the same source. Furthermore, we compared the single and double deuteration of H2CS towards the dust peak of L1544 with H2CO and c-C3H2. The difference between the deuteration of these molecules in L1544 is discussed and compared with the prediction of chemical models.

Results. The maximum deuterium fractionation for the first deuteration of H2CS is N(HDCS)/N(H2CS) ~ 30% and is located towards the north-east at a distance of about 10000 AU from the dust peak. While for c-C3H2 the first and second deuteration have a similar efficiency, for H2CS and H2CO the second deuteration is more efficient, leading to D2CX/HDCX ~ 100% (with X = O or S).

Conclusions. Our results imply that the large deuteration of H2CO and H2CS observed in protostellar cores as well as in comets is likely inherited from the pre-stellar phase. However, comparison with state-of-the-art chemical models suggests that the reaction network for the formation of the doubly deuterated H2CS and H2CO it is not complete yet.