bluuebunny/crossref_metadata_2025 huggingface dataset:
The stickers and spacers of Rubiscondensation: assembling the centrepiece of biophysical CO2-concentrating mechanisms
Authors: Ang Warren Shou Leong , How Jian Ann , How Jian Boon , Mueller-Cajar Oliver
Published: July 2022

Aquatic autotrophs that fix carbon using ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) frequently expend metabolic energy to pump inorganic carbon towards the enzyme’s active site. A central requirement of this strategy is the formation of highly concentrated Rubisco condensates (or Rubiscondensates) known as carboxysomes and pyrenoids, which have convergently evolved multiple times in prokaryotes and eukaryotes, respectively. Recent data indicate that these condensates form by the mechanism of liquid–liquid phase separation. This mechanism requires networks of weak multivalent interactions typically mediated by intrinsically disordered scaffold proteins. Here we comparatively review recent rapid developments that detail the determinants and precise interactions that underlie diverse Rubisco condensates. The burgeoning field of biomolecular condensates has few examples where liquid–liquid phase separation can be linked to clear phenotypic outcomes. When present, Rubisco condensates are essential for photosynthesis and growth, and they are thus emerging as powerful and tractable models to investigate the structure–function relationship of phase separation in biology.
Tungsten versus Selenium as a potential source of kilonova nebular emission observed by Spitzer
Authors: Hotokezaka Kenta , Tanaka Masaomi , Kato Daiji , Gaigalas Gediminas
Published: July 2022

Infrared emission lines arising from transitions between fine structure levels of heavy elements are expected to produce kilonova nebular emission. For the kilonova in GW170817, strong emission at $4.5\, {\rm \mu m}$ at late times was detected by the Spitzer Space Telescope but no source was detected at $3.6\, {\rm \mu m}$. This peculiar spectrum indicates that strong line emitters exist around $4.5\, {\rm \mu m}$ and the absence of strong lines around $3.6\, {\rm \mu m}$. To model the spectrum we prepare a line list based on the selection rules in LS coupling from the experimentally calibrated energy levels in the NIST database. This method enables to generate the synthetic spectra with accurate line wavelengths. We find that the spectrum is sensitive to the abundance pattern whether or not the first r-process peak elements are included. In both cases, the synthetic spectra can match the observed data, leading to two possible interpretations. If the first peak elements are abundant, a Se iii line dominates the flux. If otherwise, W iii with Os iii, Rh iii, and Ce iv can be the main sources. Observing nebular spectra for the future kilonova in a wider wavelength range can provide more conclusive elemental identification.
A Secondary Metabolic Enzyme Functioned as an Evolutionary Seed of a Primary Metabolic Enzyme
Authors: Kawaguchi Jun , Mori Hikaru , Iwai Noritaka , Wachi Masaaki
Published: July 2022

The antibiotic alaremycin has a structure that resembles that of 5-aminolevulinic acid (ALA), a universal precursor of porphyrins, and inhibits porphyrin biosynthesis. Genome sequencing of the alaremycin-producing bacterial strain and enzymatic analysis revealed that the first step of alaremcyin biosynthesis is catalysed by the enzyme, AlmA, which exhibits a high degree of similarity to 5-aminolevulinate synthase (ALAS) expressed by animals, protozoa, fungi, and α-proteobacteria. Site-directed mutagenesis of AlmA revealed that the substitution of two amino acids residues around the substrate binding pocket transformed its substrate specificity from that of alaremycin precursor synthesis to ALA synthesis. To estimate the evolutionary trajectory of AlmA and ALAS, we performed an ancestral sequence reconstitution analysis based on a phylogenetic tree of AlmA and ALAS. The reconstructed common ancestral enzyme of AlmA and ALAS exhibited alaremycin precursor synthetic activity, rather than ALA synthetic activity. These results suggest that ALAS evolved from an AlmA-like enzyme. We propose a new evolutionary hypothesis in which a non-essential secondary metabolic enzyme acts as an ‘evolutionary seed’ to generate an essential primary metabolic enzyme.
The HDAC7–TET2 epigenetic axis is essential during early B lymphocyte development
Authors: Azagra Alba , Meler Ainara , de Barrios Oriol , Tomás-Daza Laureano , Collazo Olga , Monterde Beatriz , Obiols Mireia , Rovirosa Llorenç , Vila-Casadesús Maria , Cabrera-Pasadas Mónica , Gusi-Vives Mar , Graf Thomas , Varela Ignacio , Sardina José Luis , Javierre Biola M , Parra Maribel
Published: July 2022

Correct B cell identity at each stage of cellular differentiation during B lymphocyte development is critically dependent on a tightly controlled epigenomic landscape. We previously identified HDAC7 as an essential regulator of early B cell development and its absence leads to a drastic block at the pro-B to pre-B cell transition. More recently, we demonstrated that HDAC7 loss in pro-B-ALL in infants associates with a worse prognosis. Here we delineate the molecular mechanisms by which HDAC7 modulates early B cell development. We find that HDAC7 deficiency drives global chromatin de-condensation, histone marks deposition and deregulates other epigenetic regulators and mobile elements. Specifically, the absence of HDAC7 induces TET2 expression, which promotes DNA 5-hydroxymethylation and chromatin de-condensation. HDAC7 deficiency also results in the aberrant expression of microRNAs and LINE-1 transposable elements. These findings shed light on the mechanisms by which HDAC7 loss or misregulation may lead to B cell–based hematological malignancies.
CGG repeats trigger translational frameshifts that generate aggregation-prone chimeric proteins
Authors: Wright Shannon E , Rodriguez Caitlin M , Monroe Jeremy , Xing Jiazheng , Krans Amy , Flores Brittany N , Barsur Venkatesha , Ivanova Magdalena I , Koutmou Kristin S , Barmada Sami J , Todd Peter K
Published: July 2022

CGG repeat expansions in the FMR1 5’UTR cause the neurodegenerative disease Fragile X-associated tremor/ataxia syndrome (FXTAS). These repeats form stable RNA secondary structures that support aberrant translation in the absence of an AUG start codon (RAN translation), producing aggregate-prone peptides that accumulate within intranuclear neuronal inclusions and contribute to neurotoxicity. Here, we show that the most abundant RAN translation product, FMRpolyG, is markedly less toxic when generated from a construct with a non-repetitive alternating codon sequence in place of the CGG repeat. While exploring the mechanism of this differential toxicity, we observed a +1 translational frameshift within the CGG repeat from the arginine to glycine reading frame. Frameshifts occurred within the first few translated repeats and were triggered predominantly by RNA sequence and structural features. Short chimeric R/G peptides form aggregates distinct from those formed by either pure arginine or glycine, and these chimeras induce toxicity in cultured rodent neurons. Together, this work suggests that CGG repeats support translational frameshifting and that chimeric RAN translated peptides may contribute to CGG repeat-associated toxicity in FXTAS and related disorders.
Top3α is the replicative topoisomerase in mitochondrial DNA replication
Authors: Hangas Anu , Kekäläinen Nina J , Potter Alisa , Michell Craig , Aho Kauko J , Rutanen Chiara , Spelbrink Johannes N , Pohjoismäki Jaakko L , Goffart Steffi
Published: July 2022

Mitochondrial DNA has been investigated for nearly fifty years, but many aspects of the maintenance of this essential small genome remain unknown. Like any genome, mammalian mitochondrial DNA requires the function of topoisomerases to counter and regulate the topological tension arising during replication, transcription, segregation, and repair. However, the functions of the different mitochondrial topoisomerases are poorly understood. Here, we investigate the role of Topoisomerase 3α (Top3α) in mtDNA replication and transcription, providing evidence that this enzyme, previously reported to act in mtDNA segregation, also participates in mtDNA replication fork progression. Top3α knockdown caused replication fork stalling, increased mtDNA catenation and decreased mtDNA levels. Overexpression in contrast induced abundant double-strand breaks around the replication origin OH and abortion of early replication, while at the same time improving the resolution of mtDNA replication termination intermediates. Both Top3α knockdown and overexpression affected mitochondrial RNA transcription, leading to a decrease in steady-state levels of mitochondrial transcripts. Together, our results indicate that the mitochondrial isoform of Top3α is not only involved in mtDNA segregation, as reported previously, but also supports the progression of the replication fork. Mitochondrial Top3α is also influencing the progression of transcription, with its absence affecting downstream transcript levels.
KAP1 is a new non-genetic vulnerability of malignant pleural mesothelioma (MPM)
Authors: Lorenzini Eugenia , Torricelli Federica , Zamponi Raffaella , Donati Benedetta , Manicardi Veronica , Sauta Elisabetta , Faria do Valle Italo , Reggiani Francesca , Gugnoni Mila , Manzotti Gloria , Fragliasso Valentina , Vitale Emanuele , Piana Simonetta , Sancisi Valentina , Ciarrocchi Alessia
Published: July 2022

Malignant pleural mesothelioma (MPM) is a rare and incurable cancer, which incidence is increasing in many countries. MPM escapes the classical genetic model of cancer evolution, lacking a distinctive genetic fingerprint. Omics profiling revealed extensive heterogeneity failing to identify major vulnerabilities and restraining development of MPM-oriented therapies. Here, we performed a multilayered analysis based on a functional genome-wide CRISPR/Cas9 screening integrated with patients molecular and clinical data, to identify new non-genetic vulnerabilities of MPM. We identified a core of 18 functionally-related genes as essential for MPM cells. The chromatin reader KAP1 emerged as a dependency of MPM. We showed that KAP1 supports cell growth by orchestrating the expression of a G2/M-specific program, ensuring mitosis correct execution. Targeting KAP1 transcriptional function, by using CDK9 inhibitors resulted in a dramatic loss of MPM cells viability and shutdown of the KAP1-mediated program. Validation analysis on two independent MPM-patients sets, including a consecutive, retrospective cohort of 97 MPM, confirmed KAP1 as new non-genetic dependency of MPM and proved the association of its dependent gene program with reduced patients’ survival probability. Overall these data: provided new insights into the biology of MPM delineating KAP1 and its target genes as building blocks of its clinical aggressiveness.
Validation of two IgA nephropathy risk-prediction tools using a cohort with a long follow-up
Authors: Haaskjold Yngvar Lunde , Lura Njål Gjærde , Bjørneklett Rune , Bostad Leif , Bostad Lars Sigurd , Knoop Thomas
Published: July 2022

Background

Recently, two immunoglobulin A (IgA) nephropathy-prediction tools were developed that combine clinical and histopathologic parameters. The International IgAN Prediction Tool predicts the risk for 50% declines in the estimated glomerular filtration rate or end-stage kidney disease up to 80 months after diagnosis. The IgA Nephropathy Clinical Decision Support System uses artificial neural networks to estimate the risk for end-stage kidney disease. We aimed to externally validate both prediction tools using a Norwegian cohort with a long-term follow-up.

Methods

We included 306 patients with biopsy-proven primary IgA nephropathy in this study. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford Classification. We used discrimination and calibration as principles for externally validating the prognostic models.

Results

The median patient follow-up was 17.1 years. A cumulative, dynamic, time-dependent receiver operating characteristic analysis showed area under the curve values ranging from 0.90 at 5 years to 0.83 at 20 years for the International IgAN Prediction Tool, while time-naive analysis showed an area under the curve value at 0.83 for the IgA Nephropathy Clinical Decision Support System. The International IgAN Prediction Tool was well calibrated, while the IgA Nephropathy Clinical Decision Support System tends to underestimate risk for patients at higher risk and overestimates risk in the lower risk categories.

Conclusions

We have externally validated two prediction tools for IgA nephropathy. The International IgAN Prediction Tool performed well, while the IgA Nephropathy Clinical Decision Support System has some limitations.
Enzymatic and chemo-enzymatic strategies to produce highly valuable chiral amines from biomass with ω-transaminases on 2D zeolites
Authors: Carceller J Miguel , Arias Karen S , Climent Maria J , Iborra Sara , Corma Avelino
Published: July 2022

Amino transaminases (ATAs) have been supported on a 2D ITQ-2 zeolite through electrostatic interactions, resulting in a highly stable active biocatalyst to obtain a variety of valuable chiral amines starting from prochiral ketones derived from biomass. We have extended the biocatalyst applications by designing a chemo-enzymatic process that allows, as the first step, prochiral ketones to be obtained from biomass-derived compounds through an aldol condensation–reduction step using a bifunctional metal/base catalyst. The prochiral ketone is subsequently converted into the chiral amine using the immobilized ATA. We show that it is feasible to couple both steps in a semi-continuous process to produce industrially relevant chiral amines with yields of >95% and ∼100% enantiomer excess.
Extended Remdesivir Infusion for Persistent Coronavirus Disease 2019 Infection
Authors: Martinez Mario A , Chen Ting-Yi , Choi Hosoon , Hwang Munok , Navarathna Dhammika , Hao Linhue , Gale Michael , Camus Gregory , Ramirez Hector E , Jinadatha Chetan
Published: July 2022

Persistent severe acute respiratory syndrome coronavirus 2 infection is difficult to treat. Here, we report a case of 5-month persistent coronavirus disease 2019 in an immunocompromised patient who was successfully treated with 30 consecutive days of remdesivir. Prolonged remdesivir infusion with concurrent cycle threshold monitoring might provide a potential solution to cure these patients with difficult-to-treat infections.
Disseminated Mycobacterium avium Complex Myositis in a Patient With Graft-Versus-Host Disease
Authors: Kompa Kathryn Grace , Trottier Caitlin A , Hyman Charles L , Kohli Rakhi
Published: July 2022

Mycobacterium avium complex (MAC) is a ubiquitous environmental pathogen that was infrequently reported as a cause of disease before the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome epidemic. We present a case of MAC pyomyositis and bacteremia in a 59-year-old man with chronic lymphocytic leukemia in remission after an allogenic stem cell transplant. His posttransplant course was complicated by graft-versus-host disease, requiring treatment with oral steroids and ruxolitinib. In this report, we review the literature on disseminated MAC infection in patients with and without HIV. We also propose a potential mechanism by which this patient may have developed disseminated disease. Disseminated MAC myositis is uncommon in persons without HIV and requires a high index of suspicion for timely diagnosis.
International Survey on Frailty Assessment in Patients with Cancer
Authors: Banna Giuseppe Luigi , Cantale Ornella , Haydock Maria Monica , Battisti Nicolò Matteo Luca , Bambury Kevin , Musolino Naja , O’Carroll Eoin , Maltese Giuseppe , Garetto Lucia , Addeo Alfredo , Gomes Fabio
Published: July 2022

Background

Frailty negatively affects the outcomes of patients with cancer, and its assessment might vary widely in the real world. The objective of this study was to explore awareness and use of frailty screening tools among the ONCOassist healthcare professionals (HCPs) users.

Materials and Methods

We sent 2 emails with a cross-sectional 15-item survey in a 3-week interval between April and May 2021. Differences in the awareness and use of tools according to respondents’ continents, country income, and job types were investigated.

Results

Seven hundred thirty-seven HCPs from 91 countries (81% physicians, 13% nurses, and 5% other HCPs) completed the survey. Three hundred and eighty-five (52%) reported assessing all or the majority of their patients; 518 (70%) at baseline and before starting a new treatment. Three hundred and four (43%) HCPs were aware of performance status (PS) scores only, 309 (42%) age/frailty/comorbidity (AFC) screening, and 102 (14%) chemotoxicity predictive tools. Five hundred and thirty-seven (73%) reported using tools; 423 (57%) just PS, 237 (32%) AFC, and 60 (8%) chemotoxicity ones. Reasons for tools non-use (485 responders) were awareness (70%), time constraints (28%), and uselessness (2%). There were significant differences in awareness and use of screening tools among different continents, country income, job types, and medical specialties (P < .001 for all comparisons).

Conclusion

Among selected oncology HCPs, there is still a worldwide lack of knowledge and usage of frailty screening tools, which may differ according to their geography, country income, and education. Targeted initiatives to raise awareness and education are needed to implement frailty assessment in managing patients with cancer.
SlMBP3 Knockout/down in Tomato: Normal-Sized Fruit with Increased Dry Matter Content through Non-Liquefied Locular Tissue by Altered Cell Wall Formation
Authors: Kim Ji-Seong , Lee Jeongeun , Ezura Hiroshi
Published: July 2022

The phenotypic effect of the knockdown/out of AGAMOUS clade MADS-box gene SlMBP3 in tomato was evaluated using a transferred DNA (T-DNA)-tagged mutant of SlMBP3 and SlMBP3-RNA interference lines. SlMBP3 was preferentially expressed in the locular tissue of fruit and the seed coat combined with the endoderm. Consistent with where SlMBP3 is expressed, the SlMBP3-knockout/down lines showed non-liquefied locular tissues and increased number of seed hairs than the wild type (WT). The early cell degradation of the locular tissue was not observed in the fruits of the SlMBP3-knockout/down lines, and the cells were elongated like placental cells resulting in non-liquefied locular tissues. As the result, the fruits of the SlMBP3-knockout/down lines exhibited higher dry matter contents and titratable acidity than those of the WT. During locular tissue cell development under the SlMBP3 knockout/down, the expression of cell-enlargement-related genes (beta-expansin gene SlEXPB1 and endo-beta-1,4-D-glucanase gene Cel8) and pectinase-inhibitor-related genes (pectin esterase inhibitor gene PE inhibitor and polygalacturonase inhibitor gene PG inhibitor) was upregulated and that of pectinase-encoding genes (polygalacturonase gene QRT3-like and pectin lyase gene PL2) was downregulated. In the seed coat of the SlMBP3-knockout/down lines, tomato trichome-formation-related genes such as MYB genes containing R2 and R3 repeats (R2R3-MYB) transcription factor SlMYB75, B-type cyclin SlCycB2 and Homeodomain Leucine Zipper (HD-Zip) IV transcription factor Woolly were downregulated. Our results demonstrate that SlMBP3 is involved in the liquefaction of the locular tissue through the modification of cell development and degradation processes and seed hair formation in tomato fruits, and the SlMBP3 knockout/down results in normal-sized fruit with increased dry matter content.
Deep origin and gradual evolution of transporting tissues: Perspectives from across the land plants
Authors: Woudenberg Sjoerd , Renema Jim , Tomescu Alexandru M F , De Rybel Bert , Weijers Dolf
Published: July 2022

The evolution of transporting tissues was an important innovation in terrestrial plants that allowed them to adapt to almost all nonaquatic environments. These tissues consist of water-conducting cells and food-conducting cells and bridge plant–soil and plant–air interfaces over long distances. The largest group of land plants, representing about 95% of all known plant species, is associated with morphologically complex transporting tissue in plants with a range of additional traits. Therefore, this entire clade was named tracheophytes, or vascular plants. However, some nonvascular plants possess conductive tissues that closely resemble vascular tissue in their organization, structure, and function. Recent molecular studies also point to a highly conserved toolbox of molecular regulators for transporting tissues. Here, we reflect on the distinguishing features of conductive and vascular tissues and their evolutionary history. Rather than sudden emergence of complex, vascular tissues, plant transporting tissues likely evolved gradually, building on pre-existing developmental mechanisms and genetic components. Improved knowledge of the intimate structure and developmental regulation of transporting tissues across the entire taxonomic breadth of extant plant lineages, combined with more comprehensive documentation of the fossil record of transporting tissues, is required for a full understanding of the evolutionary trajectory of transporting tissues.
The advantage of the right in social media news sharing
Authors: González-Bailón Sandra , d'Andrea Valeria , Freelon Deen , De Domenico Manlio
Published: July 2022

We analyze social media activity during one of the largest protest mobilizations in US history to examine ideological asymmetries in the posting of news content. Using an unprecedented combination of four datasets (tracking offline protests, social media activity, web browsing, and the reliability of news sources), we show that there is no evidence of unreliable sources having any prominent visibility during the protest period, but we do identify asymmetries in the ideological slant of the sources shared on social media, with a clear bias towards right-leaning domains. These results support the “amplification of the right” thesis, which points to the structural conditions (social and technological) that lead to higher visibility of content with a partisan bent towards the right. Our findings provide evidence that right-leaning sources gain more visibility on social media and reveal that ideological asymmetries manifest themselves even in the context of movements with progressive goals.
Constructive adaptation of 3D-printable polymers in response to typically destructive aquatic environments
Authors: Yu Kunhao , Feng Zhangzhengrong , Du Haixu , Lee Kyung Hoon , Li Ketian , Zhang Yanchu , Masri Sami F , Wang Qiming
Published: July 2022

In response to environmental stressors, biological systems exhibit extraordinary adaptive capacity by turning destructive environmental stressors into constructive factors; however, the traditional engineering materials weaken and fail. Take the response of polymers to an aquatic environment as an example: Water molecules typically compromise the mechanical properties of the polymer network in the bulk and on the interface through swelling and lubrication, respectively. Here, we report a class of 3D-printable synthetic polymers that constructively strengthen their bulk and interfacial mechanical properties in response to the aquatic environment. The mechanism relies on a water-assisted additional cross-linking reaction in the polymer matrix and on the interface. As such, the typically destructive water can constructively enhance the polymer’s bulk mechanical properties such as stiffness, tensile strength, and fracture toughness by factors of 746% to 790%, and the interfacial bonding by a factor of 1,000%. We show that the invented polymers can be used for soft robotics that self-strengthen matrix and self-heal cracks after training in water and water-healable packaging materials for flexible electronics. This work opens the door for the design of synthetic materials to imitate the constructive adaptation of biological systems in response to environmental stressors, for applications such as artificial muscles, soft robotics, and flexible electronics.
Plasmonic gadolinium oxide nanomatryoshkas: bifunctional magnetic resonance imaging enhancers for photothermal cancer therapy
Authors: Henderson Luke , Neumann Oara , Kadria-Vili Yara , Gerislioglu Burak , Bankson James , Nordlander Peter , Halas Naomi J
Published: July 2022

Nanoparticle-assisted laser-induced photothermal therapy (PTT) is a promising method for cancer treatment; yet, visualization of nanoparticle uptake and photothermal response remain a critical challenge. Here, we report a magnetic resonance imaging-active nanomatryoshka (Gd2O3-NM), a multilayered (Au core/Gd2O3 shell/Au shell) sub-100 nm nanoparticle capable of combining T1 MRI contrast with PTT. This bifunctional nanoparticle demonstrates an r1 of 1.28 × 108 mM–1 s–1, an MRI contrast enhancement per nanoparticle sufficient for T1 imaging in addition to tumor ablation. Gd2O3-NM also shows excellent stability in an acidic environment, retaining 99% of the internal Gd(3). This report details the synthesis and characterization of a promising system for combined theranostic nanoparticle tracking and PTT.
Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas
Authors: Wang Fangyu , Liu Xuan , Li Shaowen , Zhao Chen , Sun Yumei , Tian Kuan , Wang Junbao , Li Wei , Xu Lichao , Jing Jing , Wang Juan , Evans Sylvia M , Li Zhiqiang , Liu Ying , Zhou Yan
Published: July 2022

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells, to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy-number variations (CNVs) of mural cells and endothelial cells were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm
Authors: Liu Kuisheng , Xu Xiaocui , Bai Dandan , Li Yanhe , Zhang Yalin , Jia Yanping , Guo Mingyue , Han Xiaoxiao , Liu Yingdong , Sheng Yifan , Kou Xiaochen , Zhao Yanhong , Yin Jiqing , Liu Sheng , Chen Jiayu , Wang Hong , Wang Yixuan , Liu Wenqiang , Gao Shaorong
Published: July 2022

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the “trophectoderm (TE)-like structure” of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
The impact of Italian performance-based research funding systems on the intensity of international research collaboration
Authors: Abramo Giovanni , D’Angelo Ciriaco Andrea
Published: July 2022

The study of national research assessment exercises serves to evaluate the effectiveness of policies versus their objectives and to improve the formulation of future initiatives. The aim of the current study is to verify whether the introduction of the first performance-based research funding in Italy, based on the 2004–10 VQR assessment, achieved the intended objective of inducing greater international collaboration on the part of researchers. For this, we apply a bibliometric approach based on the observation of coauthorships in Italian and worldwide scientific publications over a 14-year period, beginning in the target years of the VQR assessment. Through an Interrupted Time Series Analysis, we compare the expected and observed patterns of international coauthorship for Italy and the rest of the world. Although the rate of internationalization of Italian research is seen to be increasing, whether this is a consequence of the VQR incentives, or rather part of a global phenomenon of recourse to international collaboration in response to the increasingly complex scientific challenges, it is open to interpretation.
Routinization of work processes, de-routinization of job structures
Authors: Fernández-Macías Enrique , Bisello Martina , Peruffo Eleonora , Rinaldi Riccardo
Published: July 2022

This article investigates changes in routine tasks and computer use in European jobs in the period 1995–2015, putting them in the context of the debates on the future of work and the impact of automation. Digital technologies not only affect employment shifts but also shape work organization. A shift-share analysis combining European Working Conditions Survey and European Labour Force Survey data assesses to what extent recent changes in tasks are the result of changes in the structure of employment (shifts in employment across jobs) or changes in the content of work itself (transformation in the task contents and methods within jobs). The results suggest contrasting trends between observed changes in tasks measures within jobs and compositional shifts in employment for routine tasks indexes. Employment structures are de-routinizing while work itself is becoming more routine. These results seem also related to the increased use of computers at work during the same period.
Identification of novel loci in obstructive sleep apnea in European American and African American children
Authors: Quinlan Courtney M , Chang Xiao , March Michael , Mentch Frank D , Qu Hui-Qi , Liu Yichuan , Glessner Joseph , Sleiman Patrick M A , Hakonarson Hakon
Published: July 2022

Study Objectives

To identify genetic susceptibility variants in pediatric obstructive sleep apnea in European American and African American children.

Methods

A phenotyping algorithm using electronic medical records was developed to recruit cases with OSA and control subjects from the Center for Applied Genomics at Children’s Hospital of Philadelphia (CHOP). Genome-wide association studies (GWAS) were performed in pediatric OSA cases and control subjects with European American (EA) and African American (AA) ancestry followed by meta-analysis and sex stratification.

Results

The algorithm accrued 1486 subjects (46.3% European American, 53.7% African American). We identified genomic loci at 1p36.22 and 15q26.1 that associated with OSA risk in EA and AA, respectively. We also revealed a shared risk locus at 18p11.32 (rs114124196, p = 1.72 × 10-8) across EA and AA populations. Additionally, association at 1q43 (rs12754698) and 2p25.1 (rs72775219) was identified in the male-only analysis of EA children with OSA, while association at 8q21.11 (rs6472959), 11q24.3 (rs4370952) and 15q21.1 (rs149936782) was detected in the female-only analysis of EA children and association at 18p11.23 (rs9964029) was identified in the female-only analysis of African-American children. Moreover, the 18p11.32 locus was replicated in an EA cohort (rs114124196, p = 8.8 × 10-3).

Conclusions

We report the first GWAS for pediatric OSA in European Americans and African Americans. Our results provide novel insights to the genetic underpins of pediatric OSA.
The Community Coevolution Model with Application to the Study of Evolutionary Relationships between Genes Based on Phylogenetic Profiles
Authors: Liu Chaoyue , Kenney Toby , Beiko Robert G , Gu Hong
Published: July 2022

Organismal traits can evolve in a coordinated way, with correlated patterns of gains and losses reflecting important evolutionary associations. Discovering these associations can reveal important information about the functional and ecological linkages among traits. Phylogenetic profiles treat individual genes as traits distributed across sets of genomes and can provide a fine-grained view of the genetic underpinnings of evolutionary processes in a set of genomes. Phylogenetic profiling has been used to identify genes that are functionally linked and to identify common patterns of lateral gene transfer in microorganisms. However, comparative analysis of phylogenetic profiles and other trait distributions should take into account the phylogenetic relationships among the organisms under consideration. Here, we propose the Community Coevolution Model (CCM), a new coevolutionary model to analyze the evolutionary associations among traits, with a focus on phylogenetic profiles. In the CCM, traits are considered to evolve as a community with interactions, and the transition rate for each trait depends on the current states of other traits. Surpassing other comparative methods for pairwise trait analysis, CCM has the additional advantage of being able to examine multiple traits as a community to reveal more dependency relationships. We also develop a simulation procedure to generate phylogenetic profiles with correlated evolutionary patterns that can be used as benchmark data for evaluation purposes. A simulation study demonstrates that CCM is more accurate than other methods including the Jaccard Index and three tree-aware methods. The parameterization of CCM makes the interpretation of the relations between genes more direct, which leads to Darwin’s scenario being identified easily based on the estimated parameters. We show that CCM is more efficient and fits real data better than other methods resulting in higher likelihood scores with fewer parameters. An examination of 3786 phylogenetic profiles across a set of 659 bacterial genomes highlights linkages between genes with common functions, including many patterns that would not have been identified under a nonphylogenetic model of common distribution. We also applied the CCM to 44 proteins in the well-studied Mitochondrial Respiratory Complex I and recovered associations that mapped well onto the structural associations that exist in the complex. [Coevolution; evolutionary rates; gene network; graphical models; phylogenetic profiles; phylogeny.]
Prediction Model for Severe Mycoplasma pneumoniae Pneumonia in Pediatric Patients by Admission Laboratory Indicators
Authors: Chang Qing , Chen Hong-Lin , Wu Neng-Shun , Gao Yan-Min , Yu Rong , Zhu Wei-Min
Published: July 2022

Objective

The purpose of this study was to develop a model for predicting severe Mycoplasma pneumoniae pneumonia (SMPP) in pediatric patients with Mycoplasma pneumoniae pneumonia (MPP) on admission by laboratory indicators.

Methods

Pediatric patients with MPP from January 2019 to December 2020 in our hospital were enrolled in this study. SMPP was diagnosed according to guideline for diagnosis and treatment of community-acquired pneumonia in children (2019 version). Prediction model was developed according to the admission laboratory indicators. Receiver operating characteristic curve and Goodness-of-fit test were analyzed for the predictive value.

Results

A total of 233 MPP patients were included in the study, with 121 males and 112 females, aged 4.541 (1–14) years. Among them, 84 (36.1%, 95% CI 29.9–42.6%) pediatric patients were diagnosed as SMPP. Some admission laboratory indicators (immunoglobulins M (IgM), eosinophil proportion, eosinophil count, hemoglobin, erythrocyte sedimentation rate (ESR), total protein, albumin and prealbumin) were found statistically different (p < 0.05) between non-SMPP group and SMPP group. Logistic regress analysis showed IgM, eosinophil proportion, eosinophil count, ESR and prealbumin were independent risk factors for SMPP. According to these five admission laboratory indicators, the prediction model for SMPP in pediatric patients was developed. The area under curve of the prediction model was 0.777, and the goodness-of-fit test showed that the predicted SMPP incidence by the model was consistent with the actual incidence (χ2 = 244.51, p = 0.203).

Conclusion

We developed a model for predicting SMPP in pediatric patients by admission laboratory indicators. This model has good discrimination and calibration, which provides a basis for the early identification SMPP on admission. However, this model should be validated by multicenter studies with large sample.
Treatment outcomes and risk factors of death in childhood tuberculous meningitis in Kandahar, Afghanistan: a prospective observational cohort study
Authors: Rahimi Bilal Ahmad , Niazi Najeebullah , Rahimi Ahmad Farshad , Faizee Muhammad Ishaque , Khan Mohmmad Sidiq , Taylor Walter R
Published: July 2022

Background

Tuberculous meningitis (TBM) is the most severe form of TB. We prospectively documented the treatment outcomes and the risk factors for death in children with TBM from Kandahar, Afghanistan.

Methods

This prospective observational cohort study was conducted from February 2017 to January 2020 in hospitalised TBM children. All the patients were prospectively followed up for 12 mo. Data were analysed by using descriptive statistics, χ2 and multivariate logistic regression.

Results

A total of 818 TBM hospitalised patients with median age 4.8 (0.8–14.5) y were recruited. Females accounted for 60.9% (498/818). Upon admission 53.9% (n=441) and 15.2% (n=124) had TBM stages II and III, respectively, and 23.2% (n=190) had focal neurological signs. The case fatality rate was 20.2% (160/794) and 30.6% (243/794) survived with neurological sequelae. Independent risk factors for death were being unvaccinated for BCG (adjusted OR [AOR] 3.8, 95% CI 1.8 to 8.1), not receiving dexamethasone (AOR 2.5, 95% CI 1.5 to 4.2), being male (AOR 2.3, 95% CI 1.5 to 3.6), history of recent weight loss (AOR 2.2, 95% CI 1.3 to 3.9) and having stage III TBM (AOR 2.0, 95% CI 1.2 to 3.3).

Conclusions

TBM continues to cause high morbidity and mortality in Afghan children. Strategies to reduce mortality should emphasise early diagnosis and treatment, routine use of dexamethasone and increased BCG vaccination.
Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications
Authors: Metz Torri D. , Clifton Rebecca G. , Hughes Brenna L. , Sandoval Grecio J. , Grobman William A. , Saade George R. , Manuck Tracy A. , Longo Monica , Sowles Amber , Clark Kelly , Simhan Hyagriv N. , Rouse Dwight J. , Mendez-Figueroa Hector , Gyamfi-Bannerman Cynthia , Bailit Jennifer L. , Costantine Maged M. , Sehdev Harish M. , Tita Alan T. N. , Macones George A.
Published: July 2022

(Abstracted from JAMA 2022;327:748–759)

It is well known that pregnant individuals with COVID-19 have increased risks such as admission to the intensive care unit (ICU), mechanical ventilation, and death when compared with both nonpregnant adults with SARS-CoV-2 infection and pregnant adults without SARS-CoV-2 infection. However, although COVID-19 is known to increase the risk of maternal morbidity related to the virus, the possibility for higher risk of serious morbidity from obstetric complications is not clear.
Changing Patterns in Medication Prescription for Gestational Diabetes During a Time of Guideline Change in the USA: A Cross-Sectional Study
Authors: Venkatesh K. K. , Chiang C. W. , Castillo W. C. , Battarbee A. N. , Donneyong M. , Harper L. M. , Costantine M. , Saade G. , Werner E. F. , Boggess K. A. , Landon M. B.
Published: July 2022

(Abstracted from BJOG 2022;129:473–483)

About a third of women with gestational diabetes mellitus (GDM) are unable to manage their condition with diet and exercise alone. Pharmacological management for GDM includes injectable insulin and oral agents, such as metformin and glyburide.
Interventions to Prevent Spontaneous Preterm Birth in Women With Singleton Pregnancy Who Are at High Risk: Systematic Review and Network Meta-analysis
Authors: Care Angharad , Nevitt Sarah J. , Medley Nancy , Donegan Sarah , Goodfellow Laura , Hampson Lynn , Smith Catrin Tudur , Alfirevic Zarko
Published: July 2022

(Abstracted from BMJ 2022;376:e064547)

The leading cause of neonatal mortality are complications due to preterm birth. To manage the risk of preterm birth, the NICE (National Institute for Health and Care Excellence) recommends using vaginal progesterone or cervical cerclage.
Accuracy of Self-Assessment of Gestational Duration Among People Seeking Abortion
Authors: Ralph Lauren J. , Ehrenreich Katherine , Barar Rana , Biggs M. Antonia , Morris Natalie , Blanchard Kelly , Kapp Nathalie , Moayedi Ghazaleh , Perritt Jamila , Raymond Elizabeth G. , White Kari , Grossman Daniel
Published: July 2022

(Abstracted from Am J Obstet Gynecol 2022;226:710.e1–710.e21)

Medication abortion using the 2-drug regimen of mifepristone and misoprostol is approved by the US Food and Drug Administration for women through 70 days' (or 10 weeks') gestation. Women at gestation duration (GD) longer than this are not eligible for medication abortion.
Development of a Simplified Patient-Centered Pelvic Floor Surgery Complication Scale
Authors: Fitzgerald Jocelyn , Richter Holly E. , Sung Vivian , Dunivan Gena , Mete Mihriye , Gutman Robert E.
Published: July 2022

(Abstracted from Female Pelvic Med Reconstr Surg 2022;28:233–239)

Quality of life can be significantly impacted by pelvic floor disorders, including urinary incontinence, pelvic organ prolapse, and fecal incontinence. Although surgical procedures are often used to correct these conditions, inherent short-term and long-term complications do exist with these procedures.
Optimal Endometrial Thickness in Fresh and Frozen-Thaw In Vitro Fertilization Cycles: An Analysis of Live Birth Rates From 96,000 Autologous Embryo Transfers
Authors: Mahutte Neal , Hartman Michael , Meng Lynn , Lanes Andrea , Luo Zhong-Cheng , Liu Kimberly E.
Published: July 2022

(Abstracted from Fertil Steril 2022;117:792–800)

A routine procedure of in vitro fertilization (IVF) cycles is to measure the endometrial thickness, as it has been determined that a measurement of <8 mm at human chorionic gonadotropin (HCG) trigger in fresh IVF–embryo transfer (IVF-ET) can increase the risk of ectopic pregnancy, spontaneous abortion, low birth weight, placenta previa, and other obstetric complications. In direct dichotomy to this, an endometrial thickness above 7 to 8 mm has a general association of improved IVF outcomes.
Regional analgesia for cardiac surgery
Authors: Grant Michael C. , Gregory Alexander J. , Ouanes Jean-Pierre P.
Published: July 2022

Purpose of review

Regional anesthesia is gaining attention as a valuable component of multimodal, opioid-sparing analgesia in cardiac surgery, where improving the patient's quality of recovery while minimizing the harms of opioid administration are key points of emphasis in perioperative care. This review serves as an outline of recent advancements in a variety of applications of regional analgesia for cardiac surgery.

Recent findings

Growing interest in regional analgesia, particularly the use of newer “chest wall blocks”, has led to accumulating evidence for the efficacy of multiple regional techniques in cardiac surgery. These include a variety of technical approaches, with results consistently demonstrating optimized pain control and reduced opioid requirements. Regional and pain management experts have worked to derive consensus around nerve block nomenclature, which will be foundational to establish best practice, design and report future research consistently, improve medical education, and generally advance our knowledge in this vital area of perioperative patient care.

The field of regional analgesia for cardiac surgery has matured over the last several years. A variety of regional techniques have been described and shown to be efficacious as part of the multimodal, opioid-sparing approach to pain management in the cardiac surgical setting.
Regional versus general anesthesia for ambulatory total hip and knee arthroplasty
Authors: Baratta Jaime L. , Schwenk Eric S.
Published: July 2022

Purpose of review

With the removal of both total knee and total hip arthroplasty from the Centers for Medicare and Medicaid Services’ inpatient-only list, efforts to improve efficiency of the perioperative management of total joint patients have increased recently. The publication of several recent studies examining the impact of anesthesia type on outcomes has prompted the need to review the overall state of evidence for spinal versus general anesthesia for outpatient total joint arthroplasty.

Recent findings

Overall complication rates are low in this carefully selected patient population. The majority of patients who are preselected for outpatient total joint arthroplasty appear to successfully achieve this outcome. Some retrospective studies have suggested a benefit for spinal anesthesia in terms of same-day discharge success but direct comparisons in prospective studies are lacking.

The type of anesthesia used for total joint arthroplasty may have an important effect on outcomes. Until randomized control trials are performed we must rely on existing evidence, which suggests that both spinal and general anesthesia can lead to successful outcomes after ambulatory total joint arthroplasty.
EBV-associated NK and T-cell lymphoid neoplasms
Authors: Kimura Hiroshi , de Leval Laurence , Cai Qingqing , Kim Won Seog
Published: July 2022

Purpose of review

Epstein-Barr virus (EBV)-associated neoplasms derived from natural killer (NK) or T cells comprise a group of clinically and biologically heterogenous disorders affecting children and adults, which are overall rare but more prevalent in Asia and South America. This review focuses on neoplasms presenting in the adulthood, addressing recent genomic discoveries as well as therapeutic developments in these highly aggressive disorders.

Recent findings

Distinct molecular subtypes of extranodal NK/T-cell lymphomas (ENKTCLs) have been described, with differences in cell of origin, EBV pattern, genomic alterations, clinical characteristics, response to asparaginase-based therapies and to more recent approaches targeting molecular aberrations of the lymphoma. For the last two decades, progress in the clinical management of ENKTCL was based on L-asapraginase containing combinations and the incoroperation of radiotherapy. A subset of cases with PDL1-2 structural alterations may be more responsive to treatment with immune checkpoint inhibitors. Primary nodal EBV+ lymphomas derived from T or NK cells have distinctive features separating them from both peripheral T-cell lymphoma not otherwise specified and ENKTCL. Treatment algorithms correspond to those for advanced ENKTCL.

With better understanding of lymphomagenesis, genomic landscape and immunologic aspects of the diseases, future treatment options will include targeted therapies including immune checkpoint inhibitors and novel antibodies.