bluuebunny/crossref_metadata_2025 huggingface dataset:
Human brain anatomy reflects separable genetic and environmental components of socioeconomic status
Authors: Kweon Hyeokmoon , Aydogan Gökhan , Dagher Alain , Bzdok Danilo , Ruff Christian C. , Nave Gideon , Farah Martha J. , Koellinger Philipp D.
Published: May 2022

Socioeconomic status (SES) correlates with brain structure, a relation of interest given the long-observed relations of SES to cognitive abilities and health. Yet, major questions remain open, in particular, the pattern of causality that underlies this relation. In an unprecedently large study, here, we assess genetic and environmental contributions to SES differences in neuroanatomy. We first establish robust SES–gray matter relations across a number of brain regions, cortical and subcortical. These regional correlates are parsed into predominantly genetic factors and those potentially due to the environment. We show that genetic effects are stronger in some areas (prefrontal cortex, insula) than others. In areas showing less genetic effect (cerebellum, lateral temporal), environmental factors are likely to be influential. Our results imply a complex interplay of genetic and environmental factors that influence the SES-brain relation and may eventually provide insights relevant to policy.
A two-step adaptive walk rewires nutrient transport in a challenging edaphic environment
Authors: Tergemina Emmanuel , Elfarargi Ahmed F. , Flis Paulina , Fulgione Andrea , Göktay Mehmet , Neto Célia , Scholle Marleen , Flood Pádraic J. , Xerri Sophie-Asako , Zicola Johan , Döring Nina , Dinis Herculano , Krämer Ute , Salt David E. , Hancock Angela M.
Published: May 2022

Most well-characterized cases of adaptation involve single genetic loci. Theory suggests that multilocus adaptive walks should be common, but these are challenging to identify in natural populations. Here, we combine trait mapping with population genetic modeling to show that a two-step process rewired nutrient homeostasis in a population of
Arabidopsis
as it colonized the base of an active stratovolcano characterized by extremely low soil manganese (Mn). First, a variant that disrupted the primary iron (Fe) uptake transporter gene (
IRT1
) swept quickly to fixation in a hard selective sweep, increasing Mn but limiting Fe in the leaves. Second, multiple independent tandem duplications occurred at
NRAMP1
and together rose to near fixation in the island population, compensating the loss of IRT1 by improving Fe homeostasis. This study provides a clear case of a multilocus adaptive walk and reveals how genetic variants reshaped a phenotype and spread over space and time.
Shape-programmable, deformation-locking, and self-sensing artificial muscle based on liquid crystal elastomer and low–melting point alloy
Authors: Liu Haoran , Tian Hongmiao , Li Xiangming , Chen Xiaoliang , Zhang Kai , Shi Hongyu , Wang Chunhui , Shao Jinyou
Published: May 2022

An artificial muscle capable of shape programmability, deformation-locking capacity without needing continuous external energy, and self-sensing capability is highly desirable yet challenging in applications of reconfigurable antenna, deployable space structures, etc. Inspired by coupled behavior of the muscles, bones, and nerve system of mammals, a multifunctional artificial muscle based on polydopamine-coated liquid crystal elastomer (LCE) and low–melting point alloy (LMPA) in the form of a concentric tube/rod is proposed. Thereinto, the outer LCE is used for reversible contraction and recovery (i.e., muscle function); the inner LMPA in the resolidification state is adopted for deformation locking, and that in the melt state is adopted for angle variation monitoring by detecting resistance change (i.e., bones and nerve functions, respectively). The proposed artificial muscle demonstrates multiple performances, including controllable bending angle, position, and direction; deformation locking for supporting heavy objects; and real-time monitoring of angle variation, which also provides a straightforward and effective approach for designing soft devices.
Hierarchical self-uncloaking CRISPR-Cas13a–customized RNA nanococoons for spatial-controlled genome editing and precise cancer therapy
Authors: Fan Ningke , Bian Xintong , Li Meng , Chen Junman , Wu Haiping , Peng Qiling , Bai Huijie , Cheng Wenqian , Kong Liangsheng , Ding Shijia , Li Siqiao , Cheng Wei
Published: May 2022

CRISPR-Cas13a holds enormous potential for developing precise RNA editing. However, spatial manipulation of CRISPR-Cas13a activity remains a daunting challenge for elaborately regulating localized RNase function. Here, we designed hierarchical self-uncloaking CRISPR-Cas13a–customized RNA nanococoons (RNCOs-D), featuring tumor-specific recognition and spatial-controlled activation of Cas13a, for precise cancer synergistic therapy. RNCOs-D consists of programmable RNA nanosponges (RNSs) capable of targeted delivery and caging chemotherapeutic drug, and nanocapsules (NCs) anchored on RNSs for cloaking Cas13a/crRNA ribonucleoprotein (Cas13a RNP) activity. The acidic endo/lysosomal microenvironment stimulates the outer decomposition of NCs with concomitant Cas13a RNP activity revitalization, while the inner disassembly through trans-cleavage of RNSs initiated by cis-recognition and cleavage of EGFR variant III (EGFRvIII) mRNA. RNCOs-D demonstrates the effective EGFRvIII mRNA silencing for synergistic therapy of glioblastoma cancer cells in vitro and in vivo. The engineering of RNSs, together with efficient Cas13a activity regulation, holds immense prospect for multimodal and synergistic cancer therapy.
Nematic suspension of a microporous layered silicate obtained by forceless spontaneous delamination via repulsive osmotic swelling for casting high-barrier all-inorganic films
Authors: Loch Patrick , Schuchardt Dominik , Algara-Siller Gerardo , Markus Paul , Ottermann Katharina , Rosenfeldt Sabine , Lunkenbein Thomas , Schwieger Wilhelm , Papastavrou Georg , Breu Josef
Published: May 2022

Exploiting the full potential of layered materials for a broad range of applications requires delamination into functional nanosheets. Delamination via repulsive osmotic swelling is driven by thermodynamics and represents the most gentle route to obtain nematic liquid crystals consisting exclusively of single-layer nanosheets. This mechanism was, however, long limited to very few compounds, including 2:1-type clay minerals, layered titanates, or niobates. Despite the great potential of zeolites and their microporous layered counterparts, nanosheet production is challenging and troublesome, and published procedures implied the use of some shearing forces. Here, we present a scalable, eco-friendly, and utter delamination of the microporous layered silicate ilerite into single-layer nanosheets that extends repulsive delamination to the class of layered zeolites. As the sheet diameter is preserved, nematic suspensions with cofacial nanosheets of ≈9000 aspect ratio are obtained that can be cast into oriented films, e.g., for barrier applications.
Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting
Authors: Chen Kellen , Henn Dominic , Januszyk Michael , Barrera Janos A. , Noishiki Chikage , Bonham Clark A. , Griffin Michelle , Tevlin Ruth , Carlomagno Theresa , Shannon Tara , Fehlmann Tobias , Trotsyuk Artem A. , Padmanabhan Jagannath , Sivaraj Dharshan , Perrault David P. , Zamaleeva Alsu I. , Mays Chyna J. , Greco Autumn H. , Kwon Sun Hyung , Leeolou Melissa C. , Huskins Savana L. , Steele Sydney R. , Fischer Katharina S. , Kussie Hudson C. , Mittal Smiti , Mermin-Bunnell Alana M. , Diaz Deleon Nestor M. , Lavin Christopher , Keller Andreas , Longaker Michael T. , Gurtner Geoffrey C.
Published: May 2022

Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.
Emerging role for thymic stromal lymphopoietin–responsive regulatory T cells in colorectal cancer progression in humans and mice
Authors: Obata-Ninomiya Kazushige , de Jesus Carrion Steven , Hu Alex , Ziegler Steven F.
Published: May 2022

Recruitment of regulatory T cells (T
regs
) to tumors is a hallmark of cancer progression. Tumor-derived factors, such as the cytokine thymic stromal lymphopoietin (TSLP), can influence T
reg
function in tumors. In our study, we identified a subset of T
regs
expressing the receptor for TSLP (TSLPR
+
T
regs
) that were increased in colorectal tumors in humans and mice and largely absent in adjacent normal colon. This T
reg
subset was also found in the peripheral blood of patients with colon cancer but not in the peripheral blood of healthy control subjects. Mechanistically, we found that this T
reg
subset coexpressed the interleukin-33 (IL-33) receptor [suppressor of tumorigenicity 2 (ST2)] and had high programmed cell death 1 (PD-1) and cytotoxic lymphocyte–associated antigen 4 (CTLA-4) expression, regulated in part by the transcription factor Mef2c. T
reg
-specific deletion of TSLPR, but not ST2, was associated with a reduction in tumor number and size with concomitant increase in T
H
1 cells in tumors in chemically induced mouse models of colorectal cancer. Therapeutic blockade of TSLP using TSLP-specific monoclonal antibodies effectively inhibited the progression of colorectal tumors in this mouse model. Collectively, these data suggest that TSLP controls the progression of colorectal cancer through regulation of tumor-specific T
reg
function and represents a potential therapeutic target that requires further investigation.
In Vitro
Evolution of Listeria monocytogenes Reveals Selective Pressure for Loss of SigB and AgrA Function at Different Incubation Temperatures
Authors: Guerreiro Duarte N. , Wu Jialun , McDermott Emma , Garmyn Dominique , Dockery Peter , Boyd Aoife , Piveteau Pascal , O’Byrne Conor P.
Published: May 2022

To withstand environmental aggressions,
L. monocytogenes
upregulates a large regulon through the action of the alternative sigma factor B (σ
B
). However, σ
B
becomes detrimental for
L. monocytogenes
growth under mild stresses, which confer a competitive advantage to σ
B
loss-of-function alleles.
High Abundance of Transcription Regulators Compacts the Nucleoid in Escherichia coli
Authors: Yilmaz Cihan , Schnetz Karin
Published: May 2022

The bacterial nucleoid is a highly organized and dynamic structure for simultaneous transcription, replication, and segregation of the bacterial genome. Compaction of the nucleoid and disturbance of DNA segregation and cell division by artificially high levels of transcription regulators, as described here, reveals that an excess of DNA-binding protein disturbs nucleoid structuring.
Bacterial Quorum Sensing Allows Graded and Bimodal Cellular Responses to Variations in Population Density
Authors: Rattray Jennifer B. , Thomas Stephen A. , Wang Yifei , Molotkova Evgeniya , Gurney James , Varga John J. , Brown Sam P.
Published: May 2022

Bacteria can be highly social, controlling collective behaviors via cell-cell communication mechanisms known as quorum sensing (QS). QS is now a large research field, yet a basic question remains unanswered: what is the environmental resolution of QS? The notion of a threshold, or “quorum,” separating coordinated ON and OFF states is a central dogma in QS, but recent studies have shown heterogeneous responses at a single cell scale.
Worsening Glycemia Increases the Odds of Intermittent but Not Persistent Staphylococcus aureus Nasal Carriage in Two Cohorts of Mexican American Adults
Authors: Essigmann Heather T. , Hanis Craig L. , DeSantis Stacia M. , Perkison William B. , Aguilar David A. , Jun Goo , Robinson D. Ashley , Brown Eric L.
Published: May 2022

Factors affecting nasal
S. aureus
colonization have been studied primarily in the context of persistent carriage. In contrast, few studies have examined factors affecting intermittent nasal carriage with this pathogen.
Detrital zircon provenance and transport pathways of Pleistocene-Holocene eolian sediment in the Pampean Plains, Argentina
Authors: Bruner Austin , Leier Andrew L. , Barbeau David L. , Pullen Alex , Fidler Mary Kate , Stubbins Blake
Published: May 2022

The Pampas of Argentina contain a broad distribution of Pleistocene to Holocene loessic sediments and eolian dune deposits. Models describing the sediment provenance of this eolian system have, at times, conflicted. We address the provenance of these deposits through U-Pb detrital-zircon geochronology. Our results indicate broad similarity in age distributions between samples, with a dominant Permian-Triassic mode, and widespread but lesser Cenozoic, Devonian-Mississippian, Ediacaran-Cambrian, and Mesoproterozoic modes. These data are inconsistent with a large contribution of detritus from Patagonia as previously suggested. These data are consistent with very limited contribution of first cycle volcanogenic zircon to the Pampean eolian system, but abundances of older Neogene zircon indicate proto-sources in the Andes. The ríos Desaguadero, Colorado, and Negro contain populations that were likely within the dust production pathways of most of the loess, paleosol, and eolian dune deposits, but the derivation of the zircon ages in these sediments cannot be explained solely by these river systems. One statistical outlier, a loess sample from the Atlantic coast of the Pampa region, indicates quantitative similarity to the age spectra from the ríos Colorado and Negro, consistent with derivation from these subparallel rivers systems during subaerial exposure of the continental shelf under high global ice-volume. Another statistical outlier, a paleosol sample from the Río Paraná delta region, has zircon ages more closely associated with sediments in the Paraná region than in rivers south of the Pampa region. Collectively, these data point to the complexity of the Pampean eolian system and substantial spatial-temporal variation in this Pleistocene–Holocene eolian system.
Diatom evidence for a groundwater divide that limited the extent of Lake Estancia, New Mexico, USA, highstands during the Last Glacial Maximum
Authors: Menking Kirsten M. , Bixby Rebecca J. , Cutler Savannah M.
Published: May 2022

A high-resolution time series of diatoms from the Estancia Basin of central New Mexico, USA, reveals decadal to millennial changes in water chemistry during the Last Glacial Maximum (LGM) and suggests that groundwater leakage limited the size of Lake Estancia highstands. Previous work showed that the lake expanded at least five times during the LGM, with each highstand reaching the same elevation; numerical modeling experiments showed that highstands required increases in precipitation of 1.5–2 times that of modern times but also demonstrated that these conditions could have lasted for only a few decades or the lake would have overflowed the basin’s sill. The fact that the lake returned to the same elevation suggests that highstands were climatologically similar. Here we present an alternative scenario, that once the lake reached a particular threshold volume, groundwater leakage prevented further expansion, which means that precipitation increases may have been larger than previously thought. The LGM diatom sequence is dominated by freshwater planktonic species in the Lindavia ocellata complex, the freshwater to brackish littoral species Pseudostaurosira brevistriata, and the brackish to saline benthic species Diploneis cf. smithii, all of which show decadal to centennial oscillations that were likely driven by solar cycles. Canonical correspondence analyses using mineralogical time series as proxies for wetter and drier conditions reveal that diatom assemblages varied with salinity and pH/alkalinity and suggest that groundwater outflow led to variable water chemistry for different highstands of the same magnitude. Nonmetric multidimensional scaling confirms the uniqueness of each highstand in terms of the diatom assemblages. The diatom data presented here are among only a handful of such records for Pleistocene pluvial lakes in the American West and reveal that saline alkaline lakes can yield important information despite valve preservation issues.
Supplemental Material: Mesoproterozoic oxygenation event: From shallow marine to atmosphere
Authors: Xie Baozeng , Tang Dongjie , al. et
Published: May 2022

Table S1: Geochemical data from Member II and III of the Gaoyuzhuang Formation in the Yanqing and Jixian Sections, North China. Table S2: δ34SCAS, CAS, Mg/Ca, δ18Ocarb, Mn/Sr and I/(Ca+Mg) values of carbonates from the Gaoyuzhuang Formation in the Yanqing Section, North China. Mg/Ca, δ18Ocarb, Mn/Sr and I/(Ca+Mg) data are from Shang et al. (2019). 
Supplemental Material: Mesoproterozoic oxygenation event: From shallow marine to atmosphere
Authors: Xie Baozeng , Tang Dongjie , et al.
Published: May 2022

Table S1: Geochemical data from Member II and III of the Gaoyuzhuang Formation in the Yanqing and Jixian Sections, North China. Table S2: δ34SCAS, CAS, Mg/Ca, δ18Ocarb, Mn/Sr and I/(Ca+Mg) values of carbonates from the Gaoyuzhuang Formation in the Yanqing Section, North China. Mg/Ca, δ18Ocarb, Mn/Sr and I/(Ca+Mg) data are from Shang et al. (2019). 
Methods for Reducing Anomalous Losses in ECRH Experiments at Second Resonance Harmonic
Authors: Gusakov E. Z. , Popov A. Yu.
Published: May 2022

An approach is analyzed that makes it possible to reduce anomalous absorption in experiments on electron cyclotron resonance heating (ECRH) at the second harmonic of the electron cyclotron resonance. The anomalous absorption is associated with excitation of the low-threshold parametric decay instability of the extraordinary pump wave at the local maximum of the nonmonotonic density profile. The general case is considered, which corresponds to nonlinear excitation of only one localized daughter upper-hybrid wave occurring as a result of the primary decay process. It is shown that, due to rather low instability threshold, it could hardly be completely suppressed in ECRH experiments using megawatt microwave beams. However, an increase in the radius of the pump wave cross section can considerably reduce the corresponding anomalous absorption.
RefractoryMycobacterium genavenseinfection secondary to thymoma-associated endogenous IL-12 inhibitor
Authors: Chen Jessie , Nguyen MaiAnh , Hu Hannah , Cheong Elaine , Sean Riminton D , Reddel Stephen
Published: May 2022

Case

A 39-year-old man with thymoma-associated acetylcholine receptor antibody myasthenia gravis (MG) presented with fevers, night sweats, abdominal pain and weight loss. Marked splenomegaly and intra-abdominal lymphadenopathy were found. Biopsies confirmed disseminatedMycobacterium genavenseinfection. Despite antimicrobials and reduced immunosuppressive medications, he worsened. We suspected a thymoma-associated cytokine inhibitory antibody. The addition of subcutaneous interferon-gamma (IFN-γ) induced clinical and radiological improvement. His antimicrobials were able to be ceased. MG remained stable. Subsequent testing demonstrated an endogenous interleukin-12 (IL-12) inhibitor, likely inhibiting the IL-12/IFN-γ axis crucial for defence against mycobacterial infections.

Discussion

This case illustrates the autoimmune manifestations that can occur with thymoma. It illustrates the benefit of exogenous IFN-γ in overcoming the immune deficit. In this case, its use did not exacerbate existing autoimmune disease or trigger others. We raise awareness of the need to consider cytokine pathway defects as a contributing factor to refractory atypical infections in patients with thymoma-associated MG.
Sex differences and rehabilitation needs after hospital discharge for COVID-19: an Italian cross-sectional study
Authors: Fugazzaro Stefania , Denti Monica , Mainini Carlotta , Accogli Monia Allisen , Bedogni Ginevra , Ghizzoni Daniele , Bertolini Anna , Esseroukh Otmen , Gualdi Cecilia , Schiavi Margherita , Braglia Luca , Costi Stefania
Published: May 2022

Objectives

COVID-19 can result in persistent symptoms leaving potential rehabilitation needs unmet. This study aims to describe persistent symptoms and health status of individuals hospitalised for COVID-19 according to the International Classification of Functioning, Disability and Health domains of impairments, limitations in activity, and participation restrictions.

Design

Cross-sectional study consisting in a telephone interview 3 months after hospital discharge.

Setting

This study was conducted during the first peak of the COVID-19 pandemic by the Local Health Authority of Reggio Emilia (Italy).

Participants

Adult individuals discharged from hospital between April and June 2020 after COVID-19. Exclusion criteria: hospitalisation for reasons other than COVID-19, inability to participate in the study, concomitant acute or chronic conditions causing disability.

Primary and secondary outcome measures

We assessed: dyspnoea (Medical Research Council), fatigue (Fatigue Severity Scale), mood disturbances (Hospital Anxiety and Depression Scale), limitations in activity (Barthel Index) and participation restrictions (Reintegration to Normal Living Index). We also collected data on sociodemographic characteristics, health status prior to COVID-19, COVID-related clinical manifestations and hospital care pathway up to discharge, rehabilitation interventions, accidental falls and emergency room access.

Results

149 participants (men, 62%; average age 62 (±11) years) were enrolled, 35 of which (23%) were admitted to the intensive care unit (ICU) while hospitalised. Three months after hospital discharge, nearly half of the participants still suffered from dyspnoea (44%) or fatigue (39%). Almost all individuals (91.2%) recovered a good level of independence in activity of daily living, but 76% still suffered participation restrictions. Female sex was significantly associated with worse outcomes for all symptoms.

Conclusions

Individuals who had moderate or severe COVID-19 may perceive persistent symptoms which may result in reduced social participation. Sex differences should be monitored, as women may recover more slowly than men.

Trial registration number

NCT04438239.
Controlled human infection with Neisseria lactamica in late pregnancy to measure horizontal transmission and microbiome changes in mother–neonate pairs: a single-arm interventional pilot study protocol
Authors: Theodosiou Anastasia A , Laver Jay R , Dale Adam P , Cleary David W , Jones Christine E , Read Robert C
Published: May 2022

Introduction

Infant upper respiratory microbiota are derived partly from the maternal respiratory tract, and certain microbiota are associated with altered risk of infections and respiratory disease. Neisseria lactamica is a common pharyngeal commensal in young children and is associated with reduced carriage and invasive disease by Neisseria meningitidis. Nasal inoculation with N. lactamica safely and reproducibly reduces N. meningitidis colonisation in healthy adults. We propose nasal inoculation of pregnant women with N. lactamica, to establish if neonatal pharyngeal colonisation occurs after birth, and to characterise microbiome evolution in mother–infant pairs over 1 month post partum.

Methods and analysis

20 healthy pregnant women will receive nasal inoculation with N. lactamica (wild type strain Y92-1009) at 36–38 weeks gestation. Upper respiratory samples, as well as optional breastmilk, umbilical cord blood and infant venous blood samples, will be collected from mother–infant pairs over 1 month post partum. We will assess safety, N. lactamica colonisation (by targeted PCR) and longitudinal microevolution (by whole genome sequencing), and microbiome evolution (by 16S rRNA gene sequencing).

Ethics and dissemination

This study has been approved by the London Central Research Ethics Committee (21/PR/0373). Findings will be published in peer-reviewed open-access journals as soon as possible.

Trial registration number

NCT04784845.
Sustaining immediate newborn care processes (delayed cord clamping and early breastfeeding initiation) in the delivery room: a quality improvement study
Authors: Nagendla Pranavi , Manju Ambika , Somasekhara Aradhya Abhishek , Shebannavar Roopa N , Venkatagiri Praveen
Published: May 2022

Background

Immediate newborn care processes like delayed cord clamping (DCC) and early breastfeeding initiation (EBFI) in the delivery room have several benefits including survival. Despite the evidence, the practices have not been widely adopted. We used a point-of-care quality improvement (QI) to implement and sustain these two immediate newborn care processes in our delivery room over a period of 2 years through a series of plan–do–study–act (PDSA) cycles.

Methods

All neonates above 30 weeks of gestation irrespective of the need for resuscitation except Rh-isoimmunisation were eligible for DCC. Neonates >35 weeks not requiring respiratory support or resuscitation were eligible for EBFI. The root causes of gaps in the quality were analysed by fishbone analysis. The key quantitative outcome measure was the percentage of eligible deliveries in which DCC and EBFI were done. Duration of DCC was also recorded in the sustenance phase. This implementation was done through three PDSA cycles and the practices were sustained for 2 years.

Results

A total of 770 deliveries were part of this QI study from October 2018 to December 2020. There was a significant improvement in DCC (median) from a baseline of 25% to 96% over a 2-year period. Sensitisation, making DCC part of pre-birth checklist and recording outcomes on a dashboard daily helped to implement and sustain the processes over 2 years. As a co-process, EBFI improved (median) from a baseline of 50% to 97% without any major intervention in the system.

Conclusions

Immediate newborn care processes could be sustained by making them part of pre-birth preparation and dashboard recording by a QI initiative without any additional resources.
Update on the diagnosis and management of the autosomal dominant acute hepatic porphyrias
Authors: Schulenburg-Brand Danja , Stewart Felicity , Stein Penelope , Rees David , Badminton Mike
Published: May 2022

The autosomal dominant acute hepatic porphyrias (AHPs), acute intermittent porphyria, hereditary coproporphyria (HCP) and variegate porphyria (VP), are low penetrance adult onset disorders caused by partial deficiency of enzymes of haem biosynthesis. All are associated with acute neurovisceral attacks, which are a consequence of the increased hepatic demand for haem triggered by hormones, stress, drugs or systemic infections which leads to upregulation of the pathway and overproduction of haem precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG). Acute episodes are characterised by severe abdominal pain, nausea, vomiting, hyponatraemia, hypertension and tachycardia, behavioural disturbance and can progress to include seizures, peripheral motor neuropathy and posterior reversible encephalopathy syndrome if undiagnosed and untreated. VP and HCP may also present with photocutaneous skin lesions either alone or during acute symptoms. Diagnosis involves demonstrating increased excretion of PBG in urine. Treatment focuses on removing or managing triggers, supportive treatment and suppressing the hepatic haem pathway by administering human haemin. Chronic complications include hypertension, chronic kidney disease and hepatocellular carcinoma. A small proportion of symptomatic patients with AHP progress to repeated acute attacks which require preventative therapy. A new RNA interference therapy has recently been licensed and is likely to become the treatment of choice in this situation.
Deconvolution of malignant pleural effusions immune landscape unravels a novel macrophage signature associated with worse clinical outcome in lung adenocarcinoma patients
Authors: Bruschini Sara , Pallocca Matteo , Sperandio Eleonora , D’Ambrosio Lorenzo , Ascenzi Francesca , De Vitis Claudia , Salvati Valentina , Esposito Antonella , Di Martino Simona , De Nicola Francesca , Paolini Francesca , Fattore Luigi , Alessandrini Gabriele , Facciolo Francesco , Foddai Maria Laura , Bassi Massimiliano , Venuta Federico , D’Ascanio Michela , Ricci Alberto , D’ Andrilli Antonio , Napoli Christian , Aurisicchio Luigi , Fanciulli Maurizio , Rendina Erino Angelo , Ciliberto Gennaro , Mancini Rita
Published: May 2022

Background

Immune checkpoint inhibitors are still unable to provide clinical benefit to the large majority of non-small cell lung cancer (NSCLC) patients. A deeper characterization of the tumor immune microenvironment (TIME) is expected to shed light on the mechanisms of cancer immune evasion and resistance to immunotherapy. Here, we exploited malignant pleural effusions (MPEs) from lung adenocarcinoma (LUAD) patients as a model system to decipher TIME in metastatic NSCLC.

Methods

Mononuclear cells from MPEs (PEMC) and peripheral blood (PBMC), cell free pleural fluid and/or plasma were collected from a total of 24 LUAD patients and 12 healthy donors. Bulk-RNA sequencing was performed on total RNA extracted from PEMC and matched PBMC. The DEseq2 Bioconductor package was used to perform differential expression analysis and CIBERSORTx for the regression-based immune deconvolution of bulk gene expression data. Cytokinome analysis of cell-free pleural fluid and plasma samples was performed using a 48-Plex Assay panel. THP-1 monocytic cells were used to assess macrophage polarization. Survival analyses on NSCLC patients were performed using KM Plotter (LUAD, N=672; lung squamous cell carcinoma, N=271).

Results

Transcriptomic analysis of immune cells and cytokinome analysis of soluble factors in the pleural fluid depicted MPEs as a metastatic niche in which all the components required for an effective antitumor response are present, but conscripted in a wound-healing, proinflammatory and tumor-supportive mode. The bioinformatic deconvolution analysis revealed an immune landscape dominated by myeloid subsets with the prevalence of monocytes, protumoral macrophages and activated mast cells. Focusing on macrophages we identified an MPEs-distinctive signature associated with worse clinical outcome in LUAD patients.

Conclusions

Our study reports for the first time a wide characterization of MPEs LUAD microenvironment, highlighting the importance of specific components of the myeloid compartment and opens new perspectives for the rational design of new therapies for metastatic NSCLC.
Risk-adapted chemoimmunotherapy using brentuximab vedotin and rituximab in children, adolescents, and young adults with newly diagnosed Hodgkin’s lymphoma: a phase II, non-randomized controlled trial
Authors: Hochberg Jessica , Basso Jaclyn , Shi Qiuhu , Klejmont Liana , Flower Allyson , Bortfeld Kristina , Harrison Lauren , van de Ven Carmella , Moorthy Chitti , Islam Humayun , Gerard Perry , Voss Stephan , Cairo Mitchell S
Published: May 2022

Background

Cure rates for Hodgkin’s lymphoma are excellent, but excess short-term and long-term morbidities from treatment remain a concern. Immunotherapy targeting both tumor antigens and the immunosuppressive tumor microenvironment in children, adolescents, and young adults with Hodgkin’s lymphoma may improve early response rates and eliminate toxic chemotherapy and radiation, thus minimizing toxicity. We conducted a phase II study to evaluate the safety and overall response rate of brentuximab vedotin and rituximab in combination with risk-adapted chemotherapy in children, adolescents, and young adults with newly diagnosed classic Hodgkin’s lymphoma (cHL).

Methods

This is a prospective, phase II, non-randomized, risk-assigned study. Patients were treated and evaluated between 2012 and 2020. Eligible patients were aged ≥1 and ≤30 years old with advanced stage, intermediate-risk, and high-risk newly diagnosed cHL. Patients received four or six cycles of brentuximab vedotin (1.2 mg/kg), doxorubicin (25 mg/m2), vinblastine (6 mg/m2), dacarbazine (375 mg/m2), and rituximab (375 mg/m2). Early response was evaluated following two cycles of therapy. Involved field radiotherapy (IFRT) was restricted to high-risk patients with both bulky disease and slow response or those not in complete response at the end of chemoimmunotherapy.

Results

Thirty patients were enrolled, with a median age of 15 years (4–23). There were 18 intermediate-risk and 12 high-risk patients. Toxicities included grade III mucositis (3%), infusion reaction (3%), and peripheral neuropathy (6%). There was a 100% complete response rate on completion of chemoimmunotherapy. Eighteen patients (60%) achieved a rapid early response. Four patients (13%) required IFRT. The 5-year event-free and overall survival rates were 100%, with a median follow-up of 62 months (18–105).

Conclusions

Immunotherapy with brentuximab vedotin, rituximab, and risk-adapted chemotherapy is safe in children, adolescents, and young adults with newly diagnosed cHL. We have demonstrated 100% complete response and 100% event-free and overall survival rates at a median 5-year follow-up, with a significant reduction in use of more toxic chemotherapy and IFRT. A larger cohort is required to confirm these preliminary findings.

Trial registration number

NCT02398240.
Morisprudence: a theoretical framework for studying the relationship linking moral case deliberation, organisational learning and quality improvement
Authors: Kok Niek , Zegers Marieke , van der Hoeven Hans , Hoedemaekers Cornelia , van Gurp Jelle
Published: May 2022

There is a claim that clinical ethics support services (CESS) improve healthcare quality within healthcare organisations. However, there is lack of strong evidence supporting this claim. Rather, the current focus is on the quality of CESS themselves or on individual learning outcomes. In response, this article proposes a theoretical framework leading to empirical hypotheses that describe the relationship between a specific type of CESS, moral case deliberation and the quality of care at the organisational level. We combine insights from the literature on CESS, organisational learning and quality improvement and argue that moral case deliberation causes healthcare professionals to acquire practical wisdom. At the organisational level, where improving quality is a continuous and collective endeavour, this practical wisdom can be aggregated into morisprudence, which is an ongoing formulation of moral judgements across cases encountered within the organisation. Focusing on the development of morisprudence enables refined scrutinisation of CESS-related quality claims.
Can we screen less frequently for STI among PrEP users? Assessing the effect of biannual STI screening on timing of diagnosis and transmission risk in the AMPrEP Study
Authors: Jongen Vita W. , Zimmermann Hanne M.L. , Goedhart Marit , Bogaards Johannes A. , Davidovich Udi , Coyer Liza , de Vries Henry J.C. , Prins Maria , Hoornenborg Elske , Schim van der Loeff Maarten F.
Published: May 2022

Background

In many countries, HIV pre-exposure prophylaxis (PrEP) users are screened quarterly for STIs. We assessed the consequences of less frequent STI testing. We also assessed determinants of asymptomatic STI and potential for onward transmission.

Methods

Using data from the AMPrEP study, we assessed the proportion of syphilis, and genital, anal, and pharyngeal chlamydia and gonorrhoea diagnoses which would have been delayed with biannual versus quarterly screening. We assessed the potential for onward transmission by examining reported condomless anal sex (CAS) in periods after to-be-omitted visits when screening biannually. We assessed determinants of incident asymptomatic STIs using Poisson regression and calculated individual risk scores on the basis of the coefficients from this model.

Results

We included 366 participants. Median follow-up was 47 months (IQR 43–50). 1,183STIs were diagnosed, of which 932(79%) asymptomatic. With biannual screening, 483 asymptomatic STIs (52%) diagnoses would have been delayed at 364 study visits. Of these visits, 129 (35%), 240 (66%) and 265 (73%) were followed by periods of CAS with steady, known casual or unknown casual partners, respectively. Older participants had a lower risk of asymptomatic STI (incidence rate ratio (IRR) 0.86/10-year increase, 95% CI 0.80 to 0.92), while CAS with known (IRR 1.36, 95% CI 1.10 to 1.68) and unknown (IRR 1.86, 95% CI 1.48 to 2.34) casual partners and chemsex (IRR 1.51, 95% CI 1.28 to 1.78) increased the risk. The individual risk scores had limited predictive value (sensitivity=0.70 (95% CI 0.66 to 0.74), specificity=0.50 (95% CI 0.48 to 0.51)).

Conclusion

Reducing the STI screening frequency to biannually among PrEP users will likely result in delayed diagnoses, potentially driving onward transmission. Although determinants for asymptomatic STIs were identified, predictive power was low.
Suffusion of sand–clay mixture by three-staged change of ionic strength
Authors: Won Jongmuk , Kim Taehyeong , Kang Minkyu , Choe Yongjoon , Choi Hangseok
Published: May 2022

The suffusion of particles classified as coarse-grained soils in the Unified Soil Classification System has been relatively well investigated in previous studies, whereas suffusion of clay particles has not been thoroughly explored. For clay particles, the surface interaction energy between clay and sand can be a critical factor in conjunction with hydraulic gradient. Therefore, this paper presented a series of designed soil-column experiments for assessing the reduction of ionic strength on suffusion of clay particles in the sand–clay mixture. The three most typical clay particles (kaolinite, illite, and montmorillonite) were selected and the ionic strength was decreased during the injection. The results indicate that the sequence of decreasing ionic strength induced substantial suffusion of clay particles, mainly attributed to the decreased attraction between sand grains and clay particles. In addition, among three types of clay particles, the high swelling potential of montmorillonite particles led to the most substantial increase in relative hydraulic conductivity caused by suffusion.
The orchid embryo — “an embryonic protocorm”
Authors: Yeung Edward C.
Published: May 2022

Orchid embryo development is unusual among flowering plants with many distinctive characteristics. This review highlights the unique features of orchid embryos. After fertilization, the polarity is established in the zygote before its first asymmetric division. In species such as Epidendrum ibaguense H.B.K., the zygote elongates before the first asymmetric division, while others such as Cymbidium sinense (Andr.) Willd. divide without an apparent cell elongation phase. An obvious structural polarity with a prominent vacuole at the micropylar end is not necessarily present in orchid zygotes. The suspensor is derived from the basal cell of a two-celled embryo, and varied morphologies can be found. The suspensor functions in nutrient uptake and can have a morphogenetic role to play in embryo proper development. For embryos without an expanded suspensor, nutrients have to be acquired directly through their surface. The embryo proper develops from the terminal cell of a two-celled embryo. It undergoes a limited number of cell divisions resulting in a tiny embryo with a protocorm body plan. Despite their simple structural organization, orchid embryos have developmental programs as complex as other flowering plants. The ultimate goal of embryo development is to generate a protocorm body plan ready for germination.
Self-gravitating anisotropic model in general relativity under modified Van der Waals equation of state: a stable configuration
Authors: Errehymy Abdelghani , Mustafa G. , Khedif Youssef , Daoud Mohammed , Alrebdi H. I. , Abdel-Aty Abdel-Haleem
Published: May 2022

The purpose of this paper consists in presenting models of compact stars described by a new class of exact solutions to the field equations, in the context of general relativity, for a fluid configuration which is locally anisotropic in the pressure. With current sensitivities, we considered a non-linear form of modified Van der Waals equation of state viz., $$p_{r}=\alpha \rho ^{2} +\frac{\beta \rho }{1+\gamma \rho }$$

p
r

=
α

ρ
2

+

β
ρ

1
+
γ
ρ

, as well as a gravitational potential Z(x) as a generating function by exploiting an anisotropic source of matter which served as a basis for generating the confined compact stars. The exact solutions are formed by correlating an interior space-time geometry to an exterior Schwarzschild vacuum. Then, we analyze the physical viability of the model generated and compare it with observational data of some heavy pulsars coming from the Neutron Star Interior Composition Explorer. The model satisfies all the required pivotal physical and mathematical properties in the compact structures study, offering empirical evidence in support of the evolution of realistic stellar configurations. It is shown to be regular, viable, and stable under the influence generated by the parameters coming from the theory namely, $$\alpha $$
α
, $$\beta $$
β
, $$\gamma $$
γ
, $$\delta $$
δ
, everywhere within the astral fluid in the investigated high-density regime that supports the existence of realistic heavy pulsars such as PSR J0348+0432, PSR J0740+6620 and PSR J0030+0451.
Circular motion around a regular rotating Hayward black hole
Authors: Khan Saeed Ullah , Ren Jingli , Rayimbaev Javlon
Published: May 2022

In this paper, we explore the geodesics motion of neutral test particles and the process of energy extraction from a regular rotating Hayward black hole (BH). We analyze the effect of spin as well as deviation parameter [Formula: see text], on ergoregion, event horizon and static limit of the said BH. By making use of geodesic equations on the equatorial plane, we determine the innermost stable circular and photon orbits. Moreover, we investigate the effective potentials and effective force to have information on motion and the stability of circular orbits. On studying the negative energy states, we figure out the energy limits of Penrose mechanism. Using Penrose mechanism, we found expression for the efficiency of energy extraction and observed that both spin and deviation parameters contribute to the efficiency of energy extraction. Finally, the obtained results are compared with that acquired from Kerr and braneworld Kerr BHs.
Further swampland constraint on Dirac neutrino
Authors: Harada Taiga , Nakayama Yu
Published: May 2022

Recent studies on swampland conjectures (e.g. non-SUSY AdS conjecture or AdS distance conjecture) predict that the (lightest) neutrino must be Dirac and the mass must be cosmologically small [Formula: see text]. The Dirac neutrino naturally accompanies a [Formula: see text] symmetry that can be embedded in the anomaly-free [Formula: see text] global symmetry of the standard model. We point out that the swampland conjectures applied to a circle compactification with the [Formula: see text] symmetry twisting lead to further constraints. In particular, the [Formula: see text] symmetry must be broken down to [Formula: see text], [Formula: see text] or [Formula: see text] in the case of normal hierarchy, and [Formula: see text] in the case of inverted hierarchy, providing evidence for the absence of continuous global symmetry in quantum gravity. We also predict a more constrained upper bound of the neutrino mass for each case.
Federated Multi-view Learning for Private Medical Data Integration and Analysis
Authors: Che Sicong , Kong Zhaoming , Peng Hao , Sun Lichao , Leow Alex , Chen Yong , He Lifang
Published: May 2022

Along with the rapid expansion of information technology and digitalization of health data, there is an increasing concern on maintaining data privacy while garnering the benefits in the medical field. Two critical challenges are identified: First, medical data is naturally distributed across multiple local sites, making it difficult to collectively train machine learning models without data leakage. Second, in medical applications, data are often collected from different sources and views, resulting in heterogeneity and complexity that requires reconciliation. In this article, we present a generic Federated Multi-view Learning (FedMV) framework for multi-view data leakage prevention. Specifically, we apply this framework to two types of problems based on local data availability: Vertical Federated Multi-view Learning (V-FedMV) and Horizontal Federated Multi-view Learning (H-FedMV). We experimented with real-world keyboard data collected from BiAffect study. Our results demonstrated that the proposed approach can make full use of multi-view data in a privacy-preserving way, and both V-FedMV and H-FedMV perform better than their single-view and pairwise counterparts. Besides, the framework can be easily adapted to deal with multi-view sequential data. We have developed a sequential model (S-FedMV) that takes sequence of multi-view data as input and demonstrated it experimentally. To the best of our knowledge, this framework is the first to consider both vertical and horizontal diversification in the multi-view setting, as well as their sequential federated learning.