bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the COVID-19 Pandemic on the Experiences of Hospitalized Patients: A Scoping Review
Authors: Engel Franciely Daiana , da Fonseca Graziele Gorete Portella , Cechinel-Peiter Caroline , Backman Chantal , da Costa Diovane Ghignatti , de Mello Ana Lúcia Schaefer Ferreira
Published: December 2022

Objective

This study aimed to identify the factors that exerted an impact on the experiences of hospitalized patients during the COVID-19 pandemic from the quality and safety perspectives.

Method

A scoping review that followed the 5 stages described by Arksey and O’Malley was used. A systematized search of original studies was conducted in 9 databases: PubMed/MEDLINE, BDENF, CINAHL, LILACS, SciELO, Embase, Scopus, Web of Science, and Google Scholar. The factors that exerted an impact on patients’ experiences were summarized, considering the perspective of quality and patient safety in health institutions. The factors were categorized using the Content Analysis technique.

Results

A total of 6950 studies were screened, and 32 met the eligibility criteria. The main factors that exerted an impact on the patients’ experience were as follows: caregiver/family concern with the patients’ well-being during hospitalization, search for alternative communication and interaction means between the patients and their family, and changes in health care organization. The restrictions inherent to the policy regarding visits and companions exerted a negative impact on the experiences, increasing the patients’ feelings of loneliness and isolation. Negative impacts were also evidenced in the hospital admission and discharge process and in the limitation of treatment possibilities offered to the patients, because of contact restrictions.

Conclusions

The factors that exerted an impact on the patients’ experiences permeate communication between professionals, patients, and family members, with implications for health care quality.
Enterovibrio paralichthyis sp. nov., isolated from the gut of an olive flounder Paralichthys olivaceus
Authors: Kim Young-Ok , Park In-Suk , Kim Dong-Gyun , Park Sooyeon , Han Sung Hoon , Yoon Jung-Hoon
Published: December 2022

A Gram-stain-negative, facultatively anaerobic, flagellated and coccoid, ovoid or rod-shaped bacterial strain, NIFS-20-8T, was isolated from the intestine of an olive flounder (Paralichthys olivaceus) from the East Sea, Republic of Korea. The neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain NIFS-20-8T fell within the clade comprising the type strains of

Enterovibrio

species. Strain NIFS-20-8T exhibited 16S rRNA gene sequence similarities of 97.2 and 97.1 % to the type strains of

Enterovibrio nigricans

and

Enterovibrio norvegicus

, respectively, and of 96.6–97.0 % to the type strains of the other

Enterovibrio

species. The average nucleotide identity and digital DNA–DNA hybridization values between the genomic sequence of strain NIFS-20-8T and those of the type strains of four

Enterovibrio

species were 73.8–75.0 and 19.8–21.1 %, respectively. The DNA G+C content of strain NIFS-20-8T from genomic sequence data was 50.55 mol%. Strain NIFS-20-8T contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), C16 : 0 and C18 : 1
 ω7c as the major fatty acids. The major polar lipids detected in stain NIFS-20-8T were phosphatidylethanolamine and phosphatidylglycerol. Distinguishing phenotypic properties, together with phylogenetic and genetic distinctiveness, revealed that strain NIFS-20-8T is separated from recognized

Enterovibrio

species. On the basis of the data presented here, strain NIFS-20-8T is considered to represent a novel species of the genus

Enterovibrio

, for which the name Enterovibrio paralichthyis sp. nov. is proposed. The type strain is NIFS-20-8T (= KCTC 82873T=NBRC 115237T).
Streptococcus pneumoniae: ‘captain of the men of death’ and financial burden
Authors: Yesilkaya Hasan , Oggioni Marco R. , Andrew Peter W.
Published: December 2022

Streptococcus pneumoniae

may inhabit the upper respiratory tract of humans without causing harm but it also causes diseases with high morbidity and mortality. It has excellent adaptive capabilities thanks to its ability to shuffle its genetic content by acquiring and incorporating DNA from other bacteria and is highly competent for genetic transformation. Sugar sensing, cleavage and transport ensure its fitness and survival in the host, and intracellular survival in macrophages has been linked to virulence. The polysaccharide capsule and toxin pneumolysin are the most important virulence determinants. Polysaccharide-based vaccines provide protection against the serotypes represented in vaccine formulations.
Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain
Authors: Lin Ya-Hui , Wang Li-Wen , Chen Yen-Hui , Chan Yi-Chieh , Hu Shang-Hsiu , Wu Sheng-Yan , Chiang Chi-Shiun , Huang Guan-Jie , Yang Shang-Da , Chu Shi-Wei , Wang Kuo-Chuan , Lin Chin-Hsien , Huang Pei-Hsin , Cheng Hwai-Jong , Chen Bi-Chang , Chu Li-An
Published: December 2022

Tissue clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain, and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.
Clinical impact using low dose mycophenolate mofetil with tacrolimus on acute rejection, infectious diseases and non-infectious complications in renal transplant: A Single Hospital Experience in Mexico
Authors: Andrade-Sierra Jorge , Hernández-Reyes Hernesto , Rojas-Campos Enrique , Cardona-Muñoz Ernesto G , Cerrillos-Gutiérrez José I , González-Espinoza Eduardo , Evangelista-Carrillo Luis A , Medina-Pérez Miguel , Jalomo-Martínez Basilio , Miranda-Díaz Alejandra G , Martínez-Mejía Víctor M , Gómez-Navarro Benjamin , Andrade-Ortega Antonio de Jesús , Nieves-Hernández Juan J , Mendoza-Cerpa Claudia
Published: December 2022

Background

The evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) in renal transplant (RT) is still limited but maintaining the dose of less than 2g could result in worse clinical outcomes in terms of acute rejection (AR).

Research Question

This study’s aim was to determine the association between AR, infectious and non-infectious complications after RT with the dose of 1.5gvs. 2g of MMF.

Design

A prospective cohort was performed with a 12-month follow-up in recipients of RT from living donors with low doses of MMF (1.5 g/day) or use of standard dosage (2 g/day). The association between adverse effects and complications and doses of MMF were examined in Cox proportional hazard models and survival free of AR, infectious diseases, and non-infectious complications was evaluated by the Kaplan-Meier test.

Results

At the end of the follow-up, the incidence of infectious diseases was 52%vs. 50% (p=0.71) and AR was 5%vs. 5% (p=0.86), respectively. Survival free of GI complications requiring medical attention was higher in the low dose group compared to the standard dose (88%vs. 45%, respectively;p<0.001).

Discussion

The use of 1.5 g/day of MMF is safe in Mexican population with RT from living donors without increasing the risk of AR, and it confers a reduction of adverse events.
Knowledge, Attitude and Practice (KAP) Survey about hepatitis B (HBV) and C (HCV) among migrant populations from Sub-Saharan Africa
Authors: Saaed Frhat M. A. , Ongerth Jerry E. , Ali Muna H.
Published: December 2022

Background

Hepatitis B and C virus infections are serious blood borne diseases with global health concern particularly in developing countries. The association between survey participant’s knowledge, attitude, and practices (KAP) about HBV and HCV infection is rarely studied, particularly among migrants seeking resettlement. Libya is a main transient station for migrants northward toward Europe and the flow is increasing into Al Kufra from neighboring countries that have endemic intermediate and high HBV and HCV prevalence. The purpose of this exploratory descriptive study in Al Kufra was to assess the level of participating migrant’s KAP, regarding cause, transmission, prevention, and treatment of viral hepatitis due to HBV and HCV.

Method

A cross-sectional study was conducted among 674 sub-Saharan African migrants in Al Kufra, Libya from January to October 2021. Migrant’s KAP about HBV and HCV infection was assessed by interview questionnaire. Statistical and data analysis used SPSS version of 25.

Results

Out of 700 questionnaires distributed, 674 were returned with a response rate of 96.3%. The study population included 580 (86.1%) males, mean age of 29.6 ± 7.2 SD years. A majority, 508 (75.4%) were illiterate and elementary level, 8 2.483+.232, respectively. Positive significant linear correlations were found between knowledge-attitude (r = 0.524, p < 0.01) knowledge-practice (r = 0.123, p < 0.01) and attitude-practice (r = 0.278, p < 0.01). Ethnicity and education variables were significantly associated with mean KAP. Gender identity and marital status were both significantly associated with mean knowledge and attitude.

Conclusion

The migrant population from the neighboring and sub-Saharan African countries have inadequate KAP about HBV and HCV to limit infection.
Centrosome formation in the bovine early embryo
Authors: Uzbekov Rustem , Singina Galina , Shedova Ekaterina , Banliat Charles , Avidor-Reiss Tomer , Uzbekova Svetlana
Published: December 2022

Centrosome formation during early development in mice and rats occurs due to the appearance of centriolesde novo. In contrast, in humans and other non-rodent mammals, centrioles are thought to be derived from spermatozoa. Ultrastructural study of zygotes and early embryos of cattle at full series of ultrathin sections showed that the proximal centriole of the spermatozoon disappears by the end of the first cleavage division. Centrioles appear in 2–4 cell embryos in fertilized oocytes and in parthenogenetic embryos. Centriole formation includes the appearance of atypical centrioles with randomly arranged triplets and centrioles with microtubule triplets of various lengths. After the third cleavage, four centriolar cylinders for the first time appear in the blastomeres while each embryo still has two atypical centrioles. Our results showed that the mechanisms of centriole formation in different groups of mammals are universal, differing only in the stage of development in which they occur.
A Novel Localized Tracing Technique to Explore Intra-Amygdala Functional and Structural Connectivity Patterns as Mediators of Individual Variability in Stress Response
Authors: Lipshutz Allie , Saltz Victoria , Anderson Kristin R , Manganaro Alessia , Dumitriu Dani
Published: December 2022

Neuropsychiatric disorders including anxiety and depression can be induced by stress, but not all individuals exposed to stress develop psychopathology. Therefore, probing the neural substrates that underlie trait vulnerability to stress may open the door for preventive approaches that use biological markers to identify at-risk populations. Here, we developed a novel tracing technique to probe local connectivity patterns as predictors of individual variability in stress responses. Specifically, we combined a retrograde transsynaptic rabies tracing system with cFos colocalization immediately after an acute stressor to elucidate local structural and stress-activated (functional) differences in connectivity within the amygdala complex in female and male mice along a spectrum of social approach/avoidance following acute social defeat stress. While we find no structural or functional connections within the amygdala complex as predictors of individual variability in our behavioral readout, our methods provide a novel approach to investigating cellular and behavioral individual variability in stress responses. Furthermore, we identify overall stress-activation as a predictor of social approach/avoidance in two subregions, medial amygdala and piriform-amygdala area, which may serve as potential biological markers of trait vulnerability, with possible clinical applicability.

Significance Statement

Exposure to stress is ubiquitous, but the outcomes of stress exposure vary greatly between individuals. Our work introduces a novel tracing technique to probe for structural and functional connectivity patterns across a broad spectrum of behavioral responses to social stress. Utilizing pre-clinical classification in conjunction with representative behavioral classification introduces to the field a mechanism to identify potential clinical targets for preventative screening for neuropsychiatric disorders as well as further individualized treatment. Notably, our work identifies two intra-amygdalar neural correlates of social stress, opening the door for future investigation of the role these regions play in mediating social stress.
Data Gap or Biodiversity Gap? Evaluating apparent spatial biases in community science observations of Odonata in the east-central United States
Authors: Bullion Christian M. , Bahlai Christie A.
Published: December 2022

Odonates (dragonflies and damselflies) have become popular study organisms for insect-based climate studies, due to the taxon’s strong sensitivity to environmental conditions, and an enthusiastic following by community scientists due to their charismatic appearance and size. Where formal records of this taxon can be limited, public efforts have provided nearly 1,500,000 open-sourced odonate records through online databases, making real-time spatio-temporal monitoring more feasible. While these databases can be extensive, concerns regarding these public endeavors have arisen from a variety of sources: records may be biased by human factors (ex: density, technological access) which may cause erroneous interpretations. Indeed, records of odonates in the east-central US documented in the popular database iNaturalist bear striking patterns corresponding to political boundaries and other human activities. We conducted a ‘ground-truthing’ study to examine these patterns in an area where community science reports indicated variable abundance, richness, and diversity which appeared to be linked to observation biases. Our observations were largely consistent with patterns recorded by community scientists, suggesting these databases were indeed capturing representative biological trends and raising further questions about environmental drivers in the observed data gaps.
The Epithelial Na+Channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components from old to new boutons in remodeling neurons
Authors: Cuentas-Condori Andrea , Chen Siqi , Krout Mia , Gallick Kristin , Tipps John , Flautt Leah , Richmond Janet E. , Miller David M.
Published: December 2022

Presynaptic terminals are actively relocated during development to refine circuit function, but the underlying cell biological mechanisms are largely unknown. InC. elegans, the presynaptic boutons of GABAergic DD neurons are moved to new locations during early larval development. We show that developmentally regulated expression of a presynaptic Epithelial Na+Channel (ENaC), UNC-8, promotes a Ca2+-dependent mechanism, resembling Activity-Dependent Bulk Endocytosis (ADBE), that dismantles presynaptic material for reassembly at nascent DD synapses. ADBE normally functions in highly active neurons to accelerate local recycling of synaptic vesicles. We show that DD presynaptic remodeling depends on canonical features of ADBE including elevated intracellular Ca2+, the phosphatase Calcineurin and its targets, dynamin and the F-BAR protein syndapin, and Arp2/3-driven actin polymerization. Thus, our findings suggest that a native mechanism (ADBE) for maintaining neurotransmitter release at local synapses has been repurposed, in this case, to dismantle presynaptic terminals for reassembly at new locations.

Highlights

Developing GABAergic neurons dismantle presynaptic terminals for reassembly at new locations.

The DEG/ENaC protein, UNC-8, promotes presynaptic disassembly and recycling

Ca2+-dependent endocytosis drives presynaptic disassembly and recycling to new boutons
Human voltage-gated Na+and K+channel properties underlie sustained fast AP signaling
Authors: Wilbers René , Metodieva Verjinia D. , Duverdin Sarah , Heyer Djai B. , Galakhova Anna A. , Mertens Eline J. , Versluis Tamara D. , Baayen Johannes C. , Idema Sander , Noske David P. , Verburg Niels , Willemse Ronald B. , de Witt Hamer Philip C. , Kole Maarten H. P. , de Kock Christiaan P.J. , Mansvelder Huibert D. , Goriounova Natalia A.
Published: December 2022

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have surprisingly fast input-output properties: rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na+) and potassium (K+) currents in human pyramidal neurons can explain their fast input-output properties. Human Na+and K+currents exhibited more depolarized voltage-dependence, slower inactivation and faster recovery from inactivation compared with their mouse counterparts. Computational modeling showed that despite lower Na+channel densities in human neurons, the biophysical properties of Na+channels resulted in higher channel availability and contributed to fast AP kinetics stability. Finally, human Na+channel properties also resulted in a larger dynamic range for encoding of subthreshold membrane potential changes. Thus, biophysical adaptations of voltage-gated Na+and K+channels enable fast input-output properties of large human pyramidal neurons.

One-Sentence Summary

Biophysical properties of Na+and K+ion channels enable human neurons to reliably encode fast inputs into output.
Dual-color single molecule localization microscopy on transparent polymer waveguide chips
Authors: Engdahl Anders Kokkvoll , Dutta Surjendu Bikash , Belle Stefan , Schürstedt Jasmin , Szafranska Karolina , McCourt Peter , Hellmann Ralf , Huser Thomas , Schüttpelz Mark
Published: December 2022

Photonic waveguide chips offer near-field excitation of biological samples, which enables cost-effective, large field-of-view super-resolution microscopy without the need for high numerical aperture (NA) objective lenses. Single molecule localization based super-resolution microscopy that requires high illumination intensities is currently limited to solid state photonic waveguide chips composed of hard-coated, high NA planar waveguides deposited on opaque substrates. These platforms do not permit epi-detection of fluorescence through the substrate, which limits the use of photonic waveguide chips to the upright configuration. Additionally, the detection efficiency is reduced because the majority of the fluorescence emission is directed towards the high refractive index substrate. A low cost waveguide chip based on a polymer core material deposited on common #1.5 coverslips that is easy to produce was recently demonstrated. Here, a platform that is capable of performing single-molecule localization microscopy (SMLM) of biological samples using polymer-based photonic waveguide chips is presented, enabling super-solution microscopy in the inverted microscope configuration. Super-resolved imaging of two different structures of the cytoskeleton in primary liver sinusoidal endothelial cells (LSECs) by two popular SMLM methods,dSTORM and DNA-PAINT, down to 23 nm is demonstrated.
Plasmodium falciparumadapts its investment into replicationversustransmission according to the host environment
Authors: Abdi Abdirahman I. , Achcar Fiona , Sollelis Lauriane , Silva-Filho Joao Luiz , Mwikali Kioko , Muthui Michelle , Mwangi Shaban , Kimingi Hannah W. , Orindi Benedict , Kivisi Cheryl Andisi , Alkema Manon , Chandrasekar Amrita , Bull Peter C. , Bejon Philip , Modrzynska Katarzyna , Bousema Teun , Marti Matthias
Published: December 2022

The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factorap2-g, is known to be influenced by host factors but a comprehensive model remains uncertain. Here we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission. We examine markers of host immunity and metabolism, and markers of parasite growth and transmission investment. We find that inflammatory responses and reduced plasma lysophosphatidylcholine levels are associated with markers of increased investment in parasite sexual reproduction (i.e., transmission investment) and reduced growth (i.e., asexual replication). This association becomes stronger with falling transmission and suggests that parasites can rapidly respond to the within-host environment, which in turn is subject to changing transmission.
HTRX: an R package for learning non-contiguous haplotypes associated with a phenotype
Authors: Yang Yaoling , Lawson Daniel
Published: December 2022

Haplotype Trend Regression with eXtra flexibility (HTRX) is an R package which uses cross-validation to learn sets of interacting features for a prediction. HTRX identifies haplotypes composed of non-contiguous single nucleotide polymorphisms (SNPs) associated with a phenotype. To reduce the space and computational complexity when investigating many features, we constrain the search by growing good feature sets using ‘Cumulative HTRX’, and limit the maximum complexity of a feature set.

Availability

HTRX is implemented in R and is available under GPL-3 license from CRAN and Github at:https://github.com/YaolingYang/HTRX.

Contact

yaoling.yang@bristol.ac.uk
Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice
Authors: Campbell Matthew D. , Samuelson Ashton T. , Chiao Ying Ann , Sweetwyne Mariya T. , Ladiges Warren C. , Rabinovitch Peter S. , Marcinek David J.
Published: December 2022

The pathology of aging impacts multiple organ systems including the kidney, skeletal, and cardiac muscle. Long-term treatment with the mitochondrial targeted peptide elamipretide has previously been shown to improvein vivomitochondrial function in aged mice that is associated with increased fatigue resistance and treadmill performance, improved cardiovascular diastolic function, and glomerular architecture of the kidney. However, elamipretide is a short tetrameric peptide that is not orally bioavailable limiting its routes of administration. This study tested whether twice weekly intermittent injections of elamipretide could recapitulate the same functional improvements as continuous long-term infusion. We found that intermittent treatment with elamipretide for 8 months preserved endurance running in mice, skeletal muscle force production, and left ventricular mass but did not affect heart or kidney function as previously reported using continuous treatment.
Contrastive learning of protein representations with graph neural networks for structural and functional annotations
Authors: Luo Jiaqi , Luo Yunan
Published: December 2022

Although protein sequence data is growing at an ever-increasing rate, the protein universe is still sparsely annotated with functional and structural annotations. Computational approaches have become efficient solutions to infer annotations for unlabeled proteins by transferring knowledge from proteins with experimental annotations. Despite the increasing availability of protein structure data and the high coverage of high-quality predicted structures, e.g., by AlphaFold, many existing computational tools still only rely on sequence data to predict structural or functional annotations, including alignment algorithms such as BLAST and several sequence-based deep learning models. Here, we develop PenLight, a general deep learning framework for protein structural and functional annotations. PenLight uses a graph neural network (GNN) to integrate 3D protein structure data and protein language model representations. In addition, PenLight applies a contrastive learning strategy to train the GNN for learning protein representations that reflect similarities beyond sequence identity, such as semantic similarities in the function or structure space. We benchmarked PenLight on a structural classification task and a functional annotation task, where PenLight achieved higher prediction accuracy and coverage than state-of-the-art methods.
Population mortality impacts of the rising cost of living in Scotland: modelling study
Authors: Richardson Elizabeth , McCartney Gerry , Taulbut Martin , Douglas Margaret , Craig Neil
Published: December 2022

Objectives

To estimate the potential impacts of unmitigated and mitigated cost of living increases on real household income, mortality, and mortality inequalities in Scotland.

Design

Modelling study.

Setting

Scotland, 2022/23.

Participants

A representative sample of 5,602 Scottish individuals (within 2,704 households) in the 2015/16 Family Resources Survey. We estimated changes in real household income associated with differential price inflation (based on proportion of household spending on different goods and services, by income group), both with and without mitigating UK Government policies, and scaled these to the Scottish population. We estimated mortality effects using a cross-sectional relationship between household income and mortality data, by deprivation group.

Interventions

Baseline was Scotland in 2022/23 with the average wage and price inflation of preceding years. The comparison scenarios were unmitigated cost of living increases, and mitigation by the UK Government’s Energy Price Guarantee (EPG) and Cost of Living Support payments.

Main outcome measures

Premature mortality rate and life expectancy at birth by Scottish Index of Multiple Deprivation (SIMD) group, and inequalities in both.

Results

Unmitigated price inflation was 14.9% for the highest income group and 22.9% for the lowest. UK Government policies partially mitigated impacts of the rising cost of living on real incomes, although households in the most deprived areas of Scotland would still be £1,400 per year worse off than at baseline. With the mitigating measures in place, premature mortality was estimated to increase by up to 6.4%, and life expectancy to decrease by up to 0.9%. Effects would be greater in more deprived areas, and inequalities would increase as a result.

Conclusions

Large and inequitable impacts on mortality in Scotland are predicted if real-terms income reductions are sustained. Progressive Cost of Living Support payments are not sufficient to offset the mortality impacts of the greater real income reductions in deprived areas.

What is already known on this topic

Over the last decade, life expectancy in Scotland has stalled and inequalities have increased.

Income reductions have been related to increased mortality risk, hence the economy matters for public health.

The impacts of the rising cost of living and mitigating policies on mortality and inequalities require estimation to inform policymaking.

What this study adds

The mortality impacts of inflation and real-terms income reduction are likely to be large and negative, with marked inequalities in how these are experienced.

Current public policy responses are not sufficient to protect health and prevent widening inequalities.

Bolder and more progressive policy responses are required if health is to improve and health inequalities are to narrow.
Experience of induction of labour: a cross-sectional postnatal survey of women at UK maternity units
Authors: Harkness Mairi , Yuill Cassandra , Cheyne Helen , McCourt Christine , Black Mairead , Pasupathy Dharmintra , Sanders Julia , Wallace Chloe , Heera-Shergill Neelam , Stock Sarah
Published: December 2022

Background

Induction of Labour (IOL) is an increasingly common obstetric intervention, offered to 30-50% of pregnant women in the UK. IOL affects experience of childbirth: it is more painful than spontaneous labour and more likely to lead to additional interventions including operative birth. Experience of childbirth is important to women, and negative experience of childbirth has been linked to serious psychological harm. The high and rising rate of IOL has implications for provision of safe, effective, person-centred maternity services, yet there is little information about women’s experiences of induction.

Aim

To explore women’s views and experiences of key elements of the IOL process, including at home or in hospital cervical ripening (CR)

Methods

A questionnaire-based postnatal survey of 309 women who had IOL at UK maternity units in 2021/22, undertaken as part of the CHOICE Study process evaluation The questionnaire was administered online and included fixed response and free text options. Findings are reported as descriptive statistics with content analysis of women’s comments providing context.

Findings

Information to support choice and understand what to expect about IOL is often inadequate or unavailable. Having IOL can create anxiety and remove options for birth that women had hoped would enhance their experience. Although it can provide a more comfortable environment, home CR is not always an acceptable solution. Women described maternity care negatively impacted by staffing shortages; delays to care sometimes led to unsafe situations.

Women who had a positive experience of IOL described supportive interaction with staff as a significant contribution to that.

Conclusions

Women do not experience IOL as a benign and consequence free intervention. There is urgent need for research to better target IOL and optimise safety and experience for women and their babies. Relatively few women were offered CR at home and further research is needed on this experience.
Implications of differential size-scaling of cell-cycle regulators on cell size homeostasis
Authors: Ji Xiangrui , Lin Jie
Published: December 2022

Accurate timing of division and size homeostasis is crucial for cells. A potential mechanism for cells to decide the timing of division is the differential scaling of regulatory protein copy numbers with cell size. However, it remains unclear whether such a mechanism can lead to robust growth and division, and how the scaling behaviors of regulatory proteins influence the cell size distribution. Here we study a mathematical model combining gene expression and cell growth, in which the cell-cycle activators scale superlinearly with cell size while the inhibitors scale sublinearly. The cell divides once the ratio of their concentrations reaches a threshold value. We find that the cell can robustly grow and divide within a finite range of the threshold value with the cell size proportional to the ploidy. In a stochastic version of the model, the cell size at division is uncorrelated with that at birth. Also, the more differential the cell-size scaling of the cell-cycle regulators is, the narrower the cell-size distribution is. Intriguingly, our model with multiple regulators rationalizes the observation that after the deletion of a single regulator, the coefficient of variation of cell size remains roughly the same though the average cell size changes significantly. Our work reveals that the differential scaling of cell-cycle regulators provides a robust mechanism of cell size control.

Author summary

How cells determine the timing of cell division is a fundamental question of cell biology. It has been found that the concentration of cell-cycle activators tends to increase with cell size, while the concentration of inhibitors tends to decrease. Therefore, an attractive hypothesis is that the ratio of activators to inhibitors may trigger cell division. To investigate this hypothesis quantitatively, we study a model including gene expression and cell growth simultaneously. The cell divides once the activator-to-inhibitor ratio reaches a threshold. Combining theories and simulations, we analyze the conditions of robust cell cycle and the cell size distribution. Our model successfully rationalizes several experimental observations, including the relation between cell size and ploidy, the sizer behavior of cell size control, and the change of the mean and breadth of cell size distribution after regulator deletion.
The Effects of Dual-Site Beta tACS over the rIFG and preSMA on Response Inhibition in Young and Older Adults
Authors: Tan Jane , Iyer Kartik K. , Nitsche Michael A. , Puri Rohan , Hinder Mark R. , Fujiyama Hakuei
Published: December 2022

A growing body of research suggests that changes in both structural and functional connectivity in the aging brain contribute to declines in cognitive functions such as response inhibition. In recent years, transcranial alternating current stimulation (tACS) has garnered substantial research interest as a potential tool for the modulation of functional connectivity. Here, we report the findings from a double-blind crossover study that investigated the effects of dual-site beta tACS over the right inferior frontal gyrus (rIFG) and pre-supplementary motor area (preSMA) on functional connectivity measured with electroencephalography and response inhibition (stop-signal task performance) of healthy young (n= 18, aged 18-34 years) and older (n=15, aged 61-79 years) adults. Two tACS conditions were administered in separate sessions: in-phase tACS, where electrical currents delivered to the rIFG and preSMA had a 0° phase difference, and anti-phase tACS, where currents had a 180° phase difference. Stop-signal task performance was assessed before and after tACS. We found significant improvements in response inhibition that were not due to the phase of the tACS applied. There were also no significant changes in rIFG-preSMA phase connectivity in either age group from in- or anti-phase tACS. Furthermore, we did not observe significant differences in rIFG-preSMA phase connectivity between successful and unsuccessful inhibition, which suggests that rIFG-preSMA phase-coupling might not underlie effective response inhibition. The results offer insight into the neurophysiology of response inhibition and contribute to the future development of non-pharmacological interventions aimed at alleviating age-related declines in cognitive function.
Axonal ER tubules regulate local translation via P180/RRBP1-mediated ribosome interactions
Authors: Koppers Max , Özkan Nazmiye , Nguyen Ha H. , Jurriens Daphne , McCaughey Janine , Stucchi Riccardo , Altelaar Maarten , Kapitein Lukas C. , Hoogenraad Casper C. , Farias Ginny G.
Published: December 2022

Local mRNA translation in axons is critical for the spatial and temporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons, however how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with ER tubules in the axon in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation in an mRNA-dependent manner. Our results establish an important role for the axonal ER in localizing mRNA translation and in dynamically regulating the axonal proteome in response to neuronal stimuli.
ZNF524 directly interacts with telomeric DNA and supports telomere integrity
Authors: Braun Hanna , Xu Ziyan , Chang Fiona , Viceconte Nikenza , Rane Grishma , Levin Michal , Lototska Liudmyla , Roth Franziska , Hillairet Alexia , Fradera-Sola Albert , Khanchandani Vartika , Dreesen Oliver , Yang Yang , Shi Yunyu , Li Fudong , Butter Falk , Kappei Dennis
Published: December 2022

Telomeres are nucleoprotein structures at the ends of linear chromosomes. In humans, they consist of TTAGGG repeats, which are bound by dedicated proteins such as the shelterin complex. This complex blocks unwanted DNA damage repair at telomeres, e.g. by suppressing non-homologous end joining (NHEJ) through its subunit TRF2. We here describe ZNF524, a zinc finger protein that directly binds telomeric repeats with nanomolar affinity and reveal the base-specific sequence recognition by co-crystallization with telomeric DNA. ZNF524 localizes to telomeres and specifically maintains the presence of the TRF2/RAP1 subcomplex at telomeres without affecting other shelterin members. Loss of ZNF524 concomitantly results in an increase in DNA damage signaling and recombination events. Overall, ZNF524 is a direct telomere-binding protein involved in the maintenance of telomere integrity.
The evolution of whole-brain turbulent dynamics during recovery from traumatic brain injury
Authors: Martínez-Molina Noelia , Escrichs Anira , Sanz-Perl Yonatan , Sihvonen Aleksi J. , Särkämö Teppo , Kringelbach Morten L. , Deco Gustavo
Published: December 2022

It has been previously shown that traumatic brain injury (TBI) is associated with reductions in metastability in large-scale networks in resting state fMRI. However, little is known about how TBI affects the local level of synchronization and how this evolves during the recovery trajectory. Here, we applied a novel turbulent dynamics framework to investigate the temporal evolution in whole-brain dynamics using an open access resting state fMRI dataset from a cohort of moderate-to-severe TBI patients and healthy controls (HCs). We first examined how several measures related to turbulent dynamics differ between HCs and TBI patients at 3-, 6- and 12-months post-injury. We found a significant reduction in these empirical measures after TBI, with the largest change at 6-months post-injury. Next, we built a Hopf whole-brain model with coupled oscillators and conductedin silicoperturbations to investigate the mechanistic principles underlying the reduced turbulent dynamics found in the empirical data. A simulated attack was used to account for the effect of focal lesions. This revealed a shift to lower coupling parameters in the TBI dataset and, critically, decreased susceptibility and information encoding capability. These findings confirm the potential of the turbulent framework to characterize whole-brain dynamics after TBI and validates the use of whole-brain models to monitor longitudinal changes in the reactivity to external perturbations.

Highlights

Whole-brain turbulent dynamics capture longitudinal changes after TBI during one-year recovery period

TBI patients show partial recovery of resting state network dynamics at large spatial scales

Whole-brain computational models indicate less reactivity toin silicoperturbations after TBI
How gut hormones shape reward: a systematic review of the role of ghrelin and GLP-1 in human fMRI
Authors: Schulz Corinna , Vezzani Cecilia , Kroemer Nils B.
Published: December 2022

The gastrointestinal hormones ghrelin and glucagon-like peptide-1 (GLP-1) have opposite secretion patterns, as well as opposite effects on metabolism and food intake. Beyond their role in energy homeostasis, gastrointestinal hormones have also been suggested to modulate the reward system. However, the potential of ghrelin and GLP-1 to modulate reward responses in humans has not been systematically reviewed before. To evaluate the convergence of published results, we first conduct a multi-level kernel density meta-analysis of studies reporting a positive association of ghrelin (Ncomb= 353, 18 contrasts) and a negative association of GLP-1 (Ncomb= 258, 12 contrasts) and reward responses measured using task functional magnetic resonance imaging (fMRI). Second, we complement the meta-analysis using a systematic literature review, focusing on distinct reward phases and applications in clinical populations that may account for variability across studies. In line with preclinical research, we find that ghrelin increases reward responses across studies in key nodes of the motivational circuit, such as the nucleus accumbens, pallidum, putamen, substantia nigra, ventral tegmental area, and the dorsal mid insula. In contrast, for GLP-1, we did not find sufficient convergence in support of reduced reward responses. Instead, our systematic review identifies potential differences of GLP-1 on anticipatory versus consummatory reward responses. Based on a systematic synthesis of available findings, we conclude that there is considerable support for the neuromodulatory potential of gut-based circulating peptides on reward responses. To unlock their potential for clinical applications, future studies may move beyond anticipated rewards to cover other reward facets.

Graphical Abstract
Mechanisms and neuroanatomy of response selection in tool and non-tool action tasks: Evidence from left-hemisphere stroke
Authors: Garcea Frank E. , Buxbaum Laurel J.
Published: December 2022

The ability to select between potential actions is central to the complex process of tool use. After left hemisphere stroke, individuals with limb apraxia make more hand action errors when gesturing the use of tools with conflicting hand actions for grasping-to-move and use (e.g., screwdriver) relative to tools that are grasped-to-move and used with the same hand action (e.g., hammer). Prior research indicates that this grasp-use interference effect is driven by abnormalities in the competitive action selection process. The goal of this project was to determine whether common mechanisms and neural substrates support the competitive selection of task-appropriate responses in both tool and non-tool domains. If so, the grasp-use interference effect in a tool use gesturing task should be correlated with response interference effects in the classic Eriksen flanker and Simon tasks, and at least partly overlapping neural regions should subserve the 3 tasks. Sixty-four left hemisphere stroke survivors (33 with apraxia) participated in the tool- and non-tool interference tasks and underwent T1 anatomical MRI. There were robust grasp-use interference effects (grasp-use conflict test) and response interference effects (Eriksen flanker and Simon tasks), but these effects were not correlated. Lesion-symptom mapping analyses showed that lesions to the left inferior parietal lobule, ventral premotor cortex, and insula were associated with grasp-use interference. Lesions to the left inferior parietal lobule, postcentral gyrus, insula, caudate, and putamen were associated with response interference in the Eriksen flanker task. Lesions to the left caudate and putamen were also associated with response interference in the Simon task. Our results suggest that the selection of hand posture for tool use is mediated by distinct cognitive mechanisms and partly distinct neuroanatomic substrates from those mapping a stimulus to an appropriate motor response in non-tool domains.
Mapping localization of 21 endogenous proteins in the Golgi apparatus of rodent neurons
Authors: van Bommel Danique M , Toonen Ruud F , Verhage Matthijs
Published: December 2022

The Golgi apparatus is the major sorting hub in the secretory pathway and particularly important for protein sorting in neurons. Knowledge about protein localization in Golgi compartments is largely based on work in cell lines. Here, we systematically compared protein localization of 21 endogenous proteins in the Golgi apparatus of mouse neurons using confocal microscopy and line scan analysis. We localized these proteins by measuring the distance relative to the canonical TGN marker TGN38. Based on this, proteins fell into three groups: upstream of, overlapping with or downstream of TGN38. Seven proteins showed complete overlap with TGN38, while proteins downstream of TGN38 were located at varying distances from TGN38. Proteins upstream of TGN38 were localized in between TGN38 and thecis-/medial Golgi markers Giantin and GM130. This localization was consistent with protein function. Our data provide an overview of the relative localization of endogenous proteins in the Golgi of primary mouse neurons.
Emission of floral volatiles is facilitated by cell-wall non-specific lipid transfer proteins
Authors: Liao Pan , Maoz Itay , Shih Meng-Ling , Lee Ji Hee , Huang Xing-Qi , Morgan John A. , Dudareva Natalia
Published: December 2022

For volatile organic compounds (VOCs) to be released from the plant cell into the atmosphere, they have to cross the plasma membrane, the cell wall, and the cuticle. However, how these hydrophobic compounds cross the hydrophilic cell wall is largely unknown. Using biochemical and reverse-genetic approaches combined with mathematical modeling, we show that cell-wall localized non-specific lipid transfer proteins (nsLTPs) facilitate VOC emission. Out of three highly expressed nsLTPs in petunia petals, which emit high levels of phenylpropanoid/benzenoid compounds, only PhnsLTP3 contributes to the VOC export across the cell wall to the cuticle. A decrease inPhnsLTP3expression reduces volatile emission and leads to VOC redistribution with less VOCs reaching the cuticle without affecting their total pools. This intracellular build-up of VOCs lowers their biosynthesis by feedback downregulation of phenylalanine precursor supply to prevent self-intoxication. Overall, these results demonstrate that nsLTPs are intrinsic members of the VOC emission network, which facilitate VOC diffusion across the cell wall.
Decoding frontotemporal and cell type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs
Authors: Ji Jiatong , Chao Honglu , Chen Huimei , Liao Jun , Ye Yangfan , You Yongping , Liu Ning , Ji Jing , Petretto Enrico
Published: December 2022

Abnormalities in temporal and frontal lobes (TL and FL) have been linked to cognition and neuropsychiatric disorders. While structural and functional differences between the brain lobes have been documented in disease, the cellular heterogeneity in FL and TL and its impact to the vulnerability to genetic risk factors for neuropsychiatric disorders is not well studied. We hypothesize that intrinsic cellular-level differences between TL and FL explain the vulnerability of specific cell types to genetic risk factors and psychoactive drugs. To test this, we integrated single-nucleus transcriptome analysis in fresh human FL and TL with data related to genetic susceptibility and gene dysregulation in neuropsychiatric disease, and response to psychoactive drugs. We also investigate how these differences are associated with gene dysregulation in disease brain. Neuronal cell populations were the most vulnerable to psychiatric genetic risk factors, and more specifically parvalbumin interneurons (PVALB neurons). These PVALB-expressed genetic risk factors were mostly upregulated in the TL compared with FL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. We foundGRIN2AandHCN1, implicated in schizophrenia by genome-wide association studies, to be significantly upregulated in PVLAB from the TL and in brain cortex from schizophrenia patients. Our analysis provides comprehensive evidence for PVALB neurons as the most vulnerable cell type that is implicated in several psychiatric disorders. PVALB neurons showed the highest vulnerability to psychoactive drug response, which was 3.6-fold higher than the vulnerability to genetic risk factors. In summary, we show high vulnerability of PVALB neurons that is specific to the temporal lobe, implying that differences between TL and FL greatly influence the cell vulnerability to genetic risk factors as well as the response to psychoactive drugs. These findings offer insights into how regional brain differences affect the cell type vulnerabilities in neuropsychiatric disorders.