bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene-based Hardy–Weinberg equilibrium test using genotype count data identifies novel cancer-related genes
Authors: Nishino Jo , Miya Fuyuki , Kato Mamoru
Published: March 2024

Background

An alternative approach to investigate associations between genetic variants and disease is to examine deviations from the Hardy–Weinberg equilibrium (HWE) in genotype frequencies within a case population, instead of case-control association analysis. The HWE analysis distinctively requires disease cases without the need for controls and demonstrates a notable ability in mapping recessive variants. Allelic heterogeneity is a common phenomenon in diseases. While gene-based case-control association analysis successfully incorporates this heterogeneity, there are no such approaches for HWE analysis. Therefore, we proposed a gene-based HWE test (gene-HWT) by aggregating single-nucleotide polymorphism (SNP)-level HWE test statistics in a gene to address allelic heterogeneity.

Results

This method used only genotype count data and publicly available linkage disequilibrium information and has a very low computational cost. Extensive simulations demonstrated that gene-HWT effectively controls the type I error at a low significance level and outperforms SNP-level HWE test in power when there are multiple causal variants within a gene. Using gene-HWT, we analyzed genotype count data from genome-wide association study for six types of cancers in Japanese individuals and found that most of the genes detected are associated with cancers. In addition, we identified novel genes (AGBL3andPSORS1C1), novel variants inCTSOknown to be associated with breast cancer prognosis and drug sensitivity, and novel genes as germline factors, which have associations in gene expression or methylation status with cancers in the combined analysis of six types of cancers.

Conclusions

These findings indicate the potential of gene-HWT to elucidate the genetic basis of complex diseases, including cancer.
The role of etiology in the identification of clinical markers of consciousness: comparing EEG alpha power, complexity, and spectral exponent
Authors: Maschke Charlotte , Belloli Laouen , Manasova Dragana , Sitt Jacobo D. , Blain-Moraes Stefanie
Published: March 2024

1

In the search for EEG markers of human consciousness, alpha power has long been considered a reliable marker which is fundamental for the assessment of unresponsive patients from all etiologies. However, recent evidence questioned the role of alpha power as a marker of consciousness and proposed the spectral exponent and spatial gradient as more robust and generalizable indexes. In this study, we analyzed a large-scale dataset of 260 unresponsive patients and investigated etiology-specific markers of level of consciousness, responsiveness and capacity to recover. We compare a set of candidate EEG makers: 1) absolute, relative and flattened alpha power; 2) spatial ratios; 3) the spectral exponent; and 4) signal complexity. Our results support the claim that alpha power is an etiology-specific marker, which has higher diagnostic value for anoxic patients. Meanwhile, the spectral slope showed diagnostic value for non-anoxic patients only. Changes in relative power and signal complexity were largely attributable to changes in the spectral slope. Grouping unresponsive patients from different etiologies together can confound or obscure the diagnostic value of different EEG markers of consciousness. Our study highlights the importance of analyzing different etiologies independently and emphasizes the need to develop clinical markers which better account for inter-individual and etiology-dependent differences.
Dissociation of white matter bundles in different recovery measures in post-stroke aphasia
Authors: Osa García Alberto , Brambati Simona Maria , Brisebois Amélie , Houzé Bérengère , Bedetti Christophe , Desautels Alex , Marcotte Karine
Published: March 2024

Background

Post-stroke aphasia (PSA) recovery shows high variability across individuals and at different moments during recovery. Although diffusion biomarkers from the ventral and dorsal streams have demonstrated strong predictive power for language outcomes, it is still unclear how these biomarkers relate to the various stages of PSA recovery. In this study, we aim to compare diffusion metrics and language measures as predictors of language recovery in a longitudinal cohort of participants with PSA.

Methods

Twenty-four participants (mean age = 73 years, 8 women) presenting PSA were recruited in an acute stroke unit. Participants underwent diffusion MRI scanning and language assessment within 3 days (acute phase) after stroke, with a behavioral follow-up at subacute (10±3 days) and chronic phases (> 6 months). We used regression analyses on language performance (cross-sectional) and Δscores at subacute and chronic timepoints (difference between acute and subacute, and subacute and chronic respectively), with language baseline scores, diffusion metrics from language-related white matter tracts, lesion size and demographic predictors.

Results

Best prediction model of performance scores used axial diffusivity (AD) from the left arcuate fasciculus (AF) in both subacute (R2= 0.785) and chronic timepoints (R2= 0.626). Moreover, prediction of change scores depended on AD from left inferior frontal-occipital fasciculus (IFOF), in subacute stage (R2= 0.5), and depended additionally on AD from right IFOF in the chronic stages (R2= 0.68). Mediation analyses showed that lesion load of left AF mediated the relationship between AD from left AF and chronic language performance.

Conclusion

Language performance in subacute and chronic timepoints depends on the integrity of left AF, whereas Δscores of subacute and chronic phases depends on left IFOF, showing a dissociation of the white matter pathways regarding language outcomes. These results support the hypothesis of a functional differentiation of the dual-stream components in PSA recovery.
Utilizing LLMs for Enhanced Argumentation and Extraction of Causal Knowledge from Scientific Literature
Authors: Wang Shuang , Chen Wenjie , Zhang Yang , Chen Ting , Du Jian
Published: March 2024

Current semantic extraction tools have limited performance in identifying causal relations, neglecting variations in argument quality, especially persuasive strength across different sentences. The present study proposes a five-element based (evidence cogency, concept, relation stance, claim-context relevance, conditional information) causal knowledge mining framework and automatically implements it using large language models (LLMs) to improve the understanding of disease causal mechanisms. As a result, regarding cogency evaluation, the accuracy (0.84) of the fine-tuned Llama2-7b largely exceeds the accuracy of GPT-3.5 turbo with few-shot. Regarding causal extraction, by combining PubTator and ChatGLM, the entity first-relation later extraction (recall, 0.85) outperforms the relation first-entity later means (recall, 0.76), performing great in three outer validation sets (a gestational diabetes-relevant dataset and two general biomedical datasets), aligning entities for further causal graph construction. LLMs-enabled scientific causality mining is promising in delineating the causal argument structure and understanding the underlying mechanisms of a given exposure-outcome pair.
A Novel Method to Visualize Active Small GTPases Unveils Distinct Sites of Sar1 Activation During Collagen Secretion
Authors: Maeda Miharu , Arakawa Masashi , Komatsu Yukie , Saito Kota
Published: March 2024

Small GTPases are essential in various cellular signaling pathways, and detecting their activation within living cells is crucial for understanding cellular processes. Fluorescence resonance energy transfer is widely used to study the interaction between activated small GTPases and their effectors, but it is limited to those with well-defined effectors, excluding Sar1. Here, we present a novel method, SAIYAN (Small GTPase ActIvitY ANalyzing), for detecting the activation of endogenous small GTPases via fluorescent signals utilizing a split mNeonGreen system. We demonstrated Sar1 activation at the endoplasmic reticulum (ER) exit site and successfully detected its activation state in various cellular conditions. Utilizing the SAIYAN system in collagen-secreting cells, we discovered activated Sar1 localized both at ER exit sites and ER-Golgi intermediate compartment (ERGIC) regions. Additionally, impaired collagen secretion led to the confinement of activated Sar1 at the ER exit sites, underscoring the significance of Sar1 activation through the ERGIC in collagen secretion.
Long-read sequencing of 945 Han individuals identifies novel structural variants associated with phenotypic diversity and disease susceptibility
Authors: Gong Jiao , Sun Huiru , Wang Kaiyuan , Zhao Yanhui , Huang Yechao , Chen Qinsheng , Qiao Hui , Gao Yang , Zhao Jialin , Ling Yunchao , Cao Ruifang , Tan Jingze , Wang Qi , Ma Yanyun , Li Jing , Luo Jingchun , Wang Sijia , Wang Jiucun , Zhang Guoqing , Xu Shuhua , Qian Feng , Zhou Fang , Tang Huiru , Li Dali , Sedlazeck Fritz J , Jin Li , Guan Yuting , Fan Shaohua
Published: March 2024

Genomic structural variants (SVs) are a major source of genetic diversity in humans. Although numerous studies explore SV diversity across global populations and their potential impacts, validation using model systems are needed to confirm the reported genotype-phenotype associations. Here, through long-read sequencing of 945 Han Chinese genomes, we identify 111,288 SVs, including 24.56% unreported variants, many predicted to be functionally important. Our analysis unveils the multifaceted origins of these SVs within the Han population, with approximately 24% emerging at the common ancestor of modern humans. By integrating human population-level phenotypic, metabolic, and immunologic data and two humanized mouse models, we demonstrate the causal roles of two SVs: one SV that emerges at the common ancestor of modern human and Neanderthal and Denisova in GSDMD for bone density and one modern-human-specific SV in WWP2 impacting height, weight, fat, craniofacial phenotypes, and innate immunity. Some of these phenotypes were previously unreported and irreproducible phenotypes in mouse knockout experiments. Our results suggest that the SV in GSDMD could serve as a rapid and cost-effective predictive biomarker for evaluating GSDMD-mediated pyroptosis in multiple organ injuries, including cisplatin-induced acute kidney injury. While initially identified in the Han, the functional conservation from human to mouse, signals of positive natural selection specifically in non-African populations including the Han, and associations with multiple disease risks, suggest that both SVs likely influence local adaptation, phenotypic diversity, and disease susceptibility across many non-African populations.
Clinical benefits of modifying the evening light environment in an acute psychiatric unit: A single-centre, two-arm, parallel-group, pragmatic effectiveness randomised controlled trial
Authors: Kallestad Håvard , Langsrud Knut , Simpson Melanie Rae , Vestergaard Cecilie Lund , Vethe Daniel , Kjørstad Kaia , Faaland Patrick , Lydersen Stian , Morken Gunnar , Ulsaker-Janke Ingvild , Saksvik Simen Berg , Scott Jan
Published: March 2024

Background

The impact of light exposure on mental health is increasingly recognized. Modifying inpatient evening light exposure may be a low-intensity intervention for mental disorders, but few randomized controlled trials (RCTs) exist. We report a large-scale pragmatic effectiveness RCT exploring whether individuals with acute psychiatric illnesses experience additional benefits from admission to an inpatient ward where changes in the evening light exposure are integrated into the therapeutic environment.

Methods and findings

All adults admitted for acute inpatient psychiatric care over eight months were randomly allocated to a ward with a blue-depleted evening light environment or a ward with standard light environment. Baseline and outcome data from individuals who provided deferred informed consent were used to analyze the primary outcome measure (differences in duration of hospitalization) and secondary measures (differences in key clinical outcomes). The Intent to Treat sample comprised 476 individuals (mean age 37; 41% were male). There were no differences in the mean duration of hospitalization (6.7 vs. 7.1 days). Inpatients exposed to the blue-depleted evening light showed higher improvement during admission (Clinical Global Impressions scale-Improvement: 0.28, 95% CI: 0.02 to 0.54; p=0.035, Number Needed to Treat for clinically meaningful improvement (NNT): 12); lower illness severity at discharge (Clinical Global Impressions Scale-Severity: –0.18, 95% CI: –0.34 to – 0.02; p=0.029, NNT for mild severity at discharge: 7); and lower levels of aggressive behaviour (Broset Violence Checklist difference in predicted serious events per 100 days: –2.98; 95% CI: –4.98 to –0.99; p=0.003, NNT: 9). Incidents of harm to self or others, side effects, and patient satisfaction did not differ between the lighting conditions.

Conclusions

Modifying the evening light environment in acute psychiatric hospitals according to chronobiological principles does not change duration of hospitalizations, but can have clinically significant benefits without increasing side effects, reducing patient satisfaction or requiring additional clinical staff.
The effect of non-genetic determinants of human milk oligosaccharide profiles in milk of Ugandan mothers
Authors: Owalla Tonny Jimmy , Mwangi Victor Irungu , Moukarzel Sara , Okurut Emmanuel , Yonemitsu Chloe , Bode Lars , Egwang Thomas G.
Published: March 2024

Background

Human milk oligosaccharides (HMOs) protect against infection and promote growth and cognitive development in breastfeeding children. Non-genetic factors which influence HMO composition in breastfeeding mothers in rural Africa have not been investigated.

Objective

We undertook a cross-sectional study to determine the association between HMO profiles and non-genetic maternal factors and children’s sex in Ugandan mother-children pairs.

Method

Human milk was collected from 127 breastfeeding mothers by manual expression. HMO analysis was by high performance liquid chromatography. The proportion of each HMO per total HMO concentration was calculated. Spearman’s correlation and Mann-Whitney U test were used to assess the relationship between individual HMOs and maternal factors and infant sex.

Result

Nineteen HMOs were assayed. The prevalence of secretor and non-secretor status, based on the proportion of mothers with high milk concentrations of 2’FL and LNFP 1, was 80.3 % and 19.7 %, respectively. In secretor mothers, 2’FL, DFLac and LNFP I constituted > 57 % while in non-secretor mothers LNT and LNFPII constituted 46.9 % of the measured total HMOs. The median 3’SL concentration in milk of all mothers of male children was significantly higher than that in all mothers of female children. The median DFLac concentration in all mothers was significantly higher in multiparous mothers compared to primiparous mothers. Higher FDSLNH and lower LNH concentrations were observed in overweight secretor and non-secretor mothers, respectively. Median concentrations of LNFP I and DSLNT were significantly higher in all mothers < 18 years old compared all mothers > 18 years old. Concentrations of specific HMOs increased, decreased, or remained unchanged with increasing lactation duration in secretor and non-secretor mothers.

Conclusions

Specific HMOs were associated with infant sex and maternal age, parity and post-partum BMI in Ugandan mothers but were different from those reported in other populations.
The ciliary kinesin KIF7 controls the development of the cerebral cortex by acting differentially on SHH-signaling in dorsal and ventral forebrain
Authors: Pedraza María , Grampa Valentina , Scotto-Lomassese Sophie , Puech Julien , Muzerelle Aude , Mohammad Azka , Renier Nicolas , Métin Christine , Masson Justine
Published: March 2024

Mutations ofKIF7, a key ciliary component of Sonic hedgehog (SHH) pathway, are associated in humans with cerebral cortex malformations and clinical features suggestive of cortical dysfunction. KIF7 regulates the processing of GLI-A and GLI3-R transcription factors in a SHH-dependent manner both in humans and mice. Here, we examine the embryonic cortex development of a mouse model that lacks the expression of KIF7 (Kif7-/-). The cortex is composed of principal neurons generated locally in the dorsal telencephalon where SHH expression is low and inhibitory interneurons (cIN) generated in the ventral telencephalon where SHH expression is high. We observe a strong impact ofKif7deletion on the dorsal cortex development whose abnormalities resemble those of GLI3R mutants: subplate cells are absent, the intermediate progenitor layer and cortical plate do not segregate properly, and corticofugal axons do not develop timely, leading to a delayed colonization of the telencephalon by thalamo-cortical axons. These structural defects alter the cortical distribution of cIN, which moreover exhibit intrinsic migration defects resembling those of cyclopamine-treated cIN. Our results show thatKif7deletion impairs the cortex development in multiple ways, exhibiting opposite effects on SHH pathway activity in the developing principal neurons and inhibitory interneurons.
Ultrafast hybrid fermion-to-qubit mapping
Authors: O'Brien Oliver , Strelchuk Sergii
Published: March 2024

Fermion-to-qubit mappings play a crucial role in representing fermionic interactions on a quantum computer. Efficient mappings translate fermionic modes of a system to qubit interactions with a high degree of locality while using few auxiliary resources. We present a family of locality-preserving fermion-to-qubit mappings that require fewer auxiliary qubits than all existing schemes known to date. One instance requires only 1.016 qubits-per-fermion compared with 1.25 for the best-known locality-preserving mapping by Chen and Xu []. Our family of mappings (parameterized by integer n) establishes a direct trade-off between the number of auxiliary qubits (1/n2) and the circuit length [O(logn)]. Furthermore, we present a nonlocal variant that combines the strengths of the Jordan-Wigner and Bravyi-Kitaev mappings to give 98% shorter circuits than the Jordan-Wigner mapping. This is achieved by applying seemingly incompatible mappings at different scales, making it possible for their respective strengths to complement each other.

Published by the American Physical Society
2024
Consistent first-order action functional for gauge theories
Authors: Gallagher Priidik , Koivisto Tomi S. , Marzola Luca , Varrin Ludovic , Zlosnik Tom
Published: March 2024

A novel first-order action principle has been proposed as the possible foundation for a more fundamental theory of general relativity and the Standard Model. It is shown in this article that the proposal consistently incorporates gravity and matter fields, and guides one to a new and robust path toward unification of fundamental interactions.

Published by the American Physical Society
2024
The role of individualism, collectivism, and promotional reward type on consumer response to amplified word-of-mouth strategies
Authors: Rawal Monika , Saavedra Torres Jose Luis , Bagherzadeh Ramin , Rani Suchitra , Melancon Joanna
Published: March 2024

Purpose

This study aims to understand the effect of cultural dimension (individualism/ collectivism) on promotional rewards (social or economic) resulting in incentivizing consumers to engage in electronic word-of-mouth (eWOM), further impacting their repurchase intentions.

Design/methodology/approach

In Study 1, a 2 (culture: individualism vs collectivism) × 2 (promotional rewards: social vs economic) between-subjects design was used. Structural equation modeling was used to test the hypotheses. In Study 2, culture was measured instead of just being manipulated. The authors used regression analysis in this study.

Findings

Owing to the characteristics of collectivistic individuals, consumers in collectivistic cultures were more likely to respond to social rewards as an incentive to engage in eWOM. However, consumers in individualistic cultures were more motivated to engage in eWOM when economic rewards were offered.

Originality/value

Despite the global nature of eWOM, little research has explored the effects of cultural traits on consumer response to amplified eWOM strategy. Additionally, though many organizations now offer various promotional incentives to reviewers, little research has explored the effects of promotional offers on a reviewer’s subsequent behavior, and no research has explored the relationship between cultural dimensions and current and future response to promotional eWOM rewards.
Influences of critical success factors on nonprofit outcomes of ODA education construction projects: a case of Vietnam
Authors: Le Duc-Anh , Dang Chau Ngoc , Le-Hoai Long , Hoang Viet Quoc
Published: March 2024

Purpose

Official development assistance (ODA) education projects have played a crucial role in improving education and training fields in developing countries, but are often facing several considerable challenges (e.g. long implementation time). Thus, this study aims to identify critical success factors (CSFs) in ODA education projects and investigate the influences of CSFs on ODA project performance measured by 11 nonprofit outcomes (NPOs).

Design/methodology/approach

A comprehensive literature review and expert interviews were conducted to compile a list of 35 potential success factors for ODA education projects. Using a survey questionnaire, 143 valid responses were collected from practitioners joining ODA projects in Vietnam. Various statistical methods (e.g. mean score method, Spearman rank correlation test, analysis of variance test, factor analysis and regression analysis) were used to analyze the collected data.

Findings

This research identified seven CSFs for ODA education projects in Vietnam: comprehensive project management competency (C1), clarity and compliance in project execution (C2), transparency and committed funding (C3), external context conditions (C4), well-controlled design and project management procedures (C5), preparations in equipment and complexity insight (C6) and punctual site delivery (C7). Furthermore, the results of regression analysis indicated that comprehensive project management competency (C1) and transparency and committed funding (C3) could significantly affect various NPOs.

Originality/value

This study offers significant insights for practitioners (e.g. project managers) to improve ODA projects’ performance and effectiveness in the education and training sector of a developing country context (like Vietnam).
Assessing the environmental and economic impacts of adopting circular economy for sustainable resource management in the Indian construction sector
Authors: Mhatre-Shah Purva , Gedam Vidyadhar , Unnikrishnan Seema
Published: March 2024

Purpose

The aim of this study is to understand the environmental benefits and economic savings associated with adoption of circular economy in the construction sector. The research findings will support different stakeholders and decision makers to develop business models based on responsible consumption of resources and build sustainable business models.

Design/methodology/approach

The research uses mixed methodology wherein inventory for life cycle assessment and life cycle costing for environmental and economic impacts is based on primary data using on-site visits for qualitative and quantitative data.

Findings

Different types of land transportation infrastructures are compared for their environmental impacts. It is found that bridges have the highest environmental impacts as compared to tunnels, roads and railways. Further, the results affirm the environmental and economic benefits of adopting circular economy practices.

Originality/value

This is one of a kind research that compares the environmental and economic tradeoffs of adopting circular economy in different types of land transportation infrastructures.
Entrepreneurial leadership in online freelancing: bricolage and project success
Authors: Ahmed Mansoor , Lucianetti Lorenzo
Published: March 2024

Purpose

The research study provides empirical insights on the relationship between entrepreneurial leadership (EL), entrepreneurial passion for founding (EPF), entrepreneurial bricolage (EB) and project success (PS), in the case of freelancers. The study aims to get a better understanding of whether freelancers, who behave like entrepreneurial leaders, can successfully complete projects through EB.

Design/methodology/approach

The study collected data from 209 freelancers through snowball sampling, in two waves, with a time-lag of fourteen days, to better examine the causality of variables. Data were analyzed by Model No. 4 and 7 (i.e. mediation and moderation, respectively) of Process macro.

Findings

Drawing on the effectuation theory, the results show that EB mediates the relationship between EL and PS and EPF moderates this relationship.

Practical implications

The freelancers can formally establish businesses later, after knowing whether they can complete these new types of projects. These online freelancing platforms can provide special services to freelancers who first want to test their skills on unrelated projects. In sum, the paper suggests that freelancers can be successful entrepreneurial leaders.

Originality/value

The EL, EPF, EB and PS are studied in the context of the informal sector, i.e. freelancing, which is the emerging working style in the world. It provides an in-depth understanding of phenomena in freelancers that lacks background literature.
Meeting the challenges of wheat production through a skillful mix of new varieties, commercialization and technology adoption
Authors: Bhooshan Neeru , Singh Amarjeet , Sharma Akriti , Prabhu K.V.
Published: March 2024

Purpose

The role of Technology Transfer Units, examined in this study, was found to be vital to expedite the process of disseminating new varieties and their production technology.

Design/methodology/approach

A total of 1,000 households were surveyed in the sampled states. A probit model was used to analyse.

Findings

Age, education, land holding, tractor use and number of working family members in agriculture were found to significantly affecting adoption of the new seed varieties. Technology transfer through licensing has impacted the adoption of new seed varieties positively by highlighting Punjab possessing the highest adoption and western Uttar Pradesh was majorly adopting the old variety.

Research limitations/implications

The authors believed in farmers’ memory to recall the varietal information of wheat.

Practical implications

The study recommended various incentives to attract the seed industry in UP to minimize the economic loss potentially suffered by them.

Social implications

Quality seeds are germane to increase the productivity of crops, and it is paramount to disburse the seed varieties to the end users in an efficient way to achieve the overall objective of productivity enhancement.

Originality/value

In this context, a study was conducted in three states of India, namely, Punjab, Haryana and Uttar Pradesh (UP) to find out the adoption rate of newly developed varieties of wheat, HD 3086 after three years (2014–2015) of its commercialization by IARI as well as HD 2967, which was released in 2011.
Microbiological aspects and challenges of dairy powders – II: Biofilm/biofouling
Authors: Hebishy Essam , Yerlikaya Oktay , Reen F. Jerry , Mahony Jennifer , Akpinar Asli , Saygili Derya , Datta Nivedita
Published: March 2024

Biofilms generated during production of dairy/whey powders can cause contamination, spoilage and equipment failures, posing a significant challenge in the agri‐food sector. Factors including temperature, protein composition, equipment structures and surface topography influence biofilm formation and resistance to cleaning and sanitation. Several species of bacteria are well adapted to these challenges, posing the most pressing concerns of dairy whey process. Despite efforts to improve cleaning‐in‐place strategies, bacteria persist in difficult‐to‐clean areas. This review provides insights into bacterial biofouling in dairy protein powders, highlighting the mechanism of biofilm formation, predominant bacterial genera, critical processing steps and strategies to manage biofilm formation during the manufacturing process.
Sustainable banking and trust in the global South
Authors: Ubeda Fernando , Mendez Alvaro , Forcadell Francisco Javier
Published: March 2024

Trust in banking plays a significant role in promoting financial inclusion. Multinational banks (MNBs) have the potential to enhance trust by adopting sustainable banking practices. We investigate the impact of MNBs' adoption of ESG (Environmental, Social and Governance) practices on trust in banking in 38 developing countries. Using an instrumental variable approach and control function estimation, our findings indicate that sustainable practices by commercial MNBs are positively and significantly associated with increased trust in banking. The results remain consistent across different samples, lending robustness to our findings. By demonstrating the importance of sustainable banking in fostering trust, this study contributes to the limited literature on trust in banking in the global South.
Predicting risk of subsequent pregnancy loss among women with recurrent pregnancy loss: An immunological factor‐based multivariable model
Authors: Mu Fangxiang , Wang Mei , Zeng Xianghui , Wang Fang
Published: March 2024

Problem

Studies on subsequent pregnancy loss prediction models specific for recurrent pregnancy loss (RPL) patients are very limited. This study aims to develop a risk predictive model based on the immunological parameters for the subsequent pregnancy loss risk in northwest Chinese RPL patients.

Method of study

Totally of 357 RPL patients recruited from Lanzhou University Second Hospital were included in this retrospective study. Univariate analysis was performed on RPL patients with outcomes of live birth or pregnancy loss. Subsequently, the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables among baseline and clinical characteristics and to develop a pregnancy loss risk prediction model with all 357 RPL patients. The area under the curve (AUC), calibration curve and decision curve analyses were used to evaluate the performance of the prediction model; moreover, 10‐fold cross‐validation was used for internal validation.

Results

Ten factors of maternal age, age of menarche, previous pregnancy loss, IL‐10, complement 4, IgA, antiprothrombin antibody IgG/IgM, rheumatoid factor IgA, and lupus anticoagulant (LA) 1/LA2 ratio were finally selected as variables for the prediction model of pregnancy loss risk. The AUC value and Hosmer–Lemeshow test p‐value of the model were .707 and .599, respectively, indicating a satisfactory discrimination and calibration performance. Moreover, the clinical decision curve suggested this prediction model have a good positive net benefit.

Conclusions

This is the first prediction model for the risk of subsequent pregnancy loss in northwest Chinese women with RPL, providing a user‐friendly tool to clinicians for the early prediction and timely management of RPL patients.
Review article: New developments in biomarkers and clinical drug development in alpha‐1 antitrypsin deficiency‐related liver disease
Authors: Loomba Rohit , Clark Ginger , Teckman Jeff , Ajmera Veeral , Behling Cynthia , Brantly Mark , Brenner David , D'Armiento Jeanine , Fried Michael W. , Iyer Janani S. , Mandorfer Mattias , Rockey Don C. , Tincopa Monica , Vuppalanchi Raj , Younossi Zobair , Krag Aleksander , Turner Alice M. , Strnad Pavel
Published: March 2024

Background

Alpha‐1 antitrypsin liver disease (AATLD) occurs in a subset of patients with alpha‐1 antitrypsin deficiency. Risk factors for disease progression and specific pathophysiologic features are not well known and validated non‐invasive assessments for disease severity are lacking. Currently, there are no approved treatments for AATLD.

Aims

To outline existing understanding of AATLD and to identify knowledge gaps critical to improving clinical trial design and development of new treatments.

Methods

This report was developed following a multi‐stakeholder forum organised by the Alpha‐1 Antitrypsin Deficiency Related Liver Disease Expert Panel in which experts presented an overview of the available literature on this topic.

Results

AATLD results from a ‘gain of toxic function’ and primarily manifests in those with the homozygous Pi*ZZ genotype. Accumulation of misfolded ‘Z’ AAT protein in liver cells triggers intracellular hepatocyte injury which may ultimately lead to hepatic fibrosis. Male gender, age over 50 years, persistently elevated liver tests, concomitant hepatitis B or C virus infection, and metabolic syndrome, including obesity and type 2 diabetes mellitus, are known risk factors for adult AATLD. While the gold standard for assessing AATLD disease activity is liver histology, less invasive measures with low intra‐ and inter‐observer variability are needed. Measurement of liver stiffness shows promise; validated thresholds for staging AATLD are in development. Such advances will help patients by enabling risk stratification and personalised surveillance, along with streamlining the development process for novel therapies.

Conclusions

This inaugural forum generated a list of recommendations to address unmet needs in the field of AATLD.
Social and Emotional Functions of Institutional Touch in the Relational Care of Young Children
Authors: Cekaite Asta , Wirzén Madeleine
Published: March 2024

This study reports results concerning close embodied practices, involving touch, in early childhood care settings in Sweden during the COVID‐19 pandemic. The data—video recordings of everyday practices in contexts of childcare—were collected during various phases of the pandemic. The study demonstrates a broad range of uses of touch, by adults and children themselves in various age groups and for various social purposes. Touch as embodied intimacy was initiated by educators, and by children, both within their peer group and towards educators. Touch served the purposes of embodied intimacy, emotion regulation, social affiliation, social control, instructions and play. We highlight the detailed ways in which practitioners' actions sustain children's bodily integrity and provide them with embodied agency, participation and learning. Professional touch practices with young children are discussed in the context of ‘no‐touch’ views in social work and care work with children. It is suggested that insights into the social and emotional uses of institutional touch can inform social work practice, especially child and family social work, and residential care.
Community coherence, collective efficacy and civic engagement in student and youth councils: The mediating effect of community resilience
Authors: Asherov Einav Amram , Gross Zehavit
Published: March 2024

This study examines relationships between community coherence and collective efficiency, and civic engagement, and the role of community resilience within such relationships, as seen in youth council frameworks. The participants included a group of 223 members of youth councils in Israel and a group of 568 non‐members, aged 14–18. The quantitative research tool comprised the Civic Engagement questionnaire; Conjoint Community Resiliency Assessment Measure; Sence of Community Coherence Questionnaire; and Collective Efficacy Questionnaire. Positive relationships were found between community coherence and collective efficiency, and civic engagement for both groups, yet community resilience was only a mediating factor in this relationship for the non‐member group.
SESN1 functions as a new tumor suppressor gene via Toll‐like receptor signaling pathway in neuroblastoma
Authors: Hua Zhongyan , Chen Bo , Gong Baocheng , Lin Meizhen , Ma Yifan , Li Zhijie
Published: March 2024

Aims

Neuroblastoma (NB) is the most common extracranial solid tumor in children, with a 5‐year survival rate of <50% in high‐risk patients. MYCN amplification is an important factor that influences the survival rate of high‐risk patients. Our results indicated MYCN regulates the expression of SESN1. Therefore, this study aimed to investigate the role and mechanisms of SESN1 in NB.

Methods

siRNAs or overexpression plasmids were used to change MYCN, SESN1, or MyD88's expression. The role of SESN1 in NB cell proliferation, migration, and invasion was elucidated. Xenograft mice models were built to evaluate SESN1's effect in vivo. The correlation between SESN1 expression and clinicopathological data of patients with NB was analyzed. RNA‐Seq was done to explore SESN1's downstream targets.

Results

SESN1 was regulated by MYCN in NB cells. Knockdown SESN1 promoted NB cell proliferation, cell migration, and cell invasion, and overexpressing SESN1 had opposite functions. Knockdown SESN1 promoted tumor growth and shortened tumor‐bearing mice survival time. Low expression of SESN1 had a positive correlation with poor prognosis in patients with NB. RNA‐Seq showed that Toll‐like receptor (TLR) signaling pathway, and PD‐L1 expression and PD‐1 checkpoint pathway in cancer were potential downstream targets of SESN1. Knockdown MyD88 or TLRs inhibitor HCQ reversed the effect of knockdown SESN1 in NB cells. High expression of SESN1 was significantly associated with a higher immune score and indicated an active immune microenvironment for patients with NB.

Conclusions

SESN1 functions as a new tumor suppressor gene via TLR signaling pathway in NB.
Epidemiology and outcomes associated with enterococcal blood stream infection among liver and kidney transplant recipients
Authors: He Kevin D. , Naqvi Syed Suhaib , Cowan Vanessa L. , Stack Conor M. , Alonso Carolyn D. , Blair Barbra M.
Published: March 2024

Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus accounts for up to 20% of BSIs in this population, with vancomycin‐resistant enterococcus (VRE) posing a particular risk. This is a retrospective, case‐control study of adult liver and kidney transplant recipients between 01/01/2016 and 06/30/2021 that characterizes the epidemiology and outcomes of enterococcal BSIs in liver and kidney transplantations at a single institution. Subjects with an enterococcal BSI within the first 6 months post‐transplant were compared to those with non‐enterococcal BSIs in the same period. We identified 26 subjects with enterococcal BSIs and 28 controls with non‐enterococcal BSIs (n = 54; 10.3%). Cases were mostly liver transplant recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14–43); controls included 14 KT recipients (50%). Groups differed significantly (all p < .05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post‐transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < .0001). There were no differences in 1‐year mortality between the groups. Enterococcus faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. In our liver and kidney transplants, enterococcal BSIs occurred early among liver transplant recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post‐transplant period.
Clinical dose rationale of tislelizumab in patients with solid or hematological advanced tumors
Authors: Yu Tian , Liu Xiangyu , Wu Chi‐Yuan , Tang Zhiyu , Wang Hongwei , Schnell Patrick , Wan Ya , Wang Kun , Liu Lucy , Gao Yuying , Sahasranaman Srikumar , Budha Nageshwar
Published: March 2024

Tislelizumab, an anti‐programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first‐in‐human, dose‐finding BGB‐A317‐001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5–10 mg/kg every 2 weeks (q2w), 2–5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune‐mediated AEs, and infusion‐related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure–response (E–R) analyses by logistic regression using data from study BGB‐A317‐001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018–2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E–R relationship. Overall, the totality of data, including efficacy, safety, and E–R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.
Communicatio idiomatum in deep incarnation
Authors: Peters Ted
Published: March 2024

The communicatio idiomatum (the exchange of divine and human properties or attributes), apparently discarded by the Council of Chalcedon in 451, becomes central to both Christology and the life of faith during the Lutheran Reformation. In our own century, the communicatio idiomatum has been expanded and deepened to incorporate all that is biological and even physical, turning the entire history of creation into the eschatological body of Christ, the second person of the Holy Trinity.
Editing of 3D images in echocardiographic evaluation of mitral valve: Is there any correlation with photography?
Authors: Suma Sergio
Published: March 2024

Editing of 3D raw images acquired during transesophageal echocardiography could be similar to the post processing of raw images with digital software used in photography. 3D image editing in echocardiography is often underestimated in clinical practice, and people are satisfied with the first 3D image they are able to obtain during transesophageal examination. In fact, it is often believed to represent solely an aesthetic addition that does not change the information already obtained with 2D and baseline 3D. In reality, it represents a crucial moment to better understand the mechanisms of mitral pathology, avoiding artifacts and misjudgments. The importance of acquiring raw 3D images of the valve having all the necessary information (ring, the leaflet in toto, the right frame rate) allows us then to edit them making them more beautiful and clearer from the point of view of the information received. Nevertheless, by exclusively acquiring a raw 3D with all the necessary information, we can quickly finish the transesophageal examination, reducing its duration and discomfort for the patient, as well as the inherent risk of complications related to the procedure per se.
The efficiency of Thymus vulgaris, Lavandula angustifolia, and Cupressus sempervirens essential oils in suppression of Hymenoscyphus fraxineus on Fraxinus angustifolia seedlings
Authors: Vemić Aleksandar , Popović Vladan , Lučić Aleksandar , Kudláček Tomáš , Radulović Zlatan , Ćosić Milivoje , Rakonjac Ljubinko
Published: March 2024

Due to intense ash dieback, this research tested the bioactivity of Thymus vulgaris, Lavandula angustifolia, and Cupressus sempervirens essential oils (EO) against Hymenoscyphus fraxineus. In vitro testing showed that EOs had a pronounced fungitoxic effect on H. fraxineus. The most effective EO was extracted from T. vulgaris, while EOs obtained from L. angustifolia and C. sempervirens were less effective and showed the same effect. At a concentration of 1%, all tested EOs inhibited mycelial growth, while 0.01% and 0.1% concentrations of EO extracted from T. vulgaris also inhibited the growth of H. fraxineus. The in planta test of EO extracted from T. vulgaris conducted on three‐year‐old Fraxinus angustifolia seedlings showed a reduction in the size of necrotic lesions and a better crown condition compared to untreated seedlings. This research demonstrates, for the first time, the efficiency of EOs in suppressing ash dieback making a path for the development of new biological protection measures against H. fraxineus.
Plant mucilage increases pull‐out resistance of root analogues from soil
Authors: Li Rong , Zhang Chaobo , Raffan Annette , Hallett Paul D.
Published: March 2024

The interface between plants' roots and soil is strongly affected by rhizodeposits, especially mucilage, that change mechanical and hydrological behaviour. In addition to impacts to aggregation, water capture and root penetration, rhizodeposits may also affect the pull‐out resistance of plant roots. Due to the complex architecture of plant roots and an inability to restrict rhizodeposit production, this study used a simplified system of wooden skewers to simulate roots and chia seed mucilage as a model to simulate rhizodeposit compounds. Pull‐out tests were then carried out to measure the impacts of mucilage, and one (WD1) or two (WD2) cycles of wetting and drying of soils. Using a mechanical test frame, the maximum pull‐out resistance (Fmax) and pull‐out displacement (dL) were recorded, allowing for pull‐out energy (E), average pull‐out force () and bond strength (τmax) to be calculated. The results showed that all pull‐out parameters of the samples with added rhizodeposit compounds tended to decrease between WD1 and WD2, but they were still significantly greater than without the added mucilage. The model rhizodeposit increased all pull‐out parameters by a minimum of 30%. With an additional wet–dry cycle, the mucilage tended to cause a decline in pull‐out parameters relative to a single wet‐dry cycle. This suggests mucilages could enhance the mechanical resistance of roots to pull‐out, but resistance decreases over time with cycles of wetting and drying. To conclude, an important role of mucilage is pull‐out resistance, which has relevance to plant anchorage and root reinforcement of soils.