bluuebunny/crossref_metadata_2025 huggingface dataset:
The past, present, and future of sleep measurement in mild cognitive impairment and early dementia—towards a core outcome set: a scoping review
Authors: Blackman Jonathan , Morrison Hamish Duncan , Lloyd Katherine , Gimson Amy , Banerjee Luke Vikram , Green Sebastian , Cousins Rebecca , Rudd Sarah , Harding Sam , Coulthard Elizabeth
Published: April 2022

Study Objectives

Sleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment.

Methods

This review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception—March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure.

Results

Nineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). “Unspecified MCI” was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters.

Conclusions

Alongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions.
Modelling behaviour in intergroup conflicts: a review of microeconomic approaches
Authors: Rusch Hannes
Published: April 2022

Microeconomic modelling offers a powerful formal toolbox for analysing the complexities of real-world intergroup relations and conflicts. One important class of models scrutinizes individuals’ valuations of different group memberships, attitudes towards members of different groups and preferences for resource distribution in group contexts. A second broad class uses game theoretical methods to study strategic interactions within and between groups of individuals in contest and in conflict. After a concise discussion of some essential peculiarities of microeconomic modelling, this review provides an overview of the pertinent literatures in economics, highlights instructive examples of central model types and points out several ways forward.

This article is part of the theme issue ‘Intergroup conflict across taxa’.
Oxytocin has ‘tend-and-defend’ functionality in group conflict across social vertebrates
Authors: Triki Zegni , Daughters Katie , De Dreu Carsten K. W.
Published: April 2022

Across vertebrate species, intergroup conflict confronts individuals with a tension between group interests best served by participation in conflict and personal interest best served by not participating. Here, we identify the neurohormone oxytocin as pivotal to the neurobiological regulation of this tension in distinctly different group-living vertebrates, including fishes, birds, rodents, non-human primates and humans. In the context of intergroup conflict, a review of emerging work on pro-sociality suggests that oxytocin and its fish and birds homologues, isotocin and mesotocin, respectively, can elicit participation in group conflict and aggression. This is because it amplifies (i) concern for the interests of genetically related or culturally similar ‘in-group’ others and (ii) willingness to defend against outside intruders and enemy conspecifics. Across a range of social vertebrates, oxytocin can induce aggressive behaviour to ‘tend-and-defend’ the in-group during intergroup contests.

This article is part of the theme issue ‘Intergroup conflict across taxa’.
Sex bias in intergroup conflict and collective movements among social mammals: male warriors and female guides
Authors: Smith Jennifer E. , Fichtel Claudia , Holmes Rose K. , Kappeler Peter M. , van Vugt Mark , Jaeggi Adrian V.
Published: April 2022

Intergroup conflict is a major evolutionary force shaping animal and human societies. Males and females should, on average, experience different costs and benefits for participating in collective action. Specifically, among mammals, male fitness is generally limited by access to mates whereas females are limited by access to food and safety. Here we analyse sex biases among 72 species of group-living mammals in two contexts: intergroup conflict and collective movements. Our comparative phylogenetic analyses show that the modal mammalian pattern is male-biased participation in intergroup conflict and female-biased leadership in collective movements. However, the probability of male-biased participation in intergroup conflicts decreased and female-biased participation increased with female-biased leadership in movements. Thus, female-biased participation in intergroup conflict only emerged in species with female-biased leadership in collective movements, such as in spotted hyenas and some lemurs. Sex differences are probably attributable to costs and benefits of participating in collective movements (e.g. towards food, water, safety) and intergroup conflict (e.g. access to mates or resources, risk of injury). Our comparative review offers new insights into the factors shaping sex bias in leadership across social mammals and is consistent with the ‘male warrior hypothesis' which posits evolved sex differences in human intergroup psychology.

This article is part of the theme issue ‘Intergroup conflict across taxa’.
SARS-CoV-2 variants of concern alpha, beta, gamma and delta have extended ACE2 receptor host ranges
Authors: Thakur Nazia , Gallo Giulia , Newman Joseph , Peacock Thomas P. , Biasetti Luca , Hall Catherine N. , Wright Edward , Barclay Wendy , Bailey Dalan
Published: April 2022

Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in PR China in late 2019 a number of variants have emerged, with two of these – alpha and delta – subsequently growing to global prevalence. One characteristic of these variants are changes within the spike protein, in particular the receptor-binding domain (RBD). From a public health perspective, these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host range of the virus. Using viral pseudotyping, we examined whether the variants of concern (VOCs) alpha, beta, gamma and delta have differing host angiotensin-converting enzyme 2 (ACE2) receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes that we subsequently attributed to N501Y and E484K substitutions within the spike RBD.
Safety, Immunologic Effects and Clinical Response in a Phase I Trial of Umbilical Cord Mesenchymal Stromal Cells in Patients with Treatment Refractory Systemic Lupus Erythematosus
Authors: Kamen Diane , Wallace Caroline , Li Zihai , Wyatt Megan , Paulos Crystal , Wei Chungwen , Wang Hongjun , Sanz Inaki , Wolf Bethany J , Nietert Paul J , Robinson Angela , Gilkeson Gary
Published: April 2022

Background

Reports of clinical improvement following mesenchymal stromal cell (MSC) infusions in refractory lupus patients at a single center in China led us to perform an explorative Phase I trial of umbilical cord derived MSCs in patients refractory to six months of immunosuppressive therapy.

Methods

Six women with a SLEDAI>6, having failed standard of care therapy, received one IV infusion of 1×106 MSCs/kg of body weight. They maintained their current immunosuppressives, but their physician was allowed to adjust corticosteroids initially for symptom management. The clinical endpoint was an SRI of 4 with no new BILAG As and no increase in Physician Global Assessment score of >0.3 with tapering of prednisone to 10mg or less by 20 weeks.

Results

Of 6 patients, 5 (83.3%; 95% CI = 35.9% to 99.6%) achieved the clinical endpoint of an SRI of 4. Adverse events were minimal. Mechanistic studies revealed significant reductions in CD27IgD negative B cells, switched memory B cells and activated naïve B cells with increased transitional B cells in the 5 patients who met the endpoint. There was a trend towards decreased autoantibody levels in specific patients. One patient had an increase in their Helios+Treg cells, but no other significant T cell changes were noted. GARP-TGFβ complexes were significantly increased following the MSC infusions. The B cell changes and the GARP-TGFβ increase were significantly correlated with SLEDAI scores.

Conclusion

This pilot trial suggests that UC MSC infusions are safe and may have efficacy in lupus. The B cell and GARP-TGFβ changes provide insight into mechanisms by which MSCs may impact disease.

Trial Registration

NCT03171194

Funding

This study was funded by a grant from the Lupus Foundation of America and NIH UL1 RR029882
Tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting MEK1/2
Authors: Wang Zitong , Chen Yingying , Li Xiaoyu , Zhang Yuhan , Zhao Xiaokun , Zhou Hao , Lu Xuebo , Zhao Lili , Yuan Qiang , Shi Yunshu , Zhao Jimin , Dong Ziming , Jiang Yanan , Liu Kangdong
Published: April 2022

Gastric cancer (GC), ranking fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy, and radiotherapy. Although management and treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies that can increase GC patient survival rates. In the current study, we found that tegaserod maleate, a FDA-approved drug, could inhibit the proliferation of gastric cancer cells. Tegaserod maleate binds to MEK1 /2 and inhibits MEK1 /2 kinase activity. Moreover, the construction of CRISPER/Cas9 cell line further verified that tegaserod maleate depended on MEK1 /2 to inhibit the progress of gastric cancer. Notably, we found that tegaserod maleate suppressed tumor growth in patient-derived gastric xenograft (PDX) mouse model. We also compared tegaserod maleate with trametinib, a clinical MEK1/2 inhibitor, and comfirmed that tegaserod maleate have the same effect in inhibiting tumor volume and tumor weight. Our findings suggest that tegaserod maleate can inhibit GC proliferation by targeting MEK1/2.
NSMCE2, a Novel Super-Enhancer Regulated Gene, is Linked to Poor Prognosis and Therapy Resistance in Breast Cancer
Authors: Di Benedetto Carolina , Oh Justin , Choudhery Zainab , Shi Weiquan , Valdes Gilmer , Betancur Paola
Published: April 2022

In this study, we identified two novel super-enhancer associated genes: NSMCE2 and MAL2, highly upregulated in breast tumors, for which high RNA levels significantly and specifically correlate with breast cancer patients’ poor prognosis. To approach this, we took advantage of existing datasets containing super-enhancers associated genes identified in primary breast tumors and public databases comprising gene expression, genomic and clinical outcomes for patients diagnosed with breast cancer. Through in-vitro pharmacological super-enhancer disruption assays in breast cancer cells we confirmed that super-enhancers are involved in NSMCE2 and MAL2 transcript upregulation and through bioinformatics we found that high levels of NSMCE2 strongly associate with poor response to chemotherapy. This was observed especially for patients diagnosed with aggressive triple negative and HER2 positive tumor types. Finally, we showed that treating breast cancer cells with chemotherapeutic agents while simultaneously decreasing NSMCE2 gene expression by super-enhancer blockade or by directly silencing it, reduces cell viability thus increasing the effectiveness of chemotherapy. Our results indicate that moderating the transcript levels of the novel identified super-enhancer associated gene NSMCE2 could improve patients’ response to standard chemotherapy and, consequently, may improve disease outcome. In summary by mining existing public breast cancer datasets, our work demonstrates that searching for super-enhancer regulated genes and their association to patients’ survival and response to treatment, could be an effective method for identifying a signature of tumor specific -not frequently mutated, but super-enhancer dysregulated genes. Our approach offers a new avenue to identify novel biomarkers of poor prognosis and potential pharmacological targets for improving cancer treatment.
Bond topology of chain, ribbon and tube silicates. Part I. Graph-theory generation of infinite one-dimensional arrangements of (TO4)
n− tetrahedra
Authors: Day Maxwell Christopher , Hawthorne Frank Christopher
Published: April 2022

Chain, ribbon and tube silicates are based on one-dimensional polymerizations of (TO4)
n− tetrahedra, where T = Si4+ plus P5+, V5+, As5+, Al3+, Fe3+ and B3+. Such polymerizations may be represented by infinite graphs (designated chain graphs) in which vertices represent tetrahedra and edges represent linkages between tetrahedra. The valence-sum rule of bond-valence theory limits the maximum degree of any vertex to 4 and the number of edges linking two vertices to 1 (corner-sharing tetrahedra). The unit cell (or repeat unit) of the chain graph generates the chain graph through action of translational symmetry operators. The (infinite) chain graph is converted into a finite graph by wrapping edges that exit the unit cell such that they link to vertices within the unit cell that are translationally equivalent to the vertices to which they link in the chain graph, and the wrapped graph preserves all topological information of the chain graph. A symbolic algebra is developed that represents the degree of each vertex in the wrapped graph. The wrapped graph is represented by its adjacency matrix which is modified to indicate the direction of wrapped edges, up (+c) or down (−c) along the direction of polymerization. The symbolic algebra is used to generate all possible vertex connectivities for graphs with ≤8 vertices. This method of representing chain graphs by finite matrices may now be inverted to generate all non-isomorphic chain graphs with ≤8 vertices for all possible vertex connectivities. MatLabR2019b code is provided for computationally intensive steps of this method and ∼3000 finite graphs (and associated adjacency matrices) and ∼1500 chain graphs are generated.
Isogonal piecewise-linear embeddings of 1-periodic knots and links, and related 2-periodic chain-link and knitting patterns
Authors: O'Keeffe Michael , Treacy Michael M. J.
Published: April 2022

Families of 1- and 2-periodic knots and weavings that have isogonal (vertex-transitive) piecewise-linear embeddings are described. In these structures there is just one thread, or multiple threads with parallel or collinear axes. The principal structures are a large family of 1-periodic knots and related multi-thread infinite links, knitting patterns and chain-link weaving. The relevance to synthetic chemistry is described in terms of targets for designed synthesis such as mechanically interlocked polymers.
The influence of BPM-supportive culture and individual process orientation on process conformance
Authors: Benraad Minou , Ozkan Baris , Turetken Oktay , Vanderfeesten Irene
Published: April 2022

Purpose

Organizations rely on their business processes to achieve their business objectives and ensure compliance with relevant laws and regulations. Hence, conformance to process specifications is essential to remain compliant. Various factors influence an organization’s ability to operate in conformance to its process specifications. This study investigates the influence of business process management (BPM)-supportive culture and individual process orientation on process conformance.

Design/methodology/approach

A construct was created for perceived process conformance and two constructs were selected from literature to represent BPM-supportive culture and individual process orientation. A survey was conducted with 178 employees of a global enterprise, hypotheses were formulated, and a statistical model was constructed and validated.

Findings

Results pinpoint the key role of the BPM-supportive culture in influencing both individual process orientation and conformance. Individual process orientation is also found to have a significant influence on process conformance. The findings provide additional evidence for the significance of human-related aspects of BPM in achieving BPM success.

Originality/value

The contributions of this paper help better understand how soft factors of BPM contribute to employees’ process conformance drawing on and relating concepts of BPM and organizational routines.
The cultural dimension in companies' leverage. New evidence using panel data for a European macroeconomic context
Authors: Neves Maria Elisabete , Almeida Daniela , Vieira Elisabete S.
Published: April 2022

Purpose

The main objective of this work is to show that the traditional specific characteristics of companies as well as cultural and religious dimensions can influence the leverage of companies in different macro-environmental systems.

Design/methodology/approach

To achieve this aim, the authors have used data from 1.568 firms from 7 European countries between 2010 and 2016, and the models were estimated by using panel data methodology, specifically the generalized method of moments (GMM) estimation method by Arellano and Bover (1995) and Blundell and Bond (1998).

Findings

Overall, the empirical results point out that the cultural moderating factors are essential in determining companies' capital structure, regardless of the country's legal origin. The study results also show that traditional variables, intrinsic to management, macroeconomic environment and religion, have a central role in capital structure, namely for the civilian countries.

Originality/value

As far as the authors know, this is the first work that uses, in addition to the traditional specific characteristics of companies, cultural dimensions and religion, as determinants of debt levels, in different legal systems for Europe.
The impact of COVID-19 on the operations and management of NGOs: resilience and recommendations
Authors: Asogwa Ikenna Elias , Varua Maria Estela , Datt Rina , Humphreys Peter
Published: April 2022

Purpose

The COVID-19 pandemic has made humanity contend with the negative footprint of its activities in which social justice, ecological integrity and economic stability are compromised. This study aims to investigate the impact of COVID-19 on the operation and management of non-governmental organisations (NGOs) in Nigeria.

Design/methodology/approach

Multiple case study research design was used in the study with interviews from 25 senior-level management staff of NGOs.

Findings

The analysis revealed that COVID-19 impacts NGOs both negatively and positively. Dominant among the negative impacts are a decline in health-seeking behaviours, low programme implementation, increased cost and wastages resulting from PPE, transition to virtual meetings, a decline in capacity building and staff burnout/pressure. However, some positive impacts include increased efficiency through the use of virtual innovations, peer-to-peer intervention through the establishment of networks, flexibility and prompt adaptation to the crisis, prudent management of available resources, etc. This research contributes to theory and practice.

Research limitations/implications

Conducting this research and recruiting participants at the height of COVID-19 in Nigeria, in adherence to the prevention guidelines, constituted a considerable limitation to the study.

Practical implications

Although the identified impact could be useful in framing operational policies and guidelines, the study highlights a salient future outlook with policy implications for both the governance of NGOs and the facilitation of sustainable development goals by the government.

Originality/value

Although researchers continue to explore the impact of COVID-19, none has considered the NGO sector, especially in developing countries, and with a focus on providing evidence-backed resilience practices for the future.
Understanding sustained participation in crowdsourcing platforms: the role of autonomy, temporal value, and hedonic value
Authors: Wu Wei , Yang Qianwen , Gong Xiang , Davison Robert M.
Published: April 2022

Purpose

Crowdsourcing platforms have emerged as an innovative way to generate ideas and solving problems. However, promoting sustained participation among crowdworkers is an ongoing challenge for most crowdsourcing platform providers. Drawing on self-determination theory, this study investigates the impacts of job autonomy on crowdworkers' sustained participation intention.

Design/methodology/approach

A survey of 212 crowdworkers from a leading crowdsourcing platform in China was conducted to empirically validate the model.

Findings

The empirical results lead to several key findings. First, the taxonomy of job autonomy in crowdsourcing contains three archetypes: work-scheduling autonomy, work-task autonomy, and work-method autonomy. Second, work-scheduling autonomy and work-method autonomy have more significant positive effects on temporal value than work-task autonomy, and this increase in temporal value increases crowdworkers' sustained participation intention. Third, work-task autonomy exerts a stronger influence on hedonic value than work-scheduling autonomy or work-method autonomy, and this increase in hedonic value also increases crowdworkers' sustained participation intention.

Originality/value

This study extends the crowdsourcing literature by examining the formation of crowdworkers' sustained participation and highlighting the role of differential effects of multidimensional job autonomy on crowdworkers' sustained participation. We believe that this study provides actionable insights into measures that promote crowdworkers' sustained participation in the crowdsourcing platform.
Angiogenesis biomarkers and fetal growth restriction
Authors: Villalaín Cecilia
Published: April 2022

Linked article: This is a mini commentary on Bonacina et al., pp. 1870–1877 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17151
Health care in pregnancy during the COVID‐19 pandemic and pregnancy outcomes in six low‐ and‐middle‐income countries: Evidence from a prospective, observational registry of the Global Network for Women’s and Children’s Health
Authors: Naqvi Seemab , Naqvi Farnaz , Saleem Sarah , Thorsten Vanessa R. , Figueroa Lester , Mazariegos Manolo , Garces Ana , Patel Archana , Das Prabir , Kavi Avinash , Goudar Shivaprasad S. , Esamai Fabian , Mwenchanya Musaku , Chomba Elwyn , Lokangaka Adrien , Tshefu Antoinette , Yousuf Sana , Bauserman Melissa , Bose Carl L. , Liechty Edward A. , Krebs Nancy F. , Derman Richard J. , Carlo Waldemar A. , Hibberd Patricia L. , Billah Sk Masum , Peres‐da‐Silva Nalini , Haque Rashidul , Petri William A. , Koso‐Thomas Marion , Nolen Tracy , McClure Elizabeth M. , Goldenberg Robert L.
Published: April 2022

Objective

To assess, on a population basis, the medical care for pregnant women in specific geographic regions of six countries before and during the first year of the coronavirus disease 2019 (COVID‐19) pandemic in relationship to pregnancy outcomes.

Design

Prospective, population‐based study.

Setting

Communities in Kenya, Zambia, the Democratic Republic of the Congo, Pakistan, India and Guatemala.

Population

Pregnant women enrolled in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry.

Methods

Pregnancy/delivery care services and pregnancy outcomes in the pre‐COVID‐19 time‐period (March 2019–February 2020) were compared with the COVID‐19 time‐period (March 2020–February 2021).

Main outcome measures

Stillbirth, neonatal mortality, preterm birth, low birthweight and maternal mortality.

Results

Across all sites, a small but statistically significant increase in home births occurred between the pre‐COVID‐19 and COVID‐19 periods (18.9% versus 20.3%, adjusted relative risk [aRR] 1.12, 95% CI 1.05–1.19). A small but significant decrease in the mean number of antenatal care visits (from 4.1 to 4.0, p = <0.0001) was seen during the COVID‐19 period. Of outcomes evaluated, overall, a small but significant decrease in low‐birthweight infants in the COVID‐19 period occurred (15.7% versus 14.6%, aRR 0.94, 95% CI 0.89–0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites.

Conclusions

Small but significant increases in home births and decreases in the antenatal care services were observed during the initial COVID‐19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birthweight, or preterm birth rates during the COVID‐19 period compared with the previous year. Further research should help to elucidate the relationship between access to and use of pregnancy‐related medical services and birth outcomes over an extended period.
Developmental validation of an efficient differential separation method incorporating the i‐sep®DL spin column with high sperm DNA recovery for the processing of sexual assault samples
Authors: White Tammara J. , Rye Marie S. , Tay Jasmine W.
Published: April 2022

The differential separation method is key to recovering a DNA profile of the sperm donor from sexual assault samples. However, low numbers of spermatozoa from the perpetrator are often swamped by the victim’s epithelial cells or lost during the separation process, with the separation process labor‐intensive, time‐consuming, and operator‐dependent. The self‐sealing filter of the i‐sep® DL spin column allows direct lysis of the substrate throughout the differential separation process while preventing intact sperm cells from passing through, maximizing DNA recovery, and separation of non‐sperm and sperm cells present. This study investigated the efficacy of a modified differential separation method, which incorporated the i‐sep® DL spin column in comparison with the conventional pellet‐based differential separation method. Using semen dilution series and mock post‐coital samples, the sensitivity, reproducibility, repeatability, and efficiency of sperm DNA recovery of the pellet‐based differential to the i‐sep® method were evaluated side by side. The i‐sep® differential method was more sensitive in capturing sperm fraction DNA, with informative semen donor alleles detected from high dilutions of semen inputs where the pellet method has been unsuccessful. The i‐sep® differential method reduces manual handling, generating repeatable, and reproducible results between operators. Re‐extraction of samples previously processed by the pellet or i‐sep® differential method showed that the pellet method failed to recover 15–88% of sperm fraction DNA, while the i‐sep® differential method was able to recover >99% in the initial extraction. The i‐sep® method is robust for processing sexual assault samples, overcoming the challenges of sperm DNA losses encountered by pellet‐based methods.
A chromosome‐scale genome assembly of the Mongolian oak (Quercus mongolica)
Authors: Ai Wanfeng , Liu Yanqun , Mei Mei , Zhang Xiaolin , Tan Enguang , Liu Hanzhang , Han Xiaoyi , Zhan Hao , Lu Xiujun
Published: April 2022

Mongolian oak (Quercus mongolica Fisch.) is an ecologically and economically important white oak species native to and widespread in the temperate zone of East Asia. Here, we present a chromosome‐scale reference genome assembly of Q. mongolica, a representative white oak species, by combining Illumina and PacBio data with Hi‐C mapping technologies that is the first reference genome created for an Asian oak. Our results showed that the PacBio draft genome size was 809.84 Mb, with a BUSCO complete gene percentage of 92.71%. Hi‐C scaffolding anchored 774.59 Mb contigs (95.65% of draft assembly) onto 12 pseudochromosomes. The contig N50 and scaffold N50 were 2.64 and 66.74 Mb, respectively. Of the 36,553 protein‐coding genes predicted in the study, approximately 95% had functional annotations in public databases. A total of 435.34 Mb (53.75% of the genome) of repetitive sequences were predicted in the assembled genome. Genome evolution analysis showed that Q. mongolica is closely related to Q. robur from Europe, and they shared a common ancestor ~11.8 million years ago (Ma). Gene family evolution analysis of Q. mongolica revealed that the nucleotide‐binding site (NBS)‐encoding gene family related to disease resistance was significantly contracted, whereas the ECERIFERUM 1 (CER1) homologous genes related to cuticular wax biosynthesis was significantly expanded. This pioneering Asian oak genome resource represents an important supplement to the oak genomics community and will improve our understanding of Asian white oak biology and evolution.
PD‐L1 expressed from tumor cells promotes tumor growth and invasion in lung cancer via modulating TGF‐β1/SMAD4 expression
Authors: Chen Ming‐Jenn , Wang Yao‐Chen , Wang Lee , Shen Ching‐Ju , Chen Chih‐Yi , Lee Huei
Published: April 2022

Background

Programmed death ligand‐1 (PD‐L1) has a known association with the prognosis of human cancers because of its ability to alter tumor immune surveillance via its interaction with PD‐1. We questioned whether expression of PD‐L1 in tumor cells could directly promote tumor growth and invasiveness in non–small cell lung cancer (NSCLC).

Methods

Real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) was performed to evaluate PD‐L1 messenger RNA (mRNA) expression in lung tumors. The prognostic value of PD‐L1 mRNA was assessed by Cox regression model. Transcriptional regulation of PD‐L1 by human papillomavirus (HPV) 16/18 E6 oncoprotein or by epidermal growth factor receptor (EGFR) mutation in lung cancer cells was examined by Western blot and luciferase reporter assay. The cell growth and invasion were evaluated by colony formation, soft agar growth, and Boyden chamber assay.

Results

The PD‐L1 mRNA levels showed a positive association with HPV 16/18 E6 oncoprotein and with EGFR mutation in 223 surgically resected NSCLC patients. The prognostic significance of PD‐L1 was more commonly observed in patients with high PD‐L1/E6 positive and high PD‐L1/EGFR mutant tumors. Mechanistically, upregulation of PD‐L1 transcription by E6 or mutant EGFR occurred largely through the ERK‐C/EBPβ‐TLR4‐NF‐κB cascade. PD‐L1 promotes the efficacy of colony formation, soft agar growth, and cell invasion. PD‐L1 upregulates BAG‐1 to reduce transforming growth factor (TGF)‐β1 expression, and the decrease in SMAD4 because of TGF‐β1 occurs through the p53/microRNA (miR)‐224 axis. The decreases in TGF‐β1 and SMAD4 are responsible for PD‐L1‐mediated cell invasiveness.

Conclusion

Induction of PD‐L1 by E6 oncoprotein or mutant EGFR through the ERK‐C/EBPβ‐TLR4‐NF‐κB cascade may promote tumor growth and invasiveness in NSCLC because of decreasing TGF‐β1 and SMAD4 expression.
Successful treatment of refractory brain metastases from ALK‐positive lung cancer with lorlatinib
Authors: Nakagawa Yoshiko , Shimizu Tetsuo , Hiranuma Hisato , Gon Yasuhiro
Published: April 2022

A 44‐year‐old woman with ALK‐positive advanced adenocarcinoma of the lung was treated with crizotinib, and the lung lesions disappeared. The patient was treated with alectinib and chemotherapy, but brain metastases worsened; therefore, we performed an ALK resistance gene mutation test using plasma samples. Since no ALK resistance gene mutations were detected, we speculated that ALK inhibitors failed to achieve therapeutic effects due to poor transport to the central nervous system. Therefore, we switched to lorlatinib, and found a reduction in brain metastases. In ALK‐positive advanced lung cancer, plasma‐based resistance gene testing may be useful for treatment decisions.
Accelerating advances in landscape connectivity modelling with the ConScape library
Authors: Van Moorter Bram , Kivimäki Ilkka , Noack Andreas , Devooght Robin , Panzacchi Manuela , Hall Kimberly R. , Leleux Pierre , Saerens Marco
Published: April 2022

Increasingly precise spatial data (e.g. high‐resolution imagery from remote sensing) allow for improved representations of the landscape network for assessing the combined effects of habitat loss and connectivity declines on biodiversity. However, evaluating large landscape networks presents a major computational challenge both in terms of working memory and computation time. We present theConScape(i.e. “connected landscapes”) software library implemented in the high‐performance open‐source Julia language to compute metrics for connected habitat and movement flow on high‐resolution landscapes.

The combination of Julia's ‘just‐in‐time’ compiler, efficient algorithms and ‘landmarks’ to reduce the computational load allowsConScapeto compute landscape ecological metrics—originally developed in metapopulation ecology (such as ‘metapopulation capacity’ and ‘probability of connectivity’)—for large landscapes. An additional major innovation inConScapeis the adoption of the randomized shortest paths framework to represent connectivity along the continuum from optimal to random movements, instead of only those extremes.

We demonstrateConScape's potential for using large datasets in sustainable land planning by modelling landscape connectivity based on remote‐sensing data paired with GPS tracking of wild reindeer in Norway. To guide users, we discuss other applications, and provide a series of worked examples to showcase allConScape's functionalities in Supplementary Material.

Built by a team of ecologists, network scientists and software developers,ConScapeis able to efficiently compute landscape metrics for high‐resolution landscape representations to leverage the availability of large data for sustainable land use and biodiversity conservation. As a Julia implementation,ConScapecombines computational efficiency with a transparent code base, which facilitates continued innovation through contributions from the rapidly growing community of landscape and connectivity modellers using Julia.
Magnitude comparison and automaticity in number processing in adolescents with prenatal alcohol exposure: An event‐related potentials study
Authors: Shmueli Michael , Ben‐Shachar Mattan S. , Jacobson Joseph L. , Meintjes Ernesta M. , Molteno Christopher D. , Jacobson Sandra W. , Berger Andrea
Published: April 2022

Background

Individuals with fetal alcohol spectrum disorders may exhibit a distinct pattern of dysmorphic facial features, growth restriction, and cognitive deficits, particularly in arithmetic. Magnitude comparison, a fundamental element of numerical cognition, is modulated by the numerical distance effect, with numbers closer in value more difficult to compare than those further apart, and by the automaticity of the association of numerical values with their symbolic representations (Arabic numerals).

Methods

We examined event‐related potentials acquired during the Numerical Stroop numerical and physical tasks administered to 24 alcohol‐exposed adolescents (eight fetal alcohol syndrome (FAS), eight partial FAS (PFAS), eight heavily exposed (HE) nonsyndromal) and 23 typically developing (TD), same‐ age controls. The distance effect was assessed on the numerical task to examine differences in reaction time (RT) and accuracy when two numbers are close in value (e.g., 1 vs. 2) compared to when the numbers are less close (e.g., 1 vs. 6). Automaticity was assessed in the physical task by examining the degree to which RT and accuracy are reduced when the relative physical size of two numerals is incongruent with their numerical values (e.g., 1 vs. 6).

Results

Adolescents in all four groups performed behaviorally as expected on these relatively simple magnitude comparison tasks, but accuracy was poorer and RT was slower on both tasks in the FAS and PFAS than the HE and TD groups. At the neurophysiological level, in the numerical task, a higher level of prenatal alcohol exposure was associated with smaller P2p amplitude. In the physical task, only the TD and nonsyndromal HE groups exhibited the expected smaller P300 amplitude in the incongruent than the congruent condition.

Conclusions

These findings suggest that magnitude comparison in alcohol‐exposed individuals may be mediated by recruitment of alternative neural pathways that are likely to be inefficient when number processing becomes more challenging.
“Sworn to No Master”: the Intellectual Traditions of Liberty of Conscience in Colonial NSW to 1856
Authors: Irving‐Stonebraker Sarah
Published: April 2022

Traditionally, historians have played down the role of religion in colonial New South Wales. This article contributes to a bourgeoning scholarly literature that revises this position and deepens our understanding of the intellectual culture of colonial New South Wales. Through an examination of the colonial press and the work of public figures such as John Dunmore Lang, I argue that there was a robust debate about liberty of conscience in the first half of the nineteenth century. These discussions did not primarily stem from liberalism. Rather, advocates of liberty of conscience, across the religious and political spectrums, drew primarily upon the natural rights tradition of Christian thought which identified liberty of conscience as the archetype of a natural right. Advocates of this tradition were in dialogue with not only the British imperial world but also across the Atlantic, Ireland, and the United States.
Long‐term outcomes of peritoneal dialysis catheters inserted by laparoscopic and percutaneous techniques in a single regional dialysis centre
Authors: Lee Wai Gin , Tran Phuong Uyen , Grills Richard
Published: April 2022

Background

Minimally invasive insertion of catheters for peritoneal dialysis can be performed laparoscopically or percutaneously under image guidance. In Geelong (Victoria, Australia) both methods are used. Our aim was to analyse the outcomes of all catheters inserted by both laparoscopic and percutaneous techniques and compare them against published studies from tertiary referral centres.

Methods

Data were collected retrospectively on all patients who had their catheter inserted (since 2006) within the Geelong regional service. We compared the outcomes of percutaneous catheter insertion under image guidance (percutaneous group, n = 29) with the laparoscopic catheter placement technique (laparoscopic group, n = 61). Perioperative, follow‐up and catheter outcome data were collected. There were no exclusion criteria. Analysis was performed using the unpaired student t‐test and chi‐squared test.

Results

Ninety catheters were inserted between 2006 and 2017 in mostly male patients (63%) with a mean age of 60 ± 0.4 years. The most common aetiology of chronic kidney disease was diabetic nephropathy (34%). Percutaneous insertion required less operative time, shorter hospital stay and earlier initiation of peritoneal dialysis. In the longer term, percutaneous catheters were more likely to migrate and laparoscopic catheters were more durable but more often associated with peritonitis. Thirty‐day complication rates did not differ between both groups. No Clavien‐Dindo grade 3 or 4 complication was reported.

Conclusions

Laparoscopic insertion of peritoneal dialysis catheters at our centre is performed safely and with patient outcomes comparable to published literature. Percutaneous insertion represents a safe and effective alternative based on the study findings.
Predictors of interhospital transfer delays in acute surgical patient deaths in Australia: a retrospective study
Authors: Young Edward , Kopunic Helena S. , Trochsler Markus I. , Maddern Guy J.
Published: April 2022

Background

Interhospital transfers in Australia facilitate access to acute surgical services, however transfer delays can occur. The aims of this study were to examine Australian mortality audit data on acute surgical patients who were transferred after presenting with a surgical emergency, and to identify modifiable predictors of transfer delay.

Methods

Surgical admissions between 1 January 2001 and 18 August 2020 were retrospectively extracted from the Australian and New Zealand Audit of Surgical Mortality database. Relevant factors and themes of interest were collated. Results were presented as odds ratios (OR) and 95% confidence intervals (CI), with statistical significance defined as P <0.05.

Results

After exclusion, a final 8270 cases were analysed. Non‐modifiable predictors identified were female gender (OR 1.34, 95% CI 1.05–1.70, P = 0.0184), comorbidities (OR 1.50, 95% CI 1.40–161, P <0.0001) and major non‐trauma non‐vascular specialty (OR 1.54 to 7.77, depending on specialty, P < 0.05). Modifiable predictors were inadequate clinical assessment (OR 49.48, 95% CI 32.91–74.38, P <0.0001), poor communication (OR 6.62, 95% CI 3.70–11.85, P <0.0001) and multiple transfers (OR 6.30, OR 95% 4.31–9.21, P <0.0001). Age, lack of bed and after‐hours transfer did not predict transfer delays. Metropolitan transfers was protective against transfer delays (OR 0.64, 95% CI 0.47–0.86, P = 0.0035).

Conclusion

In the view of the receiving surgeon or assessor, all transfer delays potentially contributed to patient deaths, and may have been preventable. Strategies directed at modifiable factors could minimize delays. Increased surgical services in non‐metropolitan regions could reduce need for transfer. Prospective data is required to examine if the same predictors are observed in surgical patients who survive.
Is a randomized controlled trial of waterbirth possible? An Australian feasibility study
Authors: Allen Jyai , Gao Yu , Dahlen Hannah , Reynolds Maree , Beckmann Michael , Cooper Catherine , Kildea Sue
Published: April 2022

Background

The safety of waterbirth is contested because of the lack of evidence from randomized trials and conflicting results. This research assessed the feasibility of a prospective study of waterbirth (trial or cohort).

Methods

We conducted a prospective cohort study at an Australian maternity hospital. Eligible women with uncomplicated pregnancies at 36 weeks of gestation were recruited and surveyed about their willingness for randomization. The primary midwife assessed waterbirth eligibility and intention on admission in labor, and onset of second stage. Primary outcomes measured feasibility. Intention‐to‐treat analysis, and per‐protocol analysis, compared clinical outcomes of women and their babies who intended waterbirth and nonwaterbirth at onset of second stage.

Results

1260 participants were recruited; 15% (n = 188) agreed to randomization in a future trial. 550 women were analyzed by intention‐to‐treat analysis: 351 (waterbirth) and 199 (nonwaterbirth). In per‐protocol analysis, 14% (n = 48) were excluded. Women in the waterbirth group were less likely to have amniotomy and more likely to have water immersion and physiological third stage. There were no differences in other measures of maternal morbidity. There were no significant differences between groups for serious neonatal morbidity; four cord avulsions occurred in the waterbirth group with none in the landbirth group. An RCT would need approximately 6000 women to be approached at onset of second stage.

Conclusions

A randomized trial of waterbirth compared with nonwaterbirth, powered to detect a difference in serious neonatal morbidity, is unlikely to be feasible. A powered prospective study with intention‐to‐treat analysis at onset of second stage is feasible.
The Good, the Bad and the Boring: Narcissism and the Rejection of the ‘Nice but Boring’ Relationship
Authors: Mann David
Published: April 2022

Rejection of the ‘nice but boring’ relationship is discussed in relation to narcissism. The ‘nice but boring object’ (NBBO) is linked to the patient's earlier experiences of a sterile or depressed relationship with an unavailable primary care giver. This is discussed with regard to Green's concept of ‘the dead mother’ (Green, 1983) and the impact this has on the development of the infant's ‘unit status’ (Winnicott, 1960). The re‐awakening of ‘the dead mother’ experience is evoked both in the relationship with the NBBO and also with the introjected depressed mother that the patient has internalized. In order to avoid the dangerous, suffocating deadness of the dead mother the patient seeks out relationships which are full of energy and lively, even if this exciting object leaves them feeling insecure or in other ways is felt as bad for them. The lure of the exciting bad object is heavily influenced by the need to flee the NBBO who evokes the unconscious stifling experience of ‘the dead mother’. This dynamic is then referenced to the patient's narcissism, their fear of dependency, their sensitivity to feeling wounded and the difficulty with establishing intimate relationships. Two clinical examples illustrate these issues.

‘Dear Brack, you can't imagine how bored I'm going to be here.’ Hedda Gabler, Act Two, by Henrik Ibsen

‘The heaviest burden for a talky manIs silence; everywhere he goes he talksAnd is a bore, disliked by all. To sitWith him at dinner is like being jailed.' Theognis, Elegies
Sulfonated non‐saccharide molecules and human factor XIa: Enzyme inhibition and computational studies
Authors: Al‐Horani Rami A. , Parsaeian Elnaz , Mohammad Mariam , Mottamal Madhusoodanan
Published: April 2022

Human factor XIa (FXIa) is a serine protease in the intrinsic coagulation pathway. FXIa has been actively targeted to develop new anticoagulants that are associated with a reduced risk of bleeding. Thousands of FXIa inhibitors have been reported, yet none has reached the clinic thus far. We describe here a novel class of sulfonated molecules that allosterically inhibit FXIa with moderate potency. A library of 18 sulfonated molecules was evaluated for the inhibition of FXIa using a chromogenic substrate hydrolysis assay. Only six molecules inhibited FXIa with IC50 values of 4.6–29.5 μM. Michaelis–Menten kinetics indicated that sulfonated molecules are allosteric inhibitors of FXIa. Inhibition of FXIa by these molecules was reversed by protamine. The molecules also showed moderate anticoagulant effects in human plasma with preference to prolong activated partial thromboplastin time. Their binding to an allosteric site in the catalytic domain of FXIa was modeled to illustrate potential binding mode and potential important Arg/Lys residues. Particularly, inhibitor 16 (IC50 = 4.6 µM) demonstrated good selectivity over a panel of serine proteases including those in the coagulation process. Inhibitor 16 did not significantly compromise the viability of three cell lines. Overall, the reported sulfonated molecules serve as a new platform to design selective, potent, and allosteric inhibitors of FXIa for therapeutic applications.