bluuebunny/crossref_metadata_2025 huggingface dataset:
Early conversion of maternal androgens affects the embryo already in the first week of development
Authors: Wang Yuqi , Riedstra Bernd , Hulst Ronja , Noordhuis Roy , Groothuis Ton
Published: March 2023

Maternal androgen exposure has potent effects on offspring development. As substantial levels of maternal androgens are deposited in avian egg yolks, avian eggs are frequently used to study maternal effects, with a strong focus on post-natal development. However, the underlying pathways are largely unknown. Since the hormones are taken up during the embryonic phase, and these are rapidly metabolized by avian embryos into metabolites such as etiocholanolone, we studied the effects of yolk androgens (testosterone and androstenedione) and their metabolite etiocholanolone during the first few days of embryonic development. As embryonic heart rate is often used as an indicator of embryonic development, we measured the heart rate from day 3 to day 6 of incubation by using a shell-less culture technique in rock pigeon eggs (
Columba livia)
. Increased androgen exposure increased heart rate, and increased etiocholanolone mimicked this effect, albeit in a small sample size. This indicates that exposure to maternal androgens increases embryonic overall metabolism which may account for the developmental outcomes found in previous studies such as increased growth. Moreover, etiocholanolone is likely to be an important metabolite in a non-genomic pathway underlying the androgen-mediated maternal effect.
The paracaspase MALT1 controls cholesterol homeostasis in glioblastoma stem-like cells through lysosome proteome shaping
Authors: Maghe Clément , Trillet Kilian , André-Grégoire Gwennan , Kerhervé Mathilde , Merlet Laura , Jacobs Kathryn A , Bidère Nicolas , Gavard Julie
Published: March 2023

Glioblastoma stem-like cells (GSCs) compose a tumor-initiating and -propagating population, remarkably vulnerable to any variation in the stability and integrity of the endolysosomal compartment. Previous work showed that the expression and activity of the paracaspase MALT1 control GSC viability via lysosomal abundance. However, the underlying mechanisms remain elusive. By combining RNAseq with proteome-wide label-free quantification, we now report that MALT1 repression in patient-derived GSCs alters the cholesterol homeostasis, which aberrantly accumulates in lysosomes. This failure in cholesterol supply culminates in cell death and autophagy defects, which can be partially reverted by providing exogenous membrane-permeable cholesterol to GSCs. From a molecular standpoint, targeted lysosome proteome analysis unraveled that NPC lysosomal cholesterol transporters were exhausted when MALT1 was held in check. Accordingly, we found that hindering NPC1 and NPC2 phenocopies MALT1 inhibition. This supports the notion that GSC fitness relies on lysosomal cholesterol homeostasis.
A rugged yet easily navigable fitness landscape of antibiotic resistance
Authors: Papkou Andrei , Garcia-Pastor Lucia , Escudero José Antonio , Wagner Andreas
Published: March 2023

A fitness landscape is a biological analogue of a physical landscape, in which each genotype occupies a location whose elevation corresponds to fitness. Theoretical models predict that rugged fitness landscapes with multiple peaks should impair Darwinian evolution, because natural selection prevents evolving populations from traversing the valleys that lie between peaks. Experimental tests of this prediction are very limited. Here we combine CRISPR-Cas9 genome editing and deep sequencing to map the fitness landscape of more than 260’000 genotypes of theE. coli folAgene in an environment harboring the antibiotic trimethoprim. ThefolAgene encodes the key metabolic enzyme dihydrofolate reductase (DHFR), which is also a target of this antibiotic. With 514 mostly low fitness peaks, the DHFR fitness landscape is rugged. Despite this ruggedness, its highest fitness peaks are easily accessible to evolving populations. Fitness-increasing paths to high fitness peaks are abundant, and individual peaks have large basins of attractions. The basins of different peaks overlap, which renders the outcome of adaptive evolution highly contingent on chance events. In sum, ruggedness need not be an obstacle to Darwinian evolution but can reduce its predictability. If true in general, evolutionary biology and other fields of sciences in which landscapes play an important role may have to re-appraise the complexity of optimization problems on realistic landscapes.
Bovine leukemia virus-derived long-noncoding RNA, AS1-S, binds to bovine hnRNPM and alters interaction properties between hnRNPM and host mRNAs
Authors: Andoh Kiyohiko , Nishimori Asami , Matsuura Yuichi
Published: March 2023

Viruses utilize several strategies to develop latent infection and evade host immune responses. Long non-coding RNA (lncRNA), a class of non-protein encoding RNA that regulates various cellular functions by interacting with RNA binding proteins, is a key factor for viral latency because of its lack of antigenicity. Bovine leukemia virus (BLV), which belongs to the family Retroviridae, encodes the BLV-derived lncRNA AS1-S, which is a major transcript expressed in latently infected cells. We herein identified bovine hnRNPM, an RNA-binding protein located in the nucleus, as the binding partner for AS1-S using an RNA-protein pull-down assay. The pull-down assay using recombinant hnRNPM mutants showed that RNA recognition motif 1 and 2, located in the N-terminal region of bovine hnRNPM, are responsible for binding AS1-S. Furthermore, an RNA immunoprecipitation assay showed that introduction of AS1-S increased the number of mRNA that co-immunoprecipitated with bovine hnRNPM in MDBK cells. These results suggested that AS1-S could alter the interaction between hnRNPM and host mRNAs, potentially interfering with cellular functions during the initial phase of mRNA maturation in the nucleus. Since most of the identified mRNAs that exhibited increased binding to hnRNPM were correlated with the KEGG term “Pathways in cancer”, AS1-S may affect proliferation and expansion of BLV-infected cells and contribute to tumor progression.

Importance

BLV infects bovine B cells and causes malignant lymphoma, resulting in severe economic losses in the livestock industry. Due to its low incidence rate and long latent period, the molecular mechanisms underlying the progression to lymphoma remain enigmatic. Several non-coding RNAs, such as miRNA and lncRNA, have recently been discovered in the BLV genome and the relationship between BLV pathogenesis and these non-coding RNAs is attracting attention. However, most of the molecular functions of these transcripts remain un-identified. To the best of our knowledge, this is the first report describing a molecular function for the BLV-derived lncRNA AS1-S. The findings reported herein reveal a novel mechanism underlying BLV pathogenesis that could provide important insights for not only BLV research but also comparative studies of retroviruses.
T1R3 subunit of the sweet taste receptor is activated by D2O in transmembrane domain-dependent manner
Authors: Abu Natalie Ben , Shoshan-Galeczki Yaron Ben , Malach Einav , Niv Masha Y.
Published: March 2023

Deuterium oxide (D2O) is a water molecule in which both hydrogens are replaced by the heavier and rare isotope deuterium. We have previously shown that D2O has distinct sweet taste, which is mediated by the T1R2/T1R3 sweet taste receptor. Here we explore the effect of heavy water on T1R2 and T1R3 subunits. We show that D2O activates T1R3 transfected HEK293T cells similarly to T1R2/T1R3 transfected cells. The response to glucose dissolved in D2O is higher than to glucose dissolved in water. Mutations of Phenylalanine at position 7305.40in the transmembrane domain of T1R3 to Alanine, Leucine or Tyrosine, impair or diminish activation by D2O, suggesting a critical role for T1R3 TMD domain in relaying the heavy water signal.
Application of a Machine Learning Approach Towards the Targeted Identification of Phage Depolymerases
Authors: Magill Damian J. , Skvortsov Timofey A.
Published: March 2023

Biofilm production plays a clinically significant role in the pathogenicity of many bacteria, limiting our ability to apply antimicrobial agents and contributing in particular to the pathogenesis of chronic infections. Bacteriophage depolymerases, leveraged by these viruses to circumvent biofilm mediated resistance, represent a potentially powerful weapon in the fight against antibiotic resistant bacteria. Such enzymes are able to degrade the extracellular matrix that is integral to the formation of all biofilms and as such would allow complementary therapies or disinfection procedures to be successfully applied. In this manuscript, we describe the development and application of a machine learning based approach towards the identification of phage depolymerases. We demonstrate that on the basis of a relatively limited number of experimentally proven enzymes and using an amino acid derived feature vector that the development of a powerful model with an accuracy on the order of 90% is possible, showing the value of such approaches in the discovery of novel therapeutic agents.
Methionine and Iron Supplementation Enhances Kanamycin Activity AgainstMycobacterium tuberculosis
Authors: Paritala Hanumantharao , Carroll Kate S.
Published: March 2023

Despite understanding the functional roles of important proteins in sulfate assimilation and trans-sulfuration pathways, no study has been conducted to estimate the changes in the intracellular thiol levels when mycobacterium is treated with methionine. Methionine was known to be sulfur source for mycobacteria when it resides in the hostile granuloma environment and through transsufuration pathway methionine was shown to stimulate the sulfate assimilation. To study the dynamics of sulfate assimilation pathway we created gene knockout strains of important enzymes in the sulfate assimilation pathway of M. smegmatis. We stimulated these mutants with methionine, pro-filed the changes in intracellular thiols, applied external oxidative stress, and monitored the associated intracellular redox potentials (EMSH). These experiments revealed that when M. smegmatis cultures are supplemented with methionine intracellular levels surged. When those cells were challenged with hydrogen peroxide the M. smegmatis cells showed increased intracellular oxidative potentials and took prolonged time to revert back normal redox balance state when compared to non-methionine containing controls. Here in this report, we are describe how the dynamic changes of intracellular thiols are linked to augment the activity of kanamycin.
Exploring predictors of e-marketing continuance intention in the Zimbabwean pharmaceutical industry during the COVID-19 pandemic
Authors: Aigbogun Osaro , Matinari Mathews , Fawehinmi Olawole
Published: March 2023

Purpose

The purpose of this study is to empirically explore the predictors of e-marketing use continuance intention in the pharmaceutical business to business (B2B) supply chain during the COVID-19 pandemic.

Design/methodology/approach

This study adopted survey research strategy, and data were collected from managers dealing with marketing in 127 pharmaceutical firms in Harare Zimbabwe using a self-reported questionnaire. Partial least squares structural equation modeling (PLS-SEM) was employed to test the hypotheses.

Findings

Leadership support and perceived usefulness are significant predictors of e-marketing continuance intentions. The effect of perceived susceptibility and perceived severity on e-marketing use continuance intention was not significant. Perceived usefulness is a positive moderator in the relationship among leadership support, perceived susceptibility and e-marketing use continuance intention. However, the moderating effect of perceived usefulness created a significant but negative relationship between perceived severity and e-marketing use continuance intention.

Originality/value

This study provides empirical evidence of the moderating role of perceived usefulness in the relationships between e-marketing continuance intention and its predictors.
Metaverse academic library: would it be patronized?
Authors: Adetayo Adebowale Jeremy , Adekunmisi Sowemimo Ronke , Abata-Ebire Blessing Damilola , Adekunmisi Adedokun Adedayo
Published: March 2023

Purpose

This study aims to examine if students would patronize metaverse academic library (MAL) if it becomes available in Nigeria.

Design/methodology/approach

This study used a descriptive survey research design. The population was made up of 1,037 undergraduate in Adeleke University. Descriptive statistic was used to analyse data.

Findings

Findings indicated most students have never used virtual reality (VR) equipment, they are eager to use MAL for virtual academic research, library user education, accessing circulation services, reading serials and contacting reference librarians. The study concluded that MAL would be patronised by students if it is made available and therefore recommends that greater effort be made to make VR gear accessible and cheap for developing nations such as Nigeria.

Originality/value

The study is novel as it contributes to scarce research on MAL.
Bank opacity and stability in an emerging market
Authors: Dang Van Dan , Huynh Japan
Published: March 2023

Purpose

The paper analyzes the impact of bank opacity on financial stability in an emerging economy.

Design/methodology/approach

Based on a unique dataset of 31 Vietnamese commercial banks from 2007 to 2019, the paper captures earnings opacity via discretionary loan loss provisions and reflects individual bank stability through the accounting-based Z-score index and its disaggregate components. The least squares dummy variable corrected (LSDVC) approach is employed for empirical analysis.

Findings

In contradiction to most studies on developed economies, earnings management improves bank financial stability in Vietnam. Earnings management is more important for the financial stability of smaller banks. Further, the effect of financial information disclosure on bank stability is strengthened by unfavorable macroeconomic conditions, particularly economic downturns, the global financial crisis and uncertain times in banking.

Originality/value

This is the first study to shed light on how bank opacity influences bank financial stability in an emerging market. The evidence with the conditioning roles of bank size and macroeconomic factors, such as uncertainty in banking, is entirely novel in the related literature. Additionally, the paper contributes to a growing body of banking literature by using the LSDVC estimator to examine the association between bank opacity and bank stability.
Error identification and compensation of 1T2R parallel power head based on trajectory optimization and principal component analysis
Authors: Ni Yanbing , Cui Yizhang , Jia Shilei , Lu Chenghao , Lu Wenliang
Published: March 2023

Purpose

The purpose of this paper is to propose a method for selecting the position and attitude trajectory of error measurement to improve the kinematic calibration efficiency of a one translational and two rotational (1T2R) parallel power head and to improve the error compensation effect by improving the properties of the error identification matrix.

Design/methodology/approach

First, a general mapping model between the endpoint synthesis error is established and each geometric error source. Second, a model for optimizing the position and attitude trajectory of error measurement based on sensitivity analysis results is proposed, providing a basis for optimizing the error measurement trajectory of the mechanism in the working space. Finally, distance error measurement information and principal component analysis (PCA) ideas are used to construct an error identification matrix. The robustness and compensation effect of the identification algorithm were verified by simulation and through experiments.

Findings

Through sensitivity analysis, it is found that the distribution of the sensitivity coefficient of each error source in the plane of the workspace can approximately represent its distribution in the workspace, and when the end of the mechanism moves in a circle with a large nutation angle, the comprehensive influence coefficient of each sensitivity is the largest. Residual analysis shows that the robustness of the identification algorithm with the idea of PCA is improved. Through experiments, it is found that the compensation effect is improved.

Originality/value

A model for optimizing the position and attitude trajectory of error measurement is proposed, which can effectively improve the error measurement efficiency of the 1T2R parallel mechanism. In addition, the PCA idea is introduced. A least-squares PCA error identification algorithm that improves the robustness of the identification algorithm by improving the property of the identification matrix is proposed, and the compensation effect is improved. This method has been verified by experiments on 1T2R parallel mechanism and can be extended to other similar parallel mechanisms.
Metaverse office: exploring future teleworking model
Authors: Chen Zhisheng
Published: March 2023

Purpose

This study aims to explore the application scenarios of metaverse offices in organizations, including immersive work experiences, weak social networks and virtual meetings. Based on the exploration of this application scenario, this study discusses four levels of organizational change that will be brought about by the future metaverse office, such as the inter-enterprise ecological collaboration model, distributed autonomous organization, flexible leadership and individual belongingness. The metaverse office has some special advantages over traditional office models, but the metaverse office still raises some issues, such as privacy, security, addiction, equity and usability. These issues brake the widespread adoption of metaverse technologies. The study recommends that researchers take these issues into account in future metaverse research and development.

Design/methodology/approach

This study surveys the relevant literature by means of a literature review in order to analyze how metaverse technology can be applied to teleworking. Two databases including Web of Science (https://www.webofscience.com/) and Google Scholar (http://scholar.google.com) were selected for this study. Keywords such as “teleworking and metaverse” were used, and 18 publications were found to be relevant to the study. After excluding duplicates, less relevant and older literature, only 14 articles could be used as references for this study. Based on the exploration of this application scenario, this study discusses four levels of organizational change and issues that will be brought about by the metaverse office of the future.

Findings

It presents the application scenarios of the metaverse office in organizations, including immersive work experience, weak social networking and virtual meetings.

Social implications

The pandemic triggers a desire for contactless working. The three main applications of the metaverse office also have a practical value which has been proven in some high-tech companies. It is foreseeable that an efficient, electronic and personalized office model will be enthusiastically adopted by society. Metaverse office will gradually step into people's view in the future.

Originality/value

The concept of the metaverse office has rarely been touched upon by theoretical research, although the technology is gradually becoming known. Even its application to teleworking has only recently been reached by some organizations.
A terrible beauty is burned: gifts, sacrifice and community in Northern Ireland
Authors: Downey Hilary , Sherry, Jr John F.
Published: March 2023

Purpose

Sacrifice, integral to gift giving, remains unexplored and undertheorized in marketing. This paper aims to address this shortfall by analyzing the dynamics of sacrifice and theorizing how it serves as an engine of the gift chimney.

Design/methodology/approach

The ethnographic investigation of public ceremonial gift giving in sectarian Northern Ireland describes and interprets the complex nature of the gift.

Findings

The authors show that sacrifice is a plausible mechanism of the gift chimney and that the co-occurrence of monadic, dyadic and systemic giving in the same ritual acts as an accelerant.

Social implications

The authors analyze how public ceremonial gift giving induces sectarian communities to risk convocation, enabling them to exorcize trauma sustained at one another’s hands and to build a platform for future cross-community cohesion in a context of ineffective institutional efforts.

Originality/value

Sacrifice propels circulation of the gift, creating a social bond between antagonists whose ethos of mutuality depends upon ritualized reciprocal recognition of entangled loss.
Mechanisms of iron homeostasis in Pseudomonas aeruginosa and emerging therapeutics directed to disrupt this vital process
Authors: Sánchez‐Jiménez Ana , Marcos‐Torres Francisco J. , Llamas María A.
Published: March 2023

Pseudomonas aeruginosa is an opportunistic pathogen able to infect any human tissue. One of the reasons for its high adaptability and colonization of host tissues is its capacity of maintaining iron homeostasis through a wide array of iron acquisition and removal mechanisms. Due to their ability to cause life‐threatening acute and chronic infections, especially among cystic fibrosis and immunocompromised patients, and their propensity to acquire resistance to many antibiotics, the World Health Organization (WHO) has encouraged the scientific community to find new strategies to eradicate this pathogen. Several recent strategies to battle P. aeruginosa focus on targeting iron homeostasis mechanisms, turning its greatest advantage into an exploitable weak point. In this review, we discuss the different mechanisms used by P. aeruginosa to maintain iron homeostasis and the strategies being developed to fight this pathogen by blocking these mechanisms. Among others, the use of iron chelators and mimics, as well as disruption of siderophore production and uptake, have shown promising results in reducing viability and/or virulence of this pathogen. The so‐called ‘Trojan‐horse’ strategy taking advantage of the siderophore uptake systems is emerging as an efficient method to improve delivery of antibiotics into the bacterial cells. Moreover, siderophore transporters are considered promising targets for the developing of P. aeruginosa vaccines.
Prospective, open‐label, and observational study of cetuximab for metastatic colorectal carcinoma: The OPTIM1SE study
Authors: Yang Tsai‐Sheng , Chen Hong‐Hwa , Bo‐Wen Lin , Kim Tae Won , Kim Jong Gwang , Ahn Joong Bae , Lee Myung‐Ah , Lin Johnson , Ho Gwo Fuang , Anh Le Tuan , Temraz Sally , Burge Matthew , Chua Clarinda , Huang Jason , Park Young Suk
Published: March 2023

Aim

The OPTIM1SE study observed long‐term real‐world outcomes of cetuximab‐based infusional 5‐fluorouracil (5‐FU) regimens for first‐line treatment of metastatic colorectal cancer (mCRC) across Asia‐Pacific and Middle East regions, aiming to characterize their use, effectiveness, and safety in routine practice.

Methods

OPTIM1SE was a prospective, open‐label, observational study. Patients with untreated KRAS wild‐type mCRC and distant metastases were treated per locally approved labels and monitored for 3 years via electronic medical records. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression‐free survival (PFS), and overall survival (OS).

Results

From November 19, 2013, to June 30, 2016, 520 patients were enrolled in 51 sites. Patients were mostly male (61.2%), with a mean age of 58.5 (±12.0) years; 420 patients received leucovorin, 5‐FU, and irinotecan–based regimens and 94 received leucovorin, 5‐FU, and oxaliplatin. The most common primary tumor site was the rectum (38.8%), with liver metastases (65.0%). ORR was 45.4% (95% CI, 41.1%–49.7%), including 26 patients (5.0%) with a complete response. Median PFS was 9.9 months (95% CI, 8.2–11.0); median OS (mOS) was 30.8 months (95% CI, 27.9–33.6). Higher mOS was associated with tumors of left compared with right‐sided origin (hazard ratio, 0.69 [95% CI, 0.49–0.99]); higher ORR was also associated with liver metastases compared with all other metastases (55.4% vs. 40.2%). Adverse events were consistent with the known safety profile of cetuximab.

Conclusion

Cetuximab‐based 5‐FU regimens were effective first‐line treatments for mCRC in routine practice, particularly in patients with left‐sided disease and liver metastases only.
Does habitat type in no‐tillage agroecosystems influence ground‐dwelling macroarthropod community structure? A case study in KwaZulu‐Natal, South Africa
Authors: Mwabvu Tarombera , Nxele Thembeka , Yekwayo Inam
Published: March 2023

Loss of biodiversity in agroecosystems has negative implications for crop production and the functioning of the ecosystem. As such, agroecologists advocate minimum tillage practices in order to conserve biological diversity. To establish the influence of agricultural practices on biodiversity, we compared the species richness, abundance and composition of beetles, ants, spiders and small groups of ground dwelling arthropods in a veld and three agroecosystems (maize, sugarcane and multispecies pasture) under minimum tillage. Sampling was by pitfall trapping during the summer rainfall season in December 2019. Although ants were the most abundant (47%), followed by beetles (31%); beetles were the most speciose making up 40% of the morphospecies followed by spiders (31%). The veld had significantly greater relative proportion of species richness of spiders (54%) than the three agroecosystems, while significantly low relative proportion of species richness of ants was in the pasture (6%) compared to the veld (63%). Species richness and abundance of beetles were similar across habitat types. The four habitats supported different assemblages of ants, beetles and spiders. The differences in species composition among the habitats support the notion that agricultural practices with minimum soil disturbance enhance conservation of biological diversity, particularly, specialist species.
Married to a ‘British Subject’
Authors: Walsh Jacinta
Published: March 2023

In the archives lie the stories of our past, stories that knowingly or unknowingly live in our present. For Aboriginal families, finding records can be a critical source of great healing, enhance and affirm identity, and provide families with new understandings of how things came to be. This essay affords agency to First Nations families looking to the archives for their stories, reading historical documents against the grain, and telling their stories their way. Through family memory, reflection, and archival research, it delivers the microhistory, rich in feeling, of one First Nations family, through the experiences of Mabel Ita Eatts (née Frederick), an ancestral matriarch, a Jaru woman, and the Great Grandmother of the author. Mabel was a member of the Stolen Generations and was later deeply influenced by exemption policy. Her story brings to life the struggles faced by Aboriginal ‘half‐caste’ women living in Broome and Derby in the 1920s and 1930s, explicitly highlighting not only the invasive oppression expressed through this policy but, more importantly, how Mabel actively negotiated the system. This paper is a powerful example of how one Aboriginal family writes back to the colonising archive.
Effect of pneumatic leg compression on post‐induction hypotension in elderly patients undergoing robot‐assisted laparoscopic prostatectomy: a double‐blind randomised controlled trial
Authors: Park J.‐Y. , Yu J. , Kim C.‐S. , Baek J.‐W. , Jo Y. , Kim Y.‐K.
Published: March 2023

Post‐induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post‐induction hypotension in elderly patients undergoing robot‐assisted laparoscopic prostatectomy. In this double‐blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post‐induction hypotension in these groups. Post‐induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post‐induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post‐induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression‐related complications. Pneumatic leg compression reduced post‐induction hypotension in elderly patients undergoing robot‐assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post‐induction hypotension among elderly patients undergoing general anaesthesia.
Bowel habits in healthy infants and the prevalence of functional constipation, infant colic and infant dyschezia
Authors: Gatzinsky Cathrine , Sillén Ulla , Thornberg Sarah , Sjöström Sofia
Published: March 2023

Aim

During infancy bowel habits change. Most infants with gastrointestinal problems have a functional gastrointestinal disorder (FGID), a major reason for visiting paediatricians. This study aims to provide data on stool frequency and consistency during the first year, prevalence rates for functional constipation (FC) and to establish associations with relevant demographic data. The occurrence of infant colic (IC) and infant dyschezia (ID) was also reported.

Methods

This prospective observational birth‐cohort study enrolled 122 healthy full‐term infants. Questionnaires were completed at 2 weeks and 2, 6 and 12 months.

Results

Stool frequency decreased with age and consistency changed, with fewer runny stools. At 2 weeks, 24.3% had at least one of the studied FGID. FC was found in 2.6%–14.3% (up to 12 months), IC was found in 4.9%–3.4% (up to 2 months) and ID in 22.1%–3.9% (up to 6 months). Infants with an FGID had a lower weight and more healthcare visits than infants without. Breastfeeding and a high percentage of runny stools at 2 weeks of age decreased the odds of developing FC.

Conclusion

Data on bowel habits and the prevalence of FC, IC and ID are presented. FGID during infancy is common and affects children's well‐being, while their families need support and advice.
Accurate diagnosis of prostate cancer by combining Proclarix with magnetic resonance imaging
Authors: Morote Juan , Pye Hayley , Campistol Miriam , Celma Anna , Regis Lucas , Semidey Maria , de Torres Ines , Mast Richard , Planas Jacques , Santamaria Anna , Trilla Enrique , Athanasiou Alcibiade , Singh Saurabh , Heavey Susan , Stopka‐Farooqui Urszula , Freeman Alex , Haider Aiman , Schiess Ralph , Whitaker Hayley C. , Punwani Shonit , Ahmed Hashim U. , Emberton Mark
Published: March 2023

Objectives

To assess of the clinical performance of Proclarix® (a novel Conformité Européenne [CE]‐marked biomarker test aiding in the identification of clinically significant prostate cancer [csPCa]) alone or in combination with multiparametric magnetic resonance imaging (mpMRI) to predict csPCa (International Society of Urological Pathology Grade Group ≥2).

Patients and Methods

The study included blood samples from 721 men undergoing mpMRI followed by biopsy at University College London, London, and Vall d’Hebron University Hospital, Barcelona. Samples were tested blindly. The Proclarix‐MRI model combining prostate volume, Proclarix and mpMRI results was trained using the UCL cohort (n = 159) and validated in the Vall d’Hebron cohort (n = 562). Its diagnostic performance was established in correlation to biopsy outcome and compared to available clinical parameters and risk calculators.

Results

Clinical performance of the Proclarix‐MRI model in the validation cohort did not significantly differ from the training cohort and resulted in a sensitivity for csPCa of 90%, 90% negative predictive value and 66% positive predictive value. The Proclarix‐MRI score's specificity (68%) was significantly (P < 0.001) better than the MRI‐European Randomized study of Screening for Prostate Cancer risk score (51%), Proclarix (27%) or mpMRI (28%) alone. In addition, Proclarix by itself was found to be useful in the MRI Prostate Imaging‐Reporting and Data System (PI‐RADS) score 3 subgroup by outperforming prostate‐specific antigen density in terms of specificity (25% vs 13%, P = 0.004) at 100% sensitivity.

Conclusion

When combined with mpMRI and prostate volume, Proclarix reliably predicted csPCa and ruled out men with no or indolent cancer. A large reduction of two thirds of unneeded biopsies was achieved. Proclarix can further be used with high confidence to reliably detect csPCa in men with an indeterminate PI‐RADS score 3 mpMRI. Despite these encouraging results, further validation is needed.
Fecundity trends of Chinook salmon in the Pacific Northwest
Authors: Malick Michael J. , Losee James P. , Marston Gary , Agha Mickey , Berejikian Barry A. , Beckman Brian R. , Cooper Matthew
Published: March 2023

Fecundity is an important demographic parameter that contributes to the productivity of anadromous fish stock dynamics. Yet, studies on fecundity patterns in Pacific salmon (Oncorhynchusspp.) often only include a few years of data, limiting our ability to understand spatio‐temporal trends. Here, we used data on 43 hatchery Chinook salmon (O. tshawytscha, Salmonidae) populations in Washington State to evaluate whether average fecundity changed over the past three decades. We then used data from a subset of stocks (18) to evaluate the relationship between fecundity and body length. Our results revealed significant changes in fecundity across the 25‐year study period with most stocks showing declines in fecundity over the past decade. Results further showed that Chinook salmon have decreased in length over this same period and that annual variation in mean length explains a majority (62%) of annual variation in mean fecundity. Specifically, we estimated that a 1‐mm reduction in length results in 7.8 fewer eggs (95% CI = 6.6–8.9). Given that the majority of Pacific Northwest Chinook salmon in the environment and harvested in fisheries originate from hatchery releases and that nearby hatchery and wild populations generally have similar ocean distributions, these results likely reflect patterns for many populations not included. Combined, our results highlight the need to consider changes in body size and egg production when assessing the dynamics of anadromous fish populations and designing management or conservation plans, particularly for depressed populations.
Diagnostic utility of the lymphoid screening tube supplemented with TRBC1 for the assessment of T‐cell clonality
Authors: Blomme S. , Nollet F. , Boeckx N. , Cauwelier B. , Snauwaert S. , Emmerechts J.
Published: March 2023

Introduction

Flow cytometric panels for the investigation of lymphoproliferative disorders, such as the EuroFlow Lymphoid Screening Tube (LST), often fail to demonstrate T‐cell clonality, as a suitable clonality marker was unavailable until recently. Aim of this study was to evaluate the added value of supplementing TRBC1, a flow cytometric T‐cell clonality marker, to the LST.

Methods

Flow cytometric analysis was performed on 830 routine samples referred to our lab for suspicion of hematological malignancy. T‐cells with monotypic TRBC1‐expression were additionally characterized with a 12‐color T‐cell tube and molecular T‐cell receptor gamma gene rearrangement (TRG).

Results

LST analysis revealed 97 (11.7%) samples with the presence of a monotypic T‐cell population according to TRBC1, including 21 (2.5%) “high‐count” (≥500 cells/μL blood or ≥15% of lymphocytes) and 76 (9.2%) “low‐count” (<500 cells/μL blood or <15% of lymphocytes) populations. Clinical symptoms indicative for T‐CLPD could be correlated to 11/21 “high‐count” and 17/76 “low‐count” monotypic T‐cell populations. Molecular TRG analysis demonstrated a monoclonal result in 76% (16/21) of “high‐count” samples and in 64% (42/66; 10 samples not tested) of “low‐count” samples, but also in 9/20 samples with polytypic TRBC1 results.

Conclusion

Analysis of an LST tube supplemented with TRBC1 led to the detection of a high number of monotypic T‐cell populations. The detection of numerous small monotypic T‐cell populations raises the question of their clinical significance. A possible flowchart for assessment of these populations, based on the available literature, is proposed. Molecular TRG analysis is complementary and cannot be omitted from T‐cell clonality assessment.
In vivo reflectance confocal microscopy can detect the invasive component of lentigo maligna melanoma: Prospective analysis and case–control study
Authors: Gouveia Bruna Melhoranse , Carlos Giuliana , Wadell Andreanne , Sinz Christoph , Ahmed Tasnia , Lo Serigne N. , Rawson Robert V. , Ferguson Peter M. , Scolyer Richard A. , Guitera Pascale
Published: March 2023

Background

Lentigo maligna (LM), a form of melanoma in situ, has no risk of causing metastasis unless dermal invasive melanoma (LMM) supervenes. Furthermore, the detection of invasion impacts prognosis and management.

Objective

To assess the accuracy of RCM for the detection of invasion component on LM/LMM lesions.

Methods

In the initial case–control study, the performance of one expert in detecting LMM at the time of initial RCM assessment of LM/LMM lesions was recorded prospectively (n = 229). The cases were assessed on RCM‐histopathology correlation sessions and a panel with nine RCM features was proposed to identify LMM, which was subsequently tested in a subset of initial cohort (n = 93) in the matched case–control study by two blinded observers. Univariable and multivariable logistic regression models were performed to evaluate RCM features predictive of LMM. Reproducibility of assessment of the nine RCM features was also evaluated.

Results

A total of 229 LM/LMM cases evaluated by histopathology were assessed blindly and prospectively by an expert confocalist. On histopathology, 210 were LM and 19 were LMM cases. Correct identification of an invasive component was achieved for 17 of 19 LMM cases (89%) and the absence of a dermal component was correctly diagnosed in 190 of 210 LM cases (90%). In the matched case–control (LMM n = 35, LM n = 58), epidermal and junctional disarray, large size of melanocytes and nests of melanocytes were independent predictors of LMM on multivariate analysis. The interobserver analysis demonstrated that these three features had a fair reproducibility between the two investigators (K = 0.4). The multivariable model including those three features showed a high predictive performance AUC = 74% (CI 95% 64–85%), with sensitivity of 63% (95% CI 52–78%) and specificity of 79% (CI 95% 74–88%), and likelihood ratio of 18 (p‐value 0.0026).

Conclusion

Three RCM features were predictive for identifying invasive melanoma in the background of LM.
Evidence on economies of scale in local public service provision: A meta‐analysis
Authors: Gómez‐Reino Juan Luis , Lago‐Peñas Santiago , Martinez‐Vazquez Jorge
Published: March 2023

The standard theory of optimal jurisdictional size hinges on the existence of economies of scale in the provision of local public goods and services. However, despite its relevance for forced local amalgamation programs and related policies, the empirical evidence on the existence of such economies of scale remains elusive. The main goal of this paper is to produce an updated and comprehensive quantitative review of the existence of economies of scale in the provision of local public goods using a meta‐analysis approach to systematize the wide range of empirical approaches and modeling frameworks found in the previous literature. Our analysis confirms the presence of moderately increasing to constant returns to scale in the provision of local services with no reduction in the average costs of production in the delivery of most local public services beyond a certain, modest jurisdictional size, which many studies have estimated at 10,000 residents. Also, the potential for economies of scale differs at least across three traditional services: education, water and sanitation, and garbage collection, being highest for education and lowest for garbage collection. Our analysis also offers guidelines for future empirical research in this area. Physical output and production cost data should be used, together with translog specifications for the modeling of cost functions. Last, we find evidence that the determinants of output cost elasticity include bidirectional publication bias and population density but do not include the presence or absence of modern “lean” production technologies or the (perceived) capital intensity of the sector, contrary to conventional wisdom. These findings have significant policy implications for countries considering jurisdictional consolidation programs.
The diatom Fragilariopsis cylindrus: A model alga to understand cold‐adapted life
Authors: Otte Antonia , Winder Johanna C. , Deng Longji , Schmutz Jeremy , Jenkins Jerry , Grigoriev Igor V. , Hopes Amanda , Mock Thomas
Published: March 2023

Diatoms are significant primary producers especially in cold, turbulent, and nutrient‐rich surface oceans. Hence, they are abundant in polar oceans, but also underpin most of the polar food webs and related biogeochemical cycles. The cold‐adapted pennate diatom Fragilariopsis cylindrus is considered a keystone species in polar oceans and sea ice because it can thrive under different environmental conditions if temperatures are low. In this perspective paper, we provide insights into the latest molecular work that has been done on F. cylindrus and discuss its role as a model alga to understand cold‐adapted life.
Hepatitis D virus infection: Progress on the path toward disease control and cure
Authors: Sulkowski Mark S.
Published: March 2023

This article discusses the impact of Hepatitis D virus (HDV) infection as a major cause of liver‐related morbidity and mortality in people with Hepatitis B virus (HBV) infection. The article reviews the current knowledge and unanswered questions about the epidemiology, pathogenesis, and natural history of HDV infection. Although effective treatments for HDV infection have been elusive, interferon alfa is recommended for at least 48 weeks. However, response rates with standard‐of‐care peginterferon alfa are suboptimal, leading to few patients with a sustained virologic response. The article proposes novel approaches to treating HDV and HBV, including targeting reduction or loss of hepatitis B surface antigen (HBsAg) reduction, and discusses potential strategies for achieving HBsAg loss in patients with chronic HBV infection. Finally, the article discusses the landmark decision of accepting viral and biochemical surrogates by regulatory authorities, opening the door for the clinical development of drugs for patients with HDV infection.
The birthplace bias of teleworking: Consequences for working conditions
Authors: Moreno Galbis Eva , Carranza Felipe Trillos
Published: March 2023

The massive shift towards teleworking during the COVID pandemic relatively deteriorated working conditions of people occupying positions that could not be teleworked because they were more exposed to the risk of infection. Exploiting French data, we analyse the differential changes in sorting across occupations of immigrants and natives during years preceding the pandemic. Immigrants sorted relatively more into occupations intensive in non‐routine manual tasks. These occupations cannot be teleworked. We find an increase in immigrants' sorting into occupations intensive in non‐routine interactive and analytical tasks. However, in contrast with natives, immigrants were moving away from occupations intensively using new technologies.
Rapid adaptation of recombining populations on tunable fitness landscapes
Authors: Li Juan , Amado André , Bank Claudia
Published: March 2023

How does standing genetic variation affect polygenic adaptation in recombining populations? Despite a large body of work in quantitative genetics, epistatic and weak additive fitness effects among simultaneously segregating genetic variants are difficult to capture experimentally or to predict theoretically. In this study, we simulated adaptation on fitness landscapes with tunable ruggedness driven by standing genetic variation in recombining populations. We confirmed that recombination hinders the movement of a population through a rugged fitness landscape. When surveying the effect of epistasis on the fixation of alleles, we found that the combined effects of high ruggedness and high recombination probabilities lead to preferential fixation of alleles that had a high initial frequency. This indicates that positive epistatic alleles escape from being broken down by recombination when they start at high frequency. We further extract direct selection coefficients and pairwise epistasis along the adaptive path. When taking the final fixed genotype as the reference genetic background, we observe that, along the adaptive path, beneficial direct selection appears stronger and pairwise epistasis weaker than in the underlying fitness landscape. Quantitatively, the ratio of epistasis and direct selection is smaller along the adaptive path () than expected. Thus, adaptation on a rugged fitness landscape may lead to spurious signals of direct selection generated through epistasis. Our study highlights how the interplay of epistasis and recombination constrains the adaptation of a diverse population to a new environment.
Expanded ischemic lesion due to herniation leads to axonal injury in a site remote to the primary lesion on autopsy brain with acute focal cerebral ischemia
Authors: Seki Erika , Komori Takashi , Arai Nobutaka
Published: March 2023

Cerebral ischemia may lead to axonal injury not only at the site of the primary lesion but also in a region remote to the site of insult. In this study, we investigated the effect of herniation on the development of axonal injury at a site remote to the primary lesion during the acute phase of cerebral ischemia. We obtained postmortem brains of 13 cases with acute phase of unilateral cerebral infarction in the territory of the internal carotid artery or middle cerebral artery and seven controls. We classified the brain tissues into herniation and non‐herniation groups. Then we examined whether axonal and ischemic changes existed in the corpus callosum contralateral to the ischemic hemisphere and the upper pons. In the herniation group, we detected white‐matter lesions by Klüver‐Barrera staining, microglial loss by immunohistochemistry for ionized calcium‐binding adaptor molecule 1, and axonal injury by immunohistochemistry for amyloid precursor protein. However, none of the aforementioned findings were observed in the non‐herniation group. These findings suggest the existence of regional overlap in axonal and ischemic pathologies in remote regions in the presence of herniation. We concluded that herniation may play a significant role in the development of axonal and ischemic changes in the remote region. Our results suggest that axonal injury in a remote region may result from expanded ischemic lesions due to herniation.