bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Follow-up of a Wide-Diameter Bone-Anchored Hearing Implant: 10-Year Experience on Stability, Survival, and Tolerability of an Implant-Abutment Combination
Authors: Teunissen Emma Margaretha , Caspers Coosje Jacoba Isabella , Vijverberg Maarten Adriaan , Mylanus Emmanuel Antonius Maria , Hol Myrthe Karianne Sophie
Published: November 2022

Objective

To compare stability, survival, and soft tissue reactions between a wide-diameter (test) and previous-generation small-diameter (control) bone-anchored hearing implant and to ascertain the safety of loading the test implant 3 weeks after surgery, at a long-term follow-up of 10 years.

Study Design

This study is a continuation of two previously completed, multicenter, randomized, controlled trials and consisted of one to two additional follow-up visits until 10 years after surgery.

Patients

Fifty-one of the 72 participants from the previous trials were included. Patients received a test or control implant. All control implants were loaded 6 weeks after surgery (group A). Test implants were loaded 3 (group B) or 6 weeks (group C) after surgery.

Results

The test implant showed significantly higher implant stability quotient (ISQ) values than the control implant throughout the 10-year follow-up. At 10 years, the mean ISQ-high values for both implants were higher than at the first follow-up visit. No significant differences in change of ISQ-high from baseline to 10 years were noticed between both implants and loading groups. Soft tissue reactions were rarely seen. At 10-year follow-up, no patients presented with adverse soft tissue reactions. Excluding explantations, the implant survival rate was 78.6% (group A), 100% (group B), and 90.0% (group C).

Conclusions

The test implant showed superior mean ISQ values and significantly better implant survival throughout 10-year follow-up. In addition, the current study concludes that it is safe to load the test implant at 3 weeks after surgery, as long-term results show high ISQ values and good implant survival.
Feasibility and Efficacy of Low Thoracic Ultrasound-Guided Erector Spinae Plane Blocks in Patients Undergoing Radical Total Mastectomy With Deep Inferior Epigastric Perforator Flap Reconstruction
Authors: Pai B.H. Poonam , Lai Yan H.
Published: November 2022

The analgesic efficacy of bilateral low thoracic erector spinae blocks for combined major breast and abdominal surgery has not been reported. The aim of this case series was to assess the feasibility and efficacy of T8 thoracic preincisional erector spinae blocks in patients undergoing total radical mastectomies with axillary lymph node dissections in addition to reconstruction with abdominal deep inferior epigastric flaps. The aim was to supply dermatomal coverage to provide analgesia for T2–L1 that formed the basis for an opioid-sparing multimodal technique in the context of our early recovery after breast surgery with deep inferior epigastric flap program.
Effectiveness of Absorbable Plates for the Treatment of Nasal Septal Cartilage Fractures
Authors: Kim Se Young , Bae Joon Suk , Nam Seung Min , Cha Han Gyu , Park Eun Soo
Published: November 2022

Background

Nasal bone fractures are the most common type of facial fracture. Nasal bone fractures often occur in combination with septal cartilage fractures, because the nasal septal cartilage acts as a vertical strut and provides structural support for the nose and bilateral nasal airway. However, the treatment for nasal septal cartilage fracture remains controversial, and if untreated, nasal septal cartilage fracture can lead to various complications, such as nasal obstruction and posttraumatic nasal and septal deformity. This study aimed to evaluate the effectiveness and safety of our procedure in which septal cartilage fractures were treated with septoplasty using an absorbable plate as an internal splint.

Methods

Between January 2017 and November 2020, 21 patients with nasal septal cartilage fractures were treated with septoplasty using an absorbable plate as an internal splint. The severity of the septal cartilage fracture was graded from 0 to 3 according to the computed tomography septal grading system. The numeric graded scale of nasal septal cartilage fracture was evaluated preoperatively and 6 months postoperatively using a computed tomography scan.

Results

Of 21 patients with septal cartilage fractures, 12 were treated with a polycaprolactone (PCL) mesh plate, and 9 were treated with a polydioxanone (PDS) plate. In the PDS plate group, the preoperative numeric scale of nasal septal cartilage fracture was 2.50 (2.00–3.00), whereas the postoperative numeric scale was 1.00 (1.00–1.25, P = 0.023). In the PCL mesh plate group, the preoperative numeric scale of nasal septal cartilage fracture was 2.00 (2.00–3.00), whereas the postoperative numeric scale was 1.00 (1.00–1.50, P = 0.034). The effectiveness of the PCL mesh plate and that of the PDS plate group according to the septal grading scale were 1.45 (SD, 0.522) and 1.18 (SD, 0.603), respectively. However, these differences were not statistically significant.

Conclusions

Our study shows that septoplasty using absorbable plates provides satisfactory and safe clinical outcomes in patients with nasal septal cartilage fractures.
RETRACTED: An Eocene army ant
Authors: Sosiak Christine E. , Borowiec Marek L. , Barden Phillip
Published: November 2022

Among social insects, army ants are exceptional in their voracious coordinated predation, nomadic life history and highly specialized wingless queens: the synthesis of these remarkable traits is referred to as the army ant syndrome. Despite molecular evidence that the army ant syndrome evolved twice during the mid-Cenozoic, once in the Neotropics and once in the Afrotropics, fossil army ants are markedly scarce, comprising a single known species from the Caribbean 16 Ma. Here we report the oldest army ant fossil and the first from the Eastern Hemisphere (EH),
Dissimulodorylus perseus
, preserved in Baltic amber dated to the Eocene. Using a combined morphological and molecular ultra conserved elements dataset spanning doryline lineages, we find that
D. perseus
is nested among extant EH army ants with affinities to
Dorylus.
Army ants are characterized by limited extant diversification throughout most of the Cenozoic; the discovery of
D. perseus
suggests an unexpected diversity of now-extinct army ant lineages in the Cenozoic, some of which were present in Continental Europe.
Evolution of self-sustained circadian rhythms is facilitated by seasonal change of daylight
Authors: Seki Motohide , Ito Hiroshi
Published: November 2022

Self-sustained oscillation is a fundamental property of circadian rhythms and has been repeatedly tested since the early days of circadian research, resulting in the discovery of almost all organisms possessing self-sustained circadian oscillations. However, the evolutionary advantage of self-sustainability has been only speculatively discussed. In this theoretical study, we sought the environmental constraints and selection pressure that drive the acquisition or degeneration of self-sustainability through the process of evolution. We considered the dynamics of a gene regulatory network having a light input pathway under 12 h light and 12 h dark cycles or multiple day length conditions and then optimized the network structure using an evolutionary algorithm. By designing the fitness function in the evolutionary algorithm, we investigated the environmental conditions that led to the evolution of the self-sustained oscillators. Then, we found that self-sustained oscillation is rarer than damped oscillation and hourglass-type behaviour. Moreover, networks with self-sustainability have a markedly high fitness score when we assume that a network has to generate a constantly periodic expression profile regardless of day length. This study is, to our knowledge, the first to show that seasonality facilitated the evolution of the self-sustained circadian clock, which was consistent with empirical records.
Haemosporidian parasites and incubation period influence plumage coloration in tanagers (Passeriformes: Thraupidae)
Authors: Aguiar de Souza Penha Victor , Maia Chaves Bicalho Domingos Fabricius , Fecchio Alan , Bell Jeffrey A. , Weckstein Jason D. , Ricklefs Robert E. , Braga Erika Martins , de Abreu Moreira Patrícia , Soares Letícia , Latta Steven , Tolesano-Pascoli Graziela , Alquezar Renata Duarte , Del-Claro Kleber , Manica Lilian Tonelli
Published: November 2022

Birds are highly visually oriented and use plumage coloration as an important signalling trait in social communication. Hence, males and females may have different patterns of plumage coloration, a phenomenon known as sexual dichromatism. Because males tend to have more complex plumages, sexual dichromatism is usually attributed to female choice. However, plumage coloration is partly condition-dependent; therefore, other selective pressures affecting individuals' success may also drive the evolution of this trait. Here, we used tanagers as model organisms to study the relationships between dichromatism and plumage coloration complexity in tanagers with parasitism by haemosporidians, investment in reproduction and life-history traits. We screened blood samples from 2849 individual birds belonging to 52 tanager species to detect haemosporidian parasites. We used publicly available data for plumage coloration, bird phylogeny and life-history traits to run phylogenetic generalized least-square models of plumage dichromatism and complexity in male and female tanagers. We found that plumage dichromatism was more pronounced in bird species with a higher prevalence of haemosporidian parasites. Lastly, high plumage coloration complexity in female tanagers was associated with a longer incubation period. Our results indicate an association between haemosporidian parasites and plumage coloration suggesting that parasites impact mechanisms of sexual selection, increasing differences between the sexes, and social (non-sexual) selection, driving females to develop more complex coloration.
Suppression of innate immunity by the vaccinia virus protein N1 promotes skin microbiota expansion and increased immune infiltration following vaccination
Authors: Shmeleva Evgeniya V. , Syafiq Danial , Moldoveanu Ana L. , Ferguson Brian J. , Smith Geoffrey L.
Published: November 2022

Vaccinia virus (VACV) protein N1 is an intracellular immunomodulator that contributes to virus virulence via inhibition of NF-κB. Intradermal infection with a VACV lacking gene N1L (vΔN1) results in smaller skin lesions than infection with wild-type virus (WT VACV), but the impact of N1 deletion on the local microbiota as well as the innate and cellular immune responses in infected ear tissue is mostly uncharacterized. Here, we analysed the bacterial burden and host immune response at the site of infection and report that the presence of protein N1 correlated with enhanced expansion of skin microbiota, even before lesion development. Furthermore, early after infection (days 1–3), prior to lesion development, the levels of inflammatory mediators were higher in vΔN1-infected tissue compared to WT VACV infection. In contrast, infiltration of ear tissue with myeloid and lymphoid cells was greater after WT VACV infection and there was significantly greater secondary bacterial infection that correlated with greater lesion size. We conclude that a more robust innate immune response to vΔN1 infection leads to better control of virus replication, less bacterial growth and hence an overall reduction of tissue damage and lesion size. This analysis shows the potent impact of a single viral immunomodulator on the host immune response and the pathophysiology of VACV infection in the skin.
Do Public Health Efforts Matter? Explaining Cross-Country Heterogeneity in Excess Death During the COVID-19 Pandemic
Authors: Sun Min Woo , Troxell David , Tibshirani Robert
Published: November 2022

The COVID-19 pandemic has taken a devastating toll around the world. Since January 2020, the World Health Organization estimates 14.9 million excess deaths have occurred globally. Despite this grim number quantifying the deadly impact, the underlying factors contributing to COVID-19 deaths at the population level remain unclear. Prior studies indicate that demographic factors like proportion of population older than 65 and population health explain the cross-country difference in COVID-19 deaths. However, there has not been a holistic analysis including variables describing government policies and COVID-19 vaccination rate. Furthermore, prior studies focus on COVID-19 death rather than excess death to assess the impact of the pandemic. Through a robust statistical modeling framework, we analyze 80 countries and show that actionable public health efforts beyond just the factors intrinsic to each country are necessary to explain the cross-country heterogeneity in excess death.
Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging
Authors: Mishra Sapna S , Hafiz Rakibul , Misra Rohit , Gandhi Tapan K. , Prasad Alok , Mahajan Vidur , Biswal Bharat B.
Published: November 2022

The increasing number of reports of mild to severe psychological, behavioral, and cognitive sequelae in COVID-19 survivors motivates a need for a thorough assessment of the neurological effects of the disease. In this regard, we have conducted a neuroimaging study to understand the neurotropic behavior of the coronavirus. We hypothesize that the COVID recovered subjects have developed alterations in the brain which can be measured through susceptibility differences in various regions of brain when compared to healthy controls (HCs). Hence we performed our investigations on susceptibility weighted imaging (SWI) volumes. Fatigue, being of the most common symptoms of Long COVID has also been studied in this work. SWI volumes of 46 COVID and 30 HCs were included in this study. The COVID patients were imaged within six months of their recovery. We performed unpaired two-sample t-test over the pre-processed SWI volumes of both the groups and multiple linear regression was performed to observe group differences and correlation of fatigue with SWI values. The group analysis showed that COVID recovered subjects had significantly higher susceptibility imaging values in regions of the frontal lobe and the brain stem. The clusters obtained in the frontal lobe primarily show differences in the white matter regions. The COVID group also demonstrated significantly higher fatigue levels than the HC group. The regression analysis on the COVID group yielded clusters in anterior cingulate gyrus and midbrain which exhibited negative correlations with fatigue scores. This study suggests an association of Long COVID with prolonged effects on the brain and also indicates the viability of SWI modality for analysis of post-COVID symptoms.

Highlights

Susceptibility weighted imaging is used for neuroimaging study of Long COVID.

A group-level study is performed to analyze the effects of COVID on the brain.

COVID survivors showed susceptibility differences in the frontal lobe and brainstem.

Analyzed the relationship between MRI data of COVID survivors and fatigue scores.
Cost of In-patient Management of Covid-19 Patients in a Tertiary Hospital in Kuwait
Authors: Muhammad Nur Amrizal , Aljunid Syed Mohamed , Almari Mohammad
Published: November 2022

Background

Among the GCC countries affected by COVID-19 infections, Kuwait was impacted with 658,520 cases and 2,563 deaths as reported by WHO on September 30, 2022. However, the impact of the COVID-19 epidemic on the economy of Kuwait especially in health sector is unknown.

Objective

The aim of this study is to determine the total cost of COVID-19 in-patient management in Kuwait.

Method

Retrospective design was employed in this study. A total 485 Covid-19 patients admitted to a tertiary hospital assigned to manage Covid-19 cases was randomly selected for this study from 1st May to 31st September 2021. Data on sociodemographic, length of stay (LOS), discharge status and comorbidity were obtained from the patients’ medical records. Among others, data on cost in this study cover administration, utility, pharmacy, radiology, laboratory, nursing, and ICU costs. The unit cost per admission was imputed using a step-down costing method with three levels of cost centers. The unit cost was multiplied by the individual patient’s length of stay to obtain the cost of care per patient per admission.

Findings

The mean cost of Covid-19 inpatient per episode of care was KD 2,216 (SD=2,018) equals to US$ 7,344 (SD=6,688) with the average length of stay of 9.4 (SD=8.5) days per admission. The total treatment costs of Covid-19 inpatient (n=485) were estimated to be KD 1,074,644 (US$ 3,561,585), in which the physician and nursing care cost were the largest share of costs (42.1%) with KD 452,154 (US$ 1,498,529). The second- and third-largest costs were intensive care (20.6%) of KD 221,439 (US$ 733,893) and laboratory costs (10.2%) of KD 109,264 (US$ 362,123). The average cost for severe Covid-19 patient was KD 4,626 (US$ 15,332), which is almost three times higher than the non-severe patients of KD 1,544 (US$ 5,117).

Conclusion

The cost of managing Covid-19 cases is substantial. The cost information can assist hospital managers and policymakers in designing more efficient interventions, especially for the management of high-risk groups.
Prevalence and factors associated with electrocardiographic abnormalities among adults attending Methadone Assisted Therapy in Dodoma, central Tanzania
Authors: Kalungi Immaculate , Mujuni Martin , Mwombeki Innocent , Nyundo Azan
Published: November 2022

Background

Patients with opioid use disorder are at a higher cardiovascular risk due to the effect of opioids on the cardiovascular system. Cardiac conduction abnormalities, electrical activity impairment, cardiac arrhythmias, and ventricular hypertrophy are reported in the opioid population.

Objective

This study aimed to assess the prevalence and factors associated with ECG abnormalities among adults with opioid use disorder attending the Itega addiction center for methadone-assisted therapy (MAT).

Methodology

A cross-sectional analytical study was conducted among adult outpatients attending the Itega addiction center in Dodoma. A calculated sample size of 321was attained through a convenience sampling approach. A standard 12-lead ECG was recorded for each participant and interpreted by two independent cardiologists. Univariate and multivariable logistic regression was computed to determine the factors associated with ECG abnormalities. Under adjusted analysis, a p-value of less than 0.05 was considered significant for factors associated with ECG abnormalities after controlling for all the variables with a minimum p-value of 0.2 at univariate analysis.

Results

The majority of 308 (95.95%) of the participants were males, 197 (61.37%) had attained primary education level, and the mean age of the participants was 35.44 ± 6.54 years. The overall prevalence for any ECG abnormalities in this study was 26.47%, with Sinus bradycardia 59(18.4%) being the most observed ECG abnormality, followed by QTc prolongation 27(8.41%). A month’s increase in the duration on MAT and being a female were significantly associated with lower odds of ECG abnormalities (AOR =0.85, 95% CI =0.74-0.96 p =0.014) and (AOR = 0.05, 95% CI = 0.01-0.59, p = 0.017) respectively.

Conclusion

The high prevalence of ECG Abnormalities implies high cardiovascular risk among a population with opioid use disorder. Given that majority of the ECG abnormalities are treatable, integrating cardiovascular care in the opioid addiction clinic would be beneficial for this population.
Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment
Authors: Kolb Julia , John Nora , Kim Kyoohyun , Möckel Conrad , Rosso Gonzalo , Möllmert Stephanie , Kurbel Veronika , Parmar Asha , Sharma Gargi , Beck Timon , Müller Paul , Schlüßler Raimund , Frischknecht Renato , Wehner Anja , Krombholz Nicole , Steigenberger Barbara , Blümcke Ingmar , Singh Kanwarpal , Guck Jochen , Kobow Katja , Wehner Daniel
Published: November 2022

Extracellular matrix (ECM) deposition after central nervous system (CNS) injury leads to inhibitory scarring in mammals, whereas it facilitates axon regeneration in the zebrafish. However, the molecular basis of these different fates is not understood. Here, we identify small leucine-rich proteoglycans (SLRPs) as a causal factor in regeneration failure. We demonstrate that the SLRPs Chondroadherin, Fibromodulin, Lumican, and Prolargin are enriched in human, but not zebrafish, CNS lesions. Targeting SLRPs to the zebrafish injury ECM inhibits axon regeneration and functional recovery. Mechanistically, we find that SLRPs confer structural and mechanical properties to the lesion environment that are adverse to axon growth. Our study reveals SLRPs as previously unknown inhibitory ECM factors in the human CNS that impair axon regeneration by modifying tissue mechanics and structure.

ONE SENTENCE SUMMARY

Composition, structural organization, and mechanical properties of the injury ECM direct central nervous system regeneration.
Cross-movie prediction of individualized functional topography
Authors: Jiahui Guo , Feilong Ma , Nastase Samuel A. , Haxby James V. , Gobbini M. Ida
Published: November 2022

Participant-specific, functionally-defined brain areas are usually mapped with functional localizers and estimated by making contrasts between responses to single categories of input. Naturalistic stimuli engage multiple brain systems in parallel, provide more ecologically plausible estimates of real-world statistics, and are friendly to special populations. The current study shows that cortical functional topographies in individual participants can be estimated with high fidelity from naturalistic stimuli. Importantly, we demonstrate that robust, individualized estimates can be obtained even when participants watched different movies, were scanned with different parameters/scanners, and were sampled from different institutes across the world. Our results create a foundation for future studies that allow researchers to estimate a broad range of functional topographies based on naturalistic movies and a normative database, making it possible to integrate high-level cognitive functions across datasets from laboratories worldwide.
Perceptual reorganisation from prior knowledge emerges late in childhood
Authors: Milne G. A. , Lisi M. , McLean A. , Zheng R. , Groen I.I.A. , Dekker T. M.
Published: November 2022

Perception in the mature human visual system relies heavily on prior knowledge. Here we show for the first time that prior-knowledge-induced reshaping of visual perception emerges gradually, and late in childhood. To isolate the effects of prior knowledge on vision, we presented 4-to-12-year-olds and adults with two-tone images, which are degraded photos that are hard to recognise on first viewing. In adults, seeing the original photo causes a perceptual reorganisation leading to sudden, mandatory recognition of the two-tone version - a well-documented process relying on top-down signalling from higher-order brain areas to early visual cortex. We find that children younger than 7 to 9 years, however, do not experience this knowledge-guided shift, despite viewing the original photo immediately before each two-tone. To assess potential computations underlying this development we compared human performance to three state-of-the-art neural networks with varying architectures. We found that the best-performing architecture behaved much like 4- to 5-year-old humans, who display a feature-based rather than holistic processing strategy akin to neural networks. Our results reveal a striking age-related shift in the reconciliation of prior knowledge with sensory input, which may underpin the development of many perceptual abilities.
A replication study on key neurodevelopmental pathways affected by valproate treatment of neural precursor cells
Authors: Sukumaran Salil K. , Srividya M , Iyer Shruti , Banerjee Anushka , Purushottam Meera , Jain Sanjeev , Viswanath Biju , Sud Reeteka
Published: November 2022

Adults with bipolar disorder or epileptic seizures are commonly prescribed sodium valproate.In uteroexposure to this drug is linked to a multitude of defects in normal brain development, from neural tube defects to autism spectrum disorders. During the course of brain development, neural precursor cells (NPCs) give rise to neurons and glia, and therefore to understand the valproate-induced defects, it is crucial to understand its effect on NPCs. Two NPC lines, both derived from healthy individuals, were used for all experiments. Cells were treated with 0.7mM valproate for one week. Fresh media (+/− drug) was replenished every alternate day. RNA was extracted on day 7 of drug treatment, and transcriptomics performed. All experiments were performed in biological replicates. Genes that showed >1-fold difference (with FDR adjusted q-value ≤ 0.05) were considered differentially expressed. We further investigated the interacting partners of the differentially expressed genes using PINOT, as well as cellular pathways using DAVID. Our primary endpoint of analysis were genes that were differentially expressed (DEGs) with valproate treatment in both the NPC lines used. We found 21 such genes that were common in the two lines. PINOT revealed 504 interacting partners of the DEGs. Functional annotation analysis showed significant enrichment of four signaling pathways - Wnt, Notch, Rho-GTPase and PI3K-AKT. While the role of Rho-GTPase is a novel finding, we have replicated previously reported findings on Wnt, Notch and PI3K-Akt pathways, which further strengthens their role in mediating neurodevelopmental anomalies.
Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses
Authors: Aquino Yann , Bisiaux Aurélie , Li Zhi , O’Neill Mary , Mendoza-Revilla Javier , Merkling Sarah Hélène , Kerner Gaspard , Hasan Milena , Libri Valentina , Bondet Vincent , Smith Nikaïa , de Cevins Camille , Ménager Mickaël , Luca Francesca , Pique-Regi Roger , Barba-Spaeth Giovanna , Pietropaoli Stefano , Schwartz Olivier , Leroux-Roels Geert , Lee Cheuk-Kwong , Leung Kathy , Wu Joseph T.K. , Peiris Malik , Bruzzone Roberto , Abel Laurent , Casanova Jean-Laurent , Valkenburg Sophie A. , Duffy Darragh , Patin Etienne , Rotival Maxime , Quintana-Murci Lluis
Published: November 2022

Humans display vast clinical variability upon SARS-CoV-2 infection1–3, partly due to genetic and immunological factors4. However, the magnitude of population differences in immune responses to SARS-CoV-2 and the mechanisms underlying such variation remain unknown. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells from 222 healthy donors of various ancestries stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces a weaker, but more heterogeneous interferon-stimulated gene activity than influenza A virus, and a unique pro-inflammatory signature in myeloid cells. We observe marked population differences in transcriptional responses to viral exposure that reflect environmentally induced cellular heterogeneity, as illustrated by higher rates of cytomegalovirus infection, affecting lymphoid cells, in African-descent individuals. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell proportions on population differences in immune responses, with genetic variants having a narrower but stronger effect on specific loci. Additionally, natural selection has increased immune response differentiation across populations, particularly for variants associated with SARS-CoV-2 responses in East Asians. We document the cellular and molecular mechanisms through which Neanderthal introgression has altered immune functions, such as its impact on the myeloid response in Europeans. Finally, colocalization analyses reveal an overlap between the genetic architecture of immune responses to SARS-CoV-2 and COVID-19 severity. Collectively, these findings suggest that adaptive evolution targeting immunity has also contributed to current disparities in COVID-19 risk.
MMP2 loss leads to defective parturition and severe dystocia in mice
Authors: Kalev-Altman Rotem , Levy Tamar , Shpigel Nahum Y. , Monsonego-Ornan Efrat , Sela-Donenfeld Dalit
Published: November 2022

Parturition is the final step of mammalian reproduction and an essential process for the species’ survival. During pregnancy, the uterus is maintained quiescence which is important for fetal growth and development. However, at term, fundamental changes in myometrial contractility are initiated for efficient expulsion of the fetus. These changes involve tissue remodeling that requires changes in the extracellular matrix (ECM). The gelatinases subgroup of matrix metalloproteinases (MMPs), has only two members: MMP2 and MMP9, which are both known to participate in uterine ECM remodeling throughout the estrus cycle as well as during pregnancy, parturition and postpartum involution. Yet, no knowledge exists regarding their loss-of-function impact on the uterus. Here we investigated the effect of MMP2 and/or MMP9 genetic loss on parturition process. Single and double knockout (dKO) mice for MMP2 and/or MMP9 were used. We found high percentages of dystocia in mmp2-/-, mmp2-/-mmp9+/-and dKO females, but not in mmp9-/-females. Histological analysis of nulliparous uterine tissue of WT, mmp2-/-, mmp9-/-and dKO, at 8 weeks, 4 months and 8-9.5 months, revealed that the uterine tissue of mmp2-/-presents alterations in tissue size and structure, mainly when reaching to 8-9.5 months of age, including enlarged total tissue, myometrium, endometrium and luminal cavity. Additionally, Masson’s Trichrome staining suggested a mechanism of extensive fibrosis in mmp2-/-myometrium, which may lead to dystocia. Altogether, our research highlights a novel cause for dystocia pathology mediated by loss of MMP2 activity in uterine tissue during mammalian parturition.
A flexible empirical Bayes approach to multivariate multiple regression, and its improved accuracy in predicting multi-tissue gene expression from genotypes
Authors: Morgante Fabio , Carbonetto Peter , Wang Gao , Zou Yuxin , Sarkar Abhishek , Stephens Matthew
Published: November 2022

Predicting phenotypes from genotypes is a fundamental task in quantitative genetics. With technological advances, it is now possible to measure multiple phenotypes in large samples. Multiple phenotypes can share their genetic component; therefore, modeling these phenotypes jointly may improve prediction accuracy by leveragingeffects that are shared across phenotypes. However, effects can be shared across phenotypes in a variety of ways, so computationally efficient statistical methods are needed that can accurately and flexibly capture patterns of effect sharing. Here, we describe new Bayesian multivariate, multiple regression methods that, by using flexible priors, are able to model and adapt to different patterns of effect sharing and specificity across phenotypes. Simulation results show that these new methods are fast and improve prediction accuracy compared with existing methods in a wide range of settings where effects are shared. Further, in settings where effects are not shared, our methods still perform competitively with state-of-the-art methods. In real data analyses of expression data in the Genotype Tissue Expression (GTEx) project, our methods improve prediction performance on average for all tissues, with the greatest gains in tissues where effects are strongly shared, and in the tissues with smaller sample sizes. While we use gene expression prediction to illustrate our methods, the methods are generally applicable to any multi-phenotype applications, including prediction of polygenic scores and breeding values. Thus, our methods have the potential to provide improvements across fields and organisms.

Author summary

Predicting phenotypes from genotypes is a fundamental problem in quantitative genetics. Thanks to recent advances, it is increasingly feasible to collect data on many phenotypes and genome-wide genotypes in large samples. Here, we tackle the problem of predictingmultiple phenotypesfrom genotypes using a new method based on a multivariate, multiple linear regression model. Although the use of a multivariate, multiple linear regression model is not new, in this paper we introduce a flexible and computationally efficientempirical Bayesapproach based on this model. This approach uses a prior that captures how the effects of genotypes on phenotypes are shared across the different phenotypes, and then the prior is adapted to the data in order to capture the most prominent sharing patterns present in the data. We assess the benefits of this flexible Bayesian approach in simulated genetic data sets, and we illustrate its application in predicting gene expression measured in multiple human tissues. We show that our methods can outperform competing methods in terms of prediction accuracy, and the computations involved in fitting the model and making the predictions scale well to large data sets.
Mechanism of RanGTP priming H2A-H2B release from Kap114 in an atypical RanGTP•Kap114•H2A-H2B complex
Authors: Jiou Jenny , Shaffer Joy M. , Bernades Natalia E. , Fung Ho Yee Joyce , Dias Juliana Kikumoto , D’Arcy Sheena , Chook Yuh Min
Published: November 2022

Previously we showed that the nuclear import receptor Importin-9 wraps around the H2A-H2B core to chaperone and transport it from the cytoplasm to the nucleus. However, unlike most nuclear import systems where RanGTP dissociates cargoes from their importins, RanGTP binds stably to the Importin-9•H2A-H2B complex and formation of the ternary RanGTP•Importin-9•H2A-H2B complex facilitates H2A-H2B release to the assembling nucleosome. It was unclear how RanGTP and the cargo H2A-H2B can bind simultaneously to an importin, and how interactions of the three components position H2A-H2B for nucleosome assembly. Here we show cryo-EM structures of Importin-9•RanGTP and of its yeast homolog Kap114, including Kap114•RanGTP, Kap114•H2A-H2B, and RanGTP•Kap114•H2A-H2B to explain how the conserved Kap114 binds H2A-H2B and RanGTP simultaneously and how the GTPase primes histone transfer to the nucleosome. In the ternary complex, RanGTP binds to the N-terminal repeats of Kap114 in the same manner as in the Kap114/Importin-9•RanGTP complex, and H2A-H2B binds via its acidic patch to the Kap114 C-terminal repeats much like in the Kap114/Importin-9•H2A-H2B complex. Ran binds to a different conformation of Kap114 in the ternary RanGTP•Kap114•H2A-H2B complex. Here, Kap114 no longer contacts the H2A-H2B surface proximal to the H2A docking domain that drives nucleosome assembly, positioning it for transfer to the assembling nucleosome.

Significance Statement

Histones and their chaperone networks are typically conserved in eukaryotes. The yeast importin Kap114 and its human homolog Importin-9 share low sequence identity, but both are primary nuclear import receptors for the core histone heterodimer H2A-H2B. Cryo-EM structures of Kap114•H2A-H2B, Kap114•RanGTP and Importin-9•RanGTP complexes show homologous structure and function for Kap114 and Importin-9. In the nucleus, RanGTP binding to Kap114/Imp9•H2A-H2B does not release H2A-H2B, but RanGTP binds to form an atypical ternary complex. Structure of the ternary RanGTP•Kap114•H2A-H2B complex explains how the GTPase and cargo bind simultaneously to Kap114 and how the presence of Ran in the complex primes H2A-H2B transfer to assembling nucleosomes.
CRISPR/Cas9-based repeat depletion for the high-throughput genotyping of complex plant genomes
Authors: Rossato Marzia , Marcolungo Luca , De Antoni Luca , Lopatriello Giulia , Bellucci Elisa , Cortinovis Gaia , Frascarelli Giulia , Nanni Laura , Bitocchi Elena , Vittori Valerio Di , Vincenzi Leonardo , Lucchini Filippo , Bett Kirstin E. , Ramsay Larissa , Konkin David James , Delledonne Massimo , Papa Roberto
Published: November 2022

High-throughput genotyping enables the large-scale analysis of genetic diversity in population genomics and genomewide association studies that combine the genotypic and phenotypic characterization of large collections of accessions. Sequencing-based approaches for genotyping are progressively replacing traditional genotyping methods due to the lower ascertainment bias. However, genome-wide genotyping based on sequencing becomes expensive in species with large genomes and a high proportion of repetitive DNA. Here we describe the use of CRISPR/Cas9 technology to deplete repetitive elements in the 3.76-Gb genome of lentil (Lens culinaris), 84% consisting of repeats, thus concentrating the sequencing data on coding and regulatory regions (single-copy regions). We designed a custom set of 566,766 gRNAs targeting 2.9 Gbp of repeats and excluding repetitive regions overlapping annotated genes and putative regulatory elements based on ATAC-Seq data. The novel depletion method removed ∼40% of reads mapping to repeats, increasing those mapping to single-copy regions by ∼2.6-fold. When analyzing 25 million fragments, this repeat-to-single-copy shift in the sequencing data increased the number of genotyped bases of ∼10-fold compared to non-depleted libraries. In the same condition, we were also able to identify ∼12-fold more genetic variants in the single-copy regions and increased the genotyping accuracy by rescuing thousands of heterozygous variants that otherwise would be missed due to low coverage. The method performed similarly regardless of the multiplexing level, type of library or genotypes, including different cultivars and a closely-related species (L. orientalis). Our results demonstrated that CRISPR/Cas9-driven repeat depletion focuses sequencing data on meaningful genomic regions, thus improving high-density and genome-wide genotyping in large and repetitive genomes.
Comparative single-cell profiling reveals distinct cardiac resident macrophages essential for zebrafish heart regeneration
Authors: Wei Ke-Hsuan , Lin I-Ting , Chowdhury Kaushik , Liu Kuan-Ting , Ko Tai-Ming , Chang Yao-Ming , Yang Kai-Chien , Lai Shih-Lei
Published: November 2022

Zebrafish exhibit a robust ability to regenerate their hearts following injury, and the immune system plays a key role in this process. We previously showed that delaying macrophage recruitment by clodronate liposome (CL) treatment compromises neutrophil resolution and heart regeneration, even when the infiltrating macrophage number was restored within the first-week post injury (Lai et al., 2017). Here, we examined the molecular mechanisms underlying the cardiac repair of regenerative PBS-control hearts vs. non-regenerative CL-treated hearts. Bulk transcriptomic analyses revealed that CL-treated hearts exhibited disrupted inflammatory resolution and energy metabolism during cardiac repair. Temporal single-cell profiling of inflammatory cells in regenerative vs. non-regenerative conditions further identified heterogenous macrophages and neutrophils with distinct infiltration dynamics, gene expression, and cellular crosstalk. Among them, two residential macrophage subpopulations were enriched in regenerative hearts and barely recovered in non-regenerative hearts. Early CL treatment at 8 days or even 1 month before cryoinjury led to the depletion of resident macrophages without affecting the circulating macrophage recruitment to the injured area. Strikingly, these resident macrophage-deficient zebrafish still exhibited compromised neovascularization and scar resolution. Our results characterized the inflammatory cells of the zebrafish injured hearts and identified key resident macrophage subpopulations prerequisite for successful heart regeneration.
Online modeling of environmental constraint region for complex-shaped parts assembly
Authors: Gan Shuai , Liu Yang , Chen Ziyu
Published: November 2022

Purpose

The paper aims to propose a method to build environmental constraint region online in complex-shaped peg-in-hole assembly tasks.

Design/methodology/approach

Compared with conventional way which using computer-aided design (CAD) models of assembly parts to construct the environmental constraint region offline, the paper provides an online approach that consists of three aspects: modeling assembly parts through visual recognition, decomposing complex shapes into multiple primitive convex shapes and a numerical algorithm to simulate the peg-in-hole insertion contact. Besides, a contrast experiment is performed to validate the feasibility and effectiveness of the method.

Findings

The experiment result indicates that online construction takes less time than the offline way under the same task conditions. Furthermore, due to the CAD models of the parts are not required to be known, the method proposed in the paper has a broader application in most assembly scenarios.

Originality/value

With the improvement of customization and complexity of manufactured parts, the assembly of complex-shaped parts has drawn greater attention of many researchers. The assembly methods based on attractive region in environment (ARIE) have shown great performance to achieve high-precision manipulation with low-precision systems. The construction of environmental constraint region serves as an essential part of ARIE-based theory, directly affect the formulation and application of assembly strategies.
IFRS for SMEs adoption, corporate governance, and quality of financial statements: evidence from Dominican Republic and El Salvador
Authors: Sassi Nesrine , Damak-Ayadi Salma
Published: November 2022

Purpose

The purpose of this study is to examine the indirect relationship between the mandatory adoption of International Financial Reporting Standards for small and medium-sized enterprises (IFRS for SMEs) and the corporate governance index (CGI) by checking the mediating effect of the quality of financial statements (QFS) on this relationship.

Design/methodology/approach

The main objective of the IFRS for SMEs standard is to meet the specific needs of SMEs in transition and developing economies. Here, the authors used the structural equation method to investigate SMEs in countries that mandate the application of IFRS for SMEs for the years 2010 (pre-adoption) and 2016 (post-adoption). The final sample covered two emerging countries: the Dominican Republic and El Salvador.

Findings

The results show a positive association between the adoption of IFRS for SMEs, CGI and QFS. Furthermore, the findings confirm that the relationship between IFRS for SMEs adoption and CGI is under the control of the QFS.

Originality/value

This study provides standard setters and managers of SMEs with an overview of the importance of QFS on the significance of this relationship in emerging countries. The study contributes to the literature by examining the indirect relationship between IFRS for SMEs and CGI and building a CGI that integrates a set of governance practices linked to SMEs.
Pufferfish versus lionfish: comparing risks for Turkish marine economics
Authors: Kaplan Merve , Yildirim Seda , Yildirim Durmus Cagri
Published: November 2022

Purpose

This study aims to explore the risk level of pufferfish and lionfish by comparing them among Turkish marines. In addition, this study focuses on comparing pufferfish with lionfish to determine which one is more dangerous for marine economics in Türkiye.

Design/methodology/approach

This study employs descriptive content analysis to give some qualitative evidence for the related literature. As a sample case, Türkiye was selected in the context of being a country in the Mediterranean Basin. By reviewing recent news, reports and publications, this study firstly will conclude how invasive alien marine species affect Turkish marines. Then, pufferfish and lionfish will be compared together to determine the risk level of these species for Turkish marine economics.

Findings

As a result of descriptive findings, it is seen that captured fishery has been declined in Turkey recently due to many factors including climate change, global warming, overfishing, environmental pollution and attack of invasive alien species. Pufferfish and lionfish are seen as the most spread marine species in Turkish marines. When comparing pufferfish with lionfish, it is seen that pufferfish is more dangerous than lionfish for Turkish marine economics.

Research limitations/implications

This study provides descriptive and original findings as a result of comparison of pufferfish and lionfish due to their impact on Turkish marine economy. It is thought to give useful importation for the fight against invasive alien marine species in the Mediterranean Basin. Future studies can investigate different invasive alien marine species and their impacts on marine economics in the Mediterranean Basin.

Practical implications

Based on the Turkish cases, it is determined that there should be different policies for fight against invasive alien marine species in the Mediterranean Sea. Each marine species has different impacts on seafood market. Some of marine species can be consumed as a seafood product but some of them can't be consumed that policy makers should develop other strategies such as catching them to reduce their population in the local marines.

Social implications

The spread of invasive alien marine species is still continuing in the Mediterranean Basin. Each country has been affected by the attack of invasive alien marine species. To keep sustainable seafood market and marine economics, countries should both implement common policies and develop policies specific to threats in their own countries.

Originality/value

This study reveals key points in the rise of invasive alien marine species in Turkish marines at first. The main contribution of this study is to be a recent sample for a country which is under attack by invasive alien marine species by giving a comparison of pufferfish and lionfish.