bluuebunny/crossref_metadata_2025 huggingface dataset:
Hirsutella sinensis intensifies testicular function and spermatogenesis in male mice with high-fat diet-induced obesity
Authors: Liu Chin-Yu , Chen Chin-Chu , Chiang Lynn-Huey , Yang Bi-Hua , Chang Ting-Chia , Tsao Chih-Wei
Published: July 2024

Background:

Hirsutella sinensis (HS) is a mycelium isolated from the fruiting body of the medicinal mushroom Cordyceps sinensis. This study explored whether HS treatment affects reproductive dysfunction in a high-fat diet (HFD)-induced mouse model and regulates various mechanisms, focusing on oxidative stress, apoptosis, inflammation, and autophagy.

Methods:

Twenty-four C57BL/6J (B6) mice were randomly divided into a standard chow diet (NCD)- or HFD-fed group for 24 weeks. During the final 8 weeks, half of the HFD-fed mice were orally administered HS (HFD + HS). Biochemical markers, including glucose, insulin, triglycerides, and total cholesterol, were assessed, and hormones, including testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed. Liver and testicular histology, as well as sperm quality markers such as sperm motility, sperm count, and percentage of sperm with normal morphology, were observed. The activities of the testicular antioxidants superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and the products of lipid peroxidation, such as malondialdehyde (MDA), were measured. The protein expression levels of apoptosis-, autophagy- and inflammation-related markers were measured.

Results:

The HFD-fed mice had abnormal sex hormone levels, poor sperm quality, and a destroyed testicular structure, with increased oxidative stress and apoptosis in the testis. HS supplementation in HFD-fed mice attenuated testicular apoptosis by suppressing the Bax/Bcl-xl ratio and cleaved caspase 3 protein expression. The HS-treated mice exhibited improved reproductive function, possibly due to reduced oxidative stress and apoptosis, suggesting that HS has a protective effect against HFD-induced testicular damage.

Conclusion:

Male mice supplemented with HS exhibited attenuated poor semen quality and reduced testosterone levels brought about by HFD-induced obesity by reducing oxidative stress.
WGCNA reveals a biomarker for cancer-associated fibroblasts to predict prognosis in cervical cancer
Authors: Liu Zao-Ling , Chen Nan , Li Rong , Ma Ying-Jie , Qiayimaerdan Aerna , Ma Cai-Ling
Published: July 2024

Background:

Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer.

Methods:

We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. WGCNA was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs.

Results:

A prognostic model for cervical cancer was developed based on CAF genes including COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1. Cervical cancer patients were divided into low- and high-risk groups based on the optimal cutoff value. Patients in the high-risk group had a significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative polymerase chain reaction (PCR) results revealed a significant difference in the expression levels of COL4A1, LAMC1, POSTN, and SERPINF1 between the cancer group and the normal group (p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups (p < 0.001).

Conclusion:

The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis.
Optimizing cutaneous excisions on extremities: a comparative review of elliptical closure and S-plasty techniques
Authors: Twede Abram James , Harrison Kathryn A.
Published: July 2024

This review elucidates the comparative applications of elliptical closures and S-plasty or “lazy s” in the excision of cutaneous neoplasms on the extremities. The article completes an analysis of closure techniques by discussing their merits, limitations, and optimal applications based on their orientation and tension dynamics. It also provides a detailed guide on suture placement and specific intraoperative maneuvers associated with the S-plasty to enhance surgical outcomes. The S-plasty, preferred for its diminished suture line tension and adaptability to convex areas, is analyzed against traditional relaxed skin tension lines and the emerging biodynamic excisional skin tension (BEST) lines. The review underscores the BEST lines’ role in minimizing perpendicular traction and their impact on improved surgical outcomes on the extremities. It also addresses the challenges of excessive traction along wound margins and the consequential suboptimal healing outcomes, emphasizing the importance of appropriate tension management. This review also compares the stability, efficiency, and esthetic outcomes of the S-plasty with elliptical excisions, highlighting the S-plasty’s superior ability to distribute tensile forces evenly, thus reducing the risk of scar-related complications. It also discusses the benefits of using BEST lines for tension vector dispersion coupled with the design of an S-plasty, even when relaxed skin tension line favors a horizontal orientation. Furthermore, the review elaborates on the procedural execution of the S-plasty, emphasizing the importance of precise suture placement and selecting suitable suture materials and techniques to ensure optimal wound edge perfusion. The overarching theme is the prioritization of technique based on specific anatomic considerations and the surgeon’s expertise to ensure the most effective and beneficial cutaneous excisions on the extremities.
Lack of differences in outcomes between 3 immunosuppression protocols in the first year after pediatric liver transplantation: A multicenter study
Authors: Costaguta Alejandro C. , Costaguta Guillermo A. , Rumbo Carolina , Gondolesi Gabriel , D’Agostino Daniel , Pallitto María Belén , Bottasso Oscar , Álvarez Fernando
Published: July 2024

Advances in immunosuppression have extended patient and graft survival rates after solid organ transplantation; however, this is not free of side effects. Balancing safety and efficacy is of paramount importance, particularly in the pediatric setting. Current literature comparing different protocols is scarce, and decisions are mostly guided by physician preference. We aimed to compare 3 different protocols from 4 different centers to identify differences in outcomes after 1 year of follow-up. A retrospective analysis of the databases of the participating centers was performed. Consecutive patients aged <18 years with a first liver-only transplant and no other underlying congenital or acquired immunodeficiency were included. Patients were classified according to the immunosuppression protocol as follows: group A (prednisone + tacrolimus + basiliximab), group B (prednisone + tacrolimus + basiliximab + antithymocyte globulin), and group C (prednisone + tacrolimus). Differences in survival, frequency of rejection, infections, and other complications were analyzed in the entire group (n = 97) and the group with biliary atresia (n = 48). After 1 year of follow-up, no differences in patient or graft survival were observed when comparing either the entire group (n = 97) or patients with biliary atresia only (n = 48). The frequencies of rejection and episodes of infection were similar. Renal function showed no differences either before or after transplantation or between the groups. Immunosuppression protocols used in this study appeared to be equally safe and effective. This could offer the opportunity to tailor them to the patient’s individual characteristics without compromising the outcome.
Direct Apical Cannulation With Protek Duo Rapid Deployment Cannula via Mini Thoracotomy for Ambulatory Venoarterial-Extracorporeal Membrane Oxygenation
Authors: Cappelli Jared , Emling Jonathan , Edwards Amber , Babu Ashok
Published: July 2024

National trends show rapid increases in the use of mechanical circulatory support devices (MCSD) over the last 20 years. While current literature has not proven a mortality benefit in cardiogenic shock as a complication of acute myocardial infarction (AMI-CS) with percutaneous MCSD, these devices are vital to maximizing cardiopulmonary parameters for definitive therapy. To minimize complications, many different techniques have been described including a novel off-pump direct apical cannulation for venoarterial-extracorporeal membrane oxygenation (VA-ECMO). This technique allows early ambulation and avoids peripheral artery access complications but has only been described in small case series. Our case series represents the largest summary of patients (50) using this technique and contains the only comparison data to date. Fifty-four percentage of our patients were Society for Cardiovascular Angiography and Interventions (SCAI) stage D and 22% were arrested before cannulation. We achieved flows on average >5 L/min and most patients required biventricular drainage (86%) and an oxygenator (92%). Thirty day survival was 56% and most survivors were bridged to heart transplant (30%). Our most common complication was bleeding (16%). This technique showed significant improvement in ejection fraction (EF), cardiac output/index (CO/CI), and pulmonary artery pressures. This case series demonstrates the safety and efficacy of this novel technique for central cannulation in cardiogenic shock at large scale within a single institution.
Impacts of COVID-19 on hemostasis: coagulation abnormalities and management perspectives
Authors: Obeagu Emmanuel Ifeanyi , Tukur Muhammad , Akaba Kingsley
Published: July 2024

The COVID-19 pandemic caused by SARS-CoV-2 has transcended its initial characterization as a respiratory illness, revealing substantial implications for hemostasis and coagulation pathways. COVID-19-associated coagulopathies have emerged as critical determinants of disease severity and prognosis, presenting a multifaceted challenge in clinical management. This paper aims to elucidate the intricate interplay between COVID-19 and hemostasis, delving into the underlying mechanisms of coagulation abnormalities, exploring the spectrum of thrombotic complications, and discussing evolving management strategies. Therapeutic interventions and anticoagulation strategies tailored for managing COVID-19-related coagulopathies form a significant focus, encompassing prophylactic and therapeutic approaches, heparin-based therapies, and individualized treatment paradigms. This paper underscores the imperative for ongoing research endeavors to refine diagnostic modalities, identify novel therapeutic targets, and ascertain long-term sequelae of COVID-19-induced coagulation abnormalities. Ultimately, a comprehensive understanding of the intricate relationship between COVID-19 and hemostasis is pivotal in devising effective management strategies to mitigate thrombotic risks, improve clinical outcomes, and pave the way for tailored interventions in affected individuals.
The Effect of Gastrointestinal Mucositis Care Training Given to Pediatric Leukemic Patients and Caregivers on Mucosal Barrier Injury
Authors: Ardahan Sevgili Seda , Şenol Selmin
Published: July 2024

Background

Management of chemotherapy-induced mucosal barrier damage and oral/anal mucositis in leukemia is challenging.

Objective

The aim of this study was to investigate the effect of mucositis care training given to children receiving leukemia treatment and their caregivers on caregiver knowledge and skills, the development of gastrointestinal mucositis in children, the mean oral mucositis area in children, and the mucosal barrier injury laboratory-confirmed bloodstream infection in the clinic.

Methods

A stepped-wedge, quasi-experimental, unpaired control group design was used. The participants in the control group were given routine training, and the intervention group members were given mucositis care training in accordance with the guideline recommendations.

Results

No significant difference was found between groups in developing anal mucositis, but a significant difference in developing oral mucositis was documented, with the mean mucositis area of children being 8.36 ± 3.97 cm2 in the control group and 4.66 ± 2.90 cm2 in the intervention group. The mucosal barrier injury laboratory-confirmed bloodstream infection ratio was 4 per 1000 catheter days in the control group and 3 per 1000 catheter days in the intervention group.

Conclusion

Mucositis care training had a significant positive effect on caregivers’ knowledge and skills, the development of oral mucositis, and the mean oral mucositis area in children. However, the training had no effect on the development of anal mucositis or the infection rate in the clinic.

Implications for Practice

Nurses might increase the knowledge and skill levels of caregivers with training on mucositis care, prevent the development of mucositis, and reduce the mean mucositis area. Training might also contribute to the reduction in the infection rate of the clinic.
Patients Journey Before Early Rheumatoid Arthritis Diagnosis Contributes to disease's Activity Level
Authors: Guaracha-Basáñez Guillermo A. , Contreras-Yáñez Irazú , Ortiz Haro Ana B. , Pascual-Ramos Virginia
Published: July 2024

Introduction

The help-seeking process in rheumatoid arthritis (RA) patients is challenging, and its study is limited in Latin America. The study describes the real-life journey before patients' incorporation into an early arthritis clinic (EAC) and its impact on baseline and 1-year cumulative disease activity levels.

Patients and Methods

The patient's journey was assessed through a questionnaire that captured the patient's path from the first disease-related symptom to the initial assessment in the EAC. A disease activity (28 joints evaluated)–erythrocyte sedimentation rate (DAS28-ESR) score >5.1 defined a high-disease activity level. The mean of individual consecutive DAS28-ESR scores summarized cumulative DAS28-ESR. Multiple logistic regression analysis identified factors associated with a DAS28-ESR score >5.1 at the first assessment. Linear regression analysis assessed the impact of general practitioner (GP)–first consultant and time on disease-modifying antirheumatic drugs (DMARDs) on baseline and cumulative DAS28-ESR scores.

Results

Through January 2023, the EAC had 241 RA patients, among whom 209 (86.7%) completed the patients' journey questionnaire (PJQ) and 176 (84.2%) at least 1 year of follow-up. A GP was the first consultant in 76.6% of the patients, and only 12.4% were prescribed DMARDs. Patients had additional evaluations with either rheumatologists (38.6%) or other specialists (31.6%), and half of them were initiated DMARDs. GP-first consultant (adjusted odds ratio: 2.314, 95% confidence interval: 1.190–4.500, p = 0.013) and time on DMARDs (adjusted odds ratio: 0.738, 95% confidence interval: 0.585–0.929, p = 0.010) were associated with baseline DAS28-ESR score >5.1. The B coefficient magnitudes for GP-first consultant and time on DMARDs to predict cumulative DAS28 progressively decreased during the first year of follow-up.

Conclusions

Patients' journey before recent-onset RA diagnosis predicts first-year disease activity levels.
Detectability of Breast Cancer in Dedicated Breast CT Compared With Mammography Dependent on Breast Density
Authors: Wetzl Matthias , Heilingbrunner Theresa , Heindl Felix , Wenkel Evelyn , Uder Michael , Ohlmeyer Sabine
Published: July 2024

Objectives

To evaluate the detectability of non–contrast-enhanced and contrast-enhanced spiral breast computed tomography ([non]–CE-SBCT) compared with mammography. Secondary objectives are to determine detectability depending on breast density and to evaluate appearance of breast malignancies according to BI-RADS descriptors.

Methods

This retrospective institutional review board–approved study included 90 women with 105 biopsy-proven malignant breast lesions. Breast density, BI-RADS descriptors, and detectability were evaluated by 2 independent readers. Diagnostic confidence was rated on a 4-point Likert scale.

Results

For readers 1 and 2, detectability was 83.8% and 80.0% for mammography, 99.1% and 99.1% for CE-SBCT (P < 0.05), and 66.7% and 61.9% for non–CE-SBCT (P < 0.05). With both readers, detectability in CE-SBCT was high for density A/B/C/D (both 100%/100%/100%/87.5%). Detectability of readers declined with increasing density for mammography (density A = 100%, B = 89.1% and 95.1%, C = 73.1%, D = 50.0% and 71.4%; P < 0.05) and for non–CE-SBCT (density A = 87.5% and 90.7%, B = 65.5% and 69.1%, C = 54.8% and 60.0%, D = 37.5%; P < 0.05). Mass lesions were detected with CT as often as with mammography, whereas architectural distortions and microcalcifications were detected less often with SBCT. Diagnostic confidence was very high or high in 97.2% for CE-SBCT, in 74.1% for non–CE-SBCT, and in 81.4% for mammography.

Conclusions

Detectability and diagnostic confidence were very high in CE-SBCT, regardless of breast density. The detectability of non–CE-SBCT was lower than that of mammography and declined with increasing breast density.
Comparative study of tamsulosin, tadalafil, and combination of tamsulosin with tadalafil in the treatment of patients with lower urinary tract symptoms
Authors: Mondal Soumya , Agarwal Neeraj , Pal Dilip Kumar
Published: July 2024

Purpose:

Benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) commonly coexist in aging men. Tamsulosin and tadalafil are widely used for lower urinary tract symptoms (LUTS) and ED, respectively. A combination of these 2 drugs might be useful to design new management strategies, as treatment of LUTS might affect ED. Furthermore, the effect of tadalafil alone or in combination with tamsulosin on LUTS has not been widely studied, especially in our country. We conducted a study to compare the effects of tamsulosin, tadalafil, and a combination of tamsulosin and tadalafil in patients with LUTS with or without ED.

Materials and methods:

In this observational study, 81 men with LUTS due to BPH were included. Patients were divided into 3 groups of 27 patients each. Group A received tamsulosin 0.4 mg/d alone, group B tadalafil 5 mg/d alone, and group C combination therapy (tamsulosin and tadalafil both). All patients were evaluated for the International Prostate Symptom Score (IPSS), the International Index of Erectile Function 5 score, the maximum urinary flow rate, and postvoid residual urine volume.

Results:

IPSS improvement was seen in all groups (−50.90%, P < 0.05; −28.57%, P < 0.05; and −54.83%, P < 0.05, respectively). An improvement in International Index of Erectile Function 5 was also seen in all 3 groups (+39.28%, P < 0.05; +45.9%, P < 0.05; and +55.4%, P < 0.05, respectively). Maximum urinary flow rate and postvoid residual also showed improvement in all 3 groups (33.9%, P < 0.05; 29.92%, P < 0.05; and 39.71%, P < 0.05 and −60.60%, P < 0.05; −48.51%, P < 0.05; and −62.18%, P < 0.05, respectively).

Conclusion:

In patients with LUTS due to BPH, tadalafil and tamsulosin, either alone or in combination, significantly reduce LUTS. In addition, these drugs significantly enhance erectile function in males with LUTS, whether taken alone or in combination. We found no statistically significant improvement in either the IPSS or the ED scores when comparing the combination group to the tamsulosin-alone and the tadalafil-alone groups.
Sharing Data from the Human Tumor Atlas Network through Standards, Infrastructure, and Community Engagement
Authors: de Bruijn Ino , Nikolov Milen , Lau Clarisse , Clayton Ashley , Gibbs David L , Mitraka Elvira , Pozhidayeva Dar’ya , Lash Alex , Sumer Selcuk Onur , Altreuter Jennifer , Anton Kristen , DeFelice Mialy , Li Xiang , Lisman Aaron , R Longabaugh William J , Muhlich Jeremy , Santagata Sandro , Nandakumar Subhiksha , Sorger Peter K , Suver Christine , Schultz Nikolaus , Taylor Adam J , Thorsson Vésteinn , Cerami Ethan , Eddy James A
Published: July 2024

The Data Coordinating Center (DCC) of the Human Tumor Atlas Network (HTAN) has played a crucial role in enabling the broad sharing and effective utilization of HTAN data within the scientiﬁc community. Data from the ﬁrst phase of HTAN are now available publicly. We describe the diverse datasets and modalities shared, multiple access routes to HTAN assay data and metadata, data standards, technical infrastructure and governance approaches, as well as our approach to sustained community engagement. HTAN data can be accessed via the HTAN Portal, explored in visualization tools—including CellxGene, Minerva, and cBioPortal—and analyzed in the cloud through the NCI Cancer Research Data Commons nodes. We have developed a streamlined infrastructure to ingest and disseminate data by leveraging the Synapse platform. Taken together, the HTAN DCC’s approach demonstrates a successful model for coordinating, standardizing, and disseminating complex cancer research data via multiple resources in the cancer data ecosystem, offering valuable insights for similar consortia, and researchers looking to leverage HTAN data.
Essential Tremor Disrupts Rhythmic Brain Networks During Naturalistic Movement
Authors: West Timothy O. , Steidel Kenan , Flessner Tjalda , Calvano Alexander , Kucukahmetler Deniz , Stam Marielle J. , Spedden Meaghan E. , Wahl Benedikt , Jousmäki Veikko , Eraifej John , Oswal Ashwini , Saifee Tabish A. , Barnes Gareth , Farmer Simon F. , Pedrosa David J. , Cagnan Hayriye
Published: July 2024

Essential Tremor (ET) is a very common neurological disorder characterised by involuntary rhythmic movements attributable to pathological synchronization within corticothalamic circuits. Previous work has focused on tremor in isolation, overlooking broader disturbances to motor control during naturalistic movements such as reaching. We hypothesised that ET disrupts the sequential engagement of large-scale rhythmic brain networks, leading to both tremor and deficits in motor planning and execution. To test this, we performed whole-head neuroimaging during an upper-limb reaching task using high-density electroencephalography in ET patients and healthy controls, alongside optically pumped magnetoencephalography in a smaller cohort. Key motor regions—including the supplementary motor area, premotor cortex, posterior parietal cortex, and motor cerebellum—were synchronized to tremor rhythms. Patients exhibited a 15% increase in low beta (14-21 Hz) desynchronization over the supplementary motor area during movement, which strongly correlating with tremor severity (R2= 0.85). A novel dimensionality reduction technique revealed four distinct networks accounting for 97% of the variance in motor-related brain-wide oscillations, with ET altering their sequential engagement. Consistent with our hypothesis, the frontoparietal beta network- normally involved in motor planning-exhibited additional desynchronization during movement execution in ET patients. This altered engagement correlated with slower movement velocities, suggesting an adaptation towards feedback-driven motor control. These findings reveal fundamental disruptions in distributed motor control networks in ET and identify novel biomarkers as targets for next-generation brain stimulation therapies.
Laminar CBV and BOLD response-characteristics over time and space in the human primary somatosensory cortex at 7T
Authors: Dresbach Sebastian , Gulban Omer Faruk , Steinbach Till , Eck Judith , Kashyap Sriranga , Kaas Amanda , Weiskopf Nikolaus , Goebel Rainer , Huber Renzo
Published: July 2024

Uncovering the cortical representation of the body has been at the core of human brain mapping for decades, with special attention given to the digits. In the last decade, advances in functional magnetic resonance imaging (fMRI) technologies have opened the possibility of noninvasively unraveling the 3rd dimension of digit representations in humans along cortical layers. In laminar fMRI it is common to combine the use of the highly sensitive blood oxygen level dependent (BOLD) contrast with cerebral blood volume sensitive measurements, like vascular space occupancy (VASO), that are more specific to the underlying neuronal populations. However, the spatial and temporal VASO response characteristics across cortical depth to passive stimulation of the digits are still unknown. Therefore, we characterized haemodynamic responses to vibrotactile stimulation of individual digit-tips across cortical depth at 0.75 mm in-plane spatial resolution using BOLD and VASO fMRI at 7T. We could identify digit-specific regions of interest (ROIs) in putative Brodmann area 3b, following the known anatomical organization. In the ROIs, the BOLD response increased towards the cortical surface due to the draining vein effect, while the VASO response was more shifted towards middle cortical layers, likely reflecting bottom-up input from the thalamus, as expected. Interestingly, we also found slightly negative BOLD and VASO responses for non-preferred digits in the ROIs, potentially indicating neuronal surround inhibition. Finally, we explored the temporal signal dynamics for BOLD and VASO as a function of distance from activation peaks resulting from stimulation of contralateral digits. With this analysis, we showed a triphasic response consisting of an initial peak and a subsequent negative deflection during stimulation, followed by a positive post-stimulus response in BOLD and to some extent in VASO. While similar responses were reported with invasive methods in animal models, here we demonstrate a potential neuronal excitation-inhibition mechanism in a center-surround architecture across layers in the human somatosensory cortex. Given that, unlike in animals, human experiments do not rely on anesthesia and can readily implement extensive behavioral testing, obtaining this effect in humans is an important step towards further uncovering the functional significance of the different aspects of the triphasic response.
Whole Tissue Imaging of Cellular Boundaries at Sub-Micron Resolutions for Automatic Cell Segmentation: Applications in Epithelial Bending of Ectodermal Appendages
Authors: Norris Sam , Hu Jimmy K. , Shubin Neil H
Published: July 2024

For decades, biologists have relied on confocal microscopy to understand cellular morphology and fine details of tissue structure. However, traditional confocal microscopy of tissues faces limited light penetration, typically less than 100 µm, due to tissue opacity. To address this challenge, researchers have developed tissue clearing protocols compatible with confocal microscopy. Unfortunately, these protocols often struggle to retain cell boundary markers, especially at high resolutions necessary for precise cell segmentation. In this work, we introduce a method that preserves cell boundary markers and matches the refractive index of tissues with water. This technique enables the use of high-magnification, long working distance water-dipping objectives. The sub-micron resolutions achieved with this approach allows us to automatically segment each individual cell using a trained neural network segmentation model. These segmented images facilitate the quantification of cell properties and morphology of the entire three-dimensional tissue. As a demonstration of this methodology, we first examine mandibles of transgenic mice that express fluorescent proteins in their cell membranes. We then extend this technique to a non-model animal, the catshark, investigating the cellular properties of its dental lamina and dermal denticles – invaginating and evaginating ectodermal structures, respectively. Our technique thus provides a powerful tool to quantify in high throughput the 3D structures of cells and tissues during organ morphogenesis.
Fodder oats as catch crop: potential to reduce nitrogen losses from soil
Authors: Kidson Michael , Hernandez-Soriano Maria C. , Mndzebele Buhlebelive , Ndaba Busiswa , Adeleke Rasheed , Nciizah Adornis D. , Roopnarain Ashira
Published: July 2024

Reducing nitrogen (N) losses and associated nitrate (NO3-) leaching and nitrous oxide emissions from agricultural land is a critical target worldwide. This is particularly urgent in areas with low fertility soils and a climate that increases the risk of N loss, such as the arid and temperate regions of South Africa. Here, we assessed the potential of fodder oats (Avena sativa) as a winter catch crop to deplete residual N in a field laid fallow for the previous four years, where vetch had proliferated. The soil presented a high clay content (34-44%), with the main exchangeable bases being calcium and magnesium hence, ammonium (NH4+) deposited by the vetch was expected to be rapidly adsorbed and slowly released. A significant decrease in the concentrations of NO3-(49%) and NH4+(30%) throughout the soil profile (0-90 cm) was observed following harvest of the oats compared to the concentrations measured before sowing. The effectiveness of the oats to uptake both forms of N from top and deep soil layers enhances their potential to reduce N losses. Our results are useful to fill current knowledge gaps on N dynamics in understudied, vulnerable soils such as agricultural land in South Africa, and to advance crop rotation strategies that reduce risk of N leaching.
Functional lung imaging identifies peripheral ventilation changes in mice with muco-obstructive lung disease
Authors: Reyne Nicole , Smith Ronan , Cmielewski Patricia , Eikelis Nina , Nilsen Kris , Louise Jennie , Duerr Julia , Mall Marcus A. , Lawrence Mark , Parsons David , Donnelley Martin
Published: July 2024

β-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease, with impaired mucociliary clearance, mucus obstruction, chronic airway inflammation, structural lung damage, and altered lung function. The aim of this study was to undertake a comprehensive lung function and mechanics analysis of the adult β-ENaC-Tg model. β-ENaC-Tg and wild-type littermates underwent X-ray Velocimetry (XV) scans using a Permetium XV scanner (4DMedical, Melbourne, Australia). For comparative lung mechanics, lung function assessments were conducted with a flexiVent system. XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in β-ENaC-Tg mice. Spatial analysis of ventilation maps indicated increased ventilation variability in the peripheral lung regions, as well as an increased proportion of under-ventilated areas. The flexiVent analysis indicated that compared to wild-types, β-ENaC-Tg mice have a significantly more compliant lungs with increased inspiratory capacity, reduced tissue elastance and increased hysteresivity (heterogeneity), suggesting loss of parenchymal integrity. This research highlights the utility of XV imaging in evaluating ventilation defects in the β-ENaC-Tg model and provides a comprehensive lung function analysis.
Parallelism between phylogeny and ontogeny
Authors: Bergman Juraj , Bakarić Robert , Brčić-Kostić Krunoslav
Published: July 2024

Haeckel’s biogenetic law, or the recapitulation theory remains a controversial subject to this day. Currently, the modern version of biogenetic law is the hourglass model with its phylotypic period. Importantly, the hourglass model is nothing more than a model of development, and it does not provide any evidence that ontogeny recapitulates phylogeny. However, the hourglass model and biogenetic law are not mutually exclusive, and there are several examples of recapitulation-like processes observable after the phylotypic period of ontogeny. At the level of transcriptomics, all attempts to demonstrate recapitulation failed. Using a novel approach, combining transcriptomics with phylostratigraphy, we demonstrate that recapitulation, or parallelism between phylogeny and ontogeny, exists. We show that the mean indispensability of genes decreases for phylogenetically younger genes, as well as genes expressed during later stages of ontogeny. We also define the ontotypic period of phylogeny, an analog to the phylotypic period of ontogeny. Since it starts from the beginning of phylogeny, it is reasonable to hypothesize that recapitulation starts from the phylotypic period. We conclude that parallelism, or recapitulation, is explainable by the fact that genes that emerged later in phylogeny have tendencies to be expressed during later stages of ontogeny.
Detecting epidemic-driven selection: a simulation-based tool to optimize sampling design and analysis strategies
Authors: Santander Cindy G. , Moltke Ida
Published: July 2024

Throughout history, populations from numerous species have been decimated by epidemic outbreaks, like the 19th-century rinderpest outbreak in Cape buffalo (≈90% mortality) and Black Death in humans (≈50% mortality). Recent studies have raised the enticing idea that such epidemic outbreaks have led to strong natural selection acting on disease-protective variants in the host populations. However, so far there are few, if any, clear examples of such selection having taken place. This could be because so far studies have not had sufficient power to detect the type of selection an epidemic outbreak must induce: strong but extremely short-term selection on standing variation. We present here a simulation-framework that allows users to explore under what circumstances it is possible to detect epidemic-driven selection using standard selection scan methods likeFSTand iHS. Using two examples, we illustrate how the framework can be used. Furthermore, via these examples, we show that comparing survivors to the dead has the potential to render higher power than more commonly used sampling schemes. And importantly, we show that even for outbreaks with high mortality, like the Black Death, strong selection may have led to only modest shifts in allele frequency, suggesting large sample sizes are required to obtain appropriate power to detect the selection. We hope this framework can help in designing well-powered future studies and thus lead to a clarification of the role epidemic-driven selection has played in the evolution of different species.

Significance Statement

Our study introduces a simulation-based framework,SimOutbreakSelection(SOS), which enables researchers to design studies that have power to detect epidemic-driven selection while taking sampling time points and demographic history into account. We use rinderpest in African Buffalo and the Black Death in Medieval Sweden as examples to showcase the framework. Via these examples we also show that large sample sizes are needed even for severe epidemics like the Black Death and that the often used sampling strategy where samples from before the epidemic and samples from after are compared is not always optimal.
Live-cell RNA imaging with the inactivated endonuclease Csy4 enables new insights into plant virus transport through plasmodesmata
Authors: Burnett David , Hussein Mohamed , Barr Zoe Kathleen , Näther Laura Newsha , Wright Kathryn M. , Tilsner Jens
Published: July 2024

Plant-infecting viruses spread through their hosts by transporting their infectious genomes through intercellular nano-channels called plasmodesmata. This process is mediated by virus-encoded movement proteins, which bind nucleic acids and target and dilate plasmodesmata. Whilst the sub-cellular localisations of movement proteins have been intensively studied, live-cell RNA imaging systems have so far not been able to detect viral genomes inside the plasmodesmata. Here, we describe a new, highly sensitive RNA live-cell reporter based on an enzymatically inactive form of the small bacterial endonuclease Csy4, which binds to its cognate stem-loop with nanomolar affinity. This system allows imaging of plant viral RNA genomes inside plasmodesmata and shows thatPotato virus XRNA remains accessible within the channels and is therefore not fully encapsidated during movement. We also combine Csy4-based RNA-imaging with interspecies movement complementation to show that an unrelated movement protein fromTobacco mosaic viruscan recruitPotato virus Xreplication complexes to plasmodesmata entrances. Therefore, recruitment of replication complexes is mediated non-specifically, likely by indirect coupling of movement proteins and viral replicaseviathe viral RNA or co-compartmentalisation, potentially contributing to transport specificity. Lastly, we show that a ‘self-tracking’ virus can express the Csy4-based reporter during the progress of infection. However, expression of the RNA-binding proteinin cisinterferes with viral movement by an unidentified mechanism when cognate stem-loops are present in the viral RNA.
Whole Genome Landscape Analysis of Homologous Recombination Deficiency in a Pan-Cancer Cohort
Authors: Al Assaad Majd , Hadi Kevin , Levine Max F. , Guevara Daniela , Patel Minal , Tranquille Marvel , King Abigail , Otilano John , Semaan Alissa , Gundem Gunes , Medina-Martínez Juan S. , Sigouros Michael , Manohar Jyothi , Kuo Hui-Hsuan , Wilkes David C. , Andreopoulou Eleni , Chapman-Davis Eloise , Tagawa Scott T. , Sboner Andrea , Ocean Allyson J. , Shah Manish , Papaemmanuil Elli , Sternberg Cora N. , Holcomb Kevin , Nanus David M. , Elemento Olivier , Mosquera Juan Miguel
Published: July 2024

Purpose

Homologous recombination deficiency (HRD) impacts cancer treatment strategies, particularly the effectiveness of PARP inhibitors. However, the variability different HRD assays has hampered the selection of oncology patients who may benefit from these therapies. Our study aims to assess the whole genome landscape to better define HRD in a pan-cancer cohort and to contribute to harmonization of HRD detection.

Methods

We employed a whole-genome sequencing WGS HRD classifier that included genome-wide features associated with HRD to analyze 580 tumor/normal paired pan-cancer samples. The HRD results were correlated retrospectively with treatment responses and were compared with commercial HRD tests in a subset of cases.

Results

HRD phenotype was identified in 62 samples across various cancers including breast (19%), pancreaticobiliary (17%), gynecological (15%), prostate (8%), upper gastrointestinal (GI) (2%), and other cancers (1%). HRD cases were not confined toBRCA1/2mutations; 24% of HRD cases wereBRCA1/2wild-type. A diverse range of HRR pathway gene alterations involved in HRD were elucidated, including biallelic mutations inFANCF, XRCC2, andFANCC, and deleterious structural variants. Comparison with results from commercial HRD assays suggests a better performance of WGS to detect HRD, based on treatment response.

Conclusion

HRD is a biomarker used to determine which cancer patients would benefit from PARPi and platinum-based chemotherapy. However, a lack of harmonization of tests to determine HRD status makes it challenging to interpret their results. Our study highlights the use of comprehensive WGS analysis to predict HRD in a pan-cancer cohort, elucidates new genomic mechanisms associated with HRD, and enables an accurate identification of this phenotype, paving the way for improved outcomes in oncology care.
GABAergic modulation of beta power enhances motor adaptation in frontotemporal lobar degeneration
Authors: Hughes Laura E. , Adams Natalie E. , Rouse Matthew A. , Naessens Michelle , Shaw Alexander , Murley Alexander G. , Cope Thomas E. , Holland Negin , Nesbitt David , Street Duncan , Whiteside David J. , Rowe James B.
Published: July 2024

The impairment of behavioural control is a characteristic feature of disorders associated with frontotemporal lobar degeneration (FTLD). Behavioural disinhibition and impulsivity in these disorders are linked to abnormal neurophysiology of the frontal lobe, such as the loss beta-band power and changes in prefrontal GABAergic neurotransmission. Here we test the hypothesis that a pharmacological increase of GABA would concurrently improve cortical beta-band power and adaptive behavioural control in people with behavioural-variant frontotemporal dementia (bvFTD), and progressive supranuclear palsy (PSP, Richardson’s syndrome). We recorded magnetoencephalography during a visuomotor task that measures participants’ ability to adapt motor responses to visual feedback. Tiagabine, a GABA re-uptake inhibitor, was used as a pharmacological probe in a double-blind placebo controlled crossover design. The study included 11 people with bvFTD, 11 people with PSP and 20 healthy age-matched controls. Behavioural performance and beta power were examined with linear mixed models examined changes in, to estimate motor learning over time and the response to tiagabine. Significant beta power differences were source-localised using linear-constraint minimum variance beamformer. As predicted, participants with bvFTD and PSP were impaired behaviourally, and the beta power associated with movement, learning and accuracy, was diminished compared to controls. Tiagabine facilitated partial recovery of the impairments in behaviour and beta power over trials, moderated by executive function, such that the greatest improvements were seen in those with higher cognitive scores. The beamformer localised the physiological effects of disease and tiagabine treatment to frontal cortices, and confirmed the right prefrontal cortex as a key site of drug by group interaction. We interpret the differential response to tiagabine between bvFTD and PSP as a function of baseline differences in atrophy and physiology. In summary, behavioural and neurophysiological deficits can be mitigated by enhancement of GABAergic neurotransmission. Clinical trials are warranted to test for enduring clinical benefits from this restorative-psychopharmacology strategy.
Risk reduction in SARS-CoV-2 infection and reinfection conferred by humoral antibody levels among essential workers during Omicron predominance
Authors: Hollister James , Porter Cynthia , Sprissler Ryan , Beitel Shawn C , Romine James K. , Uhrlaub Jennifer L. , Grant Lauren , Yoo Young M. , Fowlkes Ashley , Britton Amadea , Olsho Lauren E.W. , Newes-Adeyi Gabriella , Fuller Sammantha , Zheng Pearl Q. , Gaglani Manjusha , Rose Spencer , Dunnigan Kayan , Naleway Allison L. , Gwynn Lisa , Caban-Martinez Alberto , Schaefer Solle Natasha , Tyner Harmony L. , Philips Andrew L. , Hegmann Kurt T , Yoon Sarang , Lutrick Karen , Burgess Jefferey L. , Ellingson Katherine D.
Published: July 2024

The extent to which semi-quantitative antibody levels confer protection against SARS-CoV-2 infection in populations with heterogenous immune histories is unclear. Two nested case-control studies were designed within the multisite HEROES/RECOVER prospective cohort of frontline workers to study the relationship between antibody levels and protection against first-time post-vaccination infection and reinfection with SARS-CoV-2 from December 2021 to January 2023. All participants submitted weekly nasal swabs for rRT-PCR testing and blood samples quarterly and following infection or vaccination. Cases of first-time post-vaccination infection following a third dose of monovalent (origin strain WA-1) mRNA vaccine (n=613) and reinfection (n=350) were 1:1 matched to controls based on timing of blood draw and other potential confounders. Conditional logistic regression models were fit to estimate infection risk reductions associated with 3-fold increases in end titers for receptor binding domain (RBD). In first-time post-vaccination and reinfection study samples, most were female (67%, 57%), non-Hispanic (82%, 68%), and without chronic conditions (65%, 65%). The odds of first-time post-vaccination infection were reduced by 21% (aOR=0.79, 95% CI=[0.66-0.96]) for each 3-fold increase in RBD end titers. The odds of reinfection associated with a 3-fold increase in RBD end titers were reduced by 23% (aOR=0.77, 95% CI=[0.65-0.92] for unvaccinated individuals and 58% (aOR=0.42, 95% CI=0.22-0.84) for individuals with three mRNA vaccine doses following their first infection. Frontline workers with higher antibody levels following a third dose of mRNA COVID-19 vaccine were at reduced risk of SARS-CoV-2 during Omicron predominance. Among those with previous infections, the point estimates of risk reduction associated with antibody levels was greater for those with three vaccine doses compared to those who were unvaccinated.
Does time awareness coaching support hybrid workers’ wellbeing?: Protocol for a pilot randomized controlled trial
Authors: Young Anna Navin , Blasi Zelda Di , Foley Sarah , Hunt Eithne
Published: July 2024

Background

High rates of poor employee mental health and wellbeing have spurred growing demands for initiatives that support wellbeing in the workplace. The promotion of positive mental health and wellbeing is an essential component of workplace wellbeing initiatives, focusing on enhancing positive aspects of work, workers’ capacities, and positive behaviors. As one of the fastest growing practices in personal and professional development, coaching is found to improve workers’ wellbeing and performance through reflection, awareness, and meaningful goal pursuit. As time-related challenges exacerbate workplace stressors and threaten wellbeing, specific time-focused coaching approaches are essential to the promotion of positive mental health and wellbeing in the workplace. Effectively addressing work-time challenges is especially critical for hybrid workers, who divide their work-time across multiple onsite and remote locations.

Methods

The current paper is a protocol for a pilot three-armed randomized controlled trial that aims to evaluate the effectiveness of a time awareness coaching (TAC) intervention to support hybrid workers’ wellbeing. Sixty hybrid working participants will be randomized to either the TAC intervention, reflective time tracking (active control), or a passive control group. Professional coaches will be recruited and trained to facilitate the TAC intervention. Pre-post intervention measures of chronic time pressure, perceived control of time, perceived stress, wellbeing, and self-efficacy will be evaluated and compared across intervention arms. Qualitative feedback from participants and coaches will be collected to assess the intervention’s acceptability and implementation.

Discussion

The results of the study will offer insights into intervention effectiveness as well as the feasibility of critical intervention elements such as recruitment, retention, and implementation. The findings will inform recommendations for the use of TAC in future research studies and workplace wellbeing initiatives.