bluuebunny/crossref_metadata_2025 huggingface dataset:
Salpingectomy for ectopic pregnancy reduces ovarian cancer risk—a nationwide study
Authors: Yen Ju-Chuan , Wu Tzu-I , Stone Rebecca , Wang Tian-Li , Visvanathan Kala , Chen Li-Ying , Hsu Min-Huei , Shih Ie-Ming
Published: April 2024

Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.
Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain
Authors: Karabacak Elif , Eken Hazal , Dallali Ilhem , Arslan Rana
Published: April 2024

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.
Hydrogen-rich solution alleviates acute radiation pneumonitis by regulating oxidative stress and macrophages polarization
Authors: Yin Zhen , Xu Wenjing , Ling Junjun , Ma Lihai , Zhang Hao , Wang Pei
Published: April 2024

This study was aimed to investigate the effect of hydrogen-rich solution (HRS) on acute radiation pneumonitis (ARP) in rats. The ARP model was induced by X-ray irradiation. Histopathological changes were assessed using HE and Masson stains. Inflammatory cytokines were detected by ELISA. Immunohistochemistry and flow cytometry were performed to quantify macrophage (CD68) levels and the M2/M1 ratio. Western blot analysis, RT-qPCR, ELISA and flow cytometry were used to evaluate mitochondrial oxidative stress injury indicators. Immunofluorescence double staining was performed to colocalize CD68/LC3B and p-AMPK-α/CD68. The relative expression of proteins associated with autophagy activation and the adenosine 5′-monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were detected by western blotting. ARP decreased body weight, increased the lung coefficient, collagen deposition and macrophage infiltration and promoted M1 polarization in rats. After HRS treatment, pathological damage was alleviated, and M1 polarization was inhibited. Furthermore, HRS treatment reversed the ARP-induced high levels of mitochondrial oxidative stress injury and autophagy inhibition. Importantly, the phosphorylation of AMPK-α was inhibited, the phosphorylation of mTOR and ULK1 was activated in ARP rats and this effect was reversed by HRS treatment. HRS inhibited M1 polarization and alleviated oxidative stress to activate autophagy in ARP rats by regulating the AMPK/mTOR/ULK1 signaling pathway.
The origin of the characteristic shape and scatter of intergalactic damping wings during reionization
Authors: Keating Laura C , Puchwein Ewald , Bolton James S , Haehnelt Martin G , Kulkarni Girish
Published: April 2024

Ly α damping wings in the spectra of bright objects at high redshift are a useful probe of the ionization state of the intergalactic medium during the reionization epoch. It has recently been noted that, despite the inhomogeneous nature of reionization, these damping wings have a characteristic shape which is a strong function of the volume-weighted average neutral hydrogen fraction of the intergalactic medium. We present here a closer examination of this finding using a simulation of patchy reionization from the Sherwood–Relics simulation suite. We show that the characteristic shape and scatter of the damping wings are determined by the average neutral hydrogen density along the line of sight, weighted by its contribution to the optical depth producing the damping wing. We find that there is a redshift dependence in the characteristic shape due to the expansion of the Universe. Finally, we show that it is possible to differentiate between the shapes of damping wings in galaxies and young (or faint) quasars at different points in the reionization history at large velocity offsets from the point where the transmission first reaches zero.
Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families
Authors: Parra R Gonzalo , Freiberger Maria I , Poley-Gil Miriam , Fernandez-Martin Miguel , Radusky Leandro G , Ruiz-Serra Victoria , Wolynes Peter G , Ferreiro Diego U , Valencia Alfonso
Published: April 2024

According to the Principle of Minimal Frustration, folded proteins can only have a minimal number of strong energetic conflicts in their native states. However, not all interactions are energetically optimized for folding but some remain in energetic conflict, i.e. they are highly frustrated. This remaining local energetic frustration has been shown to be statistically correlated with distinct functional aspects such as protein-protein interaction sites, allosterism and catalysis. Fuelled by the recent breakthroughs in efficient protein structure prediction that have made available good quality models for most proteins, we have developed a strategy to calculate local energetic frustration within large protein families and quantify its conservation over evolutionary time. Based on this evolutionary information we can identify how stability and functional constraints have appeared at the common ancestor of the family and have been maintained over the course of evolution. Here, we present FrustraEvo, a web server tool to calculate and quantify the conservation of local energetic frustration in protein families.
Accelerated tumor progression after COVID-19 infection in patients with glioblastoma: A retrospective case–control study
Authors: Gregory Timothy A , Knight Stephanie R , Aaroe Ashley E , Highsmith Kaitlin N , Janatpour Zachary C , O’Brien Barbara J , Majd Nazanin K , Loghin Monica E , Patel Chirag B , Weathers Shiao-Pei , Puduvalli Vinay K , Kamiya-Matsuoka Carlos
Published: April 2024

Background

We observed rapid tumor progression following COVID-19 infection among patients with glioblastoma and sought to systematically characterize their disease course in a retrospective case–control study.

Methods

Using an institutional database, we retrospectively identified a series of COVID-19-positive glioblastoma cases and matched them by age and sex 1:2 to glioblastoma controls who had a negative COVID-19 test during their disease course. Demographic and clinical data were analyzed. Hyperprogression was defined using modified response evaluation criteria in solid tumors criteria. Time to progression and overall survival were estimated using the Kaplan–Meier method.

Results

Thirty-two glioblastoma cases with positive COVID-19 testing were matched to 64 glioblastoma controls with negative testing; age, sex, and molecular profiles did not differ between groups. Progression events occurred in 27 cases (84%) and 46 controls (72%). Of these, 14 cases (52%) presented with multifocal disease or leptomeningeal disease at progression compared with 10 controls (22%; P = .0082). Hyperprogression was identified in 13 cases (48%) but only 4 controls (9%; P = .0001). Cases had disease progression at a median of 35 days following COVID-19 testing, compared with 164 days for controls (P = .0001). Median survival from COVID-19 testing until death was 8.3 months for cases but 17 months for controls (P = .0016). Median overall survival from glioblastoma diagnosis was 20.7 months for cases and 24.6 months for controls (P = .672).

Conclusions

Patients with glioblastoma may have accelerated disease progression in the first 2 months after COVID-19 infection. Infected patients should be monitored vigilantly. Future investigations should explore tumor-immune microenvironment changes linking tumor progression and COVID-19.
Effects of Bacillus subtilis on in vitro ruminal fermentation and methane production
Authors: Sarmikasoglou Efstathios , Sumadong Phussorn , Dagaew Gamonmas , Johnson Mikayla L , Vinyard James R , Salas-Solis Gerald , Siregar Martha , Faciola Antonio P
Published: April 2024

The objective of this study was to evaluate the effect of a proprietary strain of a Bacillus subtilis on in vitro ruminal fermentation and methane production in batch culture serum bottles. One hundred forty-nine batch culture bottles were used in a complete randomized block design. The arrangement of treatments was a 3 × 3 × 4 factorial to evaluate the effects of inoculum, time, diet, and their respective interactions. There were three experimental runs total, where the run was used as block. Inoculum treatments were 1.85 mg/mL of microcrystalline cellulose (CON); 10 billion B. subtilis plus microcrystalline cellulose (A1); and 60 billion B. subtilis plus microcrystalline cellulose (A2). Diet treatments were 0.50 g of early lactation diet (E, 30% starch), mid-lactation diet (M, 25% starch), or dry cow diet (D, 18% starch). The combination resulted in total of nine treatments. Each treatment had five replicates, two of which were used to determine nutrient degradability at 24 and 48 h after inoculation, and three were used to determine pH, ammonia nitrogen (NH3-N), volatile fatty acids, lactate, total gas, and methane production at 3, 6, 24, and 48 h after inoculation. Fixed effects of inoculum, diet, and their interaction were tested using the GLIMMIX procedure of SAS. Significance was declared at P ≤ 0.05. We observed that, compared to control, the supplementation of B. subtilis, decreased the production of acetate and propionate, while increasing the production of butyrate, iso-butyrate, valerate, iso-valerate, and caproate within each respective diet. Additionally, the total methane production exhibited mixed responses depending on the diet type. Overall, the inclusion of B. subtilis under in vitro conditions shows the potential to reduce ruminal methane production when supplemented with a mid-lactation diet, constituting a possible methane mitigation additive for dairy cattle diets.
Missed Visits Predict Recurrence in Idiopathic Clubfoot
Authors: Martinez Armando S. , Loyd Grey , Bridges Callie , Milad Matthew , Pathare Nihar , Doston Luke , Gugala Zbigniew , Hill Jaclyn F.
Published: April 2024

Background:

Congenital talipes equinovarus, also known as “clubfoot,” is a common congenital deformity. While reported relapse rates vary widely, relapse continues to be a common problem faced in the treatment of this condition. The objective of this study is to assess relationships between demographic/socioeconomic factors, follow-up, and rates of relapse in our population of clubfoot patients.

Methods:

Retrospective chart review was conducted for patients undergoing treatment for idiopathic clubfoot from February 2012 to December 2022 at a tertiary children’s hospital. Records were analyzed for follow-up adherence and recurrence in the Ponseti method, in addition to patient demographic and socioeconomic factors. Statistical analysis was performed to evaluate associations between recurrence, missed clinical visits, and demographic/socioeconomic factors of interest.

Results:

Ninety-five patients were included in the study [74.7% male (N=71) and 25.2% female (N=24)]. A total of 64.2% (N=61) of patients developed recurrence during their treatment. Recurrence rates differed significantly by reported bracing noncompliance >1 month (35/46 vs. 26/49, P=0.019), having missed 1 or more clinical visits (38/61 vs. 8/34, P < 0.001), Medicaid or equivalent insurance type (41/56 vs. 20/39, P=0.028), non-white race (47/66 vs. 14/29, P=0.032, higher Social Deprivation Index score (56.13 vs. 41.06, P=0.019). Significant variables were analyzed using a multivariate logistic regression analysis (MVLR). After MVLR, having 1 or more missed clinical visits (OR 4.462, 95% CI: 1.549-12.856) remained significantly associated with increased rates of recurrence. Primary language preference and distance to the hospital were not associated with recurrence.

Conclusions:

Higher SDI scores, non-white race, Medicaid insurance, and missed clinical follow-up visits were all associated with increased rates of recurrence for clubfoot patients. Using an MVLR model, missed clinical follow-up visits remained independently associated with increased recurrence rates.

Level of Evidence:

Level 2—retrospective, prognostic study
Preoperative Echocardiogram Does Not Contribute to Surgical Risk Assessment in Patients With Large Curve Scoliosis and No Cardiac Risk Factors
Authors: Nnake Chidebelum O. , Concepcion-Gonzalez Alondra , Malka Matan S. , Berube Emma , Ferris Anne , Bainton Nicole , Vitale Michael G. , Roye Benjamin D.
Published: April 2024

Objective:

Severe scoliosis can affect thoracic organs, potentially leading to cardiovascular abnormalities. Thus, echocardiograms have been suggested for use in preoperative screening in patients with significant scoliosis. However, the utility of preoperative heart screenings in patients without known or suspected heart problems is not well understood. This study aims to find the incidence of cardiac findings in patients with severe scoliosis ≥90° without cardiac history.

Methods:

A single-institution retrospective chart review was performed. Inclusion criteria were scoliosis patients with curves ≥90 degrees and a screening echocardiogram performed within 6 months of spine surgery. Patients with a previous cardiac history, diagnosis associated with cardiac comorbidities (eg, connective tissue disease), or major coronal curves <90 degrees were excluded. Echocardiogram reports and perioperative clinical notes from involved services (including orthopaedics, cardiology, and anesthesia) were reviewed. Any postoperative use of vasopressors and reasons for their use were recorded.

Results:

Overall, 50 patients met the inclusion criteria. The mean age at surgery was 14.0 ± 4.9 years old (range: 2 to 33). The mean major curve was 108 ± 19 degrees (range: 90 to 160 degrees). A normal echocardiogram was seen in 38 (76%), whereas 6 patients (12%) had mild dilation of the aortic sinus or root, 4 (8%) had mild valvular regurgitation, 1 patient had a small atrial septal defect, and 1 had a trace pericardial effusion. No patient had any changes made to their perioperative plan and one patient was advised to see a cardiologist postoperatively. Postoperatively, 8 patients (16%) received vasopressors to raise blood pressure to meet preset goal MAP, but only one of these 8 had a positive echocardiogram (mild valvular insufficiency), which was not seen as a contributing factor to the use of pressors.

Conclusions:

This study suggests that screening echocardiograms for patients without a cardiac history or related symptoms does not contribute to the evaluation of perioperative risk or anesthetic management. Creating clear, evidence-based guidelines for the utilization of perioperative testing, like echocardiograms, can reduce the social, time, and financial burdens on families. Such guidelines are vital for appropriate risk assessment and proper utilization of health care resources.

Level of Evidence:

Level III.
A Novel Subcutaneous Furosemide Formulation for Outpatient Management of Heart Failure
Authors: Sandquist Katherine , Nawarskas James , Garcia Mark E.
Published: April 2024

In patients with fluid overload and congestion, parenteral diuretic therapy is frequently utilized. However, administration of parenteral diuretic therapy commonly requires hospital admission or outpatient clinic visits. Furoscix (scPharmaceuticals, Burlington, MA), a subcutaneous formulation of furosemide designed for home use, offers new treatment possibilities with the potential for profound cost savings for patients and health systems. Currently, subcutaneous furosemide formulations have been studied in palliative care populations and outpatient clinics, however, new literature has evaluated utility in prescribing on discharge from the emergency department. This review aims to describe the pharmacokinetic profile and utilization of subcutaneous furosemide for treatment of congestion in patients with heart failure.
Combining Wise-pattern Volume Displacement and Autologous Volume Replacement to Facilitate Oncoplastic Breast Conservation
Authors: Schwartz Jean-Claude D.
Published: April 2024

Background:

Oncoplastic breast conservation has been classically divided into volume displacement (VD) or volume replacement (VR) techniques. There have been few descriptions of merging these two approaches. This report describes our experience combining Wise-pattern VD and autologous VR to repair extensive partial mastectomy defects in patients with ptosis.

Methods:

A retrospective chart review was performed for patients who underwent combined Wise-pattern VD surgery and autologous VR by the author from June 2017 to June 2023, with at least 6 months follow-up. Patient demographics, oncological and intraoperative details, and complications were recorded.

Results:

Forty patients underwent Wise-pattern VD surgery combined with a medial intercostal artery perforator flap (five patients), lateral thoracic artery perforator/lateral intercostal artery perforator flap (18 patients), anterior intercostal artery perforator flap (five patients), or muscle-sparing latissimus dorsi flap (12 patients). The average tumor size was 4.0 cm (range, 1.5–9.1 cm), and specimen weight was 152 g (range, 33–415 g). Six patients (15%) required re-operation for positive margins. There was delayed healing of three (7.5%) donor sites. There were no flap failures. Two (5%) patients had clinically apparent fat necrosis without requirement for surgical revision.

Conclusions:

This report demonstrates the feasibility of combining Wise-pattern VD and autologous VR. We propose that oncoplastic breast-conserving surgery be no longer divided into two mutually exclusive approaches and that surgeons make liberal use of combining these approaches to address challenging cases of breast-conserving surgery.
Coronal-splitting Reduction Genioplasty Combined with Bilateral Osteotomies of the Mandibular Inferior Border for Macrogenia
Authors: Hirohi Toshitsugu
Published: April 2024

There are various types of chin deformities, and the least established surgical method for deformity correction may be reduction for anteroposterior macrogenia. Anteroposterior macrogenia is commonly corrected by either setback genioplasty or burring reduction, but these approaches are less likely to produce aesthetically pleasing results. Both procedures have poor reduction effects because of the low response rate of soft tissues to skeletal alterations. There is a high likelihood of chin ptosis and flattening. Setback genioplasty can also yield step deformities at the inferior mandibular border. To overcome these drawbacks of conventional methods, I developed a novel technique of coronal-splitting reduction genioplasty. I have performed more than 83 procedures with a high success rate over the past 10 years. Alloplastic chin implant-shaped bone fragments were resected from the prominent bony chin, in which the average thickness of resected bone was 8.2 mm. Sufficient sagittal reduction effects were then achieved in most cases, although the soft tissue response rate remains 25%–50%, as reported in the literature. The no-degloving technique with cephalic suspension of the mentalis muscle prevents chin ptosis. Combined bilateral oblique osteotomies of the inferior mandibular border contribute to minimizing obvious postoperative chin flattening. Moreover, macrogenia can be large in multiple planes, including anteroposterior, vertical, transverse, or their combinations. This new technique can handle all three planes by combining both bilateral oblique osteotomies of the inferior mandibular border and burr ostectomy. Overall, these findings suggest that the coronal-splitting genioplasty method may replace conventional methods for correcting macrogenia.
The “Pocket” Technique: A Novel Surgical Technique for Repair of Glaucoma Drainage Device Tube Exposure
Authors: Grippo Tomas M. , Gutkind Naomi E. , Monteros Alvi Nicolas , Salina Indovino Carla , Lopez Tomasella Matias J. , Mutti Justina C. , Mena Agustina L. , Mayorga Fernando
Published: April 2024

Précis:

Presented is a novel surgical technique, termed the “pocket” technique, of scleral patch graft placement into a subconjuntival pocket to cover exposed glaucoma tube shunts, which is particularly useful in cases of scarred and thinned conjunctiva and Tenons.

Exposure of glaucoma tube shunts is an uncommon postoperative complication which poses a significant risk to the patient and may be difficult to repair. In this case series, the authors present 2 cases using a novel surgical technique, the “pocket” technique, to place a scleral patch graft to address tube exposure. Patient 1 remained free of tube exposure at most recent follow-up visit after 21 months, and patient 2 remained free of tube exposure at most recent follow-up visit after 4 months. This technique offers an elegant surgical option that has multiple benefits; it allows for stability of the scleral patch graft even in cases of scarred down, thinned conjunctiva with minimal Tenons, allows for repair along the entire length of the tube shunt including perilimbal exposures, and allows for secondary healing when there is not enough conjunctiva to cover both the opening and the patch. These advantages make the “pocket” technique a quick to perform, minimally invasive surgical approach that is useful for addressing both difficult and straightforward tube exposure cases.
Comparison of physical activity and sedentary behavior between work-in-office and work-from-home: a self-controlled study
Authors: Tomonaga Ryo , Watanabe Yuya , Jiang Ying , Nakagawa Toru , Yamato Hiroshi
Published: April 2024

Objective

To compare physical activity levels and sedentary behavior between individuals working in the office and those working from home, with the aim of elucidating the potential implications on employees' health.

Methods

We used triaxial accelerometers to assess the physical activity levels of 94 white-collar employees from a large-scale manufacturing company in Japan. They were instructed to wear the accelerometers during their working hours, which included the commuting time on work-in-office days.

Results

The mean energy expenditure on work-in-office was 426 kcal for individuals, while it was 228 kcal on work-from-home (p < 0.01). Additionally, not including commuting, the time spent sedentary on work-from-home days was higher than that on work-in-office days by 20 minutes.

Conclusion

Work-from-home decreases physical activity and increases sedentary time compared to work-in-office.
New tools to study renal fibrogenesis
Authors: Liao Xian , Scheidereit Emilia , Kuppe Christoph
Published: April 2024

Purpose of review

Kidney fibrosis is a key pathological aspect and outcome of chronic kidney disease (CKD). The advent of multiomic analyses using human kidney tissue, enabled by technological advances, marks a new chapter of discovery in fibrosis research of the kidney. This review highlights the rapid advancements of single-cell and spatial multiomic techniques that offer new avenues for exploring research questions related to human kidney fibrosis development.

Recent findings

We recently focused on understanding the origin and transition of myofibroblasts in kidney fibrosis using single-cell RNA sequencing (scRNA-seq) [1]. We analysed cells from healthy human kidneys and compared them to patient samples with CKD. We identified PDGFRα+/PDGFRβ+ mesenchymal cells as the primary cellular source of extracellular matrix (ECM) in human kidney fibrosis. We found several commonly shared cell states of fibroblasts and myofibroblasts and provided insights into molecular regulators. Novel single-cell and spatial multiomics tools are now available to shed light on cell lineages, the plasticity of kidney cells and cell-cell communication in fibrosis.

As further single-cell and spatial multiomic approaches are being developed, opportunities to apply these methods to human kidney tissues expand similarly. Careful design and optimisation of the multiomic experiments are needed to answer questions related to cell lineages, plasticity and cell-cell communication in kidney fibrosis.
Serial Trauma Abdominal Ultrasound in Children (STAUNCH)
Authors: Nti Benjamin K. , Benzoni Nicole , Starr Rebecca , Hays Matthew , Vish Dylan , End Bradley , Russell Frances
Published: April 2024

Background

Ultrasound has established utility within pediatric emergency medicine and has an added benefit of avoiding excessive radiation exposure. The serial focused assessment with sonography in trauma (sFAST) examination is a potential alternative to improve pediatric trauma evaluation. We sought to evaluate the accuracy of sFAST in pediatric patients with blunt abdominal trauma.

Methods

We performed a multicenter, retrospective observational study of electronic medical records, trauma registry data, and image archiving records of previous sFAST examinations. Examinations from pediatric patients (18 years or younger) who presented to an emergency department with blunt abdominal trauma were eligible for inclusion as long as the period between the first and second FAST was at least 30 minutes but no more than 24 hours. Demographic data and patient and outcomes were collected.

Results

Data collected from 3 institutions found a total of 38 sFAST performed between July 2017 and September 2021 on eligible patients. Of these, there were 6 (15.4%) FAST examinations that were positive after an initial negative or indeterminate interpretation. The overall sensitivity and specificity of sFAST were 66.7% (95% confidence interval 22.3–95.7%) and 93.8% (79.2–99.3%), respectively.

Conclusions

This pilot study found that sFAST can enhance blunt trauma evaluation and improve sensitivity and diagnostic accuracy. More data are needed to determine how sFAST can be utilized in pediatric patients with blunt abdominal trauma.
Pseudomonas kulmbachensis sp. nov. and Pseudomonas paraveronii sp. nov., originating from chilled beef and chicken breast
Authors: Lick Sonja , Wibberg Daniel , Busche Tobias , Blom Jochen , Grimmler Christina , Goesmann Alexander , Kalinowski Jörn
Published: April 2024

By investigating wet and dry age-related ripening of beef, Pseudomonas strains V3/3/4/13T and V3/K/3/5T were isolated. Strain V3/3/4/13T exhibited more than 99 % 16S rRNA gene-based similarity to Pseudomonas fragi and other members of this group, while isolate V3/K/3/5T was very close to Pseudomonas veronii and a number of relatives within the Pseudomonas fluorescens group. Additional comparisons of complete rpoB sequences and draft genomes allowed us to place isolate V3/3/4/13T close to Pseudomonas deceptionensis DSM 26521T. In the case of V3/K/3/5T the closest relative was P. veronii DSM 11331T. Average nucleotide identity (ANIb) and digital DNA–DNA hybridization (dDDH) values calculated from the draft genomes of V3/3/4/13T and P. deceptionensis DSM 26521T were 88.5 and 39.8 %, respectively. For V3/K/3/5T and its closest relative P. veronii DSM 11331T, the ANIb value was 95.1 % and the dDDH value was 60.7 %. The DNA G+C contents of V3/3/4/13T and V3/K/3/5T were 57.4 and 60.8 mol%, respectively. Predominant fatty acids were C16 : 0, C18 : 1 ω7c, C17 : 0 cyclo and summed feature C16 : 1 ω7ct/C15 : 0 iso 2OH. The main respiratory quinones were Q9, with minor proportions of Q8 and, in the case of V3/K/3/5T, additional Q10. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and, in the case of V3/K/3/5T, additional phosphatidylcholine. Based on the combined data, isolates V3/3/4/13T and V3/K/3/5T should be considered as representatives of two novel Pseudomonas species. The type strain of the newly proposed Pseudomonas kulmbachensis sp. nov. is V3/3/4/13T (=DSM 113654T=LMG 32520T), a second strain belonging to the same species is FLM 004-28 (=DSM 113604=LMG 32521); the type strain for the newly proposed Pseudomonas paraveronii sp. nov. is V3/K/3/5T (=DSM 113573T=LMG 32518T) with a second isolate FLM 11 (=DSM 113572=LMG 32519).
ICTV Virus Taxonomy Profile: Hantaviridae 2024
Authors: Bradfute Steven B. , Calisher Charles H. , Klempa Boris , Klingström Jonas , Kuhn Jens H. , Laenen Lies , Tischler Nicole D. , Maes Piet
Published: April 2024

Hantaviridae is a family for negative-sense RNA viruses with genomes of about 10.5–14.6 kb. These viruses are maintained in and/or transmitted by fish, reptiles, and mammals. Several orthohantaviruses can infect humans, causing mild, severe, and sometimes-fatal diseases. Hantavirids produce enveloped virions containing three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hantaviridae, which is available at ictv.global/report/hantaviridae.
Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis
Authors: Peters Hayley , Potla Pratibha , Rockel Jason S. , Tockovska Teodora , Pastrello Chiara , Jurisica Igor , Santos Keemo Delos , Vohra Shabana , Lively Starlee , Perry Kim , Looby Nikita , Li Sheng Han , Chandran Vinod , Hueniken Katrina , Kaur Paramvir , Perruccio Anthony V. , Mahomed Nizar N. , Rampersaud Y. Raja , Syed Khalid A. , Gracey Eric , Krawetz Roman , Buechler Matthew B. , Gandhi Rajiv , Kapoor Mohit
Published: April 2024

Objectives

In this study, we employ a multi-omic approach to identify major cell types and subsets, and their transcriptomic profiles within the infrapatellar fat pad (IFP), and to determine differences in the IFP based on knee osteoarthritis (KOA), sex, and obesity status.

Methods

Single-nucleus RNA sequencing of 82,924 nuclei from 21 IFPs (n=6 healthy control and n=15 KOA donors), spatial transcriptomics and bioinformatic analysis were used to identify contributions of the IFP to KOA. We mapped cell subclusters from other white adipose tissues using publicly available literature. The diversity of fibroblasts within the IFP was investigated by bioinformatic analyses, comparing by KOA, sex, and obesity status. Metabolomics was used to further explore differences in fibroblasts by obesity status.

Results

We identified multiple subclusters of fibroblasts, macrophages, adipocytes, and endothelial cells with unique transcriptomic profiles. Using spatial transcriptomics, we resolved distributions of cell types and their transcriptomic profiles, and computationally identified putative cell-cell communication networks. Furthermore, we identified transcriptomic differences in fibroblasts from KOA versus healthy control donor IFPs, female versus male KOA-IFPs, and obese versus normal body mass index (BMI) KOA-IFPs. Finally, using metabolomics, we defined differences in metabolite levels in supernatants of naïve, profibrotic- and proinflammatory stimuli-treated fibroblasts from obese compared to normal BMI KOA-IFP.

Conclusions

Overall, by employing a multi-omic approach, this study provides the first comprehensive map of cellular and transcriptomic diversity of human IFP and identifies IFP fibroblasts as a key cell type contributing to transcriptomic and metabolic differences related to KOA disease, sex, or obesity.
Alleviating cell-free DNA sequencing biases with optimal transport
Authors: Passemiers Antoine , Jatsenko Tatjana , Vanderstichele Adriaan , Busschaert Pieter , Coosemans An , Timmerman Dirk , Lambrechts Diether , Raimondi Daniele , Vermeesch Joris Robert , Moreau Yves
Published: April 2024

Cell-free DNA (cfDNA) is a rich source of biomarkers for various (patho)physiological conditions. Recent developments have used Machine Learning on large cfDNA data sets to enhance the detection of cancers and immunological diseases. Preanalytical variables, such as the library preparation protocol or sequencing platform, are major confounders that influence such data sets and lead to domain shifts (i.e., shifts in data distribution as those confounders vary across time or space). Here, we present a domain adaptation method that builds on the concept of optimal transport, and explicitly corrects for the effect of such preanalytical variables. Our approach can be used to merge cohorts representative of the same population but separated by technical biases. Moreover, we also demonstrate that it improves cancer detection via Machine Learning by alleviating the sources of variation that are not of biological origin. Our method also improves over the widely used GC-content bias correction, both in terms of bias removal and cancer signal isolation. These results open perspectives for the downstream analysis of larger data sets through the integration of cohorts produced by different sequencing pipelines or collected in different centers. Notably, the approach is rather general with the potential for application to many other genomic data analysis problems.
Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain
Authors: Ying Baoling , Liang Chieh-Yu , Desai Pritesh , Scheaffer Suzanne M. , Elbashir Sayda M. , Edwards Darin K. , Thackray Larissa B. , Diamond Michael S.
Published: April 2024

Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg relative to a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells and CD8+T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.

IMPORTANCE

Sequential boosting with mRNA vaccines has been effective strategy to overcome waning immunity and neutralization escape by emerging SARS-CoV-2 variants. However, it remains unclear how the site of boosting relative to the primary vaccination series shapes optimal immune responses or breadth of protection against variants. In K18-hACE2 transgenic mice, we observed that boosting with historical monovalent or variant-matched bivalent vaccines in the ipsilateral or contralateral limb elicited comparable levels of serum spike specific antibody and antigen-specific B and T cells responses. Moreover, boosting on either side conferred equivalent protection against a SARS-CoV-2 Omicron challenge strain. Our data in mice suggest that the site of boosting with an mRNA vaccine does not substantially impact immunity or protection against SARS-CoV-2 infection.
Stroke-induced slow oscillations in dynamic brain organization
Authors: Tscherpel Caroline , Mustin Maike , Rosjat Nils , Ziemann Ulf , Fink Gereon R. , Daun Silvia , Grefkes Christian
Published: April 2024

A focal ischemic lesion is thought to alter neuronal activity beyond the area of structural damage and thereby interfere with the whole network architecture.

We used a combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) together with dynamic connectivity analyses and graph theory to study alterations and reorganization of cortical reactivity and connectivity in a cohort of 42 stroke patients longitudinally after stroke. We found a link between an increase of low-frequency coupling in the delta band and alterations in neural information processing in the first weeks after stroke and their relevance for motor recovery more than three months later. We demonstrate that stroke to the motor system leading to impaired hand motor function induce an enhancement of slow activity and delta coupling between frontocentral and parietal regions. In addition, we could show a loss of the physiological network architecture with a decrease of small-worldness and modularity in the delta frequency, implying that a focal ischemic lesion distant to the cerebral cortex interferes with both cortical information integration as well as functional segregation within the days and weeks after stroke. While we found a link between bifrontal coupling in the alpha spectrum and the degree of the motor deficit in the early post-acute phase, the amount of small worldness disruption early after stroke indicated the motor outcome three months later. In contrast, recovery of motor function and cortical reorganization after more than three months post-stroke were paralleled by a normalization of increased low-frequency coupling and a reinstatement of the complex network structure featuring a small-world and modular topology.
CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment
Authors: Zhang Jie , Hu Gongcheng , Lu Yuli , Ren Huawei , Huang Yin , Wen Yulin , Ji Binrui , Wang Diyang , Wang Haidong , Liu Huisheng , Ma Ning , Pan Guangjin , Qu Yibo , Zhang Wei , Miao Zhichao , Yao Hongjie
Published: April 2024

The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations inCTCFhave been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explored the regulatory roles of a clinically relevant R567W point mutation, located within the 11thzinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCFR567Wmutation exhibited growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single- cell transcriptome levels. This mutation induced premature stem-like cell exhaustion, accelerated the maturation of GABAergic neurons, and disrupted neurodevelopmental and synaptic pathways. Additionally, it specifically hindered CTCF binding to peripheral motifs upstream to the core consensus site, causing alterations in local chromatin structure and gene expression, particularly at the clustered protocadherin locus. Comparative analysis using human cortical organoids mirrored the consequences induced by this mutation. In summary, this study elucidates the influence of the CTCFR567Wmutation on human neurodevelopmental disorders, paving the way for potential therapeutic interventions.
Plant Development Drives Dynamic Shifts in the Root Compartment Microbiomes of Wild and Domesticated Finger Millet Cultivars
Authors: Dadi Fantaye Ayele , Muthusamy Saraladevi , Ghosh Samrat , Muleta Diriba , Tesfaye Kassahun , Assefa Fassil , Xu Jie , Ghadamgahi Farideh , Ortiz Rodomiro , Vetukuri Ramesh Raju
Published: April 2024

Background

Plant-microbe interactions in two root compartments - the rhizosphere and endosphere - play vital roles in maintaining plant health and ecosystem dynamics. The microbial communities in these niches are shaped in complex ways by factors including the plant’s developmental stage and cultivar, and the compartment where the interactions occur. Different plant cultivars provide distinct nutritional and ecological niches and may selectively enrich specific microbial populations through the secretion of root exudates. This gives rise to complex and dynamic plant-microbe interactions; some cultivars promote the recruitment of beneficial symbionts while others may deter pathogens. To clarify these processes, this work investigated the structure of the endosphere and rhizosphere microbial communities of wild type finger millet and five domesticated cultivars across two plant developmental stages.

Results

Our results showed that the plant developmental stage, compartment, and cultivar have varying degrees of impact on root-associated microbiomes. The dominant bacterial phyla in all samples wereProteobacteria,Actinobacteria, andBacteroidetes, while the dominant fungal phyla wereAscomycotaandBasidiomycota. All of these phyla exhibited pronounced variations in abundance. In general, an increased abundance ofActinobacteriain the endosphere was accompanied by a reduced abundance ofProteobacteria. The most pronounced changes in microbial community structure were observed in the rhizosphere during the flowering stage. Changes in the microbiome patterns of the rhizosphere were driven predominantly by the genusPseudomonas.Moreover, the host plant’s developmental stage strongly influenced the microbial communities, suggesting that plants can recruit specific taxa based on their need for particular soil consortia.

Conclusions

Our results show that both host developmental stage and domestication strongly affect the assembly and structure of the plant microbiome. Moreover, plant root compartments can selectively recruit specific taxa from associated core microbial communities to fulfill their needs in a manner that depends on both the plant’s developmental stage and the specific root compartment that is involved. These findings show that deterministic selection pressures exerted by plants during their growth and development can significantly affect their microbial communities and have important implications for efforts to create tools for manipulating the microbiome to sustainably improve primary productivity.
Probing off-diagonal eigenstate thermalization with tensor networks
Authors: Luo Maxine , Trivedi Rahul , Bañuls Mari Carmen , Cirac J. Ignacio
Published: April 2024

Energy filter methods in combination with quantum simulation can efficiently access the properties of quantum many-body systems at finite energy densities [S. Lu , ]. Classically simulating this algorithm with tensor networks can be used to investigate the microcanonical properties of large spin chains, as recently shown by Y. Yang []. Here we extend this strategy to explore the properties of off-diagonal matrix elements of observables in the energy eigenbasis, fundamentally connected to the thermalization behavior and the eigenstate thermalization hypothesis. We test the method on integrable and nonintegrable spin chains of up to 60 sites, much larger than accessible with exact diagonalization. Our results allow us to explore the scaling of the off-diagonal functions with the size and energy difference, and to establish quantitative differences between integrable and nonintegrable cases.

Published by the American Physical Society
2024
General approach to neutrino mass mechanisms with sterile neutrinos
Authors: Fan Yale , Thapa Anil
Published: April 2024

We present a mathematical framework for constructing the most general neutrino mass matrices that yield the observed spectrum of light active neutrino masses in conjunction with arbitrarily many heavy sterile neutrinos, without the need to assume a hierarchy between Dirac and Majorana mass terms. The seesaw mechanism is a byproduct of the formalism, along with many other possibilities for generating tiny neutrino masses. We comment on phenomenological applications of this approach, in particular deriving a mechanism to address the long-standing (g−2)μ anomaly in the context of the left-right symmetric model.

Published by the American Physical Society
2024
Leptonic signatures of color-sextet scalars. II. Exploiting unique large-
ETmiss
signals at the LHC
Authors: Carpenter Linda M. , Schwind Katherine , Murphy Taylor
Published: April 2024

The diverse and distinct collider phenomenology of color-sextet scalars motivates a thorough investigation of their effective couplings to the Standard Model at the LHC. Some of the more unique sextet signals involve not only jets but also leptons. In previous work, we proposed an LHC search for color-sextet scalars in a channel with jets and a hard opposite-sign lepton pair, which results from a dimension-six coupling. In this sequel we study the counterpart processes with neutrinos, which produce jets in association with missing transverse energy (ETmiss) in addition to possible leptons. We consider multiple search channels, including both single and pair sextet production, all characterized by significant missing energy and some featuring distinctive kinematic features. Our multifaceted study consists of three reinterpreted existing searches and a joint-likelihood analysis designed by us to maximize HL-LHC sensitivity to single sextet production. We show that our dedicated strategy in the jets+lepton+ETmiss channel can supersede today’s limits from reinterpreted searches, and we make sensitivity projections for the HL-LHC. Altogether, our analysis can exclude sextet scalars lighter than 4.4 TeV or probe effective cutoffs as high as 16.8 TeV.

Published by the American Physical Society
2024