bluuebunny/crossref_metadata_2025 huggingface dataset:
Searching for triple systems unbound by supernovae
Authors: Barboza Karina , Kochanek Christopher S
Published: October 2024

A large fraction of massive stars are found in higher order systems where the presence of a tertiary may significantly modify the system’s evolution. In particular, it can lead to increased numbers of compact object binaries and accelerate their mergers with important implications for gravitational wave observations. Using Gaia, we constrain the number of Galactic supernovae that produce unbound triples. We do this by searching 8 supernova remnants for stars with consistent Gaia parallaxes and paths intersecting near the centre of the supernova remnant at a time consistent with the age of the remnant. We find no candidates for unbound triple systems. Combined with prior work, less than 11.4 per cent of supernovae leave behind unbound triples at a 90 per cent confidence limit. The absence of such systems limits their role in the evolution of massive stars and the formation of merging compact objects.
‘The Shipwreck of the Turks’: Sovereignty, Barbarism and Civilization in the Legal Order of the Eighteenth-Century Mediterranean
Authors: Calafat Guillaume , Trivellato Francesca
Published: October 2024

This article focuses on the consequences of a single major international affair — the shipwreck of a French ship carrying 165 Muslim pilgrims along the southern shores of Sicily in 1716 — to address two pivotal issues in the reordering of eighteenth-­century legal and political systems: the limits of domestic sovereignty in absolutist states and the status of non-Christian polities in the theory and practice of the law of nations. Both the time and place of this episode, which had a vast resonance at the time, have broad implications for how we write about the development of modern international law. While much of the debate on the maritime dimension of the eighteenth-century law of nations focuses on the Atlantic and the Indian Oceans, we spotlight the Mediterranean, where endemic corsairing activities coexisted with age-old diplomatic and day-to-day practices of accommodation and mutual recognition between Christian and Muslim polities. Here we draw attention to shipwrecks that occurred in foreign territorial waters and their heuristic potential for better understanding controversial issues of maritime law, such as the status of shorelines, neutrality and the law of the flag. Even after the Peace of Utrecht (1713–15), which is often regarded as a watershed moment in the history of international law, these rules were far from settled and shipwrecks continued to fuel legal and philosophical battles that extended well beyond the confines of the famous controversy between supporters of mare liberum and advocates of mare clausum. The close examination of the 1716 shipwreck leads us to challenge the land/sea divide as constructed by Carl Schmitt and demonstrate that territorial waters were objects of sovereign disputes in much the same way as land territories. We also show how the emerging Eurocentric discourse about the ‘barbarity’ of non-Christian peoples and nations coexisted with intellectual, economic and diplomatic forces interested in establishing formal agreements between Western European nations, the Ottoman Empire and its North African provinces.
Adrift in the Andaman Sea:  Law, Archipelagos and the Making of Maritime Sovereignty
Authors: Ramnath Kalyani
Published: October 2024

This essay focuses on the long history of archipelagic formations in the Bay of Bengal as sites of legal experimentation. This history is often narrated beginning with convict transportation and the permanent occupation of the Andaman Islands as a British penal settlement in 1857 and the violent erasure of indigenous cultures that followed it. This essay focuses instead on the hundred years preceding it where the English East India Company experimented with abandoning jurisdiction over the lesser-known islands off the Bengal and Burma coasts and people who lived on them, despite being in the position of a territorial sovereign. These experimentations were recorded most eloquently in legal and administrative records about crime - which included, for example, how assault and “river dacoity” on the deltaic islands of the Sunderbans in lower Bengal were to be dealt with and how men convicted of murder on the islands off the Tenasserim coast in southern Burma were to be prosecuted. In each case, prompted by tensions between the Company and the British Crown, policing and prosecution were abandoned, but this escaped public attention as it took place on the empire’s maritime edges. Although jurisdictional claims were central to the expansionist aims of the British empire in the nineteenth century around the Indian Ocean, these instances offer an alternate account of sovereignty, one where assertions and abandonments were both critical to the making of empires.
Long-term trends analysis of the incidence and mortality in patients with ovarian cancer: a large sample study based on SEER database
Authors: Zhao Hongwei , Zhang Yu , Zhu Qianyong
Published: October 2024

Background

To analyze long-term trends of the incidence and mortality of ovarian cancer in the United States.

Methods

Patients diagnosed with ovarian cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2017. Joinpoint regression analysis was used to analyze the incidence and mortality trend, and the changes were reported as average annual percentage change (AAPC) with a 95% confidence interval (CI). Kaplan–Meier survival curve and Cox regression analyses were utilized for survival analysis.

Results

A total of 74 682 patients were included, among whom 49 491 (66.27%) died and 44 487 (59.57%) died from ovarian cancer. The mean age was 61.95 ± 15.23 years. The incidence of ovarian cancer showed a decreased trend from 2000 to 2017 with an AAPC of −1.9 (95%CI: −2.0, −1.7). Both the overall mortality and cancer-specific mortality for ovarian cancer decreased from 2000 to 2017, with AAPCs of −5.0 (95%CI: −5.7, −4.2) and −4.6 (95%CI: −5.4, −3.8), respectively. There was a significant decrease in the incidence and mortality of patients with the distant SEER stage, histological subtypes of serous and malignant Brenner carcinoma, and grades II and III from 2000 to 2017. Older age, Black race, histological subtypes of carcinosarcoma, higher tumor grade, and radiotherapy were associated with poorer overall survival and cancer-specific survival, whereas higher income, histological subtype of endometrioid, and surgery were associated with better survival.

Conclusion

This study provided evidence of a statistically significant decrease in the incidence and mortality of ovarian cancer from 2000 to 2017.

Key message What is already known on this topic?  Ovarian cancer is one of the most common tumors in women, with high morbidity and mortality. However, trends in long-term morbidity and mortality of patients with ovarian cancer have not been reported. What this study adds  Overall incidence and mortality for ovarian cancer showed a decreased trend from 2000 to 2017, and trends in incidence and mortality varied by stage, histological subtype, and tumor grade. Factors associated with overall survival and cancer-specific survival also differ. How this study might affect research, practice, or police  This study provides evidence of long-term trends in ovarian cancer incidence and mortality from 2000 to 2017.
Inflammatory cytokines, metabolites, and rheumatoid arthritis
Authors: Peilin Zhou , Wenqiang Wang , Yongzhen Liu , Xiang Chen , Yongjun Mo , Hongjie Su , Xinyu Nie , Qikai Hua
Published: October 2024

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint destruction. Although the roles of inflammatory cytokines and metabolites in RA pathogenesis have caught a lot of attention, there is a lack of systematic studies, and their causal relationships remain unclear.

Methods

We conducted a two-step mendelian randomization analysis utilizing genetic data from genome-wide association studies (GWAS) of inflammatory cytokines, metabolites, and RA. The first step assessed the causal effect of 91 inflammatory cytokines and 1400 metabolites on RA risk using inverse variance weighted method, complemented by MR-Egger, weighted median, simple mode and MR-PRESSO to ensure robustness and assess pleiotropy. The second step evaluated the mediation effects of selected metabolites on the relationship between cytokines and RA.

Results

The analysis identified 9 inflammatory cytokines, including IL-1α and IL-10, which significantly increase RA risk, while TNF-β exhibited a protective effect. Additionally, 6 metabolites were associated with increased RA risk, including 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE and arachidonate (20:4n6). Conversely, 5 metabolites, such as docosatrienoate (22:3n3) and Cholesterol, were found to reduce RA risk. The mediation analysis revealed that TNF-β may exerts its protective effect through its influence on specific metabolites, and X-24949, which accounted for a −2.58% mediated effect in the TNF-β-RA causal pathway.

Conclusion

This study explores the complex interplay between inflammatory cytokines, metabolites, and RA. The findings suggest potential biomarkers for early diagnosis and novel therapeutic targets, particularly those related to lipid metabolites and specific cytokines like TNF-β.

Key message What is already known on this topic  Inflammatory factors and metabolites are considered to be related to the onset and progression of RA. What this study adds  We conducted a MR analysis to identify all inflammatory factors and metabolites associated with RA and calculated the mediation effect of inflammatory cytokines on RA through metabolites. This study contributes to a comprehensive understanding of the pathophysiological processes of RA. How this study might affect research, practice or policy  This has laid the groundwork for developing early diagnosis methods and future treatments.
Development of a physiologically based pharmacokinetic model for flunixin in cattle and swine following dermal exposure
Authors: Wu Xue , Chen Qiran , Chou Wei-Chun , Maunsell Fiona P , Tell Lisa A , Baynes Ronald E , Davis Jennifer L , Jaberi-Douraki Majid , Riviere Jim E , Lin Zhoumeng
Published: October 2024

Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID). Banamine Transdermal is a pour-on formulation of flunixin approved for pain control in beef and dairy cattle, but not for calves and some classes of dairy cattle or swine. Violative flunixin residues in edible tissues in cattle and swine have been reported and are usually attributed to non-compliant drug use or failure to observe an appropriate withdrawal time. This project aimed to develop a physiologically based pharmacokinetic (PBPK) model for flunixin in cattle and swine to predict withdrawal intervals (WDI) after exposures to different therapeutic regimens of Banamine Transdermal. Due to the lack of comprehensive skin physiological data in cattle, the model was initially developed for swine and then adapted for cattle. Monte Carlo simulation was employed for population variability analysis. The model predicted WDIs were rounded to 1 and 2 d for liver and muscle in cattle, respectively, under FDA tolerance levels, while under EU maximum residue limits, the WDIs were rounded to 1, 3, 2, and 2 d for liver, kidney, muscle, and fat, respectively, following a labeled single transdermal 3.3 mg/kg dose in cattle. The model was converted into a user-friendly interactive PBPK (iPBPK) interface. This study reports the first transdermal absorption model for drugs in cattle. This iPBPK model provides a scientifically based tool for the prediction of WDIs in cattle and swine administered with flunixin in an extra-label manner, especially by the transdermal route.
Amyloid-related imaging abnormalities in antiamyloid therapy for Alzheimer's disease: a narrative review
Authors: Erichsen Philip Ahle
Published: October 2024

Antiamyloid therapies have sparked a new hope for a potential disease-modifying therapy for Alzheimer's disease. Antiamyloid therapy targets amyloid-beta, which is a key feature of the disease. However, adverse effects such as amyloid-related imaging abnormalities (ARIA) have raised significant concerns about the safety of these therapies. ARIA, which includes vasogenic edema (ARIA-E) and microhemorrhages or hemosiderosis (ARIA-H), is a common adverse effect to antiamyloid therapies. Patient-related risk factors for ARIA include carrying the APOE-ε4 allele and cerebral amyloid angiopathy (CAA). Drug-related risk factors for ARIA include higher drug doses, early initiation of treatment, and concomitant use of antithrombotic medications, all of which increase the likelihood of vascular disruptions. Management of ARIA involves regular MRI monitoring and possibly temporary or permanent discontinuation of therapy if adverse effects develop during therapy. A gradual dose titration is recommended to minimize the risk of ARIA. Although antiamyloid therapies have demonstrated efficacy in reducing amyloid burden, the clinical benefit remains at best modest and must be weighed against the risks of developing adverse effects such as ARIA.
Exploring the clinicopathological characteristics of submucosal tumor-like esophageal squamous cell carcinoma and the diagnostic significance of endoscopic ultrasound: a comprehensive analysis
Authors: Geng Ping , Heng Yuting , Wang Xian , Zhan Heqin , Fang Qianqian , Tao Li , Liu Jun , Hu Xiangpeng
Published: October 2024

Background

Completely intramural growth submucosal squamous cell carcinoma of the esophagus, also known as SMT-like esophageal squamous cell carcinoma (ESCC), represents a rare and distinct form of esophageal cancer. Its white light endoscopic manifestations resemble those of esophageal subepithelial lesions, and biopsy pathology is often negative, leading to potential oversight or misdiagnosis. This study aimed to comprehensively summarize the clinicopathological and endoscopic ultrasound (EUS) characteristics of patients with SMT-like ESCC while also evaluating the immunohistochemical expression of these patient.

Methods

This study collected clinical data, including demographic and clinicopathological data, as well as EUS findings, from six patients with SMT-like ESCC. Immunohistochemical analysis was also conducted on tumor tissues to assess the expression of CK7, CK19, CK20, TTF-1, SMA, S-100, Melan-A, CD117, Mucin (MUC) 2, and MUC5.

Results

In EUS, SMT-like ESCC is characterized by nonuniform hypoechoic lesions with indistinct borders, often exhibiting a burr or serrated appearance. Most of these lesions involved multiple levels. Cytological specimens obtained through EUS-guided fine needle aspiration (EUS-FNA) revealed suspected squamous cell carcinoma with positive expression of CK5/6, P40, and P63, further confirming the diagnosis of ESCC. Additionally, four patients exhibited CK7+/CK20− immune-expression profiles, and all patients had positive CK19 expression. TTF-1, SMA, S-100, Melan-A, CD117, MUC2, and MUC5 were negative.

Conclusion

Combining EUS with EUS-FNA is a valuable approach for diagnosing and differentiating SMT-like ESCC. Furthermore, the characteristic CK7+/CK20− immune profile suggested a potential origin from the esophageal submucosa glands.
Leaders Benefit From Organizational Membership
Authors: Prestia Angela S. , Udod Sonia A. , Bacon Cynthia Thornton
Published: October 2024

This article explores the value of nurse leader membership in professional organizations in the United States and Canada. Benefits include the sharing of scholarly information, enlarging networks, and professional development.
Veterans Day
Authors: Sweeney Cynthia Divens
Published: October 2024

Veterans Day provides the opportunity to acknowledge the service of our nurse colleagues who have served or currently serve in the US military. It is a moment to reflect on their leadership and experiences as military nurses.
Implementing a Virtual Discharge Nurse Pilot
Authors: Ransford Jennifer , Tidwell Timothy , Johnson Logan , Gitney Nicole , Morgan Anna , Hauch Rodney
Published: October 2024

OBJECTIVE

The virtual nurse (VN) pilot was developed to assist bedside nurses in administrative tasks, including discharges and education, from a remote location.

BACKGROUND

Bedside nurse vacancies have increased, leading to a shortage of resources for the care team and less time for nurses to provide hands-on care to patients.

METHODS

A survey showed 77% of nurses spend more than 3 hours per shift on admissions, discharges, and patient education. A pilot was conducted on a 45-bed unit with the VN focusing on discharges and patient education.

RESULTS

During the pilot, the VN completed 1375 tasks, increasing patient and nurse satisfaction while reducing turnover and adverse events.

CONCLUSION

With the program's early success, the VN role is expanding into additional units.
Advanced Practice Nurse–Led Research
Authors: Klein Colleen J. , Cooling Melinda , Dalstrom Matthew , Foulger Roopa , Handler Jonathan A. , Bond William F.
Published: October 2024

Advanced practice nurse leaders are in key positions within health systems to provide time and resources for implementation and evaluation of digital health services. As virtual monitoring programs become more embedded within nursing, nurse leaders and educators need to ensure that nurses are prepared to work within interprofessional teams to administer and evaluate them. This article discusses challenges and implementation strategy considerations for data curation and analysis using large datasets from the Medicaid population for research.
Creating a Model for Advanced Practice Provider Mentorship
Authors: DiGerolamo Kimberly A. , Warren Karen , Ogle Sue , Hobbie Wendy
Published: October 2024

Advanced practice providers (APPs), widely considered essential to the delivery of healthcare, are one of the fastest-growing workforces in the United States. However, the APP role is evolving, and professional growth and advancement programs for APPs are still emerging at many institutions. Professional mentorship has been long embraced by other healthcare disciplines and numerous organizations because of the benefits gained from helping employees increase knowledge, enhance skills, and achieve scholarly goals, such as retention. Thus, there is a dearth of evidence on building effective APP mentorship models. This article details the development of an APP mentorship model and program designed to support both the mentor and mentee across the career trajectory.
Subconjunctival Hemorrhages Are Rare Among Infants With Cough and Gastrointestinal Conditions
Authors: Koti Ajay S. , Brown Emily C. B. , Campbell Kristine A.
Published: October 2024

Objective

Subconjunctival hemorrhages (SCHs) are uncommon injuries in young children beyond the neonatal period and have been associated with abuse. In otherwise well infants, they are sometimes attributed to commonly observed symptoms that invoke Valsalva maneuvers, such as cough, vomiting, and constipation. Our study aims to ascertain the prevalence of SCH among children presenting to emergency care with cough, vomiting, and constipation.

Methods

We conducted a cross-sectional secondary analysis of a prospectively collected dataset of children aged 1 month to 3 years presenting to a tertiary pediatric emergency department (ED). Children with and without SCH were identified at the time of their examination by ED providers. Children were assigned to Valsalva symptom groups of cough, vomiting, and/or constipation based on review of the ICD-10 codes associated with the ED encounter. Descriptive statistics and prevalence were calculated for each group. Chi-square testing of proportions was used to compare the prevalence of SCH based on the presence or absence of the 3 symptoms of interest.

Results

Four thousand seven hundred seventeen qualifying ED encounters were captured, with 2 total cases of SCH identified (0.4 per 1000). SCHs were uncommonly observed in patients with cough (0.5 per 1000), vomiting (0 per 1000), and constipation (0 per 1000). We found no significant differences in the prevalence of SCH based on the presence or absence of cough (P = 0.87), vomiting (P = 0.52), or constipation (P = 0.82).

Conclusion

SCH is an uncommon finding in children under 3 years and is similarly uncommon among children with cough, vomiting, or constipation. It should not be attributed to uncomplicated presentations of cough, vomiting, or constipation, and alternative diagnoses, including abuse, should be carefully considered in the differential diagnosis of SCH.
Bilateral Somatically Derived Germ Cell Tumors With 12p Gains Arising in High-grade Serous Carcinomas of the Ovary: A Case Report and Review of the Literature
Authors: Masaadeh Amr H. , Dundar Bilge , Samuelson Megan I. , Kadera Evangeline , Bashir Amani
Published: October 2024

Epithelial ovarian neoplasms are commonly observed in older patients, while germ cell tumors (GCTs) typically present in young individuals. When GCTs are detected in patients over 35 yrs old, they often have an associated epithelial component, a phenomenon known as somatically derived GCTs. We report a unique case of mixed GCT involving bilateral ovaries with a background of high-grade serous carcinoma, including a yolk sac tumor and choriocarcinoma in the mixed GCT component. Somatically derived GCTs are rare with only 45 cases of ovarian carcinoma with somatic yolk sac tumor reported to date. Pathologists face diagnostic challenges in identifying somatically derived GCTs, as they can mimic high-grade epithelial neoplasms. Somatically derived GCTs have poor outcomes, therefore, precise diagnosis is crucial for prognostic and therapeutic considerations.
Artificial Intelligence Assisted Surgical Scene Recognition
Authors: Williams Simon C. , Zhou Jinfan , Muirhead William R. , Khan Danyal Z. , Koh Chan Hee , Ahmed Razna , Funnell Jonathan P. , Hanrahan John G. , Ali Alshaymaa Mortada , Ghosh Shankhaneel , Sarıdoğan Tarık , Valetopoulou Alexandra , Grover Patrick , Stoyanov Danail , Murphy Mary , Mazomenos Evangelos B. , Marcus Hani J.
Published: October 2024

Objective:

This study aimed to compare the ability of a deep-learning platform (the MACSSwin-T model) with healthcare professionals in detecting cerebral aneurysms from operative videos. Secondly, we aimed to compare the neurosurgical team’s ability to detect cerebral aneurysms with and without AI-assistance.

Background:

Modern microscopic surgery enables the capture of operative video data on an unforeseen scale. Advances in computer vision, a branch of artificial intelligence (AI), have enabled automated analysis of operative video. These advances are likely to benefit clinicians, healthcare systems, and patients alike, yet such benefits are yet to be realised.

Methods:

In a cross-sectional comparative study, neurosurgeons, anaesthetists, and operating room (OR) nurses, all at varying stages of training and experience, reviewed still frames of aneurysm clipping operations and labelled frames as “aneurysm not in frame” or “aneurysm in frame”. Frames then underwent analysis by the AI platform. A second round of data collection was performed whereby the neurosurgical team had AI-assistance. Accuracy of aneurysm detection was calculated for human only, AI only, and AI-assisted human groups.

Results:

5,154 individual frame reviews were collated from 338 healthcare professionals. Healthcare professionals correctly labelled 70% of frames without AI assistance, compared to 78% with AI-assistance (OR 1.77, P<0.001). Neurosurgical Attendings showed the greatest improvement, from 77% to 92% correct predictions with AI-assistance (OR 4.24, P=0.003).

Conclusion:

AI-assisted human performance surpassed both human and AI alone. Notably, across healthcare professionals surveyed, frame accuracy improved across all subspecialties and experience levels, particularly among the most experienced healthcare professionals. These results challenge the prevailing notion that AI primarily benefits junior clinicians, highlighting its crucial role throughout the surgical hierarchy as an essential component of modern surgical practice.
Opening and changing: mammalian SWI/SNF complexes in organ development and carcinogenesis
Authors: Abu Sailik Fadia , Emerald Bright Starling , Ansari Suraiya Anjum
Published: October 2024

The switch/sucrose non-fermentable (SWI/SNF) subfamily are evolutionarily conserved, ATP-dependent chromatin-remodelling complexes that alter nucleosome position and regulate a spectrum of nuclear processes, including gene expression, DNA replication, DNA damage repair, genome stability and tumour suppression. These complexes, through their ATP-dependent chromatin remodelling, contribute to the dynamic regulation of genetic information and the maintenance of cellular processes essential for normal cellular function and overall genomic integrity. Mutations in SWI/SNF subunits are detected in 25% of human malignancies, indicating that efficient functioning of this complex is required to prevent tumourigenesis in diverse tissues. During development, SWI/SNF subunits help establish and maintain gene expression patterns essential for proper cellular identity and function, including maintenance of lineage-specific enhancers. Moreover, specific molecular signatures associated with SWI/SNF mutations, including disruption of SWI/SNF activity at enhancers, evasion of G0 cell cycle arrest, induction of cellular plasticity through pro-oncogene activation and Polycomb group (PcG) complex antagonism, are linked to the initiation and progression of carcinogenesis. Here, we review the molecular insights into the aetiology of human malignancies driven by disruption of the SWI/SNF complex and correlate these mechanisms to their developmental functions. Finally, we discuss the therapeutic potential of targeting SWI/SNF subunits in cancer.
Novel
in vivo
TDP-43 stress reporter models to accelerate drug development in ALS
Authors: Ferro Febe , Wolf C. Roland , Henstridge Christopher , Inesta-Vaquera Francisco
Published: October 2024

The development of therapies to combat neurodegenerative diseases is widely recognized as a research priority. Despite recent advances in understanding their molecular basis, there is a lack of suitable early biomarkers to test selected compounds and accelerate their translation to clinical trials. We have investigated the utility of
in vivo
reporters of cytoprotective pathways (e.g. NRF2, p53) as surrogate early biomarkers of the ALS degenerative disease progression. We hypothesized that cellular stress observed in a model of ALS may precede overt cellular damage and could activate our cytoprotective pathway reporters. To test this hypothesis, we generated novel ALS-reporter mice by crossing the hTDP-43tg model into our oxidative stress/inflammation (Hmox1; NRF2 pathway) and DNA damage (p21; p53 pathway) stress reporter models. Histological analysis of reporter expression in a homozygous hTDP-43tg background demonstrated a time-dependent and tissue-specific activation of the reporters in tissues directly associated with ALS, before moderate clinical signs are observed. Further work is warranted to determine the specific mechanisms by which TDP-43 accumulation leads to reporter activation and whether therapeutic intervention modulates reporters’ expression. We anticipate the reporter strategy could be of great value in developing treatments for a range of degenerative disorders.
Are testosterone pulses a physiological mechanism for expanding activity beyond territories?
Authors: Petric Radmila , Kalcounis-Rueppell Matina , Marler Catherine A.
Published: October 2024

We ask whether artificially induced testosterone pulses (T-pulses), administered to males in the wild at the territory boundary, adjust location preferences within the territory. Multiple transient T-pulses occurring after social interactions in males can alter behaviour and spatial preferences. We previously found that T-pulses administered at the nest induce male California mice, a biparental and territorial species, to spend more time at the nest likely through conditioned place preferences. We hypothesized that T’s reinforcing effects would increase future time by the T-injected males at the boundary and promote territorial defence. Contrary to predictions, T-pulses induced a decrease in male time at the boundary, and instead appeared to promote male territorial/home range expansion, accompanied by shorter sustained vocalizations (SVs) and decreased proportion of three SV bouts. Shorter SVs are associated with aggression in the laboratory. Furthermore, in response to T-male behavioural changes, uninjected female partners decreased boundary time. Our results suggest new functions for socially induced T-pulses, such as extending territorial boundaries/home ranges. Location preferences induced through reinforcing/rewarding mechanisms may be more plastic and dependent on physical and social contexts than previously thought. Moreover, the results suggest that location preferences produced through rewarding/reinforcing mechanisms can be viewed from adaptive perspectives to influence future behaviour.
A general solution for rotating lattices of identical point vortices
Authors: Robertson Phillip
Published: October 2024

The rotating equilibrium solutions of

N

identical point vortices are the stationary energy states of a higher-dimensional object projected to the

x
−
y

plane, in this case, an

(
N
−
1
)

-dimensional regular simplex. Parameterizing the point vortex Hamiltonian with this fundamental geometrical object leads to a simple bivector condition, which contains the equilibrium states and resolves the origin of the asymmetric solutions. This novel approach uses the geometric product and the multivector derivative,

∂
ψ

, of the Hamiltonian in the geometric algebra,

C
l
(
N
−
1
,
0
)

to find a geometric condition that determines the equilibrium states. The resulting bivector equation is then used as the input to an optimizer, which rotates a simplex until the equilibrium condition is met, leading to a wealth of new solutions. If the vertices of the oriented simplex are projected to the

x

-axis, the values form the roots of the Hermite polynomials,

H
N

(
x
)

, and obey the Stieltjes relations, capturing the collinear solutions. The vortex simplex exhibits a striking geometrical connection with the amplituhedron of quantum field theory and gives deep insight into the quantization of a classical system.
Recent advances in solar coronal extreme ultraviolet waves
Authors: Zheng Ruisheng
Published: October 2024

Solar coronal extreme ultraviolet (EUV) waves are spectacular propagating disturbances in the appearance of EUV emission enhancements in the solar corona, similar to the tsunamis on the Earth. These ‘solar tsunamis’ are closely associated with various solar eruptions, from large-scale coronal mass ejections (CMEs) and solar flares to small-scale solar jets. Interestingly, the existence of EUV waves was predicted by the detection of the chromospheric propagating disturbances, i.e. Moreton waves, based on the generally believed theory that Moreton waves are the chromospheric imprints of coronal shocks/waves. Benefiting from EUV observations from generations of space-borne telescopes, the EUV wave has been currently best interpreted in a bimodal/hybrid composition of an outer, fast-mode magnetosonic front and an inner, non-wave CME structure, after a vigorous debate on the physical nature between true magnetohydrodynamic (MHD) waves and ‘pseudo-waves’. However, some important issues of EUV waves are still controversial, e.g. their trigger mechanisms and their relationship with Moreton waves. This article on EUV waves first reviews the previous achievements, then summarizes the recent advances in observations and simulations and finally provides some prospects for future research.
Commutativity equations and their trigonometric solutions
Authors: Alkadhem Maali , Feigin Misha
Published: October 2024

In the theory of Frobenius manifolds and Witten–Dijkgraaf–Verlinde–Verlinde (WDVV) equations, one normally assumes that Frobenius algebras associated with a solution

F

have an identity

e

. Equivalently, the corresponding flat metric can be expressed as a linear combination of the matrices of the third-order derivatives of the pre-potential function

F

. We show that under certain non-degeneracy conditions, this assumption can be omitted, that is, the identity field

e

exists automatically without further assumptions. We also study trigonometric solutions

F

determined by a finite collection of vectors with multiplicities, and we give an explicit formula for the field

e

for all the known such solutions. The corresponding collections of vectors are given by the non-simply laced root systems or are related to their projections to the intersection of mirrors.
Corynebacterium amycolatum peritonitis in a patient undergoing peritoneal dialysis: case report and literature review
Authors: Adil Fatima Zahra , Aragon Imane , Benaissa Elmostafa , Ben Lahlou Yassine , Bssaibis Fatna , Maleb Adil , Chadli Mariama , Elouennass Mostafa
Published: October 2024

Peritoneal dialysis is a blood purification technique used in cases of end-stage chronic kidney failure, based on the filtering capabilities of the peritoneum. Infections, often caused by poor asepsis during catheter manipulation, are generally attributed to Staphylococcus epidermidis and Staphylococcus aureus. Corynebacterium, usually considered non-pathogenic, is rarely involved in these infections. We present a case of peritonitis due to Corynebacterium amycolatum in a patient undergoing peritoneal dialysis. The diagnosis was made based on cytobacteriological examination of the dialysate fluid, which on two occasions showed high levels of white blood cells with a predominance of neutrophilic polymorphonuclear and a monomorphic appearance of colonies on agar medium, whose identification by biochemical tests and antibiotic sensitivity study confirmed the presence of C. amycolatum. The patient was successfully treated with vancomycin, resulting in symptom resolution and sterilization of the dialysate fluid. Although rare, the involvement of Corynebacterium species underscores the importance of confirming its pathogenicity. Further studies are needed to better understand the epidemiology of these infections and guide future treatments. This case also highlights the need for a rigorous approach to confirming the pathogenicity of Corynebacterium despite its traditional classification as a contaminant.
“A Difficile-cult Case” – Clostridioides difficile prosthetic joint infection; case report, microbiology, and review of the literature.
Authors: Jordan Holly , Graham Rikki , Schlebusch Sanmarie , Oon Aileen , Varadhan Hemalatha , Naqvi Syeda
Published: October 2024

Extra-colonic infections caused by Clostridioides difficile (C. difficile) are exceptionally rare, with prosthetic joint infections (PJI) comprising only a small fraction of reported cases. Moreover, there is limited guidance on the optimal management of such infections. We present the case of a 76-year-old male who developed a left hip PJI due to C. difficile six weeks after undergoing surgical revision for a periprosthetic fracture. Given the complexity of the case, curative surgical intervention was not considered feasible. The patient was treated with repeated debridement, intravenous vancomycin and oral metronidazole, followed by successful suppression with oral doxycycline – a novel therapeutic approach not previously documented. To date, only seven cases of C. difficile-associated PJI have been reported in the literature; this is the first known instance where suppression of a C. difficile PJI has been achieved and the first to utilize whole genome sequencing for further analysis of the isolate.
Investigating trends in antibiotic resistance of Escherichia coli isolated from clinical urine specimens in the Orkney Islands
Authors: Corse Lily , Cartwright Allison
Published: October 2024

Urinary tract infections (UTIs) are extremely common, affecting people of all ages and health statuses. Although UTIs do not usually cause severe illness, in some cases they can lead to more serious complications, especially if their initial treatment is ineffective due to antimicrobial resistance (AMR). AMR is an increasing issue, exacerbated by misdiagnosis and inappropriate prescribing of antibiotics, thus facilitating further resistance. The aim of this study was to investigate the rates of AMR in Escherichia coli isolated from clinical urine specimens tested at the Balfour Hospital, Orkney, and determine trends related to patient risk factors. Antibiotic susceptibilities were tested for 100 isolates of uropathogenic E. coli using the VITEK 2 Compact (bioMérieux), and data were analysed using percentage resistance rates. Resistance rates were compared by patient sex, age and source (hospital versus community). The findings showed higher AMR in males compared with females, particularly for trimethoprim (TMP), with 52% in males and only 12% in females. AMR tended to be higher in E. coli isolated from hospital inpatients than from community specimens, except for amoxicillin (AMX) and co-amoxiclav. Finally, the study found that AMR of E. coli isolates was greater in patients aged over 50 than 18–50 years old, particularly for AMX and TMP. The highest resistance rates across all patient demographics were for AMX, implying that the use of this antibiotic for the treatment of E. coli UTIs is not appropriate.
Robust discovery of mutational signatures using power posteriors
Authors: Xue Catherine , Miller Jeffrey W. , Carter Scott L. , Huggins Jonathan H.
Published: October 2024

Mutational processes, such as the molecular effects of carcinogenic agents or defective DNA repair mechanisms, are known to produce different mutation types with characteristic frequency profiles, referred to as mutational signatures. Non-negative matrix factorization (NMF) has successfully been used to discover many mutational signatures, yielding novel insights into cancer etiology and targeted therapies. However, the NMF model is only a rough approximation to reality, and even small departures from this assumed model can have large negative effects on the accuracy and reliability of the results. We propose a new approach to mutational signatures analysis that improves robustness to misspecification by using a power posterior for a fully Bayesian NMF model, while employing a sparsity-inducing prior to automatically infer the number of active signatures. In extensive simulation studies, we find that our proposed approach recovers more true signatures with greater accuracy than current leading methods. On whole-genome sequencing data for six cancer types from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, we find that our method is able to accurately recover more signatures than the current state-of-the-art.
Among-Population Differentiation in the Tapeworm Proteome through Prediction of Excretory/Secretory and Transmembrane Proteins inSchistocephalus solidus
Authors: Wang Anni , Bolnick Daniel
Published: October 2024

Background

Parasites secrete and excrete a variety of molecules evolve to help establish and sustain infections within hosts. Parasite adaptation to their host may lead to between-population divergence in these excretory and secretory products (ESPs), but few studies have tested for intraspecific variation in helminth proteomes.

Methods

Schistocephalus solidusis a cestode that parasitizes three spined stickleback,Gasterosteus aculeatus. We used an ultra-performance liquid chromatography-mass spectrometry protocol to characterize the ESP and whole-body proteome of S. solidus. Specifically, we characterized the proteome of S. solidus at the plerocercoid stage from wild caught stickleback from three lakes on Vancouver Island (British Columbia, Canada) and one lake in Alaska (United States). We tested for differences in proteome composition among the four populations and specifically between ESPs and body tissue.

Results

Overall, we identified 1362 proteins in the total proteome of S. solidus, with 542 of the 1362 proteins detected exclusively in the ESPs. Of the ESP proteins, we found signaling peptides and transmembrane proteins that were previously not detected or characterized in S. solidus. We also found protein spectrum counts greatly varied between all lake populations.

Conclusions

These population-level differences were observed in both ESP and tissue types. Our study suggests that S. solidus can excrete and secrete a wide range of proteins which are distinct among populations. These differences might reflect plastic responses to host genotype differences, or evolved adaptations by Schistocephalus to different local host populations.
Dual transcranial electromagnetic stimulation of the precuneus-hippocampus network boosts human long-term memory
Authors: Borghi Ilaria , Mencarelli Lucia , Maiella Michele , Casula Elias P. , Ferraresi Matteo , Candeo Francesca , Savastano Elena , Assogna Martina , Bonnì Sonia , Koch Giacomo
Published: October 2024

Non-invasive brain stimulation techniques have the potential to improve memory functions. However, the results so far have been relatively modest and time-consuming. Here, we implemented a novel 3-minute combination of personalized repetitive transcranial magnetic stimulation (intermittent theta burst-iTBS) coupled with simultaneous application of gamma transcranial alternating current stimulation (γtACS) over the precuneus, a brain area connected with the hippocampus, to modulate long term memory in healthy subjects. Only dual electromagnetic stimulation of the precuneus produced a consistent increase in long-term associative memory as compared to iTBS alone and sham conditions in a sample of healthy volunteers. The effects were replicated in another independent sample, in which the increased associative memory was retained for up to one week. Moreover, dual stimulation increased gamma oscillations and precuneus-hippocampus functional connectivity through the white matter tracts linking the precuneus with the temporal lobe. These findings show that dual stimulation may lead neuronal assemblies in a state favorable to enhance long-term plasticity and identify the precuneus as a key brain area involved in memory formation. Personalized dual electromagnetic stimulation of the precuneus-hippocampus network may represent a new powerful approach for enhancing memory functions in several healthy and clinical conditions.
Genomic Insights Guiding Personalized First-Line Immunotherapy Response in Lung and Bladder Tumors
Authors: Brea-Iglesias Jenifer , Gallardo-Gómez María , Oitabén Ana , Lázaro-Quintela Martin E. , León Luis , Alves Joao M. , Juaneda-Magdalena Laura , García-Benito Carme , Abdulkader Ihab , Muinelo Laura , Paramio Jesús M , Martínez-Fernández Mónica
Published: October 2024

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, particularly in advanced non-small cell lung cancer (NSCLC) and muscle-invasive bladder cancer (MIBC). However, identifying reliable predictive biomarkers for ICI response remains a significant challenge. In this study, we analyzed real-world cohorts of advanced NSCLC and MIBC patients treated with ICIs as first-line therapy. Tumor samples underwent Whole Genome Sequencing (WGS) to identify specific somatic variants and assess tumor mutational burden (TMB). Additionally, mutational signature extraction and pathway enrichment analyses were performed to uncover the underlying mechanisms of ICI response. We also characterized HLA-I haplotypes and investigated LINE-1 retrotransposition. Distinct mutation patterns were identified in patients who responded to treatment, suggesting potential biomarkers for predicting ICI effectiveness. In NSCLC, tumor mutational burden (TMB) did not differ significantly between responders and non-responders, while in MIBC, higher TMB was linked to better responses. Specific mutational signatures and HLA haplotypes were associated with ICI response in both cancers. Pathway analysis showed that NSCLC responders had active inflammatory and immune pathways, while non-responders had pathways such related to FGFR3 and neural crest differentiation associated to resistance mechanisms. In MIBC, responders had alterations in DNA repair, leading to more neoantigens and a stronger ICI response. Importantly, for the first time, we found that LINE-1 activation was positively linked to ICI response, especially in MIBC. These findings reveal promising biomarkers and mechanistic insights, offering a new perspective on predicting ICI response and opening up exciting possibilities for more personalized immunotherapy strategies in NSCLC and MIBC.
Association of the benzoxazinoid pathway with boron homeostasis in maize
Authors: Chu Liuyang , Shrestha Vivek , Schäfer Cay Christin , Niedens Jan , Meyer George W. , Darnell Zoe , Kling Tyler , Dürr-Mayer Tobias , Abramov Aleksej , Frey Monika , Jessen Henning , Schaaf Gabriel , Hochholdinger Frank , Nowak-Król Agnieszka , McSteen Paula , Angelovici Ruthie , Matthes Michaela S.
Published: October 2024

Both deficiency and toxicity of the micronutrient boron lead to severe reductions in crop yield. Despite this agricultural importance, the molecular basis underlying boron homeostasis in plants is not resolved. To identify molecular players involved in boron homeostasis in maize (Zea mays), we measured boron levels in the Goodman-Buckler association panel and performed genome-wide association studies. These analyses detected thebenzoxazinless(bx) gene,bx3, involved in the biosynthesis of benzoxazinoids, like DIMBOA, major defense compounds in maize. Genes involved in DIMBOA biosynthesis are all located in close proximity in the genome and the biosynthesis mutants, includingbx3are all DIMBOA deficient. We show that thebx3mutant has enhanced boron concentration in leaves compared to the B73 control plants, which correlates with enhanced leaf tip necrosis, a phenotype associated with boron toxicity. In contrast, other DIMBOA-deficient maize mutants did not show altered boron levels nor the leaf tip necrosis phenotype, suggesting that boron is not associated with DIMBOA. Instead, our analyses suggest that the accumulation of boron is linked to the benzoxazinoid intermediates indolin-2-one (ION) and 3-hydroxy-ION. Therefore, our results connect boron homeostasis to the benzoxazinoid plant defense pathway throughbx3and specific intermediates, rendering the benzoxazinoid biosynthesis pathway a potential target for crop improvement in inadequate boron conditions.

One sentence summary

GWAS identifiedbenzoxazinless3in the benzoxazinoid biosynthesis pathway to play a role in boron homeostasis in maize.