bluuebunny/crossref_metadata_2025 huggingface dataset:
P.088 Wounded glioma syndrome: neurologic worsening in patients with subtotal resection in high-grade gliomas
Authors: Ma C , Rizzuto M , Chen D , Fatehi Hassanabad M , Makarenko S
Published: May 2024

Background: For treatment of high-grade gliomas (HGGs), subtotal resection (STR) may be preferred to minimize injury to eloquent areas. We aimed to characterize neurologic deficits developed in STR patients within the first month post-operatively and to establish a potential threshold for a safe volume of residual tumor to avoid neurological worsening. Methods: This is a single institution retrospective chart review, with 146 charts reviewed and 78 patients deemed eligible. Preoperative deficits and postoperative neurological deficits presenting prior to 1 month after surgery were captured. Imaging features such as tumour volume, edema, and other pertinent imaging characteristics were collected from preoperative and postoperative imaging. Results: Most patients that developed a postoperative deficit presented with motor deficits (55.1%), while only 1.3% of patients developed new or worsening tremor after surgery. On average, in patients with a new deficit, 26.5% of tumor was resected, and all patients had more than 19% of residual tumor. Conclusions: Postoperative neurologic deficits may develop after a subtotal resection when an average of 73.5% of tumor remains. The proposed threshold for tumor resection is greater than 26.5% to minimize the potential of neurologic worsening 1 month postoperatively.
P.090 Third ventricular pituicytoma: case report and review of the literature
Authors: Hart S , Reddy K
Published: May 2024

Background: Pituicytoma is a rare, low grade tumour typically of the sellar region. Here we present a pituicytoma located in the third ventricle. Methods: 56 year old female presented with amenorrhea, hyperprolactinemia, and progressive bitemporal hemianopsia. MRI revealed a suprasellar mass located within the third ventricle and appearing separate from the pituitary. A supraciliary and translamina terminalis surgical approach to tumour resection was completed without complication. Post-operatively, she developed transient DI which resolved by post-opertaive day 3 and she was discharged hoem without any neurological deficits. Pathology revealed pituicytoma, WHO grade I. Results: Pituicytomas are rare tumours arising from neuroepithelial cells of the pituitary. The majority of cases are pure sellar or sellar with suprasellar extension, or at least have some connection to the pituitary. In many cases, imaging findings are synonymous to pituitary adenomas. We present a unique case in which the tumour was suprasellar but appeared separate from the pituitary. Surgical intervention is the most highly predictive factor of recurrence, as gross totoal reseciton can be curable. Conclusions: Here we present a unique location of pituictyoma. Due to the exceedingly rare nature of pituicytoma, unique presentations and management help to provide better understanding of the breadth of this disease presentation.
P.100 Plasma extracellular vesicle sampling from high grade gliomas demonstrates a small RNA signature indicative of disease and identifies lncRNA RPPH1 as a novel biomarker
Authors: Han J , Attwood K , Roy J , Weeks A
Published: May 2024

Background: High grade gliomas (HGGs) and cells of the tumour microenvironment secrete extracellular vesicles (EVs) into the plasma that contain genetic and protein cargo which function in paracrine signalling. Isolation of these EVs and their cargo could lead to an important tool that can inform on diagnosis and disease-course of HGGs. Methods: EVs were isolated using Vn96 capture from plasma obtained longitudinally from HGG patients. sRNA was enriched from the EVs, followed by next-generation sequencing, multidimensional scaling, differential expression, and in silico functional enrichment analyses. Results: Over 750 differentially expressed sRNA were identified between HGG and controls. Pathway analysis revealed miRNA highly enriched in both EV and HGG pathways demonstrating the validity of results in capturing a signal from HGG. Other sRNA included several novel HGG plasma-EV biomarkers including lncRNA RPPH1, RNY4, and RNY5. Furthermore, in paired longitudinal patient sampling, RPPH1 informed on surgical resection (decreased on resection) and importantly increased again with clinically defined progression. TCGA analysis demonstrated increased expression of RPPH1 in HGG tissue and additionally, higher expression of RPPH1 was associated with a worse disease-specific prognosis. Conclusions: The present study supports the role of plasma-EV sRNA sampling (and particularly RPPH1) as part of a multi-pronged approach to HGG disease course surveillance.
P.106 Using optic nerve sheath diameter over ventricular size to assess elevated intracranial pressure in pediatric patients with pineal region tumors
Authors: Zipfel J , Kerscher SR , Dhillon K , Ferraris KP , Feucht D , Weir A , Schuhmann MU , Singhal A
Published: May 2024

Background: Pineal region tumors are a heterogenous group of pathologies often symptomatic due to occlusive hydrocephalus leading to elevated intracranial pressure (ICP). High ICP may not always be associated with clinical signs. A non-invasive technique for assessment of ICP is measuring the optic nerve sheath diameter (ONSD). The goal of this study was to determine the utility of preoperative and postoperative ONSD measurements for assessment of elevated ICP in children with pineal region tumors. Methods: Retrospective data analysis was performed in patients operated for pineal region tumors at our tertiary care center between 2003 and 2022. Preoperative and postoperative MRI scans were reviewed. Clinical data and ONSD at multiple time points were analyzed and correlated. Results: Thirty-four patients with forty operative cases met the inclusion criteria. Hydrocephalus was seen in 80% of patients preoperatively (n=32/40). Presence of hydrocephalus was associated with significantly elevated ONSD preoperatively (p=0.006) and postoperatively (p=0.017). There was significant decrease in ONSD immediately postoperatively (p<0.001), at 3 months (p<0.001) and 12 months (p<0.001). In patients without hydrocephalus, no significant changes in ONSD were observed (p=0.369). Conclusions: ONSD is a useful adjunct for the identification of high ICP preoperatively and evaluation of treatment response postoperatively in patients presenting with pineal region tumors.
P.111 The surgeon experience of flow
Authors: McQueen SA , Mobilio M Hammond , McParland A , Sonnadara R , Moulton C
Published: May 2024

Background: Cognitive flow has been linked with enhanced performance, career satisfaction, and decreased burnout. However, while elite sport has long trained athletes to enter flow states, the concept has not been adopted strongly in healthcare. Flow has primarily been explored from a unidimensional (cognitive) perspective. The present study sought to understand the experience of flow among surgeons through a multidimensional lens. Methods: Using a constructivist grounded theory methodology, semi-structured interviews were conducted with 19 staff surgeons at the University of Toronto, purposively sampled. Data were coded and analyzed iteratively by three researchers until theoretical saturation was achieved. Results: Although many surgeons had not previously heard of cognitive flow, the phenomenon deeply resonated with most. Participants described different physical, cognitive, emotional, sociocultural, and environmental components that interacted to shape the subjective experience of flow: “I think that there are many different facets of [flow] that don’t always come together all at the same time, you may feel different parts of it… depending on what the kind of case is, who your help is, if you recently had a complication.” (P4) Conclusions: Understanding flow in clinical practice may lead to new avenues for enhancing career satisfaction and promoting physician wellness.
P.116 Days at home after traumatic brain injury: moving beyond mortality to evaluate patient-centered outcomes using population health data
Authors: Malhotra AK , Nathens AB , Shakil H , Jaffe RH , Essa A , Mathieu F , Badhiwala J , Thorpe K , Kulkarni AV , Witiw CD , Wilson JR
Published: May 2024

Background: Despite the utility of administrative health data, there remains a lack of patient-centered outcome measures to meaningfully capture morbidity after traumatic brain injury (TBI). We sought to characterize and validate days at home (DAH) as a feasible measure to assess population-level moderate to severe TBI (msTBI) outcomes and health resource utilization. Methods: We utilized linked health administrative data sources to identify adults with msTBI patients presenting to trauma centers in Ontario injured between 2009-2021. DAH at 180 days reflects the total number of days spent alive and at home excluding the days spent institutionalized in acute care, rehabilitation, inpatient mental health settings or post-acute readmissions. Construct and predictive validity were determined; we additionally estimated minimally important difference (MID) in DAH180days. Results: There were 6340 patients that met inclusion criteria. Median DAH180days were 70 days (interquartile range 0-144). Increased health resource utilization at baseline, older age, increasing cranial injury severity and major extracranial injuries were significantly associated with fewer DAH180days. DAH180days was correlated to DAH counts at 1-3 years. The average MID estimate from anchor-based and distribution-based methods was 18 days. Conclusions: We introduce DAH180days as a feasible and sufficiently responsive patient-centered outcome measure with construct, predictive and face validity in an msTBI population.
P.144 Comparative analysis of spinal cord-derived and induced pluripotent-derived neural stem & progenitor cells for SCI therapy
Authors: Sandarage RV , Galuta A , Tsai E
Published: May 2024

Background: Induced pluripotent stem cells (iPSCs) have revolutionized spinal cord injury (SCI) treatment by generating neural stem/progenitor cells (NSPCs). However, understanding how iPSC-derived NSPCs compare to authentic spinal cord NSPCs remains unclear. This study thoroughly characterizes bona fide spinal cord NSPCs and their isogenic iPSC-derived counterparts, iPSC-SC and iPSC-Br. Methods: Human spinal cord and skin tissue were obtained with ethics approval to establish primary NSPC cultures. iPSCs were derived from these primary cells and differentiated into iPSC-SC and iPSC-Br NSPCs. Assessments encompassed differentiation, proliferation capabilities, immunostaining, and RNA sequencing for differential gene expression. Results: Functional and transcriptional differences were identified between bona fide NSPCs and iPSC-SC/iPSC-Br. Bona fide and iPSC-SC NSPCs exhibited spinal cord regionalization, while iPSC-Br displayed forebrain regionalization. iPSC-derived NSPCs shared features reminiscent of early developmental stages, including embryonic patterning genes and increased proliferation rates. Notably, differentiation profiles were most similar between bona fide and iPSC-Br, with substantial distinctions observed between bona fide and iPSC-SC. Conclusions: This study unveils unique regional, developmental, and functional characteristics distinguishing spinal cord NSPCs from iPSC-derived counterparts. Addressing these disparities holds promise for enhancing iPSC-derived NSPC therapies in spinal cord injuries, contributing to a deeper understanding of their potential applications in regenerative medicine.
P.149 Saskatchewan spine pathway classification is associated with post-operative outcome and improved quality-adjusted life years following lumbosacral fusion
Authors: Ridha B , Liu E , Persad AR , Fourney DR
Published: May 2024

Background: Low back pain (LBP) is a common cause of disability and decreased quality of life. The Saskatchewan Spine Pathway classification (SSPc) is a method for triaging patients who are candidates for surgery. Methods: Consecutive patients who underwent lumbosacral instrumented fusion for degenerative spinal pathology from Jan 1, 2012, to Sept 20, 2018, by a single surgeon at our institution were retrospectively reviewed. Patients were stratified by SSPc into 4 groups based on pain pattern. Demographic and clinical data were collected. Outcomes were compared between cohorts both for absolute values and achieving MCID. Results: 169 consecutive patients were included in our study. After stratifying by SSPc grouping, there were 61 SSPc I patients, 45 SSPc III patients, and 63 SSPc IV patients. Patients in all groups had clinical improvement following surgery. Patients classified as SSPc III had superior outcomes in ODI, EQ-5D and EQ-VAS, and were more likely to achieve the MCID for ED-5D. Multivariate analysis demonstrated that SSPc grouping is an independent predictor of final VAS back, ODI, EQ-5D, and EQ-VAS as well as achieving the MCID for EQ-5D. Conclusions: The SSPc classification is associated with outcomes following lumbosacral fusion. In particular, patients with SSPc pattern 3 had better outcomes and improved QALY.
P.152 In-vivo accuracy of pedicle screws utilizing a supervisory controlled 7DOF robot with OCT guidance
Authors: Johnston R , Oppermann M , Yang V
Published: May 2024

Background: Pedicle screw fixation is an important technique in spine surgery. Violation of the pedicle can lead to neurovascular injury. Due to excellent pose repeatability, robotic technology may improve accuracy. Existing surgical spine robots use surgical assist architecture. This work explores the performance of a supervisory-control architecture robot (8i Robotics) for autonomous pedicle instrumentation. Methods: 3 porcine subjects underwent pedicle instrumentation utilizing the 7dof robot and were observed for 24 hours. Post-operative CT assessed screw location. Screws were graded clinically with the Gertzbein-Robbins Scale (GRS). Precision was assessed by a customized image processing pipeline. Euclidean error was calculated at screw head and screw tip. All points were normalized to a nominal screw, and confidence ellipses generated. Results: All animals were neurologically intact at 24 hours. All screws where GRS A. Mean tip and head Euclidean error where 2.47+/−1.25mm and 2.25+/-1.25mm respectively. Major and minor axes of the confidence ellipse at 99% was 2.19mm, and 1.28mm, and 2.07mm, and 0.42mm for tip and head respectively. Conclusions: 100% of screws obtained satisfactory clinical grading, with intact function in all animals post-operatively. This shows the capability of a supervisory-controlled 7DOF robot with OCT registration. Further investigation is warranted to further explore robotic capabilities, safety, and cost effectiveness.
GR.1 Standardized approach to direct first pass aspiration technique for endovascular thrombectomy: description and initial experience with CANADAPT
Authors: Macdonald IR , Linehan V , Sneek B , Volders D
Published: May 2024

Background: Endovascular thrombectomy (EVT) is standard of care for acute ischemic stroke. There is growing evidence that A Direct Aspiration first Pass Technique (ADAPT) is a safe, efficient and effective approach for EVT, offering several advantages. This study describes initial institutional experience in the use of a standardized aspiration only technique: CANADAPT. Methods: Single center prospective cohort study was performed on patients treated for large/medium vessel ischemic stroke. A sequential stepwise aspiration only technique was applied, CANADAPT, consisting of three maneuvers, A, B and C. The reperfusion success rate, number of passes, use of rescue technique, complication rate and procedural cost was determined. Results: 22 patients were included representing M1 (77%), M1/2 (9%), carotid-T (9%) and basilar (5%) occlusions. First pass recanalization was achieved in 50% of patients. A further 4 patients had successful reperfusion with a second pass (total 68% success). 7 patients had stent rescue technique (SOLUMBRA). Of these, 5 patients (22% of total) had successful reperfusion. The cost per procedure was $6,630 ± 1069 for CANADAPT, and $13,530 ± 2706 for SOLUMBRA. Conclusions: CANADAPT represents a standardized approach to aspiration only thrombectomy. This study demonstrates the safety, efficiency and efficacy of this technique in EVT.
GR.6 Meningioma molecular classification predicts response to surgery and adjuvant radiotherapy: an integrated clinicomolecular analysis & prospective validation
Authors: Wang JZ , Landry AP , Patil V , Liu J , Ajisebutu A , Cohen Gadol A , Wilson C , Almiron Bonnin DA , Yakubov R , Kaloti R , Holland EC , Tabatabai G , Tatagiba M , Barnholtz-Sloan J , Chotai S , Chambless LB , Horbinski C , Yip S , Sahm F , Aldape K , Nassiri F , Zadeh G
Published: May 2024

Background: Meningiomas are the most common intracranial tumor with surgery, dural margin treatment, and radiotherapy as cornerstones of therapy. Response to treatment continues to be highly heterogeneous even across tumors of the same grade. Methods: Using a cohort of 2490 meningiomas in addition to 100 cases from the prospective RTOG-0539 phase II clinical trial, we define molecular biomarkers of response across multiple different, recently defined molecular classifications and use propensity score matching to mimic a randomized controlled trial to evaluate the role of extent of resection, dural marginal resection, and adjuvant radiotherapy on clinical outcome. Results: Gross tumor resection led to improved progression-free-survival (PFS) across all molecular groups (MG) and improved overall survival in proliferative meningiomas (HR 0.52, 95%CI 0.30-0.93). Dural margin treatment (Simpson grade 1/2) improved PFS versus complete tumor removal alone (Simpson 3). MG reliably predicted response to radiotherapy, including in the RTOG-0539 cohort. A molecular model developed using clinical trial cases discriminated response to radiotherapy better than standard of care grading in multiple cohorts (ΔAUC 0.12, 95%CI 0.10-0.14). Conclusions: We elucidate biological and molecular classifications of meningioma that influence response to surgery and radiotherapy in addition to introducing a novel molecular-based prediction model of response to radiation to guide treatment decisions.
A.4 Neurological events following COVID-19 vaccination: does ethnicity matter?
Authors: Vyas MV , Chen R , Campitelli M , Odugbemi T , Sharpe I , Chu JY
Published: May 2024

Background: Neurological complications following vaccinations have been described before, but the rates of neurological complications, and their variation by ethnicity, following COVID-19 vaccine are not well-known. Methods: We conducted a population-based cohort study of Ontarians aged 18 years and over who received their first COVID-19 vaccine, and followed them for six weeks to estimate the incidence of neurological events, ascertained using validated case definitions based on ICD-10 codes. Ethnicity was defined using last name surname algorithm. We used multivariable logistic regression models, adjusting for age, sex, and vaccine-type to evaluate ethnic differences. Results: In the included 10,063,466 Ontario residents, incidence of GBS (n=72), CVST (n=52) and transverse myelitis (n=25) after first COVID-19 vaccine was rare. The crude rate of ischemic stroke (240/1,000,000 people) was the highest followed by Bell’s palsy (54/1,000,000). Compared to the general population, the adjusted odds of ischemic stroke and Bell’s palsy were lower in Chinese (aORBell’s 0.62; 0.39-0.98 and a ORischemic stroke 0.74; 0.59-0.91) and South Asians (aORBell’s 0.83; 0.52-1.31 and aORischemic stroke 0.84; 0.65-1.08). Conclusions: The incidence of neurological events following COVID-19 vaccine is low, and it varies by ethnicity. Our findings should encourage vaccination against COVID-19 in all ethnic groups.
C.3 Retrospective study of sulthiame in treatment of pediatric epilepsy
Authors: Laliberté A , Myers KA
Published: May 2024

Background: This retrospective study assessed the efficacy and tolerability of sulthiame as a treatment in children with epilepsy. In Canada, sulthiame is only available through Health Canada’s Special Access Program. Methods: Patients who received sulthiame at the Montreal Children’s Hospital from April 2012 to March 2023 were included. Patients’ medical charts were reviewed, and clinical data was extracted from neurology clinic notes and electroencephalogram (EEG) reports. Efficacy was assessed by comparing seizure frequency and frequency of EEG epileptiform abnormalities before and after initiating sulthiame, while also noting any reported changes in cognition or behaviour. Results: Sixteen patients were included (10 males, 6 females), all of whom had drug-resistant epilepsy and continuous spike-wave in sleep (CSWS) on EEG. Sulthiame starting dose ranged from 0.74 to 6.75 mg/kg/day. Improvement, either in terms of seizure control, cognition, or reduction in EEG epileptiform abnormalities, was reported in 8/16 children (50%). Two patients (13%) became seizure free, while three more (19%) had reduced seizure frequency. Three other patients (19%) had reported improvements in concentration, learning abilities or behaviour. No serious adverse event was reported. Conclusions: These data indicate that sulthiame is effective and well-tolerated in children with CSWS, regardless of the etiology and type of epilepsy.
C.5 Altered inflammatory profiles in critically ill children with neurologic involvement
Authors: Buttle SG , Martin D , Foster L , Woodward K , Esser MJ
Published: May 2024

Background: More than 1 in 4 children admitted to the pediatric ICU (PICU) have suspected neuroinflammation for a variety of reasons. While often beneficial, uncontrolled inflammation can lead to secondary neurologic injuries and interfere with repair mechanisms. Methods: A prospective cohort study was initiated at Alberta Children’s Hospital to evaluate neuroinflammation in children admitted to the PICU. Forty-eight cytokines, chemokines and growth factors collected at multiple pre-determined timepoints were analyzed along with data on clinical trajectory. Preliminary exploratory analyses of patients enrolled January 2022-July 2023 were completed. Results: Fifty-three patients were included in the initial analysis. Encephalopathy (18.9%), hypoxia (17%) and TBI (15.1%) were the most common reasons for enrollment. All groups had temporal alterations in serum cytokines, with primary inflammatory brain diseases having the highest levels of innate inflammation (cytokine storm) on admission and day one compared to other subgroups. There was a trend towards normalization of cytokine levels over time. Conclusions: Temporal profiling of cytokine levels can inform on neuroinflammatory pathways contributing to the clinical course in critically ill children. Further analysis is ongoing with the entire cohort to evaluate longitudinal and between-group differences. Improved understanding of altered neuroinflammatory pathways in this population may assist with rationalizing targeted immunotherapies to improve outcomes.
D.5 Low density scalp electrical source imaging of the ictal onset zone network using source coherence maps
Authors: Sadeghzadeh P , Thurairajah A , Freibauer A , RamachandranNair R , Whitney R , Jain P , Donner E , Al Nassar M , Jones KC
Published: May 2024

Background: This study investigates the utility of low-density scalp electrical source imaging (LD-ESI) of the Ictal Onset Zone (IOZ) and interictal spike ripple high frequency oscillation (ISRHFO) networks using Source Coherence Maps (SCM) in the surgical evaluation of children with medically refractory epilepsy. Invasive intracranial monitoring, the gold standard for determining epileptogenic zones, has limited spatial sampling. SCM presents a promising new non-invasive diagnostic technique. Methods: This was a retrospective review of 11 patients who underwent focal resections. SCMs were generated using Standardized Low Resolution Electromagnetic Tomography (sLORETA). SCM concordance to resection margins was assessed, noting outcomes at 3 years. Results: For 7/11 cases, ictal SCMs included the resection, and 5/7 achieved seizure freedom, indicating inclusion of the epileptogenic zone. For the 2/7 not seizure-free, the IOZ networks on the SCMs extended beyond resection margins, suggesting the epileptogenic zone also extended beyond the resection. Interictal spike ripple ESI and ISRHFO SCM were performed for 7/11, with 3/7 included in the resection and all 3 seizure-free. Conclusions: These findings may support LD-ESI of the IOZ and ISRHFO network using SCM as promising methods complementary to ictal and interictal ESI in pediatric epilepsy surgical workup, guiding electrode placement for intracranial monitoring to identify the epileptogenic zone.
Seasonal phenology and starch allocation patterns in populations of Oxycaryum cubense f. cubense and paraguayense in Mississippi, Louisiana, and Florida
Authors: Squires Allison C. , Wersal Ryan M. , Turnage Gray , Mudge Christopher R. , Sperry Benjamin P.
Published: May 2024

Phenological studies for Cuban bulrush [Oxycaryum cubense (Poepp. & Kunth) Lye] have been limited to the monocephalous form in Lake Columbus (Mississippi). Accordingly, there is little available information on potential phenological differences among O. cubense forms (monocephalous vs. polycephalous) and populations in other geographic locations in the United States. Therefore, seasonal patterns of biomass and starch allocation in O. cubense were quantified from two populations in Lake Columbus on the Tennessee-Tombigbee Waterway in Mississippi (monocephalous), two populations from Lake Martin in Louisiana (polycephalous), and two populations from Orange Lake in Florida (polycephalous). Monthly samples of O. cubense inflorescence, emergent, and submersed tissue were harvested from two plots per state from October 2021 to September 2022. During monthly data collection, air temperature and photoperiod were recorded. Starch allocation patterns were similar among all sites, with starch storage being less than 1.5% dry weight for all plant tissues. Biomass was greatest in Lake Columbus (monocephalous; 600.7 g dry weight [DW] m−2) followed by Lake Martin (polycephalous; 392.3 g DW m−2) and Orange Lake (polycephalous; 233.85 g DW m−2). Peak inflorescence biomass occurred in the winter for the Lake Martin and Orange Lake populations and in the summer for the Lake Columbus population. Inflorescence biomass in Lake Columbus had a positive relationship (r2 = 0.53) with warmer air temperatures. Emergent and submersed biomass generally had negative relationships with both photoperiod and temperature (r2 = 0.02 to 0.77) in all sites. Peak biomass was also negatively related to temperature and photoperiod. Results from this study indicate that there are differences in biomass allocation between the two growth forms of O. cubense and that growth can occur at temperatures below freezing. Low temperature tolerance may allow this species to expand its range farther north than previously suspected.
Partisanship, Cross-Party Coalitions, and Social Policymaking in Brazil
Authors: Alves Daniel H.
Published: May 2024

Brazil is among the few countries where income distribution has become fairer in recent decades. Its Gini coefficient fell significantly in the 2000s while the left-wing Workers’ Party government approved key equity-enhancing reforms in Congress. By analyzing hundreds of news pieces, legislative documents, and secondary sources, I show the strategies that incumbents from the left adopted to build and manage cross-party coalitions that allowed structural changes to materialize. This research is the first systematic effort to detail how three consequential redistributive policies in the areas of conditional cash-transfer programs, education, and minimum wages found their way through a fragmented legislature where the chief executive’s party was minoritarian. Findings add nuance to social policymaking and reveal that partisanship-based approaches to how inequality declined in Latin America require deeper complexification. In the Brazilian case, leftist presidents improved redistribution by investing in multiparty cooperative arrangements while ideology got diluted in the process.
THE MATHEMATICAL EXAMPLE OF GNOMONS IN ARISTOTLE, PHYSICS 3.4, 203a10–16
Authors: Salerno Lorenzo
Published: May 2024

This article examines a complex passage of Aristotle's Physics in which a Pythagorean doctrine is explained by means of a mathematical example involving gnomons. The traditional interpretation of this passage (proposed by Milhaud and Burnet) has recently been challenged by Ugaglia and Acerbi, who have proposed a new one. The aim of this article is to analyse difficulties in their account and to advance a new interpretation. All attempts at interpreting the passage so far have assumed that ‘gnomons’ should indicate ‘odd numbers’. In this article it is argued that the usage of ‘gnomon’ related to polygonal numbers, which is normally considered late, could be backdated to at least the fifth/fourth centuries b.c.; in particular, it explains the link between the philosophical explanandum and the mathematical explanans in Aristotle's passage.
“How Many Black Hippies Do You See?” The Counterculture in Black and White
Authors: RASMUSSEN CHRIS A.
Published: May 2024

Historians have treated the counterculture largely as a white phenomenon and drawn sharp boundaries between its escapism and the political engagement of the Black freedom struggle. A look at the counterculture's origins and growth in the late 1950s and the 1960s reveals that the counterculture intersected with Black culture in many ways. White beats, hipsters, and hippies generally admired the civil rights movement's support for equality and nonviolence, but sometimes scoffed at its effort to gain integration into American society. Hippies considered themselves outsiders from society and imagined that they shared affinity with Black Americans. Blacks’ responses to the counterculture ranged from contempt to curiosity to embrace. Some Blacks despised the hippies’ lifestyle and political apathy, but others considered the counterculture an important challenge to “the System.” American culture, style, literature, and music were all affected by the counterculture's experimentalism. The counterculture changed white culture, Black culture, and American culture. Drawing boundaries between cultural forms proves less instructive than focussing on the connections between them.
A double-blind, randomized, placebo-controlled plus open trial of adjunctive suvorexant for treatment-resistant insomnia in patients with bipolar disorder
Authors: Cafaro Rita , Macellaro Monica , Suppes Trisha , Dell’Osso Bernardo , Ketter Terence , Ostacher Michael , Miller Shefali , Chang Lauren , Lyu Jihun , Wang Po W.
Published: May 2024

Background

Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients.

Methods

Thirty-six BD outpatients (19 BDI, 69.4% female, 48.9 [±15.2] years) were randomized for 1 week to double-blind suvorexant (10–20 mg/day) versus placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for 3 months. Subjective total sleep time (sTST) and objective total sleep time (oTST) were assessed.

Results

During the randomized control trial (RCT) phase, an overall increase in the oTST emerged, which was statistically significant for the Cole–Kripke algorithm (p = 0.035). The comparison between the suvorexant and placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported.

Discussion

Efficacy results are inconsistent. During the RCT phase, only a small increase in the objective oTST emerged, while during the open phase, no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of dropouts limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.
Treading water: new data on the impact of AI ethics information sessions in classics and ancient language pedagogy
Authors: Ross Edward A. S. , Baines Jackie
Published: May 2024

Over 2023, many universities and policy organisations in the higher education (HE) sector are working to create guiding principles and guidelines for the use of generative artificial intelligence (AI) in HE Teaching and Learning (T&L). Despite these guidelines, students remain unsure if and how they should use AI. This article discusses the AI information sessions held over the Autumn 2023 term in the Department of Classics at the University of Reading, which aimed to provide students with the knowledge and tools to make informed judgements about using AI in their studies. These sessions discussed the benefits and drawbacks of generative AI, highlighting training data, content policy, environmental impact, and examples of potential uses. Staff and student participants were surveyed before and after these information sessions to gather their opinions surrounding AI use. Although at least 60% of participants had previously used generative AI, 80% of participants were apprehensive of or against using generative AI tools for learning purposes following the AI information sessions. By providing staff and students with the ethical considerations surrounding generative AI, they can make an informed judgement about using AI in their work without misplaced faith or excessive fear.
Natural Hazards in a Changing World: Methods for Analyzing Trends and Non‐Linear Changes
Authors: Vogel K. , Sieg T. , Veh G. , Fiedler B. , Moran T. , Peter M. , Rottler E. , Bronstert A.
Published: May 2024

Estimating the frequency and magnitude of natural hazards largely hinges on stationary models, which do not account for changes in the climatological, hydrological, and geophysical baseline conditions. Using five diverse case studies encompassing various natural hazard types, we present advanced statistical and machine learning methods to analyze and model transient states from long‐term inventory data. A novel storminess metric reveals increasing European winter windstorm severity from 1950 to 2010. Non‐stationary extreme value models quantify trends, seasonal shifts, and regional differences in extreme precipitation for Germany between 1941 and 2021. Utilizing quantile sampling and empirical mode decomposition on 148 years of daily weather and discharge data in the European Alps, we assess the impacts of changing snow cover, precipitation, and anthropogenic river network modifications on river runoff. Moreover, a probabilistic framework estimates return periods of glacier lake outburst floods in the Himalayas, demonstrating large differences in 100‐year flood levels. Utilizing a Bayesian change point algorithm, we track the onset of increased seismicity in the southern central United States and find correlation with wastewater injections into deep wells. In conclusion, data science reveals transient states for very different natural hazard types, characterized by diverse forms of change, ranging from gradual trends to sudden change points and from altered seasonality to overall intensity variations. In synergy with the physical understanding of Earth science, we gain important new insights into the dynamics of the studied hazards and their possible mechanisms.
E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer
Authors: Patterson Molly R. , Meijers Aniek S. , Ryder Emma L. , Wootton Louisa M. , Scarth James A. , Evans Debra , Turner Amy L. , Wasson Christopher W. , Darell Janne E. , Theobald Daisy A. , Cogan Joseph A. , James Claire D. , Wang Miao , Ladbury John E. , Morgan Iain M. , Samson Adel , Morgan Ethan L. , Macdonald Andrew
Published: May 2024

Human papillomaviruses (HPV) are a major cause of malignancy, contributing to ~5% of all human cancers worldwide, including most cervical cancer cases and a growing number of anogenital and oral cancers. The major HPV viral oncogenes, E6 and E7, manipulate many host cellular pathways that promote cell proliferation and survival, predisposing infected cells to malignant transformation. Despite the availability of highly effective vaccines, there are still no specific anti-viral therapies targeting HPV or treatments for HPV-associated cancers. As such, a better understanding of viral-host interactions may allow the identification of novel therapeutic targets. Here, we demonstrate that the actin-binding protein LASP1 is upregulated in cervical cancer and significantly correlates with a poorer overall survival. In HPV positive cervical cancer, LASP1 depletion significantly inhibited the oncogenic phenotype in vitro, whilst having minimal effects in HPV negative cervical cancer cells. Furthermore, we demonstrate that the LASP1 SH3 domain is essential for LASP1-mediated oncogenicity in these cells. Mechanistically, we show that HPV E7 regulates LASP1 at the post-transcriptional level by repressing the expression of miR-203, which negatively regulates LASP1 mRNA levels by binding to its 3’UTR. Finally, we demonstrate that LASP1 expression is required for the growth of HPV positive cervical cancer cells in an in vivo tumourigenicity model. Together, these data demonstrate that HPV induces LASP1 expression to promote proliferation and survival in cervical cancer, thus identifying a potential therapeutic target in these cancers.
DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure
Authors: Yan Mingjing , Gao Junpeng , Lan Ming , Wang Que , Cao Yuan , Zheng Yuxuan , Yang Yao , Li Wenlin , Yu Xiaoxue , Huang Xiuqing , Dou Lin , Liu Bing , Liu Junmeng , Cheng Hongqiang , Ouyang Kunfu , Xu Kun , Sun Shenghui , Liu Jin , Tang Weiqing , Zhang Xiyue , Man Yong , Sun Liang , Cai Jianping , He Qing , Tang Fuchou , Li Jian , Shen Tao
Published: May 2024

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.
Two distinct charge density waves in the quasi-one-dimensional metal Sr0.95NbO3.37 revealed by resonant soft X-ray scattering
Authors: Fauzi Angga Dito , Diao Caozheng , Whitcher Thomas J. , Lichtenberg Frank , Yang Ping , Breese Mark B. H. , Rusydi Andrivo
Published: May 2024

The interplay of electron-electron and electron-lattice interactions plays an important role in determining exotic properties in strongly correlated electron systems. Of particular interest is quasi-one-dimensional SrNbO
x
metals, which are perovskite-related layered Carpy-Galy phases. Quasi-one-dimensional metals often exhibit a charge density wave (CDW) accompanied by lattice distortion; however, to date, the presence of a CDW in a quasi-one-dimensional metallic Carpy-Galy phase has not been detected. Here, we report the discovery of two distinct and simultaneous commensurate CDWs in Sr0.95NbO3.37 using resonant soft X-ray scattering (RSXS), namely, an electronic-(001) superlattice below ~ 200 K and an electronic-(002) Bragg peak. We also observe a non-electronic-(002) Bragg peak showing lattice distortion below ~ 150 K. Through the temperature dependence and resonance profile of these CDWs and the lattice distortion, as well as the relationship between the wavelength and charge density, these CDWs are determined to be Wigner crystals and Peierls-like instabilities, respectively. The electron‒electron interaction is strong and dominant even up to 350 K, and upon cooling, it drives the electron–lattice interaction. The correlation length of the electronic-(001) superlattice is surprisingly larger than that of the electronic-(002) Bragg peak, and the superlattice is highly anisotropic. Supported by theoretical calculations, the CDWs are determined by the charge anisotropy and redistribution between the O-2p and Nb-4d orbitals, and the strength of the electronic-(001) superlattice is within the strong coupling limit.
Ocular injuries among patients with major trauma in England and Wales from 2004 to 2021
Authors: Bashir Mohammed Talha , Bouamra Omar , Kirwan James F. , Lecky Fiona E. , Bourne Rupert R. A.
Published: May 2024

Background

Ocular trauma is a significant cause of blindness and is often missed in polytrauma. No contemporary studies report eye injuries in the setting of severe trauma in the UK. We investigated ocular injury epidemiology and trends among patients suffering major trauma in England and Wales from 2004 to 2021.

Methods

We conducted a retrospective study utilising the Trauma Audit and Research Network (TARN) registry. Major trauma cases with concomitant eye injuries were included. Major trauma was defined as Injury Severity Score >15. Ocular injuries included globe, cranial nerve II, III, IV, and VI, and tear duct injuries. Orbital fractures and adnexal and lid injuries were not included. Demographics, injury profiles, and outcomes were extracted. We report descriptive statistics and 3-yearly trends.

Results

Of 287 267 major trauma cases, 2368 (0.82%) had ocular injuries: prevalence decreased from 1.87% to 0.66% over the 2004–2021 period (P < 0.0001). Males comprised 72.2% of ocular injury cases, median age was 34.5 years. The proportion of ocular injuries from road traffic collisions fell from 43.1% to 25.3% while fall-related injuries increased and predominated (37.6% in 2019/21). Concomitant head injury occurred in 86.6%. The most common site of ocular injury was the conjunctiva (29.3%). Compared to previous TARN data (1989–2004), retinal injuries were threefold more prevalent (5.9% vs 18.5%), while corneal injuries were less (31.0% vs 6.6%).

Conclusions

Whilst identifying eye injuries in major trauma is challenging, it appears ocular injury epidemiology in this setting has shifted, though overall prevalence is low. These findings may inform prevention strategies, guideline development and resource allocation.
Heterogeneity in strategy use during arbitration between experiential and observational learning
Authors: Charpentier Caroline J. , Wu Qianying , Min Seokyoung , Ding Weilun , Cockburn Jeffrey , O’Doherty John P.
Published: May 2024

To navigate our complex social world, it is crucial to deploy multiple learning strategies, such as learning from directly experiencing action outcomes or from observing other people’s behavior. Despite the prevalence of experiential and observational learning in humans and other social animals, it remains unclear how people favor one strategy over the other depending on the environment, and how individuals vary in their strategy use. Here, we describe an arbitration mechanism in which the prediction errors associated with each learning strategy influence their weight over behavior. We designed an online behavioral task to test our computational model, and found that while a substantial proportion of participants relied on the proposed arbitration mechanism, there was some meaningful heterogeneity in how people solved this task. Four other groups were identified: those who used a fixed mixture between the two strategies, those who relied on a single strategy and non-learners with irrelevant strategies. Furthermore, groups were found to differ on key behavioral signatures, and on transdiagnostic symptom dimensions, in particular autism traits and anxiety. Together, these results demonstrate how large heterogeneous datasets and computational methods can be leveraged to better characterize individual differences.
Tunnel junctions based on interfacial two dimensional ferroelectrics
Authors: Gao Yunze , Weston Astrid , Enaldiev Vladimir , Li Xiao , Wang Wendong , Nunn James E. , Soltero Isaac , Castanon Eli G. , Carl Amy , De Latour Hugo , Summerfield Alex , Hamer Matthew , Howarth James , Clark Nicholas , Wilson Neil R. , Kretinin Andrey V. , Fal’ko Vladimir I. , Gorbachev Roman
Published: May 2024

Van der Waals heterostructures have opened new opportunities to develop atomically thin (opto)electronic devices with a wide range of functionalities. The recent focus on manipulating the interlayer twist angle has led to the observation of out-of-plane room temperature ferroelectricity in twisted rhombohedral bilayers of transition metal dichalcogenides. Here we explore the switching behaviour of sliding ferroelectricity using scanning probe microscopy domain mapping and tunnelling transport measurements. We observe well-pronounced ambipolar switching behaviour in ferroelectric tunnelling junctions with composite ferroelectric/non-polar insulator barriers and support our experimental results with complementary theoretical modelling. Furthermore, we show that the switching behaviour is strongly influenced by the underlying domain structure, allowing the fabrication of diverse ferroelectric tunnelling junction devices with various functionalities. We show that to observe the polarisation reversal, at least one partial dislocation must be present in the device area. This behaviour is drastically different from that of conventional ferroelectric materials, and its understanding is an important milestone for the future development of optoelectronic devices based on sliding ferroelectricity.
Convergent evolution of fern nectaries facilitated independent recruitment of ant-bodyguards from flowering plants
Authors: Suissa Jacob S. , Li Fay-Wei , Moreau Corrie S.
Published: May 2024

Plant–herbivore interactions reciprocally influence species’ evolutionary trajectories. These interactions have led to many physical and chemical defenses across the plant kingdom. Some plants have even evolved indirect defense strategies to outsource their protection to ant bodyguards by bribing them with a sugary reward (nectar). Identifying the evolutionary processes underpinning these indirect defenses provide insight into the evolution of plant-animal interactions. Using a cross-kingdom, phylogenetic approach, we examined the convergent evolution of ant-guarding nectaries across ferns and flowering plants. Here, we discover that nectaries originated in ferns and flowering plants concurrently during the Cretaceous, coinciding with the rise of plant associations in ants. While nectaries in flowering plants evolved steadily through time, ferns showed a pronounced lag of nearly 100 My between their origin and subsequent diversification in the Cenozoic. Importantly, we find that as ferns transitioned from the forest floor into the canopy, they secondarily recruited ant bodyguards from existing ant-angiosperm relationships.