bluuebunny/crossref_metadata_2025 huggingface dataset:
72224 - Characteristics and management of locally advanced breast cancer – a retrospective register study from Breast Cancer DataBase Sweden (BCBaSe) 3.0
Authors: Waller Elisabet , Wennstig Anna-Karin , Garmo Hans , Nilsson Greger , Karlsson Per , Fredriksson Irma , Wadsten Charlotta
Published: August 2024

Introduction

Locally advanced breast cancer (LABC) refers to large primary breast tumours (T3), tumours of any size with chest wall/skin involvement (T4), and/or extensive lymph node involvement (N2-3). LABC may be a consequence of delayed presentation or aggressive tumour biology. The aim of the study was to explore patient characteristics, treatment, and time trends of LABC in a Swedish population-based cohort.

Method

The study cohort was retrieved from BCBaSe 3.0 including 94 271 patients with invasive breast cancer diagnosed 2008-2019 after exclusion of those with distant metastasis at diagnosis or within 3 months. Comparisons were made between non-LABC (T0-2N0-1) and LABC subcategorized by T-stage (T≥3) and N-stage (N≥2).

Result

Of all BC, 6565 (7.0 %) were LABC, with a fairly constant proportion over time. A higher proportion of LABC was seen both among the youngest (<40 y; 11.9 %) and among the oldest (80+ y; 15.7 %), and in those with a low level of education (9.5 %). Lobular BC was overrepresented among LABC (16.0 % vs 11.1 % in non-LABC), as were the Her2-positive (17.3 % vs 10.2 %) and triple-negative subtypes (11.0 % vs 7.3 % in non-LABC). On average, 47.2 % of LABC underwent primary surgery, 44.2 % received neoadjuvant treatment ranging from 26.7 % for T0-2N2 to 83.0 % for inflammatory BC, whereas 8.6 % received no treatment. Of those undergoing neoadjuvant treatment, 71.8 % proceeded to surgery.

Discussion

LABC encompasses a wide range of tumours, comprising both primarily operable and non-operable tumours, with notable distinctions observed between different subgroups of LABC.
72301 - Breast cancer recurrence detection in relation to surveillance - applications on personalized follow-up
Authors: Sartor Hanna , Hagberg Oskar , Hemmingsson Oskar , Lång Kristina , Wadsten Charlotta
Published: August 2024

Introduction

The effectiveness of current follow-up guidelines after breast cancer (BC) treatment is uncertain. A tailored surveillance according to patient age and tumour characteristics may be more adequate. The aim of this study was to assess the frequency of and the risk factors for detection of ipsilateral locoregional recurrences (LR) and second primary breast cancers (SP) outside of scheduled surveillance in patients with recurrent BC.

Method

Patients with surgically treated stage I-III BC from Malmö Diet and Cancer Study (MDCS) 1991-2014 (n=1095) and region Västernorrland 2009-2018 (n=1930) were included. Data on the index BC and recurrences were retrieved from medical records. Recurrent events were defined as symptomatic when detected at a patient-initiated visit or breast imaging outside of scheduled annual mammography surveillance.

Result

Median follow-up time was 6.5 years (Interquartile range: 3.8-10.0). In total, 262 patients had a relapse. The most common first event was distant metastasis (46%) followed by LR (22%) and SP (18%). Fifty-four per cent of LR and 27 % of SP were detected outside of scheduled surveillance. Logistic regression analysis showed that lymph node positive BC (HR 2.12; 95%CI, 1.00-4.60), BC of HER2 positive subtype (HR 5.13; 95%CI, 1.37-25.32) and young age (HR 2.25; 95%CI, 0.98-5.47) were associated with increased probability of having a symptomatically detected recurrence.

Discussion

Most recurrent events are detected outside of scheduled surveillance. Risk-based tailored surveillance might be more appropriate for subsets of patients.
72309 - Postoperative complications after breast cancer surgery and effect on recurrence and survival – a large population-based cohort study
Authors: Adwall Linda , Fredriksson Irma , Hultin Hella , Mani Maria , Norlén Olov
Published: August 2024

Introduction

This study aimed to assess the risk of systemic breast cancer recurrence after surgical site infection (SSI) and also the impact of SSI on locoregional recurrence, overall survival (OS), and breast cancer-specific survival (BCSS).

Method

This nationwide cohort study included patients who underwent surgery for primary breast cancer in Sweden between January 2008 and September 2019. The study cohort was identified in BCBaSe 3.0, a database linking the National Breast Cancer Quality Register to national population-based health care registers held by the National Board of Health and Welfare and Statistics Sweden. The primary exposure was SSI within 90 days from surgery, and the primary outcome was systemic recurrence of breast cancer. Secondary outcomes included locoregional recurrence, OS and BCSS. Multivariable Cox regression analysis was performed to assess the association between exposure, predictors and outcomes.

Result

Of the 82 102 patients included in the study, 15.7% experienced an SSI within 90 days from surgery. SSI was not significantly associated with systemic recurrence, locoregional recurrence or BCSS after adjustment for confounding variables. SSI was significantly associated with worse OS, but the significant association disappeared in a sensitivity analysis excluding all patients with any kind of malignancy before breast cancer diagnosis.

Discussion

SSI does not significantly increase the risk of systemic recurrence. But still, it is important to strive to reduce complications after breast cancer surgery.
71935 - Endoscopic screening for anal high grade squamous intraepithelial dysplasia in HIV-positive men who have sex with men
Authors: Borch-Johnsen Peter , Schmidt Peter Thelin , Filén Finn , Storgärd Elisabet , Nygren Jonas
Published: August 2024

Introduction

Anal Squamous Intraepithelial Lesions (ASIL) are precursors to anal cancer. The highest risk is found in HIV-positive men having sex with men (MSM). The aim of the study is to evaluate flexible endoscopy as a screening method for ASIL.

Method

304 HIV-positive MSM were included. At inclusion, anal samples were taken for HPV-PCR, cytology, chlamydia and gonorrhea. Previous chlamydia/gonorrhea infections, smoking habits, years with HIV, nadir CD4 count, initiation of antiretroviral therapy, previous ASIL/condyloma and symptoms from the anal canal were collected. A diagnostic endoscopy was performed using underwater technique. Number of lesions and morphology were documented. Detected lesions were removed with diathermy-snare after submucosal injection of lidocaine in un-anesthetized patients.

Result

Presently, we have performed anal endoscopy in 283 individuals. Macroscopic lesions were found in 230 cases (81%). Endoscopic resection in 189 cases with findings of one case (0,5 %) of squamous cell carcinoma, surgical R0 resection, no oncologic treatment necessary. 74 patients (39 %) with HSIL, 47 (25%) with LSIL, 7 (4 %) indeterminate for LSIL/HSIL and 60 (32 %) without dysplasia. Swabs for cytology had a sensitivity for SCC/HSIL of 12%, specificity of 50% and for HPV-PCR a sensitivity for SCC/HSIL of 61%, specificity of 42%.Possible correlation with nadir CD4, duration of HIV infections, tobacco use, and number of previous anal chlamydia/gonorrhea remain to be analyzed.

Discussion

Preliminary data from a still ongoing study indicate that flexible endoscopy is useful for screening high-risk individuals and for resection of dysplastic lesions. Anal cytology did not meet our expectations but HPV-PCR showed a more promising result.
71635 - Can prediction models aid in the process of selecting treatment for hyperthyroidism?
Authors: Mauritzson Daniel , Sjölin Gabriel , Persson Andreas
Published: August 2024

Introduction

Hyperthyroidism (HT) is treated with antithyroid drugs, radioactive iodine, or surgery. Previous studies have demonstrated that many patients undergo repeated treatment without remission and have impaired quality of life 6-10 years after diagnosis. This study aimed to evaluate different predictive machine learning models as a means of support in selecting treatment for HT.

Method

The study is based on a dataset of 2916 newly diagnosed HT patients between 2003-2005, who later were invited to participate in a 6-10 year follow-up study. This dataset underwent standard preprocessing for data representation and preparation for learning algorithms. Large Language Models were assessed as an alternative to encode medical records into sentence embeddings. Various regression models were trained and evaluated to predict the probability of a successful treatment based on nine features (Age, Sex, Diagnosis, thyroid-stimulating hormone receptor antibodies, T4-levels, TRAb (reference), TRAb (corrected), TRAb (positive), Thyroid-associated Ophthalmopathy.

Result

Two different multi-output regression models were trained and evaluated for each pre-processed dataset: Gradient-Boosting (GB) and Random Forest (RF). Root Mean Squared Error (RMSE) and the coefficient of determination, R2 score, were measured for evaluation metrics. RF trained on the traditionally pre-processed dataset showed best result, RMSE 0.1764 and R2 score 0.1460. However, the differences between both evaluated models and the approach in data preparation were negligible.

Discussion

This study show promising results in using prediction models for assessing the probability of successful treatment in individual patients. Further investigation is necessary regarding the choice of prediction models and how the data are prepared and represented.
Effect of short-term intensive design-based STEM learning on executive function: an fNIRS study of the left-behind children
Authors: Ding Keya , Wu Dandan , Shen Yining , Cao Simin , Liu Qianming , Wan Zhihong , Li Hui
Published: August 2024

Design-based STEM learning is believed to be an effective cross-disciplinary strategy for promoting children’s cognitive development. Yet, its impact on executive functions, particularly for disadvantaged children, still need to be explored. This study investigated the effects of short-term intensive design-based STEM learning on executive function among left-behind children. Sixty-one Grade 4 students from a school dedicated to the left-behind children in China were sampled and randomly assigned to an experimental group (10.70 ± 0.47 years old, n = 30) or a control group (10.77 ± 0.43 years old, n = 31). The experimental group underwent a two-week design-based STEM training program, while the control group participated in a 2-week STEM-related reading program. Both groups were assessed with the brain activation from 4 brain regions of interest using functional near-infrared spectroscopy (fNIRS) and behavioral measures during a Stroop task before and after the training. Analysis disclosed: (i) a significant within-group time effect in the experimental group, with posttest brain activation in Brodmann Area 10 and 46 being notably lower during neutral and word conditions; (ii) a significant between-group difference at posttest, with the experimental group showing considerably lower brain activation in Brodmann Area 10 and Brodmann Area 46 than the control group; and (iii) a significant task effect in brain activity among the three conditions of the Stroop task. These findings indicated that this STEM learning effectively enhanced executive function in left-behind children. The discrepancy between the non-significant differences in behavioral performance and the significant ones in brain activation implies a compensatory mechanism in brain activation. This study enriches current theories about the impact of Science, Technology, Engineering, and Mathematics (STEM) learning on children’s executive function development, providing biological evidence and valuable insights for educational curriculum design and assessment.
Treatment Outcomes Among Patients With a PositiveCandidaCulture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study
Authors: Soriano Alex , Honore Patrick M , Cornely Oliver A , Chayakulkeeree Methee , Bassetti Matteo , Haihui Huang , Dupont Hervé , Kim Young Keun , Kollef Marin , Kullberg Bart Jan , Manamley Nick , Pappas Peter , Pullman John , Sandison Taylor , Dignani Cecilia , Vazquez Jose A , Thompson George R
Published: August 2024

Background

Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE.

Methods

ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included day 30 ACM, day 14 global cure rate, and day 5 and 14 mycological response. Adverse events were evaluated.

Results

This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively, day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval], 4.6% [−13.7%, 23.5%]), day 14 global response was 55.3% and 50.0% (between-group difference, 5.3% [−16.1%, 26.0%]), and day 5 mycological eradication was 71.1% and 50.0% (between-group difference, 21.1% [−0.2%, 40.2%]). Safety was comparable between treatments.

Conclusions

These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.
A Comparative Analysis of Clinical Symptoms and Modified Pouchitis Disease Activity Index Among Endoscopic Phenotypes of the J Pouch in Patients With Inflammatory Bowel Disease
Authors: Akiyama Shintaro , Cohen Nathaniel A , Ollech Jacob E , Traboulsi Cindy , Rodriguez Tina , Rai Victoria , Glick Laura R , Yi Yangtian , Runde Joseph , Cohen Russell D , Skowron Kinga B , Hurst Roger D , Umanskiy Konstantin , Shogan Benjamin D , Hyman Neil H , Rubin Michele A , Dalal Sushila R , Sakuraba Atsushi , Pekow Joel , Chang Eugene B , Rubin David T
Published: August 2024

Background

The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD).

Methods

We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal (n = 25), afferent limb (AL) involvement (n = 4), inlet involvement (n = 14), diffuse (n = 7), focal inflammation of the pouch body (n = 25), cuffitis (n = 18), and pouch-related fistulas (n = 10) with a single phenotype were included. Complete-case analysis was conducted.

Results

One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%).

Conclusions

We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization.
An acute coronary syndrome in an unusual patient: analysing cisplatin toxicity—a case report and review of the literature
Authors: Erquicia Peralt Josu , Fernandez Gonzalez Luis , Garcia San Román Koldobika , Astorga Burgo Juan Carlos , Acín Labarta Aida
Published: August 2024

Background

Germ cell tumours (GCT) are the most common malignancy affecting young adult men. The introduction of cisplatin-based chemotherapy in recent decades has significantly changed the prognosis of these malignant tumours into highly curable cancer, even in the setting of advanced disease. However, in the last decade, the success of these chemotherapy regimens in curing GCTs has been slowed by a growing recognition of their important late toxicities, such as cardiovascular disease.

Case summary

We present the case of a 23-year-old male, recently diagnosed with a mixed non-seminomatous testicular germinal tumour, on stage IIIA (pT3 cN2 cM1a), with retroperitoneal adenopathies and pulmonary metastases. After performing a right inguinal orchiectomy, he started chemotherapy treatment with cisplatin + etoposide. Shortly after starting treatment, the patient presented an ST-elevation acute coronary syndrome. The cardiac catheterization revealed a non-occlusive thrombus in the middle segment of the right coronary artery. Intracoronary imaging techniques were used to study the arterial wall, which revealed the presence of atherosclerotic plaque that could have ruptured, with the consequent response of platelet aggregation and thrombus formation. Barely 7 months after this event, the patient was again admitted to hospital for pulmonary thromboembolism with pulmonary infarction.

Discussion

To date, there are two hypotheses linking the association between cisplatin-based chemotherapy and cardiovascular disease. The direct hypothesis argues for the presence of direct chemotherapy-induced vascular damage. The indirect hypothesis, on the other hand, is based on the induction and development of cardiovascular risk factors by chemotherapy. This cardiovascular toxicity of chemotherapy is aggravated by a cancer-induced proinflammatory and prothrombotic state.
Towns and Princely Rebellion in Fifteenth-Century France: The War of the Public Weal, 1465
Authors: Murphy Neil
Published: August 2024

The historiography of fifteenth-century France overwhelmingly finds that towns worked with the monarchy against rebellious princes in pursuit of a centralised royal state. Focusing on the War of the Public Weal of 1465, this article demonstrates instead that urban communities played a central role in the rebellion and that there was considerable urban support for the league. This evidence suggests both that we need to re-evaluate the view that the princes lacked popular support in their rebellions against the Crown in fifteenth-century France and that we need to reconsider the current model of town–Crown relations. The article begins by highlighting regional patterns of support for the king and the princes during the war, before moving on to examine ideology and the reasons why towns favoured one side over the other. It then goes on to consider what townspeople hoped to gain from their actions during the War of the Public Weal, taking particular account of the presence of urban factions and the competition for urban privileges. A study of urban participation in the War of the Public Weal thus contributes to debates on the wider narratives of European state formation in the later Middle Ages, when increasingly powerful monarchs sought to break the power of their overmighty subjects by co-opting urban populations to join their cause, and highlights the ongoing limitations of French royal power at the end of the Middle Ages.
Overexpression of TIAM2S, a Critical Regulator for the Hippocampal–Medial Prefrontal Cortex Network, Progresses Age-Related Spatial Memory Impairment
Authors: Chu Chun-Hsien , Su Chia-Hao , Hsiao Ya-Hsin , Yu Chun-Chieh , Liao Yi-Chun , Mao Pin-Cheng , Chen Jia-Shing , Sun H Sunny
Published: August 2024

TIAM Rac1-associated GEF 2 short-form protein (TIAM2S) is abundant in specific brain tissues, especially in the hippocampus, a brain region critical for processing and consolidation of spatial memory. However, how TIAM2S plasticizes the microstructure and circuits of the hippocampus to shape spatial memory as a neuroplastic regulator during aging remains to be determined. In this study, transgenic mice overexpressing human TIAM2S protein (TIAM2S-TG mice) were included, and interdisciplinary approaches, such as spatial memory tests and multiparametric magnetic resonance imaging sequences, were conducted to determine the role and the mechanism of TIAM2S in age-related spatial memory deficits. Despite no changes in their neural and glial markers and neuropathological hallmark expression of the hippocampus, behavioral tests showed that the TIAM2S-TG mice, and not wild-type (WT) mice, developed spatial memory impairment at 18 months old. The T2-weighted and diffusion tensor image analyses were performed to further study the possible role of TIAM2S overexpression in altering the hippocampal structure or neuronal circlets of the mice, increasing their vulnerability to developing spatial memory deficits during aging. The results revealed that the 12-month-old TIAM2S-TG mice had hippocampal dysplasticity, with larger volume, increased fiber numbers, and changed mean fractional anisotropy compared to those in the age-matched WT mice. The fiber tractography analysis exhibited significantly attenuated structural connectivity between the hippocampus and medial prefrontal cortex in the TIAM2S-TG mice. In conclusion, overexpression of TIAM2S, a detrimental factor affecting hippocampus plasticity, causes attenuation of the connectivity within hippocampus–mPFC circuits, leading to age-related spatial memory impairment.
Effect of Hearing Intervention Versus Health Education Control on Fatigue: A Secondary Analysis of the ACHIEVE Study
Authors: Bessen Sarah Y , Zhang Wuyang , Huang Alison R , Arnold Michelle , Burgard Sheila , Chisolm Theresa H , Couper David , Deal Jennifer A , Faucette Sarah P , Goman Adele M , Glynn Nancy W , Gmelin Theresa , Gravens-Mueller Lisa , Hayden Kathleen M , Mitchell Christine M , Pankow James S , Pike James R , Reed Nicholas S , Sanchez Victoria A , Schrack Jennifer A , Sullivan Kevin J , Coresh Josef , Lin Frank R , Martinez-Amezcua Pablo ,   for the ACHIEVE Collaborative Research Group
Published: August 2024

Background

Fatigue is a common complaint among older adults with hearing loss. The impact of addressing hearing loss on fatigue symptoms has not been studied in a randomized controlled trial. In a secondary analysis of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study, we investigated the effect of hearing intervention versus health education control on 3-year change in fatigue in community-dwelling older adults with hearing loss.

Methods

Participants aged 70–84 years old with untreated hearing loss recruited across 4 study sites in the United States (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; Washington County, Maryland) were randomized (1:1) to hearing intervention or health education control and followed for 3 years. Three-year change in fatigue symptoms was measured by 2 instruments (RAND-36 and PROMIS). We estimated the intervention effect as the difference in the 3-year change in fatigue between intervention and control groups using a linear mixed-effects model under the intention-to-treat principle.

Results

Participants (n = 977) had a mean age (SD) of 76.8 (4.0) years, were 53.5% female and 87.8% White. Over 3 years, a beneficial effect of the hearing intervention versus health education control on fatigue was observed using the RAND-fatigue score (β = −0.12 [95% CI: −0.22, −0.02]). Estimates also suggested beneficial effect of hearing intervention on fatigue when measured by the PROMIS-fatigue score (β = −0.32 [95% CI: −1.15, 0.51]).

Conclusions

Our findings suggest that hearing intervention may reduce fatigue over 3 years among older adults with hearing loss.
Catecholaminergic Modulation of Metacontrol Is Reflected by Changes in Aperiodic EEG Activity
Authors: Gao Yang , Roessner Veit , Stock Ann-Kathrin , Mückschel Moritz , Colzato Lorenza , Hommel Bernhard , Beste Christian
Published: August 2024

Background

“Metacontrol” describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and modulate cortical noise.

Methods

In a double-blind, randomized, placebo-controlled study design, we investigated the effect of MPH (0.5 mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the fitting oscillations and one over f algorithm.

Results

Compared with placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in 2 ways. First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control.

Conclusions

Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise, fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment.
Do Foreign Military Deployments Provide Assurance? Unpacking the Micro-Mechanisms of Burden Sharing in Alliances
Authors: Sorg Alexander , Wucherpfennig Julian
Published: August 2024

How do US foreign military deployments impact the defense policies of host states? Dominant scholarship holds that these deployments play a pivotal role in assuring allies that their security is guaranteed, which in turn leads host countries to neglect their national defense contributions. In this research note, we examine the micro-foundations of this conventional wisdom, investigating how nuclear and conventional troop deployments impact attitudes toward defense policies in (potential) host states. We highlight that the presumed linkage between assurance and free-riding critically implies that foreign military deployments must positively affect perceptions of security among host nations. We test this core logic, alongside some alternative pathways, at the micro level through two survey experiments that randomize hypothetical withdrawals (Germany) and deployments (Czech Republic). Although we find some evidence that foreign military deployments can decrease citizens’ subjective need for defense, the survey experiments also reveal that citizens hardly feel protected by these deployments. Thus, our results cast doubt on the core logic underlying the theory of free-riding in alliances.
Phenotypic and molecular characterization of Streptococcus pneumoniae serotype 3 isolates from blood and respiratory samples in Canada: CANWARD 2007–21
Authors: Schellenberg John J , Adam Heather J , Baxter Melanie R , Karlowsky James A , Golden Alyssa R , Martin Irene , Zhanel George G
Published: August 2024

Background

Lower respiratory infections and invasive disease caused by Streptococcus pneumoniae serotype 3 remain major clinical challenges around the world, despite widespread availability of updated vaccines.

Methods

As part of CANWARD, antimicrobial susceptibility testing and serotyping were performed on all S. pneumoniae isolates from 2007 to 2021. A subset of 226/264 (85.6%) serotype 3 isolates were selected for WGS to determine sequence type (ST)/clonal cluster (CC) and correspondence of antimicrobial resistance determinants (erm, mefAE, tetM, cat, folA, folP) with resistance phenotype.

Results

Of the 3,039 S. pneumoniae isolates obtained from 2007 to 2021, 8.7% (n = 264) were serotype 3, with 64.0% of respiratory origin and 36.0% from blood. Of 226 sequenced serotype 3 isolates, 184 (81.4%) were ST180 (GPSC12). The proportion of ST8561 (single locus variant of ST180) increased from 7.2% to 16.6% during the study period. An increasing proportion of serotype 3 isolates had phenotypic resistance (P = 0.0007) and genetic resistance determinants (P = 0.004), comparing 2017–21 to 2007–11, largely due to a recently expanded ST180 clade with cat, tetM and mef determinants.

Conclusions

S. pneumoniae serotype 3 from GPSC12 continues to dominate throughout Canada, with an increase in the proportion of ST8561. The proportion of serotype 3 isolates that are phenotypically resistant and with genetic resistance determinants is increasing over time, reflecting a global increase in GPSC12 genotypes with known resistance determinants. Phylogenomic characterization of isolates collected over time and from around the world may facilitate improved treatment and enhanced prevention strategies, including new vaccines with activity against S. pneumoniae serotype 3.
Evaluation of the In2Care Mosquito Station at low deployment density: a field study to manage Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae) in North Central Florida
Authors: McNamara Timothy D , Vargas Nicole , McDuffie Decyo , Bartz Cason E , Mosore Mba-tihssommah , Kline Daniel L , Buckner Eva A , Jiang Yongxing , Martin Estelle M
Published: August 2024

In the last 2 decades, there has been an increase in the geographic range and frequency of vector-borne diseases. Management of mosquito populations has become challenging due to increasing rates of resistance to existing insecticidal products and formulations. Several alternative tools have emerged to suppress or replace mosquito populations. One of these tools is the In2Care Mosquito Station (In2Care station). This dual-action station contains the insect growth regulator pyriproxyfen which disrupts the development of immatures and the entomopathogenic fungus Beauveria bassiana (B. bassiana) strain GHA which kills exposed adult mosquitoes. The In2Care stations have previously been shown to effectively control Aedes aegypti in field settings at a density of 6 stations/acre rather than the label-recommended 10 stations/acre. To further test the efficacy of low station density deployment, we deployed In2Care stations in the Pleasant Street Historic District of Gainesville, Florida, at a density of 3 stations/acre over a period of 2 years in the presence or absence of ground larvicidal applications. The deployment of stations resulted in no measurable impact on Ae. aegypti and Culex quinquefasciatus adult or immature abundance suggesting that the low-density deployment of In2Care stations is insufficient to reduce Ae. aegypti and Cu. quinquefasciatus abundance within treatment areas.
Typographic Hegemony and Bibliographical Monoculture: The Ascendancy of Mechanical Print in Modern Korea
Authors: Cho Hwisang
Published: August 2024

This article explores how “Western” mechanical printing figured prominently in the expansion of imperialists’ interests in turn-of-the-twentieth-century Korea as both the main technological imperative and the hegemonic discourse. Negotiating and compromising with the native practices and deep history of print in Korea, the implantation of industrial printing fundamentally transformed the country’s literary cultures and epistemology. All participants in this change—Christian missionaries, Japanese colonizers, and Korean intellectuals—contributed to the domination of typography that gave rise to the circulation of printed matter on an unprecedented scale, which brought about the wide usage of the easy Korean alphabet and expanded readership even by women and nonelites. The discourse centering on typography as the symbol of modernity and progress also led the imperialists to redefine and recategorize Korean antiquarian books. The practices and projects that developed, such as Japanese collectors’ cannibalization of Korean books to put together imperial albums or binding Korean editions in Western styles, mirrored the colonial body politics that rendered the colonized inferior subjects in the material dimension. Typographic domination was vital to imperialists’ expansion in Korea not simply because it helped disseminate their ideas to Korean readers but also because it subordinated Korean written culture to the one introduced by the imperialist powers. More important, the typographic domination engineered by Japanese colonialists became so naturalized as to continue and shape the field of bibliography in postcolonial Korea, in what can be best described as bibliographical monoculture.
Afterword
Authors: Hunter Emma
Published: August 2024

What is at stake in exploring colonialism and print from the perspective of social history? This collection of articles shows how a social history perspective can tie together people, places, and themes that are often kept separate, opening new avenues of inquiry. As the editors argue in their introduction, by focusing on “the materiality of printing and the ground-level practices and “tactics” of production and circulation,” we can locate “histories of print within the world of comparative social analysis, rather than singularly within book, cultural, or intellectual history.” And, we might add, this in turn enables us to reach a deeper appreciation of the operation of colonial print and print’s place in the history of the modern world.

In this short afterword, I would like to pull together some of the themes that stand out for me in this collection, and what they might suggest in terms of ways forward for research. My perspective is as a historian of print culture, and more particularly print media, in twentieth-century Africa.
The frequency of transiting planetary systems around polluted white dwarfs
Authors: Robert Akshay , Farihi Jay , Van Eylen Vincent , Aungwerojwit Amornrat , Gänsicke Boris T , Redfield Seth , Dhillon Vikram S , Marsh Thomas R , Swan Andrew
Published: August 2024

This paper investigates the frequency of transiting planetary systems around metal-polluted white dwarfs using high-cadence photometry from ULTRACAM and ULTRASPEC on the ground and space-based observations with TESS. Within a sample of 313 metal-polluted white dwarfs with available TESS light curves, two systems known to have irregular transits are blindly recovered by box-least-squares and Lomb–Scargle analyses, with no new detections, yielding a transit fraction of $0.8_{-0.4}^{+0.6}$ per cent. Planet detection sensitivities are determined using simulated transit injection and recovery for all light curves, producing upper limit occurrences over radii from dwarf to Kronian planets, with periods from 1 h to 27 d. The dearth of short-period, transiting planets orbiting polluted white dwarfs is consistent with engulfment during the giant phases of stellar evolution, and modestly constrains dynamical re-injection of planets to the shortest orbital periods. Based on simple predictions of transit probability, where $(R_* + R_{\rm p})/a\simeq 0.01$, the findings here are nominally consistent with a model where 100 per cent of polluted white dwarfs have circumstellar debris near the Roche limit; however, the small sample size precludes statistical confidence in this result. Single transits are also ruled out in all light curves using a search for correlated outliers, providing weak constraints on the role of Oort-like comet clouds in white dwarf pollution.
Quantifying the randomness and scale invariance of the repeating fast radio bursts
Authors: Sang Yu , Lin Hai-Nan
Published: August 2024

The statistical properties of energy and waiting time carry essential information about the source of repeating fast radio bursts (FRBs). In this paper, we investigate the randomness of energy and waiting time using four data samples from three extremely active repeating FRBs observed by the Five-hundred-meter Aperture Spherical radio Telescope (FAST). We report the deviation from complete randomness of the burst activity using three statistics, i.e. Hurst exponent, Pincus index, and non-Gaussian probability density distribution of fluctuations. First, the Hurst exponent greater than 0.5 reveals that there is long-term memory in the time series of energy and waiting time. Second, the deviation of the Pincus index from 1.0 manifests that the time series is not completely random. Finally, the fluctuations of energy and waiting time follow the scale-invariant q-Gaussian distribution. All these statistical properties imply that, although the time series of repeating FRBs seems to be irregular, they are not completely random, similar to the features of self-organized criticality.
Gene Transfer Among Viruses Substantially Contributes to Gene Gain of Giant Viruses
Authors: Wu Junyi , Meng Lingjie , Gaïa Morgan , Hikida Hiroyuki , Okazaki Yusuke , Endo Hisashi , Ogata Hiroyuki
Published: August 2024

The phylum Nucleocytoviricota comprises a diverse group of double-stranded DNA viruses that display a wide range of gene repertoires. Although these gene repertoires determine the characteristics of individual viruses, the evolutionary processes that have shaped the gene repertoires of extant viruses since their common ancestor are poorly characterized. In this study, we aimed to address this gap in knowledge by using amalgamated likelihood estimation, a probabilistic tree reconciliation method that infers evolutionary scenarios by distinguishing origination, gene duplications, virus-to-virus horizontal gene transfer (vHGT), and gene losses. We analyzed over 4,700 gene families from 195 genomes spanning all known viral orders. The evolutionary reconstruction suggests a history of extensive gene gains and losses during the evolution of these viruses, notably with vHGT contributing to gene gains at a comparable level to duplications and originations. The vHGT frequently occurred between phylogenetically closely related viruses, as well as between distantly related viruses with an overlapping host range. We observed a pattern of massive gene duplications that followed vHGTs for gene families that was potentially related to host range control and virus–host arms race. These results suggest that vHGT represents a previously overlooked, yet important, evolutionary force that integrates the evolutionary paths of multiple viruses and affects shaping of Nucleocytoviricota virus gene repertoires.
RNA splicing as a biomarker and phenotypic driver of meningioma DNA-methylation groups
Authors: Leclair Nathan K , Choudury Abrar , Chen William C , Magill Stephen T , McCortney Kathleen , Horbinski Craig M , Chen Zhenhong , Goldschmidt Ezequiel , Eaton Charlotte D , Bulsara Ketan R , Bi Wenya Linda , Patel Akash J , Sahm Felix , Raleigh David , Anczukow Olga
Published: August 2024

Background

Advances in our understanding of the molecular biology of meningiomas have led to significant gains in the ability to predict patient prognosis and tumor recurrence and to identify novel targets for therapeutic design. Specifically, classification of meningiomas based on DNA methylation has greatly improved our ability to risk stratify patients, however new questions have arisen in terms of the underlying impact these DNA-methylation signatures have on meningioma biology.

Methods

This study utilizes RNA-sequencing data from 486 meningioma samples corresponding to 3 meningioma DNA-methylation groups (merlin-intact, immune-enriched, and hypermitotic), followed by in vitro experiments utilizing human meningioma cell lines.

Results

We identify alterations in RNA splicing between meningioma DNA-methylation groups including individual splicing events that correlate with hypermitotic meningiomas and predict tumor recurrence and overall patient prognosis and compile a set of splicing events that can accurately predict DNA-methylation classification based on RNA-seq data. Furthermore, we validate these events using reverse transcription polymerase chain reaction (RT-PCR) in patient samples and meningioma cell lines. Additionally, we identify alterations in RNA-binding proteins and splicing factors that lie upstream of RNA splicing events, including upregulation of SRSF1 in hypermitotic meningiomas which we show drives alternative RNA splicing changes. Finally, we design splice-switching antisense oligonucleotides to target RNA splicing changes in NASP and MFF observed in hypermitotic meningiomas, providing a rationale for RNA-based therapeutic design.

Conclusions

RNA splicing is an important driver of meningioma phenotypes that can be useful in prognosticating patients and as a potential exploit for therapeutic vulnerabilities.
Racial distribution of molecularly classified brain tumors
Authors: Fang Camila S , Wang Wanyi , Schroff Chanel , Movahed-Ezazi Misha , Vasudevaraja Varshini , Serrano Jonathan , Sulman Erik P , Golfinos John G , Orringer Daniel , Galbraith Kristyn , Feng Yang , Snuderl Matija
Published: August 2024

Background

In many cancers, specific subtypes are more prevalent in specific racial backgrounds. However, little is known about the racial distribution of specific molecular types of brain tumors. Public data repositories lack data on many brain tumor subtypes as well as diagnostic annotation using the current World Health Organization classification. A better understanding of the prevalence of brain tumors in different racial backgrounds may provide insight into tumor predisposition and development, and improve prevention.

Methods

We retrospectively analyzed the racial distribution of 1709 primary brain tumors classified by their methylation profiles using clinically validated whole genome DNA methylation. Self-reported race was obtained from medical records. Our cohort included 82% White, 10% Black, and 8% Asian patients with 74% of patients reporting their race.

Results

There was a significant difference in the racial distribution of specific types of brain tumors. Blacks were overrepresented in pituitary adenomas (35%, P < .001), with the largest proportion of FSH/LH subtype. Whites were underrepresented at 47% of all pituitary adenoma patients (P < .001). Glioblastoma (GBM) IDH wild-type showed an enrichment of Whites, at 90% (P < .001), and a significantly smaller percentage of Blacks, at 3% (P < .001).

Conclusions

Molecularly classified brain tumor groups and subgroups show different distributions among the three main racial backgrounds suggesting the contribution of race to brain tumor development.
Identification of High Linoleic Acid Varieties in Tetraploid perilla through Gamma-ray Irradiation and CRISPR/Cas9
Authors: Park Mid-Eum , Choi Hyun-A , Lee Kyeong-Ryeol , Heo Jae Bok , Kim Hyun Uk
Published: August 2024

Perilla [Perilla frutescens (L.) var frutescens] is a traditional oil crop in Asia, recognized for its seeds abundant in α-linolenic acid (18:3), a key omega-3 fatty acid known for its health benefits. Despite the known nutritional value, the reason behind the higher 18:3 content in tetraploid perilla seeds remained unexplored. Gamma irradiation yielded mutants with altered seed fatty acid composition. Among the mutants, DY-46-5 showed a 27% increase in 18:2 due to the 4-bp deletion of PfrFAD3b, and NC-65-12 displayed a 16% increase in 18:2 due to the loss of function of PfrFAD3a through a large deletion. Knocking out both copies of FATTY ACID DESATURASE3 (PfrFAD3a and PfrFAD3b) simultaneously using CRISPR/Cas9 resulted in an increase in 18:2 by up to 75% and a decrease in 18:3 to as low as 0.3% in seeds, emphasizing the pivotal roles of both genes in 18:3 synthesis in tetraploid perilla. Furthermore, diploid Perilla citriodora, the progenitor of cultivated tetraploid perilla, harbors only PfrFAD3b, with a fatty acid analysis revealing lower 18:3 levels than tetraploid perilla. In conclusion, the enhanced 18:3 content in cultivated tetraploid perilla seeds can be attributed to the acquisition of two FAD3 copies through hybridization with wild-type diploid perilla.
The risk of anaphylaxis on holidays
Authors: Ridolo Erminia , Barone Alessandro , Ottoni Martina , Nicoletta Francesca
Published: August 2024

Purpose of review

The goal of this review is to summarize the potential causes of anaphylaxis in the different holiday contexts, providing practical suggestions aimed to mitigate the stress challenged by allergic patients because of unfamiliar situations.

Recent findings

A regard was reserved to potential food triggers, particularly uncommon ones and typical of certain destinations, and to arthropods responsible for anaphylaxis.

This review highlights the potential risk of anaphylaxis due to the unusual contexts more experienced during holidays (i.e., travels, outdoor activities and eating out). Moreover, it underlines the need for a further allergological education in these cases, in order to prepare allergic patients to avoid and manage undesired situations.
Identifying Factors Associated With Fast Visual Field Progression in Patients With Ocular Hypertension Based on Unsupervised Machine Learning
Authors: Huang Xiaoqin , Poursoroush Asma , Sun Jian , Boland Michael V. , Johnson Chris A. , Yousefi Siamak
Published: August 2024

Précis:

We developed unsupervised machine learning models to identify different subtypes of patients with ocular hypertension in terms of visual field (VF) progression and discovered 4 subtypes with different trends of VF worsening. We then identified factors associated with fast VF progression.

Purpose:

To identify ocular hypertension (OHT) subtypes with different trends of visual field (VF) progression based on unsupervised machine learning and to discover factors associated with fast VF progression.

Design:

Cross-sectional and longitudinal study.

Participants:

A total of 3133 eyes of 1568 ocular hypertension treatment study (OHTS) participants with at least 5 follow-up VF tests were included in the study.

Methods:

We used a latent class mixed model (LCMM) to identify OHT subtypes using standard automated perimetry (SAP) mean deviation (MD) trajectories. We characterized the subtypes based on demographic, clinical, ocular, and VF factors at the baseline. We then identified factors driving fast VF progression using generalized estimating equation (GEE) and justified findings qualitatively and quantitatively.

Main Outcome Measure:

Rates of SAP mean deviation (MD) change.

Results:

The LCMM model discovered four clusters (subtypes) of eyes with different trajectories of MD worsening. The number of eyes in clusters were 794 (25%), 1675 (54%), 531 (17%), and 133 (4%). We labeled the clusters as improvers (cluster 1), stables (cluster 2), slow progressors (cluster 3), and fast progressors (cluster 4) based on their mean of MD decline rate, which were 0.08, −0.06, −0.21, and −0.45 dB/year, respectively. Eyes with fast VF progression had higher baseline age, intraocular pressure (IOP), pattern standard deviation (PSD) and refractive error (RE), but lower central corneal thickness (CCT). Fast progression was associated with being male, heart disease history, diabetes history, African American race, and stroke history.

Conclusions:

Unsupervised clustering can objectively identify OHT subtypes including those with fast VF worsening without human expert intervention. Fast VF progression was associated with higher history of stroke, heart disease and diabetes. Fast progressors were more from African American race, males, and had higher incidence of glaucoma conversion. Subtyping can provide guidance for adjusting treatment plans to slow vision loss and improve quality of life of patients with a faster progression course.