bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular immune response to the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in pediatric autoimmune inflammatory rheumatic disease patients and controls
Authors: Eviatar Tali , Pappo Adi , Freund Tal , Friedlander Yishai , Elkayam Ori , Hagin David , Heshin-Bekenstein Merav
Published: May 2024

This paper aims to compare the cellular immune response to the SARS-CoV-2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD) and healthy controls. A prospective longitudinal study was conducted between April 2021 and December 2022 at the Tel Aviv Medical Center. Children <18 years, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 vaccine, were included. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 receptor-binding domain antibodies. Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T cells following stimulation with SARS-CoV-2 Spike peptide mix. The study included 20 pAIIRD patients and 11 controls. The mean age of participants was 12.6 ± 2.94 years, with 58.1% females. The cellular response to the BNT162b2 vaccine was statistically similar in both groups. However, the humoral response was statistically lower in pAIIRD compared with the healthy control group. There was no statistically significant correlation between the humoral response and cellular response. During the study period, 43.75% of AIIRD children and 72.7% of controls had a breakthrough COVID-19 infection (P = 0.48). Bivariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect. Compared with healthy controls, pAIIRD demonstrated similar cellular responses. Patients showed reduced humoral response compared with healthy adolescents, but similar breakthrough infection rates. These findings may support the importance of the cellular response in protecting against COVID-19 infections.
Field phenology of emerald ash borer (Coleoptera: Buprestidae) parasitoids in New York State
Authors: Morris Timothy D , Gould Juli R , Fierke Melissa K
Published: May 2024

Emerald ash borer (EAB), Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), has caused extensive mortality of ash across North America. Biological control offers a potential long-term management option, allowing for long-term survival of ash. Careful monitoring of populations of biocontrol agents is necessary to understand their relative impacts. Understanding the emergence and flight phenology of these species allows for the optimization of monitoring schemes and improves our understanding of host–parasitoid interactions. We used yellow pan trapping data to assess the adult phenology of both EAB and its associated native and introduced parasitoids in 3 New York counties. We monitored 2 introduced larval biocontrol agents, Tetrastichus planipennisi Yang (Hymenoptera: Eulophidae) and Spathius galinae Belokobylskij & Strazanac (Braconidae), for 3–4 years post-release, as well as the native parasitoid Phasgonophora sulcata Westword (Chalcididae). Results indicate a single discrete emergence event for both EAB and P. sulcata in all monitored counties, which is consistent with previously reported results. Our results also suggest there are 4 generations per year of T. planipennisi and 3 generations of S. galinae in the monitored counties. We recorded an additional generation of T. planipennisi that had not previously been reported in New York, and both T. planipennisi and S. galinae appeared to emerge earlier than previously documented.
Left ventricular intimal sarcoma: a case report
Authors: Ullah Mohsin , Waidyanatha Sawan , Stamos Konstantinos , Tsanaxidis Nikolaos
Published: May 2024

Background

Secondary cardiac tumours are much more common compared with primary (100–1000 times). The majority of the primary cardiac tumours are benign; however, almost a quarter are malignant, and 95% of these are sarcomas. The rarest type of primary malignant cardiac sarcoma is intimal (spindle cell) sarcoma.

Case summary

A 37-year-old woman presented with episodes of breathlessness. Initially treated for a chest infection, however, the patient continued to deteriorate and presented to the emergency department. A large pericardial effusion was discovered and drained, with samples sent for analysis. A repeat interval echo confirmed the resolution of the pericardial effusion with preserved left ventricular (LV) systolic function. The computed tomography (CT) of the thorax showed suspicious lesions in the heart and lung while the repeat echo raised suspicion of an infiltrative disease. A cardiac magnetic resonance imaging scan was performed, which suggested evidence of an undifferentiated sarcoma involving the posterior wall of the LV and an overlying thrombus. Computed tomography of the abdomen and pelvis did not show any evidence of abdominal metastasis. A CT-guided lung biopsy was arranged. On histological analysis, the report was overall strongly supportive of a diagnosis of intimal sarcoma. She underwent chemotherapy until recently.

Discussion

Cardiac intimal sarcomas are the least reported type of primary malignant tumours of the heart. They are encountered more commonly in the large arterial blood vessels, including the pulmonary artery and aorta, and are extremely rare in the heart. A prompt diagnosis is essential as they are considered extremely aggressive.
Differential culprit plaque morphology in acute coronary syndrome: a comparison between very young patients (≤35 years) and older counterparts using optical coherence tomography
Authors: Chaudhary Gaurav , Gupta Basant , Roy Shubhajeet , Chandra Sharad , Sharma Akhil , Pradhan Akshyaya , Bhandari Monika , Vishwakarma Pravesh , Sethi Rishi , Dwivedi Sudhanshu Kumar , Baliyan Vinit , Sharma Prachi , Jaiswal Vikash , Singh Abhishek , Shukla Ayush , Shrestha Sajina , Gimelli Alessia
Published: May 2024

Aims

Underlying mechanisms responsible for acute coronary syndrome (ACS) in young patients compared with older counterparts are yet to be explored with optical coherence tomography (OCT). This study aims to explore underlying mechanisms of ACS in ≤35- (very young) and >35-year-old (older counterparts) ACS patients using OCT.

Methods and results

This was a prospective, single-centre, investigational study. Patients were divided into groups according to age (≤35 and >35 years) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). A total of 93 patients were analysed. Thin-cap fibroatheroma (TCFA) was significantly higher among older counterparts than very young patients for both PR (80.0% vs. 31.8%, P = 0.002) and PE (66.7% vs. 6.3%, P < 0.001) groups. Microchannels were also significantly more prevalent among older than very young patients for both PR (65.0% vs. 18.2%, P = 0.004) and PE groups (55.6% vs.12.5%, P = 0.013). Macrophages were significantly higher in older than very young patients for both PR (25.0% vs. 0%, P = 0.018) and PE (44.4% vs. 0%, P = 0.003) groups. In contrast, fibrous cap thickness was greater in very young than older patients for both PR (105.71 ± 48.02 vs. 58.00 ± 15.76 µm, P < 0.001) and PE (126.67 ± 48.22 vs. 54.38 ± 24.21 µm, P < 0.001) groups. Intimal thickness was greater in older than very young patients for both PR (728.00 ± 313.92 vs. 342.27 ± 142.02 µm, P < 0.001) and PE (672.78 ± 334.57 vs. 295.00 ± 99.60 µm, P < 0.001) groups.

Conclusion

Frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in older ACS patients compared with very young patients. However, fibrous cap thickness was significantly greater in very young ACS patients compared with older patients.
Correlation of sex hormone levels with orthodontic tooth movement in the maxilla: a prospective cohort study
Authors: Peruga Małgorzata , Lis Joanna
Published: May 2024

Background

Sex hormones secreted during the menstrual cycle and the application of orthodontic forces to teeth can affect the metabolism of periodontal ligaments. This study aimed to determine whether there are any differences in orthodontic tooth displacement during the menstrual cycle and when using hormonal contraceptives and whether the amount of female sex hormones influences the efficiency of tooth displacement.

Methods

A total of 120 women aged between 20 and 30 years with Angle Class II requiring transpalatal arch (TPA) to derotate teeth 16 and 26 were included in this study. The participants were divided into two groups: group A, which included women with regular menstruation, and control group B, which included women taking monophasic combined oral contraceptives. Group A was divided into subgroups according to the moment of TPA activation: menstruation (A1), ovulation phase (A2), and luteal phase (A3) (examination I). On intraoral scans, measurement points were marked on the proximal mesial cusps of teeth 16 and 26, and the intermolar distance (M1) was determined. The change in the position of the measurement points 6 weeks after activation (examination II) made it possible to determine the derotating extent of teeth 16 (O16) and 26 (O26) and the widening of the intermolar distance (M2–M1). In examinations I and II, tooth mobility in the alveoli was assessed using Periotest based on the periotest values (PTV) PTV1 and PTV2, respectively.

Results

A significant difference in all parameters was observed among groups A1, A2, and A3 (P < 0.001). Group A3 showed the highest values of parameters O16, O26, and M2–M1, and group A2 showed the lowest values, which did not differ from the control group (P = 0.64). PTV2 and PTV1 were the highest in group A3 and the lowest in groups A1 and B. Intergroup differences were statistically significant (P < 0.001).

Conclusions

With the quantification of changes in tooth mobility in the alveoli during the menstrual cycle in women undergoing orthodontic treatment, it was possible to determine that female sex hormones affect the effectiveness of orthodontic treatment, and the optimal moment for TPA activation is the luteal phase of the menstrual cycle.
Semen adaptation to microbes in an insect
Authors: Otti Oliver , Rossel Natacha , Reinhardt Klaus
Published: May 2024

Sperm function is suggested to evolve by sexual selection but is also reduced by microbial damage. Here, we provide experimental evidence that male fertility can adapt to microbes. We found that in vivo, male fertility was reduced by one-fifth if sperm encountered microbes in the females that they had not previously been exposed to, compared to sperm from males that coevolved with these microbes. The female immune system activation reduced male fertility by an additional 13 percentage points. For noncoevolved males, fertility was larger if microbes were injected into females after they had stored away the sperm, indicating microbial protection as a previously unrecognized benefit of female sperm storage. Both medical and evolutionary research on reproductive health and fertility will benefit from considering our findings that the impact of microbes on sperm depends on their joint evolutionary history. Our results may assist in reconciling contradictory results of sexually transmitted disease effects on sperm and bring empirical realism to a recently proposed role of locally adapted reproductive microbiomes to speciation.
Addressing Equity and Justice in Age-Friendly Communities: Considerations for LGBTQ+ Older Adults of Color
Authors: Oswald Austin G , Cooper Lujira
Published: May 2024

Background and Objectives

This research critically examined the concept of age-friendliness from the perspectives of older Black lesbian women living in New York City (NYC). The primary aim was to extend existing age-friendly frameworks to more inclusively meet the needs of older lesbian, gay, bisexual, transgender, and queer adults of color, promoting greater equity and justice.

Research Design and Methods

Applying principles from critical participatory action research, we collected and analyzed data from 5 focus groups consisting of 5 older Black lesbian women. Participants shared their daily experiences living in NYC and proposed ideas to enhance the age-friendliness of the city to better accommodate their unique needs and experiences.

Results

Participants called for greater attention to the interaction between identities and structures in relation to age-friendly communities. Historic and contemporary experiences of violence and discrimination, as well as the ever-shifting political context were identified as a key factor shaping their aging experiences. The need for affirming spaces with positive representation of their layered identities was emphasized in the context of age-friendly interventions.

Discussion and Implications

While dominant age-friendly frameworks are universally accepted for improving the health and wellbeing of older adults, the specific challenges of aging with multiple intersecting marginalized identities necessitate a critical perspective. Gerontology needs to take seriously how privilege and oppression operate within society, shaping health and aging trajectories of vulnerable and underserved populations.
Successful Aging and Subjective Aging: Toward a Framework to Research a Neglected Connection
Authors: Sabatini Serena , Rupprecht Fiona , Kaspar Roman , Klusmann Verena , Kornadt Anna , Nikitin Jana , Schönstein Anton , Stephan Yannick , Wettstein Markus , Wurm Susanne , Diehl Manfred , Wahl Hans-Werner
Published: May 2024

Research related to subjective aging, which describes how individuals perceive, interpret and evaluate their own aging, has substantially grown in the past two decades. Evidence from longitudinal studies shows that subjective aging predicts health, quality of life, and functioning in later life. However, the existing literature on successful aging has mostly neglected the role of subjective aging. This paper proposes an extended framework of successful aging linking subjective aging conceptually and empirically to Rowe and Kahn’s (1997) three original key criteria of successful aging (i.e., avoiding disease and disability, maintaining high cognitive and physical function, and engagement with life). A particular focus is placed on subjective aging as an antecedent of successful aging. A review of the empirical subjective aging literature shows that subjective aging concepts consistently predict all three of Rowe and Kahn’s criteria of successful aging. Mechanisms underlying these relations are discussed at three levels, namely psychological, behavioral, and physiological pathways. The proposed addition also takes into consideration the interconnections between subjective aging and successful aging throughout the lifespan and across historical time. Finally, we discuss the importance of facilitating successful aging through systematic interventions that support more positive views of aging at the individual and societal level.
Predictors of Complicated Disease Course in Children and Adults With Ulcerative Colitis: A Nationwide Study From the epi-IIRN
Authors: Atia Ohad , Buchuk Rachel , Lujan Rona , Greenfeld Shira , Kariv Revital , Loewenberg Weisband Yiska , Lederman Natan , Matz Eran , Ledder Oren , Zittan Eran , Yanai Henit , Shwartz Doron , Freiman Moti , Dotan Iris , Nevo Daniel , Turner Dan
Published: May 2024

Background

Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC.

Methods

Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together.

Results

A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course.

Conclusion

In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy.
On the Weak Local Arthur Packets Conjecture for Split Classical Groups
Authors: Liu Baiying , Lo Chi-Heng
Published: May 2024

Recently, motivated by the theory of real local Arthur packets, making use of the wavefront sets of representations over non-Archimedean local fields $F$, Ciubotaru, Mason-Brown, and Okada defined the weak local Arthur packets consisting of certain unipotent representations and conjectured that they are unions of local Arthur packets. In this paper, we prove this conjecture for $\textrm{Sp}_{2n}(F)$ and split $\textrm{SO}_{2n+1}(F)$ with the assumption of the residue field characteristic of $F$ being large. In particular, this implies the unitarity of these unipotent representations. We also discuss the generalization of the weak local Arthur packets beyond unipotent representations, which reveals the close connection with a conjecture of Jiang on the structure of wavefront sets for representations in local Arthur packets.
Secrecy, Uncertainty, and Trust: The Gendered Nature of Back-Channel Peace Negotiations
Authors: Corredor Elizabeth S , Anderson Miriam J
Published: May 2024

Back-channel negotiations are commonplace in peace negotiations and can serve as crucial mechanisms for reaching agreements. While there has been a moderate increase in scholarship examining back-channel negotiations in the last two decades, none has explored the gendered nature of these spaces. This article analyzes how and why back-channel negotiations are highly gendered processes and why their gendered nature matters for sustainable peace. We begin with a review of the current literature on back-channel negotiations and discuss how and why they are critical mechanisms in peace negotiation and agreement processes. Next, we show how women’s inclusion in peace negotiations and agreement practices matters for sustainable peace. Thereafter, we discuss how secret negotiation spaces are infused with gendered power and masculine logics of war and peace. We argue that three key features of back-channel negotiations—secrecy, uncertainty, and limited trust—come together to create an echo chamber of hypermasculinity ideas, values, styles, and norms that prevent women from achieving descriptive and substantive representation inside fundamental secret negotiation spaces. This article adds to the developing literature on back-channel negotiations and helps us better understand how and why women and their interests are regularly excluded from peace processes despite the global prominence of the United Nations’ Women, Peace, and Security agenda.
Enhancing Physical Performance Through Digital Theatre
Authors: Powell Grant
Published: May 2024

Ben Pettitt-Wade, Artistic Director at Hijinx Theatre, spoke to Grant Powell MBCS about how a move toward tech during Covid has led to an innovative and immersive dimension of theatre.
Accessibility in Gaming
Authors: Andrews Steve
Published: May 2024

Steve Andrews CITP MBCS reflects on the place of gaming in mainstream culture, the social model of disability and how the industry is working towards improving accessible design.
Bridging Change and Stasis
Authors: Smith Georgia
Published: May 2024

Georgia Smith MBCS visited Annka Kultys' hybrid physical and VR gallery in Hackney earlier this year - here, she discusses the changing nature of digital arts, finding her niche as a bridge between tradition and innovation, and the rollercoaster of pioneering a whole new way to experience art.
Meet the New BCS President: Alastair Revell
Authors: Smith Georgia
Published: May 2024

New BCS President Alastair Reveil FBCS discusses the value of chartered professionalism, ethics in a fast moving landscape and his goals for the presidency. Georgia Smith MBCS reports.
The Wrath of the CIO
Authors: Hall Jon
Published: May 2024

Is a CIO needed on the starship Enterprise? In this latest column, Jon G Hall ponders this very question
Navigating the Risks of Shadow AI
Authors: Kwan T W
Published: May 2024

Dr T. W. Kwan FBCS explores the challenges associated with shadow AI and identifies the strategies that, when implemented, will help business leaders prepare for an increase in shadow usage.
Transformation Needs Horizontal Thinking
Authors: Burke Gary
Published: May 2024

Transformation programmes don't have a great reputation for success, but why is this the case if the supposed reasons for failure have been known for years? Gary Burke believes transformation needs to be looked at differently.
Bta-miR-181d and Bta-miR-196a mediated proliferation, differentiation, and apoptosis in Bovine Myogenic Cells
Authors: Chengcheng Liang , Raza Sayed Haidar Abbas , Zhimei Yang , Sihu Wang , Shengchen Yu , Aloufi Bandar Hamad , Bingzhi Li , Zan Linsen
Published: May 2024

Skeletal muscle is an important component of livestock and poultry organisms. The proliferation and differentiation of myoblasts are highly coordinated processes, which rely on the regulation of miRNA. MiRNAs are widely present in organisms and play roles in various biological processes, including cell proliferation, differentiation, and apoptosis. MiR-181d and miR-196a, identified as tumor suppressors, have been found to be involved in cell proliferation, apoptosis, directed differentiation, and cancer cell invasion. However, their role in beef cattle skeletal muscle metabolism remains unclear. In this study, we discovered that overexpression of bta-miR-181d and bta-miR-196a in Qinchuan cattle myoblasts inhibited proliferation and apoptosis while promoting myogenic differentiation through EDU staining, flow cytometry analysis, immunofluorescence staining, and Western blotting. RNA-seq analysis of differential gene expression revealed that after overexpression of bta-miR-181d and bta-miR-196a, the differentially expressed genes were mainly enriched in the PI3K-Akt and MAPK signaling pathways. Furthermore, the phosphorylation levels of key proteins p-AKT in the PI3K signaling pathway and p-MAPK in the MAPK signaling pathway were significantly decreased after overexpression of bta-miR-181d and bta-miR-196a. Overall, this study provides preliminary evidence that bta-miR-181d and bta-miR-196a may regulate proliferation, apoptosis, and differentiation processes in Qinchuan cattle myoblasts by affecting the phosphorylation status of key proteins in PI3K-Akt and MAPK-ERK signaling pathways
Increased eye size is favoured in Trinidadian killifish experimentally transplanted into low light, high competition environments
Authors: Tran Stephanie M , Howell Kaitlyn J , Walsh Matthew R
Published: May 2024

Intraspecific variation in vertebrate eye size is well known. Ecological factors such as light availability are often correlated with shifts in relative eye size. However, experimental tests of selection on eye size are lacking. Trinidadian killifish (Anablepsoides hartii) are found in sites that differ in predation intensity. Sites that lack predators are characterized by lower light, high killifish densities, low resource availability, and intense competition for food. We previously found that killifish in sites that lack predators have evolved a larger “relative” eye size (eye size corrected for body size) than fish from sites with predators. Here, we used transplant experiments to test how selection operates on eye size when fish that are adapted to sites with predators are translocated into sites where predators are absent. We observed a significant “population × relative eye size” interaction; the relationship between relative eye size and a proxy for fitness (rates of individual growth) was positive in the transplanted fish. The trend was the opposite for resident fish. Such results provide experimental support that larger eyes enhance fitness and are favoured in environments characterized by low light and high competition.
Applying zero-crossing method for frequency map analysis of dynamical systems
Authors: Yurin Denis , Makukov Maxim , Kuvatova Dana , Gluchshenko Anton , Omarov Chingis
Published: May 2024

We present a simple method for estimating fundamental frequencies from orbit’s time series of triaxial dynamical systems based on the zero-crossing technique. The simplicity and high performance of the method make it a viable alternative to more advanced, but rather complex and computationally expensive techniques based on Fourier spectral analysis and iterative torus-mapping with action-angle variables. More importantly, the method provides a simple and quick way to identify irregular orbits and quantify their level of chaoticity, allowing to detect even a subtle onset of chaos. To validate the proposed algorithm, we performed comparison tests with synthetic quasi-periodic signals and with other methods using the triaxial Dehnen potential. We found noticeable differences in frequency maps constructed with our method and methods based on Fourier spectral analysis that we attributed to the way we assign static properties to chaotic orbits. At the same time, our frequency maps turn out to be in very good agreement with the maps obtained using the action-based technique.
Towards an observationally motivated AGN dusty torus model – I. Dust chemical composition from the modelling of Spitzer spectra
Authors: Reyes-Amador Omar Ulises , Fritz Jacopo , González-Martín Omaira , Srinivasan Sundar , Baes Maarten , Lopez-Rodriguez Enrique , Osorio-Clavijo Natalia , Victoria-Ceballos Cesar Iván , Stalevski Marko , Ramos Almeida C
Published: May 2024

Spectral energy distribution (SED) fitting is one of the most commonly used techniques to study the dust properties in active galactic nuclei (AGN). Works implementing this technique commonly use radiative transfer models that assume a variety of dust properties. Despite the key role of this aspect, limited effort has been put forward to explore the chemical composition, the role of different optical properties, and the grain size distribution of dust, all of which can have a substantial impact on the theoretical radiative transfer calculations. In this work, we explore the role of the dust chemical composition in the AGN dusty torus through SED fitting to Spitzer/IRS spectra of a sample of 49 nearby AGN with silicate features in emission. We implement a mineralogy model including the popular astronomical silicates and a set of oxides and amorphous silicates with different grain sizes. Wefind that best fits use principally porous alumina, periclase, and olivine. In terms of mass fractions, $\sim 99~{{\ \rm per\ cent}}$ of the dust is composed of dust grains of size $\rm {0.1 \, \mu m}$, with a $\lt 1~{{\ \rm per\ cent}}$ contribution from $\rm {3 \, \mu m}$ grains. Moreover, the astronomical silicates have a very low occurrence in the best fits, suggesting that they are not the most suited dust species to reproduce the silicate features in our sample.
Radiative transfer of 21-cm line through ionized cavities in an expanding universe
Authors: Wu Kinwah , Han Qin , Chan Jennifer Y H
Published: May 2024

The optical depth parameterization is typically used to study the 21-cm signals associated with the properties of the neutral hydrogen (H i) gas and the ionization morphology during the Epoch of Reionization (EoR), without solving the radiative transfer equation. To assess the uncertainties resulting from this simplification, we conduct explicit radiative transfer calculations using the cosmological 21-cm line radiative transfer (C21LRT) code and examine the imprints of ionization structures on the 21-cm spectrum. We consider a globally averaged reionization history and implement fully ionized cavities (H ii bubbles) of diameters d ranging from 0.01 to 10 Mpc at epochs within the emission and the absorption regimes of the 21-cm global signal. The single-ray C21LRT calculations show that the shape of the imprinted spectral features are primarily determined by d and the 21-cm line profile, which is parametrized by the turbulent velocity of the H i gas. It reveals the spectral features tied to the transition from ionized to neutral regions that calculations based on the optical depth parametrization were unable to capture. We also present analytical approximations of the calculated spectral features of the H ii bubbles. The multiple-ray calculations show that the apparent shape of an H ii bubble (of d = 5 Mpc at z = 8), because of the finite speed of light, differs depending on whether the bubble’s ionization front is stationary or expanding. Our study shows the necessity of properly accounting for the effects of line-continuum interaction, line broadening, and cosmological expansion to correctly predict the EoR 21-cm signals.
Wiring Between Close Nodes in Molecular Networks Evolves More Quickly Than Between Distant Nodes
Authors: Gil-Gomez Alejandro , Rest Joshua S
Published: May 2024

As species diverge, a wide range of evolutionary processes lead to changes in protein–protein interaction (PPI) networks and metabolic networks. The rate at which molecular networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug–drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying molecular network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high-throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in PPI and cofunctional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.
Signatures of Adaptation and Purifying Selection in Highland Populations of Dasiphora fruticosa
Authors: Yang Fu-Sheng , Liu Min , Guo Xing , Xu Chao , Jiang Juan , Mu Weixue , Fang Dongming , Xu Yong-Chao , Zhang Fu-Min , Wang Ying-Hui , Yang Ting , Chen Hongyun , Sahu Sunil Kumar , Li Ruirui , Wang Guanlong , Wang Qiang , Xu Xun , Ge Song , Liu Huan , Guo Ya-Long
Published: May 2024

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.
TARGET: A phase I/II open-label multicenter study to assess safety and efficacy of fexagratinib in patients with relapsed/refractory FGFR fusion-positive glioma
Authors: Picca Alberto , Di Stefano Anna Luisa , Savatovsky Julien , Ducray François , Chinot Olivier , Moyal Elisabeth Cohen-Jonathan , Augereau Paule , Le Rhun Emilie , Schmitt Yohann , Rousseaux Nabila , Yepnang Ariane Murielle Mbekwe , Estellat Candice , Charbonneau Frédérique , Letourneur Quentin , Branger Dominique Figarella , Meyronet David , Fardeau Christine , Mokhtari Karima , Bielle Franck , Iavarone Antonio , Sanson Marc
Published: May 2024

Background

Oncogenic FGFR–TACC fusions are present in 3–5% of high-grade gliomas (HGGs). Fexagratinib (AZD4547) is an oral FGFR1–3 inhibitor with preclinical activity in FGFR–TACC+ gliomas. We tested its safety and efficacy in patients with recurrent FGFR–TACC + HGGs.

Patients and Methods

TARGET (NCT02824133) is a phase I/II open-label multicenter study that included adult patients with FGFR–TACC + HGGs relapsing after ≥1 line of standard chemoradiation. Patients received fexagratinib 80 mg bd on a continuous schedule until disease progression or unacceptable toxicity. The primary endpoint was the 6-month progression-free survival rate (PFS6).

Results

Twelve patients with recurrent IDH wildtype FGFR–TACC + HGGs (all FGFR3–TACC3+) were included in the efficacy cohort (male/female ratio = 1.4, median age = 61.5 years). Most patients (67%) were included at the first relapse. The PFS6 was 25% (95% confidence interval 5–57%), with a median PFS of 1.4 months. All patients without progression at 6 months (n = 3) were treated at first recurrence (versus 56% of those in progression) and remained progression-free for 14–23 months. The best response was RANO partial response in 1 patient (8%), stable disease in 5 (42%), and progressive disease in 6 (50%). Median survival was 17.5 months from inclusion. Grade 3 toxicities included lymphopenia, hyperglycaemia, stomatitis, nail changes, and alanine aminotransferase increase (n = 1 each). No grade 4–5 toxicities were seen. A 32-gene signature was associated with the benefit of FGFR inhibition in FGFR3–TACC3 + HGGs.

Conclusions

Fexagratinib exhibited acceptable toxicity but limited efficacy in recurrent FGFR3–TACC3 + HGGs. Patients treated at first recurrence appeared more likely to benefit, yet additional evidence is required.
Endocrine therapy in advanced high-grade ovarian cancer: real-life data from a multicenter study and a review of the literature
Authors: Aubert Marine , Mathiot Laurent , Vegas Hélène , Ouldamer Lobna , Linassier Claude , Augereau Paule , Bocquet François , Frenel Jean-Sébastien , Cancel Mathilde
Published: May 2024

Background

In women, ovarian cancer is the eighth most frequent cancer in incidence and mortality. It is often diagnosed at advanced stages; relapses are frequent, with a poor prognosis. When platinum resistant, subsequent lines of chemotherapy are of limited effect and often poorly tolerated, leading to quality of life deterioration. Various studies suggest a hormonal role in ovarian carcinogenesis, with a rationale for endocrine therapy in these cancers.

Patients and Methods

This multicenter, retrospective study assessed the use of endocrine treatment for high-grade ovarian epithelial carcinomas treated between 2010 and 2020.

Results

Eighty-one patients with ovarian cancers were included. The median duration of platinum sensitivity was 29 months. We observed a 35% disease control rate with endocrine therapy, and 10% reported symptom improvement. For 19 patients (23.5%), the disease was stabilized for more than 6 months. Median overall survival from diagnosis was 62.6 months. Regarding endocrine therapy predictive factors of response, in a multivariate analysis, 3 factors were statistically significant in favoring progression-free survival: platinum sensitivity (P = .021), an R0 surgical resection (P = .020), and the indication for hormone therapy being maintenance therapy (P = .002)

Conclusion

This study shows real-life data on endocrine therapy in ovarian cancer. As it is a low-cost treatment with many advantages such as its oral administration and its safety, it may be an option to consider. A perspective lies in the search for cofactors to aim as future therapeutic targets to improve the effectiveness of hormone treatment by means of combination therapy.
Machine Learning for Survival Analysis
Authors: Quiroz Flores Alejandro
Published: May 2024

In the social sciences, survival analysis has focused mostly on inference. However, the prediction of time to an event is of equal importance, particularly when predictions inform interventions. Producing “good” predictions, however, is challenging because even in the simplest hazard model, the survival process consists of two variables: the occurrence (or lack thereof) of a transition to a state, and the elapsed time to the occurrence of that transition or to the end of follow-up time. However, advances in Machine Learning and Biostatistics offer powerful tools for prediction and the analysis of model performance in these complex settings, and event history modeling can benefit from advances in these fields. This chapter focuses on machine learning models specifically designed for survival data. It also discusses measures of performance appropriate for these models. To demonstrate these techniques, the chapter presents an application to the prediction of sex crime recidivism in South Carolina.
Simulating the head of a TrueBeam linear particle accelerator and calculating the photoneutron spectrum on the central axis of a 10-MV photon using particle and heavy-ion transport system code
Authors: Quoc Soai Dang , Fujibuchi Toshioh , Arakawa Hiroyuki , Hamada Keisuke
Published: May 2024

Photon energy is higher than the (γ,n) threshold, allowing it to interact with the nuclei of materials with high z properties and liberate fast neutrons. This represents a potentially harmful source of radiation for humans and the environment. This study validated the Monte Carlo simulation, using the particle and heavy-ion transport code system (PHITS) on a TrueBeam 10-MV linear particle accelerator’s head shielding model and then used this PHITS code to simulate a photo-neutron spectrum for the transport of the beam. The results showed that, when comparing the simulated to measured PDD and crosslines, 100% of the γ-indexes were <1 (γ3%/3mm) for both simulations, for both phase-space data source and a mono energy source. Neutron spectra were recorded in all parts of the TrueBeam’s head, as well as photon neutron spectra at three points on the beamline.
The Origin of the Problem: Characterization of Paraguayan Septoria steviae, Causal Agent of Septoria Leaf Spot of Stevia, Based on Multilocus Sequence Analysis
Authors: Sanabria-Velazquez Andres D. , Enciso-Maldonado Guillermo A. , Thiessen Lindsey D. , Shew H. David
Published: May 2024

Septoria leaf spot is a significant disease affecting cultivated stevia, potentially reducing yields by > 50%. The disease is caused by Septoria steviae, first identified in 1978 in Japan as a new pathogen of stevia. Understanding the origin of S. steviae could clarify how it spread to new production areas. To investigate this, 12 isolates of Septoria sp. were obtained from stevia’s native range in the Amambay forests and field plantings in Paraguay from 2018 to 2020. These isolates underwent colony morphology and molecular characterization of Actin, β-Tubulin, Calmodulin, ITS, LSU, RPB2, and TEF1α loci. GenBank sequences from S. steviae isolates collected in France, Japan, and the United States were included. Multilocus sequence phylogenetic analysis generated a maximum likelihood (ML) tree. The morphological characteristics of Paraguayan isolates were similar to those of previously reported S. steviae type cultures from Japan. The ML analysis showed that Paraguayan isolates formed a monophyletic group with S. steviae isolates from France, Japan, and the United States. During blotter tests, pycnidia and cirri of S. steviae were observed on multiple stevia seed surfaces from different sources. Further characterization confirmed viable pathogenic conidia of S. steviae. This observation suggests that S. steviae could be associated with stevia seed, possibly spreading from the center of origin to other countries. This research is the first to genetically characterize S. steviae from Paraguay and propose its potential spread mechanism from the center of origin to the rest of the world.
Hartmann’s Procedure Versus Intersphincteric Abdominoperineal Excision in Patients with Rectal Cancer: Report from the Swedish Colorectal Cancer Registry (SCRCR)
Authors: Åkerlund Viktor , Nikberg Maziar , Wagner Philippe , Chabok Abbas
Published: May 2024

Objective:

The primary outcome was to compare overall postoperative surgical complications within 30 days after Hartmann’s procedure (HP) compared with intersphincteric abdominoperineal excision (iAPE). The secondary outcome was major surgical complications (Clavien-Dindo ≥ III).

Background:

There is uncertainty regarding the optimal surgical method in patients with rectal cancer when an anastomosis is unsuitable.

Methods:

Rectal cancer patients with a tumor height >5 cm, registered in the Swedish Colorectal Cancer Registry who received HP or iAPE electively in 2017–2020 were included, (HP, n = 696; iAPE, n = 314). Logistic regression analysis adjusting for body mass index, American Society of Anesthesiologists classification, sex, age, preoperative radiotherapy, tumor height, cancer stage, operating hospital, and type of operation was performed.

Results:

Patients in the HP group were older and had higher American Society of Anesthesiologists scores. The mean operating time was less for HP (290 vs 377 min). Intraoperative bowel perforations were less frequent in the HP group, 3.6% versus 10.2%. Overall surgical complication rates were 20.3% after HP and 15.9% after iAPE (P = 0.118). Major surgical complications were 7.5% after HP and 5.7% and after iAPE (P = 0.351). Multiple regression analysis indicated a higher risk of overall surgical complications after HP (odds ratio: 1.63; 95% confidence interval = 1.09–2.45).

Conclusions:

HP was associated with a higher risk of surgical complications compared with iAPE. In patients unfit for anastomosis, iAPE may be preferable. However, the lack of statistical power regarding major surgical complications, prolonged operating time, increased risk of bowel perforation, and lack of long-term outcomes, raises uncertainty regarding recommending intersphincteric abdominoperineal excision as the preferred surgical approach.
Laminoplasty Versus Laminectomy and Posterior Fusion for Cervical Myelopathy
Authors: Daher Mohammad , Nassar Joseph E. , McDonald Christopher L. , Balmaceno-Criss Mariah , Diebo Bassel G. , Daniels Alan H.
Published: May 2024

Study Design.

Meta-analysis.

Objective.

This meta-analysis investigates the outcomes of laminoplasty (LP) and laminectomy with fusion (LF) to guide effective patient selection for these 2 procedures.

Background.

Although LF traditionally offers the ability for excellent posterior decompression, it may alter cervical spine biomechanics and increase the risk of adjacent segment degeneration. LP aims to preserve the natural kinematics of the spine but has not been universally accepted, and may be associated with inadequate decompression, neck pain, and recurrent stenosis.

Materials and Methods.

PubMed, Cochrane, and Google Scholar (pages 1–20) were searched up until March 2024. The outcomes studied were surgery-related outcomes [operative time (OR) time, estimated blood loss (EBL), and length of stay], adverse events (overall complications, C5 palsy, and reoperations), radiographic outcomes (cervical lordosis, cervical sagittal vertical axis, and T1 slope angle), and patient-reported outcome measures (Neck Disability Index, Visual Analog Scale for neck pain, and Japanese Orthopaedic Association).

Results.

Twenty-two studies were included in this meta-analysis, of which 19 were retrospective studies, 2 were prospective nonrandomized studies, and 1 was a randomized controlled trial. A total of 2128 patients were included, with 1025 undergoing LP and 1103 undergoing LF. Patients undergoing LP experienced significantly shorter operative time (P = 0.009), less EBL (P = 0.02), a lower rate of overall complications (P < 0.00001) and C5 palsy (P = 0.003), a lower T1 slope angle (P = 0.02), and a lower Neck Disability Index (P = 0.0004). No significant difference was observed in the remaining outcomes.

Conclusion.

This meta-analysis demonstrates that for cervical myelopathy, LP has the benefits of shorter operative time time, less EBL, and reduced incidence of C5 palsy as well as overall complication rate. Given these findings, LP remains an important surgical option with a favorable complication profile in patients with cervical myelopathy, although careful patient selection is still paramount in choosing the right procedure for individual patients.

Level of Evidence.

4.
The Efficacy of Botulinum Toxin A Injection for Gastrocnemius Hypertrophy: A Prospective, Randomized, Double-blinded Controlled Trial
Authors: Han Woo Yeon , Lee Young Soon , Han Hyun Ho
Published: May 2024

Background:

Many individuals hold an interest in aesthetic appeal, with one aspect of physical attractiveness being the alluring contour of the lower leg. Utilizing botulinum toxin A (BTX-A) injections offers several advantages, including a short procedure time, low pain, and a speedy recovery. With a demand for high-level evidence regarding the effectiveness of BTX-A injections for correction of lower leg contour, we evaluated the safety and efficacy of BTX-A injection for improvement of gastrocnemius muscle hypertrophy.

Methods:

We conducted a prospective, randomized, and controlled clinical trial to evaluate whether the injection of BTX-A into the gastrocnemius muscle could decrease muscular hypertrophy. The patients were randomized into a low-dose injection (60 units) group and a high-dose injection group (100 units) for each leg. Demographics, clinical outcome, and satisfaction score were compared between the two groups.

Results:

A total of 20 patients and 40 legs were enrolled in this study. Clinical and surgical demographics were similar between the two groups. BTX-A injection showed a significant decrease in the circumference of the calf after 8 weeks (preinjection: 36.35 ± 0.63 cm versus postinjection: 35.87 ± 0.61 cm; P = 0.03). However, no significant difference was observed between the low- and the high-dose group (−0.52 ± 0.74 cm versus −0.44 ± 1.04 cm, P = 0.78).

Conclusions:

BTX-A injection can be a good noninvasive method for the correction of hypertrophic gastrocnemius muscles. This study supports the use of BTX-A injections in patients unsatisfied with lower leg hypertrophy.