bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamic arms race during the early invasion of woodland strawberry by Botrytis cinerea revealed by dual dense high-resolution RNA-seq analyses
Authors: Bai Yibo , Wang Haibin , Zhu Kaikai , Cheng Zong-Ming
Published: November 2023

Necrotrophic pathogens replicate massively upon colonizing plants, causing large-scale wilting and death of plant tissues. Understanding both mechanisms of pathogen invasion and host response processes prior to symptom appearance and their key regulatory networks is therefore important for defense against pathogen attack. Here, we investigated the mechanisms of interaction between woodland strawberry (Fragaria vesca) leaves and gray mold pathogen (Botrytis cinerea) at 14 infection time points during the first 12 hours of the infection period using a dense, high-resolution time series dual transcriptomic analysis, characterizing the arms race between strawberry F. vesca and B. cinerea before the appearance of localized lesions. Strawberry leaves rapidly initiated strong systemic defenses at the first sign of external stimulation and showed lower levels of transcriptomic change later in the infection process. Unlike the host plants, B. cinerea showed larger-scale transcriptomic changes that persisted throughout the infection process. Weighted gene co-expression network analysis identified highly correlated genes in 32 gene expression modules between B. cinerea and strawberry. Yeast two-hybrid and bimolecular fluorescence complementation assays revealed that the disease response protein FvRLP2 from woodland strawberry interacted with the cell death inducing proteins BcXYG1 and BcPG3 from B. cinerea. Overexpression of FvRLP2 in both strawberry and Arabidopsis inhibited B. cinerea infection, confirming these genes’ respective functions. These findings shed light on the arms race process by which B. cinerea invades host plants and strawberry to defend against pathogen infection.
Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn’s Disease: A Retrospective, International Multicenter Study
Authors: Little Robert D , Swaine Adrian , Reynolds Rebecca , Gibson David J , Barrau Mathilde , D’Errico Francesca , Hampal Rumneek , Sparrow Miles P , Roblin Xavier , Irving Peter M , Ward Mark G
Published: November 2023

Background

The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn’s disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification.

Methods

We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated.

Results

A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively.

Conclusions

Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.
Brazilian airway surgery survey indicates low overall numbers and need for improved teaching skills
Authors: Bibas Benoit Jacques , Minamoto Helio , Cardoso Paulo Francisco G , Cremonese Mariana Rodrigues , Pêgo-Fernandes Paulo Manuel , Terra Ricardo Mingarini
Published: November 2023

OBJECTIVES

The Brazilian Society of Thoracic Surgeons conducted an online survey to determine the number of surgeons that perform adult and paediatric airway surgery and to understand the practice patterns along the country.

METHODS

Active members were electronically invited to complete the questionnaire through the REDCapR platform. Invitations were sent from January to April 2020. The survey encompassed 40 questions that explored 4 different topics in the assessment of tracheal diseases: (i) surgeon’s demography; (ii) institutional profile, (iii) education and training in laryngo-tracheal surgery and (iv) preoperative and postoperative evaluation.

RESULTS

Eighty-nine percentage of the responders declared to perform tracheal surgery with a median of 5 tracheal resection procedures per year [interquartile range (IQR) 3–12]. Interaction with other specialties occurs in 37.3% of cases. Access to technology and devices is highly variable across the country. Resident training in airway surgery consists in traditional lectures in 97% of the cases. Training in animals (15.2%), cadavers (12.1%) and simulators (6.1%) are rare. Preoperatory evaluation encompasses flexible bronchoscopy (97.8%) and/or computed tomography (CT) scan of the airways (90.6%). Swallowing (20.1%) and voice (14.4%) disorders are rarely evaluated. Eighty-nine percentage of the surgeons consider bronchoscopy to be the preoperatory gold-standard exam, followed by CT scan (38.8%) and CT-3D reconstruction (37.4%).

CONCLUSIONS

Brazilian surgeons refer that airway resection and reconstruction are part of their current practice, but the total number of procedures per surgeon per year is low. Access to high-end technology and equipment is heterogenous. Training offered to residents in most academic institutions relies on traditional lectures.
Numerical analysis of a hybridized discontinuous Galerkin method for the Cahn–Hilliard problem
Authors: Kirk Keegan L A , Riviere Beatrice , Masri Rami
Published: November 2023

The mixed form of the Cahn–Hilliard equations is discretized by the hybridized discontinuous Galerkin method. For any chemical energy density, existence and uniqueness of the numerical solution is obtained. The scheme is proved to be unconditionally stable. Convergence of the method is obtained by deriving a priori error estimates that are valid for the Ginzburg–Landau chemical energy density and for convex domains. The paper also contains discrete functional tools, namely discrete Agmon and Gagliardo–Nirenberg inequalities, which are proved to be valid in the hybridizable discontinuous Galerkin spaces.
Re-Imagining Peace Education: Using Critical Pedagogy as a Transformative Tool
Authors: Nicoson Christie , Magalhães Teixeira Barbara , Mårtensson Alva
Published: November 2023

Existing studies demonstrate that although peace and conflict studies (PCS) emerged from a deep connection between political activism and research, the field has increasingly moved toward promoting liberal ideals of peace that sustain the status quo. Amidst this trend, many scholars have pushed research and education programs to explore beyond a hegemonic liberal peace, for example by diversifying reading lists and drawing on decolonial frameworks. This paper adds to such efforts: through the case study of a higher education PCS classroom, we use narratives from two course conveners and a student to explore challenges and opportunities of realizing a critical pedagogy approach to peace education. This approach recenters the classroom not necessarily in terms of what students ought to think, but how; critical theory provides a basis for fostering curiosity, using query as a tool of learning, and focusing class structure on students’ needs. Our findings suggest that using critical pedagogy in PCS addresses calls for a greater understanding of peace beyond the absence of violence, fosters active envisioning of peace, and works toward decolonizing and demystifying peace work. Ultimately, we call for PCS classrooms to foster critical thinking and radical imagination for a pedagogy of peace praxis.
The Key Role of Political Prisoners in Transcending Protracted Conflicts
Authors: Schorr-Liebfeld Tomer , Sela Avraham
Published: November 2023

Resolving protracted, asymmetric, and ethno-national conflicts is a notoriously problematic process, and only a handful of such attempts have ended in success. This paper is the first comparative study examining the relevance of “politically motivated violent offenders” (PMVOs) in propelling the shift from a long and bloody armed struggle to a negotiated agreement; indeed, they play an indispensable role in the ratification and the eventual implementation of any such agreement. We compare the role of PMVOs in three cases of protracted conflict resolution processes in the 1990s—Northern Ireland, South Africa, and the Israeli-Palestinian Oslo Accords. We argue that PMVOs constitute a distinguished socio-political actor characterized by high symbolic capital as the embodiment of the national struggle. This renders them a major source of political legitimacy, a necessary condition for attaining peace with hitherto sworn enemies and securing its implementation and stabilization. The paper analyzes the provisions within the respective agreements pertaining to prisoners’ release as an incentive, or lack thereof, especially for organizations outside the peace process to cease violence. Whereas the British and South African governments fully recognized the PMVO issue, Israel’s failure to recognize its importance was a major factor leading to the breakdown of the Oslo process.
Standardized amino acid digestibility and nitrogen-corrected true metabolizable energy of frozen raw, freeze-dried raw, fresh, and extruded dog foods using precision-fed cecectomized and conventional rooster assays
Authors: Geary Elizabeth L , Parsons Carl M , Utterback Pam L , Templeman James R , Swanson Kelly S
Published: November 2023

Processing conditions, particularly temperature and duration of heating, impact pet food digestibility. Various commercial pet food formats are now available, but few have been tested thoroughly. The objective of this study was to determine the amino acid (AA) digestibilities and nitrogen-corrected true metabolizable energy (TMEn) values of frozen raw, freeze-dried raw, fresh (mildly cooked), and extruded dog foods using the precision-fed cecectomized and conventional rooster assays. The diets tested were Chicken and Barley Recipe [Hill’s Science Diet, extruded diet (EXT)], Chicken and White Rice Recipe [Just Food for Dogs, fresh diet (FRSH)], Chicken Formula [Primal Pet Foods, frozen raw diet (FRZN)], Chicken and Sorghum Hybrid Freeze-dried Formula [Primal Pet Foods, hybrid freeze-dried raw diet (HFD)], and Chicken Dinner Patties [Stella & Chewy’s, freeze-dried raw diet (FD)]. Two precision-fed rooster assays utilizing Single Comb White Leghorn roosters were conducted. Cecectomized roosters (n = 4/treatment) and conventional roosters (n = 4/treatment) were used to determine standardized AA digestibilities and TMEn, respectively. All roosters were crop intubated with 12 g of test diet and 12 g of corn, with excreta collected for 48 h. In general, FD had the highest, while EXT had the lowest AA digestibilities; however, all diets performed relatively well and few differences in AA digestibility were detected among the diets. Lysine digestibility was higher (P < 0.05) in FD and FRZN than EXT, with other diets being intermediate. Threonine digestibility was higher (P < 0.05) in FD than EXT, with other diets being intermediate. Digestibilities of the other indispensable AA were not different among diets. The reactive lysine:total lysine ratios were 0.94, 0.96, 0.93, 0.93, and 0.95 for EXT, FRSH, FRZN, HFD, and FD, respectively. TMEn was higher (P < 0.05) in FRZN than FD, FRSH, and EXT, higher (P < 0.05) in HFD than FRSH and EXT, and higher (P < 0.05) in FD than EXT. In conclusion, our results support the notion that AA digestibilities are affected by diet processing, with FD, HFD, FRZN, and FRSH diets having higher AA digestibility coefficients and greater TMEn values, than the EXT diet; however, other factors such as ingredient inclusion and macronutrient composition may also have affected these results. More research in dogs is necessary to test the effects of format on diet palatability, digestibility, stool quality, and other physiologically relevant outcomes.
Estimation of carcass chemical composition in beef-on-dairy cattle using dual-energy X-ray absorptiometry (DXA) scans of cold half-carcass or 11th rib cut
Authors: Xavier Caroline , Morel Isabelle , Dohme-Meier Frigga , Siegenthaler Raphael , Le Cozler Yannick , Lerch Sylvain
Published: November 2023

The aim of the present study was to estimate the chemical composition (water, lipid, protein, mineral, and energy contents) of carcasses measured postmortem using dual-energy X-ray absorptiometry (DXA) scans of cold half-carcass or 11th rib cut. One hundred and twenty beef-on-dairy (dam: Swiss Brown, sire: Angus, Limousin, or Simmental) bulls (n = 66), heifers (n = 42), and steers (n = 12) were included in the study. The reference carcass composition measured after grinding, homogenization, and chemical analyses was estimated from DXA variables using simple or multiple linear regressions with model training on 70% (n = 84) and validation on 30% (n = 36) of the observations. In the validation step, the estimates of water and protein masses from the half-carcass (R2 = 0.998 and 0.997; root mean square error of prediction [RMSEP], 1.0 and 0.5 kg, respectively) and 11th rib DXA scans (R2 = 0.997 and 0.996; RMSEP, 1.5 and 0.5 kg, respectively) were precise. Lipid mass was estimated precisely from the half-carcass DXA scan (R2 = 0.990; RMSEP = 1.0 kg) with a slightly lower precision from the 11th rib DXA scan (R2 = 0.968; RMSEP = 1.7 kg). Mineral mass was estimated from half-carcass (R² = 0.975 and RMSEP = 0.3 kg) and 11th rib DXA scans (R2 = 0.947 and RMSEP = 0.4 kg). For the energy content, the R2 values ranged from 0.989 (11th rib DXA scan) to 0.996 (half-carcass DXA scan), and the RMSEP ranged from 36 (half-carcass) to 55 MJ (11th rib). The proportions of water, lipids, and energy in the carcasses were also precisely estimated (R2 ≥ 0.882) using either the half-carcass (RMSEP ≤ 1.0%) or 11th rib-cut DXA scans (RMSEP ≤ 1.3%). Precision was lower for the protein and mineral proportions (R2 ≤ 0.794, RMSEP ≤ 0.5%). The cattle category (sex and breed of sire) effect was observed only in some estimative models for proportions from the 11th rib cut. In conclusion, DXA imaging of either a cold half-carcass or 11th rib cut is a precise method for estimating the chemical composition of carcasses from beef-on-dairy cattle.
Comparison of Efficacy of Vacuum Dressing Versus Conventional Dressing Over Autologous Split Skin Grafts in Burn Wounds: A Single-Center Prospective Cohort Study
Authors: Babu Basil , Gaba Sunil , John Jerry R , Subair Mohsina
Published: November 2023

This study was carried out to compare the efficacy of vacuum dressing and conventional dressing over split skin grafts in burn patients. It was a single-center prospective cohort study on patients, with less than 40% TBSA burn, undergoing skin grafting at 2 different sites simultaneously over the burn wounds. One site underwent conventional dressing following grafting, and the other underwent vacuum dressing. The primary objective was to compare the percentages of skin graft uptake on Day 5 and Day 14. The secondary objectives were to compare the duration of dressings, time for complete epithelization, need for regrafting, and wound swab culture positivity rates. Three independent examiners assessed the efficacy of dressings in terms of epithelization percentage, need for continued dressing, graft loss, wound swab culture positivity rate, and qualitative assessment of grafts. A total of 16 patients were included in the study. The graft loss, number of days of dressings, and complete epithelization time were statistically lower in the negative-pressure wound therapy (NPWT) group compared with the conventional group (P values .007, .006, and 0009, respectively). The percentage of epithelization was also found to be higher in the NPWT group (P = .006). The incidence of positive cultures and clinically significant graft loss was found to be lower in the NPWT group. However, this was not found to be statistically significant. NPWT dressings can be used in burn wounds following skin grafting and have been found to reduce the time for epithelization compared to conventional dressing.
A study on unmanned combat vehicle path planning for collision avoidance with enemy forces in dynamic situations
Authors: Ahn Jisoo , Jung Sewoong , Kim Hansom , Hwang Ho-Jin , Jun Hong-Bae
Published: November 2023

This study focuses on the path planning problem for unmanned combat vehicles (UCVs), where the goal is to find a viable path from the starting point to the destination while avoiding collisions with moving obstacles, such as enemy forces. The objective is to minimize the overall cost, which encompasses factors like travel distance, geographical difficulty, and the risk posed by enemy forces. To address this challenge, we have proposed a heuristic algorithm based on D* Lite. This modified algorithm considers not only travel distance but also other military-relevant costs, such as travel difficulty and risk. It generates a path that navigates around both fixed unknown obstacles and dynamically moving obstacles (enemy forces) that change positions over time. To assess the effectiveness of our proposed algorithm, we conducted comprehensive experiments, comparing and analyzing its performance in terms of average pathfinding success rate, average number of turns, and average execution time. Notably, we examined how the algorithm performs under two UCV path search strategies and two obstacle movement strategies. Our findings shed light on the potential of our approach in real-world UCV path planning scenarios.
A bio-medical snake optimizer system driven by logarithmic surviving global search for optimizing feature selection and its application for disorder recognition
Authors: Khurma Ruba Abu , Alhenawi Esraa , Braik Malik , Hashim Fatma A , Chhabra Amit , Castillo Pedro A
Published: November 2023

It is of paramount importance to enhance medical practices, given how important it is to protect human life. Medical therapy can be accelerated by automating patient prediction using machine learning techniques. To double the efficiency of classifiers, several preprocessing strategies must be adopted for their crucial duty in this field. Feature Selection (FS) is one tool that has been used frequently to modify data and enhance classification outcomes by lowering the dimensionality of datasets. Excluded features are those that have a poor correlation coefficient with the label class, i.e., they have no meaningful correlation with classification and do not indicate where the instance belongs. Along with the recurring features, which show a strong association with the remainder of the features. Contrarily, the model being produced during training is harmed, and the classifier is misled by their presence. This causes overfitting and increases algorithm complexity and processing time. The pattern is made clearer by FS, which also creates a broader classification model with a lower chance of overfitting in an acceptable amount of time and algorithmic complexity. To optimize the FS process, building wrappers must employ metaheuristic algorithms as search algorithms. The best solution, which reflects the best subset of features within a particular medical dataset that aids in patient diagnosis, is sought in this study using the Snake Optimizer (SO). The swarm-based approaches that SO is founded on have left it with several general flaws, like local minimum trapping, early convergence, uneven exploration and exploitation, and early convergence. By employing the cosine function to calculate the separation between the present solution and the ideal solution, the logarithm operator was paired with SO to better the exploitation process and get over these restrictions. In order to get the best overall answer, this forces the solutions to spiral downward. Additionally, SO is employed to put the evolutionary algorithms’ preservation of the best premise into practice. This is accomplished by utilizing three alternative selection systems – tournament, proportional, and linear – to improve the exploration phase. These are used in exploration to allow solutions to be found more thoroughly and in relation to a chosen solution than at random. These are Tournament Logarithmic Snake Optimizer (TLSO), Proportional Logarithmic Snake Optimizer, and Linear Order Logarithmic Snake Optimizer. A number of 22 reference medical datasets were used in experiments. The findings indicate that, among 86% of the datasets, TLSO attained the best accuracy, and among 82% of the datasets, the best feature reduction. In terms of the standard deviation, the TLSO also attained noteworthy reliability and stability. On the basis of running duration, it is, nonetheless, quite effective.
Bermudagrass mite (Acari: Eriophyidae) infestation worsens in response to increasing nitrogen fertility and decreasing irrigation volume but not mowing height
Authors: Brown Matthew S , Chong Juang Horng
Published: November 2023

Severe bermudagrass mite (Aceria cynodoniensis Sayed) infestation stunts turfgrass growth and reduces the aesthetic and recreational value of managed bermudagrass. Management practices, such as fertilization, mowing, and irrigation, may impact bermudagrass mite infestation and damage, but empirical evidence is lacking. Two 20 wk experiments were conducted with potted bermudagrass in a greenhouse or nursery to evaluate the effect of varying nitrogen rates (0, 24.5, or 49 kg N/ha), mowing heights (1.3, 2.5, 3.8, or 5 cm), and irrigation rates (60%, 100%, or 140% evapotranspiration [ET] rate) on the densities of witch’s brooms (i.e., stunted and deformed terminals symptomatic of infestation) and bermudagrass mites. Increasing nitrogen fertility from 0 to 49 kg N/ha increased witch’s broom and bermudagrass mite densities by 292% and 339%, respectively. Bermudagrass fertilized with nitrogen maintained higher turf quality than unfertilized grass despite greater mite damage. Decreasing irrigation from 140% to 60% of the ET rate also increased witch’s broom densities by 124%. Mowing height did not consistently affect witch’s broom or mite densities. Witch’s broom and mite densities were positively correlated and followed a general trend with greater densities in April–August and a decline in densities in August–October. These findings suggest that nitrogen fertilization and water stress influence bermudagrass mite damage. Thus, limiting nitrogen fertilization to a level necessary to maintain turfgrass health and quality (0.5 kg N/ha) and minimizing turfgrass water stress can complement current chemical control strategies as part of an integrated pest management program.
An Ill-bred Culture of Experimentation: Malaria Therapy and Race in the United States Public Health Service Laboratory at the South Carolina State Hospital, 1932-1952
Authors: Pelletier Bradford Charles
Published: November 2023

While most are aware of the Tuskegee syphilis experiments in which African American syphilis patients went untreated, less is known about experiments with malaria fever therapy conducted upon syphilis patients during the same period by the Unites States Public Health Service at the Williams Laboratory on the grounds of the South Carolina State Hospital (SCSH) in Columbia, SC. Over a twenty-year period, physicians maintained patients as malaria reservoirs for patient-to-patient inoculation and subjected patients to extreme fevers and thousands upon thousands of insect bites as part of a program in which one disease was tested as therapy for another. Using extant administrative files, medical journals from the period, and a database created from SCSH annual reports, this paper considers the ethics of malaria fever therapy experiments while exposing the conditions under which patients suffered the intersecting oppressions of race, class, and mental illness. It illuminates the prevalent scientific racism of the period that enabled pseudo-medical assumptions about African Americans’ perceived penchant for poverty, deviant sex, and pain tolerance, which combined to enable a culture of experimentation that influenced events at Stateville Penitentiary and continued long after penicillin became widely available.
NKG2D receptor signaling shapes T cell thymic education
Authors: Perez Cynthia , Plaza-Rojas Lourdes , Boucher Justin C , Nagy Mate Z , Kostenko Elena , Prajapati Kushal , Burke Brianna , Reyes Michael Delos , Austin Anna L , Zhang Shubin , Le Phong T , Guevara-Patino José A
Published: November 2023

The role of natural killer group 2D (NKG2D) in peripheral T cells as a costimulatory receptor is well established. However, its contribution to T cell thymic education and functional imprint is unknown. Here, we report significant changes in development, receptor signaling, transcriptional program, and function in T cells from mice lacking NKG2D signaling. In C57BL/6 (B6) and OT-I mice, we found that NKG2D deficiency results in Vβ chain usage changes and stagnation of the double-positive stage in thymic T cell development. We found that the expression of CD5 and CD45 in thymocytes from NKG2D deficient mice were reduced, indicating a direct influence of NKG2D on the strength of T cell receptor (TCR) signaling during the developmental stage of T cells. Depicting the functional consequences of NKG2D, peripheral OT-I NKG2D-deficient cells were unresponsive to ovalbumin peptide stimulation. Paradoxically, while αCD3/CD28 agonist antibodies led to phenotypic T cell activation, their ability to produce cytokines remained severely compromised. We found that OT-I NKG2D-deficient cells activate STAT5 in response to interleukin-15 but were unable to phosphorylate ERK or S6 upon TCR engagement, underpinning a defect in TCR signaling. Finally, we showed that NKG2D is expressed in mouse and human thymic T cells at the double-negative stage, suggesting an evolutionarily conserved function during T cell development. The data presented in this study indicate that NKG2D impacts thymic T cell development at a fundamental level by reducing the TCR threshold and affecting the functional imprint of the thymic progeny. In summary, understanding the impact of NKG2D on thymic T cell development and TCR signaling contributes to our knowledge of immune system regulation, immune dysregulation, and the design of immunotherapies.
Growth of force chain network upon non-Bagnold transition of inclined surface granular flows via discrete element simulation
Authors: Tsai Cheng-Ting , Cheng Chih-Ying , Yang F-L
Published: November 2023

A steady granular flow down an inclined surface is an important flow configuration to study the dynamic of dry granular flow. This work adopts two-dimensional discrete element simulation to study how inter-grain friction may play a role in momentum transport, in addition to the collision-based transport, to induce the non-Bagnold flow velocity profile reported in the literature. Special efforts were made to apply the knowledge of network science to identify the contact force chain network from particle dynamics information using the graph theory with the Louvain greedy algorithm. We studied how the number of grains born in the force chain network grows when the flow scaled velocity profile degrades from Bagnold to non-Bagnold flows. Concurrently, the stress loading ratio carried by these frictional contacts rises abruptly upon the non-Bagnold flow transition identifies when the flow Froude number falls roughly below 2.15. Both phenomena suggest that the non-local phenomenon of Bagnold velocity profile degradation occurs when sufficient grains are confined in the force chain network to assist the stress transport, replacing the collisional transport. Hence, a refined rheology model is needed in the future to account for this friction-assisted momentum transport at a mesoscopic yet flow-dependent length scale like that of the currently investigated force network.
The conspicuously large bracts influence reproductive success in Thunia alba (Orchidaceae)
Authors: Wu Shi-Mao , Gao Jiang-Yun
Published: November 2023

In angiosperms, diverse floral traits are adaptations to various selective pressures and ecological functions. So far, studies on floral traits in orchids have focused primarily on the labellum but never on bracts. A bumblebee-pollinated and rewarding terrestrial or epiphytic herb, Thunia alba (Lindley) H. G. Reichenbach (Orchidaceae), has conspicuously large and curly bracts that enclose the spur and pedicel of flowers. We hypothesized that these large bracts could protect spurs against nectar robbers. To confirm this hypothesis, we experimentally removed the bracts to record the changes in visiting behavior of mutualistic pollinators and antagonistic nectar robbers and evaluated their effects on reproduction success. Our result revealed that Bombus breviceps, the only pollinator of T. alba, shifted to nectar robbery when the bracts were removed, and the proportion of robbed flowers also significantly increased. Thunia alba was found to be pollinator limited regardless of whether in intact treatment or removed bract treatment. Removal of bracts had no effect on the visiting frequency of B. breviceps, but it reduced male and female reproductive success. These findings indicate that, under complex environmental pressures with limited pollination, large bracts can protect against nectar robbers and enhance the fitness of T. alba.
Representative pure risk estimation by using data from epidemiologic studies, surveys, and registries: estimating risks for minority subgroups
Authors: Wang Lingxiao , Li Yan , Graubard Barry I , Katki Hormuzd A
Published: November 2023

Representative risk estimation is fundamental to clinical decision-making. However, risks are often estimated from non-representative epidemiologic studies, which usually under-represent minorities. Model-based methods use population registries to improve external validity of risk estimation but assume hazard ratios are generalisable from samples to the target finite population. ‘Pseudoweighting’ methods improve representativeness of studies by using an external probability-based survey as the reference, but the resulting estimators can be biased due to propensity model misspecification and inefficient due to highly variable pseudoweights or small sample sizes of minorities in the cohort and/or survey. We propose a two-step pseudoweighting procedure that post-stratifies the event rates among age/race/sex strata in the pseudoweighted cohort to the population rates, to produce efficient and robust pure risk estimation (i.e. a cause-specific absolute risk in the absence of competing events). For developing an all-cause mortality risk model representative for the USA, our findings suggest that hazard ratios for minorities are not generalisable, and that surveys can have inadequate numbers of events for minorities. Post-stratification on event rates is crucial for obtaining reliable risk estimation for minority subgroups.
Uncovering root compaction response mechanisms: new insights and opportunities
Authors: Pandey Bipin K , Bennett Malcolm J
Published: November 2023

Compaction disrupts soil structure, reducing root growth, nutrient and water uptake, gas exchange, and microbial growth. Root growth inhibition by soil compaction was originally thought to reflect the impact of mechanical impedance and reduced water availability. However, using a novel gas diffusion-based mechanism employing the hormone ethylene, recent research has revealed that plant roots sense soil compaction. Non-compacted soil features highly interconnected pore spaces that facilitate diffusion of gases such as ethylene which are released by root tips. In contrast, soil compaction stress disrupts the pore network, causing ethylene to accumulate around root tips and trigger growth arrest. Genetically disrupting ethylene signalling causes roots to become much less sensitive to compaction stress. Such new understanding about the molecular sensing mechanism and emerging root anatomical traits provides novel opportunities to develop crops resistant to soil compaction by targeting key genes and their signalling pathways. This expert view discusses these recent advances and the molecular mechanisms associated with root–soil compaction responses.
Progressive disseminated histoplasmosis: The experience in one non-endemic medical center
Authors: Li Lucy X , Rajack Shakila Tenkayala Abdul , Ostrander Darin , Datta Kausik , Totten Marissa , Avery Robin K , Zhang Sean X , Marr Kieren A , Permpalung Nitipong
Published: November 2023

Histoplasmosis, the most common endemic mycosis in North America, presents in a myriad of ways, spanning the spectrum from self-limiting pneumonia to progressive disseminated histoplasmosis (PDH). Toward better describing contemporary histoplasmosis syndromes, risks, and outcomes, this single-center retrospective cohort study was performed (2009–2019). The population who developed PDH was similar to that with other forms of histoplasmosis (OFH) except for higher rates of preexisting immunocompromising conditions (91.3% vs. 40%, P < .001) and a trend toward receiving more chronic immunosuppression (65.2% vs. 33.3%, P = .054) compared to those with OFH. Diagnosis was most frequently achieved by urinary or serum antigen positivity. People with PDH more frequently tested positive compared to those with OFH, but negative tests did not rule out histoplasmosis. Median time to diagnosis was prolonged among people with both PDH and OFH (32 vs. 31 days, respectively). Following diagnosis, people with PDH received more liposomal amphotericin (78.3% vs. 20%, P < .001). Subsequent survival at 90 and 365 days and treatment response were similar in both groups. Patients with PDH were more often hospitalized (95.7% vs. 60%, P = .006); however, once admitted, there were no differences in hospital length of stay or intensive care unit admission rate. The challenges of diagnosing histoplasmosis based on clinical presentation alone highlight the need for heightened awareness of these entities especially given the recent reports on expanded endemicity and delays in diagnosis.
Neutron star mass in dark matter clumps
Authors: Deliyergiyev Maksym , Del Popolo Antonino , Le Delliou Morgan
Published: November 2023

This paper investigates a hypothesis proposed in previous research relating neutron star (NS) mass and its dark matter (DM) accumulation. As DM accumulates, NS mass decreases, predicting lower NS masses toward the Galactic centre. Due to limited NSs data near the Galactic centre, we examine NSs located within DM clumps. Using the CLUMPY code simulations, we determine the DM clumps distribution, with masses from 10 to 108 M⊙ and scales from 10−3 to 10 kpc. These clumps’ DM exhibit a peak at the centre, tapering toward the outskirts, resembling our Galaxy’s DM distribution. We analyse these DM clumps’ NS mass variations, considering diverse DM particle masses and galaxy types. We find relatively stable NS mass within 0.01 – 5 kpc from the clump centre. This stability supports the initial hypothesis, particularly for NSs located beyond 0.01 kpc from the clump centre, where NS mass reaches a plateau around 0.1 kpc. Nevertheless, NS mass near the clump’s periphery reveals spatial dependence: NS position within DM clumps influences its mass in Milky Way-type galaxies. Moreover, this dependence varies with the DM model considered. In summary, our study investigates the proposed link between NS mass and DM accumulation by examining NSs within DM clumps. While NS mass remains stable at certain distances from the clump centre, spatial dependencies arise near the clump’s outer regions, contingent on the specific DM model.
Pithoviruses Are Invaded by Repeats That Contribute to Their Evolution and Divergence from Cedratviruses
Authors: Rigou Sofia , Schmitt Alain , Alempic Jean-Marie , Lartigue Audrey , Vendloczki Peter , Abergel Chantal , Claverie Jean-Michel , Legendre Matthieu
Published: November 2023

Pithoviridae are amoeba-infecting giant viruses possessing the largest viral particles known so far. Since the discovery of Pithovirus sibericum, recovered from a 30,000-yr-old permafrost sample, other pithoviruses, and related cedratviruses, were isolated from various terrestrial and aquatic samples. Here, we report the isolation and genome sequencing of 2 Pithoviridae from soil samples, in addition to 3 other recent isolates. Using the 12 available genome sequences, we conducted a thorough comparative genomic study of the Pithoviridae family to decipher the organization and evolution of their genomes. Our study reveals a nonuniform genome organization in 2 main regions: 1 concentrating core genes and another gene duplications. We also found that Pithoviridae genomes are more conservative than other families of giant viruses, with a low and stable proportion (5% to 7%) of genes originating from horizontal transfers. Genome size variation within the family is mainly due to variations in gene duplication rates (from 14% to 28%) and massive invasion by inverted repeats. While these repeated elements are absent from cedratviruses, repeat-rich regions cover as much as a quarter of the pithoviruses genomes. These regions, identified using a dedicated pipeline, are hotspots of mutations, gene capture events, and genomic rearrangements that contribute to their evolution.
ANGI-01. INDUCIBLE CAS9 IN PATIENT-DERIVED CULTURES OF IDH WILDTYPE GLIOBLASTOMA WITH DISTINCT GROWTH CHARACTERISTICS
Authors: Kundu Soumi , Yildirim Irem , Voukelatou Faidra , Stockgard Rebecka , Krona Cecilia , Nelander Sven
Published: November 2023

To identify new treatment opportunities for IDH wildtype glioblastoma, it is essential to establish robust methods to evaluate candidate genes in patient-derived cells. Here, we report initiative to establish large-scale candidate gene evaluation by CRISPR-Cas9 using well characterized cells from the Uppsala Human Glioma Cell Culture biobank. Previously, we have characterized fully the HGCC cultures (n = 100) in terms of multi-omics, and by systematic injection as patient-derived orthotopic xenografts. Here, we report a procedure to introduce doxycycline-inducible Cas9 into cultures from our biobank. This allows for temporally controlled target gene ablation in patient-derived cells with known growth characteristics. As proof-of-concept, we describe the derivation of clonal Cas9-inducible cells in the cell lines U3013MG (proneural, bulk forming) and U3180MG (classical, diffuse-growing). The Cas9 induction and editing efficiency was evaluated by ablation of the gene encoding the cell surface marker CD44, for which we transduced the Cas9-inducible clones with CD44 dual sgRNA vector and treated then with doxycycline over time, evaluating CD44 knockout by longitudinal flow cytometry. From a library of 106 clones, we identified the best performing clones, as evaluated by CD44 loss at day 21. Ten out of 64 clones assessed, showed potent Cas9 activity, estimating a drop in CD44 levels by 40-60% after 21 days of doxycycline treatment. The amount of editing by inducible Cas9 was higher with CD44 sgRNA administered by lentivirus than by electroporation. To ensure that the Cas9-inducible patient-derived cell lines have reproducible tumor phenotypes and did not divert from their parental growth pattern, they were transplanted orthotopically into athymic nude mice. We also validated the activity of Cas9ind in vivo by checking the editing of CD44 expression in one of our clones. The established procedure provides a basis for large-scale single-gene and pooled in vivo CRISPR studies of IDH wildtype glioblastomas with distinct invasive characteristics.
ANGI-07. GLIOBLASTOMA WITH BONY METASTATIC DISEASE IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1: A CASE REPORT
Authors: Shah Trusha , Hutchens Troy , Yang Jonathan , Graber Jerome
Published: November 2023

Neurofibromatosis Type 1 (NF1) is an autosomal dominant tumor predisposition syndrome causing diffuse neurofibromas, plexiform neurofibromas, and in a minority of patients malignant peripheral nerve sheath tumors (MPNST) and gliomas. Gliomas from NF1 typically present early in life and can be grade 1-4, with higher grades less frequent. Malignant gliomas associated with NF1 have a different molecular landscape compared to sporadic gliomas. Extracranial spread of gliomas is extremely rare for reasons unknown, but renal transplants from gliomas patients have resulted in clonal gliomas in organ recipients. We present here the first reported case of extracranial metastases of GBM to bone in a 21 year old male with NF1. At the age of 18, he was diagnosed with a high-grade astrocytoma consistent with GBM (IDH wildtype, MGMT unmethylated). This was 2 years following a diagnosis of a right neck plexiform neurofibroma. His GBM was initially treated with six cycles of temozolomide. Following temozolomide he underwent another resection (1.5 years after initial surgery) due to tumor recurrence. Resection was followed by proton radiation therapy and selumetinib, a MEK inhibitor approved for treatment of plexiform neurofibromas in NF1. The selumetinib did reduce his plexiform neurofibroma, but did not have an apparent effect on his GBM. Selumetinib was stopped five months after initiation due to increased tumor burden and he began lomustine, followed by bevacizumab and etoposide at next recurrence. About 2.5 years after his initial GBM diagnosis, he had low back pain and imaging showed multiple sites of bony metastases. Pathology confirmed extracranial spread of GBM.
ANGI-09. UNRAVELING THE INVOLVEMENT OF BAIAP2 AND CDC42 IN MEDULLOBLASTOMA PATHOGENESIS
Authors: Ruiz Luz , Jangde Nitish , Suter Robert , Ayad Nagi
Published: November 2023

The most common malignant pediatric brain tumor is medulloblastoma. Despite advancements in treatment, medulloblastoma survivors have significant long-term medical side effects and increased all-cause mortality. That is why novel, more effective, and safe treatments are direly necessary. One treatment challenge is that medulloblastoma tumors can disseminate via the bloodstream and cerebrospinal fluid leading to a poorer prognosis. The underlying mechanisms that promote metastasis and invasion in medulloblastoma are not clearly understood. One method we used to identify potential key regulators in the pathogenesis of medulloblastoma is by analyzing microarray and single-cell RNA sequencing data. We mined publicly-available datasets along with our data from genetically engineered models of medulloblastoma to identify differentially expressed genes compared to non-tumor brain cells. We identified BAIAP2 and CDC42 to be differentially expressed and have higher expression in medulloblastoma compared to other brain cancers. BAIAP2 and CDC42 are known to be implicated in migration and invasion. Extensive literature demonstrates an interaction between BAIAP2 and CDC42 in multiple cell types. However, this interaction has yet to be thoroughly studied in medulloblastoma. We hypothesize that CDC42 interacts with BAIAP2 in medulloblastoma cells to facilitate tumor pathogenesis. To further investigate this, we conducted siRNA-mediated gene knockdown of BAIAP2 and CDC42 in ONS-76 cells. We determined that BAIAP2 and CDC42 are highly expressed in medulloblastoma, and knockdown of BAIAP2 modulates CDC42 expression. Further, we determined that cell proliferation and migration were reduced upon BAIAP2 and CDC42 knockdown. Our findings suggest that BAIAP2 and CDC42 have a role in the migration and proliferation of medulloblastoma ONS-76 cells. Altogether, these findings indicate BAIAP2 and CDC42 as possible targets for future studies.
BIOM-27. CELL-FREE DNA-BASED LIQUID BIOPSIES FOR THE REAL-TIME TRACKING OF TUMOR BURDEN AND TREATMENT RESPONSE IN GLIOBLASTOMA
Authors: Mankame Sharvari , Kyriakidou Maria , Tang Nanyun , Reid George , Berens Michael , Brown Christine , Portnow Jana , Barthel Floris
Published: November 2023

Cell-free DNA (cfDNA) are short fragments of DNA that are released by apoptotic or necrotic cells into bodily fluids. It has emerged as a potential diagnostic tool allowing for the detection and analysis of tumor-derived biomarkers in cancer. Despite the detailed view provided by clinical imaging, its inability to quantify tumor burden and distinguish between pseudo-progression and pseudo-response poses a challenge for patients. In this study, we sought to investigate the effectiveness of cfDNA as a liquid biopsy tool to track tumor burden and disease progression in real time in different glioblastoma models and through different types of biofluids. To examine the feasibility of cfDNA-based tumor tracking we cultivated several patient-derived glioblastoma lines, purified cfDNA and performed sequencing. Further analysis revealed that dead cells were associated with an elevated cfDNA yield and altered fragment size profiles. Genomic sequencing revealed consistent variants shared across serial cfDNA timepoints, strengthening the suggestion that cfDNA can be used as a non-invasive biomarker. In order to demonstrate the clinical implications of our methodology, we collected a preliminary batch of n = 43 longitudinal intraventricular cerebrospinal fluid (CSF) samples from a patient that underwent CAR-T treatment over the span of two years. We observed a marked increase in cfDNA yield post-treatment compared to samples taken prior to treatment administration. Furthermore, cfDNA-based estimates of tumor burden measured as allele fraction specific to the tumor, tracked with clinical imaging-based tumor size estimates. These preliminary findings provide compelling evidence supporting the clinical utility of cfDNA analysis in monitoring the effectiveness and dynamics of CAR-T treatment. By tracking cfDNA levels in CSF, we can identify patterns reflecting treatment response and aid in assessing the therapeutic efficiency of CAR-T treatment in glioma patients. Further investigations with larger patient cohorts and more comprehensive data analysis to validate these findings are actively underway.