bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological Analysis and Survival of Patients with Cervical Cancer Submitted to Pelvic Exenteration
Authors: Águila Bruno Marinho Pinto , Monteiro Felipe de Lima , Castro Neto Héladio Feitosa de , Soares Bruno de Sousa , Oliveira Jefferson Silva , Lima Rodrigo de Oliveira
Published: September 2024

Justification The importance of this study arises from the high incidence and mortality of cervical cancer (CC), and the need to evaluate the effectiveness of current treatments, such as pelvic exenteration, performed in cases of persistent or recurrent carcinoma.

Objective To analyze the relationship between clinical and pathological factors and the results of mortality and recurrence in patients with CC who underwent pelvic exenteration at the Hospital Haroldo Juaçaba, from 2000 to 2019, aiming to improve the understanding of this procedure's outcomes.

Materials and Methods Observational, cross-sectional, retrospective study, using medical record consultation.

Results Patients with perineural invasion, those with prior surgical treatment, and those who underwent radical surgery had lower disease-free survival rates. Also, patients over 50-years-old had lower overall survival than those under that age range.

Conclusion Pelvic exenteration is a high-risk treatment for malignant pelvic neoplasms, with results influenced by technique and institutional resources. Despite the risks, it can control the disease in the long term and even cure it. However, it can affect quality of life and sexual function. Young patients should be made aware of CC prevention methods.
Thromboangiitis Obliterans (Buerger's Disease): A Young Woman's Rare Case and Current Knowledge
Authors: Autiero Giuliana , Padovan Anna , Vittone Francesca , Grolla Elisabetta , Dalla Vestra Michele
Published: September 2024

In this paper, we described the clinical features and the typical vascular imaging picture of a rare case of thromboangiitis obliterans (TAO) in a 47-year-old, young, Caucasian woman without relevant medical records except for smoking habits and admitted to our Department of Internal Medicine with a necrotic lesion of the first and third toes of the right foot. After a rapid clinical and instrumental evaluation, necrotic tissue debridement was performed and the patient was treated with Iloprost infusion and antibiotics (for overlapping infection) with clinical improvement. Moreover, we summarized the current knowledge about the disease making an update and critical examination of the literature. TAO, also known as Buerger's disease, is a rare disease. In recent decades, the incidence of TAO has decreased in Europe and the United States in men but several studies have reported an increase in the prevalence of disease in women. TAO is a segmental nonatherosclerotic inflammatory disorder that involves primarily small and medium arteries, veins, and nerves of the extremities with limb ischemia, pain, claudication, ulcers, and necrosis that can lead to amputation. Smoking is considered the main risk factor, but despite that, more than 100 years have passed since the first description of the disease by Leo Buerger, and knowledge on pathogenesis, precipitating factors, and therapy remain still unclear.
Affirming the explanandum
Authors: Trpin Borut
Published: September 2024

Affirming the consequent is an inferential pattern in which one infers the antecedent of a given conditional from its consequent. Abductive inference is structurally similar: given some evidence, one infers a hypothesis that explains the evidence. I show that a Bayesian analysis of affirming the consequent helps us understand under which conditions abduction may be justified. This provides a Bayesian vindication of explanatory inference.
Ethics in humanitarian settings—relevance and consequences for dialysis and kidney care
Authors: Luyckx Valerie A , Van Biesen Wim , Ponikvar Jadranka Buturovic , Heering Peter , Abu-Alfa Ali , Silberzweig Ji , Fontana Monica , Tuglular Serhan , Sever Mehmet Sukru
Published: September 2024

With the increasing frequency and severity of disasters and the increasing number of patients living with kidney disease, on dialysis and with transplants around the world, the need for kidney care in humanitarian settings is increasing. Almost all humanitarian emergencies pose a threat to kidney health because all treatments are highly susceptible to interruption, and interruption can be deadly. Providing support for people requiring dialysis in humanitarian settings can be complex and is associated with many trade-offs. The global kidney care community must become familiar with the ethics, principles and duties essential to meeting the overarching goals of ethical and effective disaster relief. Ethics principles and values must be considered on the individual, public health and global levels. The wellbeing of a single patient must be considered in the context of the competing needs of many others, and optimal treatment may not be possible due to resource constraints. Public health ethics principles, including considerations of triage and resource allocation, maximization of benefit and feasibility, often become directly relevant at the bedside. Individuals delivering humanitarian relief must be well trained, competent, respectful and professional, while involved organizations need to uphold the highest professional and ethical standards. There may be dissonance between ethical guidance and practical realities in humanitarian settings, which for inexperienced individuals may present significant challenges. Sustaining dialysis care in emergencies brings these issues starkly to the fore. Preparedness for dialysis in emergencies is an ethical imperative that mandates multisectoral stakeholder engagement and action, development of surge response plans, clinical and ethics guidance, and transparent priority setting. This manuscript outlines common ethics challenges and considerations that apply in all humanitarian actions, and illustrates their relevance to kidney care as a whole, using examples of how these may apply to dialysis and kidney disaster relief efforts in humanitarian settings.
Fontan haemodynamics in adults with obesity compared with overweight and normal body mass index: a retrospective invasive exercise study
Authors: Opp Derek N , Jain C Charles , Egbe Alexander C , Borlaug Barry A , Reddy Yogesh V , Connolly Heidi M , Lara-Breitinger Kyla M , Cordina Rachael , Miranda William R
Published: September 2024

Aims

The effects of obesity on Fontan haemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive haemodynamics and exercise capacity.

Methods and results

Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity [body mass index (BMI) > 30 kg/m2] and overweight/normal BMI (BMI ≤ 30 kg/m2). There were 18 individuals with obesity (BMI 36.4 ± 3 kg/m2) and 59 with overweight/normal BMI (BMI 24.1 ± 3.6 kg/m2). Peak oxygen consumption (VO2) on non-invasive cardiopulmonary exercise testing was lower in patients with obesity (15.6 ± 3.5 vs. 19.6 ± 5.8 mL/kg/min, P = 0.04). At rest, systemic flow (Qs) [7.0 (4.8; 8.3) vs. 4.8 (3.9; 5.8) L/min, P = 0.001], pulmonary artery (PA) pressure (16.3 ± 3.5 vs. 13.1 ± 3.5 mmHg, P = 0.002), and PA wedge pressure (PAWP) (11.7 ± 4.4 vs. 8.9 ± 3.1 mmHg, P = 0.01) were higher, while arterial O2 saturation was lower [89.5% (86.5; 92.3) vs. 93% (90; 95)] in obesity compared with overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7 ± 6.5 vs. 24.7 ± 6.8 mmHg, P = 0.01) and PAWP (23.0 ± 6.5 vs. 19.8 ± 7.3 mmHg, P = 0.047), but lower arterial O2 saturation [82.4 ± 7.0% vs. 89% (85; 92), P = 0.003].

Conclusion

Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared with those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve haemodynamics and outcomes requires further study.
Speciation across life and the origins of biodiversity patterns
Authors: Wiens John J
Published: September 2024

Speciation is the original source of all species richness. Here, I address two questions: (i) what might typical speciation look like across life? and (ii) how has speciation led to the diversity of life we see today? What is ‘typical’ depends on the richness of different groups. In groups associated with host organisms (which may dominate numerically), the processes of co-speciation and host switching are crucial. Among free-living organisms, allopatric speciation, ecological divergence, and prezygotic isolation appear widely important. Yet, the processes by which species become allopatric (and initially split) remain highly unclear. Among macroscopic organisms, the processes underlying the speciation of cryptic insect lineages may predominate, and are briefly reviewed here. Analyses of diversification rates among clades can illuminate the factors that drive speciation and species richness, and I review the advantages and disadvantages of different methods for estimating diversification rates. Patterns of species richness among named clades are generally related to variation in diversification rates, and specific types of ecological variables seem to underlie variation in diversification rates at different scales. Nevertheless, many richness patterns are unrelated to diversification rates and may be related to the time available for speciation instead, including richness among regions, clades, and traits.
Mobility Abilities Mediate the Association of a More Active Lifestyle With Mobility Disability in Older Adults
Authors: Lange-Maia Brittney S , Wang Tianhao , Oveisgharan Shahram , Hausdorff Jeffrey M , Bennett David A , Buchman Aron S
Published: September 2024

Background

Few studies have analyzed sensor-derived metrics of mobility abilities and total daily physical activity (TDPA). We tested whether sensor-derived mobility metrics and TDPA indices are independently associated with mobility disabilities.

Methods

This cohort study derived mobility abilities from a belt-worn sensor that recorded annual supervised gait testing. TDPA indices were obtained from a wrist-worn activity monitor. Mobility disability was determined by self-report and inability to perform an 8-feet walk task. Baseline associations of mobility metrics and TDPA (separately and together) were examined with logistic regressions and incident associations (average 7 years follow-up) with Cox models. Mediation analysis quantified the extent mobility metrics mediate the association of TDPA with mobility disability.

Results

724 ambulatory older adults (mean age 82 years, 77.4% female) were studied. In separate models, mobility abilities (eg, step time variability, turning angular velocity) and TDPA were related to mobility disabilities. Examined together in a single model, mobility abilities remained associated with mobility disabilities, while TDPA was attenuated. This attenuation of TDPA could be explained by mediation analysis that showed about 50% of TDPA associations with mobility disabilities is mediated via mobility abilities (prevalent mobility disability 54%, incident mobility disability 40%, incident loss of ambulation 50%; all p’s < .001).

Conclusions

Sensor-derived mobility metrics assess more diverse facets of mobility. These metrics mediate approximately half of the association of higher levels of daily physical activity with reduced mobility disability in older adults. Findings may inform the design of targeted interventions to reduce mobility disability in late life.
Primary care telehealth utilization by access-challenged populations in Medicare Advantage
Authors: Boudreau Emily , Sutherland Amanda , Bozzi Debra , Canterberry Melanie , Sylwestrzak Gosia
Published: September 2024

Although telehealth utilization in primary care has decreased markedly since 2020, it remains higher than before the COVID-19 pandemic. There is debate about its role in a post-pandemic healthcare system, particularly for certain groups of patients that may experience greater access challenges related to in-person care. To inform this debate, we examined the use of audiovisual telehealth for primary care as a share of total primary care outpatient visits among Medicare Advantage beneficiaries with and without 3 characteristics associated with potential access challenges (low-income status, disability, and frailty). Primary care visits when the beneficiary was frail were 39.4% (OR: 1.39 [95% CI, 1.37-1.42]) more likely to be telehealth; when the beneficiary was disabled or low-income status, visits were 20.1% (OR: 1.20 [95% CI, 1.18-1.22]) and 8.3% (OR: 1.08 [95% CI, 1.05-1.12]) more likely to be telehealth, respectively. The differential use of telehealth among beneficiaries with low-income status or disability, compared with those without, was significantly larger among providers with a 2-sided risk contract compared with fee for service (low-income status: OR: 1.19 [95% CI, 1.04-1.35]; disability: OR: 1.07 [95% CI, 1.01-1.13]).
Genome-wide association analysis of flowering date in a collection of cultivated olive tree
Authors: Aqbouch Laila , Abou-Saaid Omar , Sarah Gautier , Zunino Lison , Segura Vincent , Mournet Pierre , Bonal Florelle , Zaher Hayat , El Bakkali Ahmed , Cubry Philippe , Costes Evelyne , Khadari Bouchaib
Published: September 2024

Flowering date in perennial fruit trees is an important trait for fruit production. Depending on the winter and spring temperatures, flowering of olive may be advanced, delayed, or even suppressed. Deciphering the genetic control of flowering date is thus key to help selecting cultivars better adapted to the current climate context. Here, we investigated the genetic determinism of full flowering date stage in cultivated olive based on capture sequencing data of 318 genotypes from the worldwide olive germplasm bank of Marrakech, Morocco. The genetic structure of this collection was organized in three clusters that were broadly attributed to eastern, central, and western Mediterranean regions, based on the presumed origin of genotypes. Flowering dates, collected over 7 years, were used to estimate the genotypic best linear unbiased predictors, which were then analyzed in a genome-wide association study. Loci with small effects were significantly associated with the studied trait, by either a single- or a multi-locus approach. The three most robust loci were located on chromosomes 01 and 04, and on a scaffold, and explained 7.1%, 6.2%, and 6.5% of the trait variance, respectively. A significantly higher accuracy in the best linear unbiased predictors of flowering date prediction was reported with Ridge- compared to LASSO-based genomic prediction model. Along with genomic association results, this suggests a complex polygenic determinism of flowering date, as seen in many other fruit perennials. These results and the screening of associated regions for candidate genes open perspectives for further studies and breeding programs targeting flowering date.
Repair of mitral paravalvular leak using left atrial appendage tissue
Authors: Otsuka Ryohei , Saito Shunei , Ohno Tsukasa , Miyahara Ken
Published: September 2024

Paravalvular leak after mitral valve replacement causes serious symptoms such as heart failure and haemolysis. However, whether re-replacement or direct leak site repair is the appropriate surgical treatment for this condition remains controversial. Herein, we describe a case of paravalvular leak repaired using left atrial appendage tissue with excellent results. The proposed technique enables the repair of a leak at the 9 o’clock position with healthy, full-thickness autologous tissue. For this method, the leak must be located near the left atrial appendage, and the left atrial appendage must not adhere to the pericardial sac. Although this technique can only be used under specific conditions, it is a useful option for cardiac surgeons.
Convergence rates under a range invariance condition with application to electrical impedance tomography
Authors: Kaltenbacher Barbara
Published: September 2024

This paper is devoted to proving convergence rates of variational and iterative regularization methods under variational source conditions variational source conditions (VSCs) for inverse problems whose linearization satisfies a range invariance condition. In order to achieve this, often an appropriate relaxation of the problem needs to be found that is usually based on an augmentation of the set of unknowns and leads to a particularly structured reformulation of the inverse problem. We analyze three approaches that make use of this structure, namely a variational and a Newton-type scheme, whose convergence without rates has already been established in Kaltenbacher, B. (2023, Convergence guarantees for coefficient reconstruction in PDEs from boundary measurements by variational and Newton-type methods via range invariance. IMA J. Numer. Anal., 44, 1269–1312); additionally, we propose a split minimization approach that can be show to satisfy the same rates results. The range invariance condition has been verified for several coefficient identification problems for partial differential equations from boundary observations as relevant in a variety of tomographic imaging modalities. Our motivation particularly comes from the, by now, classical inverse problem of electrical impedance tomography (EIT) and we study both the original formulation by a diffusion type equation and its reformulation as a Schrödinger equation. For both of them we find relaxations that can be proven to satisfy the range invariance condition. Combining results on VSCs from Weidling, F. (2019, Variational Source Conditions and Conditional Stability Estimates for Inverse Problems in PDEs. Gttingen: Universitätsverlag Göttingen). with the abstract framework for the three approaches mentioned above, we arrive at convergence rates results for the variational, split minimization and Newton-type method in EIT.
Discrete maximum-minimum principle for a linearly implicit scheme for nonlinear parabolic FEM problems under weakened time restrictions
Authors: Faragó István , Horváth Róbert , Karátson János
Published: September 2024

In this paper, we extend our earlier results in Faragó, I., Karátson, J. and Korotov, S. (2012, Discrete maximum principles for nonlinear parabolic PDE systems. IMA J. Numer. Anal., 32, 1541–1573) on the discrete maximum-minimum principle (DMP) for nonlinear parabolic systems of PDEs. We propose a linearly implicit scheme, where only linear problems have to be solved on the time layers. We obtain a DMP without the restrictive condition $\varDelta t\le O(h^{2})$. We show that we only need the lower bound $\varDelta t\ge O(h^{2})$, further, depending on the Lipschitz condition of the given nonlinearity, the upper bound is just $\varDelta t\le C$ (for globally Lipschitz) or $\varDelta t\le O(h^{\gamma })$ (for locally Lipschitz) for some constant $C>0$ arising from the PDE, or some $\gamma < 2$, respectively. In most situations in practical models, the latter condition becomes $\varDelta t \le O( h^{2/3} )$ in 2D and $\varDelta t \le O( h )$ in 3D. Various real-life examples are also presented where the results can be applied to obtain physically relevant numerical solutions.
Detection of “smoke powder” etomidate and its metabolite etomidate acid in blood and urine by UHPLC–MS-MS: application in authentic cases
Authors: Liying Zhou , Junbo Zhao , Wanting Xie , Ping Xiang , Yan Shi , Hejian Wu , Hui Yan
Published: September 2024

Recently, etomidate has been widely used as an alternative in illicit drug market. It is usually added to regular cigarette tobacco (commonly known as “cigarette powder”) or mixed in e-cigarette oil sold through the Internet, retail stores, or entertainment outlets and other channels. An ultra-high performance liquid chromatography tandem mass spectrometry method was developed to quantify etomidate and etomidate acid in human blood and urine. The limit of detection (LOD) of etomidate and etomidate acid in blood is 0.5  and 2 ng/mL, respectively, and the lower limit of quantification (LLOQ) is 1  and 5 ng/mL, respectively. The LOD of etomidate and etomidate acid in urine is 1 and 2 ng/mL, respectively, and the LLOQ is 2  and 5 ng/mL, respectively. The precision, accuracy, recoveries, and matrix effects of etomidate and etomidate acid determinations in blood and urine met the requirements for methodological validation. The method was successfully applied to the identification and quantification of etomidate and etomidate acid in blood and urine of 62 forensic cases. The concentration of etomidate ranged from 1.52 to 8.41 ng/mL (positive cases, n = 5) and the concentration of etomidate acid ranged from 2.76 to 112 ng/mL (positive cases, n = 5) in blood. The concentrations of etomidate and etomidate acid in urine samples were 2.64–79,300 ng/mL (positive cases, n = 59) and 6.11–518,000 ng/mL (positive cases, n = 60), respectively. Therefore, the concentration of etomidate in blood and urine is mostly higher than that of etomidate.
Incremental Attribute Learning by Knowledge distillation method
Authors: Kuang Zhejun , Wang Jingrui , Sun Dawen , Zhao Jian , Shi Lijuan , Xiong Xingbo
Published: September 2024

In numerous academic and practical settings, it is common to progressively add data features to existing models as data evolves due to new discoveries and ongoing data collection efforts. Incremental attribute learning focuses on incorporating these new feature dimensions efficiently without retraining the entire model. The key challenge for incremental attribute learning is adapting models to include new attributes dynamically while maintaining their performance on existing data formats. This research leverages strategies from existing incremental learning practices, applying them to incremental attribute learning through a new framework that utilizes knowledge distillation to prevent catastrophic forgetting. Additionally, this study proposes an embedding layer algorithm to manage the variability of input features in incremental learning effectively. Extensive experiments across 11 tabular datasets, covering binary classification, multi-class classification, and regression tasks, indicate that our approach surpasses traditional incremental attribute learning methods and conventional retraining in terms of accuracy and efficiency. Compared to existing incremental attribute learning models, our model requires only a fraction of the training time and achieves a relative improvement of 7.97% in classification tasks. Furthermore, our approach exhibits minimal forgetfulness of old format data, with a forgetting rate of approximately 1% per increment stage, while maintaining strong performance on new format data. Despite its advantages, our method is limited to tabular data and requires additional storage space. We encourage future research to delve deeper into incremental attribute learning and its broader applications, aiming to consistently enhance model performance as new attributes are introduced. Additionally, we suggest exploring methods for refining and selecting soft labels or intermediate vectors to optimize storage efficiency while effectively leveraging the original model’s knowledge.
Empowering Pediatricians With Direct Penicillin Challenges: A Promising Delabeling Strategy
Authors: Park Katherine , Schwartz David J
Published: September 2024

Objective

Current literature supports a multidisciplinary approach to penicillin allergy delabeling. Our study aims to review the success rate of penicillin challenges performed at Walter Reed National Military Medical Center Allergy Clinic and assess the reaction rate associated with a direct oral challenge in low-risk patients.

Materials and Methods

We conducted a retrospective review of the outcomes of pediatric penicillin challenges at the Walter Reed National Military Medical Center Allergy and Immunology clinic from June 2019 to May 2023. A total of 74 challenges were included in this study. Patients were initially screened to assess the date of reaction, nature of reaction, if the reaction was life-threatening, and if the patient was hospitalized or sought emergency medical care for the reported reaction. After completion of the screening questionnaire, a direct graded challenge was performed (without skin testing) if a patient’s history was deemed low risk. Patients with a recent reaction or a history of multiple drug allergies were more likely to be directed to skin prick testing and intra-dermal testing with Pre-pen and Penicillin-G prior to challenge.

Results

All patients passed all challenges. Thus, there was a 100% pass rate for both direct challenges and skin test with oral challenges.

Conclusion

Given the low rate of adverse events in this study, expansion of penicillin delabeling in the primary care setting should be considered in patients deemed to be at low risk. It is important for allergists to empower and educate their peers and push forward a movement to create a multidisciplinary approach to penicillin delabeling.
A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence
Authors: Nguyen Minh P , Morshed Ramin A , Youngblood Mark W , Perlow Haley K , Lucas Calixto-Hope G , Patel Akash J , Palmer Joshua D , Horbinski Craig M , Magill Stephen T , Chen William C , Raleigh David R
Published: September 2024

Background

Despite reassuring clinical and histological features, low-grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood.

Methods

This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples.

Results

The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with the extent of resection revealed that 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI: 1.58–2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations.

Conclusions

Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery.
A phase 1 dose escalation of pritumumab in patients with refractory or recurrent gliomas or brain metastases
Authors: Carrillo Jose , Gill Jaya Mini , Redfern Charles , Babic Ivan , Nomura Natsuko , Shah Dhaval K , Carrick Sean , Kesari Santosh
Published: September 2024

Background

This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.

Methods

Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.

Results

Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).

Conclusions

Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.
Inductive Calculation of Superconformal Indices Based on Giant Graviton Expansion
Authors: Imamura Yosuke , Murayama Shuichi
Published: September 2024

We investigate a simple-sum giant graviton expansion of the superconformal indices of ${\cal N}=2$ superconformal field theories realized on D3-branes probing 7-brane backgrounds with constant axio-dilation field. The expansion is of self-dual type, and imposes strong constraints on the indices. By using the constraints we determine the first few terms in the superconformal indices for arbitrary rank $N$.
Systematic Local Simulations of Fast Neutrino Flavor Conversions with Scattering Effects
Authors: Azari Milad Delfan , Sasaki Hirokazu , Takiwaki Tomoya , Okawa Hirotada
Published: September 2024

We investigate the dynamics of fast neutrino flavor conversions (FFCs) in the one-dimensional (1D) and zero-dimensional (0D) models, in which spatial advection is considered and ignored, respectively. In this study, we employ snapshots obtained by our self-consistent, realistic Boltzmann-neutrino-radiation-hydrodynamics simulations. We show that the FFC growth rate is considerably larger in the 1D model than in the 0D model, as expected from the previous linear analysis results. We find that the momentum space dimension does not significantly influence the neutrino transition probability in 1D models. On the other hand, in the 0D model without collisions, the FFC depends on the momentum space, and the azimuthal angle dependence breaks the periodicity of the FFC. Our study demonstrates that collisional instability can lead to further flavor conversions on a long timescale in 1D models after the asymptotic state of FFC has been reached. Such an effect should be taken into consideration when the fast and collisional flavor instabilities coexist.
Comprehensive Analysis of Impurity Detection in Linear Alkyl Benzene–Based Liquid Scintillators Using Infrared Spectroscopy for Enhanced Neutrino Detection
Authors: Choi Ji Young , Joo Kyung Kwang , Park Jubin , Cheoun Myung-Ki
Published: September 2024

We present a comprehensive analysis of infrared (IR) spectra for linear alkyl benzene (LAB)-based scintillation solutions, focusing on the detection and identification of impurities. Previous research primarily utilized ultraviolet-visible spectroscopy to investigate electronic structures and transitions, whereas our approach emphasizes vibrational transitions and IR spectral characteristics. We specifically examined the presence of common impurities, such as acetone, water, and three impurity compounds (IMP1, IMP2, and IMP3) identified by the JUNO Collaboration. Acetone, a common contaminant from cleaning procedures, was detected by its characteristic absorption peaks at 1200, 1360, and 1700 $\rm {cm}^{-1}$. Water, an inevitable by-product of Gd-loaded LAB using a neutralization reaction process, was identified through distinct O-H stretching and H-O-H bending vibrations at 3200–3600 $\rm {cm}^{-1}$ and 1600 $\rm {cm}^{-1}$, respectively. The IR spectra of IMP1, IMP2, and IMP3 were theoretically calculated, revealing unique absorption bands for key functional groups, including carbonyl (C=O), amide (C-N), sulfoxide (S=O), aryl chloride (Ar-Cl), azo (N=N), and ether (C-O-C) groups. The findings confirm the absence of these impurities in the LAB (+ 2,5-Diphenyloxazole [PPO] + 1,4-Bis(2-methylstyryl)benzene [bis-MSB]) sample, ensuring the high performance and accuracy of neutrino detectors. This study demonstrates the effectiveness of IR spectroscopy as a powerful analytical tool for quality assurance in liquid scintillation solutions, providing a robust framework for enhancing the reliability and precision of neutrino detection experiments.
Progranulin enhances the engraftment of transplanted human iPS cell-derived cerebral neurons
Authors: Yamagami Keitaro , Samata Bumpei , Doi Daisuke , Tsuchimochi Ryosuke , Kikuchi Tetsuhiro , Amimoto Naoya , Ikeda Megumi , Yoshimoto Koji , Takahashi Jun
Published: September 2024

Cerebral organoids (COs) in cell replacement therapy offer a viable approach to reconstructing neural circuits for individuals suffering from stroke or traumatic brain injuries. Successful transplantation relies on effective engraftment and neurite extension from the grafts. Earlier research has validated the effectiveness of delaying the transplantation procedure by 1 week. Here, we hypothesized that brain tissues 1 week following a traumatic brain injury possess a more favorable environment for cell transplantation when compared to immediately after injury. We performed a transcriptomic comparison to differentiate gene expression between these 2 temporal states. In controlled in vitro conditions, recombinant human progranulin (rhPGRN) bolstered the survival rate of dissociated neurons sourced from human induced pluripotent stem cell-derived COs (hiPSC-COs) under conditions of enhanced oxidative stress. This increase in viability was attributable to a reduction in apoptosis via Akt phosphorylation. In addition, rhPGRN pretreatment before in vivo transplantation experiments augmented the engraftment efficiency of hiPSC-COs considerably and facilitated neurite elongation along the host brain’s corticospinal tracts. Subsequent histological assessments at 3 months post-transplantation revealed an elevated presence of graft-derived subcerebral projection neurons—crucial elements for reconstituting neural circuits—in the rhPGRN-treated group. These outcomes highlight the potential of PGRN as a neurotrophic factor suitable for incorporation into hiPSC-CO-based cell therapies.
SheepEye: a based-web app for real-time diagnosis of sheep anemia
Authors: Freitas Luara A , da Rocha Naila C , Barbosa Abner M P , Dorea Joao R R , Paz Claudia C P , Rosa Guilherme J M
Published: September 2024

Haemonchus contortus is an extremely harmful blood-feeding nematode affecting small ruminants, leading to anemia, weight loss, and, in severe cases, animal death. Traditional methods of monitoring anemia in sheep, such as regular physical examinations by veterinarians and laboratory tests, can be expensive and time-consuming. In this work, we propose an anemia monitoring system that uses a web-based app. The methodology for the SheepEye app is based on deep learning algorithms, including the U-net model for segmentation and the VGG19 model for classification. All learning algorithms, as well as the development of the app, were implemented in Python. The SheepEye web-based app is a promising technology that can facilitate and improve the diagnosis of parasitic infections in sheep and enhance sheep productivity. By using the app, farmers can detect anemia in their flocks and implement target selective treatment, which reduces the use of anthelmintics and consequently minimizes the risk of parasitic resistance. The SheepEye app is still in a prototype stage, but its prospective is extremely promising and our goal is to further develop it so that it can be made available for producers to use.
Factors Associated With Successful Withdrawal of Biologic Agents in Children With Colchicine-Resistant Familial Mediterranean Fever
Authors: Taş Özen , Aydın Fatma , Sezer Müge , Çelikel Acar Banu , Bahçeci Onur , Çakar Nilgün , Dumlupınar Ebru , Özçakar Zeynep Birsin
Published: September 2024

Background

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%–10% of patients may respond inadequately to colchicine, and anti–interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy.

Methods

Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment.

Results

In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidities were found to be statistically more frequent in the group whose biological therapy could not be discontinued (p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively).

Conclusions

Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients.
Characterisation of virulence ofPuccinia coronataf. sp.avenaein Australia in the 2023 growing season
Authors: Nguyen Duong T. , Henningsen Eva C. , Lewis David , Mago Rohit , Sperschneider Jana , Stone Eric , Dodds Peter N. , Figueroa Melania
Published: September 2024

Crown rust caused by the basidiomycete fungusPuccinia coronataf. sp.avenae(Pca) results in significant crop losses worldwide. Genetic solutions to protect against this disease require disease resistance gene discovery and introduction of resistance genes into elite germplasm by breeders. To inform disease resistance breeding activities, it is paramount to monitor changes of virulence in thePcapopulation and link those to genotypes of the pathogen. In 2023, a collection of 37Pcaisolates from diverse regions in Australia were gathered and their infection types across a commonly used set of oat differential lines determined to assign virulence pathotypes. We compared those virulence phenotypes to data collected in previous collections. While some of the virulence phenotypes had been reported in 2022, our analysis detected new virulence or an increase in frequency for virulence on some resistance genes. Notably, some of the frequency increases in virulence were recorded in Western Australia (WA), a region of interest due to its role in oat production for milling.
PTSD-related differences in resting-state functional connectivity and associations with sex hormones
Authors: Noble Natalie C , Sendi Mohammad SE , Merker Julia B , Linton Samantha R , Webber Theresa K , Etkin Amit , Wu Wei , Ressler Kerry J , Seligowski Antonia V
Published: September 2024

Background: Posttraumatic stress disorder (PTSD) is a debilitating condition that disproportionately impacts individuals who are female. Prior research indicates that males with PTSD exhibit hypoconnectivity of frontal brain regions measured with resting electroencephalography (EEG). The present study examined functional connectivity among females with PTSD and trauma-exposed controls, as well as the impact of sex hormones. Methods: Participants included 61 females (Mage = 31.41, SD = 8.64) who endorsed Criterion A trauma exposure. Resting state EEG data were recorded for five minutes in the eyes open position. Using a Linear Mixed Effects model, paired region-of-interest power envelope connectivity of the theta band (4-7 Hz) served as the response variables. Results: Compared to controls, the PTSD group displayed hyperconnectivity between visual brain regions and the rest of the cerebral cortex (pFDR < 0.05). Additionally, participants with PTSD demonstrated enhanced connectivity between the default mode network and frontoparietal control network compared to controls (pFDR < 0.05), as well as increased connectivity between the ventral attention network and the rest of the cerebral cortex (pFDR < 0.05). Estradiol was associated with higher connectivity, while progesterone was associated with lower connectivity, but these did not survive correction. Conclusions: Results are consistent with prior research indicating that PTSD is associated with altered connectivity in visual brain regions, which may reflect disrupted visual processing related to reexperiencing symptoms (e.g., intrusive memories). Our findings provide additional support for the relevance of the theta frequency range in PTSD given its role in fear learning and regulation processes.
Trial-level factors affecting accrual rate of systemic sclerosis randomized clinical trials over 20 years
Authors: Russo Barbara , Chirică Iulia-Simona , Courvoisier Delphine Sophie , Iudici Michele
Published: September 2024

Objectives

To estimate the average time to complete patient enrollment and identify factors associated with accrual rates in systemic sclerosis (SSc) randomized controlled trials (RCTs).

Methods

We searched published SSc-RCTs indexed in PubMed from 2000 to 2024, selecting those with recruitment completed before the COVID-19 pandemic. We recorded key trial features (country, phase, randomization ratio, intervention, blinding, funding source, outcome type) and enrollment year(s). We measured enrollment duration and accrual rate (participants per month). A multivariable negative binomial generalized linear model was used to identify factors associated with accrual rate.

Results

We included 80 studies, mostly single-country (75.0%) and industry-funded (57.5%), mainly recruiting in Europe (36.2%) and North America (22.5%). In 65% of studies, both limited and diffuse SSc patients were enrolled. The median sample size was 40.5 patients, with 20% of RCTs enrolling ≥100 patients. The median recruitment time was 15 months (IQR 9.9 – 30.0), with a median accrual rate of 3.1 (IQR 1.6 - 5.5) participants per month. Recruitment rates varied over time, with faster accrual early in the 2000s and after 2012, and a slower period in between. Multivariable analysis showed that accrual rate was positively associated with skewed randomization, non-industry funding, international recruitment, and inclusion of both SSc subsets, especially compared to studies involving only dcSSc patients.

Conclusions

Recruiting SSc patients for RCTs has been challenging, with generally slow accrual over the past 20 years and no significant improvement over time.
CAMDA 2023: finding patterns in urban microbiomes
Authors: Contreras-Peruyero Haydeé , Nuñez-Morales Imanol , Vazquez-Rosas-Landa Mirna , Santana-Quinteros Daniel , Pashkov Antón , Carranza-Barragán Mario E. , Perez-Estrada Rafael , Guerrero-Flores Shaday , Balanzario Eugenio , Muñiz Sánchez Víctor , Nakamura Miguel , Ramírez-Ramírez L. Leticia , Sélem-Mojica Nelly
Published: September 2024

The Critical Assessment of Massive Data Analysis (CAMDA) addresses the challenge of effectively utilizing Big Data in life science. Serving as both a conference and a catalyst for research groups, CAMDA annually presents challenges that foster innovative solutions. For the Forensics CAMDA 2023 challenge, we analyzed 365 metagenomic samples from 16 cities worldwide to characterize their origin. The forensic challenge was addressed from two perspectives: using the reduced abundance OTU tables and employing functional annotations. To identify the most informative Operational Taxonomic Units, we fit negative binomial models ultimately reducing variables to 294. After OTU selection, we implemented supervised models and conducted 5-fold cross-validation (CV) with a 4:1 training-to-validation ratio in each scenario. Support vector classification (SVC) achieved the highest F1 score (0.96) for the abundance tables, accurately classifying most cities, although New York City (NYC) posed a challenge. Via functional profiles with Mifaser at level 4, we achieved the best functional classification using the Neural Network (NN) model. Additionally, to gain insight into further associations between bacterial distribution with other covariates, we applied Dirichlet regression overEscherichia,Enterobacter, andKlebsiellabacteria abundances. We considered climatic and demographic variables of the cities, observing that population increase is indeed associated with a rise in the mean ofEscherichiawhile decreasing temperature is linked to higher proportions ofKlebsiella. For replicability of the scripts, a Docker container and a Conda environment are available at the repository: GitHub:github.com/ccm-bioinfo/cambda2023
Nuclear Type I Myosins are Essential for Life and Genome Organization
Authors: Peng Audrey Yi Tyan , Li Jianhui , Freeman Brian C.
Published: September 2024

The active transport of large biomolecules within a cell is critical for homeostasis. While the cytoplasmic process is well-studied, how the spacing of nucleoplasmic cargo is coordinated is poorly understood. We investigated the impact of myosin motors in the nucleus of budding yeast. We found that life requires a nuclear type I myosin whereas the essential type II or V myosins were not requisite in the nucleus. Nuclear depletion of type I myosins triggered 3D genome disorganization, nucleolar disruption, broad gene expression changes, and nuclear membrane morphology collapse. Genome disorganization occurred first supporting a model where type I myosins actively maintain genome architecture that scaffolds nuclear membrane and nucleolar morphologies. Overall, nuclear myosin is critical for the form and function of the nucleus.