bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of large language models on radiology: a guide for radiologists on the latest innovations in AI
Authors: Nakaura Takeshi , Ito Rintaro , Ueda Daiju , Nozaki Taiki , Fushimi Yasutaka , Matsui Yusuke , Yanagawa Masahiro , Yamada Akira , Tsuboyama Takahiro , Fujima Noriyuki , Tatsugami Fuminari , Hirata Kenji , Fujita Shohei , Kamagata Koji , Fujioka Tomoyuki , Kawamura Mariko , Naganawa Shinji
Published: March 2024

The advent of Deep Learning (DL) has significantly propelled the field of diagnostic radiology forward by enhancing image analysis and interpretation. The introduction of the Transformer architecture, followed by the development of Large Language Models (LLMs), has further revolutionized this domain. LLMs now possess the potential to automate and refine the radiology workflow, extending from report generation to assistance in diagnostics and patient care. The integration of multimodal technology with LLMs could potentially leapfrog these applications to unprecedented levels.

However, LLMs come with unresolved challenges such as information hallucinations and biases, which can affect clinical reliability. Despite these issues, the legislative and guideline frameworks have yet to catch up with technological advancements. Radiologists must acquire a thorough understanding of these technologies to leverage LLMs’ potential to the fullest while maintaining medical safety and ethics. This review aims to aid in that endeavor.
Effects of Shot Sleeve Pre-solidification on the Microstructure and Tensile Properties of High Pressure Die Cast AE44
Authors: Yu Wenhao , Zhan Hongyi , Gourlay Christopher M.
Published: March 2024

In cold-chamber high pressure die casting (HPDC), some pre-solidification occurs in the shot sleeve prior to being injected into the die cavity. Here, we study the effects of pre-solidification on the development of microstructure and defects in the HPDC of magnesium alloy AE44 (Mg–4Al–4RE–0.2Mn, wt pct, where RE are mixed La and Ce) and on subsequent tensile properties. Samples with a high fraction of pre-solidification contained both externally solidified crystals (ESCs) and cold flakes, which also induced large pockets of positive macrosegregation. Variations in the morphology and length scale of$$\alpha$$α-Mg grains and eutectic Al$$_{11}$$11RE$$_{3}$$3are discussed in terms of the different cooling conditions for each microstructural feature using a grain morphology map for$$\alpha$$α-Mg. A high fraction of pre-solidification resulted in a small decrease in yield stress due to the larger microstructural length scale, and a substantial decrease in ultimate tensile strength and ductility due to the presence of a non-bonded interface between cold flakes and the surrounding material. The results provide insights into microstructure formation in the HPDC of AE44 and highlight the importance of controlling the extent of pre-solidification that is injected into the die cavity.
Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS)
Authors: Bilgin Emre , Demirci Yıldırım Tuba , Özdemir Ulusoy Bahar , Öğüt Tahir Saygın , Karabacak Murat , Sadioğlu Çağdaş Öznur , Yıldırım Reşit , Güven Deniz Can , Akleylek Cansu , Ediboğlu Elif , Kutu Muhammet Emin , Özgür Duygu , Kardaş Rıza Can , Bölek Ertuğrul Çağrı , Sandal Uzun Güllü , Özsoy Zehra , Sarıyıldız Emine , Ayan Gizem , Armağan Berkan , Erden Abdulsamet , Kılıç Levent , Erbasan Funda , Alibaz-Öner Fatma , Aşıcıoğlu Ebru , Yazıcı Ayten , Bilge Nazife Şule , Küçük Hamit , Çelik Selda , Bes Cemal , Akar Servet , Yılmaz Neslihan , Kaşifoglu Timucin , Cefle Ayse , Direskeneli Haner , Yazısız Veli , Dizdar Ömer , Omma Ahmet , Önen Fatoş , Karadağ Ömer
Published: March 2024

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case–control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3–3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head–neck regions, particularly in males and the elderly, is vital.
Prediction of cardiovascular risk in patients with hepatocellular carcinoma receiving anti-angiogenic drugs: lessons from sorafenib
Authors: Stefanini Bernardo , Tovoli Francesco , Trevisani Franco , Marseglia Mariarosaria , Di Costanzo Giovan Giuseppe , Cabibbo Giuseppe , Sacco Rodolfo , Pellizzaro Filippo , Pressiani Tiziana , Chen Rusi , Ponziani Francesca Romana , Foschi Francesco Giuseppe , Magini Giulia , Granito Alessandro , Piscaglia Fabio ,   Italian Liver Cancer (ITA.LI.CA) group
Published: March 2024

Antiangiogenics are associated with an increased risk of major adverse cardiac and cerebrovascular events (MACE). The identification of at-risk subjects is relevant in the case of hepatocellular carcinoma (HCC), for which anti-angiogenic TKIs and bevacizumab are used in first and subsequent lines of therapy, to select alternative drugs for patients with excessive risk. We verified the ability to predict MACE in sorafenib-treated patients of the 2022 European Society of Cardiology (ESC-2022) score for anti-angiogenics and the recently proposed CARDIOSOR score. A retrospective analysis was conducted of prospectively collected data of the ARPES and ITA.LI.CA databases. All patients received sorafenib for unresectable HCC from 2008 to 2018. Baseline information to calculate the ESC-2022 and CARDIOSOR scores and registration of evolutive events (including MACE) were available for all patients. The predictive ability of both scores was verified using competing risk regressions and tests for goodness of fit. This study included 843 patients (median follow-up 11.3 months). Thirty-four (4.0%) patients presented a MACE. The four-tier ESC-2022 classification showed a progressive risk increase for every class (cumulative risk 1.7%, 2.7%, 4.3%, and 15.0% in the low, medium, high, and high-risk tiers, respectively). The dichotomous CARDIOSOR scale identified a high-risk group with a fourfold increased risk of MACE (sHR 4.66, p = 0.010; cumulative risk 3.8% and 16.4%). ESC-2022 showed a better goodness of fit compared to the CARDIOSOR score [C-index 0.671 (0.583–0.758) vs 0.562 (0.501–0.634), p = 0.021], but this gap was eliminated using the linear version of CARDIOSOR. Both the ESC-2022 and CARDIOSOR scores discriminated patients at increased risk for MACE. The use of these scores in clinical practice should be encouraged, since therapeutic measures can mitigate the cardiovascular risk.
Personalizing non-small cell lung cancer treatment through patient-derived xenograft models: preclinical and clinical factors for consideration
Authors: Fuchs Vered , Sobarzo Ariel , Msamra Maha , Kezerle Yarden , Linde Liat , Sevillya Gur , Anoze Alaa , Refaely Yael , Cohen Ahron Yehonatan , Melamed Israel , Azriel Amit , Shoukrun Rami , Raviv Yael , Porgador Angel , Peled Nir , Roisman Laila Catalina
Published: March 2024

Purpose

In the pursuit of creating personalized and more effective treatment strategies for lung cancer patients, Patient-Derived Xenografts (PDXs) have been introduced as preclinical platforms that can recapitulate the specific patient’s tumor in an in vivo model. We investigated how well PDX models can preserve the tumor’s clinical and molecular characteristics across different generations.

Methods

A Non-Small Cell Lung Cancer (NSCLC) PDX model was established in NSG-SGM3 mice and clinical and preclinical factors were assessed throughout subsequent passages. Our cohort consisted of 40 NSCLC patients, which were used to create 20 patient-specific PDX models in NSG-SGM3 mice. Histopathological staining and Whole Exome Sequencing (WES) analysis were preformed to understand tumor heterogeneity throughout serial passages.

Results

The main factors that contributed to the growth of the engrafted PDX in mice were a higher grade or stage of disease, in contrast to the long duration of chemotherapy treatment, which was negatively correlated with PDX propagation. Successful PDX growth was also linked to poorer prognosis and overall survival, while growth pattern variability was affected by the tumor aggressiveness, primarily affecting the first passage. Pathology analysis showed preservation of the histological type and grade; however, WES analysis revealed genomic instability in advanced passages, leading to the inconsistencies in clinically relevant alterations between the PDXs and biopsies.

Conclusions

Our study highlights the impact of multiple clinical and preclinical factors on the engraftment success, growth kinetics, and tumor stability of patient-specific NSCLC PDXs, and underscores the importance of considering these factors when guiding and evaluating prolonged personalized treatment studies for NSCLC patients in these models, as well as signaling the imperative for additional investigations to determine the full clinical potential of this technique.
High-throughput metabolomics identifies new biomarkers for cervical cancer
Authors: Li Xue , Zhang Liyi , Huang Xuan , Peng Qi , Zhang Shoutao , Tang Jiangming , Wang Jing , Gui Dingqing , Zeng Fanxin
Published: March 2024

Background

Cervical cancer (CC) is a danger to women’s health, especially in many developing countries. Metabolomics can make the connection between genotypes and phenotypes. It provides a wide spectrum profile of biological processes under pathological or physiological conditions.

Method

In this study, we conducted plasma metabolomics of healthy volunteers and CC patients and integratively analyzed them with public CC tissue transcriptomics from Gene Expression Omnibus (GEO).

Result

Here, we screened out a panel of 5 metabolites to precisely distinguish CC patients from healthy volunteers. Furthermore, we utilized multi-omics approaches to explore patients with stage I-IIA1 and IIA2-IV4 CC and comprehensively analyzed the dysregulation of genes and metabolites in CC progression. We identified that plasma levels of trimethylamine N-oxide (TMAO) were associated with tumor size and regarded as a risk factor for CC. Moreover, we demonstrated that TMAO could promote HeLa cell proliferation in vitro. In this study, we delineated metabolic profiling in healthy volunteers and CC patients and revealed that TMAO was a potential biomarker to discriminate between I-IIA1 and IIA2-IV patients to indicate CC deterioration.

Conclusion

Our study identified a diagnostic model consisting of five metabolites in plasma that can effectively distinguish CC from healthy volunteers. Furthermore, we proposed that TMAO was associated with CC progression and might serve as a potential non-invasive biomarker to predict CC substage.

Impact

These findings provided evidence of the important role of metabolic molecules in the progression of cervical cancer disease, as well as their ability as potential biomarkers.
Detection of groundwater conditioning factors in a hilly environment
Authors: Barman Jonmenjoy , VLH Zuali F. , Bindajam Ahmed Ali , Mallick Javed , Abdo Hazem Ghassan
Published: March 2024

Champhai, the rice bowl of Mizoram, is known for wet rice practices. Rapid urbanization and global climate change increased the demand for groundwater. Champhai city, being a hilly township in northeast India, is very difficult to identify the potential groundwater water availability. The present study aimed at groundwater potentiality zonation in Champhai town. For these purposes ten (10) factors from topographic, climatic, hydrological and other conditions were assigned weightage based on the AHP (analytical hierarchy process) technique. The aspect was given maximum weightage as the aspect working as the controlling factors of precipitation intensity, vegetation and soil type, while LULC (land use land cover) was assigned minimum weightage that unscientific human activities reduced infiltration rate. Subsequently, an addition of ten weighted rasters was performed for groundwater potentiality zonation. As a result, it was seen that the maximum part of the study area covered low potentiality zones (31.88%), whereas high and very high potential zone covered 14.73% and 5.08, respectively. A scientific validation technique, namely AUC (area under curve) value of 0.737, denoted a good classified groundwater water potentiality zone. Further, the single-layer sensitivity analysis highlighted that elevation, slope, aspect, infiltration number, distance to streams and rainfall had the maximum effective factors based on their effective weightage. The map removal sensitivity analysis highlighted that TWI (Topographic Wetness Index) and aspect had the maximum influence on the model. However, in a hilly environment like Champhai, the output of the current study will work as a blueprint for planning and decision making.
On some new arithmetic properties of certain restricted color partition functions
Authors: Dasappa Ranganatha , Channabasavayya  , Keerthana Gedela Kavya
Published: March 2024

Very recently, Pushpa and Vasuki (Arab. J. Math. 11, 355–378, 2022) have proved Eisenstein series identities of level 5 of weight 2 due to Ramanujan and some new Eisenstein identities for level 7 by the elementary way. In their paper, they introduced seven restricted color partition functions, namely $$P^{*}(n), M(n), T^{*}(n), L(n), K(n), A(n)$$

P

∗

(
n
)

,
M

(
n
)

,

T

∗

(
n
)

,
L

(
n
)

,
K

(
n
)

,
A

(
n
)

, and B(n), and proved a few congruence properties of these functions. The main aim of this paper is to obtain several new infinite families of congruences modulo $$2^a\cdot 5^\ell $$

2
a

·

5
ℓ

for $$P^{*}(n)$$

P

∗

(
n
)

, modulo $$2^3$$

2
3

for M(n) and $$T^*(n)$$

T
∗

(
n
)

, where $$a=3, 4$$

a
=
3
,
4

and $$\ell \ge 1$$

ℓ
≥
1

. For instance, we prove that for $$n\ge 0$$

n
≥
0

, $$\begin{aligned} P^{*}(5^\ell (4n+3)+5^\ell -1)&\equiv 0\pmod {2^3\cdot 5^{\ell }}. \end{aligned}$$

P

∗

(

5
ℓ

(
4
n
+
3
)

+

5
ℓ

-
1
)

≡
0

(
mod

2
3

·

5
ℓ

)
.

In addition, we prove witness identities for the following congruences due to Pushpa and Vasuki: $$\begin{aligned} M(5n+4)\equiv 0\pmod {5},\quad T^{*}(5n+3)\equiv 0\pmod {5}. \end{aligned}$$

M

(
5
n
+
4
)

≡
0

(
mod

5
)

,

T

∗

(
5
n
+
3
)

≡
0

(
mod

5
)

.
Ultrasound-guided diagnosis on a parapharyngeal mass
Authors: Alessio Frisone , Scarano Antonio , Valentini Giulia , Boccatonda Andrea , Andreetto Lorenzo , Vicari Susanna
Published: March 2024

Masses in the parapharyngeal area are rare and often due to infectious phenomena arising from the oral cavity or pharynx which lead to abscess formation. Less frequently, the lesion can be neoplastic. Tumours of the parapharyngeal space are rare, accounting for less than 1% of all head and neck neoplasms. We report the case of a patient who came to our observation for mandibular pain. Multiparametric diagnostic imaging was done thus showing a parapharyngeal mass. An ultrasound guided biopsy was performed by a transcutaneous route with a high median approach at neck level, to characterize the mass in the right tonsillar region. The histological examination reported the final histological diagnosis of sarcomatoid carcinoma.
“Excited When They See Their Name in Print”: Research Outputs from an Australian Medical Program
Authors: Dinh Harry Hieu , Uebel Kerry , Iqbal Maha Pervaz , Grant Ari , Shulruf Boaz , Nathan Sally , Vo Khanh , Smith Greg , Carland Jane Ellen
Published: March 2024

To promote evidence-based practice, medical schools offer students opportunities to undertake either elective or mandatory research projects. One important measure of the research program success is student publication rates. In 2006, UNSW Medicine implemented a mandatory research program in the 4th year of the undergraduate medical education program. This study identified student publication rates and explored student and supervisor experiences with the publication process.

A retrospective audit of student publications from the 2007, 2011, and 2015 cohorts was undertaken to look at trends over time. Data collected included type of publication and study methodology. Semi-structured interviews were conducted with a sample of undergraduate students (n = 11), medical graduates (n = 14), and supervisors (n = 25) and analysed thematically.

Student publication rates increased significantly (P = 0.002) from 28% in 2007 to 50.2% in 2015. Students able to negotiate their own project were more likely to publish (P = 0.02). Students reported personal affirmation and development of research skills from publishing their research findings, while graduates noted improved career opportunities. Supervisors expected students to publish but identified the time to publications and student motivation as key factors in achieving publication(s).

A high publication rate is possible in a mandatory research program where students can negotiate their own topic and are given protected time. Publications happen after the research project has finished. Critical factors in successful publication include supervisor support and student motivation. Given the importance of the supervisor’s role, staff development and faculty support to train and develop a body of skilled supervisors is required.
Shared Space: promoting teachers’ academic understanding of inter-religious dialogue through a teacher fellowship model for religious education (RE)
Authors: Orchard Janet , Bowen Victoria
Published: March 2024

We report on the design of a close-to-practice research project situated in Southwest England exploring the relationship between developing teachers’ ‘powerful knowledge’ of inter-religious dialogue in religious education (RE) through a teacher fellowship model for RE specialists, including a specialist curriculum development programme and co-constructed evaluation of an intervention seeking to promote ‘warmer’ community relations. This current phase of the ‘Shared Space’ project combines insight from two existing subject-specific knowledge exchange projects—undertaken by us—with a Teacher Fellowship approach to pedagogical and curriculum knowledge development pioneered by the Historical Association, and an emerging one, ‘After RE’. The current Shared Space project addresses two established concerns in RE that are not normally connected: (1) the lack of rigorous subject knowledge held by RE teachers in England; (2) the assumption that good RE in schools can promote community relations, a widely accepted assumption hitherto without much evidence to support it. Here we set out a justification for the project and the form it will take, based on established Shared Space principles of how best to support in-service teachers’ ongoing professional development through knowledge exchange with academics, mindful of equal power relations. While appreciating aspects of the notion of ‘powerful knowledge’ on which ‘theory-rich’ Teacher Fellowships have been based, we cite thinking from the emerging After RE project to suggest a modified theoretical framework for our investigation which will innovate methodologically when evaluating its impact in partnership with teacher participants.
Thermal Penetration of Aircraft Tyre Tread at Touchdown
Authors: Li Yu , Wang Weiji
Published: March 2024

Most studies of friction and heat conduction in aircraft tyres at touchdown are limited to the tread surface. However, it is necessary to know the thermal penetration inside the tread to study the quantity of the potential decomposed and lost material by the frictional heat. Additionally, a high tread surface temperature does not necessarily guarantee a stronger thermal penetration inside the tread because of several factors. Therefore, it is necessary to establish a relationship between the tyre tread surface temperature and the internal heat penetration under the aircraft touchdown scenario. A model is established on MATLAB to simulate the aircraft tyre dynamics and tread heat conduction at touchdown. This model is capable of calculating the temperature increase in the tread, both on the surface and inside. It can also be used to determine the depth of thermal decomposition caused by frictional heat. Additionally, the study found that the Thermal Decomposition Depth to Surface Temperature Ratios (DTRs) are similar across the tread (the depth of thermal decomposition at each part of the tread surface is proportional to the surface temperature). Therefore, it can estimate the thermal penetration throughout the tread by simply calculating the surface temperature of the entire tread and the average DTR at several points of interest. The study provides a more straightforward approach for aircraft tyre thermal wear prediction and future research.
Modified rice husk as component in recyclable and biodegradable epoxy thermosets
Authors: Yiga Vianney Andrew , Subramaniyan Sathiyaraj , Kalita Naba Kumar , Lubwama Michael , Hakkarainen Minna
Published: March 2024

Rice husk (RH), an abundant agricultural residue, was successfully chemically modified and used as a component in reprocessable and biodegradable epoxy thermosets. First, RH was subjected to alkaline treatment to increase the cellulose content followed by succinylation and curing with trimethylolpropane triglycidyl ether to form the thermoset films. The chemical structure of the different intermediates and thermosets was confirmed by Fourier transform infrared spectroscopy. The developed thermoset films had good solvent resistance against common organic solvents and good thermal stability as measured by thermogravimetry with peak temperatures of 347–387 ℃, char residues of 16–20% and limiting oxygen index values of 24–26%, respectively. The films could be thermally reprocessed by hot-pressing with excellent recovery of the mechanical properties (92–96% recovery of tensile stress). Furthermore, 80–84% biodegradation during 150 days under mesophilic home composting conditions was demonstrated by cumulative CO2 evolution. These results indicate promising potential for the developed RHs thermosets as replacements for petroleum-based plastics in e.g. packaging and agricultural applications.
End-of-life cohorts from the Dartmouth Institute: risk adjustment across health care markets, the relative efficiency of chronic illness utilization, and patient experiences near the end of life
Authors: Bronner Kristen K. , Goodman David C.
Published: March 2024

Since their inception, small area studies intended to measure health system performance have been challenged by concerns that regional variation in health care may be primarily explained by differences in patient health risk. Controlling for regional population differences depends on appropriate risk adjustment, but the adequacy of the methods used in early analyses was contested. A novel response to these concerns was the development of end-of-life cohorts by Dartmouth Atlas investigators. These were used initially to control for differences in population health status in studies investigating relative efficiency across regions. Later, they became useful for studying hospital-level variation in chronic illness care, and for measuring utilization and patient experiences at the very end of life. Altogether, end-of-life cohorts have been invaluable for clarifying the contribution of health system and provider factors to health care variation and outcomes.
Heterogeneous and Composite Bioinks for 3D-Bioprinting of Complex Tissue
Authors: Rasouli Rahimeh , Sweeney Crystal , Frampton John P.
Published: March 2024

Bioink composition is a key consideration for the 3D-bioprinting of complex and stable structures used to model tissues and as tissue constructs for regenerative medicine. An emerging and industrially important area of research is the use of micro- and nanofillers to improve bioink performance without dramatically altering the physicochemical properties of the polymeric material that forms the bulk of the printed structure. The purpose of this review is to provide a comprehensive overview of emerging nanomaterial fillers designed to create heterogeneous and composite bioinks for 3D-bioprinting of complex functional tissues. We outline the criteria that must be considered when developing such a bioink and discuss applications where the fillers impart stimuli responsiveness, e.g., when exposed to magnetic fields, electrical fields, and light. We further highlight how the use of such fillers can enable non-destructive imaging to monitor scaffold placement and integrity following implantation.
Inclusive Fitness and Kin Selection
Authors: Rubin Hannah
Published: March 2024

The biological world is full of phenomena that seem to run counter to Darwin's insight that natural selection can lead to the appearance of design. For instance, why do organisms in some species divide reproductive labor? The existence of non-reproducing organisms in such 'eusocial' species looks to be at odds with an evolutionary theory which posits traits exist because they help organisms survive and reproduce. What is the evolutionary advantage of an insect being distasteful to its predators? The distastefulness appears designed to deter predators, but can only affect the predator's actions when the insect is eaten; it is hard to see how such a trait could be passed on. This Element will cover the shared foundations of evolutionary explanations for these and other seemingly puzzling phenomena, focusing on the concepts of inclusive fitness and kin selection.
Pragmatics, Grammar and Meaning in SLA
Authors: Ahern Aoife K. , Amenós-Pons José , Guijarro-Fuentes Pedro
Published: March 2024

This Element explores the role of pragmatics, and its relationship with meaning and grammar, in second language acquisition. Specifically, this Element examines the generative paradigm, with its focus on purely linguistic aspects, in contrast with, and complemented by, the view of language adopted in the wider perspective on communication that Relevance Theory offers. It reviews several theoretical standpoints on how linguistic phenomena that require combining semantic, pragmatic and syntactic information are acquired and developed in second languages, illustrating how these perspectives are brought together in analysing data in different linguistic scenarios. It shows that the notion of procedural meaning casts light on the range of interpretative effects of grammatical features and how they vary across languages, suggesting ways to complete the picture of the interface factors that affect second language development.
A Cost Model for Ocean Iron Fertilization as a Means of Carbon Dioxide Removal That Compares Ship‐ and Aerial‐Based Delivery, and Estimates Verification Costs
Authors: Emerson David , Sofen Laura E. , Michaud Alexander B. , Archer Stephen D. , Twining Benjamin S.
Published: March 2024

We present a cost model for implementing a deployment scale effort for conducting ocean iron fertilization (OIF) for marine‐based carbon dioxide removal (CDR). The model incorporates basic oceanographic parameters critical for estimating the effective export of newly fixed CO2 into biomass that is stimulated by Fe addition to an Fe‐limited region of the Southern Ocean. Estimated costs can vary by nearly 100‐fold between best‐case and worst‐case scenarios, with best‐case values of $7/net tonne C captured versus worst‐case $1,500/net tonne C captured, without accounting for verification costs. Primary oceanographic factors that influence cost are the net primary productivity increases achieved via OIF, the amount of C exported into the deep ocean, and the amount of CO2 ventilated back to the atmosphere. The model compares ship‐based versus aerial delivery of Fe to the ocean, and estimates aerial delivery can be 30%–40% more cost effective; however, the specific requirements for aerial delivery require additional research and development. The model also estimates costs associated with verification and environmental monitoring of OIF. These costs increase $/net tonne C captured by 3–4‐fold. Best, intermediate, and worst cases for aerial delivery and ship delivery are $21, $83, $2,033, and $24, $94, $4,691, respectively, inclusive of verification costs. The primary goal of this model is to demonstrate the variability in cost of OIF as a CDR method, and to better understand where additional research is needed to determine the major factors that may make OIF a tractable, nature‐based CDR method.
Distribution of Seed Electron Phase Space Density Minima in Earth's Radiation Belts
Authors: Drozdov A. Y. , Allison H. J. , Saikin A. A. , Schiller Q. , Wang D.
Published: March 2024

We conducted a statistical analysis of local phase space density (PSD) minima across a wide energy range (∼20 keVs to ∼10 MeV), using observations from the Van Allen Probes and the Geostationary Operational Environmental Satellite. We identified deepening minima in PSD profiles of multi‐MeV (∼5% occurrence) and of “seed” electrons (up to 15% occurrence, corresponding to ∼70–100 s keV) and compared their distribution with a 3D diffusion model using the Versatile Electron Radiation Belts (VERB) code. The comparison of the observed and modeled distributions suggests that the PSD minima of seed electrons are likely associated with hiss waves and the corresponding L‐shell dependent electron lifetimes. However, the observed distribution was not fully reproduced by the model, potentially indicating other fast loss mechanisms of seed electrons.
aEEG in the first 3 days after extremely preterm delivery relates to neurodevelopmental outcomes
Authors: Pineda Roberta , Vesoulis Zachary , El Ters Nathalie , Mathur Amit
Published: March 2024

Objectives

Investigate relationships between aEEG in the first 72 h in extremely preterm infants with 1) infant, medical, and environmental factors, and 2) infant feeding and neurobehavioral outcomes at term and school-age.

Methods

Sixty-four preterm infants (≤28 weeks gestation) were enrolled within the first 24-hours of life and had two-channel aEEG until 72 h of life. Standardized neurobehavioral and feeding assessments were conducted at term, and parent-reported outcomes were documented at 5–7 years.

Results

Lower aEEG Burdjalov scores (adjusted for gestational age) were related to vaginal delivery (p = 0.04), cerebral injury (p = 0.01), Black race (p < 0.01) and having unmarried parents (p = 0.02). Lower Burdjalov scores related to less NICU Network Neurobehavioral Scale arousal (p = 0.002) at term and poorer BRIEF global executive function (p = 0.004), inhibition (p = 0.007), working memory (p = 0.02), material organization (p = 0.0008), metacognition (p = 0.01), and behavioral regulation (p = 0.02) at 5–7 years. We did not observe relationships of early aEEG to feeding outcomes or sensory processing measures.

Conclusion

Early aEEG within the first 72 h of life was related to medical and sociodemographic factors as well as cognitive outcome at 5–7 years.
The role of quiescent thymic progenitors in TAL/LMO2-induced T-ALL chemotolerance
Authors: O’Connor Kevin W. , Kishimoto Kensei , Kuzma Irena O. , Wagner Kelsey P. , Selway Jonathan S. , Roderick Justine E. , Karna Keshab K. , Gallagher Kayleigh M. , Hu Kai , Liu Haibo , Li Rui , Brehm Michael A. , Zhu Lihua Julie , Curtis David J. , Tremblay Cedric S. , Kelliher Michelle A.
Published: March 2024

Relapse in T-cell acute lymphoblastic leukemia (T-ALL) may signify the persistence of leukemia-initiating cells (L-ICs). Ectopic TAL1/LMO expression defines the largest subset of T-ALL, but its role in leukemic transformation and its impact on relapse-driving L-ICs remain poorly understood. In TAL1/LMO mouse models, double negative-3 (DN3; CD4−CD8−CD25+CD44−) thymic progenitors harbored L-ICs. However, only a subset of DN3 leukemic cells exhibited L-IC activity, and studies linking L-ICs and chemotolerance are needed. To investigate L-IC heterogeneity, we used mouse models and applied single-cell RNA-sequencing and nucleosome labeling techniques in vivo. We identified a DN3 subpopulation with a cell cycle–restricted profile and heightened TAL1/LMO2 activity, that expressed genes associated with stemness and quiescence. This dormant DN3 subset progressively expanded throughout leukemogenesis, displaying intrinsic chemotolerance and enrichment in genes linked to minimal residual disease. Examination of TAL/LMO patient samples revealed a similar pattern in CD7+CD1a− thymic progenitors, previously recognized for their L-IC activity, demonstrating cell cycle restriction and chemotolerance. Our findings substantiate the emergence of dormant, chemotolerant L-ICs during leukemogenesis, and demonstrate that Tal1 and Lmo2 cooperate to promote DN3 quiescence during the transformation process. This study provides a deeper understanding of TAL1/LMO-induced T-ALL and its clinical implications in therapy failure.
Nonvolatile and reconfigurable two-terminal electro-optic duplex memristor based on III-nitride semiconductors
Authors: Xie Zhiwei , Jiang Ke , Zhang Shanli , Ben Jianwei , Liu Mingrui , Lv Shunpeng , Chen Yang , Jia Yuping , Sun Xiaojuan , Li Dabing
Published: March 2024

With the fast development of artificial intelligence (AI), Internet of things (IOT), etc, there is an urgent need for the technology that can efficiently recognize, store and process a staggering amount of information. The AlScN material has unique advantages including immense remnant polarization, superior temperature stability and good lattice-match to other III-nitrides, making it easy to integrate with the existing advanced III-nitrides material and device technologies. However, due to the large band-gap, strong coercive field, and low photo-generated carrier generation and separation efficiency, it is difficult for AlScN itself to accumulate enough photo-generated carriers at the surface/interface to induce polarization inversion, limiting its application in in-memory sensing and computing. In this work, an electro-optic duplex memristor on a GaN/AlScN hetero-structure based Schottky diode has been realized. This two-terminal memristor shows good electrical and opto-electrical nonvolatility and reconfigurability. For both electrical and opto-electrical modes, the current on/off ratio can reach the magnitude of 104, and the resistance states can be effectively reset, written and long-termly stored. Based on this device, the “IMP” truth table and the logic “False” can be successfully reproduced, indicating the huge potential of the device in the field of in-memory sensing and computing.
Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx
Authors: Xiang Ziqian , Zhang Pengfei , Jia Chunwang , Xu Rongkun , Cao Dingren , Xu Zhaoning , Lu Tingting , Liu Jingwei , Wang Xiaoxiong , Qiu Cheng , Fu Wenyang , Li Weiwei , Cheng Lei , Yang Qiang , Feng Shiqing , Wang Lianlei , Zhao Yunpeng , Liu Xinyu
Published: March 2024

To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress. Moreover, conditional knockout of Piezo1 (Col2a1-CreERT Piezo1flox/flox) attenuated the mechanical injury-induced intervertebral disc degeneration (IVDD). Notably, the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout (cDKO) mice (Col2a1-CreERT Piezo1flox/flox/Gpx4flox/flox). These findings suggest that Piezo1 is a potential determinant of iron influx, indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.
LncRNA SNHG26 promotes gastric cancer progression and metastasis by inducing c-Myc protein translation and an energy metabolism positive feedback loop
Authors: Wu Zhen-Hua , Wang Yi-Xuan , Song Jun-Jiao , Zhao Li-Qin , Zhai Yu-Jia , Liu Yan-Fang , Guo Wei-Jian
Published: March 2024

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial–mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.
Pathogenicity of de novo CACNA1D Ca2+ channel variants predicted from sequence co-variation
Authors: Tang Xuechen , Ortner Nadine J. , Nikonishyna Yuliia V. , Fernández-Quintero Monica L. , Kokot Janik , Striessnig Jörg , Liedl Klaus R.
Published: March 2024

Voltage-gated L-type Cav1.3 Ca2+ channels support numerous physiological functions including neuronal excitability, sinoatrial node pacemaking, hearing, and hormone secretion. De novo missense mutations in the gene of their pore-forming α1-subunit (CACNA1D) induce severe gating defects which lead to autism spectrum disorder and a more severe neurological disorder with and without endocrine symptoms. The number of CACNA1D variants reported is constantly rising, but their pathogenic potential often remains unclear, which complicates clinical decision-making. Since functional tests are time-consuming and not always available, bioinformatic tools further improving pathogenicity potential prediction of novel variants are needed. Here we employed evolutionary analysis considering sequences of the Cav1.3 α1-subunit throughout the animal kingdom to predict the pathogenicity of human disease-associated CACNA1D missense variants. Co-variation analyses of evolutionary information revealed residue–residue couplings and allowed to generate a score, which correctly predicted previously identified pathogenic variants, supported pathogenicity in variants previously classified as likely pathogenic and even led to the re-classification or re-examination of 18 out of 80 variants previously assessed with clinical and electrophysiological data. Based on the prediction score, we electrophysiologically tested one variant (V584I) and found significant gating changes associated with pathogenic risks. Thus, our co-variation model represents a valuable addition to complement the assessment of the pathogenicity of CACNA1D variants completely independent of clinical diagnoses, electrophysiology, structural or biophysical considerations, and solely based on evolutionary analyses.
Pediatric hypertrophic cardiomyopathy caused by a novel TNNI3 variant
Authors: Inagaki Natsuko , Okano Tomoya , Kobayashi Masatake , Fujii Masatsune , Yazaki Yoshinao , Takei Yasuyoshi , Kosuge Hisanori , Suzuki Shinji , Hayashi Takeharu , Kuroda Masahiko , Satomi Kazuhiro
Published: March 2024

TNNI3 is a gene that causes hypertrophic cardiomyopathy (HCM). A 14-year-old girl who was diagnosed with nonobstructive HCM presented with cardiopulmonary arrest due to ventricular fibrillation. Genetic testing revealed a novel de novo heterozygous missense variant in TNNI3, NM_000363.5:c.583A>T (p.Ile195Phe), which was determined to be the pathogenic variant. The patient exhibited progressive myocardial fibrosis, left ventricular remodeling, and life-threatening arrhythmias. Genetic testing within families is useful for risk stratification in pediatric HCM patients.
High temperature delays and low temperature accelerates evolution of a new protein phenotype
Authors: Zheng Jia , Guo Ning , Huang Yuxiang , Guo Xiang , Wagner Andreas
Published: March 2024

Since the origin of life, temperatures on earth have fluctuated both on short and long time scales. How such changes affect the rate at which Darwinian evolution can bring forth new phenotypes remains unclear. On the one hand, high temperature may accelerate phenotypic evolution because it accelerates most biological processes. On the other hand, it may slow phenotypic evolution, because proteins are usually less stable at high temperatures and therefore less evolvable. Here, to test these hypotheses experimentally, we evolved a green fluorescent protein in E. coli towards the new phenotype of yellow fluorescence at different temperatures. Yellow fluorescence evolved most slowly at high temperature and most rapidly at low temperature, in contradiction to the first hypothesis. Using high-throughput population sequencing, protein engineering, and biochemical assays, we determined that this is due to the protein-destabilizing effect of neofunctionalizing mutations. Destabilization is highly detrimental at high temperature, where neofunctionalizing mutations cannot be tolerated. Their detrimental effects can be mitigated through excess stability at low temperature, leading to accelerated adaptive evolution. By modifying protein folding stability, temperature alters the accessibility of mutational paths towards high-fitness genotypes. Our observations have broad implications for our understanding of how temperature changes affect evolutionary adaptations and innovations.
Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum β-lactamase- and carbapenemase-producing bacteria
Authors: Nieto-Rosado Maria , Sands Kirsty , Portal Edward A. R. , Thomson Kathryn M. , Carvalho Maria J. , Mathias Jordan , Milton Rebecca , Dyer Calie , Akpulu Chinenye , Boostrom Ian , Hogan Patrick , Saif Habiba , Sanches Ferreira Ana D. , Hender Thomas , Portal Barbra , Andrews Robert , Watkins W. John , Zahra Rabaab , Shirazi Haider , Muhammad Adil , Ullah Syed Najeeb , Jan Muhammad Hilal , Akif Shermeen , Iregbu Kenneth C. , Modibbo Fatima , Uwaezuoke Stella , Audu Lamidi , Edwin Chinago P. , Yusuf Ashiru H. , Adeleye Adeola , Mukkadas Aisha S. , Mazarati Jean Baptiste , Rucogoza Aniceth , Gaju Lucie , Mehtar Shaheen , Bulabula Andrew N. H. , Whitelaw Andrew , Roberts Lauren , Chan Grace , Bekele Delayehu , Solomon Semaria , Abayneh Mahlet , Metaferia Gesit ,   Group BARNARDS, Walsh Timothy R.
Published: March 2024

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum β-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.
Projective light-sheet microscopy with flexible parameter selection
Authors: Chen Bingying , Chang Bo-Jui , Daetwyler Stephan , Zhou Felix , Sharma Shiv , Lee Donghoon M. , Nayak Amruta , Noh Jungsik , Dubrovinski Konstantin , Chen Elizabeth H. , Glotzer Michael , Fiolka Reto
Published: March 2024

Projection imaging accelerates volumetric interrogation in fluorescence microscopy, but for multi-cellular samples, the resulting images may lack contrast, as many structures and haze are summed up. Here, we demonstrate rapid projective light-sheet imaging with parameter selection (props) of imaging depth, position and viewing angle. This allows us to selectively image different sub-volumes of a sample, rapidly switch between them and exclude background fluorescence. Here we demonstrate the power of props by functional imaging within distinct regions of the zebrafish brain, monitoring calcium firing inside muscle cells of moving Drosophila larvae, super-resolution imaging of selected cell layers, and by optically unwrapping the curved surface of a Drosophila embryo. We anticipate that props will accelerate volumetric interrogation, ranging from subcellular to mesoscopic scales.