bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracting Features from Foul Actions of Basketball Players in Real Time Using Machine Vision
Authors: Du Dongxu , Chai Linyan , Li Minggang , Jiang Liao , Choosakul Chairat , Liu Shixiang
Published: March 2024

As the global economic landscape rapidly advances and people's quality of life continues to improve, there is a noticeable increase in the demand for various sports, including basketball. Athletes of diverse skill levels find physical, social, and emotional satisfaction in engaging in basketball activities. In contemporary times, the requisites for success in basketball, such as height, speed, accuracy, distance, and strength, are escalating. The frequency of body contact has also intensified, leading to heightened intensity in ball shooting among players and an inevitability of fouls in offensive and defensive interactions. This dynamic poses challenges to the seamless progression of the sport, and the existence of various foul rules adds an element of unpredictability and uncontrollability to the game of basketball. The data reveals interesting insights. In terms of dribble defense, the Chinese team committed 16 fouls, whereas their opponents committed 33 fouls. However, in the context of shooting defense, the Chinese team had a higher foul count compared to their opponents. Conversely, when it came to defending the ball, the Chinese team committed fewer fouls than their opponents. In the category of preventing the ball, the Chinese team had 16 fouls compared to the opponent team's 12 fouls. Overall, the Chinese team demonstrated fewer fouls than their opponents in the realm of defense. The data underscores a potential highlight the specific factors influencing foul occurrences in different defensive scenarios. The study introduces a machine vision approach, which outperformed existing methods in classifying actions as fouls or not. This innovative application showcases the effectiveness of advanced technology in addressing the challenges associated with fouls in basketball, offering a promising avenue for further research and practical implementation. The comprehensive experimental results suggest that the machine vision approach outperformed existing methods in classifying actions as fouls or not, showcasing its effectiveness in addressing the challenge of fouls in basketball.
Hybrid Strategies Based Seagull Optimization Algorithm for Solving Engineering Design Problems
Authors: Hou Pingjing , Liu Jiang , Ni Feng , Zhang Leyi
Published: March 2024

The seagull optimization algorithm (SOA) is a meta-heuristic algorithm proposed in 2019. It has the advantages of structural simplicity, few parameters and easy implementation. However, it also has some defects including the three main drawbacks of slow convergence speed, simple search method and poor ability of balancing global exploration and local exploitation. Besides, most of the improved SOA algorithms in the literature have not considered the drawbacks of the SOA comprehensively enough. This paper proposes a hybrid strategies based algorithm (ISOA) to overcome the three main drawbacks of the SOA. Firstly, a hyperbolic tangent function is used to adjust the spiral radius. The spiral radius can change dynamically with the iteration of the algorithm, so that the algorithm can converge quickly. Secondly, an adaptive weight factor improves the position updating method by adjusting the proportion of the best individual to balance the global and local search abilities. Finally, to overcome the single search mode, an improved chaotic local search strategy is introduced for secondary search. A comprehensive comparison between the ISOA and other related algorithms is presented, considering twelve test functions and four engineering design problems. The comparison results indicate that the ISOA has an outstanding performance and a significant advantage in solving engineering problems, especially with an average improvement of 14.67% in solving welded beam design problem.
Effect of plasmapheresis on drug pharmacokinetics in children: a structured review of the current literature
Authors: Yaghyazaryan André , Gracchi Valentina , le Poole Kaatje , Touw Daan J. , Kneyber Martin C. J. , Mian Paola
Published: March 2024

Introduction

In this structured review, we present a structured overview on the effect of plasmapheresis on pharmacokinetics (PK) of drugs in children. Furthermore, we intended to analyse if, based on the changed PK, evidence-based drug dosing regimens for drugs at therapeutic dosages in this population have been developed.

Methods

A structured literature search assessing drug PK/exposure in children undergoing plasmapheresis was conducted in EMBASE and PubMed on 23 March 2023. Studies were labelled as relevant when data on PK/exposure after plasmapheresis in patients younger than 18 years-old was reported. Extracted parameters included patient characteristics, plasmapheresis related characteristics and PK/exposure related parameters.

Results

Twenty-six studies were identified, 96% being case reports. PK/exposure data for eighteen drugs in children undergoing plasmapheresis were included, 69% of the studies reported significant change in drug exposure after plasmapheresis. In 38% of the studies plasmapheresis was used in combination with drugs at therapeutic dosages, with no significant drug removal. No evidence-based drug dosing regimen for drugs at therapeutic dosages in children undergoing plasmapheresis have been developed. However, the usefulness of plasmapheresis in drug poisoning has been demonstrated, in case reports, for 31% of the overdosages.

Conclusions

This structured review shows that a very limited number of studies have been performed on the PK/exposure of drugs in children undergoing plasmapheresis. Furthermore, it became clear that predicting the risk of drug removal by plasmapheresis based on theoretical (drug properties or PK) criteria for adults is not always applicable to children.
Predicting lateral displacement of sand for mat foundation under simplified seismic loading
Authors: Haque Md. Foisal
Published: March 2024

This research presents the settlement factor of sand for the lateral seismic excitation considering various peak ground accelerations. For this reason, analytical formulations are proposed to calculate the settlement factor. A one-dimensional model is considered to derive these formulations, which is the simplified form of the three-dimensional model. The seismic excitation is simplified by considering only peak ground acceleration (PGA) for the development of formulations. The proposed formulations are verified by the previous numerical studies. Also, a parametric study is conducted to consider the variable parameters such as super-structure loads, mat thickness, PGA factors, and depths of sand. According to the verification results, the observed and calculated sand settlement factor variation rates are slightly higher because of the considerations for the development of the proposed model. The maximum value of the sand settlement factor is found to be 434 for the PGA factor of 0.36 at the highest depth of the sand layer. Also, the sand settlement factor is gradually increased with the increment of the depth for all cases due to the increment of the stiffness. The lateral sand settlement factor is varied within a range of (60 ~ 434) considering all PGAs of the lateral seismic excitation.
Boeing B-47 Stratojet
Authors: Braas Nico
Published: March 2024

Built by Boeing, designated as B-47 and named the Stratojet, this plane was quantum leap in aircraft development. Initially Boeing entered the unknown when they started this project, but soon it would be evident that Strategic Air Command would have its multi-engine jet bomber with a speed performance similar to the latest jet fighters.
Change in international order? An institutional analysis
Authors: Friedner Parrat Charlotta
Published: March 2024

Many are now discussing the possible demise of the so called ‘liberal international order’, but how can we know whether any international order is changing? This article argues for understanding order as maintained by institutions of international society and further theorises the role those institutions play in the stability or transformation of international order. To usefully put institutional analysis to work, this article, first, models the stylised evolution of a primary institution. Second, it illustrates this evolution with a discussion of the historical institution of trusteeship in order to historicise adaptation and transformation in international order. Finally, this leads to a generalised idea of how institutional analysis can be employed to study stability and transformation in international order. Beyond making a contribution to the wider debates about the possible demise of the current international order, this piece also fills a gap in English School theory, which is quite silent on the question of when international society furthers transformation, and when it furthers stability. Accepting the view of history that the future is contingent on today’s events, this study suggests possible points where push comes to shove for change and continuity in international order more generally.
A new species of the iconic triradial Ediacaran genus Tribrachidium from Nilpena Ediacara National Park, Flinders Ranges (South Australia)
Authors: Botha Tory L. , García-Bellido Diego C.
Published: March 2024

Tribrachidium heraldicum Glaessner in Glaessner and Daily, 1959 is a triradial Ediacaran organism found in abundance within the Ediacara Member of the Flinders Ranges, South Australia. Here we report and describe a new species within the genus Tribrachidium Glaessner in Glaessner and Daily, 1959: Tribrachidium gehlingi new species from Nilpena Ediacara National Park (NENP), South Australia. Tribrachidium gehlingi n. sp. has low relief and three slightly curved, main arm-like structures that leave a conspicuous gap between the end of the arm-like structures and rim. In place of the ‘bulla’ found on T. herladicum, there are three secondary arm-like structures approximately half of the length of the main arm-like structures. Key morphological differences between the two species are statistically significantly different. Additionally, the species occur together within the same fossiliferous event horizons, indicating that the observed morphological differences are unlikely a result of taphonomy.

UUID: http://zoobank.org/196bef68-54da-42a9-9327-dcb55411a457
Plasma neurofilament light chain is increased in Niemann-Pick Type C but glial fibrillary acidic protein remains normal
Authors: Eratne Dhamidhu , Lewis Courtney , Kelso Wendy , Loi Samantha , Chiu Wei-Hsuan Michelle , Blennow Kaj , Zetterberg Henrik , Santillo Alexander F , Velakoulis Dennis , Walterfang Mark ,   The MiND Study Group
Published: March 2024

Objective:

Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls.

Methods:

Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges.

Results:

Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1 vs. 7.4 pg/ml, p < 0.001), and reference ranges (all >98th percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6 vs. 75.1 pg/ml).

Discussion:

The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.
Inventing Ancestors and Limited Empiricism in Chosŏn Korea: A Case of the Kigye Yu Lineage
Authors: Kim Sun Joo
Published: March 2024

This paper investigates how the members of the Kigye Yu lineage imagined and invented their ancestral roots during the Chosŏn dynasty (1392–1910) and how such a pursuit of ancestral origins led to subsequent developments in genealogical records. As early as the fifteenth century, Chosŏn elites began to show interests in genealogy that included identifying remote ancestors from ancient times for various political, social, and cultural reasons. From the seventeenth century, the transformation of kinship organization in line with the Confucian ideal of patriliny and elites’ competition for power and prestige intensified genealogical consciousness. Elites became heavily invested in searching for ancestral origins in the form of their lineages’ founders and their tombs. While claiming to rely on documentary and physical evidence, elites often deviated from their professed empiricism and adopted evidence from dubious sources such as oral testimonies and geomancy to rationalize invented ancestral roots. Such pliable approaches, often observed in other early modern cultures such as late imperial China and Europe, opened a floodgate of lineages glorifying their ancestry by pushing their origins back even to mythical founders of ancient Korean and Chinese kingdoms, and adorning their lineages with invented heroes. At the same time, loopholes and blank spots in genealogies enabled quasi- and nonelites to become a member of prominent lineages by grafting their names onto their family trees.
Transient versus steady-state solutions: a qualitative study
Authors: Van Eester D. , Lerche E.A. , Pawelec E. , Solano E.
Published: March 2024

In view of the ultimate goal of producing long-lasting quasi-stationary discharges required for future fusion power stations, the numerical study of steady-state solutions of equations describing the particle and energy balance rightfully gets ample attention. Transient states may, however, differ significantly from the steady state ultimately reached and will – in practice – impact on the actual fate of the discharge. Using brutally simple models, the present paper highlights a number of aspects to illustrate this dynamics. It e.g. shows the different signature of wave and beam heating, potentially giving room to transiently trigger desirable effects that may allow us to better steer a discharge.
Optimizing precision medicine for second-step depression treatment: a machine learning approach
Authors: Curtiss Joshua , Smoller Jordan W. , Pedrelli Paola
Published: March 2024

Background

Less than a third of patients with depression achieve successful remission with standard first-step antidepressant monotherapy. The process for determining appropriate second-step care is often based on clinical intuition and involves a protracted course of trial and error, resulting in substantial patient burden and unnecessary delay in the provision of optimal treatment. To address this problem, we adopt an ensemble machine learning approach to improve prediction accuracy of remission in response to second-step treatments.

Method

Data were derived from the Level 2 stage of the STAR*D dataset, which included 1439 patients who were randomized into one of seven different second-step treatment strategies after failing to achieve remission during first-step antidepressant treatment. Ensemble machine learning models, comprising several individual algorithms, were evaluated using nested cross-validation on 155 predictor variables including clinical and demographic measures.

Results

The ensemble machine learning algorithms exhibited differential classification performance in predicting remission status across the seven second-step treatments. For the full set of predictors, AUC values ranged from 0.51 to 0.82 depending on the second-step treatment type. Predicting remission was most successful for cognitive therapy (AUC = 0.82) and least successful for other medication and combined treatment options (AUCs = 0.51–0.66).

Conclusion

Ensemble machine learning has potential to predict second-step treatment. In this study, predictive performance varied by type of treatment, with greater accuracy in predicting remission in response to behavioral treatments than to pharmacotherapy interventions. Future directions include considering more informative predictor modalities to enhance prediction of second-step treatment response.
‘Only my family can help’: the lived experience and care aesthetics of being resident on an NHS psychiatric/mental health inpatient dementia assessment ward – a single case study
Authors: Jones Lesley , Cullum Nicky , Watson Ruth , Thompson James , Keady John
Published: March 2024

In the United Kingdom, people living with dementia admitted to National Health Service (NHS) psychiatric/mental health inpatient dementia assessment wards (dementia assessment wards) are nearly always compulsorily detained under a section of the Mental Health Act 1983 owing to the risk and complexity of the presenting condition. As such, dementia assessment wards admit some of the most vulnerable patients in society, yet these environments of care are under-researched and under-reported in the literature. Using care aesthetics as an overarching explanatory lens, this article focuses on the care of one patient (Charlotte – not her real name) resident on a dementia assessment ward and uses a range of qualitative methods to illuminate that experience, including ethnographic observations and a care record review. To further develop the reach of the case study, interviews were also conducted with Charlotte's husband as her main family carer and key ward staff involved in Charlotte's care. Data were analysed using a sensory and narrative-based method to provide a sequential, embodied, individually positioned and storied account of Charlotte's care and interpreted experience on the ward. The analysis revealed that Charlotte's presentation of dementia was complex insofar as she resisted any attempt by the ward staff to offer her food or drink or to help with washing and dressing. Charlotte also swore frequently and loudly and spent time actively ‘watching’ and ‘looking’ at people and the environment in which she was now living. The findings contribute to the fields of critical dementia studies, dementia education, health-care practice and policy making, and may be used to highlight the value of sensory and embodied approaches to capturing a caring dynamic.
WHERE IS CREDIT IN THE PRICE SPECIE FLOW?
Authors: Berdell John , Menudo José M.
Published: March 2024

Standard models of the price specie flow do not consider credit. Yet Hume and preceding authors were reacting to the implosion of Law’s financial bubble. We delineate the anti-credit thesis contained within the evolution of eighteenth-century balance of payments analyses. A string of eighteenth-century authors argued over whether the balance of payments constituted a binding constraint on credit creation. As part of their analysis they considered how changes in the money supply might alter output, prices, employment, capital, and population. How new money entered the economy was often critical. We start with Law and then consider Melon, Gervaise, Vanderlint, Cantillon, Montesquieu, Hume, Steuart, Forbonnais, and Smith. In closing we pay particular attention to the idea that Hume and Smith effectively displaced preceding, often “mercantilist,” analyses of credit and the balance of payments.
Association between risk of malnutrition defined by patient-generated subjective global assessment and adverse outcomes in patients with cancer: a systematic review and meta-analysis
Authors: Zhang Junfang , Xu Wei , Zhang Heng , Fan Yu
Published: March 2024

Objective:

To assess the association between the risk of malnutrition, as estimated by the Patient-Generated Subjective Global Assessment (PG-SGA) numerical scores, and adverse outcomes in oncology patients.

Design:

Systematic review and meta-analysis.

Settings:

A comprehensive search was conducted in PubMed, Web of Science, Embase, CKNI, VIP, Sinomed and Wanfang databases. Studies that examined the association between the risk of malnutrition, as estimated by the PG-SGA numerical scores, and overall survival (OS) or postoperative complications in oncology patients were included. Patients were classified as low risk (PG-SGA ≤ 3), medium risk (PG-SGA 4–8) and high risk of malnutrition (PG-SGA > 8).

Subject:

Nineteen studies reporting on twenty articles (n 9286 patients).

Results:

The prevalence of medium and high risk of malnutrition ranged from 16·0 % to 71·6 %. A meta-analysis showed that cancer patients with medium and high risk of malnutrition had a poorer OS (adjusted hazard ratios (HR) 1·98; 95 % CI 1·77, 2·21) compared with those with a low risk of malnutrition. Stratified analysis revealed that the pooled HR was 1·55 (95 % CI 1·17, 2·06) for medium risk of malnutrition and 2·65 (95 % CI 1·90, 3·70) for high risk of malnutrition. Additionally, the pooled adjusted OR for postoperative complications was 4·65 (95 % CI 1·61, 13·44) for patients at medium and high risk of malnutrition.

Conclusions:

The presence of medium and high risk of malnutrition, as estimated by the PG-SGA numerical scores, is significantly linked to poorer OS and an increased risk of postoperative complications in oncology patients.
Is God a Free-Range Parent?
Authors: Chen Cheryl K.
Published: March 2024

If a benevolent and all-powerful God exists, how can there be so much suffering? Could God have created a better world? Or is evil the price we pay for freedom of the will?
In Defence of (Over)Thinking
Authors: GuhaRoy SuddhaSatwa
Published: March 2024

‘You are overthinking that!’ The article argues against the popular idea that too much of the activity of thinking is bad for individuals. Wrong thinking, I argue, is what is bad or unhealthy, irrespective of the length of time it is done for. Wrong thinking can lead to worrying, stress, and impedes practical action. But if thinking is done right, then you can't have too much of it.
Yuval Harari on Human Rights and Biology
Authors: Zangwill Nick
Published: March 2024

Yuval Harari believes that humans make myths, and that these can be powerful engines for social change. One of these myths, claims Harari, is the existence of ‘liberal rights’. This article challenges that claim and defends the idea of grounding rights in human nature.
Philosophy and Raising Good Citizens
Authors: Law Stephen
Published: March 2024

What's the best way to raise good citizens – individuals who will do the right thing even in the most challenging of circumstances? I argue that philosophy has an important role to play.
Mourning in the time of coronavirus: Examining how grief differs in those who lost loved ones to COVID-19 vs. natural causes in Iran
Authors: Aliyaki Hajar , Momeni Fereshteh , Dolatshahi Behrouz , Hosseinzadeh Samaneh , Yousefi Shahab , Abdoli Fatemeh
Published: March 2024

Objectives

Our study aimed to analyze and compare the grief experiences of individuals in Iran who lost family members to COVID-19 and those who lost loved ones to other natural causes.

Methods

In this study, telephone interviews were conducted with 640 first-degree relatives, and finally, a total of 395 people remained in the research. Participants answered the Prolonged Grief Questionnaire (PG-13-R) and Grief Experience Questionnaire.

Results

The results showed that the most common symptoms and features of grief were feeling guilt, searching for an explanation, somatic reactions, and rejection, with no significant difference observed between the 2 death groups. However, the average scores for these symptoms were higher in the COVID-19 death group. Moreover, the majority of bereaved reported signs and symptoms of prolonged grief, with a higher percentage in the COVID-19 death group, although there was no significant difference between the 2 death groups in terms of the distribution of symptoms and signs of prolonged grief. These findings suggest that the bereavement process can be challenging, and losing a loved one to COVID-19 may lead to more intense experiences of grief.

Significance of results

The study reveals high levels of guilt, searching for meaning, somatic reactions, and rejection among COVID-19 grievers. Losing loved ones to the pandemic appears linked to more intense, prolonged grief symptoms.
Nitrogen Cycling Feedback on Carbon Dynamics Leads to Greater CH4 Emissions and Weaker Cooling Effect of Northern Peatlands
Authors: Zhao Bailu , Zhuang Qianlai
Published: March 2024

Northern peatlands have been a carbon sink since their initiation. This has been simulated by existing process‐based models. However, most of these models are limited by lacking sufficient processes of the N cycle in peatlands. Here, we use a peatland biogeochemistry model incorporated with N‐related processes of fixation, deposition, gas emission, loss through water flow, net mineralization, plant uptake and litterfall to project the role of the peatlands in future radiative forcing (RF). Simulations from 15‐ka BP to 2100 are conducted driven by CMIP5 climate forcing data of IPSL‐CM5A‐LR and bcc‐csm1‐1, including warming scenarios of RCP 2.6, RCP 4.5 and RCP 8.5. During the Holocene, northern peatlands have an increasing cooling effect with RF up to −0.57 W m−2. By 1990, these peatlands accumulate 408 Pg C and 7.8 Pg N. Under warming, increasing mineral N content enhances plant net primary productivity; the cooling effect persists. However, RF increases by 0.1–0.5 W m−2 during the 21st century, mainly due to the stimulated CH4 emissions. Northern peatlands could switch from a C sink to a source when the annual temperature exceeds −2.2 to −0.5°C. This study highlights that the improved N cycle causes higher CO2‐C sink capacity in northern peatlands. However, it also causes a significant increase in CH4 emissions, which weakens the cooling effect of northern peatlands in future climate.
Antarctic Geothermal Heat Flow, Crustal Conductivity and Heat Production Inferred From Seismological Data
Authors: Hazzard James A. N. , Richards Fred D.
Published: March 2024

Geothermal heat flow is a key parameter in governing ice dynamics, via its influence on basal melt and sliding, englacial rheology, and erosion. It is expected to exhibit significant lateral variability across Antarctica. Despite this, surface heat flow derived from Earth's interior remains one of the most poorly constrained parameters controlling ice sheet evolution. To obtain a continent‐wide map of Antarctic heat supply at regional‐scale resolution, we estimate upper mantle thermomechanical structure directly from VS. Until now, direct inferences of Antarctic heat supply have assumed constant crustal composition. Here, we explore a range of crustal conductivity and radiogenic heat production values by fitting thermodynamically self‐consistent geotherms to their seismically inferred counterparts. Independent estimates of crustal conductivity derived from VP are integrated to break an observed trade‐off between crustal parameters, allowing us to infer Antarctic geothermal heat flow and its associated uncertainty.
The Small Self and the Vast Universe: Eclipses and the Science of Awe
Authors: Evans Kate
Published: March 2024

What is awe? What does it feel like? Why does it exist? And what is it about a total solar eclipse that seems perfectly designed to provoke it?
Molecular ontogeny underlies the benefit of adding venetoclax to hypomethylating agents in newly diagnosed AML patients
Authors: Shimony Shai , Garcia Jacqueline S. , Keating Julia , Chen Evan C. , Luskin Marlise R. , Stahl Maximilian , Neuberg Donna S. , DeAngelo Daniel J. , Stone Richard M. , Lindsley R. Coleman
Published: March 2024

The clinical impact of molecular ontogeny in acute myeloid leukemia (AML) was defined in patients treated with intensive chemotherapy. In a cohort of 314 newly diagnosed AML patients, we evaluated whether molecular ontogeny subgroups have differential benefit of venetoclax (VEN) added to hypomethylating agents (HMA). In secondary ontogeny (n = 115), median overall survival (OS)(14.1 vs. 6.9 months, P = 0.0054), composite complete remission (cCR 61% vs. 18%, P < 0.001) and allogeneic hematopoietic stem cell transplant (alloHCT) (24% vs. 6%, P = 0.02) rates were better in patients treated with HMA + VEN vs. HMA. In contrast, in TP53 AML(n = 111) median OS (5.7 vs. 6.1, P = 0.93), cCR (33% vs. 37%, P = 0.82) and alloHCT rates (15% vs. 8%, P = 0.38) did not differ between HMA + VEN vs. HMA. The benefit of VEN addition in the secondary group was preserved after adjustment for significant clinicopathologic variables (HR 0.59 [95% CI 0.38–0.94], P = 0.025). The OS benefit of HMA + VEN in secondary ontogeny was similar in those with vs. without splicing mutations (P = 0.92). Secondary ontogeny AML highlights a group of patients whose disease is selectively responsive to VEN added to HMA and that the addition of VEN has no clinical benefit in TP53-mutated AML.
Real-world overall survival with abiraterone acetate versus enzalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer
Authors: George Daniel J. , Ramaswamy Krishnan , Yang Hongbo , Liu Qing , Zhang Adina , Greatsinger Alexandra , Ivanova Jasmina , Thompson Betty , Emir Birol , Hong Agnes , Freedland Stephen J.
Published: March 2024

Background

There are no large head-to-head phase 3 clinical trials comparing overall survival (OS) for abiraterone and enzalutamide. This study used Medicare claims data to compare OS in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) who initiated abiraterone or enzalutamide.

Methods

This retrospective analysis of the Medicare database (2009–2020) included adult men with ≥1 claim for prostate cancer, metastatic diagnosis, and no prior chemotherapy or novel hormone therapy who initiated first-line (1L) abiraterone or enzalutamide in the index period (September 10, 2014 to May 31, 2017). Cox proportional-hazards models with inverse probability treatment-weighting (IPTW) were used to compare OS between abiraterone- and enzalutamide-treated patients, adjusting for baseline characteristics. Subgroup analyses by baseline characteristics were also conducted.

Results

Overall, 5506 patients who received 1L abiraterone (n = 2911) or enzalutamide (n = 2595) were included. Median follow-up was comparable in both cohorts (abiraterone, 19.1 months; enzalutamide, 20.3 months). IPTW-adjusted median OS (95% CI) was 20.6 months (19.7‒21.4) for abiraterone and 22.5 months (21.2‒23.8) for enzalutamide, with an IPTW-adjusted hazard ratio (95% CI) of 1.10 (1.04–1.16). Median OS was significantly shorter for abiraterone versus enzalutamide in patients ≥75 years old; White patients; patients with baseline diabetes, cardiovascular disease, both diabetes and cardiovascular disease, and renal disease; and across all socioeconomic strata.

Conclusions

In the Medicare chemotherapy-naïve mCRPC population, 1L abiraterone was associated with worse OS versus enzalutamide in the overall population and among subgroups with older age and comorbidities, supporting findings from previous real-world studies and demonstrating a disparity in outcomes.
METTL3-mediated m6A modification increases Hspa1a stability to inhibit osteoblast aging
Authors: Wang Yaobin , Chen Yi , Xiao Hefang , Liu Zhongcheng , Liu Xuening , Feng Zhiwei , Sheng Xiaoyun , Peng Bo , Ren Xiaojun , Xu Lihu , Teng Fei , Yi Zhi , Niu YongKang , Xiang Dejian , Xia Yayi , Geng Bin
Published: March 2024

Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted bone remodeling. Numerous studies have focused on the regulatory role of m6A modification in osteoporosis; however, most of the studies have investigated the differentiation of bone marrow mesenchymal stem cells (BMSCs), while the direct regulatory mechanism of m6A on osteoblasts remains unknown. This study revealed that the progression of senile osteoporosis is closely related to the downregulation of m6A modification and methyltransferase-like 3 (METTL3). Overexpression of METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that METTL3 upregulates the stability of Hspa1a mRNA, thereby inhibiting osteoblast aging. Moreover, the results demonstrated that METTL3 enhances the stability of Hspa1a mRNA via m6A modification to regulate osteoblast aging. Notably, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) participates in stabilizing Hspa1a mRNA in the METTL3-mediated m6A modification process, rather than the well-known degradation function. Mechanistically, METTL3 increases the stability of Hspa1a mRNA in a YTHDF2-dependent manner to inhibit osteoblast aging. Our results confirmed the significant role of METTL3 in osteoblast aging and suggested that METTL3 could be a potential therapeutic target for senile osteoporosis.
Programmed axon death: a promising target for treating retinal and optic nerve disorders
Authors: Loreto Andrea , Merlini Elisa , Coleman Michael P.
Published: March 2024

Programmed axon death is a druggable pathway of axon degeneration that has garnered considerable interest from pharmaceutical companies as a promising therapeutic target for various neurodegenerative disorders. In this review, we highlight mechanisms through which this pathway is activated in the retina and optic nerve, and discuss its potential significance for developing therapies for eye disorders and beyond. At the core of programmed axon death are two enzymes, NMNAT2 and SARM1, with pivotal roles in NAD metabolism. Extensive preclinical data in disease models consistently demonstrate remarkable, and in some instances, complete and enduring neuroprotection when this mechanism is targeted. Findings from animal studies are now being substantiated by genetic human data, propelling the field rapidly toward clinical translation. As we approach the clinical phase, the selection of suitable disorders for initial clinical trials targeting programmed axon death becomes crucial for their success. We delve into the multifaceted roles of programmed axon death and NAD metabolism in retinal and optic nerve disorders. We discuss the role of SARM1 beyond axon degeneration, including its potential involvement in neuronal soma death and photoreceptor degeneration. We also discuss genetic human data and environmental triggers of programmed axon death. Lastly, we touch upon potential therapeutic approaches targeting NMNATs and SARM1, as well as the nicotinamide trials for glaucoma. The extensive literature linking programmed axon death to eye disorders, along with the eye’s suitability for drug delivery and visual assessments, makes retinal and optic nerve disorders strong contenders for early clinical trials targeting programmed axon death.
Bee-pollination promotes rapid divergent evolution in plants growing in different soils
Authors: Dorey Thomas , Schiestl Florian P.
Published: March 2024

Divergent evolution leads to variation among populations and thus promotes diversification. In plants, adaptation to different soils, pollinator guilds, and herbivores is thought to be a key ecological driver of adaptive divergence, but few studies have investigated this process experimentally. Here we use experimental evolution with fast cycling Brassica rapa plants to study the impact of soil, pollination, herbivory, and their interactions on divergent evolution in various traits during eight generations of selection. We found significant evolutionary changes in plant phenotypes caused by all three factors and their interactions. In the richer soil type, plants showed higher evolutionary rates, especially with bumblebee-pollination, which led to the evolution of increased attractiveness of plants to bumblebees. Plants that had experienced aphid-herbivory showed lower attractiveness. We found the strongest evolutionary divergence when plants evolved in different soils with bee-pollination rather than hand-pollination, irrespective of herbivory. This “soil-pollinator effect” impacted divergence in diverse suites of traits, for example leaf size, flowering time, flower petal length, some floral volatiles and leaf glucosinolates. We conclude that the interaction between soil and biotic pollination may be an important cause for divergent evolution of plants growing on different soil types, even without a shift in pollinator guilds.
Origin of shear induced ‘catching bonds’ on half Heusler thermoelectric compounds XFeSb (X = Nb, Ta) and SnNiY (Y = Ti, Zr, Hf)
Authors: Ma Haoqin , Huang Xiege , Lu Zhongtao , Feng Xiaobin , Duan Bo , Li Wenjuan , Liu Yinhan , Zhai Pengcheng , Li Guodong , Zhang Qingjie
Published: March 2024

Half Heusler materials exhibit excellent thermoelectric and mechanical properties, rendering them potential candidates for advanced thermoelectric devices. Currently, the developments on interrelated devices are impeded by their inherent brittleness and limited ductility. Nevertheless, it exists the potential ductility on half Heusler materials with face-centered cubic sub-lattices through the expectation of the occurrence of shear-induced ‘catching bonds’ which can result in excellent ductility on other face-centered cubic materials. This work focuses on half Heusler thermoelectric materials XFeSb (X = Nb, Ta) and SnNiY (Y = Ti, Zr, Hf), the shear deformation failure processes are deeply investigated through the first principle calculations. Shear-induced ‘catching bonds’ are found on XFeSb (X = Nb, Ta) along the (111)/<-1-12> slip system, which releases the internal stress and exactly resulting in the potential ductility. According to the thermodynamic criterion based on generalized stacking fault energy, the essence of shear-induced ‘catching bonds’ are interpreted as the (111)/<-110> slips formed by several 1/3(111)/<-1-12> partial dislocations motions. During the (111)/<-1-12> shear on SnNiY (Y = Ti, Zr, Hf), the structural integrity is maintained without inducing ‘catching bonds’. Different deformation processes occurring in the identical crystal structure are elucidated through the energy explanation, revealing that shear-induced ‘catching bonds’ originate from the crystal plane cleavage on the (111) plane. The present works offer significant advantages for the assessment and comprehension of shear-induced ‘catching bonds’ in other materials and facilitate the development of XFeSb (X = Nb, Ta)-based thermoelectric devices with excellent ductility.
Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib
Authors: Ingley K. M. , Zatzman M. , Fontebasso A. M. , Lo W. , Subasri V. , Goldenberg A. , Li Y. , Davidson S. , Kanwar N. , Waldman L. , Brunga L. , Babichev Y. , Demicco E. G. , Gupta A. , Szybowska M. , Thipphavong S. , Malkin D. , Villani A. , Shlien A. , Gladdy R. A. , Kim R. H.
Published: March 2024

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.
A brainstem–hypothalamus neuronal circuit reduces feeding upon heat exposure
Authors: Benevento Marco , Alpár Alán , Gundacker Anna , Afjehi Leila , Balueva Kira , Hevesi Zsofia , Hanics János , Rehman Sabah , Pollak Daniela D. , Lubec Gert , Wulff Peer , Prevot Vincent , Horvath Tamas L. , Harkany Tibor
Published: March 2024

Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized1. Tanycytes are a specialized cell type along the wall of the third ventricle2 that bidirectionally transport hormones and signalling molecules between the brain’s parenchyma and ventricular system3–8. Here we show that tanycytes are activated upon acute thermal challenge and are necessary to reduce food intake afterwards. Virus-mediated gene manipulation and circuit mapping showed that thermosensing glutamatergic neurons of the parabrachial nucleus innervate tanycytes either directly or through second-order hypothalamic neurons. Heat-dependent Fos expression in tanycytes suggested their ability to produce signalling molecules, including vascular endothelial growth factor A (VEGFA). Instead of discharging VEGFA into the cerebrospinal fluid for a systemic effect, VEGFA was released along the parenchymal processes of tanycytes in the arcuate nucleus. VEGFA then increased the spike threshold of Flt1-expressing dopamine and agouti-related peptide (Agrp)-containing neurons, thus priming net anorexigenic output. Indeed, both acute heat and the chemogenetic activation of glutamatergic parabrachial neurons at thermoneutrality reduced food intake for hours, in a manner that is sensitive to both Vegfa loss-of-function and blockage of vesicle-associated membrane protein 2 (VAMP2)-dependent exocytosis from tanycytes. Overall, we define a multimodal neurocircuit in which tanycytes link parabrachial sensory relay to the long-term enforcement of a metabolic code.
Single-cell multiplex chromatin and RNA interactions in ageing human brain
Authors: Wen Xingzhao , Luo Zhifei , Zhao Wenxin , Calandrelli Riccardo , Nguyen Tri C. , Wan Xueyi , Charles Richard John Lalith , Zhong Sheng
Published: March 2024

Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA1–3. Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells4–7. Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA–chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an ‘older’ transcriptomic signature and Alzheimer’s disease pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues.
A chromosome-level genome assembly of East Asia endemic minnow Zacco platypus
Authors: Xu Xiaojun , Chen Jing , Guan Wenzhi , Niu Baolong , Yi Shaokui , Lou Bao
Published: March 2024

Zacco platypus is an endemic colorful freshwater minnow that is intensively distributed in East Asia. In this study, two adult female individuals collected from Haihe River basin were used for karyotypic study and genome sequencing, respectively. The karyotype formula of Z. platypus is 2N = 48 = 18 M + 24SM/ST + 6 T. We used PacBio long-read sequencing and Hi-C technology to assemble a chromosome-level genome of Z. platypus. As a result, an 814.87 Mb genome was assembled with the PacBio long reads. Subsequently, 98.64% assembled sequences were anchored into 24 chromosomes based on the Hi-C data. The chromosome-level assembly contained 54 scaffolds with a N50 length of 32.32 Mb. Repeat elements accounted for 52.35% in genome, and 24,779 protein-coding genes were predicted, with 92.11% were functionally annotated with the public databases. BUSCO analysis yielded a completeness score of 96.5%. This high-quality genome assembly provides valuable resources for future functional genomic research, comparative genomics, and evolutionary studies of genus Zacco.
A time-correlated single photon counting SPAD array camera with a bespoke data-processing algorithm for lightsheet fluorescence lifetime imaging (FLIM) and FLIM videos
Authors: Nedbal Jakub , Mattioli Della Rocca Francesco , Ivanova Iveta T. , Allan Andrew , Graham Jeremy , Walker Richard , Henderson Robert K. , Suhling Klaus
Published: March 2024

A wide-field microscope with epi-fluorescence and selective plane illumination was combined with a single-photon avalanche diode (SPAD) array camera to enable live-cell fluorescence lifetime imaging (FLIM) using time-correlated single-photon counting (TCSPC). The camera sensor comprised of $$\text {192}\times \text {128}$$

192
×
128

pixels, each integrating a single SPAD and a time-to-digital converter. Jointly, they produced a stream of single-photon images of photon arrival times with $$\approx \text {38 ps}$$

≈
38 ps

accuracy. The photon arrival times were subject to systematic delays and nonlinearities, which were corrected by a Monte-Carlo algorithm. The SPAD camera was then applied to FLIM where histogramming the resulting photon arrival times in each pixel resulted in decays compatible with common data processing pipelines for fluorescence lifetime analysis. The capabilities of the TCSPC camera-based FLIM microscope were demonstrated by imaging living unicellular photosynthetic algae and artificial lipid vesicles. Epi-fluorescence illumination enabled rapid fluorescence lifetime imaging of living cells and selective-plane illumination enabled 3-dimensional FLIM of stationary samples.
Brain network hypersensitivity underlies pain crises in sickle cell disease
Authors: Joo Pangyu , Kim Minkyung , Kish Brianna , Nair Vidhya Vijayakrishnan , Tong Yunjie , Liu Ziyue , O’Brien Andrew R. W. , Harte Steven E. , Harris Richard E. , Lee UnCheol , Wang Ying
Published: March 2024

Sickle cell disease (SCD) is a genetic disorder causing painful and unpredictable Vaso-occlusive crises (VOCs) through blood vessel blockages. In this study, we propose explosive synchronization (ES) as a novel approach to comprehend the hypersensitivity and occurrence of VOCs in the SCD brain network. We hypothesized that the accumulated disruptions in the brain network induced by SCD might lead to strengthened ES and hypersensitivity. We explored ES's relationship with patient reported outcome measures (PROMs) as well as VOCs by analyzing EEG data from 25 SCD patients and 18 matched controls. SCD patients exhibited lower alpha frequency than controls. SCD patients showed correlation between frequency disassortativity (FDA), an ES condition, and three important PROMs. Furthermore, stronger FDA was observed in SCD patients with a higher frequency of VOCs and EEG recording near VOC. We also conducted computational modeling on SCD brain network to study FDA's role in network sensitivity. Our model demonstrated that a stronger FDA could be linked to increased sensitivity and frequency of VOCs. This study establishes connections between SCD pain and the universal network mechanism, ES, offering a strong theoretical foundation. This understanding will aid predicting VOCs and refining pain management for SCD patients.