bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Every Computer Scientist Need to Know Formal Methods?
Authors: Broy Manfred , Brucker Achim D. , Fantechi Alessandro , Gleirscher Mario , Havelund Klaus , Kuppe Markus Alexander , Mendes Alexandra , Platzer André , Ringert Jan Oliver , Sullivan Allison
Published: June 2024

We focus on the integration of Formal Methods as mandatory theme in any Computer Science University curriculum. In particular, when considering the ACM Curriculum for Computer Science, the inclusion of Formal Methods as a mandatory Knowledge Area needs arguing for why and how does every computer science graduate benefit from such knowledge. We do not agree with the sentence “While there is a belief that formal methods are important and they are growing in importance, we cannot state that every computer science graduate will need to use formal methods in their career.” We argue that formal methods are and have to be an integral part of every computer science curriculum. Just as not all graduates will need to know how to work with databases either, it is still important for students to have a basic understanding of how data is stored and managed efficiently. The same way, students have to understand why and how formal methods work, what their formal background is, and how they are justified. No engineer should be ignorant of the foundations of their subject and the formal methods based on these.

In this article, we aim at highlighting why every computer scientist needs to be familiar with formal methods. We argue that education in formal methods plays a key role by shaping students' programming mindset, fostering an appreciation for underlying principles, and encouraging the practice of thoughtful program design and justification, rather than simply writing programs without reflection and deeper understanding. Since integrating formal methods into the computer science curriculum is not a straightforward process, we explore the additional question: what are the tradeoffs between one dedicated knowledge area of formal methods in a computer science curriculum versus having formal methods scattered across all knowledge areas? Solving problems while designing software and software-intensive systems demands an understanding of what is required, followed by a specification and formalizing a solution in a programming language. How to do this systematically and correctly on solid grounds is exactly supported by formal methods.
In-memory database load balancing optimization for massive information processing of the Internet of Things
Authors: Xu Huixiang
Published: June 2024

In order to improve the operation effect of the in-memory database for massive information processing of the Internet of Things, this paper combines the load balancing signal processing algorithm to carry out the load balancing optimization analysis of the in-memory database. According to the local transformation characteristics of non-stationary multi-component signals, an adaptive FSST algorithm is proposed in this paper. According to the signal separability condition, this paper uses the local Rayleigh entropy to estimate the window function parameters of the adaptive FSST and the adaptive FSST2. In addition, this paper adopts an adaptive window function to automatically match the local changes of the signal, so that the signal has the optimal energy aggregation in any part. The results show that when the number of concurrent users is the same, the time consumption, throughput and bandwidth of the proposed method are always higher than the method proposed in reference [10]. When the number of concurrent books is 97, the time of the proposed method is 45000ms, the time of the proposed method is 40000ms, the highest throughput of the proposed method is 2.30 MB/s, the highest bandwidth is 11.9MB/s, the highest throughput of the method proposed in reference [10] is 2.2 MB/s, and the highest bandwidth is 11.8MB/s. The load balancing optimization algorithm of the memory database for massive information processing of the Internet of Things has good results.
Lexical Semantic Change through Large Language Models: a Survey
Authors: Periti Francesco , Montanelli Stefano
Published: June 2024

Lexical Semantic Change (LSC) is the task of identifying, interpreting, and assessing the possible change over time in the meanings of a target word. Traditionally, LSC has been addressed by linguists and social scientists through manual and time-consuming analyses, which have thus been limited in terms of the volume, genres, and time-frame that can be considered. In recent years, computational approaches based on Natural Language Processing have gained increasing attention to automate LSC as much as possible. Significant advancements have been made by relying on Large Language Models (LLMs), which can handle the multiple usages of the words and better capture the related semantic change. In this article, we survey the approaches based on LLMs for LSC, and we propose a classification framework characterized by three dimensions:
meaning representation
,
time-awareness
, and
learning modality
. The framework is exploited to (i) review the measures for change assessment, (ii) compare the approaches on performance, and (iii) discuss the current issues in terms of scalability, interpretability, and robustness. Open challenges and future research directions about the use of LLMs for LSC are finally outlined.
Political Inequality
Authors: Cagé Julia
Published: June 2024

Inequality in political participation and influence has strongly increased in recent decades, breeding economic inequality. In this review, we focus on three aspects of political inequality: the increasing concentration of both political and charitable donations, the growing gap in descriptive representation, and the persistent lack of substantive representation. Based on the existing literature as well as on novel evidence, we relate these aspects to the recent widening of turnout inequality. We then examine novel forms of participation—e.g., the rise of small donors in the United States—and the efficiency of policies aimed at improving representation. Finally, we discuss new avenues for research.
Alternatives to Bayesian Updating
Authors: Ortoleva Pietro
Published: June 2024

We discuss models of updating that depart from Bayes’ rule even when it is well-defined. After reviewing Bayes’ rule and its foundations, we begin our analysis with models of non-Bayesian behavior arising from a bias, a pull toward suboptimal behavior due to a heuristic or a mistake. Next, we explore deviations caused by individuals questioning the prior probabilities they initially used. We then consider non-Bayesian behavior resulting from the optimal response to constraints on perception, cognition, or memory, as well as models based on motivated beliefs or distance minimization. Finally, we briefly discuss models of updating after zero probability events.
A Vision for the Science of Rare Isotopes
Authors: Crawford H.L. , Fossez K. , König S. , Spyrou A.
Published: June 2024

The field of nuclear science has considerably advanced since its beginning just over a century ago. Today, the science of rare isotopes is on the cusp of a new era with theoretical and computing advances complementing experimental capabilities at new facilities internationally. In this article we present a vision for the science of rare isotope beams (RIBs). We do not attempt to cover the full breadth of the field; rather, we provide a perspective and address a selection of topics that reflect our own interests and expertise. We focus in particular on systems near the drip lines, where one often finds nuclei that are referred to as exotic and where the role of the nuclear continuum is only just starting to be explored. An important aspect of this article is its attempt to highlight the crucial connections between nuclear structure and the nuclear reactions required to fully interpret and leverage the rich data to be collected in the next years at RIB facilities. Further, we connect the efforts in structure and reactions to key questions of nuclear astrophysics.
The Potential Effectiveness of Nutrient Declarations and Nutrition and Health Claims for Improving Population Diets
Authors: Kelly Bridget , Ng See Hoe , Carrad Amy , Pettigrew Simone
Published: June 2024

Nutrition labeling supports healthier diets by aiding purchase decisions and stimulating reformulation. This systematic literature review applied Cochrane methods to synthesize and appraise evidence on the effectiveness of nutrient declarations and nutrition and health claims on diet-related outcomes. The search spanned 11 academic databases, from inception to July 2022. Evidence was synthesized using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) and vote counting. Data were available from 170 studies. Randomized controlled trials (RCTs) suggest that nutrient declarations likely improved consumer understanding of the nutritional quality/content of foods (moderate certainty) and may have improved the healthfulness of choices (low certainty) versus no label. RCT evidence also suggests that claims likely increased consumer perceptions of food healthfulness and increased choice and purchases of labeled foods (both moderate certainty), irrespective of nutritional quality. To improve label understanding and avoid misinterpretation, nutrient declarations may incorporate interpretive elements and claims can apply disqualifying conditions for their usage, on the basis of overall nutritional quality.
Trading Off Initial PEM Fuel Cell Performance versus Voltage Cycling Durability for Different Carbon Support Morphologies
Authors: Lazaridis Timon , Della Bella Roberta K. F. , Gasteiger Hubert A.
Published: June 2024

Tailored design of carbon supports and their pore morphologies is crucial to achieve the ambitious durability and performance targets for future proton exchange membrane fuel cells (PEMFCs). We compared platinum catalysts supported on solid Vulcan carbon, porous Ketjenblack carbon, and accessible porous modified Ketjenblack carbon in a voltage cycling-based accelerated stress test (AST) with frequent intermittent characterizations. We derived how catalyst morphologies affect cell performance and electrochemical properties (electrode roughness factor, ORR activity, oxygen transport resistances) at beginning-of-life (BoL) and in various states of degradation up to 200,000 voltage cycles. We confirmed the enhanced Pt surface area retention of porous carbon-supported catalysts, ascribed to well-shielded Pt particles in internal pores, but find that this comes at the expense of lower initial high current density performance already at BoL. Accessible porous carbon-supported catalysts with wider pores mostly retain those durability benefits while, simultaneously, maximizing H2/air performance at all current densities due to improved oxygen transport. We also tracked changes in catalyst accessibility throughout voltage cycling by analyzing local oxygen transport resistances and relative humidity-dependent platinum utilization. We propose that catalysts with porous carbon supports undergo oxidative pore opening, followed by continuous migration of internal Pt particles to the external carbon surface.
Investigation of GaAs-Based Laser Diode Adopting an Al Composition Gradient Double Waveguide Structure and its Photoelectric Properties
Authors: Zhao Peng Peng , Dong Hai Liang , Jia Zhi Gang , Jia Wei , Chen Ze Ming , Liang Jian , Xu Bing She
Published: June 2024

The double waveguide structure of a 1060 nm laser diode with different Al composition linear gradient was designed for achieving high output power. In contrast to the single waveguide layer with Al-free composition gradient structure, the double waveguide layer with a reverse Al composition gradient from n side to p side showed excellent optoelectronic properties. We found that the reverse Al composition gradient double waveguide layer could decrease injection potential barrier for electrons and holes, as well as has a high block leakage potential barrier, which can be help to increase carrier transport and optical confined factor. Meanwhile, it can improve sheet carrier concentration in order to decrease non-radiative recombination. When the injection current is 6 A, the maximal output power and peak wall-plug conversion efficiency are 6.12 W and 81.1%, respectively. The influencing mechanism of these photoelectric parameters on power and wall-plug conversion efficiency was discussed. The novel waveguide structure will be favorable for designing epitaxial structure and providing a theoretical basis for high-power laser diode.
GaSb/Si Heterojunction Based Pocket Engineered Vertical Non-Uniform Channel Double Gate TFETs for Low Power Applications
Authors: Macherla Swaroop Kumar , Goel Ekta
Published: June 2024

This article compares the performance of two Vertical Non-Uniform Channel Double Gate Tunnel Field Effect Transistors (VNUCDGTFETs), a normal all-Silicon Tunnel Field-Effect Transistor (TFET) having a pocket and another one a Gallium Antimonide/Silicon heterojunction TFET with pocket. GaSb is a III-V narrow energy band gap material, employed in the source area of the TFET structure to decrease the tunneling width and thus to make more number of carriers capable enough to tunnel through the heterojunction. The proposed source pocket heterojunction non uniform channel TFET presents superior performance as compared to the conventional non uniform channel vertical TFET with a pocket, regarding a larger ION/IOFF ratio, a reduced sub-threshold swing, and a smaller threshold voltage at VDS = 0.5 V. Furthermore, the proposed TFET device undergoes a comprehensive analysis of both DC parameters and various analog/RF parameters.
Exploring heterogeneity: a dive into preclinical models of cancer cachexia
Authors: Morena Francielly , Cabrera Ana Regina , Greene Nicholas P.
Published: June 2024

Cancer cachexia (CC) is a multifactorial and complex syndrome experienced by up to 80% of patients with cancer and implicated in ∼40% of cancer-related deaths. Given its significant impact on patients’ quality of life and prognosis, there has been a growing emphasis on elucidating the underlying mechanisms of CC using preclinical models. However, the mechanisms of cachexia appear to differ across several variables including tumor type and model and biologic variables such as sex. These differences may be exacerbated by variance in experimental approaches and data reporting. This review examines literature spanning from 2011 to March 2024, focusing on common preclinical models of CC, including Lewis Lung Carcinoma, pancreatic KPC, and colorectal colon-26 and Apcmin/+ models. Our analysis reveals considerable heterogeneity in phenotypic outcomes, and investigated mechanisms within each model, with particular attention to sex differences that may be exacerbated through methodological differences. Although searching for unified mechanisms is critical, we posit that effective treatment approaches are likely to leverage the heterogeneity presented by the tumor and pertinent biological variables to direct specific interventions. In exploring this heterogeneity, it becomes critical to consider methodological and data reporting approaches to best inform further research.
Towards More Sustainable Cities: Tools and Policies for Urban Goods Movements
Authors: Comi Antonio , Fancello Gianfranco , Piras Francesco , Serra Patrizia
Published: June 2024

Although urban freight transportation is crucial to address societal demands, it also has a major negative impact on the environment, the economy, and society. Then, the growing interest in promoting more sustainable and liveable cities is pushing to point out more in depth the role of urban goods movements within the planning process, as well as city administrators to implement new sustainable city logistics actions/policies/measures. Therefore, after a brief overview, the study presents more advanced techniques (models and methodologies) to help in the assessment of planning scenario. This paper concentrates on the importance of urban freight transport and logistics. Then, technical and logistics actions are outlined, and future last‐mile delivery challenges are discussed. The main objective is to support urban planners, on a strategic and tactical scale, in obtaining an overview of urban freight transport systems that point out the challenges for implementing sustainable city logistics scenarios. It is also of interest to technicians because they can identify the most suitable methodologies, as well as the features that they need for selecting and assessing ex ante the effects of city logistics measures. This work is useful for researchers in various sectors because it allows them to formalise and then to solve the problems for simulating the complex system of urban goods movements where there are different actors with own interests that are conflicting.
An Extensive Classification of 5G Network Jamming Attacks
Authors: Savadatti Shreya , Kuldeep Dhariwal Sakshi , Krishnamoorthy Shruthi , Delhibabu Radhakrishnan
Published: June 2024

The paper introduces a pioneering taxonomy for 5G jamming attacks, meticulously crafted through diverse research methodologies, including literature review, case studies, incident database analysis, and network architecture assessment. This taxonomy is based on six dimensions: attack classification, attack techniques, jammer characteristics, impact and target analysis, countermeasure strategies, and security layers. It gives a full picture of what is needed to protect 5G networks from new security threats, especially jamming attacks. Real‐world case studies from regions like Ukraine, the South China Sea, and Cuba validate the taxonomy’s efficacy in analyzing varied jamming scenarios and offer practical insights into cyber threats and mitigation strategies. By looking closely at attack details, network effects, countermeasure strategies, and security layers, this research makes a big difference in improving the security of 5G networks. It gives everyone involved, the tools and knowledge they need to protect themselves from jamming attacks and make networks more resilient in a world where technology and connectivity are changing quickly. The key findings of this research include identifying key 5G network vulnerabilities to jamming attacks and presenting a detailed six‐dimensional taxonomy: attack classification, techniques, jammer characteristics, impact analysis, countermeasures, and security layers. It emphasizes the need for strong security strategies to improve 5G network resilience against evolving threats, which case studies from Cuba, the South China Sea, and Ukraine have validated.
Coridius chinensis Extract Promotes Leydig Cell Endocrine Function Rescuing Testosterone Deficiency and Sexual Behavior Insufficiency in Manganese‐Exposed Rat
Authors: Luo Nanjian , Xiong Keyi , Wang Yong , Cen Changhuo , Liu Qiongyou , Wang Fengyue , Hu Yu , Hou Xiaohui
Published: June 2024

Coridius chinensis is a traditional Chinese medicinal insect, whose extract (CcE) is widely used for male reproductive disorders. Manganese (Mn2+) as a heavy metal pollutant can cause toxicity to the reproductive system in mammals. Previous studies found that CcE can resist the apoptosis and oxidation by Mn2+ exposed to repair the damage of seminiferous epithelium in rat. However, the therapeutic effect of CcE in the testicular stroma remains unclear. Our study found that the slow mating behaviors of capture, riding, insertion, and ejaculation with Mn2+ exposure were improved by CcE treatment in male rat. The level of testosterone was significantly increased in CcE‐treated groups. Meanwhile, the damage about less area and cell number in testicular stroma due to Mn2+ exposure was repaired after CcE treatment. Ultrastructure analysis of Leydig cells showed the larger mitochondria and more endoplasmic reticulum in Mn2+CcE groups became than that in Mn2+ group. Further experiments showed that mRNA and protein level of steroidogenic‐related regulators (STAR, CYP11α1, and HSD3β1) were significantly decreased in Mn2+ group and strongly upregulated occurred at medium concentration of CcE given. Taken together, our results provide a new insight of CcE in promoting testosterone production of Leydig cells to protect male reproductive behavior from Mn2+ toxicity.
Cavity behind Special Segment Structures in Upward Shield Tunneling: A Numerical Approach
Authors: Wei Xinjiang , Lu Liangliang , Wang Xiao , Yan Zihai , Yan Jiajia
Published: June 2024

Proper design of special segments under cavity conditions is essential for successfully implementing the upward shield tunneling method. When constructing upward tunnels, the segment structure in the corresponding construction area of the horizontal tunnel is special. To study the internal force distribution on the structure under the worst possible conditions given by the upward shield tunneling method, MIDAS GTS NX software is used to numerically simulate the structure based on the condition of the cavity behind it to determine the most unfavorable radius of the cavity. Moreover, an analysis of the cavity location is conducted. The results demonstrate that when the cavity is located at the bottom of the arch with a radius of 1 m and near the top of the arch with a radius of 0.5 m, the special segment structure is under the most unfavorable combination of stresses. The most dangerous working condition occurs when there is a 0.5 m radius cavity on one side of the arch in the cross‐section of the special segment.
FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint Inhibitors for the Treatment of Biliary Tract Cancer
Authors: Casak Sandra J. , Kumar Vaibhav , Song Chi , Yuan Mengdie , Amatya Anup K. , Cheng Joyce , Mishra-Kalyani Pallavi S. , Tang Shenghui , Lemery Steven J. , Auth Doris , Davis Gina , Kluetz Paul G. , Pazdur Richard , Fashoyin-Aje Lola A.
Published: June 2024

On September 2, 2022, the Food and Drug Administration (FDA) approved durvalumab in combination with cisplatin and gemcitabine, for the treatment of patients with unresectable or metastatic biliary tract cancers (BTC). On October 31, 2023, the FDA approved pembrolizumab in combination with cisplatin and gemcitabine for the same indication. Approvals were based on two randomized, multiregional, placebo-controlled trials that randomly allocated patients to receive durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966) in combination with chemotherapy or placebo in combination with chemotherapy. Overall survival (OS) was the primary endpoint in both studies. In both studies, a statistically significant and clinically meaningful improvement in OS was demonstrated. In the TOPAZ-1 trial, the median OS of patients receiving durvalumab was 12.8 months [95% confidence interval (CI), 11.1–14.0] and 11.5 months (95% CI, 10.1–12.5) in patients receiving placebo [hazard ratio (HR), 0.80 (95% CI, 0.66–0.97)]. In the KEYNOTE-966 trial, the median OS of patients receiving pembrolizumab was 12.7 months (95% CI, 11.5–13.6) and 10.9 months (95% CI, 9.9–11.6) in patients receiving placebo [HR, 0.83 (95% CI, 0.72–0.95)]. The addition of checkpoint inhibitors to standard of care chemotherapy for this indication did not reveal any new adverse event signals, and the safety profile was generally consistent with the known clinical experience with durvalumab, pembrolizumab, and the backbone chemotherapy regimen. The approvals of durvalumab and pembrolizumab in combination with standard of care cisplatin and gemcitabine for the treatment of unresectable or metastatic BTC add two new therapeutic options for these patients.
Mis-splicing of Mitotic Regulators Sensitizes SF3B1-Mutated Human HSCs to CHK1 Inhibition
Authors: Sarchi Martina , Clough Courtnee A. , Crosse Edie I. , Kim Jason , Baquero Galvis Laura D. , Aydinyan Nelli , Wellington Rachel , Yang Feini , Gallì Anna , Creamer J. Philip , Stewart Sintra , Bradley Robert K. , Malcovati Luca , Doulatov Sergei
Published: June 2024

Splicing factor SF3B1 mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences of SF3B1 mutations in human HSCs and progenitors (HSPCs) remain unclear. Here, we identify the mis-splicing program in human HSPCs as a targetable vulnerability by precise gene editing of SF3B1 K700E mutations in primary CD34+ cells. Mutant SF3B1 induced pervasive mis-splicing and reduced expression of genes regulating mitosis and genome maintenance leading to altered differentiation, delayed G2/M progression, and profound sensitivity to CHK1 inhibition (CHK1i). Mis-splicing or reduced expression of mitotic regulators BUBR1 and CDC27 delayed G2/M transit and promoted CHK1i sensitivity. Clinical CHK1i prexasertib selectively targeted SF3B1-mutant immunophenotypic HSCs and abrogated engraftment in vivo. These findings identify mis-splicing of mitotic regulators in SF3B1-mutant HSPCs as a targetable vulnerability engaged by pharmacological CHK1 inhibition.

Significance: In this study, we engineer precise SF3B1 mutations in human HSPCs and identify CHK1 inhibition as a selective vulnerability promoted by mis-splicing of mitotic regulators. These findings uncover the mis-splicing program induced by mutant SF3B1 in human HSPCs and show that it can be therapeutically targeted by clinical CHK1 inhibitors.
Noninvasive Lung Cancer Subtype Classification Using Tumor-Derived Signatures and cfDNA Methylome
Authors: Li Shuo , Li Wenyuan , Liu Bin , Krysan Kostyantyn , Dubinett Steven M.
Published: June 2024

Accurate diagnosis of lung cancer is important for treatment decision-making. Tumor biopsy and histologic examination are the standard for determining histologic lung cancer subtypes. Liquid biopsy, particularly cell-free DNA (cfDNA), has recently shown promising results in cancer detection and classification. In this study, we investigate the potential of cfDNA methylome for the noninvasive classification of lung cancer histologic subtypes. We focused on the two most prevalent lung cancer subtypes, lung adenocarcinoma and lung squamous cell carcinoma. Using a fragment-based marker discovery approach, we identified robust subtype-specific methylation markers from tumor samples. These markers were successfully validated in independent cohorts and associated with subtype-specific transcriptional activity. Leveraging these markers, we constructed a subtype classification model using cfDNA methylation profiles, achieving an AUC of 0.808 in cross-validation and an AUC of 0.747 in the independent validation. Tumor copy-number alterations inferred from cfDNA methylome analysis revealed potential for treatment selection. In summary, our study demonstrates the potential of cfDNA methylome analysis for noninvasive lung cancer subtyping, offering insights for cancer monitoring and early detection.

Significance:

This study explores the use of cfDNA methylomes for the classification of lung cancer subtypes, vital for effective treatment. By identifying specific methylation markers in tumor tissues, we developed a robust classification model achieving high accuracy for noninvasive subtype detection. This cfDNA methylome approach offers promising avenues for early detection and monitoring.
Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate–Resistant Prostate Cancer
Authors: Heath Elisabeth I. , Thakur Archana , Chen Wei , Hwang Clara , Paller Channing J. , Cackowski Frank C. , Boerner Julie L. , Heilbrun Lance , Smith Melanie P. , Schalk Dana L. , Schienschang Amy , Whitaker Sarah A. , Polend Amanda , Smith Daryn , Vaishampayan Ulka N. , Dickow Brenda , Lum Lawrence G.
Published: June 2024

Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored. Patients’ blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers before and after treatment. Baseline cumulative product parameters (total nucleated and CD54+ cell counts and CD54 upregulation) were evaluated. IgM titers against the immunogen PA2024, the target antigen PAP, prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) were quantified by ELISA. Cytotoxic T-lymphocyte activity was determined by ELISpots, and cytokine and chemokine concentrations were determined by Luminex.Twenty-nine African American (AA) men and 28 non-African American (non-AA) men with mCRPC received sipuleucel-T. Baseline total nucleated cell count, CD54+ cell count, CD54 expression, and cumulative product parameters were higher in non-AA men. Although PSA baseline levels were higher in AA men, there were no racial differences in IgM antibody and IFNγ ELISpots responses against PA2024, PAP, PSA, and PSMA before and after treatment. Expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells, and the levels of Th1 cytokine granulocyte-macrophage colony-stimulating factor and chemokines CCL4 and CCL5, were significantly higher in AA men before and/or after treatment. Despite no difference in the overall survival, PSA changes from baseline were significantly different between the two races. The data suggest that immune correlates in blood differ in AA and non-AA men with mCRPC pre- and post-sipuleucel-T.

Significance:

Our novel findings of higher expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells in African American patients with metastatic castrate-resistant prostate cancer (mCRPC) prior and post-sipuleucel-T suggest activation of CD4+ and CD8+ T cells. The data indicate that racial differences observed in these and other immune correlates before and after sipuleucel-T warrant additional investigation to further our understanding of the immune system in African American men and other men with mCRPC.
Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation
Authors: Pal Swasti , Kulshrestha Samarth , Garg Neha , Gupta Deepti , Gupta Nandita Dimri , Puri Ratna Dua
Published: June 2024

Introduction: TUBGCP6-related disorder is a known cause of autosomal recessive microcephaly and chorioretinopathy, which was originally recognized as a new syndrome based on unique ocular findings on a phenotypic overlap of microcephalic primordial short stature. Since the elucidation of its molecular mechanism, limited families have been published in literature and the disorder remains rare worldwide. Case Presentation: We present the first Indian family with an affected child and sibling fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on brain imaging in both and short stature, intellectual disability, and visual impairment in proband. As for many patients with long diagnostic odysseys, this child also underwent multiple genomic tests. Genome sequencing through the Indian Undiagnosed Disease Program (I-UDP) confirmed the diagnosis in both proband and sibling fetus. Compound heterozygous variants were identified in TUBGCP6 including an eleven base pair deletion (inherited from father) and 405 base pair large deletion (inherited from mother). Reverse phenotyping to confirm the ocular phenotype in proband confirmed TUBGCP6-related microcephaly and chorioretinopathy. We report third trimester microcephaly with ventriculomegaly and abnormal sulcation as part of the antenatal presentation for this condition. Conclusion: This case represents an Indian family with a seemingly obvious clinical diagnosis compounded by a long diagnostic odyssey and the first ever structural variant to be identified via whole genome sequencing in TUBGCP6 in trans with an indel variant.
Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial
Authors: Kang Duk-Hyun , Park Sung-Ji , Shin Sung-Hee , Hwang In-Chang , Yoon Yeonyee Elizabeth , Kim Hyung-Kwan , Kim Mijin , Kim Min-Seok , Yun Sung-Cheol , Song Jong-Min , Kang Seok-Min
Published: June 2024

BACKGROUND:

The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction.

METHODS:

The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm
2
on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).

RESULTS:

The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm
2
. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (−0.05±0.06 versus 0.03±0.12 cm
2
;
P
<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, −16.1 to −6.3;
P
=0.009), left atrial volume index by 6.0 mL/m
2
(95% CI, −12.16 to 0.15;
P
=0.005), and LV global longitudinal strain by 1.44% (95% CI, −2.42% to −0.46%;
P
=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (
P
=0.12).

CONCLUSIONS:

Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04231331.
Do Language Models’ Words Refer?
Authors: Mandelkern Matthew , Linzen Tal
Published: June 2024

What do language models (LMs) do with language? They can produce sequences of (mostly) coherent strings closely resembling English. But do those sentences mean something, or are LMs simply babbling in a convincing simulacrum of language use? We address one aspect of this broad question: whether LMs’ words can refer, that is, achieve “word-to-world” connections. There is prima facie reason to think they do not, since LMs do not interact with the world in the way that ordinary language users do. Drawing on the externalist tradition in philosophy of language, we argue that those appearances are misleading: Even if the inputs to LMs are simply strings of text, they are strings of text with natural histories, and that may suffice for LMs’ words to refer.
Anatomy-aware and acquisition-agnostic joint registration with SynthMorph
Authors: Hoffmann Malte , Hoopes Andrew , Greve Douglas N. , Fischl Bruce , Dalca Adrian V.
Published: June 2024

Affine image registration is a cornerstone of medical-image analysis. While classical algorithms can achieve excellent accuracy, they solve a time-consuming optimization for every image pair. Deep-learning (DL) methods learn a function that maps an image pair to an output transform. Evaluating the function is fast, but capturing large transforms can be challenging, and networks tend to struggle if a test-image characteristic shifts from the training domain, such as the resolution. Most affine methods are agnostic to the anatomy the user wishes to align, meaning the registration will be inaccurate if algorithms consider all structures in the image. We address these shortcomings with SynthMorph, a fast, symmetric, diffeomorphic, and easy-to-use DL tool for joint affine-deformable registration of any brain image without preprocessing. First, we leverage a strategy that trains networks with widely varying images synthesized from label maps, yielding robust performance across acquisition specifics unseen at training. Second, we optimize the spatial overlap of select anatomical labels. This enables networks to distinguish anatomy of interest from irrelevant structures, removing the need for preprocessing that excludes content which would impinge on anatomy-specific registration. Third, we combine the affine model with a deformable hypernetwork that lets users choose the optimal deformation-field regularity for their specific data, at registration time, in a fraction of the time required by classical methods. This framework is applicable to learning anatomy-aware, acquisition-agnostic registration of any anatomy with any architecture, as long as label maps are available for training. We analyze how competing architectures learn affine transforms and compare state-of-the-art registration tools across an extremely diverse set of neuroimaging data, aiming to truly capture the behavior of methods in the real world. SynthMorph demonstrates high accuracy and is available at https://w3id.org/synthmorph, as a single complete end-to-end solution for registration of brain magnetic resonance imaging (MRI) data.
Selective inference for fMRI cluster-wise analysis, issues, and recommendations for critical vector selection: A comment on Blain et al.
Authors: Andreella Angela , Vesely Anna , Weeda Wouter , Goeman Jelle
Published: June 2024

Two permutation-based methods for simultaneous inference on the proportion of active voxels in cluster-wise brain imaging analysis have recently been published: Notip and pARI. Both rely on the definition of a critical vector of ordered p-values, chosen from a family of candidate vectors, but differ in how the family is defined: computed from randomization of external data for Notip and determined a priori for pARI. These procedures were compared to other proposals in the literature, but an extensive comparison between the two methods is missing due to their parallel publication. We provide such a comparison and find that pARI outperforms Notip if both methods are applied under their recommended settings. However, each method carries different advantages and drawbacks.
Developmental trajectories of the default mode, frontoparietal, and salience networks from the third trimester through the newborn period
Authors: Scheinost Dustin , Chang Joseph , Brennan-Wydra Emma , Lacadie Cheryl , Constable R. Todd , Chawarska Katarzyna , Ment Laura R.
Published: June 2024

The default mode (DMN), frontoparietal (FPN), and salience (SN) networks interact to support a range of behaviors, are vulnerable to environmental insults, and are disrupted in neurodevelopmental disorders. However, their development across the third trimester and perinatal transition remains unknown. Employing resting-state functional MRI at 30 to 32, 34 to 36, and 40 to 44 weeks postmenstrual age (PMA), we examined developmental trajectories of the intra- and internetwork connectivity of the 3 networks measured in 84 fetuses and neonates. A secondary analysis addressed the impact of maternal mental health on these networks. The DMN, FPN, and SN intranetwork connectivity evidenced significant increases between 36 and 44 weeks PMA, with connectivity measures reaching values significantly greater than 0 at 40 weeks PMA for all 3 networks. Connectivity between SN and DMN and between SN and FPN decreased significantly with the connectivity values significantly below 0 at 36–44 weeks. However, DMN-FPN connectivity increased between 30 and 44 weeks with the connectivity greater than 0 already at 36 months. Finally, higher maternal stress levels negatively affected the SN across 30-44 weeks PMA. These data provide a normative framework to compare fetuses and neonates at risk for neurobehavioral disorders and assess the impact of the environment on the developing brain.
The relationship between interhemispheric homotopic functional connectivity and left-right difference of intrahemispheric functional integration in the human brain
Authors: Jin Xinhu , Liang Xinyu , Gong Gaolang
Published: June 2024

The brain comprises left and right hemispheres, with notable distinctions in intrahemispheric functional integration observed between homotopic regions of each hemisphere. Previous studies have shown these left-right differences may be induced by interhemispheric connectivity between homotopic regions. However, no research has comprehensively investigated the relationship between lateralization of intrahemispheric functional integration and interhemispheric homotopic functional connectivity in the resting state. Based on resting-state functional connectivity, we identified two brain functional organization properties named lateralization of intrahemispheric functional integration (LI) and interhemispheric homotopic functional connectivity (HoFC), hypothesizing the former was modulated by the latter in healthy individuals. Results showed a widespread significant negative correlation between LI and HoFC among the whole brain, which could be affected by age and task state presenting a still negative pattern but with weaker strength, especially in heteromodal regions. Furthermore, two mediation models showed that HoFC significantly mediated the age and brain state effect on LI, suggesting age and task state might influence lateralization of intrahemispheric functional integration via interhemispheric homotopic functional connectivity in adults. Lastly, these two intrinsic organization properties with different heritability together correlated with the general intelligence factor in an antagonistic manner. In summary, our findings offer important and valuable insight into functional lateralization, functional homotopy, and their relationship from the perspective of intrinsic functional architecture, together with influential factors such as age and task state. These results provide direct evidence to further understand the link between the left and right hemispheres of the human brain, along with the relation to cognitive functions.
Can the Mismatch Negativity Really Be Elicited by Abstract Linguistic Contrasts?
Authors: Politzer-Ahles Stephen , Jap Bernard A. J.
Published: June 2024

The mismatch negativity (MMN) is an event-related potential component that reflects pre-attentive change detection in the brain. As an electrophysiological index of processing that responds to differences in incoming consecutive stimuli, the MMN can be elicited through, for example, the presentation of two different categories of sounds in an oddball paradigm where sounds from the “standard” category occur frequently and sounds from the “deviant” category occur rarely. The specificity of what can elicit the MMN is yet to be fully defined. Here we test whether the MMN can be generated by an abstract linguistic contrast with no reliable acoustic cue. Previous studies have shown that the way in which an acoustic cue is used to elicit MMN is influenced by linguistic knowledge, but have not shown that a nonacoustic, abstract linguistic contrast can itself elicit MMN. In this study, we test the strongest interpretation of the claim that the MMN can be generated through a purely linguistic contrast by contrasting tenses in ablauting irregular English verbs (where there is no reliable acoustic cue for tense). We find that this contrast elicits a negativity, as do other linguistic contrasts previously shown to elicit MMN (a contrast between phonologically voiced and phonologically voiceless segments and a purely acoustic contrast between aspirated and unaspirated segments). The findings provide evidence that the MMN is indeed sensitive to purely abstract linguistic categories.
Research funding in different SCI disciplines: A comparison analysis based on Web of Science
Authors: Tian Wencan , Cai Ruonan , Fang Zhichao , Xie Qianqian , Hu Zhigang , Wang Xianwen
Published: June 2024

To provide valuable insights for shaping future funding policies, in this study, we offer a comprehensive panorama of the research funding across 171 SCI disciplines in the decade 2011–2020, based on more than 13 million scientific literature records from the Web of Science. The relationship between funding and research impact is also explored. To this end, we employ two indicators: the universality and multiplicity of funding, to indicate the funding level and six indicators to gauge the impact advantages of funding. Our findings reveal an upward trend in both the universality (increasing from 66.30% to 74.26%) and multiplicity (increasing from 2.82 to 3.26) of funding over the decade concerned. The allocation of funding varies across disciplines, with life sciences and earth sciences receiving the highest percentage of funding (78.31%) and medicine having the highest multiplicity of funding (3.07). Engineering and computer science have seen relatively rapid growth in terms of universality and multiplicity of funding. Funded articles have a greater impact than unfunded ones. And this impact strengthens as the number of funding grants increases. Through regression analysis, the citation advantage of funding is also proven at the article level, although the usage advantage is not significant.
Revisiting the Darwin wasp genus Epelaspis Townes, 1970 (Hymenoptera: Ichneumonidae: Phygadeuontinae): five new species, new records and a key to Neotropical species
Authors: LIMA ADRIANE G. M. , PÁDUA DIEGO G. , ARAUJO RODRIGO O. , MAZARIEGOS LUIS A. , FERNANDES DANIELL R. R.
Published: June 2024

The Darwin wasp genus Epelaspis Townes, 1970 (Hymenoptera: Ichneumonidae: Phygadeuontinae) is studied in some countries of South America. We recorded the genus for the first time in Colombia, and five new species are described: Epelaspis boteroi Lima & Fernandes, sp. nov., Epelaspis constantinoi Lima & Fernandes, sp. nov., Epelaspis lulo Lima & Fernandes, sp. nov., Epelaspis tavoi Lima & Fernandes, sp. nov., and Epelaspis wagneri Lima & Fernandes, sp. nov.. Furthermore, E. anorus Townes, 1970 is newly documented for Brazil, while the geographic ranges of E. renatoi Graf & Kumagai, 1996 and E. ketiae Graf & Kumagai, 1996 are extended within the country. Digital images, maps, and a key to Neotropical Epelaspis species are provided.