bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a realistic setup for a dynamical measurement of deviations from Newton’s $$1/r^2$$ law: the impact of air viscosity
Authors: Baeza-Ballesteros J. , Donini A. , Molina-Terriza G. , Monrabal F. , Simón A. 
Published: June 2024

AbstractA novel experimental setup to measure deviations from the $$1/r^2$$

1
/

r
2

distance dependence of Newtonian gravity was proposed in Donini and Marimón (Eur Phys J C 76:696, 2016). The underlying theoretical idea was to study the orbits of a microscopically-sized planetary system composed of a “Satellite”, with mass $$m_{\textrm{S}} \sim {\mathcal {O}}(10^{-9})$$

m
S

∼
O

(

10

-
9

)

g, and a “Planet”, with mass $$M_{\textrm{P}} \sim {\mathcal {O}} (10^{-5}) $$

M
P

∼
O

(

10

-
5

)

g at an initial distance of hundreds of microns. The detection of precession of the orbit in this system would be an unambiguous indication of a central potential with terms that scale with the distance differently from 1/r. This is a huge advantage with respect to the measurement of the absolute strength of the attraction between two bodies, as most electrically-induced background potentials do indeed scale as 1/r. Detection of orbit precession is unaffected by these effects, allowing for better sensitivities. In Baeza-Ballesteros et al. (Eur Phys J C 82:154, 2022), the impact of other subleading backgrounds that may induce orbit precession, such as, e.g., the electrical Casimir force or general relativity, was studied in detail. It was found that the proposed setup could test Yukawa-like corrections, $$\alpha \times \exp (-r/\lambda ),$$

α
×
exp
(
-
r
/
λ
)
,

to the 1/r potential with couplings as low as $$\alpha \sim 10^{-2}$$

α
∼

10

-
2

for distances as small as $$\lambda \sim 10$$

λ
∼
10

$$\upmu $$
μ
m, improving by roughly an order of magnitude present bounds. In this paper, we start to move from a theoretical study of the proposal to a more realistic implementation of the experimental setup. As a first step, we study the impact of air viscosity on the proposed setup and see how the setup should be modified in order to preserve the theoretical sensitivity achieved in Donini and Marimón (2016) and Baeza-Ballesteros et al. (2022).
Simple representations of BPS algebras: the case of $$Y(\widehat{\mathfrak {gl}}_2)$$
Authors: Galakhov Dmitry , Morozov Alexei , Tselousov Nikita 
Published: June 2024

AbstractBPS algebras are the symmetries of a wide class of brane-inspired models. They are closely related to Yangians – the peculiar and somewhat sophisticated limit of DIM algebras. Still they possess some simple and explicit representations. We explain here that for $$Y(\widehat{\mathfrak {gl}}_r)$$

Y
(

gl
^

r

)

these representations are related to Uglov polynomials, whose families are also labeled by natural r. They arise in the limit $$\hbar {\longrightarrow } 0$$

ħ
⟶
0

from Macdonald polynomials, and generalize the well-known Jack polynomials ($$\beta $$
β
-deformation of Schur functions), associated with $$r=1.$$

r
=
1
.

For $$r=2$$

r
=
2

they approximate Macdonald polynomials with the accuracy $$O(\hbar ^2),$$

O
(

ħ
2

)
,

so that they are eigenfunctions of two immediately available commuting operators, arising from the $$\hbar $$
ħ
-expansion of the first Macdonald Hamiltonian. These operators have a clear structure, which is easily generalizable, – what provides a technically simple way to build an explicit representation of Yangian $$Y(\widehat{\mathfrak {gl}}_2),$$

Y
(

gl
^

2

)
,

where $$U^{(2)}$$

U

(
2
)

are associated with the states $$|\lambda {\rangle },$$

|
λ
⟩
,

parametrized by chess-colored Young diagrams. An interesting feature of this representation is that the odd time-variables $$p_{2n+1}$$

p

2
n
+
1

can be expressed through mutually commuting operators from Yangian, however even time-variables $$p_{2n}$$

p

2
n

are inexpressible. Implications to higher r become now straightforward, yet we describe them only in a sketchy way.
Sengupta transformations and Carrollian relativistic theory
Authors: Banerjee Rabin , Bhattacharya Soumya , Majhi Bibhas Ranjan 
Published: June 2024

AbstractA detailed and systematic formulation of Carrollian relativity is provided. Based on the transformations, first provided by Sengupta (Nuovo Cim, 54:512, 1966), we construct a mapping between Lorentz relativistic and Carrollian relativistic vectors. Using this map the Carroll theory is built from the standard Maxwell action. We show that we get self-consistent equations of motion from the action, both in electric and magnetic limits. We introduce Carroll electric and magnetic fields. A new set of maps is derived that connects Carroll electric and magnetic fields with the usual Maxwell ones and yields Carroll equations in terms of fields. Consistency of results with the potential formulation is shown. Carroll version of symmetries like duality, gauge, shift, Noether and boost are treated in details and their implications elaborated. Especially, boost symmetry provides a link to the various maps used in this paper.
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.
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.
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

Abstract
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

Abstract
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

Abstract

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

Abstract

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.
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

Abstract
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

AbstractAffine 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.