bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer
Authors: Razmara Aryana M , Farley Lauren E , Harris Rayna M , Judge Sean J , Lammers Marshall , Iranpur Khurshid R , Johnson Eric G , Dunai Cordelia , Murphy William J , Brown C Titus , Rebhun Robert B , Kent Michael S , Canter Robert J 
Published: April 2024

BackgroundNatural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product.MethodsStarting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3’-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach.ResultsCalculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment.ConclusionsOverall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.
Higher mortality risk from gynaecological neoplasms and non-Hodgkin’s lymphoma in patients with systemic lupus erythematosus: an observational study from the Spanish National Registry
Authors: Moreno-Torres Víctor , Martínez-Urbistondo María , Vázquez-Comendador José , Mateos Seirul-lo María , Castejón Raquel , Huerta Ana , Durán-del Campo Pedro , Tutor Pablo , Mellor-Pita Susana 
Published: April 2024

ObjectiveTo evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE.MethodsRetrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed.ResultsDuring 2016–2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin’s lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133).ConclusionsPatients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin’s lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully.
Updates on the determination of $$\vert V_{cb} \vert ,$$ $$R(D^{*})$$ and $$\vert V_{ub} \vert /\vert V_{cb} \vert $$
Authors: Martinelli G. , Simula S. , Vittorio L. 
Published: April 2024

AbstractWe present an updated determination of the values of $$\vert V_{cb} \vert ,$$

|

V

cb

|
,

$$R(D^*)$$

R
(

D
∗

)

and $$\vert V_{ub} \vert /\vert V_{cb} \vert $$

|

V

ub

|
/
|

V

cb

|

based on the new data on semileptonic $$B \rightarrow D^* \ell \nu _\ell $$

B
→

D
∗

ℓ

ν
ℓ

decays by the Belle and Belle-II Collaborations and on the recent theoretical progress in the calculation of the form factors relevant for semileptonic $$B \rightarrow D^* \ell \nu _\ell $$

B
→

D
∗

ℓ

ν
ℓ

and $$B_s \rightarrow K \ell \nu _\ell $$

B
s

→
K
ℓ

ν
ℓ

decays. In particular we present results derived by applying either the Dispersive Matrix (DM) method of Di Carlo et al. (Phys Rev D 104:054502, 2021), Martinelli et al. (Phys Rev D 104:094512, 2021), Martinelli et al. (Phys Rev D 105:034503, 2022), Martinelli et al. (Eur Phys J C 82:1083, 2022), Martinelli et al. (JHEP 08:022, 2022) and Martinelli et al. (Phys Rev D 106:093002, 2022) or the more standard Boyd–Grinstein–Lebed (BGL) (Boyd et al. in Phys Rev D 56:6895, 1997) approach to the most recent values of the form factors determined in lattice QCD. Using all the available lattice results for the form factors from the DM method we get the theoretical value $$R^{\textrm{th}}(D^*) = 0.262 \pm 0.009$$

R
th

(

D
∗

)

=
0.262
±
0.009

and we extract from a bin-per-bin analysis of the experimental data the value $$\vert V_{cb} \vert = (39.92 \pm 0.64) \cdot 10^{-3}.$$

|

V

cb

|
=

(
39.92
±
0.64
)

·

10

-
3

.

Our result for $$R(D^*)$$

R
(

D
∗

)

is consistent with the latest experimental world average $$R^{\textrm{exp}}(D^*) = 0.284 \pm 0.012$$

R
exp

(

D
∗

)

=
0.284
±
0.012

(HFLAV Collaboration in Preliminary average of R(D) and $$R(D^*)$$

R
(

D
∗

)

as for Summer 2023. See https://hflav-eos.web.cern.ch/hflav-eos/semi/summer23/html/RDsDsstar/RDRDs.html) at the $$\simeq 1.5\,\sigma $$

≃
1.5

σ

level. Our value for $$\vert V_{cb} \vert $$

|

V

cb

|

is compatible with the latest inclusive determinations $$\vert V_{cb} \vert ^{\textrm{incl}} = (41.97 \pm 0.48) \cdot 10^{-3}$$

|

V

cb

|

incl

=

(
41.97
±
0.48
)

·

10

-
3

(Finauri and Gambino in The $$q^2$$

q
2

moments in inclusive semileptonic B decays. arXiv:2310.20324) and $$\vert V_{cb} \vert ^{\textrm{incl}} = (41.69\pm 0.63) \cdot 10^{-3}$$

|

V

cb

|

incl

=

(
41.69
±
0.63
)

·

10

-
3

(Bernlochner et al. in JHEP 10:068, 2022) within $$\simeq 2.6$$

≃
2.6

and $$\simeq 2.0$$

≃
2.0

standard deviations, respectively. From a reappraisal of the calculations of $$\vert V_{ub} \vert / \vert V_{cb} \vert ,$$

|

V

ub

|
/
|

V

cb

|
,

we also obtain $$\vert V_{ub} \vert / \vert V_{cb} \vert = 0.087\pm 0.009$$

|

V

ub

|
/
|

V

cb

|
=
0.087
±
0.009

in good agreement with the result $$\vert V_{ub} \vert / \vert V_{cb} \vert = 0.0844\pm 0.0056$$

|

V

ub

|
/
|

V

cb

|
=
0.0844
±
0.0056

from the latest FLAG review (Flavour Lattice Averaging Group (FLAG) Collaboration in Phys J C 82:869, 2022).
Faster Counting and Sampling Algorithms using Colorful Decision Oracle
Authors: Bhattacharya Anup , Bishnu Arijit , Ghosh Arijit , Mishra Gopinath 
Published: April 2024

In this work, we consider
d
-
Hyperedge Estimation
and
d
-
Hyperedge Sample
problems that deal with estimation and uniform sampling of hyperedges in a hypergraph ℋ(
U
(ℋ), ℱ(ℋ) in the query complexity framework, where
U
(ℋ) denotes the set of vertices and ℱ(ℋ) denotes the set of hyperedges. The oracle access to the hypergraph is called
Colorful Independence Oracle
(
CID
), which takes
d
(non-empty) pairwise disjoint subsets of vertices
A
1
,...,

A
d

⊆
U
(ℋ) as input and answers whether there exists a hyperedge in ℋ having exactly one vertex in each

A
i

for all
i
∈ {1, 2, ...,
d
}. Apart from the fact that
d
-
Hyperedge Estimation
and
d
-
Hyperedge Sample
problems with
CID
oracle access seem to be nice combinatorial problems, Dell et al. [SODA’20 & SICOMP’22] established that
decision
vs.
counting
complexities of a number of combinatorial optimization problems can be abstracted out as
d
-
Hyperedge Estimation
problem with a
CID
oracle access.

The main technical contribution of this article is an algorithm that estimates
m
= |ℱ(ℋ)| with

\(\widehat{m}\)

such that

\(\begin{equation*}
\frac{1}{C_{d}\log ^{d-1} n} \;\le \; \frac{\widehat{m}}{m} \;\le \; C_{d} \log ^{d-1} n
\end{equation*}\)

by using at most

C
d

log

d
+2

n
CID
queries, where
n
denotes the number of vertices in the hypergraph ℋ and

C
d

is a constant that depends only on
d
. Our result, when coupled with the framework proposed by Dell et al. (SODA’20 & SICOMP’22), leads to implies improved bounds for (1 ± ε)-approximation (where ε ∈ (0,1)) for the following fundamental problems:

Edge Estimation

using the
Bipartite Independent Set
(
BIS
) query. We improve the bound obtained by Beame et al. (ITCS’18 & TALG’20).

Triangle Estimation

using the
Tripartite Independent Set
(
TIS
) query. Currently, Dell et al.’s result gives the best bound for the case of triangle estimation in general graphs (SODA’20 & SICOMP’22). The previous best bound for the case of graphs with low
co-degree
(co-degree of a graph is the maximum number of triangles incident over any edge of the graph) was due to Bhattacharya et al. (ISAAC’19 & TOCS’21). We improve both of these bounds.

Hyperedge Estimation & Sampling

using
Colorful Independence Oracle
(
CID
). We give an improvement over the bounds obtained by Dell et al. (SODA’20 & SICOMP’22).
Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity
Authors: Pan Haifeng , Yu Siyuan , Zhuang Haoyun , Yang Han , Jiang Jinlu , Yang Haihui , Ren Shuling , Luo Guoxing , Yu Xuan , Chen Shuping , Lin Yanhua , Sheng Roufang , Zhang Shiyin , Yuan Quan , Huang Chenghao , Zhang Tianying , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao 
Published: April 2024

Abstract
The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens (Ag) and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. In this study, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of Ags and cytosine-guanosine oligodeoxynucleotide (CpG) to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant. Linking Ags to eTAT enhanced cytosolic delivery of the Ags. This, in turn, led to improved activation and lymph node–trafficking of Ag-presenting cells and Ag cross-presentation, thus promoting Ag-specific T-cell immune responses. Simple mixing of eTAT-linked Ags and CpG significantly enhanced codelivery of Ags and CpG to the Ag-presenting cells, and this substantially augmented the adjuvant effect of CpG, maximized vaccine immunogenicity, and elicited robust and durable CD8+ T-cell responses. Vaccination with this formulation altered the tumor microenvironment and exhibited potent antitumor effects, with generally further enhanced therapeutic efficacy when used in combination with anti-PD1. Altogether, the engineered chimeric peptide–based orchestrated codelivery of Ag and adjuvant may serve as a promising but simple strategy to improve the efficacy of peptide-based cancer vaccines.
Small Extracellular Vesicles Promote Stiffness-mediated Metastasis
Authors: Sneider Alexandra , Liu Ying , Starich Bartholomew , Du Wenxuan , Nair Praful R. , Marar Carolyn , Faqih Najwa , Ciotti Gabrielle E. , Kim Joo Ho , Krishnan Sejal , Ibrahim Salma , Igboko Muna , Locke Alexus , Lewis Daniel M. , Hong Hanna , Karl Michelle N. , Vij Raghav , Russo Gabriella C. , Gómez-de-Mariscal Estibaliz , Habibi Mehran , Muñoz-Barrutia Arrate , Gu Luo , Eisinger-Mathason T.S. Karin , Wirtz Denis 
Published: April 2024

Abstract

Tissue stiffness is a critical prognostic factor in breast cancer and is associated with metastatic progression. Here we show an alternative and complementary hypothesis of tumor progression whereby physiologic matrix stiffness affects the quantity and protein cargo of small extracellular vesicles (EV) produced by cancer cells, which in turn aid cancer cell dissemination. Primary patient breast tissue released by cancer cells on matrices that model human breast tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα2β1, ITGα6β4, ITGα6β1, CD44) compared with EVs from softer normal tissue (0.5 kPa; soft EVs), which facilitates their binding to extracellular matrix proteins including collagen IV, and a 3-fold increase in homing ability to distant organs in mice. In a zebrafish xenograft model, stiff EVs aid cancer cell dissemination. Moreover, normal, resident lung fibroblasts treated with stiff and soft EVs change their gene expression profiles to adopt a cancer-associated fibroblast phenotype. These findings show that EV quantity, cargo, and function depend heavily on the mechanical properties of the extracellular microenvironment.

Significance:
Here we show that the quantity, cargo, and function of breast cancer–derived EVs vary with mechanical properties of the extracellular microenvironment.
Evaluation of Instantaneous Wave-Free Ratio and Fractional Flow Reserve in Severe Aortic Valve Stenosis
Authors: Jo Ha Hye , Kang Do-Yoon , Lee Joong Min , Lim So-Min , Park Young-Sun , Choi Yeonwoo , Kim Hoyun , Lee Jinho , Ahn Jung-Min , Park Duk-Woo , Park Seung-Jung 
Published: April 2024

BACKGROUND:
The optimal functional evaluation of coronary artery stenosis in patients with severe aortic stenosis (AS) has not been established. The objective of the study was to evaluate the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with and without severe AS.

METHODS:
We retrospectively investigated 395 lesions in 293 patients with severe AS and 2257 lesions in 1882 patients without severe AS between 2010 and 2022 from a subgroup of the Interventional Cardiology Research In-Cooperation Society FFR Registry. All patients had FFR values, and iFR was analyzed post hoc using dedicated software only in lesions with adequate resting pressure curves (311 lesions in patients with severe AS and 2257 lesions in patients with nonsevere AS).

RESULTS:

The incidence of iFR ≤0.89 was 66.6% and 31.8% (
P
<0.001), while the incidence of FFR ≤0.80 was 45.3% and 43.9% (
P
=0.60) in the severe AS group and the nonsevere AS group, respectively. In the severe AS group, most lesions (95.2%) with iFR >0.89 had FFR >0.80, while 36.2% of lesions with iFR ≤0.89 had FFR >0.80. During a median follow-up of 2 years, FFR ≤0.80 was significantly associated with deferred lesion failure (adjusted hazard ratio, 2.71 [95% CI, 1.08–6.80];
P
=0.034), while iFR ≤0.89 showed no prognostic value (adjusted hazard ratio, 1.31 [95% CI, 0.47–3.60];
P
=0.60) in the severe AS group. Lesions with iFR ≤0.89 and FFR >0.80, in particular, were not associated with a higher rate of deferred lesion failure at 3 years compared with lesions with iFR >0.89 (15.4% versus 17.0%;
P
=0.58).

CONCLUSIONS:
This study suggested that FFR appears to be less affected by the presence of severe AS and is more associated with prognosis. iFR may overestimate the functional severity of coronary artery disease without prognostic significance, yet it can be useful for excluding significant stenosis in patients with severe AS.
The Saltzman–Lorenz Exchange in 1961: Bridge to Chaos Theory
Authors: Lewis John M. , Lakshmivarahan S. 
Published: April 2024

Abstract
A single-day meeting between two theoretical meteorologists took place in 1961 at the Travelers Research Center (TRC) in Hartford, Connecticut. The two scientists were Barry Saltzman and Edward Lorenz, former proteges of V. P. Starr at Massachusetts Institute of Technology (MIT). Several years before this meeting, Lorenz discovered the following profound result: extended-range weather forecasting was not feasible in the presence of slight errors in initial conditions. The model used was the geostrophic form of a two-level baroclinic model with 12 spectral variables. These results were presented a year earlier at the first symposium on numerical weather prediction (NWP) in Tokyo, Japan, and met with some skepticism from the NWP elite, dynamical meteorologists, and pioneers in operational NWP. Lorenz held faint hope that Saltzman’s recently developed model of Rayleigh–Bénard convection would produce the profound result found earlier. One of the numerical experiments executed that eventful day with Saltzman’s seven-mode truncated spectral model produced an unexpected result: inability of the model’s seven variables to settle down and approach a steady state. This occurred when the key parameter, the Rayleigh number, assumed an especially large value, one associated with turbulent convection. And further experimentation with the case delivered the sought-after result that Lorenz had found earlier and now convincingly found with a simpler model. It built the bridge to chaos theory. The pathway to this exceptional result is explored by revisiting Saltzman’s and Lorenz’s mentorship under V. P. Starr, the authors’ interview with Lorenz in 2002 that complements information in Lorenz’s scientific autobiography, and the authors’ published perspective on Salzman’s seven-mode model.
National Trends and Outcomes in the Operative Management of Thyroid Storm
Authors: Seo Young-Ji , Chervu Nikhil , Benharash Peyman , Wu James X. 
Published: April 2024

Background Thyroid storm is a rare but potentially lethal manifestation of thyrotoxicosis. Guidelines recommend nonoperative management of thyroid storm, but thyroidectomy can be performed if patients fail medical therapy or need immediate resolution of the storm. Outcomes of thyroidectomy for management of thyroid storm remain ill-defined. Methods Using the National Inpatient Sample from 2016 to 2020, a retrospective analysis was conducted of patients admitted with thyroid storm. Outcomes of interest included operative complications and mortality. Multivariable logistic regression was performed to assess factors associated with receiving thyroidectomy and mortality. Results An estimated 16,175 admissions had a diagnosis of thyroid storm. The incidence of thyroid storm increased from .91 per 100,000 people in 2016 to 1.03 per 100,000 people in 2020, with a concomitant increase in mortality from 2.9% to 5.3% ( P < .001). Operative intervention was pursued in 635 (3.9%) cases with a perioperative complication rate of 30%. On multivariable regression, development of acute decompensated heart failure (adjusted odds ratio [AOR] 1.66, 95% Confidence Interval [CI] 1.03-2.68, P = .037) and acute renal failure (AOR 2.10, 95% CI 1.17-3.75, P = .013) increased odds of receiving surgery. The same multivariable model did not show a significant association between thyroidectomy and mortality. Discussion The incidence of thyroid storm and associated mortality increased during the study period. Thyroidectomy is rarely performed during the same admission, with an overall perioperative complication rate of 30% and no effect on mortality. Patients with acute decompensated heart failure and renal failure were more likely to receive an operative intervention.
Assessing Lower-Extremity Visuo-Motor Reaction Time in Young Male Soccer Players: Test-Retest Reliability and Minimum Detectable Change of the Brain Pro System
Authors: Secer Erhan , Ozer Kaya Derya 
Published: April 2024

A reliable, versatile means of assessing visuo-motor reaction time (V-MRT) is important to football (soccer) players for many reasons, including the fact that faster V-MRT is a critical sport skill that may even play a role in reducing common sports injuries to the lower muscle extremities that can be associated with lost time on the field. We aimed to determine the test-retest reliability and minimum detectable change (MDC) of the Brain Pro System for assessing lower-extremity V-MRT in young male football players. We had 68 participants ( M age = 16.35, SD = 1.71 years) perform two assessment sessions one-week apart. For test-retest reliability, we calculated a one-way intra-class correlation coefficient (ICC) at the 95% confidence interval and provided the standard error of measurement (SEM) and minimum detectable change (MDC) (MDC = SEM × 1.96 × √2) for V-MRTs. We obtained excellent V-MRT test-retest reliability for dominant lower-extremity, non-dominant lower-extremity, and dominant and non-dominant lower-extremities (ICC2,1 = .93, 95%CI = .89–.96; ICC2,1 = .94, 95%CI = .91–.96; ICC2,1 = .96, 95%CI = .94–.97; respectively). The calculated MDC for the dominant lower-extremity V-MRT, the non-dominant lower-extremity V-MRT, and dominant and non-dominant lower-extremities (random) V-MRT were 1.21 seconds, 1.13 seconds, and 1.21 seconds, respectively. Brain Pro System had excellent reliability for assessing lower-extremity V-MRT in young male football players. The MDC values at the 95% confidence level (MDC95) we obtained were reliable for assessing clinically meaningful V-MRT changes.
Publications by Indian Orthodontists Making Global Waves: An Analysis from 2017 to 2023—Before, During, and After the Pandemic
Authors: Mathur Sanjana , Mohelay Nikita , Batra Puneet 
Published: April 2024

Aim This article seeks to evaluate the shifts in publication rates and the participation of Indian orthodontists in different quartiles of orthodontic journals before, during, and after the pandemic, spanning the years 2017–2023. Methods The evaluation involved manually searching through archives of 15 journals divided into quartiles, that is, Q1, Q2, and Q3. Articles with at least one author affiliated with an Indian university were collected and tabulated into graphs. Results In Q1 journals, “Progress in Orthodontics” achieved the highest Indian publication percentage at 4.66%, whereas the European Journal of Orthodontics recorded the lowest at 0.93%. Among Q2 journals, the Journal of Orthodontic Science led with a maximum publication rate of 35.83%, while the Korean Journal of Orthodontics had the least, accounting for only 0.36%. In Q3 journals, the highest contribution of 31.16% was observed in APOS Trends in Orthodontics, while International Orthodontics had the lowest contribution at 8.24%. Conclusion The examination of 15 orthodontic journals spanning the 7 years from 2017 to 2023 revealed that the publication trends remained largely unchanged in the majority of journals across all three time periods: pre-COVID-19, during the pandemic, and post-COVID-19. Notable exceptions included a slight increase in publications observed during and after the pandemic, specifically in the American Journal of Orthodontics and Dentofacial Orthopedics (Q1 journal), Journal of Orthodontic Science (Q2 journal), APOS Trends in Orthodontics (Q3 journal), and International Orthodontics (Q3 journal).