bluuebunny/crossref_metadata_2025_split huggingface dataset:
SFRP1 decreases WNT-Mediated M2 macrophage marker expression in breast tissue
Authors: Gregory Kelly J. , Mason Holly , Casaubon Jesse , Schneider Sallie S. 
Published: March 2024

AbstractThe Wnt family of secreted proteins are involved in mammary gland development and tumorigenesis. It has recently been shown that Wnt ligands promote M2 macrophage polarization and so we sought to determine the effects of a Wnt signaling antagonist, Secreted Frizzled Related Protein 1 (SFRP1), on M2 marker expression. We measured a murine M2 marker (Arg1) in mice with a targeted deletion of Sfrp1 during different stages of mammary gland development including puberty, pregnancy, and lactation, as well as in response to obesity. Next, to determine whether Wnt signaling/antagonism affects human M2 markers (CD209 and CCL18), we treated a human patient derived explant (PDE) breast tissue sample with exogenous Wnt3a in the presence and absence of rSFRP1. Finally, we expanded our PDE study to 13 patients and performed bulk RNAseq analysis following the treatment described above. We found that in loss of Sfrp1 in the murine mammary gland increased Arg1 expression. Moreover, we showed that Wnt3a increases CD209 and CCL18 mRNA and protein expression in breast PDEs and that their expression is decreased in response to rSFRP1. Our RNAseq analysis unveiled novel genes that were affected by Wnt3a treatment and subsequently reversed when rSFRP1 was added. Validation of these data exhibited that chemokines involved in promoting macrophage polarization and cancer metastasis, including CCL11 and CCL26, were stimulated by Wnt3a signaling and their expression was abrogated by treatment with rSFRP1. Our data suggest that SFRP1 may be an important mediator that tempers Wnt signaling in the tumor microenvironment.
Targeting osteosarcoma with canine B7-H3 CAR T cells and impact of CXCR2 Co-expression on functional activity
Authors: Cao Jennifer W. , Lake Jessica , Impastato Renata , Chow Lyndah , Perez Luisanny , Chubb Laura , Kurihara Jade , Verneris Michael R. , Dow Steven 
Published: March 2024

AbstractThe use of large animal spontaneous models of solid cancers, such as dogs with osteosarcoma (OS), can help develop new cancer immunotherapy approaches, including chimeric antigen receptor (CAR) T cells. The goal of the present study was to generate canine CAR T cells targeting the B7-H3 (CD276) co-stimulatory molecule overexpressed by several solid cancers, including OS in both humans and dogs, and to assess their ability to recognize B7-H3 expressed by canine OS cell lines or by canine tumors in xenograft models. A second objective was to determine whether a novel dual CAR that expressed a chemokine receptor together with the B7-H3 CAR improved the activity of the canine CAR T cells. Therefore, in the studies reported here we examined B7-H3 expression by canine OS tumors, evaluated target engagement by canine B7-H3 CAR T cells in vitro, and compared the relative effectiveness of B7-H3 CAR T cells versus B7-H3-CXCR2 dual CAR T cells in canine xenograft models. We found that most canine OS tumors expressed B7-H3; whereas, levels were undetectable on normal dog tissues. Both B7-H3 CAR T cells demonstrated activation and OS-specific target killing in vitro, but there was significantly greater cytokine production by B7-H3-CXCR2 CAR T cells. In canine OS xenograft models, little anti-tumor activity was generated by B7-H3 CAR T cells; whereas, B7-H3-CXCR2 CAR T cells significantly inhibited tumor growth, inducing complete tumor elimination in most treated mice. These findings indicated therefore that addition of a chemokine receptor could significantly improve the anti-tumor activity of canine B7-H3 CAR T cells, and that evaluation of this new dual CAR construct in dogs with primary or metastatic OS is warranted since such studies could provide a critical and realistic validation of the chemokine receptor concept.
Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma
Authors: He Yijia , Liu Lingyun , Dong Yuexin , Zhang Xiaoxin , Song Yuxian , Jing Yue , Ni Yanhong , Wang Yi , Wang Zhiyong , Ding Liang 
Published: March 2024

Abstract
Background
Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).

Methods
PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.

Results
Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285–6.851).

Conclusions
LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.
IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models
Authors: Yu Justin , Gadwa Jacob , Ross Richard B. , Knitz Michael , Darragh Laurel B. , Abdelazeem Khalid N. M. , Beynor Jessica , Neupert Brooke , Nguyen Alexander , Nguyen Diemmy , Olimpo Nicholas , Corbo Sophia , Van Court Benjamin , D’Alessandro Angelo , Saviola Anthony , Karam Sana D. 
Published: March 2024

AbstractClinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models. Immune populations from the tumor, draining lymph nodes, and blood were compared between treatment groups and controls using flow cytometry, proteomics, immunofluorescence staining, and RNA sequencing. Treatment with RT and IL7 (RT + IL7) resulted in significant tumor growth reduction, high CD8 T-cell tumor infiltration, and increased proliferation of T-cell progenitors in the bone marrow. IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.
DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy
Authors: Ma Zhe , Zhou Zhenxing , Duan Wenwen , Yao Gaofeng , Sheng Shimei , Zong Sidou , Zhang Xin , Li Changkui , Liu Yuanyuan , Ou Fengting , Dahar Maha Raja , Huang Yanshan , Yu Lushan 
Published: March 2024

Abstract
Background
Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy.

Methods
Based on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18.2, human serum albumin (HSA) and CD3 on T cells.

Results
The DR30318 demonstrated binding affinity to CLDN18.2, HSA and CD3, and exhibited T cell-dependent cellular cytotoxicity (TDCC) activity in vitro. Pharmacokinetic analysis revealed a half-life of 22.2–28.6 h in rodents and 41.8 h in cynomolgus monkeys, respectively. The administration of DR30318 resulted in a slight increase in the levels of IL-6 and C-reactive protein (CRP) in cynomolgus monkeys. Furthermore, after incubation with human PBMCs and CLDN18.2 expressing cells, DR30318 induced TDCC activity and the production of interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Notably, DR30318 demonstrated significant tumor suppression effects on gastric cancer xenograft models NUGC4/hCLDN18.2 and pancreatic cancer xenograft model BxPC3/hCLDN18.2 without affecting the body weight of mice.
Let-7i enhances anti-tumour immunity and suppresses ovarian tumour growth
Authors: Wilkinson Andrew N. , Chen Rui , Coleborn Elaina , Neilson Trent , Le Khang , Bhavsar Chintan , Wang Yue , Atluri Sharat , Irgam Gowri , Wong Kiefer , Yang Da , Steptoe Raymond , Wu Sherry Y. 
Published: March 2024

AbstractCancer immunotherapy has seen significant success in the last decade for cancer management by enhancing endogenous cancer immunity. However, immunotherapies developed thus far have seen limited success in the majority of high-grade serous carcinoma (HGSC) ovarian cancer patients. This is largely due to the highly immunosuppressive tumour microenvironment of HGSC and late-stage identification. Thus, novel treatment interventions are needed to overcome this immunosuppression and complement existing immunotherapies. Here, we have identified through analysis of > 600 human HGSC tumours a critical role for Let-7i in modulating the tumoural immune network. Tumoural expression of Let-7i had high positive correlation with anti-cancer immune signatures in HGSC patients. Confirming this role, enforced Let-7i expression in murine HGSC tumours resulted in a significant decrease in tumour burden with a significant increase in tumour T cell numbers in tumours. In concert with the improved tumoural immunity, Let-7i treatment also significantly increased CD86 expression in antigen presenting cells (APCs) in the draining lymph nodes, indicating enhanced APC activity. Collectively, our findings highlight an important role of Let-7i in anti-tumour immunity and its potential use for inducing an anti-tumour effect in HGSC.
Wall shear stress measurement using a zero-displacement floating-element balance
Authors: Aguiar Ferreira M. , Costa P. , Ganapathisubramani B. 
Published: March 2024

AbstractThe floating-element (FE) principle, introduced nearly a century ago, remains one of the most versatile direct wall shear stress measurement methods. Yet, its intrinsic sources of systematic error, associated with the flow-exposed gap, off-axis load sensitivity, and calibration, have thus far limited its widespread application. In combination with the lack of standard designs and testing procedures, measurement reliability still hinges heavily on individual judgement and expertise. This paper presents a framework to curb these limitations, whereby the design and operation of a FE balance are leveraged by an analytical model that attempts to capture the behaviour and predict the relative contribution of the systematic sources of error. The design is based on a parallel-shift linkage and a zero-displacement force-feedback system. The FE has a surface area of $$200\times 200\,$$

200
×
200

mm, and measurement sensitivity is adjustable depending on the surface condition and the Reynolds number. It is thus suitable for application in a wide range of low-speed, boundary-layer wind tunnels, small or large scale. Measurements of the skin friction coefficient over a smooth wall show a remarkable agreement with oil-film interferometry, especially for $${\rm Re}_{\theta } > 1.3 \times 10^4$$

Re
θ

>
1.3
×

10
4

. The discrepancy relative to the empirical Coles–Fernholz relation ($$\kappa = 0.39$$

κ
=
0.39

and $$C = 4.352$$

C
=
4.352

) is within $$0.5\,$$

0.5

%, and the level of uncertainty is below $$1\,$$

1

% for a confidence interval of $$95\,$$

95

%.
Skin color reporting in squamous cell carcinoma-related randomized controlled trials in top dermatology journals: a systematic review
Authors: Salmen Natasha L. , Menage Klarens , Baumann Anthony N. , Curtis Deven P. , Brodell Robert T. 
Published: March 2024

AbstractThe objectives are to determine the frequency that skin color is reported in randomized controlled trials (RCTs) involving squamous cell carcinoma (SCC) detection and treatment in leading dermatology journals. A systematic review of RCTs involving SCC was conducted among the top ten most impactful dermatology journals from inception to July 10th, 2023. Studies were included if they reviewed the treatment, prevention, or detection of SCC, involved patients directly and were classified as traditional RCTs. Studies were considered positive for reporting SOC if there was any demographic data in the methods or results of the following terms: Fitzpatrick scale, race, ethnicity, sunburn tendency, or skin of color. Of the 39 studies which were identified, 23 reported data related to skin color data (59.0%). White individuals were the most reported in these studies (56.5%). Subgroup analysis was conducted, and no statistical significance was found for study location, year of publication, or funding source. Skin color impacts skin cancer detection, predominant location of tumors, and recurrence. Less than 60% of high-quality RCTs related to SCC in top global dermatology journals included skin color among the demographic traits of study participants. Subgroup analysis demonstrated no improvement in reporting over the past 2 decades. Further research is needed to understand the reason for low skin color reporting rates among SCC-related RCTs and the impact this has on society.
Subcortical auditory system in tinnitus with normal hearing: insights from electrophysiological perspective
Authors: Colak Hasan , Sendesen Eser , Turkyilmaz Meral Didem 
Published: March 2024

Abstract
Purpose
The mechanism of tinnitus remains poorly understood; however, studies have underscored the significance of the subcortical auditory system in tinnitus perception. In this study, our aim was to investigate the subcortical auditory system using electrophysiological measurements in individuals with tinnitus and normal hearing. Additionally, we aimed to assess speech-in-noise (SiN) perception to determine whether individuals with tinnitus exhibit SiN deficits despite having normal-hearing thresholds.

Methods
A total 42 normal-hearing participants, including 22 individuals with chronic subjective tinnitus and 20 normal individuals, participated in the study. We recorded auditory brainstem response (ABR) and speech-evoked frequency following response (sFFR) from the participants. SiN perception was also assessed using the Matrix test.

Results
Our results revealed a significant prolongation of the O peak, which encodes sound offset in sFFR, for the tinnitus group (p < 0.01). The greater non-stimulus-evoked activity was also found in individuals with tinnitus (p < 0.01). In ABR, the tinnitus group showed reduced wave I amplitude and prolonged absolute wave I, III, and V latencies (p ≤ 0.02). Our findings suggested that individuals with tinnitus had poorer SiN perception compared to normal participants (p < 0.05).

Conclusion
The deficit in encoding sound offset may indicate an impaired inhibitory mechanism in tinnitus. The greater non-stimulus-evoked activity observed in the tinnitus group suggests increased neural noise at the subcortical level. Additionally, individuals with tinnitus may experience speech-in-noise deficits despite having a normal audiogram. Taken together, these findings suggest that the lack of inhibition and increased neural noise may be associated with tinnitus perception.
Exposure to psychotropic drugs and breast cancer risk in patients with bipolar disorder and major depressive disorder: a nested case–control study
Authors: Li Dian-Jeng , Tsai Shih-Jen , Chen Tzeng-Ji , Liang Chih-Sung , Chen Mu-Hong 
Published: March 2024

AbstractBreast cancer is one of the most prevalent and serious types of cancer globally. Previous literature has shown that women with mental illness may have an increased risk of breast cancer, however whether this risk is associated with the use of psychotropic drugs has yet to be elucidated. This study aimed to assess such risk among women with major depressive disorder (MDD) and bipolar disorder (BD). A nested case–control study design was used with data obtained from the Taiwan National Health Insurance Research Database. Logistic regression analysis with adjustments for demographic characteristics, medical and mental comorbidities, and all-cause clinical visits was performed to estimate the risk of breast cancer according to the cumulative defined daily dose (cDDD) of psychotropic drugs. The study included 1564 women with MDD or BD who had breast cancer, and 15,540 women with MDD or BD who did not have breast cancer. After adjusting for important confounders, the long-term use of valproic acid (odds ratio, 95% confidence interval: 0.58, 0.39–0.56, cDDD ≥ 365), citalopram (0.58, 0.37–0.91, cDDD 180–365), and sertraline (0.77, 0.61–0.91, cDDD ≥ 365) was associated with a lower risk of breast cancer compared to a cDDD < 30. The short-term use of fluvoxamine (0.82, 0.69–0.96, cDDD 30–180), olanzapine (0.54, 0.33–0.89, cDDD 30–179), risperidone (0.7, 0.51–0.98, cDDD 30–179), and chlorpromazine (0.48, 0.25–0.90, cDDD 30–179) was associated with a lower risk of breast cancer. We found no evidence of an increased risk of breast cancer in patients with MDD or BD receiving psychotropic drugs.
Factors associated with success of conservative therapy in chronic subdural hematoma: a single-center retrospective analysis
Authors: Foppen Merijn , Lodewijkx Roger , Bandral Harssh Verdan , Yah Kevin , Slot K. Mariam , Vandertop William , Verbaan Dagmar 
Published: March 2024

Abstract
Introduction
Conservative therapy is a viable option for patients with chronic subdural hematoma (cSDH) who express no, or only mild symptoms. It is not clear which factors are associated with success of conservative therapy. This study aims to determine conservative therapy's success rate and to identify features possibly associated with success.

Methods
A monocenter retrospective cohort study, including cSDH patients treated conservatively (wait-and-watch) from 2012 to 2022, was performed. The primary outcome was success of conservative therapy, defined as ‘no crossover to surgery’ during the follow-up period. Secondary outcomes were (1) factors associated with success, analyzed with univariate and multivariable logistic regression analyses, (2) 30-day mortality (3) time to crossover and (4) reasons for crossover.

Results
We included 159 patients. Conservative therapy was successful in 96 (60%) patients. Hematoma volume (OR 0.79, 95% CI 0.69–0.92) and hypodense hematoma type (OR 3.57, 95% 1.38–9.23) were associated with success. Thirty-day mortality rate was 5% and the median duration between diagnosis and surgery was 19 days (IQR 8–39). Clinical deterioration was the most frequent reason for crossover (in 61/63 patients, 97%) and was accompanied by radiological hematoma progression in 42 patients (67%).

Conclusion
In this selected group of patients, conservative therapy was successful in 60%. Smaller hematoma volume and hypodense hematoma type were associated with success. As time until crossover was approximately three weeks, deploying conservative therapy as primary treatment seems safe and could be rewarding as surgical complications can be avoided. Improvement in patient selection in future cohorts remains warranted.
Management and outcomes of bronchiolitis in Italy and Latin America: a multi-center, prospective, observational study
Authors: Camporesi Anna , Yock-Corrales Adriana , Gomez-Vargas Jessica , Roland Damian , Gonzalez Magali , Barreiro Sandra , Morello Rosa , Brizuela Martin , Buonsenso Danilo 
Published: March 2024

AbstractWe aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons. This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form. Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy.
Conclusions: We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world.

What is Known:• Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world.

What is New:• There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations.• Understanding these differences should be a priority to optime and standardize bronchiolitis care globally.
The intransitive dice kernel: $$\frac{\mathbbm {1}_{x\ge y}-\mathbbm {1}_{x\le y}}{4} - \frac{3(x-y)(1+xy)}{8}$$
Authors: Sah Ashwin , Sawhney Mehtaab 
Published: March 2024

AbstractAnswering a pair of questions of Conrey, Gabbard, Grant, Liu, and Morrison, we prove that a triplet of dice drawn from the multiset model are intransitive with probability $$1/4+o(1)$$

1
/
4
+
o
(
1
)

and the probability a random pair of dice tie tends toward $$\alpha n^{-1}$$

α

n

-
1

for an explicitly defined constant $$\alpha $$
α
. This extends and sharpens the recent results of Polymath regarding the balanced sequence model. We further show the distribution of larger tournaments converges to a universal tournamenton in both models. This limit naturally arises from the discrete spectrum of a certain skew-symmetric operator (given by the kernel in the title acting on $$L^2([-1,1])$$

L
2

(

[
-
1
,
1
]

)

). The limit exhibits a degree of symmetry and can be used to prove that, for instance, the limiting probability that $$A_i$$

A
i

beats $$A_{i+1}$$

A

i
+
1

for $$1\le i\le 4$$

1
≤
i
≤
4

and that $$A_5$$

A
5

beats $$A_1$$

A
1

is $$1/32+o(1)$$

1
/
32
+
o
(
1
)

. Furthermore, the limiting tournamenton has range contained in the discrete set $$\{0,1\}$$

{
0
,
1
}

. This proves that the associated tournamenton is non-quasirandom in a dramatic fashion, vastly extending work of Cornacchia and Hązła regarding the continuous analogue of the balanced sequence model. The proof is based on a reduction to conditional central limit theorems (related to work of Polymath), the use of a “Poissonization” style method to reduce to computations with independent random variables, and the systematic use of switching-based arguments to extract cancellations in Fourier estimates when establishing local limit-type estimates.