bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast Fourier transforms and fast Wigner and Weyl functions in large quantum systems
Authors: Lei C. , Vourdas A. 
Published: May 2024

AbstractTwo methods for fast Fourier transforms are used in a quantum context. The first method is for systems with dimension of the Hilbert space $$D=d^n$$

D
=

d
n

with d an odd integer, and is inspired by the Cooley-Tukey formalism. The ‘large Fourier transform’ is expressed as a sequence of n ‘small Fourier transforms’ (together with some other transforms) in quantum systems with d-dimensional Hilbert space. Limitations of the method are discussed. In some special cases, the n Fourier transforms can be performed in parallel. The second method is for systems with dimension of the Hilbert space $$D=d_0...d_{n-1}$$

D
=

d
0

.
.
.

d

n
-
1

with $$d_0,...,d_{n-1}$$

d
0

,
.
.
.
,

d

n
-
1

odd integers coprime to each other. It is inspired by the Good formalism, which in turn is based on the Chinese reminder theorem. In this case also the ‘large Fourier transform’ is expressed as a sequence of n ‘small Fourier transforms’ (that involve some constants related to the number theory that describes the formalism). The ‘small Fourier transforms’ can be performed in a classical computer or in a quantum computer (in which case we have the additional well known advantages of quantum Fourier transform circuits). In the case that the small Fourier transforms are performed with a classical computer, complexity arguments for both methods show the reduction in computational time from $$\mathcal{O}(D^2)$$

O
(

D
2

)

to $$\mathcal{O}(D\log D)$$

O
(
D
log
D
)

. The second method is also used for the fast calculation of Wigner and Weyl functions, in quantum systems with large finite dimension of the Hilbert space.
A Causal Relationship Between Type 1 Diabetes and Risk of Osteoporosis: A Univariable and Multivariable Mendelian Randomization Study
Authors: Qin Hailin , Yang Kui , Wang Hufei , Jiao Wenyong 
Published: May 2024

Objective: This Mendelian randomization (MR) analysis aims to investigate the causal relationship between type 1 diabetes (T1D) and osteoporosis (OP).Methods: Single nucleotide polymorphisms (SNPs) associated with T1D were selected from the summary statistics of the genome‐wide association study (GWAS) in European ancestry as instrumental variables (IVs) for univariable MR (UVMR) to explore the causal relationship between T1D and OP. Inverse variance weighting (IVW) was the primary method used to assess possible causality between T1D and OP. MR‐PRESSO and MR‐Egger intercepts were used to assess the horizontal pleiotropy of the IVs, and Q tests and the “leave‐one‐out” method were used to test for heterogeneity of MR results. Multivariable MR (MVMR) analysis was used to account for potential confounders such as smoking, obesity, drinking, and serum 25‐hydroxyvitamin D (25OHD) concentrations.Result: Inverse variance weighted estimates suggest T1D may increase risk of OP (UVMR: OR = 1.06, 95% CI: 1.02–1.10, p = 0.002) (MVMR: OR = 1.50, 95% CI: 1.07–1.90, p < 0.001).Conclusion: Our findings suggest that T1D can increase the risk of OP.
HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T-cell Lymphoma
Authors: Zhu Jiayan , Wang Feng , Wang Lining , Dai Bo , Xu Guilin , Zhao Luyao , Jiang Huimin , Gao Wenhui , Zhang Tingting , Zhao Chenxi , Li Yun-Xuan , Hu Jiong , Li Ke 
Published: May 2024

Abstract
Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Herein, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3 inhibition suppressed lymphoma growth in immunocompetent mice but not in immunodeficient mice. HDAC3 deletion delayed the progression of lymphoma, reduced the lymphoma burden in the thymus, spleen, and lymph nodes, and prolonged the survival of mice bearing N-methyl-N-nitrosourea–induced lymphoma. Furthermore, inhibiting HDAC3 promoted the infiltration and enhanced the function of natural killer (NK) cells. Mechanistically, HDAC3 mediated ATF3 deacetylation, enhancing its transcriptional inhibitory activity. Targeting HDAC3 enhanced CXCL12 secretion through an ATF3-dependent pathway to stimulate NK-cell recruitment and activation. Finally, HDAC3 suppression improved the response of PTCL to conventional chemotherapy. Collectively, this study provides insights into the mechanism by which HDAC3 regulates ATF3 activity and CXCL12 secretion, leading to immune infiltration and lymphoma suppression. Combining HDAC3 inhibitors with chemotherapy may be a promising strategy for treating PTCL.
Significance: Targeting HDAC3 suppresses progression of T-cell lymphoma by activating ATF3 to induce secretion of CXCL12 and promote infiltration of NK cells, providing an immunostimulatory approach for treating T-cell lymphoma patients.
The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention
Authors: Albini Adriana , Noonan Douglas M. , Corradino Paola , Magnoni Francesca , Corso Giovanni 
Published: May 2024

AbstractCancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. After this concept was established in the 1970s, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy, prevention, and interception and recently investigated substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, β blockers, renin–angiotensin–aldosterone inhibitors, carnitines, and biguanides, are reviewed.
D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities
Authors: Zhang Jing , Lim Sun Min , Yu Mi Ra , Chen Cheng , Wang Jia , Wang Wenqian , Rui Haopeng , Lu Jingtao , Lu Shun , Mok Tony , Chen Zhi Jian , Cho Byoung Chul 
Published: May 2024

Abstract
First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic “cycling” of KRAS between its guanosine diphosphate (GDP)– and guanosine triphosphate (GTP)–bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report that D3S-001, a next-generation GDP-bound G12C inhibitor with faster target engagement (TE) kinetics, depletes cellular active KRAS G12C at nanomolar concentrations. In the presence of growth factors, such as epithelial growth factor and hepatocyte growth factor, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust antitumor activity preclinically and translated into promising clinical efficacy in an ongoing phase 1 trial (NCT05410145).
Significance: The kinetic study presented in this work unveils, for the first time, that a GDP-bound conformation-selective KRAS G12C inhibitor can potentially deplete cellular active KRAS in the presence of growth factors and offers new insights into the critical features that drive preclinical and clinical efficacy for this class of drugs.
Molecular Landscape and Clinical Implication of CCNE1-amplified Esophagogastric Cancer
Authors: Rustgi Naryan , Wu Sharon , Samec Timothy , Walker Phillip , Xiu Joanne , Lou Emil , Goel Sanjay , Saeed Anwaar , Moy Ryan H. 
Published: May 2024

Abstract

Cyclin E overexpression as a result of CCNE1 amplification is a critical driver of genomic instability in gastric cancer, but its clinical implication is largely unknown. Thus, we integrated genomic, transcriptomic, and immune profiling analysis of 7,083 esophagogastric tumors and investigated the impact of CCNE1 amplification on molecular features and treatment outcomes. We identified CCNE1 amplification in 6.2% of esophageal adenocarcinoma samples, 7.0% of esophagogastric junction carcinoma, 4.2% of gastric adenocarcinoma samples, and 0.8% of esophageal squamous cell carcinoma. Metastatic sites such as lymph node and liver showed an increased frequency of CCNE1 amplification relative to primary tumors. Consistent with a chromosomal instability phenotype, CCNE1 amplification was associated with decreased CDH1 mutation and increased TP53 mutation and ERBB2 amplification. We observed no differences in immune biomarkers such as PD-L1 expression and tumor mutational burden comparing CCNE1-amplified and nonamplified tumors, although CCNE1 amplification was associated with changes in immune populations such as decreased B cells and increased M1 macrophages from transcriptional analysis. Real-world survival analysis demonstrated that patients with CCNE1-amplified gastric cancer had worse survival after trastuzumab for HER2-positive tumors, but better survival after immunotherapy. These data suggest that CCNE1-amplified gastric cancer has a distinct molecular and immune profile with important therapeutic implications, and therefore further investigation of CCNE1 amplification as a predictive biomarker is warranted.

Significance:
Advanced gastric cancer has a relatively dismal outcome with a 5-year overall survival of less than 10%. Furthermore, while comprehensive molecular analyses have established molecular subtypes within gastric cancers, biomarkers of clinical relevance in this cancer type are lacking. Overall, this study demonstrates that CCNE1 amplification is associated with a distinct molecular profile in gastric cancer and may impact response to therapy, including targeted therapy and/or immunotherapy.
B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai 
Published: May 2024

Abstract

Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3–targeting domain in our CAR construct to circumvent the stability issues associated with single-chain variable fragment–based domains. In efforts to expand patient access to CAR T-cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr virus–specific T cells (EBVST), offering a readily available off-the-shelf treatment. B7H3.CAR-armored EBVSTs demonstrated potent in vitro and in vivo activities against multiple B7-H3–positive human tumor cell lines and patient-derived xenograft models. Murine T cells expressing a murine equivalent of our B7H3.CAR exhibited no life-threatening toxicities in immunocompetent mice bearing syngeneic tumors. Further in vitro evaluation revealed that while human T, B, and natural killer cells were unaffected by B7H3.CAR EBVSTs, monocytes were targeted because of upregulation of B7-H3. Such targeting of myeloid cells, which are key mediators of cytokine release syndrome (CRS), contributed to a low incidence of CRS in humanized mice after B7H3.CAR EBVST treatment. Notably, we showed that B7H3.CAR EBVSTs can target B7-H3–expressing myeloid-derived suppressor cells (MDSC), thereby mitigating MDSC-driven immune suppression. In summary, our data demonstrate that our nanobody-based B7H3.CAR EBVSTs are effective as an off-the-shelf therapy for B7-H3–positive solid tumors. These cells also offer an avenue to modulate the immunosuppressive tumor microenvironment, highlighting their promising clinical potential in targeting solid tumors.

Significance:
Clinical application of EBVSTs armored with B7-H3–targeting CARs offer an attractive solution to translate off-the-shelf CAR T cells as therapy for solid tumors.
LYVE-1–expressing Macrophages Modulate the Hyaluronan-containing Extracellular Matrix in the Mammary Stroma and Contribute to Mammary Tumor Growth
Authors: Elfstrum Alexis K. , Rumahorbo Annisa H. , Reese Lyndsay E. , Nelson Emma V. , McCluskey Braedan M. , Schwertfeger Kathryn L. 
Published: May 2024

Abstract

Macrophages represent a heterogeneous myeloid population with diverse functions in normal tissues and tumors. While macrophages expressing the cell surface marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) have been identified in stromal regions of the normal mammary gland and in the peritumoral stroma, their functions within these regions are not well understood. Using a genetic mouse model of LYVE-1+ macrophage depletion, we demonstrate that loss of LYVE-1+ macrophages is associated with altered extracellular matrix remodeling in the normal mammary gland and reduced mammary tumor growth in vivo. In further studies focused on investigating the functions of LYVE-1+ macrophages in the tumor microenvironment, we demonstrate that LYVE-1 expression correlates with an increased ability of macrophages to bind, internalize, and degrade hyaluronan. Consistent with this, we show that depletion of LYVE-1+ macrophages correlates with increased hyaluronan accumulation in both the normal mammary gland and in mammary tumors. Analysis of single-cell RNA sequencing of macrophages isolated from these tumors reveals that depletion of LYVE-1+ macrophages in tumors drives a shift in the majority of the remaining macrophages toward a proinflammatory phenotype, as well as an increase in CD8+ T-cell infiltration. Together, these findings indicate that LYVE-1+ macrophages represent a tumor-promoting anti-inflammatory subset of macrophages that contributes to hyaluronan remodeling in the tumor microenvironment.

Significance:
We have identified a macrophage subset in mouse mammary tumors associated with tumor structural components. When this macrophage subset is absent in tumors, we report a delay in tumor growth and an increase in antitumor immune cells. Understanding the functions of distinct macrophage subsets may allow for improved therapeutic strategies for patients with breast cancer.
Head Injury and Risk of Incident Ischemic Stroke in Community-Dwelling Adults
Authors: Elser Holly , Pappalardo Laura W. , Gottesman Rebecca F. , Coresh Josef , Diaz-Arrastia Ramon , Mosley Thomas H. , Kasner Scott E. , Koton Silvia , Schneider Andrea L.C. 
Published: May 2024

BACKGROUND:
While stroke is a recognized short-term sequela of traumatic brain injury, evidence about long-term ischemic stroke risk after traumatic brain injury remains limited.

METHODS:
The Atherosclerosis Risk in Communities Study is an ongoing prospective cohort comprised of US community-dwelling adults enrolled in 1987 to 1989 followed through 2019. Head injury was defined using self-report and hospital-based diagnostic codes and was analyzed as a time-varying exposure. Incident ischemic stroke events were physician-adjudicated. We used Cox regression adjusted for sociodemographic and cardiovascular risk factors to estimate the hazard of ischemic stroke as a function of head injury. Secondary analyses explored the number and severity of head injuries; the mechanism and severity of incident ischemic stroke; and heterogeneity within subgroups defined by race, sex, and age.

RESULTS:
Our analysis included 12 813 participants with no prior head injury or stroke. The median follow-up time was 27.1 years (25th–75th percentile=21.1–30.5). Participants were of median age 54 years (25th–75th percentile=49–59) at baseline; 57.7% were female and 27.8% were Black. There were 2158 (16.8%) participants with at least 1 head injury and 1141 (8.9%) participants with an incident ischemic stroke during follow-up. For those with head injuries, the median time to ischemic stroke was 7.5 years (25th–75th percentile=2.2–14.0). In adjusted models, head injury was associated with an increased hazard of incident ischemic stroke (hazard ratio [HR], 1.34 [95% CI, 1.12–1.60]). We observed evidence of dose-response for the number of head injuries (1: HR, 1.16 [95% CI, 0.97–1.40]; ≥2: HR, 1.94 [95% CI, 1.39–2.71]) but not for injury severity. We observed evidence of stronger associations between head injury and more severe stroke (National Institutes of Health Stroke Scale score ≤5: HR, 1.31 [95% CI, 1.04–1.64]; National Institutes of Health Stroke Scale score 6–10: HR, 1.64 [95% CI, 1.06–2.52]; National Institutes of Health Stroke Scale score ≥11: HR, 1.80 [95% CI, 1.18–2.76]). Results were similar across stroke mechanism and within strata of race, sex, and age.

CONCLUSIONS:
In this community-based cohort, head injury was associated with subsequent ischemic stroke. These results suggest the importance of public health interventions aimed at preventing head injuries and primary stroke prevention among individuals with prior traumatic brain injuries.
Tracheostomy in Patients with Acute Myocardial Infarction and Respiratory Failure
Authors: Grammatico Megan , Banna Soumya , Shahu Andi , Gastanadui Maria Gabriela , Jimenez Jose Victor , Heck Cory , Arias-Olson Abner , Thomas Alexander , Ali Tariq , Miller P. Elliott 
Published: May 2024

Objective Patients with acute myocardial infarction (AMI) complicated by respiratory failure require antiplatelet regimens which often cannot be stopped and may increase bleeding from tracheostomy. However, there is limited available data on both the proportion of patients undergoing tracheostomy and the impact on antiplatelet regimens on outcomes. Methods Utilizing the Vizient® Clinical Data Base, we identified patients ≥18 years admitted from 2015 to 2019 with a primary diagnosis of AMI and requiring invasive mechanical ventilation (IMV). We assessed for the incidence of patients undergoing tracheostomy, outcomes stratified by the timing of tracheostomy (≤10 vs >10 days), and the association between dual antiplatelet therapy (DAPT) use and in-hospital mortality. Results We identified 26 435 patients presenting with AMI requiring IMV. The mean (SD) age was 66.8 (12.3) years and 33.4% were women. The incidence of tracheostomy was 6.0% (n = 1573), and the median IMV time to tracheostomy was 12 days, 55.6% of which underwent percutaneous and 44.4% underwent open tracheostomy. Over 90% (n = 1424) underwent tracheostomy (>10 days) and had a similar mortality when compared to early (≤10 days) tracheostomy (22.5% vs 22.8%, P = 0.94). On the day of tracheostomy, only 24.7% were given DAPT, which was associated with a lower mortality than those not on DAPT (17.4% vs 23.7%, P = 0.01). After multivariable adjustment, DAPT use on the day of tracheostomy remained associated with lower in-hospital mortality (odds ratio 0.68; 95% confidence interval: 0.49-0.94, P = 0.02). Tracheostomy complications were not different between groups ( P > 0.05), but more patients in the DAPT group required post-tracheostomy blood transfusions (5.6% vs 2.7%, P = 0.01). Conclusion Approximately 1 in 20 intubated AMI patients requires tracheostomy. The lack of DAPT interruption on the day of tracheostomy but not the timing of tracheostomy was associated with a lower in-hospital mortality. Our results suggest that DAPT should not be a barrier to tracheostomy for patients with AMI.
Clinical empathy in a medium and high-risk Brazilian unit
Authors: Sobrinho Valete Cristina Ortiz , Albuquerque Aline , Ferreira Esther Angelica Luiz 
Published: May 2024

Background Clinical empathy is an essential part of healthcare, and patient-centered care models require clinical empathy to be established. Despite this, little is known about its measurement in the neonatal scenario. Research Aim To measure clinical empathy in health professionals who work with medium and high-risk neonates and build a construct of this empathy. Research Design Single-center survey study. Participants and Research Context The Jefferson Scale of Empathy for Health Professionals questionnaire was applied to health professionals who work in an intensive care unit and a medium-risk unit, in Brazil. Analysis was done using descriptive statistics and a factor analysis model, to build the construct of empathy. Overall empathy was calculated, and the domains’ punctuations were analyzed and compared to the maximum punctuation possible. The study followed the STROBE checklist. Ethical Considerations This study was approved by the Research Ethics Committee of the institution. All participants signed the informed consent form. Participants’ confidentiality and anonymity were protected. Findings Median empathy was 117 (IQR 113–124). The domain of Walking in the Patient’s Shoes had lower scores and represented 77.6% of the maximum punctuation possible. The factor analysis included three factors named Understanding, Experiences, and Treatment, and Emotional Relationships, explaining 64.3% of the overall variance. The domain Walking in the Patient’s Shoes was not included in the model. Conclusions In this scenario, clinical empathy should improve. There is a need to improve the domain of Walking in the Patient’s Shoes, in this case, the neonate, and provide more empathic care to them.
Ustekinumab: In Psoriasis and Beyond —A Derm atological Perspective
Authors: Bubna Aditya Kumar , Viplav Vinayak 
Published: May 2024

Background Ustekinumab is an interleukin 12/23 inhibitor, approved by the US-FDA for the management of moderate-to-severe plaque psoriasis and psoriatic arthropathy. Purpose This review aims to describe the dermatological implications and applications of ustekinumab. Methodology PubMed and Google Scholar were searched for scholarly articles related to ustekinumab and its utility in dermatology using the search terms “Ustekinumab” AND “Psoriasis” AND “dermatological diseases”. Studies utilising Ustekinumab in psoriasis and other dermatological indications were analysed and formulated into a systematic review discussing the utility of the drug in psoriasis, as well as other dermatological conditions. Results Ustekinumab is a valuable biologic agent for the management of psoriasis and psoriatic arthropathy, as well as other dermatological disorders like hidradenitis suppurativa, lichen planus, pityriasis rubra pilaris, Behcet’s disease, lupus erythematosus, alopecia areata and pyoderma gangrenosum. Conclusion Ustekinumab’s usage is not limited to psoriasis. Its benefit extends to many more dermatological conditions. It is considered to be the biologic of choice in childhood psoriasis and adult psoriatic patients with concurrent Crohn’s disease. Besides, it has an acceptable safety profile.