bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomechanical comparison of compact versus standard flute drill bits, and interlocking versus buttress threadself‐tappingcortical bone screws in cadaveric equine third metacarpal condyle
Authors: Pye Jannah L. , Garcia Tanya C. , Kapatkin Amy S. , Samol Monika A. , Stover Susan 
Published: June 2023

AbstractObjectivesTo compare (1) performance of compact versus standard flute drill bits, (2) screw insertion properties and (3) pullout variables between interlocking thread (ITS) and buttress thread (BTS) self‐tapping screws in third metacarpi.Study designIn vitro experimental study.Sample populationPaired third metacarpi from 11 Thoroughbreds aged 2–4 years.MethodsScrews were inserted into the lateral condylar fossae following bone preparation using the respective drill bit for each screw type. Screw pullout was achieved using a mechanical testing system. Density and porosity of bone surrounding screw holes was measured with microcomputed tomography following each pullout test. Drilling, screw insertion and pullout variables were compared between drill bit and screw types using repeated measures ANOVA. Linear regression analyses were used to characterize relationships between bone tissue properties and drill bit and screw outcomes.ResultsMaximum torque power spectral density (PSD) was lower for compact flute drill bits. Insertion torque was 50% higher for ITS. BTS had 33% greater preyield stiffness and 7% greater mean yield force. Bone tissue properties affected measured variables similarly for both screw and drill bit types.ConclusionsLower torque PSD may increase durability of the compact flute drill bit. ITS had greater insertional torque, which may reflect greater bone engagement. BTS had greater resistance to axial pullout forces.Clinical significanceMetacarpal bone provides a simple model for comparison of drill bit and screw designs. Use of ITS to repair equine fractures subject to predominantly tensile forces is not justified based on the results of this study.
Low-redshift estimates of the absolute scale of baryon acoustic oscillations
Authors: Lemos Thais , Ruchika  , Carvalho Joel C. , Alcaniz Jailson 
Published: June 2023

AbstractMeasurements of the characteristic length scale $$r_s$$

r
s

of the baryon acoustic oscillations (BAO) provide a robust determination of the distance-redshift relation. Currently, the best (sub-per cent) estimate of $$r_s$$

r
s

at the drag epoch is provided by Cosmic Microwave Background (CMB) observations assuming the validity of the standard $$\Lambda $$
Λ
CDM model at $$z \sim 1000$$

z
∼
1000

. Therefore, inferring $$r_s$$

r
s

from low-z observations in a model-independent way and comparing its value with CMB estimates provides a consistency test of the standard cosmology and its assumptions at high-z. In this paper, we address this question and estimate the absolute BAO scale combining angular BAO measurements and type Ia Supernovae data. Our analysis uses two different methods to connect these data sets and finds a good agreement between the low-z estimates of $$r_{s}$$

r
s

with the CMB sound horizon at drag epoch, regardless of the value of the Hubble constant $$H_0$$

H
0

considered. These results highlight the robustness of the standard cosmology at the same time that they also reinforce the need for more precise cosmological observations at low-z.
AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun 
Published: June 2023

Abstract
HER3 is a unique member of the EGFR family of tyrosine kinases, which is broadly expressed in several cancers, including breast, lung, pancreatic, colorectal, gastric, prostate, and bladder cancers and is often associated with poor patient outcomes and therapeutic resistance. U3-1402/Patritumab-GGFG-DXd is the first successful HER3-targeting antibody–drug conjugate (ADC) with clinical efficacy in non–small cell lung cancer. However, over 60% of patients are nonresponsive to U3-1402 due to low target expression levels and responses tend to be in patients with higher target expression levels. U3-1402 is also ineffective in more challenging tumor types such as colorectal cancer. AMT-562 was generated by a novel anti-HER3 antibody Ab562 and a modified self-immolative PABC spacer (T800) to conjugate exatecan. Exatecan showed higher cytotoxic potency than its derivative DXd. Ab562 was selected because of its moderate affinity for minimizing potential toxicity and improving tumor penetration purposes. Both alone or in combination therapies, AMT-562 showed potent and durable antitumor response in low HER3 expression xenograft and heterogeneous patient-derived xenograft/organoid models, including digestive system and lung tumors representing of unmet needs. Combination therapies pairing AMT-562 with therapeutic antibodies, inhibitors of CHEK1, KRAS, and tyrosine kinase inhibitor showed higher synergistic efficacy than Patritumab-GGFG-DXd. Pharmacokinetic and safety profiles of AMT-562 were favorable and the highest dose lacking severe toxicity was 30 mg/kg in cynomolgus monkeys. AMT-562 has potential to be a superior HER3-targeting ADC with a higher therapeutic window that can overcome resistance to generate higher percentage and more durable responses in U3-1402–insensitive tumors.
Physical Frailty and Use of Guideline‐Recommended Drugs in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Kondo Toru , Adachi Takuji , Kobayashi Kiyonori , Okumura Takahiro , Izawa Hideo , Murohara Toyoaki , McMurray John J. V. , Yamada Sumio 
Published: June 2023

BACKGROUND
Guideline‐recommended therapies that improve prognosis remain underused in clinical practice. Physical frailty may lead to underprescription of life‐saving therapy. We aimed to investigate the association between physical frailty and the use of evidence‐based pharmacological therapy for heart failure with reduced ejection fraction and the impact of this on prognosis.

METHODS AND RESULTS

The FLAGSHIP (Multicentre Prospective Cohort Study to Develop Frailty‐Based Prognostic Criteria for Heart Failure Patients) included patients hospitalized for acute heart failure, and data on physical frailty were collected prospectively. We analyzed 1041 patients with heart failure with reduced ejection fraction (aged 70 years; 73% male) and divided them by physical frailty categories using grip strength, walking speed, Self‐Efficacy for Walking–7 score, and Performance Measures for Activities of Daily Living–8 score: categories I (n=371; least frail), II (n=275), III (n=224), and IV (n=171). Overall prescription rates of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, β‐blockers, and mineralocorticoid receptor antagonists were 69.7%, 87.8%, and 51.9%, respectively. The proportion of patients receiving all 3 drugs decreased as physical frailty increased (in category I patients, 40.2%; IV patients, 23.4%;
P
for trend<0.001). In adjusted analyses, the severity of physical frailty was an independent predictor for nonuse of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (odds ratio [OR], 1.23 [95% CI, 1.05–1.43] per 1 category increase) and β‐blockers (OR, 1.32 [95% CI, 1.06–1.64]), but not mineralocorticoid receptor antagonists (OR, 0.97 [95% CI, 0.84–1.12]). Patients receiving 0 to 1 drug had a higher risk of the composite outcome of all‐cause death or heart failure rehospitalization than those treated with 3 drugs in physical frailty categories I and II (hazard ratio [HR], 1.80 [95% CI, 1.08–2.98]) and III and IV (HR, 1.53 [95% CI, 1.01–2.32]) in the multivariate Cox proportional hazard model.

CONCLUSIONS
Prescription of guideline‐recommended therapy decreased as severity of physical frailty increased in heart failure with reduced ejection fraction. Underprescription of guideline‐recommended therapy may contribute to the poor prognosis associated with physical frailty.
Effect of Cilostazol on Patients With Diabetes Who Underwent Endovascular Treatment for Peripheral Artery Disease
Authors: Cha Jung‐Joon , Cho Jae Young , Lim Subin , Kim Ju Hyeon , Joo Hyung Joon , Park Jae Hyoung , Hong Soon Jun , Lim Do‐Sun , Kook Hyungdon , Lee Seung Hun , Ko Young‐Guk , Min Pil‐Ki , Lee Jae‐Hwan , Yoon Chang‐Hwan , Chae In‐Ho , Lee Seung Whan , Lee Sang‐Rok , Choi Seung Hyuk , Koh Yoon Seok , Yu Cheol Woong 
Published: June 2023

Background
No large‐scale study has compared the clinical impact of triple antiplatelet therapy (TAPT: aspirin, clopidogrel, and cilostazol) and dual antiplatelet therapy (DAPT) on adverse limb events in patients with diabetes after endovascular therapy (EVT) for peripheral artery disease. Thus, we investigate the effect of cilostazol added to a DAPT on the clinical outcomes after EVT in patients with diabetes using a nationwide, multicenter, real‐world registry.

Methods and Results

A total of 990 patients with diabetes who underwent EVT were enrolled from the retrospective cohorts of a Korean multicenter EVT registry and were divided according to the antiplatelet regimen (TAPT [n=350; 35.4%] versus DAPT [n=640; 64.6%]). After propensity score matching based on clinical characteristics, a total of 350 pairs were compared for clinical outcomes. The primary end points were major adverse limb events, a composite of major amputation, minor amputation, and reintervention. For the matched study groups, the lesion length was 125.4±102.0 mm, and severe calcification was observed in 47.4%. The technical success rate (96.9% versus 94.0%;
P
=0.102) and the complication rate (6.9% versus 6.6%;
P
>0.999) were similar between the TAPT and DAPT groups. At 2‐year follow‐up, the incidence of major adverse limb events (16.6% versus 19.4%;
P
=0.260) did not differ between the 2 groups. However, the TAPT group showed less minor amputation than the DAPT group (2.0% versus 6.3%;
P
=0.004). In multivariate analysis, TAPT was an independent predictor of minor amputation (adjusted hazard ratio, 0.354 [95% CI, 0.158–0.794];
P
=0.012).

Conclusions
In patients with diabetes undergoing EVT for peripheral artery disease, TAPT did not decrease the incidence of major adverse limb events but may be associated with a decreased risk of minor amputation.
Silencing of
PKG1
Gene Mimics Effect of Aging and Sensitizes Rat Vascular Smooth Muscle Cells to Cardiotonic Steroids: Impact on Fibrosis and Salt Sensitivity
Authors: Fedorova Olga V. , Shilova Victoria Y. , Zernetkina Valentina , Juhasz Ondrej , Wei Wen , Lakatta Edward G. , Bagrov Alexei Y. 
Published: June 2023

Background
Marinobufagenin, NKA (Na/K‐ATPase) inhibitor, causes vasoconstriction and induces fibrosis via inhibition of Fli1 (Friend leukemia integration‐1), a negative regulator of collagen synthesis. In vascular smooth muscle cells (VSMC), ANP (atrial natriuretic peptide), via a cGMP/PKG1 (protein kinase G1)‐dependent mechanism, reduces NKA sensitivity to marinobufagenin. We hypothesized that VSMC from old rats, due to downregulation of ANP/cGMP/PKG‐dependent signaling, would exhibit heightened sensitivity to the profibrotic effect of marinobufagenin.

Methods and Results

Cultured VSMC from the young (3‐month‐old) and old (24‐month‐old) male Sprague–Dawley rats and young VSMC with silenced
PKG1
gene were treated with 1 nmol/L ANP, or with 1 nmol/L marinobufagenin, or with a combination of ANP and marinobufagenin. Collagen‐1, Fli1, and PKG1 levels were assessed by Western blotting analyses. Vascular PKG1 and Fli1 levels in the old rats were reduced compared with their young counterparts. ANP prevented inhibition of vascular NKA by marinobufagenin in young VSMC but not in old VSMC. In VSMC from the young rats, marinobufagenin induced downregulation of Fli1 and an increase in collagen‐1 level, whereas ANP blocked this effect. Silencing of the
PKG1
gene in young VSMC resulted in a reduction in levels of PKG1 and Fli1; marinobufagenin additionally reduced Fli1 and increased collagen‐1 level, and ANP failed to oppose these marinobufagenin effects, similar to VSMC from the old rats with the age‐associated reduction in PKG1.

Conclusions

Age‐associated reduction in vascular PKG1 and the resultant decline in cGMP signaling lead to the loss of the ability of ANP to oppose marinobufagenin‐induced inhibition of NKA and fibrosis development. Silencing of the
PKG1
gene mimicked these effects of aging.
Comparison of Outcomes Following Transcatheter Aortic Valve Replacement Requiring Peripheral Vascular Intervention or Alternative Access
Authors: Isogai Toshiaki , Agrawal Ankit , Shekhar Shashank , Spilias Nikolaos , Puri Rishi , Krishnaswamy Amar , Unai Shinya , Yun James J. , Kapadia Samir R. , Reed Grant W. 
Published: June 2023

Background
Peripheral vascular intervention (PVI) is occasionally required to facilitate delivery system insertion or to treat vascular complications during transfemoral transcatheter aortic valve replacement (TF‐TAVR). However, the impact of PVI on outcomes is not well understood. Therefore, we aimed to compare outcomes between TF‐TAVR with versus without PVI and between TF‐TAVR with PVI versus non‐TF‐TAVR.

Methods and Results

We retrospectively reviewed 2386 patients who underwent TAVR with a balloon‐expandable valve at a single institution from 2016 to 2020. The primary outcomes were death and major adverse cardiac/cerebrovascular event (MACCE), defined as death, myocardial infarction, or stroke. Of 2246 TF‐TAVR recipients, 136 (6.1%) required PVI (89% bailout treatment). During follow‐up (median 23.0 months), there were no significant differences between TF‐TAVR with and without PVI in death (15.4% versus 20.7%; adjusted HR [aHR], 0.96 [95% CI, 0.58–1.58]) or MACCE (16.9% versus 23.0%; aHR, 0.84 [95% CI, 0.52–1.36]). However, compared with non‐TF‐TAVR (n=140), TF‐TAVR with PVI carried significantly lower rates of death (15.4% versus 40.7%; aHR, 0.42 [95% CI, 0.24–0.75]) and MACCE (16.9% versus 45.0%; aHR, 0.40 [95% CI, 0.23–0.68]). Landmark analyses demonstrated lower outcome rates following TF‐TAVR with PVI than non‐TF‐TAVR both within 60 days (death 0.7% versus 5.7%,
P
=0.019; MACCE 0.7% versus 9.3%;
P
=0.001) and thereafter (death 15.0% versus 38.9%,
P
=0.014; MACCE 16.5% versus 41.3%,
P
=0.013).

Conclusions
The need for PVI during TF‐TAVR is not uncommon, mainly due to the bailout treatment for vascular complications. PVI is not associated with worse outcomes in TF‐TAVR recipients. Even when PVI is required, TF‐TAVR is associated with better short‐ and intermediate‐term outcomes than non‐TF‐TAVR.
Outcomes of Cerebral Embolic Protection for Bicuspid Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Replacement
Authors: Zhang Jiajun , Li Xiaoxing , Tian Rui , Zong Mengzhi , Gu Xinghua , Xu Feng , Chen Yuguo , Li Chuanbao 
Published: June 2023

Background
There was limited high‐quality evidence that illuminated the efficiency of cerebral embolic protection (CEP) use during transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve (BAV) stenosis.

Methods and Results

In this retrospective cohort study, patients with BAV stenosis undergoing TAVR with or without CEP were identified by querying the National Inpatient Sample database. The primary end point was any stroke during the hospitalization. The composite safety end point included any in‐hospital death and stroke. We applied propensity score–matched analysis to minimize standardized mean differences of baseline variables and compare in‐hospital outcomes. From July 2017 to December 2020, 4610 weighted hospitalizations with BAV stenosis undergoing TAVR were identified, of which 795 were treated with CEP. There was a significant increase in the CEP use rate for BAV stenosis (
P
‐trend <0.001). A total of 795 discharges with CEP use were propensity score matched to 1590 comparable discharges but without CEP. CEP use was associated with a lower incidence of in‐hospital stroke (1.3% versus 3.8%;
P
<0.001), which in multivariable regression was also independently associated with the primary outcome (adjusted odds ratio=0.38 [95% CI, 0.18–0.71];
P
=0.005) and the safety end point (adjusted odds ratio=0.41 [95% CI, 0.22–0.68]
P
=0.001). Meanwhile, no significant difference was found in the cost of hospitalization ($46 629 versus $45 147;
P
=0.18) or the risk of vascular complications (1.9% versus 2.5%;
P
=0.41).

Conclusions
This observational study supported CEP use for BAV stenosis, which was independently associated with less in‐hospital stroke without burdening the patients with a high hospitalization cost.
Cardiometabolic Risk Factors Associated With Right Ventricular Function and Compensation in Patients Referred for Echocardiography
Authors: Morrison Amanda M. , Huang Shi , Annis Jeffrey S. , Garry Jonah D. , Hemnes Anna R. , Freiberg Matthew S. , Brittain Evan L. 
Published: June 2023

Background
Pulmonary hypertension and right ventricular (RV) dysfunction are drivers of adverse outcomes; however, modifiable risk factors for RV dysfunction are not well described. We investigated the association between clinical markers of metabolic syndrome and echocardiographic RV function in a large referral population.

Methods and Results

Using electronic health record data, we performed a retrospective cohort study of patients aged ≥18 years referred for transthoracic echocardiography between 2010 and 2020 with RV systolic pressure (RVSP) or tricuspid annular plane systolic excursion (TAPSE) values. Pulmonary hypertension was defined by RVSP >33 mm Hg and RV dysfunction by TAPSE ≤1.8 cm. Our sample included 37 203 patients of whom 19 495 (52%) were women, 29 752 (83%) were White, with a median age of 63 years (interquartile range, 51–73). Median (interquartile range) RVSP was 30.0 mm Hg (24.0–38.7), and median TAPSE was 2.1 cm (1.7–2.4). Within our sample, 40% had recorded RVSP >33 mm Hg, and 32% with TAPSE <1.8 cm. Increase in RVSP from normal (<33 mm Hg) to mildly elevated (33–39 mm Hg) or elevated (>39 mm Hg) was associated with lower low‐density lipoprotein and high‐density lipoprotein, and higher hemoglobin A1c and body mass index (
P
<0.001). A decrease in TAPSE between groups of TAPSE >1.8 cm, TAPSE 1.5–1.8 cm, and TAPSE <1.5 cm was associated with increased triglyceride:high‐density lipoprotein ratio and hemoglobin A1c, and decreased body mass index, low‐density lipoprotein, high‐density lipoprotein, and systolic blood pressure (
P
<0.001). Most associations between cardiometabolic predictors and RVSP and TAPSE were nonlinear with clear inflection points associated with higher pulmonary pressure and lower RV function.

Conclusions
Clinical measures of cardiometabolic function were highly associated with echocardiographic measures of right ventricular function and pressure.
Trends in Treatment Patterns and Outcomes of Patients With Pulmonary Embolism in Japan, 2010 to 2020: A Nationwide Inpatient Database Study
Authors: Nishimoto Yuji , Ohbe Hiroyuki , Matsui Hiroki , Nakajima Mikio , Sasabuchi Yusuke , Sato Yukihito , Watanabe Tetsuya , Yamada Takahisa , Fukunami Masatake , Yasunaga Hideo 
Published: June 2023

Background
The impact of major changes in the treatment practice of pulmonary embolism (PE), such as limited indications for systemic thrombolysis and the introduction of direct oral anticoagulants, is not well documented. This study aimed to describe annual trends in the treatment patterns and outcomes in patients with PE.

Methods and Results

Using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021, we identified hospitalized patients with PE. Patients with high‐risk PE were defined as those admitted for out‐of‐hospital cardiac arrest or who received cardiopulmonary resuscitation, extracorporeal membrane oxygenation, vasopressors, or invasive mechanical ventilation on the day of admission. The remaining patients were defined as patients with non–high‐risk PE. The patient characteristics and outcomes were reported with fiscal year trend analyses. Of 88 966 eligible patients, 8116 (9.1%) had high‐risk PE, and the remaining 80 850 (90.9%) had non–high‐risk PE. Between 2010 and 2020, in patients with high‐risk PE, the annual proportion of extracorporeal membrane oxygenation use significantly increased from 11.0% to 21.3%, whereas that of thrombolysis use significantly decreased from 22.5% to 15.5% (
P
for trend <0.001 for both). In‐hospital mortality significantly decreased from 51.0% to 43.7% (
P
for trend=0.04). In patients with non–high‐risk PE, the annual proportion of direct oral anticoagulant use increased from 0.0% to 38.3%, whereas that of thrombolysis use significantly decreased from 13.7% to 3.4% (
P
for trend <0.001 for both). In‐hospital mortality significantly decreased from 7.9% to 5.4% (
P
for trend <0.001).

Conclusions
Substantial changes in the PE practice and outcomes occurred in patients with high‐risk and non–high‐risk PE.
Blood Pressure Variability and Cerebral Perfusion Decline: A Post Hoc Analysis of the SPRINT MIND Trial
Authors: Sible Isabel J. , Nation Daniel A. 
Published: June 2023

Background
Blood pressure variability (BPV) is predictive of cerebrovascular disease and dementia, possibly though cerebral hypoperfusion. Higher BPV is associated with cerebral blood flow (CBF) decline in observational cohorts, but relationships in samples with strictly controlled blood pressure remain understudied. We investigated whether BPV relates to change in CBF in the context of intensive versus standard antihypertensive treatment.

Methods and Results

In this post hoc analysis of the SPRINT MIND (Systolic Blood Pressure Intervention Trial–Memory and Cognition in Decreased Hypertension) trial, 289 participants (mean, 67.6 [7.6 SD] years, 38.8% women) underwent 4 blood pressure measurements over a 9‐month period after treatment randomization (intensive versus standard) and pseudo‐continuous arterial spin labeling magnetic resonance imaging at baseline and ≈4‐year follow‐up. BPV was calculated as tertiles of variability independent of mean. CBF was determined for whole brain, gray matter, white matter, hippocampus, parahippocampal gyrus, and entorhinal cortex. Linear mixed models examined relationships between BPV and change in CBF under intensive versus standard antihypertensive treatment. Higher BPV in the standard treatment group was associated with CBF decline in all regions (ß comparing the first versus third tertiles of BPV in whole brain: −0.09 [95% CI, −0.17 to −0.01];
P
=0.03), especially in medial temporal regions. In the intensive treatment group, elevated BPV was related to CBF decline only in the hippocampus (ß, −0.10 [95% CI, −0.18, −0.01];
P
=0.03).

Conclusions
Elevated BPV is associated with CBF decline, especially under standard blood pressure–lowering strategies. Relationships were particularly robust in medial temporal regions, consistent with prior work using observational cohorts. Findings highlight the possibility that BPV remains a risk for CBF decline even in individuals with strictly controlled mean blood pressure levels.

Registration

URL:
http://clinicaltrials.gov
. Identifier: NCT01206062.
Seeing Digital Asia Spatially: Vignettes of Digital Sociospatial Relations
Authors: Morris Carwyn 
Published: June 2023

Abstract
In this short article, I use several vignettes on digital relations in Asia to discuss the spatialities of digital relations across Asia’s digital geography and to highlight the application of spatial lenses to hybrid phenomena. These vignettes from Beijing, Weibo, Weixin, Telegram, Google Drive, Myanmar, India, and the Wa State show that territory, positionality, scale, place, network, and mobility are spatialities that can be used to understand both Asia’s digital development and the spatial complexities of Asia. In doing so, I highlight some of the benefits of a spatial approach in digital relations, some of the thorny issues with which this approach intersects, and the research agendas that emerge from this approach. I conclude by reflecting on the multiple states of the field, focusing on points of optimism and pessimism.