bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the anastomosis between the posterior inferior cerebellar artery and the superior cerebellar artery on outcomes of acute basilar artery occlusion after endovascular treatment
Authors: Huang Jiacheng , Kong Weilin , Yang Jie , Wang Maolin , Huang Xianjun , Wang Yan , Luo Jun , Wu Youlin , Zeng Guoyong , Wan Yue , Song Jiaxing , Li Linyu , Hu Jinrong , Liu Shuai , Luo Weidong , Tian Yan , Sang Hongfei , Qiu Zhongming , Li Fengli , Schonewille Wouter , Liu Chang , Zi Wenjie 
Published: October 2022

BackgroundThe effects of secondary collateral compensation on outcomes remain unclear in patients with acute basilar artery occlusion (BAO) after endovascular treatment (EVT). This study aimed to evaluate the benefits of the anastomosis between the posterior inferior cerebellar artery (PICA) and the superior cerebellar artery (SCA) in BAO after EVT.MethodsThis cohort study was conducted using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry. Patients with acute BAO and treated with EVT were included. The primary outcome was a modified Rankin Scale score of 0–2 at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (SICH) and 90-day mortality.ResultsOf the 646 patients included in the study, 196 (30.3%) patients had a PICA–SCA anastomosis. The PICA–SCA anastomosis was significantly associated with independent functional outcome at 90 days (67/196 (34.2%) vs 109/450 (24.2%), adjusted OR (aOR) 1.80 (95% CI 1.13 to 2.86), p=0.01) and was significantly associated with a decreased rate of SICH (40/442 (9.0%) vs 5/193 (2.6%), aOR 0.29 (95% CI 0.11 to 0.76), p=0.01). No significant difference was found between PICA–SCA anastomosis and 90-day mortality (219/450 (48.7%) vs 80/196 (40.8%), aOR 0.72 (95% CI 0.48 to 1.08), p=0.11). Subgroup analysis showed that the association between independent functional outcome and PICA–SCA anastomosis was strongest in patients with middle BAO (27/77 (35.1%) vs 22/118 (18.6%), aOR 2.64 (95% CI 1.13 to 6.15), p=0.03).ConclusionsThe PICA–SCA anastomosis is significantly associated with better functional outcomes in patients with acute BAO after EVT, especially in those with middle BAO.
Time-dependent condensation of bosonic potassium
Authors: Kabelac A. , Wolschin G. 
Published: October 2022

Abstract
We calculate the time-dependent formation of Bose–Einstein condensates (BECs) in potassium vapours based on a previously derived exactly solvable nonlinear boson diffusion equation (NBDE). Thermalization following a sudden energy quench from an initial temperature $$T_\mathrm {i}$$

T
i

to a final temperature $$T_\mathrm {f}$$

T
f

below the critical value and BEC formation are accounted for using closed-form analytical solutions of the NBDE. The time-dependent condensate fraction is compared with available $$^{39}$$

39

K data for various scattering lengths.

Graphic Abstract
HIF2 Inactivation and Tumor Suppression with a Tumor-Directed RNA-Silencing Drug in Mice and Humans
Authors: Ma Yuanqing , Joyce Allison , Brandenburg Olivia , Saatchi Faeze , Stevens Christina , Toffessi Tcheuyap Vanina , Christie Alana , Do Quyen N. , Fatunde Oluwatomilade , Macchiaroli Alyssa , Wong So C. , Woolford Layton , Yousuf Qurratulain , Miyata Jeffrey , Carrillo Deyssy , Onabolu Oreoluwa , McKenzie Tiffani , Mishra Akhilesh , Hardy Tanner , He Wei , Li Daniel , Ivanishev Alexander , Zhang Qing , Pedrosa Ivan , Kapur Payal , Schluep Thomas , Kanner Steven B. , Hamilton James , Brugarolas James 
Published: October 2022

Abstract

Purpose:
HIF2α is a key driver of kidney cancer. Using a belzutifan analogue (PT2399), we previously showed in tumorgrafts (TG) that ∼50% of clear cell renal cell carcinomas (ccRCC) are HIF2α dependent. However, prolonged treatment induced resistance mutations, which we also identified in humans. Here, we evaluated a tumor-directed, systemically delivered, siRNA drug (siHIF2) active against wild-type and resistant-mutant HIF2α.

Experimental Design:
Using our credentialed TG platform, we performed pharmacokinetic and pharmacodynamic analyses evaluating uptake, HIF2α silencing, target gene inactivation, and antitumor activity. Orthogonal RNA-sequencing studies of siHIF2 and PT2399 were pursued to define the HIF2 transcriptome. Analyses were extended to a TG line generated from a study biopsy of a siHIF2 phase I clinical trial (NCT04169711) participant and the corresponding patient, an extensively pretreated individual with rapidly progressive ccRCC and paraneoplastic polycythemia likely evidencing a HIF2 dependency.

Results:
siHIF2 was taken up by ccRCC TGs, effectively depleted HIF2α, deactivated orthogonally defined effector pathways (including Myc and novel E2F pathways), downregulated cell cycle genes, and inhibited tumor growth. Effects on the study subject TG mimicked those in the patient, where HIF2α was silenced in tumor biopsies, circulating erythropoietin was downregulated, polycythemia was suppressed, and a partial response was induced.

Conclusions:
To our knowledge, this is the first example of functional inactivation of an oncoprotein and tumor suppression with a systemic, tumor-directed, RNA-silencing drug. These studies provide a proof-of-principle of HIF2α inhibition by RNA-targeting drugs in ccRCC and establish a paradigm for tumor-directed RNA-based therapeutics in cancer.
FGFR mRNA Expression in Cholangiocarcinoma and Its Correlation with FGFR2 Fusion Status and Immune Signatures
Authors: Sridharan Vishwajith , Neyaz Azfar , Chogule Abhijit , Baiev Islam , Reyes Stephanie , Barr Fritcher Emily G. , Lennerz Jochen K. , Sukov William , Kipp Benjamin , Ting David T. , Deshpande Vikram , Goyal Lipika 
Published: October 2022

Abstract

Purpose:
Selective FGFR inhibitors are effective against cholangiocarcinomas that harbor gene alterations in FGFR2. Clinical trials suggest that expression of wild-type FGFR mRNA can predict sensitivity to FGFR inhibitors, but this biomarker has not been well characterized in cholangiocarcinoma. This study explores the prevalence of FGFR mRNA overexpression in cholangiocarcinoma, its role in predicting sensitivity to FGFR inhibitors, and its association with immune markers.

Experimental Design:
Tissue microarrays of intrahepatic (ICC) and extrahepatic cholangiocarcinomas (ECC) resected between 2004 and 2015 were used to evaluate FGFR1–4 mRNA expression levels by RNA in situ hybridization (ISH). Expression levels of FGFR2 mRNA were correlated with FGFR2 fusion status and with patient outcomes. Immune markers expression was assessed by IHC and CSF1 and CSF1 receptor expression were examined by RNA ISH.

Results:
Among 94 patients with resected cholangiocarcinoma, the majority had ICC (77%). FGFR2 fusions were identified in 23% of ICCs and 5% of ECCs. High levels of FGFR mRNA in FGFR2 fusion–negative ICC/ECC were seen for: FGFR1 (ICC/ECC: 15%/0%), FGFR2 (ICC/ECC: 57%/0%), FGFR3 (ICC/ECC: 53%/18%), and FGFR4 (ICC/ECC: 32%/0%). Overall, 62% of fusion-negative cholangiocarcinomas showed high levels of FGFR mRNA. In patients with advanced FGFR2 fusion–positive ICC, high levels of FGFR2 mRNA did not correlate with clinical benefit. FGFR2 fusion–positive tumors showed a paucity of PD-L1 on tumor cells.

Conclusions:
FGFR mRNA overexpression occurs frequently in cholangiocarcinoma in the absence of genetic alterations in FGFR. This study identifies a molecular subpopulation in cholangiocarcinoma for which further investigation of FGFR inhibitors is merited outside currently approved indications.
Antibody–Drug Conjugate Sacituzumab Govitecan Drives Efficient Tissue Penetration and Rapid Intracellular Drug Release
Authors: Kopp Anna , Hofsess Scott , Cardillo Thomas M. , Govindan Serengulam V. , Donnell Jennifer , Thurber Greg M. 
Published: October 2022

AbstractAntibody–drug conjugates (ADC) are a rapidly growing class of targeted cancer treatments, but the field has experienced significant challenges from their complex design. This study examined the multiscale distribution of sacituzumab govitecan (SG; Trodelvy), a recently clinically approved ADC, to clarify the mechanism(s) of efficacy given its unique design strategy. We employed a multiscale quantitative pharmacokinetic approach, including near-infrared fluorescence imaging, single-cell flow cytometry measurements, payload distribution via γH2AX pharmacodynamic staining, and a novel dual-labeled fluorescent technique to track the ADC and payload in a high trophoblast cell-surface antigen 2 expression xenograft model of gastric cancer (NCI-N87). We found that rapid release of the SN-38 payload from the hydrolysable linker inside cells imparts more DNA damage in vitro and in vivo than an ADC with a more stable enzyme cleavable linker. With SG, little to no extracellular payload release in the tumor was observed using a dual-labeled fluorescence technique, although bystander effects were detected. The high dosing regimen allowed the clinical dose to reach the majority of cancer cells, which has been linked to improved efficacy. In addition, the impact of multiple doses (day 1 and day 8) of a 21-day cycle was found to further improve tissue penetration despite not changing tumor uptake [percent injected dose per gram (%ID/g)] of the ADC. These results show increased ADC efficacy with SG can be attributed to efficient tumor penetration and intracellular linker cleavage after ADC internalization. This quantitative approach to study multiscale delivery can be used to inform the design of next-generation ADCs and prodrugs for other targets.
Early Versus Delayed Non–Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study
Authors: Oldgren Jonas , Åsberg Signild , Hijazi Ziad , Wester Per , Bertilsson Maria , Norrving Bo ,   for the National TIMING Collaborators
Published: October 2022

Background:
There are no evidence-based recommendations on the optimal time point to initiate non–vitamin K antagonist oral anticoagulants (NOACs) after acute ischemic stroke in patients with atrial fibrillation. We aimed to investigate the efficacy and safety of early versus delayed initiation of NOAC in these patients.

Methods:
TIMING (Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation) was a registry-based, randomized, noninferiority, open-label, blinded end-point study at 34 stroke units using the Swedish Stroke Register for enrollment and follow-up. Within 72 hours from stroke onset, patients were randomized to early (≤4 days) or delayed (5–10 days) NOAC initiation, with choice of NOAC at the investigators’ discretion. The primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality at 90 days. The prespecified noninferiority margin was 3%. Secondary outcomes included the individual components of the primary outcome.

Results:

Between April 2, 2017, and December 30, 2020, 888 patients were randomized to either early (n=450) or delayed (n=438) initiation of NOAC. No patient was lost to 90-day follow-up. Mean age was 78.3 years (SD, 9.9 years); 46.2% were women; 49.1% had previously known atrial fibrillation; and 17.5% prior stroke. The primary outcome occurred in 31 patients (6.89%) assigned to early initiation and in 38 patients (8.68%) assigned to delayed NOAC initiation (absolute risk difference, −1.79% [95% CI, −5.31% to 1.74%];
P
noninferiority
=0.004). Ischemic stroke rates were 3.11% and 4.57% (risk difference, −1.46% [95% CI, −3.98% to 1.07%]) and all-cause mortality rates were 4.67% and 5.71% (risk difference, −1.04% [95% CI, −3.96% to 1.88%]) in the early and delayed groups, respectively. No patient in either group experienced symptomatic intracerebral hemorrhage.

Conclusions:
Early initiation was noninferior to delayed start of NOAC after acute ischemic stroke in patients with atrial fibrillation. Numerically lower rates of ischemic stroke and death and the absence of symptomatic intracerebral hemorrhages implied that the early start of NOAC was safe and should be considered for acute secondary stroke prevention in patients eligible for NOAC treatment.

Registration:

URL:
http://www.clinicaltrials.gov
; Unique identifier: NCT02961348.
Origin of the Warm Arctic–Cold North American Pattern on the Intraseasonal Time Scale
Authors: Lin Hai , Yu Bin , Hall Nicholas M. J. 
Published: October 2022

Abstract
The warm Arctic–cold continent pattern (WACC) of near-surface air temperature variability has often been associated with the connection between Arctic sea ice reduction and cold weather over the midlatitude continents. Whether the existence of this pattern is due to variability of sea ice or is caused by atmospheric internal dynamics is subject to debate. Based on a long integration of a primitive equation atmospheric model (SGCM), this study examines the origin of the warm Arctic–cold North American pattern (WACNA), which is characterized by a pair of opposite surface air temperature anomalies over the high-latitude Chukchi–Bering Sea region and the North American continent, in boreal winter on the intraseasonal time scale. The model atmosphere is maintained by a time-independent forcing, so that atmospheric internal dynamics is the only source of variability. It is found that the SGCM model simulates well the behavior of the observed WACNA pattern. The WACNA pattern develops by interacting with the time-mean flow and synoptic-scale transient eddies. Two pathways of Rossby wave propagation are associated with WACNA. The northern pathway originates from eastern Siberia moving eastward across the Bering Strait to Canada, and the southern pathway is rooted in the subtropical waveguide propagating across the eastern North Pacific. Our simulation of this pattern implies that tropospheric dynamics alone can generate the WACNA, and the predictability associated with this pattern is likely limited by its internal dynamics nature.

Significance Statement
The warm Arctic–cold continent pattern of temperature variability has often been associated with the connection between Arctic sea ice reduction and cold weather over the midlatitude continents, which implies possible impacts of polar warming on midlatitude climate. There has been debate on whether the existence of this pattern depends on variability of sea ice or can be caused by processes within the atmosphere. In this study, we use a simple atmospheric model, which has a constant forcing; thus, atmospheric internal dynamics is the only source of variability. We show that atmospheric internal dynamics alone can generate the warm Arctic–cold North American pattern. The result has implications for our understanding of the impact of global warming.
Experimental investigation of pulsation behaviour and performance of pulsating heat pipe
Authors: Madhuri M , Yadav NP 
Published: October 2022

This paper focuses on the experimental study of a closed-loop pulsating heat pipe with water. The unsteady state experiment was conducted to understand the role of different evacuation pressure, variable heat input and filling ratio on the PHP behaviour. The DAQ system did temperature measurements of the pipe at 13 locations for variable heat inputs, evacuation pressure, and filling ratio. PHP thermal behaviour is evaluated in terms of temperature variation with time, thermal resistance, effective thermal conductivity, and pulsation frequency. The strong pulsating effect is observed at 0.0799 bar. The thermal resistance of the heat pipe declines with the decrease in evacuation pressure. The lowest thermal resistance 0.05,786 K/W is observed at 0.0799 bar evacuation pressure with 30% FR, 6 times lower than 90% FR. Effective thermal conductivity rises with the decrease in evacuation pressure. The highest effective thermal conductivity of 10,233.32 W/mK is found at 30% FR and 0.0799 bar evacuation pressure, 7.5 times higher than atmospheric pressure. So, better performance is observed at low evacuation pressure of 0.0799 bar and 30% FR. This study benefits the heat transfer of integrated circuit technology and electronic devices because of its high effective thermal conductivity.
Microcatheters with extra-long detachable tip: A promising treatment option in dural arteriovenous fistulas
Authors: Gölitz Philipp , Luecking Hannes , Knott Michael , Hock Stefan , Brandner Sebastian , Knossalla Frauke , Doerfler Arnd 
Published: October 2022

Purpose Treating cerebral dural arteriovenous fistulas (dAVFs) by transarterial embolization is an established endovascular approach but no data exist regarding the utility of using the newly introduced microcatheters with extra-long detachable tip. Aim of our study was to evaluate the value of these microcatheters and, additionally, of combining them with the simplified pressure cooker technique. Methods Twenty-nine patients treated for dAVF with transarterial embolization were enrolled. In a subgroup of fifteen patients the simplified pressure cooker technique was additionally applied. Demographics and characteristics were collected for patients and dAVFs and procedural details reviewed. The association between covariates and binary-coded occlusion status was evaluated. Results Microcatheter navigation into the target pedicle as well as application of the simplified pressure cooker technique were successful in all cases. Complete dAVF occlusion was reached in 69.0% at a single stage. In case of complete dAVF occlusion, embolization via only one pedicle was enough. Subgroup analysis revealed a higher occlusion status (80%) if using the simplified pressure cooker technique than if not (57%) but reached not significance level. Conclusion Using microcatheters with extra-long detachable tip for dAVF embolization seems to offer a safe and effective treatment option with exceptional high occlusion rate at a single stage. The high navigability facilitates catheterization of a single selected target pedicle that is often enough to reach complete dAVF occlusion. Combining these microcatheters with the simplified pressure cooker technique turned out to be safe and easy to handle and might allow an increasing dAVF occlusion rate.
Stunting and associated factors among school-age children (5–14 years) in Mulo district, Oromia region, Ethiopia
Authors: Berhanu Alemayehu , Garoma Sileshi , Arero Godana , Mosisa Getu 
Published: October 2022

Objective: Stunting continues to be a major public health challenge in developing countries, including Ethiopia. Studies revealed that the extent of stunting among under-5 children in Ethiopia is well studied, but there is a scarcity of data among school-age children. Therefore, this study aimed to assess the magnitude of stunting and associated factors among school-age children in the Mulo district, Ethiopia. Methods: A community-based cross-sectional study was conducted among 606 school-age children (5–14 years) in Mulo district, Central Ethiopia, from 1 to 30 July 2019. A multistage sampling technique was used to select study participants. The collected data were entered into Epi Info version 7.2.2.16 software and analyzed using SPSS version 21 and World Health Organization AnthroPlus software. Bivariate and backward stepwise multivariable statistical methods were employed to assess stunting and its associated factors. Statistical significant association was declared at a p value of <0.05. Result: In this study, prevalence of stunting among school-age children was 42.4%. Of which, 144 (23.76%) were males and 113 (18.65%) were females. Age group between 10 and 14 years old, (adjusted odds ratio = 1.896, 95% confidence interval: 1.328–2.708), male sex (adjusted odds ratio = 2.688, 95% confidence interval: 1.892–3.821), increased family size (adjusted odds ratio = 1.711, 95% confidence interval: 1.191–2.458), absence of latrine in the compound (adjusted odds ratio = 2.541, 95% confidence interval: 1.711–3.773), and consuming less than three times per day (adjusted odds ratio = 2.68, 95% confidence interval: 1.375–5.223) were factors significantly associated with stunting. Conclusion: The study revealed that the prevalence of stunting among school-age children was high. Age, sex, family size, availability of latrine, and meal frequency were factors significantly associated with stunting. Therefore, interventional educations on the importance of timely feeding, a balanced diet, family planning, environmental sanitation, and personal hygiene should be given for the parents/caregivers. In addition, analytic studies are recommended to further assess the causes of stunting among the school-age children in the area.
Assessment of prevalence and associated factors of intestinal parasite infections among school children at Amber Primary School, Northwest Ethiopia
Authors: Getnet Tamiru , Alemayehu Tesfa , Demeke Tigist , Toru Milkiyas , Aschale Yibeltal 
Published: October 2022

Objective: This study is aimed to assess the prevalence and associated factors of intestinal parasitic infections among school children at Amber Primary School, Northwest Ethiopia. Methods: A school-based cross-sectional study was conducted at Amber Primary School from December 2019 to January 2020. Semi-structured questionnaire was used to collect socio-demographic data and clinical characteristics. Direct wet mount technique was applied for detection and identification of intestinal parasites. Result: A total of 384 participants were included in this study of which 50.3% were males and 65.4% were in the age group 9–12 years. The prevalence of at least one intestinal parasite was 26.8% (n = 103), of which 13.6% (n = 14) were mixed infections. Hymenolepis nana was the most prevalent intestinal parasite (5.2%) followed by Entamoeba histolytica/dispar (4.9%) and hookworm (4.7%). Male children (adjusted odds ratio = 0.624; 95% confidence interval: 0.392–0.993) and those whose mother completed elementary school (adjusted odds ratio = 2.171; 95% confidence interval: 1.012–4.658) were significantly associated with intestinal parasite infections (p < 0.05). Conclusion: Intestinal parasitic infections remained an important health problem among school children in the study area. Appropriate intervention measures should be taken to reduce the burden and related morbidities.
Statin Utilization Trend in Primary and Secondary Prevention of Cardiovascular Diseases in a Teaching Hospital
Authors: Umarje Siddhi , Raut Asawari , Dave Priti , James Neha Mary 
Published: October 2022

Objective To conduct risk assessment and assess the choice of statins with regard to cardiovascular diseases (CVDs). Methodology This is a cross-sectional observation study conducted on 500 patients visiting a teaching hospital. Medical records were used to obtain patient characteristics and type, dose, and regimen of prescribed statin. Prescribed statin dose was evaluated using standard prescribing guidelines by American College of Cardiology/American Heart Association. Result Out of the 500 patients studied, 70% (350) of patients were prescribed statin therapy for a CVD and 30% had at least 1 CVD risk factor. Proportion of males was higher. Mean age of patients with statin therapy for coexisting CVD was 61.16 ± 12.87. Among those with at least 1 cardiovascular risk factor but without CVD, 66% had risk score more than 7.5 out of 10 suggestive of high risk for CVDs within 10 years. Atorvastatin and rosuvastatin were the preferred choice of statin therapy, with higher preference for atorvastatin. Dosing criteria were well-met for secondary prevention; whereas, underdosing was prevalent among users of fixed-dose combinations and among patients prescribed a statin for primary prevention of CVDs. Conclusion Lack of use of risk scores may lead to underdosing and underutilization of statins.