bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gamma camera characterization at high holmium-166 activity in liver radioembolization
Authors: Stella Martina , Braat Arthur J. A. T. , Lam Marnix G. E. H. , de Jong Hugo W. A. M. , van Rooij Rob 
Published: March 2021

Abstract
Background
High activities of holmium-166 (166Ho)–labeled microspheres are used for therapeutic radioembolization, ideally directly followed by SPECT imaging for dosimetry purposes. The resulting high-count rate potentially impacts dead time, affecting the image quality and dosimetric accuracy. This study assesses gamma camera performance and SPECT image quality at high 166Ho activities of several GBq. To this purpose, the liver compartment, including two tumors, of an anthropomorphic phantom was filled with 166Ho-chloride, with a tumor to non-tumorous liver activity concentration ratio of 10:1. Multiple SPECT/CT scans were acquired over a range of activities up to 2.7 GBq. Images were reconstructed using a commercially available protocol incorporating attenuation and scatter correction. Dead time effects were assessed from the observed count rate in the photopeak (81 keV, 15% width) and upper scatter (118 keV, 12% width) window. Post reconstruction, each image was scaled with an individual conversion factor to match the known total activity in the phantom at scanning time. The resulting activity concentration was measured in the tumors and non-tumorous liver. The image quality as a function of activity was assessed by a visual check of the absence of artifacts by a nuclear medicine physician. The apparent lung shunt fraction (nonzero due to scatter) was estimated on planar and SPECT images.

Results
A 20% count loss due to dead time was observed around 0.7 GBq in the photopeak window. Independent of the count losses, the measured activity concentration was up to 100% of the real value for non-tumorous liver, when reconstructions were normalized to the known activity at scanning time. However, for tumor spheres, activity concentration recovery was ~80% at the lowest activity, decreasing with increasing activity in the phantom. Measured lung shunt fractions were relatively constant over the considered activity range.

Conclusions
At high 166Ho count rate, all images, visually assessed, presented no artifacts, even at considerable dead time losses. A quantitative evaluation revealed the possibility of reliable dosimetry within the healthy liver, as long as a post-reconstruction scaling to scanning activity is applied. Reliable tumor dosimetry, instead, remained hampered by the dead time.
Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway
Authors: Jia Xiang-Bo , Zhang Quan , Xu Lei , Yao Wen-Jian , Wei Li 
Published: March 2021

AbstractBackgroundLeaves of the natural plant lotus are used in traditional Chinese medicine and tea production. They are rich in flavonoids.MethodsIn this study, lotus leaf flavonoids (LLF) were applied to human lung cancer A549 cells and human small cell lung cancer cells H446 in vitro to verify the effect of LLF on apoptosis in these cells through the ROS/p38 MAPK pathway.ResultsLLF had no toxic effect on normal cells at concentrations up to 500 µg/mL, but could significantly inhibit the proliferation of A549 cells and H446 cells. Flow cytometry showed that LLF could induce growth in A549 cells. We also found that LLF could increase ROS and MDA levels, and decrease SOD activity in A549 cells. Furthermore, qRT-PCR and western blot analyses showed that LLF could upregulate the expression of p38 MAPK (p-p38 MAPK), caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9 and Bax and downregulate the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1, and Bcl-2 in A549 cells. Results of HPLC showed that LLF mainly contain five active substances: kaempferitrin, hyperoside, astragalin, phloridzin, and quercetin. The apoptosis-inducing effect of LLF on A549 cells came from these naturally active compounds.ConclusionsWe have shown in this study that LLF is a bioactive substance that can induce apoptosis in A549 cells in vitro, and merits further research and development.
Factors influencing the sinus membrane thickness in edentulous regions: a cone-beam computed tomography study
Authors: Munakata Motohiro , Yamaguchi Kikue , Sato Daisuke , Yajima Naoko , Tachikawa Noriko 
Published: March 2021

AbstractBackgroundDuring implant treatment in the maxillary molar area, maxillary sinus floor augmentation is often performed to ameliorate the reduced alveolar bone height attributable to bone remodeling and pneumatization-induced expansion of the maxillary sinus. However, this augmentation may cause complications such as misplaced implants, artery damage, and maxillary sinus mucosal perforation; infections like maxillary sinusitis; and postsurgical complications such as bone graft leakage and postoperative nasal hemorrhaging. To reduce the complications during maxillary sinus floor augmentation and postoperative infections, we performed retrospective investigations of various systemic and local factors that influence pre-operative sinus mucosal thickness (SMT) by using cone-beam computed tomography (CBCT). Subjects included patients who underwent maxillary sinus floor augmentation in an edentulous maxillary molar area with a lateral approach. Pre-operative SMT, existing bone mass, and nasal septum deviation were measured using CBCT images. Relationships between SMT and the following influencing factors were investigated: (1) age, (2) sex, (3) systemic disease, (4) smoking, (5) period after tooth extraction, (6) reason for tooth extraction, (7) residual alveolar bone height (RBH), (8) sinus septa, and (9) nasal septum deviation. Correlations were also investigated for age and RBH (p< 0.05).ResultsWe assessed 35 patients (40 sinuses; 11 male, 24 female). The average patient age was 58.90 ± 9.0 years (males, 57.9 ± 7.7 years; females, 59.9 ± 9.4 years; age range, 41–79 years). The average SMT was 1.09 ± 1.30 mm, incidence of SMT > 2 mm was 25.0%, incidence of SMT < 0.8 mm was 50.0%, and the average RBH was 2.14 ± 1.02 mm. The factors that influenced SMT included sex (p= 0.0078), period after tooth extraction (p= 0.0075), reason for tooth extraction (p= 0.020), sinus septa (p= 0.0076), and nasal septum deviation (p= 0.038).ConclusionsFactors associated with higher SMT included male sex, interval following tooth extraction < 6 months, periapical lesions, sinus septa, and nasal septum deviation. Factors associated with SMT > 2 mm were sex and reason for tooth extraction, while factors associated with SMT < 0.8 mm were time following tooth extraction and nasal septum deviation. Despite the limitations of this study, these preoperative evaluations may be of utmost importance for safely conducting maxillary sinus floor augmentation.
Hypoperfusion assessed by pressure reactivity index is associated with delayed cerebral ischemia after subarachnoid hemorrhage: an observational study
Authors: Fan Bin Bin , Sun Xiao Chuan , Huang Zhi Jian , Yang Xiao Min , Guo Zong Duo , He Zhao Hui 
Published: March 2021

Abstract
Background
Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Pressure reactivity index (PRx) have been confirmed to reflect the level of cerebral autoregulation and used to derive optimal cerebral perfusion pressure (CPPopt). The goal of this study is to explore the associations between autoregulation, CPPopt, PRx, and DCI.

Methods
Continuous intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP) signals acquired from 61 aSAH patients were retrospectively analyzed. PRx was calculated and collected by Pneumatic computer system. The CPP at the lowest PRx was determined as the CPPopt. The duration of a hypoperfusion event (dHP) was defined as the cumulative time that the PRx was > 0.3 and the CPP was <CPPopt. The duration of CPP more than 10 mmHg below CPPopt (ΔCPPopt < − 10 mmHg) was also used to assess hypoperfusion. The percent of the time of hypoperfusion by dHP and ΔCPPopt < − 10 mmHg (%dHP and %ΔCPPopt) were compared between DCI group and control group, utilizing univariate and multivariable logistic regression. It was the clinical prognosis at 3 months after hemorrhage that was assessed with the modified Rankin Scale, and logistic regression and ROC analysis were used for predictive power for unfavorable outcomes (mRs 3–5).

Results
Data from 52 patients were included in the final analysis of 61 patients. The mean %dHP in DCI was 29.23% and 10.66% in control. The mean %ΔCPPopt < − 10 mmHg was 22.28%, and 5.90% in control. The %dHP (p < 0.001) and the %ΔCPPopt < − 10mmHg (p < 0.001) was significantly longer in the DCI group. In multivariate logistic regression model, %ΔCPPopt <− 10 mmHg (p < 0.001) and %dHP (p < 0.001) were independent risk factor for predicting DCI, and %ΔCPPopt <− 10 mmHg (p = 0.010) and %dHP (p = 0.026) were independent risk factor for predicting unfavorable outcomes.

Conclusions
The increase of duration of hypoperfusion events and duration of CPP below CPPopt over 10 mmHg, evaluated as time of lowered CPP, is highly indicative of DCI and unfavorable outcomes.
“Pigtail through snare” technique: an easy and fast way to retrieve a catheter fragment with inaccessible ends
Authors: Mori Kensaku , Somagawa Chika , Kagaya Shun , Sakai Masafumi , Homma Satoshi , Nakajima Takahito 
Published: March 2021

Abstract
Background
A catheter fragment with inaccessible ends can be retrieved using the well-known two-step method: making a free end with a pigtail catheter and seizing it with a snare catheter. Here we propose an easier and faster modification, named the “pigtail through snare” technique.

Case presentation
A 61-year-old female patient underwent removal of a central venous catheter fragment migrating to the right atrium. Both ends located in the right atrial appendage and left hepatic vein were inaccessible. Initially, a snare loop was opened in the inferior vena cava and a pigtail catheter was advanced through the snare loop to hook the catheter fragment. The free end was created by pulling the pigtail catheter, dragged automatically into the snare loop, grasped, and retrieved immediately.

Conclusions
By passing the pigtail catheter through the snare loop in advance, the snaring maneuver becomes easy and fast in retrieving the catheter fragment with inaccessible ends.
Curve25519 based lightweight end-to-end encryption in resource constrained autonomous 8-bit IoT devices
Authors: Ullah Shafi , Zahilah Raja 
Published: March 2021

AbstractRobust encryption techniques require heavy computational capability and consume large amount of memory which are unaffordable for resource constrained IoT devices and Cyber-Physical Systems with an inclusion of general-purpose data manipulation tasks. Many encryption techniques have been introduced to address the inability of such devices, lacking in robust security provision at low cost. This article presents an encryption technique, implemented on a resource constrained IoT device (AVR ATmega2560) through utilizing fast execution and less memory consumption properties of curve25519 in a novel and efficient lightweight hash function. The hash function utilizes GMP library for multi-precision arithmetic calculations and pre-calculated curve points to devise a good cipher block using ECDH based key exchange protocols and large random prime number generator function.
OLI-P: Toxicity and efficacy of local ablative radiotherapy in PSMA-PET staged, oligometastatic prostate cancer—A phase II trial.
Authors: Hölscher Tobias , Baumann Michael , Kotzerke Jörg , Wirth Manfred , Thomas Christian , Zips Daniel , Krause Mechthild , Lohaus Fabian 
Published: March 2021

115 Background: After curative primary therapy, a subset of patients with prostate cancer will have PSA-progression. Modern imaging methods may detect patients with oligometastastic disease at an early time point. Local ablative therapy has shown to improve time to progression compared to standard of care. PSMA-PET hybrid imaging is an emerging method, with a high accuracy and sensitivity to detect oligometastatic disease at low PSA-levels. Methods: At two German centers, patients with PSA progression after local curative treatment had PSMA-PET- hybrid imaging. Patients with up to five PSMA-PET positive metastases were offered to participate in the clinical trial. Further relevant exclusion criteria were ongoing androgen deprivation therapy (ADT), PSA >10 ng/ml or severe comorbidity. The patients had a local ablative radiotherapy (aRT) to all PSMA-PET positive metastases. The primary endpoint was toxicity within two years after aRT. Secondary endpoints included PSA-progression free survival (defined as PSA nadir +1 ng/ml or start of ADT) and therapy-free survival (i.e. time to start ADT). Results: Between 2014 and 2018, 72 patients were included; patients’ characteristics are shown in table. Nine patients were excluded as no aRT was performed. The median follow up for the remaining 63 patients was 34.2 months. Within two years, 67 % (42 of 63 pats) had no report of adverse events. Following events were recorded during follow up: rectal bleeding (Grade 1, n=1), stroke (1), urinary incontinence (grade 2: n=3) secondary malignoma (n=5, primary liver tumor (n=2), bladder cancer, acute leukemia and head and cancer). All adverse events were considered as “not related“ to aRT of the metastases. PSA progression occurred in 44 patients after a median of 14.4 months. After two years, PSA relapse free survival was 38.2 %. ADT was initiated in 36 patients after a median of 26 months; 54 % (n=34 of 63) did not start ADT within two years after aRT. Conclusions: Local ablative radiotherapy in selected patients with PSMA-PET staged oligometastatic prostate cancer is well tolerated and may improve midterm outcome and delay onset of systemic therapy. Clinical trial information: NCT02264379. [Table: see text]
Molecular and clinical characterization of metastatic castration-resistant prostate cancer (mCRPC) patients achieving deep PSA responses to bipolar androgen therapy (BAT).
Authors: Markowski Mark Christopher , Kachhap Sushant , De Marzo Angelo M , Denmeade Samuel R. , Antonarakis Emmanuel S. 
Published: March 2021

127 Background: BAT is an emerging treatment strategy for men with mCRPC, whereby testosterone concentrations are cycled from supraphysiologic to castrate levels each month. BAT has been shown to be safe, and induces clinical responses in a proportion of patients, some of which are extreme. We explored the clinical and molecular characteristics of mCRPC pts that achieved deep PSA responses on BAT. Methods: We identified N= 22/114 (19%) mCRPC pts who achieved >70% PSA reductions on treatment with BAT. All pts were treated on-protocol at Johns Hopkins using 400mg testosterone cypionate intramuscularly every 28 days, together with continuous LHRH agonist therapy. Pts remained on study until clinical or radiographic progression, as per protocol. Clinical-grade molecular sequencing was obtained using commercially available assays. Results: Next-generation somatic DNA sequencing was obtained on 15/22 (68%) pts. Of these 15 pts with sequencing data who achieved a >70% PSA response on BAT, 14/15 (93%) harbored a pathogenic mutation in TP53 and/or a homologous recombination DNA repair (HRD) gene. Among patients with measureable disease (N=15), 10 pts (67%) achieved an objective response including one pt with a complete response. The median radiographic progression-free survival (rPFS) of these deep PSA responders on BAT was 11.3 (95% CI, 7.9-25) months. Conclusions: We observed an enrichment of TP53 and/or HRD mutations in mCRPC pts with extreme PSA responses to BAT, with durability lasting about a year These data support the hypothesis that BAT may work best in DNA repair-deficient mCRPC pts. Further study of BAT in biomarker selected mCRPC populations (i.e. TP53/HRD mutated) is warranted. [Table: see text]
Differential effect of body mass index (BMI) on outcomes of patients treated with docetaxel in prostate cancer: An exploratory analysis.
Authors: Verma Saurav , Sahoo Ranjit Kumar , Singh Prabhjot , Nayak Brusabhanu , Haresh KP , Batra Atul 
Published: March 2021

129 Background: Docetaxel is a lipophilic drugs with a high affinity for adipose tissue resulting in a higher volume of distribution.There are contradictory data with regards to the differential effect of docetaxel based on BMI in breast cancer patients. However, there are no such data in patients with prostate cancer. A We performed an exploratory analysis to determine if the benefit of docetaxel in patients with metastatic castration resistant prostate cancer (mCRPC) is modified by BMI. Methods: This is a post hoc analysis of data retrieved from the phase III ENTHUSE M1C study that assessed the efficacy and safety of additional zibotentan in combination with docetaxel in patients with mCRPC (ClinicalTrials.gov identifier: NCT00617669). BMI (kg/m2) was categorized as: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Cox regression models were constructed to determine the impact of BMI on progression-free survival (PFS) and overall survival (OS) after adjusting for baseline characteristics. Results: A total of 466 patients were eligible for current analysis, of whom 34%, 46% and 20% were < 65 years, 65-74 years and > 75 years, respectively. The median total and free baseline PSA were 99.5 (interquartile range [IQR], 33.6 to 237.0) ng/mL and 13.9 (IQR, 5.4 to 37.4) ng/mL, respectively. There were 31% (n = 145), 46% (n = 213) and 23% (n = 108) lean, overweight and obese patients. Visceral metastasis was present in 52% patients, while the number of bone metastases were 1-3 in 15%, 4 in 5%, 5-20 in 58% and ≥ 21 in 23%. The median number of cycles of docetaxel administered were 10 (IQR, 6-10). The median PFS was 7.3, 7.7 and 8.4 months (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.81 to 1.06; P = .26) for lean, overweight and obese patients, respectively. The median OS was 10.3, 10.7 and 12.4 months (HR, 0.75; 95% CI, 0.63 to 0.89; P = .01) for lean, overweight and obese patients, respectively. After adjusting for baseline and tumor related characteristics, there was no association of BMI with PFS (overweight, HR, 0.92; 95% CI, 0.73 to 1.17; P = .50; obese, HR, 0.90; 95% CI, 0.67 to 1.18; P = .42) while overweight (HR, 0.68; 95% CI, 0.52 to 0.91; P = .01) and obese (HR, 0.61; 95% CI, 0.43 to 0.88; P = .01) patients had significantly better OS as compared with lean patients. Conclusions: The differential effect of docetaxel based on BMI was not observed in patients with mCRPC. Interestingly, obese patients had a significantly longer OS, which warrants further investigation.
PI3K/AKT pathway biomarkers analysis from the phase III IPATential150 trial of ipatasertib plus abiraterone in metastatic castration-resistant prostate cancer.
Authors: De Bono Johann S. , Sweeney Christopher , Bracarda Sergio , Sternberg Cora N. , Chi Kim N. , Olmos David , Sandhu Shahneen Kaur , Massard Christophe , Matsubara Nobuaki , Garcia Josep , Nowicka Malgorzata , Wongchenko Matthew , Shi Zhen 
Published: March 2021

13 Background: In IPATential150 (NCT03072238), ipatasertib (ipat) + abiraterone (abi) as first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) significantly reduced the risk for disease worsening or death vs placebo (pbo) + abi in patients (pts) with tumors with PTEN loss by immunohistochemistry (IHC; HR, 0.77 [95% CI: 0.61, 0.98]; P = 0.0335) but not in the intention-to-treat population (de Bono, ESMO 2020). In patients with PTEN loss tumors by IHC, median radiographic progression-free survival (rPFS) was 16.5 mo (95% CI: 13.9, 17.0) with pbo + abi and 18.5 mo (95% CI: 16.3, 22.1) with ipat + abi. Here, we present exploratory analyses evaluating putative biomarker associations with rPFS. Methods: Before randomization, tumor samples ( > 90% archival) were tested for PTEN loss by VENTANA PTEN (SP218) IHC assay (N = 1101). PTEN loss was pre-defined as ≥ 50% of tumor cells with no specific cytoplasmic IHC staining. Exploratory analysis evaluated different IHC staining cutoffs. Tumor genomic alterations were profiled with next-generation sequencing (NGS) using the Foundation Medicine FoundationOne CDx NGS assay (Shi, ASGO-GU 2020; n = 743 evaluable by NGS, of which n = 518 were PTEN evaluable). rPFS was determined by the investigator. Results: Consistent benefit with the combination arm vs pbo + abi was observed when PTEN loss by IHC was defined more stringently (rPFS at ≥ 60% tumor cells with PTEN loss: HR, 0.72 [95% CI, 0.56, 0.92]; ≥ 70%: HR, 0.72 [95% CI, 0.56, 0.93]; ≥ 80%: HR, 0.71 [95% CI, 0.54, 0.92]; ≥ 90%: HR, 0.72 [95% CI, 0.53, 0.97]; 100%: HR, 0.65 [95% CI, 0.39, 1.08]). In contrast, ipat + abi was not associated with improved rPFS in pts with PTEN intact by IHC tumors ( < 50% no staining; stratified HR, 0.91 [95% CI: 0.72, 1.16]); the median rPFS was 19.1 mo (95% CI: 16.4, 21.9) with pbo + abi and 19.7 mo (95% CI: 16.4, 26.3) with ipat + abi. By NGS assessment, pts with tumors with PTEN loss and with genomic alterations in PIK3CA/AKT1/PTEN had a larger magnitude of rPFS benefit with ipat + abi than pts with no detectable alterations (Table). Conclusions: Analyses of more-stringent biomarkers associated with activation of the PI3K/AKT pathway further support ipat + abi as a treatment option for first-line mCRPC with PI3K/AKT pathway alterations, a mCRPC subtype with a worse prognosis. Clinical trial information: NCT03072238. [Table: see text]