tbuckley/cabot-search huggingface dataset:
Abstract 13812: A Functional Polymorphism in Matriptase-2, Rs855791, Modifies Interleukin-6 Mediated Cardiovascular Risk
Authors: Rahul Kakkar, Sandrine Pierre, Anindita Das, Arun Samidurai, Niclas Eriksson, Axel Akerblom, Zijian Xie, Lars C Wallentin, Rakesh C Kukreja, Matt Devalaraja
Journal: Circulation (2019)

Interleukin-6 (IL-6) is a pleotropic cytokine that allows a unique interplay between the immune mediated and iron mediated pathologies. Recent studies suggest a role for IL-6 in myocardial ischemic...
원저 : 만성 B형 간질환에서 라미부딘 내성의 임상경과 및 예측인자
Authors: Neunghwa Park, shin jung woo, 박종호, 방성조, 김대현, 주광로, Do Ha Kim
Journal: Clinical and Molecular Hepatology (2003)

목적: 라미부딘의 투여기간이 길수록 약제내성 변이형 바이러스의 발생률이 증가하게 된다. 변이형의 장기적인 임상적 의의는 논란이 많다. 본 연구는 B형 간염 바이러스에 의한 만성 간질환자에서 변이형이 생긴 뒤의 임상적 경과와 변이형의 발생을 예측할 수 있는 인자를 알아보고자 하였다. 대상과 방법: 만성 B형 간 질환자로 진단 받은 환자 중 라미부딘 치료도중에 viral breakthrough가 생긴 124명을 대상으로 하였다. 평균 연령은 40세였고 남녀 비는 105:19였다. 치료 전 혈청 평균 ALT치는 223 IU/L, 혈청 평균 AST치는 127 IU/L, 혈청 평균 HBV DNA치 1216 pg/ mL, 치료 전 정량적 평균 HBeAg치 259이였다. 라미부딘은 1일 100 mg씩 breakthrough가 발생한 124명에게 계속 투여하였으며 1-2개월 간격으로 간기능 검사, HBeAg, anti-HBe, HBV DNA 검사를 시행하였다. 라미부딘 총 평균투여 기간은 30.5개월(범위: 10-59개월)이었으며 breakthrough 후 라미부딘 평균 투여기간은 12.5개월(범위: 1-42개월)이였다. 결과: 라미부딘 투여 환자 519명 중 124명에서 viral breakthrough가 5-41개월 사이에 발생하였으며 누적발생률은 12개월 후 8%, 18개월 후 24%, 24개월 후 36%, 36개월 후 52%였다. Viral breakthrough가 생긴 6개월 이내에 120명에서 혈청 ALT치가 상승하였으나 4명에서는 계속 정상으로 유지되었다. 혈청 ALT치는 대부분 상승한 뒤 5개월 내에 최고치에 도달하였으나 6명에서는 12개월 이후에 최고치에 도달하기도 하였다. ALT치는 72명(65%)에서 치료 전 값 이상으로 상승하였으며, 67명(56%)에서 정상치의 5배 이상, 29예(24%)에서 10배 이상 상승하였다. Breakthrough후에 라미부딘 계속투여로 혈청 ALT치가 정상으로 유지된 경우는 22예(18%)에 불과하였으며 98예는 치료전보다 높게 유지되었고 16예에서는 지속적으로 상승하였다. Breakthrough후의 혈청 ALT치 및 AST치가 치료 전보다 의미 있게 상승하였으나 혈청 HBV DNA치는 차이가 없었다. Breakthrough후에 10명에서 HBeAg의 음전이 있었으나 5예에서는 음전 후에 HBV DNA가 재양전되고 혈청 ALT치가 상승되는 HBeAg 음성 만성 간염형태로 나타났다. Breakthrough와 관련된 예측인자로 치료 중 정량적 HBeAg의 변화양상만이 유일하게 의미가 있어 감소 후 증가군 82.5%에서, 지속적 유지군 23.7%에서 breakthrough가 발생하였으나 지속적 감소군에서는 단지 3.5%만이 발생하였다. 또한 감소 후 증가군에서 정량적 HBeAg치의 감소 후 재상승시점은 약물투여후 평균 9개월로 HBV DNA가 재양전되는 평균시점인 17개월보다 의미 있게 짧았다. Breakthrough후에 투약을 중지한 예는 40예(33%)였다. 이 중 11예에서 중단 전보다 혈청 ALT치가 상승되었으며 8개월 내에 전예에서 발생하였다. 중단시 혈청 ALT치가 치료 전 수치보다 높은 경우에서 중단한 26예 중 25명은 중단 후에 혈청 ALT치가 중단 시보다 낮았지만 치료 전 수치보다 낮은 경우에서 중단한 14명 중 10예에서 중단 후에 중단 시보다 더 높아졌다. 결론: 만성 B형 간염환자에서 라미부딘 투여 중에 발생한 breakthrough후의 임상양상은 상당수에서 급성악화를 보였다. Breakthrough를 예측할 수 있는 인자로는 치료 중 정량적 HBeAg치의 변화양상만이 유일한 인자였으며 HBeAg치가 지속적 감소 후에 다시 증가하는 양상을 보인 경우에는 HBV DNA의 재양전보다 더 빨리 breakthrough을 예측할 수 있었다.
Hebb's other postulate at work on words
Authors: Joaqu&iacute;n M. Fuster
Journal: Behavioral and Brain Sciences (1999)

The correlative coactivation of sensory inputs, Hebb's “second rule,” probably plays a critical role in the formation of word representations in the neocortex. It is essential to the acquisition of word meaning. The acquisition of semantic memory is inseparable from that of individual memory, and therefore the two probably share the same neural connective substrate. Thus, “content” words are represented mainly in postrolandic cortex, where individual perceptual memories are also represented, whereas “action” words are represented in frontal cortex, with executive memories. The activation of a memory network may not necessarily entail the high-frequency oscillatory firing of its cells, though reverberation remains a plausible mechanism of short-term memory.
Contractile arrest increases sarcoplasmic reticulum calcium uptake and SERCA2 gene expression in cultured neonatal rat heart cells.
Authors: J WBassani, MQi, A MSamarel, D MBers
Journal: Circulation Research (1994)

We developed protocols with intact cultured neonatal rat myocytes to directly evaluate the function of the sarcoplasmic reticulum (SR) Ca-ATPase (or SERCA2), Na-Ca exchange (Na-CaX), and slow Ca transport systems (mitochondria and sarcolemmal Ca-ATPase). Spontaneously beating control cells were compared with cells cultured for 2 days in the presence of verapamil (verapamil-arrested cells, VA). Intracellular calcium (Cai) transients were measured by use of indo-1 during (1) spontaneous twitches, (2) contractures induced by rapid application of caffeine (CafC, with and without Nao), and (3) twitches induced by brief depolarizations with high [K]o solution (K-twitches). We also measured mRNA levels for the SR Ca-ATPase and Na-CaX in the same experimental preparations. The t1/2 for [Ca]i decline when both the SR Ca uptake and Na-CaX were prevented was the same for control and VA cells (approximately 20 seconds), indicating unaltered slow Ca transport systems. Similarly, there was no significant difference in ...
Occurrence of Pseudopyloric Metaplasia in Atrophic Gastritis Patients
Authors: G Esposito, E Dilaghi, F Baldaro, E Lahner
Journal: Endoscopy (2021)

Aims Pseudopyloric metaplasia (PPM) is a metaplastic transformation resulting in pyloric type glands in the gastric oxyntic mucosa that mainly occurs in atrophic gastritis. Our study aims to assess the occurrence of PPM and clinical and histopathological features in patients corpus atrophic gastritis (CAG).
Pressure-induced vasoconstriction of renal microvessels in normotensive and hypertensive rats. Studies in the isolated perfused hydronephrotic kidney.
Authors: KHayashi, MEpstein, RLoutzenhiser
Journal: Circulation Research (1989)

The capacity of small arteries to respond to increased intravascular pressure may be altered in hypertension. In the kidney, hypertension is associated with a compensatory shift in the autoregulatory response to pressure. To directly determine the effects of established hypertension on the renal microvascular response to changes of perfusion pressure, we evaluated pressure-induced vasoconstriction in hydronephrotic kidneys isolated from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Vessel diameters of interlobular arteries (ILAs) and afferent and efferent arterioles were determined by computer-assisted videomicroscopy during alterations in renal arterial pressure (RAP) from 80 to 180 mm Hg. Increased RAP induced a pressure-dependent vasoconstriction in preglomerular vessels (afferent arterioles and ILAs), but not in postglomerular vessels (efferent arterioles). The calcium antagonist nifedipine prevented pressure-induced afferent arteriolar vasoconstriction with a similar half...
Interruption of sympathetic and vagal-mediated afferent responses by transmural myocardial infarction.
Authors: M JBarber, T MMueller, B GDavies, R MGill, D PZipes
Journal: Circulation (1985)

We have demonstrated previously that sympathetic and vagal afferents travel in an apical-to-basal course in the heart, and can be stimulated selectively with epicardial applications of bradykinin and nicotine, respectively. In this study we tested the hypothesis that transmural myocardial infarction interrupts sympathetic and vagal afferent fibers traveling through the infarction and produces regions of afferent denervation in areas apical to the infarction. In open-chest, chloralose-anesthetized dogs, transmural myocardial infarction was created by embolizing a diagonal branch of the left anterior descending coronary artery with a vinyl latex solution that was injected directly into the artery and hardened rapidly. The transmural nature of the infarction was verified by the nitro blue tetrazolium staining technique for dehydrogenase enzymes. Epicardial applications of bradykinin (5 micrograms) and nicotine (50 micrograms) were used to stimulate chemically sensitive sympathetic and vagal afferent nerve en...
102P Primary results from the China cohort of IMpower132: Atezolizumab (atezo) + carboplatin (carbo) or cisplatin (cis) + pemetrexed (pem) as first-line therapy in advanced NSCLC
Authors: S. Lu, J. Fang, Z. Wang, Y. Fan, Y. Liu, J. He, B. Cao, J. Zhou, J. Hu, J. Xia, W. Liu, J. Shi, J. Yi, L. Cao
Journal: Journal of Thoracic Oncology (2021)
Transcatheter ablation of posteroseptal accessory pathways using a venous approach and radiofrequency energy.
Authors: A ADhala, S SDeshpande, SBremner, SHempe, J SSra, ZBlanck, MAkhtar, M RJazayeri
Journal: Circulation (1994)

BACKGROUNDThe efficacy of transcatheter ablation of atrioventricular (AV) accessory pathways (APs) located in the posteroseptal region using a right atrial approach and radiofrequency energy was evaluated.METHODS AND RESULTSFifty consecutive patients with APs in the posteroseptal region underwent radiofrequency catheter ablation. Manifest preexcitation was present in 36 patients and a concealed AP in 14. In 18 patients (group 1), the ventriculoatrial (VA) interval during orthodromic tachycardia was prolonged by 21 +/- 7 milliseconds (range, 10 to 30 milliseconds) with functional left bundle-branch block. In 16 patients (group 2), functional left bundle-branch block caused no VA interval prolongation. The remaining 16 patients (group 3) had no inducible left bundle-branch block during orthodromic tachycardia. Functional right bundle-branch block was induced in 30 patients with no effect on the VA interval. In group 1, of 14 patients with manifest preexcitation during sinus rhythm, 10 patients had a positiv...
Associations of resting heart rate with concentrations of lipoprotein subfractions in sedentary men.
Authors: P TWilliams, W LHaskell, K MVranizan, S NBlair, R MKrauss, H RSuperko, J JAlbers, BFrey-Hewitt, P DWood
Journal: Circulation (1985)

In major prospective studies it has been reported that high heart rate at rest predicts the development of coronary heart disease (CHD) or cardiovascular disease (CVD) in men, but the mechanisms producing these relationships are unknown. Since lipoprotein levels contribute strongly to the risk of CHD and CVD, we examined the relationship of resting heart rate to plasma concentrations of high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoproteins, apolipoprotein (apo) A-I and A-II, and serum concentrations of lipoprotein subfractions in 81 men to determine if atherogenic lipoproteins could potentially induce the reported association of heart rate with development of CHD or CVD. The significant (p less than or equal to .05) Spearman's correlations for resting heart rate vs HDL2 mass (rs = -.24), HDL3 mass (rs = -.40), HDL cholesterol (rs = -.36), apo A-I (rs = -.29), triglycerides (rs = .31), VLDL cholesterol (rs = .24), VLDL mass (rs = .27), and LDL mass of Sof 0-7 subfraction (rs = .30...
Coronary reserve is depressed in postmyocardial infarction reactive cardiac hypertrophy.
Authors: RKaram, B PHealy, PWicker
Journal: Circulation (1990)

After a myocardial infarction (MI), the remaining myocardium undergoes a compensatory reactive hypertrophy. Although coronary perfusion to the surviving myocardium can be an important determinant of cardiac function in this setting, there are no available data regarding myocardial blood flow in reactive hypertrophy. Accordingly, we measured coronary blood flow and reserve using radioactive microspheres in rats 4 weeks after induction of an MI by ligation of the left coronary artery. Maximal coronary dilation was induced by Carbochrome, a potent coronary vasodilator, infused at a rate of 0.45 mg/kg/min up to a total dose of 12 mg/kg. Sham-operated rats served as controls. All animals in the infarct group had a large MI affecting 30-51% (average, 41%) of the left ventricle. Left ventricular end-diastolic pressure was significantly elevated (30 +/- 6.5 vs. 8.0 +/- 2.5 mm Hg in sham-operated rats, p less than 0.01) and baseline hemodynamic indexes of cardiac performance were significantly (p less than 0.01) r...
TCTAP A-010 Different Strategies in Thrombus Management in ST-Segment Elevation Myocardial Infarction: Is Thrombosuction No Longer Relevant?
Authors: Debdatta Bhattacharyya, Koushik Dasgupta, Babasaheb Deshmukh, Ayan Kar
Journal: Journal of the American College of Cardiology (2021)
Echocardiographic patterns of ventricular contraction in the Wolff-Parkinson-White Syndrome.
Authors: HHishida, ISotobata, YKoike, MOkumura, YMizuno
Journal: Circulation (1976)

Echocardiograms of 52 patients with the Wolff-Parkinson-White (WPW) syndrome were investigated. Abnormal patterns of motion were observed in the left ventricular posterior wall (LVPW) and the interventricular septum (IVS). The abnormal LVPW motion was presumably specific for the syndrome and included early onset of the anterior motion which preceded the first heart sound (S1) and a premature peak formation of the anterior displacement which occurred before the second heart sound. The latter was usually followed by a second lower peak. These findings seem to suggest that both contraction and relaxation of LVPW begin earlier than normal due to ventricular pre-excitation initiated at or near the LVPW. The IVS abnormality characteristic of the syndrome was a posterior protrusion, the onset of which preceded S1. Subsequent motion of IVS was either paradoxical or hypokinetic during ejection. These IVS abnormalities were quite similar to those observed in left bundle branch block. The abnormal LVPW motion was ob...
Multimodal Approach for Esophageal Duplication CYST Diagnosis
Authors: A Taleb, N Roshdy, A Montasser, M Madbouly, M Ibrahim
Journal: Endoscopy (2021)

Esophageal duplications cysts are rare congenital malformations that result in a cystic lesion in the esophagus. While most patients are asymptomatic, dysphagia may occur due to compression of the esophagus. On endoscopy, these lesions may be indistinguishable from more ominous diagnoses such as lipoma, leiomyoma and gastrointestinal stromal tumor (GIST). We report a case of successful detection of an esophageal duplication cyst using a range of modalities including: upper endoscopy, CT, endoscopic ultrasound and fine needle aspiration.
Endoscopic Bilateral Drainage Techniques of Malignant Hilar Biliary Obstruction: Stent-In-Stent or Side-By-Side? A Systematic Review and Meta-Analysis
Authors: GMV de Souza, IB Ribeiro, MP Funari, DTH de Moura, MVCV Scatimburgo, JR de Freitas Júnior, R Baracat, ETH de Moura, WM Bernardo, EGH de Moura
Journal: Endoscopy (2021)

Aims Malignant biliary tract tumors are unresectable for up to 80 % of cases. Biliary drainage is often required when dealing with a malignant hilar biliary obstruction (MHBO). There are two types of drainage: stent-in-stent (SIS) and side-by-side (SBS), which differ from each other and have distinct advantages. The aim of this meta-analysis was to compare both techniques regarding efficacy and safety.
Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.
Authors: M RTschudi, LCriscione, DNovosel, KPfeiffer, T FLüscher
Journal: Circulation (1994)

BACKGROUNDCoronary artery disease is an important complication of hypertension. Therefore, the effects of antihypertensive therapy on the endothelial nitric oxide (NO)/L-arginine pathway and vascular smooth muscle were studied in left anterior descending coronary arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Angiotensin II (AT1) receptor antagonists CGP 48369 and valsartan, angiotensin-converting enzyme inhibitor benazepril HCl, and calcium antagonist nifedipine were used as antihypertensive agents.METHODS AND RESULTSRings were examined in myograph systems for isometric tension recording. In untreated WKY and SHR rings, acetylcholine (10(-9) to 10(-5) mol/L) but not bradykinin, substance P (both 10(-6) mol/L), or thrombin (1 U/mL) induced comparable endothelium-dependent relaxations. These relaxations were markedly decreased by NG-monomethyl-L-arginine (10(-4) mol/L) and fully prevented by N omega-nitro-L-arginine methyl ester (10(-4) mol/L) or methylene blue (10(-5) mol/L...
Does reperfusion extend necrosis? A study in a single territory of myocardial ischemia--half reperfused and half not reperfused.
Authors: WGanz, IWatanabe, KKanamasa, JYano, D SHan, M CFishbein
Journal: Circulation (1990)

The purpose of this study was to confirm or disprove the existence of reperfusion-induced extension of necrosis. To avoid the effect of the variability of collateral circulation when groups of dogs are compared, we compared the effect of reperfusion and nonreperfusion on myocardial necrosis in a single ischemic territory, half of which was reperfused and half of which was not. The left anterior descending coronary artery (LAD) territory between its last diagonal branch and the apex was studied because it was found to have uniform collateral blood flow. In 20 dogs, the LAD was occluded for 90-240 minutes to produce necrosis of different degrees of transmurality. Before release of this occlusion, the LAD was occluded distally halfway to the apex to keep the distal half nonreperfused. After 5 minutes of proximal reperfusion. Monastral blue dye was injected into the left atrium for demarcation of the reperfused region, and the heart was arrested, excised, cut parallel to the LAD, and placed into triphenyl tet...
Vibrational analysis of bioprosthetic heart valve leaflets using numerical models: effects of leaflet stiffening, calcification, and perforation.
Authors: M SHamid, H NSabbah, P DStein
Journal: Circulation Research (1987)

The fundamental natural frequency of the closed cusps of porcine bioprosthetic valves, fabricated from the normal leaflets of pig aortic valves, was estimated using a finite element model. Both normal and stiffened leaflets were considered in the vibrational analysis. The effects of conditions that simulated degeneration, such as stiffening, central perforation, a tear, calcium deposits in the commissural attachments, and combinations of these were determined. The primary frequency of vibration of the normal leaflets was within the range of the dominant frequency of the heart sounds determined clinically by spectral analysis of the recorded phonocardiogram. If only one leaflet was stiffened or calcified, there was only a marginal change of frequency. With stiffening and calcification of the commissures of all 3 leaflets, the frequency of vibration increased. Introduction of a tear in a single leaflet of a stiffened and calcified valve markedly reduced the fundamental frequency. In view of the relation bet...
Mechanical matching of the left ventricle with the arterial system in exercising dogs.
Authors: KHayashida, KSunagawa, MNoma, MSugimachi, HAndo, MNakamura
Journal: Circulation Research (1992)

We investigated how changes in ventricular contractility and arterial properties associated with exercise influence the energy transmission from the left ventricle to the arterial system. On six chronically instrumented dogs preconditioned to run on a treadmill, we imposed exercise loads of various degrees by altering the speed and slope of the treadmill (up to 7 km/hr and 20% slope). We evaluated ventricular contractility by end-systolic elastance (Ees) and arterial properties in terms of the effective arterial elastance (Ea). Ea was estimated by the ratio of mean aortic pressure to stroke volume. With exercise, Ees significantly increased from 7.6 +/- 1.7 to 10.9 +/- 2.6 mm Hg/ml (p less than 0.005), and Ea tended to increase from 4.9 +/- 1.4 to 6.7 +/- 1.8 mm Hg/ml (p = 0.068), whereas the ratio of Ea to Ees remained fairly constant (from 0.69 +/- 0.26 to 0.63 +/- 0.21, NS). The mechanical optimality index, defined as the ratio of stroke work to its theoretically derived maximal value, was 0.93 +/- 0.0...
Detection of latent function in acutely ischemic myocardium in the dog: comparison of pharmacologic inotropic stimulation and postextrasystolic potentiation.
Authors: S HDyke, C WUrschel, E HSonnenblick, RGorlin, P FCohn
Journal: Circulation Research (1975)

In poorly perfused myocardium with resultant ischemic dysfunction, augmentation of contractility can, under certain conditions, be used to detect viable but ordinarily noncontracting muscle. Two methods of inotropic augmentation, pharmacologic inotropic stimulation and postextrasystolic potentiation (PESP), were studied in acutely ischemic canine myocardium with controlled coronary blood flow. A caliper length gauge to record segmental shortening and left ventricle pressure was used to construct pressure-length loops. Acute regional ischemia depressed segmental function: early segmental shortening decreased (-20 plus or minus 0.02% [SE]) and frequent dyskinesia occurred. Restoring coronary blood flow corrected segmental shortening to control levels. During acute regional ischemia, PESP consistently augmented segmental function (+49 plus or minus 0.03%) and abolished dyskinesia. Pharmacologic inotropic stimulation with isoproterenol or calcium administered into the coronary arteries did not produce a compa...
Response to Comment on Gerbaud et al. Glycemic Variability Is a Powerful Independent Predictive Factor of Midterm Major Adverse Cardiac Events in Patients With Diabetes With Acute Coronary Syndrome. Diabetes Care 2019;42:674–681
Authors: Bogdan Catargi, Romain Darier, Michel Montaudon, Marie-Christine Beauvieux, Christine Coffin-Boutreux, Pierre Coste, Hervé Douard, Alexandre Ouattara, Edouard Gerbaud
Journal: Diabetes Care (2019)

We thank Yang and Hu (1) for their interest in our study (2) on the prognostic value of glycemic variability (GV) in patients with diabetes with acute coronary syndrome (ACS).

First, with respect to the comment (1) by Yang and Hu, a Cox proportional hazards regression analysis was carried out additionally including all similar variables as previously studied (2). This multivariable analysis demonstrated that GV still remains the strongest independent predictive factor for midterm major adverse cardiovascular events (MACE) in …
Fully human antibody V<sub>H</sub>domains to generate mono and bispecific CAR to target solid tumors
Authors: Guanmeng Wang, Xin Zhou, Giovanni Fucà, Elena Dukhovlinova, Peishun Shou, Hongxia Li, Colette Johnston, Brian Mcguinness, Gianpietro Dotti, Hongwei Du
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Chimeric antigen receptor (CAR) T cells are effective in B-cell malignancies. However, heterogeneous antigen expression and antigen loss remain important limitations of targeted immunotherapy in solid tumors. Therefore, targeting multiple tumor-associated antigens simultaneously is expected to improve the outcome of CAR-T cell therapies. Due to the instability of single-chain variable fragments, it remains challenging to develop the simultaneous targeting of multiple antigens using traditional single-chain fragment variable (scFv)-based CARs. Methods We used Humabody V H domains derived from a transgenic mouse to obtain fully human prostate-specific membrane antigen (PSMA) V H and mesothelin (MSLN) V H sequences and redirect T cell with V H based-CAR. The antitumor activity and mode of action of PSMA V H and MSLN V H were evaluated in vitro and in vivo compared with the traditional scFv-based CARs. Results Human V H domain-based CAR targeting PSMA and MSLN are stable and functional both in vitro and in vivo. V H modules in the bispecific format are capable of binding their specific target with similar affinity as their monovalent counterparts. Bispecific CARs generated by joining two human antibody V H domains can prevent tumor escape in tumor with heterogeneous antigen expression. Conclusions Fully human antibody V H domains can be used to generate functional CAR molecules, and redirected T cells elicit antitumoral responses in solid tumors at least as well as conventional scFv-based CARs. In addition, V H domains can be used to generate bispecific CAR-T cells to simultaneously target two different antigens expressed by tumor cells, and therefore, achieve better tumor control in solid tumors.