Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. ...One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques.
The ability to deliver therapy tailored to specific cellular targets at the precise locus in which it would have its greatest impact is a profound development in anti-cancer treatment. Although immune checkpoint inhibitors have an improved tolerability profile relative to cytotoxic chemotherapy and whole beam radiation, severe immune-related adverse events have emerged as a potential limitation. These include pneumonitis, pancreatitis, and colitis, which are relatively infrequent but can limit therapeutic options for some patients. Intratumor injection of oncolytic viruses, in contrast, has a markedly lower rate of serious adverse effects and perhaps greater specificity to target tumor cells. Early stage clinical trials using oncolytic viruses show induction of effector anti-tumor immune responses and suggest that such therapies could also morph and redefine both the local target cells' niche as well as impart distant effects on remote cells with a similar molecular profile.
It is imperative for the modern immuno-oncologist to understand the biological processes underlying the immune dysregulation in cancer as well as the effects, uses, and limitations of oncolytic viruses. It will be with this foundational understanding that the future of oncolytic viral therapies and their delivery can be refined to forge future horizons in the direct modulation of the tumor bed.
To assess the safety and technical success of percutaneous cryoablation (PCA) without pyeloperfusion in 94 patients with central renal tumors.
A retrospective review of all central renal tumors ...treated by PCA without pyeloperfusion was performed. Central tumors were defined as those involving the renal sinus fat on preprocedural cross-sectional imaging. Patient demographics and baseline tumor characteristics were recorded. The details of the PCA procedure, primary and secondary technical success, rates of local recurrence, adverse events (AEs), cancer-specific survival (CSS), and overall survival (OS) were compiled.
Ninety-four patients (48 females 51%; mean age, 68.2 years range, 38-87 years) with 94 central renal tumors were included. The mean maximal tumor diameter and mean RENAL nephrometry score were 37 mm (range, 15-67 mm) and 8 (range, 4-11), respectively. Primary technical success was achieved in 94% (n = 88) of procedures. Of the patients who did not achieve primary technical success, 3 underwent successful repeat PCA (secondary technical success, 97%; n = 91/94). The other 3 patients were surveilled for residual disease. Twenty-four patients (26%) required hydrodissection during PCA. Six patients (6%) experienced major AEs after PCA including hemorrhage requiring embolization (n = 3), hemorrhage requiring transfusions with admission (n = 2), and perinephric abscess necessitating drain placement (n = 1). Twenty-two patients (23%) experienced minor AEs. Nine patients (10%) experienced local recurrence during the follow-up period. OS was 94% (n = 88/94), whereas CSS was 98% (n = 92/94) during the study follow-up period (mean, 16 months range, 1-102 months).
PCA of central renal tumors appears to be safe with high rates of technical success, even without the use of pyeloperfusion.
Silicon nanowires (SiNWs) with unique band structure and transport properties are considered potential candidates for future nanoelectronics devices such as field-effect transistors (FETs). We ...present a model of a SiNW-FET comprising
⟨
100
⟩
silicon atomic wires with a cylindrical-shaped metallic gate wrapped around the wires. For this purpose, we report on the energy band structure and density of states of SiNWs of diameters 5.93 Å, 9.71 Å and 13.55 Å with
⟨
100
⟩
cleavage orientation by employing generalized gradient approximation and meta-generalized gradient approximation as well as the semi-empirical extended-Huckel model. Moreover, the transmission and transport properties of doped and undoped SiNWs of diameter 5.93 Å with and without vacancy defects are explored using a non-equilibrium green function approach with self-consistent calculations. The corresponding
I
–
V
characteristics of the proposed cylindrical-shaped metallic-gate SiNW-FET under a specific gate voltage are presented. Our results show that the undoped SiNWs with vacancy defects on the surface are more suitable candidates for nanoelectronic device applications such as FETs in contrast to their counterparts with vacancies at the center.
Object tracking has gained importance in various applications especially in traffic monitoring, surveillance and security, people tracking, etc. Previous methods of multiobject tracking (MOT) carry ...out detections and perform object tracking. Although not optimal, these frameworks perform the detection and association of objects with feature extraction separately. In this article, we have proposed a Super Chained Tracker (SCT) model, which is convenient and online and provides better results when compared with existing MOT methods. The proposed model comprises subtasks, object detection, feature manipulation, and using representation learning into one end-to-end solution. It takes adjacent frames as input, converting each frame into bounding boxes’ pairs and chaining them up with Intersection over Union (IoU), Kalman filtering, and bipartite matching. Attention is made by object attention, which is in paired box regression branch, caused by the module of object detection, and a module of ID verification creates identity attention. The detections from these branches are linked together by IoU matching, Kalman filtering, and bipartite matching. This makes our SCT speedy, simple, and effective enough to achieve a Multiobject Tracking Accuracy (MOTA) of 68.4% and Identity F1 (IDF1) of 64.3% on the MOT16 dataset. We have studied existing tracking techniques and analyzed their performance in this work. We have achieved more qualitative and quantitative tracking results than other existing techniques with relatively improved margins.
Colletotrichum
lindemuthianum
causes bean anthracnose, one of the deadliest diseases that reduces the bean production significantly. Being an ascomycete and ranking among the top important fungi, the ...specific causes of its significant variation that renders resistant cultivars inefficient warrant further investigation. In India, several studies have been carried out to examine pathogen diversity. However, mechanisms of the genetic variation, on the other hand, remain elusive. To gain insight, a study was conducted, focusing on the role of mitotic recombination in the development of variability. Vegetative compatibility groups (VCGs), which divide the population into groups that can exchange genetic information via heterokaryosis and the parasexual cycle, are of special importance to asexual fungi. One of the strategies utilized in study on vegetative compatibility groups is obtaining
nit
mutants. The purpose of this study was to collect heterokaryons from diverse
C. lindemuthianum
races and isolates, group them into VCGs and examine their genetic variability using the
nit
mutant system. Twenty single spore isolates yielded 120
nit
mutants and were assigned to one of six phenotypic classes:
nit
1,
nit
2,
nit
3,
nit
5/6,
nit
M and CRN (chlorate resistant nitrate utilizing). At the same time, 78 mutants were chosen for anastomosis grouping and were divided into 11 VCGs. We obtained nine (HK 1, HK 2, HK 3, HK 4, HK 5, HK 6, HK 7, HK 8 and HK 9) heterokaryons. Seven of the nine heterokaryons were unstable after eight successive subculturing. Prototrophic development is believed to be supported by continuous anastomosis between nearby homokaryotic hyphae, which restores the heterokaryotic condition. As a result, we speculate that the
C. lindemuthianum
heterokaryons created are more viable than stable. This study identifies the source of bean anthracnose pathogen diversity in northern India, indicating that we must continue to monitor pathogenic variability and focus our breeding efforts on developing anthracnose-resistant bean genotypes.
Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the ...development of acquired resistance during the immunotherapy limit their long-term effectiveness. The underlying cause of acquired resistance is poorly understood; potential management strategies for patients with acquired resistance are even less clear. Here, we report the case of a 75-year-old female smoker with cough, fatigue, and weight loss that was found to have an 8.6 cm right upper lobe lung lesion with local invasion, adenopathy, and a malignant pericardial effusion. This lesion was biopsied and identified to be cT3N3M1b squamous cell cancer of the lung without any recognizable PD-L1 expression on tumor cells. For her metastatic NSCLC, the patient underwent two lines of conventional chemotherapy before initiation of combination immunotherapy with an anti-PD-L1 and anti-CTLA-4 antibody. Though she initially achieved a response, she thereafter progressed and developed immunotherapy resistant lymph nodal metastasis. While cervical lymph nodes could be surgically removed, another metastasis in an aortocaval area required a more sensitive therapy like thermal ablation. The aortocaval node was partially treated with a single treatment of cryotherapy and demonstrated durable complete response. Cryotherapy for checkpoint immunotherapy resistant metastasis appears to be a safe and feasible treatment for treating metastatic disease in non-small cell lung cancer. The prospect of cryotherapy adjuvancy may enable local control of metastatic disease after initial response to immune checkpoint immunotherapy and may impact on overall outcomes.
Melanoma is among the most prevalent neoplasms diagnosed annually with the vast majority arising from a cutaneous origin. Though there are described metastases to the gastrointestinal tract, there ...are only rare descriptions of primary gastrointestinal melanoma. Both diagnosis and management of this unique population can be challenging given the infrequency with which it occurs. To follow is the third reported case of transverse colon primary melanoma with a description of multimodality treatment with surgery, chemotherapy, and immunotherapy.
Summary Mononucleosis and mononucleosis-like illnesses comprise a significant proportion of pediatric and adolescent infectious illnesses. By far, the most common cause of these illnesses is ...Epstein–Barr virus, which causes mononucleosis, and a distant second is cytomegalovirus, which is the most common cause of mononucleosis-like illnesses. This case provides an interesting juxtaposition of laboratory findings of an adolescent who was heterophile antibody positive but acute Epstein–Barr virus antigen–antibody negative. A subsequent immunologic assay resulted in a final diagnosis of an acute cytomegaloviral infection. This is, to our knowledge, the first such report in the literature.
Abstract Because of advancements in fetal imaging, anatomic variants of the genitourinary tract are most often discovered in the antenatal period. As such, general internists are less likely to ...encounter adult patients with previously undiagnosed anatomic abnormalities of the renal collecting system, such as duplicated kidneys. These abnormalities put patients at risk for urinary obstruction and recurrent infections of the urinary tract. We report the case of a 40-year-old diabetic patient with a previously undiagnosed duplex kidney who had recurrent episodes of diabetic ketoacidosis triggered by urinary tract infections. She was ultimately found to have abscess formation in the duplicated renal moiety. We reviewed the epidemiology, diagnosis, and management of duplex kidneys. We also reviewed the indications for renal imaging in adult patients with similar clinical presentations.
To compare the incidence of sterile endophthalmitis after intravitreal triamcinolone acetonide injections during a 6 month period in 2006 to the same period in 2005 and determine the incidence after ...switching to intravitreal preservative-free triamcinolone acetonide.
Retrospective multicenter interventional case series in which patients receiving intravitreal triamcinolone acetonide at three institutions from March 2005 to August 2005 and from March 2006 to August 2006 and intravitreal preservative-free triamcinolone acetonide from late summer 2006 through February 2007 were reviewed for the development of sterile endophthalmitis.
From March 2005 to August 2005, the rate of sterile endophthalmitis was 0% at all institutions. From March 2006 to August 2006, a statistically significant increase in sterile endophthalmitis was seen at all institutions with frequencies of 3.5% to 6.3% (P < 0.001). With transition to preservative-free triamcinolone acetonide, sterile endophthalmitis over the next 6 months decreased to 0% at two sites and to 2.5% (from 5.5%) at the third institution (P < 0.009).
A statistically significant increase in the rate of sterile endophthalmitis after intravitreal triamcinolone acetonide was seen in a 6 month period in 2006 when compared with the same period in 2005. Transition to preservative-free triamcinolone acetonide produced a frequency of sterile endophthalmitis similar to 2005.
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