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Background: The role of adjuvant chemotherapy in early-stage small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) remains unclear, particularly for small tumors. This study assesses the survival benefits of adjuvant chemotherapy after surgical resection with a novel focus on tumors less than 1 cm. Materials and methods: Data from the National Cancer Database (NCDB) was extracted for patients with SCLC (n = 11,962) and LCNEC (n = 6821) who underwent surgical resection between 2004 and 2020. Exclusion criteria were limited survival (< 30 days), positive lymph nodes, distant metastases, large tumors (> 5 cm), residual microscopic disease, and neoadjuvant therapy. The primary outcome was overall survival (OS) from diagnosis, which was evaluated using Kaplan–Meier methods and multivariate Cox regression analyses. A propensity score matching (PSM) analysis was performed to compare outcomes in patients with SCLC and tumors ≤ 1 cm who received adjuvant chemotherapy versus surgery alone. Results: The study involved 4114 SCLC and 3954 LCNEC patients. Adjuvant chemotherapy was associated with a significant increase median OS in both SCLC (6.26 vs. 4.18 years; p < 0.001) and LCNEC (7.02 years vs. 4.89 years; p < 0.001), while also being an independent predictor of better OS in SCLC (HR: 0.74) and LCNEC (HR: 0.75) (p < 0.001). The benefit was more noticeable in tumors ≤ 1 cm, showing a significant OS increase after PSM (median OS 7.34 vs. 5.02 years; p = 0.0048). Conclusion: Adjuvant chemotherapy after surgery is associated with improved overall survival in stage I SCLC and LCNEC, particularly in SCLC tumors of 1 cm or less. [ABSTRACT FROM AUTHOR]

Small cell osteosarcoma (SCOS) is a rare variant of conventional osteosarcoma, characterized by tumor cells of small size and uniform morphology, which can lead to diagnostic confusion with other small cell tumors, requiring a detailed diagnostic approach. The manifestation in a child adds a degree of complexity, as the management of malignant tumours in paediatric patients requires specific considerations to minimize the long-term side effects of oncological treatment and preserve the structural and functional development of the orofacial region. This report concerns an 8-year-old female patient referred to the Oral and Maxillofacial Surgery outpatient clinic with progressive swelling in the right maxillofacial region, initially asymptomatic, but progressing to pain and difficulty chewing. A cone beam computed tomography scan was requested and an incisional biopsy was carried out for histopathological and immunohistochemical analysis, which confirmed the pathological entity. The lesion was then completely resected with a safety margin and the affected area removed to restore functionality and aesthetics. The surgical specimen was sent for further histopathological analysis, which confirmed the diagnosis of SCOS. Detailed immunohistochemical analysis was crucial to the diagnosis, and a comprehensive surgical approach was indicated given the aggressive behavior of the lesion. This report emphasizes the importance of an integrated multidisciplinary approach, combining oncology, pathology and oral and maxillofacial surgery. [ABSTRACT FROM AUTHOR]

Abstract Background The role of adjuvant chemotherapy in early-stage small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) remains unclear, particularly for small tumors. This study assesses the survival benefits of adjuvant chemotherapy after surgical resection with a novel focus on tumors less than 1 cm. Materials and methods Data from the National Cancer Database (NCDB) was extracted for patients with SCLC (n = 11,962) and LCNEC (n = 6821) who underwent surgical resection between 2004 and 2020. Exclusion criteria were limited survival ( 5 cm), residual microscopic disease, and neoadjuvant therapy. The primary outcome was overall survival (OS) from diagnosis, which was evaluated using Kaplan–Meier methods and multivariate Cox regression analyses. A propensity score matching (PSM) analysis was performed to compare outcomes in patients with SCLC and tumors ≤ 1 cm who received adjuvant chemotherapy versus surgery alone. Results The study involved 4114 SCLC and 3954 LCNEC patients. Adjuvant chemotherapy was associated with a significant increase median OS in both SCLC (6.26 vs. 4.18 years; p

This paper presents a generic spectrum reuse model (GSRM) to reuse millimeter wave (mmWave) and terahertz (THz) spectrum in multi-band-enabled small cells located within multi-story buildings to address high spectral and energy efficiencies of sixth-generation (6G) mobile networks. For mmWave and THz bands, we consider 28 GHz, 142 GHz, 250 GHz, and 300 GHz bands, and each small cell is assumed to be equipped with these multiple bands. In developing GSRM, we first characterize interferences to derive a minimum distance between apartments of co-channel small cells at both intra-floor and inter-floor levels for each band leading to the formation of a 3-dimensional (3D) cluster of apartments such that the whole spectrum of the corresponding band is allocated to small cells within the cluster. The same spectrum is reused further in small cells of all adjacent 3D clusters within the building. We consider a random distribution of small cells within each 3D cluster. Two scenarios are considered where scenario 1 has the same 3D cluster size for each band, and scenario 2 considers different 3D cluster sizes corresponding to the respective band. We formulate the spectral efficiency (SE) and energy efficiency (EE) metrics of the proposed GSRM in a multi-tier network and develop an algorithm to evaluate its SE and EE metrics. With extensive system-wide evaluations, we show that compared to scenario 1, the overall SE and EE in scenario 2 are improved by 33.33% and 4.5%, respectively, and the proposed GSRM can achieve the prospective SE and EE requirements for 6G mobile systems.

Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates. Further mapping with single cell resolution reveals two distinct lineages defined by mutually exclusive expression of ASCL1 or ASCL2. Temporal regulation by groups of transcription factors across developmental stages reveals that cellular reprogramming precedes the induction of neuronal programs. TFAP4 and ASCL1/2 feedback are identified as potential regulators of ASCL1 and ASCL2 expression. Our study provides temporal transcriptional patterns and uncovers pan-tissue parallels between prostate and lung cancers, as well as connections to normal neuroendocrine cell states.

BACKGROUND: Neuroendocrine phenotype is commonly associated with therapy resistance and poor prognoses in small-cell neuroendocrine cancers (SCNCs), such as neuroendocrine prostate cancer (NEPC) and small-cell lung cancer (SCLC). Expression levels of current neuroendocrine markers exhibit high case-by-case variability, so multiple markers are used in combination to identify SCNCs. Here, we report that ACAA2 is elevated in SCNCs and is a potential molecular indicator for SCNCs. METHODS: ACAA2 expressions in tumour xenografts, tissue microarrays (TMAs), and patient tissues from prostate and lung cancers were analysed via immunohistochemistry. ACAA2 mRNA levels in lung and prostate cancer (PC) patients were assessed in published datasets. RESULTS: ACAA2 protein and mRNA levels were elevated in SCNCs relative to non-SCNCs. Medium/high ACAA2 intensity was observed in 78% of NEPC PDXs samples (N = 27) relative to 33% of adeno-CRPC (N = 86), 2% of localised PC (N = 50), and 0% of benign prostate specimens (N = 101). ACAA2 was also elevated in lung cancer patient tissues with neuroendocrine phenotype. 83% of lung carcinoid tissues (N = 12) and 90% of SCLC tissues (N = 10) exhibited medium/high intensity relative to 40% of lung adenocarcinoma (N = 15). CONCLUSION: ACAA2 expression is elevated in aggressive SCNCs such as NEPC and SCLC, suggesting it is a potential molecular indicator for SCNCs.

BACKGROUND: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments. PATIENTS AND METHODS: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution. The primary endpoint was overall survival (OS) based on second-line therapy. Secondary endpoints included objective response rate (ORR) to second-line therapy, PSA response, and time on treatment. RESULTS: Fifty-eight patients (32 de novo NEPC, 26 T-NEPC) from 8 institutions were included. At de novo NEPC or T-NEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 59.2-70.3) and median PSA of 3.0 ng/dL (IQR 0.6-17.9). Following first-line platinum chemotherapy, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) taxane monotherapy, 11 (19.0%) immunotherapy, 10 (17.2%) other chemotherapy, and 6 (16.2%) other systemic therapy. Among 41 evaluable patients, the ORR was 23.5%. The mOS after start of second-line therapy was 7.4 months (95% CI 6.1-11.9). CONCLUSIONS: In this retrospective study, patients with de novo NEPC or T-NEPC who received second-line therapy were treated with wide variety of treatment regimens, reflecting the lack of consensus in this setting. Most patients received chemotherapy-based treatments. Overall prognosis was poor and ORR was low in the second line regardless of treatment choice.

BackgroundThe authors assessed the association between radon decay products (RDP) exposure and histologic types of incident lung cancer in a cohort of 16,752 (91.6% male) Eldorado uranium workers who were first employed from 1932 to 1980 and were followed through 1969-1999.MethodsSubstantially revised identifying information and RDP exposures were obtained on workers from the Port Radium and Beaverlodge uranium mines and from the Port Hope radium and uranium refinery and processing facility in Canada. Poisson regression was conducted using the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VI-type models to estimate the risks of lung cancer by histologic type from RDP exposures and γ-ray doses.ResultsLung cancer incidence was significantly higher in workers compared with the general Canadian male population. Radiation risks of lung cancer for all histologic types (n = 594; 34% squamous cell, 16% small cell, 17% adenocarcinoma) increased with increasing RDP exposure, with no indication of curvature in the dose response (excess relative risk per 100 working level months = 0.61; 95% confidence interval, 0.39-0.91). Radiation risks did not differ by histologic type (p = .144). The best-fitting BEIR VI-type model included adjustments for the significant modifying effects of time since exposure, exposure rate, and attained age. The addition of γ-ray doses to the model with RDP exposures improved the model fit, but the risk estimates remained unchanged.ConclusionsThe first analysis of radiation risks of lung cancer histologic types in the Eldorado cohort supported the use of BEIR VI-type models to predict the future risk of histologic types of lung cancer from past and current RDP exposures.Lay summaryLung cancer survival depends strongly on the cell type of lung cancer. The best survival rates are for patients who have the adenocarcinoma type. This study included 16,752 Eldorado uranium workers who were exposed to radon and γ-ray radiation during 1932-1980, were alive in 1969, and were followed for the development of new lung cancer during 1969-1999. One third of all lung cancers were of the squamous cell type, whereas the adenocarcinoma and small cell types accounted for less than 20% each. Radiation risks of lung cancer among men increased significantly with increasing radon exposure for all cell types, with the highest risks estimated for small cell and squamous cell lung cancers.

Objective: Rare disease. Background: Small cell carcinoma is an aggressive malignant neuroendocrine tumor that most commonly occurs in the lung. Primary small cell carcinoma of the esophagus (PSCCE) is rare and is an aggressive malignancy with poor prognosis and no clear management guidelines. This report describes the case of a 36-year-old man presenting with epigastric pain, dysphagia, and melena due to a primary esophageal small cell carcinoma. Case Report: A 36-year-old presented to the Emergency Department (ED) with epigastric pain associated with food intake. Initial workup was unremarkable, and a presumed clinical diagnosis of reflux esophagitis and peptic strictures was made, prompting empiric treatment with anti-secretory therapies. Despite these therapies, he presented to the emergency room with progressively worsening dysphagia. Endoscopic examination (EGD) revealed a large necrotic mass, and computed tomography (CT) imaging revealed liver metastasis. Biopsies from both the liver and esophageal masses confirmed small cell carcinoma. His clinical course was complicated by a broncho-esophageal fistula, leading to massive hemoptysis, necessitating intubation. Unfortunately, his condition deteriorated rapidly, and he chose to pursue hospice care. He died 3 months after his initial presentation. Conclusions: This report has presented a rare case of primary esophageal small cell carcinoma and our approach to management. We highlight the importance of early diagnosis, supported by histopathology, and the need for management guidelines. [ABSTRACT FROM AUTHOR]

The target of this paper is to show the impact of polarization adaptation on the received signal quality in an outdoor small-cell deployment scenario. The signal-to-interference ratio (SIR) is the key factor in defining the achievable data rate, and the capacity of the cell. At the cell border area, the SIR value is typically low and causes a significant decrease in the system capacity and achievable data rates. These bad SIR areas at the cell border can be improved by using orthogonal polarizations in the neighboring cells rather than using all polarizations over the whole cell coverage area. For the research work of this paper, a series of measurements were carried out to measure a received signal power and a cross polarization discrimination (XPD) ratio while the signal is transmitted and received with a different set of polarizations. In the measurements, we have considered horizontal, vertical, +/− 45° slanted polarizations, and two different environments, urban street and open space, and three frequency bands, 970−1030 MHz, 2000−2030 MHz and 3364−3400 MHz. The measurement results revealed that at a different distance from the transmitter, for horizontal/vertical polarization, the average XPD is around 24.7 dB and 31.7 dB in the urban street and open area environments, respectively. For +/− 45° slanted polarization, the average XPD is around 11.5 dB and 12.1 dB in the urban street and open area environments, respectively. This paper goes on to propose polarization adaptation in each cell, where the primary polarization is valid for the whole service area of the cell, and secondary polarization is only used in close proximity of the base station antenna. Considering the results, it is emphasized that system capacity can be significantly improved by having only one channel with good SIR values compared to multiple channels with bad SIR values. However, MIMO channels with orthogonal polarizations or with spatial multiplexing can be utilized in the closed vicinity of the base station, i.e., in an area with good SIR values. It is shown that the overall cell capacity can be increased by almost 35% by utilizing polarization adaptation compared to MIMO 2 × 2. [ABSTRACT FROM AUTHOR]

To construct a femtocell based ultra-dense network (UDN) is the important way to satisfy the ever-growing data traffic demands in the next generation mobile networks. However, it causes frequent handovers (HOs), thus leading to negative consequences such as increased power consumption and poor quality of service (QoS). This paper represents a research on the uplink handover (UL-HO) being watched recently and proposes a new method to further improve the energy efficient and QoS. First, we confirm the UL-HO mechanism, formulate the power consumption caused by UL-HO and compare downlink handover (DL-HO) with UL-HO in terms of the performance parameters including the power consumption, handover rate (HOR), handover failure rate (HOFR), ping-pong rate (PPR), delay, packet loss rate (PLR) and throughput during handover (HO). Then, it is proved through simulation that the reliable target cell determination scheme considering uplink reference signal received power (UL-RSRP), available bandwidth, direction of user equipment (UE), and admission control is lower in HOR, HOFR, PPR, power consumption, delay and PLR. In particular, we propose a new algorithm to determine the reasonable target cell considering UL-RSRP, available bandwidth and moving direction of UE, thus reducing HOR and PPR. The improved UL-HO scheme can be implemented easily by adding some functions besides the upper-layer protocol, while it can provide a lot of benefits such as reduced power consumption, delay, frequent HOs resulting in reducing HOR and PPR. Accordingly, this can be introduced into 5G as a HO scheme. [ABSTRACT FROM AUTHOR]

Deploying 5G in new and diverse use cases, such as Industry 4.0 and factory automation, requires 5G systems to harmonize with the communication technologies used in these industries. To this end, 3GPP Release 16 and Release 17 have made significant progress in integrating 5G systems with the IEEE 802.1 working group specifications on Time-Sensitive Networking (TSN). This paper explains a method and architecture for supporting TSN over a wireless channel in a 5G network that adds the TSN synchronization function in a Small Cell gNB implementing the TSN Translator function (SC-TT). This TSN-capable small cell provides TSN over the wireless network to synchronize UEs with the Grand Master (GM) using the physical layer signal of the 5G radio frame and the transmission of the GM reference time to provide high-precision synchronization. This paper explores the pivotal role of a Slot Indicator Signal in enhancing synchronization precision, ensuring that the UE-GM synchronization occurs within an exceptionally narrow timeframe as small as 10 ns. [ABSTRACT FROM AUTHOR]

In order to accurately measure the path of the incident particles in front of the target at the CSR outer target terminal, multiple sets of small cell multi-wire drift chamber detectors were developed with a drift cell of 5 mm. The sensitive area of this detector is 80 mm×80 mm, each set of detector includes x, x', y and y' 4 detection electrode surfaces, 2 sets of detection electrode surface wires are perpendicular to each other, and the same direction detection electrode surface wires are misaligned and distributed for providing left and right resolution, the misalignment distance of 2.5 mm for half drift cell, each electrode surface leads to 16 anode wire signals. The front-end electronics uses an amplifier based on the SFE16 chip, a 16-way ASIC signal processing developed by Saclay, France, whose functions include charge-sensitive amplification, shaping and signal screening, and outputting the TOT signal. The TOT signal is input to a data acquisition card based on the HPTDC chip developed by CERN, which records the rising and falling edge times of the TOT signal. The T0 plastic flash detector, placed in front of the drift chamber, provides the onset moment of the incident particles. By subtracting the TOT signal front from T0, the drift time of the incident particle traces in the multi-wire drift chamber can be obtained. The particles incident to the secondary target are physically concerned as heavy particles, so 2 sets of small cell multi-wire drift chambers were used to test the 16O beam position at 400 MeV/u. During the test, the operating gas of the detector was Ar(80%)+CO2(20%), the anode wire voltage was +900 V, and both the field and cathode wires were grounded. After acquiring the test data for data processing, the R-T curves were obtained by simulation with interpolation correction, and the path traces were reconstructed by least squares method. After the data processing, the path residual of the single-layer electrode fitted to obtain the position resolution is 105.9 μm, and the path residual is defined as the difference between the distance from each hitting wire to the fitted straight line and the drift distance measured in each layer. The detection efficiency is 99.3%, and the detection efficiency is defined as the ratio of the count of the multi-wire drift chamber to the count of the plastic flash detector after deducting the background. The above indexes can meet the requirements of most of the nuclear physics experiments of the CSR external target terminal for the localization of the reaction target at this stage.

Deploying 5G in new and diverse use cases, such as Industry 4.0 and factory automation, requires 5G systems to harmonize with the communication technologies used in these industries. To this end, 3GPP Release 16 and Release 17 have made significant progress in integrating 5G systems with the IEEE 802.1 working group specifications on Time-Sensitive Networking (TSN). This paper explains a method and architecture for supporting TSN over a wireless channel in a 5G network that adds the TSN synchronization function in a Small Cell gNB implementing the TSN Translator function (SC-TT). This TSN-capable small cell provides TSN over the wireless network to synchronize UEs with the Grand Master (GM) using the physical layer signal of the 5G radio frame and the transmission of the GM reference time to provide high-precision synchronization. This paper explores the pivotal role of a Slot Indicator Signal in enhancing synchronization precision, ensuring that the UE-GM synchronization occurs within an exceptionally narrow timeframe as small as 10 ns.

In wireless communication, Fifth Generation (5G) Technology is a recent generation of mobile networks. In this paper, evaluations in the field of mobile communication technology are presented. In each evolution, multiple challenges were faced that were captured with the help of next-generation mobile networks. Among all the previously existing mobile networks, 5G provides a high-speed internet facility, anytime, anywhere, for everyone. 5G is slightly different due to its novel features such as interconnecting people, controlling devices, objects, and machines. 5G mobile system will bring diverse levels of performance and capability, which will serve as new user experiences and connect new enterprises. Therefore, it is essential to know where the enterprise can utilize the benefits of 5G. In this research article, it was observed that extensive research and analysis unfolds different aspects, namely, millimeter wave (mmWave), massive multiple-input and multiple-output (Massive-MIMO), small cell, mobile edge computing (MEC), beamforming, different antenna technology, etc. This articles main aim is to highlight some of the most recent enhancements made towards the 5G mobile system and discuss its future research objectives.

BackgroundPrimary small cell carcinoma of the pancreas (SCCP) is a rare malignant neuroendocrine carcinoma (NEC). Typically, it presents with lymphovascular invasion as well as metastasis at the time of diagnosis which portends a dismal prognosis. Treatment is typically based on therapy used for other aggressive NECs such as small cell lung cancer. Although multimodal surgery, radiation and chemotherapy may improve prognosis, the outcome generally remains poor.Case presentationHere we present a primary SCCP managed with neoadjuvant multi-agent chemotherapy combined with radiotherapy and surgery CONCLUSIONS: Multi-disciplinary therapy resulted in an ongoing 28 + month radiographic complete response and overall survival.

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Concurrent chemoradiotherapy (CRT) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). Local therapy—surgery or stereotactic body radiotherapy (SBRT)—with adjuvant chemotherapy may be appropriate for very early (T1-T2, N0) disease. There is variability in the management of these cases, which may lead to variability in patient outcomes. This study aimed to determine practice patterns for the management of very early LS-SCLC in Canada. A survey was developed and distributed to Canadian medical and radiation oncologists specialising in lung cancer. The survey consisted of three sections: (1) physician demographics, (2) general practice approach, and (3) preferred approach for three clinical scenarios (1: peripheral T1 lesion; 2: central T1 lesion; 3: peripheral T2 lesion). Responses were analysed to detect differences across cases and among physician groups. There were 77 respondents. In case 1, assuming medical operability, most respondents (73%) chose surgery and adjuvant chemotherapy, with 19% choosing CRT. CRT was selected by a higher proportion in case 2 (48%) and case 3 (61%) (p < 0.05). If medically inoperable, most chose CRT over local therapy in all cases, with more choosing CRT in case 2 (84%) and case 3 (86%) than in case 1 (55%) (p < 0.05). Subgroup analysis showed a predilection towards CRT in Western Canada and among more experienced physicians, and towards SBRT in Ontario. There is variability in the management of very early LS-SCLC in Canada. CRT remains the most popular strategy in most cases, with surgery preferred for small peripheral lesions. Larger and more central tumours are more likely to be managed with CRT. Variation in practice is correlated with region and physician experience. Our study illustrates the variability in the management of very early LS-SCLC in Canada and highlights the need for more robust investigations into the ideal approach for these patients.

Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies. Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance). The primary objective of phase 1 was to determine the maximum tolerated dose, and the primary end point for each dose-expansion cohort was the objective response rate. Results: A total of 88 patients were enrolled in phase 1 (n = 11) and dose expansion (n = 77) cohorts. Transaminitis was dose-limiting and expansion proceeded with oral vorolanib 200 mg daily combined with intravenous nivolumab 240 mg every 2 weeks. The objective response rate per cohort were as follows: NSCLC naive 33% (five of 15, 95% confidence interval [CI]: 13%–60%), NSCLC primary refractory 5.9% (one of 17, 95% CI: 0%–17.6%), NSCLC acquired resistance 11.1% (two of 18, 95% CI: 0%–27.8%); SCLC 0% (zero of 18), and thymic carcinoma 11% (one of nine, 95% CI: 0%–33%). Disease control rate ranged from 11.1% in SCLC (two of 18, 0%–27.8%) to 66.7 % in thymic carcinoma (six of nine, 95% CI: 33.3%–100%). The most common adverse events were fatigue (32%), aspartate transaminase (27%) and alanine transaminase elevation (25%), and diarrhea (19%). Transaminitis was more common in patients with thymic carcinoma than other tumors. Conclusions: Vorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment.

ObjectiveThe development of effective cancer treatments depends on the availability of cell lines that faithfully recapitulate the cancer in question. This study definitively re-assigns the histologic identities of two ovarian cancer cell lines, COV434 (originally described as a granulosa cell tumour) and TOV-112D (originally described as grade 3 endometrioid carcinoma), both of which were recently suggested to represent small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), based on their shared gene expression profiles and sensitivity to EZH2 inhibitors.MethodsFor COV434 and TOV-112D, we re-reviewed the original pathology slides and obtained clinical follow-up on the patients, when available, and performed immunohistochemistry for SMARCA4, SMARCA2 and additional diagnostic markers on the original formalin-fixed, paraffin-embedded (FFPE) clinical material, when available. For COV434, we further performed whole exome sequencing and validated SMARCA4 mutations by Sanger sequencing. We studied the growth of the cell lines at baseline and upon re-expression of SMARCA4 in vitro for both cell lines and evaluated the serum calcium levels in vivo upon injection into immunodeficient mice for COV434 cells.ResultsThe available morphological, immunohistochemical, genetic, and clinical features indicate COV434 is derived from SCCOHT, and TOV-112D is a dedifferentiated carcinoma. Transplantation of COV434 into mice leads to increased serum calcium level. Re-expression of SMARCA4 in either COV434 and TOV-112D cells suppressed their growth dramatically.ConclusionsCOV434 represents a bona fide SCCOHT cell line. TOV-112D is a dedifferentiated ovarian carcinoma cell line.

Small cell neuroendocrine carcinoma of the cervix (SCNCC) is prone to lymphatic metastasis in the early stage, unique pathological manifestations, easy to recur, and poor prognosis. Data from one case of SCNCC (stage ⅢC1r) is reported. The patient presented with intermittent vaginal bleeding with lower abdominal pain for more than 1 month. Combined with the results of pelvic magnetic resonanace imaging (MRI), total abdominal CT and hysteroscopy with endometrial biopsy, it was diagnosed as SCNCC at ⅢC1r stage. According to the 2022 National Comprehensive Cancer Network (NCCN) guidelines, the patient was given 3 cycles of neoadjuvant chemotherapy (carboplatin plus etoposide neoadjuvant), followed by laparoscopic extensive hysterectomy plus bilateral oophorectomy plus bilateral salpingectomy plus pelvic lymph node dissection plus abdominal para-aortic lymphadenectomy plus antitumor drug intraperitoneal perfusion therapy (nidaplatin flushing the abdominal cavity) plus bilateral ureteral stent implantation. After surgery, the patient was given 3 cycles of chemotherapy again. No recurrence was seen in 13 months of postoperative follow-up. [ABSTRACT FROM AUTHOR]

Background: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare, aggressive cancer most commonly found in the lungs but not exclusively, with a worse prognosis than non-small cell lung carcinomas. Currently, LCNEC patients are treated using small cell and non-small cell protocols. This study aims to use the SEER database to identify demographic, clinical, pathological, and therapeutic factors affecting the prognosis and survival of patients with LCNEC of the lung. Methods: Demographic, clinical, and management data of patients with lung LCNEC were extracted from the SEER database for the period 2000–2018. Results: In the USA, LCNEC has a higher incidence in elderly white men: M:F ratio = 1.2:1, Caucasian: 83.3%, mean age: 67 ± 10.2 years. The most common treatment modality was chemotherapy only: 29.2%, followed by surgery: 21.5% (but in this group the statuses of chemotherapy were unknown), and combination surgery/chemotherapy: 8.8%. The overall and cause-specific 5-year survival was 17.5% (95% CI 16.3–18.8) and 21.9% (95% CI 20.5–23.4), respectively. By treatment, the best 5-year survival was for surgery alone (48%), followed by multimodality therapy (chemo + surgery + radiation) at 35% (95% CI 27–43). Age > 60 years, male gender, size > 7 cm, and nodal and liver metastasis were independent risk factors associated with increased mortality. Conclusion: Lung LCNEC is an aggressive neoplasm most common in older white males that presents at an advanced stage despite small primary tumors. Most patients die within 2 years. The best predictor of survival is surgery with chemotherapy. Given its dismal prognosis, new treatment guidelines are needed for this aggressive cancer. [ABSTRACT FROM AUTHOR]

Interference alignment (IA) ideas have been used into wireless communication in recent years to increase network users' capacity, sum rate, and spectral efficiency. This manuscript presents a multi-variate clustering (MC) for small-cell user communications through dynamic interference alignment (DIA). The clustering and interference alignment process focuses on retaining cluster stability and communication reliability by mitigating interference that is both intra and inter-cluster. The stability of the cluster is evaluated using the quality factor that is useful in mitigating intrauser interference. The inter-user interference is thwarted by classifying the transmitting signal based on time sequence and processing it through an appropriate cancellation matrix and rank-based analysis. Regardless of the user and cell density, the pre-coding process is based on this rank-based examination of the obtained power. The proposed MC-DIA is capable of handling both intra and inter-cluster interference for the allocated channels in the small cell scenarios. Experimentation results showed that the MC-DIA achieved a spectral efficiency of 84%. The proposed scheme performances are verified utilizing the simulation for metrics sum rate, spectral efficiency, and average degree of freedom (DoF). [ABSTRACT FROM AUTHOR]

Transcription factor fusions (TFFs) are present in ∼30% of soft-tissue sarcomas. TFFs are not readily "druggable" in a direct pharmacologic manner and thus have proven difficult to target in the clinic. A prime example is the CIC-DUX4 oncoprotein, which fuses Capicua (CIC) to the double homeobox 4 gene, DUX4. CIC-DUX4 sarcoma is a highly aggressive and lethal subtype of small round cell sarcoma found predominantly in adolescents and young adults. To identify new therapeutic targets in CIC-DUX4 sarcoma, we performed chromatin immunoprecipitation sequencing analysis using patient-derived CIC-DUX4 cells. We uncovered multiple CIC-DUX4 targets that negatively regulate MAPK-ERK signaling. Mechanistically, CIC-DUX4 transcriptionally up-regulates these negative regulators of MAPK to dampen ERK activity, leading to sustained CIC-DUX4 expression. Genetic and pharmacologic MAPK-ERK activation through DUSP6 inhibition leads to CIC-DUX4 degradation and apoptotic induction. Collectively, we reveal a mechanism-based approach to therapeutically degrade the CIC-DUX4 oncoprotein and provide a precision-based strategy to combat this lethal cancer.

PurposeMany rare ovarian cancer subtypes, such as small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), have poor prognosis due to their aggressive nature and resistance to standard platinum- and taxane-based chemotherapy. The development of effective therapeutics has been hindered by the rarity of such tumors. We sought to identify targetable vulnerabilities in rare ovarian cancer subtypes.Experimental designWe compared the global proteomic landscape of six cases each of endometrioid ovarian cancer (ENOC), clear cell ovarian cancer (CCOC), and SCCOHT to the most common subtype, high-grade serous ovarian cancer (HGSC), to identify potential therapeutic targets. IHC of tissue microarrays was used as validation of arginosuccinate synthase (ASS1) deficiency. The efficacy of arginine-depriving therapeutic ADI-PEG20 was assessed in vitro using cell lines and patient-derived xenograft mouse models representing SCCOHT.ResultsGlobal proteomic analysis identified low ASS1 expression in ENOC, CCOC, and SCCOHT compared with HGSC. Low ASS1 levels were validated through IHC in large patient cohorts. The lowest levels of ASS1 were observed in SCCOHT, where ASS1 was absent in 12 of 31 cases, and expressed in less than 5% of the tumor cells in 9 of 31 cases. ASS1-deficient ovarian cancer cells were sensitive to ADI-PEG20 treatment regardless of subtype in vitro. Furthermore, in two cell line mouse xenograft models and one patient-derived mouse xenograft model of SCCOHT, once-a-week treatment with ADI-PEG20 (30 mg/kg and 15 mg/kg) inhibited tumor growth in vivo.ConclusionsPreclinical in vitro and in vivo studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT.

A new compact multifunctional pattern reconfigurable $2\times 2$ antenna array at 3.65 GHz with high gain and 16 (Multiple Input Multiple Output) MIMO modes is proposed. The single-element antenna includes 4 U-slots etched on the ground plane, with orthogonal slot orientations for polarization un-correlation, and fed using a reconfigurable feeding network with 4 PIN diodes. Hence, the single-element antenna is a pattern reconfigurable U-slot antenna with four pattern configurations. The average efficiency of 80%, the peak gain of 9.4 dB, and an overlapped −10 dB impedance-bandwidth of 200 MHz at a resonant frequency of 3.65 GHz in the n78 5G band are achieved. The single-element size is $55.5\times 54$ mm2, $0.66 \lambda _{0} \times 0.65 \lambda _{0}$ . The horizontal and vertical distances between the U-slots in a single-element are 30 mm $(0.36\lambda _{0})$ , and 27 mm $(0.32\lambda _{0})$ , respectively. The $2\times 2$ antenna array of such an element with a 58.5 mm $(0.7\lambda _{0})$ between the elements occupies a volume of $140\times 140\times 21$ mm3. The $2\times 2$ elements provide 16 reconfigurable U-slots with two modes of operation, Array Mode and Multiple-Input-Multiple-Output (MIMO) Mode. For the MIMO Mode, the antenna has a maximum Envelope Correlation Coefficient (ECC) of 0.1194 between the radiation patterns and a minimum isolation of 20 dB between the four ports. For the array Mode, a $4\times 4$ antenna array has a peak gain of 17 dBi, and a beam-steering range of $-50^{\circ} \leq \theta \leq 50^{\circ} $ in the two principle planes. The antenna is suitable for small cell base-station applications.

To cope with unprecedented mobile traffic explosion, various state-of-the-art wireless technologies such as small cell, mmWave, and heterogeneous networks have been intensively studied. Especially, small cell enhances the network capacity at the same area by deploying more next-generation NodeBs (gNBs) with the universal frequency reuse; nevertheless, it increases interference due to the shorter distance between cells requiring more exchange of feedback message for interference management (IM). In this paper, we first propose a practical cellular network architecture, namely EdgeSON, that provides network operators the opportunity to strike a balance between centralized and distributed cellular managements for the enhancement of the network performance with a reasonable feedback information exchange and spatio-temporal power sharing. On top of EdgeSON, we formulate an optimization problem aiming to maximize the time-averaged utility of users constrained by the time average transmit power budget per cluster. Although we exploit Lyapunov optimization to induce slot-by-slot subproblems, one of the transformed subproblems to find a set of power allocation and user scheduling is known as NP-hard. To tackle this issue, we propose a low-complex and practical interference management algorithm, namely IMPowerShare by introducing a critical user and power sharing virtual queue concepts which maximally exploit structural characteristics of EdgeSON to efficiently solve the NP-hard problem. IMPowerShare definitely differs from the existing interference management or spatio-temporal power sharing works in perspectives of practical feedback information exchange in EdgeSON and optimization framework. Finally, via extensive simulations in real gNB topologies in Korea, we verify that IMPowerShare outperforms the existing interference management algorithms in small cell networks.

Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuroendocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease, and the former often arises on a background of androgen deprivation therapy, although it can also arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tissue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with three longitudinal samples over 5 years. Case 2 was a single time point after the development of treatment-related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all samples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, and 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small-cell neuroendocrine and ductal prostatic carcinoma can have a common ancestry. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature. [ABSTRACT FROM AUTHOR]

Simple Summary: Small cell lung cancer (SCLC) remains a difficult-to-treat disease and is associated with a poor prognosis in most patients. Discovering biomarkers and developing targeted treatment options for patients with SCLC has been challenging though there are emerging therapies that are showing promise. A better understanding of the underlying biology and specific molecular targets in SCLC has led to newer drug strategies and combinations that can hopefully lead to better outcomes for our patients. Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody–drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody–drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody–drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients. [ABSTRACT FROM AUTHOR]

Plant growth and development rely heavily on cyclins, which comprise an important class of cell division regulators. D-type cyclins (CYCDs) are responsible for the rate-limiting step of G1 cells. In the plant kingdom, despite the importance of CYCDs in herbaceous plants, there is little knowledge of these proteins in perennial woody plants. Here, the gene of a nucleus-localized cyclin, PsnCYCD1;1 , was cloned from Populus simonii × P. nigra. PsnCYCD1;1 was highly expressed in tissues with active cell division, especially the leaf buds, and could be induced by sucrose and phytohormones. Moreover, overexpression of PsnCYCD1;1 in poplar could stimulate cell division, resulting in the generation of small cells and causing severe morphological changes in the vascular bundles, resulting in 'S'-shaped tortuous stems and curled leaves. Furthermore, transcriptomic analysis revealed that endogenous genes related to cell division and vascular cambium development were significantly up-regulated in the transgenic plants. In addition, using yeast two-hybrid and bimolecular fluorescence complementation assays PsnCDKA1, PsnICK3, and PsnICK5 were identified as proteins interacting with PsnCYCD1;1. Our study demonstrates that PsnCYCD1;1 accelerates plant cell division and participates in secondary growth of vascular bundles in poplar. [ABSTRACT FROM AUTHOR]

Concurrent chemoradiotherapy (CRT) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). Local therapy—surgery or stereotactic body radiotherapy (SBRT)—with adjuvant chemotherapy may be appropriate for very early (T1-T2, N0) disease. There is variability in the management of these cases, which may lead to variability in patient outcomes. This study aimed to determine practice patterns for the management of very early LS-SCLC in Canada. A survey was developed and distributed to Canadian medical and radiation oncologists specialising in lung cancer. The survey consisted of three sections: (1) physician demographics, (2) general practice approach, and (3) preferred approach for three clinical scenarios (1: peripheral T1 lesion; 2: central T1 lesion; 3: peripheral T2 lesion). Responses were analysed to detect differences across cases and among physician groups. There were 77 respondents. In case 1, assuming medical operability, most respondents (73%) chose surgery and adjuvant chemotherapy, with 19% choosing CRT. CRT was selected by a higher proportion in case 2 (48%) and case 3 (61%) (p < 0.05). If medically inoperable, most chose CRT over local therapy in all cases, with more choosing CRT in case 2 (84%) and case 3 (86%) than in case 1 (55%) (p < 0.05). Subgroup analysis showed a predilection towards CRT in Western Canada and among more experienced physicians, and towards SBRT in Ontario. There is variability in the management of very early LS-SCLC in Canada. CRT remains the most popular strategy in most cases, with surgery preferred for small peripheral lesions. Larger and more central tumours are more likely to be managed with CRT. Variation in practice is correlated with region and physician experience. Our study illustrates the variability in the management of very early LS-SCLC in Canada and highlights the need for more robust investigations into the ideal approach for these patients. [ABSTRACT FROM AUTHOR]

The ever-changing diversity of users and high-specification devices have become key concerns for the current mobile network operators. In this paper, a max-min fair dynamic power control algorithm is proposed for the reduction of power consumption at a base station. The spatial heterogeneity of users is achieved by applying a stochastic geometry-based Cox process. The set-up network is analyzed using the mmWave spectrum at deployed small cells (SCs) and with sub-6 GHz in macrocell (MC). The simulated MATLAB results depict an increase in the network sumrate and average user throughput when changing from the fixed power allocation to the proposed dynamic power allocation algorithm. [ABSTRACT FROM AUTHOR]

Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes. We demonstrate that SCCB shares a urothelial origin with other bladder cancer phenotypes by showing that urothelial cells driven by a set of defined oncogenic factors give rise to a mixture of tumor phenotypes, including small cell carcinoma, urothelial carcinoma, and squamous cell carcinoma. Tumor-derived single-cell clones also give rise to both SCCB and urothelial carcinoma in xenografts. Despite this shared urothelial origin, clinical SCCB samples have a distinct transcriptional profile and a unique transcriptional regulatory network. Using the transcriptional profile from our cohort, we identified cell surface proteins (CSPs) associated with the SCCB phenotype. We found that the majority of SCCB samples have PD-L1 expression in both tumor cells and tumor-infiltrating lymphocytes, suggesting that immune checkpoint inhibitors could be a treatment option for SCCB. We further demonstrate that our genetically engineered tumor model is a representative tool for investigating CSPs in SCCB by showing that it shares a similar a CSP profile with clinical samples and expresses SCCB-up-regulated CSPs at both the mRNA and protein levels. Our findings reveal distinct molecular features of SCCB and provide a transcriptional dataset and a preclinical model for further investigating SCCB biology.

We report the case of a 55-year-old male who presented with several weeks of seizures, agitation, progressive confusion, and receptive aphasia. CSF showed a monocytic pleocytosis and tested positive for GABAB receptor autoantibodies. Pathological examination of an excisional mediastinal lymph node biopsy showed thymic small cell carcinoma, supporting a diagnosis of paraneoplastic limbic encephalitis (PLE). PLE is a subtype of limbic encephalitis and is associated with an array of autoantibodies. Neurologic symptoms related to PLE may precede the detection of the primary cancer. Recognition of the constellation of clinical features of limbic encephalitis should prompt initiation of diagnostic testing for this condition as well as evaluation for an underlying malignancy. A review of the literature reveals that this is the first case report of a patient with thymic small cell cancer presenting with PLE.

Small-cell neuroendocrine cancers (SCNCs) are an aggressive cancer subtype. Transdifferentiation toward an SCN phenotype has been reported as a resistance route in response to targeted therapies. Here, we identified a convergence to an SCN state that is widespread across epithelial cancers and is associated with poor prognosis. More broadly, non-SCN metastases have higher expression of SCN-associated transcription factors than non-SCN primary tumors. Drug sensitivity and gene dependency screens demonstrate that these convergent SCNCs have shared vulnerabilities. These common vulnerabilities are found across unannotated SCN-like epithelial cases, small-round-blue cell tumors, and unexpectedly in hematological malignancies. The SCN convergent phenotype and common sensitivity profiles with hematological cancers can guide treatment options beyond tissue-specific targeted therapies.