bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytogenetic biomonitoring of premalignant and malignant oral lesions by micronuclei assessment: A screening evaluation
Authors: Khanna Shally , Purwar Anupam , Singh Narendra Nath , Sreedhar Gadiputi , Singh Shailendra , Bhalla Saurabh
Published: January 2014

Background: Micronuclei (MN) are extracytoplasmic nuclear bodies, which are induced in cells by numerous genotoxic agents that damage the chromosomes. The damaged chromosomes in the form of acentric chromatids or chromosome fragments lag behind in anaphase when centric elements move towards the spindle poles, and thus leads to the formation of secondary nuclei called MN, which are also transmitted to the daughter cells. In oral exfoliated cells these MN are induced by variety of carcinogenic compounds like tobacco, betel nut, and alcohol; which have been suggested to be the most common cause of premalignant lesion conditions and oral cancer, and thus can be used as a biomarker for cytogenetic damage. Objectives: To evaluate and compare the frequency of MN in Papanicolaou (PAP) stained smears of oral exfoliated cells from healthy control, leukoplakia, and squamous cell carcinoma (SCC) group in a small population of eastern Uttar Pradesh. Materials and Methods: Cytological smears were prepared from buccal mucosa of healthy control, leukoplakia patients, and SCC group and stained with PAP stain. Slides were screened, and micronucleated cells were counted out of thousand and compared in different groups. Results: Mean MN count was highest for the SCC group (10.13), followed by leukoplakia group (6.15), and lowest for healthy controls (3.28); with count ranging from 7-14, 4-8, and 2-4, respectively. Tukey′s HSD and ROC analysis showed the intergroup differences were significant statistically (P < 0.05) and thus, mean MN density seems to be a useful tool for differential diagnosis with high accuracy. Conclusion: MN were higher in SCC than in leukoplakia and healthy control, moreover. Hence, MN assay can be used as an important biomarker for cytogenetic damage in oral leukoplakia and SCC.
Transparent tooth model: A study of root canal morphology using different reagents
Authors: Gupta Bhavana , Tiwari Babusha , Raj Vineet , Kashyap Bina , Chandra Shaleen , Dwivedi Nidhi
Published: January 2014

Background: The complexity of root canal morphology has fascinated the imaginations of many. Several techniques have been tried in the past to view the three-dimensional anatomy of the pulp canal system with varied success. It has been hypothesized in the present study that a combination of decalcifying agent and clearing agent can be used to prepare transparent tooth model. Aims: The aim of the present study was to access the efficacy of two decalcifying agent (formic acid and nitric acid) and two clearing agents (methyl salicylate and eugenol) to prepare transparent tooth model. Materials and Methods: The study material included 80 freshly extracted teeth both maxillary and mandibular. After decalcifying and clearing of the specimen, they were graded for transparency and haziness criteria. Results: The results of the present study indicated that methyl salicylate when used as a clearing agent showed better transparency, lower level of haziness and good root canal morphology. On the other hand samples cleared by eugenol showed good root canal morphology but lesser transparency and higher degree of haziness and yellowing of samples, more so when used in combination with nitric acid. Conclusion: It was concluded by the present study that combination of nitric acid when used with methyl salicylate proved to be the best combination for the preparation of the transparent tooth model.
Implant O-ring Attachment used for Tooth-borne Overdenture
Authors: Guttal Satyabodh S
Published: January 2014

The lack of retention in complete dentures is a common complaint. The incorporation of the tooth supported overdenture in prosthodontics offers improvements related to patient satisfaction and masticatory capacity compared to the conventional complete denture. Retention of the roots of one or more teeth for overdenture offers the patient a lot of advantages like better stability, proprioception and support among a few. When rehabilitation with a fixed/removable implant- supported prosthesis is not a possible option due to medical contraindication or financial constraints, a tooth supported over denture retained and stabilized with attachment can be proposed as a reliable and cost effective treatment for denture patients. This article presents a clinical report where the O-ring attachment along with bar is used to aid in retention and stability of a maxillary tooth supported overdenture.

How to cite this article

Yadav B, Guttal SS. Implant O-ring Attachment used for Tooth-borne Overdenture. Int J Prosthodont Restor Dent 2013;3(3):115-119.
Prosthodontic Rehabilitation of Cleft Lip and Palate Patients using Conventional Methods: A Case Series
Authors: Yuzugullu Bulem , Acar Ozlem , Kaya Burcak , Saka Muhammet
Published: January 2014

This case series describes prosthodontic management of seven cleft-lip-and-palate patients with different cleft deformities, gender and age. Patients were rehabilitated using conventional prosthesis. Five patients in whose maxillary arch was orthodontically expanded were treated with a combination of fixed and removable partial dentures with precision attachments. Two patients, who did not maxillary collapse were treated with metal-ceramic fixed-partial-dentures. All patients were followed up to two years. When there are limitations for secondary bone- grafting and implants, conventional approaches provide good physiologic, functional and esthetic outcomes with care taken to prevent maxillary relapse in treating these patients.

How to cite this article

Acar O, Kaya B, Saka M, Yuzugullu B. Prosthodontic Rehabilitation of Cleft Lip and Palate Patients using Conventional Methods: A Case Series. Int J Prosthodont Restor Dent 2013;3(3):120-124.
Globalización de la educacion superior en Paraguay
Authors: Recalde Hugo Alfredo , Lusardi Willian Cantero , Acosta Juan Angel Jara
Published: January 2014

El inicio del  desarrollo e innovación del  sistema de Educación Superior en Paraguay nació en el año 1889 con la creación de la Universidad Nacional de Asunción,  siendo  la primera universidad Nacional  en el país y en 1960 la Universidad Católica Nuestra Señora de la Asunción, la primera universidad privada; desde entonces fue postergada la creación de Universidades en Paraguay por más de  100 años, causa el sistema de gobierno político implementado en aquel entonces, al no haber centro de estudios especializados también se postergo el desarrollo intelectual de las personas,  desde 1989 con la caída del sistema dictatorial se han abierto un abanico de posibilidades con la apertura de universidades privadas y públicas. Actualmente el Paraguay cuenta con 52 universidades en pleno funcionamiento de las cuales, 8 son universidades públicas  y 44 de administración privada, a esto podemos agregar un total de 11 carreras acreditadas a nivel MERCOSUR, certificaciones otorgadas mediante el Sistema de Acreditación Regional de Carreras Universitarias (ARCU-SUR), por la Agencia Nacional de Evaluación y Acreditación de la Educación Superior (ANEAES). Es evidente el cambio cuali – cuantitativo experimentado por el sistema de Educación Superior en Paraguay, acompañando de la mano a las tecnologías de la información y la educación que hacen una Globalización eficaz y eficiente del conocimiento.
A tethered-balloon PTRMS sampling approach for rapid surveying of landscape-scale biogenic VOC fluxes
Authors: Greenberg J. P. , Guenther A. , Turnipseed A. , Jiang X. , Seco R. , Filella I. , Estiraste M. , Sardans J. , Ogaya R. , Llusia J. , Peñuelas J.
Published: January 2014

Abstract. To survey landscape-scale fluxes of biogenic gases, a 100 m Teflon tube was attached to a tethered balloon as a sampling inlet for a fast response Proton Transfer Reaction Mass Spectrometer (PTRMS). Along with meteorological instruments deployed on the tethered balloon and at 3 m and outputs from a regional weather model, these observations were used to estimate landscape scale biogenic volatile organic compound fluxes with two micrometeorological techniques: mixed layer variance and surface layer gradients. This highly mobile sampling system was deployed at four field sites near Barcelona to estimate landscape-scale BVOC emission factors in a relatively short period (3 weeks). The two micrometeorological techniques agreed within the uncertainty of the flux measurements at all four sites even though the locations had considerable heterogeneity in species distribution and complex terrain. The observed fluxes were significantly different than emissions predicted with an emission model using site-specific emission factors and land-cover characteristics. Considering the wide range in reported BVOC emission factors of VOCs for individual vegetation species (more than an order of magnitude), this flux estimation technique is useful for constraining BVOC emission factors used as model inputs.
Catchment-scale dissolved carbon concentrations and export estimates across six subarctic streams in northern Sweden
Authors: Giesler R. , Lyon S. W. , Mörth C.-M. , Karlsson J. , Karlsson E. M. , Jantze E. J. , Destouni G. , Humborg C.
Published: January 2014

Abstract. Climatic change is currently enhancing permafrost thawing and the flow of water through the landscape in subarctic and arctic catchments, with major consequences for the carbon export to aquatic ecosystems. We studied stream water carbon export in several tundra-dominated catchments in northern Sweden. There were clear seasonal differences in both dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) concentrations. The highest DOC concentrations occurred during the spring freshet while the highest DIC concentrations were always observed during winter baseflow conditions for the six catchments considered in this study. Long-term trends for the period 1982 to 2010 for one of the streams showed that DIC concentrations has increased by 9% during the 28 yr of measurement while no clear trend was found for DOC. Similar increasing trends were also found for conductivity, Ca and Mg. When trends were discretized into individual months, we found a significant linear increase in DIC concentrations with time for September, November and December. In these subarctic catchments, the annual mass of C exported as DIC was in the same order of magnitude as DOC; the average proportion of DIC to the total dissolved C exported was 61% for the six streams. Furthermore, there was a direct relationship between total runoff and annual dissolved carbon fluxes for these six catchments. These relationships were more prevalent for annual DIC exports than annual DOC exports in this region. Our results also highlight that both DOC and DIC can be important in high-latitude ecosystems. This is particularly relevant in environments where thawing permafrost and changes to subsurface ice due to global warming can influence stream water fluxes of C. The large proportion of stream water DIC flux also has implications on regional C budgets and needs to be considered in order to understand climate-induced feedback mechanisms across the landscape.
The Role of Secreted Frizzled Related Protein 4 (sFRP-4) in Regulating Oestradiol-Induced Growth of the MCF-7 Breast Cancer Cell Line
Authors: Sally McLaren  , Frank Arfuso  , Nik Zeps  , Arun Dharmarajan
Published: January 2014

The Wnt signalling pathway is involved in regulating cellular proliferation and differentiation, and aberrant activation has been described in several cancers including breast. Oestradiol up regulates Wnt pathway gene expression, and thereby activates the Wnt signalling pathway. We used the oestrogen-responsive breast cancer cell line MCF-7 to examine the effects of secreted frizzled related protein 4 (sFRP-4) on oestradiol-induced growth, including gene expression of the Wnt signalling pathway genes Frizzled Receptor, Wnt-10b, and catenin. We demonstrate here that sFRP-4 inhibits oestradiol-induced cell growth in the MCF-7 cell line and also down regulates oestradiol-induced expression of selected Wnt signalling genes includingcatenin. We propose that sFRP-4 is a potent inhibitor of the Wnt signalling pathway and may negatively regulate oestradiol-mediated proliferation in human breast cancer cells.
Secretory Kin17 is Correlated with Chemoresistance in Oral Squamous Cell Carcinoma
Authors: Xiaoyi Liu  , Lijuan Deng  , Haixia Zhang  , Tao Zeng  , Hua Wang  , Yan Zhang
Published: January 2014

Purpose: Kin17 is a conserved nuclear protein that participates in DNA damage repair, DNA replication and cell proliferation. Several reports have linked Kin17 to tumor progression. However, the role of Kin17 in oral squamous cell carcinoma (OSCC) has not yet been described. The aims of this study were to assess Kin17 transcript and protein expression in OSCC and to evaluate an association for this protein with chemoresistance. Methods: Kin17 expression in OSCC tissues and OSCC cell lines was measured by standardized immunohistochemistry, western blotting and semi-quantitative RT-PCR. Secretory Kin17 protein was measured in serum samples and cell culture conditioned media. A recombinant Kin17 protein was purified and used in a chemoresistance assay. Results: Kin17 was identified as an unconventional secretory protein, whose expression levels were correlated with chemotherapy and chemoresistance in OSCC. Kin17 protein expression was up-regulated in patients exhibiting chemoresistance. Serum Kin17 levels were significantly increased in patients receiving chemotherapy. We provide evidence that the secretory Kin17 protein plays a role in the DNA damage response in OSCC. Furthermore, we also show that the secretory Kin17 protein enhances the chemoresistance of OSCC cells and increases the expression of multidrug resistant genes. Conclusion:To our knowledge, this is the first report of Kin17 being characterized as a secretory protein. This novel role for Kin17 may have implications for studying the chemoresistance process in OSCC. The effective inhibition of Kin17 secretion may improve or prolong chemotherapeutic effects, making it an attractive therapeutic target candidate for further study.
Metabolic Alterations, Vascular Disease and Advanced Prostate Cancer: New Players for Metastatic Advanced Prostate Cancer?
Authors: Simona Di Francesco  , Raffaele L. Tenaglia
Published: January 2014

Introduction: Epidemiologic studies have implicated metabolic imbalance in prostate cancer (PCa) aggressiveness, nevertheless no clear consensus has been reached. The aim of the research was to investigate the association of hypertension, hypercholesterolemia and vascular disease in advanced PCa with and without bone metastases. Methods: Retrospective analysis of 66 patients with diagnosis of advanced PCa between 2005 and 2009 was conducted. We examined hypertension, hypercholesterolemia and vascular disease in 25 patients with advanced PCa and bone metastases versus 41 patients with advanced non-metastatic PCa. Men with incomplete data available, history of hormone therapy or chemotherapy, vascular surgery or other anticancer therapies were excluded. Results:Hypertensionwas significantly linked to advanced PCa with bone metastases (OR 4.5, p = 0.01). Hypercholesterolemia also was significantly associated with aggressive metastatic PCa (OR 3.28, p = 0.01). A significant association was noted between metastatic PCa and vascular disease (OR 3.8, p = 0.04). Conclusions:In our study,hypertension, hypercholesterolemia and vascular disease were significantly related to advanced metastatic PCa. Further research should elucidate these relations in larger samples to confirm these associations and to stabilize future prevention strategies.
The Suppression Variables in Clinical Research
Authors: Kinoshita Akiyoshi
Published: January 2014

Editorial
Establishing Non-Inferiority of a New Treatment in a Three-Arm Trial: Apply a Step-Down Hierarchical Model in a Papulopustular Acne Study and an Oral Prophylactic Antibiotics Study
Authors: Liu Jung-Tzu , Tzeng Chyng-Shyan , Tsou Hsiao-Hui
Published: January 2014

Clinical trials comparing a test treatment with an active control therapy have become very popular in drug and medical device development in the last decade. An active controlled trial without a placebo, however, exhibits some major challenges in design, analysis, and interpretation, such as the determination of the non-inferiority margin or the assumption of constancy condition. When there are no ethical concerns, the comparison of a test drug with placebo usually provides the most convincing proof of the efficacy of a new treatment. Therefore, it may be advisable to conduct a three-arm trial — including placebo, active control, and the new treatment — if it is ethically justifiable such as a papulopustular acne study and an oral prophylactic antibiotics study. In this paper, we propose a statistical methodology for a three-arm non-inferiority trial with binary outcomes. We adapt the step-down hierarchical hypotheses and give a three-step testing procedure which is more realistic in conducting a clinical trial. We derived an optimal sample size allocation rule in an ethical and reliable manner to minimize the total sample size and hence to shorten the duration of the trials. Real examples from a papulopustular acne study and an oral prophylactic antibiotics study are used to demonstrate our methodology.
A Bayesian Approach for the Cox Proportional Hazards Model with Covariates Subject to Detection Limit
Authors: Chen Qingxia , Wu Huiyun , Ware Lorraine B. , Koyama Tatsuki
Published: January 2014

The research on biomarkers has been limited in its effectiveness because biomarker levels can only be measured within the thresholds of assays and laboratory instruments, a challenge referred to as a detection limit (DL) problem. In this paper, we propose a Bayesian approach to the Cox proportional hazards model with explanatory variables subject to lower, upper, or interval DLs. We demonstrate that by formulating the time-to-event outcome using the Poisson density with counting process notation, implementing the proposed approach in the OpenBUGS and JAGS is straightforward. We have conducted extensive simulations to compare the proposed Bayesian approach to the other four commonly used methods and to evaluate its robustness with respect to the distribution assumption of the biomarkers. The proposed Bayesian approach and other methods were applied to an acute lung injury study, in which a panel of cytokine biomarkers was studied for the biomarkers’ association with ventilation-free survival.
Perfiles de adolescentes on line y su comportamiento en el medio interactivo
Authors: Frutos Torres Belinda de , Sánchez Valle María , Vázquez Barrio Tamara
Published: January 2014

Internet se ha convertido en el medio de referencia entre los jóvenes y su uso está muy extendido se pueden identificar perfiles de usuarios respecto a la actitud hacia el medio interactivo y su estilo de navegación. El objetivo del estudio se centra en identificar dicho perfiles y poner a prueba su relación con su comportamiento en Internet. El estudio utiliza una metodología correlacional, con una muestra de conveniencia formada por 320 jóvenes entre 14 y 19 años procedentes de varios centros de educación secundaria. Los resultados muestran que se pueden identificar varios patrones de los adolescentes en el consumo de medios interactivos en función de su estilo de navegación y actitud hacia el medio. El estilo de navegación exploratorio está asociado a participar en actividades comerciales de la red y a dedicar más tiempo al medio interactivo particularmente durante la semana. Así mismo, los jóvenes que se enfrentan al medio con una actitud más confiada y ven el medio como un vehículo de socialización y éxito social también dedican más tiempo al medio interactivo y participan en mayor medida de las propuestas publicitarias que se ofrecen en Internet.
A Laboratory-Level Control Experiment for Introducing Predictive Control to Undergraduates
Authors: Hedjar Ramdane
Published: January 2014

This paper deals with a simple robust nonlinear control of a liquid-level system. The controller is based on one-step-ahead continuous time minimization of the predicted tracking error. We show different steps for complete engineering design from modeling and identification to real-time implementation of the control algorithm. Simulations are performed to check the tracking performance of the controller. To validate the simulation results, the control algorithm is implemented in real-time to control the liquid-level system. This laboratory experiment is being implemented at King Saud University. During their classes, students learn how to use the nonlinear model of the liquid-level system to design a simple and robust controller that achieves the desired tracking performance both in simulation and in real-time implementation.
Microcontroller-Based Experiments for a Control Systems Course in Electrical Engineering Technology
Authors: Lozano-Nieto Albert
Published: January 2014

A microcontroller-based system is used to illustrate experimental concepts in a Control Systems course in an Electrical Engineering Technology program. Students are able to experiment with different control strategies ranging from an open-loop to PID control. Students are asked to reason and discuss the benefits and drawbacks associated with each strategy. The microcontroller system has been chosen to minimize the learning curve for the students in such a way that they are mostly concerned with acquiring and representing the appropriate signals from the system as well as experimenting with changing the parameters of the system in each case.
Single molecule FRET reveals pore size and opening mechanism of a mechano-sensitive ion channel
Authors: Wang Yong , Liu Yanxin , DeBerg Hannah A , Nomura Takeshi , Hoffman Melinda Tonks , Rohde Paul R , Schulten Klaus , Martinac Boris , Selvin Paul R
Published: January 2014

The mechanosensitive channel of large conductance, which serves as a model system for mechanosensitive channels, has previously been crystallized in the closed form, but not in the open form. Ensemble measurements and electrophysiological sieving experiments show that the open-diameter of the channel pore is >25 Å, but the exact size and whether the conformational change follows a helix-tilt or barrel-stave model are unclear. Here we report measurements of the distance changes on liposome-reconstituted MscL transmembrane α-helices, using a ‘virtual sorting’ single-molecule fluorescence energy transfer. We observed directly that the channel opens via the helix-tilt model and the open pore reaches 2.8 nm in diameter. In addition, based on the measurements, we developed a molecular dynamics model of the channel structure in the open state which confirms our direct observations.
Highly enhanced visible luminescence in Zn1−
xMgxO nanocrystals
Authors: Yamamoto Sekika , Takamura Koji
Published: January 2014

Intensified trap luminescence in Zn1−

x
Mg
x
O nanocrystals compared with nondoped ZnO nanocrystals is investigated using static and time-resolved luminescence measurements at room temperature. As the Mg concentration x increases from 0 to 0.14, the visible luminescence increases by 10 times and its quantum efficiency reaches 22% while the spectrum blueshifts and broadens. The time-resolved measurements reveal that the spectrum redshifts and narrows with time after the excitation. These temporal changes are ascribed to a large distribution of the trap energy induced by Mg doping, not to the energy distribution in the conduction band caused by crystal size fluctuation.
Highly conductive PEDOT:PTS films interfacially polymerized using electro spray deposition and enhanced by plasma doping
Authors: Kim Seul-Gi , Yang Jong-Won , Lee Jun-Taek , Kim Jin-Yeol
Published: January 2014

Highly transparent and conductive poly(3,4-ethylenedioxythiophene):p-toluene sulfonate (PEDOT:PTS) films were prepared by interfacial polymerization using electro spray deposition. Additionally, to enhance the conductivity of the PEDOT:PTS films, they were treated with oxygen plasma at 20 W power. The oxygen plasma-treated PEDOT:PTS films exhibited improvements in conductivity and reductions of up to 10% in sheet resistances, relative to untreated films. Their sheet resistances were 130 and 50 Ω/sq for layer thicknesses of 80 and 120 nm, respectively. The improvement in conductivity could be attributed to the newly generated charged domains in PEDOT chains. These results confirm that highly conductive PEDOT:PTS films can potentially be used as organic transparent electrodes.
Effects of dispensing flow rate on fingering instability during spin coating
Authors: Wang Ming-Wen , Ma Ju-Lung , Hourng Lih-Wu
Published: January 2014

To reduce the amount of material used and to understand the phenomenon of viscous fluid spread during the early stage of spin coating, in this study, we perform flow visualization experiments. The results show that, in the early stage of spin coating, the spreading of viscous fluid is mainly governed by the initial liquid dispensation flow rate. Then, fingering instability is induced by the centrifugal force. The critical radius and time for the onset of instability increase with increasing initial dispensing flow rate under a constant spin speed. However, the effect of dispensing flow rate on the critical time and radius are almost negligible as long as the whole volume of liquid has been dispensed before the onset of fingering instability. This means that the fluid was almost completely dispensed over the coating surface within a limited time and that the effect of the dispensing flow rate attainable is insignificant. Furthermore, once a dispensing fluid with a much lower viscosity is used in spin coating, a much larger dispensing Reynolds number can eliminate the effect of the dispensing rate, and thus the effect of Coriolis force cannot be neglected in spin coating.
Effect of drain bias on negative gate bias and illumination stress induced degradation in amorphous InGaZnO thin-film transistors
Authors: Wang Dapeng , Hung Mai Phi , Jiang Jingxin , Toda Tatsuya , Li Chaoyang , Furuta Mamoru
Published: January 2014

The effect of drain bias (V
DS) on the negative gate bias and illumination stress (NBIS) stability of amorphous InGaZnO thin-film transistors (a-IGZO TFTs) was investigated. The evolution of transfer characteristics was explored in terms of NBIS duration. In the initial stage (<1000 s) of the NBIS with grounded V
DS, the transfer characteristics negatively shifted with an insignificant change in subthreshold swing owing to hole trapping at an IGZO/gate insulator interface. On the other hand, on-current degradation was observed and was enhanced as NBIS duration increased. The results indicate that NBIS-induced defects were created above the Fermi level energy. NBIS-induced defect creation was enhanced at a positive V
DS bias of 40 V. However, it was found that NBIS-induced defect creation can be suppressed by a negative V
DS bias, as the absolute value of V
DS was larger than that of gate voltage during NBIS.
Pixel structures to compensate nonuniform threshold voltage and mobility of polycrystalline silicon thin-film transistors using subthreshold current for large-size active matrix organic light-emitting diode displays
Authors: Na Jun-Seok , Kwon Oh-Kyong
Published: January 2014

We propose pixel structures for large-size and high-resolution active matrix organic light-emitting diode (AMOLED) displays using a polycrystalline silicon (poly-Si) thin-film transistor (TFT) backplane. The proposed pixel structures compensate the variations of the threshold voltage and mobility of the driving TFT using the subthreshold current. The simulated results show that the emission current error of the proposed pixel structure B ranges from −2.25 to 2.02 least significant bit (LSB) when the variations of the threshold voltage and mobility of the driving TFT are ±0.5 V and ±10%, respectively.
A new decoder-type integrated gate driver with a-Si:H TFTs for active-matrix displays
Authors: Kim Jong-Seok , Choi Byong-Deok
Published: January 2014

In this paper, we propose a new integrated hydrogenated amorphous silicon (a-Si:H) thin-film transistor (TFT) gate driver circuit based on a decoder with parallel TFTs. All a-Si:H TFTs in the proposed gate driver have duty ratios of 50% or less to suppress the threshold voltage (V
TH) shift, but at the same time, the output can avoid a high-impedance state to resist against noises. The proposed gate driver also removes dead time, and reduces the circuit area and the number of TFTs compared with the previously reported decoder-type and demultiplexer-type integrated gate drivers. The simulation results show that the rising time and falling time are 2.47 and 2.43 µs, respectively, with a −5 to 30 V output voltage swing, which are suitable for full high-definition (full-HD) format active-matrix displays at a 120 Hz frame frequency.
Atezolizumab Before and After Chemoradiation for Unresectable Stage III Non–Small Cell Lung Cancer
Authors: Ross Helen J. , Kozono David , Wang Xiaofei F. , Urbanic James John , Williams Terence M. , Nelson Garth D. , Carbone David P. , Chung Dongjun , Robb Ryan , Byun Woo Yul , Talabere Tiffany , DuFrane Carter , Bara Ilze , Schulze Katja , Brockman Michelle , Gao Junheng , Vokes Everett E. , Stinchcombe Thomas E.
Published: July 2024

Importance

Outcomes for patients with unresectable stage III non–small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy.

Objective

To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC.

Design, Setting, and Participants

This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023.

Interventions

Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m2, followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m2, for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy.

Main Outcomes and Measures

The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points.

Results

A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events.

Conclusions and Relevance

These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes.

Trial Registration

ClinicalTrials.gov Identifier: NCT03102242
Bilateral Mastectomy and Breast Cancer Mortality
Authors: Giannakeas Vasily , Lim David W. , Narod Steven A.
Published: July 2024

Importance

The benefit of bilateral mastectomy for women with unilateral breast cancer in terms of deaths from breast cancer has not been shown.

Objectives

To estimate the 20-year cumulative risk of breast cancer mortality among women with stage 0 to stage III unilateral breast cancer according to the type of initial surgery performed.

Design, Settings, and Participants

This cohort study used the Surveillance, Epidemiology, and End Results (SEER) Program registry database to identify women with unilateral breast cancer (invasive and ductal carcinoma in situ) who were diagnosed from 2000 to 2019. Three closely matched cohorts of equal size were generated using 1:1:1 matching according to surgical approach. The cohorts were followed up for 20 years for contralateral breast cancer and for breast cancer mortality. The analysis compared the 20-year cumulative risk of breast cancer mortality for women treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy. Data were analyzed from October 2023 to February 2024.

Exposures

Type of breast surgery performed (lumpectomy, unilateral mastectomy, or bilateral mastectomy).

Main Outcomes and Measures

Contralateral breast cancer or breast cancer mortality during the 20-year follow-up period among the groups treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy.

Results

The study sample included 661 270 women with unilateral breast cancer (mean [SD] age, 58.7 [11.3] years). After matching, there were 36 028 women in each of the 3 treatment groups. During the 20-year follow-up, there were 766 contralateral breast cancers observed in the lumpectomy group, 728 contralateral breast cancers in the unilateral mastectomy group, and 97 contralateral cancers in the bilateral mastectomy group. The 20-year risk of contralateral breast cancer was 6.9% (95% CI, 6.1%-7.9%) in the lumpectomy-unilateral mastectomy group. The cumulative breast cancer mortality was 32.1% at 15 years after developing a contralateral cancer and was 14.5% for those who did not develop a contralateral cancer (hazard ratio, 4.00; 95% CI, 3.52-4.54, using contralateral breast cancer as a time-dependent covariate). Deaths from breast cancer totaled 3077 women (8.54%) in the lumpectomy group, 3269 women (9.07%) in the unilateral mastectomy group, and 3062 women (8.50%) in the bilateral mastectomy group.

Conclusions and Relevance

This cohort study indicates that the risk of dying of breast cancer increases substantially after experiencing a contralateral breast cancer. Women with breast cancer treated with bilateral mastectomy had a greatly diminished risk of contralateral breast cancer; however, they experienced similar mortality rates as patients treated with lumpectomy or unilateral mastectomy.
Population-Based Incidence of Cervical Intraepithelial Neoplasia Across 14 Years of HPV Vaccination
Authors: Adcock Rachael , Kang Huining , Castle Philip E. , Kinney Walter , Emeny Rebecca T. , Wiggins Charles , Wheeler Cosette M.
Published: July 2024

This cohort study examines the incidence of cervical intraepithelial neoplasia during a period of increasing human papillomavirus (HPV) vaccination coverage from 2007 to 2020.
Severe Spaceflight-Associated Neuro-Ocular Syndrome in an Astronaut With 2 Predisposing Factors
Authors: Brunstetter Tyson J. , Zwart Sara R. , Brandt Keith , Brown David M. , Clemett Simon J. , Douglas Grace L. , Gibson C. Robert , Laurie Steven S. , Lee Andrew G. , Macias Brandon R. , Mader Thomas H. , Mason Sara S. , Meir Jessica U. , Morgan Andrew R. , Nelman Mayra , Patel Nimesh , Sams Clarence , Suresh Rahul , Tarver William , Tsung Ann , Van Baalen Mary G. , Smith Scott M.
Published: July 2024

Importance

Understanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management.

Objective

To describe a severe case of SANS associated with 2 potentially predisposing factors.

Design, Setting, and Participants

Ocular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS).

Exposure

Weightlessness throughout an approximately 6-month ISS mission. Mean carbon dioxide (CO2) partial pressure decreased from 2.6 to 1.3 mm Hg weeks before the astronaut’s flight day (FD) 154 optical coherence tomography (OCT) session. In response to SANS, 4 B-vitamin supplements (vitamin B6, 100 mg; L-methylfolate, 5 mg; vitamin B12, 1000 μg; and riboflavin, 400 mg) were deployed, unpacked on FD153, consumed daily through FD169, and then discontinued due to gastrointestinal discomfort.

Main Outcomes and Measures

Refraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT.

Results

Cycloplegic refraction was −1.00 diopter in both eyes preflight and +0.50 − 0.25 × 015 in the right eye and +1.00 diopter in the left eye 3 days postflight. Uncorrected DVA was 20/30 OU preflight, 20/16 or better by FD90, and 20/15 OU 3 days postflight. Inflight peripapillary total retinal thickness (TRT) peaked between FD84 and FD126 (right eye, 401 μm preflight, 613 μm on FD84; left eye, 404 μm preflight, 636 μm on FD126), then decreased. Peripapillary choroidal folds, quantified by surface roughness, peaked at 12.7 μm in the right eye on FD154 and 15.0 μm in the left eye on FD126, then decreased. Mean choroidal thickness increased throughout the mission. Genetic analyses revealed 2 minor alleles for MTRR 66 and 2 major alleles for SHMT1 1420 (ie, 4 of 4 SANS risk alleles). One-week postflight, lumbar puncture opening pressure was normal, at 19.4 cm H2O.

Conclusions and Relevance

To the authors’ knowledge, no other report of SANS documented as large of a change in peripapillary TRT or hyperopic shift during a mission as in this astronaut, and this was only 1 of 4 astronauts to experience chorioretinal folds approaching the fovea. This case showed substantial inflight improvement greater than the sensitivity of the measure, possibly associated with B-vitamin supplementation and/or reduction in cabin CO2. However, as a single report, such improvement could be coincidental to these interventions, warranting further evaluation.
Bag‐1‐mediated HSF1 phosphorylation regulates expression of heat shock proteins in breast cancer cells
Authors: Kizilboga Tugba , Özden Can , Can Nisan Denizce , Onay Ucar Evren , Dinler Doganay Gizem
Published: July 2024

According to the World Health Organization in 2022, 2.3 million women were diagnosed with breast cancer. Investigating the interaction networks between Bcl‐2‐associated athanogene (Bag)‐1 and other chaperone proteins may further the current understanding of the regulation of protein homeostasis in breast cancer cells and contribute to the development of treatment options. The present study aimed to determine the interactions between Bag‐1 and heat shock proteins (HSPs); namely, HSP90, HSP70 and HSP27, to elucidate their role in promoting heat shock factor‐1 (HSF1)‐dependent survival of breast cancer cells. HER2‐negative (MCF‐7) and HER2‐positive (BT‐474) cell lines were used to examine the impact of Bag‐1 expression on HSF1 and HSPs. We demonstrated that Bag‐1 overexpression promoted HER2 expression in breast cancer cells, thereby resulting in the concurrent constitutive activation of the HSF1–HSP axis. The activation of HSP results in the stabilization of several tumor‐promoting HSP clients such as AKT, mTOR and HSF1 itself, which substantially accelerates tumor development. Our results suggest that Bag‐1 can modulate the chaperone activity of HSPs, such as HSP27, by directly or indirectly regulating the phosphorylation of HSF1. This modulation of chaperone activity can influence the activation of genes involved in cellular homeostasis, thereby protecting cells against stress.
Effect of modulation factor and low dose threshold level on gamma pass rates of single isocenter multi‐target SRT treatment plans
Authors: Timakova Elena , Zavgorodni Sergei F.
Published: July 2024

Purpose

SRS MapCHECK (SMC) is a commercially available patient‐specific quality assurance (PSQA) tool for stereotactic radiosurgery (SRS) applications. This study investigates the effects of degree of modulation, location off‐axis, and low dose threshold (LDT) selection on gamma pass rates (GPRs) between SMC and treatment planning system, Analytical Anisotropic Algorithm (AAA), or Vancouver Island Monte Carlo (VMC++ algorithm) system calculated dose distributions.

Methods

Volumetric‐modulated arc therapy (VMAT) plans with modulation factors (MFs) ranging from 2.7 to 10.2 MU/cGy were delivered to SMC at isocenter and 6 cm off‐axis. SMC measured dose distributions were compared against AAA and VMC++ via gamma analysis (3%/1 mm) with LDT of 10% to 80% using SNC Patient software.

Results

Comparing on‐axis SMC dose against AAA and VMC++ with LDT of 10%, all AAA‐calculated plans met the acceptance criteria of GPR ≥ 90%, and only one VMC++ calculated plan was marginally outside the acceptance criteria with pass rate of 89.1%. Using LDT of 80% revealed decreasing GPR with increasing MF. For AAA, GPRs reduced from 100% at MF of 2.7 MU/cGy to 57% at MF of 10.2 MU/cGy, and for VMC++ calculated plans, the GPRs reduced from 89% to 60% in the same MF range. Comparison of SMC dose off‐axis against AAA and VMC++ showed more pronounced reduction of GPR with increasing MF. For LDT of 10%, AAA GPRs reduced from 100% to 83% in the MF range of 2.7 to 9.8 MU/cGy, and VMC++ GPR reduced from 100% to 91% in the same range. With 80% LDT, GPRs dropped from 100% to 42% for both algorithms.

Conclusions

MF, dose calculation algorithm, and LDT selections are vital in VMAT‐based SRT PSQA. LDT of 80% enhances sensitivity of gamma analysis for detecting dose differences compared to 10% LDT. To achieve better agreement between calculated and SMC dose, it is recommended to limit the MF to 4.6 MU/cGy on‐axis and 3.6 MU/cGy off‐axis.
Ferromagnetic Fiber Systems for Multiplexing Neural Recording and Modulation with Spatial Selectivity
Authors: Song Hao , Liu Yuxin , Li Jing , Liu Zijian , Yang Anqi , Lu Baicheng , Zhou Yajing , Duan Junhan , Li Jialong , He Jufang , Chen Xi , Lin Xudong
Published: July 2024

Despite the great success achieved by recently developed neural interfaces, multi‐site monitoring and regulating neural activities with high spatial and temporal selectivity remain a challenge. Here, an implantable, remotely controllable, fiber‐based ferromagnetic system permitting 3D navigation, omnidirectional steering, multiplexing neural recording, and modulation is presented. A family of fibers is fabricated that allows for the heterogeneous integration of ferromagnetic, optical, microfluidic, electrical, and electrochemical components into the proposed multifunctional neural interface. Coupling with magnetic actuation, it is demonstrated that this system can enable optical and chemical modulation of local neural activities across multiple distant regions in rodent brains, while simultaneously allowing the real‐time monitoring of neural electrophysiological and chemical activities. Furthermore, to systematically identify altered patterns of behaviors, brain activities and dopamine release during optogenetic modulation of specific nuclei in Parkinsonian animals this platform is employed. This proposed system with high spatial selectivity, multiplexing sensing and multimodal manipulating capabilities offers a versatile platform to advance both fundamental neuroscience studies and translational applications in neurologic disease treatments.
Loofah‐Inspired Ultralight and Superelastic Micro/Nanofibrous Aerogels for Highly Efficient Thermal Insulation
Authors: Zhang Wei , Liang Guoqiang , Wang Sai , Yang Fengjin , Liu Xiaoyan , Yu Jianyong , Zhang Shichao , Ding Bin
Published: July 2024

Extreme cold events are becoming more frequent and intense around the world, imposing a huge burden on human health and global economy. However, developing fibrous materials featuring ultralight weight, high shape retention, and high thermal insulation to withstand extreme conditions remains a great challenge. Herein, inspired by the natural porous loofah, an ultralight and superelastic micro/nanofibrous aerogel (MNFA) that integrates hierarchical pores and stable physical entanglements is directly synthesized via gelation electrospinning technology. By manipulating the solution/water molecules interaction of the charged jets, a hierarchical porous structure consisting of fibrous porous networks and aerogel microfibers is developed, which endows MNFA with high porosity (99.7%). Benefiting from the stable physical entanglement structure between the rigid microfibers and flexible nanofibers, the resulting MNFA can withstand large tensile stress (4000 times of its weight) and 1000 compression cycles without being damaged. Moreover, MNFA exhibits ultralight feature (3 mg cm−3) and high thermal insulation performance (low thermal conductivity of 25.3 mW m−1 K−1), making a promising contender for highly efficient thermal insulation. This work can offer fresh perspectives on the design and advancement of advanced fibrous aerogels for a variety of uses.
Mitoxantrone Combined with Engineered TRAIL‐Nanovesicles for Enhanced Cancer Immunotherapy Via Converting Apoptosis into Pyroptosis
Authors: Wang Yi , Niu Boning , Tian Yinmei , Lan Hongbing , Zhou Zhanhao , Li Yang , Zhao Siyu , Zhang Yu , Yang Conglian , Kong Li , Zhang Zhiping
Published: July 2024

Pyroptosis, a highly inflammatory form of programmed cell death, has emerged as a promising target for cancer immunotherapy. However, in the context of pyroptosis execution, while both caspase‐3 and GSDME are essential, it is noteworthy that GSDME is frequently under‐expressed in cold tumors. To overcome this limitation, engineered cellular nanovesicles (NVs) presenting TRAIL on their membranes (NVTRAIL) are developed to trigger the upregulation of cleaved caspase‐3. When strategically combined with the chemotherapeutic agent mitoxantrone (MTO), known for its ability to enhance GSDME expression, MTO@NVTRAIL can convert cancer cells from apoptosis into pyroptosis, inhibit the tumor growth and metastasis successfully in primary tumor. The microparticles released by pyroptotic tumor cells also exhibited certain cytotoxicity against other tumor cells. In addition, tumor cells exposed to the combination treatment of MTO@NVTRAIL in vitro have also demonstrated potential utility as a novel form of vaccine for cancer immunotherapy. Flow analysis of the tumor microenvironment and draining lymph nodes reveals an increased proportion of matured dendritic cells and activation of T cells. In summary, the research provided a reference and alternative approach to induce cancer pyroptosis for clinical antitumor therapy based on engineered cellular nanovesicles and chemotherapy.