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The objective of this study was to determine the anatomical relationship between the calcaneus and its neighboring bones. Furthermore we tested a prediction model that enables to estimate safe screw length during the surgery of calcaneus fractures. A total of 169 feet were used for the study based on CT scans. We measured two horizontal and two parallel lines. The coronal length of the cuboid bone (CL) was a horizontal line anterior to the calcaneocuboidal joint, and W1 of calcaneus was a horizontal line posterior to the articular surface of the calcaneocuboidal joint. The subtalar articular length (STA) was a parallel line above the talocalcaneal joint, and W2 of calcaneus was a parallel line below to the talocalcaneal joint. Relationship of each measurement was determined through correlation analysis. A prediction model was developed based on observed correlations and the quality analyzed and validated. The CL and W1 had a significant positive correlation (r = 0.899, p <.001). The STA and W2 also had a significant positive correlation (r = 0.939, p <.001). Based on these correlations, the prediction model was made. In the quality analysis, the values of concordance correlation coefficient (CCC) for W1 and W2 were 0.894, and 0.937 respectively. In the validation analysis, the values of CCC for W1, W2 were 0.79, and 0.8, respectively. This study made it possible to predict the anatomical reference point using preoperative coronal length of the calcaneus to guide safety margin of screw length, and thereby to prevent the iatrogenic injuries on medial neurovascular structures of the calcaneus. [ABSTRACT FROM AUTHOR]

In this study, it is theorized that the communicative affordances offered by social media platforms will enable politically under-resourced candidates to contest the marginalization they face in traditional media. Multivariate analyses were conducted of the tweets of 205 political candidates of the 2014 Indian general election. Findings reveal that fringe party candidates received the least media attention and tended to use Twitter more frequently than major party candidates, especially for interaction and mobilization. Minor party candidates also received less media attention, albeit their Twitter usage patterns were not significantly different than major party candidates. The results illustrate that social media platforms can help overcome resource inequality in politics. The larger implications of this study are discussed. [ABSTRACT FROM AUTHOR]

The role of cross-cutting exposure in political polarization has long been discussed. Building on this literature, we proposed a moderated mediation model in which cross-cutting exposure is linked to political polarization, especially affective polarization, differently through different types of political expression, and furthermore these indirect effects of cross-cutting exposure are moderated by opinion climate perception. To test this model, we used data collected by a multi-method approach in the context of a South Korean presidential election: (a) digital trace data of online discussion behavior (i.e., exposure and expression) in the online discussion forum custom built for this study, combined with (b) traditional three-wave panel surveys. Results indicate that cross-cutting exposure increased cross-cutting expression while having no effect on like-minded expression. Cross-cutting expression was then found to reduce affective polarization and attitude extremity. Furthermore, the mediation by cross-cutting expression between cross-cutting exposure and attitude extremity was amplified when participants perceived their opinion to be on the majority side, but such moderation effect was not significant on affective polarization. Implications were discussed regarding 'hearing the other side' and 'speaking the other side.' • Cross-cutting exposure enhances cross-cutting expression ('speaking the other side') in the online discussion forum. • Cross-cutting exposure indirectly attenuates attitude extremity and affective polarization through cross-cutting expression. • A deliberation effect of cross-cutting exposure is evident for discussants whose opinion is on the majority side. [ABSTRACT FROM AUTHOR]

Twitter, a popular social media platform, has surfaced as a dominant political communication and campaign tool across Western democracies. However its role in politics, particularly in electoral campaigns, in economically developing democracies with low internet accessibility, is largely unknown. This study conducts an investigation of Twitter’s use as a campaign tool during the 2014 Indian general elections, which was the country’s first experiment with using social media for political campaigning. We present a multi-level manual and computer-aided analysis of 98,363 tweets posted by eleven political parties during the two-month run up to the elections, to present the topical, functional and interaction strategies of their Twitter campaigns. This analysis is complemented by a macro analysis of electoral outcomes’ relationship with first-time voter population and internet accessibility information at the state level. Our findings suggest that the new-and-upcoming parties used Twitter for self-promotion and media validation, while established parties used it to supplement their offline strategies. It is also observed that the winning party’s electoral success is significantly associated with their use of Twitter for engaging voters, the large population of first-time voters and levels of internet accessibility. The implications of these findings and the limitations of the study are discussed. [ABSTRACT FROM AUTHOR]

Mechanical Quality Assurance (QA) is important to assure spatially precise delivery of external-beam radiation therapy. As an alternative to the conventional-film based method, we have developed a new tool for mechanical QA of LINACs which uses a light field rather than radiation. When light passes through the collimator, a shadow is projected onto a piece of translucent paper and the resulting image is captured by a digital camera via a mirror. With this method, we evaluated the position of the LINAC isocenter and the accuracy of the gantry, collimator, and couch rotation. We also evaluated the accuracy of the digital readouts of the gantry, collimator, and couch rotation. In addition, the treatment couch position indicator was tested. We performed camera calibration as an essential pre-requisite for quantitative measurements of the position of isocenter, the linear motion of the couch, and the rotation angles of the gantry and collimator. Camera calibration reduced the measurement error to submillimeter based on uncertainty in pixel size of the image, while, without calibration, the measurement error of up to 2 mm could occur for an object with a length of 5 cm. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate particle emission characteristics from a spark ignition direct injection (SIDI) engine fueled with ethanol–gasoline blends. Particulate matter (PM) from internal combustion engine is a complex mixture of substances deemed harmful for the human body. Consequently, they are regulated by stringent legislation. According to the Euro-6 regulation, the standard for particle number (PN) emissions of SIDI vehicles is 6.0 × 10 11 N/km. Recent studies have reported that SIDI engines, renowned for their feasibility in reducing CO 2 emissions, could produce excessive amounts of PM due to its structural characteristics. For this reason, there have been many studies on reducing PM emissions from SIDI engines to satisfy strict emission standards. Because ethanol contains an oxygen atom in each molecule, it has a significant influence on combustion performance and characteristics of vehicular discharge, including PM. This study focused on the effect of intermediate ethanol blends from E0 (pure gasoline fuel) to E20 (gasoline fuel with 20% volume of ethanol) on engine performance, size-resolved particle emissions, and engine startability. Particle emission characteristics including particle number and size distribution at part-load test and start performance were investigated with operation points, fuel pressure and injection timing. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the optimal radiotherapy (RT) dose and volume for treatment of intracranial germinoma. Materials and methods: Eighty-one intracranial germinoma patients (33 pathologically-verified; 48 presumed by radiosensitivity testing) treated with RT alone between 1971 and 2002 were analyzed. The RT volume varied from focal (13) to whole brain (8), or to the entire neuraxis (60). All the cases after 1982 received craniospinal irradiation (CSI). Radiation dose was reduced gradually during the study period from 59 to 39.3Gy for primary tumors, and from 34.2 to 19.5Gy for the neuraxis. The median follow-up time was 120 months (48–260 months). Results: Five- and ten-year relapse-free survival rates were 98.8% and 94.1%, respectively. All the recurrences occurred in the patients who received local (4/13) or whole brain RT (1/8). None of the patients who received CSI suffered from a recurrence. Forty-six patients received 45Gy or less to the primary site and 22 patients received less than 20Gy to the spinal axis. Conclusion: Low-dose CSI-based RT should remain the standard treatment for intracranial germinoma. The RT dose can be reduced to 39.3Gy for primary tumor sites and to 19.5Gy for the spinal axis. [Copyright &y& Elsevier]

Abstract: Chronic varus instability of the hallux interphalangeal joint is a rare injury, and only a few reports of this injury have been published. In some studies, this injury has been related to taekwondo. Taekwondo is an essential martial art in the Korean military. We have described a case of varus instability of the hallux interphalangeal joint in a professional soldier who had practiced taekwondo for 5 years and the surgical outcome after reconstruction of the lateral collateral ligament with the fourth toe extensor tendon. [Copyright &y& Elsevier]

We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy. The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy. The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P =.874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P =.535). This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level. [ABSTRACT FROM AUTHOR]

Purpose: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx).Methods and Materials: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis.Results: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively.Conclusions: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable. [ABSTRACT FROM AUTHOR]

This study aimed to determine the clinical effect of incongruent subtalar joint space on total ankle arthroplasty (TAA). Thirty-four consecutive patients who underwent TAA were grouped according to the status of subtalar joint incongruency. A comparison of clinical and radiographic parameters between groups as well as multiple regression analysis was performed to identify contributing factors to the final functional outcome. The final American Orthopaedic Foot and Ankle Society (AOFAS) score was significantly higher in the congruent group compared to that of the incongruent group (p = 0.007). There were no significant differences between the two groups in measured radiographic angles. In multiple regression analysis, the female sex (p = 0.006) and incongruency of the subtalar joint (p = 0.013) were found to be significant contributing factors to the final AOFAS score. A thorough preoperative investigation should be taken into the state of the subtalar joint for TAA. [ABSTRACT FROM AUTHOR]

This study analyzes the political use of Twitter in the run-up to the 2013 Malaysian General Election. It follows a content and social network analysis approach to investigate the interplay of language and political partisanship in social media use, among Twitter users in Malaysia. In the period leading up to the 2013 elections, Twitter posts collected under the hashtag #GE13 reveal that communities that post in English versus the Malay language, differ in how they use Twitter and with whom they interact. As compared to English users, Malay users are more likely to seek political information and express their political opinion. In online discussions, we observe language-based homophily within the English and Malay language communities, but there are some cross-cutting interactions between opposing political communities. We discuss the implications of our findings for the political use of new communication technologies in multi-ethnic and multilingual societies. [ABSTRACT FROM AUTHOR]

Background: This case-control study aimed to explore an association between foot alignment and development and presentation of the ingrown toenail.Methods: Radiographs were evaluated for hallux interphalangeal angle (HIA), hallux valgus angle (HVA), talonavicular coverage angle (TNC), talo-first metatarsal (Meary's) angle, and calcaneal pitch angle (CP), as well as medial sesamoid position in a cohort of 103 young and healthy patients (mean age of 20.5 years) with ingrown toenails. A control group of 63 patients was included, and the radiographic parameters were compared. Subgroup analysis was performed in patients with lateral (n = 65) or medial (n = 38) nail fold involvement.Results: The overall study group demonstrated a larger TNC and Meary's angle and smaller CP than the control group, while no significant difference was found regarding the HIA and HVA. The lateral nail fold group had a larger HIA when compared to the medial nail fold group. Multiple regression analysis revealed that for ingrown toenail development, the only risk factor was a decrease in the CP. In the case of lateral nail fold involvement, an increase in the HIA found to be the only factor.Conclusion: A lower medial longitudinal arch seems to be a predisposing factor in developing an ingrown toenail. The lateral nail fold involvement was associated with lateral deviation of the distal phalanx. The result of this study could provide information on prevention, treatment, recurrence, and patient counseling of an ingrown toenail in otherwise young and healthy individuals. [ABSTRACT FROM AUTHOR]

Abstract: Background: Nimotuzumab (TheraCIM®) is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with minimal skin toxicity. Combining a different class of anti-EGFR drug with gefitinib is a new strategy to overcome intrinsic and acquired resistance to gefitinib. The aim of this phase I trial was to determine recommended phase II dose (RPIID) and the safety of gefitinib and nimotuzumab combination treatment. Methods: Patients with advanced/metastatic NSCLC were treated with escalating doses of weekly nimotuzumab (100mg or 200mg, IV) and fixed doses of daily gefitinib (250mg/day, PO) until disease progression or unacceptable toxicity. We planned to enroll 10 additional patients at RPIID to ascertain the safety of treatment. EGFR mutations and KRAS mutations were analyzed from available tumor samples. Results: A total of 16 patients were enrolled (3 in 100mg cohort, 13 in 200mg cohort). Six patients (37.5%) were female, and 5 (31.3%) were never smokers. Adenocarcinoma was the major histologic type (13 patients, 81.3%). Treatment was well-tolerated without dose-limiting toxicity (DLT). Four patients (25.0%) experienced grade 2 skin toxicity (1 in 100mg cohorts, 3 in 200mg cohort). Other common grade 1/2 toxicities were fatigue (37.5%) and diarrhea (25.0%). Among 16 evaluable patients, four patients (25.0%) achieved partial response and 7 patients (43.8%) had stable disease. Two of 4 responders had EGFR mutation (exon 19 deletion). Conclusions: Dual agent molecular targeting of EGFR with nimotuzumab and gefitinib in patients with advanced NSCLC is well-tolerated. The RPIID for nimotuzumab is 200mg weekly IV and for gefitinib 250mg/day PO. Based upon this phase I trial, we are planning to conduct a randomized phase II trial comparing gefitinib and nimotuzumab with gefitinib alone in patients with advanced NSCLC. [Copyright &y& Elsevier]

Purpose: Recently, cells deficient in O6-methylguanine–DNA methyltransferase (MGMT) were found to show increased sensitivity to temozolomide (TMZ). We evaluated whether hypermethylation of MGMT was associated with survival in patients with glioblastoma multiforme (GBM). Methods and Materials: We retrospectively analyzed 93 patients with histologically confirmed GBM who received involved-field radiotherapy with TMZ from 2001 to 2008. The median age was 58 years (range, 24–78 years). Surgical resection was total in 39 patients (42%), subtotal in 30 patients (32%), and partial in 17 patients (18%); only a biopsy was performed in 7 patients (8%). Postoperative radiotherapy began within 3 weeks of surgery in 87% of the patients. Radiotherapy doses ranged from 50 to 74 Gy (median, 70 Gy). MGMT gene methylation was determined in 78 patients; MGMT was unmethylated in 43 patients (55%) and methylated in 35 patients (45%). The median follow-up period was 22 months (range, 3–88 months) for all patients. Results: The median overall survival (OS) was 22 months, and progression-free survival (PFS) was 11 months. MGMT gene methylation was an independently significant prognostic factor for both OS (p = 0.002) and PFS (p = 0.008) in multivariate analysis. The median OS was 29 months for the methylated group and 20 months for the unmethylated group. In 35 patients with methylated MGMT genes, the 2-year and 5-year OS rates were 54% and 31%, respectively. Six patients with combined prognostic factors of methylated MGMT genes, age ≤50 years, and total/subtotal resections are all alive 38 to 77 months after operation, whereas the median OS in 8 patients with unmethylated MGMT genes, age >50 years, and less than subtotal resection was 13.2 months. Conclusion: We confirmed that MGMT gene methylation is a potent prognostic factor in patients with GBM. Our results suggest that early postoperative radiotherapy and a high total/subtotal resection rate might further improve the outcome. [Copyright &y& Elsevier]

• Harmful emissions were evaluated in medium-duty diesel and LPG minibus under WHVC. • Powertrains, after-treatment devices, and fuel properties impacted on emissions. • More small particles were produced from DPF-SCR-diesel than TWC-LPDi engine. • CO 2 -equivalent N 2 O and CH 4 emissions from diesel was higher than LPDi vehicle. • Combustion process and fuel property effected on SO 2 and NH 3 formation strongly. Construction of harmful emission inventory from conventional and sustainable low carbon fueled vehicles is important issues to improve urban air quality and human health. In this study, the gaseous, nanoparticle, and unregulated gaseous emission formation behavior from a medium-duty minibus were investigated using the World Harmonized Vehicle Cycle (WHVC). The state-of-the-art diesel and turbocharged direct-injection liquefied petroleum gas (LPG) vehicle were tested on a chassis dynamometer. The after-treatment system of the 3.9-L diesel engine was composed of the DOC, DPF and SCR, which satisfy the Euro 6 emission regulation. The 3.3-L stoichiometric spark ignition direct injection LPG engine was a TWC-only system. The formation of harmful emission components from the light-duty minibus operation was closely related to powertrain types, combustion mechanisms, after-treatment devices, and physicochemical properties of the tested fuels. Additionally, the chemical composition and low heating value (or energy content) of the respective fuels substantially affected the vehicle CO 2 emissions and fuel economy performance. Compared to LPG vehicle, the THC and NOx emissions from diesel vehicle were 63% and 511%. Similar PN concentrations were measured with each powertrain, but 2–3 times higher nucleation mode particles were released with diesel vehicle. Two vehicles showed comparable CO 2 emissions, while fuel economy from diesel and LPG vehicle were 6.81 km/L and 4.60 km/L. The proportions of N 2 O and CH 4 emissions with ozone forming potential (OFP) were 1.2% (diesel) and 0.3% (LPG), which showed the potential to mitigate the CO 2 -equivalent emissions from LPG minibus. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a long-term side effect of thoracic radiation therapy. Hypoxia-induced vascular endothelial mesenchymal transition (EndMT) can occur during the development of RIPF. Here, we examined the direct contribution of endothelial HIF-1α (EC-HIF1α) on RIPF.Methods and Materials: An inducible Cre-lox-mediated endothelial Hif1a deletion mouse line was used to evaluate the potential of HIF-1α inhibition to suppress RIPF. To evaluate the effects of a pharmacologic HIF-1α inhibitor on RIPF after image guided radiation therapy (IGRT) for spontaneous lung adenocarcinoma, we generated conditional tdTomato; K-RasG12D; and p53 flox/flox mice to facilitate tracking of tumor cells expressing tdTomato.Results: We found that vascular endothelial-specific HIF-1α deletion shortly before radiation therapy inhibited the progression of RIPF along with reduced EndMT, whereas prolonged deletion of endothelial HIF-1α before irradiation did not. Moreover, we revealed that postirradiation treatment with the novel HIF-1α inhibitor, 2-methoxyestradiol (2-ME) could efficiently inhibit RIPF and EndMT. In addition, IGRT using primary mouse models of non-small cell lung cancer showed that combined treatment of 2-ME with ablative high-dose radiation therapy efficiently inhibited RIPF and the growth of both multifocal and single tumors, concomitantly reducing radiation-induced EndMT of normal as well as tumor regions.Conclusion: These results suggest that a negative regulator of HIF-1α-mediated EndMT, such as 2-ME, may serve as a promising inhibitor of RIPF in radiation therapy. [ABSTRACT FROM AUTHOR]

• Regulated, particle, and BTEX emissions were evaluated in ethanol fueled DISI vehicle. • Ethanol fraction and vehicle test modes effected on vehicle emission concentration. • Particulate and BTEX emissions decreased with ethanol fraction increment over 30–85%. • FE and CO 2 levels were related to vehicle speeds and physicochemical fuel properties. In this study, the regulated, particulate, and unregulated emissions, and the fuel economy (FE) from a direct injection spark ignition (DISI) vehicle were investigated on a chassis dynamometer. Two vehicle test cycles, the congested urban (NIER03) and rural modes (NIER09), which reflect vehicle driving patterns in Korea, were tested with varying ethanol contents of gasoline (E0), and low- (E10), medium- (E30 and E50), and high-ethanol blended fuels (E85). The particle number (PN) concentration from E0 was substantially reduced by one or two orders of magnitude with medium- or high-ethanol blended fuels, respectively. The E10 fuel showed the highest PN concentration because of the physicochemical mixture properties of the azeotropic characteristics. As the ethanol fraction increased, the particle sizes shifted to smaller sizes that were dependent on the vehicle test modes and oxygen proportions in the fuels. The regulated and unregulated emissions showed close relationships with the vehicle test modes and ethanol blends. Vehicle running with frequent idle-stops at an extremely low speed and dynamic transient driving under NIER03 showed higher BTEX emissions than the NIER09 mode, and produced lower emission levels due to the higher oxygen and lower aromatic proportions of the ethanol blends. Compared to the NIER03 mode, the CO 2 emissions and FEs under the NIER09 mode were substantially improved, with a higher vehicle speed and more energy efficient engine operation points. The low energy contents of the E85 fuel resulted in slight increases in the CO 2 emissions and reductions in the FEs of the NIER modes. [ABSTRACT FROM AUTHOR]

Purpose: The interest in combining radiation therapy (RT) with immunotherapy is increasing. We investigated the significance of lymphopenia in patients receiving immunotherapy for non-small cell lung cancer (NSCLC), and the factors associated with treatment-related lymphopenia, with particular emphasis on RT.Methods and Methods: In this retrospective single institution study, 268 patients with advanced NSCLC received immunotherapy, of whom 146 received RT. Lymphopenia was defined as an absolute lymphocyte count <1000 cells/mm.3 Patients were divided into 2 groups depending on the presence of peri-immunotherapy lymphopenia at the start of immunotherapy or during immunotherapy.Results: At median 6.4 months of follow-up, patients with peri-immunotherapy lymphopenia (n = 146; 54.5%) showed significantly poorer progression-free survival (PFS) (median PFS: 2.2 vs 5.9 months, P < .001) and overall survival (OS) (median OS: 5.7 vs 12.1 months, P < .001). On multivariate analysis, peri-immunotherapy lymphopenia remained a significant prognostic factor for both PFS and OS. RT significantly increased peri-immunotherapy lymphopenia with an odds ratio (OR) of 1.91 (P = .025). Factors associated with the development of RT-associated lymphopenia included multiple courses (OR, 3.78; P < .001), multiple irradiated sites (OR, 4.77; P = .018), and higher dose (≥50 Gy) (OR, 3.75; P = .004). Conversely, stereotactic body RT/radiosurgery reduced the risk (OR 0.21; P = .002).Conclusions: Lymphopenia was indicative of poor prognosis in NSCLC patients receiving immunotherapy and was significantly associated with more intensive RT. Choosing appropriate RT regimens and techniques may be essential in reducing lymphopenia. Promising results are expected in the era of precision RT. [ABSTRACT FROM AUTHOR]

Objective: To describe distinctive morphologic variations of the prostate associated with the prostatic urethra, and to determine whether structural changes of the urethra within the prostate resulting from gland enlargement, rather than prostrate volume itself, lead to male lower urinary tract symptom (LUTS).Materials and Methods: After standardizing measurements, 7 ultrasonography-determined variables, that is, prostate volume, transitional zone volume, transitional zone-to-total volume ratio, presence of intraprostatic protrusion, prostatic urethral angle, prostatic urethral length (PUL), and PUL-to-volume ratio (rPUL), were obtained prospectively in 293 men who had not taken LUTS medication during the 3 months prior to initial visits. Correlations between these variables and international prostate symptom scores (IPSS) were then investigated.Results: By simple correlation, only rPUL showed a significant association with IPSS. Multiple linear regression revealed IPSS were significantly correlated with age (beta = .179, P = .04) and rPUL (beta = .139, P = .019). Subanalysis with respect to the symptoms of IPSS revealed only rPUL was correlated with voiding symptoms (Q1,3,5,6; beta = .122, P = .036), and that age alone was correlated with storage symptoms (Q2,4,7; beta = .262, P < .001). When dividing 4 groups by applying mean cut-offs for PUL (62 mm) and prostate volume (30 g), long PUL with small volume had significantly higher IPSS score than short PUL with large volume (P = .042).Conclusion: Structural differences of prostate related to prostatic urethra as reflected by rPUL were found to be significantly correlated with the severity of voiding symptoms. This finding suggests structural change of the prostatic urethra inducted by prostate enlargement underlies the development of male LUTS. [ABSTRACT FROM AUTHOR]

Mutations in breast cancer-associated 1 (BRCA1) increase the lifetime risk of developing breast cancer by up to 51% over the risk of the general population. Many aspects of this multifunctional protein have been revealed, including its essential role in homologous recombination repair, E3 ubiquitin ligase activity, transcriptional regulation, and apoptosis. Although most studies have focused on BRCA1 deficiency due to mutations, only a minority of patients carry BRCA1 mutations. A recent study has suggested an expanded definition of BRCA1 deficiency with reduced BRCA1 levels, which accounts for almost half of all triple-negative breast cancer (TNBC) patients. Reduced BRCA1 levels can result from epigenetic modifications or increased proteasomal degradation. In this review, we discuss how this knowledge of BRCA1 function and regulation of BRCA1 protein stability can help overcome the challenges encountered in the clinic and advance current treatment strategies for BRCA1-related breast cancer patients, especially focusing on TNBC. [Display omitted] • An expanded definition of BRCA1 deficiency with reduced BRCA1 levels covers ∼50% of TNBC patients. • Reduced BRCA1 levels can result from increased proteasomal degradation. • We provide novel insights on targeting BRCA1 for the development of novel treatment strategy for TNBC patients. [ABSTRACT FROM AUTHOR]

Although lung inflammation and fibrosis are well-documented dose-limiting side effects of lung irradiation, the mechanisms underlying these pathologies are unknown. An improved mechanistic understanding of radiation-induced pneumonitis is a prerequisite for the development of more effective radiotherapy; this was the rationale for the current study. Mouse lungs were focally irradiated with 75 Gy. The numbers of neutrophils, lymphocytes, macrophages, and total cells in the bronchoalveolar lavage fluid were counted, and pro-inflammatory cytokine levels were measured. Histological analysis and immunohistochemical staining for Tgf-β1 and Cd68 (a macrophage-specific protein) was also performed. After irradiation, mice developed pneumonitis, and exhibited higher numbers of neutrophils, lymphocytes, eosinophils, macrophages, and total cells compared to controls. In addition, inflammasome (Nlrp3, and caspase 1, Il1a, and Il1β), adhesion molecule (Vcam1), and cytokine (Il6) genes were significantly upregulated in the IR group. Cd68 and Tgfb1 proteins were significantly increased after irradiation. Upregulation of Cd68 and Tgfb1 correlates with the onset of radiation-induced pneumonitis and fibrosis. In addition, radiation-induced pneumonitis and fibrosis are accompanied by upregulation of phenotypic markers of inflammasome activity. Our findings have implications for the onset and exacerbation of damage in normal lung tissue. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of synchronous treatment of multiple metastatic lesions by helical tomotherapy. Methods and Materials: Forty-two patients with multiple metastatic lesions were treated by helical tomotherapy from April 2006 to February 2007. Among these patients, 21 had metastatic bone disease. Subjective pain response was assessed using the visual analogue scales, and morbidity was evaluated by Common Terminology Criteria for Adverse Events v3.0. The correlation between the percentage of red bone marrow in the radiation field and the severity of leukocytopenia was analyzed. Results: The median age was 57 years. Radiation dose to the gross tumor volume was 30–84 Gy, with a median fractional size of 3 Gy. Mean treatment time was 16 min and 1 sec. Treatment time and fraction size were modified because of poor performance status or hematologic toxicity in two patients. With regard to palliative effects for bone metastasis, 16 patients (76.2%) experienced positive pain relief. Four patients had Grade III leukocytopenia, and three had Grade IV leukocytopenia. In the multivariate logistic regression, red marrow percentage was the independent risk factor most associated with Grade III/IV leukocytopenia (p = 0.014). The tolerance cutoff point of red bone marrow was 26.8%, with a sensitivity and specificity of 85.7% and 85.7%, respectively. Conclusions: Helical tomotherapy was effective for symptom palliation and was feasible for patients with multiple metastatic diseases. The volume of red bone marrow, as well as performance status, must be taken into account to determine optimal treatment. [Copyright &y& Elsevier]