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Immunotherapy for Non-small Cell Lung Cancer: Current Landscape and Future Perspectives

  • Sun Min Lim;Min Hee Hong;Hye Ryun Kim
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.10.1-10.14
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    • 2020
  • Immune checkpoint inhibitors (ICIs) have shown remarkable benefit in the treatment of patients with non-small-cell lung cancer (NSCLC) and have emerged as an effective treatment option even in the first-line setting. ICIs can block inhibitory pathways that restrain the immune response against cancer, restoring and sustaining antitumor immunity. Currently, there are 4 PD-1/PD-L1 blocking agents available in clinics, and immunotherapy-based regimen alone or in combination with chemotherapy is now preferred option. Combination trials assessing combination of ICIs with chemotherapy, targeted therapy and other immunotherapy are ongoing. Controversies remain regarding the use of ICIs in targetable oncogene-addicted subpopulations, but their initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the choice. For the majority of patients without targetable driver oncogenes, deciding between therapeutic options can be difficult due to lack of direct cross-comparison studies. There are continuous efforts to find predictive biomarkers to find those who respond better to ICIs. PD-L1 protein expressions by immunohistochemistry and tumor mutational burden have emerged as most well-validated biomarkers in multiple clinical trials. However, there still is a need to improve patient selection, and to establish the most effective concurrent or sequential combination therapies in different NSCLC clinical settings. In this review, we will introduce currently used ICIs in NSCLC and analyze most recent trials, and finally discuss how, when and for whom ICIs can be used to provide promising avenues for lung cancer treatment.

Effect of once-a-day milk feeding on behavior and growth performance of pre-weaning calves

  • Syed Husnain Mushtaq;Danish Hussain;Hifz-ul-Rahman;Muhammad Naveed-ul-Haque;Nisar Ahmad;Ahmad Azeem Sardar;Ghazanfar Ali Chishti
    • Animal Bioscience
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    • v.37 no.2
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    • pp.253-260
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    • 2024
  • Objective: The objectives of the present study were to evaluate the effects of once-a-day milk feeding on growth performance and routine behavior of preweaning dairy calves. Methods: At 22nd day of age, twenty-four Holstein calves were randomly assigned to one of two treatment groups (n = 12/treatment) based on milk feeding frequency (MF): i) 3 L of milk feeding two times a day; ii) 6 L of milk feeding once a day. The milk feeding amount was reduced to half for all calves between 56 and 60 days of age and weaning was done at 60 days of age. To determine the increase in weight and structural measurements, each calf was weighed and measured at 3 weeks of age and then at weaning. The daily behavioral activity of each calf was assessed from the 22nd day of age till weaning (60th day of age) through Nederlandsche Apparatenfabriek (NEDAP) software providing real-time data through a logger fitted on the calf's foot. Results: There was no interaction (p≥0.17) between MF and sex of the calves for routine behavioral parameters, body weight and structural measurements. Similarly, there was no effect of MF on routine behavioral parameters, body weight and structural measurements. However, the sex of the calves affected body weight gain in calves. Male calves had 27% greater total body weight and average daily gain than female calves. There was no effect of the sex of the calves on behavioral measurements. Collectively, in the current study, no negative effects of a once-a-day milk feeding regimen were found on routine behavioral and growth parameters of preweaning calves in group housing. Conclusion: Once-a-day milk feeding can be safely adopted in preweaning calves from 22nd day of age.

Collective review of pancreatic carcinosarcoma, a very rare pancreatic malignancy

  • Mirang Lee;Young Jae Cho;Hye-Sol Jung;Won-Gun Yun;Youngmin Han;Wooil Kwon;Jin-Young Jang
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.27 no.2
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    • pp.141-150
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    • 2023
  • Pancreatic carcinosarcoma is a very rare malignancy with a poor prognosis. Because of these characteristics, a treatment strategy for it has not been established yet. The aim of this study was to establish a therapeutic strategy for pancreatic carcinosarcoma. We reviewed data of a 65-year-old female patient who was diagnosed with pancreatic carcinosarcoma through endoscopic ultrasound-guided fine needle aspiration biopsy before surgery. For literature review, we searched PubMed using terms of "Pancreatic" or "Pancreas" and "carcinosarcoma" or "carcinosarcomatous". The patient received 11 cycles of neoadjuvant treatment with leucovorin, fluorouracil, irinotecan, oxaliplatin and pembrolizumab because the tumor was borderline resectable. She underwent stereotactic ablative body radiotherapy (SABR) with 35 Gy in 5 fractions, followed by robotic pylorus-preserving pancreaticoduodenectomy. After surgery, the patient received adjuvant chemotherapy in the same regimen as before surgery. She is alive without any recurrence. Among 48 patients within 33 available papers, the median survival time was 15 months. The survival rate of patients who received adjuvant chemotherapy tended to be higher than that of those who did not receive adjuvant chemotherapy, although the difference was not statistically significant (median survival, 47 vs. 15 months; p = 0.485). Three patients who received neoadjuvant chemotherapy had a survival period of 13-23.5 months. Surgery with lymphadenectomy, adjuvant therapy, and neoadjuvant therapy are thought to help improve survival outcomes. Modern treatment approaches for conventional pancreatic ductal adenocarcinoma could be applied to pancreatic carcinosarcoma.

Factors Associated With Long-term Retention in Antiretroviral Therapy Among People Living With HIV: Evidence From a Tertiary Hospital in Jakarta, Indonesia

  • Ifael Yerosias Mauleti;Krishna Adi Wibisana;Djati Prasetio Syamsuridzal;Sri Mulyati;Vivi Lisdawati;Ika Saptarini;Nurhayati;Armedy Ronny Hasugian;Harimat Hendarwan
    • Journal of Preventive Medicine and Public Health
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    • v.57 no.3
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    • pp.252-259
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    • 2024
  • Objectives: This study investigated factors associated with the retention of people living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) during the first 3 years of treatment. Methods: A retrospective study using electronic health records was conducted at a tertiary hospital in Jakarta, Indonesia. Adult HIV-positive patients who started ART from 2010 until 2020 were included. A binary logistic regression model was used to identify factors associated with ART retention in the first 3 years. Results: In total, 535 respondents were included in the analysis. The ART retention rates for the first, second, and third years were 83.7%, 79.1%, and 77.2%, respectively. The multivariate analysis revealed a negative association between CD4 count when starting ART and retention. Patients with CD4 counts >200 cells/mL were 0.65 times less likely to have good retention than those with CD4 counts ≤200 cells/mL. The year of starting ART was also significantly associated with retention. Patients who started ART in 2010-2013 or 2014-2016 were less likely to have good retention than those who started ART in 2017-2020, with adjusted odds ratios of 0.52 and 0.40, respectively. Patients who received efavirenz-based therapy were 1.69 times more likely to have good retention than those who received nevirapine (95% confidence interval, 1.05 to 2.72). Conclusions: Our study revealed a decline in ART retention in the third year. The CD4 count, year of enrollment, and an efavirenz-based regimen were significantly associated with retention. Patient engagement has long been a priority in HIV programs, with interventions being implemented to address this issue.

Patterns of proliferation and fibrosis in a rat model of endometriosis following administration of Allium cepa

  • Hakan Kula;Orkun Ilgen;Sefa Kurt;Filiz Yilmaz
    • Clinical and Experimental Reproductive Medicine
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    • v.51 no.2
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    • pp.112-119
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    • 2024
  • Objective: Endometriosis is a common gynecological disease among reproductive-age women. Numerous hypotheses exist regarding the pathogenesis of endometriosis. In Turkey, the consumption of Allium cepa (commonly known as the "onion cure") is a popular treatment employed to alleviate a variety of gynecological disorders. Methods: In this study, our objective was to assess the therapeutic mechanisms of the onion bulb A. cepa using an autologous endometriosis model in Sprague-Dawley rats. Previous research has shown that A. cepa possesses anti-inflammatory, antioxidant, and antiapoptotic properties. We evaluated the pathological condition of endometriotic implants by employing hematoxylin-eosin staining and Ki67 immunohistochemistry analysis. Transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) have been identified as profibrotic markers that are highly overexpressed in endometriotic tissues relative to eutopic endometrial tissue. Furthermore, TGF-β1 influences the differentiation and progression of endometriosis. To quantify profibrotic activity, we measured TGF-β1 and α-SMA using the immunosorbent assay method. Results: Lower histologic evaluation scores for endometriotic implants were observed in the group receiving high-dose A. cepa relative to the other groups. Ki67 expression was reduced following the high-dose A. cepa regimen, which consisted of 30% A. cepa and 70% normal feed. However, no statistically significant differences in TGF-β1 or α-SMA levels were observed among the groups (p=0.7 and p=0.778, respectively). Conclusion: The findings suggest that A. cepa could serve as a therapeutic agent in endometriosis treatment, as evidenced by the reduction in proliferative potential. Nevertheless, A. cepa was not associated with significantly lower levels of endometriosis-associated TGF-β1 or α-SMA.

Safety and immunogenicity of different booster vaccination schemes for COVID-19 used in El Salvador

  • Xochitl Sandoval;Rhina Dominguez;Delmy Recinos;Susana Zelaya;Patricia Cativo;Guillermo Horacio Docena
    • Clinical and Experimental Vaccine Research
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    • v.13 no.1
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    • pp.35-41
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    • 2024
  • Purpose: The effectiveness of coronavirus disease 2019 (COVID-19) vaccination schemes and the combination of vaccines of various platforms for administering booster doses is still being studied since it will depend on the population's response to vaccines. We aimed to evaluate the safety, protection, and immunogenicity of the Salvadorean population's third dose booster COVID-19 vaccine and the potential benefit of homologous vs. heterologous regimens. Materials and Methods: This is an analytical observational cohort study in a population aged 18 to 65 years that was primarily vaccinated with AstraZeneca, Sinovac, or Pfizer/BioNTech. Volunteers were recruited (n=223) and followed up for 3 months after receiving the 3rd vaccine (BNT162b2) as a booster. Adverse reactions were monitored, serum anti-spike immunoglobulin G (IgG) was assessed by chemiluminescence, and a polymerase chain reaction was carried out when subjects developed clinical signs. Results: The cohorts finally included 199 participants, and we observed only mild adverse effects in all cohorts. A significant increase in specific IgG levels was found after the booster dose in all cohorts. The heterologous scheme with Sinovac showed the greatest increase in antibody titer, and a decrease was observed in all participants after 3 months. During the follow-up period, 30 participants showed symptomatology compatible with COVID-19, but only four were laboratory-confirmed and they showed mild clinical signs. Conclusion: These findings indicate that the booster doses used were safe and promoted an immediate increase in immunogenicity, which decreased over time. The heterologous regimen showed stronger immunogenicity compared to the messenger RNA-based homologous scheme.

Transcranial Doppler emboli monitoring for stroke prevention after flow diverting stents

  • Matias Costa;Paul Schmitt;Jaleel N;Matias Baldoncini;Juan Vivanco-Suarez;Bipin Chaurasia;Colleen Douville;Loh Yince;Akshal Patel;Stephen Monteith
    • Journal of Cerebrovascular and Endovascular Neurosurgery
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    • v.26 no.1
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    • pp.23-29
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    • 2024
  • Objective: Flow diverting stents (FDS) are increasingly used for the treatment of intracranial aneurysms. While FDS can provide flow diversion of parent vessels, their high metal surface coverage can cause thromboembolism. Transcranial Doppler (TCD) emboli monitoring can be used to identify subclinical embolic phenomena after neurovascular procedures. Limited data exists regarding the use of TCDs for emboli monitoring in the periprocedural period after FDS placement. We evaluated the rate of positive TCDs microembolic signals and stroke after FDS deployment at our institution. Methods: We retrospectively evaluated 105 patients who underwent FDS treatment between 2012 and 2016 using the Pipeline stent (Medtronic, Minneapolis, MN, USA). Patients were pretreated with aspirin and clopidogrel. All patients were therapeutic on clopidogrel pre-operatively. TCD emboli monitoring was performed immediately after the procedure. Microembolic signals (mES) were classified as "positive" (<15 mES/hour) and "strongly positive" (>15 mES/hour). Clinical stroke rates were determined at 2-week and 6-month post-operatively. Results: A total of 132 intracranial aneurysms were treated in 105 patients. TCD emboli monitoring was "positive" in 11.4% (n=12) post-operatively and "strongly positive" in 4.8% (n=5). These positive cases were treated with heparin drips or modification of the antiplatelet regimen, and TCDs were repeated. Following medical management modifications, normalization of mES was achieved in 92% of cases. The overall stroke rates at 2-week and 6-months were 3.8% and 4.8%, respectively. Conclusions: TCD emboli monitoring may help early in the identification of thromboembolic events after flow diversion stenting. This allows for modification of medical therapy and, potentially, preventionf of escalation into post-operative strokes.

Optimized Controlled Atmosphere Regimen for Storage of Fresh Fischer's Ligularia (Ligularia fischeri Turcz.) Leaves (신선 곰취(Ligularia fischeri Turcz.) 잎 저장을 위한 CA 조성 최적화)

  • Park, Yoon-Moon;Kim, Taewan;Kim, Hyun-Seok;Kim, Tae Hoon;Park, Yoo Jin
    • Horticultural Science & Technology
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    • v.33 no.3
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    • pp.375-382
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    • 2015
  • A controlled atmosphere (CA) regimen was optimized during 3 consecutive harvest seasons as the basis of practical modified atmosphere packaging (MAP) storage for quality maintenance and extension of storage potential of fresh Ligularia fischeri leaves. Leaves were harvested in April or May and forced-air cooled to $4^{\circ}C$ before punch-hole MAP (control, where gas concentrations were same as air) and CA treatments. CA regimens adjusted stepwise during 3 experimental years were: 1 and 3% $O_2$, respectively combined with 5 and 10% $CO_2$ in the first year, 3% $O_2$ fixed in combination with 0, 2.5, and 5% $CO_2$ in the second year, and 3% $O_2$ fixed in combination with 2.5 and 5% $CO_2$ in the third year. In the first year, higher incidence of black discoloration was observed with the reduction of respiration under 10% $CO_2$ CA conditions regardless of $O_2$ levels at 1 or 3%. In the second and third year, the incidence of the disorder seemed not to be clearly relevant to CA conditions showing slightly higher incidence only after 4- or 5-week storage + 5-day shelf life. Although texture and appearance quality were maintained better under the 3% $O_2$ + 2.5% $CO_2$condition after 4-week storage + 5-day shelf life, effects of CA on the extension of storage period was slight. Overall results indicated that Ligularia fischeri leaves are very susceptible to $CO_2$ injury. $CO_2$ concentration should be adjusted below 2.5% for safe and effective CA or MAP storage to maintain quality even during short-term storage.

Weight Reduction Dieting Survey and Satisfaction Degree and Diet Related Knowledge among Adult Women by Age (연령별 성인 여성의 체중감량 다이어트 실태와 만족도 및 관련지식)

  • Kim, Myung-Kyung;Lee, Gui-Chu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.5
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    • pp.572-582
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    • 2006
  • This survey was conducted from June 2004 to August 2004, through questionnaires given to 432 women aged ranging from 20 to 50 years, who were living in the Seoul metropolitan area. The questionnaires were designed to determine the physique, level of obesity and dieting survey as well as to uncover which diets were in fashion and their satisfaction degree. Dieting-related knowledge and dieting side effects were also investigated. The results were as follows: In dieting survey, as the age increased, dieting for health reason (52.3%) increased, whereas that for aesthetic reasons (32.6%) decreased (p<0.05). The most effective methods of dieting were exercise (50.2%) and diet (45.0%) regimens. In regards to exercise frequency, 46.5% for none, 23.5% for 1-2 times a week, suggesting that most respondents do not practice exercise for dieting purposes (p<0.05). Major source for dieting was shown to be obtained from relative family or friends (31.7%), newspapers or magazines (29.3%) and internet (14.9%). As the age decreased, information from the latter increased, whereas that from TV program (21.2%) decreased (p<0.05). Reasons for excess weight were bad eating habits (39.6%), lack of exercise (38.3%), pregnancy and childbirth (10.6%). In fad dieting, while organic foods and aerobic exercises scored the highest satisfaction degree among diet and exercise regimens, on the other hand, sauna, steam baths and high temperature half-immersion baths scored the highest among surgery and other special therapies. As the age increased, the satisfaction degree for organic foods such as organic vegetable and high functional boiled cooked rice increased (p<0.05). As the age increased, scores on dieting-related knowledge decreased. Side effects of dieting included dizziness 06.2%) fatigue (15.1%) indigestion/constipation (11.1%) physical weakness 00.5%), loss of concentration (7.8%), dry skin (7.4%) loss of motivation (6.7%). The above results showed that attitude toward dieting among adult women varied with age and in light of the well-being trend, organic foods and aerobic exercises scored the highest satisfaction degree through all age.

A Clinical Effect of Ofloxacin, Prothionamide, Cycloserine Streptomycin(Kanamycin or Tuberactinomycin) in Retreatment of Pulmonary Tuberculosis (폐결핵 재치료에서 Ofloxacin, Prothionamide, Cycloserine, Streptomycin(Kanamycin or Tuberactinomycin) 4제요법의 임상 효과)

  • Song, Ju-Young;Yoo, Min-Kyu;Hong, Jae-Rack;Jeong, Jae-Man;Kim, Young-Jun;Kim, Moon-Shik
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.3
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    • pp.295-301
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    • 1995
  • Background: The serious problems in retreatment of pulmonary tuberculosis are a significant proportion of drug resistance. Preferably retreatment should contain the drugs which has never used before, so drug retreatment is limited in selection. A new antibacterial substance, ofloxacin(OFX) is the activity against mycobacterium tuberculosis and it has been used in the treatment of pulmonary tuberculosis. The present report concerns the result of retreatment of pulmonary tuberculosis patients containing OFX treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow up of 92 smear positive cases, who were treated by four drugs regimen between Mar 1991 and June 1994 at National Kongju Tuberculosis Hospital. Four drugs were, namely prothionamide, cycloserine, ofloxacin and streptomycin(kanamycin or tuberactinomycin). The duration of follow up was over one year. Results: 1) Out of 92 cases with positive sputum AFB smear, 67(73%) achieved the negative conversion. 2) Considering the negative sputum conversion in all the groups, the vast majority(85%) of sputum conversion occurred within the first 4 months. 3) The roentgenological improvement occurred in 49 percent on the whole and when the extent of disease was minimal, moderately, far advanced pulmonary tuberculosis, sputum AFB smear negative response to retreatment was 100%, 93%, 68%, respectively. 4) When the duration of patient's illness was less than 1 year, 1 to 3 years, 3 to 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 87%, 76%, 65% and 55%, respectively. 5) Adverse reaction to prothionamide, with complaints of gastrointestinal troubles was common and hepatic dysfunction without jaundice was observed in 7 percent, convulsion in 1 percent, that to cycloserine occurred renal dysfunction & psycosis & convulsion, 2%, 1%, 1%, respectively. Tinnitus with KM occurred in 1% and dirrhea with OFX in 4%. Conclusion: The duration of patient's illness was shorter, sputum AFB smear negative response rate was better. Radiologic responses were not remarkable, but extent of disease by national tuberculosis association was smaller, the result of retreatment was better. Adverse reaction of the secondary antituberculosis agent was mainly observed gastrointestinal troubles, as regard to tolerance to the secondary drugs the role of the physician is of very important value and toxic effects can be overcome by the strong confidence.

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