The role of CD98 heavy chain in cancer development.

The glycoprotein CD98, or CD98 heavy chain (CD98hc), encoded by the SLC3A2 gene, plays a crucial role in cancer development and progression. CD98hc, forming heterodimeric complexes with various light chains, regulates neutral amino acid transport across cell membranes. The intricate interplay between CD98hc, integrins, and amino acid transporters shapes the tumor microenvironment and contributes to tumor growth. Elevated expression of CD98hc in various cancers correlates with poor prognosis, making it a potential prognostic marker. In colorectal cancer, CD98hc emerges as a potential therapeutic target, along with its partner LAT1, and inhibitors like JPH203 exhibit promise in preclinical studies. Targeting CD98hc/LAT1, alone or with conventional therapies, shows promise in inhibiting tumor growth. This review focuses on elucidating the multifaceted roles of CD98hc and its partner LAT1 in cancer, particularly its involvement in amino acid transport, signaling pathways, and its prognostic relevance in cancer.

Identification and Biological Evaluation of a Potent and Selective JAK1 Inhibitor for the Treatment of Pulmonary Fibrosis.

Janus kinase 1 (JAK1) plays a pivotal role in regulating inflammation and fibrosis via the JAK/STAT signaling pathway, making it a promising target for associated diseases. In this study, we explored the modification of an N-methyl 1H-pyrrolo[2,3-b]pyridine-5-carboxylate core, leading to the identification of 4-(((2S,4S)-1-(4-trifluoromethyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (36b) as a highly potent and selective JAK1 inhibitor. Compound 36b exhibited an impressive IC50 value of 0.044 nM for JAK1 and demonstrated remarkable selectivity of 382-fold, 210-fold, and 1325-fold specificity over JAK2, JAK3, and TYK2, respectively. The kinase panel assays further confirmed its specificity, and cell-based experiments established its efficacy in inhibiting JAK1-STAT phosphorylation in human L-132 or SK-MES-1 cells. Pharmacokinetic studies revealed that compound 36b boasts an oral bioavailability exceeding 36%. In a bleomycin-induced fibrosis mouse model, compound 36b significantly reduced STAT3 phosphorylation, resulting in improvement in body weight and reduced collagen deposition, all achieved without significant side effects.

Outbred Mice with Streptozotocin-Induced Diabetes Show Sex Differences in Glucose Metabolism.

Outbred mice (ICR) with different genotypes and phenotypes have been reported to be more suitable for scientific testing than inbred mice because they are more similar to humans. To investigate whether the sex and genetic background of the mice are important factors in the development of hyperglycemia, we used ICR mice and divided them into male, female, and ovariectomized female (FOVX) groups and treated them with streptozotocin (STZ) for five consecutive days to induce diabetes. Our results show that fasting blood glucose and hemoglobin A1c (HbA1c) levels were significantly higher in diabetes-induced males (M-DM) and ovariectomized diabetes-induced females (FOVX-DM) than in diabetes-induced females (F-DM) at 3 and 6 weeks after STZ treatment. Furthermore, the M-DM group showed the most severe glucose tolerance, followed by the FOVX-DM and F-DM groups, suggesting that ovariectomy affects glucose tolerance in female mice. The size of pancreatic islets in the M-DM and FOVX-DM groups was significantly different from that of the F-DM group. The M-DM and FOVX-DM groups had pancreatic beta-cell dysfunction 6 weeks after STZ treatment. Urocortin 3 and somatostatin inhibited insulin secretion in the M-DM and FOVX-DM groups. Overall, our results suggest that glucose metabolism in mice is dependent on sex and/or genetic background.

An Efficacy Study of Voice Quality Using Cepstral Analyses of Phonation in Parkinson's Disease before and after SPEAK-OUT!®.

INTRODUCTION: SPEAK-OUT!® is a behavioral treatment for hypokinetic dysarthria in persons with Parkinson's disease (PD) that has become an alternative to the gold-standard Lee Silverman Voice Treatment (LSVT) in recent years. Acoustic evaluation of the efficacy of SPEAK-OUT!® therapy has focused on prosody. The purpose of this study was to investigate SPEAK-OUT!® efficacy in terms of vocal quality and its impact on quality of life. Vocal quality was measured acoustically using cepstral peak prominence (CPP) analysis and the Acoustic Voice Quality Index (AVQI) and perceptually using clinical ratings of speech performance. Impact on quality of life was measured with the Voice Handicap Index (VHI) and Voice-Related Quality of Life (V-RQOL). An additional goal of this study was to investigate whether dysarthria severity and disease duration were predictive of changes in voice quality due to SPEAK-OUT!®. METHODS: Pre- and post-therapy data included PD participants' acoustic and perceptual ratings of audio recordings. Demographic data included age, sex, diagnosis, duration of PD, and severity of dysarthria. RESULTS: Participants achieved significant improvement in the vowel and sentence CPP smoothed (CPPS) mean score as well as in their AVQI score post SPEAK-OUT!® treatment. Improvements in AVQI correlated negatively with disease duration and positively with dysarthria severity. DISCUSSION/CONCLUSION: SPEAK-OUT!® is effective in improving voice quality in patients with hypokinetic dysarthria due to idiopathic PD. Patients with more severe dysarthria and with a shorter disease duration may benefit the most, supporting earlier intervention. As for the type of measurement, AVQI combines acoustics from both vowel and sentence contexts and may therefore be the measure of choice over CPPS (vowel) or CPPS (sentence).

2-Amino-1,3,4-thiadiazoles as Glutaminyl Cyclases Inhibitors Increase Phagocytosis through Modification of CD47-SIRPα Checkpoint.

Glutaminyl cyclases (QC, isoQC) convert N-terminal glutamine or glutamate into pyroglutamate (pGlu) on substrates. IsoQC has recently been demonstrated to promote pGlu formation on the N-terminus of CD47, the SIRPα binding site, contributing to the "don't eat me" cancer immune signaling of CD47-SIRPα. We developed new QC inhibitors by applying a structure-based optimization approach starting from fragments identified through library screening. Screening of metal binding fragments identified 5-(1H-benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine (9) as a potent fragment, and further modification provided 5-(1-(3-methoxy-4-(3-(piperidin-1-yl)propoxy)benzyl)-1H-benzo[d]imidazol-5-yl)-1,3,4-thiadiazol-2-amine (22b) as a potent QC inhibitor. Treatment with 22b in A549 and H1975 lung cancer cells decreased the CD47/αhCD47-CC2C6 interaction, indicative of the CD47/SIRPα interaction, and enhanced the increased phagocytic activity of both THP-1 and U937 macrophages.

Differential epithelial and stromal LGR5 expression in ovarian carcinogenesis.

Lgr5 has been identified as a marker of the stem/progenitor cells in the murine ovary and oviduct by lineage tracing. However, little is known regarding LGR5 expression or its functional significance in human ovary tissues. Here, using RNA in situ hybridization and/or immunohistochemistry, we thoroughly investigated LGR5 expression in normal human ovaries, fallopian tubes and various ovarian tumors. We discovered that LGR5 expression is negligible in the human ovary surface epithelium, whereas ovarian stromal cells normally express low levels of LGR5. Remarkably, fallopian tube epithelium, inclusion cysts and serous cystadenomas with a Müllerian phenotype expressed high levels of LGR5, and LGR5 expression was restricted to PAX8+/FOXJ1- secretory cells of the tubal epithelium. Strong stromal LGR5 expression without epithelial LGR5 expression was consistently observed in the path from serous cystadenoma to serous borderline tumor to low grade serous carcinoma (LGSC). Unlike LGSC, high grade serous carcinoma (HGSC), clear cell carcinoma, endometrioid carcinomas displayed various epithelial-stromal LGR5 expression. Notably, high levels of LGR5 expression were observed in serous tubal intraepithelial carcinoma, which slightly declined in invasive HGSC. LGR5 expression was significantly associated with improved progression-free survival in HGSC patients. Moreover, in vitro assays demonstrated that LGR5 expression suppressed tumor proliferation and migratory capabilities. Taken together, these findings indicate a tumor-suppressive role for LGR5 in the progression of HGSC.

Reading Warm-Up, Reading Skill, and Reading Prosody When Reading the My Grandfather Passage: An Exploratory Study Born Out of the Motor Planning Theory of Prosody and Reading Prosody Research.

PURPOSE: The Motor Planning Theory of Prosody and reading prosody research indicate that "out of the blue" oral reading, as practiced in clinical and research settings, invokes surface rather than covert prosody, particularly when readers are recorded, less skilled, and/or speech impaired. Warm-up is not considered in passage reading for motor-speech assessment. We report on a preliminary study aimed to investigate the effect of warm-up on reading prosody in two conditions: silent reading alone and reading "out of the blue" followed by silent reading. A secondary aim of the study was to examine the effect of reading skill on reading prosody. METHOD: Twenty-one monolingual, English-speaking volunteers were recorded reading the My Grandfather Passage (GP) while their eye movements were tracked. Participants were randomly assigned to one of two reading conditions: (a) silent-oral (SO) and (b) oral-silent-oral (OSO). In the SO condition, participants read the GP silently as a warm-up for the subsequent oral reading. In the OSO condition, participants first read the GP aloud ("out of the blue") and then read the same passage silently with the instruction to do this in preparation for a second oral reading. Reading skill was quantified using eye-voice span and Wide Range Achievement Test-Fourth Edition testing. Reading prosody was evaluated using pause indexes, the Acoustic Multidimensional Prosody Index, and speech rate. CONCLUSIONS: One oral reading before a silent reading but not a silent reading alone before oral reading was shown to affect reading prosody. In terms of reading skill, results indicate that predictive associations patterned differently in the reading conditions explored, suggesting different underlying skill sets.

Long Haul COVID-19 Videos on YouTube: Implications for Health Communication.

The term COVID-19 "long haul" originated on social media and was later studied by the scientific community. This study describes content related to persistent COVID-19 symptoms on YouTube. The 100 most viewed English-language videos identified with the keywords "COVID-19 long haul" were assessed for video origin, engagement, and content related to COVID-19 long-haul. The findings indicate that the majority of videos were uploaded by television or internet news (56%), followed by consumers (members of the public, 32%), health professionals (only 9%), and lastly by entertainment TV (non-news programs, 3%). Videos originating from entertainment TV were significantly more likely to be "liked" than videos from other sources. The most commonly mentioned long-haul symptoms in the videos were physical (fatigue, 73%; difficulty breathing/shortness of breath, 56%; and joint or muscle pain, 49%) and cognitive (difficulty thinking or concentrating; 69%). The case of COVID-19 long haul demonstrates that social media are significant fora whereon the public identify health concerns. It is necessary for healthcare professionals to assume an active and responsible role in social media.

SLUG is a key regulator of epithelial-mesenchymal transition in pleomorphic adenoma.

The histogenesis of pleomorphic adenoma (PA) of the salivary glands remains controversial. PAs are characterized by the transition of epithelial cells to spindled mesenchymal cells, known as epithelial-mesenchymal transition (EMT). The present study aimed to identify a major EMT-inducing transcription factor (EMT-TF) in PAs. Real-time PCR analysis of SNAIL, SLUG, ZEB1, and TWIST1 demonstrated that only SLUG was significantly upregulated in normal salivary glands and PAs. Combined in situ hybridization for SLUG and multiplex immunohistochemistry for CK19 and P63 revealed that SLUG was specifically expressed in the myoepithelial cells of normal salivary glands. In PAs, SLUG was expressed in neoplastic myoepithelial cells and stromal cells but not in the luminal cells lining the inner layers of tumor glands. SLUG expression showed no correlation with PLAG1 expression, and in vitro experiments demonstrated that PLAG1 suppression in primary cultured PA cells or PLAG1 overexpression in HEK 293 T cells did not affect SLUG levels, indicating that PLAG1 was not involved in the upregulation of SLUG in PAs. The suppression of SLUG expression in cultured PA cells resulted in a morphology change to a less elongated shape and attenuated tumor growth. In addition, SLUG downregulation led to increased E-cadherin and decreased N-cadherin and vimentin expression levels along with decreased migratory activity in cultured PA cells. These findings suggest that SLUG is a major TF that can induce EMT in PAs. In summary, SLUG is specifically and highly expressed in the myoepithelial cells and stromal cells of PAs and is a key regulator of EMT in PAs.

Online News Coverage of COVID-19 Long Haul Symptoms.

A number of the people who have recovered from the acute effects of COVID-19 are facing long term sequelae from the infection. As the COVID-19 pandemic is still evolving, so is knowledge of the long-term effects of the virus on patients who still experience symptoms. Clearly, news media play a crucial role in distributing information and this distribution of information can, in turn, influence the actions of the public. The purpose of this study was to describe the content of news coverage of COVID-19 long haul symptoms currently posted on the internet. This study utilized Google News, a news aggregator service, and included the first 100 English language pieces of news. Video content and news article content were coded in depth for information on COVID-19 long haul symptoms. A total of 41% of news reports mentioned the length of time that the COVID-19 related symptoms persist. The length of time was reported to range from 1 month to more than 1 year. The symptom most commonly mentioned was tiredness or fatigue (74%), followed by difficulty breathing or shortness of breath (62 cases; 62%), and difficulty thinking or concentrating (50 cases; 50%). Other symptoms were mentioned less frequently. There were no statistically significant differences in any of the content including having video, written news reports, or both video and written news reports by source of the news reports based on consumer, professional, or television or internet-based news (p = .14). More complete coverage by online news media of the long-term effects of COVID-19 enhances public awareness of the post-acute syndromes, augments health providers' awareness of the range of chronic COVID-19 effects and the possibility of a second infection, increases the probability of patients' seeking and obtaining the proper care for their symptoms, and contributes to preventive actions for enhancing public health.

The influence of smoking and alcohol on bone healing: Systematic review and meta-analysis of non-pathological fractures.

BACKGROUND: We aimed to comprehensively evaluate the associations between (i) smoking, (ii) preoperative smoking cessation time, (iii) nicotine replacement therapy (NRT), (iv) vaping, and (v) alcohol consumption and non-pathological fracture healing in adult patients. We also assessed the impacts of preoperative smoking cessation time, NRT, and vaping on wound healing and wound complications after any sort of surgery. METHODS: We searched the MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and AMED electronic databases from their inceptions until August 9th, 2021. Primary outcomes included delayed union rate, nonunion rate, and time to union. A random effects model was used. (Protocol registration: PROSPERO-CRD42019131454). FINDINGS: One hundred and twenty-two studies with 417,767 patients were eligible for the systematic review and 71 of the studies with 39,920 patients were eligible for the meta-analysis. After non-pathological fracture treatment, the nonunion rate was significantly greater in the smoker group than in the non-smoker group (odds ratio [OR], 2·50, 95% confidence interval [1·73-3·61]); additionally, there was no significant difference in the nonunion rate (OR, 0·97 [0·40-2·38]) between the alcohol drinker group and the non-drinker group. The rate of wound infection after surgery was significantly reduced in the smoking cessation group (≥four weeks before surgery) compared to the continuous smoker group (OR, 0·37 [0·16-0·89]). INTERPRETATION: Smoking is associated with higher rates of nonunion and deep surgical site infection after non-pathological fracture treatment. Smoking cessation (≥four weeks before surgery) is associated with a decreased rate of postoperative wound infection. FUNDING: The China Scholarship Council (no. 201809120013).

Design and Synthesis of TRAP1 Selective Inhibitors: H-Bonding with Asn171 Residue in TRAP1 Increases Paralog Selectivity.

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is overexpressed in the mitochondria of various cancer cells, reprograms cellular metabolism to enable cancer cells to adapt to harsh tumor environments. As inactivation of TRAP1 induces massive apoptosis in cancer cells in vitro and in vivo, the development of TRAP1-selective inhibitors has become an attractive approach. A series of purine-8-one and pyrrolo[2,3-d]pyrimidine derivatives was developed based on TRAP1 structure and identified to be highly selective in vitro for TRAP1 over the paralogous enzymes, Hsp90α and Grp94. The TRAP1-selective inhibition strategy via utilization of the Asn171 residue of the ATP-lid was investigated using X-ray crystallography and molecular dynamics simulation studies. Among various synthesized potent TRAP1 inhibitors, 5f possessed a 65-fold selectivity over Hsp90α and a 13-fold selectivity over Grp94. Additionally, 6f had a half-maximal inhibitory concentration (IC50) of 63.5 nM for TRAP1, with a 78-fold and 30-fold selectivity over Hsp90α and Grp94, respectively.

Information regarding acute stroke associated with COVID-19 in online news.

Patients with COVID-19 may present with neurological manifestations, lack of oxygenation, or clotting disorders such as ischemic or hemorrhagic strokes. This has been observed in even young patients with mild symptoms. The aim of this study was to explore current online news coverage of acute stroke associated with COVID-19 in the four-month period from April 2020 to July 2020, a time during which the US found itself in the center of the pandemic. The relevant Google News stories were reviewed for content. The analysis indicated that 118 online news reports covered the topic to varying degrees, including data from reputable sources, references to the neurological symptoms, and to the incidence of stroke in young patients. It is important that health professionals be aware of this risk and convey to the public the possibility of stroke due to COVID-19 so as to increase the probability of early diagnosis and optimal outcomes.

Discovery and Biological Evaluation of N-Methyl-pyrrolo[2,3-b]pyridine-5-carboxamide Derivatives as JAK1-Selective Inhibitors.

Janus kinase 1 (JAK1) plays a key role in most cytokine-mediated inflammatory and autoimmune responses through JAK/STAT signaling; thus, JAK1 inhibition is a promising therapeutic strategy for several diseases. Analysis of the binding modes of current JAK inhibitors to JAK isoforms allowed the design of N-alkyl-substituted 1-H-pyrrolo[2,3-b] pyridine carboxamide as a JAK1-selective scaffold, and the synthesis of various methyl amide derivatives provided 4-((cis-1-(4-chlorobenzyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (31g) as a potent JAK1-selective inhibitor. In particular, the (S,S)-enantiomer of 31g (38a) exhibited excellent potency for JAK1 and selectivity over JAK2, JAK3, and TYK2. On investigating the effect of 31g on hepatic fibrosis, it was found that it reduces the proliferation and fibrogenic gene expression of TGF-ß-induced hepatic stellate cells (HSCs). Specifically, 31g significantly inhibited TGF-ß-induced migration of HSCs at 0.25 µM in wound-healing assays.

Effectiveness of Non-Pharmacological Interventions for Overweight or Obese Infertile Women: A Systematic Review and Meta-Analysis.

Obesity is a well-known risk factor for infertility, and nonpharmacological treatments are recommended as effective and safe, but evidence is still lacking on whether nonpharmacological interventions improve fertility in overweight or obese women. The aim of this study was to systematically assess the current evidence in the literature and to evaluate the impact of nonpharmacological interventions on improving pregnancy-related outcomes in overweight or obese infertile women. Seven databases were searched for randomized controlled trials (RCTs) of nonpharmacological interventions for infertile women with overweight or obesity through August 16, 2019 with no language restriction. A meta-analysis was conducted of the primary outcomes. A total of 21 RCTs were selected and systematically reviewed. Compared to the control group, nonpharmacological interventions significantly increased the pregnancy rate (relative risk (RR), 1.37; 95% CI, 1.04-1.81; p = 0.03; I² = 58%; nine RCTs) and the natural conception rate (RR, 2.17, 95% CI, 1.41-3.34; p = 0.0004; I² = 19%, five RCTs). However, they had no significant effect on the live birth rate (RR, 1.36, 95% CI, 0.94-1.95; p=0.10, I² = 65%, eight RCTs) and increased the risk of miscarriage (RR: 1.57, 95% CI, 1.05-2.36; p = 0.03; I² = 0%). Therefore, nonpharmacological interventions could have a positive effect on the pregnancy and natural conception rates, whereas it is unclear whether they improve the live birth rate. Further research is needed to demonstrate the integrated effects of nonpharmacological interventions involving psychological outcomes, as well as pregnancy-related outcomes.

Evaluation of Mineral Contents of Multi-Vitamin and Minerals Currently Sold in South Korea.

Dietary supplements are popular worldwide and their use has been increasing. The purpose of this study was to evaluate the mineral contents of multi-vitamins and minerals (MVMs) in most commonly sold among dietary supplements. Ninety popular MVM supplements sold in South Korea were surveyed regarding their characteristics and ingredients including minerals listed on the labels through off-line and on-line search. Daily mineral contents of the MVM supplements were compared with Korean Dietary Reference Intakes (DRIs) by target populations. The average price of 90 MVM supplements was $41.3 per bottle, with a price of $0.9 per day and the average number of minerals contained per supplement was 4.7. A total 14 minerals were found in the MVM supplements including calcium, phosphorus, sodium, potassium, and magnesium. Nine minerals (e.g. calcium, magnesium, and iron) were included in more than 30% of the MVM supplements examined. When daily mineral dose of MVMs was compared to DRIs, calcium was the lowest (34.0% of recommended intake [RI]) and chromium was the highest (218.7% of adequate intake [AI]), and zinc, copper, selenium, and chromium were also higher than their RI or AI levels. The daily mineral contents of the 90 MVM supplements were below the tolerable upper-intake level, but some minerals were higher than RI or AI with high variance among products. Therefore, there is a great need to educate the public for the adequate selection and use of MVM supplements based on the contents of MVM supplements and individual's mineral intake derived from the diet.

Prosodic Improvement in Persons with Parkinson Disease Receiving SPEAK OUT!® Voice Therapy.

BACKGROUND/AIMS: Hypokinetic dysarthria in Parkinson disease (PD) hinders the ability to verbally communicate and interferes with activities of daily living. SPEAK OUT!® is a therapy program designed to improve functional communicative ability. In contrast to the Lee Silverman Voice Treatment program, SPEAK OUT!® promotes speaking with intent to effect loud speech. This study evaluated the efficacy of SPEAK OUT!® in persons with idiopathic PD in 3 domains: self-reported voice handicap, clinical ratings of dysarthria and prosody, and acoustic analysis of prosody. PARTICIPANTS AND METHODS: Pre-/post-therapy data included PD participants' scores on the Voice Handicap Index (VHI) and the Voice-Related Quality of Life (V-RQOL) questionnaire, audio recordings, perceptual evaluation scores, and demographic data, such as age, sex, handedness, diagnosis, and onset of PD. RESULTS: Participants achieved a statistically and clinically significant improvement in speech intensity, pitch range, normalized pairwise variability index for pitch, sustained vowel duration, reading intelligibility, and vocal quality after SPEAK OUT!® training, consistent with both of the self-report voice scores, i.e., the VHI and the V-RQOL, and with the perceptual speech evaluation scores. Longer PD duration was associated with lowered efficacy. CONCLUSIONS: SPEAK OUT!® is effective and should be administered as early as possible after disease onset.

Physical Activity Frequency and the Risk of Stroke: A Nationwide Cohort Study in Korea.

BACKGROUND: The current guideline recommends moderate- to vigorous-intensity physical activity (PA) at least 40 min/day for 3 to 4 days/week. Although recent evidence has demonstrated that low-dose PA could reduce cardiovascular mortality, the relationship between low-dose PA and the risk of stroke remains uncertain. METHODS AND RESULTS: Using data from a nation-wide sample cohort in Korea, we examined 336 326 individuals who received a general health examination between 2009 and 2010. Level of PA was assessed using a questionnaire for weekly PA frequencies regarding 3 intensity categories: light, moderate, and vigorous. Moderate- to vigorous-intensity PA (MVPA) was classified into 4 frequency categories: none, 1 to 2, 3 to 4, or ≥5 times/week. Cox proportional hazard models were constructed to estimate the risk of stroke. During the average follow-up of 3.6 years, 2213 stroke cases occurred. MVPA was none in 50%, 1 to 2 times/week in 20%, 3 to 4 times/week in 13%, and ≥5 times/week in 18% of the cohort. Individuals with MVPA 1 to 2 times/week had a 16% reduced risk of stroke (adjusted hazard ratio, 0.84; 95% confidence interval, 0.73-0.96) compared with those with no MVPA. The population attributable fraction of no MVPA was 12%, which was the second most important risk factor for a stroke after hypertension. CONCLUSIONS: Even 1 to 2 times a week of MVPA might be beneficial to prevent a first-ever stroke in the general population, although a quantitative validation of the questionnaire is needed. From a public health perspective, we need to encourage inactive people to start exercising with more-achievable goals.

Usage Trends of Open Access and Local Journals: A Korean Case Study.

Articles from open access and local journals are important resources for research in Korea and the usage trends of these articles are important indicators for the assessment of the current research practice. We analyzed an institutional collection of published papers from 1998 to 2014 authored by researchers from Seoul National University, and their references from papers published between 1998 and 2011. The published papers were collected from Web of Science or Scopus and were analyzed according to the proportion of articles from open access journals. Their cited references from published papers in Web of Science were analyzed according to the proportion of local (South Korean) or open access journals. The proportion of open access papers was relatively stable until 2006 (2.5 ~ 5.2% in Web of Science and 2.7 ~ 4.2% in Scopus), but then increased to 15.9% (Web of Science) or 18.5% (Scopus) in 2014. We analyzed 2,750,485 cited references from 52,295 published papers. We found that the overall proportion of cited articles from local journals was 1.8% and that for open access journals was 3.0%. Citations of open access articles have increased since 2006 to 4.1% in 2011, although the increase in open access article citations was less than for open access publications. The proportion of citations from local journals was even lower. We think that the publishing / citing mismatch is a term to describe this difference, which is an issue at Seoul National University, where the number of published papers at open access or local journals is increasing but the number of citations is not. The cause of this discrepancy is multi-factorial but the governmental / institutional policies, social / cultural issues and authors' citing behaviors will explain the mismatch. However, additional measures are also necessary, such as the development of an institutional citation database and improved search capabilities with respect to local and open access documents.

Protection of mice against pandemic H1N1 influenza virus challenge after immunization with baculovirus-expressed stabilizing peptide fusion hemagglutinin protein.

Current influenza vaccines are produced in embryonated chicken eggs. However, egg-based vaccines have various problems. To address these problems, recombinant protein vaccines have been developed as new vaccine candidates. Unfortunately, recombinant proteins frequently encounter aggregation and low stability during their biogenesis. It has been previously demonstrated that recombinantly expressed proteins can be greatly stabilized with high solubility by fusing stabilizing peptide (SP) derived from the C-terminal acidic tail of human synuclein (ATS). To investigate whether SP fusion proteins can induce protective immunity in mice, we produced influenza HA and SP fusion protein using a baculovirus expression system. In in vitro tests, SP-fused recombinant HA1 (SP-rHA1) was shown to be more stable than recombinant HA1 (rHA1). Mice were immunized intramuscularly with baculovirus-expressed rHA1 protein or SP-rHA1 protein (2 µg/mouse) formulated with aluminum hydroxide. Antibody responses were determined by ELISA and hemagglutination inhibition assay. We observed that SP-rHA1 immunization elicited HA-specific antibody responses that were comparable to rHA1 immunization. These results indicate that fusion of SP to rHA1 does not negatively affect the immunogenicity of the vaccine candidate. Therefore, it is possible to apply SP fusion technology to develop stable recombinant protein vaccines with high solubility.