Computational evaluation of wire position using separate vertical wire technique and candy box technique for the fixation of inferior pole patellar fractures: a finite element analysis.

The separate vertical wire (SVW) technique and the improved candy box (CB) technique have been proposed for treating inferior pole patellar fractures. However, there is still a lack of clear explanation regarding the location of the wire passing through the patella. Five models of SVW techniques were established in different positions. Finite element analysis was then conducted to determine the optimal bone tunnel position for the SVW technique. Based on these findings, six groups of finite element models were created for CB techniques. The maximum displacement and stress on both the patella and steel wire were compared among these groups under 100-N, 200-N, 300-N, 400-N, and 500-N force loads. The results indicated that, in the SVW technique, the steel wire group near the fracture end of the longitudinal bone tunnel showed minimal displacement and stress on the patella when subjected to different forces. On the other hand, in the CB technique, both the patella and wire experienced minimal stress when a transverse bone tunnel wire was placed near the upper posterior aspect of patella. In conclusion, the SVW technique may require the bone tunnel wire to be positioned near the fractured end of the lower pole of the patella. On the other hand, in CB technique, the transverse bone tunnel wire passing through the patella may be close to its upper posterior aspect. However, further validation is necessary through comprehensive finite element analysis and additional biomechanical experiments.

A 12-Vertex Metallacarborane of Silver(I).

The discovery of ferrocene in 1951 was a significant landmark in the field of organometallic chemistry, and since then, numerous sandwich- or half-sandwich metallic complexes have been reported. However, silver stands as an intriguing exception in this regard, and knowledge of its bonding situation has remained undisclosed. Herein, unprecedented 12-vertex metallacarboranes of Ag(I) (2a and 2b) were synthesized through the reaction of sodium hexamethyldisilazide (NaHMDS) with the mixture of nido-C2B9 carborane anion-supported N-heterocyclic carbene precursors (1a and 1b) and [Ag(PPh3)Cl]4. The X-ray structural analysis of the resulting metallacarboranes revealed a unique "slipped" half-sandwich structure, which is a rarity among cyclopentadienyl analogues. DFT calculations provided insights into the asymmetric π-interactions between the pentagonal C2B3 face and the silver ion.

Effects of adding cocoa fermentation medium on cigar leaves in agricultural fermentation stage.

Background and Objective: With the development of the world economy and the integration of cultures, the Chinese cigar market has shown a significant upward trend. However, high-quality cigar leaves are mostly produced in Dominica, Cuba, Nicaragua and other places. In contrast, Chinese cigar leaves have problems such as insufficient aroma, which has become one of the main factors restricting the development of Chinese cigars. Adding medium to ferment is a traditional method in the cigar industry. At present, it mostly relies on manual experience, and lacks systematic and scientific research. At the same time, the addition of medium fermentation is mainly concentrated in the industrial fermentation process, and has not yet begun to be applied in the agricultural fermentation process. In this study, the medium was added to the agricultural fermentation process for the first time to explore the possibility of the application. The effects of adding cocoa medium to ferment on the chemical composition, sensory quality and surface microbial diversity of eggplant core cigar leaves were investigated.wrapper. Method: With Dexue 7' as the experimental material, the changes of main chemical components of wrapper fermented with water and cocoa medium were determined, and microbial community structure on the surface and relative abundance of cigar leaves at different turning periods were analyzed, and the functional genes were predicted. The results of the study were as follows: 1) The results of sensory evaluation showed that the addition of cocoa medium could highlight the aroma of bean, cocoa and coffee, improve the sweetness and fluency and the combustibility of cigar leaves. 2) The addition of cocoa medium increased the contents of proline and malic acid which were positively correlated with sensory quality, and decreased the contents of citric acid, linoleic acid, basic amino acids and aromatic amino acids which were negatively correlated with sensory quality. 3) The addition of cocoa medium increased the total amount of aroma components in cigar leaves, especially carotenoid degradation products, and changed the structural composition of some aroma substances in wrappercigar leaves. 4) The similarity of species composition between the water-added group and the cocoa-added group was higher, but the dominant microorganisms were more concentrated. Staphylococcus and Arthrobacter maintained a high relative abundance throughout the fermentation process, which may be the key microorganisms in the agricultural fermentation stage. 5) The addition of cocoa medium increased the expression abundance of related functional genes in cigar leaves, accelerated the fermentation process of cigar leaves, and bacteria played a major role in the fermentation process. Conclusion: Adding cocoa medium in the agricultural fermentation stage, the changes of bacterial community and dominant flora on the surface of cigar leaves are the main factors affecting their internal chemical components, and the addition of media has a positive effect on tobacco fermentation.

Retinal Thickness and Its Interocular Asymmetry Between Parkinson’s Disease and Drug-Induced Parkinsonism

Background@#Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging.Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson’s disease (PD). @*Methods@#We investigated 97 de novo PD patients and 27 DIP patients using OCT and [ 18 F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specificon-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. @*Results@#No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all Pvalues > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). @*Conclusion@#Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive muta-tions initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resis-tance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunc-tion, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

A novel intelligent displacement prediction model of karst tunnels.

Karst is a common engineering environment in the process of tunnel construction, which poses a serious threat to the construction and operation, and the theory on calculating the settlement without the assumption of semi-infinite half-space is lack. Meanwhile, due to the limitation of test conditions or field measurement, the settlement of high-speed railway tunnel in Karst region is difficult to control and predict effectively. In this study, a novel intelligent displacement prediction model, following the machine learning (ML) incorporated with the finite difference method, is developed to evaluate the settlement of the tunnel floor. A back propagation neural network (BPNN) algorithm and a random forest (RF) algorithm are used herein, while the Bayesian regularization is applied to improve the BPNN and the Bayesian optimization is adopted for tuning the hyperparameters of RF. The newly proposed model is employed to predict the settlement of Changqingpo tunnel floor, located in the southeast of Yunnan Guizhou Plateau, China. Numerical simulations have been performed on the Changqingpo tunnel in terms of variety of karst size, and locations. Validations of the numerical simulations have been validated by the field data. A data set of 456 samples based on the numerical results is constructed to evaluate the accuracy of models' predictions. The correlation coefficients of the optimum BPNN and BR model in testing set are 0.987 and 0.925, respectively, indicating that the proposed BPNN model has more great potential to predict the settlement of tunnels located in karst areas. The case study of Changqingpo tunnel in karst region has demonstrated capability of the intelligent displacement prediction model to well predict the settlement of tunnel floor in Karst region.

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Technology-based interventions to improve adherence to antihypertensive medications - An evidence-based review.

Background: Poor adherence to anti-hypertensive medications leads to poorly controlled blood pressure which is associated with worse cardiovascular outcomes. Emerging technologies may be utilised advantageously in interventions to improve adherence and reduce morbidity and mortality from poorly controlled hypertension. Objective: To determine the efficacy of technology-based interventions in improving adherence to antihypertensive medications. Methods: PubMed and EMBASE databases were searched using keywords and MeSH terms. Included studies met the following criteria: randomized controlled trial (RCT); adults ≥ 18 years old taking anti-hypertensives; intervention delivered by or accessed using a technological device or process; intervention designed to improve adherence. Results: 12 papers met inclusion criteria for the current review: 5 studies significantly improved adherence when compared to usual care; of these 5 studies, 2 had corresponding significant improvement in blood pressure. Successful interventions were: electronic medication bottle cap with audio-visual reminder; short message service (SMS) containing educational information (2 studies); reporting of self-measured blood pressure to a telephone-linked computer system; sending a video of every drug ingestion to obtain monetary rewards. Conclusion: RCTs on technological interventions to improve adherence and those showing significant effect are rare. Some of the interventions show potential to be applied to other populations, especially if targeted at patients with poor adherence at baseline.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

Safety and immunogenicity of a heterologous boost with a recombinant vaccine, NVSI-06-07, in the inactivated vaccine recipients from UAE: a phase 2 randomised, double-blinded, controlled clinical trial

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

Analysis of thromboembolic events in head and neck cancer patients who underwent concurrent chemoradiotherapy with cisplatin

Background/Aims@#The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence @*Methods@#Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. @*Results@#TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). @*Conclusions@#The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

The efficacy of EGFR-tyrosine kinase inhibitor in non-small cell lung cancer patients with synchronous brain metastasis: a real-world study

Background/Aims@#The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. @*Methods@#A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. @*Results@#Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. @*Conclusions@#This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.

A Composite Fabry-Perot Interferometric Sensor with the Dual-Cavity Structure for Simultaneous Measurement of High Temperature and Strain.

In this paper, an optical fiber composite Fabry-Perot interferometric (CFPI) sensor capable of simultaneous measurement of high temperature and strain is presented. The CFPI sensor consists of a silica-cavity intrinsic Fabry-Perot interferometer (IFPI) cascading an air-cavity extrinsic Fabry-Perot interferometer (EFPI). The IFPI is constructed at the end of the transmission single-mode fiber (SMF) by splicing a short piece of photonic crystal fiber (PCF) to SMF and then the IFPI is inserted into a quartz capillary with a reflective surface to form a single-ended sliding EFPI. In such a configuration, the IFPI is only sensitive to temperature and the EFPI is sensitive to strain, which allows the achieving of temperature-compensated strain measurement. The experimental results show that the proposed sensor has good high-temperature resistance up to 1000 °C. Strain measurement under high temperatures is demonstrated for high-temperature suitability and stable strain response. Featuring intrinsic safety, compact structure and small size, the proposed CFPI sensor may find important applications in the high-temperature harsh environment.

Honoring Bacon Ke at 100: a legend among the many luminaries and a highly collaborative scientist in photosynthesis research.

Bacon Ke, who did pioneering research on the primary photochemistry of photosynthesis, was born in China on July 26, 1920, and currently, he is living in a senior home in San Francisco, California, and is a centenarian. To us, this is a very happy and unique occasion to honor him. After providing a brief account of his life, and a glimpse of his research in photosynthesis, we present here "messages" for Bacon Ke@ 100 from: Robert Alfano (USA), Charles Arntzen (USA), Sandor Demeter (Hungary), Richard A. Dilley (USA), John Golbeck (USA), Isamu Ikegami (Japan), Ting-Yun Kuang (China), Richard Malkin (USA), Hualing Mi (China), Teruo Ogawa (Japan), Yasusi Yamamoto (Japan), and Xin-Guang Zhu (China).

Inosine 5'-Monophosphate to Raise Serum Uric Acid Level in Multiple System Atrophy (IMPROVE-MSA study).

The aim of this trial was to investigate the safety, tolerability, and capability of serum uric acid (UA) elevation of inosine 5'-monophosphate (IMP) in multiple system atrophy (MSA). The IMPROVE-MSA trial was a randomized, double-blind, placebo-controlled trial in patients with MSA with no history of hyperuricemia-related disorders. The participants were assigned to placebo (n = 25) or IMP (n = 30) in a 1 to 1 ratio, and then followed up for 24 weeks. The primary end points included safety, tolerability, and alteration of the serum UA level during the follow-up period. The secondary end points were changes in scores of the unified MSA rating scale (UMSARS) and the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The total number of adverse events (AEs) and serious AEs was comparable between the active and placebo groups. Serum UA level (mg/dL) was significantly increased from baseline (active vs. placebo, 4.57 vs. 4.58; P = 0.98) to study end point (6.96 vs. 4.43; P < 0.001) in the active group compared with the placebo group (time × group interaction; P < 0.001). The change in UMSARS scores did not differ between the active and placebo groups. However, the active group showed better alterations in MoCA scores with nominal significance (P < 0.001) and tendency for better alterations in MMSE scores (P = 0.09) than the placebo group. Our data demonstrated that IMP treatment was generally safe and well-tolerated in patients with MSA. A further trial with a long-term follow-up is required to examine whether UA elevation will slow clinical progression in early MSA.

Regulation of the expression and function of TRPCs and Orai1 by Homer2 in mouse pancreatic acinar cells

Under physiological conditions, calcium (Ca2+ ) regulates essential functions of polarized secretory cells by the stimulation of specific Ca2+ signaling mechanisms, such as increases in intracellular Ca2+ concentration ([Ca2+]i ) via the store-operated Ca2+ entry (SOCE) and the receptor-operated Ca2+ entry (ROCE). Homer proteins are scaffold proteins that interact with G protein-coupled receptors, inositol 1,4,5-triphosphate (IP3) receptors, Orai1-stromal interaction molecule 1, and transient receptor potential canonical (TRPC) channels. However, their role in the Ca2+ signaling in exocrine cells remains unknown. In this study, we investigated the role of Homer2 in the Ca2+ signaling and regulatory channels to mediate SOCE and ROCE in pancreatic acinar cells. Deletion of Homer2 (Homer2–/– ) markedly increased the expression of TRPC3, TRPC6, and Orai1 in pancreatic acinar cells, whereas these expressions showed no difference in whole brains of wild-type and Homer2–/– mice. Furthermore, the response of Ca2+ entry by carbachol also showed significant changes to the patterns regulated by specific blockers of SOCE and ROCE in pancreatic acinar cells of Homer2–/– mice. Thus, these results suggest that Homer2 plays a critical role in the regulatory action of the [Ca2+]i via SOCE and ROCE in mouse pancreatic acinar cells.

Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

Motor Asymmetry and Interocular Retinal Thickness in Parkinson's Disease

Background@#To analyze the relationship between interocular difference of retinal thickness and motor asymmetry in Parkinson's disease (PD). @*Methods@#Prospective case-control series analyzed 62 eyes of 31 patients with PD and 62 eyes of 31 age- and sex-matched control. Ophthalmologic examinations including optical coherence tomography (OCT) scans were performed in both groups, and in the patients with PD, motor function was evaluated on the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) to determine the clinically more affected side. Peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) were measured in both eyes, after which the interocular asymmetry of the OCT parameters was determined. Additionally, the more and less affected sides of the UPDRS-III were evaluated using Symmetric index. @*Results@#The average and quadrant pRNFLT and mRT values between the two groups were not different, but the interocular asymmetry of the average mRT and asymmetry index of retinal thickness (AIRT) of temporal mRT were significantly higher in the PD patients than in the controls (P = 0.026 and 0.044). The sum of UPDRS-III showed a discrepancy between the more and less affected sides (P = 0.002); the calculated Symmetric index was 0.21 ± 0.19, which suggested asymmetric motor symptoms. The Symmetric index of UPDRS-III showed significant relations for interocular asymmetry of superior mRT and AIRT of average mRT (P = 0.001 and 0.008). @*Conclusion@#In the PD patients, the interocular asymmetry of mRT was larger than in the controls, and the motor symptoms were asymmetric. Additionally, the interocular asymmetry of mRT showed a significant correlation with motor-symptom laterality.

Mechanical and physico-chemical properties of premixed-MTA in contact with three different types of solutions / 대한치과재료학회지

The study aims to analyze the compressive strength, pH, and surface properties of mineral trioxide aggregates (MTA), which can be used as a pulp capping and root canal filling material. The tests were performed after immersing premixed types of MTA for seven days into three different solutions: simulated body fluid (SBF), saline, and distilled water (DW). A universal testing machine was used to measure the compressive strength after one and seven days of immersion. The un-immersed MTA was used as the control. To investigate the pH variation, MTA specimens were immersed in each solution and the pH was measured using a pH meter after 3, 6, 12, 24, 72, and 168 h. Changes on the MTA surface were also observed by SEM-EDS after seven days of immersion. Moreover, statistical analysis was performed by one-way ANOVA, Tukey's post-hoc test, and independent sample t-test. All experimental groups showed significantly higher compressive strengths compared to the control group (p0.05). As the immersion time increased, the pH increased among all the groups, and the pH of samples immersed in saline and DW was significantly higher than that in SBF. The MTA surface immersed in each solution for seven days showed precipitates which mainly composed of Ca and Zr ions. Therefore, the type of contact solution does not significantly affect the compressive strength of MTA, but it significantly influences both the pH and surface condition

Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.