Copper-Catalyzed Decarboxylation Cross-Coupling Cascade Reaction for Synthesis of Fused Dihydro-benzoxazinones.

A protocol for a tandem copper-catalyzed intermolecular decarboxylation cross-coupling cascade between o-bromobenzoic acids and proline or piperic acid has been disclosed. The developed protocol allows access to a variety of synthetically useful fused benzoxazinones scaffolds with high efficiency and good functional group compatibility. A mechanistically sequential approach for the decarboxylation and dehydration coupling process was presented.

Pd(II)-Catalyzed Arylation/Oxidation of Benzylic C-H of 8-Methylquinolines: Access to 8-Benzoylquinolines.

An efficient access to 8-benzoylquinoline was developed by a sequential arylation/oxidation of 8-methylquinolines with aryl iodides in the presence of Pd(OAc)2. This transformation demonstrates good tolerance of a wide range of functional groups on aryl iodides, providing good to excellent yields of 8-benzoylquinolines.

Ligand-Free Copper(I)-Catalyzed Benzylic Acyloxylation of 2-Alkylpyridines under Aerobic Conditions.

A ligand-free copper(I)-catalyzed benzylic acyloxylation of 2-alkylpyridines with carboxylic acids was realized by using 1.0 atm of O2 as a green oxidant. The transformation provided a facile access to a wide range of N-heterocyclic esters through C-O bond formation, with broad substrate scope and good functional group tolerance. Preliminary mechanistic investigations showed that this protocol included a radical process.

Monodentate Transient Directing Group Assisted Pd-Catalyzed Direct Dehydrogenative Cross-Coupling of Benzaldehydes with Arenes toward 9-Fluorenones.

Commercially available 3,5-bis(trifluoromethyl)aniline was found to be a highly efficient monodentate transient directing group (MonoTDG) for the palladium-catalyzed direct dehydrogenative cross-coupling of benzaldehydes with arenes. A diverse set of symmetrical and unsymmetrical 9-fluorenones was readily obtained in yields of 32-72% along with excellent regioselectivities and broad functional group compatibility as well as high atom economy under mild conditions via a dual carbon-hydrogen (C-H) bond activation sequence.

Reduced Port Laparoscopic Distal Gastrectomy with D2 Lymphadenectomy.

BACKGROUND: Reduced port laparoscopic surgery (RPLS), as a more minimally invasive treatment alternative to conventional laparoscopic surgery (CLS), has been increasing in recent years. 1 With the accumulation of surgical experience and improvements in surgical techniques, the indication of RPLS has been gradually extended from benign diseases to malignant tumors, including gastric cancer. 2-4 However, due to the lack of counteraction and triangulation, lymphadenectomy during reduced port laparoscopic gastrectomy (RPLG) for gastric cancer was considered challenging. In this study, we report our experience performing RPLG with D2 lymphadenectomy for distal gastric cancer. METHODS: A disposable, single-incision, multiport, laparoscopic surgery trocar was used through a 3-cm incision at the umbilicus for the laparoscopist and surgeon's right hand. One 12-mm trocar was inserted at the upper-right quadrant for the surgeon's left hand. Distal gastrectomy with D2 lymphadenectomy was performed in the same manner with CLS. 5 After extracting the resected specimen through the umbilicus incision, intracorporeal Roux-en-Y or B-II gastrojejunostomy was used for reconstruction. RESULTS: RPLG with D2 lymphadenectomy was performed on five patients from April 2017 to June 2017. No intraoperative event requiring conversion to CLS or open surgery occurred. No postoperative complication was observed. The median operating time and blood loss was 166 min and 50 ml. The mean number of retrieved lymph nodes was 32.7. Postoperatively, the mean time to first flatus, soft intake, and hospital stay was 2.6, 3.5, and 6.7 days respectively. CONCLUSIONS: RPLG with D2 lymphadenectomy might be safe and feasible in selected patients.

Tightly-Coupled Integration of Multi-GNSS Single-Frequency RTK and MEMS-IMU for Enhanced Positioning Performance.

Dual-frequency Global Positioning System (GPS) Real-time Kinematics (RTK) has been proven in the past few years to be a reliable and efficient technique to obtain high accuracy positioning. However, there are still challenges for GPS single-frequency RTK, such as low reliability and ambiguity resolution (AR) success rate, especially in kinematic environments. Recently, multi-Global Navigation Satellite System (multi-GNSS) has been applied to enhance the RTK performance in terms of availability and reliability of AR. In order to further enhance the multi-GNSS single-frequency RTK performance in terms of reliability, continuity and accuracy, a low-cost micro-electro-mechanical system (MEMS) inertial measurement unit (IMU) is adopted in this contribution. We tightly integrate the single-frequency GPS/BeiDou/GLONASS and MEMS-IMU through the extended Kalman filter (EKF), which directly fuses the ambiguity-fixed double-differenced (DD) carrier phase observables and IMU data. A field vehicular test was carried out to evaluate the impacts of the multi-GNSS and IMU on the AR and positioning performance in different system configurations. Test results indicate that the empirical success rate of single-epoch AR for the tightly-coupled single-frequency multi-GNSS RTK/INS integration is over 99% even at an elevation cut-off angle of 40°, and the corresponding position time series is much more stable in comparison with the GPS solution. Besides, GNSS outage simulations show that continuous positioning with certain accuracy is possible due to the INS bridging capability when GNSS positioning is not available.

Practical Pd(II)-Catalyzed C-H Alkylation with Epoxides: One-Step Syntheses of 3,4-Dihydroisocoumarins.

Pd(II)-catalyzed ortho-alkylation of benzoic acids with both terminal and internal epoxides affords 3,4-dihydroisocoumarins in one step. The presence of potassium countercations is crucial for this reaction. Monoprotected amino acid ligands significantly promote this reaction, enabling the development of a practical C-H alkylation reaction using 0.5 mol % Pd catalyst. The inversion of stereochemistry in the C-H alkylation step is consistent with a redox-neutral SN2 nucleophilic ring-opening process as opposed to a Pd(II)/Pd(IV) pathway.

Single-incision versus three-port laparoscopic appendectomy for acute appendicitis: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Three-port laparoscopic appendectomy (TPLA) has been shown superior to open appendectomy for acute appendicitis (AA); alternatively, single-incision laparoscopic appendectomy (SILA) is gaining popularity. The choice between SILA and traditional TPLA remains controversial. This meta-analysis of high-quality randomized controlled trials (RCTs) aims to compare efficacy and safety of SILA with TPLA for AA. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing SILA with TPLA. Reference lists of relevant articles and reviews, conference proceedings, and ongoing trial databases were also searched. Primary outcomes were operative time, postoperative complications, hospital duration, and days back to normal activities. Meta-analysis was conducted where possible comparing items using weighted mean differences (WMDs) and relative risks (RRs) according to type of data. Methodological quality was evaluated to assess bias risk. RESULTS: A total of 8 distinct RCTs comparing SILA (n = 616) with TPLA (n = 618) published from 2010 to 2013 were identified in our analysis. SILA took longer to conduct than TPLA (43 vs 38, WMD: 5.96, 95 % CI 2.54-9.38, P = 0.0006). Patients undergoing SILA needed more extra trocars addressed during operation (7 % vs 0 %, RR: 12.36, 95 % CI 3.83-39.90, P < 0.0001), but could return to full activities earlier (6 vs 7, WMD: -0.68, 95 % CI -1.10 to -0.26, P = 0.001). However, these differences were not clinically significant. All other parameters were comparable. CONCLUSIONS: These results provide level 1a support for the clinical similarity that SILA is basically as feasible, effective and safe as TPLA when dealing with AA, although statistically, SILA takes longer to perform, requires more extra trocars, and benefits patients with faster recovery compared with TPLA. Further RCTs are needed to update our finding with advancement of surgical techniques and skills.

Activated CD69+ T cells foster immune privilege by regulating IDO expression in tumor-associated macrophages.

Substantial evidence indicates that immune activation at stroma can be rerouted in a tumor-promoting direction. CD69 is an immunoregulatory molecule expressed by early-activated leukocytes at sites of chronic inflammation, and CD69(+) T cells have been found to promote human tumor progression. In this study, we showed that, upon encountering autologous CD69(+) T cells, tumor macrophages (MΦs) acquired the ability to produce much greater amounts of IDO protein in cancer nests. The T cells isolated from the hepatocellular carcinoma tissues expressed significantly more CD69 molecules than did those on paired circulating and nontumor-infiltrating T cells; these tumor-derived CD69(+) T cells could induce considerable IDO in monocytes. Interestingly, the tumor-associated monocytes/MΦs isolated from hepatocellular carcinoma tissues or generated by in vitro culture effectively activated circulating T cells to express CD69. IL-12 derived from tumor MΦs was required for early T cell activation and subsequent IDO expression. Moreover, we found that conditioned medium from IDO(+) MΦs effectively suppressed T cell responses in vitro, an effect that could be reversed by adding extrinsic IDO substrate tryptophan or by pretreating MΦs with an IDO inhibitor 1-methyl-DL-tryptophan. These data revealed a fine-tuned collaborative action between different types of immune cells to counteract T cell responses in tumor microenvironment. Such an active induction of immune tolerance should be considered for the rational design of effective immune-based anticancer therapies.

MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein.

The functional association between intronic miRNAs and their host genes is still largely unknown. We found that three gene loci, which produced miR-26a and miR-26b, were embedded within introns of genes coding for the proteins of carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase (CTDSP) family, including CTDSPL, CTDSP2 and CTDSP1. We conducted serum starvation-stimulation assays in primary fibroblasts and two-thirds partial-hepatectomies in mice, which revealed that miR-26a/b and CTDSP1/2/L were expressed concomitantly during the cell cycle process. Specifically, they were increased in quiescent cells and decreased during cell proliferation. Furthermore, both miR-26 and CTDSP family members were frequently downregulated in hepatocellular carcinoma (HCC) tissues. Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression. Further investigation disclosed that miR-26a/b directly suppressed the expression of CDK6 and cyclin E1, which resulted in reduced phosphorylation of pRb. Moreover, c-Myc, which is often upregulated in cancer cells, diminished the expression of both miR-26 and CTDSP family members, enhanced the ppRb level and promoted the G1/S-phase transition. Our findings highlight the functional association of miR-26a/b and their host genes and provide new insight into the regulatory network of the G1/S-phase transition.

A novel non-invasive embryo evaluation method (NICS-Timelapse) with enhanced predictive precision and clinical impact.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

Metal-free [3 + 2 + 1]/[2 + 2 + 1] biscyclization: stereospecific construction with concomitant functionalization of indolizin-5(1H)-one.

A metal-free [3 + 2 + 1]/[2 + 2 + 1] biscyclization strategy has been developed for the stereospecific construction with concomitant derivation of biologically significant indolizin-5(1H)-ones from simple and commercial starting materials. The transformations are notable because they can yield five new σ bonds and six stereocenters including a quaternary carbon center in a single operation.

The Prospective Association between Emotional Reactivity and Adolescent Suicidal Ideation.

Despite the importance of emotions in our daily lives, less is known about the role of emotional reactivity in suicidal risk. This brief study investigated whether emotional reactivity is associated with adolescent suicidal ideation six months later. Participants were 139 adolescents (55% female; Mage = 12.79, SDage = 0.73) who completed baseline assessments, a 10-day daily diary protocol, and six-month follow-up assessments. Results showed that higher emotional reactivity indicated by increased negative emotions and decreased positive emotions was associated with a greater risk for suicidal ideation. The findings suggest that adolescents with greater emotional reactivity to daily school problems had elevated risks for suicidal ideation. This study supports the importance of emotional reactivity in daily life for preventing adolescent suicidal ideation.

Control effect of virtual reality technology on procedural pain in children's wound: A meta-analysis.

BACKGROUND: Children who undergo wound manipulation usually experience pain. Virtual reality technology is a novel and effective non pharmaceutical therapy for reducing pain in children scheduled to undergo wound manipulation. However, the effectiveness of Virtual reality technology in controlling procedural pain in children's wounds has not been evaluated in a systematic review. METHODS: It employed a meta-analysis design. We included studies with randomized controlled trials, reporting children's wound manipulation pain, and published them in English. Two reviewers independently evaluated the methodological quality of the included studies. RESULTS: Of the 108 studies identified, 39 were eligible for the meta-analysis, with a total sample of 273 patients. The use of virtual reality technology has significantly reduced pain intensity during wound manipulation in children. There was a significant difference between the experimental group (virtual reality) and the control group (no virtual reality) in reducing the pain of the children's wound manipulation (P < .05). CONCLUSION: As a distraction method of non drug assisted analgesia intervention, virtual reality technology can reduce children's procedural pain and discomfort symptoms.

Differential Trajectories of Fathers' Postpartum Depressed Mood: A Latent Class Growth Analysis Approach.

Parental psychological well-being is essential to the wellness of the family. However, longitudinal investigations into fathers' postpartum depressed mood are limited. This study aimed to identify the typologies of depressed mood trajectories over the first year postpartum among Taiwanese fathers and to examine the factors associated with such typologies. We retrieved data from a nationwide longitudinal study on child development and care in Taiwan. A total of 396 fathers, who completed at least one of the three interviews when their children were 3, 6, and 12 months old between 2016 and 2017, were included in this analysis. Conditional latent class growth analysis was conducted to identify the classifications of the fathers' depressed mood trajectories in the first year postpartum and to estimate the effects of covariates on individuals' membership of a trajectory class. Three classes of depressed mood trajectories were identified. The high increasing group consisted of 11% of the participants; the moderate increasing and the low decreasing groups consisted of 28% and 61% of the participants, respectively. Financial stress was associated with the fathers' likelihood of being in the high increasing group compared with their likelihood of being in the low decreasing group (OR = 2.28, CI = 1.16-4.47). The result may be related to the difference in gender roles and social expectations.

Depressed mood trajectories in the first year postpartum among Taiwanese mothers: Associations with perceived support, financial stress, and marital satisfaction.

This study examined the typology of depressed mood trajectories and the associated factors over the first year postpartum among Taiwanese mothers. Data of 4332 mothers from a nationwide longitudinal study on child development and care were analyzed. Three classes of depressed mood trajectories were identified, two with lower initial scores and a decreasing trajectory and one with a higher initial score and an increasing trajectory. Subjective financial stress, perceived support, and marital satisfaction were significant in predicting mothers' membership of the depressed mood trajectory classes. The results highlighted the individual susceptibility to the postpartum depressed mood among Taiwanese mothers.

Switchable Copper-Catalyzed Approach to Benzodithiole, Benzothiaselenole, and Dibenzodithiocine Skeletons.

A copper-catalyzed reaction between 2-bromo-benzothioamides and S8 or Se involving sulfur rearrangement is reported, enabling access to benzodithioles 2 and benzothiaselenoles 6 in the presence of Cs2CO3. In the absence of S8 or Se, the reaction affords dibenzodithiocines 7 via two consecutive C(sp2)-S Ullmann couplings.

Long-Term Outcomes in Laparoscopic D2 Gastrectomy for Gastric Cancer: a Large Comprehensive Study Proposing Novel Hypotheses.

BACKGROUND: The long-term outcomes of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for gastric cancer (GC) remain obscure, especially for advanced cancer and disease affecting the upper stomach and in older patients. This study aimed to comprehensively assess the long-term efficacy of LG for GC using a large prospective database. METHODS: Totally, 1877 consecutive patients (1186 receiving LG and 691 OG) operated in 2004-2016 were analyzed, with a median follow-up of 63 months. Association of LG versus OG with disease-specific survival (DSS) and disease-free survival (DFS) overall and in various subgroups were investigated using multivariable Cox regression. Propensity score matching (PSM) was performed for sensitivity analysis. RESULTS: Before PSM, overall, there was no significant association of LG versus OG with survival after multivariable adjustment; however, in subgroup analyses, LG was associated with superior DSS in patients aged ≥ 70 years and those with upper GC. No significant associations regarding DFS were observed overall or in stratifications. PSM analyses revealed that LG was associated with better DSS also in patients aged ≥ 70 years (hazard ratio (HR) = 0.33, 95% confidence interval (CI) = 0.15-0.72) and in those with upper GC (HR = 0.51, 95% CI = 0.29-0.91), and with better DFS in those with upper GC (HR = 0.60, 95% CI = 0.37-0.99). Multivariable analysis showed that age, hepatitis B, performance status, tumor histology, stage, and vascular invasion were significantly associated with post-LG survival. LG-specific nomograms were then constructed with concordance indexes of 0.814 (DSS) and 0.809 (DFS) and excellent calibration. CONCLUSIONS: In this large institutional analysis, while LG for GC was associated with DSS and DFS similar to those for OG overall, non-inferior LG-associated survival especially DSS was observed in some subgroups rarely investigated in prospective or randomized settings. There could still be biases even after PSM due to confounders not accounted for in this observational study. However, these findings offer novel hypotheses for further validation.

Childhood otitis media: Relationship with daycare attendance, harsh parenting, and maternal mental health.

Psychological stress has been linked to developmental problems and poor health in children, but it is unclear whether it is also related to otitis media (OM). As part of a long-term study surveying the characteristics of childcare and development in Taiwan, we analyzed the relationship between OM and sources of psychological stress in children, such as poor maternal mental health and harsh parental discipline. We analyzed the data of 1998 children from the "Kids in Taiwan: National Longitudinal Study of Child Development & Care (KIT) Project" at the age of 3 years. Using bivariate and multivariate logistic regression models, we tested several risk factors as potential independent predictors of two outcomes: parent-reported incidence of OM and child health. The proportion of children who had developed OM in the first 3 years of their life was 12.5%. Daycare attendance (odds ratio [OR]: 1.475; 95% confidence interval [CI]: 1.063-2.046), poor maternal mental health (OR: 1.913; 95% CI: 1.315-2.784), and harsh parental discipline (OR: 1.091; 95% CI: 1.025-1.161) correlated with parent-reported occurrence of OM. These findings suggest that providing psychosocial support to both parents and children might be a novel strategy for preventing OM.

Treatment of polycystic liver disease with resection-fenestration and a new classification.

AIM: To evaluate outcomes in patients with autosomal dominant polycyst liver disease (APLD) treated by combined hepatic resection and fenestration. A new classification was recommended to presume postoperative complications and long outcome of patients. METHODS: Twenty-one patients with APLD were treated by a combined hepatic resection and fenestration technique. All patients were reviewed retrospectively, and clinical symptoms, performance status and morbidity were recorded. A new classification of APLD is recommended here. RESULTS: All patients were discharged when free of symptoms. The mean follow-up time was 55.7 mo and three patients had a recurrence of symptoms at 81, 68 and 43 mo after operation, respectively. The overall morbidity rate was 76.2%. Two patients with Type B-II and Type B-I developed biliary leakage. Four patients had severe ascites, including three with Type B-III and one with Type B-II. Nine patients had pleural effusion, including one with Type A-I; one with Type B-I; five with Type B-II; one with Type A-III and one with Type B-III. Three patients with Type B had recurrence of symptoms, while none with Type A had severe complications. CONCLUSION: Combined hepatic resection and fenestration is an acceptable procedure for treatment of APLD. According to our classification, postoperative complications and long outcome can be predicted before surgery.