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Food allergy is a growing health and safety concern that affects up to 8% of school-age children. Because children spend a significant part of their day in school, and the overall number of school-age children with food allergy has been increasing, management of food allergies relies on the collaboration of allergists, families, and schools to treat and prevent acute allergic reactions. For schools, this involves policies centered on food allergen avoidance, preparedness with epinephrine autoinjectors, adequate school personnel training, and accommodations for an equal opportunity learning environment. Partnerships with allergists, primary care providers, students, families, school nurses, and school staff are vital for creating individualized and effective care plans that will allow all children, including those with food allergies, a safe and nurturing learning environment.

Inflammatory diseases are risk factors for osteoporosis. We aimed to explore whether fibrinogen, which is linked to chronic inflammation, is associated with bone mineral density (BMD) in menopausal women.In this cross-sectional study, we analyzed 339 menopausal women from Zhejiang Province between January 2016 and October 2019. Linear regression analysis was performed to assess the relationship between fibrinogen and BMD.Significant inverse association was observed between the serum fibrinogen level and BMD in menopausal women. The mean BMD in each quartile of fibrinogen level was 0.901, 0.897, 0.892, and 0.855 g/cmHigher fibrinogen levels were associated with lower BMD in menopausal women, which was independent of age, body mass index, estradiol, and other factors. Therefore, serum fibrinogen can be used as a new predictor of reduced BMD in menopausal women.

Background Immunosuppression in glioblastoma (GBM) is an obstacle to effective immunotherapy. GBM-derived immunosuppressive monocytes are central to this. Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule, expressed by GBM cells and GBM extracellular vesicles (EVs). We sought to determine the role of EV-associated PD-L1 in the formation of immunosuppressive monocytes. Methods Monocytes collected from healthy donors were conditioned with GBM-derived EVs to induce the formation of immunosuppressive monocytes, which were quantified via flow cytometry. Donor-matched T cells were subsequently co-cultured with EV-conditioned monocytes in order to assess effects on T-cell proliferation. PD-L1 constitutive overexpression or short hairpin RNA–mediated knockdown was used to determined the role of altered PD-L1 expression. Results GBM EVs interact with both T cells and monocytes but do not directly inhibit T-cell activation. However, GBM EVs induce immunosuppressive monocytes, including myeloid-derived suppressor cells (MDSCs) and nonclassical monocytes (NCMs). MDSCs and NCMs inhibit T-cell proliferation in vitro and are found within GBM in situ. EV PD-L1 expression induces NCMs but not MDSCs, and does not affect EV-conditioned monocytes T-cell inhibition. Conclusion These findings indicate that GBM EV-mediated immunosuppression occurs through induction of immunosuppressive monocytes rather than direct T-cell inhibition and that, while PD-L1 expression is important for the induction of specific immunosuppressive monocyte populations, immunosuppressive signaling mechanisms through EVs are complex and not limited to PD-L1.

This article reports the first case of pregnancy after frozen-thawed ovarian tissue transplantation to prevent iatrogenic premature ovarian insufficiency in China.Ovarian tissue cryopreservation was performed in a patient with myelodysplastic syndrome (MDS) before multi-agent chemotherapy and hematopoietic stem cell transplantation. Two years later, she showed complete remission from MDS, and six frozen-thawed ovarian tissue strips were transplanted into the peritoneal pocket.The patient's ovarian activity was restored 3 months after transplantation, and pregnancy occurred spontaneously 27 months after grafting. Until now, the pregnancy has progressed for 30 weeks, and the repeated ultrasound showed normal fetal development.This is the first pregnancy resulting from ovarian tissue cryopreservation and transplantation in China.

With the rapid spread of SARS-CoV-2 variants, including those that are resistant to antibodies authorized for emergency use, it is apparent that new antibodies may be needed to effectively protect patients against more severe disease. Differences between the murine and human antibody repertoires may allow for the isolation of murine monoclonal antibodies that recognize a different or broader range of SARS-CoV-2 variants than the human antibodies that have been characterized so far. We describe mouse antibodies B13 and O24 that demonstrate neutralizing potency against SARS-CoV-2 Wuhan (D614G) and B.1.351 variants. Such murine antibodies may have advantages in protecting against severe symptoms when individuals are exposed to new SARS-CoV-2 variants.

Toll-like receptors (TLRs) in the liver compartment have repeatedly been attributed to the development of non-alcoholic fatty liver disease (NAFLD). Knowledge on TLR expression in blood cells and their relation to intestinal microbiota and NAFLD development is limited. Here, we determined TLR expression patterns in peripheral blood mononuclear cells (PBMCs) of NAFLD patients and controls, their relation to intestinal microbiota and the impact of TLRs found altered in NAFLD development. Markers of intestinal permeability in blood and TLR mRNA expression in PBMCs were determined in 37 NAFLD patients and 15 age-matched healthy controls. Fecal microbiota composition was evaluated in 21 NAFLD patients and 9 controls using 16S rRNA gene amplicon sequencing. Furthermore, TLR1−/− and C57BL/6 mice (n = 5–6/group) were pair-fed a liquid control or a fat-, fructose- and cholesterol-rich diet. Intestinal microbiota composition and markers of intestinal permeability like zonulin and bacterial endotoxin differed significantly between groups with the latter markers being significantly higher in NAFLD patients. Expression of TLR1-8 and 10 mRNA was detectable in PBMCs; however, only TLR1 expression, being higher in NAFLD patients, were significantly positively correlated with the prevalence of Holdemanella genus while negative correlations were found with Gemmiger and Ruminococcus genera. TLR1−/− mice were significantly protected from the development of diet-induced NAFLD when compared to wild-type mice. While intestinal microbiota composition and permeability differed significantly between NAFLD patients and healthy subjects, in PBMCs, only TLR1 expression differed between groups. Still, targeting these alterations might be a beneficial approach in the treatment of NAFLD in some patients. Fil: Baumann, Anja. Universidad de Viena; Austria Fil: Nier, Anika. Universidad de Viena; Austria Fil: Hernández Arriaga, Angélica. Universidad de Hohenheim; Alemania Fil: Brandt, Annette. Universidad de Viena; Austria Fil: Lorenzo Pisarello, Maria Jose. Universidad de Viena; Austria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Jin, Cheng J.. Universitat Jena; Alemania Fil: Pilar, Esther. Universidad de Viena; Austria Fil: Camarinha-Silva, Amélia. Universidad de Hohenheim; Alemania Fil: Schattenberg, Jörn M.. University Medical Center of the Johannes Gutenberg; Alemania Fil: Bergheim, Ina. Universidad de Viena; Austria

Background: BCR signaling mediated through Bruton's tyrosine kinase (BTK) plays a critical role in the development and maintenance of marginal zone lymphoma (MZL). BTK inhibitors have established activity in relapsed/refractory (R/R) MZL with the phase 2 study of ibrutinib demonstrating an objective response rate (ORR) of 48% (Noy et al. Blood. 2017;129:2224-2232).

OBJECTIVE. Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS. Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS. At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10(−9)) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10(−9)). SNP rs6902488 at 6p25.2 (r(2) = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP

Background The cancer burden in adolescents and young adults (AYAs) deserves more attention. However, global cancer statistics for AYAs are often presented as aggregates, concealing important heterogeneity. This study aimed to describe the worldwide profile of cancer incidence, mortality, and corresponding trends from 1990 to 2019 among 15-39-year olds by focusing on the patterns by age, sex, sociodemographic index (SDI), and regions. Patients and methods Global, regional, and country data on the number of cancer cases and cancer-related deaths for 29 cancer types were collected from the 2019 Global Burden of Disease (GBD) Study. We also summarized the results using five levels of the SDI and 21 GBD regions. Results In 2019, an estimated 1 335 100 new cancer cases and 397 583 cancer-related deaths occurred among AYAs worldwide. While the incidence rate increased mildly, the death rate decreased significantly between 1990 and 2019, with an estimated annual percentage change of 0.38 (95% confidence interval 0.36-0.39) and −0.93 (95% confidence interval −0.95 to −0.92), respectively. The cancer burden was disproportionally greater among women than among men. The cancer profiles varied substantially across geographical regions, with the highest burden being in South Asia and East Asia. Besides, the cancer incidence in the high SDI regions was four times higher than that in the low SDI regions; however, the mortality burden in the high SDI region was lower than that in the low SDI region, which reflected the differences in cancer profiles across SDI regions and the inferior outcomes in the low SDI regions. Conclusion This study updates the previous epidemiological data of the cancer burden of AYAs. The cancer burden in AYAs varied substantially according to age, sex, SDI, and geographical regions. These findings highlight that the specific cancer profile of AYA patients requires targeted cancer control measures to reduce the cancer burden in this age group., Highlights • The cancer burden in AYAs varied substantially according to age, sex, SDI, and geographical regions. • Cancer burden in AYAs was disproportionally greater among women than among men. • Cancer profiles of AYAs varied across different geographical regions and SDI regions. • Cancer burden in AYAs was still considerable in the low SDI regions.

Glioblastoma is one of the most common malignant brain tumors. It has poor prognosis: the survival rate is 14–15 months, even with treatment by surgery, radiation, and chemotherapy. To develop more efficacious therapies, it is essential to generate preclinical mouse models that enable mechanistic studies. Multiple murine glioblastoma models have been generated, each with distinct advantages and disadvantages. The traditional Cre-LoxP system specifically targets glioblastoma-related genes but requires extended experimental timelines. CRISPR-Cas9 methods require less time to generate mouse models, yet the off-target effects lead to variable glioblastoma phenotypes. Transposon-based insertional mutagenesis models can intercept and promote transcription but has strict limitation of insertional transgene size. Allograft cell line injection into immunocompetent mice prevents immune rejection but fails to recapitulate various features of human glioblastoma. Intracranial injection of patient-derived xenograft cell lines into immunocompromised mice preserves features of human glioblastoma but does not allow the study of immune cell function in preclinical immunotherapeutic approaches. Finally, humanized mouse models offer the potential to analyze the human adaptive immune response but not the innate immune response. This chapter outlines the major experimental glioblastoma models currently employed and the therapeutic approaches that can be tested.

One lung ventilation (OLV) often results in trauma to the unventilated contralateral lung. This study aims to evaluate the effects of different OLV regimens on the injury of the unventilated contralateral lung to identify the best conditions for OLV. Forty rabbits were divided into five groups: a sham group, OLV group I (fraction of inspired oxygen (FIO2) 1.0, tidal volume (VT) 8mL/kg, respiratory rate (R) 40 breaths/min and inspiratory/expiratory ratio (I:E) 1:2), OLV group II (FIO2=1.0, VT 8mL/kg, R 40 breaths/min, I:E 1:2, and positive end-expiratory pressure (PEEP) 5 cm H2O), OLV group III (FIO2 1.0, VT 6mL/kg, R 40 breaths/min, I:E 1:2 and PEEP 5 cm H2O) and OLV group IV (FIO2 0.8, VT 6mL/kg, R 40 breaths/min, I:E 1:2 and PEEP 5 cm H2O). Animals from all OLV groups received two-lung ventilation (TLV) to establish a baseline, followed by one of the indicated OLV regimens. The rabbits in the sham group were intubated through trachea and ventilated with fresh air. Arterial blood gas samples were collected, lung injury parameters were evaluated, and the concentrations of TNF-α and IL-8 in bronchoalveolar lavage fluid (BALF) and pulmonary surfactant protein A (SPA) in the unventilated lung were also measured. In OLV group I, the unventilated left lung had higher TNF-α, IL-8 and lung injury score but lower SPA than the ventilated right lung. In OLV groups I to III, the concentrations of TNF-α, IL-8 and lung injury score in the left lung decreased but SPA increased. No differences in these parameters between OLV groups III and IV were observed. Strategic ventilation designed for OLV groups III and IV reduced OLV-induced injury of the non-ventilated contralateral lung in rabbits. RESUMO Ventilação pulmonar unilateral (OLV) frequentemente resulta em trauma no pulmão contralateral não ventilado. Este estudo visa avaliar os efeitos de diferentes regimes de OLV sobre a lesão do pulmão contralateral não ventilado para identificar as melhores condições para OLV. Quarenta coelhos foram divididos em cinco grupos: um grupo falso, OLV grupo I (fração de oxigênio inspirado (FIO2) 1.0, volume corrente (VT) 8mL/kg, frequência respiratória (R) 40 respirações/min e relação inspiração/expiração (I:E) 1:2), OLV grupo II (FIO2=1.0, VT 8mL/kg, R 40 respirações/min, I:E 1:2, e pressão positiva expiratória final (PEEP) 5 cm H2O), OLV grupo III (FIO2 1.0, VT 6mL/kg, R 40 respirações/min, I:E 1:2 e PEEP 5 cm H2O) e OLV grupo IV (FIO2 0.8, VT 6mL/kg, R 40 respirações/min, I:E 1:2 e PEEP 5 cm H2O). Os animais de todos os grupos OLV receberam ventilação nos dois pulmões (TLV) para estabelecer uma linha de base, seguida por um dos regimes OLV indicados. Os coelhos do grupo falso foram intubados através da traqueia e ventilados com ar fresco. Amostras de gases no sangue arterial foram coletadas, parâmetros de lesão pulmonar foram avaliados e as concentrações de TNF-α e IL-8 no fluido de lavagem bronco alveolar (BALF) e proteína A do surfactante pulmonar (SPA) no pulmão não ventilado também foram medidas. No grupo OLV I, o pulmão esquerdo não ventilado tinha maior índice de TNF-α, IL-8 e lesão pulmonar, mas menor SPA do que o pulmão direito ventilado. Nos grupos OLV I a III, as concentrações de TNF-α, IL-8 e a pontuação de lesão pulmonar no pulmão esquerdo diminuíram, mas o SPA aumentou. Não foram observadas diferenças nestes parâmetros entre os grupos OLV III e IV. A ventilação estratégica projetada para os grupos OLV III e IV reduziu a lesão induzida por OLV do pulmão contralateral não ventilado em coelhos.

Purpose/Objective(s) In an era of increasingly use of axilla irradiation in high-risk breast cancer patients after breast-conserving surgery and sentinel lymph node (LN) biopsy, the optimal clinical target volume (CTV) for level I axilla (Ax-L1) LN is uncertain. We mapped the location of pretreatment LN metastases in the Ax-L1 of newly diagnosed breast cancer patients and propose modification of the CTV borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas. Further, we assessed the differences in dosimetric parameters of modified Ax-L1 planning target volume (PTV) and surrounding organs at risk (OAR) between whole breast irradiation with standard “high tangential” simplified IMRT (HT-sIMRT WBI) and whole breast plus Ax-L1 irradiation with VMAT (VMAT WBI+ Ax-L1). Materials/Methods We identified 76 newly diagnosed breast cancer patients with 1-4 positive LNs after curative-intent surgery and axillary lymph node dissection treated between 2016 and 2018. All patients had a pretreatment diagnostic computed tomography (CT) chest scan demonstrating involved Ax-L1 LNs. The locations of 116 involved Ax-L1 LNs were mapped onto simulation CT images of a standard patient and the appropriateness of RTOG atlas was assessed. A modified Ax-L1 CTV with better coverage for involved Ax-L1 LNs was proposed, and PTV was generated for plans. Standard “high tangential” sIMRT plans for WBI and VMAT plans for WBI+ Ax-L1 on each side (left side and right side) were designed with a prescription dose of 50 Gy in 25 fractions, and dosimetric parameters were compared. Results For the RTOG atlas, the mapped LNs were 70.7% (82/116) inside, 13.8% (16/116) marginal and 15.5% (18/116) outside the CTV borders. The RTOG atlas missed 29.3% of LNs: 50.0% (17/34) in the anterior, 23.5% (8/34) in the caudal, 14.7% (5/34) in the cranial, 11.8% (4/34) in the medial direction. Modification by extending 1 cm caudal and 0.5 cm anterior to the CTV borders of the RTOG atlas allowed the modified Ax-L1 CTV to encompass 90.5% (105/116) of LNs. For HT-sIMRT WBI and VMAT WBI+ Ax-L1 plans, the mean V50 of modified Ax-L1 PTV was 69.5% and 97.8%; the mean dose, V20 and V5 of ipsilateral lung were 8.9 Gy, 16.4%, 32.5% and 10.5 Gy, 20.8%, 33.8%; the mean heart dose in left-sided plans was 4.1 Gy and 3.0 Gy; the mean dose and V5 of liver in the right-sided plans were 1.5 Gy, 3.6% and 2.8 Gy, 10.3%, respectively. Conclusion According to the distribution of Ax-L1 LNs, the RTOG atlas might be insufficient for their coverage. We propose a modified Ax-L1 CTV with expansion of RTOG Ax-L1 CTV borders, most notably in the caudal and anterior directions. Standard “high tangential” sIMRT WBI plans failed to deliver a therapeutic dose adequately to the modified Ax-L1 PTV. VMAT plans intended for whole breast plus Ax-L1 irradiation provided adequate dose to Ax-L1 PTV without increasing the doses to OARs.

PURPOSE/OBJECTIVE(S) We conducted a phase 2 randomized trial comparing partial breast irradiation (PBI) with whole breast irradiation (WBI) after breast-conserving surgery (BCS) in patients with low-risk breast cancer. Here, we report the quality of life (QoL) at 1 year. MATERIALS/METHODS Women aged≥45 years with low-risk breast cancer after BCS were randomly assigned (1:1) to receive either PBI (40 Gy in 10 fractions over 2 weeks), or WBI (43.5 Gy in 15 fractions over 3 weeks) using tangential-field based IMRT technique. The primary endpoint, the incidence of ³ grade 2 acute and late toxicities, will be reported when participants have completed 5 years of follow-up. QoL was assessed at baseline (T0), end of radiotherapy (T1), and at 6 (T2), 12 (T3) months after radiotherapy (RT), using EORTC QLQ-C30 and QLQ-BR23 questionnaires. We calculated scores for all QOL domains, and focused on the difference in mean scale. Manne-Whitney U test was used to compare the difference between the two groups. Wilcoxon-signed rank test was used to examine the difference between T1, T2, T3 and T0 respectively in each group. The longitudinal analysis of QoL changes over time and between groups were assessed with generalized estimating equations (GEE) with log link function for mean scores. An interaction term between time and treatment group was used to assess if mean scale score change over time was statistically different between the two arms. Longitudinal analyses were mainly focused on selected subscales of the QLQ-C30 (global health status, physical functioning, role functioning, emotional functioning, social functioning, fatigue, pain, dyspnea, financial difficulties), and of the QLQ-BR23 (body image, future perspective, breast symptoms, and arm symptoms). The patients who completed the questionnaires at T0 and at least one other timepoint were eligible for analysis. All analysis was done according to treatment received (per protocol population). Two-sided P value

Purpose/Objective(s) To investigate the appropriate timing of radiotherapy (RT) after mastectomy and adjuvant chemotherapy for women with high-risk breast cancer. Materials/Methods A total of 584 patients with stage II-III breast cancer were analyzed from a randomized, open-label, phase 3 trial, which evaluated the non-inferiority of hypofractionated to conventional fractionated RT after mastectomy. All patients received mastectomy followed by adjuvant chemotherapy and RT without neoadjuvant treatments. Optimal cut-off value of the interval from the date of surgery to the starting date of RT (SRI) and the interval from the date of last-dose chemotherapy to the starting date of RT (CRI) for oncologic outcomes was calculated by Maxstat. Kaplan-Meier method was used to estimate the rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS), and the differences were compared with log-rank test. Cox proportional hazards regression was performed for multivariate analysis. Results Median follow-up was 83.5 months (IQR 63-109). The median SRI was 168 days (range 93-357). The median CRI was 27 days (range 5-126). Compared to an SRI ≤165 days (5.5 months), an SRI > 165 days was associated with a significantly lower DFS rate (8-year 72.3% vs. 79.0%; P = 0.019), a higher DM rate (8-year 26.2% vs. 20.6%; P = 0.031), and a non-significantly higher LRR rate (8-year 9.0% vs. 6.0%, P = 0.065). Patients with an SRI > 180 days had a significantly lower OS rate compared with those with an SRI ≤180 days (8-year 72.2% vs. 84.1%; P = 0.012). Furthermore, CRI > 40 days was related to a significant decrease in DFS rate (8-year 67.0% vs. 76.9%; P = 0.002) and OS rate (8-year 69.0% vs. 83.0%; P = 0.002); and a significant increase in DM rate (8-year 33.4% vs. 21.8%; P = 0.001). No significant association between CRI > 40 days and LRR was found (8-year 10.4% vs. 7.2%; P = 0.238). After accounting for other known prognostic variables, SRI > 165 days, T stage and N stage remained significantly associated with inferior DM and DFS, while SRI > 180 days, T stage and N stage remained significantly associated with inferior OS. Meanwhile, CRI > 40 days, T stage and N stage were independently associated with inferior DM, DFS and OS. Conclusion Delay in initiating RT in patients with high-risk breast cancer is associated with inferior oncologic outcomes. We recommend RT should start within 165 days after mastectomy, and within 40 days after chemotherapy. NCT00793962

PURPOSE/OBJECTIVE(S) To explore the motion and influencing factors of implanted gold markers in guiding liver stereotactic body radiation therapy using abdominal compression. MATERIALS/METHODS Twenty patients with oligometastatic colorectal cancer or primary hepatocellular carcinoma from January 2016 to December 2019 were included. All patients were treated with stereotactic body radiation therapy (SBRT) under abdominal compression, with 1-3 gold markers implanted within 2cm of the lesion before positioning, meanwhile four-dimensional computed tomography (4DCT) scan used for treatment planning. The respiratory cycle was divided into 0%-90% respiratory phase image based on the respiratory signal, which were reconstructed by the system as well as CBCT validation images before radiation exposure daily. The liver volume was divided into 3 parts: within 2 cm of the main hepatic portal vein, 2-5 cm of the main hepatic portal vein, and 5 cm outside of the main hepatic portal vein, for evaluating the motion of different tumor locations. RESULTS The average intrafractional motion amplitude (mean ± standard deviation) was 2.63 ± 2.81 mm in the cranial-caudal (CC), 1.35 ± 1.23 mm in the anterior-posterior (AP), and 0.76 ± 0.88 mm in the left-right (LR) direction, respectively. Meanwhile the average interfractional motion amplitude was 3.45 ± 3.06 mm, 2.64 ± 2.60 mm, and 2.23 ± 2.07 mm, respectively. Whether intra- or interfraction, the motion amplitude showed CC > AP > LR direction (P < 0.001). The motion varied at different tumor location, the further away from the main hepatic portal vein, the larger of the intrafractional motion. To cover the 95% population-based confidence interval, internal target volume was suggested to include the expansion of 3.9 mm, 5.2 mm and 7.9 mm in the LR, AP, and CC direction, while 4.3 mm, 4.4 mm, and 6.1 mm within 2 cm of the main hepatic portal vein, 3.5 mm, 7.3 mm, and 9.7 mm outside 5 cm of the main hepatic portal vein, respectively. The expansion varied significantly depending on tumor location, but motion in CC direction showed the largest no matter where the tumor was. Among the 3 parts of liver volume, while the further of tumor away from the main portal vein, the larger expansion in CC direction, and tumor in 5 cm outside of the main portal vein moved more than other inner parts in AP direction. CONCLUSION Different tumor locations of liver require external expansion of internal target volume individually. AUTHOR DISCLOSURE Y. Zhao: None. Y. Tang: None. W. Liu: None. N. Li: None. Y. Song: None. S. Wang: None. Y. Liu: None. H. Fang: None. N. Lu: None. Y. Tang: None. S. Qi: None. Y. Yang: None. B. Chen: None. Y. LI: None. J. Jin: None.

This chapter focuses on the concept of “governing through contagion.” Flexing power over life, governing through contagion regulates subjects of a population to ensure their bodies are free from contagion, do not spread contagion to fellow subjects, and stay economically productive-or at least, avoid incurring economic costs of medicine and containment. In many territories, the legal strategies of control in response to the Covid-19 pandemic, such as quarantine orders and movement restrictions, grew out of earlier episodes of contagion that significantly shaped governing through contagion. The chapter then introduces three themes of governing through contagion: centralization and technology of law;normalization and technologies of moralization;and inter/dysconnectedness and the rearticulation of difference. The analysis draws on the historical ethnography of one British post-colony, Singapore, situated in three contexts: the colonial era (particularly 1868-1915), which was troubled by numerous epidemics such as plague, cholera, and smallpox;the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak;and the Covid-19 pandemic. © the several contributors 2021.

The effect and molecular mechanism of melatonin on the vascular smooth muscle cells proliferation and vascular smooth muscle cells migration induced by oxidized low density lipoprotein was explored in this paper. The first scheme: induce vascular smooth muscle cells with series of oxidized low density lipoprotein concentrations for 48 h (0 μg/mL, 10 μg/mL, 20 μg/mL, 50 μg/mL and 100 μg/mL). The second scheme: 50 μg/mL oxidized low density lipoprotein was used to induce vascular smooth muscle cells s for 0 h, 6 h, 12 h, 24 h and 48 h. The third option: first induce vascular smooth muscle cells with 50 μg/mL oxidized low density lipoprotein for 24 h, then treat vascular smooth muscle cells with series of melatonin concentrations for 48 h (1 nmol/L, 1 μmol/L, 0.1 mmol/L, 1 mmol/L). Cell Counting Kit-8 method was used to detect cell proliferation. Cells were randomly divided into blank control group, melatonin group (0.1 mmol/L melatonin treatment vascular smooth muscle cells 48 h), oxidized low density lipoprotein group (vascular smooth muscle cells were induced by 50 μg/ml oxidized low density lipoprotein for 24 h), oxidized low density lipoprotein +melatonin group (50 μg/ml of oxidized low density lipoprotein induced vascular smooth muscle cells for 24 h and then treated vascular smooth muscle cells s with 0.1 mmol/L of melatonin for 48 h). After relative treatment, cell cycle was detected by flow cytometry and cell migration was detected by scratch test. Proliferating cell nuclear antigen, alpha smooth muscle actin, cyclin A and extracellular regulatory protein kinase were detected by immunofluorescence staining and Western blot 1/2 (extracellular regulatory protein kinase 1/2) signal pathway related protein expression. Compared with the blank control group, vascular smooth muscle cells s treated with 50 μg/ml oxidized low density lipoprotein could significantly induce cell proliferation. After 24 h of induction by oxidized low density lipoprotein (50 μg/ml), the number of cells in S phase and G1 phase was decreased significantly and the number of cells in G2 phase was increased significantly. Cell migration was promoted and proliferating cell nuclear antigen, cyclin A, Cyclina, p-extracellular regulatory protein kinase 1/2 protein expression was up-regulated, down regulating the p-p21 protein level. The difference was statistically significant (p

In this research, we used the mediastinal lymph node reclassification proposed by the International Association for the Study of Lung Cancer (iaslc) to screen for patients with pathologic N2 (pN2) non-small-cell lung cancer (nsclc) who might benefit from postoperative radiotherapy (port). The study enrolled 440 patients with pN2 nsclc who received complete surgical resection and allocated them to one of three groups: N2a1 (single-station skip mediastinal lymph node metastasis), N2a2 (single-station non-skip mediastinal lymph node metastasis), and N2b (multi-station mediastinal lymph node metastasis). Rates of local recurrence at first recurrence in patients receiving and not receiving port were compared using the chi-square test. Overall (os) and disease-free survival (dfs) were then compared using Kaplan&ndash, Meier survival analysis with log-rank test. In addition, the factors potentially influencing os and dfs were analyzed using univariate and multivariate Cox regression. The rate of local recurrence for the N2a2 and N2b groups was significantly lower in patients receiving port (p = 0.044 and p = 0.043 respectively). The log-rank test revealed that, for the N2a1 group, differences in os and dfs were not statistically significant between the patients who did and did not receive port (p = 0.304 and p = 0.197 respectively). For the N2a2 group, os and dfs were markedly superior in patients who received port compared with those who did not (p = 0.001 and p = 0.014 respectively). For the N2b group, os was evidently better in patients who received port compared with those who did not (p = 0.025), but no statistically significant difference in dfs was observed (p = 0.134). Multivariate regression analysis revealed that, in the N2a1 group, port was significantly associated with poor os [hazard ratio (hr): 2.618, 95% confidence interval (ci): 1.185 to 5.785, p = 0.017], in the N2a2 group, port was associated with improved os (hr: 0.481, 95% ci: 0.314 to 0.736, p = 0.001) and dfs (hr: 0.685, 95% ci: 0.479 to 0.980, p = 0.039). For patients with pN2 nsclc who receive complete resection, port might be beneficial only for patients with single-station non-skip metastasis (N2a2). Patients with single-station skip metastasis (N2a1) and multi-station metastasis (N2b) might not currently benefit from port.

Background Complementary and alternative medicine (CAM) is frequently used in the treatment of chronic rhinosinusitis (CRS) in developed countries. With a plethora of CAM therapies available, their effectiveness and safety are poorly understood in the context of CRS. Objectives This article aims to critically appraise the evidence for CAM use in CRS through a systematic review of current literature that investigate the effects of CAM on symptoms and clinical status of adults with CRS. Study Design Systematic review and qualitative analysis. Review Methods A comprehensive systematic review of the literature was conducted by the authors using 5 databases from inception to July 2017: CINAHL, Cochrane, Embase, PubMed, and SCOPUS. Inclusive medical subject headings and keywords consisted of, but were not limited to, sinusitis and complementary therapies, naturopathy, or traditional Chinese medicine. PRISMA guideline was followed. Using templates by Cochrane Public Health Group and Newcastle-Ottawa Scale, each author extracted data, assessed bias, and computed minimal clinically important difference. Any conflicts were resolved through discussion. Results In total, 7 of 7141 articles from 1995 to 2016 were included. Three randomized controlled trials and 4 observational studies were organized into 4 categories of CAM: naturopathy, Chinese medicine, homeopathy, and others. Limited evidence supported the use of Pimpinella anisum and crenotherapy for CRS. Data available on Chinese medicine, homeopathy, and liposomal therapy in CRS were inconclusive due to inherent flaws in the studies. Conclusion Overall, there is very limited evidence to support the use of CAM in the treatment of CRS. No significant adverse effects have been found. Given its widespread use, more rigorous data from high-quality research are needed before it can be routinely recommended.

UBE2N is a K63-specific ubiquitin conjugase linked to various immune disorders and cancer. Here, we demonstrate that UBE2N and its partners UBE2V1 and UBE2V2 are highly expressed in malignant melanoma. Silencing of UBE2N and its partners significantly decreased melanoma cell proliferation and subcutaneous tumor growth. This was accompanied by increased expression of E-cadherin, p16, and MC1R and decreased expression of melanoma malignancy markers including SOX10, Nestin, and ABCB5. Mass spectrometry–based phosphoproteomic analysis revealed that UBE2N loss resulted in distinct alterations to the signaling landscape: MEK/ERK signaling was impaired, FRA1 and SOX10 gene regulators were downregulated, and p53 and p16 tumor suppressors were upregulated. Similar to inhibition of UBE2N and MEK, silencing FRA1 decreased SOX10 expression and cell proliferation. Conversely, exogenous expression of active FRA1 increased pMEK and SOX10 expression, and restored anchorage-independent cell growth of cells with UBE2N loss. Systemic delivery of NSC697923, a small-molecule inhibitor of UBE2N, significantly decreased melanoma xenograft growth. These data indicate that UBE2N is a novel regulator of the MEK/FRA1/SOX10 signaling cascade and is indispensable for malignant melanoma growth. Our findings establish the basis for targeting UBE2N as a potential treatment strategy for melanoma. Significance: These findings identify ubiquitin conjugase UBE2N and its variant partners as novel regulators of MAPK signaling and potential therapeutic targets in melanoma. Cancer Res; 78(22); 6462–72. ©2018 AACR.

In this work, a Lab-on-a-Chip (LOC) platform is used to electromagnetically actuate magnetic bead chains for an enhanced immunoassay. Custom-made electromagnets generate a magnetic field to form, rotate, lift and lower the magnetic bead chains (MBCs). The cost-effective, disposable LOC platform was made with a polymer substrate and an on-chip electrochemical sensor patterned via the screen-printing process. The movement of the MBCs is controlled to improve the electrochemical signal up to 230% when detecting beta-type human chorionic gonadotropin (β-hCG). Thus, the proposed on-chip MBC-based immunoassay is applicable for rapid, qualitative electrochemical point-of-care (POC) analysis.

Purpose/Objective(s) To investigate the prognostic value of tumor-infiltrating lymphocytes (TIL) in patients with triple-negative breast cancer (TNBC). Materials/Methods The clinicopathologic data of 258 patients with I-III stage TNBC treated in one institution from 2010 to 2013 were collected. Two-hundred and twelve patients (82.2%) received mastectomy and 46 (17.8%) received breast-conserving surgery. Eighty-four patients (32.6%) had stage I, 138 (53.5%) had stage II and 36 (14.0%) had stage III disease. All had received adjuvant chemotherapy without neoadjuvant therapy, and 96 (37.2%) received postoperative radiotherapy. The density of TILs with its expression of stromal (s) and intratumoral (i) CD8, FOXP3 (sCD8, iCD8, sFOXP3, iFOXP3) were evaluated by hematoxylin and eosin and immunohistochemical (IHC) staining. An IHC staining for PD-1 and PD-L1 (22C3) were also conducted. Locoregional recurrence (LRR), distant metastasis (DM) and disease-free survival (DFS) and overall survival (OS) rates were calculated by using the Kaplan-Meier method and compared by log-rank test. The association of relapse and survival outcomes with TILs concentration was evaluated using multivariable proportional hazards regression. Optimum cutoff values for sCD8, iCD8, sFOXP3 and iFOXP3 were identified using the maxstat package in R. Results At a median follow-up of 80 months (range, 9-111 months), patients with lymphocyte-predominant breast cancer (sTIL ≥60%) had significantly lower 5-year LRR (3.6% vs 15.6%; P = 0.047) and higher DFS (96.4% vs 84.5%; P = 0.025) compared to those with 10% had significantly lower 5-year LRR (4.2% vs 15.7%, P = 0.010) and DM (2.8% vs 14.6%; P = 006) and higher 5-year DFS (95.8% vs 83.9%, P = 0.015) and OS (97.1% vs 91.2%, P = 0.044) compared to patients with sCD8 ≤10%. Patients with iCD8 > 5% had significantly lower 5-year LRR (2.2% vs 14.8%, P = 0.013) and DM (13.4%, P = 0.021) and higher 5-year DFS (97.8% vs 84.8%, P = 0.008) and OS (97.7 vs 91.7%, P = 0.030) compared to patients with iCD8 ≤5%. Patients with sFOXP3 > 3/HPF also had significantly lower 5-year LRR (4.5% vs 15.0%, P = 0.012) and DM (5.9% vs 13.5%, P = 0.043) and higher 5-year DFS (92.7% vs 85.0%, P = 0.034) and OS (95.6% vs 91.5%, P = 0.047) compared to sFOXP3 ≤3/HPF. However, no survival benefits were found from patients with iFOXP3 > 14/HPF. Presence of PD-1-positive immune cells in TNBC were associated with a significantly better DFS (93.4% vs 83.5%, P = 0.044), while PD-L1 expression had no impact on patient outcomes. Multivariate analysis revealed that sTIL ≥60% (HR 0.23, 95% CI 0.05-0.99, P = 0.048) or PD-1 positivity (HR 0.40, 95% CI: 0.16-0.96, P = 0.041) were independent prognostic factors for DFS, in addition to stage (P 0.05). Conclusion High density of stromal TIL and presence of PD-1-positive immune cells may have a positive prognostic value in TNBC. These findings need further validation.

Purpose/Objective(s) To observe the safety and preliminary efficacy of the total neoadjuvant therapy (TNT) model of "neoadjuvant chemoradiotherapy plus consolidation neoadjuvant chemotherapy followed by radical surgery" for locally advanced gastric cancer (Clinical Trial registration number:NCT04062058). Materials/Methods Patients aged 18-75 years with a KPS status score ≥70 and clinical diagnosed as locally advanced gastric adenocarcinoma (GC) or Siewert Ⅱ/Ⅲ adenocarcinoma gastroesophageal junction cancer (GEJC) was prospectively enrolled. The neoadjuvant chemoradiotherapy (NCRT) was delivered with a total dose of 45Gy,1.8Gy/time firstly. Concurrent chemotherapy was S-1 at a dose of 40-60mg twice daily. Then, patients received four to six cycles consolidation neoadjuvant chemotherapy (CNCT) of oxaliplatin and S-1(SOX regimen) three weeks after neoadjuvant chemoradiotherapy; R0 resection with D2 lymphadenectomy was performed 4-6 weeks after the end of neoadjuvant therapy. Results A total of 28 patients who finished the whole therapy were enrolled from March 2018 to December 2020, of which, 78.6% were diagnosed as cT4, 85.7% were cN positive and 85.7% were stage Ⅲ in total clinical stage. Grade 3 or higher adverse reactions occurred in 3 cases (10.7%) during CRT, including thrombocytopenia, leukopenia and anorexia; 2 cases (7.4%) of leukopenia and 3 cases (11.1%) of thrombocytopenia occurred during CNCT. Twenty patients (71.4%) completed surgery among 28 patients and all of them completed R0 resection. The incidence of severe pathological reactions (Mandard score = 1-2) was 95.0% and 50.0% reached pCR. Three patients occurred surgery complications, including anastomotic leak, anastomotic stenosis and intra-abdominal sepsis. They all improved after symptomatic treatment. Conclusion Total neoadjuvant therapy for locally advanced GC and GEJC can reach a remarkable down-staging. It can be safely delivered and will not improve the surgery complications significantly.

PURPOSE/OBJECTIVE(S) To analyze the prognosis and locoregional failure patterns of patients with isolated regional recurrence (RR) after mastectomy and investigate the effect of radiotherapy (RT) and optimal radiation target volumes. MATERIALS/METHODS A total of 144 patients with first isolated RR after mastectomy treated in two institutions between 2001 and 2018 were retrospectively analyzed. All had not received postmastectomy RT. 100 (69.4%) had supraclavicular fossa (SC) recurrence, 54 (37.5%) had axilla recurrence, and 7(4.9%) had internal mammary region (IM) recurrence. After RR, 93 (63.6%) patients received local plus systemic therapy, 10 (6.9%) received local therapy, and 40 (27.8%) received systemic therapy alone. Among the 103 patients who received local therapy, 27 (26.2%) received surgery plus RT, 60 (58.3%) received RT and 16 (15.5%) received surgery alone. Of the 87 patients who received RT, 14 (16.1%) received involved-field RT, and 73 (83.9%) received additional prophylactic RT to the initially uninvolved locoregional sites. The median dose to the recurrent tumor or tumor bed after surgery was 60 Gy. Of the 73 patients who received prophylactic RT, the median dose was 50 Gy, to chest wall (CW) in 67/87 (77.0%), to SC in 24/28 (85.7%), to axilla in 6/53 (11.3%), and to IM in 3/81 (3.7%). Post-recurrence progression-free survival (PFS) and overall survival (OS) rates were calculated by Kaplan-Meier method and the differences were compared with Log-rank test. Competing risk model was used to estimate the subsequent locoregional recurrence (sLRR) rates, and the differences were compared with Gray test. Multivariate analysis was performed using Cox logistic and Fine-Gray regression. RESULTS With a median follow-up of 82.5 months (range, 5.0-205.0) after RR, the 5-year sLRR, PFS and OS rates for the entire group were 42.1%, 22.9% and 62.6%. Local plus systemic therapy was an independent favorable prognostic factor for sLRR and PFS. Surgery plus RT was an independent favorable prognostic factor for sLRR. The most common sLRR sites were initially involved nodal regions, followed by CW, and then initially uninvolved nodal regions. Surgery plus RT significantly reduced the risk of recurrence within the initially involved nodal regions (P

PURPOSE/OBJECTIVE(S) To compare the outcomes of W&W strategy in patients with locally advanced rectal cancer who achieve complete clinical response (cCR) after neoadjuvant therapy, with those pathological complete response (pCR) after total mesorectal excision (TME). MATERIALS/METHODS This is a retrospective cohort analysis study. 1014 Patients of histologically proven with locally advanced rectal adenocarcinoma who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing long-course concurrent chemoradiotherapy or short-course sequential chemoradiotherapy, no distant metastases within 6 months after treatment, follow-up ≥1 year, and patients who did not have cCR but pCR after TME. The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (non- regrowth DFS), and organ preservation rate. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM). RESULTS 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (IQR 12.1-79.9). No difference in 3-year OS (97.1% vs 96.7%) and 5-year OS (93.8% vs 90.9%, P = 0.696) between W&W and pCR, but patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs 43.5%, P < 0.0001). Six patients had local regrowth managed by W&W, while no local recurrence in the pCR group, which had better 3-year DFS (83.6% vs 97%) and 5-year DFS (83.6% vs 91.2%, P = 0.047). However, after salvage surgery, no significantly difference in 3-year non-regrowth DFS (95.9% vs 97%) and 5-year non-regrowth DFS (92.8% vs 97%, P = 0.407) between these two groups. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs 26.5%, P < 0.0001) were noted in the W&W group, but no differences in other survival between groups. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19 vs 9.8 wk, P < 0.0001). CONCLUSION The long-term outcomes of W&W strategy in patients with locally advanced rectal cancer were not inferior to that of those with pCR. 87.7% of patients had successful rectum preservation in W&W group, although patients may require a longer interval for efficacy assessment.

Increased breakdown of glucose through glycolysis in both aerobic and anaerobic conditions is a hallmark feature of mammalian cancer and leads to increased production of L-lactate. The high-level lactate present within the tumor microenvironment is reused as a crucial biofuel to support rapid cancer cell proliferation, survival, and immune evasion. Inhibitors that target the glycolysis process are being developed for cancer therapy. In this study, we report an approach of using synthetic D-lactate dimers to inhibit melanoma and squamous cell carcinoma cell proliferation and survival. We also provide in vivo evidence that intratumoral injection of D-lactate dimers induced an innate immune response and inhibited subcutaneous melanoma xenograft growth in immunodeficient mice. Our findings support a potential utility of D-lactate dimers in skin cancer treatment and therefore warrant further mechanistic studies.

Aims To investigate the roles of cyclooxygenases (COX) and their metabolites in C57/BL6 mice with 5/6 nephrectomy, an animal model of chronic renal failure. Main methods C57/BL6 mice were grouped into sham-operated (2K), one kidney removal (1K) and 5/6 nephrectomy groups (5/6Nx). Renal resistive index was measured by ultrasonography. Blood, aortae, renal arteries and renal cortex were collected for measurement of kidney function, assessment of vascular responsiveness, Western blotting, immuohistochemistry and enzyme-linked immunosorbent assays. Key findings After four weeks, acetylcholine-induced relaxations were blunted in renal arteries of 1K and 5/6Nx mice; indomethacin, a non-selective COX inhibitor, improved the response in 5/6Nx, but not in 1K renal arteries. In 5/6Nx renal arteries, but not in 1K preparations, the protein presence of endothelial nitric oxide synthase (eNOS) was decreased, while that of COX-2 and its products [prostacyclin and thromboxane A 2 ] were increased. The renal resistive index was lower in 5/6Nx mice, suggesting a lower resistance in the renal microvasculature. In the renal cortex of 5/6Nx mice, eNOS protein presence was increased; while the presence of COX-2 was not detectable. The prostaglandin E 2 level was lower in the 5/6Nx cortex than in the other two groups. Significance The early stage of renal mass removal is associated with increased renal arterial constriction and reduced microvascular resistance. The former is due to downregulation of eNOS and upregulation of COX-2, leading to an increased production of prostacyclin and thromboxane A 2 . A reduced production of PGE 2 in the renal cortex is important for maintaining normal renal function.

We made a coupled genetic reporter that detects rare transcription misincorporation errors to measure RNA polymerase transcription fidelity in Escherichia coli. Using this reporter, we demonstrated in vivo that the transcript cleavage factor GreA, but not GreB, is essential for proofreading of a transcription error where a riboA has been misincorporated instead of a riboG. A greA mutant strain had more than a 100-fold increase in transcription errors relative to wild-type or a greB mutant. However, overexpression of GreB in ΔgreA cells reduced the misincorporation errors to wild-type levels, demonstrating that GreB at high concentration could substitute for GreA in RNA proofreading activity in vivo.

This abstract was not presented at the symposium.

Sublingual immunotherapy (SLIT) is a treatment for allergic respiratory diseases that has demonstrated efficacy and safety. Several formulations of SLIT are now available worldwide for treatment of allergic rhinitis (AR). Grass tablets containing 15 to 25 μg of group 5 major allergen reduced combined AR symptoms and medication use by 23% to 41% in 3 treatment years and 2 follow-up years. Ragweed pollen tablets (12 μg of Ambrosia artemisiifolia 1) and liquid extracts (50 μg of Ambrosia artemisiifolia 1) reduced combined AR symptoms and medication use by 26% and 43%, respectively. House dust mite tablets containing 300 index of reactivity (16 μg of Dermatophagoides pteronyssinus 1 and 68 μg of Dermatophagoides farinae 1) reduced AR symptoms by 17.9% and 17.0% in 1 treatment year and 1 follow-up year, respectively. A different house dust mite tablet (12 standardized quality house dust mite) was able to reduce the risk of asthma exacerbation compared with placebo (hazard ratio, 0.69; 95% CI, 0.50-0.96). Most adverse events were local and mild to moderate in severity. For SLIT products reviewed herein, effective doses range from 1.12 to 84 μg of major allergen(s). However, allergen content is not uniformly standardized, can be expressed in arbitrary or proprietary units (depending on the manufacturer), and assays for determination of allergen content are highly variable. Thus, results from one study of a given product cannot be extrapolated to other products. Despite these limitations, this Clinical Management Review aims to provide practitioners with relevant information on the dosing of selected SLIT formulations in the treatment of allergic respiratory disease.

Background The pneumonia severity index (PSI) scoring system is one of the tools used to evaluate and predict the prognosis of patients with community-acquired pneumonia (CAP). Although PSI has been widely used in clinical studies of pneumonia, it is still rare to combine it with blood indexes to predict the prognosis of pneumonia. Neutrophil-to-lymphocyte ratio (NLR) is a promising candidate predictor of mortality in CAP patients. The aim of this study was to investigate the efficacy of pneumonia severity index combined with NLR in predicting 30-day mortality in CAP patients. Methods We conducted a retrospective study. We analyzed data on 400 non-immune individuals over the age of 18 in this study. All patients received blood routine measurement and PSI score calculation after admission. The primary outcome measures were mortality and survival in CAP patients. The sensitivity and specificity of PSI score, NLR, and the combination of PSI score and NLR in predicting 30-day mortality were assessed using the subject operating characteristic curve (ROC). Results Data from 400 patients were analyzed, in which the 30-day mortality was 10.5% (42/400). The AUC of NLR and PSI in predicting 30-day mortality of CAP patients were 0.81 (95% CI 0.73 - 0.89) and 0.94 (95% CI 0.90 - 0.98), respectively, with statistically significant differences (p = 0.00). The sensitivity and specificity of NLR were 0.80 and 0.7, respectively. The sensitivity and specificity of PSI were 0.78 and 0.94, respectively. The combined AUC of the two indicators for predicting death in CAP patients was 0.95 (95% CI 0.92 - 0.99), and the sensitivity and specificity were 0.85 and 0.94, respectively. Conclusions Neutrophil-to-lymphocyte ratio improves the accuracy and sensitivity of the pneumonia severity index in predicting 30-day mortality of CAP patients.

Objective The number of high-risk pregnancies is increasing in tertiary medical centers. Therefore, we investigated perioperative outcomes based on risk factors to ascertain proper maternal and neonatal management. Methods We reviewed the medical records of patients receiving cesarean sections over an 8-year period. Clinical parameters for anesthesia and the neonatal outcome were compared among high-risk groups after subdivision by the number of clinical risk factors. The groups were as follows: group A (one risk factor), group B (two risk factors), and group C (three or more risk factors). Results Patient age, estimated blood loss (EBL), and volume of transfused red blood cell (RBC) were higher in group B than group A. Birth weight, 1- and 5-minute Apgar scores, and gestational age were lower while the frequency of neonatal intensive care unit (NICU) admission was higher in group B than group A. Group C patients were significantly older than group A or B patients. Birth weight, 1- and 5-minute Apgar scores and gestational age were significantly lower while frequency of NICU admission was higher in group C than group A and B. Conclusion The number of maternal risk factors was positively associated with adverse outcomes in the neonates.

Rapid adaptation to environmental changes is crucial for bacterial survival. Almost all bacteria possess a conserved stringent response system to prompt transcriptional and metabolic responses toward stress. The adaptive process relies on alarmones, guanosine pentaphosphate (pppGpp), and tetraphosphate (ppGpp), to regulate global gene expression. The ppGpp is more potent than pppGpp in the regulatory activity, and pppGpp phosphohydrolase (GppA) plays a key role in (p)ppGpp homeostasis. Sharing a similar domain structure, GppA is indistinguishable from exopolyphosphatase (PPX), which mediates the metabolism of cellular inorganic polyphosphate. Here, our phylogenetic analysis of PPX/GppA homologs in bacteria shows a wide distribution with several distinct subfamilies, and our structural and functional analysis of Escherichia coli GppA and Helicobacter pylori PPX/GppA reveals unique properties of each homolog. These results explain how each homolog possesses its distinct functionality.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: 1. To appraise the effectiveness of traditional Chinese medicinal herbs (TCMH) for induction of remission in idiopathic ulcerative colitis. 2. To determinate adverse events associated with TCMH treatment in ulcerative colitis.

Altered aerobic glycolysis is a well-recognized characteristic of cancer cell energy metabolism, known as the Warburg effect. Even in the presence of abundant oxygen, a majority of tumor cells produce substantial amounts of energy through a high glycolytic metabolism, and breast cancer (BC) is no exception. Breast cancer continues to be the second leading cause of cancer-associated mortality in women worldwide. However, the precise role of aerobic glycolysis in the development of BC remains elusive. Therefore, the present review attempts to address the implication of key enzymes of the aerobic glycolytic pathway including hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK), glucose transporters (GLUTs), together with related signaling pathways including protein kinase B(PI3K/AKT), mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) and transcription factors (c-myc, p53 and HIF-1) in the research of BC. Thus, the review of aerobic glycolysis in BC may evoke novel ideas for the BC treatment.