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B7 family members act as co-stimulatory or co-inhibitory molecules in the adaptive immune system. Thisstudy aimed to investigate the dysregulation, prognostic value and regulatory network of B7 family members in non-small cell lung cancer (NSCLC). Data for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were extracted from public databases. Patient prognosis was determined by Kaplan–Meier analysis. The downstream signaling pathways of B7 family were identified via GO and KEGG analysis. The key B7 related genes were selected by network, correlation and functional annotation analysis. Most B7 family members were dysregulated in LUAD and LUSC. The expression of B7-1/2/H3 and B7-H5 were significantly associated with overall survival in LUAD and LUSC, respectively. The major pathway affected by B7 family was the EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway. MAPK1, MAPK3 and MAP2K1 were pivotal B7 related genes in both LUAD and LUSC. This study reveals an overall dysregulation of B7 family members in NSCLC and highlights the potential of combination use of tyrosine kinase inhibitors or MEK/ERK inhibitors with B7 member blockade for NSCLC treatment. [ABSTRACT FROM AUTHOR]

To explore the effect of prior thyroid cancer on the survival of primary liver cancer (PLC). Eligible PLC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database during 2004–2016. Propensity score matching (PSM) was used to create a highly comparable control group that PLC patients without prior thyroid cancer. All PLC patients were divided into three groups based on the survival information: (1) PLC-specific death; (2) death due to other causes; (3) alive. The effect sizes were presented by the corresponding hazard ratio (HR) and 95% confidence intervals (CI). Totally, 142 PLC patients with prior thyroid cancer and 1420 PLC patients without prior thyroid cancer were included. During the follow-up period, 714 (45.71%) PLC patients died of liver cancer while 638 (40.85%) PLC patients were alive. Median survival time for PLC patients was 11.00 months, respectively. PLC patients with prior thyroid cancer have a lower risk of death (HR = 0.64; 95% CI: 0.48–0.86). Subgroup analyses stratified by gender displayed the similar relation in female patients with PLC. Prior thyroid cancer may be a protective factor for liver cancer death in PLC patients, especially in female patients. [ABSTRACT FROM AUTHOR]

Flexible transparent electrodes (FTEs) with embedded metal meshes play an indispensable role in many optoelectronic devices due to their excellent mechanical stability and environmental adaptability. However, low-cost, simple, efficient, and environmental friendly integrated manufacturing of high-performance embedded metal meshes remains a huge challenge. Here, a facile and novel fabrication method is proposed for FTEs with an embedded metal mesh via liquid substrateelectric-field-driven microscale 3D printing process. This direct printing strategy avoids tedious processes and offers low-cost and high-volume production, enabling the fabrication of high-resolution, high-aspect ratio embedded metal meshes without sacrificing transparency. The final manufactured FTEs with 80 mm × 80 mm embedded metal mesh offers excellent optoelectronic performance with a sheet resistance (Rs) of 6 𝛀 sq-1 and a transmittance (T) of 85.79%. The embedded metal structure still has excellent mechanical stability and good environmental suitability under different harsh working conditions. The practical feasibility of the FTEs is successfully demonstrated with a thermally driven 4D printing structure and a resistive transparent strain sensor. This method can be used to manufacture large areas with facile, high-efficiency, low-cost, and high-performance FTEs. [ABSTRACT FROM AUTHOR]

. Purpose: To evaluate: (i) the relationship between intraocular pressure (IOP) reduction attained with a fixed treatment protocol and the untreated IOP level; (ii) the consistency of IOP reduction over time; and (iii) whether there is a threshold pretreatment IOP level below which IOP reduction might be less effective. Results are based on 128 patients with glaucoma with field defects, who were randomized to the treatment arm of the Early Manifest Glaucoma Trial (EMGT). Methods: The EMGT fixed treatment protocol consisted of 360° laser trabeculoplasty and topical betaxolol eye drops B.I.D. Treatment was unchanged as long as progression did not occur. Analyses assessed the initial IOP reduction after 3 months and also the mean reduction based on all follow-up values; IOP changes over time were evaluated with linear regression analysis. Factors influencing initial and mean IOP reduction were also explored using linear models. Results: Mean age at baseline was 68 years, and untreated baseline IOP ranged from 13 to 30.5 mmHg. On average, eyes with higher baseline IOP experienced larger pressure reductions than eyes with lower baseline IOP, whether expressed in mmHg or as percentages. Each mmHg of higher baseline IOP was associated with approximately 0.6 mmHg larger IOP reduction. IOP changed little over time, with 66% of patients changing less than 0.5 mmHg/year, and only 13% (17/128) changing >1.0 mmHg/year. The treatment protocol did not achieve any average IOP reduction in eyes with baseline pressures ≤ 15 mmHg. Factors related to more IOP reduction at 3 months were higher baseline IOP and positive refractive error, while higher baseline IOP and male gender (more reduction) and cardiovascular disease history (less reduction) were associated with mean IOP on treatment. Conclusion: With a fixed treatment protocol, the IOP reduction achieved depended very strongly on baseline untreated IOP levels. There seemed to be a lower threshold around 15 mmHg, where therapy did not result in any reduction of IOP. Our results suggest that when effects of IOP-lowering treatment are reported, whether expressed in mmHg or as a percentage of untreated pressure levels, the baseline IOP levels should be specified as well. [ABSTRACT FROM AUTHOR]

cGVHD exhibits both autoimmune and fibrotic features across multiple organ systems. KD025 is an orally available Rho-associated coiled-coil kinase 2 (ROCK2) selective inhibitor. KD025-208 enrolled 3 cohorts (C1: 200 mg QD, C2: 200 mg BID, and C3: 400 mg QD) of cGVHD patients (pts) after 1-3 prior lines of therapy. Treatment was until progression or toxicity. Primary endpoint is overall response rate (ORR) per 2014 NIH response criteria. Additional endpoints include Duration of Response (DOR), corticosteroid (CS) dose reductions, Failure Free Survival (FFS) and Lee Symptom Scale (LSS) score. 17, 16, and 21 pts enrolled in C1, C2, and C3. As of 8Mar19, median duration of follow up was 112, 97 and 64 weeks (wks) respectively. Median age was 52 yrs, median time from cGVHD diagnosis was 20 mos, and median prior lines of therapy was 2. Median duration of treatment was 37, 33, and 39 wks, respectively. 14 pts remained on KD025. Reasons for discontinuation: cGVHD progression (18), voluntary withdrawal (7), relapse of underlying disease (5), investigator decision (5), AE (3), and death (2). ORR [95% CI] was 65% [38, 85] in C1, 69% [41, 89] in C2, and 62% [38, 82] in C3, 65% [51, 77] across all 3 cohorts. Responses were achieved across key subgroups with ORRs of 62% (24/39) in pts with ≥2 prior lines of therapy, 70% (19/27) in pts with ≥4 organs involved and 60% (25/42) in pts with severe cGVHD, and 65% (22/34) in pts refractory to their previous line. CRs were observed in all affected organs except lung; PRs were observed in lung. Median Time to Response was 8.14 wks (IQR 8-12); 4/35 responses occurred after 24 wks. Responses were durable with a Kaplan-Meier median DOR of 34 wks across all cohorts. 57% of responders sustained a response for ≥20 wks. FFS at 6, 12 and 24 mos was 76%, 47% and 33% respectively. Overall survival was 94%, 91% and 83%. Baseline median CS dose was 0.21 mg/kg/day (prednisone eq). During treatment, median CS dose was reduced by 50%. 20% pts discontinued CS. 52% of pts reported a ≥7-point reduction in LSS with median time to improvement 9 wks. AEs were consistent with those expected in cGVHD pts receiving CS. Common AEs were URI 35%, diarrhea 31%, nausea 31%, fatigue 30%, dyspnea 28%, increased LFTs 24%, and peripheral edema 22%. 63% had a Grade ≥3 AE, the most common was dyspnea, 13%. <10% pts experienced Grade 3 anemia, neutropenia, or thrombocytopenia. SAEs, reported in 43%, were not related to KD025. SAEs in >2% were dyspnea (7%), lung infection (6%), hypoxia (4%) and flu-like illness (4%). Three pts discontinued KD025 due to possibly related AEs (C1: diarrhea, headache; C3: fatigue). 3 pts died on study (C3: relapse of leukemia; lung infection; cardiac arrest), all considered unrelated to KD025. Durable and clinically meaningful responses have been seen across all 3 cohorts. KD025 was well tolerated, with sustained responses and encouraging FFS in patients with advanced cGVHD. [ABSTRACT FROM AUTHOR]