Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC.

Cancer associated fibroblasts (CAF) are known to orchestrate multiple components of the tumor microenvironment, whereas the influence of the whole stromal-fibroblast compartment is less understood. Here, an extended stromal fibroblast signature was investigated to define its impact on immune cell infiltration. The lung cancer adenocarcinoma (LUAD) data set of the cancer genome atlas (TCGA) was used to test whole stroma signatures and cancer-associated fibroblast signatures for their impact on prognosis. 3D cell cultures of the NSCLC cancer cell line A549 together with the fibroblast cell line SV80 were used in combination with infiltrating peripheral blood mononuclear cells (PBMC) for in-vitro investigations. Immune cell infiltration was assessed via flow cytometry, chemokines were analyzed by immunoassays and RNA microarrays. Results were confirmed in specimens from NSCLC patients by flow cytometry or immunohistochemistry as well as in the TCGA data set. The TCGA analyses correlated the whole stromal-fibroblast signature with an improved outcome, whereas no effect was found for the CAF signatures. In 3D microtumors, the presence of fibroblasts induced infiltration of B cells and CD69+CD4+ T cells, which was linked to an increased expression of CCL13 and CXCL16. The stroma/lymphocyte interaction was confirmed in NSCLC patients, as stroma-rich tumors displayed an elevated B cell count and survival in the local cohort and the TCGA data set. A whole stromal fibroblast signature was associated with an improved clinical outcome in lung adenocarcinoma and in vitro and in vivo experiments suggest that this signature increases B and T cell recruitment via induction of chemokines.

Publisher Correction: Ballistic geometric resistance resonances in a single surface of a topological insulator.

In the original version of this Article, the second and third sentences of the first paragraph of the "Gate voltage and antidot period dependencies" section of the Results originally incorrectly read "The characteristic evolution of the sheet resistance ρ□=ρ□ (B=0) with Vg shown for three antidot samples and an unpatterned reference sample in Fig. 3a. The maxima of ρxx, located between Vg~0.5 and 1 V, reflect the charge neutrality point (CNP), corresponding to an EF position located slightly in the valence band (see band structure in Fig. 3b)." In the corrected version, "[Formula: see text]" is replaced by "[Formula: see text]", and "The maxima of [Formula: see text]" is replaced by "The maxima of [Formula: see text]".

Tolerability, quality of life, and persistency of use in patients with glaucoma who are switched to the fixed combination of latanoprost and timolol.

This study was undertaken to assess tolerability, quality of life, and persistency of use and to monitor changes in intraocular pressure (IOP) during the first 6 mo after a switch to fixed combination latanoprost/timolol. In Germany, 271 general ophthalmology practices enrolled patients who were switched from previous ocular hypotensive therapies to latanoprost/timolol for medical reasons. Usual care routines were followed, and IOP was measured at baseline and approximately 6 mo later. Adverse events were recorded throughout. Immediately before switching and at follow-up, patients completed a 29-item quality-of-life questionnaire. Of 1052 patients who met analysis criteria, 748 (71%) switched from combination therapy and 304 (29%) from monotherapy. An insufficient IOP reduction with the previous therapy was a reason for switching in 71% of patients; the desire to simplify to once-daily administration was cited in 66%. Ocular adverse events were reported in 19 patients after the switch, and 97% remained on therapy throughout the follow%up period. After switching, patients were less likely to forget to instill their eyedrops or to feel that their drops had adverse effects; they found it easier to include eyedrop administration in their routine; they were more satisfied with the frequency of instillation; and they were more likely to want to continue with the drops. Across all previous therapies, mean IOP decreased from 20.6+/-3.7 mm Hg to 17.2+/-2.8 mm Hg after the switch (P<.001)-a 14.8% difference. Fixed combination latanoprost/timolol is well tolerated and effective in patients who are switched from other monotherapies or combination therapies for medical reasons. Such a switch may be associated with improved quality of life.

Ballistic geometric resistance resonances in a single surface of a topological insulator.

Transport in topological matter has shown a variety of novel phenomena over the past decade. Although numerous transport studies have been conducted on three-dimensional topological insulators (TIs), study of ballistic motion and thus exploration of potential landscapes on a hundred nanometer scale is for the prevalent TI materials almost impossible due to their low carrier mobility. Therefore, it is unknown whether helical Dirac electrons in TIs, bound to interfaces between topologically distinct materials, can be manipulated on the nanometer scale by local gates or locally etched regions. Here we impose a submicron periodic potential onto a single surface of Dirac electrons in high-mobility strained mercury telluride (HgTe), which is a strong TI. Pronounced geometric resistance resonances constitute the clear-cut observation of a ballistic effect in three-dimensional TIs.

Diurnal IOP-lowering efficacy and safety of travoprost 0.004% compared with tafluprost 0.0015% in patients with primary open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the diurnal intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and tafluprost 0.0015% administered to patients with primary open-angle glaucoma or ocular hypertension. METHODS: This was a randomized, double-masked, active-controlled, crossover design trial, in which patients were randomized to either travoprost or tafluprost monotherapy administered once daily in the evening for six weeks and then crossed over to the alternative treatment for another six weeks. Diurnal IOP was measured (8 am to 8 pm, every two hours) and a solicited symptom survey was administered at the end of both six-week periods, as was conjunctival hyperemia and visual acuity assessment, slit-lamp biomicroscopy, and adverse event solicitation. RESULTS: Fifty-one patients were randomized and 48 patients completed the study. The 12-hour mean diurnal IOP was significantly lower with travoprost therapy than with tafluprost therapy (P = 0.01), and a significantly lower IOP was also reported for travoprost at five of the seven individual time points (P < 0.05). Neither therapy produced a significant increase from baseline in any of the individual patient-reported symptom scores, except for hyperemia (P ≤ 0.01), which was increased with both treatments. Investigator-observed hyperemia was also increased from baseline with both therapies (P < 0.01), although the increase with travoprost therapy was significantly smaller than with tafluprost (P < 0.01). No additional safety concerns were noted from slit-lamp biomicroscopy or visual acuity results, and no difference was noted in patient-reported tolerability of the two medications. CONCLUSION: Travoprost 0.004% monotherapy produced lower diurnal IOP than tafluprost 0.0015% in patients with primary open-angle glaucoma or ocular hypertension and exhibited a similar safety profile.

Safety and efficacy of changing to the travoprost/timolol maleate fixed combination (DuoTrav) from prior mono- or adjunctive therapy.

PURPOSE: To assess the safety and efficacy of changing to the travoprost/timolol fixed combination (TTFC) from other mono- or adjunctive therapies. PATIENTS AND METHODS: A prospective, open-label, observational cohort of primary open-angle glaucoma and ocular hypertensive patients whose intraocular pressure (IOP) was uncontrolled on prior therapy or was not on target. Patients were changed from prior mono- or adjunctive treatment at Day 0 to TTFC dosed every evening and underwent active treatment efficacy and safety evaluations at Week 12. RESULTS: In 474/522 (91%) patients who completed this trial an IOP (mm Hg) of 21.9 +/- 2.0 on prior treatment was reduced by TTFC at Month 3: from all prior treatments 5.6 +/- 2.6; from monotherapy 5.9 +/- 2.3; from adjunctive treatments 4.5 +/- 2.9; and from several of the most frequent individual treatments: timolol 5.7 +/- 2.2; latanoprost 6.3 +/- 2.6; and latanoprost/timolol fixed combination 4.4 +/- 1.9. Ocular hyperemia was the most frequent adverse effect (n = 21, 4%). Both patients and physicians preferred TTFC compared to all prior and common individual treatments. The solicited symptom survey showed, following a modified Bonferroni correction (alpha/5), a reduced incidence with TTFC of ocular pain (P = 0.01) while the prior medicine had a lower incidence of burning on instillation (P < 0.001). CONCLUSIONS: Changing patients from prior mono- or adjunctive therapy to TTFC can provide on average a further reduction in IOP while demonstrating a favorable safety profile and a high patient preference.