Background and Aims Flexible endoscopic septum division (FESD) is a rapidly evolving technique for the treatment of Zenker's diverticulum (ZD). The aim was to perform a systematic review and ...meta-analysis of the literature focusing on FESD for ZD, including an in-depth evaluation of its efficacy, safety, and limitations. Methods A comprehensive literature search was completed to identify papers that examined the efficacy and safety of FESD for ZD. Demographic, clinical, and technical information was retrieved. Main outcomes were extracted, pooled, and analyzed. Heterogeneity among studies was assessed using the I2 statistic. A random effect model was used as the pooling method in cases of high heterogeneity; otherwise the fixed effect model was applied. Meta-regression was also performed. Main outcomes such as rates of success, adverse events, and recurrences were evaluated. Results Twenty studies with a total of 813 patients were selected. The pooled success, adverse events, and recurrence rates were 91% (95% confidence interval CI, 86%–95%; I2 = 69.5%), 11.3% (95% CI, 8%–16%; I2 = 64%), and 11% (95% CI, 8%–15%; I2 = 38.4%), respectively. Substantial heterogeneity across studies was found. However, for success rates, excluding 3 studies reduced heterogeneity to non-significant rates I2 = 25.6%; P = .154. Adverse event rates decreased with larger samples (coefficient, −0.0123; 95% CI, −0.03 to −0.003; P = .017), whereas recurrence rates increased (coefficient, 0.006; 95% CI, −0.0010 to 0.0125; P = .093). Year of publication was negatively associated with success rate, whereas the opposite pattern was found for recurrence rates. Conclusions FESD is a feasible, safe, and effective treatment for symptomatic ZD, with low adverse event and recurrence rates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have ...had limited power to show overall benefit or benefits within subsets.
We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status.
Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and 2% were unknown menopausal status; 49.5% were HmR positive; 33.5% were HmR negative, and 17% were unknown HmR status. The median follow-up was 6 years. After analysis was adjusted for covariates, HDC was found to prolong relapse-free survival (RFS; hazard ratio HR, 0.87; 95% CI, 0.81 to 0.93; P < .001) but not overall survival (OS; HR, 0.94; 95% CI, 0.87 to 1.02; P = .13). For OS, no covariates had statistically significant interactions with treatment effect, and no subsets evinced a significant effect of HDC. Younger patients had a significantly better RFS on HDC than did older patients.
Adjuvant HDC with AHST prolonged RFS in high-risk primary breast cancer compared with control, but this did not translate into a significant OS benefit. Whether HDC benefits patients in the context of targeted therapies is unknown.
•Developments in coordination polymers (CPs) and metal–organic frameworks (MOFs).•Electroactive CPs and MOFs possess unique redox-state dependent properties.•An exploration of key redox-active ...ligands investigated in the past eight years.•Emerging redox-active ligands inspired by organic photovoltaic devices (OPVs).•CP and MOFs with applications in solar cells, photo switches and photoelectrocatalysis.
Over the past three decades, the field of coordination polymers (CPs) and metal–organic frameworks (MOFs) has developed rapidly due to the potential applications of these materials in gas storage, separations, catalysis and switching. Introducing redox properties into CPs and MOFs to electrochemically modulate their properties for the development of solid state electronic devices has been an interesting strategy applied in recent years. Notably, a challenge within this area is the engineering of framework materials with desired redox properties targeted at a specific function. This review explores some of the key redox-active ligands that have been investigated within the previous eight years as redox-active components of solid state materials and examines a number of key strategies for their integration into CPs and MOFs. This review further highlights emergent redox-active ligands in the literature, which take inspiration from the rich field of organic electronics. While these ligands remain largely unexplored in the field of MOFs and CPs, they offer new opportunities for the improvement of solar cells, light induced photo switches, efficient photoelectrocatalysts and long range, rapid charge transfer in MOF materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Following results presented in Spallicci et al. (Eur Phys J Plus 137, 2022) by the same authors, we investigate the observed red shift
z
, working under the hypothesis that it might be composed by ...the expansion red shift
z
C
and an additional frequency shift
z
S
, towards the red or the blue, due to Extended Theories of Electromagnetism (ETE). We have tested this prediction considering the novel Pantheon+ Catalogue, composed by 1701 light curves collected by 1550 SNe Ia, and 16 BAO data, for different cosmological models characterised by the absence of a dark energy component. In particular, we shall derive which values of
z
S
match the observations, comparing the new results with the ones obtained considering the older Pantheon Catalogue. We find interesting differences in the resulting
z
S
distributions, highlighted in the text. Later, we also add a discussion regarding Extended Theories of Gravity and how to incorporate them in our methodology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Increasing evidence argues that the success of an anticancer treatment may rely on immunoadjuvant side effects including the induction of immunogenic tumor cell death. Based on the assumption that ...this death mechanism is a similar prerequisite for the efficacy of an active immunotherapy using killed tumor cells, we examined a vaccination strategy using dendritic cells (DC) loaded with apoptotic and necrotic cell bodies derived from autologous tumors. Using this approach, clinical and immunologic responses were achieved in 6 of 18 patients with relapsed indolent non-Hodgkin's lymphoma (NHL). The present report illustrates an impaired ability of the neoplastic cells used to vaccinate nonresponders to undergo immunogenic death on exposure to a cell death protocol based on heat shock, γ-ray, and UVC ray. Interestingly, when compared with doxorubicin, this treatment increased surface translocation of calreticulin and cellular release of high-mobility group box 1 and ATP in histologically distinct NHL cell lines. In contrast, treated lymphoma cells from responders displayed higher amounts of calreticulin and heat shock protein 90 (HSP90) compared with those from nonresponders and boosted the production of specific antibodies when loaded into DCs for vaccination. Accordingly, the extent of calreticulin and HSP90 surface expression in the DC antigenic cargo was significantly associated with the clinical and immunologic responses achieved. Our results indicate that a positive clinical effect is obtained when immunogenically killed autologous neoplastic cells are used for the generation of a DC-based vaccine. Therapeutic improvements may thus be accomplished by circumventing the tumor-impaired ability to undergo immunogenic death and prime the antitumor immune response.
Xanthomonas arboricola pv. juglandis (Xaj) is the most significant aboveground walnut bacterial pathogen. Disease management uses copper-based pesticides which induce pathogen resistance. We examined ...the genetic repertoire associated with adaptation and virulence evolution in Xaj. Comparative genomics of 32 Xaj strains reveal the possible acquisition and propagation of virulence factors via insertion sequences (IS). Fine-scale annotation revealed a Tn3 transposon (TnXaj417) encoding copper resistance genes acquired by horizontal gene transfer and associated with adaptation and tolerance to metal-based pesticides commonly used to manage pathogens in orchard ecosystems. Phylogenomic analysis reveals IS involvement in acquisition and diversification of type III effector proteins ranging from two to eight in non-pathogenic strains, 16 to 20 in pathogenic strains, besides six other putative effectors with a reduced identity degree found mostly among pathogenic strains. Yersiniabactin, xopK, xopAI, and antibiotic resistance genes are also located near ISs or inside genomic islands and structures resembling composite transposons.
•Resistance to copper is acquired by Xanthomonadaceae via lateral gene transfer.•Orchard management to limit bacterial diseases selects for more pathogenic strains.•Strain Xaj417 acquired a copper resistance cassette from other bacterial species.•Mobile genetic elements expand virulence effector repertoire in pathogenic strains.•IS enrichment is correlated with dissemination of T3e and virulence factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This phase II clinical trial evaluated the efficacy, safety and pharmacokinetics of plitidepsin 3.2 mg/m(2) administered as a 1-hour intravenous infusion weekly on days 1, 8 and 15 every 4 weeks in ...67 adult patients with relapsed/refractory aggressive non-Hodgkin's lymphoma. Patients were divided into two cohorts: those with non-cutaneous peripheral T-cell lymphoma (n=34) and those with other lymphomas (n=33). Efficacy was evaluated using the International Working Group criteria (1999). Of the 29 evaluable patients with non-cutaneous peripheral T-cell lymphoma, six had a response (overall response rate 20.7%; 95% confidence interval, 8.0%-39.7%), including two complete responses and four partial responses. No responses occurred in the 30 evaluable patients with other lymphomas (including 27 B-cell lymphomas). The most common plitidepsin-related adverse events were nausea, fatigue and myalgia (grade 3 in <10% of cases). Severe laboratory abnormalities (lymphopenia, anemia, thrombocytopenia, and increased levels of transaminase and creatine phosphokinase) were transient and easily managed by plitidepsin dose adjustments. The pharmacokinetic profile did not differ from that previously reported in patients with solid tumors. In conclusion, plitidepsin monotherapy has clinical activity in relapsed/refractory T-cell lymphomas. Combinations of plitidepsin with other chemotherapeutic drugs deserve further evaluation in patients with non-cutaneous peripheral T-cell lymphoma. (clinicaltrials.gov identifier: NCT00884286).
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of malignancies characterized by a poor prognosis. We performed a pilot study to investigate the role of reduced-intensity conditioning ...(RIC) followed by allogeneic stem-cell transplantation in relapsed or refractory PTCLs.
We have conducted a phase II trial on 17 patients receiving salvage chemotherapy followed by RIC and allogeneic transplantation of hematopoietic cells. The RIC regimen consisted of thiotepa, fludarabine, and cyclophosphamide. The acute graft-versus-host disease prophylaxis consisted of cyslosporine and short course methotrexate.
Patients had a median age of 41 years (range, 23 to 60 years). Two patients were primary chemorefractory, and 15 had relapsed disease; eight patients (47%) had a disease relapse after an autologous transplantation. After a median follow-up of 28 months from the day of study entry (range, 3 to 57 months), 14 of 17 patients were alive (12 in complete remission, one in partial remission, and one with stable disease), two died as a result of progressive disease, and one died as a result of sepsis concomitant to acute graft-versus-host disease. The estimated 3-year overall and progression-free survival rates were 81% (95% CI, 62% to 100%) and 64% (95% CI, 39% to 89%), respectively. The estimated probability of nonrelapse mortality at 2 years was 6% (95% CI, 1% to 17%). Donor lymphocyte infusions induced a response in two patients progressing after allografting.
RIC followed by allogeneic stem-cell transplantation is feasible, has a low treatment-related mortality, and seems to be a promising salvage treatment for relapsed PTCL. These findings suggest that the existence of a graft-versus-T-cell lymphoma effect.
An idealized "test" object in general relativity moves along a geodesic. However, if the object has a finite mass, this will create additional curvature in the spacetime, causing it to deviate from ...geodesic motion. If the mass is nonetheless sufficiently small, such an effect is usually treated perturbatively and is known as the gravitational self-force due to the object. This issue is still an open problem in gravitational physics today, motivated not only by basic foundational interest, but also by the need for its direct application in gravitational wave astronomy. In particular, the observation of extreme-mass-ratio inspirals by the future space-based detector LISA will rely crucially on an accurate modeling of the self-force driving the orbital evolution and gravitational wave emission of such systems. In this paper, we present a novel derivation, based on conservation laws, of the basic equations of motion for this problem. They are formulated with the use of a quasilocal (rather than matter) stress-energy-momentum tensor-in particular, the Brown-York tensor-so as to capture gravitational effects in the momentum flux of the object, including the self-force. Our formulation and resulting equations of motion are independent of the choice of the perturbative gauge. We show that, in addition to the usual gravitational self-force term, they also lead to an additional "self-pressure" force not found in previous analyses, and also that our results correctly recover known formulas under appropriate conditions. Our approach thus offers a fresh geometrical picture from which to understand the self-force fundamentally, and potentially useful new avenues for computing it practically.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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