Chemoradiotherapy for elderly patients with rectal cancer: A single‑institution study

Introduction: The incidence of cancer, particularly rectal cancer (RC), in older adults is gradually increasing. The aim of the present study was to evaluate radiotherapy (RT) and chemoradiotherapy (CRT) results, clinicopathological features, and survival factors in older patients with RC. Methods: We evaluated patients aged ≥65 years with RC treated at a radiation oncology clinic. The demographic, clinical, and histopathological data of the patients were obtained by reviewing their medical records. The toxicity criteria of the Radiation Therapy Oncology Group were applied. Results: Among 401 patients with RC, 183 (45.6%) were older adults (65–92 years). Furthermore, 122 (66.7%) patients had clinically stage 3 and above RC, and 183 and 91 patients received RT and neoadjuvant CRT, respectively. Surgical treatment was performed for 116 (63.4%) patients, 41 (34.4%) and 76 (65.6%) of whom underwent postoperative CRT and preoperative RT, respectively. Grade 3 or higher toxicity was observed in 22 (18.9%) patients during CRT. RT was performed in 64 patients(35%) at a 1–15‑day interval. The mean follow‑up duration was 34.7 (range, 1.4–149.0) months. The 2‑ and 5‑year overall survival (OS) rates were 71.4 and 37.4%, respectively, and the 2‑ and 5‑year disease‑free survival (DFS) rates were 65.7 and 35.3%, respectively. OS was 49.4 and 34.9 months for patients aged 65–74 and ≥75 years, respectively. Survival was shorter in patients with the advanced geriatric disease (p = 0.013). In the multivariate analysis, factors affecting overall and DFS were age, distance from the tumor to the anal canal, and metastasis (p < 0.05). Conclusion: The results of this study suggested that the selection of treatment modalities for older patients with RC should be based on performance status and not age. RT and CRT were safe treatment modalities for older patients with RC, particularly for those who could not undergo surger

Interrelationship between the variability of Northern Hemispheric total ozone, temperature and eddy heat flux

Toplam ozonun en yoğun olarak bulunduğu 15km ile 55 km arasındaki orta atmosfer, dinamik etkilerin de en fazla g&ouml;r&uuml;ld&uuml;ğ&uuml; b&ouml;lgedir. Brewer-Dobson sirk&uuml;lasyonu, orta atmosferdeki ozon taşınımını etkileyen temel &ccedil;evrimdir. Girdap ısı akısı, Brewer-Dobson sirk&uuml;lasyonu olarak da bilinen, kalan sirk&uuml;lasyonun, d&uuml;şey bileşenidir ve dinamik bir bakış i&ccedil;in kullanılan rezid&uuml;el ortalama teorinin temelini oluşturmaktadır. Bu &ccedil;alışmada, toplam ozon değişiminin orta atmosferdeki sıcaklık ve girdap ısı akısı ile etkileşimi dinamik olarak incelenmiştir. Brewer-Dobson sirk&uuml;lasyonunun matematiksel olarak modellenmesinde, d&ouml;n&uuml;şt&uuml;r&uuml;lm&uuml;ş Eulerian ortalama akış denklemlerinden yararlanılmıştır. &Ccedil;alışmada sirkulasyonun hesaplanmasında 1998-2007 yılları arasındaki ECMWF-ERA- Interim re-analiz verilerinden, toplam ozon değerleri i&ccedil;in ise TOMS, OMI uydu verileri ile ECMWF ozon karışma oranı verilerinden yararlanılmıştır. 1998-2007 yılları arasında Kuzey yarık&uuml;re ozon değişimleri incelendiğinde, yukarı orta enlemlerde ve kutup b&ouml;lgesinde ozon miktarının tropiklerden daha fazla olduğu g&ouml;r&uuml;lm&uuml;şt&uuml;r. Orta ve yukarı enlemlerdeki toplam ozonun değişmini de etkileyen birincil mekanizma olan sirk&uuml;lasyonun, yıl i&ccedil;inde en kuvvetli olduğu d&ouml;nem Ocak ayı, etkilerinin en az g&ouml;r&uuml;ld&uuml;ğ&uuml; d&ouml;nem ise Temmuz ayıdır. G&ouml;z&ouml;n&uuml;ne alınan periyotta toplam ozon değeri ortalama olarak tropiklerde 240DU değerinden kutup b&ouml;lgelerinde 420 DU değerine kadar değişmektedir. Orta enlemlerde ise 260-360DU arasında değişmektedir. Planeter aktivitenin değişiminin en fazla g&ouml;r&uuml;ld&uuml;ğ&uuml; 100mb seviyesi i&ccedil;in orta enlemlerdeki toplam ozonla, sıcaklıklar arasında yakın bir ilişki elde edilmiştir. Benzer şekilde, tropiklerdeki girdap ısı akısının orta enlemlerdeki sıcaklıkları, orta enlemlerdeki girdap ısı akısının da kutuplardaki sıcaklıları kontrol ettiği g&ouml;r&uuml;lm&uuml;şt&uuml;r.&nbsp;Anahtar Kelimeler: Stratosferik ozon, Brewer-Dobson sirk&uuml;lasyonu, ozon azalması.Ozone levels in the atmosphere have significantly decreased over the last three decades not only over Polar Regions but also over mid-latitudes. This finding led to an intense debate on the characteristics of the stratospheric dynamics and atmospheric transport. Since most of the atmospheric ozone is found in the stratosphere and the vertical motion in the stratosphere is quite slow so the dynamics in this layer becomes of great significance to our climate. Evidently dynamical changes in the circulation contribute to observe ozone trends at northern mid-latitudes. Total ozone trends have been directly connected to changes in various dynamical parameters such as temperature, so thus eddy heat flux. The eddy heat flux is the product of meridional wind departures and temperature departures. Dynamically eddy heat flux is the vertical component of Brewer-Dobson circulation. Brewer-Dobson circulation which is also known as residual circulation has a strong influence on stratospheric ozone variability and transport processes. Brewer-Dobson circulation is very strong during winter (January) and it increases the total ozone over high latitudes. In summer (July) the circulation is weak. The global distribution of atmospheric heat transport is supported by zonally averaged parameters namely eddy heat flux and temperature. Since eddy heat flux transports heat, it has been obtained that dynamical temperature change is highly affected by the eddy heat flux. Physically temperature and eddy heat flux are strongly related to each other. Evidently the strong correlation between eddy heat flux and temperature interprets a relationship between total ozone and pronounced parameters. Dynamical features of Northern Hemispheric ozone transport, temperature and eddy heat flux and their relationships for the specified time interval (1998-2007) makes up the basics of the study. The dynamical processes produced by eddies or wave motion in the stratosphere and mesosphere give rise to the meridional circulation in the middle atmosphere that closely balances the force caused by the temperature deviation from the radiative equilibrium. Dynamic features affecting ozone include especially the atmospheric transport temperature variability and changes in eddy heat flux. Ozone transport and variability of eddy heat flux and temperature are defined by zonally averaged parameters. It is easier to examine atmospheric variability through zonal mean fields which is also mathematically less complicated than using 3 dimensional flow equations.. In order to view the residual atmospheric circulation and describe zonally averaged structure of the atmosphere, a mathematical formalism is used for the eddy-mean flow cancellation which provides a separation between eddies and the mean meridional circulation. The formulation defines the transformed Eulerian mean (TEM) or residual circulation. Residual circulation calculation is given by the sum of the Eulerian mean circulation components and the eddy terms. In the study eddy heat flux and temperature are separately processed to be linked with total ozone transport. In the present research total ozone data from Total Ozone Mapping Spectrometer (TOMS) (1998-2004), Ozone Monitoring Instrument (OMI) (2005-2007) and European Centre for Medium-Range Weather Forecasts (ECMWF) ERA-Interim Re-Analysis data (1998-2207) have been used. The selected period for Northern Hemisphere and 180°W- 180°E is compiled for the middle atmosphere which includes the region from 100mb in the lower stratosphere and up to 10mb in the stratosphere. Middle atmosphere is a dynamically driven region compared to the troposphere, which is more sensitive to thermal driven heat engine. Relationship between mid-latitudinal ozone, eddy heat flux and temperature is chosen as the starting point to create an emphasis on the area around this region. It is confirmed that tropical eddy heat flux highly controls the mid-latitudinal total ozone and mid-latitudinal lower stratospheric temperature. Additionally polar ozone is strongly affected by polar eddy heat flux. Eddy heat flux at the mid-latitudes is highly correlated with the polar temperatures.  Keywords: Stratospheric ozone, Brewer-Dobson circulation, ozone depletion

Small-molecule targeting of translation initiation for cancer therapy

Translation initiation plays a critical role in the regulation of cell growth and tumorigenesis. We report here that inhibiting translation initiation through induction of eIF2α phosphorylation by small-molecular-weight compounds restricts the availability of the eIF2·GTP·Met-tRNAi ternary complex and abrogates the proliferation of cancer cells in vitro and tumor growth in vivo. Restricting the availability of the ternary complex preferentially down-regulates the expression of growth-promoting proteins and up-regulates the expression of ER stress response genes in cancer cells as well as in tumors excised from either animal models of human cancer or cancer patients. These findings provide the first direct evidence for translational control of gene-specific expression by small molecules in vivo and indicate that translation initiation factors are bona fide targets for development of mechanism-specific anti-cancer agents

3,3-Dimethyl-2-benzofuran-1(3H)-one

In the title compound, C10H10O2, all the non-H atoms except the methyl C atoms lie on a crystallographic mirror plane. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules into zigzag chains running parallel to [100]. Weak π–π stacking inter­actions between the benzene rings [centroid–centroid distance = 3.9817 (5) Å] link the chains in the [010] direction

(2E)-2-[(3E)-4-Phenyl­but-3-en-2-yl­idene]hydrazinecarboxamide

In the title compound, C11H13N3O, the phenyl ring is disordered over two sites, with occupancy factors in a 0.520 (17):0.480 (17) ratio. The dihedral angle between the ring planes of the major and minor components of the disordered ring is 12.9 (2)°. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds, forming R 2 2(8) ring motifs. C—H⋯O, C—H⋯N and C—H⋯π inter­actions also occur

A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells

Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and we use CRISPR-Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+TILs. Our results open novel avenues for targeting dysfunctional T cell states while leaving activation programs intact

“COMING TOGETHER” (Batanai): Learning from Zimbabwe’s experiences with community biodiversity conservation, participatory crop improvement and climate change adaptation

This brief presents the findings and lessons learned of a study tour by a team from the Department of Agriculture, Forestry and Fisheries of South Africa to neighbouring Zimbabwe, to learn about the roles of Farmer Field Schools, functions and operations of community seedbanks and various forms of participatory crop improvement, promoted by the Community Technology Development Organisation of Zimbabwe