Explore the vast range of titles available.

The 2001-2003 excavations at Tell Sabi Abyad in northern Syria have provided important new information on the nature and development of the Pottery Neolithic settlement at the site in the seventh and sixth millennia B.C. The fieldwork has produced a long sequence of small and continually shifting occupations, in the order of 0.5-1.0 ha, each with rich assemblages of very early ceramics and other artifacts. There is proof for localized abandonment and the episodic contraction and expansion of occupation over the site. Living in small, dispersed groups, leaving extensive areas of the site uninhabited, was a basic practice of Neolithic settlers at Tell Sabi Abyad (and probably elsewhere as well). Of particular note was the discovery of well-preserved building levels belonging to the initial stage of the Pottery Neolithic, ca. 6600-6200 B.C., providing insight into the character of settlement and material culture of one of the poorest known periods in the history of Syria and the northern Levant. Single- and multiroomed houses came to light, often with white-plastered floors and walls. The ceramics from these buildings are among the earliest found in the Near East to date. Distinct changes in the organization of the communities and the material culture took place at ca. 6200 B.C. and were associated with, among other things, the appearance of circular buildings and clay sealings as indicators of controlled storage.

Approaches that are transdisciplinary and participatory can help to address complex socio-ecological issues by integrating multiple disciplinary perspectives while taking into account the different needs and experiences of community members and other stakeholders. Despite this promise, such approaches are rarely applied within the scientific community, as researchers and public actors often lack the training, practice and reference cases required to handle the working relationships and translations of terminology, ideas and values across multiple bodies of knowledge. A case study described in this manuscript depicts a group of researchers, artists and citizens consciously engaged in the construction of a transdisciplinary process as part of a 40-day ‘citizen science’ experiment focussed on assessing soil fertility in the urban area of Milan, Italy. The group drew from recognised scientific approaches, applied agronomic methodologies, artistic practices and technological tools, integrating them into a hybrid process of collective and participatory inquiry. As a quantitative outcome of the experiment, a dataset of bio-chemical parameters was generated, which was enriched by agronomic interpretations but also by artistic and reflective materials. Importantly, the process developed transdisciplinary and participatory skills, as it created a potentially replicable procedure of engagement, analysis and presentation for use in other citizen science settings. This article presents the context, the multiple objectives of the research and the applied approach and its timeline. Described in detail are the process of designing and conducting the experiment by involving an extended research community—including both junior and senior researchers—in progressive steps. Quantitative and qualitative results are provided. The findings are meant to contribute case material and methods to inform the advancement of transdisciplinary research approaches within the scientific community as well as examples of ways to transcend the boundaries of science to include artists and community stakeholders. The aspiration is to inform and inspire concrete application of transdisciplinary and participatory methods in concert to address complex socio-environmental challenges.

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.

During the summer of 1999 members of the Upper Tigris Archaeological Research Project (UTARP) conducted archaeological excavations and surveys at two sites in the upper Tigris river region of southeastern Turkey. This article presents the results of that research. At the site of Boztepe excavations yielded four Halaf period burials, all of which contained grave goods, and an Iron Age house dated by C14 to the Assyrian Imperial period. Intensive surveys at Talavaş Tepe and Boztepe have refined the chronology and size of both sites. Although the exposures of the Halaf period are very small, these data add important insights into Halaf mortuary practices, while evidence from both Boztepe and Talavaş Tepe supplements our understanding of the upper Tigris river region during the Iron Age. 1999 yılı yaz aylarında Yukarı Dicle Arkeolojik Araştırma Projesi (UTARP) üyeleri Türkiye'nin güneydoǧu Anadolu bölgesinde yer alan yukarı Dicle bölgesindeki iki yerleşimde arkeolojik kazı ve yüzey araştırması yapmıştır. Bu makale bu araştırmanın sonuçlarını içermektedir. Boztepe yerleşiminde yapılan kazılar, hepsinde mezar buluntuları olan dört tane Halaf dönemi mezarını ortaya çıkarmıştır. Ayrıca C14 yöntemi ile Asur Krallık dönemine tarihlenen bir Demir Çaǧ evi de bulunmuştur. Talavaş Tepe ve Boztepe'de yapılan yoǧun araştırmalar ise, her iki yerleşimin de kronolojisini ve büyüklüklerini ortaya koymuştur. Her ne kadar, Halaf dönemine ait ortaya çıkan buluntular çok azsa da, bu bulgular Halaf ölü gömme uygulamalariyla ilgili bilgilerimizin önemli derecede artmasina neden olmuştur. Boztepe ve Talavaş Tepe bulgulan ise, Demir Çaǧda yukarı Dicle bölgesini daha iyi anlamamızı saǧlamıştır.

In patients 65 or younger with multiple myeloma, high-dose consolidation therapy was associated with longer survival and more myelotoxicity than conventional-dose therapy. Lenalidomide maintenance improved progression-free survival but not overall survival. High-dose chemotherapy plus autologous stem-cell transplantation, as compared with conventional chemotherapy, prolongs progression-free survival and overall survival among patients with newly diagnosed multiple myeloma. 1 – 4 and it is currently the standard of care for patients who are younger than 65 years of age. However, since autologous stem-cell transplantation has substantial toxic effects and requires prolonged hospitalization, the comparison with less toxic, orally administered treatments is important. Immunomodulatory drugs and proteasome inhibitors have significantly improved outcomes in patients, regardless of whether they are eligible for transplantation. 5 – 18 These improvements have raised questions about the role of transplantation in comparison with conventional . . .

PurposeDoes controlled ovarian stimulation (COS) and progesterone (P) luteal supplementation modify the vaginal and endometrial microbiota of women undergoing in vitro fertilization?MethodsFifteen women underwent microbiota analysis at two time points: during a mock transfer performed in the luteal phase of the cycle preceding COS, and at the time of fresh embryo transfer (ET). A vaginal swab and the distal extremity of the ET catheter tip were analyzed using next-generation 16SrRNA gene sequencing. Heterogeneity of the bacterial microbiota was assessed according to both the Bray-Curtis similarity index and the Shannon diversity index.ResultsLactobacillus was the most prevalent genus in the vaginal samples, although its relative proportion was reduced by COS plus P supplementation (71.5 ± 40.6% vs. 61.1 ± 44.2%). In the vagina, an increase in pathogenic species was observed, involving Prevotella (3.5 ± 8.9% vs. 12.0 ± 19.4%), and Escherichia coli-Shigella spp. (1.4 ± 5.6% vs. 2.0 ± 7.8%). In the endometrium, the proportion of Lactobacilli slightly decreased (27.4 ± 34.5% vs. 25.0 ± 29.9%); differently, both Prevotella and Atopobium increased (3.4 ± 9.5% vs. 4.7 ± 7.4% and 0.7 ± 1.5% vs. 5.8 ± 12.0%). In both sites, biodiversity was greater after COS (p < 0.05), particularly in the endometrial microbiota, as confirmed by Bray-Curtis analysis of the phylogenetic distance among bacteria genera. Bray-Curtis analysis confirmed significant differences also for the paired endometrium-vagina samples at each time point.ConclusionsOur findings suggest that COS and P supplementation significantly change the composition of vaginal and endometrial microbiota. The greater instability could affect both endometrial receptivity and placentation. If our findings are confirmed, they may provide a further reason to encourage the freeze-all strategy.

Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Merkel cell carcinoma (MCC). These neoplasms are highly diverse in their clinical presentation, as well as in their biological evolution. While the deregulation of the Hedgehog pathway is commonly observed in BCC, SCC and MCC are characterized by a strikingly elevated mutational and neoantigen burden. As result of our improved understanding of the biology of non-melanoma skin cancers, innovative treatment options including inhibitors of the Hedgehog pathway and immunotherapeutic agents have been recently investigated against these malignancies, leading to their approval by regulatory authorities. Herein, we review the most relevant biological and clinical features of NMSC, focusing on innovative treatment approaches.

Breast cancer remains the leading cause of cancer-related death in women, largely due to therapy resistance driven by both tumor-intrinsic and tumor microenvironment (TME)-mediated mechanisms. Toll-like receptor 2 (TLR2), which is overexpressed in breast tumors, promotes cancer progression and chemoresistance through both cancer-cell intrinsic and immune-mediated signaling, making it a promising therapeutic target. We developed a targeted therapy combining two types of nanoparticles (NPs) for targeted drug delivery, hybrid poly (lactic-co-glycolic acid) (PLGA)- lipid NPs loaded with the TLR2 inhibitor CU-CPT22 (PLGA-CU) and liposomes encapsulating doxorubicin (LIPO-DOXO). Both NP types were functionalized with cyclic RGD peptides to target α β integrins. Their effects were evaluated in vitro on triple-negative and HER2-positive breast cancer cells and in vivo in 4T1 triple negative breast cancer tumor-bearing mice. PLGA-CU effectively inhibited TLR2 signaling. Both PLGA-CU and LIPO-DOXO reduced cell viability and induced apoptosis, with stronger effects observed when used in combination. In vivo imaging confirmed the accumulation of NPs in tumors. While monotherapies reduced tumor growth, the combined treatment targeted both cancer cells and TME, leading to reduced angiogenesis and immunosuppression, as well as enhanced anti-tumor activity. NP-mediated delivery of a TLR2 inhibitor and doxorubicin produces synergistic anti-cancer effects in breast cancer models. This approach may help overcome chemoresistance and improve therapeutic outcomes, offering a promising strategy for the treatment of advanced breast cancer.

MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Results showed that miR-130a and miR-145 were enriched, while miR-155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria. Similarly, in an animal model of early experimental diabetic nephropathy, urinary exosomal miR-145 levels were increased and this was paralleled by miR-145 overexpression within the glomeruli. Exposure of cultured mesangial cells to high glucose increased miR-145 content in both mesangial cells and mesangial cells-derived exosomes, providing a potential mechanism for diabetes-induced miR-145 overexpression. In conclusion, urinary exosomal miRNA content is altered in type 1 diabetic patients with incipient diabetic nephropathy and miR-145 may represent a novel candidate biomarker/player in the complication.