Ancient familial Mediterranean fever mutations in human pyrin and resistance to Yersinia pestis.

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by homozygous or compound heterozygous gain-of-function mutations in MEFV, which encodes pyrin, an inflammasome protein. Heterozygous carrier frequencies for multiple MEFV mutations are high in several Mediterranean populations, suggesting that they confer selective advantage. Among 2,313 Turkish people, we found extended haplotype homozygosity flanking FMF-associated mutations, indicating evolutionarily recent positive selection of FMF-associated mutations. Two pathogenic pyrin variants independently arose >1,800 years ago. Mutant pyrin interacts less avidly with Yersinia pestis virulence factor YopM than with wild-type human pyrin, thereby attenuating YopM-induced interleukin (IL)-1ß suppression. Relative to healthy controls, leukocytes from patients with FMF harboring homozygous or compound heterozygous mutations and from asymptomatic heterozygous carriers released heightened IL-1ß specifically in response to Y. pestis. Y. pestis-infected MefvM680I/M680I FMF knock-in mice exhibited IL-1-dependent increased survival relative to wild-type knock-in mice. Thus, FMF mutations that were positively selected in Mediterranean populations confer heightened resistance to Y. pestis.

Severe multi-year drought coincident with Hittite collapse around 1198-1196 BC.

The potential of climate change to substantially alter human history is a pressing concern, but the specific effects of different types of climate change remain unknown. This question can be addressed using palaeoclimatic and archaeological data. For instance, a 300-year, low-frequency shift to drier, cooler climate conditions around 1200 BC is frequently associated with the collapse of several ancient civilizations in the Eastern Mediterranean and Near East1-4. However, the precise details of synchronized climate and human-history-scale associations are lacking. The archaeological-historical record contains multiple instances of human societies successfully adapting to low-frequency climate change5-7. It is likely that consecutive multi-year occurrences of rare, unexpected extreme climatic events may push a population beyond adaptation and centuries-old resilience practices5,7-10. Here we examine the collapse of the Hittite Empire around 1200 BC. The Hittites were one of the great powers in the ancient world across five centuries11-14, with an empire centred in a semi-arid region in Anatolia with political and socioeconomic interconnections throughout the ancient Near East and Eastern Mediterranean, which for a long time proved resilient despite facing regular and intersecting sociopolitical, economic and environmental challenges. Examination of ring width and stable isotope records obtained from contemporary juniper trees in central Anatolia provides a high-resolution dryness record. This analysis identifies an unusually severe continuous dry period from around 1198 to 1196 (±3) BC, potentially indicating a tipping point, and signals the type of episode that can overwhelm contemporary risk-buffering practices.

Mobility and kinship in the world's first village societies.

Around 10,000 y ago in southwest Asia, the cessation of a mobile lifestyle and the emergence of the first village communities during the Neolithic marked a fundamental change in human history. The first communities were small (tens to hundreds of individuals) but remained semisedentary. So-called megasites appeared soon after, occupied by thousands of more sedentary inhabitants. Accompanying this shift, the material culture and ancient ecological data indicate profound changes in economic and social behavior. A shift from residential to logistical mobility and increasing population size are clear and can be explained by either changes in fertility and/or aggregation of local groups. However, as sedentism increased, small early communities likely risked inbreeding without maintaining or establishing exogamous relationships typical of hunter-gatherers. Megasites, where large populations would have made endogamy sustainable, could have avoided this risk. To examine the role of kinship practices in the rise of megasites, we measured strontium and oxygen isotopes in tooth enamel from 99 individuals buried at Pinarbasi, Boncuklu, and Çatalhöyük (Turkey) over 7,000 y. These sites are geographically proximate and, critically, span both early sedentary behaviors (Pinarbasi and Boncuklu) and the rise of a local megasite (Çatalhöyük). Our data are consistent with the presence of only local individuals at Pinarbasi and Boncuklu, whereas at Çatalhöyük, several nonlocals are present. The Çatalhöyük data stand in contrast to other megasites where bioarchaeological evidence has pointed to strict endogamy. These different kinship behaviors suggest that megasites may have arisen by employing unique, community-specific kinship practices.

Isotopic and DNA analyses reveal multiscale PPNB mobility and migration across Southeastern Anatolia and the Southern Levant.

Growing reliance on animal and plant domestication in the Near East and beyond during the Pre-Pottery Neolithic B (PPNB) (the ninth to eighth millennium BC) has often been associated with a "revolutionary" social transformation from mobility toward more sedentary lifestyles. We are able to yield nuanced insights into the process of the Neolithization in the Near East based on a bioarchaeological approach integrating isotopic and archaeogenetic analyses on the bone remains recovered from Nevali Çori, a site occupied from the early PPNB in Turkey where some of the earliest evidence of animal and plant domestication emerged, and from Ba'ja, a typical late PPNB site in Jordan. In addition, we present the archaeological sequence of Nevali Çori together with newly generated radiocarbon dates. Our results are based on strontium (87Sr/86Sr), carbon, and oxygen (δ18O and δ13Ccarb) isotopic analyses conducted on 28 human and 29 animal individuals from the site of Nevali Çori. 87Sr/86Sr results indicate mobility and connection with the contemporaneous surrounding sites during the earlier PPNB prior to an apparent decline in this mobility at a time of growing reliance on domesticates. Genome-wide data from six human individuals from Nevali Çori and Ba'ja demonstrate a diverse gene pool at Nevali Çori that supports connectedness within the Fertile Crescent during the earlier phases of Neolithization and evidence of consanguineous union in the PPNB Ba'ja and the Iron Age Nevali Çori.

Dissecting genetic architecture of rare dystonia: genetic, molecular and clinical insights.

BACKGROUND: Dystonia is one of the most common movement disorders. To date, the genetic causes of dystonia in populations of European descent have been extensively studied. However, other populations, particularly those from the Middle East, have not been adequately studied. The purpose of this study is to discover the genetic basis of dystonia in a clinically and genetically well-characterised dystonia cohort from Turkey, which harbours poorly studied populations. METHODS: Exome sequencing analysis was performed in 42 Turkish dystonia families. Using co-expression network (CEN) analysis, identified candidate genes were interrogated for the networks including known dystonia-associated genes and genes further associated with the protein-protein interaction, animal model-based characteristics and clinical findings. RESULTS: We identified potentially disease-causing variants in the established dystonia genes (PRKRA, SGCE, KMT2B, SLC2A1, GCH1, THAP1, HPCA, TSPOAP1, AOPEP; n=11 families (26%)), in the uncommon forms of dystonia-associated genes (PCCB, CACNA1A, ALDH5A1, PRKN; n=4 families (10%)) and in the candidate genes prioritised based on the pathogenicity of the variants and CEN-based analyses (n=11 families (21%)). The diagnostic yield was found to be 36%. Several pathways and gene ontologies implicated in immune system, transcription, metabolic pathways, endosomal-lysosomal and neurodevelopmental mechanisms were over-represented in our CEN analysis. CONCLUSIONS: Here, using a structured approach, we have characterised a clinically and genetically well-defined dystonia cohort from Turkey, where dystonia has not been widely studied, and provided an uncovered genetic basis, which will facilitate diagnostic dystonia research.

An endemic pathway to sheep and goat domestication at Asikli Höyük (Central Anatolia, Turkey).

Sheep and goats (caprines) were domesticated in Southwest Asia in the early Holocene, but how and in how many places remain open questions. This study investigates the initial conditions and trajectory of caprine domestication at Asikli Höyük, which preserves an unusually high-resolution record of the first 1,000 y of Neolithic existence in Central Anatolia. Our comparative analysis of caprine age and sex structures and related evidence reveals a local domestication process that began around 8400 cal BC. Caprine management at Asikli segued through three viable systems. The earliest mode was embedded within a broad-spectrum foraging economy and directed to live meat storage on a small scale. This was essentially a "catch-and-grow" strategy that involved seasonal capture of wild lambs and kids from the surrounding highlands and raising them several months prior to slaughter within the settlement. The second mode paired modest levels of caprine reproduction on site with continued recruitment of wild infants. The third mode shows the hallmarks of a large-scale herding economy based on a large, reproductively viable captive population but oddly directed to harvesting adult animals, contra to most later Neolithic practices. Wild infant capture likely continued at a low level. The transitions were gradual but, with time, gave rise to early domesticated forms and monumental differences in human labor organization, settlement layout, and waste accumulation. Asikli was an independent center of caprine domestication and thus supports the multiple origins evolutionary model.

Venomics and Peptidomics of Palearctic Vipers: A Clade-Wide Analysis of Seven Taxa of the Genera Vipera, Montivipera, Macrovipera, and Daboia across Türkiye.

Snake venom variations are a crucial factor to understand the consequences of snakebite envenoming worldwide, and therefore it is important to know about toxin composition alterations between taxa. Palearctic vipers of the genera Vipera, Montivipera, Macrovipera, and Daboia have high medical impacts across the Old World. One hotspot for their occurrence and diversity is Türkiye, located on the border between continents, but many of their venoms remain still understudied. Here, we present the venom compositions of seven Turkish viper taxa. By complementary mass spectrometry-based bottom-up and top-down workflows, the venom profiles were investigated on proteomics and peptidomics level. This study includes the first venom descriptions of Vipera berus barani, Vipera darevskii, Montivipera bulgardaghica albizona, and Montivipera xanthina, as well as the first snake venomics profiles of Turkish Macrovipera lebetinus obtusa, and Daboia palaestinae, including an in-depth reanalysis of M. bulgardaghica bulgardaghica venom. Additionally, we identified the modular consensus sequence pEXW(PZ)1-2P(EI)/(KV)PPLE for bradykinin-potentiating peptides in viper venoms. For better insights into variations and potential impacts of medical significance, the venoms were compared against other Palearctic viper proteomes, including the first genus-wide Montivipera venom comparison. This will help the risk assessment of snakebite envenoming by these vipers and aid in predicting the venoms' pathophysiology and clinical treatments.

Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort.

The terms developmental epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) designate a spectrum of conditions that are typified by different combinations of motor, cognitive, language, and behavioral regression linked to robust spike-and-wave activity during sleep. In this study, we aimed at describing the clinical and molecular findings in "(developmental) epileptic encephalopathy with spike-and-wave activation in sleep" (D)EE-SWAS) patients as well as at contributing to the genetic etiologic spectrum of (D)EE-SWAS. Single nucleotide polymorphism (SNP) array and whole-exome sequencing (WES) techniques were used to determine the underlying genetic etiologies. Of the 24 patients included in the study, 8 (33%) were female and 16 (67%) were male. The median age at onset of the first seizure was 4 years and the median age at diagnosis of (D)EE-SWAS was 5 years. Of the 24 cases included in the study, 13 were compatible with the clinical diagnosis of DEE-SWAS and 11 were compatible with the clinical diagnosis of EE-SWAS. Abnormal perinatal history was present in four cases (17%), and two cases (8%) had a family history of epilepsy. Approximately two-thirds (63%) of all patients had abnormalities detected on brain computerized tomography/magnetic resonance (CT/MR) imaging. After SNP array and WES analysis, the genetic etiology was revealed in 7 out of 24 (29%) cases. Three of the variants detected were novel (SLC12A5, DLG4, SLC9A6). This study revealed for the first time that Smith-Magenis syndrome, SCN8A-related DEE type 13 and SLC12A5 gene variation are involved in the genetic etiology of (D)EE-SWAS. (D)EE-SWAS is a genetically diverse disorder with underlying copy number variations and single-gene abnormalities. In the current investigation, rare novel variations in genes known to be related to (D)EE-SWAS and not previously reported genes to be related to (D)EE-SWAS were discovered, adding to the molecular genetic spectrum. Molecular etiology enables the patient and family to receive thorough and accurate genetic counseling as well as a personalized medicine approach.

Investigation of genotype-phenotype and familial features of Turkish dystrophinopathy patients.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive allelic muscle diseases caused by dystrophin gene mutations. Eight hundred thirty-seven patients admitted between 1997 and 2022 were included in the study. Two hundred twenty patients were analyzed by multiplex PCR (mPCR) alone. Five hundred ninety-five patients were investigated by multiplex ligation-dependent probe amplification (MLPA), and 54 patients were examined by sequencing. Deletion was detected in 60% (132/220) of the cases in the mPCR group only and in 58.3% (347/595) of the cases with MLPA analysis. The rates of deletion and duplication were 87.7% and 12.3%, respectively, in the MLPA analysis. Single exon deletions were the most common mutation type. The introns 43-55 (81.8%) and exons 2-21 (13.1%) regions were detected as hot spots in deletions. It was determined that 89% of the mutations were suitable for exon skipping therapy. The reading frame rule did not hold in 7.6% of D/BMD cases (17/224). We detected twenty-five pathogenic/likely pathogenic variants in sequencing, five of which were novel variants. Nonsense mutation was the most common small mutation (44%). 21% of DMD patients were familial. We detected germline mosaicism in four families (4.3%) in the large rearrangement group and one gonosomal mosaicism in a family with a nonsense mutation. This is the largest study examining genotype and phenotype data in Turkish D/BMD families investigated by MLPA analysis. The reading frame hypothesis is not valid in all cases. Sharing the genotype and phenotype characteristics of these cases in the literature will shed light on the molecular structure of DMD and guide gene therapy research. In genetic counseling, carrier screening in the family and possible gonadal mosaicism should be emphasized.

The real-world outcomes of Lutetium-177 PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer: Turkish Oncology Group multicenter study.

Metastatic castration-resistant prostate cancer (mCRPC) remains a challenging condition to treat despite recent advancements. This retrospective study aimed to assess the activity and tolerability of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) in mCRPC patients across multiple cancer centers in Turkey. The study included 165 patients who received at least one cycle of Lu-177 PSMA-617 RLT, with the majority having bone metastases and undergone prior treatments. Prostate-specific antigen (PSA) levels were assessed before each treatment cycle, and the biochemical response was evaluated in accordance with the Prostate Cancer Work Group 3 Criteria. The PSA decline of ≥50% was classified as a response, while an increase of ≥25% in PSA levels was indicative of progressive disease. Neither response nor progression was considered as stable disease. The Lu-177 PSMA-617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall survival (OS) and progression-free survival were 13.5 and 8.2 months, respectively. Patients receiving Lu-177 PSMA-617 RLT in combination with androgen receptor pathway inhibitors (ARPIs) had a higher OS compared to those receiving Lu-177 PSMA-617 RLT alone (18.2 vs 12.3 months, P = .265). The treatment was generally well-tolerated, with manageable side effects such as anemia and thrombocytopenia. This study provides real-world evidence supporting the effectiveness and safety of Lu-177 PSMA-617 RLT in mCRPC patients, particularly when used in combination with ARPIs. These findings contribute to the growing body of evidence on the potential benefits of PSMA-targeted therapies in advanced prostate cancer.

The safety and efficacy of TNF inhibitors in patients with Behçet's disease: Retrospective study from eastern Turkey.

OBJECTIVE: We aimed to evaluate the clinical features, disease course, and associated factors for outcome in severe/refractory BD patients receiving TNF-i treatment. MATERIAL AND METHODS: This retrospective study was conducted by reviewing medical records from a tertiary referral center in Van province in Eastern Turkey. Data were obtained from patients' charts followed up between June 2019 and June 2022. RESULTS: We included 469 BD patients (59.3% male) whose 80 patients (17%) received TNF-i treatment in the study. The mean ± standard deviation of the patient age was 36.7 ± 10.1 years and the median (IQR) disease duration was 12 (12) years. IFX and ADAwere initiated in 67.5% (n = 54) and 32.5% (n = 26) patients, respectively. Overall and first-line retention rates of TNF-i were 84.7% and 92.6% for IFX and 83.3% and 80.8% for ADA, respectively. IFX was discontinued in 9 patients which were in 2 patients due to allergic reaction and tuberculosis, 3 patients for inefficacy, one patient for heart failure, and one patient for orbital zona. Although no serious adverse event was observed with ADA, 5 patients switched to IFX due to inefficacy. Overall, 72 patients (90%) resumed TNF-i at the end of the study; TNF-i was discontinued in 3 patients (3.8%) due to severe adverse events and in 5 patients (6.2%) with prolonged remission. CONCLUSION: In our study, no case of death was observed in TNF-i receiving patients. Most patients achieved attack-free and CS-free disease and retained TNF-i treatment. TNF inhibitors appear to be safe and effective in patients with severe/refractory Behçet's disease.

Whole-genome sequence of a novel lytic bacteriophage infecting Clavibacter michiganensis subsp. michiganensis from Turkey.

Clavibacter michiganensis subsp. michiganensis (Cmm) is an important plant-pathogenic bacterium that causes canker and wilt diseases. Biological control of the disease with bacteriophages is an alternative to conventional methods. In this study, Phage33 infecting Cmm was characterized based on morphological and genomic properties. Morphological characteristics such as shape and size were investigated using electron microscopy. The whole genome was sequenced using the Illumina Novaseq 6000 platform and the sequence was assembled and annotated. VICTOR and VIRIDIC were used for determining the phylogeny and comparing viral genomes, respectively. Electron microscopy showed that Phage33 has an icosahedral head with a diameter of ~55 nm and a long, thin, non-contractile tail ~169 nm in length. The genome of Phage33 is 56 324 bp in size, has a GC content of 62.49 % and encodes 67 open reading frames. Thirty-seven ORFs showed high homology to functionally annotated bacteriophage proteins in the NCBI database. The remaining 30 ORFs were identified as hypothetical with unknown functions. The genome contains no antimicrobial resistance, no lysogenicity and no virulence signatures, suggesting that it is a suitable candidate for biocontrol agents. The results of a blastn search showed similarity to the previously reported Xylella phage Sano, with an average nucleotide sequence identity of 92.37 % and query coverage of 91 %. This result was verified using VICTOR and VIRIDIC analysis, and suggests that Phage33 is a new member of the genus Sanovirus under the class Caudoviricetes.

High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population.

Neurodevelopmental disorders (NDDs) are clinically and genetically heterogenous; many such disorders are secondary to perturbation in brain development and/or function. The prevalence of NDDs is > 3%, resulting in significant sociocultural and economic challenges to society. With recent advances in family-based genomics, rare-variant analyses, and further exploration of the Clan Genomics hypothesis, there has been a logarithmic explosion in neurogenetic "disease-associated genes" molecular etiology and biology of NDDs; however, the majority of NDDs remain molecularly undiagnosed. We applied genome-wide screening technologies, including exome sequencing (ES) and whole-genome sequencing (WGS), to identify the molecular etiology of 234 newly enrolled subjects and 20 previously unsolved Turkish NDD families. In 176 of the 234 studied families (75.2%), a plausible and genetically parsimonious molecular etiology was identified. Out of 176 solved families, deleterious variants were identified in 218 distinct genes, further documenting the enormous genetic heterogeneity and diverse perturbations in human biology underlying NDDs. We propose 86 candidate disease-trait-associated genes for an NDD phenotype. Importantly, on the basis of objective and internally established variant prioritization criteria, we identified 51 families (51/176 = 28.9%) with multilocus pathogenic variation (MPV), mostly driven by runs of homozygosity (ROHs) - reflecting genomic segments/haplotypes that are identical-by-descent. Furthermore, with the use of additional bioinformatic tools and expansion of ES to additional family members, we established a molecular diagnosis in 5 out of 20 families (25%) who remained undiagnosed in our previously studied NDD cohort emanating from Turkey.

Germline genetic variants in Turkish familial multiple myeloma/monoclonal gammopathy of undetermined significance cases.

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.

Pyruvate kinase deficiency in 29 Turkish patients with two novel intronic variants.

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.

Psychosocial Evaluation of Adults with Primary Immunodeficiency.

PURPOSE: Primary immunodeficiency disorder (PID) is a heterogeneous group of diseases characterized by immune dysregulation and increased susceptibility to infections, with various cognitive, emotional, behavioral, and social effects on patients. This study aimed to evaluate loneliness, social adaptation, anxiety, and depression and to identify associated factors in adults with immunodeficiency. METHODS: A cross-sectional study in Turkey (Feb-Aug 2022) obtained sociodemographic data from patient records. The Social Adaptation Self-Evaluation Scale (SASS), UCLA-Loneliness Scale (UCLA-LS), and Hospital Anxiety and Depression Scale (HADS) were administered in individual patient interviews. HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D) scores were assessed using cut-offs of 10 and 7, respectively; SASS cut-offs for social imbalance and normalcy were < 25 and > 35, respectively. RESULTS: A total of 104 patients (60 women, 44 men) with a median age of 34 years (range: 18-89) were included in the study. Mean scores were SASS: 34.46 ± 8.11, UCLA-LS: 44.89 ± 12.66, HADS-A: 9.87 ± 4.77, and HADS-D: 9.12 ± 4.80. SASS score was negatively correlated with HADS-A, HADS-D, and UCLA-LS scores. There were positive correlations between UCLA-LS and HADS-A (r = -0.355, p < 0.01) and HADS-D (r = -0.614, p < 0.01) and between HADS-A and HADS-D (r = -0.454, p < 0.01). Low-income level was associated with higher HADS-A, HADS-D, and UCLA-LS scores and lower SASS score (p = 0.012, p = 0.041, p = 0.008, and p = 0.001, respectively). CONCLUSION: Adults with PID are at risk for depression and experience high levels of loneliness. Social maladjustment and loneliness contribute to anxiety and depression, and loneliness is correlated with impaired social functioning. These findings emphasize the importance of biopsychosocial evaluation of individuals diagnosed with PID.

The potential range of west Asian apple species Malus orientalis Uglitzk. under climate change.

The wild relatives of cultivated apples would be an ideal source of diversity for breeding new varieties, which could potentially grow in diverse habitats shaped by climate change. However, there is still a lack of knowledge about the potential distribution of these species. The aim of the presented work was the understand the impacts of climate change on the potential distribution and habitat fragmentation of Caucasian crab apple (Malus orientalis Uglitzk.) and the designation of areas of high interest according to climatic conditions. We used the MaxEnt models and Morphological-Spatial Analysis (MSPA) to evaluate the potential distribution, suitability changes, habitat fragmentation, and connectivity throughout the species range in Turkey, Armenia, Georgia, Russia, and Iran. The results revealed that the potentially suitable range of M. orientalis encompasses 858,877 km², 635,279 km² and 456,795 km² under the present, RCP4.5 and RCP8.5 scenario, respectively. The range fragmentation analysis demonstrated a notable shift in the edge/core ratio, which increased from 50.95% in the current scenario to even 67.70% in the future. The northern part of the range (Armenia, northern Georgia, southern Russia), as well as the central and western parts of Hyrcania will be a core of the species range with suitable habitats and a high connectivity between M. orientalis populations and could work as major refugia for the studied species. However, in the Zagros and central Turkey, the potential range will shrink due to the lack of suitable climatic conditions, and the edge/core ratio will grow. In the southern part of the range, a decline of M. orientalis habitats is expected due to changing climatic conditions. The future outlook suggests that the Hyrcanian forest and the Caucasus region could serve as important refuges for M. orientalis. This study helps to understand spatial changes in species' range in response to climate change and can help develop conservation strategies. This is all the more important given the species' potential use in future breeding programs aimed at enriching the gene pool of cultivated apple varieties.

Identify risk factors affecting participation of Turkish women in mammography screening for breast cancer prevention.

PURPOSE: Cancer screening is a public health intervention aiming to reduce cancer-caused deaths. This study aims to determine the factors affecting the mammography screening time among women aged 40-69. METHODS: The micro dataset obtained from the Türkiye Health Survey conducted by the Turkish Statistical Institute (TurkStat) in 2019 and 2022 was used in the present study. Stereotype logistic regression was used to determine the variables affecting mammography screening and period for breast cancer prevention in women in Türkiye. RESULTS: Given the results achieved from the analysis, it was found that factors such as age, marital status, general health condition, comorbidity, receiving psychosocial support, high blood lipid levels, and performing breast self-examinations affected women's adherence to cancer screening programs. CONCLUSION: Since adherence to mammography increases with age, it is recommended to pay importance to education for women approaching the age of mammography screening. Educated individuals are expected to have access to multiple sources of information as to cancer and to access this information more easily. In order to gain more insight into the recommended preventive measures and outcomes related to cancer, it is suggested to review policies, which will increase the educational level of women, and provide privileges in the field of education.

Evaluation of the effectiveness of colorectal cancer screening intervention.

PURPOSE: The effectiveness of the Colorectal Cancer (CRC) screening program is assessed based on the reduction in CRC mortality and incidence rates over time. To accurately estimate the long-term impact, it is advisable to monitor additional indicators such as age and stage-specific incidence rates. Our objective is to evaluate the effectiveness of the National CRC Screening Program in Turkey and analyze its influence on disease stage at diagnosis and survival rates. METHODS: The National CRC Screening Program was considered an intervention and the distribution of local, regional, and distant diseases, and survival estimates were assessed before and after the intervention to evaluate the effectiveness of the intervention. RESULTS: 518 patients were included in the study. At the time of diagnosis, localized, regional, and distant disease in pre-intervention were 31.3%, 42.9%, 25.8%, while post-intervention were 42.8%, 33.3%, 23.9%, respectively (p = 0.020). The relative effectiveness of the intervention in males, females, and 50-70 ages were calculated as 1.2[95% CI 0.95-1.73], 1.5[95% CI 1.04-2.18], and 1.6[95% CI 1.21-2.28] in localized disease, 0.8[95% CI 0.67-1.18], 0.6[95% CI 0.43-0.90], and 0.6[95% CI 0.46-0.81] in regional diseases, 0.8[95% CI 0.57-1.20], 1.1[95% CI 0.66-1.84], and 1.0[95% CI 0.70-1.57] in distant disease, respectively. CONCLUSION: A noticeable shift in the disease stage at the time of diagnosis was observed; however, this shift varied among gender and age groups. To effectively evaluate the impact of a cancer screening program on reducing the incidence and mortality rates of the disease, it is essential to monitor and analyze these indicators alongside 5-10-year survival estimates and stage changes at the time of diagnosis.