Bibliometric analysis of focal therapy in prostate cancer research.

Introduction: The use of focal therapies for prostate cancer (PCa) has soared, as it controls disease and is associated with minimal side effects. Bibliometric analysis examines the global research landscape on any topic to identify gaps in the research and areas for improvement and prioritize future research efforts. This study aims to examine the research outputs and trends and collaboration landscape in the field of focal therapy for PCa on a global scale. Methods: We searched Medline, PubMed and Scopus for peer-reviewed publications on our research topic using controlled keywords. Search results were limited to the period between 1980 and 2022, screened for duplicates and then included in our study based on prespecified eligibility criteria. The Bibliometrix Package was used for comprehensive science mapping analysis of co-authorship, co-citation and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. Results: This analysis included 2578 research articles. The annual scientific production increased from one article in 1982 to 143 in 2022 (13.21%). The average citation per year was incrementally increasing, and these documents were cited around 32.52 times. The documents included in this analysis were published in 633 sources. The international collaboration index was 22.7. In total, 6280 author keywords were identified. The most used keywords were 'prostate cancer', 'focal therapy', 'prostate' and 'photodynamic therapy'. Conclusion: This bibliometric analysis has provided a comprehensive review of focal therapy in PCa research, highlighting both the significant growth in the field and the existing gaps that require further exploration. The study points to the need for more diverse international collaboration and exploration of various treatment modalities within the context of focal therapy.

Characteristics of injuries during the 2006 Lebanon conflict: a three-center retrospective study of survivors, 16 years after the conflict.

Background: Armed conflict injury is a growing public health concern, particularly in regions like the Middle East and North Africa (MENA). The protracted conflicts and political unrest in this region have led to a substantial number of injuries. Despite this, there is still limited understanding of the specific injury patterns stemming from conflicts, such as the 2006 Lebanon conflict. This study aimed to assess the characteristics and burdens of injuries resulting from this conflict, which occurred 16 years prior to this research. Methods: This retrospective study analyzed data of individuals affected by the 2006 Lebanon conflict, across three tertiary care centers. Demographics, injuries, complications, injury management, and hospitalization expenses were extracted from medical records and analyzed using SPSS version 29.0. Categorical variables were presented as counts and proportions, and continuous variables as mean ± standard deviation (SD). Hospital comparisons utilized chi-square or Fisher's exact tests for categorical variables, and one-way ANOVAs for continuous variables. Analysis was conducted from September to November 2023. Results: Across three hospitals, 341 patients were studied, comprising 73.6% males and 26.4% females. Among them, a notable proportion (57.3% males and 34.1% females) fell within the 18-39 age range. Children and adolescents under 18 years accounted for 15.9% of males and 25.9% of females. Blast-related injuries predominated, with 24.5% resulting from direct damage caused by explosive parts and 33.3% from blast wave forces. Extremity trauma occurred in 49.0% of patients, and head/neck trauma in 24.9%. Common injuries, including penetrating, musculoskeletal, and traumatic brain injuries affected 34.9%, 31.1, and 10.0% of patients, respectively. Wound repair, fracture treatment, and debridement were the most performed procedures on 15.5, 13.5 and 9.7% of the patients, respectively. The total cost of care was USD 692,711, largely covered by the Ministry of Public Health (95.9%). Conclusion: Conflict-related injuries significantly contribute to the global burden of disease. Therefore, there is a pressing need to improve national guidelines to prioritize life-threatening cases and potential long-term disabilities. Furthermore, enhancing electronic registry systems to collect clinical data on injured patients is essential for conducting research and better understanding the needs of conflict casualties.

The integration of ortho-plastic limb salvage teams in the humanitarian response to violence-related open tibial fractures: evaluating outcomes in the Gaza Strip.

BACKGROUND: Limb salvage by ortho-plastic teams is the standard protocol for treating open tibial fractures in high-income countries, but there's limited research on this in conflict settings like the Gaza Strip. This study assessed the clinical impact of gunshot-related open tibial fractures, compared patient management by orthopedic and ortho-plastic teams, and identified the risk factors for bone non-union in this context. METHODS: A retrospective review of medical records was conducted on Gaza Strip patients with gunshot-induced-open tibial fractures from March 2018 to October 2020. Data included patient demographics, treatments, and outcomes, with at least one year of follow-up. Primary outcomes were union, non-union, infection, and amputation. RESULTS: The study included 244 injured individuals, predominantly young adult males (99.2%) with nearly half (48.9%) having Gustilo-Anderson type IIIB fractures and more than half (66.8%) with over 1 cm of bone loss. Most patients required surgery, including rotational flaps and bone grafts with a median of 3 admissions and 9 surgeries. Ortho-plastic teams managed more severe muscle and skin injuries, cases with bone loss > 1 cm, and performed less debridement compared to other groups, though these differences were not statistically significant. Non-union occurred in 53% of the cases, with the ortho-plastic team having the highest rate at 63.6%. Infection rates were high (92.5%), but no significant differences in bone or infection outcomes were observed among the different groups. Logistic regression analysis identified bone loss > 1 cm, vascular injury, and the use of a definitive fixator at the first application as predictors of non-union. CONCLUSIONS: This study highlights the severity and complexity of such injuries, emphasizing their significant impact on patients and the healthcare system. Ortho-plastic teams appeared to play a crucial role in managing severe cases. However, further research is still needed to enhance our understanding of how to effectively manage these injuries.

Establishing a High-Quality Pediatric Cardiac Surgery Program in Post-Conflict Regions: A Model for Limited Resource Countries.

BACKGROUND: Congenital Heart Disease stands as a prominent cause of infant mortality, with notable disparities in surgical outcomes evident between high-income and low- to middle-income countries. OBJECTIVE: This study presents a collaborative partnership between a local governmental entity and an international private organization to establish a high-quality Pediatric Cardiac Surgery Program in a post-conflict limited resource country, Iraq. METHODS: A descriptive retrospective study analyzed pediatric cardiac surgery procedures performed by a visiting pediatric heart surgery team from October 2021 to October 2022, funded by the Ministry of Health (MOH). We used the STS-EACTS complexity scoring model (STAT) to assess mortality risks associated with surgical procedures. RESULTS: A total of 144 patients underwent 148 procedures. Infants comprised 58.3% of the patients. The most common anomalies included tetralogy of Fallot, ventricular septal defect, and various single ventricle categories, constituting 76% of the patient cohort. The overall surgical mortality rate was 4.1%, with an observed/expected surgical mortality rate of 1.1 (95% CI 0.5, 2.3). There was no significant difference between our observed surgical mortality in Category 2, 3, and 4 and those expected/reported by the STS-EACTS Database (p = 0.07, p = 0.72, and p = 0.12, respectively). The expenses incurred by the MOH for conducting surgeries in Iraq were lower than the alternative of sending patients abroad for the same procedures. CONCLUSION: The partnership model between a local public entity committed to infrastructure development and funding and an international private organization delivering clinical and training services can provide the foundation for building sustainable, high-quality in situ programs in upper-middle-income countries.

Cancer Research in Vulnerable Populations: A Call for Collaboration and Sustainability From MENAT Countries.

PURPOSE: Cancer is a major burden across Middle East, North Africa, Türkiye (MENAT). Many MENAT countries experience multiple conflicts that compound vulnerabilities, but little research investigates the linkages between vulnerability and cancer research. This study examines the current level and the potential for cancer research among vulnerable populations in the MENAT region, aiming to provide direction toward developing a research agenda on the region's vulnerable populations. METHODS: Expert-driven meetings were arranged among the 10 authors. After obtaining institutional review board approval, a self-administered online survey questionnaire was circulated to more than 500 cancer practitioners working in 22 MENAT countries. RESULTS: Two hundred sixteen cancer practitioners across the MENAT region responded. Fifty percent of the respondents identified clinical research in vulnerable patients with cancer as a significant issue; 21.8% reported previous research experience that included vulnerable populations, and 60% reported encountering vulnerable populations in their daily clinical practice. The main barriers to conducting research were lack of funding (60%), protected time (42%), and research training (35%). More than half of the respondents believed that wars/conflicts constituted an important source of vulnerability. The most vulnerable cancer populations were the elderly, palliative/terminally ill, those with concomitant mental health-related issues, those with other chronic illnesses, and socioeconomically deprived patients. CONCLUSION: Results support that a major effort is needed to improve cancer research among vulnerable cancer populations in the MENAT region. We call for interdisciplinary research that accounts for the region's unique, compounding, and cumulative forms of vulnerability. This cancer research agenda on different vulnerable populations must balance sociobehavioral studies that explore sociopolitical barriers to quality care and clinical studies that gauge and refine treatment protocols. Building a research agenda through collaboration and solidarity with international partners is prime time.

Long-term burden of war injuries among civilians in LMICs: case of the July 2006 war in Lebanon.

Introduction: Lebanon, a country located on the eastern shore of the Mediterranean Sea, is one of the world's smaller sovereign states. In the past few decades, Lebanon endured a perpetual political turmoil and several armed conflicts. July 12, 2006, marked the start of a one-month war in Lebanon, which resulted in thousands of casualties. Little is known about the long-term consequences of war injuries inflicted on civilians during the July 2006 war. Methods: The objectives of this paper were to identify and evaluate: 1- civilians' access to healthcare and medicine under conditions of war; 2- the long-term socioeconomic burden on injured civilians; and 3- their quality of life more than a decade post-war. We adopted a mixed-method research design with an emphasis on the qualitative component. We conducted interviews with patients, collected clinical and financial data from hospital medical records, and administered a self-rated health questionnaire, the EQ-5D-5L. Simple descriptive statistics were calculated using Excel. NVivo 12® was used for data management and thematic analysis. Results: We conducted 25 interviews. Injured civilians were mostly males, average age of 27. The most common mechanism of injury was blast injury. Most patients underwent multiple surgeries as well as revision surgeries. The thematic analysis revealed three themes: 1- recall of the time of the incident, the thousand miles journey, and patients' access to services; 2- post-trauma sequelae and services; and 3- long-term impact. Patients described the long-term burden including chronic pain, poor mobility, anxiety or depression, and limited activities of daily living. Discussion: Civilians injured during the July 2006 war described the traumatising events they endured during the war and the limited access to medical care during and post-war. Up until this study was conducted, affected civilians were still experiencing physical, psychological, and financial sequelae. Acknowledging the limitations of this study, which include a small sample size and recall bias, the findings underscore the necessity for the expansion of services catering to civilians injured during wartime.

Responding to the Humanitarian Crisis in Gaza: Damned if You do Damned if You don't!

Palestine, since 1948, has endured frequent military occupations and uprisings, intifadas, in a limited geographic area that has resulted in one of the worst humanitarian crises. The prolonged nature of this military occupation has created a biosphere of war that is uninhabitable, whereby Palestinians suffer from physical, psychological, and social wounds. Israel also imposed restrictive measures in Gaza, making it difficult for Palestinians to obtain permits to work and travel throughout Palestine. Israel continued to intensify the restrictions on Gaza, reaching a blockade on the Gaza Strip, which cut off Palestinians from Jerusalem, where hospitals, banks, and vital services are found. This form of permanent siege resulted in a surge in the unemployment rate, poverty, and poor nutritional and wellbeing status. The siege also resulted in the largest open-air prison, as people became stuck between an incomplete life and the absence of total death. The major challenge is that humanitarian interventions, in the case of Gaza, are ineffective, as they are part of the siege framework. This is because any humanitarian aid meant for Gaza needs to be approved by Israel. Thus, when the emergency becomes chronic and humanitarian interventions become part of the siege framework, how can Gaza rebuild its health capacity in a permanent emergency, and to what extent can the humanitarian sector make a change?

War and oncology: cancer care in five Iraqi provinces impacted by the ISIL conflict.

War and cancer have been intertwined in Iraq for over three decades, a country where the legacies and ongoing impacts of conflict have been commonly associated with both increased cancer rates as well as the deterioration of cancer care. Most recently, the Islamic State of Iraq and the Levant (ISIL) violently occupied large portions of the country's central and northern provinces between 2014 and 2017, causing devastating impacts on public cancer centers across central and northern Iraq. Focusing on the five Iraqi provinces previously under full or partial ISIL occupation, this article examines the immediate and long-term impacts of war on cancer care across three periods (before, during, and after the ISIL conflict). As there is little published data on oncology in these local contexts, the paper relies primarily upon the qualitative interviews and lived experience of oncologists serving in the five provinces studied. A political economy lens is applied to interpret the results, particularly the data related to progress in oncology reconstruction. It is argued that conflict generates immediate and long-term shifts in political and economic conditions that, in turn, shape the rebuilding of oncology infrastructure. The documentation of the destruction and reconstruction of local oncology systems is intended to benefit the next generation of cancer care practitioners in the Middle East and other conflict-affected regions areas in their efforts to adapt to conflict and rebuild from the legacies of war.

Congenital heart disease research landscape in the Arab world: a 25-year bibliometric review.

Background: While research on congenital heart disease has been extensively conducted worldwide, comprehensive studies from developing countries and the Arab world remain scarce. Aim: This study aims to perform a bibliometric review of research on congenital heart disease in the Arab world from 1997 to 2022. Methods: We analyzed data from the Web of Science, encompassing various aspects such as topics, countries, research output, citations, authors, collaborations, and affiliations. This comprehensive science mapping analysis was done using the R statistical software's Bibliometrix Package. Results: The research output from Arab countries over the 25 years showed an average annual growth rate of 11.5%. However, Arab countries exhibited lower research productivity than the United States and Europe, with a 24-fold difference. There was substantial variation in research output among 22 Arab countries, with five countries contributing to 78% of the total publications. Most of the published research was clinical, with limited innovative contributions and a preference for regional journals. High-income Arab countries displayed higher research productivity and citation rates than their low-income developing counterparts. Despite being categorized as upper-middle-income, post-conflict countries exhibited low research productivity. About one-quarter of the published articles (26%) resulted from collaborative efforts among multiple countries, with the United States being the most frequent collaborator. Enhanced research productivity and impact output were strongly associated with increased international cooperation. Conclusion: Research productivity in the Arab region closely correlates with a country's GDP. Success hinges on governmental support, funding, international collaboration, and a clear research vision. These findings offer valuable insights for policymakers, educational institutions, and governments to strengthen research programs and nurture a research culture.

Cancer registration in the Middle East, North Africa, and Turkey (MENAT) region: A tale of conflict, challenges, and opportunities.

Cancer registration is a core component of national and regional cancer control strategies. In the Middle East, North-Africa and Turkey (MENAT) region, capacity and resources for cancer registration is variable and shaped by multiple contextual challenges. This viewpoint maps out practical recommendations around cancer registration, in an attempt to inform cancer control planning, policy, and implementation. The recommendations laid out in this viewpoint are informed by the discussions held at the Initiative for Cancer Registration in the MENAT (ICRIM) virtual workshop, which convened registry managers, policy makers, and international agencies from 19 countries in the MENAT region. The discussions were distilled in four categories of recommendations, revolving around cancer registration procedures, collaborative governance, putting cancer registration on the map, and capacity building. This viewpoint provides a much-needed mapping of practical recommendations around cancer registration, informed by direct key stakeholders in the region. These practical recommendations offer a road map for policy making, cancer control planning, and future regional capacity strengthening initiatives.

SIK2 kinase synthetic lethality is driven by spindle assembly defects in FANCA-deficient cells.

The Fanconi anemia (FA) pathway safeguards genomic stability through cell cycle regulation and DNA damage repair. The canonical tumor suppressive role of FA proteins in the repair of DNA damage during interphase is well established, but their function in mitosis is incompletely understood. Here, we performed a kinome-wide synthetic lethality screen in FANCA-/- fibroblasts, which revealed multiple mitotic kinases as necessary for survival of FANCA-deficient cells. Among these kinases, we identified the depletion of the centrosome kinase SIK2 as synthetic lethal upon loss of FANCA. We found that FANCA colocalizes with SIK2 at multiple mitotic structures and regulates the activity of SIK2 at centrosomes. Furthermore, we found that loss of FANCA exacerbates cell cycle defects induced by pharmacological inhibition of SIK2, including impaired G2-M transition, delayed mitotic progression, and cytokinesis failure. In addition, we showed that inhibition of SIK2 abrogates nocodazole-induced prometaphase arrest, suggesting a novel role for SIK2 in the spindle assembly checkpoint. Together, these findings demonstrate that FANCA-deficient cells are dependent upon SIK2 for survival, supporting a preclinical rationale for targeting of SIK2 in FA-disrupted cancers.

High rates of advanced prostate cancer in the Middle East: Analysis from a tertiary care center.

OBJECTIVES: Prostate cancer incidence is increasing in the Middle East (ME); however, the data of stage at the diagnosis and treatment outcomes are lacking. In developed countries, the incidence of de novo metastatic prostate cancer ranges between 4% and 14%. We hypothesized that the rates of presentation with advanced disease are significantly higher in the ME based on clinical observation. This study aims to examine the stage at the presentation of patients with prostate cancer at a large tertiary center in the ME. METHODS: After Institutional Review Board approval, we identified the patients diagnosed with prostate adenocarcinoma and presented to a tertiary care center between January 2010 and July 2015. Clinical, demographic, and pathological characteristics were abstracted. Patients with advanced disease were stratified according to tumor volume based on definitions from practice changing clinical trials. Descriptive and Kaplan-Meier survival analysis was used. RESULTS: A total of 559 patients were identified, with a median age at the diagnosis of 65 years and an age range of 39-94 years. Median prostate-specific antigen (PSA) at the presentation was 10 ng/ml, and almost a quarter of the men (23%) presented with metastatic disease. The most common site of metastasis was the bone (34/89, 38%). High-volume metastasis was present in 30.3%, 9%, and 5.2% of the cohort based on STAMPEDE, CHAARTED, and LATITUDE trial criteria, respectively. CONCLUSION: This is the first report showing the high proportion of men from ME presenting with de novo metastasis. This could be due to many factors, including the highly variable access to specialist multidisciplinary management, lack of awareness, and lack of PSA screening in the region. There is a clear need to raise the awareness about prostate cancer screening and early detection and to address the rising burden of advanced prostate cancer affecting men in the ME region.

Mitotic Errors Promote Genomic Instability and Leukemia in a Novel Mouse Model of Fanconi Anemia.

Fanconi anemia (FA) is a disease of genomic instability and cancer. In addition to DNA damage repair, FA pathway proteins are now known to be critical for maintaining faithful chromosome segregation during mitosis. While impaired DNA damage repair has been studied extensively in FA-associated carcinogenesis in vivo, the oncogenic contribution of mitotic abnormalities secondary to FA pathway deficiency remains incompletely understood. To examine the role of mitotic dysregulation in FA pathway deficient malignancies, we genetically exacerbated the baseline mitotic defect in Fancc-/- mice by introducing heterozygosity of the key spindle assembly checkpoint regulator Mad2. Fancc-/-;Mad2+/- mice were viable, but died from acute myeloid leukemia (AML), thus recapitulating the high risk of myeloid malignancies in FA patients better than Fancc-/-mice. We utilized hematopoietic stem cell transplantation to propagate Fancc-/-; Mad2+/- AML in irradiated healthy mice to model FANCC-deficient AMLs arising in the non-FA population. Compared to cells from Fancc-/- mice, those from Fancc-/-;Mad2+/- mice demonstrated an increase in mitotic errors but equivalent DNA cross-linker hypersensitivity, indicating that the cancer phenotype of Fancc-/-;Mad2+/- mice results from error-prone cell division and not exacerbation of the DNA damage repair defect. We found that FANCC enhances targeting of endogenous MAD2 to prometaphase kinetochores, suggesting a mechanism for how FANCC-dependent regulation of the spindle assembly checkpoint prevents chromosome mis-segregation. Whole-exome sequencing revealed similarities between human FA-associated myelodysplastic syndrome (MDS)/AML and the AML that developed in Fancc-/-; Mad2+/- mice. Together, these data illuminate the role of mitotic dysregulation in FA-pathway deficient malignancies in vivo, show how FANCC adjusts the spindle assembly checkpoint rheostat by regulating MAD2 kinetochore targeting in cell cycle-dependent manner, and establish two new mouse models for preclinical studies of AML.

Cancer Registration in the Middle East, North Africa, and Turkey: Scope and Challenges.

PURPOSE: National cancer control strategies have been identified as essential tools for reducing and managing the growing burden of cancer in low- and middle-income countries. Cancer registration is an instrumental component of any cancer control strategy, providing the data to inform effective cancer policy. In the Middle East, North Africa, and Turkey (MENAT) region, cancer registration varies immensely and faces multifaceted challenges including protracted conflict. This study investigates and maps out the present capacities and outputs of cancer registration in the MENAT region and identifies thematic barriers facing implementation and utilization of cancer registry data. MATERIALS AND METHODS: We used a self-administered online survey with open and close-ended questions targeting national and institutional cancer registry managers in the MENAT countries. RESULTS: Registry managers from 19 MENAT countries reported the presence of 97 population-based, 48 hospital-based, and 24 pathology-based registries. Most population-based registries were well- or partially developed. Lack of accurate death records, complete medical records, and communication between stakeholders and deficiencies in trained personnel were critical challenges that were more severe in active conflict zones and neighboring conflict-affected regions. Cancer registration challenges included weak health infrastructure, absence of legislation mandating cancer registration, and disruption of cancer registration because of active conflict and loss of funding. Refugee host countries, such as Lebanon, Turkey, and Jordan, also reported conflict-related challenges including refugee mobility and lack of accurate data on forced migrants. CONCLUSION: This study provides a much-needed understanding of the current landscape and contextual challenges affecting cancer registration in the MENAT. These data are important for identifying areas on which to focus regional capacity-strengthening initiatives.

Research Capacity and Training Needs for Cancer in Conflict-Affected MENA Countries.

Background: The global cancer burden is disproportionately greater in low- and middle-income countries, including those affected by conflict in the Middle East and North Africa (MENA) region. Contributing factors include inadequate control of risk factors plus limited surveillance and treatment options. Weak healthcare infrastructure may be further compounded by the conflict prevalent in multiple MENA countries. Improved cancer surveillance, research, and capacity strengthening are essential for implementing cancer control plans in the MENA region, requisite for reducing the disproportionate cancer burden. Aims: This article aims to understand the barriers to cancer research and training in conflict-affected MENA countries, and to identify opportunities for developing capacities for reliable cancer research strategies. Methods: This study employs a mixed-method approach utilizing an online questionnaire with open and close ended questions targeting oncologists and cancer researchers in conflict-affected MENA countries. For open-ended questions, we performed a qualitative content analysis to identify thematic barriers. Results: Forty-eight respondents, mostly Medical and Radiation Oncologists, completed the questionnaire. The most significant training needs were conducting clinical, basic, and qualitative cancer research. The most prominent barriers identified were insufficient training in data analysis and research design (77% and 75% of respondents, respectively) and insufficient institutional and government funding (94% and 85%, respectively). For the qualitative data, we organized the barriers into six themes, the most common was the lack of research infrastructure (28%). Conclusions: Despite an escalating cancer burden, conflict-affected MENA countries are lagging in knowledge production and implementation of evidence-based cancer research. Novel modes of knowledge transmission and collaboration across geographical and political boundaries are sorely needed. Based on our study, we recommend developing innovative and accessible training opportunities focusing on developing basic, clinical, and qualitative research skills. Research capacity-strengthening initiatives should encourage the investigation of context-specific research questions with the potential to make a meaningful impact on cancer control in the region.

High-Cost Cancer Treatment Across Borders in Conflict Zones: Experience of Iraqi Patients in Lebanon.

PURPOSE: Conflict-induced cross-border travel for medical treatment is commonly observed in the Middle East. There has been little research conducted on the financial impact this has on patients with cancer or on how cancer centers can adapt their services to meet the needs of this population. This study examines the experience of Iraqi patients seeking care in Lebanon, aiming to understand the social and financial contexts of conflict-related cross-border travel for cancer diagnosis and treatment. PATIENTS AND METHODS: After institutional review board approval, 60 Iraqi patients and caregivers seeking cancer care at a major tertiary referral center in Lebanon were interviewed. RESULTS: Fifty-four respondents (90%) reported high levels of financial distress. Patients relied on the sale of possessions (48%), the sale of homes (30%), and vast networks to raise funds for treatment. Thematic analysis revealed several key drivers for undergoing cross-border treatment, including the conflict-driven exodus of Iraqi oncology specialists; the destruction of hospitals or road blockages; referrals by Iraqi physicians to Lebanese hospitals; the geographic proximity of Lebanon; and the lack of diagnostic equipment, radiotherapy machines, and reliable provision of chemotherapy in Iraqi hospitals. CONCLUSION: As a phenomenon distinct from medical tourism, conflict-related deficiencies in health care at home force patients with limited financial resources to undergo cancer treatment in neighboring countries. We highlight the importance of shared decision making and consider the unique socioeconomic status of this population of patients when planning treatment.

Strengthening capacity for cancer research in conflict settings: key informant insights from the Middle East.

BACKGROUND: Management of cancer in the Middle East and North Africa (MENA) region is accompanied by multiple challenges including heterogeneous access to early detection and treatment options and limited implementation of national cancer control plans. Furthermore, protracted armed conflicts across the region have had dramatic effects, including disruption of healthcare systems and the migration of healthcare professionals. Strengthening capacity for cancer research has been identified as a key intervention to correct data poverty, inform policy, manage limited resources and improve health outcomes. OBJECTIVE: The main objective of this study is to gain insights into the landscape, barriers and enablers of cancer training, research and care in the MENA region. METHOD: We utilised purposive sampling to interview 16 key informants from a diverse academic, medical and research background originating from countries affected by conflicts, such as Lebanon, and from active conflict zones including Iraq and Syria. RESULTS: The themes that emerged from the interviews focused on the barriers to cancer care, barriers to cancer research and training, strengths and importance of cancer research and training recommendations. The detrimental effect of conflict on cancer provision and research was a cross-cutting sub-theme disrupting cancer care provision and research due to unsafe environments, fragmented facilities, absence of drugs and migration of personnel. When asked about perceived optimal training format for cancer research, most informants recommended a post-graduate, face-to-face training focusing on cancer research methods and concepts. CONCLUSION: This study offers a unique insight into the barriers affecting cancer research and capacity-strengthening priorities from oncologists and researchers working in conflict-affected areas of the MENA region. These data will form the base for future capacity-strengthening initiatives addressing specific regional challenges.

The Evolving Role of TRAFs in Mediating Inflammatory Responses.

TRAFs [tumor necrosis factor (TNF) receptor associated factors] are a family of signaling molecules that function downstream of multiple receptor signaling pathways and play a pivotal role in the biology of innate, and adaptive immune cells. Following receptor ligation, TRAFs generally function as adapter proteins to mediate the activation of intracellular signaling cascades. With the exception of TRAF1 that lacks a Ring domain, TRAFs have an E3 ubiquitin ligase activity which also contributes to their ability to activate downstream signaling pathways. TRAF-mediated signaling pathways culminate in the activation of several transcription factors, including nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs; e.g., ERK-1 and ERK-2, JNK, and p38), and interferon-regulatory factors (IRF; e.g., IRF3 and IRF7). The biological role of TRAFs is largely due to their ability to positively or negatively regulate canonical and non-canonical NF-κB signaling. While TRAF-mediated signaling regulates various immune cell functions, this review is focused on the recent advances in our knowledge regarding the molecular mechanisms through which TRAF proteins regulate, positively and negatively, inflammatory signaling pathways, including Toll-IL-1 receptors, RIG-I like receptors, and Nod-like receptors. The review also offers a perspective on the unanswered questions that need to be addressed to fully understand how TRAFs regulate inflammation.

FANCA safeguards interphase and mitosis during hematopoiesis in vivo.

The Fanconi anemia (FA/BRCA) signaling network controls multiple genome-housekeeping checkpoints, from interphase DNA repair to mitosis. The in vivo role of abnormal cell division in FA remains unknown. Here, we quantified the origins of genomic instability in FA patients and mice in vivo and ex vivo. We found that both mitotic errors and interphase DNA damage significantly contribute to genomic instability during FA-deficient hematopoiesis and in nonhematopoietic human and murine FA primary cells. Super-resolution microscopy coupled with functional assays revealed that FANCA shuttles to the pericentriolar material to regulate spindle assembly at mitotic entry. Loss of FA signaling rendered cells hypersensitive to spindle chemotherapeutics and allowed escape from the chemotherapy-induced spindle assembly checkpoint. In support of these findings, direct comparison of DNA crosslinking and anti-mitotic chemotherapeutics in primary FANCA-/- cells revealed genomic instability originating through divergent cell cycle checkpoint aberrations. Our data indicate that FA/BRCA signaling functions as an in vivo gatekeeper of genomic integrity throughout interphase and mitosis, which may have implications for future targeted therapies in FA and FA-deficient cancers.