bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of Montgomery salivary bypass tubes and pharyngocutaneous fistula following salvage laryngectomy
Authors: Shires Courtney B. , Latour Mackenzie , Sebelik Merry , Dewan Karuna 
Published: January 2024

AbstractObjectivesPharyngocutaneous fistula (PCF) is the most common complication to follow total laryngectomy (TL) and is associated with increases in length of hospital stay and with a need for revision surgery or readmission, as well as with delays in return to oral diet. Patients who require salvage TL (STL) or primary (chemo)radiation therapy are at higher risk for developing PCF. Due to the quality‐of‐life burden of PCF on patients, limiting this occurrence is crucial.MethodsWe conducted a retrospective cohort study of patients undergoing STL with placement of Montgomery salivary bypass tube (MSBT)™ for at least 2 weeks duration between 2013 and 2017 at a single institution. Our patients all underwent free flap reconstruction. Our primary outcome of interest was development of PCF. Secondary outcomes included demographics, previous treatment, base of tongue (BOT) involvement, extent of defect, concurrent neck dissection (ND), and margin status. Univariate χ2 analysis was used to evaluate factors associated with PCF.ResultsForty‐four patients underwent STL with Montgomery tube placement and free flap reconstruction. Eight developed PCF (18.2%). The average age was 61.6 years; 36 patients were male (81.8%), whereas eight patients were female (18.2%). There was no association between PCF and previous chemoradiation versus radiation (15.8% vs. 33.3%, P < 0.30), BOT involvement versus not (11.1 vs. 22.2%, P < 0.38), circumferential versus partial defect (18.8% vs. 17.9%, P < 0.94), ND versus none (10% vs. 25%, P < 0.20), or margin status.ConclusionPCF complicated 18.2% of STL cases at our institution and was not associated with differences in primary treatment modality, presence of concomitant ND, extent of pharyngeal defect, BOT involvement, or positive frozen or permanent surgical margin.
Glass half empty or half full? Gender in integrated water resource management in South Asia
Authors: Narain Vishal , Goodrich Chanda Gurung 
Published: January 2024

AbstractThis paper reviews the experience with gender mainstreaming in the water sector in South Asia. It analyzes the reasons for the limited impact of these efforts. These are located in the limited understanding and consequent operationalization of the concept of gender itself. Rather than equating the word gender with women, it needs to be understood to refer to the social and power differences between men and women and the differences within women. Gender needs to be approached in policy and practice through a lens of intersectionality. Reserving seats for women in local patriarchal structures of decision making does little to alter the status quo; securing women's participation in water management activities without altering power relations between water users and service providers only creates additional work burdens for them. The changing nature of water resources education in the region means that water problems shall be seen differently in the future and that there will be more women in this sector. There is a need to develop curricula based on ways of theorizing about gender and water in different agro‐ecological and institutional settings embedded in the unique context of South Asia.
Coupled Earth System and Human Processes: An Introduction to SPACES and the Book
Authors: von Maltitz Graham P. , Bieri Mari , Midgley Guy F. , Veitch Jennifer , Brümmer Christian , Rötter Reimund P. , Veste Maik 
Published: January 2024

AbstractEcosystems in southern Africa are threatened by numerous global change forces, with climate change being a major threat to the region. Many climate change impacts and environmental-based mitigation and adaptation options remain poorly researched in this globally important biodiversity hotspot. This book is a collection of chapters covering research undertaken in southern Africa by the German Federal Ministry of Education and Research’s (BMBF) SPACES and SPACES II programs. SPACES II covered a wide range of global change-linked environmental issues ranging in scope from the impacts of ocean currents on global climate systems through to understanding how small-scale farmers may best adapt to the impacts of climate change. All the research has identified policy implications, and the book strives for a balance between presenting the detailed science underpinning the conclusions as well as providing clear and simple policy messages. To achieve this, many chapters in the book contextualize the issues through the provision of a mini-review and combine this with the latest science emulating out of the SPACES II program of research. The book therefore consolidated both past and the most current research findings in a way that will be of benefit to both academia and policy makers.
Regional Land–Atmosphere Interactions in Southern Africa: Potential Impact and Sensitivity of Forest and Plantation Change
Authors: Zhang Zhenyu , Laux Patrick , Baade Jussi , Moutahir Hassane , Kunstmann Harald 
Published: January 2024

AbstractSouthern Africa is experiencing increasing land transformation and natural vegetation losses. Deforestation is one type of this land degradation where there are indigenous forests present, and afforestation of other nature ecosystems with timber plantations. This study performs regional coupled land–atmosphere model simulations using the Weather Research and Forecast (WRF) model with a resolution of 12 km, to assess the impact of forest and plantation cover change on regional climate in southern Africa. Three WRF simulations were designed for different land covers: (i) MODIS-derived land cover for the year 2000 (baseline), (ii) Landsat-based forest and plantation change map during 2000–2015 overlain on the baseline and (iii) theoretical forest and plantations removal relative to the baseline. Modeling results suggest that conversion of forest and plantations landscape to croplands and sparse vegetated land may result in a warmer and drier local climate, increasing daytime temperature by up to 0.6°C during the austral summer, and regulation of energy exchanges by decreasing the latent heat flux. In addition, results suggest that the removal of forest cover in northern part of southern Africa may decrease local precipitation recycling by around 1.2%. While the benefits of conserving native forests are obvious from an ecological perspective, afforestation considerations still require more detailed and local-scale treatments along the soil–vegetation–atmosphere continuum.
A Fine Line Between Carbon Source and Sink: Potential CO2 Sequestration through Sustainable Grazing Management in the Nama-Karoo
Authors: Rybchak Oksana , du Toit Justin , Maluleke Amukelani , Bieri Mari , Midgley Guy F. , Feig Gregor , Brümmer Christian 
Published: January 2024

AbstractSemiarid South African ecosystems are managed for livestock production with different practices and intensities. Many studies have found grazing to be an important driver of vegetation change; however, its impacts on carbon fluxes remain poorly studied. Unsustainable management over the past 200 years has led to an increase of degraded areas and a reduction in species diversity, but destocking trends in the past three decades may be facilitating a recovery of net primary productivity and vegetation cover in some areas. This chapter provides a brief historical overview on livestock management practices and their likely impact on carbon exchange in the Nama-Karoo Biome. We present a case study based on five years of eddy covariance measurements, in which effects of past and current livestock grazing on CO2 exchange were studied. Two sites with different livestock management but similar climatic conditions formed the basis for this preliminary effort to improve the understanding of carbon exchange and its drivers under contrasting management regimes. The case study revealed that net CO2 exchange is near-neutral over an annual scale, with precipitation distribution emerging as the main controlling factor of subannual variance. Although CO2 release at the lenient grazing site was slightly higher than at the experimental grazing site, longer time series are likely needed in such variable ecosystems to make a pronouncement regarding long-term net fluxes. Given their vast extent, livestock rangelands may have an important effect on regional carbon balance.
The Evolution of n.c.a. 177Lu to n.c.a. 177Lu-Edotreotide for the Treatment of Neuroendocrine Tumours. Sixteen Years of Collaboration Between Zentralklinik Bad Berka and ITM
Authors: Harris P. , Henkelmann R. , Marx S. , Zhernosekov K. 
Published: January 2024

AbstractDiagnostic and therapeutic radionuclides offer an excellent platform for the development of innovative drugs, which enable non-invasive visualization of diseases and complementary targeted treatments. The concept of personalized medicine is realized! This innovation in nuclear medicine together with an increasing demand for high-quality radionuclides and radiopharmaceuticals has triggered the expansion of nuclear medicine as a hospital speciality, together with the development of a new radiotheranostics industry.
Review of F-18 FDG PET/CT in Evaluating Response to Immunotherapy Treatment
Authors: Agolti Mariela , Solari Lucrecia 
Published: January 2024

AbstractIntroduction: Immunotherapy is a wide-spreading therapeutic resource in oncology. The therapy is guided to improve the patient’s immune response to cancer cells, on the basis of the concept of immune surveillance by activating both cell-mediated and humoral immunity to fight cancer. Immunomodulatory monoclonal antibody therapy utilizes preformed monoclonal antibodies directed against molecular targets to regulate T-cell activation. There are three mechanisms involved in this kind of therapy: antibodies directed against the programmed death protein 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), such as nivolumab and CTLA-4 inhibitors that prevent inhibition of the activated T-cells.Material and Method: Different reveiw articles were reviewed to understand the differences in response assessment of immunotherapy as compared to conventional chemotherapy or radiotherapy when using F-18 FDG PET/CT.Results: When using FDG PET/CT for response assessment, following important items should be considered: (1) Pseudoprogression: meaning that we can see transient enlargement of tumors or the appearance of new tumors followed by tumor shrinkage or long-term stability of tumor size. (2) Hyperprogression which is characterized by rapid increase in tumor burden (more than 50% increase compared to basal) and also time to treatment failure less than 2 months and more than 2 times increase in tumor growth rate, with deteriorating clinical condition. (3) Response to treatment is generally slower than with conventional cytotoxic chemotherapy. (4) Adverse effects (irAE) that are more easily diagnosed through FDG PET CT, than through conventional CT, and the importance of being able to recognize and report them sometimes life-threatening like pneumonitis or colitis. Also nuclear medicine physician should report inflammatory changes like drug induced sarcoid-like lymph nodes and differentiate from progression disease or splenic/liver SUV, moreover keeping in mind that there is evidence of good association between the presence of irAE and good answer to treatment. (5) Evolution of irAE comparing the actual PET with previous reporting the change in 18FDG uptake.Conclusion: Reporting of F-18 FDG PET/CT after immunotherapy, should consider these different items: Pseudoprogression, hyperprogression, irAE, evolution of irAE, and other inflammatory signs related to immunotherapy to improve our methodology efficiency.
Working at Isotopentherapiestation D3: A Daily Challenge or Adventure Never Stops
Authors: Lehmann Coline 
Published: January 2024

AbstractWorking at one of the largest Radio-Isotopentherapiestation in Germany is a real daily challenge. In addition to the standard therapies in nuclear medicine like treating benign and malignant thyroid diseases, there have been more than 7000 treatments in total performed with a very high number of peptide receptor radionuclide therapies (PRRT) in patients with neuroendocrine tumor as well as Lutetium-177 (Lu)-labeled prostate-specific membrane antigen radioligand therapies (Lu-PRLT) in metastatic castration-resistant prostate cancer (mCRPC) since 1997.On the one hand, the high number of patients is challenging; on the other hand, both the internationality and increasing multimorbidity of the patients coming to Bad Berka.This unique achievement of such a high number of treated patients is only possible when you are part of such a highly skilled and motivated team.
Surgery in Combination with Peptide Receptor Radionuclide Therapy: A Novel Approach for the Treatment of Advanced Neuroendocrine Tumours
Authors: Frilling Andrea , Clift Ashley K. 
Published: January 2024

AbstractNeuroendocrine tumours/neoplasms (NEN) are clinically challenging entities, often due to their late stage at initial diagnosis. Whilst surgery is the cornerstone of curative treatment, many patients are not eligible for a radical surgical approach, and instead other targeted or systemic treatments may be utilised. Neoadjuvant concepts such as downstaging borderline resectable tumours are more established in some adenocarcinomas than in neuroendocrine oncology, yet the diverse armamentarium for the latter offers promise for novel multimodal concepts that may offer prolonged disease control by complementarily targeting micro- and macro-neuroendocrine disease. One promising option, as yet only explored in small case series, is the combination of surgery and peptide receptor radionuclide therapy (PPRT). Here, the authors review the challenges posed by advanced NEN, review the fledgling evidence regarding the combination of PRRT and surgery, and present the case for a wider examination of embedding PRRT and surgery within a multimodal treatment strategy.
Can VPAC-Targeted Cu-67-TP3805 Play a Theranostic Role for Prostate Cancer?: A Quest
Authors: Thakur Mathew L. 
Published: January 2024

AbstractEarly and accurate detection of prostate cancer (PCa) together with effective treatment can save lives. Despite the recent advances in its treatment, the mortality trends due to PCa, in the USA, continue to be alarming with annual increase of 3%. In this brief communication, we propose a novel approach to treat PCa, its metastasis and recurrence. This is guided by a large quantity of preliminary data driven by targeting an endogenous genetic product, VPAC, expressed in high density on the cell surface at the onset of genetic mutation that ignites the cancerous transformation.A large body of preclinical and clinical data generated in our laboratory used a positron-emitting radionuclide Copper-64 (Cu-64), conjugated to a small biomolecule, TP 3805 that has a high in vivo stability and high affinity (Kd 3.1 × 10−9 M) for VPAC. The data depict high uptake of Cu-64-TP3805 in primary and metastatic lesions and malignant lymph nodes with minimal uptake in normal tissues except the liver, prompted by the hepatobiliary excretion.Reflecting on the present and planning for the future, our quest is to systematically investigate the use of the beta-emitting sister radionuclide Cu-67 to target VPAC receptors for theranostic applications of primary and metastatic PCa.
Uptake of 68Ga-DOTATATE and 68Ga-DOTATOC in Primary Neuroendocrine Tumors, Metastases, and Normal Liver Tissue: Is There a Significant Difference?
Authors: Todorović-Tirnanić Mila V. , van Echteld Cees J. A. , Gajić Milan M. , Baum Richard P. 
Published: January 2024

AbstractPurpose: Intrapatient comparison of in vivo distribution of two Ga-68-labeled somatostatin (agonist) analogues with different in vitro affinities for human somatostatin receptor (sstr) subtypes 2, 3, and 5 by determining their SUVmax values in normal liver, primary tumors, and metastases in gastroenteropancreatic (GEP) neuroendocrine tumor (NET) patients.Methods:68Ga-DOTATATE and 68Ga-DOTATOC PET/CT studies were performed at consecutive visits in 38 GEP NET patients (1 duodenal, 18 pancreatic, 2 cecal, 12 ileal, 3 jejunal, 1 mesenteric, 1 NET in appendix) with stable disease on both occasions, with 197 days (117–311 days range) in between. Time to start of scanning after injection was identical for both studies. SUVmax for both radiopharmaceuticals in primary tumors, liver-, lymph node-, soft tissue-, and bone-metastases and in normal liver tissue were compared.Results: Overall, 225 metastases (98 liver, 67 lymph node, 43 bone, 17 soft tissue) and 18 primary GEP NETs were analyzed on both 68Ga-DOTATOC and 68Ga-DOTATATE studies. Mean SUVmax in the TATE/TOC groups were: normal liver 6.8 ± 1.7/6.9 ± 1.8, metastases in the liver 15.4 ± 9.4/17.9 ± 11.4, lymph nodes12.0 ± 9.5/15.2 ± 13.3, bones 7.5 ± 5.7/9.9 ± 8.0, soft tissues 15.3 ± 16.4/17.3 ± 18.8, primary tumor 20.4 ± 13.7/24.23 ± 20.1. Average 68Ga-DOTATOC accumulation was always higher. The differences between TATE/TOC groups were significant in primary tumors, liver-, lymph node-, and bone-metastases, but not in soft tissue-metastases. Notwithstanding these highly significant differences, considerable variability amongst patients in preferred tracer uptake was observed.Conclusions: On average, 68Ga-DOTATOC shows significantly higher uptake in GEP NET primary tumors and metastases than 68Ga-DOTATATE. However, we have also observed considerable variability in preferred peptide uptake. Optimal therapy planning would therefore require somatostatin receptor imaging with both these peptides.
Molecular In Vitro and In Vivo Diagnostics as the Impartible Basis of Multimodal Therapy Approaches in Precision Oncology
Authors: Wirtz Ralph M. 
Published: January 2024

AbstractIn 2000, more than two decades ago, genome-wide gene expression profiling became available and thereafter led to the dissection of cancer biology across almost all entities [1–3]. First, the molecular portraits based on RNA expression profiling (termed “heat maps”) were used in breast cancer to identify luminal, ERBB2-positive, and basal tumors. Interestingly, these subtypes not only elucidated the underlying biology but also directly suggested targeted treatment intervention with luminal tumors being hormone-dependent, ERBB2-positive tumors exposing the transmembrane receptor Her-2/neu and basal tumors lacking homogenous expression of typical targeted treatment options, with the latter being termed “triple negative” later on. Interestingly, genome-wide mutation analysis later on revealed that the luminal subtype, while bearing most mutations (such as PIK3CA) exhibited lowest immunogenicity and frequently absence of tumor-infiltrating lymphocytes. In contrast, the basal subtype turned out to have lowest rate of classical oncogens, but was dominated by loss-of-function mutation of p53 [4], while almost half of basal tumors being infiltrated by large amounts of immune cells. This led to the assumption that hormone regulation affects immune cell recognition and three biological axes (hormone, immune, and proliferation axis) were built up for breast cancer as being the coordinates of the biological universe of breast cancer [5, 6]. The therapeutic implication of these fundamental insights were further explored and validated the distinct sensitivity towards antihormonal treatment, ERBB2 targeting, and chemotherapy. Interestingly, the hormone-insensitive, highly proliferating basal and ERBB2-positive tumors with higher amounts of immune cell infiltrates did respond best to neoadjuvant treatment with superior outcome [7]. As one consequence, the concept arose to develop RNA-based vaccination concepts in the post-neoadjuvant situation of triple negative breast cancer not responding to neoadjuvant chemotherapy by targeting individual neo-epitope patterns [8], which has been investigated in the subsequent “Merit” trial with positive proof of concept [9]. In line with this, the first approval of checkpoint therapy treatment in breast cancer happened in the triple negative breast cancer subtype [10].
The LuGenIum Triptych: Ode to a Theranostic Transcriptome
Authors: Bodei Lisa 
Published: January 2024

AbstractIt all began in Weimar, at the Goethe National Museum in Weimar, a magnificent and placid place, redolent in history and culture, where Prof. Richard Baum organized the fourth Mitteldeutsches Neuroendokriner Tumor Symposium, in June 2013 (Fig. 7.1). Richard has always been a pioneer and the first to understand and disseminate the importance of many innovations, including the now popular theranostic concept. Unlike many conservative and “predictable” scientific gatherings, his meetings have always been avant-garde and pivotal in defining the trends for the future. To my delight and pleasure, I was invited to participate in what I knew would be a tour de force of the trailblazers of innovative nuclear medicine. Inspired by such greatness, we subsequently established the LuGenIum Consortium for Independent Research to addressed some of the major challenges in the use of peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs), which are the prediction of efficacy and toxicity and the consequent patient stratification. In the following years, we conducted clinical trials to understand the role of individual predisposition and specific tumor genomic profile in the response and toxicity to PRRT. Our specific aims were to, first, conduct a retrospective analysis of toxicity to PRRT (i.e., define the problem) in a large patient cohort, then to conduct two prospective studies (assess the efficacy of the ideas). To this aim, we firstly identified NETs at a genomic level and assessed the response to PRRT with a PCR-based blood analysis, and, secondly, we analyzed markers of long-term toxicity in patients previously undergone to PRRT, with a PCR-based blood analysis. During our investigations, we identified a new biomarker, the PRRT predictive quotient, or PPQ, which demonstrated 95% accuracy in predicting the response to PRRT in the three prospective series that were studied under the LuGenIum umbrella. These results provide the demonstration that PPQ is a predictive biomarker and a measure of radiosensitivity. We also demonstrated in these patients that the NET identifying circulating transcriptomic signature NETest was able to accurately monitor the course of PRRT during its delivery, as opposed to imaging, which becomes reliable only after treatment completion. The results of these studies opened a new era for treatment individualization and optimization.