bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil and water conservation effects of different tillage measures on phaeozems sloping farmland in northeast China
Authors: Yu Peizhe , Yang Tianqi , Zhang Zhongxue , Zhou Xin , Qi Zhijuan , Yin Zhihao , Li Ao
Published: January 2024

Conventional tillage is still widely practiced in phaeozems sloping farmland, which leads to serious soil erosion. Adopting effective farming methods is crucial for mitigating soil erosion. To prevent and control soil and water loss in phaeozems sloping farmland, field experiments were conducted in 2022 using three tillage methods and their combination modes: subsoiling tillage (SF), ridge tillage and pitting field (RF), ridge tillage and pitting field + subsoiling tillage (RF‐S), contour tillage (TP), contour tillage + ridge tillage and pitting field (TP‐R), and contour tillage + subsoiling tillage (TP‐S). The study aimed to assess the impact these different tillage methods on soil and water conservation. The results showed that the contour tillage + ridge field treatment significantly reduced surface runoff and soil loss (p < 0.05), with no observed nutrient loss. Compared with other treatments, this method significantly reduced runoff, erosion, and nutrient loss. In contrast, the contour tillage + subsoiling tillage treatment significantly decreased the soil three‐phase R‐value, improved the soil texture, and exhibited higher yield, harvest index, and water use efficiency (WUE) compared to alternative treatments. Overall, the comprehensive findings indicate that contour tillage + subsoiling tillage can reduce soil erosion, enhance soil quality, and improve the WUE, all while maintaining high production capacity. Furthermore, the results of this study provide a theoretical basis for conserving soil and water resources, improving soil fertility, and increasing farmland yield in the phaeozems area of northeast China.
Study on the solution algorithm of Reynolds equation of self‐acting gas journal bearings based on a finite difference method
Authors: Haijun Zhang , Qin Yang , Wei Zhao , Feilong Jiang
Published: January 2024

It is very crucial to solve the Reynolds equation quickly and accurately using the numerical methods in the research field of fluid lubrication. For the static Reynolds equation of self‐acting gas journal bearings, the typical solution algorithm of the finite difference method is put forward and a new solution algorithm of the finite difference method is proposed. Secondly, the Reynolds equation is solved numerically with the same parameters and the pressure distribution of gas bearings is obtained. Finally, the numerical solution from the new solution algorithm can be obtained with less number of iterations and the less computing time under the different computational grids and bearing numbers. Therefore, the new solution algorithm of the finite difference method is superior to the typical solution algorithm of the finite difference method.
CXCR4/CXCL12 axis: “old” pathway as “novel” target for anti‐inflammatory drug discovery
Authors: Lu Liuxin , Li Junjie , Jiang Xiaoying , Bai Renren
Published: January 2024

Inflammation is the body's defense response to exogenous or endogenous stimuli, involving complex regulatory mechanisms. Discovering anti‐inflammatory drugs with both effectiveness and long‐term use safety is still the direction of researchers' efforts. The inflammatory pathway was initially identified to be involved in tumor metastasis and HIV infection. However, research in recent years has proved that the CXC chemokine receptor type 4 (CXCR4)/CXC motif chemokine ligand 12 (CXCL12) axis plays a critical role in the upstream of the inflammatory pathway due to its chemotaxis to inflammatory cells. Blocking the chemotaxis of inflammatory cells by CXCL12 at the inflammatory site may block and alleviate the inflammatory response. Therefore, developing CXCR4 antagonists has become a novel strategy for anti‐inflammatory therapy. This review aimed to systematically summarize and analyze the mechanisms of action of the CXCR4/CXCL12 axis in more than 20 inflammatory diseases, highlighting its crucial role in inflammation. Additionally, the anti‐inflammatory activities of CXCR4 antagonists were discussed. The findings might help generate new perspectives for developing anti‐inflammatory drugs targeting the CXCR4/CXCL12 axis.
Blockage loss and shadow fading behavior of millimeter‐wave signals due to human bodies at 28 GHz
Authors: Benzaghta Mohamed , Gokdogan Bengisu Yalcinkaya , Coruk Remziye Busra , Kara Ali
Published: January 2024

As the millimeter‐wave (mm‐Wave) spectrum is considered to be an essential enabler to the fifth generation (5G) wireless communication systems. Human movements are one of the most significant factors that cause transient blockage in indoor mm‐wave channels. In this letter, human blockage measurements and shadow fading statistics due to human body movements in an indoor office environment are reported for the 28 GHz band. The effect of human bodies on the channel is measured for several scenarios including a variety of population and using diverse antenna heights. The reported shadow fading statistics include both the duration and the depth of the blockage fade, and accordingly, we propose several empirical models that cater for such blockage events. The findings reported in this letter could improve the modeling of indoor radio channels at 28 GHz bands by considering the presence of humans, as well as their movements.
Exploring the cognitive processes of both Arabic and English‐speaking patients when completing the brief pain inventory: A qualitative study
Authors: Patel Gopi , Brady Bernadette , McMullan Matthew , Tang Clarice
Published: January 2024

Background

Brief Pain Inventory (BPI) is one of the most commonly used self‐initiated questionnaire for people with chronic pain. Although the questionnaire has been translated into multiple different languages and tested for its inter‐tester reliability, no study has currently explored the differences in interpretation of this questionnaire between non‐English speakers as compared to English‐speakers.

Purpose

Using the Arabic‐language group as the comparator, this study explored the interpretation of the English and Arabic language Brief Pain Inventory (BPI) among participants living with chronic neuromusculoskeletal pain from Arabic‐ and English‐speaking backgrounds.

Methods

This qualitative study utilises the Think Aloud method to explore the differences in the interpretation of the BPI between two language groups. Consecutive consenting adults attending a tertiary pain clinic for management of a chronic neuromusculoskeletal pain condition and self‐identifying with a native English‐speaking (n = 15) or Arabic‐speaking (n = 15) background were included. Structured interviews using the think‐aloud method were conducted, audio‐recorded and analysed using coding and thematic analysis.

Results

Interpretation errors across three or more questions were recorded for all Arabic‐speaking participants and two English‐speaking participants. Three themes characterised appraisals of pain and interpretation of the BPI across the two cohorts: 1) pain constancy vs. variability, 2) the ability‐disability spectrum and 3) variance in expression of pain.

Conclusion

Cross‐cultural differences in the appraisal of pain influenced participants' interpretation of the BPI. The cultural influences on conceptualisation of pain need to be considered when using the BPI across different cultures.
Early in life stressful events induce chronic visceral pain and changes in bladder function in adult female mice through a mechanism involving TRPV1 and alpha 1A adrenoceptors
Authors: Matos Rita , Santos‐Leite Liliana , Cruz Francisco , Charrua Ana
Published: January 2024

Background

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder with multiple phenotypes, one of which is associated with an overactive adrenergic system.

Objective

We investigated if the maternal deprivation model (MDM) in female and male mice mimics IC/BPS phenotype and if the overstimulation of alpha 1A adrenoceptor (A1AAR) and the crosstalk with transient receptor potential vanilloid‐1 (TRPV1) are involved in the generation of pain and bladder functional changes.

Design, Setting, and Participants

C57BL/6 female and male mice were submitted to MDM. TRPV1 knockout (KO) mice were used to study TRPV1 involvement. Silodosin administration to MDM mice was used to study A1AAR involvement.

Outcome Measurements and Statistical Analysis

The primary outcome was chronic visceral pain measured by Von Frey filaments analysis (effect size: 3 for wild type, 3.9 for TRPV1 KO). Bladder changes were secondary outcome measurements. Unpaired T test, Mann–Whitney test, one‐way analysis of variance followed by Newman–Keuls multiple comparisons test, and Kruskal–Wallis followed by Dunn's multiple comparisons test were used where appropriate.

Results and Limitations

MDM induces pain behavior in female and not in male mice. Bladder afferents seem sensitize as MDM also increase the number of small volume spots voided, the bladder reflex activity, and urothelial damage. These changes were similarly absent after A1AAR blockade with silodosin or by TRPV1 gene KO. The main limitation is the number/type of pain tests used.

Conclusions

MDM induced in female mice is able to mimic IC/BPS phenotype, through mechanisms involving A1AAR and TRPV1. Therefore, the modulation of both receptors may represent a therapeutic approach to treat IC/BPS patients.
Matrix‐less methods for the spectral approximation of large non‐Hermitian Toeplitz matrices: A concise theoretical analysis and a numerical study
Authors: Bogoya Manuel , Ekström Sven‐Erik , Serra‐Capizzano Stefano , Vassalos Paris
Published: January 2024

It is known that the generating function of a sequence of Toeplitz matrices may not describe the asymptotic distribution of the eigenvalues of the considered matrix sequence in the non‐Hermitian setting. In a recent work, under the assumption that the eigenvalues are real, admitting an asymptotic expansion whose first term is the distribution function, fast algorithms computing all the spectra were proposed in different settings. In the current work, we extend this idea to non‐Hermitian Toeplitz matrices with complex eigenvalues, in the case where the range of the generating function does not disconnect the complex field or the limiting set of the spectra, as the matrix‐size tends to infinity, has one nonclosed analytic arc. For a generating function having a power singularity, we prove the existence of an asymptotic expansion, that can be used as a theoretical base for the respective numerical algorithm. Different generating functions are explored, highlighting different numerical and theoretical aspects; for example, non‐Hermitian and complex symmetric matrix sequences, the reconstruction of the generating function, a consistent eigenvalue ordering, the requirements of high‐precision data types. Several numerical experiments are reported and critically discussed, and avenues of possible future research are presented.
Gilbert's syndrome leads to elevated bilirubin after initiation of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis
Authors: Patel Nidhi , Ansar Maria , Pham Anh , Thomsen Kelly , McKinzie Cameron J. , Polineni Deepika , Esther Charles R. , Brown Rebekah F.
Published: January 2024

Nine people with cystic fibrosis (pwCF) were found to have isolated elevations in serum total bilirubin after starting elexacaftor/tezacaftor/ivacaftor (ETI) that were associated with Gilbert's Syndrome. In longitudinal examination, total bilirubin levels increased substantially after initiation of ETI without elevations in liver transaminases in those with this syndrome. Because elevated bilirubin levels in Gilbert's Syndrome are benign, ETI was able to be continued in these individuals. Genetic testing for this relatively common syndrome should be strongly considered for pwCF experiencing isolated hyperbilirubinemia after starting ETI, since appropriate diagnosis may help pwCF avoid unnecessary interruption in this therapy with significant health benefits in CF.
Comparison of particles in exhaled air and multiple breath washout for assessment of small airway function in children with cystic fibrosis
Authors: Zwitserloot Annelies M. , Verhoog Frank A. , van den Berge Maarten , Gappa Monika , Oosterom Helma W. , Willemse Brigitte W. M. , Koppelman Gerard H.
Published: January 2024

Background

The introduction of modulator therapy for cystic fibrosis (CF) has led to an increased interest in the detection of small airway disease (SAD) as sensitive marker of treatment response. The particles in exhaled air (PExA) method, which records exhaled particle mass (PEx ng/L) and number (PExNR), detects SAD in adult patients. Our primary aim was to investigate if PExA outcomes in children with CF are different when compared to controls and associated with more severe disease. Secondary aims were to assess feasibility and repeatability of PExA in children with CF and to correlate PExA to multiple breath nitrogen washout (MBNW) as an established marker of SAD.

Methods

Thirteen healthy children (HC), 17 children with CF with normal lung function (CF‐N) (FEV1 z‐score ≥ −1.64) and six with airway obstruction (CF‐AO) (FEV1 z‐score < −1.64) between 8 and 18 years performed MBNW followed by PExA and spirometry. Children with CF repeated the measurements after 3 months.

Results

PEx ng/L and PExNR/L per liter of exhaled breath were similar between the three groups. The lung clearance index (LCI) was significantly higher in both CF‐N and CF‐AO compared to HC. All participants, except one, were able to perform PExA. Coefficient of variation for PEx ng/l was (median) 0.38, range 0–1.25 and PExNR/l 0.38, 0–1.09. Correlation between LCI and PEx ng/l was low, rs 0.32 (p = .07).

Conclusion

PExA is feasible in children. In contrast to LCI, PExA did not differentiate healthy children from children with CF suggesting it to be a less sensitive tool to detect SAD.
Capsaicin: A chili pepper bioactive phytocompound with a potential role in suppressing cancer development and progression
Authors: Mondal Arijit , Banerjee Sabyasachi , Terang Wearank , Bishayee Anusha , Zhang Jie , Ren Li , da Silva Milton Nascimento , Bishayee Anupam
Published: January 2024

Cancer profoundly influences morbidity and fatality rates worldwide. Patients often have dismal prognoses despite recent improvements in cancer therapy regimens. However, potent biomolecules derived from natural sources, including medicinal and dietary plants, contain biological and pharmacological properties to prevent and treat various human malignancies. Capsaicin is a bioactive phytocompound present in red hot chili peppers. Capsaicin has demonstrated many biological effects, including antioxidant, anti‐inflammatory, antimicrobial, and anticarcinogenic capabilities. This review highlights the cellular and molecular pathways through which capsaicin exhibits antineoplastic activities. Our work also depicts the synergistic anticancer properties of capsaicin in conjunction with other natural bioactive components and approved anticancer drugs. Capsaicin inhibits proliferation in various cancerous cells, and its antineoplastic actions in numerous in vitro and in vivo carcinoma models impact oncogenesis, tumor‐promoting and suppressor genes, and associated signaling pathways. Capsaicin alone or combined with other phytocompounds or approved antineoplastic drugs triggers cell cycle progression arrest, generating reactive oxygen species and disrupting mitochondrial membrane integrity, ultimately stimulating caspases and promoting death. Furthermore, capsaicin alone or in combination can promote apoptosis in carcinoma cells by enhancing the p53 and c‐Myc gene expressions. In conclusion, capsaicin alone or in combination can have enormous potential for cancer prevention and intervention, but further high‐quality studies are needed to firmly establish the clinical efficacy of this phytocompound.
‘I knew which one I wanted’: Interviews with Illinois patients to explore abortion method decision‐making after insurance expansion
Authors: Turner Tecora , Quasebarth Madeline , Boesche Madeleine , Moore Amy , Stulberg Debra B. , Hasselbacher Lee A.
Published: January 2024

Introduction

To understand patient preferences around early abortion methods and care‐seeking during the coronavirus disease 2019 pandemic in a state that expanded insurance coverage for abortion care.

Methods

We conducted phone interviews between July 2021 and February 2022 with 50 Illinois residents (aged 18–45) who had recently sought abortion at 18 clinics throughout Illinois at or before 11 weeks of pregnancy. We used a semistructured interview guide to explore preferences, motivations and decision‐making around the abortion method. We coded transcripts and used code summaries to conduct a thematic content analysis.

Results

Half of the participants chose medication abortion, and half chose procedural abortion. Some participants relied upon their past abortion experiences to choose a method. Participants' reasons for choosing medication abortion included home setting with support persons, the noninvasive nature, desiring a more ‘natural’ experience or negative perceptions of procedural abortions. Participants choosing procedural abortions valued increased certainty of completion, the option of sedation and the defined timeline of a clinic visit with fewer physical side effects. Some participants without insurance coverage were motivated to select a method based on cost. Around half of the participants expressed interest in considering a telehealth abortion.

Conclusions

Patients cited complex and personal preferences influencing their method selection; when cost barriers were reduced, preferences centred physical or emotional experiences, setting, effectiveness and timing. As abortion access is increasingly restricted, many patients may still highly value a choice between medication and procedural abortion when possible.
In Vitro and In Silico Studies on Benzimidazole‐Based Compounds
Authors: Bouchekioua Saad , Akkoc Senem , Menacer Rafik
Published: January 2024

Colon cancer remains a significant health concern, necessitating the synthesis of novel therapeutic agents. Benzimidazole derivatives have shown promising anticancer potential. In this study, two benzimidazole derivatives were synthesized, and their antiproliferative activities were investigated in vitro against the human colon colorectal cancer cell line and the human normal lung fibroblast cell line. The cell viability revealed that molecule 3 had high antiproliferative activity and inhibited the growth of DLD‐1 cells for 48 h. Furthermore, molecule 3 was found to have more selectivity against the human normal cell line. Computational calculations were performed to predict the molecular properties of molecules using the B3LYP/6‐311++(2d,2p) density functional theory level. The quantum theory of atoms in molecules (QTAIM) and energy decomposition analysis (EDA) were utilized to investigate the nature of the interatomic bonding existing among the studied molecules. The ultraviolet‐visible (UV–vis) results for molecules were calculated using time‐dependent density‐functional theory (TD‐DFT). The chemical reactivity and molecular stability were also investigated by DFT computational analysis. The molecular docking and dynamics simulations were conducted, and their results reveal their concordance with the experimental results. Molecule 3 has better anti‐cancer activity against colon cancer targets (PDB ID: 2HQ6) compared to molecule 2.
N‐Heterocyclic Carbene Promoted Construction of Amide‐Linked COFs via the Oxidation of Imine‐Linked COFs with Molecular Oxygen
Authors: Yu Song‐Chen , Cheng Liang , Liu Li
Published: January 2024

While amide‐linked covalent organic frameworks (COFs) have gained significant research attention due to their stability, there is currently no universal method for creating amide‐linked COFs with diverse chemical structures. Here, we present a gentle, precise, and versatile synthetic approach to amide‐linked COFs using N‐heterocyclic carbene (NHC)‐mediated oxidation with molecular oxygen as the oxidant. This approach is gentle and selective, and even fragile functional groups like thioethers are able to survive the transformation. Additionally, this method does not require dangerous conditions such as high pressure or strong oxidants, making it a promising way to create functional amide‐linked COFs.
Behavior of textile‐reinforced concrete columns
Authors: dos Santos Fernanda Cristinna Alonso , Campos Claudia Maria de Oliveira , Cardoso Daniel Carlos Taissum
Published: January 2024

This work aims to investigate the behavior of textile‐reinforced concrete (TRC) members subject to compressive loads. An experimental program including concentric compression tests on I‐section columns with different lengths and simply‐supported ends was carried out. From compression tests, load versus lateral deflection curves obtained experimentally are reported along with maximum loads and apparent imperfections determined using the Southwell technique. Failure modes were characterized by excessive lateral deflections for longer columns, whereas concrete crushing failure due to combined bending and axial load occurred for shorter columns. Surrounding concrete was effective in restraining the textile reinforcement against buckling, allowing it to sustain the compressive loads. A single degree‐of‐freedom model accounting for normal‐moment‐curvature relation and tension stiffening behavior is validated against experiments and used to carry out a parametric study. Results show that the nonsway moment magnification method recommended by the ACI Code 440.11‐22 can be applied to TRC columns, although leading to overestimated second‐order effects.
Data acquired on some old reinforced concrete structures to validate the threshold levels of the French performance‐based method for the durability of concrete structures
Authors: Godart Bruno , Dierkens Michael , Cordier Nathalie , Thauvin Benoit , Bouichou Myriam , Marie‐Victoire Elisabeth
Published: January 2024

The objective of this paper is to present the methodology used to validate the threshold levels of durability indicators from data acquired from existing reinforced concrete structures that may present corrosion problems resulting from carbonation or chloride ingress. This study was conducted in the framework of the French National Project PERFDUB in close collaboration with the MODEVIE ANR project. Durability tests form the basis of a performance‐based approach for the durability of concrete structures, and in order to set the threshold level for each of these durability indicators, it is important to take into account the experience feedback that can be obtained from the actual behavior of existing structures. This paper presents the investigations carried out on eight reinforced concrete structures, all of them having an age well in excess of 50 years, and the main data gathered on some relevant durability and lifetime indicators. Based on all these data, predictive models of carbonation and chloride penetration are applied in order to validate the threshold levels to be adopted for the durability indicators, and several other conclusions are drawn.
Quality assurance and maintaining trust in the Official Veterinarian system
Authors: Quinney Sue
Published: January 2024

By assuring the quality of work carried out by official veterinarians and others, the APHA helps maintain confidence in the UK's standards of animal health, certification and disease surveillance – something that is vital for securing international trade. Sue Quinney, veterinary head of OV regulatory affairs for the APHA, explains more…
Chef to factory to veterinary practice: perseverance paid off for veterinary nurse
Authors: Stevenson Emily
Published: January 2024

At 16 Emily Stevenson was working full time in a restaurant, but this wasn't the career for her. After becoming a mum and several roles later, she started her journey to vet nursing in her 40s.
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

Objectives

Pharyngocutaneous 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.

Methods

We 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.

Results

Forty‐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.

Conclusion

PCF 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

This 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

Ecosystems 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

Southern 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

Semiarid 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

Diagnostic 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

Introduction: 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

Working 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

Neuroendocrine 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

Early 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

Purpose: 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

In 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

It 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.