bluuebunny/crossref_metadata_2025 huggingface dataset:
Floristic diversity and threats in new hilly tourist areas: A case study in the Riam Setongah nature tourism area, Lamandau Regency
Authors: Triyadi A , Toni H
Published: October 2023

The Riam Setongah nature tourism area in Lamandau district, Central Kalimantan province, is a newly developed destination in response to the growing popularity of ecotourism among the younger generation. However, the increase in tourist activity has raised concerns about potential damage to the local flora. The changes in the flora composition have sparked efforts to protect the seven hills, which hold significant cultural value for the Kaharingan community. In order to evaluate the variety of plant species in the area, a combination of line and patch methods were employed. Subplots were systematically created along each trail, and data were collected at tree, stake, sapling, and seedling levels. The Important Value Index was utilized to calculate the dominance of plant species, incorporating metrics such as species density, relative density, species dominance, relative dominance, species abundance, relative abundance, and species diversity. Overall, the Species Richness Index was relatively high, and Species varied across different growth levels. Additionally, the Evenness Index value indicates a relatively balanced distribution of species at each growth level. However, despite the high Evenness Index, the diversity of flora still requires attention. It is important to implement regulations and educational initiatives to mitigate visitor impacts on vulnerable areas.
Physicochemical, physiological and sensory characteristics of tomato fruit edible coating results from various modified sago starches
Authors: Salingkat C A , Noviyanti A , Riska
Published: October 2023

The development of edible coatings as a substitute for plastic is one of the efforts to protect tomato fruit damage by using sago starch (SS) which has been modified with sodium trimetaphosphate (STMP), sodium tripolyphosphate (STPP), STMP/STPP ratio: 99/1 and acetic anhydride. The research objective was to obtain modified sago starch concentrations (SS-STMP, SS-STPP, SS STMP/STPP ratio and SS Acetate) based on the physicochemical, physiological and sensory characteristics of edible coating tomatoes. Research using Completely Randomized Design and Randomized Block Design. Edible coating is made by making the modified SS concentration which consists of 7 levels, namely, 0%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, and 3.0% (w/v) with 3 repeated. The analysis variables include moisture content, total acid, weight loss, storage durability, and sensory. The results showed that the results of edible coating from modified sago starch at concentrations of 2 and 2.5% gave the best physicochemical, physiological and sensory characteristics.
Value added product of pumpkin commodity in the central area of Banyuwangi Regency
Authors: Soetriono  , Soejono Djoko , Maharani Ariq Dewi , Zahrosa Dimas B
Published: October 2023

The agricultural industry that is experiencing rapid development is the processing industry of agricultural products which aims to produce new products that are more innovative and ready for consumption by the public. This diversification of food based on local food is very necessary to support the national food security program. In Banyuwangi District has the abundance of pumpkin. Efforts to diversify pumpkin into functional food need to be processed into pumpkin into various food products. The emergence of pumpkin processing industry can play a role as a processing of local resources. The focus of the objectives in this study is to apply appropriate technology in the creation of added value products downstream of pumpkin commodities; and designing strategies for sustainability of sustainability strategies for the development of down pumpkin commodity products in the centre of Banyuwangi regency, both in terms of sustainability, facilities and infrastructure, institutions and policies. Data analysis methods include value added analysis and FFA (Force Field Analysis). The results of this study indicate that the processed products produced include dodol and pumpkin sticks. The sustainable strategy for the development of downstream products for the pumpkin commodity is diversification of food consumption will provide incentives and incentives for the provision of food products that are more diverse and safer for consumption, including local flour-based food products.
Role of 5G Technology in Enhancing Agricultural Mechanization
Authors: Rathinavel S , Kavitha R , Gitanjali J , Saiprasanth Ravuri
Published: October 2023

Advanced mechanization strategies such as site specific crop management machinery, Unmanned Aerial Vehicles (UAVs), robotic harvesters relies greatly on the precision technologies and IoT. Present networks (3G/4G), WiFi are in limited availability and bandwidth that cause delays in data transfer (latency) and hinder effective data transfer. But high-speed communication system, reliable and secured data connection is required for precision agriculture, cyber physical management systems and use of IoT in farm operations. Loss of data connection between devices, sensors or data servers’ impacts the precision and effectiveness of technology applied. High data transfer volumes and low latency data exchange were the major advantages of 5G technology, facilitates its use in precision farming and IoT applications in a most efficient way. It also enables the autonomous and robotic machinery for various operations in the aspects of agriculture and livestock production. The major application of 5G in mechanization is control systems for robotic harvesters, drones, autonomous vehicles, surveillance etc. Remote locations such as hill farms has the inherent constraints such as remoteness, marginality, slope etc., remains underutilized, can be developed with advanced communication systems. Even though there are several constraints in adoption of 5G technology, such as shortage in electricity supply, lower range coverage, the technology can ensure raise in agricultural production through mechanization. The chapter discusses the advancements in application of 5G technology in agricultural mechanization.
Bioclimatic aspects of recycled agricultural materials for sustainable green construction
Authors: Jayaraman A , Parthasarathy S , Vignesh S , Aravind R , Keerthika M , Vasudevan M
Published: October 2023

There is an increasing awareness for adapting bioclimatic construction practices using agro-based green building materials to reduce the global warming impacts pertaining to the construction sector. In addition, lightweight construction is an emerging field of infrastructural development aiming to reduce the deadweight of the building by employing low density materials. Unlike conventional building blocks, the lightweight materials can be prepared in larger size and integrated easily to reduce the overall cost of construction. However, there is a need to identify cheaper and energy-efficient materials to minimize the net carbon emissions and to optimize the functionalities for any specific applications. The present study deals with the preparation of lightweight panels from agricultural by-products such as coconut fibres and paddy straws by optimizing their mixture proportioning and internal pattern of arrangement after pre-treatment with polyethylene glycol. Based on the test results, the concrete panels made of paddy straw have shown the highest reduction in weight compared to the conventional specimens (by 40%) and specimens with coconut fibre (by 25%). The results indicate that the concrete specimens made of the selected agro-based materials have improved mechanical (strength and durability), thermal and bioclimatic properties. The reduction in carbon emission depicts the critical dependency of bioclimatic construction on the selection of green materials. Therefore, a design methodology for sustainability assessment of agro-based building materials is formulated here in order to justify their suitability as green building materials.
Estimated energy and emissions impacts of pumping Pacific Ocean water to Great Salt Lake
Authors: Sowby Robert B , Williams Gustavious P , South Andrew J
Published: October 2023

Great Salt Lake in Utah, USA, has receded in recent years. Among many options proposed to augment inflows is a pipeline from the Pacific Ocean. We estimate a lower bound for the ongoing energy requirements, assuming one-third of the recommended additional inflow will be pumped through a single, smooth, large-diameter pipeline along a fictitious, shortest route without mountains, considering only elevation change and head loss. Pumping would require at least 400 megawatts of electricity during operation, an amount equivalent to a large power plant, or 11% of Utah’s annual electricity demand. Given current energy prices and fuel mixes, the electricity would cost over $300,000,000 annually and emit nearly 1,000,000 metric tons of carbon dioxide annually, equivalent to 200,000 passenger vehicles. The figures could easily triple with longer routes, mountainous terrain, higher flows, smaller diameters, multiple pipelines, less-efficient pumps, and any required treatment. Just this one early glimpse reveals serious challenges to the pipeline's completion. Our estimate may help select—or eliminate—alternatives for Great Salt Lake. Any alternative selected for further consideration would require a feasibility study with more details.
Forest Owners’ Intention to Safeguard Forest Biodiversity: An Application of the Theory of Planned Behavior
Authors: Koskela Terhi , Karppinen Heimo
Published: October 2023

Private nonindustrial forest owners’ intention to safeguard biodiversity in their own forest was studied by applying the theory of planned behavior. The data were collected in a nationwide mail survey sent to 3,000 Finnish forest owners (response rate 35%). The impact of attitudes, subjective norm, and perceived behavioral control on the intention to safeguard biodiversity was empirically tested by estimating structural equation models (SEM). The empirical estimations supported the theoretical model. The influence of perceived behavioral control was inhibiting on the intention and slightly stronger than the explanatory power of attitude or the subjective norm. External factors had an impact on the explanatory pattern of the intention. The effect of subjective norm increased and the role of attitude decreased with age. Academic education increased the importance of attitudes and decreased the role of normative pressures. In the development of voluntary measures aimed at safeguarding biodiversity, special attention should be paid to the reduction of the obstacles for the implementation perceived by forest owners. Forest owners often perceive important to retain decision-making power for the next generation. Forest owners should be provided with information about the different measures for safeguarding biodiversity and the contract terms.

Study Implications: Forest owners consider active timber production, compensation level, willingness to retain decision-making power for the next generation, and small forest ownership as factors that inhibit their intention to safeguard biodiversity in their own forests. Forest owners’ attitude toward safeguarding forest biodiversity and the normative pressures the reference groups create have a slightly smaller effect on intention. It is important to take the views of forest owners into account when developing voluntary measures for safeguarding biodiversity. It is essential to distribute information to forest owners about the available measures, their requirements, and compensation.
An investigation into the impact of volumetric rescanning and fractionation treatment on dose homogeneity in liver cancer proton therapy
Authors: Lee Pei-Yi , Huang Bing-Shen , Lee Shen-Hao , Chan Tsz-Yui , Yen Eric , Lee Tsair-Fwu , Cho I-Chun
Published: October 2023

The Pencil Beam Scanning (PBS) technique in modern particle therapy offers a highly conformal dose distribution but poses challenges due to the interplay effect, an interaction between respiration-induced organ movement and PBS. This study evaluates the effectiveness of different volumetric rescanning strategies in mitigating this effect in liver cancer proton therapy. We used a Geant4-based Monte Carlo simulation toolkit, ‘TOPAS,’ and an image registration toolbox, ‘Elastix,’ to calculate 4D dose distributions from 5 patients’ four-dimensional computed tomography (4DCT). We analyzed the homogeneity index (HI) value of the Clinical Tumor Volume (CTV) at different rescan numbers and treatment times. Our results indicate that dose homogeneity stabilizes at a low point after a week of treatment, implying that both rescanning and fractionation treatments help mitigate the interplay effect. Notably, an increase in the number of rescans doesn’t significantly reduce the mean dose to normal tissue but effectively prevents high localized doses to tissue adjacent to the CTV. Rescanning techniques, based on statistical averaging, require no extra equipment or patient cooperation, making them widely accessible. However, the number of rescans, tumor location, diaphragm movement, and treatment fractionation significantly influence their effectiveness. Therefore, deciding the number of rescans should involve considering the number of beams, treatment fraction size, and total delivery time to avoid unnecessary treatment extension without significant clinical benefits. The results showed that 2–3 rescans are more clinically suitable for liver cancer patients undergoing proton therapy.
Natural Selection Signatures in the Hondo and Ryukyu Japanese Subpopulations
Authors: Liu Xiaoxi , Matsunami Masatoshi , Horikoshi Momoko , Ito Shuji , Ishikawa Yuki , Suzuki Kunihiko , Momozawa Yukihide , Niida Shumpei , Kimura Ryosuke , Ozaki Kouichi , Maeda Shiro , Imamura Minako , Terao Chikashi
Published: October 2023

Natural selection signatures across Japanese subpopulations are under-explored. Here we conducted genome-wide selection scans with 622,926 single nucleotide polymorphisms for 20,366 Japanese individuals, who were recruited from the main-islands of Japanese Archipelago (Hondo) and the Ryukyu Archipelago (Ryukyu), representing two major Japanese subpopulations. The integrated haplotype score (iHS) analysis identified several signals in one or both subpopulations. We found a novel candidate locus at IKZF2, especially in Ryukyu. Significant signals were observed in the major histocompatibility complex region in both subpopulations. The lead variants differed and demonstrated substantial allele frequency differences between Hondo and Ryukyu. The lead variant in Hondo tags HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01, a haplotype specific to Japanese and Korean. While in Ryukyu, the lead variant tags DRB1*15:01-DQB1*06:02, which had been recognized as a genetic risk factor for narcolepsy. In contrast, it is reported to confer protective effects against type 1 diabetes and human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. The FastSMC analysis identified 8 loci potentially affected by selection within the past 20–150 generations, including 2 novel candidate loci. The analysis also showed differences in selection patterns of ALDH2 between Hondo and Ryukyu, a gene recognized to be specifically targeted by selection in East Asian. In summary, our study provided insights into the selection signatures within the Japanese and nominated potential sources of selection pressure.
PED in 2024: improving the community deposition of structural ensembles for intrinsically disordered proteins
Authors: Ghafouri Hamidreza , Lazar Tamas , Del Conte Alessio , Tenorio Ku Luiggi G ,   PED Consortium, Aspromonte Maria C , Bernadó Pau , Chaves-Arquero Belén , Chemes Lucia Beatriz , Clementel Damiano , Cordeiro Tiago N , Elena-Real Carlos A , Feig Michael , Felli Isabella C , Ferrari Carlo , Forman-Kay Julie D , Gomes Tiago , Gondelaud Frank , Gradinaru Claudiu C , Ha-Duong Tâp , Head-Gordon Teresa , Heidarsson Pétur O , Janson Giacomo , Jeschke Gunnar , Leonardi Emanuela , Liu Zi Hao , Longhi Sonia , Lund Xamuel L , Macias Maria J , Martin-Malpartida Pau , Mercadante Davide , Mouhand Assia , Nagy Gabor , Nugnes María Victoria , Pérez-Cañadillas José Manuel , Pesce Giulia , Pierattelli Roberta , Piovesan Damiano , Quaglia Federica , Ricard-Blum Sylvie , Robustelli Paul , Sagar Amin , Salladini Edoardo , Sénicourt Lucile , Sibille Nathalie , Teixeira João M C , Tsangaris Thomas E , Varadi Mihaly , Tompa Peter , Tosatto Silvio C E , Monzon Alexander Miguel
Published: October 2023

The Protein Ensemble Database (PED) (URL: https://proteinensemble.org) is the primary resource for depositing structural ensembles of intrinsically disordered proteins. This updated version of PED reflects advancements in the field, denoting a continual expansion with a total of 461 entries and 538 ensembles, including those generated without explicit experimental data through novel machine learning (ML) techniques. With this significant increment in the number of ensembles, a few yet-unprecedented new entries entered the database, including those also determined or refined by electron paramagnetic resonance or circular dichroism data. In addition, PED was enriched with several new features, including a novel deposition service, improved user interface, new database cross-referencing options and integration with the 3D-Beacons network—all representing efforts to improve the FAIRness of the database. Foreseeably, PED will keep growing in size and expanding with new types of ensembles generated by accurate and fast ML-based generative models and coarse-grained simulations. Therefore, among future efforts, priority will be given to further develop the database to be compatible with ensembles modeled at a coarse-grained level.
The antiSMASH database version 4: additional genomes and BGCs, new sequence-based searches and more
Authors: Blin Kai , Shaw Simon , Medema Marnix H , Weber Tilmann
Published: October 2023

Many microorganisms produce natural products that are frequently used in the development of medicines and crop protection agents. Genome mining has evolved into a prominent method to access this potential. antiSMASH is the most popular tool for this task. Here we present version 4 of the antiSMASH database, providing biosynthetic gene clusters detected by antiSMASH 7.1 in publicly available, dereplicated, high-quality microbial genomes via an interactive graphical user interface. In version 4, the database contains 231 534 high quality BGC regions from 592 archaeal, 35 726 bacterial and 236 fungal genomes and is available at https://antismash-db.secondarymetabolites.org/.
GLIOMA-11 JUVENILE OLIGODENDROGLIOMA OF THE OPTIC NERVE: UNIQUE CASE REPORT AND CHALLENGE IN DIAGNOSIS ACCORDING TO CURRENT 2021 WHO CLASSIFICATION IN LIMITED RESOURCES COUNTRIES.
Authors: Ottoman Oscar , Chalamila Athuman , Mgaya Evarista , Kanji Raheel , Magambo Magreth , Rambau Peter
Published: October 2023

BACKGROUND

The list of most commonly occurring primary brain tumors includes gliomas, and the vast majority of these are astrocytomas or oligodendrogliomas. Oligodendrogliomas, account for about 3% of all intracranial tumors and 20% of gliomas. They are more commonly found in adults and occur mainly in the superficial gray matter of the cerebral hemispheres. For this tumor, 69% of the lesion is located in the frontal lobes. Involvement of the hypothalamus and optic chiasm are rarely seen and the tumor is most rare within the eye itself. The positive stain of IHC stain GFAP and OLIGO-2 overexpression is required for confirmation of diagnosis. Molecular genetics study of IDH-mutant is used for WHO grading and management of the oligodendrogliomas lesions.

CASE PRESENTATION

A 10 years old male presented with progressive blurred vision for 2 years and left eye globe protrusion for 1 month. On examination, he present with keratopathy, loss of vision, and pus discharge on the left eye. The Brain MRI was done and showed a left orbital heterogeneous enhancing lesion with mixed cystic and soft tissue involving both the globe and retrobulbar region with associated distortion of the optic nerve. The eye globe enucleation was done and tissue samples were taken for histopathology. The histopathology diagnosis reveals the optic nerve oligodendroglioma (NOS). The patient was kept on 8 cycles of Carboplatin chemotherapy.

CONCLUSION

Definitive diagnosis of Juvenile Oligodendroglioma of the optic nerve can be made only after the results of pathological and immunohistochemical analyses are known. Also, the current WHO grading of Oligodendroglioma requires molecular genetics IDH study. Although Juvenile Oligodendroglioma of the optic nerve is extremely rare, preoperatively oligodendroglioma should be included in the differential diagnosis of optic nerve tumors in pediatrics especially in limited settings with no molecular IDH testing.
OTHER-03 A COMPARATIVE ANALYSIS OF BRAIN TUMOR PALLIATIVE CARE PRACTICES IN CAMEROON AND NIGERIA
Authors: Tadipatri Ramya , Fonkem Ekokobe
Published: October 2023

Early access to palliative care is essential in management of brain tumor patients, particularly given low rates of survival despite optimal therapies. This is especially true in resource limited areas such as sub-Saharan Africa, where treatment options are further limited. A palliative care questionnaire was distributed to 72 physicians in Nigeria and 37 physicians in Cameroon who treated brain tumor patients. Significantly more participants from Nigeria expressed understanding of palliative care (90%), compared with the participants from Cameroon (35%), with more Nigerian participants reporting prior education in palliative care (58% compared with 27%). Participants from Nigeria were also much more comfortable initiating discussions, addressing concerns, providing consultations, and prescribing palliative medication (93%, 76%, 56%, and 71% respectively) compared with participants from Cameroon (65%, 41%, 32%, and 47% respectively). Participants from Nigeria were more likely to address pain, dysphagia-related symptoms, and anxiety (81%, 87%, and 72% respectively) compared with participants from Cameroon (69%, 50%, and 51% respectively). They were less likely to delay palliative care, with 47% waiting until evidence of irreversible deterioration compared with 62%. Participants from both Cameroon and Nigeria expressed limitations in access, with approximately 40% reporting no access to palliative care, and access to liquid opioids was particularly limited in Cameroon, with over 60% reporting no access. Additionally, many participants in both countries reported that cultural beliefs of both the provider and patient had an impact on palliative care delivery. Overall, this analysis helps to further characterize the country-specific challenges in palliative care delivery in sub-Saharan Africa and may assist in developing a framework for meeting brain tumor patient needs.
OTHER-04 FEASIBILITY STUDY ON BRAIN TUMOR BIOBANKING AND REGISTRY IN SUB-SAHARAN AFRICAN COUNTRIES: A QUESTIONNAIRE-BASED SURVEY
Authors: Odukoya Lateef , Kamson David , Eckel-Passow Jeanette , Ghomsi Nathalie , Jenkins Robert , Balogun James , Lachance Daniel , Karekezi Claire , Ekhator Chukwuyem , Osei-Tutu Lawrence , Ngaiza Advera , Tiamiyu Liadi , Mwakimonga Angela , Huse Jason , Nyalundja Arsene , Totimeh Teddy , Badmos Kabir , Bankole Olufemi , Kitange Gaspar , Brown Desmond , Anunobi Charles , Schroeder Kristin , Fonkem Ekokobe , Cheserem Beverly , Zerd Francis
Published: October 2023

INTRODUCTION

Brain tumors constitute significant morbidity and mortality in sub-Saharan Africa (SSA). Improvements in neuro-oncology practice and research have seen increased diagnosis of brain tumors. However, to our knowledge, there have been no previous projects on brain tumor genetics in SSA. To understand the feasibility of developing brain tumor biobanking and registries, this project aims to start by mapping out the current neuro-oncology capacity in terms of workforce and available services.

METHODOLOGY

We will conduct a descriptive questionnaire-based online survey among a cross section of neuro-oncology practitioners spread across SSA countries. The dissemination of the survey questionnaire will be facilitated by the Society for Neuro-oncology in SSA (SNOSSA). The Google designed questionnaire will capture information on the distribution, and number of available neuro-oncology care practitioners, capacity for brain tumor diagnosis and management, cancer registration, tumor biobanking, and research.

CLINICAL IMPACT AND CONCLUSION

This study will generate robust data from SSA, which can be used to improve future research and promote advocacy towards brain tumor diagnosis and management. This work will also serve as a pilot study for subsequent research that will focus on the development of brain tumor-specific registries and biorepositories in SSA.
PAEDIATRIC-11 EPIDEMIOLOGY OF PINEALOBLASTOMA IN CAPE TOWN, SOUTH AFRICA
Authors: Davidson Alan , Ohonba Efosa , Parkes Jeannette , Pillay Komala , Figaji Anthony
Published: October 2023

OBJECTIVE

To compare the experience with pinealoblastoma (PB) of the neuro-oncology services of the University of Cape Town to the WHO 2021 classification.

METHODS

A retrospective analysis was performed on folders of patients diagnosed at Red Cross War Memorial Children’s Hospital and Groote Schuur Hospital from 2000-2022. Routine molecular testing is not available nor is testing for DICER mutations. Patients with PB associated with retinoblastoma (RB) were assumed to be Rb1-altered and were treated with ophthalmic local control and chemotherapy, and those without associated RB (assumed to be non-Rb1-altered) were mostly treated with surgery, chemotherapy and craniospinal radiotherapy. Convenience sampling was performed by age with respect to disease characteristics and outcome to try and disaggregate miRNA-processing-altered-1 and -2 from MYC/FOXR2-altered PB.

RESULTS

Twenty-five patients were identified, 6 with Rb1-altered PB, aged 0.33-1.88 years (median 0.79) and 19 with non-Rb1-altered PB, aged 0.17-12.99 years (median 6.23). The whole cohort was balanced in terms of gender but there were slightly more girls (11) than boys (8) among the non-Rb1-altered PBs. One of these children was a 5-year-old boy with DICER syndrome who was identified through family screening. One Rb1-altered PB had metastatic disease outside the pineal gland. Among the non-Rb1-altered PBs 47% had metastases, 0% of those under 3 years, 40% of those aged 3-9 years and 80% of those older than 9 years. Estimated 5-year OS for the whole group was 49%, 50% for Rb1-altered PB and 49% for non-Rb1-altered PBs. OS by age among non-Rb1-altered PBs was 0% for 0-3 years, 90% for 3-9 years and 20% for those older than 9 years.

CONCLUSION

DICER testing and molecular typing would be very useful in helping to stratify our non-Rb1-altered PBs, both for prognostication and to allow consideration of high-risk strategies. Multi-disciplinary treatment of PB in LMIC is essential.
PAEDIATRIC-16 ADVANCING IN PAEDEATRIC BRAIN CANCER CARE
Authors: Madzudzo Michelle , Musosi Godwin , Muzvondiwa Ivan
Published: October 2023

OBJECTIVE

To empower health workers in the cancer care continuum to nationally reduce the disease burden from brain cancer through active engagement, advocacy , collaboration and education -to introduce theories and concepts including current trends, issues , challenges and debates in brain cancer.

METHOD

The talk cancer zim trust organised a hybrid national webinar on paedeatric brain cancer on 26 May 2023 under the mantra "advancing in brain cancer care , where are we? The objectives were to be met through presantations from the neurosurgeon , oncologist, psychiatrist, palliative care specialist , Kidzcan and the GICC focal person for the country.Thematic areas covered were palliative care,radiation oncology, neurosurgery, advocacy and psychooncology.

RESULTS

a total of 193 health proffessionals attended the meeting online while 24 health proffessionals attended the meeting in.person.The targeted audience consisted of radiographers, oncology nurses, pharmacists, rehabilitation specialists, medical physicists and specialist doctors such as oncologists, neurosurgeons and psychiatriasts.

CONCLUSION

There is need for a holistic approach to paedatric brain cancers throughout the cancer trajectory from awareness, diagnosis, screening through treatment and palliative care and research
TRANSLATIONAL RESEARCH-02 THE KEYSTONE CYTOKINE, INTERLEUKIN-6, A KEY TARGET AND “ORGANIZING PRINCIPLE” FOR GLIOBLASTOMA THERAPY: A DECADE OF TRANSLATIONAL PROGRESS FROM GENOMICS TO THE LABORATORY AND TO A MULTICENTER CLINICAL TRIAL
Authors: Brem Steven
Published: October 2023

Interleukin-6 (IL-6), the ‘keystone cytokine’, affects homeostatic processes, including innate and adaptive immunity, and is regarded as a prominent target for clinical intervention (Hunter, 2015). IL-6 is also a senescence-associated-gene (SAG), linked to cellular aging, the aging brain, and cancer pathogenesis. We hypothesized that SAGs, including IL-6, are overexpressed in older patients, in higher grades of glioma, portending a poor prognosis (Coppola, 2014). Indeed, in an analysis of 47 gliomas at the Moffitt Cancer Center, we found that the ‘senescence score’ composed of genes central to the pathogenesis of glioma, defined a novel signature, provided prognostic biomarkers as well as targets for drug discovery and immunotherapy (Coppola, 2014). We suggested that IL-6 could be linked to neoplastic transformation and could be predictive of glioma progression (US Patent #8741575). At the University of Pennsylvania, we found an inhibitor of IL-6 to be well-tolerated in patients with glioblastoma undergoing CAR T cell therapy (O’Rourke, 2017). Yi Fan’s team discovered (Wang, 2018) that targeting IL-6 led to a remarkable change in the tumor microenvironment (TME), with a “switch” from the M2 (immunosuppressive, pro-tumorigenic) macrophage phenotype to an immunostimulatory (M1) phenotype, resulting in a significant increase in survival. Adding CD40 agonist enhanced the activity of infiltrated T cells, and an almost complete cure in GBM models. The use of immune checkpoint inhibitors in these experiments and by others (Lamano, 2019) produced a significant increase in survival. These findings led to a multicenter trial (PI, Stephen Bagley; NCT 047299959), by NRG Oncology (BN010), combining IL-6 inhibition (tocilizumab), PD-L1 blockade (atezolizumab) and stereotactic radiotherapy to treat recurrent glioblastoma. More recently, a MDACC team discovered that IL-6 blockade not only promotes tumor immunity but also abrogates the toxicity of checkpoint blockade, decoupling the autoimmune toxicity while promoting tumor immunity through the IL-12 pathway (Hailemichael, 2022).
The brain
Authors: Baron-Cohen Simon , Bolton Patrick
Published: October 2023

The assumption is that in all children with autism there is some (possibly very subtle) brain damage. Where none can be found, it is assumed that this is because our tools for examining the brain are still too crude. Such brain damage, either observed or assumed, is held to cause the autism, as was made clear in the previous chapter. Parents often wonder if there really is any brain damage in their child, since he or she looks so normal. As we shall see, the brain-damage view is widely held simply because in many cases brain abnormalities are found. Here is the evidence.
Adolescence and adulthood
Authors: Baron-Cohen Simon , Bolton Patrick
Published: October 2023

In this chapter we consider the range of outcomes that usually occur in people with autism, to give a sense of what can be expected. This by no means defines the limits, but nevertheless summarizes the kinds of out¬ comes we have seen in our clinic. Following this we look at specific issues relating to adjustment in adolescence and early adulthood. Currently, our knowledge is limited by the fact that very few studies have followed people with autism into their later adult life, and by the fact that elderly people known to have autism are rare, since the disorder itself was only identified in the middle of this century. We do know, however, that the range of outcomes is very wide. Thus, for people with autism who also have severe mental handicap, some sort of life-long support and supervision will be essential. For more able individuals, outcome really depends on how much useful language the person has acquired. As a common-sense rule, the less language a person has, the more support he or she will need. It is however important to note that language can develop even as late as adolescence, although the rate of development by this age may be slow and limited. For the most able people with autism, a life of independence and employment in the open market-place is not unknown; but this is unusual. Sheltered accommodation and employment is more usual. Other options include day centres, in which the individual is given interesting activities and some training, but may not be employed. Some issues surrounding employment and placement are discussed later.
Circadian rhythms in sports performance
Authors: Reilly T , Atkinson G , Waterhouse J
Published: October 2023

The majority of the resting physiological variables mentioned in Chapter 2 are thought to influence human performance. For example, when body temperature, circulating levels of hormones and metabolic functions are manipulated artificially prior to exercise (e.g. by prewarming subjects or by pharmacological agents), performance is affected. Endogenous circadian changes in these resting parameters might mediate parallel changes in both performance and physiological responses to exercise over a 24-hour period. In this chapter, the evidence for such rhythmicity in human physical performance is analysed.
The different types of epileptic seizure and of epilepsy syndromes
Authors: Hopkins Anthony , Appleton Richard
Published: October 2023

Figure 2.1 illustrates the two main classes of origin of seizure. In the top third of the figure, the hatched area indicates a number of nerve cells in the cortex (the name given to the layers of nerve cells on the surface of the brain) which are in some way abnormal, tending to discharge paroxysmally. They may drive other nerve cells to follow their abnormal patterns of discharge. The paths of influence of the discharging nerve cells are indicated by the arrows. As long as the discharge remains in one part of the brain, the seizure is said to be a partial seizure and its cause location-related. What happens during a partial seizure depends upon the exact site and pattern of discharge of abnormal nerve cells. Temporal lobe seizures as described on p. 16 are of this type. The features of these are described in more detail on pp. 14-17, along with those of other types of partial seizures.
The first seizure and the diagnosis of epilepsy
Authors: Hopkins Anthony , Appleton Richard
Published: October 2023

Anyone reading this book who has been present at the first grand mal seizure of a child or other relative will remember the sense of shock and feeling of incompetence at coping with a totally unforeseen situation. A common story is for parents to be woken by the stertorous breathing or grunting of a child in the next bedroom. They go to him, thinking usually that he is having a bad dream, and find him staring, unresponsive, convulsing, and perhaps blue. Few if any parents can cope calmly with such a scene. It is usual for the family doctor to be telephoned at once, and, if there is any delay in his arrival, for an ambulance to be summoned as well. Many parents subsequently confess that they thought their child was dying, so they are acting in an entirely rational way. Almost invariably, however, by the time the family doctor or ambulance has arrived, the seizure is over, the child is sleeping peacefully, and the adults are making tea. But they will not sleep again that night. Many-though not all-are immediately aware of the nature of what they have just seen, and all the worries which this book is attempting to put into perspective crowd their minds.
The long-term outlook
Authors: Hopkins Anthony , Appleton Richard
Published: October 2023

Many patients, family doctors, and even paediatricians and neurologists, are remarkably pessimistic about the likelihood of seizures stopping—a pessimism which is unjustified by the facts. Pessimism stems from hospital experience. In the past, when neurologists were fewer on the ground, they tended to see only those with the worst epilepsy with the worst prognosis. As they taught the future family doctors, these too were infected with the same pessimism.
The promise of the future
Authors: Hopkins Anthony , Appleton Richard
Published: October 2023

The understanding and treatment of epilepsy has improved considerably over the past fifty years. Most of this improvement has resulted from basic scientific research into how and why epileptic seizures start, and from the development of safer and more effective anti-epileptic drugs by the pharmaceutical industry. However, there is still much work which needs to be carried out, not just to improve our understanding and knowledge, but to improve the quality of life of a child or man or woman with epilepsy.
Resuscitation in hospital
Authors: Skinner David V , Vincent Richard
Published: October 2023

In addition to medical skills, efficient resuscitation in hospital requires careful organization. This chapter addresses some of the practicalities of running a hospital resuscitation service, beginning with the general requirements for organization, training, and equipment. In several areas of the hospital (e.g. A&E, the CCU, and the ICU) the availability of equipment and staff will be different from that regularly provided by the hospital crash team; these areas need to develop specific plans for the best management of their patients.
Management of myocardial infarction
Authors: Skinner David V , Vincent Richard
Published: October 2023

Unstable coronary syndromes, particularly acute myocardial infarction, so often cause cardiac arrest that to consider their management is essential. A substantial reduction in mortality from heart attack can now be achieved not only from successful resuscitation, but on a wider scale by appropriate treatment with iv opioids, aspirin, nitrates, beta blockers, thrombolytic agents, ACE inhibitors, and anticoagulants. How these agents exert their beneficial effect is becoming clearer as we understand more of the pathological mechanisms of acute coronary occlusion and its resulting effect on the myocardium.
Who to resuscitate and post-resuscitation care
Authors: Skinner David V , Vincent Richard
Published: October 2023

The decision to resuscitate or not can be difficult. To avoid confusion, if a cardiac arrest should occur in an in-patient, a decision as to whether resuscitation is appropriate should have been made in advance. A variety of factors will influence this decision, but it should be reached by consensus with the medical team involved, together with their nursing colleagues, the patient‘s relatives, and, if appropriate, the patient himself or herself. The patient‘s illness, age, and general quality of life will influence the decision, and various guidelines have been suggested, namely: resuscitation may be withheld for a patient whose general health has been declining progressively over many years, or, for instance, when even if the patient were resuscitated, the quality of life would be so poor as to be regarded by most as unacceptable.
Cancer
Authors: Greaves Mel
Published: October 2023

Every day, 1500 Americans die of cancer, and yet for most of us this deadly disease remains mysterious. Why is it so common? Why are there so many different causes? Why does treatment so often fail? What, ultimately, is cancer? In this fascinating new book, a leading cancer researcher offers general readers clear and convincing answers to these and many other questions. Mel Greaves places cancer in its evolutionary context, arguing that we can best answer the big questions about cancer by looking through a Darwinian lens. Drawing on both ancient and more modern evolutionary legacies, he shows how human development has changed the rules of evolutionary games, trapping us in a nature-nurture mismatch. Compelling examples, from the King of Naples intestinal tumor in the 15th century, through the epidemic of scrotal skin cancer in 18th-century chimney sweeps, to the current surge of cases of prostate cancer illustrate his thesis. He also shows why the old paradigms of infectious diseases or genetic disorders have proved fruitless when trying to explain this complex and elusive disease. And finally, he looks at the implications for research, prevention, and treatment of cancer that an evolutionary perspective provides. Drawing on the most recent research, this is the first book to put cancer in its evolutionary framework. At a time when Darwinian perspectives on everything from language acquisition to economics are providing new breakthroughs in understanding, medicine seems to have much to gain from the insights provided by evolutionary biology. Written in an exceptionally lucid and entertaining style, this book will be of broad interest to all those who wish to know more about this dread disease.
St Peregrine’s Progress
Authors: Greaves Mel
Published: October 2023

Cancer biologists often pictorialize cancer development as a simple linear sequence of mutational steps coupled with progressive selection of increasingly dominant subclones. This provides a time-ordered parallel with the progression of disease that the pathologist can recognize and grade in a biopsy section as disruption of tissue architecture and spread of disease. It also fits with an astute prediction by mathematically minded epidemiologists, Armitage and Doll, in the 1950s, that the exponential increase with age in most incidence of common forms of cancer was most probably a function of the time needed to accumulate a set of mutations in the subclone that eventually dominates at diagnosis.
Off to a Shaky Start
Authors: Greaves Mel
Published: October 2023

A though the majority of mutant genes in cancer arise in single cells in pecialized tissues, some cancers involve transmission and inheritance of mutant gene from parent to offspring. For this to occur requires that at some time in the history of the patient’s family one individual predecessor acquired a new mutation in one of his or her germ cells (sperm precursors or ova). Dad’s germ cells are more at risk than Mum’s because of the greater number of cell divisions that will have occurred prior to conception. We cannot prove how any one such mutation has arisen but most are likely to be accidental consequences of DNA replication, mismanagement, and error-prone repair in germ cells. This seems a thoroughly undesirable and unnatural thing to happen, an appalling lapse of genetic vigilance. But in fact it’s part of nature.
Blind chance - and ultimate extinction?
Authors: Greaves Mel
Published: October 2023

Like all evolutionary changes with the appearance of prudent planning or a smart, selfish manoeuvre, cancer cells and their mutations are not strategic by design or intent. They operate by a throwing of the geneticdice at random or by blind chance, coupled with selection for what might be relatively short-term advantage. The process may have all the attributes of a covert collaboration of mutant genes, but in reality it’s cock-up and chaos that apply, not conspiracy.
Collateral Damage
Authors: Greaves Mel
Published: October 2023

The final causal pathways for cancer to consider are those that have arisen uniquely in the twentieth century, and as a by-product of our extra ordinary technical virtuosity. These are all relatively infrequent but instructive examples of delayed and collateral damage where initial intentions were either benevolent or malign.
Anatomy of the heart relevant to cardiac surgery and anaesthesia
Authors: Hwang Dr Nian Chih , Sinclair Dr Michael
Published: October 2023

The anatomy of the normal heart is described in this chapter. Congenital abnormalities of the heart and the great arteries are described in Chapter 17. The heart is an irregular conical structure located in the middle mediastinum. It can be surface marked on the anterior chest wall by an irregular quadrangle bounded by the following points listed in an anticlockwise direction (Fig. 1.1): third right costal cartilage 1.25 cm from the sternal edge; sixth right costal cartilage 1.25 cm from the sternal edge; fifth left intercostal space 9 cm from the midline; second left costal cartilage 1.25 cm from the sternal edge.
Physiology of the heart relevant to cardiac surgery and anaesthesia
Authors: Hwang Dr Nian Chih , Sinclair Dr Michael
Published: October 2023

Owing to the presence of a specialized conduction system, the heart normally beats in a regular manner. Depolarization spreads rapidly from the sinoatrial node, the normal pacemaker of the heart, through the internodal atrial pathways to the atrioventricular node (P wave). Following a physiological conduction delay at the atrioventricular node, depolarization spreads to the branches of bundle of His and, via the Purkinje fibres, to the ventricular muscle. The normal duration of atrial depolarization and conduction through the atrioventricular node, the PR interval on the electrocardiograph, is 0.12-0.20 s. Normal ventricular depolarization, the QRS duration, takes 0.08-0.1 s.
Guidelines for thoracic aortic surgery
Authors: Hwang Dr Nian Chih , Sinclair Dr Michael
Published: October 2023

Ascending aortic aneurysms are proximal to the origin of the brachiocephalic artery, aortic arch aneurysms are located between the origin of the brachiocephalic artery and the left subclavian artery, and descending aortic aneurysms are located between the origin of the left subclavian artery and the diaphragm. The majority of aneurysms are atherosclerotic in origin. Aortic dissection is one of the most common aortic problems. Patients with aortic dissection can be divided into two main groups: those with hypertension, and those with syndromea involving hereditary defects of the aortic wall. The common finding in both Marfan’s syndrome and hypertension is dilatation of the aorta. Aortic dissections can be classified either into types I, II, and III, based on the site of the intimal tear and the extent of the dissection (DeBakey and colleagues), or into type A, which involves the ascending aorta, or type B, which does not involve the ascending aorta (Daily and colleagues). Both type A and type B aortic dissection are associated with the hypertensive male, and aortic regurgitation can be a concomitant finding.
Preoperative investigations
Authors: Hwang Dr Nian Chih , Sinclair Dr Michael
Published: October 2023

The assessment of congenital heart disease should include ECG, chest radiography, echocardiography, Doppler flow study, and cardiac catheterization. The heart rate, heart rhythm, and any evidence of ventricular strain pattern, characteristic of volume overloading of the ventricles, can be seen on the ECG. Chest radiography will reveal any cardiomegaly, pulmonary vascular congestion, airway compression, and areas of lung collapse consolidation. Intercurrent pulmonary infection is a common finding in children whose lungs have been subjected to chronic excessive pulmonary blood flow.