bluuebunny/crossref_metadata_2025 huggingface dataset:
Orexants, Orexin Receptor Antagonists: Novel Therapeutic Agents for Insomnia Disorder
Authors: Kandukuri Akshitha , Pasupulati Haritha , Padi Satyanarayana SV
Published: December 2024

Insomnia is when a person feels difficulty falling asleep or staying asleep, often associated with complications, such as fatigue, sleepiness, etc. Insomnia may cause disruptions in daytime physical and mental abilities. Orexins or hypocretins are the neuropeptides secreted from the lateral hypothalamus and play a major role in the sleep-wake cycle through a complex interplay between wake-promoting and sleep-promoting neuronal systems. Orexin receptor antagonists (Orexants) are the new treatment options for insomnia disorder, narcolepsy, and other sleep disturbances. There are two classes of Orexants, namely those that bind selectively to a specific orexin receptor are selective orexin receptor antagonists (SORA), and the others that bind to both the orexin receptors are dual orexin receptor antagonists (DORA). The first DORA was almorexant but restricted in use and the other three approved DORAs, such as suvorexant, lemborexant, and daridorexant were approved by the FDA, and several other DORAs and SORAs are under various stages of discovery and clinical investigation. Among the labeled limitations, the currently approved Orexants are contraindicated in people with narcolepsy and are controlled substances owing to their misuse liability. The present review discussed the sleep-wake cycle, phases of a sleep cycle, orexins, and Orexants, and summarized the pharmacology of the three approved DORAs, a type of Orexants and their potential advantages and limitations of their use in pharmacotherapy of insomnia disorder.
Fish Waste Compost - A Fertilizer for Organic Agriculture
Authors: Devi Nongmaithem Leindah , Singh Athokpam Herojit , Nongthombam Jotish , Kumar Santosh , Chaudhary K.P.
Published: December 2024

Fish markets produce a large amount of fish waste such as fish head, gut, intestine, fines, bones and scales that are generally dumped in the river or land-filling areas causing great intuitive pollution to the environment. Such impulsively growing contamination can be mitigated and checked though waste management in the form of organic composting. This study investigates the potential of fish waste compost as a sustainable organic fertilizer by converting fish waste, including gut, head, skin, bones, and fins, into compost using sawdust, banana and jaggery as supplementary materials. The matured compost was then analyzed for nutrient content and maturity through physical, sensory, biological, and chemical tests. Results showed that the compost, reduced to 70% of its original volume, had significant nutrient content with a C:N ratio of 28.6:1, a pH of 6.80, and an electrical conductivity of 1.45 dS/m. Biological tests demonstrated high germination rates, indicating non-phytotoxicity. Fish waste containing 10.56, 2.12, 0.82 and 0.10 percents of C, N, P and K respectively can be converted into an effective organic fertilizer which can enhance soil fertility. This approach not only addresses waste management but also offers a viable solution for recycling fish waste into valuable agricultural resources.
Diversity and Adaptation of Plant Life Forms in Bassi Wildlife Sanctuary: A Phytoclimatic Analysis
Authors: Harikrishna P. , Panda S.P.
Published: December 2024

Bassi Wildlife Sanctuary is located in the South-Eastern part of Rajasthan, India. This study resulted in plant life form diversity and distribution using Raunkiaer's classification system.  Extensive field surveys were conducted in BWS between April 2017 and March 2019 to identify and record plant species. The collected specimens were identified by using state and regional floras (Shetty & Singh, 1987, 1991, 1993; Tiagi and Aery, 2007; Yadav& Meena, 2011; Harikrishna et al., 2022). A total of 468 plant species belonging to 322 genera and 85 families were recorded. The results indicate that therophytes (55.8%) are the dominant life form, followed by phanerophytes (23.5%), hemicryptophytes (7.3%), cryptophytes (6.8 %) and chamaephytes (6.6%). On comparison with Raunkiaer’s normal spectrum, the present study area depicts Thero-phanerophytic type of phytoclimate. This study also provides valuable insights into the plant ecology of BWS and contributes to the understanding of the region's biodiversity.
Clinical Characterization of Ocular Trauma at Tertiary Care Centre, Bilaspur, India
Authors: Singh Suchita , Sonwani Prabha , Garg Akhil
Published: December 2024

In this study, we aim to document know the clinical spectrum and mechanism of ocular trauma and benefits of early intervention following injuries among patients presenting to CIMS, Bilaspur. This was a prospective interventional study of all ocular emergencies except chemical injuries presenting between July 2023 and June 2024. Overall, there were 662 ocular emergencies, of which 598 were mechanical injuries (598/662; 90.33%). Most cases of trauma belonged to the 21–30 years age group (322; 53.84%). The most common cause of injury were road traffic accidents. Appropriate preventive measures while driving, and at hazardous workplaces, can potentially reduce ocular injuries.
The Entrepreneurial Mindset: Views and Perspectives of Cacao Entrepreneurs on Innovation and Entrepreneurship in Bicol Region, Philippines
Authors: Ramirez Ramona Isabel S. , Lirag Ma. Teresa B.
Published: December 2024

Innovation and entrepreneurship are fundamental drivers of economic growth. Oftentimes, sustainable development is equated with these two indices where untapped potential and emerging industries are available that present countless opportunities for the people. A research study was conducted composed of cacao farmers, farmers/processors and farmers/processors/traders residing in various towns in the Bicol region, Philippines aimed at determining their perception, innovation and entrepreneurial initiatives and strategies. A survey-questionnaire was designed and administered to 70 cacao farmers and entrepreneurs and qualitative data analysis techniques, such as thematic coding and content analysis was employed to analyze result of the interview and focus group discussions. Findings of the study showed that farming is the primary focus for the majority of respondents (67%), with only a minority involved in processing or trading activities. The most highly recommended innovative cacao-based products with potential market success are primarily in the food and confectionery categories, with substantial interest in beverages and skincare products. Ninety-one percent (91%) are willing to pay a premium for innovative cacao products because they value supporting local entrepreneurship and a good sign of a strong community support for local businesses with high level of willingness to invest in locally developed products. Job creation and empowerment of small-scale farmers are considered as top benefits of a community-based value-added cacao products enterprise. Limited financial investment/capital is the most significant problem faced, followed closely by unstable demand and low and unregulated farm gate price of agricultural commodities.
EFEITOS DA RADIOTERAPIA NO TECIDO PULPAR DE PACIENTES COM CÂNCER DE CABEÇA E PESCOÇO
Authors: Lima Dayane Vitória de Souza Carvalho , De Carvalho Elaine Lola , Cerqueira Joana Dourado Martins , Barreto Neto Laerte Oliveira , Oliveira Márcio Campos , De Almeida Tatiana Frederico
Published: December 2024

Objetivo: Realizar uma revisão integrativa da literatura através de evidências clínicas disponíveis, para uma melhor compreensão do estado da polpa dentária em pacientes com câncer de cabeça e pescoço tratados por radioterapia. Materiais e métodos: Executou-se a sistematização das informações coletadas na Biblioteca Virtual em Saúde (BVS), incluindo artigos indexados na base de dados SciELO e PubMed/MEDLINE. Os descritores selecionados foram: “polpa dentária” / “dental pulp”; “radioterapia” / “Radiotherapy”; “câncer de cabeça e pescoço” / “Head and neck câncer”. Resultados: 24 artigos foram encontrados sobre o tema nos últimos 10 anos. Destes, 07 artigos foram excluídos por duplicidade entre as bibliotecas de busca. Ao realizar o rastreamento por leitura de títulos e resumos, percebeu-se que 05 destes desviavam-se da temática proposta, sendo também excluídos. Contudo, a presente busca priorizou por estudos observacionais. Nesse contexto, apenas 06 artigos foram selecionados para compor a análise deste estudo, onde ainda não existe um consenso sobre a quantidade suficiente de radiação em Gray (Gy) que determine a perda da vitalidade da polpa dentária. Considerações finais: Apesar dos relatos conflitantes dessas investigações, a polpa dentária no caminho da radiação ionizante durante a RT na região da cabeça e pescoço pode não sofrer perda completa da vasculatura e do fluxo sanguíneo, tão pouco predispor o tecido pulpar à necrose.
Nonverbal Expressions Of Trauma: A Secondary Analysis Of PTSD-Specific Cues In Clinical Assessments
Authors: Offor Daniel Ojotule , Omopo Oluwaseun Emmanuel , Ilori Kikelomo Magaret
Published: December 2024

Post-Traumatic Stress Disorder (PTSD) is diagnosed through both verbal and nonverbal cues observed in clinical
interviews. Nonverbal behaviours, such as facial expressions, body posture, and eye contact, play a critical role
in indicating emotional states and aiding PTSD diagnosis. This study examines nonverbal cues associated with
PTSD, their diagnostic reliability, and their correlation with symptom severity and treatment progress. A
secondary analysis of observational and video-based studies focusing on PTSD diagnostic interviews was
conducted. Data extraction focused on identifying nonverbal cues, including facial expressions and body
language. Meta-analysis techniques assessed the reliability of these cues and their correlation with PTSD
symptoms and treatment progress. Consistent nonverbal cues identified include emotional detachment, tense
posture, rapid blinking, and avoidance behaviours such as turning away. These behaviours were linked to PTSD
symptom severity and treatment progress, with improvements like relaxed posture and increased eye contact
indicating symptom reduction. However, some cues overlap with other conditions such as anxiety and depression,
complicating diagnosis without additional diagnostic tools. It is recommended to integrate nonverbal cues into
PTSD diagnostic practices, particularly when combined with structured interviews and psychometric
assessments. Clinician training to recognise these cues could enhance diagnostic accuracy. Future research should explore AI tools for analysing nonverbal cues and conduct longitudinal studies for further insights.
Intra-Cerebral Foreign Body With Orbital Entry Point In A Child: A Case Report
Authors: Meriem EL Alami , Oumkeltoum Jrondi , Laabi Imane , Bouchra Allali , Asmaa El Kettani
Published: December 2024

The case is about a 9-month-old infant who sustained an orbital trauma from a pen tip, resulting in a cranioencephalic foreign body. Initial clinical examination revealed periorbital swelling and inability to open the eyelid,
while radiography and CT scans identified an intra-parenchymal frontal foreign body and a bony defect in the
right orbit. Cranio-orbital foreign bodies, though rare, can lead to severe complications if not diagnosed early [1]. This case highlights the importance of thorough clinical evaluation and appropriate imaging for rapid diagnosis and early surgical intervention to prevent serious injuries.
Tailoring Structural Energetics for Enhanced Reactivity of Nano‐Aluminum Particles Based Microspheres
Authors: Yan Tao , Ren Hui , Li Yaru , Wang Huixin , Jiao Qingjie
Published: June 2019

Porous nano‐aluminum@polymer microspheres with a narrow size range are fabricated to exploit the energy advantages of nano‐aluminum (nAl). Nitrocellulose (NC) and glycidyl azide polymer (GAP) act as functional binders and adhere tightly to the surface of nAl particles and aggregate them into spheres. The formed holes on the microsphere surface are considered gas diffusion channels to the microsphere interior. Confined combustion results show that nAl@GAP microspheres generate the highest peak pressure, and maximum pressurization rate of nAl@NC microspheres is comparatively higher than that of others. Given the microsphere structure, thermal behavior in air shows that the oxidation‐reaction mechanism of the microspheres is close to that of nAl particles. Interfacial reactions between nAl particles and gases produced by polymer decomposition enhance microsphere reactivity. The heat released by polymer decomposition maintains the structure, activates nAl particles, and accelerates combustion propagation, which are positively correlated with the energy content of the polymer. The unconfined test results showed that nAl@GAP microsphere combustion propagates faster than that of nAl@NC microspheres.
Radio Frequency and Microwave Heating of Preceramic Polymer Nanocomposites with Applications in Mold‐Free Processing
Authors: Patil Nutan , Camacho Alejandro Cardenas , Mishra Naveen K. , Singhla Prashant , Sweeney Charles B. , Saed Mohammed A. , Radovic Miladin , Green Micah J.
Published: June 2019

Here the authors demonstrate an oven‐free and mold‐free heating route to convert preceramic polymers to silicon carbide using carbon nanomaterials as susceptors. Silicon carbide is prized for its high thermal stability and low density and could be produced via slow oven heating of polycarbosilane (PCS). The authors show that addition of multiwalled carbon nanotubes (MWCNT) as susceptors to polycarbosilane results in rapid and volumetric heating upon exposure to microwaves and radio frequency. The authors assess microwave heating of polycarbosilane‐MWCNT composites; this process is capable of reaching pyrolysis temperatures, and the resulting crystal structure is cubic (β‐SiC). Dielectric properties of these composites in the radio frequency range is measured. The authors cure these composites using RF, and thermogravimetric data shows that the extent of cure for these samples is around 95%. The applicability of this study for 3D printing silicon carbides by successive iterations of layer deposition and rapid RF curing is demonstrated. The fly measurements of dielectric values of the 3D printing ink at different temperature while curing it is performed. The authors have also shown that these volumetric heating methods can rapidly cure polycarbosilane fibers to make silicon carbide fibers without melting them before crosslinking.
Hydrogen‐Bonded Polyimide/Metal‐Organic Framework Hybrid Membranes for Ultrafast Separations of Multiple Gas Pairs
Authors: Ma Canghai , Urban Jeffrey J.
Published: June 2019

Membranes have seen a growing role in mitigating the extensive energy used for gas separations. Further expanding their effectiveness in reducing the energy penalty requires a fast separation process via a facile technique readily integrated with industrial membrane formation platforms, which has remained a challenge. Here, an ultrapermeable polyimide/metal‐organic framework (MOF) hybrid membrane is reported, enabling ultrafast gas separations for multiple applications (e.g., CO2 capture and hydrogen regeneration) while offering synthetic enhanced compatibility with the current membrane manufacturing processes. The membranes demonstrate a CO2 and H2 permeability of 2494 and 2932 Barrers, respectively, with a CO2/CH4, H2/CH4, and H2/N2 selectivity of 29.3, 34.4, and 23.8, respectively, considerably surpassing the current Robeson permeability–selectivity upper bounds. At a MOF loading of 55 wt%, the membranes display a record‐high 16‐fold enhancement of H2 permeability comparing with the neat polymer. With mild membrane processing conditions (e.g., a heating temperature less than 80 °C) and a performance continuously exceeding Robeson upper bounds for over 5300 h, the membranes exhibit enhanced compatibility with state‐of‐the‐art membrane manufacturing processes. This performance results from intimate interactions between the polymer and MOFs via extensive, direct hydrogen bonding. This design approach offers a new route to ultraproductive membrane materials for energy‐efficient gas separations.
Visible Light‐Mediated Conversion of Alcohols to Bromides by a Benzothiadiazole‐Containing Organic Photocatalyst
Authors: Li Run , Gehrig Dominik W. , Ramanan Charusheela , Blom Paul W. M. , Kohl Fabien F. , Wagner Manfred , Landfester Katharina , Zhang Kai A. I.
Published: June 2019

The search for metal‐free, stable and high effective photocatalysts with sufficient photo‐redox potentials remains a key challenge for organic chemists. Here, we present a benzothiadiazole‐containing molecular organic photocatalyst with redox potentials of −1.30 V and +1.64 V vs. SCE. The singlet state lifetime is 13 ns. Direct conversion from aliphatic alcohols to bromides has been conducted with the designed organic photocatalyst under visible light irradiation with high efficiency and selectivity. The catalytic efficiency of the novel benzothiadiazole‐based photocatalyst is comparable with the state‐of‐art metal and non‐metal catalysts. Furthermore, advanced photophysical studies including time‐resolved photoluminescence and transient absorption spectroscopy offer a powerful support for photo‐induced electron transfer from photocatalyst to the reactive substrates. Lastly, no photo‐bleaching effect is observed, demonstrating the high stability and recyclable of the designed organic photocatalyst.

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A Molecular Cobalt Hydrogen Evolution Catalyst Showing High Activity and Outstanding Tolerance to CO and O2
Authors: Wang Jia‐Wei , Yamauchi Kosei , Huang Hai‐Hua , Sun Jia‐Kai , Luo Zhi‐Mei , Zhong Di‐Chang , Lu Tong‐Bu , Sakai Ken
Published: June 2019

There is a demand to develop molecular catalysts promoting the hydrogen evolution reaction (HER) with a high catalytic rate and a high tolerance to various inhibitors, such as CO and O2. Herein we report a cobalt catalyst with a penta‐dentate macrocyclic ligand (1‐Co), which exhibits a fast catalytic rate (TOF=2210 s−1) in aqueous pH 7.0 phosphate buffer solution, in which proton transfer from a dihydrogen phosphate anion (H2PO4−) plays a key role in catalytic enhancement. The electrocatalyst exhibits a high tolerance to inhibitors, displaying over 90 % retention of its activity under either CO or air atmosphere. Its high tolerance to CO is concluded to arise from the kinetically labile character of undesirable CO‐bound species due to the geometrical frustration posed by the ligand, which prevents an ideal trigonal bipyramid being established.
TheKINDProgram for Adolescent Family and Dating Violence
Authors: Moulds Lauren Grace , Malvaso Catia , Hackett Louisa , Francis Luke
Published: June 2019

Adolescent relational violence has significant and pervasive impacts for young people's current and future relationships. It is known that there is a cross‐over between adolescent family violence and other offending behaviour, meaning there is a need for youth justice systems to recognise and respond to these forms of violence. This paper outlines a pilot intervention, theKINDProgram, run in Youth Justice South Australia, and aimed at intervening with adolescent family and dating violence.KINDaims to provide tailored systemic intervention to young people and their support network, reducing violence while increasing connection and strength within relationships. The pilot ofKINDran for seven months in 2017, and had eight families participating in the program. Participation in, feedback from, and impact of the program suggest that participation was worthwhile and useful for young people and their families. TheKINDProgram would benefit from a more extensive pilot period to explore the outcomes of this form of intervention.
Anti‐Alzheimer's multitarget‐directed ligands with serotonin 5‐HT6 antagonist, butyrylcholinesterase inhibitory, and antioxidant activity
Authors: Marcinkowska Monika , Bucki Adam , Panek Dawid , Siwek Agata , Fajkis Nikola , Bednarski Marek , Zygmunt Małgorzata , Godyń Justyna , Del Rio Valdivieso Alvaro , Kotańska Magdalena , Kołaczkowski Marcin , Więckowska Anna
Published: June 2019

Serotonin 5‐HT6 receptors, butyrylcholinesterase (BuChE) and oxidative stress are related to the pathophysiology of Alzheimer's disease. Inhibition of BuChE provides symptomatic treatment of the disease and the same effect was demonstrated for 5‐HT
6 antagonists in clinical trials. Oxidative stress is regarded as a major and primary factor contributing to the development of Alzheimer's disease; therefore, antioxidant agents may provide a disease‐modifying effect. Combining BuChE inhibition, 5‐HT
6 antagonism, and antioxidant properties may result in multitarget‐directed ligands providing cognition‐enhancing properties with neuroprotective activity. On the basis of the screening of the library of 5‐HT
6 antagonists against BuChE, we selected two compounds and designed their structural modifications that could lead to improved BuChE inhibitory activity. We synthesized two series of compounds and tested their affinity and functional activity at 5‐HT
6 receptors, BuChE inhibitory activity and antioxidant properties. Compound
12 with
K
i and
K
b values against 5‐HT
6 receptors of 41.8 and 74 nM, respectively, an IC
50 value of 5 µM against BuChE and antioxidant properties exceeding the activity of ascorbic acid is a promising lead structure for further development of anti‐Alzheimer's agents.
Osteoclast‐Derived Autotaxin, a Distinguishing Factor for Inflammatory Bone Loss
Authors: Flammier Sacha , Peyruchaud Olivier , Bourguillault Fanny , Duboeuf François , Davignon Jean‐Luc , Norman Derek D. , Isaac Sylvie , Marotte Hubert , Tigyi Gabor , Machuca‐Gayet Irma , Coury Fabienne
Published: June 2019

Objective

The severity of rheumatoid arthritis (RA) correlates directly with bone erosions arising from osteoclast (OC) hyperactivity. Despite the fact that inflammation may be controlled in patients with RA, those in a state of sustained clinical remission or low disease activity may continue to accrue erosions, which supports the need for treatments that would be suitable for long‐lasting inhibition of OC activity without altering the physiologic function of OCs in bone remodeling. Autotaxin (ATX) contributes to inflammation, but its role in bone erosion is unknown.

Methods

ATX was targeted by inhibitory treatment with pharmacologic drugs and also by conditional inactivation of the ATX gene Ennp2 in murine OCs (ΔATXCtsk). Arthritic and erosive diseases were studied in human tumor necrosis factor–transgenic (hTNF+/−) mice and mice with K/BxN serum transfer–induced arthritis. Systemic bone loss was also analyzed in mice with lipopolysaccharide (LPS)–induced inflammation and estrogen deprivation. Joint inflammation and bone erosion were assessed by histology and micro–computed tomography. The role of ATX in RA was also examined in OC differentiation and activity assays.

Results

OCs present at sites of inflammation overexpressed ATX. Pharmacologic inhibition of ATX in hTNF+/− mice, as compared to vehicle‐treated controls, significantly mitigated focal bone erosion (36% decrease; P < 0.05) and systemic bone loss (43% decrease; P < 0.05), without affecting synovial inflammation. OC‐derived ATX was revealed to be instrumental in OC bone resorptive activity and was up‐regulated by the inflammation elicited in the presence of TNF or LPS. Specific loss of ATX in OCs from mice subjected to ovariectomy significantly protected against the systemic bone loss and erosion that had been induced with LPS and K/BxN serum treatments (30% reversal of systemic bone loss [P < 0.01]; 55% reversal of erosion [P < 0.001]), without conferring bone‐protective properties.

Conclusion

Our results identify ATX as a novel OC factor that specifically controls inflammation‐induced bone erosions and systemic bone loss. Therefore, ATX inhibition offers a novel therapeutic approach for potentially preventing bone erosion in patients with RA.
Associations of Gout and Baseline Serum Urate Level With Cardiovascular Outcomes: Analysis of the Coronary Disease Cohort Study
Authors: Stamp Lisa K. , Frampton Christopher , Drake Jill , Doughty Robert N. , Troughton Richard W. , Richards A. Mark
Published: June 2019

Objective

To determine whether gout and serum urate (SU) levels are associated with increased risk of death, time to first readmission for any cardiovascular event, or incident heart failure in individuals with cardiovascular disease.

Methods

Individuals presenting with an acute coronary syndrome (ACS) were enrolled in the Coronary Disease Cohort Study. Clinical data were collected from the medical records at the index hospital admission, and clinical, echocardiographic, and biochemical data were collected postdischarge. Gout was defined by self‐report, use of urate‐lowering therapy, or use of colchicine with evidence of gout on review of the medical record. The primary end points were all‐cause mortality, time to readmission for a cardiac ischemic event, and time to readmission for heart failure.

Results

Data from 1,514 participants were available. During the follow‐up period, 53 of 160 participants with gout (33.1%) and 298 of 1,354 participants without gout (22.0%) died. After adjustment for other factors known to be associated with mortality, there was no gout‐specific increase in risk of mortality (adjusted hazard ratio 0.98 [95% confidence interval 0.69–1.38]). Time to readmission for heart failure was significantly briefer in those with, compared to those without, gout (adjusted hazard ratio 1.42 [95% confidence interval 1.02–1.97]). Irrespective of whether a participant had gout or not, as SU level increased, there was an increased risk of death and readmission for either a cardiovascular event or heart failure.

Conclusion

Survival post‐ACS is similar with and without the presence of gout. People with gout are at an increased risk of readmission for heart failure and have longer hospital stays. Risk of these events increases in parallel with increases in SU levels.
Selective Synthesis of Discrete Mono‐, Interlocked‐, and Borromean Ring Ensembles Based on a π‐Electron‐Deficient Ligand
Authors: Feng Hui‐Jun , Gao Wen‐Xi , Lin Yue‐Jian , Jin Guo‐Xin
Published: June 2019

Herein, we present a new synthetic approach to achieve selective supramolecular transformations and construct different interlocked metallacycles featuring a π‐electron‐deficient thiazolo[5,4‐d]thiazole‐derived ligand. We demonstrate that the formation of mono‐rings, interlocked rings ([2]catenanes) and Borromean rings can be controlled by adjusting the length of the binuclear half‐sandwich RhIII and IrIII building blocks. Furthermore, a concentration effect or D‐A stacking interaction between the pyrene guest and the thiazolo[5,4‐d]thiazole‐based ligand promotes a unique and reversible conversion between catenane structures and metalla‐rectangles. The synthetic results are supported by single‐crystal X‐ray diffraction analysis.
Astin C Production by the Endophytic Fungus Cyanodermella asteris in Planktonic and Immobilized Culture Conditions
Authors: Vassaux Antoine , Tarayre Cédric , Arguëlles‐Arias Anthony , Compère Philippe , Delvigne Frank , Fickers Patrick , Jahn Linda , Lang Alexander , Leclère Valérie , Ludwig‐Müller Jutta , Ongena Marc , Schafhauser Thomas , Telek Samuel , Théatre Ariane , van Berkel Willem J. H. , Vandenbol Micheline , van Pée Karl‐Heinz , Willems Luc , Wohlleben Wolfgang , Jacques Philippe
Published: June 2019

The fungal endophyte Cyanodermella asteris (C. asteris) has been recently isolated from the medicinal plant Aster tataricus (A. tataricus). This fungus produces astin C, a cyclic pentapeptide with anticancer and anti‐inflammatory properties. The production of this secondary metabolite is compared in immobilized and planktonic conditions. For immobilized cultures, a stainless steel packing immersed in the culture broth is used as a support. In these conditions, the fungus exclusively grows on the packing, which provides a considerable advantage for astin C recovery and purification. C. asteris metabolism is different according to the culture conditions in terms of substrate consumption rate, cell growth, and astin C production. Immobilized‐cell cultures yield a 30% increase of astin C production, associated with a 39% increase in biomass. The inoculum type as spores rather than hyphae, and a pre‐inoculation washing procedure with sodium hydroxide, turns out to be beneficial both for astin C production and fungus development onto the support. Finally, the influence of culture parameters such as pH and medium composition on astin C production is evaluated. With optimized culture conditions, astin C yield is further improved reaching a five times higher final specific yield compared to the value reported with astin C extraction from A. tataricus (0.89 mg g−1 and 0.16 mg g−1 respectively).
BiP Inducer X: An ER Stress Inhibitor for Enhancing Recombinant Antibody Production in CHO Cell Culture
Authors: Ha Tae Kwang , Hansen Anders H. , Kildegaard Helene F. , Lee Gyun Min
Published: June 2019

Prolonged endoplasmic reticulum (ER) stress reduces protein synthesis and induces apoptosis in mammalian cells. When dimethyl sulfoxide (DMSO), a specific monoclonal antibody productivity (qmAb)‐enhancing reagent, is added to recombinant Chinese hamster ovary (rCHO) cell cultures (GSR cell line), it induces ER stress and apoptosis in a dose‐dependent manner. To determine an effective ER stress inhibitor, three ER stress inhibitors (BiP inducer X [BIX], tauroursodeoxycholic acid, and carbazole) are examined and BIX shows the best production performance. Coaddition of BIX (50 μm) with DMSO extends the culture longevity and enhances qmAb. As a result, the maximum mAb concentration is significantly increased with improved galactosylation. Coaddition of BIX significantly increases the expression level of binding immunoglobulin protein (BiP) followed by increased expression of chaperones (calnexin and GRP94) and galactosyltransferase. Furthermore, the expression levels of CHOP, a well‐known ER stress marker, and cleaved caspase‐3 are significantly reduced, suggesting that BIX addition reduces ER stress‐induced cell death by relieving ER stress. The beneficial effect of BIX on mAb production is also demonstrated with another qmAb‐enhancing reagent (sodium butyrate) and a different rCHO cell line (CS13‐1.00). Taken together, BIX is an effective ER stress inhibitor that can be used to increase mAb production in rCHO cells.
Identification of a potent indigoid persister antimicrobial by screening dormant cells
Authors: Song Sooyeon , Gong Ting , Yamasaki Ryota , Kim Jun‐Seob , Wood Thomas K.
Published: June 2019

The subpopulation of bacterial cells that survive myriad stress conditions (e.g., nutrient deprivation and antimicrobials) by ceasing metabolism, revive by activating ribosomes. These resuscitated cells can reconstitute infections; hence, it is imperative to discover compounds which eradicate persister cells. By screening 10,000 compounds directly for persister cell killing, we identified 5‐nitro‐3‐phenyl‐1H‐indol‐2‐yl‐methylamine hydrochloride (NPIMA) kills Escherichia coli persister cells more effectively than the best indigoid found to date, 5‐iodoindole, and better than the DNA‐crosslinker cisplatin. In addition, NPIMA eradicated Pseudomonas aeruginosa persister cells in a manner comparable to cisplatin. NPIMA also eradicated Staphylococcus aureus persister cells but was less effective than cisplatin. Critically, NPIMA kills Gram‐positive and Gram‐negative bacteria by damaging membranes and causing lysis as demonstrated by microscopy and release of extracellular DNA and protein. Furthermore, NPIMA was effective in reducing P. aeruginosa and S. aureus cell numbers in a wound model, and no resistance was found after 1 week. Hence, we identified a potent indigoid that kills persister cells by damaging their membranes.
Neural correlates of appreciating natural landscape and landscape garden: Evidence from an fMRI study
Authors: Zhang Wei , He Xianyou , Liu Sizhe , Li Ting , Li Jinhui , Tang Xiaoxiang , Lai Shuxian
Published: June 2019

Introduction

Rambling natural landscapes or landscape gardens may invoke positive emotions. However, the manner in which people experience landscape gardens and the cortical differences in the appreciation of the naturalness and artificiality of landscapes remain unknown.

Methods

This study scanned participants with functional magnetic resonance imaging while they viewed photographs of natural landscapes and landscape gardens and performed scene type judgment task.

Results

As predicted, we identified brain regions that were associated with perceptual process, cognitive process, and rewarding experience when appreciating natural landscapes and landscape gardens without color preference. Meanwhile, the contrast between the appreciation of landscape gardens and natural landscapes was characterized by stronger activations of the inferior occipital lobe, the left superior parietal lobule (SPL), the right fusiform gyrus, the right cuneus, and the right hippocampus.

Conclusions

Responses in these regions indicate that the appreciation of landscape gardens and natural landscapes relies on common cortical regions, and suggest the possibility that the inferior occipital lobe, the SPL, the fusiform gyrus, and the cuneus may be specifically associated with the appreciation of landscape gardens.
Issues in General Education Assessment at Community Colleges
Authors: Blevins‐Knabe Belinda
Published: June 2019

This chapter addresses key assessment issues that influence the success of assessment programs at community colleges. Suggestions for advancing general education assessment are included.
Using Community Voices to Shape Program Goals of a Community College Business Program
Authors: Roggow Michael , Farron Matthew
Published: June 2019

This article discusses ways in which a group of faculty created program goals and objectives for a business program by conducting interviews with local business leaders.
Academic Assessment: Best Practices for Successful Outcomes with Accreditation Evaluation Teams
Authors: Cumming Tammie , Miller M. David
Published: June 2019

This chapter describes the role of faculty in conducting quality assessment and includes suggestions for preparing for successful meetings with reviewers on accreditation teams.
Impact of alternative irrigation practices on rice quality
Authors: Graham‐Acquaah Seth , Siebenmorgen Terry J. , Reba Michele L. , Massey Joseph H. , Mauromoustakos Andy , Adviento‐Borbe Arlene , January Robin , Burgos Redentor , Baltz‐Gray Joanne
Published: June 2019

Background and objectives

Current global concerns about water scarcity present a need to investigate more water‐efficient rice production methods. Alternate wetting and drying (AWD) is fast emerging as a water‐saving irrigation practice, but its effects on rice quality are largely unknown. To ascertain the impact of water‐saving irrigation practices on rice quality, three irrigation treatments, namely continuous flooding with cascade delivery (four fields); continuous flooding with multiple‐inlet delivery (four fields); and AWD with multiple‐inlet delivery (four fields), were established on 12 production‐sized (16.2 ha) fields in 2017.

Findings

Results of rice quality evaluations showed that irrigation treatment had a significant (p < 0.05) effect on chalkiness. Samples harvested from the AWD fields had slightly greater mean chalkiness (5.6%) than samples harvested from the two continuously flooded fields (5.1–5.2%). Milling yields were not affected (p > 0.05) by irrigation treatments. The average milled rice and head rice yields across irrigation treatments were 73% and 59%, respectively. Regarding pasting properties, while peak and breakdown viscosities were not affected (p > 0.05) by the irrigation treatments, setback viscosity (SB), which is often linked with cooked rice texture, was impacted. Among the irrigation treatments, mean SB was least for the AWD treatment (146 cP), while the mean SB for the continuously flooded fields was similar at 168–169 cP.

Conclusions

In summary, the use of AWD with multiple‐inlet delivery did not impact milling yields of rice relative to the conventional practices of continuous flooding. However, rice harvested from the AWD treatment fields had slightly greater chalkiness and lesser SB.

Significance and novelty

This study addresses a gap in literature concerning the impact of emerging water‐saving irrigation techniques, especially AWD as it involves subjecting rice to a certain level of water stress, on rice grain quality characteristics.
Unilateral segmental Darier's disease associated with neuropsychiatric disorders
Authors: Horton Luke , Mehregan Darius
Published: June 2019

Unilateral segmental Darier's disease (DD) is a rare variant of DD that presents with erythematic lesions in a unilateral distribution without other associated features of DD. Although diagnosis is challenging, unilateral segmental DD should be considered for an acantholytic dermatosis in a unilateral distribution and a history of neuropsychiatric disorders.
Metal‐Free Hybrid of Nitrogen‐Doped Nanocarbon@Carbon Networks for Highly Efficient Oxygen Reduction Electrocatalyst
Authors: Shi Qing , Ma Yu , Qin Lin , Tang Bin , Yang Weiyou , Liu Qiao
Published: June 2019

Further improving the oxygen reduction reaction (ORR) catalytic activity of carbon catalysts is highly challenging and remains a key issue to push forward their commercial progress as Pt alternatives in fuel cells and metal‐air batteries. Herein, a facile and economic strategy was proposed to maximize the active sites exposed in porous carbon catalysts by growing dense N‐doped carbon nanonodules firmly located within carbon fiber networks (NCN@CF) via the in situ polymerization of dopamine on bacterial cellulose fibers and a subsequent carbonization process. This metal‐free hybrid catalyst exhibits enhanced ORR activity and better stabilities against long duration and the methanol crossover effect than the commercial Pt/C catalyst in 0.1 M KOH. Notably, when the NCN@CF hybrid was used as an air electrode catalyst in a Zn‐air battery, the as‐fabricated battery presented a larger peak power density of 168 mW cm−2, higher specific capacity of 720.5 mA h g−1 and energy density of 900.0 Wh kg−1 compared to those based on commercial Pt/C and most N‐doped carbon catalysts ever reported, evidencing its highly promising use as a Pt‐alternative catalyst for the ORR.
Flow‐Assisted Self‐Organization of Hybrid Membranes
Authors: Wang Qingpu , Steinbock Oliver
Published: June 2019

Microfluidic flows are a powerful tool to drive reactions far from equilibrium and, thus, induce chemical selforganization. Studies of membrane formation in microfluidic devices have been limited to non‐redox and purely inorganic reactions. Here, the formation of hybrid membranes at the interface of AgNO3 and 3,3′,5,5′‐tetramethylbenzidine solutions, which are steadily co‐injected into a microfluidic device, is reported. The membrane thickening occurs in both directions and reveals oscillatory dynamics. The hybrid membrane mainly consists of hair‐like Ag microstructures, Ag nanowires, and unbranched TMB–TMB2+ microfibers. Branched dendrite‐like fibers form on the TMB side when the flow is stopped. These components were characterized with techniques including micro‐Raman and energy dispersive X‐ray spectroscopy as well as scanning electron microscopy. The effects of initial concentration ratios on the membrane thickening speed and its opaqueness were also studied.
Asymmetric Synthesis of β2‐Aryl Amino Acids through Pd‐Catalyzed Enantiospecific and Regioselective Ring‐Opening Suzuki–Miyaura Arylation of Aziridine‐2‐carboxylates
Authors: Takeda Youhei , Matsuno Tetsuya , Sharma Akhilesh K. , Sameera W. M. C. , Minakata Satoshi
Published: June 2019

A Pd‐catalyzed enantiospecific and regioselective ring‐opening Suzuki–Miyaura arylation of aziridine‐2‐carboxylates was developed. The cross‐coupling allows for the asymmetric preparation of enantioenriched β2‐aryl amino acids, starting from commercially available enantiopure d‐ and l‐serine esters. The mechanism and selectivity of the reaction was rationalized based on computational models.
Transition‐Metal‐Free Aryl–Aryl Cross‐Coupling: C−H Arylation of 2‐Naphthols with Diaryliodonium Salts
Authors: Ghosh Manoj K. , Rzymkowski Jan , Kalek Marcin
Published: June 2019

Transition‐metal‐free regioselecitive C−H arylation of 2‐naphthols with diaryliodonium salts has been developed. The reaction proceeds under very simple experimental conditions and affords a range of products with various substitution patterns. The method allows for the incorporation of electron‐deficient aryls, which complements well currently existing metal‐free aryl–aryl cross‐couplings of phenols that have been so far restricted to the introduction of electron‐rich aryl moieties. The mechanism of the reaction was studied by means of DFT calculations, demonstrating that the C−C bond formation occurs via a dearomatization of 2‐naphthol substrate, followed by a subsequent rearomatization by tautomerization. The computations show that the use of a low polarity solvent and an insoluble inorganic base is key to securing the high selectivity of the C−C coupling over a competing C−O arylation pathway, by preventing the incipient deprotonation of 2‐naphthol.
Combining 1,3‐Ditriazolylbenzene and Quinoline to Discover a New G‐Quadruplex‐Interactive Small Molecule Active against Cancer Stem‐Like Cells
Authors: Mendes Eduarda , Cadoni Enrico , Carneiro Filipa , Afonso Marta B. , Brito Hugo , Lavrado João , dos Santos Daniel J. V. A. , Vítor Jorge B. , Neidle Stephen , Rodrigues Cecília M. P. , Paulo Alexandra
Published: June 2019

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment‐based approach to create new flexible G‐quadruplex (G4) DNA‐interactive small molecules with good calculated oral drug‐like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)‐stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose‐ and DNA sequence‐dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G‐quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′‐(4,4′‐(1,3‐phenylene)bis(1H‐1,2,3‐triazole‐4,1‐diyl))bis(1‐methylquinolin‐1‐ium) (1 d) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT‐29 cell line enriched in cancer stem‐like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.
Nivolumab in patients with advanced hepatocellular carcinoma and Child‐Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series
Authors: Kambhampati Thiruvengadam Swetha , Bauer Kelly E. , Bracci Paige M. , Keenan Bridget P. , Behr Spencer C. , Gordan John D. , Kelley Robin K.
Published: June 2019

Background

Nivolumab demonstrated durable responses and safety in patients with hepatocellular carcinoma (HCC) with Child‐Pugh class A cirrhosis in the CheckMate 040 trial, with rates of hepatotoxicity that were similar to those of non‐HCC populations. To the authors' knowledge, the safety and efficacy of nivolumab has not been established in patients with Child‐Pugh class B (CPB) cirrhosis, a population with limited therapeutic options and a poor prognosis.

Methods

The authors conducted a retrospective case series of patients with advanced HCC and CPB cirrhosis who were treated with nivolumab and enrolled in the University of California at San Francisco Hepatobiliary Tissue Bank and Registry. Safety endpoints included rates of grade ≥3 adverse events (AEs) (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]) and serious AEs, immune‐related AEs (irAE), steroid requirement, and discontinuation. Efficacy endpoints included time on treatment, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, overall survival, and progression‐free survival.

Results

A total of 18 patients were included, with 72% of them (13 of 18 patients) previously treated with sorafenib. The majority of patients (94%; 17 of 18 patients) experienced a grade ≥3 AE, with treatment‐related grade ≥3 AEs reported in 28% of patients (5 of 18 patients). irAEs were reported to occur in approximately 50% of patients (9 of 18 patients), and 28% (5 of 18 patients) required steroids. Treatment‐related AEs required discontinuation in 4 patients (22%). The median time on treatment was 2.3 months (95% CI, 1.9 months to upper bound not estimable). The objective response rate was 17% (3 of 18 patients), including 2 partial responses and 1 complete response. The median overall survival from the time of nivolumab initiation was 5.9 months (95% CI, 3 months to upper bound not estimable), with a median progression‐free survival of 1.6 months (95% CI, 1.4‐3.5 months).

Conclusions

Patients with CPB HCC experienced high rates of AEs, although the frequency of irAEs was similar to that of patients with Child‐Pugh class A HCC in the CheckMate 040 trial. A subset of patients experienced prolonged tumor responses. Nivolumab warrants further study in patients with CPB HCC.
Strategizing health technology assessment for containment of cancer drug costs in a universal health care system: Case of the pan‐Canadian Oncology Drug Review
Authors: Niraula Saroj
Published: June 2019

A universal health care system has been a source of both identity and pride for Canadians for the last 6 decades. Currently, Canada actively negotiates the prices of cancer drugs but is not immune to their overwhelming financial toxicities. Prices of cancer drugs are set to ensure maximal profit based on what the market will bear rather than by the value they offer or solely because of the cost of research and development, as often is claimed by the manufacturers. The pan‐Canadian Oncology Drug Review (pCODR) is mandated to provide funding recommendations to Canada's provinces and territories. For the most part, the pCODR has been crucial in assessing the cost‐effectiveness and feasibility of new drugs in the Canadian context but it could assist more in safeguarding payers against extreme drug costs. Herein, the author suggests a few strategies by which national efforts such as the pCODR and its partners can help Canada to become a leader in facilitating value‐based sustainable cancer care.