bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a clinical–radiomics model to predict recurrence for patients with hepatocellular carcinoma after curative resection
Authors: Ren Yiyue , Bo Linlin , Shen Bo , Yang Jing , Xu Shufeng , Shen Weiqiang , Chen Hao , Wang Xiaoyan , Chen Haipeng , Cai Xiujun
Published: October 2022

Purpose

Recurrence is the leading cause of death in hepatocellular carcinoma (HCC) patients with curative resection. In this study, we aimed to develop a preoperative predictive model based on high‐throughput radiomics features and clinical factors for prediction of long‐ and short‐term recurrence for these patients.

Methods

A total of 270 patients with HCC who were followed up for at least 5 years after curative hepatectomy between June 2014 and December 2017 were enrolled in this retrospective study. Regions of interest were manually delineated in preoperative T2‐weighted images using ITK‐SNAP software on each HCC tumor slice. A total of 1197 radiomics features were extracted, and the recursive feature elimination method based on logistic regression was used for radiomics signature building. Tenfold cross‐validation was applied for model development. Nomograms were constructed and assessed by calibration plot, which compares nomogram‐predicated probability with observed outcome. Receiver‐operating characteristic was then generated to evaluate the predictive performance of the model in the development and test cohorts.

Results

The 10 most recurrence‐free survival‐related radiomics features were selected for the radiomics signatures. A multiparametric clinical–radiomics model combining albumin and radiomics score for recurrence prediction was further established. The integrated model demonstrated good calibration and satisfactory discrimination, with the area under the curve (AUC) of 0.864, 95% CI 0.842–0.903, sensitivity of 0.889, and specificity of 0.644 in the test set. Calibration curve showed good agreement concerning 5‐year recurrence risk predicted by the nomogram. In addition, the AUC of 1‐, 2‐, 3‐, and 4‐year recurrence was 0.935 (95% CI 0.836–1.000), 0.861 (95% CI 0.723–0.999), 0.878 (95% CI 0.762–0.994), and 0.878 (95% CI 0.762–0.994) in the test set, respectively.

Conclusions

The clinical–radiomics model integrating radiomics features and clinical factors can improve recurrence predictions beyond predictions made using clinical factors or radiomics features alone. Our clinical–radiomics model is a valid method to predict recurrence that should improve preoperative prognostic performance and allow more individualized treatment decisions.
Assessing Habitat Availability in a Hydrodynamic Reservoir System
Authors: Schriener William , Koupal Keith , Wuellner Melissa , Ranglack Dustin H.
Published: October 2022

Habitats may become unavailable to fish in reservoirs at different water elevations. Coves are particularly vulnerable to habitat loss, as these peripheral zones may become isolated from the main reservoir. Quantifying habitat loss at different water elevation reductions and estimating the cost of replacing specific types of habitat or maintaining a target percentage of total habitat cover can help fisheries managers to plan for habitat restoration projects in reservoirs. We used side-scan sonar to estimate areas of rock, tree, and brush habitat in one cove within Harlan County Reservoir, Nebraska, and used quotes for materials, placement, and personnel from recent habitat restoration projects to estimate replacement and maintenance costs. Materials included riprap rock, cedar trees, and those needed to construct Georgia cubes. Overall, rock, brush, and trees covered a total of 2% of the cove at conservation pool. Rock habitat covered 10 times more area than brush and 100 times more area than trees. All habitats became unavailable when water elevation decreased by 3.5–4.0 m. The cost to replace each habitat type increased as water elevation decreased, and the total cost to replace all habitat at 3.5 m of elevation loss was US$390,000. The cost to maintain the original area of habitat available in the cove (2% of the total cove area) increased for each type of habitat but only until water elevation decreased by 2.5 m. At this point, the total cost to maintain similar habitat coverage was $219,000. Climatic variability may lead to greater oscillations of water elevations in reservoirs, making the vertical distribution of available habitat even more relevant to management planning. The findings of this study serve as an example for how managers can identify the vertical distribution of available habitats and estimate costs for habitat restorations.
The ability of critical care nurses to identify pressure injury and incontinence‐associated dermatitis: A multicentre cross‐sectional survey
Authors: Liu Huan , Du Aiping , Tian Yongming , Gao Mingrong , Ji Shuming , Mi Jie , Shao Xiaoping , Huang Debin , Cao Xiaoyi
Published: October 2022

Aim

To investigate the ability of critical care nurses to identify pressure injury and incontinence‐associated dermatitis and analyse the possible influencing factors.

Design

Cross‐sectional survey.

Methods

This study was conducted at 24 hospitals across 12 provinces in China. A self‐made electronic questionnaire was used. Nurses identified and judged injuries according to the information provided.

Results

The average identification score for pressure injury and incontinence‐associated dermatitis was 9.00 ± 3.51 points, and only 2.16% of nurses scored ≥16 points. The average correct identification rate for pressure injury and incontinence‐associated dermatitis was 45%. The correct identification rate for stage 1 pressure injury was the highest, while those for stage 3, stage 4, deep tissue pressure injury and unstageable pressure injury were all lower than 50%; incontinence‐associated dermatitis was also easily misjudged. Nurses' educational backgrounds, professional titles, job positions, hospital levels and learning frequency were the factors that affected their ability to identify pressure injury and incontinence‐associated dermatitis.
Prevalence of depression and its associated factors among stroke survivors in Saudi Arabia
Authors: Abuadas Fuad H. , Ayasrah Shahnaz M. , Ahmad Muayyad M. , Abu‐Snieneh Hana M. , Obiedallah Hayyaf F. , Basheti Iman A.
Published: October 2022

Aim

The purpose of this study was to investigate the prevalence of poststroke depression (PSD) in Saudi Arabia and its association with socio‐demographic and clinical factors.

Design

A predictive correlational cross‐sectional study.

Methods

The study adopted a non‐probability convenience sampling method to recruit 211 stroke survivors between April and October 2021 from the neurology outpatient departments of two main governmental hospitals in Saudi Arabia. PSD was measured using a self‐assessment reliable and valid scale (The Hospital Anxiety and Depression Scale [HADS]).

Results

More than two‐thirds (70.6%) of the study sample (Mean age = 53 years, SD = 8.5, 51.2% were males) experienced some degree of depression (Score ≥8); of these, approximately half (48.8%) were in severe depression. The final prediction model was statistically significant (χ2 [15] = 31.39, p ˂ .01). PSD is a statistically significant health issue and requires immediate attention by healthcare providers to improve the health outcomes of stroke survivors.
Effect of multi‐walled carbon nanotube localization on toughening mechanism and electrical properties of compatibilized PP/EOC immiscible blend
Authors: Morshedi Fatemeh , Tarashi Sara , Nazockdast Hossein
Published: October 2022

Toughness modification of polypropylene (PP), a widely used polymer in industry, is an important factor in overcoming mechanical limitations and extending its scope of application. In the present work, we utilized a combination of nanoparticle and elastomer techniques to enhance the toughness of PP. Accordingly, the nanocomposite blends, including PP, ethylene octene copolymer (EOC), and multi‐walled carbon nanotubes (MWCNTs), were prepared through three different feeding methods (direct, sequential, and masterbatch). The results demonstrated that the different feeding methods significantly affect the localization and dispersion degree of the MWCNTs, and hence, toughness modification. The results also showed that the sequential is the most effective method to prepare the nanocomposites with the reinforced fracture toughness so that the addition of 2 phr MWCNTs to the PP/EOC blend leads to a high impact strength (=351.61 J/m). Because in this feeding method, most of the highly dispersed MWCNTs can be selectively located in the EOC particles as well as the interface, which can not only intensify the interfacial interactions between the two phases but also help the stress transfer and superposition of stress fields. Moreover, it was shown that in the sequential method, the MWCNTs could facilitate the creation of electrically conductive pathways as a result of nanoparticle bridging and the formation of an interconnected percolating network, therefore increasing the electrical properties.
Utilization of nonguideline concordant antibiotic treatment following acute otitis media in children in the United States
Authors: McGrath Leah J. , Frost Holly M. , Newland Jason G. , O'Neil Caroline A. , Sahrmann John M. , Ma Yinjiao , Butler Anne M.
Published: October 2022

Purpose

Acute otitis media (AOM) is a common indication for antibiotics in children. We sought to characterize the frequency of nonguideline concordant antibiotic therapy for AOM in the United States, by agent and duration.

Methods

Using national administrative claims data (2016–2019), we identified children aged 6 months to 17 years with an oral antibiotic dispensed within 3 days of a new diagnosis of suppurative AOM. Use of nonguideline concordant agents and durations, defined based on national treatment guidelines, were summarized by age, race, rurality, region, and insurance type. Subsequent oral antibiotic dispensing within the year after AOM diagnosis was also evaluated. We created sunburst diagrams to visualize longitudinal patterns of within‐person antibiotic utilization for AOM, by agent and duration.

Results

We identified 789 424 eligible commercially‐insured and 502 239 medicaid‐insured children. Among commercially insured children, 35% received nonguideline concordant agents for AOM, including cefdinir (16%), amoxicillin‐clavulanate (12%), and azithromycin (7%). Fewer children age <2 years received a nonguideline concordant initial agent (27%) compared to age ≥6 years (41%). More children age <2 years received three or more antibiotics over the following year (34% vs. 3% for children age ≥6 years). The most common treatment duration was 10 days for all ages; treatment duration for the initial antibiotic was nonguideline concordant for 95% and 89% of children age 2–5 years and ≥6 years, respectively. Patterns were similar for medicaid‐insured children.

Conclusions

Nonguideline concordant antibiotic use is common when treating AOM in children, including use of broad‐spectrum agents and longer‐than‐recommended antibiotic durations.
The mental health and suicide prevention training module of the French sanitary service: Effectiveness on health students
Authors: Wathelet Marielle , Dezetree Arnaud , Guénard Cécile , Duhem Stéphane , Chouraki Vincent , Thomas Pierre , Aly Pierrine , Notredame Charles‐Edouard
Published: October 2022

Since 2018, a Sanitary Service for Health Students (SSHS) is being implemented throughout France. All French health students must complete their SSHS choosing one of the modules proposed by their institution to be trained to the principles of prevention and then bring them to carry out prevention and health promotion actions in their respective region. A controlled pre/postdesign was conducted to assess the impact of the Mental Health and Suicide Prevention (MHSP) training module on health students. Students assigned to this module were considered as exposed, and students assigned to any other module as unexposed. Health students from the Nord‐Pas‐de‐Calais region involved in the SSHS during the school year 2018–2019 were asked to answer a self‐administered questionnaire before (September 2018), and after completing their SSHS (May 2019). A total of 144 matched participants (48 in the exposed group and 96 in the unexposed group) were analyzed. When comparing the exposed group to the unexposed group, satisfaction with the training was greater (4.7 vs. 3.6 out of 5, p < 0.001), self‐confidence in professional capacities improved (+1.8 vs. −0.2, p = 0.038), students were more likely to report having identified (68% vs. 48%, p = 0.043) or helped (66% vs. 18%, p < 0.001) someone, as well as having consulted for a mental health issue (13% vs. 4%, p = 0.008). In conclusion, the MHSP training module improves health students' confidence in their professional abilities to help distressed people, promotes supportive behaviors of health students, and reinforces their help‐seeking behaviors. It could be a useful tool for suicide prevention.
Development of a candidate item bank for measuring mobility of lower limb orthosis users
Authors: Balkman Geoffrey S. , Morgan Sara J. , Amtmann Dagmar , Baylor Carolyn , Hafner Brian J.
Published: October 2022

Background

Orthoses are often prescribed to improve mobility of people with chronic health conditions that affect lower limb function. Patient‐reported survey instruments can be used to measure aspects of mobility that cannot be easily assessed in clinical or research settings. A population‐specific item bank could be designed to measure aspects of mobility that are most important to lower limb orthosis users and used to evaluate the effects of orthoses.

Objective

To develop items for a new survey instrument to measure mobility of lower limb orthosis users.

Design

Survey items were developed using a qualitative item review process.

Setting

Focus groups were held by video conferencing. Cognitive interviews were conducted by telephone.

Participants

Focus group and cognitive interview participants were adults with at least 6 months of experience using a lower limb orthosis that extended from the foot to a level above the ankle.

Methods

Research methods included focus groups with lower limb orthosis users, an item generation and reduction process that involved a stakeholder advisory panel, and cognitive interviews with target respondents.

Results

A total of 1180 extant items were identified in a literature review. Focus group participants (n = 29) provided feedback that informed the suitability of a construct definition and conceptual model. An advisory panel contributed to the selection of 118 candidate items for measuring orthotic mobility. Feedback from cognitive interview participants (n = 30) informed removal or revision of problematic items, resulting in a candidate bank of 100 mobility items.

Conclusions

The rigorous qualitative methods applied here resulted in a large set of candidate items that spanned a range of situations relevant to moving with a lower limb orthosis. Next steps include administration of the candidate items to a large sample of lower limb orthosis users and calibration of the item bank.
People with mild Parkinson's disease have impaired force production in upper limb muscles: A cross‐sectional study
Authors: Salmon Renee , Preston Elisabeth , Mahendran Niruthikha , Ada Louise , Flynn Allyson
Published: October 2022

Background

There has been little examination of force production of the upper limb in people with Parkinson's disease (PD), despite its impact on activities of daily living and clear evidence that force production is significantly reduced in lower limb muscle groups. The aim of this study was to determine the force production of the major muscle groups of the upper limb in people with PD during the “on” phase after medication, compared with aged‐matched neurologically‐normal controls.

Method

A cross‐sectional study was carried out.

Participants

Thirty people with mild PD (Hoehn Yahr mean 1.1) and 24 age‐matched neurologically‐normal controls.

Outcome measures

Maximum isometric force production of the shoulder flexors, extensors, abductors, adductors, internal rotators and external rotators, elbow flexors and extensors, wrist flexors and extensors and hand grip using dynamometry.

Results

There was a significant impairment in force production in all upper limb muscle groups, compared with control participants, except in the wrist flexors. On average the deficit in force production was 22%, despite people with PD having mild disease, being physically active and being measured during the “on” phase of medication. The most severely affected muscle groups were the upper limb extensors.

Conclusion

People with PD have a significant deficit in force production of the upper limb muscle groups compared with age‐matched neurologically normal controls.

Clinical Implications

Regular assessment of strength of the upper limb should be considered by clinicians and strengthening interventions could be implemented if a deficit is identified.
Failure by design: lessons from the recently rescinded light brown apple moth (Epiphyas postvittana) eradication program in California
Authors: Carey James R. , Harder Daniel , Zalom Frank , Wishner Nan
Published: October 2022

This article was motivated by the US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) announcement that on 17 December 2021 it rescinded Federal Orders of 2 May 2007 that regulated (what was believed to be) a new outbreak of the light brown apple moth (LBAM, Epiphyas postvittana (Walker)) in the mainland United States. Our article follows from, and builds on, a 2013 article published by Carey and Harder that outlined major concerns about the LBAM eradication program including the need, cost, safety, practicality, and feasibility of the program and the public opposition to it. The program began with an emergency order based on USDA claims of billions of dollars in potential crop losses and the need to circumvent safety review processes to urgently prevent the pest's establishment. The program ended with the realization by government decision‐makers, 14 years after initiating the program, that LBAM posed no quarantine‐level threat in the first place and with no evidence of any economic damage done by the insect. This article summarizes the mistakes made in devising and carrying out what has ultimately proven to be one of the most oversold, overhyped, misguided, ill‐advised, unnecessary, and costly programs in the recent history of insect eradication programs in California. Termination of the LBAM program by USDA‐APHIS presents an opportunity to review the program to identify lessons learned and provide recommendations to help avoid similar mistakes in future invasive species response programs. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Synthesis and Characterization of All‐Inorganic Perovskite CsEuBr3 Single‐Crystal Scintillator
Authors: Wen Xuemin , Wang Qian , Li Wen , Li Yunyun , Cheng Shuangliang , Wang Jingkang , Kurosawa Shunsuke , Wu Yuntao
Published: October 2022

All‐inorganic halide perovskites appear as a promising class of scintillators for radiation detection applications due to their excellent optoelectronic properties. Herein, a self‐activated perovskite CsEuBr3 single crystal is developed as an efficient X‐ and γ‐ray scintillator. Single crystals of CsEuBr3 are grown by the Bridgman method. The phase structure, stability, photophysics properties, and scintillation performance of CsEuBr3 single crystals are studied. Under X‐ray irradiation, its emission peaks at 445 and 510 nm, associated with Eu2+ 5d–4f and defect‐related emission, respectively, are studied. Under 137Cs gamma irradiation, it has a decent light yield of 22 000 ± 2000 photons MeV−1 and an energy resolution of 6.2 ± 0.4% at 662 keV with a scintillation decay of 510 ns.
Development of a rapid, in‐situ analysis method using sheath‐flow probe electrospray ionisation‐mass spectrometry for the direct identification of cocaine metabolites in dried blood spots
Authors: Kim Ayoung , Kelly Paul F. , Turner Matthew A. , Reynolds James C.
Published: October 2022

Rationale

Small amounts of biofluid samples are frequently found at crime scenes; however, existing gold standard methods such as LC–MS frequently require destructive extraction of the sample before a time‐consuming analysis which puts strain on forensic analysis providers and can preclude further sample analysis. This study presents the application of sheath‐flow probe electrospray ionization‐mass spectrometry (sfPESI–MS) to the direct analysis of drug metabolites in dried blood spots (DBS) as a high throughput, minimally destructive alternative.

Methods

A rapid direct analysis method using a sfPESI ionisation source coupled to an Orbitrap Exactive mass spectrometer was applied to detect cocaine metabolites (benzoylecgonine, BZE, cocaethylene, CE, and ecgonine methyl ester, EME) from DBS. An optimisation study exploring the use of different chemical modifiers (formic acid and sodium acetate) in the sfPESI probe extraction solvent was conducted to enhance the sensitivity and reproducibility of the sfPESI–MS method.

Results

Optimisation of the extraction solvent significantly enhanced the sensitivity and reproducibility of the sfPESI–MS method. A quantitative response over a five‐point calibration range 0.5 to 10 μg/ml was obtained for BZE (R2 = 0.9979) and CE (R2 = 0.9948). Limits of detection (LOD) of 1.31, 0.29 and 0.15 μg/ml were achieved for EME, BZE and CE, respectively, from 48 h aged DBSs with % RSD (relative standard deviation) across the calibration range ranging between 19%–28% for [BZE + H]+, 13%–21% for [CE + H]+ and 12%–29% for [EME + H]+.

Conclusions

A rapid (< 20 s) quantitative method for the direct analysis of cocaine metabolites from DBS which requires no prior sample preparation was developed. Although the LOD achieved for BZE (LOD: 0.29 μg/ml) was above the UK threshold limit of exposure for drug driving (0.05 μg/ml), the method may be suitable for use in identifying overdose in forensic analysis.
Identification and characterization of stress degradation products of febuxostat employing ultra‐performance liquid chromatography‐ultraviolet/photodiode array and liquid chromatography–mass spectrometry/time‐of‐flight studies
Authors: Saha Madhurima , Bali Alka , Patra Smruti Ranjan , Singh Joga
Published: October 2022

Rationale

Febuxostat (FEB) is a xanthine oxidase inhibitor approved by the U.S. Food and Drug Administration for long‐term treatment of gout and hyperuricemia. There were no reports on identification and characterization of stress degradation products of the drug.

Methods

FEB was subjected to forced decomposition conditions such as hydrolysis (neutral, acidic, and alkaline), oxidation, photolysis, and thermal stress, per the ICH guideline Q1A(R2). The degradation products formed were subjected to ultra‐performance liquid chromatography (UPLC) on a C18 Kinetex column (100 × 4.6 mm, 2.6 μm) using isocratic elution method. Detection wavelength was 317 nm. The developed method was extended to UPLC–mass spectrometry/time of flight (MS/TOF) studies to identify and characterize the degradation products.

Results

The drug exhibited significant degradation under alkaline/neutral hydrolytic, alkaline/acidic photolytic, and oxidative conditions, whereas it remained stable under acid hydrolytic, neutral photolytic, and thermal conditions. In total, eight degradation products (I–VIII) were formed, which could be adequately determined from the drug using the developed UPLC method. Of the eight degradation products identified from the liquid chromatography‐ultraviolet (LC‐UV) chromatogram, five (III and IV and VI–VIII) could be characterized using their MS/TOF spectral data. The degradation pathway leading to the formation of the products was postulated, and this is not reported so far.

Conclusions

Forced degradation studies were conducted on FEB, and the degradation products produced were identified by their mass spectral data obtained using LC–MS studies.
PtCuRu Nanoflowers with Ru‐Rich Edge for Efficient Fuel‐Cell Electrocatalysis
Authors: Qiao Meng , Meng Fan‐Yi , Wu Hao , Wei Yan , Zeng Xiao‐Fei , Wang Jie‐Xin
Published: October 2022

Enhancing the catalytic activity of Pt‐based alloy by a rational structural design is the key to addressing the sluggish kinetics of direct alcohol fuel cells. Herein, a facile one‐pot method is reported to synthesize PtCuRu nanoflowers (NFs). The synergetic effect among Pt, Cu, and Ru can lower the d‐band center of Pt, regulate the morphology, generate Ru‐rich edge, and allow the exposure of more high index facets. The optimized Pt0.68Cu0.18Ru0.14NFs exhibit outstanding electrocatalytic performances and excellent anti‐poisoning abilities. The specific activities for the methanol oxidation reaction (MOR) (7.65 mA cm−2) and ethanol oxidation reaction (EOR) (7.90 mA cm−2) are 6.0 and 7.1 times higher than commercial Pt/C, respectively. The CO stripping experiment and the chronoamperometric (5000 s) demonstrate the superior anti‐poisoning property and durability performance. Density functional theory calculations confirm that high metallization degree leads to the decrease of d‐band center, the promotion of oxidation of CO, and improvement of the inherent activity and anti‐poisoning ability. A Ru‐rich edge exposes abundant high index facets to accelerate the reaction kinetics of rate‐determining steps by decreasing the energy barrier for forming *HCOOH (MOR) and CC bond breaking (EOR).
Study on Wear Resistance Performance along the Thickness Direction of In Situ TiC‐Reinforced High‐Strength Steel
Authors: Ning Bo , Niu Gang , Yu Xinpan , Gong Na , Wu Huibin
Published: October 2022

The hardness of high‐strength steel gradually decreases from the subsurface layer to the layer that is half its thickness. This hardness distribution reduces the wear resistance of steel plates. To date, there have been few reported solutions to this problem. Herein, an in situ approach is used to prepare TiC‐reinforced steel. The findings demonstrate that the introduction of TiC reinforcement enhances the wear resistance performance along the thickness direction of high‐strength steel. Although the hardness of TiC‐reinforced steel gradually decreases from the surface to the core, the wear resistance of the steel initially increases before decreasing. In addition, compared with normal steel, the wear resistance performance of TiC‐reinforced steel is increased by 15% at the subsurface, 24% at 1/4 thickness, and 31% at 1/2 thickness. This unusual phenomenon is attributed to the size features of TiC, which vary along the thickness of the plate. The proportion of small TiC particles decreases from the subsurface layer to the core, whereas the proportion of large TiC particles increases gradually. This technique can provide an avenue for improving the wear resistance of other large‐thickness wear‐resistant materials along the thickness direction.
The tension between state ownership and private quasi‐property rights in water
Authors: Bosch Hilmer J. , Gupta Joyeeta
Published: October 2022

A critical legal issue in water governance is who owns and who holds property rights in water. Hence, we address the question: How has the state of legal knowledge on private property rights in water evolved worldwide, and how are these rights embedded in the current existing legal constructions? In answering the question, this article reviews the legal literature to: (i) understand the current state of water ownership and water property rights in the main legal systems, (ii) understand and capture how private water “property” rights are embedded in the existing legal constructions; and (iii) reflect on the application of these rights in practice. We conclude: (a) While most states have placed water in the public domain, past statutory systems of water rights are difficult to abolish, and increasingly Indigenous peoples are successfully demanding recognition of, and reclaiming their water rights. (b) States are (re)allocating water rights through statutory mechanisms, including clearly defined bundle‐of‐rights. And (c), while the state ostensibly controls the water, the allocation of water through historic and new statutory instruments “encroaches” on state water ownership, and has created confusion affecting the state's power to adaptively govern the water. This confusion reflects the tension between the need of states to own and govern water in the public interest, the rights of Indigenous peoples to their water, with the need of agriculture and industries to have reliable supplies of water, leading to water use rights that imply “quasi‐property” rights in water.

This article is categorized under:

Human Water > Water Governance

Human Water > Rights to Water
Rare‐Earth Hydroxometalates Ba[RE(OH)5] with RE=Tb, Dy, Ho
Authors: Li Yuxi , Albrecht Ralf , Ruck Michael
Published: October 2022

Colorless crystals of the new hydroxometalates Ba[RE(OH)5] with the rare‐earth elements RE=Tb, Dy, Ho were synthesized under ultra‐alkaline conditions in a KOH hydroflux at 200 °C. Single‐crystal X‐ray diffraction revealed that the three compounds crystallize isostructural in the monoclinic space group P21/n (no. 14). In the crystal structure, the rare‐earth cations are coordinated by the oxygen atoms of seven hydroxide anions, which define a distorted pentagonal bipyramid. These polyhedra share edges of their basal ring forming infinite chains that run parallel to the [010] direction. Hydrogen bonds connect the chains into layers parallel to the (101) plane. The Ba2+ cations are located between these layers and surrounded by nine oxygen atoms. Ba[Dy(OH)5] is paramagnetic and shows no luminescence under UV light. When heated in synthetic air or argon, water is released in well‐defined steps. Ba[Dy(OH)5] decomposes via DyOOH to Dy2O3, which then reacts with the remaining Ba(OH)2 to form BaDy2O4. Thus, the hydroxometalates can be used as carbon‐free precursors for oxides.
Introduction to Organization, Leadership, and Change in ODDE
Authors: Paul Ross
Published: October 2022

This chapter provides an overview of the 11 other chapters in Section III of the Handbook which address issues of Organisation, Leadership and Change. It pays particular attention to the impact of the Covid-19 pandemic on perceptions of ODDE, noting both the benefits of the greatly enhanced international interest in on-line learning and the negative perceptions associated with its misuse during the sudden demand for emergency remote teaching in conventional educational institutions. It envisions a blurring of distinctions between conventional and ODDE institutions with consequent opportunities for the latter. While these issues are pursued through various perspectives in the Section III chapters, there is a unifying theme of the critical importance of institutional leadership throughout and a concomitant focus on how leadership has to change in a rapidly evolving international context. The chapter envisions a bright future for ODDE but only if critical issues of institutional leadership are addressed and if those leading conventional institutions are made aware of the research and experience emanating from the established ODDE sector.
Introduction to Design, Delivery, and Assessment in ODDE
Authors: West Richard E.
Published: October 2022

This chapter overviews the 14 chapters in Section VI of theHandbook,which are focused on the design, delivery, and assessment of open, online, and digital learning. While the chapters address a wide variety of factors relevant to ODDE, I discuss several common themes, including evidence for the effectiveness of ODDE, standards to guide effective ODDE design, assessment and credentialing of ODDE learning, and the need for future research to move beyond studying individual factors (micro level) in higher education. Finally, I conclude with a call to how we can design the future of ODDE, including first, seeking to understand systemic nature of learning; second, embracing the sociocultural nature of learning, and third, utilizing the full repertoire of diverse scholarship methods to develop knowledge in our field.
Characterization of microtubule-associated protein tau isoforms and Alzheimer’s disease-like pathology in normal sheep (Ovis aries): relevance to their potential as a model of Alzheimer’s disease
Authors: Davies Emma S. , Morphew Russell M. , Cutress David , Morton A. Jennifer , McBride Sebastian
Published: October 2022

Alzheimer’s disease is a chronic neurodegenerative disease that accounts for up to 80% of all dementias. Characterised by deteriorations of memory and cognitive function, the key neuropathological features are accumulations of β-amyloid and hyperphosphorylated tau, as ‘plaques’ and ‘tangles’, respectively. Despite extensive study, however, the exact mechanism underlying aggregate formation in Alzheimer’s disease remains elusive, as does the contribution of these aggregates to disease progression. Importantly, a recent evaluation of current Alzheimer’s disease animal models suggested that rodent models are not able to fully recapitulate the pathological intricacies of the disease as it occurs in humans. Therefore, increasing attention is being paid to species that might make good alternatives to rodents for studying the molecular pathology of Alzheimer’s disease. The sheep (Ovis aries) is one such species, although to date, there have been few molecular studies relating to Alzheimer’s disease in sheep. Here, we investigated the Alzheimer’s disease relevant histopathological characteristics of 22 sheep, using anti-β-amyloid (Abcam 12267 and mOC64) and phosphorylation specific anti-tau (AT8 and S396) antibodies. We identified numerous intraneuronal aggregates of both β-amyloid and tau that are consistent with early Alzheimer’s disease-like pathology. We confirmed the expression of two 3-repeat (1N3R, 2N3R) and two 4-repeat (1N4R, 2N4R) tau isoforms in the ovine brain, which result from the alternative splicing of two tau exons. Finally, we investigated the phosphorylation status of the serine396 residue in 30 sheep, and report that the phosphorylation of this residue begins in sheep aged as young as 2 years. Together, these data show that sheep exhibit naturally occurring β-amyloid and tau pathologies, that reflect those that occur in the early stages of Alzheimer’s disease. This is an important step towards the validation of the sheep as a feasible large animal species in which to model Alzheimer’s disease.
Clonogenic assays improve determination of variant allele frequency of driver mutations in myeloproliferative neoplasms
Authors: Kalmer Milena , Pannen Kristina , Lemanzyk Rebecca , Wirths Chiara , Baumeister Julian , Maurer Angela , Kricheldorf Kim , Schifflers Joelle , Gezer Deniz , Isfort Susanne , Brümmendorf Tim H. , Koschmieder Steffen , Chatain Nicolas
Published: October 2022

Molecular diagnostics moves more into focus as technology advances. In patients with myeloproliferative neoplasms (MPN), identification and monitoring of the driver mutations have become an integral part of diagnosis and monitoring of the disease. In some patients, none of the known driver mutations (JAK2V617F, CALR, MPL) is found, and they are termed “triple negative” (TN). Also, whole-blood variant allele frequency (VAF) of driver mutations may not adequately reflect the VAF in the stem cells driving the disease. We reasoned that colony forming unit (CFU) assay–derived clonogenic cells may be better suited than next-generation sequencing (NGS) of whole blood to detect driver mutations in TN patients and to provide a VAF of disease-driving cells. We have included 59 patients carrying the most common driver mutations in the establishment or our model. Interestingly, cloning efficiency correlated with whole blood VAF (p = 0.0048), suggesting that the number of disease-driving cells correlated with VAF. Furthermore, the clonogenic VAF correlated significantly with the NGS VAF (p < 0.0001). This correlation was lost in patients with an NGS VAF <15%. Further analysis showed that in patients with a VAF <15% by NGS, clonogenic VAF was higher than NGS VAF (p = 0.003), suggesting an enrichment of low numbers of disease-driving cells in CFU assays. However, our approach did not enhance the identification of driver mutations in 5 TN patients. A significant correlation of lactate dehydrogenase (LDH) serum levels with both CFU- and NGS-derived VAF was found. Our results demonstrate that enrichment for clonogenic cells can improve the detection of MPN driver mutations in patients with low VAF and that LDH levels correlate with VAF.
Essential thrombocythaemia progression to the fibrotic phase is associated with a decrease in JAK2 and PDL1 levels
Authors: Lewandowski Krzysztof , Kanduła Zuzanna , Gniot Michał , Paczkowska Edyta , Nawrocka Paulina Maria , Wojtaszewska Marzena , Janowski Michał , Mariak Magdalena , Handschuh Luiza , Kozlowski Piotr
Published: October 2022

It has been postulated that the changes in the molecular characteristics of the malignant clone(s) and the abnormal activation of JAK-STAT signaling are responsible for myeloproliferative neoplasm progression to more advanced disease phases and the immune escape of the malignant clone. The continuous JAK-STAT pathway activation leads to enhanced activity of the promoter of CD274 coding programmed death-1 receptor ligand (PD-L1), increased PD-L1 level, and the immune escape of MPN cells. The aim of study was to evaluate the PDL1 mRNA and JAK2 mRNA level in molecularly defined essential thrombocythaemia (ET) patients (pts) during disease progression to post-ET- myelofibrosis (post-ET-MF). The study group consisted of 162 ET pts, including 30 pts diagnosed with post-ET-MF. The JAK2V617F, CALR, and MPL mutations were found in 59.3%, 19.1%, and 1.2% of pts, respectively. No copy-number alternations of the JAK2, PDL1, and PDCDL1G2 (PDL2) genes were found. The level of PD-L1 was significantly higher in the JAK2V617F than in the JAK2WT, CALR mutation-positive, and triple-negative pts. The PD-L1 mRNA level was weakly correlated with both the JAK2V617F variant allele frequency (VAF), and with the JAK2V617F allele mRNA level. The total JAK2 level in post-ET-MF pts was lower than in ET pts, despite the lack of differences in the JAK2V617F VAF. In addition, the PD-L1 level was lower in post-ET-MF. A detailed analysis has shown that the decrease in JAK2 and PDL1 mRNA levels depended on the bone marrow fibrosis grade. The PDL1 expression showed no differences in relation to the genotype of the JAK2 haplotypeGGCC_46/1, hemoglobin concentration, hematocrit value, leukocyte, and platelet counts. The observed drop of the total JAK2 and PDL1 levels during the ET progression to the post-ET-MF may reflect the changes in the JAK2V617F positive clone proliferative potential and the PD-L1 level–related immunosuppressive effect. The above-mentioned hypothesis is supported by The Cancer Genome Atlas (TCGA) data, confirming a strong positive association between CD274 (encoding PD-L1), CXCR3 (encoding CXCR3), and CSF1 (encoding M-CSF) expression levels, and recently published results documenting a drop in the CXCR3 level and circulating M-CSF in patients with post-ET-MF.
Both radiographical and pathological lymph node statuses are independent predictors for survival following neoadjuvant chemotherapy and radical cystectomy for cT3/4 or cN+ bladder cancer
Authors: Wagner Julia , Simon Ricarda , Büchler Jakob Wolf , Kirchhoff Florian , Kehl Viktoria , Retz Margitta , Gschwend Juergen Erich , Sauter Andreas , Horn Thomas
Published: October 2022

Introduction

Urothelial bladder cancer (UBC) with clinical suspicion of locally advanced growth or pelvic lymphogenic spread has a high risk of progression and death.

Patients and methods

Bladder cancer patients with locally advanced (cT3/4) tumor growth or suspected pelvic lymphogenic spread (cN+) were treated with preoperative cisplatin-containing chemotherapy and consolidative cystectomy with pelvic lymphadenectomy. We aimed to identify prognostic factors and describe the patients’ oncological outcome.

Results

A complete dataset including follow-up data was available for 96 patients. In a univariate analysis, we identified cN stage (cN+ vs cN-, HR 2.7, 95% CI 1.3–6.0), response to chemotherapy (HR 0.2, 95% CI 0.1–0.5), ypT stage (ypT0/is/1 vs ypT2-4, HR 3.1, 95% CI 1.4–6.8), ypN stage (ypN + vs ypN-, HR 7.9, 95% CI 3.7–17.0), resection status (HR 4.4, 95% CI HR 1.5–13.0) as significantly associated with cancer-specific survival. In a multivariate regression analysis, both cN and ypN statuses were validated as independent prognostic factors for cancer-specific survival (cN: HR 2.6, 95% CI 1.1–6.1; ypN: HR 5.5, 95% CI 2.0–15.1).

Discussion

Lymph node status was identified as a prognostic marker in a high-risk cohort of UBC patients treated with inductive chemotherapy and cystectomy. Establishing cN status as a prognosticator underlines the necessity to aggressively treat these patients despite reported impreciseness of imaging procedures in UCB. Patients with histologically positive lymph nodes following preoperative chemotherapy have a very poor prognosis, and thus, the need for adjuvant systemic treatment is emphasized.

Conclusion

Both clinically and pathologically affected lymph nodes convey a poor prognosis in bladder cancer and necessitate aggressive treatment.
Comparative psychophysics of Western honey bee (Apis mellifera) and stingless bee (Tetragonula carbonaria) colour purity and intensity perception
Authors: Koethe Sebastian , Reinartz Lara , Heard Tim A. , Garcia Jair E. , Dyer Adrian G. , Lunau Klaus
Published: October 2022

Bees play a vital role as pollinators worldwide and have influenced how flower colour signals have evolved. The Western honey bee, Apis mellifera (Apini), and the Buff-tailed bumble bee, Bombus terrestris (Bombini) are well-studied model species with regard to their sensory physiology and pollination capacity, although currently far less is known about stingless bees (Meliponini) that are common in pantropical regions. We conducted comparative experiments with two highly eusocial bee species, the Western honey bee, A. mellifera, and the Australian stingless bee, Tetragonula carbonaria, to understand their colour preferences considering fine-scaled stimuli specifically designed for testing bee colour vision. We employed stimuli made of pigment powders to allow manipulation of single colour parameters including spectral purity (saturation) or colour intensity (brightness) of a blue colour (hue) for which both species have previously shown innate preferences. Both A. mellifera and T. carbonaria demonstrated a significant preference for spectrally purer colour stimuli, although this preference is more pronounced in honey bees than in stingless bees. When all other colour cues were tightly controlled, honey bees receiving absolute conditioning demonstrated a capacity to learn a high-intensity stimulus significant from chance expectation demonstrating some capacity of plasticity for this dimension of colour perception. However, honey bees failed to learn low-intensity stimuli, and T. carbonaria was insensitive to stimulus intensity as a cue. These comparative findings suggest that there may be some common roots underpinning colour perception in bee pollinators and how they interact with flowers, although species-specific differences do exist.
Internal multi-centennial variability of the Atlantic Meridional Overturning Circulation simulated by EC-Earth3
Authors: Meccia Virna L. , Fuentes-Franco Ramón , Davini Paolo , Bellomo Katinka , Fabiano Federico , Yang Shuting , von Hardenberg Jost
Published: October 2022

We report a multi-centennial oscillation of the Atlantic Meridional Overturning Circulation (AMOC) simulated by the EC-Earth3 climate model under the pre-industrial climate. This oscillation has an amplitude of ~ 6 Sv and a period of ~ 150 years and significantly impacts the atmosphere. We find that it is a self-sustained low-frequency internal variability, driven by the accumulation of salinity anomalies in the Arctic and their release into the North Atlantic, affecting the water column stability and the deep convection. Sea ice plays a major role in creating the salinity anomaly in the Arctic, while the anomalous Arctic oceanic circulation, which drives the exchange of liquid freshwater between the Arctic and the open ocean, is the main responsible for its southward propagation. Interestingly, EC-Earth3 simulations with increased greenhouse concentrations, and therefore under a warmer climate, do not exhibit these strong AMOC fluctuations. We hypothesize that in a quasi-equilibrium climate with a global air surface temperature 4.5° higher than the pre-industrial period, the low amount of sea ice in the high latitudes of the North Atlantic is no longer able to trigger the mechanism.
Groundwater and climate change: threats and opportunities
Authors: Stigter Tibor Y. , Miller Jodie , Chen Jianyao , Re Viviana
Published: October 2022

The important role of groundwater in adaptation to climate change is explored, and the competing threats and opportunities that climate change pose to groundwater systems are evaluated. This has been achieved through a review of current thinking on the complex interactions between human activities, climate and the hydrological cycle affecting groundwater quantity and quality, across different regions and time scales.
Characterizing cyclin-dependent kinase 12(CDK12)-altered aggressive prostate cancer: a twelve-case series
Authors: Iwasawa Tomohiro , Kosaka Takeo , Yasumizu Yota , Hongo Hiroshi , Yanai Yoshinori , Baba Yuto , Matsumoto Kazuhiro , Nakamura Kohei , Nishihara Hiroshi , Oya Mototsugu
Published: October 2022

Background

Prostate cancer harboring cyclin-dependent kinase 12 (CDK12) abnormalities is a hot topic due to its distinctive clinical features, such as sensitivity to immune checkpoint inhibitors. In the last few years, precision medicine using comprehensive genome sequencing has become familiar, and the era of precision oncology has arrived in the field of prostate cancer. This study aimed to present the demographic characteristics of patients with CDK12 alterations.

Methods

In 12 patients with detected CDK12 alterations in our hospital between 2015 and 2021, we evaluated their genomic features and clinical course. CDK12 allelic status was classified into three groups: monoallelic loss, potentially biallelic loss, and biallelic loss based on the genome analyses.

Results

Seven patients already had metastatic cancer at the time of diagnosis, and all 12 patients had Gleason grade  ≥ 4. Most cases of biallelic loss or potentially biallelic loss were metastatic cancers at the initial staging, and all these cases were categorized into Gleason grade 5. Two of the 12 patients had BRCA2/RB1 co-loss, and the other two had whole genome duplication. Five patients had a long-term survival of  > 6 years, but two patients died within 4 years of diagnosis.

Conclusion

This is the first Japanese prostate cancer case series with CDK12 alterations. CDK12-altered prostate cancer is a heterogeneous disease, and accumulating cases with detailed information leads to precision oncology.