bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empowering drug development: Leveraging insights from imaging technologies to enable the advancement of digital health technologies
Authors: Izmailova Elena S. , Maguire R. Paul , McCarthy Timothy J. , Müller Martijn L. T. M. , Murphy Philip , Stephenson Diane 
Published: November 2022

AbstractThe US Food and Drug Administration (FDA) has publicly recognized the importance of improving drug development efficiency, deeming translational biomarkers a top priority. The use of imaging biomarkers has been associated with increased rates of drug approvals. An appropriate level of validation provides a pragmatic way to choose and implement these biomarkers. Standardizing imaging modality selection, data acquisition protocols, and image analysis (in ways that are agnostic to equipment and algorithms) have been key to imaging biomarker deployment. The best known examples come from studies done via precompetitive collaboration efforts, which enable input from multiple stakeholders and data sharing. Digital health technologies (DHTs) provide an opportunity to measure meaningful aspects of patient health, including patient function, for extended periods of time outside of the hospital walls, with objective, sensor‐based measures. We identified the areas where learnings from the imaging biomarker field can accelerate the adoption and widespread use of DHTs to develop novel treatments. As with imaging, technical validation parameters and performance acceptance thresholds need to be established. Approaches amenable to multiple hardware options and data processing algorithms can be enabled by sharing DHT data and by cross‐validating algorithms. Data standardization and creation of shared databases will be vital. Pre‐competitive consortia (public‐private partnerships and professional societies that bring together all stakeholders, including patient organizations, industry, academic experts, and regulators) will advance the regulatory maturity of DHTs in clinical trials.
Dermatofibrosarcoma protuberans im Gesicht: Klinisch‐pathologische und molekulare Studie mit 34 Fällen
Authors: Han Qianqian , Chen Min , Yang Jieliang , Du Tianhai , Peng Heng 
Published: November 2022

ZusammenfassungHintergrundDermatofibrosarcoma protuberans (DFSP) ist eines der häufigsten dermalen Sarkome, kommt aber im Gesicht nur selten vor.Patienten und MethodenDie klinisch‐pathologischen Charakteristika von insgesamt 34 fazialen DFSP wurden näher untersucht. Hierzu wurden zusätzlich eine Immunmarkierung (CD34) sowie eine PDGFB/COL1A1‐PDGFB Fluoreszenz‐in situ‐Hybridisierung (FISH) durchgeführt.ErgebnisseDie untersuchten Patienten waren zwischen 24 und 64 Jahre alt (im Mittel 42,9 Jahre), das Verhältnis Mäner zu Frauen betrug 4,7 : 1. Morphologisch fanden sich „klassische“ DFSP (25/34; 73,5 %), pigmentierte DFSP (2/34; 5,9 %), DFSP mit myoider Differenzierung (1/34; 2,9 %) und fibrosarkomatös transformierte DFSP (DFSP‐FS) (6/34; 17,6 %). Zusätzlich zeigte sich bei drei Fällen mit DFSP‐FS eine myxoide Degeneration (3/6; 50,0 %). In allen 29 Fällen mit CD34‐Immunhistochemie‐Untersuchung fand sich eine positive Anfärbung (100 %). In der genetischen Untersuchung wiesen 94,1 % (16/17) der Patienten eine PDGFB‐Rearrangement/COL1A1‐PDGFB‐Fusion auf. Die Raten an Rezidiven (83,3 % vs. 59,1 %) und Metastasierung (33,3 % vs. 0) lagen bei den DFSP‐FS deutlich höher als bei den gewöhnlichen DFSP. In allen Fällen von Rezidiven waren die Schnittränder vorher als positiv eingestuft worden. Umgekehrt waren alle Patienten mit negativen Schnitträndern (bei der Exzision oder Re‐Exzision) noch am Leben, ohne weitere Krankheitszeichen aufzuweisen (Mittel 81,8 Monate, Median 81 Monate).SchlussfolgerungDFSP tritt vor allem bei Männern auf. Bei DFSP‐FS besteht eine höhere Wahrscheinlichkeit für myxoide Degeneration bei insgesamt schlechterer Prognose. Ein negativer Status der chirurgischen Schnittränder zeigte eine gute Prognose an.
Klinisch‐pathologische Merkmale und histologische Tumorreste in Reexzisionspräparaten unvollständig resezierter Basalzellkarzinome
Authors: Lütgerath Constantin , Weiß Christel , Böer‐Auer Almut 
Published: November 2022

ZusammenfassungHintergrund und ZielsetzungDie chirurgische Exzision ist die bedeutendste Therapiemodalität zur Versorgung von Basalzellkarzinomen (BCC). Oft kommt es zu einer unvollständigen Exzision, die eine Reexzision nach sich zieht. Allerdings enthalten Reexzisionspräparate häufig keine Tumorreste, weswegen die Reexzision im Nachhinein überflüssig ist. Ziel unserer Studie ist die Identifikation von klinisch‐pathologischen Merkmalen, die mit dem Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten assoziiert sind.Patienten und Methoden255 unvollständig resezierte BCC von 222 Patienten wurden in diese Fall‐Kontroll‐Beobachtungsstudie eingeschlossen. Acht klinisch‐pathologische Merkmale wurden in einer binären logistischen Regressionsanalyse mit dem Vorhandensein oder Nichtvorhandensein von histologischen Tumorresten in Reexzisionspräparaten korreliert.ErgebnisseEin höheres Alter bei der ersten Exzision und ein BCC in der Rezidiv‐Hochrisikozone erwiesen sich als unabhängige Risikofaktoren für das Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten.SchlussfolgerungenDie Ergebnisse unserer Studie zeigen, dass eine Reexzision von unvollständig resezierten BCC in der oben genannten Subpopulation definitiv notwendig ist. Für die Nachbehandlung unvollständig resezierter BCC, die sich in der Rezidiv‐Niedrigrisikozone jüngerer Patienten befinden, können jedoch auch weniger invasive Therapien wie Imiquimod in Betracht gezogen werden.
Patientenpräferenzen bei Hidradenitis suppurativa (APProach‐HS): ein “Discrete‐Choice”‐Experiment
Authors: Faverio Kristin , Peitsch Wiebke K. , Görig Tatiana , Schneider‐Burrus Sylke , Benzel Friderike , Goebeler Matthias , Schummer Patrick , Badran Alaa , Schaarschmidt Marthe‐Lisa , Harth Wolfgang , Mössner Rotraut , Kromer Christian 
Published: November 2022

ZusammenfassungHintergrund und ZielsetzungenDie Behandlungsoptionen für mittelschwere bis schwere Hidradenitis suppurativa (HS) umfassen Antibiotika, Biologika und verschiedene chirurgische Verfahren. Diese Ansätze unterscheiden sich stark bezüglich des Behandlungsprozesses, der Erfolgsraten und der unerwünschten Ereignisse. Informationen zu den Präferenzen der Patienten in Bezug auf HS‐Therapien gibt es aktuell nur wenige. Unser Ziel war es, Patientenpräferenzen für die medikamentöse und chirurgische Behandlung der HS durch Conjoint‐Analyse zu untersuchen.Patienten und MethodenIn dieser Querschnittsstudie wurden durch computergestützte „Discrete‐Choice“ Experimente die Präferenzen der Patienten für HS‐Therapien quantifiziert, und zwar aufgeschlüsselt nach Behandlungsmodalität (Tabletten, subkutane Injektionen, chirurgische Eingriffe mit sekundärer Heilungsabsicht oder primärer Verschluss), Wahrscheinlichkeit eines anhaltenden Therapieerfolgs, Wahrscheinlichkeit leichter oder schwerer unerwünschter Ereignisse und Dauer der Behandlung oder Wundheilung.ErgebnisseGemittelt über die Kohorte (n = 216 Patienten mit HS) wurde der anhaltende Therapieerfolg als am wichtigsten angesehen (Relative Importance Score [RIS]: 36,2), gefolgt von der Behandlungsmodalität (RIS: 24,0) und der Dauer der Behandlung/Wundheilung (RIS: 19,9), während leichte oder schwere unerwünschte Ereignisse (RIS: 10,7 beziehungsweise 9,3) als weniger wichtig angesehen wurden. Die Patienten bevorzugten Tabletten gegenüber subkutanen Injektionen und lehnten eine Operation mit primärem Verschluss ab. Die Präferenzen unterschieden sich deutlich je nach Alter und den betroffenen Körperregionen.SchlussfolgerungDie Kenntnis der Patientenpräferenzen ist für eine patientenzentrierte Versorgung bei HS von wesentlicher Bedeutung.
Health, education, and social care provision after diagnosis of childhood visual disability
Authors: Solebo Ameenat Lola , Teoh Lucinda Jade , Sargent Jenefer , Rahi Jugnoo Sangeeta ,   British Childhood Visual Impairment and Blindness Study Interest Group
Published: November 2022

AbstractAimTo investigate the health, education, and social care provision for children newly diagnosed with visual disability.MethodThis was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vision. Data collection was performed by managing clinicians up to 1‐year follow‐up, and included health and developmental needs, and health, education, and social care provision.ResultsBCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two‐thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2 p < 0.001), or had an EHCP (11% vs 7%, χ2 p < 0.01).InterpretationFamilies need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.What this paper adds

One year after visual disability diagnosis, one in three children had not received the recommended care from a multidisciplinary team.
Two‐thirds had not yet received the recommended Education, Health, and Care Plan.
There is an under‐provision of recommended care, despite significant and complex need.
Virtual screening and in vitro experiments highlight cannabidiol as a drug‐like phosphodiesterase 9 inhibitor
Authors: Ribaudo Giovanni , Landucci Elisa , Giannangeli Matteo , Mazzantini Costanza , Maccarinelli Giuseppina , Mastinu Andrea , Bonini Sara Anna , Memo Maurizio , Pellegrini‐Giampietro Domenico E. , Gianoncelli Alessandra 
Published: November 2022

AbstractThe growing interest on the therapeutic potential against neurodegeneration of Cannabis sativa extracts, and of phytocannabinoids in particular, is paralleled by a limited understanding of the undergoing biochemical pathways in which these natural compounds may be involved. Computational tools are nowadays commonly enrolled in the drug discovery workflow and can guide the investigation of macromolecular targets for such molecules. In this contribution, in silico techniques have been applied to the study of C. sativa constituents at various extents, and a total of seven phytocannabinoids and four terpenes were considered. On the side of ligand‐based virtual screening, physico‐chemical descriptors were computed and evaluated, highlighting the phytocannabinoids possessing suitable drug‐like properties to potentially target the central nervous system. Our previous findings and literature data prompted us to investigate the interaction of these molecules with phosphodiesterases (PDEs), a family of enzymes being studied for the development of therapeutic agents against neurodegeneration. Among the compounds, structure‐based techniques such as docking and molecular dynamics (MD), highlighted cannabidiol (CBD) as a potential and selective PDE9 ligand, since a promising calculated binding energy value (−9.1 kcal/mol) and a stable interaction in the MD simulation timeframe were predicted.Additionally, PDE9 inhibition assay confirmed the computational results, and showed that CBD inhibits the enzyme in the nanomolar range in vitro, paving the way for further development of this phytocannabinoid as a therapeutic option against neurodegeneration.
Continuous straw return for 8 years mitigates the negative effects of inorganic fertilisers on C‐cycling soil bacteria
Authors: Zhang Qian , Guo Tengfei , Sheng Kai , Shi Wenxuan , Han Yanlai , Wang Yilun , Li Hui 
Published: November 2022

AbstractTo elucidate the identity and mechanisms by which specific bacterial members drive efficient decomposition and utilisation of straw, the succession and co‐occurrence patterns of 13C‐labelled bacteria were analysed using DNA‐stable isotope probing (SIP) techniques. Microcosms with 13C‐labelled maize straw incorporated into soils subjected to no nitrogen (N) fertiliser (CK), chemical fertiliser (NPK) and chemical fertiliser with straw return (NPKS) treatments for 8 years were incubated for 360 days. The results showed that fertilisation regimes changed the 13C‐labelled bacterial groups by abundance but not taxonomic composition, where N fertiliser application (NPK and NPKS treatments) reduced the relative abundance of maize straw carbon assimilators affiliated with Arthrobacter, Sphingomonas, Streptomyces, Burkholderia‐Caballeronia‐Paraburkholderia and Kribbella, but increased the relative abundance of Nocardioides, Rhodanobacter, Granulicella and Chujaibacter. Compared with CK and NPKS‐treated soils, continuous inorganic fertilisation reduced the α‐diversity of the 13C‐labelled bacterial community and resulted in a loose and less competitive co‐occurrence network of straw C‐assimilators with more hubs needed to sustain its structural stability. Interestingly, straw return mitigated the negative effects of inorganic fertilisation by forming a tight and complex co‐occurrence network of maize straw utilizers associated with NPKS‐treated soils. Taken together, we emphasise the vital function of long‐term straw return for sustaining soil biodiversity under intensive fertilised agricultural conditions and provide reference bacterial members for efficient straw utilisation.Highlights
DNA‐SIP enabled the concise identification of straw C assimilating bacterial members.
Inorganic fertilisation reduced straw C‐utilizer community diversity and their interactions.
Straw return mitigates the negative effects of inorganic fertilisers on straw C‐cycling bacteria.
Varying taxa sustained the interaction network of straw C‐utilizers in different fertilised soils.
Validity of the Brief Assessment of Impaired Cognition case‐finding instrument for identification of dementia subgroups and staging of dementia
Authors: Jørgensen Kasper , Nielsen Thomas Rune , Nielsen Ann , Waldorff Frans Boch , Høgh Peter , Gottrup Hanne , Vestergaard Karsten , Oxbøll Anne‐Britt , Waldemar Gunhild 
Published: November 2022

AbstractBackground and purposeThe aims of this study were to examine the psychometric properties of the Brief Assessment of Impaired Cognition (BASIC) case‐finding instrument in clinical settings focusing on (i) test–retest reliability, (ii) the discriminative validity of BASIC and its components for identification of Alzheimer disease (AD) dementia and non‐AD dementia, and (iii) the association of expert clinical rating of cognitive status with BASIC performance.MethodsThe test–retest reliability analysis was based on a sample of general practice patients (n = 59) retested with a mean interval of 19 days. Discriminative validity analyses and analysis of the association of cognitive status with BASIC performance were based on data from the primary validation study of BASIC in memory clinics.ResultsThe test–retest reliability of BASIC was high (r = 0.861). No significant difference in discriminative validity was found for identification of AD dementia (sensitivity = 0.99, specificity = 0.98) and non‐AD dementia (sensitivity = 0.90, specificity = 0.98). All components of BASIC contributed to the high discriminative validity of both AD and non‐AD dementia. BASIC performance was significantly correlated with expert clinical rating of the cognitive status of patients. A crude staging model for cognitive status using BASIC score intervals had superior classification accuracy (70%) compared to a Mini‐Mental State Examination (MMSE) score range‐based model (58% accuracy).ConclusionsBASIC is a reliable and valid case‐finding instrument for AD dementia and non‐AD dementia in clinical settings. BASIC performance is significantly associated with the degree of cognitive impairment, and BASIC seems to be superior to MMSE for staging of impairment.
Effect of long aramid fiber on the properties of styrene‐butadiene rubber composites based on extrusion
Authors: Zhang Hao , Luo Zhu , Zhong Jincheng , Wang Xingyu , Xu Yinhan 
Published: November 2022

AbstractIn this paper, long aramid fiber (LAF) reinforced styrene‐butadiene rubber/carbon black composites was prepared via a high pressure and low shear rate extrusion process, and the average length of the remaining fiber exceeded 6 mm. With LAF as reinforcement phase, the bonding between the fiber coated with butadiene styrene vinyl‐pyridine rubber latex and rubber matrix was increased. The results showed that the addition of LAF improved the properties of the composites, particularly in terms of dynamic fatigue life of the notched samples, which was increased by 352.7%. The long fibers with good interfacial bonding were peeled off in fatigue process, which can significantly absorb strain energy; thus, the propagation of fatigue cracks was effectively inhibited. This study proposes a feasible strategy to significantly improve the service life of rubber products under alternating stress, such as tires, by using the reinforcement of long fiber.
Bridging the gap between microclimate and microrefugia: A bottom‐up approach reveals strong climatic and biological offsets
Authors: Finocchiaro Marie , Médail Frédéric , Saatkamp Arne , Diadema Katia , Pavon Daniel , Meineri Eric 
Published: November 2022

AbstractIn the context of global warming, a clear understanding of microrefugia—microsites enabling the survival of species populations outside their main range limits—is crucial. Several studies have identified forcing factors that are thought to favor the existence of microrefugia. However, there is a lack of evidence to conclude whether, and to what extent, the climate encountered within existing microrefugia differs from the surrounding climate. To investigate this, we adopt a “bottom‐up” approach, linking marginal disconnected populations to microclimate. We used the southernmost disconnected and abyssal populations of the circumboreal herbaceous plant Oxalis acetosella in Southern France to study whether populations in sites matching the definition of “microrefugia” occur in particularly favorable climatic conditions compared to neighboring control plots located at distances of between 50 to 100 m. Temperatures were recorded in putative microrefugia and in neighboring plots for approximately 2 years to quantify their thermal offsets. Vascular plant inventories were carried out to test whether plant communities also reflect microclimatic offsets. We found that current microclimatic dynamics are genuinely at stake in microrefugia. Microrefugia climates are systematically colder compared to those found in neighboring control plots. This pattern was more noticeable during the summer months. Abyssal populations showed stronger offsets compared to neighboring plots than the putative microrefugia occurring at higher altitudes. Plant communities demonstrate this strong spatial climatic variability, even at such a microscale approach, as species compositions systematically differed between the two plots, with species more adapted to colder and moister conditions in microrefugia compared to the surrounding area.
CRISPR/Cas9‐mediated methoprene‐tolerant 1 knockout results in precocious metamorphosis of beet armyworm (Spodoptera exigua) only at the late larval stage
Authors: Zhao Jing , Tan Yongan , Jiang Yiping , Zhu‐Salzman Keyan , Xiao Liubin 
Published: November 2022

AbstractJuvenile hormone (JH) controls almost every aspect of an insect, especially metamorphosis. Since RNA interference works on transcripts and is often insufficient in Lepidoptera, how JH affects larval development in these insects is not well studied. Using the CRISPR/Cas9 technique, we knocked out Spodoptera exigua methoprene‐tolerant 1 (SeMet1) gene of beet armyworm by modifying two sites in the coding region. However, SeMet1 knockout did not affect egg hatch rate or larval development at L1–L3 stages. In contrast to the consistent five larval instars of the control group, L4 SeMet1 mutants began to show signs of precocious metamorphosis, that is, small patches of pupal cuticle. Most L4 and all L5 SeMet1 mutants died for failing to shed their mosaic cuticles. RNA‐seq indicated that most genes encoding pupal cuticle proteins and chitinase genes were altered in SeMet1 mutant L4 larvae. SeKr‐h1, a key transcription factor in JH action was significantly down‐regulated in L3‐L5 larvae, while SeBR‐C, a pupal indicator was only upregulated in L4‐L5 larvae. These results suggested that S. exigua larvae may initially develop independently of JH, and involve SeMet1 in transducing JH signalling, leading to controlled larval metamorphosis at the late larval stage. We believe our findings will enhance better understanding of JH regulation of larval development.
Simultaneously enhancing the Td and the thermal stability of the real‐time d33 in BNT‐based piezoceramics
Authors: Chen Jun , Zhou Changrong , Chen Kelin , Li Qingning , Yuan Changlai , Xu Jiwen , Cheng Shuai , Zhao Jingtai , Rao Guanghui 
Published: November 2022

AbstractOne of the inherent disadvantages of Bi0.5Na0.5TiO3‐based (BNT‐based) piezoceramics is that an increment of the depolarization temperature (Td) is generally accompanied by a deterioration of the temperature stability of the real‐time piezoelectric constant (d33), which severely restricts the practical applications of the materials. Herein, we propose a new strategy to mitigate the conflict between the elevation of Td and the temperature stability of the real‐time d33 in BNT‐based ceramics via integrating the pressure‐assisted sintering and quenching process. By this strategy, we not only increased the Td from 109 to 166°C but also improved the temperature stability of the real‐time d33 (the temperature coefficient Ttc = ± 13 pC/N) in 0.94Bi0.5Na0.5TiO3–0.06BaTiO3 ceramic. Both the built‐in field and the increment of the field‐induced R3c phase fraction play the significant role in enhancing the Td and the temperature stability of the real‐time d33. Thus, our work provides a simple and effective approach for designing piezoceramics with high Td and a superior temperature stability of the real‐time d33.
Enhancing the mechanical properties of ceramics by high‐temperature rolling: A first demonstration using alumina
Authors: Li Yingwei , Tan Chi 
Published: November 2022

AbstractWe herein report a technique, namely, high‐temperature rolling that can roll ceramics at high temperature with controllable speed. A first demonstration using alumina reveals that, after rolling at 800, 900, and 1000°C, the bending strength (), Vickers’ hardness (), and fracture toughness () of alumina enhanced significantly. For instance, for the specimen rolled at 900°C, , , and increased by ∼20% (360–430 MPa), ∼10% (13.1–14.5 GPa), and ∼61% (3.1–5 MPa m0.5), respectively. This technique is expected to develop into a universal solution to enhance the mechanical properties of ceramics.