bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolite profiles and mass balance of fuzuloparib, a novel poly (ADP‐ribose) polymerase inhibitor, in subjects with advanced solid cancers
Authors: Bian Yicong , Meng Jian , Ma Sheng , Li Guangze , Wang Yuya , Li Shaorong , Liu Linsheng , Huang Chenrong , Zhang Hua , Zhong Dafang , Miao Liyan 
Published: February 2022

AimThis trial (NCT04013048) investigated the metabolite profiles, mass balance and pharmacokinetics of fuzuloparib, a novel poly (ADP‐ribose) polymerase inhibitor, in subjects with advanced solid cancers.MethodsA single dose of 150 mg [14C]fuzuloparib was administered to five subjects with advanced solid cancers. Blood, urine and faecal samples were collected, analysed for radioactivity and unchanged fuzuloparib, and profiled for metabolites. The safety of the medicine was assessed during the study.ResultsThe maximum concentrations (Cmax) of the total radioactivity (TRA) and unchanged fuzuloparib in plasma were 5.39 μg eq./mL and 4.19 μg/mL, respectively, at approximately 4 hours post dose. The exposure (AUC0‐t) of fuzuloparib accounted for 70.7% of the TRA in plasma, and no single metabolite was observed accounting for more than 10% of the plasma TRA. The recovery of TRA in excreta was 103.3 ± 3.8% in 288 hours, including 59.1 ± 9.9% in urine and 44.2 ± 10.8% in faeces. Sixteen metabolites of fuzuloparib were identified, including mono‐oxidation (M1), hydrogenation (M2), di‐oxidation (M3), trioxidation (M4), glucuronidation (M5, M7, M8) and de‐ethylation (M6) products, and there was no specific binding between these metabolites and blood cells. Aliphatic hydroxylated fuzuloparib (M1‐1) was the primary metabolite in the excreta, accounting for more than 40% of the dose for subjects. There were no serious adverse events observed in the study.ConclusionFuzuloparib was widely metabolized and excreted completely through urine and faeces in subjects with advanced solid cancer. Unchanged fuzuloparib was indicated to be the primary drug‐related compound in circulation. [14C]fuzuloparib was well‐tolerated at the study dose.
Differential sleep/wake response and sex differences following acute suvorexant, MK‐1064 and zolpidem administration in the rTg4510 mouse model of tauopathy
Authors: Keenan Ryan J. , Daykin Heather , Chu Jiahui , Cornthwaite‐Duncan Linda , Allocca Giancarlo , Hoyer Daniel , Jacobson Laura H. 
Published: February 2022

Background and PurposeTransgenic mouse models of tauopathy display prominent sleep/wake disturbances which manifest primarily as a hyperarousal phenotype during the active phase, suggesting that tau pathology contributes to sleep/wake changes. However, no study has yet investigated the effect of sleep‐promoting compounds in these models. Such information has implications for the use of hypnotics as potential therapeutic tools in tauopathy‐related disorders.Experimental ApproachThis study examined polysomnographic recordings in 6‐6.5‐month‐old male and female rTg4510 mice following acute administration of suvorexant (50 mg·kg−1), MK‐1064 (30 mg·kg−1) or zolpidem (10 mg·kg−1), administered at the commencement of the active phase.Key ResultsSuvorexant, a dual OX receptor antagonist, promoted REM sleep in rTg4510 mice, without affecting wake or NREM sleep. MK‐1064, a selective OX2 receptor antagonist, reduced wake and increased NREM and total sleep time. MK‐1064 normalised the hyperarousal phenotype of male rTg4510 mice, whereas female rTg4510 mice exhibited a more transient response. Zolpidem, a GABAA receptor positive allosteric modulator, decreased wake and increased NREM sleep in both male and female rTg4510 mice. Of the three compounds, the OX2 receptor antagonist MK‐1064 promoted and normalised physiologically normal sleep, especially in male rTg4510 mice.Conclusions and ImplicationsOur findings indicate that hyperphosphorylated tau accumulation and associated hyperarousal does not significantly alter the responses of tauopathy mouse models to hypnotics. However, the sex differences observed in the sleep/wake response of rTg4510 mice to MK‐1064, but not suvorexant or zolpidem, raise questions about therapeutic implications for the use of OX2 receptor antagonists in human neurodegenerative disorders.
Designing of kinase hinge binders: A medicinal chemistry perspective
Authors: Sharma Vikas , Gupta Mohit 
Published: February 2022

AbstractProtein kinases are key regulators of cellular signaling and play a critical role in oncogenesis. Inhibitors of protein kinases are pursued by both industry and academia as a promising target for cancer therapy. Within the protein kinases, the ATP site has produced more than 40 FDA‐approved drugs. The ATP site is broadly composed of a hinge region, gatekeeper residues, DFG‐loop, ribose pocket, and other hydrophobic regions. The hinge region in the ATP site can be used for designing potent inhibitors. In this review, we discuss some representative studies that will highlight the interactions of heterocyclic compounds with hinge regions of different kinases like BRAF kinase, EGRF kinase, MAP kinase, and Mps1 kinase.
Capacity for sustainment of recently established syringe service programs in Appalachian Kentucky: The central role of staff champions
Authors: Cooper Hannah L. F. , Gross Skylar , Klein Emma , Fadanelli Monica , Ballard April , Lockard Scott , Batty Evan , Young April , Ibragimov Umed 
Published: February 2022

AbstractIntroductionEnsuring adequate harm reduction infrastructure in rural areas is imperative, as drug‐related epidemics expand into them. Here, we explore the capacity for sustainment of syringe service programs (SSP) in Appalachian Kentucky.MethodsWe interviewed all staff (n = 16) of all SSPs (n = 7) in two Kentucky health districts in 2018–2019 using semi‐structured one‐on‐one qualitative interviews; local departments of health (DOH) operated the SSPs. Interview domains encompassed: (i) SSP establishment; (ii) day‐to‐day operations, participation and health impacts; (iii) perceived prospects for sustainment; and (iv) perceived influences on #i–#iii. We analysed verbatim transcripts using thematic analytic methods; Schell's ‘capacity for sustainment’ constructs were treated as sensitising concepts during the analysis.ResultsMost community members, law enforcement and DOH staff opposed SSPs before they opened, because of stigma and concerns about enabling and needlestick injuries; DOH staff also opposed SSPs because they believed they lacked the capacity to operate them. Training, technical assistance, visible evidence of the programs' public health impact and contact with SSP participants transformed DOH staff into program champions. As champions, SSP staff developed programs that had strong capacity for sustainment, as defined by Schell (e.g. visible public health impact, stable funding, political support). Staff reported that the SSPs had high prospects for sustainment.Discussion and ConclusionAs in SSPs that opened in cities decades ago, staff in emerging SSPs in these rural areas appear to have become crucial champions for these controversial programs, and may serve as vital resources for expanding harm reduction programming more broadly in these underserved areas.
The effect of temperature and behaviour on the interaction between two dragonfly larvae species within the native and expanded range
Authors: Everling Sanne , Johansson Frank 
Published: February 2022

Abstract
Studies on interaction between species are needed to observe and predict the effects of climate change on species distributions. Here we studied intra‐ and interspecific competition and behaviour in larvae of a native and a northward expanding dragonfly species, Sympetrum vulgatum and Sympetrum fonscolombii, respectively. We estimated growth, mortality, and behaviour (prey capture success, activity, and boldness) at 20°C and 23°C.
The northward expanding S. fonscolombii had a higher growth rate and a higher survival compared with the native S. vulgatum in interspecific competition. In intraspecific conditions, there was no significant difference between species in mortality and growth. Temperature had no significant effect on growth and survival of S. fonscolombii, but S. vulgatum showed both a higher growth rate and a higher mortality at 23°C under intraspecific conditions. There was a correlation between growth and mortality, suggesting that cannibalism and intraguild predation caused the growth differences between treatments in the competition experiments.
Temperature had no significant effect on any of the behaviours. There were very few significant correlations between any of the behaviours and the life‐history traits survival and growth and there were also very few significant correlations between any of the behaviours. Repeatability of behaviours over ontogeny was low.
The results of the present study suggest that the range expanding S. fonscolombii has the potential to outcompete the native species, but that this competition advantage does not seem to be driven by the temperature effects explored in this study.
A prospective study of Skeletal survey versus Low‐dose whole‐body CT for Osteolytic lesions in Multiple Myeloma
Authors: Gundesen Michael T. , Asmussen Jon T. , Haukås Einar , Schubert Michael , Abildgaard Niels , Schjesvold Fredrik , Lund Thomas 
Published: February 2022

AbstractWhole‐body low‐dose CT (WBLDCT) is recommended over classical skeletal surveys (CSS) for investigating bone disease in multiple myeloma (MM) based on retrospective studies. No prospective studies with serial follow‐up scans exist.ObjectiveTo compare WBLDCT to CSS for identifying progressive bone disease in MM in a prospective setting.MethodsNinety‐six patients with MM at Odense University Hospital and Stavanger Hospital were followed for up to four years. Patients were scanned with WBLDCT and CSS every year for the first two years and every six months thereafter or at suspicion of progression.ResultsNineteen cases of progressive bone disease were found using WBLDCT vs eight cases using CSS (p < 0.001). All cases of progressive bone disease using CSS were also identified by WBLDCT. Progression not found by CSS was primarily in the spine, sternum, and pelvis. Of the 19 cases, five patients had progressive bone disease only without other criteria for clinical progression. WBLDCT consistently identified more bone lesions per patient, 8.2 CI(6.8;9.6) vs CSS, 3.6 CI(2.7;4.5).ConclusionWBLDCT outperformed CSS for finding progressive bone disease and osteolytic lesions. More new lesions were found during follow‐up by WBLDCT than CSS. Using CSS for lytic lesions will underestimate progression rates. Our data offer prospective evidence for the current recommendation using WBLDCT for skeletal evaluations in patients with multiple myeloma.
Evaluation of thermal fatigue crack propagation in underfill resin materials for electronic packages
Authors: Watanabe Yusuke , Yamaguchi Hiroshi , Enomoto Toshiaki , Ogawa Kensuke , Kobayashi Takaya , Omiya Masaki 
Published: February 2022

AbstractTo improve the fatigue life of electronic packages, it is necessary to clarify thermal fatigue characteristics of underfill resin materials. In this study, a new setup for measuring thermal fatigue crack growth was developed, and the effects of thermal cycle conditions and silica filler contents on fatigue crack propagation were investigated. The results show that the likelihood of crack initiation increased with the filler content and the temperature of the thermal cycles. Comparing the results with those from mechanical fatigue tests, crack initiation and propagation occurred at lower ΔK and the crack growth rates were higher for thermal fatigue. Observations of the fracture surface revealed that the cracks propagated inside the underfill resin, which resulted in smaller crack growth resistance than that in mechanical fatigue. The addition of fillers introduced a crack propagation path at the interface between fillers and resins and enhanced the crack propagation resistance in thermal fatigue.
Long‐term survival of Atlantic salmon following catch and release: Considerations for anglers, scientists and resource managers
Authors: Keefe Donald , Young Mark , Van Leeuwen Travis E. , Adams Blair 
Published: February 2022

AbstractTo evaluate the scientific basis for catch and release as a management tool, a comprehensive 3‐year study compared long‐term survival of Atlantic salmon that were either angled, radio‐tagged and released, or trapped, radio‐tagged and released (control). Overall, the mean survival probability of angled salmon relative to the control group was between 0.94 and 0.98. At cool to moderate water temperatures (10–18°C) mean survival of angled salmon was between 0.96 and 0.98. Although the number of salmon caught and released above 21°C was low, catchability was slightly reduced at warm water temperatures (21–25°C) and the mean survival probability was between 0.43 and 0.69. Lastly, the number of fish that survived the spawning period did not differ between the angled group and the control group. However, the mean percentage of fish that overwintered and migrated downstream through a counting fence to sea was between 9% and 10% for those that were caught and released and between 13% and 19% for the control group. Results of this study suggest that mortality of caught and released Atlantic salmon can be delayed but remains low at cool to moderate water temperatures.
Iron‐phosphate glass‐ceramic anodes for lithium‐ion batteries
Authors: Qi Shibin , Li Xiangyu , Yue Yuanzheng , Zhang Yanfei 
Published: February 2022

AbstractThe oxide glass‐based anodes for lithium‐ion Batteries (LiBs) still suffer from two critical drawbacks, that is, low reversible capacity and low electrical conductivity. Here, we report a new way to overcome the two drawbacks. Specifically, we chose 50Fe2O3–50P2O5 (50Fe50P) glass as the anode material for LiBs, and then thermally treat it at 1118 K (Tg+345 K) for 0.5 h under reducing atmosphere (5 mol% H2+95 mol% Ar). The thermal reduction treatment led to formation of Fe2(P4O12) and Fe2Fe5(P2O7)4 crystals. The reduced glass‐based anode for LiBs exhibits the capacity of 373 mA h g−1 after 1 000 charge/discharge cycles at 1 A g−1, which is higher than that of the oxidized one. The reduction treatment greatly lowers the charge transfer resistance in the glass anode, indicating the enhancement of the electrical conductivity. This performance improvement could arise from the increase of accessible active sites for Li+ ion storage and transfer due to the existence of crystal–crystal/crystal–glass boundaries, as well as from the improvement of the electron transfer between Fe2+ and Fe3+ during cycling. This reduction–crystallization approach could help develop high‐performance oxide glass‐ceramics based anodes for advanced LiBs.
Unveiling idiopathic guttate hypomelanosis: pathology, immunohistochemistry, and ultrastructural study
Authors: Arbache Samir , Michalany Nilceo S. , de Almeida Hiram L. , Hirata Sergio H. 
Published: February 2022

AbstractBackgroundIdiopathic guttate hypomelanosis (IGH) is a pigment disorder of unknown etiology. Despite its high prevalence and the unaesthetic appearance of the lesions, there are relatively few histological studies on this disorder. This is an important gap to understanding its pathogenesis.ObjectivesTo assess the microscopic structure of IGH lesions compared to normal adjacent skin areas and the possible interaction between melanocytes and the subjacent dermis.MethodsIn this cross‐sectional study, we took biopsy specimens of hypochromic lesions and adjacent normal skin from 20 patients with IGH. We analyzed the fragments using routine stains, immunohistochemistry, and electron microscopy.ResultsWe found superficial dermal fibrosis in 90% (18/20) of our IGH cases and unreported keratinocyte cytoplasmic changes on electron microscopy.ConclusionOur results suggest an interaction between melanocytes and the subjacent dermis in IGH. These findings can help to understand melanocyte biology and the pathogenesis of other achromic lesions.
Morphology and phylogeny of two anaerobic freshwater ciliates: Brachonella comma sp. nov. and the widely distributed but little‐known caenomorphid, Ludio parvulus Penard, 1922
Authors: Bourland William , Pomahač Ondřej , Čepička Ivan 
Published: February 2022

AbstractHypoxic, sulfidic freshwater sediments typically support a diffuse consortium of distinctive ciliated protists, including caenomorphids, metopids, and odontostomatids among others. A recent resurgence of interest in these important members of sapropelic food webs has resulted in the description of many new species and an effort, still in its infancy, to characterize them from a morphologic, molecular, and metabolic standpoint and to determine their phylogenetic relationships. Their seemingly invariable association with prokaryotic endosymbionts and, less commonly, ectosymbionts has become a focus for many researchers. In this report, based on morphologic and molecular data, we describe a Brachonella species (Ciliophora, Metopida) new to science and analyze its phylogeny. We also provide a morphologic and molecular characterization of the smallest representative of the Caenomorphidae Poche, 1913, Ludio parvulus Penard, 1922. The phylogenetic analysis confirms the inclusion of this species in the Caenomorphidae.
Does amortization matter? Evidence from the syndicated loan market
Authors: Nguyen Ca 
Published: February 2022

AbstractIn this article, I investigate whether a firm's decision to adopt an amortizing payment schedule affects its cost of bank loans. Focusing on US syndicated loans from 1991 to 2018, I find that amortized loans on average have spreads that are 46 basis points lower than bullet unamortized loan facilities. This discount represents a decrease of $1.66 million in annual interest expenses. I also find that borrowers with higher fundamental volatility, debt rollover risk, or financial constraints enjoy a substantially larger amortization discount and stand a better chance of refinancing their loan debt. However, the discount on loan pricing is moderated if nonbank institutions such as hedge funds or collateralized loan obligations participate in the lending syndicate. My results remain robust when I measure the intensity of loan amortization, control for overall debt maturity profiles, and address the endogeneity issue with propensity score matching and within‐loan analyses. Overall, my article supports the liquidity risk hypothesis, which suggests that borrowing firms have incentives to spread loan payments across time to diversify their debt maturity structure and enhance the prospects of debt refinancing, thereby limiting the transmission of liquidity risk to credit risk.
Effect of microbial fermentation on nutritional and antinutritional contents of cassava leaf
Authors: Terefe Zemenu Kerie , Omwamba Mary , Nduko John Masani 
Published: February 2022

AbstractCassava leaves serves as a source of alternative proteins for people in developing countries who could not easily access the available protein sources. However, its use is limited by the presence of toxic compounds, particularly cyanogenic glycosides. Thus, use of appropriate processing technique is indispensable to reduce the toxic compounds to a safer limit before utilization of cassava leaf. The objective of this study was therefore to evaluate the effect of Lactobacillus plantarum and Saccharomyces cerevisiae strains, and their co‐culture on nutritional contents and antinutritional factors of cassava leaf during fermentation. A 4 × 5 factorial experimental design was used to determine the effect of fermentation setups and time on chemical composition, antinutritional contents, in vitro protein digestibility and mineral contents of cassava leaf. During 48 h of fermentation, a significant change (p < 0.05) in moisture, protein, fiber, fat, and ash contents were observed. Protein content was improved by 34.91%, while in vitro digestibility of protein was improved by 28.07% during 48 h of L. plantarum fermentation. Cyanide, oxalate, tannin, and phytate contents were decreased significantly (p < 0.05) for all fermentation setups. The highest reduction in cyanide (97.17%) and oxalate (86.44%) was achieved under L. plantarum fermentation. The highest reduction in tannin (93.25%) and phytate (91.11%) was achieved under co‐culture fermentation of cassava leaf. A significant (p < 0.05) reduction of mineral contents except iron was observed during 48 h of fermentation. A significant (p < 0.0001) strong negative correlation was found between protein with cyanide (−0.8164), oxalate (−0.7991), phytate (−0.7851), and tannin (−0.6906). In vitro digestibility of protein also showed a strong significant (p < 0.0001) negative correlation with phytate (−0.9628), oxalate (−0.9407), cyanide (−0.9305), and tannin (−0.8493). Application of L. plantarum and S. cerevisiae in cassava leaf fermentation showed significant improvement of nutritional qualities by reducing the antinutritional factors and toxic compounds. Fermentation of cassava leaf using these strains ascertain utilization of cassava leaf for human consumption to tackle protein energy malnutrition.
Hospital organizational structure factors related to discharge planning activities for alcoholics by nurses in Japan
Authors: Adachi Madoka , Tamakoshi Koji , Watai Izumi 
Published: February 2022

AbstractAimNurses play a significant role in providing discharge support for alcoholics. We aimed to explore the organizational structures of hospitals that are related to effective discharge planning activities provided by nurses.MethodsWe conducted a cross‐sectional survey of Japanese hospitals with psychiatric wards that accept alcoholics. The survey questionnaire was administered to one nurse per hospital from August to September 2019. The Discharge Planning Scale for Ward Nurses (DPWN) was used to assess the actual status of the hospital nurse teams' discharge planning activities. The DPWN consists of four subscales: subscale I, “collect information from patients and their families”; subscale II, “supports for decision‐making for the patients and families”; subscale III, “utilization of social resources”; and subscale IV, “discharge guidance by cooperating with community support teams and multidisciplinary teams.”ResultsFrom the valid responses of 116 hospitals, scores on subscale IV were significantly lower than scores on subscales I, II, and III, indicating that medical care guidance through multidisciplinary collaboration between hospitals and the community was inadequate. In addition, multiple regression analysis showed that “hospital management and administrators understanding about nurses' discharge support activities,” and “planning discharge schedules, such as using clinical paths” were significantly and independently related to the total DPWN and each of subscale scores, regardless of the hospital's establishment body and size. “Multidisciplinary discharge support” was significantly related to subscale II.ConclusionsThese findings have implications for the management of discharge planning activities provided by nurses for alcoholics through multidisciplinary collaboration.