bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidation of DPP‐4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss–Newton method
Authors: Nakamura Ryo , Yoshikado Takashi , Aoki Yasunori , Sugiyama Yuichi , Chiba Koji 
Published: October 2024

AbstractThe dipeptidyl peptidase‐4 (DPP‐4) inhibitor linagliptin (LNG) exhibits target‐mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP‐4 (sDPP‐4) and tissue transmembrane DPP‐4 (tDPP‐4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild‐type mice, but not in Dpp‐4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP‐4‐related renal reabsorption of LNG, we employed physiologically‐based pharmacokinetic (PBPK) modeling combined with a cluster Gauss–Newton method (CGNM). The CGNM facilitated the exploration of parameters in rat and human PBPK models for LNG and the determination of parameter identifiability. Through PBPK–CGNM analysis using reported autoradiography data ([14C]‐LNG) in wild‐type and Dpp‐4‐deficient rats, DPP‐4‐specific distributions of LNG in various tissues were clearly differentiated from nonspecific parts. By fitting to human plasma concentrations and urinary and fecal excretions of LNG after intravenous and oral administrations, multiple unknown PBPK parameters were simultaneously estimated by the CGNM. Notably, the amount of tDPP‐4 and the reabsorption clearance for LNG–DPP‐4 complexes were identifiable, indicating their critical role in explaining the complex nonlinear pharmacokinetics of LNG. Compared with previous PBPK analyses, the CGNM allowed us to incorporate greater model complexity (e.g., consideration of tDPP‐4 expressions and in vitro binding kinetics), ultimately resulting in a more accurate reproduction of LNG's TMDD. In conclusion, by considering LNG as a high‐affinity probe for DPP‐4, comprehensive PBPK–CGNM analyses suggested a dynamic whole‐body distribution of DPP‐4, including its involvement in the renal reabsorption of LNG.
Mitochondrial DNA replication is essential for neurogenesis but not gliogenesis in fetal neural stem cells
Authors: Walter‐Manucharyan Meri , Martin Melanie , Pfützner Julia , Markert Franz , Rödel Gerhard , Deussen Andreas , Hermann Andreas , Storch Alexander 
Published: October 2024

AbstractMitochondria are unique organelles that have their own genome (mtDNA) and perform various pivotal functions within a cell. Recently, evidence has highlighted the role of mitochondria in the process of stem cell differentiation, including differentiation of neural stem cells (NSCs). Here we studied the importance of mtDNA function in the early differentiation process of NSCs in two cell culture models: the CGR8‐NS cell line that was derived from embryonic stem cells by a lineage selection technique, and primary NSCs that were isolated from embryonic day 14 mouse fetal forebrain. We detected a dramatic increase in mtDNA content upon NSC differentiation to adapt their mtDNA levels to their differentiated state, which was not accompanied by changes in mitochondrial transcription factor A expression. As chemical mtDNA depletion by ethidium bromide failed to generate living ρ° cell lines from both NSC types, we used inhibition of mtDNA polymerase‐γ by 2′‐3′‐dideoxycytidine to reduce mtDNA replication and subsequently cellular mtDNA content. Inhibition of mtDNA replication upon NSC differentiation reduced neurogenesis but not gliogenesis. The mtDNA depletion did not change energy production/consumption or cellular reactive oxygen species (ROS) content in the NSC model used. In conclusion, mtDNA replication is essential for neurogenesis but not gliogenesis in fetal NSCs through as yet unknown mechanisms, which, however, are largely independent of energy/ROS metabolism.
Synergies between diabetes and hyperhomocysteinaemia: New insights to predict and prevent adverse cardiovascular effects
Authors: Fan Xue , Liu Yuhe , Chen Xueyu , Xu Yuehao , Wu Wenqian , Li Fengchang , Liu Gang , Chen Xiaoli , Zhang Caiping , Zhou Yong 
Published: October 2024

AbstractAimTo explore the association of hyperhomocysteinaemia (HHcy) and diabetes synergies with cardiovascular events in the adult population of northern China.MethodsData were collected from the Asymptomatic Polyvascular Abnomalities Community study for 2010 to 2019. Serum homocysteine (Hcy) levels were determined by enzyme‐linked immunosorbent assay. The participants were categorized into four groups based on their Hcy levels and diabetes status: non‐diabetes/non‐HHcy, non‐diabetes/HHcy, diabetes/non‐HHcy and diabetes/HHcy. The composite endpoint consisted of the occurrence of first‐ever stroke, myocardial infraction (MI) or all‐cause mortality. Cox regression analyses were performed to evaluate the associations of diabetes and HHcy with cardiovascular disease (CVD) events.ResultsIn total, 5278 participants were eligible (average age 55.1 years, 60% male). Over a follow‐up of 9.1 years, 618 events were identified, 202 stroke, 52 MI and 406 all‐cause deaths. Compared with the non‐diabetes/non‐HHcy group, hazard ratios with 95% confidence intervals in the diabetes/HHcy group for stroke, MI, major adverse cardiovascular event (MACE), all‐cause death and composite endpoint were 1.85 (1.12‐3.04), 1.33 (0.42‐4.23), 1.78 (1.13‐2.80), 2.24 (1.56‐3.23) and 1.97 (1.47‐2.65), respectively. Significant interactions between HHcy and diabetes status were found for stroke, MI and MACE (P for interaction = .002, .027 and .044, respectively). In addition, the association of diabetes/HHcy with stroke was modified by age (< 60 and ≥ 60 years; P for interaction = .016).ConclusionsThe findings highlight the synergistic impact of diabetes and HHcy on CVD. Joint assessments of diabetes and Hcy levels should be emphasized for risk stratification and primary prevention of CVD.
Differential temporal decline of cerebral oxytocin and μ‐opioid receptor density during the aging process in mice
Authors: Effah Felix , Nidadavolu Prakash , de Gusmão Taveiros Silva Nívea Karla , Wojtowicz Milosz , Camarini Rosana , Zimmer Andreas , Bailey Alexis 
Published: October 2024

AbstractAging is often associated with changes in social, sexual, emotional and pain functioning, as well as with the increased prevalence of certain psychopathologies. However, the neurodevelopmental basis underpinning these age‐related changes remains to be determined. Considering the key roles of oxytocin (OTR) and μ‐opioid (MOPr) receptor systems in regulating social, sexual, pain, reward and emotional processing, it seems plausible that they are also implicated in age‐related behavioural alterations. Although the ontogeny of both receptors has been well characterized in rodent brains from early development till adulthood, little is known concerning the neuroadaptations occurring from middle age to old age. Therefore, we mapped the neuroadaptations in OTR and MOPr in the brains of mice at those developmental endpoints. Quantitative OTR and MOPr autoradiographic binding was carried out in the brains of male mice at 2, 6, 9, 12 and 18 months of age. A significant whole brain decline in OTR density was detected between 2 and 6 months of age, with no additional decline thereafter. Interestingly, for MOPrs, the decline in density was not detected until 9 months of age. Region‐specific age‐related decline in OTR density was concentrated in the lateral anterior olfactory nuclei (AOL) and, for MOPr, in the AOL and the nucleus accumbens. Identifying the tipping point of these age‐related variations in both receptors may assist with our understanding of the neurobiology underlining age‐related changes in social, pain and emotional functioning/processing. It may also help us target interventions to specific developmental windows to abrogate certain age‐related psychopathologies.
Intensive care due to myasthenia gravis: Risk factors and prognosis
Authors: Myllynen Chris , Tuulasvaara Anni , Atula Sari , Laakso Sini M. 
Published: October 2024

AbstractBackground and purposeExacerbation of myasthenia gravis (MG) with respiratory failure requires intensive care. We aimed to study the risk factors for intensive care unit admission for MG exacerbation and myasthenic crisis (MC) and the prognosis of people with MG (pwMG) thereafter.MethodsThis retrospective study investigated patients in the Helsinki and Uusimaa hospital district during the years 2008–2021. PwMG (International Classification of Diseases, 10th revision code G70.0) were identified through a data repository search, followed by a chart review of patient records. Risk factors for intensive care due to MG exacerbation were evaluated as compared with the patients only treated in the outpatient clinic and those treated in the neurological ward for MG exacerbation. The outcomes of patients in intensive care for any reason were also compared with those of patients in intensive care for exacerbation of bronchial asthma.ResultsOf 577 pwMG, 35 (6.1%) needed intensive care for MG within a median of 5.3 months from diagnosis. The mean (±SD) age at MG diagnosis was higher in the intensive care group (60.5 [±16.1] years) compared to the outpatient (48.3 [±20.9] years; p < 0.001) and neurological ward groups (53.4 [±20.8] years; p = 0.044). Thymoma (odds ratio [OR] 4.8, 95% confidence interval [CI] 1.19–19.43; p = 0.028) and female sex (OR 2.1, 95% CI 1.02–4.48; p = 0.045) were independent risk factors for intensive care. In‐hospital mortality was 4% for MC patients. Six‐month mortality after intensive care for MG exacerbation (14.3%) was twice that for asthma exacerbation (7.7%).ConclusionOur study shows an increased risk of intensive care treatment for patients with late‐onset MG, female sex or thymoma, occurring usually within 6 months from diagnosis, which emphasises the importance of early treatment choices.
Pair‐Coordinated Calling: Eurasian Magpies Respond Differently to Simulated Intruder Pairs That Overlap or Alternate Their Calls
Authors: Kuspiel Miriam , Kingma Sjouke A. , Vermeulen Heleen , Naguib Marc 
Published: October 2024

ABSTRACTAnimal vocalisations are widely used to signal strength or motivation of a caller in competitive interactions, such as in territorial defence. Substantial understanding of signalling functions in territorial conflicts is based on singing by male songbirds. Yet, in many species, both pair members call during territorial conflicts, as well as in predator‐induced situations, leading to complex signalling interactions in which calls overlap or alternate. This raises the question as to whether or not variation in how individuals in pairs time their calls is perceived as meaningful by receivers. Here, we tested with playback experiments whether Eurasian magpies (Pica pica), a species producing alarm calls (so‐called chatter calls) in territorial defence, respond stronger to simulated pair‐intruders who overlap their calls with each other than to those who alternate them. Magpies emitted a significantly longer first chatter calls in response to playback with overlapping calls but chattered significantly sooner and approached the loudspeakers significantly more closely in response to playbacks of alternating (and therefore longer) call sequences. These findings exemplify that the timing of calls by pair members matters, but in more complex ways than we predicted. The overlapping playback appeared to trigger a longer yet later initial chatter response and a weaker approach response, suggesting that the different ways in which magpies respond reflect different levels of arousal or defence strategies. The results may also reflect uncertainty by receivers due to a potential mismatch between signalled and perceived information: While overlapping calls may signal high arousal by both callers, a longer alternating sequence could be perceived as a more aroused longer signal. These findings expand on classical experiments on call function, suggesting that pairs can vary the message by coordinating their alarm calls in different ways, similar to how duetting pairs time their song contributions in advertisement signalling.
Study on Low‐Cycle Fatigue Behavior and Life Prediction of Cr–Ni–Mo–V Gun Steel at Room Temperature and 600 °C
Authors: Zhao Chao , Jia Xiaobin , Zhao Caiyan , Bai Shaobin , Huang Yanli , Zhang Qing , Zhang Jian , Hu Yongping , Huang Jinfeng 
Published: October 2024

ABSTRACTIn this paper, the low‐cycle fatigue fracture behavior and life prediction of Cr–Ni–Mo–V gun steel at room temperature and 600 °C are studied. The results indicated that at room temperature and 600 °C, the Cr–Ni–Mo–V gun steel exhibited obvious monotonic softening and cyclic softening. This behavior could be attributed to the formation of dislocation networks, dislocation walls, dynamic recovery, and dynamic recrystallization. As the temperature increased, the failure mode gradually shifted from mixed transgranular and intergranular fractures to intergranular fractures possibly owing to the reduced grain boundary strength and easy oxidation of the grain boundary at high temperatures. In addition, the fatigue life prediction model considering the influence of temperature is established by using the energy dissipation quadratic function, offering a practical method to improve the fatigue performance evaluation of Cr–Ni–Mo–V gun steel at various temperature.
Cyanobacteria can benefit from freshwater salinization following the collapse of dominant phytoplankton competitors and zooplankton herbivores
Authors: Urrutia‐Cordero Pablo , Langvall Ola , Weyhenmeyer Gesa A. , Hylander Samuel , Lundgren Maria , Papadopoulou Sofia , Striebel Maren , Lind Lovisa , Langenheder Silke 
Published: October 2024

Abstract

Freshwater salinization is an increasing threat to lakes worldwide, but despite being a widespread issue, little is known about its impact on biological communities at the base of the food chain.

Here we used a mesocosm set‐up coupled with modern high‐frequency sensor technology to identify short‐ and longer‐term responses of phytoplankton to salinization in an oligotrophic lake. We tested the effects of salinization over a gradient of increasing salt concentrations that can be found in natural lakes exposed to road salt contamination (added salt range: from 0 to 1500 mg Cl− L−1).

The high‐frequency chlorophyll‐a (chl‐a) fluorescence measurements showed an increasing divergence of chl‐a concentrations along the salinization gradient over time, with substantially lower concentrations at higher salt levels. At the sub‐daily scale, we found a profound suppression of day–night signal cycles with increasing salinity, which could be related to physiological stress due to the impairment of photosynthesis via effects on the photosystem II or potential changes in the active migration of phytoplankton. Community analyses revealed a similar decline pattern for the total phytoplankton biomass and a collapse of the total zooplankton biomass. Interestingly, we found a loss of phytoplankton diversity coupled with a compositional re‐organization involving the loss of dominant green algae but increased biomass of salt‐tolerant cyanobacteria.

Altogether, these results suggest that specific cyanobacterial taxa can benefit from freshwater salinization following the collapse of dominant phytoplankton competitors and zooplankton herbivores. The results also highlight the value of autonomous sensor technology to capture novel, small‐scale ecological responses to freshwater salinization, and thereby to track fast changes in primary producer communities.
Inorganic Carbon Pools and Their Drivers in Grassland and Desert Soils
Authors: Dong Longwei , Ran Jinzhi , Luo Jiali , Bai Lin , Sun Ying , Aqeel Muhammad , Zhang Yahui , Wang Xiaoting , Du Qiajun , Xiong Junlan , Gong Haiyang , Hou Qingqing , Deng Yan , Xia Rui , Wang Liang , Li Fan , Dong Chuancong , Hu Weigang , Peng Jie , Filimonenko Ekaterina , Alharbi Sulaiman Almwarai , Zhu Jianxiao , Li Xiaogang , Li Chunjie , He Jin‐Sheng , Niklas Karl J. , Kuzyakov Yakov , Deng Jianming 
Published: October 2024

ABSTRACTInorganic carbon is an important component of soil carbon stocks, exerting a profound influence on climate change and ecosystem functioning. Drylands account for approximately 80% of the global soil inorganic carbon (SIC) pool within the top 200 cm. Despite its paramount importance, the components of SIC and their contributions to CO2 fluxes have been largely overlooked, resulting in notable gaps in understanding its distribution, composition, and responses to environmental factors across ecosystems, especially in deserts and temperate grasslands. Utilizing a dataset of 6011 samples from 173 sites across 224 million hectares, the data revealed that deserts and grasslands in northwestern China contain 20 ± 2.5 and 5 ± 1.3 petagrams of SIC in the top 100 cm, representing 5.5 and 0.76 times the corresponding soil organic carbon stock, respectively. Pedogenic carbonates (PIC), formed by the dissolution and re‐precipitation of carbonates, dominated in grasslands, accounting for 60% of SIC with an area‐weighted density of 3.4 ± 0.4 kg C m−2 at 0–100 cm depth, while lithogenic carbonates (LIC), inherited from soil parent materials, prevailed in deserts, constituting 55% of SIC with an area‐weighted density of 7.1 ± 1.0 kg C m−2. Soil parent materials and elevation determined the SIC stocks by regulating the formation and loss of LIC in deserts, whereas natural acidification, mainly induced by rhizosphere processes including cation uptake and H+ release as well as precipitation, reduced SIC (mainly by PIC) in grasslands. Overall, the massive SIC pool underscores its irreplaceable role in maintaining the total carbon pool in drylands. This study sheds light on LIC and PIC and highlights the critical impact of natural acidification on SIC loss in grasslands.
Homelessness and Sofa‐Surfing: Everyday Belonging, Mobilities, Identities and Morals in Hidden Spaces of Welfare
Authors: Green Kieran , Holton Mark , Yarwood Richard 
Published: October 2024

ABSTRACTThis paper advances existing work on the geographies of homelessness by considering the phenomenon of sofa‐surfing—defined as the practice of living in a host's home, without a right to reside, in the absence of more permanent accommodation—as a distinctive, and until recently somewhat hidden, form of homelessness. Examining sofa‐surfing is important as it recognises the varied and intersecting spatial, temporal and mobility characteristics of vulnerable populations, often thought to be living at the margins of homelessness. Across the globe, the significant increase in sofa‐surfing since the 2010s, coupled with the unique, and frequently hidden, movements between ‘host’ homes, and the interrelationships that exist between sofa‐surfers and hosts, makes sofa‐surfing an essential lens through which to interpret the diverse geographies of 21st Century homelessness. To achieve this, we draw together work from a range of global contexts that examine the roots of stigmatised homeless identities and punitive public policies, alongside studies of homeless mobilities and performative homeless identities, to help understand the complex precarities associated with feelings of dislocation and (not) belonging. Investigating patterns of sofa‐surfing mobilities alongside sofa‐surfers’ fluid performative identities matters, and this paper provides new ways of understanding how such unique interactions impact sofa‐surfers’ felt capacities to belong within and between sofa‐surfing spaces.
Optimizing use of an electronic medical record system for quality improvement initiatives in hemodialysis: Review of a single center experience
Authors: Laurier Noémie , Robert Jorane‐Tiana , Tom Alexander , McKinnon Jerrica , Filteau Nancy , Horowitz Laura , Vasilevsky Murray , Weber Catherine , Podymow Tiina , Cybulsky Andrey V. , Suri Rita S. , Trinh Emilie 
Published: October 2024

AbstractIntroductionThe complexity of managing patients with end‐stage kidney disease on hemodialysis underscores the importance of implementing quality improvement (QI) initiatives to enhance patient safety and prioritize patient‐centered care. To address this, we established a QI committee at our tertiary academic center focusing on evidence‐based practices, patient‐centered approaches, and cost efficiency. To facilitate the seamless implementation of QI initiatives, we leveraged the capabilities of our electronic medical record (EMR) system.MethodsThis review details effective strategies for optimizing use of an EMR system to successfully implement QI efforts. Drawing from our experience, we provide detailed descriptions and practical insights that can be applied to other EMRs.FindingsThe creation of a secure and accessible dashboard, offering real‐time data on quality metrics, stands out as the most notable feature. This dashboard operates through an algorithm that merges data from both our dialysis and hospital EMR systems. Its primary objectives are to streamline the identification of high‐priority patients, enhance team communication, and facilitate tracking of quality indicators. Additionally, we integrated clinical pathways, checklists, and standardized protocols into the renal EMR to ensure smooth implementation of QI interventions. Notable examples of these interventions include an incremental hemodialysis protocol, a new hemodialysis start checklist, vaccination care plans, and personalized kidney transplant workups. Programmed electronic automatic reminders have proven invaluable in ensuring timely follow‐ups of assigned tasks. The EMR has also contributed to medication optimization and deprescribing by generating patient lists based on specific medication classes. Finally, the EMR's capability to swiftly generate lists of patients with specific features has significantly facilitated targeted QI interventions.ConclusionsLeveraging the capabilities of an EMR system can be crucial for enhancing care of hemodialysis patients and implementing effective QI initiatives.
Operational efficiency effect on nursing workload of tertiary hospital wards in China: A prospective observational study
Authors: Ren Hong‐Fei , Liu Chang‐Qing , Jiang Yan , Chen Feng‐Jiao , Lv Juan , Zhang Rui‐Xue , Wen Li‐Min , Li You‐Ping , Gu Bo 
Published: October 2024

AbstractAimsTo investigate the effect of ward operational efficiency on nursing workload and identify the factors that influence nursing workload.BackgroundIt remains unclear how and to what extent ward operational efficiency can influence nursing workload.MethodsA prospective observational study was conducted from July 1, 2022 to June 30, 2023, in one tertiary general hospital in China. Purposive and convenience sampling was used, and 266 470 patients from 66 wards and 52 nurses from 13 wards were recruited. The relationships between operational efficiency and nursing workload and the predictors of nursing workload were analyzed. The STROBE guidelines were followed.ResultsThe operational characteristics vary by the type of wards. Nursing workloads were positively correlated with case mix index (CMI), rate of level 4 surgery, the number of patients transferred in and out, the number of deaths, total bed days, and the number of emergency admissions and critical illnesses (γs: 0.35–0.56, p < 0.05). And the CMI, rate of level 4 surgery, average bed occupancy rate, number of critically ill patients, and total bed days were the predictors of nursing workload (R2 = 57.3%, p < 0.05).DiscussionThis study is the first to discuss the relationship between operational efficiency and nursing workload on the ward level and offers valuable insights into the nursing workload.ConclusionThe operational efficiency of wards affects the nursing workload and needs to be considered both in the measurement of nursing activities and in the sizing of the nursing staff.Implications for nursing and nursing policyThe study findings provide a full understanding of the relationship between ward operation and nurse staffing, which is helpful for nursing managers to formulate scientific nurse staffing policies.