bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery and Model‐Informed Drug Development of a Controlled‐Release Formulation of Nonracemic Amisulpride that Reduces Plasma Exposure but Achieves Pharmacodynamic Bioequivalence in the Brain
Authors: Hopkins Seth C. , Toongsuwan Siriporn , Corriveau Taryn J. , Watanabe Takao , Tsushima Yuki , Asada Takumi , Lew Robert , Shi Lei , Zann Vanessa , Snowden Thomas J. , van der Graaf Piet H. , Darpo Borje , Searle Graham E. , Rabiner Eugenii A. , Wilding Ian , Szabo Steven T. , Galluppi Gerald R. , Koblan Kenneth S. 
Published: June 2024

Nonracemic amisulpride (SEP‐4199) is an investigational 85:15 ratio of aramisulpride to esamisulpride and currently in clinical trials for the treatment of bipolar depression. During testing of SEP‐4199, a pharmacokinetic/pharmacodynamic (PK/PD) disconnect was discovered that prompted the development of a controlled‐release (CR) formulation with improved therapeutic index for QT prolongation. Observations that supported the development of a CR formulation included (i) plasma concentrations of amisulpride enantiomers were cleared within 24‐hours, but brain dopamine D2 receptor (D2R) occupancies, although achieving stable levels during this time, required 5 days to return to baseline; (ii) nonracemic amisulpride administered to non‐human primates produced significantly greater D2R occupancies during a gradual 6‐hour administration compared with a single bolus; (iii) concentration–occupancy curves were left‐shifted in humans when nonracemic amisulpride was gradually administered over 3 and 6 hours compared with immediate delivery; (iv) CR solid oral dose formulations of nonracemic amisulpride were able to slow drug dissolution in vitro and reduce peak plasma exposures in vivo in human subjects. By mathematically solving for a drug distribution step into an effect compartment, and for binding to target receptors, the discovery of a novel PK/PD model (termed here as Distribution Model) accounted for hysteresis between plasma and brain, a lack of receptor saturation, and an absence of accumulation of drug occupancy with daily doses. The PK/PD disconnect solved by the Distribution Model provided model‐informed drug development to continue in Phase III using the non‐bioequivalent CR formulation with diminished QT prolongation as dose‐equivalent to the immediate release (IR) formulation utilized in Phase II.
Exploring the Critical Factors Toward Spectrally Stable Mixed‐Halide Blue Perovskite LEDs
Authors: Wei Lulu , Tian Shubing , Sun Mingze , Song Ruili , Wang Yunhu , Zhang Mingming , Wang Lei , Wei Zhanhua , Xing Jun 
Published: June 2024

AbstractMetal mixed‐halide perovskite has demonstrated considerable potential in the development of solution‐treated blue light‐emitting diodes (LEDs) with high external quantum efficiency, excellent color purity, and tunable wavelength. However, the severe phase segregation of mixed‐halide perovskite under bias voltage would lead to the spectral instability of LEDs. Therefore, suppressing phase segregation of Br/Cl perovskite towards spectrally stable blue perovskite LEDs (PeLEDs) is a big challenge. In this work, we systematically explore the influence of perovskite component, preparation conditions, and device structures on the spectral stability of PeLEDs. We have observed that the stable spectra increased the proportion of Cs in the A‐site cations, passivator, and the annealing temperature of perovskite films. Finally, we achieve a spectra‐stable and high‐performance blue PeLED under optimized conditions. Our findings provide important guidance for preparing spectrally stable PeLEDs.
Efficacy and safety of uncovered self‐expandable metal stents for distal malignant biliary obstruction in unresectable non‐pancreatic cancer
Authors: Niiya Fumitaka , Tamai Naoki , Yamawaki Masataka , Noda Jun , Azami Tetsushi , Takano Yuichi , Nishimoto Fumiya , Nagahama Masatsugu 
Published: June 2024

AbstractObjectivesThe efficacy of uncovered self‐expandable metal stents (UCSEMS) versus fully covered self‐expandable metal stents for distal malignant biliary obstruction remains controversial. Additionally, the heterogeneity of the disease conditions has been indicated in previous studies because pancreatic and non‐pancreatic cancers have different characteristics in clinical course. Therefore, the etiology of biliary obstruction necessitates investigations stratified by primary disease. This study aimed to evaluate the outcomes of UCSEMS, specifically for non‐pancreatic cancer‐induced distal malignant biliary obstruction.MethodsWe conducted a single‐center retrospective review to evaluate the time to recurrent biliary obstruction and frequency of adverse events (AEs) in patients receiving UCSEMS for unresectable non‐pancreatic cancer‐induced malignant biliary obstruction.ResultsOverall, 32 patients were enrolled in the study between January 2016 and December 2023. The median time to recurrent biliary obstruction was 140 days. AE rates were low at 3.1% for both pancreatitis and cholecystitis, suggesting a potential benefit of UCSEMS in reducing post‐procedural AEs.ConclusionUCSEMS may reduce the risk of post‐procedural AEs and should be considered in patients at high risk of post‐endoscopic retrograde cholangiopancreatography pancreatitis. However, the patency period may be shorter, necessitating future comparative research with fully covered self‐expandable metal stents to determine the optimal stent choice.
Shifting institutional culture to develop climate solutions with Open Science
Authors: Lowndes Julia Stewart , Holder Anna M. , Markowitz Emily H. , Clatterbuck Corey , Bradford Amanda L. , Doering Kathryn , Stevens Molly H. , Butland Stefanie , Burke Devan , Kross Sean , Hollister Jeffrey W. , Stawitz Christine , Siple Margaret C. , Rios Adyan , Welch Jessica Nicole , Li Bai , Nojavan Farnaz , Davis Alexandra , Steiner Erin , London Josh M. , Fenwick Ileana , Hunzinger Alexis , Verstaen Juliette , Holmes Elizabeth , Virdi Makhan , Barrett Andrew P. , Robinson Erin 
Published: June 2024

AbstractTo address our climate emergency, “we must rapidly, radically reshape society”—Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross‐government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations. We share much‐needed success stories and action for what we can all do to reshape science as part of the Open Science movement and 2023 Year of Open Science.
Coping with provoked vestibulodynia in a relational context—A cluster analysis of coping patterns and their associations with relational cognitions and goals
Authors: Ekholm Elin , Engman Linnéa , ter Kuile Moniek M. , Flink Ida K. 
Published: June 2024

AbstractBackgroundProvoked vestibulodynia (PVD) is a common pain condition, negatively impacting the relationships and sexual lives of sufferers. Women's coping behaviour has been associated with psychosexual outcomes, yet coping patterns in clinical PVD samples are unexplored, and it is not known how women's coping relates to their relational context.MethodWomen (N = 128) with PVD answered questionnaires about psychosexual function, pain coping (avoidance and endurance), relational‐ and pain catastrophizing, sexual goals and perceived partner responses. Cluster analysis was used to explore coping patterns; clusters were validated on measures of pain and psychosexual function and compared on catastrophizing, sexual goals and partner responses using multivariate analyses of variance.ResultsThe analysis yielded four clusters: endurance; combined high avoidance and endurance; avoidance; and combined low. The group with high levels of both avoidance and endurance coping displayed the worst psychosexual outcomes and high levels of pain‐ and relational catastrophizing, approach and avoidance goals and perceived negative partner responses.ConclusionThere are distinct patterns of coping among women with PVD, and these coping patterns are associated with psychosexual outcomes and relational cognitions and goals, and perceived partner responses. Women who alternate between avoidance and endurance are more distressed and report worse psychosexual functioning. This pattern needs to be identified and addressed in the treatment of PVD.Significance StatementThis study extends previous findings on vulvar pain coping patterns to a clinical population of women with PVD. It is further the first study to address the relationship between relational variables, such as partner responses and relational catastrophizing and different coping patterns. Thus, the contribution of this study is the contextualizing of coping patterns among women with PVD. The results showed that a combined pattern of avoidance and endurance coping is associated with high distress, poor psychosexual outcomes, and indications of insufficient relational coping, highlighting the need for clinical assessment and intervention to target both women's individual coping patterns and their relational context.
Performance of an aptamer‐based neuropeptide Y potentiometric sensor: dependence on spacer molecule selection
Authors: Richardson Hayley , Kline Alex , Pavlidis Spyridon 
Published: June 2024

AbstractNeuropeptide Y (NPY) plays a central role in a variety of emotional and physiological functions in humans, such as forming a part of the body′s response to stress and anxiety. This work compares the impact of MCH and PEG spacer molecules on the performance of a potentiometric NPY sensor. An NPY‐specific DNA aptamer with thiol termination was immobilized onto a gold electrode surface. The performance of the sensor is compared when either an MCH‐ or PEG‐based self‐assembled monolayer is formed following aptamer immobilization. Backfilling the surface with alkanethiol spacer molecules like these is key for proper conformational folding of aptamer‐target binding. Non‐specific adhesion of NPY to the MCH‐based sensor surface was observed via surface plasmon resonance (SPR), and then confirmed via potentiometry. It is then shown that PEG improves the sensor′s sensitivity to NPY compared to the surfaces with an MCH‐based SAM. We achieve the detection of picomolar range NPY levels in buffer with a sensitivity of 36.1 mV/decade for the aptamer and PEG‐based sensor surface, thus demonstrating the promise of potentiometric sensing of NPY for future wearable deployment. The sensor′s selectivity was also studied via exposure to cortisol, a different stress marker, resulting in a 13x smaller differential voltage (aptamer‐specific) response compared to that of NPY.
Recent progress on battery thermal management with composite phase change materials
Authors: Kumar SR Shravan , Rao G. Amba Prasad 
Published: June 2024

AbstractElectric mobility decarbonizes the transportation sector and effectively addresses sustainable development goals. A good battery thermal management system (BTMS) is essential for the safe working of electric vehicles with lithium‐ion batteries (LIBs) to address thermal runaway and associated catastrophic hazards effectively. However, PCMs suffer from low thermal conductivity issues, and hence, enhancement techniques include the use of fins, nano‐additives, extended graphite powder, and so forth. The use of composite phase change materials effectively addresses LIB thermal management widely used in electric vehicles while mitigating thermal runaway, besides providing flame retardancy, thermal/mechanical stability, and electrical insulation, and preventing leakage. It is noted that no single strategy of BTMS is brought down to a safe zone of temperature, and hybrid BTMSs are being employed, invariably involve phase change materials (PCMs) to a large extent. It is essential to utilize CPCMs to address the effects of low‐temperature environments and vibrations considering vehicle driving cycles and operating conditions. It is observed from the review that ultrasonic monitoring and early detection of internal short circuits are the steps towards mitigation of thermal runaway propagation. It is required to utilize optimization methods, machine learning and IoT tools for a feasible PCM based BTMS work. Present review briefly describes potential methods for effective utilization of PCMs, comparison among different methods, challenges associated and potential solutions. It is highly essential to develop compact and economical BTMS with effective CPCMs for better and safer LIB operation to attract large‐scale commercialization of electric vehicles.
Kinetics of EBV antibody‐based NPC risk scores in Taiwan NPC multiplex families
Authors: Hsu Wan‐Lun , Tao Jun , Fu Sheng , Yu Kelly J. , Simon Julia , Chen Tseng‐Cheng , Chen Chien‐Jen , Goldstein Alisa M. , Yu Kai , Hildesheim Allan , Waterboer Tim , Wang Cheng‐Ping , Liu Zhiwei 
Published: June 2024

AbstractNasopharyngeal carcinoma (NPC) risk prediction models based on Epstein–Barr virus (EBV)‐antibody testing have shown potential for screening of NPC; however, the long‐term stability is unclear. Here, we investigated the kinetics of two EBV‐antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2‐marker enzyme‐linked immunosorbent assay score and 13‐marker multiplex serology score using the intra‐class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20‐year follow‐up, the 2‐marker score showed high stability over time, whereas the 13‐marker score was more variable (p < .05). Case–control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2‐marker score than the 13‐marker score (p < .05). The 2‐marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13‐marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high‐risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high‐risk regions.
Digital strategy in Brazilian family business
Authors: Oro Ieda Margarete , Begnini Sérgio , Cassaro Edna , Scherner Taís Trevisol 
Published: June 2024

AbstractThe study aimed to analyze the effect of digitalization strategies on business performance, mediated by organizational innovation in Brazilian family Micro, Small, and Medium Enterprises (MSMEs). This research adopted a descriptive approach with a quantitative methodology, using a sample of 301 Brazilian family MSMEs. Data were collected from studies by the Foundation for Strategic Analysis and Development of Small and Medium Enterprises (FAEDPYME). The theoretical model generated four research hypotheses. Data were processed and analyzed using the structural equation method in SmartPLS 4.0 software. The results confirm the existence of a positive and significant relationship between digitalization strategies, business performance, and organizational innovation, including the mediating effect. The findings highlight the importance of digitalization strategies and organizational innovation in driving the business performance of Brazilian family MSMEs. This study contributes to strategic management practices in family businesses by identifying that effective digitalization strategies and innovation practices allow significant advancements in business performance and subsequent organizational innovation. Thus, they can guide the development of more effective business policies and practices, contributing to the competitiveness of family businesses in the contemporary market.
A perspective on downstream processing performance for recovery of bioalcohols
Authors: Janković Tamara , Straathof Adrie JJ , Kiss Anton A 
Published: June 2024

AbstractEven though industrial biotechnology is successfully used for the production of some chemicals, for many other chemicals it is not yet competitive with conventional petrochemical production. Usually, fermentation as well as downstream processing requires improvement. Downstream processing has to deal with low product concentrations, microorganisms, impurities and thermodynamic constraints (e.g., azeotropes), which often makes it very challenging and expensive, especially on a large scale. However, downstream processing of biochemicals has not attracted as much attention as upstream fermentation processes. In that context, this perspective paper offers a lightly referenced scholarly opinion about the downstream processing performance of different bioalcohols after fermentation. Due to the stronger toxicity effects on microbes, the achievable concentrations of monohydric aliphatic alcohols in the fermentation broth decrease with the increasing chain length. Specifically, the concentrations used here are 6.14, 5.00, 1.61 and 0.24 wt% of ethanol, isopropanol, isobutanol and hexanol, respectively. More dilute fermentation broths lead to more complex recovery processes. According to our previous work, the total purification costs increase from 0.080 USD kg−1 for ethanol, 0.109 USD kg−1 for isopropanol and 0.161 USD kg−1 for isobutanol to 0.529 USD kg−1 for hexanol. A similar trend is noticeable for the energy usage (0.960, 1.348, 2.018 and 3.069 kWthh kg−1, respectively) and the related CO2 emissions (0.164, 0.221, 0.449 and 0.555 kgCO2 kg−1, respectively). This work shows that advanced separation and purification based on process intensification principles are crucial for overall efficient production processes. The achievable product concentration in the fermentation broth – and not so much the alcohol chain length – has the biggest influence on the performance of downstream processing. Therefore, simultaneous development of both upstream and downstream processing is necessary to ensure the competitiveness and viability of industrial fermentation processes. © 2024 The Author(s). Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Policy and laboratory practice: How quality control procedures for genetic testing perpetuate biological essentialism and discrimination against transgender, gender diverse, and intersex people
Authors: Dusic Emerson J. , Powers Lex N. , Clowes Candadai Sarah V. , Fullerton Stephanie M. 
Published: June 2024

AbstractTransgender, gender diverse, and intersex (TGDI) individuals face significant health disparities due to individual and systemic experiences of discrimination, impacting their access to healthcare. While clinical genetic testing has become increasingly accessible to the general population, the field of clinical genetics perpetuates a narrative of biological essentialism, which creates barriers for TGDI patients. Biological essentialism upholds that sex is a binary, fixed, and innate characteristic, a misconception that has been historically weaponized against the TGDI community in both individual experiences of discrimination and anti‐trans legislation, among other systemic forms of oppression. Rejecting this discriminatory framework requires careful consideration of, and changes to, long‐established practices that often go unquestioned, such as quality control metrics in genetic testing, in order to improve TGDI patients' outcomes and access to genetic services. The sex‐check, comparing an individuals reported sex against their sex chromosomes, is an example of how laboratory genetics practices reinforce the narrative that sex is determined purely by chromosomal composition. Additionally, the sex‐check “outs” TGDI people in clinical settings, creating a discriminatory and unsafe environment for these patients. Alternative quality control procedures and inclusive practices, such as clearer delineation of sex and gender on test requisition forms, are proposed to improve TGDI patient experiences. Genetic counselors and other clinical providers have a responsibility to address historical discrimination and advocate for changes to laboratory practice, so as to create affirming experiences for TGDI patients.
Amide Proton Transfer‐Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer
Authors: Kong Lingmin , Li Hui , Cai Qian , Cao Wenxin , Chen Yanling , Weng Bei , Li Meiqin , Zhang Min , Qian Long , Guo Yan , Ling Jian , Wen Zhihua , Wang Huanjun 
Published: June 2024

BackgroundKi‐67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision‐making. Recently, amide proton transfer‐weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki‐67 and HER2 status of BCa.PurposeTo investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki‐67 and HER2 in BCa.Study TypeRetrospective.Subjects114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied.Field Strength/SequenceAPTw MRI acquired by a three‐dimensional fast‐spin‐echo sequence at 3.0 T MRI system.AssessmentPatient pathologic findings, included histologic grade and the expression status of Ki‐67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high−/low‐tumor grade group, high−/low‐Ki‐67 expression group, and high−/low‐HER2 expression group.Statistical TestsThe interclass correlation coefficient, independent sample t‐test, Mann–Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant.ResultsSignificantly higher APTw values were found in high‐grade BCa patients (7.72% vs. 4.29%, P < 0.001), high‐Ki‐67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki‐67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki‐67 and HER2 expression status were 0.883 (95% CI: 0.790–0.945) and 0.713 (95% CI: 0.592–0.816), respectively.Data ConclusionsAPTw MRI is a potential method to assess the biological and proliferation potential of BCa.Level of Evidence4.Technical EfficacyStage 2.