bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1
Authors: Deshmukh Nitin J. , Kalshetti M. S. , Patil Mohan , Autade Pankaj , Sangle Ganesh V. 
Published: March 2024

AbstractSotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon‐like peptide‐1 (GLP‐1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat‐regulating peptides such as GLP‐1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP‐1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP‐IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton‐induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co‐administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and β‐hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high‐fat diet (HFD)‐fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin‐6 (IL‐6) and tumour necrosis factor alpha (TNF‐α) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP‐1 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.
Economic returns to reproducing parents' field of study
Authors: Birkelund Jesper Fels 
Published: March 2024

AbstractResearch on the influence of family background on college graduates' earnings has not considered the importance of the match between parents' and children's field of study. Using a novel design based on within‐family comparisons, I examine long‐term earnings returns to reproducing parents' field of study in Denmark. I find that individuals whose field of study matches that of a parent have earnings that are 2 percent higher than those of their siblings with college degrees in different fields, on average. Earnings returns to field inheritance are highest in the fields of law (9 percent), medicine (6 percent), and engineering (4 percent) and are driven mainly by income from self‐employment. I find no direct evidence of nepotism as the earnings advantage does not arise from inheritance of parents' firms or employment in parents' occupational network. My findings indicate that, although a college degree generally equalizes family background differences in economic outcomes, there are additional payoffs to field inheritance, particularly in traditional fields characterized by a high degree of social closure and self‐employment.
Combinatorial optimization of pathway, process and media for the production of p‐coumaric acid by Saccharomyces cerevisiae
Authors: Moreno‐Paz Sara , van der Hoek Rianne , Eliana Elif , Martins dos Santos Vitor A. P. , Schmitz Joep , Suarez‐Diez Maria 
Published: March 2024

AbstractMicrobial cell factories are instrumental in transitioning towards a sustainable bio‐based economy, offering alternatives to conventional chemical processes. However, fulfilling their potential requires simultaneous screening for optimal media composition, process and genetic factors, acknowledging the complex interplay between the organism's genotype and its environment. This study employs statistical design of experiments to systematically explore these relationships and optimize the production of p‐coumaric acid (pCA) in Saccharomyces cerevisiae. Two rounds of fractional factorial designs were used to identify factors with a significant effect on pCA production, which resulted in a 168‐fold variation in pCA titre. Moreover, a significant interaction between the culture temperature and expression of ARO4 highlighted the importance of simultaneous process and strain optimization. The presented approach leverages the strengths of experimental design and statistical analysis and could be systematically applied during strain and bioprocess design efforts to unlock the full potential of microbial cell factories.
Systemic intracellular analysis for balancing complex biosynthesis in a transcriptionally deregulated Escherichia colil‐Methionine producer
Authors: Harting Claudia , Teleki Attila , Braakmann Marius , Jankowitsch Frank , Takors Ralf 
Published: March 2024

Abstractl‐Methionine (l‐Met) has gained remarkable interest due to its multifaceted and versatile applications in the fields of nutrition, pharmaceuticals and clinical practice. In this study, the fluxes of the challenging l‐Met biosynthesis in the producer strain Escherichia coli (E. coli) DM2853 were fine‐tuned to enable improved l‐Met production. The potential bottlenecks identified in sulfur assimilation and l‐Met synthesis downstream of O‐succinyl‐l‐homoserine (OSHS) were addressed by overexpressing glutaredoxin 1 (grxA), thiosulfate sulfurtransferase (pspE) and O‐succinylhomoserine lyase (metB). Although deemed as a straightforward target for improving glucose‐to‐Met conversion, the yields remained at approximately 12%–13% (g/g). Instead, intracellular l‐Met pools increased by up to four‐fold with accelerated kinetics. Overexpression of the Met exporter ygaZH may serve as a proper valve for releasing the rising internal Met pressure. Interestingly, the export kinetics revealed maximum saturated export rates already at low growth rates. This scenario is particularly advantageous for large‐scale fermentation when product formation is ideally uncoupled from biomass formation to achieve maximum performance within the technical limits of large‐scale bioreactors.
Prenatal post‐implantation development of collared peccaries (Pecari tajacuLinnaeus, 1758)
Authors: de Araújo Júnior Hélio Noberto , Lopes Igor Renno Guimarães , de Sousa Ana Caroline Freitas Caetano , de Oliveira Gleidson Benevides , de Oliveira Radan Elvis Matias , Tertulino Moisés Dantas , Rocha Emanuel Lucas Bezerra , Firmino Paulo Ricardo , Pereira Alexsandra Fernandes , de Oliveira Moacir Franco 
Published: March 2024

AbstractGiven the importance of information on intrauterine development in diagnosing anomalies in the gestational development of the species for the development of assisted reproduction technologies as well as understanding the autonomy and responsiveness of the newborn, the aim of the present study was to describe the external morphology of collared peccary conceptuses. For this study, two conceptuses were used per gestational age of 25–120 days post‐copulation (dpc) and neonates with 145 dpc, totalling 22 animals. Females were euthanised, and embryos/foetuses were examined, measured, and photographed. During the first third of the gestational period (25–50 dpc,n = 8), a marked body curvature, brain vesicles, somites, internal organs, placid lens, auricular protrusion and limb buds are noted. In the second third of the gestational period (51–100 dpc,n = 10), foetuses lose their body curvature, displaying greater anatomical definition, including skeletal, external ears, nostrils, eyelids and tactile hair formation and cranial suture closure. In addition, dorsal scent gland and genital tubercle differentiation were visualized at 50 days post‐copulation. In the third of the gestational period (101–145 dpc,n = 4), the organs become completely formed, alongside skin darkening, eyelid opening, dental eruption, dorsal odorous gland development, sexual organ externalization, and fanero attachment development. These data allowed for the construction of a prenatal growth curve, providing comparative anatomy information for ungulates and further contributing towards rational reproductive management and reproductive biotechnologies for this species.
Altered placental immune cell composition and gene expression with isolated fetal spina bifida
Authors: White Marina , Abdo Hasan , Grynspan David , Mieghem Tim Van , Connor Kristin L. 
Published: March 2024

AbstractProblemFetal spina bifida (SB) is more common in pregnant people with folate deficiency or anomalies of folate metabolism. It is also known that fetuses with SB have a higher risk of low birthweight, a condition that is typically placental‐mediated. We therefore hypothesized that fetal SB would associate with altered expression of key placental folate transporters and an increase in Hofbauer cells (HBCs), which are folate‐dependent placental macrophages.Method of studyFolate receptor‐α (FRα), proton coupled folate receptor (PCFT), and reduced folate carrier (RFC) protein localization and expression (immunohistochemistry) and HBC phenotypes (HBC abundance and folate receptor‐β [FRβ] expression; RNA in situ hybridization) were assessed in placentae from fetuses with SB (cases; n = 12) and in term (n = 10) and gestational age (GA) – and maternal body mass index – matched (n = 12) controls without congenital anomalies.ResultsCases had a higher proportion of placental villous cells that were HBCs (6.9% vs. 2.4%, p = .0001) and higher average HBC FRβ expression (3.2 mRNA molecules per HBC vs. 2.3, p = .03) than GA‐matched controls. HBCs in cases were largely polarized to a regulatory phenotype (median 92.1% of HBCs). In sex‐stratified analyses, only male cases had higher HBC levels and HBC FRβ expression than GA‐matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FRα, PCFT, or RFC protein immunolabeling.ConclusionsHBC abundance and FRβ expression by HBCs are increased in placentae of fetuses with SB, suggesting immune‐mediated dysregulation in placental phenotype, and could contribute to SB‐associated comorbidities.
Pneumocystis jirovecii pneumonia in paediatric acute lymphoblastic leukaemia: A report from the multi‐international clinical trial AIEOP‐BFM ALL 2009
Authors: Barnbrock Anke , Möricke Anja , Barbaric Draga , Jones Neil , Koenig Christa , Moser Reinhard , Rohde Marius , Salvador Christina , Alten Julia , Elitzur Sarah , Groll Andreas H. , Lehrnbecher Thomas 
Published: March 2024

SummaryPneumocystis jirovecii can cause life‐threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic measures have significantly decreased morbidity and mortality, but there is a paucity of contemporary data on the incidence and clinical course of PjP in well‐defined and homogenous patient populations, such as children suffering from acute lymphoblastic leukaemia (ALL). In the multi‐international trial AIEOP‐BFM ALL2009, PjP was diagnosed in six children (incidence 1/1000) and was associated with insufficient prophylaxis in five of them. Although none of the patients died of PjP, the long‐term impact of the infection is unclear.
Nectar robbing effects on pollinators of a key nectar source plant (Tecoma fulva, Bignoniaceae) in a dry tropical Andean valley
Authors: Maidana‐Tuco Yamil N. , Larrea‐Alcázar Daniel M. , Pacheco Luis F. 
Published: March 2024

AbstractZoophilous flowering plants have features to attract their pollinators, which may also be used by exploiters like nectar robbers. Nectar robbers access nectar by probing flower corollas (primary robbing) or use existing holes (secondary robbing). Nectar robbing can negatively impact a plant's fitness directly by damaging the reproductive structures of the flower or indirectly by modifying the visitation patterns of pollinators. We tested the hypothesis that the robbed flowers are less visited by legitimate pollinators by comparing floral visitors and visitation frequency in primary‐, secondary‐, and un‐robbed flowers of Tecoma fulva spp. Altoandina, a native shrub species that is an important nectar source for nectarivores in the dry valleys of the Bolivian Andes (Bignoniaceae). The Giant Hummingbird, Patagona gigas (Trochilidae), was the main visitor of T. fulva and visited more frequently un‐robbed flowers, followed by secondary robbed and primary robbed flowers. The variation in visitation frequency may result in less pollen transport to robbed flowers, which may have negative consequences for the biological fitness, probably manifested in decreased seed production.Abstract in Spanish is available with online material.
Difficulties in disclosing secondary findings by facilities performing comprehensive germline genetic testing for rare diseases in Japan
Authors: Hiromoto Kana , Yamada Takahiro , Tsuchiya Mio , Kawame Hiroshi , Nanba Eiji , Goto Yuichi , Kosugi Shinji 
Published: March 2024

AbstractIn Japan, a limited number of laboratories perform comprehensive genetic testing for rare diseases; this study investigated the attitudes of these laboratories toward the disclosure of secondary finding (SF). Following a preliminary survey, we identified laboratories conducting comprehensive genetic testing for participation. Subsequently, an online survey involving 20 selected facilities was conducted. The response rate was 80% (16/20). Of the 14 facilities, 71.4% had SFs. While 42.9% of them had a policy to disclose SFs with clinical utility, only 14.3% actively searched for actionable variants that could be included in the American College of Medical Genetics and Genomics list. Japan was less enthusiastic than the USA regarding SF disclosure. With regard to the reasons for not disclosing SFs, the factors “the thought that participants may have a low desire for SFs” and “uncertainty regarding their wish” were considered more important than in the USA. A content analysis of what was sought as a solution to this difficulty revealed a need to improve databases on pathogenicity and actionability and collect public thoughts on the issue. The factor “to promote entry in research” was not considered a critical reason for disclosing SFs, indicating that the thirst for information was not possibly due to anxiety but rather due to scientific interest. Japanese medical professionals may not be confident that society requires the disclosure of SFs. To improve the environment, it is necessary to survey the public regarding their thoughts on SF disclosure and discuss this issue in society.
Role of dendritic cells in spinal cord injury
Authors: Han Xiaonan , Zhang Mingkang , Yan Liyan , Fu Yikun , Kou Hongwei , Shang Chunfeng , Wang Junmin , Liu Hongjian , Jiang Chao , Wang Jian , Cheng Tian 
Published: March 2024

AbstractBackgroundInflammation can worsen spinal cord injury (SCI), with dendritic cells (DCs) playing a crucial role in the inflammatory response. They mediate T lymphocyte differentiation, activate microglia, and release cytokines like NT‐3. Moreover, DCs can promote neural stem cell survival and guide them toward neuron differentiation, positively impacting SCI outcomes.ObjectiveThis review aims to summarize the role of DCs in SCI‐related inflammation and identify potential therapeutic targets for treating SCI.MethodsLiterature in PubMed and Web of Science was reviewed using critical terms related to DCs and SCI.ResultsThe study indicates that DCs can activate microglia and astrocytes, promote T‐cell differentiation, increase neurotrophin release at the injury site, and subsequently reduce secondary brain injury and enhance functional recovery in the spinal cord.ConclusionsThis review highlights the repair mechanisms of DCs and their potential therapeutic potential for SCI.
Value of rapid on‐site evaluation combined with interventional pulmonology techniques in the diagnosis of pulmonary cryptococcosis
Authors: Cao Jiaqi , Zhou Rong , He Qian , Zhang Ming , Feng Chunlai 
Published: March 2024

AbstractObjectivesThe aim of this study is to evaluate the diagnostic value of rapid on‐site evaluation (ROSE) combined with computed tomography‐guided percutaneous needle biopsy (CT‐PNB) or radial endobronchial ultrasound‐guided transbronchial lung biopsy (EBUS‐TBLB) for pulmonary cryptococcosis (PC).MethodsClinical data of 33 patients diagnosed with PC at the Third Affiliated Hospital of Soochow University between February 2018 and June 2023 were retrospectively analysed. Patients were divided into the CT‐PNB and EBUS‐TBLB groups based on the intervention method, and the diagnostic positivity rate and incidence of complications were compared between the two groups.ResultsCompared with the final diagnosis, the positive diagnostic rates of ROSE, histopathology and serum CrAg of all patients were 81.8% (27/33), 72.7% (24/33) and 63.6% (21/33), respectively. The average turnaround times of the three methods were 0.1 (0.1–0.2) h, 96.0 (48.0–120.0) h and 7.8 (4.5–13.6) h, respectively (P < 0.001). The coincidence rate between histopathology and ROSE was 84.8% with a kappa value of 0.574. The positive diagnostic rate for PC was significantly higher in the CT‐PNB group than in the EBUS‐TBLB group (92.9% vs. 57.9%), and the difference was statistically significant (P < 0.05). Combined with the ROSE results, the positive diagnostic rate in the EBUS‐TBLB group increased to 84.2% (16/19).ConclusionROSE has commendable accuracy and timeliness, and CT‐PNB offers further advantages in this regard. ROSE enhances the diagnostic efficiency of EBUS‐TBLB for PC and is safe and effective.
Comparison of estimated glomerular filtration rate change with sodium‐glucose cotransporter‐2 inhibitors versus glucagon‐like peptide‐1 receptor agonists among people with diabetes: A propensity‐score matching study
Authors: Suzuki Yuta , Kaneko Hidehiro , Nagasawa Hajime , Okada Akira , Fujiu Katsuhito , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Nishiyama Akira , Gohda Tomohito , Suzuki Yusuke , Node Koichi , Yasunaga Hideo , Nangaku Masaomi , Komuro Issei 
Published: March 2024

AbstractAimTo compare the risk of developing kidney outcomes with use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) versus use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors among individuals with diabetes.Materials and MethodsIn this retrospective observational study, we analysed 12 338 individuals with diabetes who newly initiated SGLT2 inhibitors or GLP‐1RAs using data from the JMDC claims database. The primary outcome was change in the estimated glomerular filtration rate (eGFR), estimated using a linear mixed‐effects model. A 1:4 propensity‐score‐matching algorithm was used to compare the changes in eGFR between GLP‐1RA and SGLT2 inhibitor users.ResultsAfter propensity‐score matching, 2549 individuals (median [range] age 52 [46–58] years, 80.6% men) were analysed (510 GLP‐1RA new users and 2039 SGLT2 inhibitor new users). SGLT2 inhibitor use was associated with a slower eGFR decline when compared with GLP‐1RA use (−1.41 [95% confidence interval −1.63 to −1.19] mL/min/1.73 m2 vs. −2.62 [95% confidence interval −3.15 to −2.10] mL/min/1.73 m2).ConclusionsOur analysis demonstrates the potential advantages of SGLT2 inhibitors over GLP‐1RAs in terms of kidney outcomes in individuals with diabetes.
Effects of free maternal healthcare on stunting in children under five years of age: Evidence from Ghana
Authors: Bigool Mark 
Published: March 2024

AbstractMotivationAddressing stunting in early childhood can have lasting effects on an individual's health, productivity, and well‐being in adulthood. By understanding the relationship between maternal healthcare policies and stunting, policy‐makers can design interventions that contribute to a healthier and more productive society.PurposeThis study investigated the effect of providing free healthcare to pregnant mothers on child stunting.Approach and methodThe article uses doubly robust difference‐in‐difference estimator, drawing on Ghana Demographic and Health Survey.FindingsFree healthcare to mothers reduced stunting in the treatment regions by 12.3%. Evidence suggests the reform may have influenced children under the age of five through antenatal and delivery care attendance during pregnancy. Assistance during antenatal care and childbirth by health professionals improved significantly.Policy implicationsMaternal health investment yields great health benefits for children from in utero to their fifth birthday. Maternal fee exemptions should be continued to maintain and further improve stunting reduction in children. Government should prioritize improving access to quality maternal healthcare services, including antenatal and skilled birth attendance and emergency obstetric care.
The Pedagogy of “As If”
Authors: Dahlbeck Johan 
Published: March 2024

AbstractIn this paper Johan Dahlbeck sets out to propose a pedagogy of “as if,” seeking to address the educational paradox of how students can be influenced to approximate a life guided by reason without assuming that they are already sufficiently rational to adhere to dictates of practical reason. He does so by outlining a fictionalist account, drawing primarily on Hans Vaihinger's systematic treatment of heuristic fictions and on Spinoza's ideas about how passive affects can be made to strengthen reason. Dahlbeck suggests that such an account can help us overcome the problem of assuming that reason needs to be enlisted as an instrument in the educational endeavor to live according to the guidance of reason. The reason this is so is that fictions can use passive affects that are prosocial and that thereby strengthen the sense of community necessary for laying a cooperative foundation for successful joint striving. Dahlbeck suggests further that exemplary teachers are crucial to this endeavor insofar as they can offer educational fictions as imaginative and temporary placeholders for the truth, allowing students to act “as if” they were already guided by reason.