bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced-Function SLC22A1 Polymorphisms Encoding Organic Cation Transporter 1 and Glycemic Response to Metformin: A GoDARTS Study
Authors: Zhou Kaixin , Donnelly Louise A. , Kimber Charlotte H. , Donnan Peter T. , Doney Alex S.F. , Leese Graham , Hattersley Andrew T. , McCarthy Mark I. , Morris Andrew D. , Palmer Colin N.A. , Pearson Ewan R. 
Published: April 2009

OBJECTIVE
Metformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1). In 12 normoglycemic individuals, reduced-function variants in SLC22A1 were shown to decrease the ability of metformin to reduce glucose excursion in response to oral glucose. We assessed the effect of two common loss-of-function polymorphisms in SLC22A1 on metformin response in a large cohort of patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS
The Diabetes Audit and Research in Tayside Scotland (DARTS) database includes prescribing and biochemistry information and clinical phenotypes of all patients with diabetes within Tayside, Scotland, from 1992 onwards. R61C and 420del variants of SLC22A1 were genotyped in 3,450 patients with type 2 diabetes who were incident users of metformin. We assessed metformin response by modeling the maximum A1C reduction in 18 months after starting metformin and investigated whether a treatment target of A1C &lt;7% was achieved. Sustained metformin effect on A1C between 6 and 42 months was also assessed, as was the time to metformin monotherapy failure. Covariates were SLC22A1 genotype, BMI, average drug dose, adherence, and creatinine clearance.

RESULTS
A total of 1,531 patients were identified with a definable metformin response. R61C and 420del variants did not affect the initial A1C reduction (P = 0.47 and P = 0.92, respectively), the chance of achieving a treatment target (P = 0.83 and P = 0.36), the average A1C on monotherapy up to 42 months (P = 0.44 and P = 0.75), or the hazard of monotherapy failure (P = 0.85 and P = 0.56).

CONCLUSIONS
The SLC22A1 loss-of-function variants, R61C and 420del, do not attenuate the A1C reduction achieved by metformin in patients with type 2 diabetes.
PTPN2, a Candidate Gene for Type 1 Diabetes, Modulates Interferon-γ–Induced Pancreatic β-Cell Apoptosis
Authors: Moore Fabrice , Colli Maikel L. , Cnop Miriam , Esteve Mariana Igoillo , Cardozo Alessandra K. , Cunha Daniel A. , Bugliani Marco , Marchetti Piero , Eizirik Décio L. 
Published: April 2009

OBJECTIVE
The pathogenesis of type 1 diabetes has a strong genetic component. Genome-wide association scans recently identified novel susceptibility genes including the phosphatases PTPN22 and PTPN2. We hypothesized that PTPN2 plays a direct role in β-cell demise and assessed PTPN2 expression in human islets and rat primary and clonal β-cells, besides evaluating its role in cytokine-induced signaling and β-cell apoptosis.

RESEARCH DESIGN AND METHODS
PTPN2 mRNA and protein expression was evaluated by real-time PCR and Western blot. Small interfering (si)RNAs were used to inhibit the expression of PTPN2 and downstream STAT1 in β-cells, allowing the assessment of cell death after cytokine treatment.

RESULTS
PTPN2 mRNA and protein are expressed in human islets and rat β-cells and upregulated by cytokines. Transfection with PTPN2 siRNAs inhibited basal- and cytokine-induced PTPN2 expression in rat β-cells and dispersed human islets cells. Decreased PTPN2 expression exacerbated interleukin (IL)-1β + interferon (IFN)-γ–induced β-cell apoptosis and turned IFN-γ alone into a proapoptotic signal. Inhibition of PTPN2 amplified IFN-γ–induced STAT1 phosphorylation, whereas double knockdown of both PTPN2 and STAT1 protected β-cells against cytokine-induced apoptosis, suggesting that STAT1 hyperactivation is responsible for the aggravation of cytokine-induced β-cell death in PTPN2-deficient cells.

CONCLUSIONS
We identified a functional role for the type 1 diabetes candidate gene PTPN2 in modulating IFN-γ signal transduction at the β-cell level. PTPN2 regulates cytokine-induced apoptosis and may thereby contribute to the pathogenesis of type 1 diabetes.
Efficacy of oral rehydration therapy solutions containing sodium bicarbonate or sodium acetate for treatment of calves with naturally acquired diarrhea, moderate dehydration, and strong ion acidosis
Authors: Sen Ismail , Altunok Vahdettin , Ok Mahmut , Coskun Alparslan , Constable Peter D. 
Published: April 2009

Abstract
Objective—To determine and compare the effects of 4 oral replacement therapy (ORT) solutions on acid-base balance, abomasal emptying rate, and plasma volume expansion in calves with naturally acquired diarrhea and moderate dehydration.
Design—Prospective study.
Animals—20 calves.
Procedures—20 calves up to 45 days of age were randomly allocated (n = 5/group) to receive 2 L of 1 of 4 treatments via oroesophageal intubation: sodium bicarbonate (150 mmol/L or 300 mmol/L) or sodium acetate (150 mmol/L or 300 mmol/L). The 4 test solutions contained acetaminophen (50 mg/kg [22.7 mg/lb]) and 50 g of glucose monohydrate. Jugular venous blood samples were obtained periodically before and after administration of the ORT solution. Abomasal emptying rate was determined by use of the time to maximal plasma acetaminophen concentration.
Results—Plasma bicarbonate concentration increased more rapidly in calves administered bicarbonate-containing ORT solutions, whereas the rate of systemic alkalinization, as assessed via blood pH, did not differ consistently among treatments. The 300 mmol/L ORT solutions were emptied at a significantly slower rate from the abomasum than 150 mmol/L ORT solutions, with no difference in emptying rate between acetate and bicarbonate-con-taining ORT solutions of similar molality. The 300 mmol/L sodium acetate ORT solution significantly increased plasma volume.
Conclusions and Clinical Relevance—Clinically important differences in the resuscitative response to 300 mmol/L or 150 mmol/L ORT solutions of sodium acetate or sodium bicarbonate were not identified.
Prevalence of and risk factors for serum antibodies against Leptospira serovars in US veterinarians
Authors: Whitney Ellen A. Spotts , Ailes Elizabeth , Myers Lee M. , Saliki Jeremiah T. , Berkelman Ruth L. 
Published: April 2009

Abstract
Objective—To determine the seroprevalence of antibodies against Leptospira serovars among veterinarians and identify risk factors for seropositivity in veterinary care settings.
Design—Seroepidemiologic survey.
Study Population—Veterinarians attending the 2006 AVMA Annual Convention.
Procedures—Blood samples were collected from 511 veterinarians, and serum was harvested for a microcapsule agglutination test (MAT) to detect antibodies against 6 serovars of Leptospira. Aggregate data analysis was performed to determine the ratio of the odds of a given exposure (eg, types of animals treated or biosafety practices) in seropositive individuals to the odds in seronegative individuals.
Results—Evidence of previous leptospiral infection was detected in 2.5% of veterinarians. Most veterinarians reported multiple potential exposures to Leptospira spp and other pathogens in the previous 12 months, including unintentional needlestick injuries (379/511 [74.2%]), animal bites (345/511 [67.5%]), and animal scratches (451/511 [88.3%]). Treatment of a dog with an influenza-like illness within the past year was associated with seropositivity for antibodies against Leptospira spp.
Conclusions and Clinical Relevance—Veterinarians are at risk for leptospirosis and should take measures to decrease potential exposure to infectious agents in general. Diagnostic tests for leptospirosis should be considered when veterinarians have febrile illnesses of unknown origin.
Adverse Childhood Experiences and Sleep Disturbances Among Puerto Rican Young Adults
Authors: Olsen Eudora L. , April-Sanders Ayana K. , Bird Hector R. , Canino Glorisa J. , Duarte Cristiane S. , Suglia Shakira F. 
Published: April 2024

ImportanceSleep quality is a known marker of overall health. Studies suggest that adverse childhood experiences (ACEs) are associated with sleep disturbances among children and adults.ObjectiveTo examine the association of retrospective and prospective ACEs with sleep quality among a cohort of Puerto Rican young adults from 2 sociocultural contexts.Design, Setting, and ParticipantsThis prospective cohort study used data from the Boricua Youth Study (BYS), a population-based study representing Puerto Rican children from the South Bronx, New York, and Puerto Rico conducted from August 2000 to August 2003. Participants who were 5 to 9 years of age at enrollment in the BYS and who participated in wave 4 of the BYS took part in the Health Assessment (HA) when they were 18 to 29 years of age, from April 2013 to August 2017. Of the eligible 982 participants, 813 (82.8%) participated in the HA. Statistical analysis was conducted from January 2023 to January 2024.ExposuresProspective ACEs measured from parent and youth responses and retrospective ACEs measured among young adults using questions from the validated ACE questionnaire from the original ACEs study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention and published in 1998. Analysis included 8 overlapping items from both questionnaires.OutcomesSleep quality was assessed in the HA with the Pittsburgh Sleep Quality Index. The summary score included 7 components of the Pittsburgh Sleep Quality Index. The hypothesis was formulated after data collection. Sleep quality information was gathered at the same time as retrospective ACEs in the HA.ResultsOf the 813 participants, 438 (53.9%) lived in Puerto Rico as children, 411 (50.6%) identified as female, and the mean (SE) age of participants was 22.9 (0.07) years. After adjusting for sociodemographic factors, retrospective ACEs had a significant association with worse sleep outcomes (β [SE] = 0.29 [0.07]; 95% CI, 0.15-0.44; P &amp;lt; .001). Prospective ACEs did not have a significant association with sleep quality, after adjusting for sociodemographic factors (β [SE] = 0.05 [0.10]; 95% CI, –0.14 to 0.24; P = .59).Conclusions and RelevanceThis study suggests that there is a significant association between retrospective ACEs and sleep quality among Puerto Rican young adults, after adjusting for sociodemographic factors. Prospective ACEs were not significantly associated with sleep disturbances, after adjusting for sociodemographic factors. Addressing ACEs reported in young adulthood may help reduce sleep disorders.
A case of immunotherapy‐responsive autoimmune hemichorea
Authors: Rodin Rachel E. , Venna Nagagopal , Balaban Denis T. 
Published: April 2024

AbstractIntroductionSubacute adult‐acquired hemichorea is a striking presentation with a broad differential, including ischemic, metabolic, and inflammatory causes.CaseWe encountered a 74‐year‐old woman with rapid onset of hemichorea and associated encephalopathy. Following a thorough workup without identification of clear imaging or laboratory abnormalities, we empirically treated with IVIg. Her hemichorea dramatically improved. Due to relapses of hemichorea, she required repeat immunotherapy with IVIg or high dose steroids followed by maintenance mycophenolate.DiscussionThis case of seronegative autoimmune hemichorea highlights the importance of a high index of suspicion for an inflammatory etiology of chorea when other causes are ruled out and performing an immunotherapy trial.
Temperature‐Induced Structural Evolution and Magnetism in Self‐Intercalated V1+xSe2 Nanoplates
Authors: Guzman Roger , Liu Hongtao , Bian Ce , Bao Lihong , Shen Cheng‐Min , Gao Hong‐Jun , Zhou Wu 
Published: April 2024

Abstract2D van der Waals (vdW) magnets provide the ideal platform for studying magnetism at low dimensions, where the magnetic properties can be further tuned by intercalating magnetic species and manipulating their stoichiometry and local atomic configuration. However, achieving stoichiometric intercalated 2D magnets necessitates precise control of growth parameters to avoid local compositional variations, which fosters phase coexistence that significantly impacts magnetic properties. Here a comprehensive scanning transmission electron microscopy (STEM) examination of the structural evolution in chemical vapor deposition (CVD)‐grown self‐intercalated V1+xSe2 nanoplates is shown, exploring their response to annealing temperature variations and the subsequent influence on magnetic properties. By combining ex situ and in situ post‐growth annealing, the rearrangement of intercalants is directly observed at the interlayer and identify a structural phase transition of the nanodomains embedded in the VSe2 matrix from V3Se4 to a V5Se8 structure occurring at ≈250 °C. The interlayer reconstruction is manifested by a positive‐to‐negative cross‐over in the magnetoresistance and an upturn in resistivity at low temperatures. The results provide new ways for tailoring 2D vdW magnets through post‐growth thermal annealing.
Composite Electrolytes with Li2CO3‐Free Garnets Achieved by One‐Step Poly(propylene carbonate) Treatment for High‐Rate and Long‐Life Solid Lithium Batteries
Authors: Wang Nan , Jia Mengyang , Bi Zhijie , Guo Xiangxin 
Published: April 2024

AbstractGarnet‐based composite electrolytes show great potential in building high‐energy‐density solid lithium batteries. However, naturally formed Li2CO3 on garnets owing to air exposure hinders the Li‐ion transport and triggers undesirable performance deterioration. Based on the reaction between basic Li2CO3 and poly(propylene carbonate) (PPC) with a product of propylene carbonate (PC), composite electrolytes with homogeneously distributed Li2CO3‐free garnets as well as PC are fabricated in one step without the post‐treatment of garnet powders in both polyethylene oxide (PEO) and polyvinylidene fluoride (PVDF)‐based electrolytes. The formed PC component further decreases the crystallization of PEO and reduces the grain size of PVDF, leading to improved ion transport in PEO and the suppression of PVDF dehydrofluorination. Consequently, the PPC‐treated garnets enable high ionic conductivities of 3.40 × 10−4 and 1.75 × 10−4 S cm−1 at 30 °C, respectively, in PEO:garnet and PVDF:garnet electrolytes, as well as great electrochemical stability against Li‐metal with a lifespan over 1000 h in Li symmetrical cells at 0.1 mA cm−2. Superior stable cycles are thus realized in both LiFePO4|PEO:garnet|Li and LiNi0.6Co0.2Mn0.2O2|PVDF:garnet|Li cells. These above results demonstrate that the one‐step treatment used here helps the enhancement of Li‐ion transport in composite electrolytes, thus essential for building high‐rate and long‐life solid lithium batteries (SLBs).
A Multifunctional Hydrogel with Photothermal Antibacterial and AntiOxidant Activity for Smart Monitoring and Promotion of Diabetic Wound Healing
Authors: Wang Yue , Liu Kun , Wei Wenying , Dai Honglian 
Published: April 2024

AbstractPersistent oxidative stress and bacterial infection are significant challenges that impede diabetic wound healing. By combining diagnosis and treatment, pH variation on the wound tissue can be monitored in real time, and precise treatment can be carried out promptly to promote diabetic wound healing. In this study, a lipoic acid‐modified chitosa (LAMC) hydrogel is constructed via an amidation reaction, and ceria oxide‐molybdenum disulfide nanoparticles with a polydopamine layer (C@M@P), along with carbon quantum dots (CDs) synthesized by a hydrothermal method, are loaded into the hydrogel, thus developing a diagnostic and therapeutic hydrogel (LAMC/CD‐C@M@P). By incorporating CDs, the hydrogel exhibits high sensitivity and reversibility to pH under ultraviolet light. Furthermore, the images of hydrogels can be collected using smartphones and converted into wound pH signals, providing a means for early detection of bacterial infection. Notably, the LAMC/CD‐C@M@P hydrogel exhibits excellent photothermal antibacterial capability against Staphylococcus aureus and Escherichia coli and remarkable antioxidant and anti‐inflammatory abilities to alleviate reactive oxygen species and relieve inflammation response. In summary, this multifunctional hydrogel offers great potential as an innovative wound dressing platform, representing a significant advancement in chronic wound management.
Highly Conductive Carbon/Carbon Composites as Advanced Multifunctional Anode Materials for Structural Lithium‐Ion Batteries
Authors: Wu Hongyuan , Wei Lu , Li Wei , Shi Chongfu , Yao Xiyuan , Fu Qiangang , Li Hejun , Guo Xin 
Published: April 2024

AbstractCurrently, structural lithium‐ion batteries (LIBs) typically use carbon fibers (CFs) as multifunctional anode materials to provide both Li+ storage and high mechanical strength. However, due to the obvious volume expansion of CFs in lithiation process, the fiber structure suffers rapid degradation during cycling. Herein, CFs‐reinforced carbon matrix (C/C) composites are proposed as multifunctional anodes for structural LIBs for the first time. The C/C composite presents distinctive core/shell structure, in which CF as the core supplies a fast and continuous electron conduction pathway along with excellent mechanical strength, while the layered pyrolytic carbon shell accommodates the volume change of CF and provides additional ion storage. The impact of the C/C microstructure on the ion/electron transport and the Li+ storage mechanism behind such a unique hybrid structure are explored. Owing to the structural advantages of the C/C composite, the LiFePO4||C/C full cell exhibits surprising electrochemical performances at high electrode mass loadings, which are far superior to those of the present structural LIBs and even surpass the commercial LIBs at the same mass loadings. Moreover, the pouch cell presents excellent mechanical strength and mechanical‐electrochemical coupling characteristics. This work demonstrates great potential of the C/C composites as new multifunctional anodes for high‐performance structural batteries.
On the Practicability of the Solid‐State Electrochemical Pre‐Sodiation Technique on Hard Carbon Anodes for Sodium‐Ion Batteries
Authors: Wang Yuke , Lu Jia , Dai Wangqi , Cheng Xinyu , Zuo Jinning , Lei Huanhao , Liu Wen , Fu Zhengwen 
Published: April 2024

AbstractHard carbon (HC) with low cost and high specific capacity is considered the appropriate anode material for sodium‐ion batteries (SIBs), but the low initial coulombic efficiency (ICE) caused by solid electrolyte interface (SEI) formation and inherent active defects impede its practical battery application. Here, the practicability of solid‐state electrochemical (SSE) pre‐sodiation technique for hard carbon anode is assessed to conquer such challenges. The uniformly pre‐sodiated HC (Pre‐HC) can be fabricated through the SSE reaction between the HC and preloaded sodium metal film without introducing a liquid electrolyte. After being immerged in the electrolyte, a thin artificial SEI with abundant inorganic species is formed on the surface of Pre‐HC due to the spontaneous chemical reaction, and the ICE of HC is improved from 76.0% to 107.9%. Full cell paired with Na3V2(PO4)3 cathode exhibits a high ICE of 94.0% with 70% of energy density augment (from 126.5 to 214.4 Wh kg−1) after anode pre‐sodiation. Pre‐HC anode still retains the pre‐sodiation capacity of 671.1 mAh gNa−1 after being stored in the dry air for 2 h. This work demonstrates the practical applicability of this SSE pre‐sodiation strategy to enhance the energy density of SIBs.
Covalent Polymer‐RNA Conjugates for Potent Activation of the RIG‐I Pathway
Authors: Palmer Christian R. , Pastora Lucinda E. , Kimmel Blaise R. , Pagendarm Hayden M. , Kwiatkowski Alexander J. , Stone Payton T. , Arora Karan , Francini Nora , Fedorova Olga , Pyle Anna M. , Wilson John T. 
Published: April 2024

AbstractRNA ligands of retinoic acid‐inducible gene I (RIG‐I) are a promising class of oligonucleotide therapeutics with broad potential as antiviral agents, vaccine adjuvants, and cancer immunotherapies. However, their translation has been limited by major drug delivery barriers, including poor cellular uptake, nuclease degradation, and an inability to access the cytosol where RIG‐I is localized. Here this challenge is addressed by engineering nanoparticles that harness covalent conjugation of 5′‐triphospate RNA (3pRNA) to endosome‐destabilizing polymers. Compared to 3pRNA loaded into analogous nanoparticles via electrostatic interactions, it is found that covalent conjugation of 3pRNA improves loading efficiency, enhances immunostimulatory activity, protects against nuclease degradation, and improves serum stability. Additionally, it is found that 3pRNA could be conjugated via either a disulfide or thioether linkage, but that the latter is only permissible if conjugated distal to the 5′‐triphosphate group. Finally, administration of 3pRNA‐polymer conjugates to mice significantly increases type‐I interferon levels relative to analogous carriers that use electrostatic 3pRNA loading. Collectively, these studies have yielded a next‐generation polymeric carrier for in vivo delivery of 3pRNA, while also elucidating new chemical design principles for covalent conjugation of 3pRNA with potential to inform the further development of therapeutics and delivery technologies for pharmacological activation of RIG‐I.
Strontium/Silicon/Calcium‐Releasing Hierarchically Structured 3D‐Printed Scaffolds Accelerate Osteochondral Defect Repair
Authors: Li Cheng Ji , Park Jeong‐Hui , Jin Gang Shi , Mandakhbayar Nandin , Yeo Donghyeon , Lee Jun Hee , Lee Jung‐Hwan , Kim Hye Sung , Kim Hae‐Won 
Published: April 2024

AbstractArticular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self‐healing capacity and damaging bone structures. To tackle this problem, a scaffold‐mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε‐caprolactone) and strontium (Sr)‐doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn‐embedded scaffolds (SrBGn‐µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation‐related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow‐derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn‐µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications.