bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐inflammatory effects of dexamethasone in COVID‐19 patients: Translational population PK/PD modeling and simulation
Authors: Świerczek Artur , Jusko William J. 
Published: June 2023

AbstractDexamethasone (DEX) given at a dose of 6 mg once‐daily for 10 days is a recommended dosing regimen in patients with coronavirus disease 2019 (COVID‐19) requiring oxygen therapy. We developed a population pharmacokinetic and pharmacodynamic (PopPK/PD) model of DEX anti‐inflammatory effects in COVID‐19 and provide simulations comparing the expected efficacy of four dosing regimens of DEX. Nonlinear mixed‐effects modeling and simulations were performed using Monolix Suite version 2021R1 (Lixoft, France). Published data for DEX PK in patients with COVID‐19 exhibited moderate variability with a clearance of about half that in healthy adults. No accumulation of the drug was expected even with daily oral doses of 12 mg. Indirect effect models of DEX inhibition of TNFα, IL‐6, and CRP plasma concentrations were enacted and simulations performed for DEX given at 1.5, 3, 6, and 12 mg daily for 10 days. The numbers of individuals that achieved specified reductions in inflammatory biomarkers were compared among the treatment groups. The simulations indicate the need for 6 or 12 mg daily doses of DEX for 10 days for simultaneous reductions in TNFα, IL‐6, and CRP. Possibly beneficial is DEX given at a dose of 12 mg compared to 6 mg. The PopPK/PD model may be useful in the assessment of other anti‐inflammatory compounds as well as drug combinations in the treatment of cytokine storms.
Recommendations from DiabetesUK's 2022 diabetes and physical activity workshop
Authors: Morris Anna , Bright Chris , Cocks Matthew , Gibson Neil , Goff Louise , Greaves Colin , Griffin Simon , Jane Ben , Kinnafick Florence , Robb Paul , Roberts Michelle , Salman David , Saxton John , Taylor Adrian , West Daniel , Yates Thomas , Andrews Rob C. , Gill Jason M. R. 
Published: June 2023

AbstractAimsTo describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them.MethodsA 1‐day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes.ResultsWorkshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long‐term conditions.ConclusionsThis paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.
First‐in‐human study of a pharmacological duodenal exclusion therapy shows reduced postprandial glucose and insulin and increased bile acid and gut hormone concentrations
Authors: Fineman Mark S. , Bryant Christine L. N. , Colbert Kevin , Jozefiak Thomas H. , Petersen John S. , Horowitz Michael , Vora Jiten , Rayner Christopher K. , Wabnitz Paul , Nimgaonkar Ashish 
Published: June 2023

AbstractAimsTo address the need for noninvasive alternatives to metabolic surgery or duodenal exclusion devices for the management of type 2 diabetes (T2D) and obesity by developing an orally administered therapeutic polymer, GLY‐200, designed to bind to and enhance the barrier function of mucus in the gastrointestinal tract to establish duodenal exclusion noninvasively.Materials and MethodsA Phase 1, randomized, double‐blind, placebo‐controlled, single‐ (SAD) and multiple‐ascending‐dose (MAD) healthy volunteer study was conducted. In the SAD arm, four cohorts received a single dose of 0.5 g up to 6.0 g GLY‐200 or placebo, while in the MAD arm, four cohorts received 5 days of twice‐daily or three‐times‐daily dosing (total daily dose 2.0 g up to 6.0 g GLY‐200 or placebo). Assessments included safety and tolerability (primary) and exploratory pharmacodynamics, including serum glucose, insulin, bile acids and gut hormones.ResultsNo safety signals were observed; tolerability signals were limited to mild to moderate dose‐dependent gastrointestinal events. In the MAD arm (Day 5), reductions in glucose and insulin and increases in bile acids, glucagon‐like peptide‐1, peptide YY and glicentin, were observed following a nonstandardized meal in subjects receiving twice‐daily dosing of 2.0 g GLY‐200 (N = 9) versus those receiving placebo (N = 8).ConclusionsGLY‐200 is safe and generally well tolerated at doses of ≤2.0 g twice daily. Pharmacodynamic results mimic the biomarker signature observed after Roux‐en‐Y gastric bypass and duodenal exclusion devices, indicating a pharmacological effect in the proximal small intestine. This study represents the first clinical demonstration that duodenal exclusion can be achieved with an oral drug and supports further development of GLY‐200 for the treatment of obesity and/or T2D.
Three‐dimensional species distribution modelling reveals the realized spatial niche for coral recruitment on contemporary Caribbean reefs
Authors: Martínez‐Quintana Ángela , Lasker Howard R. , Wilson Adam M. 
Published: June 2023

AbstractThe three‐dimensional structure of habitats is a critical component of species' niches driving coexistence in species‐rich ecosystems. However, its influence on structuring and partitioning recruitment niches has not been widely addressed. We developed a new method to combine species distribution modelling and structure from motion, and characterized three‐dimensional recruitment niches of two ecosystem engineers on Caribbean coral reefs, scleractinian corals and gorgonians. Fine‐scale roughness was the most important predictor of suitable habitat for both taxa, and their niches largely overlapped, primarily due to scleractinians' broader niche breadth. Crevices and holes at mm scales on calcareous rock with low coral cover were more suitable for octocorals than for scleractinian recruits, suggesting that the decline in scleractinian corals is facilitating the recruitment of octocorals on contemporary Caribbean reefs. However, the relative abundances of the taxa were independent of the amount of suitable habitat on the reef, emphasizing that niche processes alone do not predict recruitment rates.
Microbially mediated climate feedbacks from wetland ecosystems
Authors: Candry Pieter , Abrahamson Britt , Stahl David Allan , Winkler Mari‐Karoliina Henriikka 
Published: June 2023

AbstractWetlands are crucial nodes in the carbon cycle, emitting approximately 20% of global CH4 while also sequestering 20%–30% of all soil carbon. Both greenhouse gas fluxes and carbon storage are driven by microbial communities in wetland soils. However, these key players are often overlooked or overly simplified in current global climate models. Here, we first integrate microbial metabolisms with biological, chemical, and physical processes occurring at scales from individual microbial cells to ecosystems. This conceptual scale‐bridging framework guides the development of feedback loops describing how wetland‐specific climate impacts (i.e., sea level rise in estuarine wetlands, droughts and floods in inland wetlands) will affect future climate trajectories. These feedback loops highlight knowledge gaps that need to be addressed to develop predictive models of future climates capturing microbial contributions. We propose a roadmap connecting environmental scientific disciplines to address these knowledge gaps and improve the representation of microbial processes in climate models. Together, this paves the way to understand how microbially mediated climate feedbacks from wetlands will impact future climate change.
Artificial intelligence‐based reticulin proportionate area – a novel histological outcome predictor in hepatocellular carcinoma
Authors: Patil Ameya , Salvatori Rebecca , Smith Lindsey , Jenkins Sarah M , Cannon Andrew , Hartley Christopher P , Graham Rondell P , Moreira Roger K 
Published: June 2023

AimsReticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour‐related outcomes.Methods and resultsWe developed and validated a supervised artificial intelligence (AI) model that utilises a cloud‐based, deep‐learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow‐up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease‐free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS.ConclusionOur data indicate that decreased RPA is a strong predictor of various HCC‐related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated.
Gender‐affirming hormone therapy decreases d‐dimer but worsens insulin sensitivity in transgender women
Authors: Lake Jordan E. , Miao Hongyu , Bowman Emily R. , Clark Jesse L. , Hyatt Ana N. , Kettelhut Aaren , Lama Javier R. , Reisner Sari L. , Mayer Kenneth H. , Perez‐Brumer Amaya , Funderburg Nicholas 
Published: June 2023

AbstractObjectivesGender‐affirming hormonal therapies (GAHT) and HIV increase cardiovascular risk for transgender women (TW), yet there is a paucity of data quantifying cardiometabolic changes following GAHT initiation, particularly among TW with HIV.MethodsThe Féminas study enrolled TW from October 2016 to March 2017 in Lima, Peru. Participants reported sexual activity that was high risk for HIV acquisition or transmission. All were tested for HIV/ sexually transmitted infection and were given access to GAHT (oestradiol valerate and spironolactone), HIV pre‐exposure prophylaxis (PrEP) or antiretroviral therapy (ART) for 12 months. Biomarker measurement was done on stored serum, whereas fasting glucose and lipids were measured in real time.ResultsIn all, 170 TW (32 with HIV, 138 without HIV) had median age 27 years and 70% prior GAHT use. At baseline, PCSK9, sCD14, sCD163, IL‐6, sTNFRI/II, CRP and EN‐RAGE levels were significantly higher in TW with HIV than in TW without HIV. High‐density lipoprotein and total cholesterol were lower and insulin and glucose parameters were similar. All TW with HIV started ART, but only five achieved virological suppression at any time. No TW without HIV initiated PrEP. Over 6 months, all participants initiated GAHT and had worsening insulin, glucose and HOMA‐IR. Large d‐dimer decreases also occurred. Similar changes occurred in TW with and without HIV.ConclusionsIn this unique cohort of TW, GAHT decreased d‐dimer but worsened insulin sensitivity. Because PrEP uptake and ART adherence were very low, observed effects are primarily attributed to GAHT use. Further study is needed to better understand cardiometabolic changes in TW by HIV serostatus.
Mechanism of the HIF‐1α/VEGF/VEGFR‐2 pathway in the proliferation and apoptosis of human haemangioma endothelial cells
Authors: Zhang Wenpei , Sun Lei , Gao Hongxia , Wang Shengquan 
Published: June 2023

AbstractHaemangiomas (HAs) are prevalent vascular endothelial cell tumours. With respect to the possible involvement of HIF‐1α in HAs, we have explored its role in haemangioma endothelial cell (HemEC) proliferation and apoptosis. shRNA HIF‐1α and pcDNA3.1 HIF‐α were manipulated into HemECs. HIF‐α, VEGF, and VEGFR‐2 mRNA and protein levels were assessed by qRT‐PCR and Western blotting. Cell proliferation and viability, cell cycle and apoptosis, migration and invasion, and ability to form tubular structures were assessed by colony formation assay, CCK‐8, flow cytometry, Transwell assay, and tube formation assay. Cell cycle‐related protein levels, and VEGF and VEGFR‐2 protein interaction were detected by Western blot and immunoprecipitation assays. An Haemangioma nude mouse model was established by subcutaneous injection of HemECs. Ki67 expression was determined by immunohistochemical staining. HIF‐1α silencing suppressed HemEC neoplastic behaviour and promoted apoptosis. HIF‐1α facilitated VEGF/VEGFR‐2 expression and the VEGF had interacted with VEGFR‐2 at protein ‐ protein level. HIF‐1α silencing arrested HemECs at G0/G1 phase, diminished Cyclin D1 protein level, and elevated p53 protein level. VEGF overexpression partially abrogated the effects of HIF‐1α knockdown on inhibiting HemEC malignant behaviours. Inhibiting HIF‐1α in nude mice with HAs repressed tumour growth and Ki67‐positive cells. Briefly, HIF‐1α regulated HemEC cell cycle through VEGF/VEGFR‐2, thus promoting cell proliferation and inhibiting apoptosis.
Measuring the alveolar bone level in adolescents: A comparison between ultrasound and cone beam computed tomography
Authors: Nguyen Kim‐Cuong T. , Le Lawrence H. , Kaipatur Neelambar R. , Almeida Fabiana T. , Lai Hollis , Lou Edmond H. M. , Major Paul W. 
Published: June 2023

AbstractBackgroundCone beam computed tomography (CBCT) is an imaging modality, which is used routinely in orthodontic diagnosis and treatment planning but delivers much higher radiation than conventional dental radiographs. Ultrasound is a noninvasive imaging method that creates an image without ionizing radiation.AimTo investigate the reliability of ultrasound and the agreement between ultrasound and CBCT in measuring the alveolar bone level (ABL) on the buccal/labial side of the incisors in adolescent orthodontic patients.DesignOne hundred and eighteen incisors from 30 orthodontic adolescent patients were scanned by CBCT with 0.3‐mm voxel size and ultrasound at 20 MHz frequency. The ABL, distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC), was measured twice to evaluate the agreement between ultrasound and CBCT. In addition, the intra‐ and inter‐rater reliabilities in measuring the ABL by four raters were compared.ResultsThe mean difference (MD) in the ABL between ultrasound and CBCT was −0.07 mm with 95% limit of agreement (LoA) from −0.47 to 0.32 mm for all teeth. For each jaw, the MDs between the ultrasound and CBCT were −0.18 mm (for mandible with 95% LoA from −0.53 to 0.18 mm) and 0.03 mm (for maxilla with 95% LoA from −0.28 to 0.35 mm). In comparison, ultrasound had higher intra‐rater (ICC = 0.83–0.90) and inter‐rater reliabilities (ICC = 0.97) in ABL measurement than CBCT (ICC = 0.56–0.78 for intra‐rater and ICC = 0.69 for inter‐rater reliabilities).ConclusionCBCT parameters used in orthodontic diagnosis and treatment planning in adolescents may not be a reliable tool to assess the ABL for the mandibular incisors. On the contrary, ultrasound imaging, an ionizing radiation‐free, inexpensive, and portable diagnostic tool, has potential to be a reliable diagnostic tool in assessing the ABL in adolescent patients.
Effect of sintering and annealing on electrochemical and mechanical characteristics of Na3Zr2Si2PO12 solid electrolyte
Authors: Hitesh Basitti , Sil Anjan 
Published: June 2023

AbstractNASICON (Sodium superionic conductor) type Na3Zr2Si2PO12 (NZSP) has received a lot of interest as the solid electrolyte for all‐solid‐state sodium‐ion batteries (ASSIBs). The electrolyte has superior interfacial characteristics, high thermal stability, and good ionic conductivity. Because of their higher energy density, improved mechanical stability, no liquid leakage problem, and higher operating voltages, All solid‐state batteries are expected to replace liquid electrolyte‐based batteries in many applications. The solid electrolyte also acts as a separator, and hence additional separator is not required for cell operations. Because of its 3D open architecture and continuous diffusion channels, NZSP is considered a better solid electrolyte. The NZSP solid electrolyte has been synthesized by spark plasma sintering (SPS) followed by annealing the sintered materials. The SPS method leads the material to have higher density and ionic conductivity. Conventional sintering of the materials requires a temperature as high as 1225°C; however, the temperature required for the SPS is as low as 1050°C. Moreover, conventional sintering yields samples of relative density up to 91%, while SPSed samples have achieved a maximum density of around 98%. The ionic conductivity of solid electrolyte SPSed at 1050°C for 10 min is found to be 3.5 × 10−4 S/cm with an activation energy of 0.27 eV. The annealing of the SPSed samples improves the ionic conductivity of the SPS1050‐20mins sample to roughly double the value obtained from the as‐prepared SPS sample because there are fewer secondary phases and a structural change from a rhombohedral to a monoclinic system. To ascertain the samples' crystal structure, particle shape, and ionic conductivity, materials were characterized using X‐ray diffraction, scanning electron microscopy, and electrochemical impedance spectroscopy. The samples' mechanical characteristics, for example, the hardness and fracture toughness of the samples, were also determined.
Pyroptosis by NLRP3/caspase‐1/gasdermin‐D pathway in synovial tissues of rheumatoid arthritis patients
Authors: Zhang Xue , Wang Qiuyuan , Cao Guorui , Luo Manli , Hou Hongli , Yue Chen 
Published: June 2023

AbstractWe investigated the potential involvement of pyroptosis, a proinflammatory form of regulated cell death, in rheumatoid arthritis (RA). Synovial fluid, synovial tissues and/or serum were compared among 32 patients with RA, 46 patients with osteoarthritis (OA) and 30 healthy controls. Samples were assayed for interleukin (IL)‐1β, IL‐18 and lactate hydrogenase (LDH). Synovial expression of NLRP3, caspase‐1 and cleaved gasdermin D (GSDMD) was assayed using immunohistochemistry and multiplex immunohistochemistry. Patients with RA showed significantly higher levels of IL‐1β and IL‐18 in synovial fluid than patients with OA, and significantly higher levels of both cytokines in serum than healthy controls. RA was associated with higher levels of LDH in synovial fluid than OA. Among patients with RA, levels of IL‐1β, IL‐18 and LDH were significantly higher in synovial fluid than in serum, and the levels in synovial fluid positively correlated with disease activity and inflammation. Synovial cells, particularly macrophages, showed upregulation of NLRP3, caspase‐1 and cleaved GSDMD in RA compared to OA. Our results implicate pyroptosis in the pathogenesis of RA, perhaps as a driver of local inflammation in joints.
Women education in the Soviet prophylactoria and the care homes for sexually transmitted disease patients in the Soviet Occupation Zone of Germany
Authors: Schochow Maximilian , Steger Florian 
Published: June 2023

AbstractObjectivesIn the 1920s, so‐called prophylactoria were established in the USSR. In these institutions, sex workers with sexually transmitted diseases (STDs) were treated. After the end of World War II, care homes for patients with STDs were established in the Soviet Occupation Zone of Germany (SOZ). These institutions were also intended to treat people suffering from STDs. This article compares these two types of medical institutions.MethodsSources from the State Archive of the Russian Federation in Moscow, the German Federal Archives in Berlin and the City Archive Zwickau were used. The analysed sources were evaluated by using the historical‐critical method.ResultsThe prophylactoria were novel institutions that combined education and medical treatment of people with STDs. Similar strategies were followed in the care homes for STD patients. In both institutions, the sick persons had to follow a regular daily routine and work every day. The political indoctrination served to educate ‘socialist personalities’. Nevertheless, various differences can be found between the facilities: the length of stay was different. The women in Soviet prophylactoria were cared for there for up to 2 years. However, the standard duration of stay in the care homes for STD patients was 3–6 months.ConclusionsThe prophylactoria had a long‐term programme not only to treat sick women but also to reeducate them. The aim was to enlighten and integrate them into the new Soviet society. The care homes for STD patients had a short‐term programme of combating venereal diseases. Their main goal was to treat patients with STDs as quickly as possible, while education was an additional measure. Whether both institutions were successful in educating and treating these patients can hardly be assessed from today's perspective.
Design and application of modified CAD/CAM socket‐shield preparation template in immediate implantation in the esthetic area
Authors: Song Zijun , Li Ziliang , Li Xudong , Li Chunyan , Zhou Siyue , Xu Qian 
Published: June 2023

AbstractObjectiveDesigned and applicated a modified customized CAD‐CAM socket‐shield preparation guide template in immediate implant and followed up for 3 years.Clinical ConsiderationsSocket‐shield technique could improve the esthetic effect of immediate implant restorations by preserving the labial fascicular bone‐periodontal complex at the implant site. While the socket‐shield technique is highly technique‐sensitive. A modified customized CAD/CAM guided template was designed and fabricated by 3D printing. The movement of the carbide bur during preparing the socket‐shield was limited by the socket‐shield preparation template. In this case report, the socket‐shield preparation template was used for preparing the socket‐shield in the tooth root with irregular morphology and the case was followed up for 3 years.ConclusionsThe modified CAD/CAM socket‐shield preparation template effectively improved the accuracy and efficiency of preparing the socket‐shield by limiting the movement of the high‐speed carbide bur in both in both lip‐to‐palatal and crown‐to‐root orientation. The socket‐shield with accurate morphology could effectively maintain the gingival marginal level and contour.Clinical SignificanceThe modified CAD/CAM socket‐shield preparation template with the depth‐locking ring effectively reduced the technique sensitivity and time consumption of the socket‐shield technique, especially for tooth roots with irregular morphology.