bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological testing of therapeutics using normothermic machine perfusion: A pilot study of 2,4‐dinitrophenol delivery to steatotic human livers
Authors: Tingle Samuel J. , Thompson Emily R. , Bates Lucy , Ibrahim Ibrahim K. , Govaere Olivier , Shuttleworth Victoria , Wang Lu , Figueiredo Rodrigo , Palmer Jeremy , Bury Yvonne , Anstee Quentin M. , Wilson Colin 
Published: May 2022

AbstractIntroductionNormothermic machine perfusion (NMP) provides a platform for drug‐delivery. However, pharmacological considerations for therapeutics delivered during NMP are scarcely reported. We aimed to demonstrate the ability of NMP as a platform for pharmacological testing, using a drug which increases metabolism (2,4‐dinitrophenol; DNP) as an example therapeutic.MethodsWe performed 25 h of NMP on human livers which had been declined for transplant due to steatosis (n = 7). Three livers received a DNP bolus, three were controls, and one received a DNP infusion.ResultsToxicity studies revealed DNP delivery was safe, without hepatotoxic effects. The liver surface temperature was increased in the DNP group (p = 0.046), but no livers suffered hyperthermia—the mechanism of DNP toxicity in vivo. Pharmacokinetic studies revealed DNP elimination with first‐order kinetics and 7.7 h half‐life (95% CI = 5.1–15.9 hrs). The clearance of DNP in bile was negligible. As expected, DNP significantly increased oxygen consumption (p = 0.023); this increase was closely correlated with perfusate DNP concentration (r2 = 0.975; p = 0.002) and the effect was lost as DNP was eliminated by the liver. A DNP infusion rate, calculated using our pharmacokinetic data, successfully maintained perfusate DNP concentration.DiscussionDetailed pharmacological testing can be performed during NMP. Our therapeutic (DNP) is rapidly eliminated by the ex vivo liver, meaning the drug effect of increased metabolism is only transient. This demonstrates the importance of assessing pharmacokinetics when delivering therapeutics during NMP, especially for prolonged perfusion of organs with established roles in drug elimination. Rigorous pharmacological testing is needed to unlock the potential of NMP as a clinical drug‐delivery platform.
Clinical trial: intra dermal hepatitis B vaccination with topical imiquimod versus intra muscular hepatitis B vaccination in patients with inflammatory bowel disease
Authors: Ko Kwan‐Lung , Lam Yuk‐Fai , Cheung Ka‐Shing , Hung Ivan Fan‐Ngai , Leung Wai K. 
Published: May 2022

SummaryBackgroundEfficacy with conventional intra muscular (IM) hepatitis B vaccination in patients with inflammatory bowel disease (IBD) is suboptimal.AimTo compare the immunogenicity of intradermal (ID) hepatitis B vaccination after topical imiquimod pre‐treatment with IM hepatitis B vaccination in patients with IBD.MethodsAdult IBD patients with no evidence of hepatitis B infection or immunity (negative to HBsAg/anti‐HBc/anti‐HBs) were randomised 1:1 to receive either ID hepatitis B vaccine with topical imiquimod pre‐treatment to injection site (ID‐Imq) or IM hepatitis B vaccine with aqueous cream pre‐treatment (IM‐Aq) at 0, 1 and 6 months. Patients and investigators were blinded to the randomisation and intervention. The primary endpoint was seroprotection rate at 12‐month, defined as percentage of subjects with anti‐HBs ≥10 mIU/ml.ResultsBetween September 2019 and December 2020, 104 patients with IBD (68% male; 50% Crohn’s) enrolled, and 53 assigned to ID‐Imq group. The percentage of patients using steroids, immunomodulators or biologics at randomisation was 15%, 55% or 22%, respectively. Seroprotection rate at 12 months was significantly higher in the ID‐Imq group than the IM‐Aq group (91% vs 69%; OR 4.39, 95% CI 1.47‐13.11). Multivariate analysis showed that ID vaccine with topical imiquimod and higher albumin level were associated with a higher seroprotection rate. The safety profile was similar but local reactions were more common in the ID‐Imq group.ConclusionsIntradermal hepatitis B vaccination with topical imiquimod pre‐treatment is safe and offers superior seroprotection to conventional IM administration in patients with IBD.
Non‐oesophageal eosinophilic gastrointestinal diseases are undersuspected clinically and underdiagnosed pathologically
Authors: Genta Robert M. , Dellon Evan S. , Turner Kevin O. 
Published: May 2022

SummaryBackgroundNon‐oesophageal gastrointestinal eosinophilic diseases (EGID) are considered rare. However, low disease awareness among clinicians and pathologists may contribute to underdiagnosis.AimsTo determine how frequently requests to evaluate for EGID accompany gastrointestinal biopsies and in what proportion of suspected cases pathologists address these requests, either confirming or refuting the clinical suspicion.MethodsAll cases in which biopsy requisitions included an explicit suspicion of EGID were extracted from a large clinicopathologic database and manually reviewed for accuracy. The diagnoses for these cases were then analysed to determine whether clinical suspicions were confirmed, refuted or ignored.ResultsEosinophilic oesophagitis (EoE) was suspected in 12.8% of 903,516 patients with biopsies and confirmed in 14.9% of them. A suspicion of eosinophilic gastritis accompanied <0.001% of 1,438,206 gastric biopsy sets and was confirmed in 11.5% of them; eosinophilic duodenitis was suspected in 0.02% of ~675,519 patients with duodenal biopsies and confirmed in 8.0% of these; eosinophilic colitis was mentioned in <0.001% of 2,504,485 patients with colonic biopsies and confirmed in 0.1% of them. Less than 3% of endoscopists mentioned non‐oesophageal EGID in the requisition, while most expressed a clinical suspicion of Barrett oesophagus, Helicobacter pylori gastritis, celiac disease and microscopic colitis (in 21.2%, 49.2%, 1% and 6.4% of the cases, respectively).ConclusionsGastroenterologists and pathologists commonly address and diagnose EoE. In contrast, both clinical suspicion and diagnosis of non‐oesophageal EGID are extremely rare. Increased clinical awareness might result in a better understanding of the epidemiology and improved diagnosis of these still elusive conditions.
Application of kojic acid scaffold in the design of non‐tyrosinase enzyme inhibitors
Authors: Ashooriha Morteza , Ahmadi Reza , Ahadi Hamideh , Emami Saeed 
Published: May 2022

AbstractKojic acid (KA) is a hydroxypyranone natural metabolite mainly known as tyrosinase inhibitor. Currently, this compound is used as a whitening agent in cosmetics and as an anti‐browning agent in food industry. Given the easy‐manipulation in different positions of the KA molecule, many investigations have been carried out to find new tyrosinase inhibitors derived from KA. Beside anti‐tyrosinase activity, many KA‐based compounds have been designed for targeting other enzymes including human neutrophil elastase, catechol‐O‐methyltransferase, matrix metalloproteinases, monoamine oxidase, human lactate dehydrogenase, endonucleases, D‐amino acid oxidase, and receptors such as histamine H3 and apelin (APJ) receptors. This review could help biochemists and medicinal chemists in designing diverse KA‐derived enzyme inhibitors.
Partial restoration of spinal cord neural continuity via vascular pedicle hemisected spinal cord transplantation using spinal cord fusion technique
Authors: Ren Xiaoping , Zhang Weihua , Qin Jie , Mo Jian , Chen Yi , Han Jie , Feng Xinjian , Feng Sitan , Liang Haibo , Cen Liangjue , Wu Xiaofei , Han Linxuan , Lan Rongyu , Deng Haixuan , Yao Huihui , Qi Zhongquan , Gao Hongjun , Wei Lishan , Ren Shuai 
Published: May 2022

AbstractAimsOur team tested spinal cord fusion (SCF) using the neuroprotective agent polyethylene glycol (PEG) in different animal (mice, rats, and beagles) models with complete spinal cord transection. To further explore the application of SCF for the treatment of paraplegic patients, we developed a new clinical procedure for SCF called vascular pedicle hemisected spinal cord transplantation (vSCT) and tested this procedure in eight paraplegic participants.MethodsEight paraplegic participants (American Spinal Injury Association, ASIA: A) were enrolled and treated with vSCT (PEG was applied to the sites of spinal cord transplantation). Pre‐ and postoperative pain intensities, neurologic assessments, electrophysiologic monitoring, and neuroimaging examinations were recorded.ResultsOf the eight paraplegic participants who completed vSCT, objective improvements occurred in motor function for one participant, in electrophysiologic motor‐evoked potentials for another participant, in re‐establishment of white matter continuity in three participants, in autonomic nerve function in seven participants, and in symptoms of cord central pain for seven participants.ConclusionsThe postoperative recovery of paraplegic participants demonstrated the clinical feasibility and efficacy of vSCT in re‐establishing the continuity of spinal nerve fibers. vSCT could provide the anatomic, morphologic, and histologic foundations to potentially restore the motor, sensory, and autonomic nervous functions in paraplegic patients. More future clinical trials are warranted.
The effect of 3‐year parental smoking on asthma status of their children
Authors: Boskabady Mostafa , Hajizadeh Ali A. , Ahanchian Hamid , Memarzia Arghavan , Jafarnezhad Maryam , Golafshani Armin , Boskabady Mohammad H. 
Published: May 2022

AbstractObjectiveWhilst the prevalence and severity of asthma influenced by environmental factors, the effect of parental smoking on asthma status of their children was examined.Patients and MethodsNinety asthmatic children, 32 with smoker and 58 with non‐smoker parents (baseline age, 8.5 ± 3.5 and 8.2 ± 3.3 respectively) were studies in two sessions 3 years apart by evaluating respiratory symptoms (RS) prevalence and severity, various drugs used, and pulmonary function tests (PFT) including forced vital capacity; forced volume in the first second, peak expiratory flow; and maximum expiratory low at 75, 50 and 25% of vital capacity (FVC, FEV1, PEF, MEF75, MEF50 and MEF25, respectively).ResultsThe prevalence and severity of all RS were significantly increased in asthmatic children with smoking parents after 3 years except prevalence and severity of night wheeze and the prevalence of chest wheeze (p < 0.05 to p < 0.001), but the PFT values were non‐significantly reduced. In asthmatic children with non‐smoking parents, the prevalence and severity of RS were decreased after 3 years, which was significant for night and chest wheeze for prevalence and night cough and chest wheeze for severity (all, p < 0.05), and the PFT values were increased, which were statistically significant for FVC, FEV1, MEF50 and MEF25 (p < 0.05 to p < 0.01). Drugs used by the group with smoking parents were increased and were significantly higher than their reduction in the groups with non‐smoking parents at the end of the study (p < 0.05 for fluticasone propionate 125/salmeterol and budesonide160/formoterol).ConclusionLong‐term parental smoking increased prevalence and severity of RS and drug used but decreased PFT values of their asthmatic children.
Deep vein thrombosis and pulmonary embolism after heart transplantation
Authors: Kainuma Atsushi , Ning Yuming , Kurlansky Paul A. , Wang Amy S. , Latif Farhana , Farr Maryjane A. , Sayer Gabriel T. , Uriel Nir , Takayama Hiroo , Naka Yoshifumi , Takeda Koji 
Published: May 2022

AbstractIntroductionVenous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and serious postoperative complication after heart transplantation. We sought to characterize in‐hospital VTE after heart transplantation and its association with clinical outcomes.MethodAdult (≧18 years) patients undergoing heart transplantation from 2015 to 2019 at our center were retrospectively reviewed. Post‐transplant VTE was defined as newly diagnosed venous system thrombus by imaging studies.ResultsThere were 254 patients. The cohort's median age was 55 years. A total of 61 patients were diagnosed with VTE, including one with right atrial thrombus, 54 with upper extremity DVT in which one patient subsequently developed PE, four with lower extremity DVT, and two with upper and lower extremity DVT. The cumulative incidence of VTE was 42% at 60‐days of post heart transplant. Patients with VTE had longer hospital stay (P < .001), higher in‐hospital mortality (P = .010), and worse 5‐year survival (P = .009). On the multivariable Cox analysis, history of DVT/PE and intubation for more than 3 days were associated with an increased risk of in hospital VTE.ConclusionThe incidence of VTE in heart transplant recipients is high. Post‐transplant surveillance, and appropriate preventive measures and treatment strategies after diagnosis are warranted.
The role of acute in‐patient rehabilitation on short‐term outcomes after liver transplantation: A systematic review of the literature and expert panel recommendations
Authors: Mina Daniel Santa , Tandon Puneeta , Kow Alfred Wei Chieh , Chan Albert , Edbrooke Lara , Raptis Dimitri Aristotle , Spiro Michael , Selzner Nazia , Denehy Linda ,   the ERAS4OLT.org Working Group
Published: May 2022

AbstractBackgroundThe indication and surgical complexity of orthotopic liver transplantation underscore the need for strategies to optimize the recovery for transplant recipients. We conducted a systematic review aimed at identifying, evaluating, and synthesizing the evidence examining the effect of in‐patient rehabilitation for liver transplant recipients and provide related practice recommendations.MethodsHealth research databases were systematically reviewed for studies that included adults who received liver transplantation and participated in acute, post‐transplant rehabilitation. Postoperative morbidity, mortality, length of hospital stay, length of intensive care unit stay, and other markers of surgical recovery were extracted. Practice recommendations are provided by an international panel using GRADE.ResultsTwelve studies were included in the review (including 3901 participants). Rehabilitation interventions varied widely in design and composition; however, details regarding intervention delivery were poorly described in general. The quality of evidence was rated as very low largely owing to “very serious” imprecision, poor reporting, and limited data from comparative studies. Overall, the studies suggest that in‐patient rehabilitation for recipients of liver transplantation is safe, tolerable, and feasible, and may benefit functional outcomes.ConclusionTwo practice recommendations related to in‐patient rehabilitation following LT were yielded from this review: (1) it is safe, tolerable, and feasible; and (2) it improves postoperative functional outcomes. Each of the recommendations are weak and supported by low quality of evidence. No recommendation could be made related to benefits or harms for clinical, physiological, and other outcomes. Adequately powered and high quality randomized controlled trials are urgently needed in this area.
Community‐based models of alcohol and other drug support for First Nations peoples in Australia: A systematic review
Authors: Krakouer Jacynta , Savaglio Melissa , Taylor Karinda , Skouteris Helen 
Published: May 2022

AbstractIssuesThe transgenerational impacts of colonisation—inclusive of dispossession, intergenerational trauma, racism, social and economic exclusion and marginalisation—places First Nations peoples in Australia at significant risk of alcohol and other drug (AOD) use and its associated harms. However, knowledge and evidence supporting community‐based AOD treatment for First Nations adults is limited. Therefore, this review aimed to examine the impact and acceptability of community‐based models of AOD support for First Nations adults in Australia.ApproachA systematic search of the empirical literature from the past 20 years was conducted.Key FindingsSeventeen studies were included. Nine studies evaluated the program's impact on substance use and 10 studies assessed program acceptability (two studies evaluated both). Only three out of nine studies yielded a statistically significant reduction in substance use. Acceptable components included cultural safety, First Nations AOD workers, inclusion of family and kin, outreach and group support. Areas for improvement included greater focus on holistic wrap‐around psychosocial support, increased local community participation and engagement, funding and breaking down silos.ImplicationsCulturally safe, holistic and integrated AOD outreach support led by First Nations peoples and organisations that involves local community members may support First Nations peoples experiencing AOD concerns. These findings may inform the (re)design and (re)development of community‐based AOD services for First Nations peoples.ConclusionThere is a limited evidence‐base for community‐based AOD programs for First Nations peoples. First Nations‐led research that is controlled by and co‐produced with First Nations peoples is necessary to extend our understanding of community‐based programs within First Nations communities.
Factors associated with weight loss in people with overweight or obesity living with type 2 diabetes mellitus: Insights from the global DISCOVER study
Authors: Hejjaji Vittal , Gorgojo‐Martinez Juan J. , Tang Fengming , Garnelo Julia Blanco , Cooper Andrew , Medina Jesús , Mutiozabal Miren Sequera , Khunti Kamlesh , Nicolucci Antonio , Shestakova Marina V. , Ji Linong , Gomes Marilia B. , Watada Hirotaka , Vora Jiten , Malik Ali O. , Kosiborod Mikhail , Arnold Suzanne V. 
Published: May 2022

AbstractAimsTo estimate real‐world change in weight over 3 years and the factors influencing it in participants who are overweight and live with type 2 diabetes.Materials and MethodsDISCOVER is a multinational prospective observational study that enrolled participants with type 2 diabetes between December 2014 and June 2016 at the time of initiation of a second‐line glucose‐lowering medication (GLM). Demographic, anthropometric, and quality‐of‐life data were collected at baseline, and after 6, 12, 24 and 36 months of follow‐up. Using a hierarchical, repeated‐measures linear regression model, we examined factors associated with weight change over time.ResultsOf 10 675 participants with type 2 diabetes who were overweight/obese (mean age 57.1 ± 11.1 years, 46% women), 21% lost ≥5% weight over 3 years, which was associated with modestly improved physical and mental health. Advancing age, female sex, and higher baseline weight were associated with weight loss. Most importantly, the type of GLM prescribed at previous visit had the strongest impact on weight change over time independent of participant factors, with use of a sodium‐glucose cotransporter‐2 inhibitor or glucagon‐like peptide‐1 receptor agonist associated with 1.0% weight loss versus a 0.6% weight gain with sulphonylureas, thiazolidinediones, meglitinides or insulin.ConclusionIn this large contemporary prospective study, approximately one in five participants with early‐stage type 2 diabetes and overweight/obesity lost ≥5% weight over 3 years. The type of GLM has the most impact on weight loss over time, highlighting the need for a careful selection of agents that takes baseline weight into consideration.
Effect of once‐weekly semaglutide versus thrice‐daily insulin aspart, both as add‐on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open‐label, multinational, phase 3b trial
Authors: Kellerer Monika , Kaltoft Margit Staum , Lawson Jack , Nielsen Lasse Lykke , Strojek Krzysztof , Tabak Ömür , Jacob Stephan 
Published: May 2022

AbstractAimTo compare the efficacy and safety of once‐weekly (OW) semaglutide versus thrice‐daily (TID) insulin aspart (IAsp) in participants with inadequately controlled type 2 diabetes (T2D) treated with insulin glargine (IGlar) and metformin.Materials and MethodsSUSTAIN 11 (NCT03689374) was a randomized (1:1), parallel, open‐label, multinational, phase 3b trial. After a 12‐week run‐in to optimize once‐daily IGlar U100, 1748 adults with T2D (HbA1c >7.5% to ≤10.0%) were randomized to OW semaglutide or TID IAsp as add‐on to optimized IGlar and metformin for 52 weeks. The primary outcome was change in HbA1c from randomization to week 52. Confirmatory secondary endpoints included the occurrence of severe hypoglycaemic episodes and change in body weight (BW). Safety was assessed.ResultsHbA1c (randomization: 8.6% [70.0 mmol/mol]) decreased by 1.5% points (16.6 mmol/mol) and 1.2% points (13.4 mmol/mol) with semaglutide (n = 874) and IAsp (n = 874), respectively (estimated treatment difference [ETD] −0.29% points [95% confidence interval {CI} −0.38; −0.20]; P < .0001 for non‐inferiority). Few severe hypoglycaemic episodes were recorded in either group, with no statistically significant difference between the groups. Change in BW from randomization (87.9 kg) to week 52 was in favour of semaglutide (−4.1 kg) versus IAsp (+2.8 kg) (ETD −6.99 kg [95% CI −7.41; −6.57]). A higher proportion of participants experienced adverse events with semaglutide (58.5%) versus IAsp (52.1%); most were mild to moderate.ConclusionsIn this basal insulin‐treated population, OW semaglutide improved glycaemic control to a greater extent than TID IAsp and provided numerically greater weight loss.
Prior actions influence cost–benefit‐related decision‐making during mouse foraging behaviours
Authors: Dylda Evelyn , Wang Kuan Hong 
Published: May 2022

AbstractFood foraging is essential for the fitness of animals. Previous studies have suggested that optimal foraging strategies involve a cost–benefit analysis comparing reward versus effort to guide action choices. Little is known how prior experience with different actions to obtain rewards may affect subsequent foraging choices. Here, we report a sunflower seed foraging test to investigate how effort and prior actions influence decision‐making in laboratory mice. Sunflower seeds are a natural food favourite for mice, and mice spend effort to peel the hard shells to obtain the seeds. In our test, peeled and unpeeled sunflower seeds were placed at different ends of a Y‐maze. Mice were free to explore the maze and make foraging decisions. Naïve mice were more likely to choose peeled seeds requiring low effort versus unpeeled seeds requiring high effort. Furthermore, mice with prior seed peeling experience significantly reduced preference for peeled seeds during the subsequent Y‐maze foraging test, compared with mice pre‐exposed to peeled seeds only. This experience‐dependent shift in foraging choice was associated with reduced seed peeling time and improved motor skills with practice, and predictable on a trial‐by‐trial basis by a probabilistic decision‐making model with the amount of peeled and unpeeled seeds consumed as inputs. Together, these results suggest that laboratory mice make rational foraging choices based on effort estimation and moreover, prior actions to obtain reward alter effort estimation and decision‐making through motor skill learning. This naturalist behavioural task may be applied to dissect neural mechanisms in adaptive decision‐making during foraging.