bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive review of wheat phytochemicals: From farm to fork and beyond
Authors: Tian Wenfei , Zheng Yi , Wang Weiqun , Wang Donghai , Tilley Michael , Zhang Guorong , He Zhonghu , Li Yonghui 
Published: April 2022

AbstractThe health benefits of whole wheat consumption can be partially attributed to wheat's phytochemicals, including phenolic acids, flavonoids, alkylresorcinols, carotenoids, phytosterols, tocopherols, and tocotrienols. It is of increasing interest to produce whole wheat products that are rich in bioactive phytochemicals. This review provides the fundamentals of the chemistry, extraction, and occurrence of wheat phytochemicals and includes critical discussion of several long‐lasting issues: (1) the commonly used nomenclature on distribution of wheat phenolic acids, namely, soluble‐free, soluble‐conjugated, and insoluble‐bound phenolic acids; (2) different extraction protocols for wheat phytochemicals; and (3) the chemistry and application of in vitro antioxidant assays. This review further discusses recent advances on the effects of genotypes, environments, field management, and processing techniques including ultrafine grinding, germination, fermentation, enzymatic treatments, thermal treatments, and food processing. These results need to be interpreted with care due to varied sample preparation protocols and limitations of in vitro assays. The bioaccessibility, bioavailability, metabolism, and potential health benefits of wheat phytochemicals are also reviewed. This comprehensive and critical review will benefit scientific researchers in the field of bioactive compounds of cereal grains and also those in the cereal food industry to produce high‐quality functional foods.
Landscape effects on the thermotolerance of carabid beetles and the role of behavioral thermoregulation
Authors: Alford Lucy , Roudine Sacha , Pierre Jean‐Sébastien , Burel Françoise , van Baaren Joan 
Published: April 2022

AbstractPhysiological thermotolerance and behavioral thermoregulation are central to seasonal cold adaptation in ectothermic organisms. For species with enhanced mobility, behavioral responses may be of greater importance in the cold stress response. Employing the carabid beetles as a study organism, the current study compared physiological thermotolerance and behavioral thermoregulation in carabid species inhabiting cereal fields in different landscape contexts, from fine grain heterogeneous “complex” landscapes to homogenous “simple” landscapes. Physiological thermotolerance was determined via measurement of the CTmin and chill coma temperature. Behavioral responses to cold temperature exposure were determined employing a purpose built arena, and thoracic temperature measured to estimate the efficacy of the behavior as a form of behavioral thermoregulation. Results revealed an influence of landscape composition on the cold tolerance of carabid beetles, although species differed in their sensitivity to landscape intensification. A reduced effect of landscape on the thermotolerance of larger carabid beetles was observed, thought to be the consequence of greater mobility preventing local acclimation to microclimatic variation along the landscape intensification gradient. Investigation into behavioral thermoregulation of the 3 largest species revealed burrowing behavior to be the main behavioral response to cold stress, acting to significantly raise carabid body temperature. This finding highlights the importance of behavioral thermoregulation as a strategy to evade cold stress. The use of behavioral thermoregulation may negate the need to invest in physiological thermotolerance, further offering explanation for the lack of landscape effect on the physiological thermotolerance of larger carabids.
Edible insects: Challenges and prospects
Authors: van Huis Arnold 
Published: April 2022

AbstractAn overview is given on recent developments in insects as food and food by reviewing the literature which has appeared during the last few years on edible insects. An outlook to the future is provided. About a decade ago, the attention shifted from harvesting insects in the tropics to farming insects all over the world for food and feed applications. Most production is targeted towards pet food, but it will turn to aquafeed in the next two decades. More than 80% of all publications dealing with edible insects appeared during the last five years. Crickets and mealworms are used for human food while the black soldier fly is the main species used as animal feed. The criteria to choose insect species are automation, cheap substrates, disease avoidance, and market potential. Genetics are increasingly explored to improve production. The environmental impact of producing insects compares well to other alternative proteins, in particular their capacity to degrade organic waste streams. Edible insects are not only a good source of nutrients but also seem to provide health benefits not only for humans and animals, but also for plants (left over substrate). The challenge of convincing Western consumers is reviewed and whether sustainability is an issue. Processing techniques are being developed. The sector of insects as food and feed is developing fast thanks to an increasingly conducive legislative framework. It will progress further, provided that the insect industry, academia, governmental organizations, and public society closely cooperate.
Cepharanthine ameliorates dextran sulphate sodium‐induced colitis through modulating gut microbiota
Authors: Wang Hong‐Gang , Zhang Min‐Na , Wen Xin , He Le , Zhang Meng‐Hui , Zhang Jia‐Ling , Yang Xiao‐Zhong 
Published: April 2022

SummaryCepharanthine (CEP) is an active alkaloid isolated from Stephania Cepharantha Hayata. It is reported that the anti‐inflammatory properties of CEP could be employed to treat a variety of diseases. In this study, we first found that CEP ameliorates ulcerative colitis (UC) induced by DSS. The effect of CEP on gut microbiota was further evaluated by 16S rRNA gene sequencing, antibiotic pretreatment and faecal microbiota transplantation (FMT). Results showed that the abundances of gut microbiota, such as Romboutsia, Turicibacter and Escherichia‐Shigella (especially Romboutsia), were significantly reduced after CEP treatment. Additionally, we explored the mechanisms of CEP by a strategy integrating transcriptomics with network pharmacology. The transcriptome data confirmed that CEP functioned through cytokine and cytokine receptor pathways. The expression levels of 10 pro‐inflammatory hub genes (such as CXCL1, CXCL9, CCL7) were positively correlated with the abundance of Romboutsia. Our data identified Romboutsia as a potential pathobiont in UC. Collectively, we confirmed that CEP relieved colon inflammation by modulating gut microbiota and pro‐inflammatory cytokine expression. CEP can be adopted to design novel effective therapeutic strategies for UC.
A CT‐based radiomics model to predict subsequent brain metastasis in patients with ALK‐rearranged non–small cell lung cancer undergoing crizotinib treatment
Authors: Jiang Yongluo , Wang Yixing , Fu Sha , Chen Tao , Zhou Yixin , Zhang Xuanye , Chen Chen , He Li‐na , Du Wei , Li Haifeng , Lin Zuan , Zhao Yuanyuan , Yang Yunpeng , Zhao Hongyun , Fang Wenfeng , Huang Yan , Hong Shaodong , Zhang Li 
Published: April 2022

AbstractBackgroundBrain metastasis (BM) comprises the most common reason for crizotinib failure in patients with anaplastic lymphoma kinase (ALK)‐rearranged non–small cell lung cancer (NSCLC). We hypothesize that its occurrence could be predicted by a computed tomography (CT)‐based radiomics model, therefore, allowing for selection of enriched patient populations for prevention therapies.MethodsA total of 75 eligible patients were enrolled from Sun Yat‐sen University Cancer Center between June 2014 and September 2019. The primary endpoint was brain metastasis‐free survival (BMFS), estimated from the initiation of crizotinib to the date of the occurrence of BM. Patients were randomly divided into two cohorts for model training (n = 51) and validation (n = 24), respectively. A radiomics signature was constructed based on features extracted from chest CT before crizotinib treatment. Clinical model was developed using the Cox proportional hazards model. Log‐rank test was performed to describe the difference of BMFS risk.ResultsPatients with low radiomics score had significantly longer BMFS than those with higher, both in the training cohort (p = 0.019) and validation cohort (p = 0.048). The nomogram combining smoking history and the radiomics signature showed good performance for the estimation of BMFS, both in the training (concordance index [C‐index], 0.762; 95% confidence interval [CI], 0.663–0.861) and validation cohort (C‐index, 0.724; 95% CI, 0.601–0.847).ConclusionWe have developed a CT‐based radiomics model to predict subsequent BM in patients with non‐brain metastatic NSCLC undergoing crizotinib treatment. Selection of an enriched patient population at high BM risk will facilitate the design of clinical trials or strategies to prevent BM.
Prognostic and predictive impact of neutrophil‐to‐lymphocyte ratio and HLA‐I genotyping in advanced esophageal squamous cell carcinoma patients receiving immune checkpoint inhibitor monotherapy
Authors: Wang Lin , Zhu Yanrong , Zhang Bo , Wang Xi , Mo Hongnan , Jiao Yuchen , Xu Jiachen , Huang Jing 
Published: April 2022

AbstractBackgroundImmune checkpoint inhibitors (ICIs) have become standard‐of‐care in patients with pretreated advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers for clinical outcomes are lacking for ICIs. The exploration of effective biomarkers is therefore needed to optimize patient benefit in the treatment of ESCC.MethodsSixty‐nine patients with advanced ESCC enrolled at one center from two prospective trials were consecutively analyzed. NLR was dynamically collected and high‐resolution HLA‐I genotyping were performed on genomic DNA. Overall response rate (ORR), median progression‐free survival (mPFS) and median overall survival (mOS) were investigated.ResultsThirty‐three (47.8%) of 69 patients with baseline NLR ≥4 demonstrated significantly worse clinical outcomes (ORR 9.1% vs. 36.1%, p = 0.018; mPFS 1.8 vs. 3.2 months, hazard ratio [HR] 1.79, p = 0.026; mOS 7.4 vs. 11.0 months, HR 2.28, p = 0.008). An NLR decrease ≥20% at the first radiological evaluation was associated with longer OS (median, 14.0 vs. 7.9 months, p = 0.038). Eleven (15.9%) patients with HLA‐I homozygosity presented poorer clinical outcomes (ORR 0 vs. 27.6%, p = 0.056; mPFS 1.8 vs. 2.4 months, HR 3.37, p = 0.010; mOS 5.6 vs. 10.5 months, HR 3.97, p = 0.004). Patients with baseline NLR ≥4 and HLA‐I homozygosity had the worst outcome (ORR 0; mPFS 1.4 months; mOS 1.8 months) among all. The association between NLR, HLA‐I genotyping and clinical outcomes was independent of programmed death receptor ligand‐1 expression.ConclusionsNLR and HLA‐I genotyping could have predictive and prognostic value in patients with advanced ESCC receiving camrelizumab, and the combination of biomarkers may help to identify more patient benefit from immunotherapy.
Factors influencing interhospital transfer delays in emergency general surgery: a systematic review and narrative synthesis
Authors: Young Edward , Khoo Teng‐Wei , Trochsler Markus Ivo , Maddern Guy John 
Published: April 2022

AbstractBackgroundEmergency general surgery is an emerging public health issue globally, with substantial healthcare burden. Interhospital transfer of critically unwell surgical patients has been the mainstay of bridging gaps in surgical coverage in regional and rural locations, despite evidence of greater morbidity and mortality. Delays in transfer invariably occurs and compounds the situation. Our aim was to examine the factors influencing interhospital transfer delays in emergency general surgical patients.MethodsA systematic search of PubMED and EmBase, was performed by two researchers from 2020 to 23rd Feb 2021, for English articles related to interhospital transfer delays in emergency general surgical patients, with an age of >16. Articles were critically appraised and data were extracted into a pre‐specified data extraction form. No data was suitable for statistical analysis and a narrative synthesis was performed instead.ResultsSix relevant articles were identified from the search. All studies were retrospective cohort studies with moderate to high risk of bias. Lack of consultant surgeon input, after hours transfer, need for intensive care bed and poor transfer documentation may have a role in interhospital transfer delays. Patients with public health insurance, multiple comorbidities and non‐emergency medical conditions experience longer transfer request time and may be at risk of precipitating interhospital transfer delays. Transfer delays are seen in transfers over longer distances.ConclusionThere is a paucity of knowledge on what and how factors influence interhospital transfer delays in emergency general surgical patients. Well‐designed prospective cohort studies are required to bridge this knowledge gap.
A randomised phaseIIstudy of azacitidine (AZA) alone or with Lenalidomide (LEN), Valproic acid (VPA) or Idarubicin (IDA) inhigher‐Risk MDSor low blastAML:GFM's “pick a winner” trial, with the impact of somatic mutations
Authors: Adès Lionel , Duployez Nicolas , Guerci‐Bresler Agnes , Laribi Kamel , Peterlin Pierre , Vey Norbert , Thepot Sylvain , Wickenhauser Stefan , Zerazhi Hacene , Stamatoullas Aspassia , Wattel Eric , Recher Christian , Toma Andrea , Dimicoli‐Salazar Sophie , Braun Thorsten , Beyne‐Rauzy Odile , Marolleau Jean‐Pierre , Cheze Stéphane , Park Sophie , Cluzeau Thomas , Nimubona Stanislas , Bordessoule Dominique , Benramdane Riad , Quesnel Bruno , Amé Shanti , de Botton Stéphane , Chermat Fathia , Preudhomme Claude , Chevret Sylvie , Fenaux Pierre 
Published: April 2022

AbstractIn order to improve the outcome observed with azacitidine (AZA) in higher‐risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA‐PLUS was a phase II trial that, in a “pick a winner” approach, randomly assigned patients with higher‐risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA‐LEN And AZA‐IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy‐related MDS and, in the case ofTP53,PTPN11orCSF3Rmutation. The combinations used did not improve the outcome obtained with AZA alone. However, our “pick a winner” randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.
Single‐dose (4.5 mg/m2) gemtuzumab ozogamicin in combination with fludarabine, cytarabine and anthracycline as reinduction therapy in relapsed or refractory paediatric acute myeloid leukaemia
Authors: Dhunputh Chloé , Strullu Marion , Petit Arnaud , Merched Maria , Pasquet Marlène , Azarnoush Saba , Leverger Guy , Ducassou Stéphane 
Published: April 2022

SummaryDespite major therapeutic improvements, children with relapsed/refractory Acute Myeloid Leukaemia still have poor outcomes and overall survival does not exceed 40%. New treatments are required to improve their outcome; Gemtuzumab ozogamicin (GO), an anti‐CD33 immunoconjugate antibody, is a potent cytotoxic agent whose efficacy has been demonstrated mainly in adults. The main objective of this retrospective multicentre study was to assess the outcome of children treated, between February 2008 and August 2019, with GO at a single 4.5 mg/m2 dose, in combination with Fludarabine, Cytarabine and antssshracyclines, in context of a first relapse (n = 26) or refractory disease (n = 3). The remission rate was 83% (24/29 children) and 20 children (69%) were allografted. With a median follow‐up of 1.2 years (range: 0.1–8), the overall survival was 49% (CI95% = 33; 72). Most common adverse event was febrile neutropenia with microbiological identification in 55% of cases. Veno‐occlusive disease occurred in 6 patients (21%), of which 5 subvened after bone marrow transplantation, and resolved within 2–32 days (median 10.5 days). Administration of GO in combination with FLA‐anthracyclines chemotherapy appears to be a good reinduction regimen for relapsed or refractory AML with a good safety profile. These results warrant larger prospective study.
Transcranial direct current stimulation for migraine: a systematic review and meta‐analysis of randomized controlled trials
Authors: Hong Peiwei , Liu Yao , Wan Yang , Xiong Hai , Xu Yanming 
Published: April 2022

AbstractBackgroundTranscranial direct current stimulation (tDCS) is a promising method for migraine treatment. In this study, we investigated the efficacy and safety of tDCS for migraine by conducting a systematic review and meta‐analysis of randomized controlled trials (RCTs).MethodsWe searched PubMed, EMBASE, Cochrane Library, and Web of Science up to December 02, 2021 for RCTs reporting tDCS for migraine treatment. Two authors independently evaluated the eligibility of the retrieved trials and extracted relevant data. Outcomes for the quantitative synthesis were reduction in migraine days per month and adverse events.ResultsEleven RCTs that included 425 patients with migraine were evaluated in the meta‐analysis. The efficacy and safety of anodal or cathodal stimulation targeting different brain areas, including primary motor cortex (M1), primary sensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and visual cortex (VC), were assessed in the RCTs enrolled. We found that tDCS with M1 and VC activation could reduce No. of migraine days per month in patients with migraine. Meanwhile, tDCS with VC inhibition could also reduce No. of migraine days per month in patients with migraine. However, there were no differences in the incidence of adverse events between the two groups.ConclusiontDCS activates M1 or activates/inhibits VC which could improve migraine symptoms. tDCS is an effective, preventive, and safe treatment for migraine.
Young‐onset colorectal cancer: Insights from an English population‐based study
Authors: Franklyn Joshua , Lomax Joe , Labib Peter L. Z. , Baker Amy , Balasubramanya Supriya , Natale Joe , Abdalkoddus Muhammad , Hosking Joanne , Coleman Mark G. , Smolarek Sebastian 
Published: April 2022

AbstractAimYoung colorectal cancer (CRC) patients are reported to have more aggressive disease, an advanced stage at diagnosis and conflicting survival outcomes. The aim of this study was to analyse the demographics, clinicopathological features and prognosis of young CRC at a population‐based level in England.MethodThis is a retrospective review of all CRC patients using data from Public Health England collated from regional cancer registries in England between 2010 and 2014. Those aged 40 years and below were classified as young and those over 40 were classified as older.ResultsOverall, 167,501 patients had CRC. Of these, 3757 patients (2.2%) were young. Right‐sided cancers were more common in younger patients (48.2% vs. 32.9%, p < 0.001). Favourable histological grade (well or moderately differentiated) was present in 83.1% and 73.5% of young and older patients, respectively. The percentage of young and older patients being diagnosed at an early stage (Stages 1 and 2) was similar at 40.6% vs. 42.9%. The 5‐year age‐ and gender‐adjusted relative survival (cancer specific) was significantly better for young patients when compared with older patients diagnosed with CRC. Additionally, overall 5‐year survival was better for younger patients (71.6% and 47.2%, p < 0.001 in young and older CRC patients respectively).ConclusionThe increased right‐sided colon cancer in young CRC patients in England warrants attention. Contrary to previous reports, they do not present at later stage. Young CRC patients have better overall and relative survival than older patients with CRC.
Abnormal time‐zero histology is predictive of kidney transplant outcomes
Authors: Raza Syed Sikandar , Agarwal Gaurav , Anderson Douglas , Deierhoi Mark , Fatima Huma , Hanaway Michael , Locke Jayme , MacLennan Paul , Orandi Babak , Young Carlton , Mannon Roslyn B. , Seifert Michael E. 
Published: April 2022

AbstractIntroductionTime‐zero biopsies can detect donor‐derived lesions at the time of kidney transplantation, but their utility in predicting long‐term outcomes is unclear under the updated Kidney Allocation System.MethodsWe conducted a single‐center retrospective cohort study of 272 consecutive post‐reperfusion time‐zero biopsies. We tested the hypothesis that abnormal time‐zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long‐term outcomes.ResultsWe detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2‐fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan‐Meier analysis, the relationship between abnormal time‐zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time‐zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12‐month estimated GFR.ConclusionIn conclusion, abnormal time‐zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long‐term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time‐zero biopsies as an additional surveillance tool.
Health harms of non‐medical prescription opioid use: A systematic review
Authors: Werb Dan , Scheim Ayden I. , Soipe Ayorinde , Aeby Samantha , Rammohan Indhu , Fischer Benedikt , Hadland Scott E. , Marshall Brandon D. L. 
Published: April 2022

AbstractIssuesNon‐medical prescription opioid use (NMPOU) contributes substantially to the global burden of morbidity. However, no systematic assessment of the scientific literature on the associations between NMPOU and health outcomes has yet been undertaken.ApproachWe undertook a systematic review evaluating health outcomes related to NMPOU based on ICD‐10 clinical domains. We searched 13 electronic databases for original research articles until 1 July 2021. We employed an adaptation of the Oxford Centre for Evidence‐Based Medicine ‘Levels of Evidence’ scale to assess study quality.Key FindingsOverall, 182 studies were included. The evidence base was largest on the association between NMPOU and mental and behavioural disorders; 71% (129) studies reported on these outcomes. Less evidence exists on the association of NMPOU with infectious disease outcomes (26; 14%), and on external causes of morbidity and mortality, with 13 (7%) studies assessing its association with intentional self‐harm and 1 study assessing its association with assault (<1%).ImplicationsA large body of evidence has identified associations between NMPOU and opioid use disorder as well as on fatal and non‐fatal overdose. We found equivocal evidence on the association between NMPOU and the acquisition of HIV, hepatitis C and other infectious diseases. We identified weak evidence regarding the potential association between NMPOU and intentional self‐harm, suicidal ideation and assault.Discussion and ConclusionsFindings may inform the prevention of harms associated with NMPOU, although higher‐quality research is needed to characterise the association between NMPOU and the full spectrum of physical and mental health disorders.