bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I study of the irreversible fibroblast growth factor receptor 1–4 inhibitor futibatinib in Japanese patients with advanced solid tumors
Authors: Doi Toshihiko , Shitara Kohei , Kojima Takashi , Kuboki Yasutoshi , Matsubara Nobuaki , Bando Hideaki , Yoh Kiyotaka , Naito Yoichi , Hirai Hiroshi , Kurokawa Yukinori , Kato Terufumi , Morizane Chigusa
Published: July 2022

This phase I study was designed to: (1) determine the maximum tolerated dose (MTD) and recommended dose (RD) of the fibroblast growth factor receptor (FGFR) inhibitor futibatinib in Japanese patients with advanced solid tumors, and (2) examine the antitumor activity of the RD in patients with gastric cancer (GC) or other advanced solid tumors who have FGFR or FGF/FGFR abnormalities, respectively. In the dose‐escalation phase, patients were assigned to 21‐day cycles of oral futibatinib 8–160 mg three times a week (TIW) or 16 or 20 mg once daily (QD). In the expansion phase, patients received oral futibatinib 56, 80, or 120 mg TIW, or 16 or 20 mg QD. Eighty‐three patients received futibatinib TIW (n = 40) or QD (n = 43). No dose‐limiting toxicities were observed according to the final study protocol definition, and the MTD was not reached. The most common adverse events with both regimens were hyperphosphatemia (TIW, 82.5%; QD, 100.0%) and decreased appetite (TIW, 40.0%; QD, 58.1%). Hyperphosphatemia was asymptomatic, not leading to futibatinib discontinuation. The overall response rate (ORR) was 11.5% in patients with FGF/FGFR abnormalities. Notably, in GC patients harboring FGFR2 copy number (CN) ≥10, the ORR was 36.4% versus 0 in patients with CN <10. Therefore, futibatinib had a generally predictable and manageable safety profile in patients with advanced solid tumors. Antitumor activity was seen in patients with FGF/FGFR abnormalities, particularly those with GC and high FGFR2 CNs. Thus, futibatinib 20 mg QD was chosen as the RD for phase II studies.
Pathways to parenting stress reduction among parents in South Africa
Authors: Massarwi Adeem Ahmad , Cluver Lucie , Meinck Franziska , Doubt Jenny , Green Ohad
Published: July 2022

Parenting stress has a range of effects on parents and their children. Despite existing evidence on the effectiveness of family‐based interventions on reducing parenting stress, little is known about the mechanism of change that contributes to its reduction. This study investigates the mechanism of change in a parenting programme (Parenting for Lifelong Health [PLH]) on reducing parenting stress among parents of adolescents in South Africa. A pragmatic cluster randomized controlled trial was conducted among a total sample of 552 parents and primary caregivers (aged,M = 49.37;SD = 14.69) who were recruited from 40 communities in South Africa's Eastern Cape Province. A mediation analysis was performed to investigate direct and indirect effects using PROCESS macrostatistical software. The findings of the study indicate that parenting stress reduction operates via three significant mediators: improved parent–child relationship (β = 0.058,P < 0.000), reduced parental depression (β = −0.103,P < 0.000) and reduced family financial strain (β = −0.049,P < 0.000). The findings of the study highlight the importance of considering child, parental and contextual factors in the design and development of interventions aimed at reducing parenting stress in families in low‐ and middle‐income settings.
Occupational allergic contact dermatitis to Piperamido Nitrotoluene in pharmaceutical workers: A case series
Authors: Hollywood Aoife , Bourke John F.
Published: July 2022

Background

Imatinib mesylate is a first‐generation tyrosine kinase inhibitor. Piperamido Nitrotoluene, also known as F5, is an intermediate used in the manufacturing of imatinib. We present a case series of allergic contact dermatitis to F5 in pharmaceutical workers.

Methods

Four male pharmaceutical workers were referred between 2007 and 2021 with new dermatitis predominantly affecting the periorbital region. All were involved in the production of imatinib and particularly exposed to F5. Following medical history and examination, they underwent patch testing to standard series and F5 diluted in white soft paraffin (WSP).

Results

All patients tested positive confirming a diagnosis of contact allergy to F5. The first case tested positive to F5 diluted to 1% in WSP, the second to F5 diluted to 10% in WSP and the third and fourth to F5 diluted to 1% and 10% in WSP. In all four cases, dermatitis resolved when they were removed from exposure to F5.

Conclusions

To the best of our knowledge, these are the first cases of allergic contact dermatitis to F5 confirmed by patch testing in the literature. In February 2016, a generic formulation of imatinib entered the market. Globalized production of imatinib may result in further cases presenting to dermatology departments worldwide.
Learning curves for minimally invasive total mesorectal excision beyond the competency phase – a risk‐adjusted cumulative sum analysis of 1000 rectal resections
Authors: Kazi Mufaddal , Sukumar Vivek , Bankar Sanket , Kapadia Raj , Desouza Ashwin , Saklani Avanish
Published: July 2022

Aim

The learning curve of total mesorectal excision (TME) by minimally invasive surgery (MIS) beyond the competency phase has not been adequately reported with large numbers or using a statistical control limit. The aim of this work was to study the learning curve of MIS TME in the proficiency phase.

Method

Risk‐adjusted (RA) cumulative sum (CUSUM) and RA Bernoulli CUSUM charts were plotted for sequential MIS TME performed by a surgical team over 1000 cases. Surgical failure, a composite endpoint of conversions, complications of grade IIIA or above, R1 resections and inadequate nodal yield were used to monitor the performance.

Results

The RA CUSUM detected an inflection point around the 600th operation. Two peaks were identified that could be traced back to probable causes of surgical failure. Similar inflection points were detected at the 450th case for laparoscopic TME and the 367th case for sphincter preservation. No single definite threshold point was noticed for robotic or abdominoperineal operations. At no point did the curves cross the safety threshold. The probability of surgical failure reduced with increasing experience in the multivariate regression (OR 0.899, p = 0.000). This association persisted irrespective of the surgical approach (laparoscopic versus robotic) or the type of operation (sphincter preservation versus abdominoperineal resection).

Conclusion

The learning curves for MIS TME did not cross the safety threshold beyond the competency phase. However, a 10% reduction of relative risk in surgical failure was observed for every 100 cases operated on.
Free word association analysis of Germans' attitudes toward insects
Authors: Vlasák‐Drücker Jasmin , Eylering Annike , Drews Jasmin , Hillmer Gesa , Carvalho Hilje Vera , Fiebelkorn Florian
Published: July 2022

In this paper, the results of two free word association tests were analyzed to gain insight into Germans' attitudes toward insects. We used a novel approach in the form of an association network with the help of the software “Gephi” that was originally developed for social network analysis. The influence of attitude on the willingness to donate (WTD) and actual donation to an insect conservation project was investigated as well. Data collection was conducted via an online questionnaire (n = 515; Mage = 49.36, SD = 16.73; female = 50.1%). For the first test, participants listed three associations for the prompt “insect.” The associations were assigned to the three components of attitude: affective, cognitive, and behavioral. For the second test, participants named insects they pictured when thinking about “insects.” The results were taxonomically classified. The WTD was assessed with a Likert‐type scale and an actual donation could be made at the end of the online questionnaire. “Bee” was the most frequently named association, followed by “useful,” “nature,” “pollination,” and “pesky.” “Pesky” was most often named with “useful,” indicating that being aware of insects' usefulness is not enough to supersede negative associations. In the second test, only 6% of the associations were on the species level, which suggests little taxonomic knowledge about or interest in insects. Linear regression revealed that positive affective associations had a positive influence on the WTD and negative affective associations had a negative influence on the WTD, both with a small effect size. We advise educating people not only about the usefulness of insects but also fostering positive, personal encounters to increase positive affective associations and decrease negative ones.
Written information and health professionals are the information sources about alcohol use in pregnancy most often used by pregnant women
Authors: Tsang Tracey W. , Kingsland Melanie , Doherty Emma , Anderson Amy E. , Tully Belinda , Ward Sarah , Wiggers John , Elliott Elizabeth J.
Published: July 2022

Introduction

Alcohol use in pregnancy remains common in Australia, despite national guidelines recommending that pregnant women abstain. The aims of this study were to investigate where pregnant women obtain information about alcohol use in pregnancy and the relationship between the information source used and women's demographic characteristics and alcohol use.

Methods

In this cross‐sectional survey of pregnant women attending public maternity services in the Hunter New England region (New South Wales), women were asked, ‘Where did you get information to help you make decisions about alcohol use during pregnancy?’. The number and types of information sources were analysed using descriptive statistics. Associations between women's information sources, and their demographic characteristics and alcohol use in pregnancy were assessed using chi‐square tests and logistic regression.

Results

Of 4511 pregnant women surveyed, 80.1% used at least one type of information source (range 0–5). Written/electronic information (45.4%), health providers (37.6%) and family/friends (19.5%) were the sources most reported. Higher use of written/electronic information, antenatal health providers and family/friends was associated with first pregnancy, younger age and higher education. The type of information source used was associated with alcohol use in pregnancy. Women who reported alcohol use were more likely to receive information from written/electronic sources. Almost 20% of women (older, multiparous [>1 pregnancy] and more highly educated) obtained no information regarding alcohol use in pregnancy.

Discussion and Conclusions

Antenatal providers should routinely provide information on alcohol use in pregnancy, including for women least likely to access available information.
TOTUM‐63, a plant‐based polyphenol‐rich extract, improves glycaemic control in subjects with prediabetes or early stage newly‐diagnosed type 2 diabetes in a randomized, double‐blind, placebo‐controlled trial
Authors: Sirvent Pascal , Chavanelle Vivien , Otero Yolanda F. , Bargetto Maxime , Le Joubioux Florian , Boisseau Nathalie , Maugard Thierry , Cazaubiel Murielle , Pereira Bruno , Guigas Bruno , Hadjadj Samy , Peltier Sebastien L. , Marette André , Bard Jean‐Marie
Published: July 2022

Aim

The plant‐based polyphenol‐rich extract TOTUM‐63 improves glucose homeostasis in various preclinical models of obesity and type 2 diabetes (T2D). A pilot exploratory study showed that TOTUM‐63 has good safety and tolerability profiles, and beneficial effects on postprandial glucose control in healthy individuals with overweight. The aim of this study was to assess the effects of TOTUM‐63 on glycaemic control in individuals with prediabetes or early stage newly‐diagnosed T2D (which does not require pharmacological treatment).

Materials and Methods

This study was a multicentre, randomized, double‐blind, placebo‐controlled trial. Individuals with prediabetes or early stage newly‐diagnosed T2D and with overweight/abdominal obesity received TOTUM‐63 (5 g/day) or placebo for 6 months. The primary outcome was the change in fasting blood glucose.

Results

Fifty‐one participants (age: 57.1 ± 10 years; body mass index: 31.3 ± 5.7 kg.m2; 35 women and 16 men) completed the study (n = 38 TOTUM‐63, n = 13 placebo). After 6 months, blood glucose concentration after fasting and after the 2‐h oral glucose tolerance test was reduced in the TOTUM‐63‐treated group compared with the placebo group (placebo‐corrected difference between baseline and month 6: −0.71 mmol/L, p < .05, and −1.93 mmol/L, p < .05, respectively). TOTUM‐63 was safe and well tolerated and significantly reduced body weight gain (−1.9 kg; p < .05), waist circumference (−4.5 cm; p < .001), circulating triglycerides (−0.54 mmol/L; p < .01) and low‐density lipoprotein‐cholesterol (−0.38 mmol/L; p < .05) compared with placebo.

Conclusions

TOTUM‐63 lowered fasting blood glucose in participants with impaired fasting glycaemia and glucose intolerance. Moreover, TOTUM‐63 showed a good safety and tolerability profile and improved several metabolic syndrome features. Therefore, TOTUM‐63 is a promising candidate for T2D prevention.
Editor's Choice: August 2022
Authors: Beukeboom Leo W.
Published: July 2022

Using biological invasions to improve plant defense theory – S. B. Endriss, C. Alba & R. A. Hufbauer (https://doi.org/10.1111/eea.13195).
Long‐term efficacy of bilateral subthalamic deep brain stimulation in the parkinsonism of SCA 3: A rare case report
Authors: Kuo Ming‐Che , Tai Chun‐Hwei , Tseng Sheng‐Hong , Wu Ruey‐Meei
Published: July 2022

Background and purpose

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited disorder that manifests as a mixture of cerebellar ataxia, parkinsonism, and polyneuropathy; in type IV SCA3, pure parkinsonism is the only symptom. Currently, no disease‐modifying treatment is available, but variable responses to antiparkinsonism agents have been reported. However, the benefits of deep brain stimulation (DBS) for treating parkinsonism in this subtype of SCA3 remain unclear.

Methods

A 39‐year‐old male patient with a rare disorder of type IV SCA3 presented with pure parkinsonism including unilateral resting tremor, rigidity, and bradykinesia at the age of 30 years. Young‐onset Parkinson disease was diagnosed at the age of 32 years. His family history revealed a mild ataxia in his father since the age of 55 years. Genetic testing confirmed an expanded CAG repeated number, with 66 in this case and 63 in his father for SCA3 mutation. Excellent response to levodopa and dopamine agonists in the first 3 years was noted, but wearing‐off phenomena, levodopa‐induced dyskinesia, and severe impulse control disorders later developed. To alleviate drug‐induced complications, he received bilateral subthalamic nucleus deep brain stimulation (STN‐DBS) in the absence of cerebellar signs, depression, and cognitive impairment.

Results

As of 2019, no impulsive control disorders, motor fluctuations, or DBS‐related complications were observed during a 4‐year follow‐up, with 66% Unified Parkinson's Disease Rating Scale Part III reduction at medication OFF state noted, whereas levodopa equivalent daily dosage decreased by almost half.

Conclusions

STN‐DBS may be considered as adjunct treatment for severe dopa‐related motor/nonmotor complications in patients with parkinsonian phenotype of SCA 3.
Association of plasma neurofilament light chain with disease activity in chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Kapoor Mahima , Carr Aisling , Foiani Martha , Heslegrave Amanda , Zetterberg Henrik , Malaspina Andrea , Compton Laura , Hutton Elspeth , Rossor Alexander , Reilly Mary M. , Lunn Michael P.
Published: July 2022

Background and purpose

This study was undertaken to explore associations between plasma neurofilament light chain (pNfL) concentration (pg/ml) and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and examine the usefulness of pNfL concentrations in determining disease remission.

Methods

We examined pNfL concentrations in treatment‐naïve CIDP patients (n = 10) before and after intravenous immunoglobulin (IVIg) induction treatment, in pNfL concentrations in patients on maintenance IVIg treatment who had stable (n = 15) versus unstable disease (n = 9), and in clinically stable IVIg‐treated patients (n = 10) in whom we suspended IVIg to determine disease activity and ongoing need for maintenance IVIg. pNfL concentrations in an age‐matched healthy control group were measured for comparison.

Results

Among treatment‐naïve patients, pNfL concentration was higher in patients before IVIg treatment than healthy controls and subsequently reduced to be comparable to control group values after IVIg induction. Among CIDP patients on IVIg treatment, pNfL concentration was significantly higher in unstable patients than stable patients. A pNFL concentration > 16.6 pg/ml distinguished unstable treated CIDP from stable treated CIDP (sensitivity = 86.7%, specificity = 66.7%, area under receiver operating characteristic curve = 0.73). Among the treatment withdrawal group, there was a statistically significant correlation between pNfL concentration at time of IVIg withdrawal and the likelihood of relapse (r = 0.72, p < 0.05), suggesting an association of higher pNfL concentration with active disease.

Conclusions

pNfL concentrations may be a sensitive, clinically useful biomarker in assessing subclinical disease activity.
Guillain‐Barré syndrome and COVID‐19: A 1‐year observational multicenter study
Authors: Filosto Massimiliano , Cotti Piccinelli Stefano , Gazzina Stefano , Foresti Camillo , Frigeni Barbara , Servalli Maria Cristina , Sessa Maria , Cosentino Giuseppe , Marchioni Enrico , Ravaglia Sabrina , Briani Chiara , Castellani Francesca , Zara Gabriella , Bianchi Francesca , Del Carro Ubaldo , Fazio Raffaella , Filippi Massimo , Magni Eugenio , Natalini Giuseppe , Palmerini Francesco , Perotti Anna Maria , Bellomo Andrea , Osio Maurizio , Nascimbene Caterina , Carpo Marinella , Rasera Andrea , Squintani Giovanna , Doneddu Pietro Emiliano , Bertasi Valeria , Cotelli Maria Sofia , Bertolasi Laura , Fabrizi Gian Maria , Ferrari Sergio , Ranieri Federico , Caprioli Francesca , Grappa Elena , Manganotti Paolo , Bellavita Giulia , Furlanis Giovanni , De Maria Giovanni , Leggio Ugo , Poli Loris , Rasulo Frank , Latronico Nicola , Nobile‐Orazio Eduardo , Beghi Ettore , Padovani Alessandro , Uncini Antonino
Published: July 2022

Background and purpose

Many single cases and small series of Guillain–Barré syndrome (GBS) associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection were reported during the coronavirus disease 19 (COVID‐19) outbreak worldwide. However, the debate regarding the possible role of infection in causing GBS is still ongoing. This multicenter study aimed to evaluate epidemiological and clinical findings of GBS diagnosed during the COVID‐19 pandemic in northeastern Italy in order to further investigate the possible association between GBS and COVID‐19.

Methods

Guillain–Barré syndrome cases diagnosed in 14 referral hospitals from northern Italy between March 2020 and March 2021 were collected and divided into COVID‐19‐positive and COVID‐19‐negative. As a control population, GBS patients diagnosed in the same hospitals from January 2019 to February 2020 were considered.

Results

The estimated incidence of GBS in 2020 was 1.41 cases per 100,000 persons/year (95% confidence interval 1.18–1.68) versus 0.89 cases per 100,000 persons/year (95% confidence interval 0.71–1.11) in 2019. The cumulative incidence of GBS increased by 59% in the period March 2020–March 2021 and, most importantly, COVID‐19‐positive GBS patients represented about 50% of the total GBS cases with most of them occurring during the two first pandemic waves in spring and autumn 2020. COVID‐19‐negative GBS cases from March 2020 to March 2021 declined by 22% compared to February 2019–February 2020.

Conclusions

Other than showing an increase of GBS in northern Italy in the “COVID‐19 era” compared to the previous year, this study emphasizes how GBS cases related to COVID‐19 represent a significant part of the total, thus suggesting a relation between COVID‐19 and GBS.
Influence of educational status and migration background on the long‐term health‐related quality of life after stroke
Authors: Braadt Lino , Meisinger Christa , Linseisen Jakob , Kirchberger Inge , Zickler Philipp , Naumann Markus , Ertl Michael
Published: July 2022

Background and purpose

Acute stroke treatment and secondary prevention have tremendously improved functional outcomes after stroke. However, this does not always imply a likewise improvement in health‐related quality of life (HRQoL). Knowledge on factors influencing HRQoL after stroke is still scarce, especially regarding social aspects like the level of education and the presence of migration background.

Methods

In the present stroke cohort study, participants were interviewed during their hospital stay and completed a postal questionnaire at 3 and 12 months post stroke. Functional outcomes were assessed by the modified Rankin Scale and HRQoL by evaluating the detailed Stroke Impact Scale (SIS). Logistic regression models were used to determine associations between education, migration background and quality of life end‐points.

Results

A total of 945 (mean age 69 years; 56% male) stroke patients were enrolled. After adjusting for confounders, a lower educational level was associated with worse functional outcomes in the SIS domain ‘strength’ (odds ratio 2.67, 95% confidence interval 1.6–4.4, p < 0.001). Migration background was associated with worse outcomes in the SIS domain ‘emotion’ (p = 0.007, odds ratio 1.71, 95% confidence interval 1.2–2.5). Additionally, for female patients worse HRQoL outcomes were found in multiple other SIS domains.

Conclusions

Migration background and a lower educational level were significantly associated with lower long‐term HRQoL after stroke. These aspects should be considered in targeted rehabilitation programmes and follow‐up support of stroke patients.
Cannabinoid receptors are expressed in equine synovium and upregulated with synovitis
Authors: Miagkoff Ludovic , Girard Christiane A. , St‐Jean Guillaume , Richard Hélène , Beauchamp Guy , Laverty Sheila
Published: July 2022

Background

Osteoarthritis (OA) is a major cause of equine lameness. Cannabinoid (CB) receptors are now considered to be promising therapeutic targets in human rheumatology for pain and inflammation, however, little is known about the equine endocannabinoid system.

Objectives

The primary goal was to assess the presence and expression pattern of CB1 and CB2 in the synovium of healthy joints. A secondary goal was to explore the relationship between the CB expression, degree of synovitis and OA pathology.

Study design

Ex vivo experimental study.

Methods

Metacarpophalangeal joints (n = 25) from a tissue bank were studied. The joints were dissected, and the articular cartilage lesions were scored. Synovial membrane specimens (n = 45) were harvested, fixed and the degree of synovitis was graded on histological sections. Colocalised synovial sections were also immunostained with antibodies to CB1 and CB2. Five regions of interest were randomly selected from digital images of manually segmented synovial intima and scored blindly for positive cellular immunoreactive staining by two independent observers. Interobserver agreement was calculated with an intraclass correlation coefficient (ICC). Relationships between CB1 and CB2 immunoreactive scores and synovitis or joint OA grade were explored with mixed linear models.

Results

CB1 was expressed in synovial intimal cells in all specimens studied whereas CB2 expression was identified in 94%. Both receptors were also expressed in the subintimal blood vessel walls. ICCs were 84.6% (CB1) and 92.9% (CB2) for the immunoreactivity scores. Both CB1 and CB2 expression were significantly upregulated (p = 0.04 and p = 0.03, respectively) with increasing degree of synovitis. Conversely, CB1 expression significantly decreased (p = 0.03) with increasing severity of OA.

Main limitations

The type of synovial cell expressing CB1 or CB2 was not investigated.

Conclusion

Equine synovial intimal cells constitutively express both CB1 and CB2 receptors that are upregulated with synovitis and may have a role in joint pain. They are potential targets for therapy with cannabinoid molecules or their derivatives.
In vivo visualisation of tattoo particles using multiphoton tomography and fluorescence lifetime imaging
Authors: Nguyen Lynhda , Mess Christian , Schneider Stefan W. , Huck Volker , Herberger Katharina
Published: July 2022

With increased popularity of decorative tattoos, awareness of tattoo‐based dermatological complications has been raised. Health issues include a broad spectrum dominated by allergies and infections. To examine the etiopathology and prognose the outcome of an appropriate therapy, a non‐invasive intravital diagnostic approach is indicated. The present pilot study introduces multiphoton tomography equipped with fluorescence lifetime imaging as a diagnostic technique to examine the morphological and metabolic status of tattooed human skin at patient's bedside. The distributing course of tattoo particles can be visualised over time. By providing optical biopsies, inflammation‐based alterations in freshly tattooed skin and tattoo complications can be analysed. The study concludes that multiphoton tomography combined with fluorescence lifetime imaging is a suitable technique for in vivo visualisation of tattoo pigments as well as for the assessment of quantitative and qualitative skin changes after injection of tattoo ink into human skin.
The effect of Mg2+ on Ca2+ binding to cardiac troponin C in hypertrophic cardiomyopathy associated TNNC1 variants
Authors: Rayani Kaveh , Hantz Eric R. , Haji‐Ghassemi Omid , Li Alison Y. , Spuches Anne M. , Van Petegem Filip , Solaro R. John , Lindert Steffen , Tibbits Glen F.
Published: July 2022

Cardiac troponin C (cTnC) is the critical Ca2+‐sensing component of the troponin complex. Binding of Ca2+ to cTnC triggers a cascade of conformational changes within the myofilament that culminate in force production. Hypertrophic cardiomyopathy (HCM)‐associated TNNC1 variants generally induce a greater degree and duration of Ca2+ binding, which may underly the hypertrophic phenotype. Regulation of contraction has long been thought to occur exclusively through Ca2+ binding to site II of cTnC. However, work by several groups including ours suggest that Mg2+, which is several orders of magnitude more abundant in the cell than Ca2+, may compete for binding to the same cTnC regulatory site. We previously used isothermal titration calorimetry (ITC) to demonstrate that physiological concentrations of Mg2+ may decrease site II Ca2+‐binding in both N‐terminal and full‐length cTnC. Here, we explore the binding of Ca2+ and Mg2+ to cTnC harbouring a series of TNNC1 variants thought to be causal in HCM. ITC and thermodynamic integration (TI) simulations show that A8V, L29Q and A31S elevate the affinity for both Ca2+ and Mg2+. Further, L48Q, Q50R and C84Y that are adjacent to the EF hand binding motif of site II have a more significant effect on affinity and the thermodynamics of the binding interaction. To the best of our knowledge, this work is the first to explore the role of Mg2+ in modifying the Ca2+ affinity of cTnC mutations linked to HCM. Our results indicate a physiologically significant role for cellular Mg2+ both at baseline and when elevated on modifying the Ca2+ binding properties of cTnC and the subsequent conformational changes which precede cardiac contraction.
Hazard rate for postoperative recurrence in patients with hepatocellular carcinoma at Barcelona Clinic Liver Cancer stage 0 or A1: A multicenter observational study
Authors: Xiang Yan‐Jun , Wang Kang , Yu Hong‐Ming , Wang Miao‐Miao , Li Le‐Qun , Sun Hui‐Chuan , Wen Tian‐Fu , Zhang Yu‐Qing , Shan Yun‐Feng , Zhou Li‐Ping , Cheng Shu‐Qun
Published: July 2022

Aim

Surgical treatment is the first‐line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A1 hepatocellular carcinoma (HCC), and postoperative monitoring improves long‐term survival. We aimed to establish a reasonable short‐interval follow‐up duration for patients with HCC.

Methods

The cohort for this retrospective study included 1396 HCC patients with BCLC stage 0 or A1 disease who underwent curative resection from 2013 to 2016 at five centers in China. Hazard rates for recurrence were calculated using the hazard function.

Results

The recurrence rates in patients with BCLC stage 0 and A1 HCC were 46.4% and 58.0%, respectively. The hazard curve for stage 0 patients was relatively flat, and the hazard rate was consistently low (peak hazard rate 0.0163). The hazard rate curve for recurrence was initially high (peak hazard rate 0.0441) in patients with BCLC stage A1 disease and showed a rapid decreasing trend within 1 year, followed by a slow decreasing trend, reaching a low level (<0.0163) at approximately 36 months. The time to low risk was 47, 41, and 51 months in patients with cirrhosis, hepatitis B virus (HBV) infection, and satellite lesions, respectively.

Conclusions

A short‐interval follow‐up of 1 year is sufficient for HCC patients with BCLC stage 0 disease, whereas a short‐interval follow‐up time of 3 years should be considered for patients with stage A1 disease. The follow‐up period should be appropriately prolonged for patients with cirrhosis, HBV infection, and satellite lesions.
Hydroxypropyl chitosan modified by cinnamic acid derivative nanoparticles for stabilising Pickering emulsion
Authors: Wang Min , Yue Lin , Zhao Lingyu , Khan Imran Mahmood , Zhang Yin , Wang Zhouping
Published: July 2022

Chitosan (CS) derivatives, chemically modified appropriately, can be used to produce nanoparticles with good properties. In this work, using CS, hydroxypropyl CS (HPCS) and HPCS modified by cinnamic acid (HPCS‐CA) derivative as raw materials, the nanoparticles were synthesised by ion crosslinking method with tripolyphosphate. FT‐IR spectra indicated that CS and its derivatives successfully cross‐linked with TPP at the molecular level. XRD and TG results exhibited changes in crystallinity and thermal stability. The nanoparticles had narrow size distribution and were nearly spherical. The surfaces of the nanoparticles were all positively charged. The nanoparticles‐stabilised oil‐in‐water Pickering emulsions were obtained by high‐speed homogenisation. The emulsions' morphology was reported by confocal laser scanning microscopy, indicating that the Pickering emulsions were synthesised successfully. The stability of the emulsion stabilised by HPCS‐CA nanoparticles was better than that of CS and HPCS nanoparticles. Taking curcumin as the target component, its stability in Pickering emulsions was good. The Pickering emulsion stabilised by HPCS‐CA nanoparticles may be a novel bioactive compound delivery system.
Application of green tea extract and catechin on the polyphenolic and volatile composition of Monastrell red wines
Authors: Anaya Juan Alberto , Álvarez Inmaculada , García María José , Lizama Victoria
Published: July 2022

The present work studies the effect of adding catechin and plant extract rich in catechin, Camellia sinensis (green tea) extract, on the volatile and polyphenolic composition of red wines made from Monastrell grapes. The aim of this research is to study the way to increase the red wine quality made with Monastrell variety of grapes. In one of them, the green tea extract was applied to grapes in vineyards 10 days before harvest. In another, catechin was applied to vineyards in the same way, and finally, catechin was applied during grape processing. Each trial was fermented by traditional vinification and prefermentative maceration for 5 days prior to alcoholic fermentation. A simple ANOVA analysis was used to evaluate if the application of copigments and winemaking techniques influenced wine composition. In addition, a multifactorial ANOVA was used to study the copigment treatment effect x winemaking technique interaction. Wine polyphenolic and volatile composition were analysed 12 months after fermentation. The application of green tea extract and catechin to vineyards increased (13%–16%) the concentration of anthocyanins in relation to the control to a greater extent when the initial polyphenolic concentration of grapes was lower. The volatile concentration rose when copigments (green tea extract and pure catechin) were applied to vineyards, in particular, hexyl acetate, ethyl octanoate and vanillin. The application of techniques like prefermentative maceration enhances the effects of copigments added to vineyards. The combination of the application of green extract or pure catechin with prefermentative cold maceration, had positive effects increasing polyphenols and volatile compounds concentration.
Release characteristics and bioaccessibility of lutein from calcium alginate hydrogels during simulated digestion in vitro
Authors: Luo Shuwei , Song Jiangfeng , Xu Pengxiang , Dai Zhuqing , Wu Caie , Li Ying
Published: July 2022

In this study, the release of lutein from calcium alginate hydrogels during simulated digestion in vitro was investigated. The results showed that the cross‐linked hydrogel with Ca2+ concentration >7.5 mM had a large amount of lutein retained on the surface, and digestive enzymes caused rapid degradation of the hydrogel structure, resulting in a high initial release rate. The particle size of the digestate was the largest in the simulated small intestinal digestion stage, with the gradual degradation of the outer wall proteins of lutein nanoparticles, showing a decreasing trend in the colonic digestion stage. The hydrogel cross‐linked with high concentration of Ca2+ mainly released lutein nanoparticles with small particle size. In the later stage, the probability of agglomeration between lutein nanoparticles increased. The cumulative release rate of lutein in the hydrogel with Ca2+ concentration <7.5 mM was higher after digestion, but lutein retention was <80%. The formation of lutein mixed micelles was hindered by the hydrogel with a Ca2+ content more than 7.5 mM, and lutein bioaccessibility was reduced. As a result, appropriate concentration of Ca2+ cross‐linked hydrogel carrier improved lutein bioavailability while also extending the residence period.
Discovery of flavouring compounds to substitute fatty and tallow characteristics in plant‐based patties
Authors: Chekmarev Dmitriy S. , Da Costa Neil C. , Darling Jason M. , Janczuk Adam J. , Ji Song , Joseph Susan L. , Sudol Marion A.
Published: July 2022

Plant‐based meat substitutes have greatly improved in recent years in texture and flavour; however, they still lack the authentic fatty and tallow flavour notes associated with meat. To investigate what may be lacking in these products, charred beef was prepared, extracted and analysed in depth, to discover novel high‐impact volatile molecules of sensory value for improved flavour application in plant‐based meat substitutes. Beef was prepared by charring on a grill and extracted by simultaneous distillation extraction (SDE) and solvent‐assisted flavour evaporation (SAFE). The extracts were analysed by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS), respectively, which showed the results of 209 volatile compounds and 21 targeted amino acids in the cooked beef. Using GC‐Olfactometry, five compounds were postulated, synthesised and sensorially evaluated to find their optimal use concentrations. Of particular interest were 3‐(methylthio)‐alkanals, some of which had not previously been reported in natural products. A model meat flavour was evaluated with and without 3 of these fatty, tallow compounds at optimal dosage use, when applied to soy and pea protein patties, respectively. Sensory and statistical data analysis showing the resulting organoleptic improvements are also presented.
Effect of high shear homogenisation on physicochemical, microstructure, particle size and volatile composition of residual pineapple pulp
Authors: Ravichandran Chandrakala , Upadhyay Ashutosh , Meda Venkatesh , Rastogi Navin K. , Khan Zober Alam , Emanuel Neela
Published: July 2022

Waste or by‐product utilisation is on focus to reduce the environmental threat and acquiring wealth out of waste. This study was planned to understand the effect of high shear homogenisation (SH) on physicochemical, microstructural, particle size, dietary fibre and volatile composition of residual pineapple pulp (RPP) for its utilisation. Shear homogenisation with three levels of rotor speed, that is 5000, 15 000 and 30 000 rpm, was employed for 5, 10 and 15 min. These responses reveal that the shear speed of 15 000 rpm for 10 min was relatively better in colour retention and enhanced soluble dietary fibre (SDF) by 48%. Increased levels of SDF after treatment help in the utilisation of RPP and its suitability for food supplementation. A gradual reduction in particle size from 40 to 400 μm was observed with shear homogenisation. Optical microscopy images revealed that larger cell fragments, fibrous nature and dense hairy mass of pomace were disrupted at 15 000 rpm. Moderate shear speed triggers the release of additional aroma volatiles, whereas higher rpm and time resulted in degradation of volatiles. The shear homogenised RPP is used for the development of fibre‐enriched yoghurt and incorporation at a 5% level resulted in high acceptable sensory scores.
Design of an integrated membrane system to produce dairy by‐product from waste processing
Authors: Gaudio Maria Teresa , Curcio Stefano , Chakraborty Sudip
Published: July 2022

Membrane technology is used in different applications. In this work, a whey‐based product with a final protein content of 16% has been formulated from Scotta – the last waste of the dairy industry – by cross‐flow ultrafiltration (UF) membrane followed by vacuum evaporation (EV). Until now, Scotta was only revalorized in conjunction with whey and into the biogas production process. It was never revalorized as food in the food supply chain. UF and EV processes led to an overall water amount removed from the whey of 84.9%. A vertical configuration of the polyethersulfone (PES) hollow‐fibre membrane was used in the OUT‐to‐IN structure. At 1.50 bar of pressure with 120 min of time interval, higher permeate flow decay has been obtained with a further reduction of the microbiological environments. A combination of intermediate and standard blocking seems to happen in all membranes, but concentration polarisation (CP) may be neglected for membranes with high fibres. The best EV operating conditions have been obtained at ten bars, with 37°C of the heating bath and 2.5 h of time, further preventing microorganism formation and protein denaturation. For future applications of Scotta revalorized in a food, it would be interesting to investigate the use of the multistage methods of membrane and evaporators to obtain a low specific energy consumption and to reduce costs further.
Effects of frozen temperature and multiple freeze–thaw cycles on gel structure, protein and lipid oxidation and formation of advanced glycation end‐products in unwashed silver carp surimi
Authors: Li Jiayi , Niu Lihong , Yu Jian , Wang Faxiang , Li Xianghong , Huang Yiqun , Liu Yongle
Published: July 2022

The effects of frozen temperature (−18 or −60 °C) and multiple freeze–thaw (FT) cycles on the gel structure, protein denaturation and oxidation, lipid oxidation and formation of protein‐bound Nε‐carboxymethyllysine (CML) and Nε‐carboxyethyllysine (CEL) in unwashed silver carp surimi were investigated. The levels of CML and CEL in raw and heat‐treated surimi increased due to multiple FT treatment, which were positively correlated with the thiobarbituric acid‐reactive substances (TBARS) and protein carbonyl content that also increased during FT cycles, and negatively correlated with the total sulfhydryl content and Ca2+‐ATPase activity that decreased during FT cycles. Besides, the gel structure of unwashed surimi was improved by 3 FT cycles and frozen at −60 °C, which was significantly helpful to inhibit the formation of protein carbonyl and CEL in raw surimi, but showed no significant influence on the TBARS and CML levels as compared to that at −18 °C.
Pneumolysin suppresses the initial macrophage pro‐inflammatory response to Streptococcus pneumoniae
Authors: Periselneris Jimstan , Turner Carolin T. , Ercoli Giuseppe , Szylar Gabriella , Weight Caroline M. , Thurston Teresa , Whelan Matthew , Tomlinson Gillian , Noursadeghi Mahdad , Brown Jeremy
Published: July 2022

Published data for the Streptococcus pneumoniae virulence factor Pneumolysin (Ply) show contradictory effects on the host inflammatory response to infection. Ply has been shown to activate the inflammasome, but also can bind to MRC‐1 resulting in suppression of dendritic cell inflammatory responses. We have used an in vitro infection model of human monocyte‐derived macrophages (MDM), and a mouse model of pneumonia to clarify whether pro‐ or anti‐inflammatory effects dominate the effects of Ply on the initial macrophage inflammatory response to S. pneumoniae, and the consequences during early lung infection. We found that infection with S. pneumoniae expressing Ply suppressed tumour necrosis factor (TNF) and interleukin‐6 production by MDMs compared to cells infected with ply‐deficient S. pneumoniae. This effect was independent of bacterial effects on cell death. Transcriptional analysis demonstrated S. pneumoniae expressing Ply caused a qualitatively similar but quantitatively lower MDM transcriptional response to S. pneumoniae compared to ply‐deficient S. pneumoniae, with reduced expression of TNF and type I IFN inducible genes. Reduction of the MDM inflammatory response was prevented by inhibition of SOCS1. In the early lung infection mouse model, the TNF response to ply‐deficient S. pneumoniae was enhanced and bacterial clearance increased compared to infection with wild‐type S. pneumoniae. Overall, these data show Ply inhibits the initial macrophage inflammatory response to S. pneumoniae, probably mediated through SOCS1, and this was associated with improved immune evasion during early lung infection.
Delivering the goods? German industrial relations institutions during the COVID‐19 crisis
Authors: Behrens Martin , Pekarek Andreas
Published: July 2022

The COVID‐19 pandemic has caused labor market disruptions at an unprecedented scale and is akin to a stress test for industrial relations institutions. Drawing on a large‐scale (n = 6111) study of German employees, we empirically investigate whether and how the two institutions comprising Germany's dual system of employee representation—works councils and collective bargaining—have delivered on their protective potential and mitigated the impact of the pandemic on workers. We demonstrate that employees in representative environments fare better on a range of protective outcomes.
Study of visible, NIR, and MIR spectroscopic properties of Er3+‐doped tellurite glasses and glass–ceramics
Authors: Lemiere Arnaud , Bondzior Bartosz , Aromäki Iisa , Petit Laeticia
Published: July 2022

In this paper, the structural, thermal, optical, and spectroscopic properties of Er3+‐doped tellurite glasses with the composition 68.25TeO2–19.5ZnO–9.75X–2.5Er2O3(in mol%) with X = BaO, Na2O, and Bi2O3are reported. The glasses were prepared using the standard melt quenching method. The investigated glasses exhibit low phonon energy (∼745 cm−1) and low glass transition temperature varying between 300 and 350°C depending on the glass composition. The Raman spectra show a regular tellurite structure with variations in the number of bridging and non‐bridging oxygens depending on the glass composition, the Na2O and Bi2O3‐containing glasses having the most and the least polymerized network, respectively. A thermal treatment of the glasses leads to the formation of crystals, the composition of which depends on the glass composition, as revealed by X‐ray diffraction analysis and confirmed using scanning electron microscope‐energy‐dispersive spectroscopy. The precipitation of Er‐containing crystals in the Na2O and BaO‐containing glasses leads to an increase in the intensity of the upconversion emissions. Although the Er3+ions remain in the amorphous part of the Bi2O3‐containing glass after heat treatment, it is the precipitation of Bi3.2Te0.8O6.4crystals in this glass, which is thought to decrease the distance between the Er3+ions leading to an increase in the intensity of the upconversion and mid‐infrared emissions.
Na2Ca3Si2O8 or γ‐Na2Ca6Si4O15? A hybrid approach combining 3D single‐crystal electron and powder X‐ray diffraction
Authors: Kahlenberg Volker , Vinke Jonathan , Krüger Hannes , Ito Sho , Schürmann Christian J.
Published: July 2022

Phase assemblages of mixtures containing Na2CO3, CaCO3, and SiO2 in the molar ratio 1:3:2 have been studied at elevated temperatures. Synthesis experiments have been performed at 1000, 1100, and 1200°C within a differential thermal analysis (DTA‐TGA) apparatus. Mass losses during heating and annealing periods of the high‐temperature treatment have been investigated in situ using thermogravimetry. For the run at 1200°C, the solid‐state reactions resulted in almost phase pure polycrystalline material of a previously unknown high‐temperature polymorph of Na2Ca6Si4O15, whose formation was triggered by significant Na2O losses at the reaction temperature. The new so‐called γ‐phase has been structurally characterized by a combination of 3D single‐crystal electron and powder X‐ray diffraction. Basic crystallographic data at ambient conditions are as follows: monoclinic symmetry, space group C 2, a = 17.2066(1) Å, b = 5.47863(3) Å, c = 7.32583(4) Å, β = 91.435(4)°, V = 690.38(1) Å3, Z = 2. Structure solution was accomplished by electron diffraction, whereas the subsequent refinement calculations were based on the Rietveld method using high‐resolution data from a laboratory powder diffractometer. Similar to the other two already known Na2Ca6Si4O15 modifications, the crystal structure of the γ‐phase contains both [Si2O7] dimers and insular [SiO4] moieties. Tetrahedra and [CaO6] octahedra form a three‐dimensional framework whose topological characteristics have been studied. The remaining Ca and Na cations are located on five symmetrically independent positions located in cavities of the network. There are sufficiently strong arguments that previously described “triclinic Na2Ca3Si2O8” is actually misinterpreted γ‐Na2Ca6Si4O15 and that a sodium calcium silicate with a molar ratio of Na2O:CaO:SiO2 = 1:3:2 does probably not exist. Our investigation is an excellent example that 3D electron diffraction has transformed from an exotic technique for crystal‐structure determination into an indispensable method for problems where small sizes of the crystallites is an issue.