bluuebunny/crossref_metadata_2025 huggingface dataset:
Family and nonfamily female directors' effect on CSR strategy
Authors: Cambrea Domenico Rocco , Tenuta Paolo , Naciti Valeria
Published: August 2024

By investigating a sample of industrial Italian listed firms for the years 2003–2020, this research aims to explore two main relationships. First, the study examines the association between the ratio of female directors and CSR strategy score in both family and nonfamily firms. Second, it investigates the link between family female directors and nonfamily female directors within the subsample of family firms. The empirical findings show the existence of a positive link between the ratio of female directors and CSR strategy score only in the subsample of family firms and that this result is driven by the percentage of nonfamily female directors. Additional analyses, aiming to elucidate the heterogeneity of family female directors, report that family females who have an executive role on the board are beneficial for the CSR strategy score, whereas family females who are interlocked and with long tenure are detrimental for the CSR strategy score.
Factor Structure and Psychometric Properties of the ED‐15 in People With an Eating Disorder
Authors: Zhou Yuan , Pellizzer Mia , Keegan Ella , Wade Tracey D.
Published: August 2024

Objective

This study examines the factorial structure and psychometric properties of the Eating Disorder‐15 questionnaire (ED‐15) in a large clinical sample, as well as the instrument's sensitivity to early clinical change in therapy and ability to measure remission.

Method

Participants with eating disorders (N = 278) referred to the Flinders University Services for Eating Disorders in South Australia completed the ED‐15 as well as other measures of eating disorder symptoms and co‐occurring psychopathology, including depression, anxiety, and stress.

Results

Confirmatory factor analysis (CFA) revealed a two‐factor model for the ED‐15. The ED‐15 had good internal consistency. It showed satisfactory concurrent validity with moderate correlations with the EDE‐Q global score and contribution of unique variance to that score. Correlations indicated good convergent validity with clinical impairment and good divergent validity from depression, anxiety, and stress. The ED‐15 showed a significant medium effect size change within the first four sessions of therapy. Good discriminant validity was indicated by cut‐off scores used for remission, with significantly different levels of ED psychopathology and other impairments between the two groups.

Discussion

This study adds to the four previous psychometric studies of the ED‐15, confirming robustness of the English version in a clinical sample. The brevity and psychometric robustness of the ED‐15 makes it a preferable measure to the Eating Disorder Examination for sessional assessment of progress in treatment.
Associations Between Weight Discrimination, Eating‐Disorder‐Related Psychiatric Impairment, and Eating‐Disorder Treatment Interest Across the Weight Spectrum
Authors: Thomeczek Marianna L. , Forbush Kelsie T. , Chen Yiyang , Negi Sonakshi , Johnson‐Munguia Sarah , L'Insalata Alexa M. , Rasheed Samiya , Like Emily , McDonald Jacquelyn
Published: August 2024

Objective

Only approximately 20% of college students with an eating disorder (ED) seek treatment. One barrier to seeking treatment is weight discrimination. Past research demonstrates that experiencing weight discrimination is associated with increased ED risk and decreased in‐person treatment engagement. Weight discrimination may be a particularly relevant treatment barrier for students who have a higher body weight given their higher likelihood of experiencing weight discrimination.

Methods

College students with a probable ED diagnosis (N = 372; Mage = 23.94; 73.12% women, 18.55% men, 6.18% another gender; 11.29% Asian, 4.57% Black, 12.63% Hispanic, 83.60% White, 4.84% Native American, and 0.54% another race) completed an online self‐report survey that included the Clinical Impairment Assessment (CIA), Experience of Weight Discrimination (EWD) Scale, and a 0–100 scale to indicate interest in participating in virtual guided self‐help ED treatment.

Results

Linear regression showed significant positive relationships between weight discrimination and ED‐related psychiatric impairment and treatment interest.

Discussion

Elevations in CIA scores corroborate past literature that suggested that weight discrimination was positively related to ED psychopathology. Contrary to past research, college students who experienced weight discrimination had greater treatment interest. Students who experience weight discrimination may view virtual self‐guided treatment as less weight‐stigmatizing due to the “do‐it‐yourself” approach and no in‐person interactions. Findings highlight the potential impacts of weight discrimination on acceptability of ED‐related care. Future research is needed to identify ways to reduce weight discrimination and promote weight‐inclusive practices in the medical system.
Evidence for feminized genetic males in a flea beetle using newly identified X‐linked markers
Authors: Rohlfing Kim , Grewoldt Malte , Cordellier Mathilde , Dobler Susanne
Published: August 2024

The equilibrium of sex ratios in sexually reproducing species is often disrupted by various environmental and genetic factors, including endosymbionts like Wolbachia. In this study, we explore the highly female‐biased sex ratio observed in the flea beetle, Altica lythri, and its underlying mechanisms. Ancient hybridization events between Altica species have led to mitochondrial DNA introgression, resulting in distinct mitochondrial haplotypes that go along with different Wolbachia infections (HT1‐wLytA1, HT1*‐ uninfected, HT2‐wLytA2, and HT3‐wLytB). Notably, beetles with some haplotypes exclusively produce female offspring, suggesting potential Wolbachia‐induced phenomena such as feminization of genetic males. However, the observed female bias could also be a consequence of the ancient hybridization resulting in nuclear–cytoplasmic conflicts between introgressed mtDNA and nuclear genes. Through transcriptomic analysis and the program SEX‐DETector, we established markers for genotypic sex differentiation for A. lythri, enabling genetic sexing via qPCR. Our findings suggest that feminization of genetic males is contributing to the skewed sex ratios, highlighting the intricate dynamics of sex determination and reproductive strategies in this flea beetle. This study provides valuable insights into the dynamics of genetic conflicts, endosymbionts, and sex ratios, revealing the novel phenomenon of genetic male feminization in the flea beetle A. lythri.
How can we measure resource quality when resources differ in many ways? Deconstructing shelter quality in a social fish
Authors: Bose Aneesh P. H. , Brodin Tomas , Katongo Cyprian , Mabo Lwabanya , Jordan Alex
Published: August 2024

Resource quality is an important concept in ecology and evolution that attempts to capture the fitness benefits a resource affords to an organism. Yet “quality” is a multivariate concept, potentially affected by many variables pertaining to the resource, its surroundings, and the resource chooser. Researchers often use a small number of proxy variables to simplify their estimation of resource quality, but without vetting their proxies against a wider set of potential quality estimators this approach risks overlooking potentially important characteristics that can explain patterns of resource use in their study systems. Here we used Neolamprologus multifasciatus, a group‐living cichlid fish that utilizes empty snail shells as shelter resources, to examine how shells were used by, and partitioned among, group members in relation to a range of attributes, including shell size, intactness, texture, spatial position, and usage by heterospecifics. This approach generated a comprehensive picture of what characteristics contribute to the attractiveness and quality of each shell resource, confirming the importance of two previously proposed shell characteristics, size and intactness, but highlighting the influences of other unexplored variables, including shell spatial position and usage by heterospecifics. We also present a generally applicable “resource attractiveness index” as a means to estimate resource quality based on resource choice data. This index incorporates information from any number of resource characteristics and is of particular use when researchers wish to quantify resource value, but many characteristics jointly contribute to the value and attractiveness of the resource.
Heart rate reactivity, recovery, and endurance of the incremental shuttle walk test in patients prone to heart failure
Authors: Wei Fang‐Fei , Mariottoni Beatrice , An De‐Wei , Pellicori Pierpaolo , Yu Yu‐Ling , Verdonschot Job A. J. , Liu Chen , Ahmed Fozia Z. , Petutschnigg Johannes , Rossignol Patrick , Heymans Stephane , Cuthbert Joe , Girerd Nicolas , Li Yan , Clark Andrew L. , Nawrot Tim S. , Ferreira João Pedro , Zannad Faiez , Cleland John G. F. , Staessen Jan A. ,   the HOMAGE investigators
Published: August 2024

Aims

Few randomized trials assessed the changes over time in the chronotropic heart rate (HR) reactivity (CHR), HR recovery (HRR) and exercise endurance (EE) in response to the incremental shuttle walk test (ISWT). We addressed this issue by analysing the open HOMAGE (Heart OMics in Aging) trial.

Methods

In HOMAGE, 527 patients prone to heart failure were randomized to usual treatment with or without spironolactone (25–50 mg/day). The current sub‐study included 113 controls and 114 patients assigned spironolactone (~70% on beta‐blockers), who all completed the ISWT at baseline and at Months 1 and 9. Within‐group changes over time (follow‐up minus baseline) and between‐group differences at each time point (spironolactone minus control) were analysed by repeated measures ANOVA, unadjusted or adjusted for sex, age and body mass index, and additionally for baseline for testing 1 and 9 month data.

Results

Irrespective of randomization, the resting HR and CHR did not change from baseline to follow‐up, with the exception of a small decrease in the HR immediately post‐exercise (−3.11 b.p.m.) in controls at Month 9. In within‐group analyses, HR decline over the 5 min post‐exercise followed a slightly lower course at the 1 month visit in controls and at the 9 month visits in both groups, but not at the 1 month visit in the spironolactone group. Compared with baseline, EE increased by two to three shuttles at Months 1 and 9 in the spironolactone group but remained unchanged in the control group. In the between‐group analyses, irrespective of adjustment, there were no HR differences at any time point from rest up to 5 min post‐exercise or in EE. Subgroup analyses by sex or categorized by the medians of age, left ventricular ejection fraction or glomerular filtration rate were confirmatory. Combining baseline and Months 1 and 9 data in both treatment groups, the resting HR, CHR and HRR at 1 and 5 min averaged 61.5, 20.0, 9.07 and 13.8 b.p.m. and EE 48.3 shuttles.

Conclusions

Spironolactone on top of usual treatment compared with usual treatment alone did not change resting HR, CHR, HRR and EE in response to ISWT. Beta‐blockade might have concealed the effects of spironolactone. The current findings demonstrate that the ISWT, already used in a wide variety of pathological conditions, is a practical instrument to measure symptom‐limited exercise capacity in patients prone to developing heart failure because of coronary heart disease.
Genotype is associated with left ventricular reverse remodelling and early events in recent‐onset dilated cardiomyopathy
Authors: Kubanek Milos , Binova Jana , Piherova Lenka , Krebsova Alice , Kotrc Martin , Hartmannova Hana , Hodanova Katerina , Musalkova Dita , Stranecky Viktor , Palecek Tomas , Chaloupka Anna , Grochova Ilga , Krejci Jan , Petrkova Jana , Melenovsky Vojtech , Kmoch Stanislav , Kautzner Josef
Published: August 2024

Aims

Recent‐onset dilated cardiomyopathy (RODCM) is characterized by heterogeneous aetiology and diverse clinical outcomes, with scarce data on genotype–phenotype correlates. Our aim was to correlate individual RODCM genotypes with left ventricular reverse remodelling (LVRR) and clinical outcomes.

Methods and results

In this prospective study, a total of 386 Czech RODCM patients with symptom duration ≤6 months underwent genetic counselling and whole‐exome sequencing (WES). The presence of pathogenic (class 5) or likely pathogenic (class 4) variants in a set of 72 cardiomyopathy‐related genes was correlated with the occurrence of all‐cause death, heart transplantation, or implantation of a ventricular assist device (primary outcome) and/or ventricular arrhythmia event (secondary outcome). LVRR was defined as an improvement of left ventricular ejection fraction to >50% or ≥10% absolute increase, with a left ventricular end‐diastolic diameter ≤33 mm/m2 or ≥10% relative decrease. Median follow‐up was 41 months. RODCM was familial in 98 (25%) individuals. Class 4–5 variants of interest (VOIs) were identified in 125 (32%) cases, with 69 (18%) having a single titin‐truncating variant (TTNtv) and 56 (14%) having non‐titin (non‐TTN) VOIs. The presence of class 4–5 non‐TTN VOIs, but not of TTNtv, heralded a lower probability of 12‐month LVRR and proved to be an independent baseline predictor both of the primary and the secondary outcome. The negative result of genetic testing was a strong protective baseline variable against occurrence of life‐threatening ventricular arrhythmias. Detection of class 4–5 VOIs in genes coding nuclear envelope proteins was another independent predictor of both study outcomes at baseline and also of life‐threatening ventricular arrhythmias after 12 months. Class 4–5 VOIs of genes coding cytoskeleton were associated with an increased risk of life‐threatening ventricular arrhythmias after baseline assessment. A positive family history of dilated cardiomyopathy alone only related to a lower probability of LVRR at 12 months and at the final follow‐up.

Conclusions

RODCM patients harbouring class 4–5 non‐TTN VOIs are at higher risk of progressive heart failure and life‐threatening ventricular arrhythmias. Genotyping may improve their early risk stratification at baseline assessment.
Diagnostic and prognostic value of the left atrial myopathy evaluation in cardiac amyloidosis using echocardiography
Authors: Ferkh Aaisha , Geenty Paul , Stefani Luke , Emerson Peter , Pham Jennifer , Byth Karen , Boyd Anita C. , Richards David , Taylor Mark S. , Kwok Fiona , Kizana Eddy , Thomas Liza
Published: August 2024

Background

Cardiac amyloidosis (CA) is an under‐recognized cause of heart failure. Left atrial (LA) myopathy contributes to a worse prognosis in heart failure and is a feature of transthyretin (ATTR) and light‐chain (AL) CA. LA mechanical dispersion (LA‐MD) is a novel marker of intra‐atrial dyssynchrony implicated in LA myopathy and the future development of atrial fibrillation (AF).

Aims

This study aimed to determine the characteristics and prognostic value of LA myopathy in ATTR and AL cardiomyopathy through a comprehensive LA echocardiographic evaluation.

Methods

ATTR (n = 86) and AL (n = 86) CA patients were compared with hypertensive heart disease (HHT) patients (n = 58). Transthoracic echocardiographic measurements including LA strain and LA‐MD were obtained with patient follow‐up for mortality.

Results

ATTR and AL patients had a median follow‐up of 66 months, with 26 mortality events. Left ventricular (LV) mass, diastolic function (average‐e′ and E/e′), LV global longitudinal strain, and LA volume and function (LA function index and strain) were more impaired in ATTR versus AL; these echocardiographic parameters were more impaired in both amyloid groups compared to HHT patients (P < 0.05). LA‐MD was increased in ATTR versus AL [median 72.2 (inter‐quartile range 55–88.9) vs. 54 (43.5–64.2), respectively, P < 0.001]. Multivariable logistic regression adjusted for age, presence of AF, LV mass, global and basal strain, and E/e′ demonstrated that LA‐MD was an independent determinant of ATTR CA (P = 0.014). On multivariable analysis, LA reservoir strain was independently associated with the presence of heart failure in the CA group (P < 0.001). LA minimum volume (cut‐off ≥18 mL/m2) was a determinant of mortality in AL CA [Cox proportional hazard ratio (HR) 1.042 (1.003–1.082), P = 0.034 and Kaplan–Meier analysis, P = 0.016].

Conclusion

Characterizing LA myopathy has significant diagnostic and prognostic utility in CA. ATTR patients have increased atrial dyssynchrony, which may have implications for AF development. LA reservoir strain was associated with heart failure in CA, whilst LA minimum volume was a predictor of mortality in AL CA.
Reductive‐Transmetalation Reactions of ZnR2/(AlCp*)4 Heterobimetallic Combinations and Application Towards CO2 Insertion
Authors: Hevia Eva , Dankert Fabian
Published: August 2024

Organo‐aluminum compounds are usually derived via salt metathesis reactions starting from aluminum halides and s‐block organometallics such as organolithiums or Grignard reagents. Herein, an alternative route is reported using an Cp*Al(I)/Zn(II)R2 (Cp* = C5Me5; R = aryl) system which facilitates the formation of a range of halide and donor free heteroleptic triorgano‐alanes of the general formula [Al(Cp*)R2]. Exposing the obtained alanes to an atmosphere of CO2 enables for the selective insertion of CO2 in their AlCp* moieties. State of the art quantum chemical calculations support experimental observations providing mechanistic insights on the observed reactivity of the [Al(Cp*)R2] compounds towards this unsaturated organic molecule.
Research on occupant injury severity prediction of autonomous vehicles based on transfer learning
Authors: Yang Na , Liu Dongwei , Liu Qi , Li Zhiwei , Liu Tao , Wang Jianfeng , Xu Ze
Published: August 2024

The focus of the future of autonomous vehicles has shifted from feasibility to safety and comfort. The seat of an autonomous vehicle may be equipped with a rotational function, and the occupant's sitting position would be diverse. This poses a higher challenge to occupant injury protection during vehicle collisions. The main objective of the current study is to develop occupant injury prediction models for autonomous vehicles that can be used to predict the injury severity of occupants in different seat orientations and sitting positions. The first step is to establish an occupant crash model database with different seat orientations. It is used to simulate the occupant crash injury database of an autonomous vehicle, considering seat rotation and the back inclination angle. The second step is to establish a pre‐training occupant injury prediction model based on the existing database and then train the autonomous vehicle occupant injury prediction model using an in‐house database based on the transfer learning method. Occupant injury prediction models achieve good accuracy (82.8% on the numerical database and 62.9% on the real verification database) and shorter computational time (4.86 ± 0.33 ms) on the prediction tasks. Finally, the influence of the model input variables is analyzed. This study demonstrates the feasibility of using a small‐sample database based on transfer learning for occupant injury prediction in autonomous vehicles.
Sesame‐enriched delights: A comparative exploration of physicochemical and sensory attributes in fine and whole wheat flour cookies
Authors: Naqvi Sittara Noori , Liaquat Muhammad , Kazmi Abeer , Sammi Shella , Ali Amir , Luna‐Arias Juan Pedro , Sherzad Izzat Ullah
Published: August 2024

Cookies are an exceptional energy source due to their elevated fat and carbohydrate content. Beyond their delectable taste, they are also rich in essential nutrients, including valuable proteins and minerals. This study evaluated the potential of the wheat variety NARC‐2011 for cookie production, focusing on nutritional enhancement by adding white sesame seeds at different proportions (5%, 10%, and 15%) to both whole and fine wheat flour. White sesame seeds were added to cookies mainly for their visual appeal, creating a nice contrast with the dough. They also have a mild flavor that complements the cookie without overwhelming it. Besides, they pack essential nutrients like protein, fiber, calcium, and iron, making the cookies more nutritious. The physical, chemical, and sensory properties of the different cookies were evaluated using standard methods. In terms of physical parameters, fine wheat flour cookies exhibited a diameter (46.45–50.47 mm), thickness (8.47–9.77 mm), and spreading factor (5.16–5.46 mm), and whole wheat flour cookies exhibited a diameter (48.47–52.31 mm), thickness (9.22–10.73 mm), and spreading factor (4.87–5.25 mm). Chemical analysis revealed moisture (5.78%–7.66%), fat (10.89%–16.16%), fiber (6.10%–8.46%), ash (4.82%–7.40%), protein (0.74%–1.40%), non‐fiber carbohydrates (63.67%–67.55%) for fine wheat flour cookies, and moisture (5.67%–7.39%), fat (10.89%–16.16%), fiber (11.47%–15.98%), ash (0.54%–0.83%), protein (5.65%–8.13%), non‐fiber carbohydrates (57.86%–66.55%), total phenolic content (2.86 mg/g), flavonoids (1.46 mg/g), and antioxidant activity (80.76%) in whole wheat flour cookies with sesame fortification. Gas chromatography revealed higher unsaturated fatty acids (83.22%) in NARC‐2011 wheat oil compared to white sesame seed oil (79.78%). In sensory evaluations, cookies fortified with 10% sesame seeds in fine wheat flour received the highest level of acceptability from the panelists. On the other hand, cookies made from whole wheat flour fortified with 15% sesame seeds garnered the maximum acceptability ratings from the panelists. In conclusion, supplementing NARC‐2011 wheat flour with sesame seeds, whether in fine or whole wheat form, improves the quality of cookies and nutritional content while offering appropriate sensory attributes at particular sesame seed levels.
Dietary advanced glycation end‐products (dAGEs) are not associated with the risk of cancer incidence. A systematic review and meta‐analysis of prospective cohort studies
Authors: Sharifi‐Zahabi Elham , Soltani Sepideh , Hajizadeh‐Sharafabad Fatemeh , Abdollahzad Hadi
Published: August 2024

A growing body of evidence indicates the association of dietary advanced glycation end‐products (dAGEs) with the risk of cancer. This systematic review and meta‐analysis aimed to assess the overall association between dAGEs and cancer incidence. An extensive search was carried out through online databases including PubMed, Scopus, and Web of Science up to June 2024. All reported HRs and their 95% CIs for risk of cancer were used to estimate log HRs and their standard errors (SEs). The overall risk estimate was obtained using a random effects model. Inter‐study heterogeneity was determined using Cochrane's Q test and I‐squared. Five prospective cohort studies with a total of 1,220,096 participants and 23,229 incident cancer cases (2193 pancreatic cancers, 11,443 breast cancers, 6162 colorectal cancers, and 3431 total cancers) were included in this meta‐analysis. Compared with the lowest category of dAGEs, the pooled hazard ratio (HR) for overall cancers was 1.04 (95% CI: 0.94, 1.15; I2 = 67.9%) for the highest category of dAGEs. Pooled estimates for different types of cancer showed no significant relationship between dAGEs and risk of breast cancer (HR: 1.119; 95% CI: 0.868, 1.444; I2 = 77.6%; N = 2 studies), pancreatic cancer (HR: 1.242; 95% CI: 0.971, 1.588; I2 = 0.0%; N = 2 studies), colon cancer (HR: 10.985; 95% CI: 0.887, 1.094; I2 = 0.0%; N = 2 studies) and rectal cancer (HR: 0.940; 95% CI: 0.616, 1.433; I2 = 57.7%; N = 2 studies). Dietary AGEs had no significant link with cancer risk. More well‐designed prospective studies are required.
Phenolic contents and antioxidant activities of Caucasian bee propolis at different locations, solvents, and temperatures
Authors: Bozkuş Tuğba Nigar
Published: August 2024

Propolis is a natural substance produced by honey bees by processing the secretions collected from various plants with their own enzymes. Caucasian honey bee is one of the productive bee races known in the world and its homeland in Türkiye is Northeastern Anatolia. This study is the first comprehensive research to determine, compare, and correlate the effects of various solvents and temperatures on 17 different Caucasian bee propolis obtained from different locations in terms of phenolic content and antioxidant activity. The highest total polyphenol and flavonoid contents (TPC and TFC) in Caucasian bee propolis extracts varied between 23.37–97.62 mg gallic acid per gram (GA/g) of propolis and 6.73–43.75 mg quercetin per gram (Q/g) of propolis in ethanolic extract at 60°C. While ferric reducing antioxidant power (FRAP) did not differ at both temperatures, the highest was determined in ethanolic extracts. Analyses of propolis samples according to locations did not show any significant differences in terms of TPC, TFC, and FRAP. By Pearson's correlation analysis, it was found that each of the extracts showed a positive correlation between TPC, TFC, and FRAP. As a result, it was revealed that the main difference in the phenolic content and antioxidant activities of propolis obtained from gene centers of Caucasian bee race was due to the polarity of the solvent used and temperature, and that there was no difference between locations within a single bee race. This pioneering study shows that Caucasian bee propolis has a high potential that can pave the way for different research in this field.
Investigation of monosodium glutamate content in flavors, seasonings, and sauces from local markets in Turkey
Authors: Katrancı Yusuf , Aydemir Aleyna , Kızılkaya Beray , Baştemur Gizem Yıldırım , Ozkorucuklu Sabriye Percin
Published: August 2024

Monosodium glutamate (MSG) is a flavor‐enhancing compound used to elevate the flavor profiles of various foods. This flavor enhancer is the sodium salt of L‐glutamic acid and is widely used in foods, such as flavorings, seasonings, sauces, and instant soups. The potential health effects of MSG consumption, particularly the health issues that excessive consumption could lead to, have been the focus of social concerns. It is stated that excessive consumption of MSG can cause cardiovascular diseases, obesity and diabetes, kidney damage, hypertension, anxiety, and memory impairment. The maximum permissible amount of MSG in foods is set at 10 g/kg according to the Turkish Food Codex. The aim of this study is to develop an appropriate method for analyzing the MSG content within the various food samples like flavorings, seasonings, and spices sold in Turkish local markets. The validation parameters of the developed method were examined and it was found that the developed method corresponds to the recommended values. The limit of detection and the limit of quantitation values were calculated as 4.78 ng/mL and 15.93 ng/mL, respectively. Recovery % was determined to be 100.96% in intra‐day and 132.22% in inter‐day analyses for the precision of the method. The results compared to the values specified in the Turkish Food Codex Food Additives Regulation and samples that purportedly did not contain MSG on their labels were found to contain MSG.
Endocannabinoids regulate enteric neuron–glia networks and visceral hypersensitivity following inflammation through a glial‐dependent mechanism
Authors: Morales‐Soto Wilmarie , Thomasi Beatriz , Gulbransen Brian D.
Published: August 2024

Acute gastrointestinal (GI) inflammation induces neuroplasticity that produces long‐lasting changes in gut motor function and pain. The endocannabinoid system is an attractive target to correct pain and dysmotility, but how inflammation changes endocannabinoid control over cellular communication in enteric neurocircuits is not understood. Enteric glia modulate gut neurons that control motility and pain and express monoacylglycerol lipase (MAGL) which controls endocannabinoid availability. We used a combination of in situ calcium imaging, chemogenetics, and selective drugs to study how endocannabinoid mechanisms affect glial responses and subsequent enteric neuron activity in health and following colitis in Wnt1Cre;GCaMP5g‐tdT;GFAP::hM3Dq mice. Trpv1Cre;GCaMP5gtdT mice were used to study nociceptor sensitivity and Sox10CreERT2;Mgllf/f mice were used to test the role of glial MAGL in visceral pain. The data show that endocannabinoid signaling regulates neuro‐glial signaling in gut neurocircuits in a sexually dimorphic manner. Inhibiting MAGL in healthy samples decreased glial responsiveness but this effect was lost in females following colitis and converted to an excitatory effect in males. Manipulating CB1 and CB2 receptors revealed further sex differences amongst neuro‐glia signaling that were impacted following inflammation. Inflammation increased gut nociceptor sensitivity in both sexes but only females exhibited visceral hypersensitivity in vivo. Blocking MAGL normalized nociceptor responses in vitro and deleting glial Mgll in vivo rescued visceral hypersensitivity in females. These results show that sex and inflammation impact endocannabinoid mechanisms that regulate intercellular enteric glia–neuron communication. Further, targeting glial MAGL could provide therapeutic benefits for visceral nociception in a sex‐dependent manner.
Mecapegfilgrastim for the prophylaxis of chemotherapy‐induced neutropenia in locally advanced nasopharyngeal carcinoma: A prospective phase II clinical study
Authors: Jin Qifeng , Hua Yonghong , Jin Ting , Wang Lei , Tao Changjuan , Huang Shuang , Qin Weifeng , Chen Xiaozhong
Published: August 2024

Background

Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen.

Methods

A total of 30 treatment‐naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24–48 h after the completion of induction chemotherapy with the TP regimen.

Results

The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%–22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%–17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles.

Conclusion

Mecapegfilgrastim effectively reduced the incidence of chemotherapy‐induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.
ANN‐driven insights into heat and mass transfer dynamics in chemical reactive fluids across variable‐thickness surfaces
Authors: Khan Mumtaz , Imran Mudassar
Published: August 2024

This study investigates the heat and mass transfer dynamics in exothermic, chemically reactive fluids over variable‐thickness surfaces using advanced numerical methods and artificial neural networks (ANN). The importance of understanding these processes lies in their significant industrial applications, such as in chemical reactors and heat exchangers. We transformed nonlinear partial differential equations into ordinary differential equations and used the bvp4c numerical method to generate a comprehensive data set. The ANN model, trained with the Levenberg–Marquardt algorithm, was evaluated for its accuracy in simulating complex fluid dynamics and thermosolutal transport phenomena. Our results revealed that increasing the second‐grade fluid parameter enhanced skin friction by 20.38%, heat transfer rate by 1.16%, and mass transfer rate by 4.06%. The ANN model demonstrated high predictive precision with a validation mean squared error of . These findings highlight the effectiveness of the ANN methodology in providing precise simulations of fluid dynamics, which is crucial for optimizing industrial processes.
Genomic alterations associated with resistance and circulating tumor DNA dynamics for early detection of progression on CDK4/6 inhibitor in advanced breast cancer
Authors: Kindt Charlotte K. , Alves Carla L. , Ehmsen Sidse , Kragh Amalie , Reinert Thomas , Vogsen Marianne , Kodahl Annette R. , Rønlev Jeanette D. , Ardik Dilan , Sørensen Anna L. , Evald Kirstine , Clemmensen Mia L. , Staaf Johan , Ditzel Henrik J.
Published: August 2024

Combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improves outcome for patients with estrogen receptor‐positive (ER+) metastatic breast cancer, but drug resistance and thus disease progression inevitably occur. Herein, we aimed to identify genomic alterations associated with combined CDK4/6i and endocrine therapy resistance, and follow the levels of specific mutations in longitudinal circulating tumor DNA (ctDNA) for early detection of progression. From a cohort of 86 patients with ER+ metastatic breast cancer we performed whole exome sequencing or targeted sequencing of paired tumor (N = 8) or blood samples (N = 5) obtained before initiation of combined CDK4/6i and endocrine therapy and at disease progression. Mutations in oncogenic genes at progression were rare, while amplifications of growth‐regulating genes were more frequent. The most frequently acquired alterations observed were PIK3CA and TP53 mutations and PDK1 amplification. Longitudinal ctDNA dynamics of mutant PIK3CA or private mutations revealed increased mutation levels at progression in 8 of 10 patients (80%). Impressively, rising levels of PIK3CA‐mutated ctDNA were detected 4–17 months before imaging. Our data add to the growing evidence supporting longitudinal ctDNA analysis for real‐time monitoring of CDK4/6i response and early detection of progression in advanced breast cancer. Further, our analysis suggests that amplification of growth‐related genes may contribute to combined CDK4/6i and endocrine therapy resistance.
S100a8/a9 regulated by LPS/TLR4 axis plays an important role in Salmonella‐based tumor therapy and host defense
Authors: Guo Yanxia , Sun Yujie , Li Zhongying , Zuo Chaohui , Liu Xiaoqing , Chen Yu , Xun Zhen , Liu Jinling , Mei Yang , Min Jung‐Joon , Wen Min , Zheng Jin Hai , Tan Wenzhi
Published: August 2024

Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor‐specific targeting, and deep‐tissue penetration. However, the specific molecular mechanisms of bacteria‐mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella‐mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF‐α, and IL‐1β, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella‐mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella‐mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.
Risk assessment of 2β,3β‐19α‐trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth
Authors: Oshiiwa Bruna , da Silva Aline Pereira , Alves Greice Rafaele , Filho Valdir Cechinel , Niero Rivaldo , O'Neill de Mascarenhas Gaivão Isabel , de Oliveira Liana Martins , de Lima Luan Vitor Alves , Mantovani Mário Sérgio , Maistro Edson Luis
Published: August 2024

Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β‐19α‐trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT‐qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M‐TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells.
A multiscale modeling to determine in vitro mechanical responses of different cells at the cell‐substrate interface under fluid perfusion
Authors: Gupta Abhisek , Barui Ananya , Banerjee Rupak K. , Das Apurba , Chowdhury Amit Roy
Published: August 2024

Investigating the influence of different cellular mechanical and physical properties on cells in vitro is important for assessing cellular activities like differentiation, proliferation, and migration. Evaluating the mechanical response of the cells lodged on a scaffold due to variations in substrate roughness, substrate elasticity, fluid flow, and the shapes of the cells is the main goal of the study. In this comprehensive analysis, a combination of the fluid structure interaction method and the submodeled finite element technique was employed to anticipate the mechanical responses across various cells at the interface between cells and the substrate. Fluid inlet velocity, substrate roughness, and substrate material were varied in this analysis. Different cell shapes were considered along with various components such as cell membrane, cytoplasm, nucleus, and cytoskeletons. This analysis shows the effect of these individual parameters on the elastic strain and strain energy density of cells at the cell‐substrate interface. The results highlight that substrate roughness has a more significant impact on the mechanical response of cells at the interface than substrate elasticity. However, effect of the substrate elasticity becomes crucial for extremely soft substrate materials. The results of this research can be applied to identify the optimal parameters for fluid flow and create a suitable condition for cell culture.
Regimen on Dnaja3 haploinsufficiency mediated sarcopenic obesity with imbalanced mitochondrial homeostasis and lipid metabolism
Authors: Fann Yu‐Ning , Teo Wan‐Huai , Lee Hsin‐Chen , Liao Chen‐Chung , Tsay Yeou‐Guang , Huang Tung‐Fu , Lo Jeng‐Fan
Published: August 2024

Background

Sarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co‐chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation. This study aims to elucidate the physiological effects of muscular Dnaja3 haploinsufficiency on mitochondrial dysfunction and dysregulated lipid metabolism and to assess the efficacy of GMI in rescuing sarcopenic obesity both in vitro and in vivo.

Methods

We generated mouse strain with Dnaja3 heterozygosity (HSA‐Dnaja3f/+) specifically in skeletal muscle. The body weight, body composition, and locomotor activity of WT and HSA‐Dnaja3f/+ mice were examined. The isolated skeletal muscles and primary myoblasts from the WT and HSA‐Dnaja3f/+ mice, at young or old age, were utilized to study the molecular mechanisms, mitochondrial respiration and ROS level, mitochondrial proteomes, and serological analyses, respectively. To evaluate the therapeutic efficacy of GMI, both short‐term and long‐term GMI treatment were administrated intraperitoneally to the HSA‐Dnaja3f/+ young (4 weeks old) or adult (3 months old) mice for a duration of either 1 or 6 months, respectively.

Results

Muscular Dnaja3 heterozygosity resulted in impaired locomotor activity (P < 0.05), reduced muscular cross‐sectional area (P < 0.0001), and up‐regulation of lipogenesis (ACC2) and pro‐inflammation (STAT3) in skeletal muscles (P < 0.05). Primary myoblasts from the HSA‐Dnaja3f/+ mice displayed impaired mitochondrial respiration (P < 0.01) and imbalanced mitochondrial ROS levels. A systemic proteomic analysis of the purified mitochondria from the primary myoblasts was conducted to show the abnormalities in mitochondrial function and fatty acid metabolism (P < 0.0001). At age of 13 to 14 months, the HSA‐Dnaja3f/+ mice displayed increased body fat mass (P < 0.001), reduced fat‐free mass (P < 0.01), and impaired glucose and insulin tolerance (P < 0.01). The short‐term GMI treatment improved locomotor activity (P < 0.01) and down‐regulated the protein levels of STAT3 (P < 0.05), ACC2, and mitochondrial respiratory complex III (UQCRC2) (P < 0.01) via DNAJA3 activation. The long‐term GMI treatment ameliorated fat mass accumulation, glucose intolerance, and systemic inflammation (AST) (P < 0.05) in skeletal muscle, while enhancing thermogenesis (UCP1) (P < 0.01) in eWAT. GMI treatment promoted myogenesis, enhanced oxygen consumption, and ameliorated STAT3 (P < 0.01) through DNAJA3 activation (P < 0.05) in vitro.

Conclusions

Muscular Dnaja3 haploinsufficiency dysregulates mitochondrial function and lipid metabolism then leads to sarcopenic obesity. GMI emerges as a therapeutic regimen for sarcopenic obesity treatment through DNAJA3 activation.
The effect of conjoint behavioral consultation on achieving communication skills in children with autism spectrum disorder
Authors: Aykut Pelin , Kahveci Gul
Published: August 2024

This study, uniquely designed with tact and mand‐modeling procedures presented through the Conjoint Behavioral Consultation (CBC) method, aims to evaluate the effects on the communication skills of preschool children with autism spectrum disorder (ASD) and the impact on disruptive behaviors (tantrums) at home. A pilot study with the families of three participants informed the adaptations for the main study, which was implemented with the families of nine participants. The research was conducted using an Embedded Mixed Methods Design, a distinctive approach that allowed for a comprehensive understanding of the outcomes. The primary research design was a single‐subject research model with multiple probes across participants' designs, ensuring a thorough and individualized assessment. The study was carried out in both home and clinical settings, involving the participation of special education teachers and families. The findings indicate that the tact and mand‐modeling procedures presented through the CBC method significantly improved the children's communication skills and led to substantial reductions in tantrum behaviors. All families indicated that the dependent variables held significant social importance. Significant enhancements were noted in the children's communication skills and social engagements after the intervention. The CBC intervention was determined to be feasible and feasible for families, with no additional expenses accrued. The long‐term suitability and usefulness of the product in many environments increased its societal acceptance. This study revealed that the CBC approach had a favorable and reliable effect on academic and behavioral advancement.
State‐of‐the‐Art Quantification of Liver Iron With MRI—Vendor Implementation and Available Tools
Authors: Tipirneni‐Sajja Aaryani , Shrestha Utsav , Esparza Juan , Morin Cara E. , Kannengiesser Stephan , Roberts Nathan T. , Peeters Johannes M. , Sharma Samir D. , Hu Houchun H.
Published: August 2024

The role of MRI to estimate liver iron concentration (LIC) for identifying patients with iron overload and guiding the titration of chelation therapy is increasingly established for routine clinical practice. However, the existence of multiple MRI‐based LIC quantification techniques limits standardization and widespread clinical adoption. In this article, we review the existing and widely accepted MRI‐based LIC estimation methods at 1.5 T and 3 T: signal intensity ratio (SIR) and relaxometry (R2 and R2*) and discuss the basic principles, acquisition and analysis protocols, and MRI‐LIC calibrations for each technique. Further, we provide an up‐to‐date information on MRI vendor implementations and available offline commercial and free software for each MRI‐based LIC quantification approach. We also briefly review the emerging and advanced MRI techniques for LIC estimation and their current limitations for clinical use. Lastly, we discuss the implications of MRI‐based LIC measurements on clinical use and decision‐making in the management of patients with iron overload. Some of the key highlights from this review are as follows: 1) Both R2 and R2* can estimate accurate and reproducible LIC, when validated acquisition parameters and analysis protocols are applied, 2) Although the Ferriscan R2 method has been widely used, recent consensus and guidelines endorse R2*‐MRI as the most accurate and reproducible method for LIC estimation, 3) Ongoing efforts aim to establish R2*‐MRI as the standard approach for quantifying LIC, and 4) Emerging R2*‐MRI techniques employ radial sampling strategies and offer improved motion compensation and broader dynamic range for LIC estimation.

Evidence Level

1

Technical Efficacy

Stage 2
Deciphering the spatial fingerprint of drought propagation through precipitation, vegetation and groundwater
Authors: Bilal Syed Bakhtawar , Gupta Vivek
Published: August 2024

Droughts, depending on their nature, have had devastating consequences, including crop destruction, famine and millions of deaths, particularly in countries like India that heavily rely on rainfall for agriculture. The present study aims to quantify the linkage between meteorological, agricultural and hydrological drought at a high spatial resolution across India. These connections were established by developing various drought propagation metrics followed by subsequent correlation analysis, lag analysis and clustering. Standard Precipitation Index (SPI), Deviation in NDVI (Dev‐NDVI) and GRACE Drought Severity Index (GRACE‐DSI) were used to represent meteorological, agricultural and hydrological droughts. Run theory with thresholds of −1, −0.5 and −0.05 were used to delineate the drought events for meteorological, hydrological and agricultural droughts, respectively. Furthermore, multivariate K‐means clustering based on factors such as drought duration, latitude, longitude, severity, propagation and recovery speeds was done to create spatial clusters having similar drought characteristics. Correlation analysis showed the highest average correlations at a lag of around 7–8 months between meteorological and hydrological drought, a lag of 1–2 months in case of meteorological and agricultural drought and a lag of 3–4 months between agricultural and hydrological drought. The analysis of drought duration indicated that, on average, meteorological drought in India lasted for 2.34 months, while agricultural drought lasted for 3 months, reflecting a 26.5% increase, whereas hydrological drought lasted for 5.22 months, indicating a notable 123% increase. This increase in average drought duration as it propagates from meteorological to agricultural to hydrological drought can be attributed to the lengthening property of drought propagation. Clustering analysis reveals presence of five homogeneous drought clusters. Additionally, cluster analysis reveals that for meteorological and agricultural droughts arid regions showed the highest severity whereas for hydrological droughts north Indian states including Punjab and Haryana showed the highest severity.