bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumers’ prosocial engagement in CSR: why should they care and what does it mean to them?
Authors: Song Baobao
Published: August 2021

Purpose

Public relations practitioners worldwide are attempting to enhance the overall organization–stakeholder relationships by applying strategic communication techniques and skills to corporate social responsibility (CSR) management and communications. In this light, drawing on the prosocial motivation literature, this paper aims to investigate consumers’ implicit and explicit motivations for prosocial behavior, and how these two motivations interact to affect consumers’ willingness to contribute to CSR activities. Second, through the lens of sensemaking theory, this study evaluates the influence of successful prosocial behavior engagement on consumers’ perceptions of both self and companies’ prosocial identities, CSR authenticity and company evaluations.

Design/methodology/approach

This study adopts a dictator game experiment with 2 × 2 factorial design to gauge consumers’ prosocial behavioral response toward companies’ CSR communication with implicit and explicit motivations and to examine its effect on company evaluation.

Findings

In all, the results of this study suggest that implicit motivation, i.e. self-affirmation intervention, in CSR communication will cause consumers to donate more money to CSR programs; whereas explicit motivation does not exert an effect on consumers’ prosocial behavior. In addition, such donation will trigger consumers’ prosocial sensemaking process and lead to strong identification with the company, positive attitudes and behavioral intentions toward the company.

Originality/value

This study aims to build a consumer- and social cause-oriented CSR communication model, which maximizes the impact of CSR investments on consumer relationship building, business bottom line and social causes.
Learning across teams in project-oriented organisations: the role of programme management
Authors: de Groot Bert , Leendertse Wim , Arts Jos
Published: August 2021

Purpose

Learning across teams and organisational levels enables organisations to deal with challenges that arise from changing contexts. Project-oriented organisations increasingly use programme management to cope with such challenges and improve performance. This paper aims to find out how different programme configurations affect learning across project teams and between project teams and their parent organisation in project-oriented organisations.

Design/methodology/approach

A case study of a project-oriented organisation involved in five infrastructure programmes was performed.

Findings

The studied programmes linked learning processes at group and organisational levels by creating relationships across project teams and their parent organisation and acting as a knowledge centre. Team learning benefits from the learning culture and stable environment that programmes create for project teams. This study indicates that a programme’s features and focus strongly determines whether a programme predominantly enhances learning across project teams or learning between project teams and their parent organisation.

Originality/value

Although programme management is increasingly used by project-oriented organisations, there are few studies relating to learning in programmes. This study provides new insights into learning across teams through programmes.
Tourists’ interpretations toward tourism destinations: viewpoint to apply locus of control theory
Authors: Saleh Mahmoud Ibraheam
Published: August 2021

Purpose

Studying tourist behavior provides the privilege of diverging in the competition between destinations to attract tourists. Previous studies have explored the effects of tourist behavior on brand satisfaction, attachment and loyalty. However, there is a lack of studies that investigated the intuition behind shaping tourist behavior. To address this issue, this study aims to contribute to providing a viewpoint to apply locus of control (LOC) theory in the tourism context. LOC studies how individuals believe in controlling their feelings and judgment toward events.
Microhabitat temperature variation combines with physiological variation to enhance thermal resilience of the intertidal musselMytilisepta virgata
Authors: Li Xiao‐xu , Tan Yue , Sun Yong‐xu , Wang Jie , Dong Yun‐wei
Published: August 2021

Predicting the effects of rising temperature entails measuring both habitat thermal characteristics and the physiological variation of the species as it relates to this microhabitat variation; these two types of measurements can generate what is termed a ‘physiological landscape’ for the species. Mapping the micro‐scale physiological landscape across space and time, rather than relying on large‐scale averages of temperature and means of thermal limits in a species, can allow more accurate estimates of an organism's sensitivity to temperature change and support development of more refined models of the impacts of anthropogenic climate change that have higher predictive power.

We thus continually monitored the body (operative) temperature of the intertidal musselMytilisepta virgatain both sun‐exposed and shaded microhabitats and determined the seasonal variations of cardiac performance of field‐acclimatized and laboratory‐acclimated mussels from different microhabitats for calculating the thermal sensitivity, as indicated by the difference between the maximum ambient temperature and an individual's upper thermal limit (thermal safety margin, TSM), in each microhabitat and each month.

The mussels experienced divergent thermal stress, in average temperature, acute and chronic thermal stress and thermal predictivity among different microhabitats, and presented high spatial–temporal variations of cardiac function as results of seasonal acclimatization and inter‐individual variations. Results of TSMs indicated that the thermal sensitivities of the mussels to high temperature were season‐ and microhabitat specific, and the mussels in the shaded microhabitats were predicted to survive the hottest summer temperatures; however, some individuals in the sun‐exposed microhabitats experienced temperatures above their sublethal temperature.

With the large, high‐resolution dataset of thermal environmental characteristics and the cardiac performances with high variations, we were able to integrate the effects of synchronized changes in microenvironmental temperatures and cardiac thermal responses and thereby characterize the physiological landscape of thermal sensitivity. The complex physiological landscape that exists in the intertidal zone must be taken into account when predicting the effects of changes in environmental temperature, such as those occurring with global climate change.

A freePlain Language Summarycan be found within the Supporting Information of this article.
Divergent responses of symbiotic and asymbiotic N2 fixation to seawater additions
Authors: Sun Xibin , Li Dejun , Chen Hao , Ma Zilong , Xiao Kongcao , Yan Junhua , Wang Zhenchuan , Duan Pengpeng
Published: August 2021

Sea level rise‐associated seawater intrusion exerts substantial impacts on the structure and function of coastal ecosystems. As nitrogen (N) availability is closely related to the structure and function of ecosystems, it is crucial to understand how seawater intrusion impacts biological N2 fixation, a major pathway of new N input to natural ecosystems.

Here, a seawater addition experiment with two N2‐fixing plant species (Acacia auriculiformis and Casuarina equisetifolia) and 10 non‐N2‐fixing plant species was conducted to simulate sea level rise‐associated seawater intrusion. The experiment included control (0 mm seawater/year), low seawater addition (LSW, 200 mm seawater/year) and high seawater addition (HSW, 400 mm seawater/year).

Symbiotic N2 fixation (SNF) rate of A. auriculiformis was significantly higher under LSW (but not for HSW) than the control. For C. equisetifolia, SNF rates under LSW and HSW significantly increased by 8.0 and 19.5 times, respectively, compared with the control. In contrast, asymbiotic N2 fixation rates under LSW and HSW significantly decreased by 18.5% and 30.4%, respectively, across all the plant species.

Our findings suggest that the responses of biological N2 fixation to seawater intrusion are divergent either among different N2‐fixing plant species or between symbiotic and asymbiotic forms, which should be considered in terrestrial ecosystem models in order to improve the prediction of N dynamics under climate changes.

A free Plain Language Summary can be found within the Supporting Information of this article.
Curcumin‐coated gold nanoparticles attenuate doxorubicin‐induced cardiotoxicity via regulating apoptosis in a mouse model
Authors: Sharifiaghdam Zeynab , Dalouchi Fereshteh , Sharifiaghdam Maryam , Shaabani Elnaz , Ramezani Fatemeh , Nikbakht Farnaz , Azizi Yaser
Published: August 2021

Doxorubicin (DOX) is one of the most widely used chemotherapy agents; however, its nonselective effect causes cardiotoxicity. Curcumin (Cur), a well known dietary polyphenol, could exert a significant cardioprotective effect, but the biological application of this substance is limited by its chemical insolubility. To overcome this limitation, in this study, we synthesised gold nanoparticles based on Cur (Cur‐AuNPs). Ultraviolet‐visible (UV‐Vis) absorbance spectroscopy and transmission electron microscopy (TEM) were performed for the characterisation of synthesised NPs, and Fourier transform infrared (FTIR) spectroscopy were applied to detect Cur on the surface of AuNPs. Its cytotoxicity effect on H9c2 cells was evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The biological efficacy of Cur‐AuNPs was assessed after acute cardiotoxicity induction in BALB/c mice with DOX injection. The serum biomarkers, myocardial histological changes, and cardiomyocyte apoptosis were then measured. The results revealed that the heart protection by Cur‐AuNPs is more effective than Cur alone. Heart protective effect of Cur‐AuNPs was evident both in the short‐term (24 hours) and long‐term (14 days) study. The results of Cur‐AuNPs400 after 24 hours of toxicity induction displayed the reduction of the cardiac injury serum biomarkers (LDH, CK‐MB, cTnI, ADT, and ALT) and apoptotic proteins (Bax and Caspase‐3), as well as increase of Bcl‐2 anti‐apoptotic proteins without any sign of interfibrillar haemorrhage and intercellular spaces in the heart tissue microscopic images. Our long‐term study signifies that Cur‐AuNPs400 in DOX‐intoxicated mice could successfully inhibit body and heart weight loss in comparison to DOX group.
Elevated police turnover following the summer of George Floyd protests: A synthetic control study
Authors: Mourtgos Scott M. , Adams Ian T. , Nix Justin
Published: August 2021

Research summary

Several of the largest U.S. police departments reported a sharp increase in officer resignations following massive public protests directed at policing in the summer of 2020. Yet, to date, no study has rigorously assessed the impact of the George Floyd protests on police resignations. We fill this void using 60 months of employment data from a large police department in the western United States. Bayesian structural time‐series modeling shows that voluntary resignations increased by 279% relative to the synthetic control, and the model predicts that resignations will continue at an elevated level. However, retirements and involuntary separations were not significantly affected during the study period.

Policy implications

A retention crisis may diminish police departments’ operational capacity to carry out their expected responsibilities. Criminal justice stakeholders must be prepared to confront workforce decline and increased voluntary turnover. Proactive efforts to improve organizational justice for sworn personnel can moderate officer perceptions of public hostility.
Altered sperm tsRNAs in aged male contribute to anxiety‐like behavior in offspring
Authors: Guo Yi , Bai Dandan , Liu Wenqiang , Liu Yingdong , Zhang Yalin , Kou Xiaochen , Chen Jiayu , Wang Hong , Teng Xiaoming , Zuo Ji , Gao Shaorong
Published: August 2021

Parental age at first pregnancy is increasing worldwide. The offspring of aged father has been associated with higher risk of several neuropsychiatric disorders, such as schizophrenia and autism, but the underlying mechanism remains elusive. Here we report that advanced paternal age in mice alters the profile of transfer RNA‐derived small RNAs (tsRNAs). Injection of sperm tsRNAs from aged male mice into zygotes induced anxiety‐like behaviors in F1 males. RNA sequencing of the cerebral cortex and hippocampus of those F1 male mice altered the gene expression of dopaminergic synapse and neurotrophin. tsRNAs from aged male mice injection also altered the neuropsychiatry‐related gene expression in two‐cell and blastocyst stage embryos. More importantly, the sperm tsRNA profile changes significantly during aging in human. The up‐regulated sperm tsRNA target genes were involved in neurogenesis and nervous system development. These results suggest that aging‐related changes of sperm tsRNA may contribute to the intergenerational transmission of behavioral traits.
Comparative morphometric study of the mimic facial muscles of brachycephalic and dolichocephalic dogs
Authors: Schatz Katharina Zoë , Engelke Elisabeth , Pfarrer Christiane
Published: August 2021

Excessive breeding of dogs has led to a disadvantageous morphology in some breeds, for example extreme brachycephaly, which is responsible for many health issues. We hypothesize that alterations of the mimic muscular system are present in brachycephalic dogs and could contribute to behavioural problems due to a restricted mimic display. Therefore, the purpose of this paper was to compare the mimic muscular systems of brachycephalic with dolichocephalic dogs. Mimic muscles were measured and set in ratio to measurements of the head and calculated indices. When bringing the length of the muscles m(x) in proportion to the length of the head, highly significant differences (p < .0001) and significant difference (p < .05) were found in all but two of the examined muscles. Calculations of the m(x) divided by the cranial index and the square index showed significant differences for all muscles. For example, the musculus (m.) levator nasolabialis was morphologically different from the one of dolichocephalic dogs. Muscle fibres of the m. levator nasolabialis were localized in the fold over the nasal bridge of brachycephalic dogs. The raphe of the m. orbicularis oris was not always apparent in brachycephalic dogs. The proportions of the muscle lengths and the length of the eye slots to the size of the skull have shifted considerably in brachycephalic dogs. We conclude that many alterations contribute to the strong shift in the proportions of the head of brachycephalic dogs versus that of dolichocephalic dogs. Our findings suggest that brachycephalic dogs have reduced mimic skills that can lead to ambiguous communication.
Histomorphological, ultrastructural and morphometrical age‐related changes of fundic region of New Zealand rabbits (Oryctolagus cuniculus)
Authors: Nabil Taghreed Mohamed , Moawad Usama Kamal
Published: August 2021

This study investigated the histomorphological, ultrastructural and morphometrical postnatal developmental changes in the rabbit fundic region, especially during changing of the feeding intake. Seventy‐two New Zealand rabbits (V‐Line breed) at the ages of 1, 7, 15, 23, 30 and 60 days were obtained for light and electron microscopy and morphometric studies of the fundic region. The newborn rabbit's fundic wall was thin and organized into mucosa, submucosa, musclosa and serosa, with a significant increase in thickness with ageing. The fundic glands were few at the first week of life, then increased in length and diameter compared to the preceding age with prominent zonation at 23 days. The gastric pits appeared wide and deep at the first week of life then became typically narrow and shallow at the third week. The mucous cells were the main cell types lining the fundic glands in the first week of life. These cells showed remoulding with a marked increase in Periodic Acid–Schiff reactivity with age. Parietal cells were differentiated earlier (on the first day of life) than the chief cells and distributed at the neck and basal zones. Chief cells differentiated at 15 days old at the base of the glands, followed by an increase in the number and activity. Few active enteroendocrine cells were first seen at 15 days old and then widely distributed throughout the glands. Conclusion: Pronounced histomorphological changes in the fundic mucosal layer, especially the surface and glandular epithelium, correlate with the postnatal rabbit‐feeding intake changes.
Mesh fixation with fibrin glue versus tacker in laparoscopic totally extraperitoneal inguinal hernia repair
Authors: Nizam Saifullah , Saxena Neeraj , Yelamanchi Raghav , Sana Sana , Kardam Dinesh
Published: August 2021

Background

The advent of mesh was a breakthrough in the field of hernia surgery. Mechanical methods of mesh fixation are hypothesized to cause more tissue trauma than nonmechanical methods. The present study was conducted to study the outcomes of mesh fixation using fibrin glue, a nonmechanical method versus tackers in totally extraperitoneal repair (TEP) of unilateral inguinal hernia.

Methods

A randomized controlled single blinded study was conducted in India from June 2017 to March 2019. Patients diagnosed with unilateral uncomplicated inguinal hernia with a hernial sac of size not more than 5 cm were invited to participate in the study. Sample size was 60 patients randomized into groups just before mesh fixation. In group A mesh was fixed using tackers while in group B mesh was fixed using fibrin glue. Patients were followed‐up prospectively for 3 months.

Results

There was no statistical difference between the two groups with respect to operating time. Average hospital stay and pain scores at all follow‐ups were better for fibrin glue group. There was no difference in the incidence of postoperative urinary retention, seroma formation and hematoma formation between the two groups. Patients of fibrin glue group had early restart of daily activities at 15 days follow‐up when compared to tacker group.

Conclusion

Fibrin glue fixation technique should be advocated over tackers for mesh fixation in TEP considering the better outcomes and cost‐effectiveness of the technique.
Clinical utiliy of a model‐based piperacillin dose in neonates with early‐onset sepsis
Authors: Wu Yue‐E , Hou Shan‐Shan , Fang Zeng‐Yu , Tang Bo‐Hao , Yao Bu‐Fan , Dong Yi‐Ning , Li Xue , Shi Hai‐Yan , Zheng Yi , Hao Guo‐Xiang , Huang Xin , Van Den Anker John , Yu Yong‐Hui , Zhao Wei
Published: August 2021

Aims

Early‐onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model‐based dosing regimen of piperacillin/tazobactam in EOS patients.

Methods

A prospective, single‐centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg−1, q8h) was determined based on a previous piperacillin PPK model in young infants using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT > MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected.

Results

A total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14–41.29) weeks. Forty‐seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2–305.8) hours and 31 (30, 5–123) days. There were no obvious adverse events and no infection‐related deaths occurred in the first month of life.

Conclusions

A model‐based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.
Dosing regimen optimisation for oseltamivir in immunocompromised paediatric patients with influenza: Extrapolation of efficacy
Authors: Jordie Eric Burroughs , Gibiansky Leonid , Knab Timothy , Lemenuel‐Diot Annabelle , Ravva Patanjali , Zwanziger Elke , Jolivet Sebastien , Bhardwaj Rajinder , Hernández‐Sánchez Jules , Nasmyth‐Miller Clare , Sturm Stefan
Published: August 2021

Aims

To optimise the dosing regimen of oseltamivir for immunocompromised (IC) paediatric patients (<18 years) with influenza, we used an extrapolation approach alongside clinical data.

Methods

Efficacy was extrapolated from adult IC patients to paediatric IC patients by leveraging existing efficacy, safety, pharmacokinetic (PK)/pharmacodynamic (PD), and disease‐progression models of oseltamivir and oseltamivir carboxylate (OC). Data of IC paediatric patients from two studies (NV25719 and NV20234) were included in the population PK (n = 30), PK/PD analysis (n = 22) and disease modelling approach (n = 36). Simulations were performed to identify the optimal dosing regimen.

Results

Clearance of oseltamivir (CL) and OC (CLM) were similar in IC and otherwise‐healthy (OwH) patients <10 years, but decreased by 44.4% (95% CI: 26.8–62.0) and 49.1% (95% CI: 34.5–63.8), respectively, in IC patients aged 10–17 years versus OwH patients. There were no notable exposure–response relationships for any of the virologic PD analyses. Thus, no additional benefit was seen with oseltamivir carboxylate exposures higher than achieved with the conventional dose (75 mg twice daily, age‐ and weight‐adjusted for children <13 years). The disease model illustrated that doses above the conventional oseltamivir dose had limited impact on viral kinetics in IC paediatric patients and a prolonged treatment duration of 10 days was favoured to limit potential viral rebound.

Conclusion

An oseltamivir dosage recommendation (conventional dose, twice daily for 10 days) was established in IC paediatric patients with influenza, based on extrapolation of efficacy from IC adults, leveraging population PK, PK/PD, and disease modelling, whilst taking resistance and safety data into account.
Trough polymyxin B plasma concentration is an independent risk factor for its nephrotoxicity
Authors: Han Lu , Xu Fang‐Min , Zhang Xiao‐Shan , Zhang Chun‐Hong , Dai Ying , Zhou Zi‐Ye , Wang Ye‐Xuan , Chen Fan , Shi Da‐Wei , Lin Guan‐Yang , Yu Xu‐Ben
Published: August 2021

Aims

Data regarding clinical pharmacokinetic/toxicodynamic (PK/TD) of polymyxin B is short of direct quantitative data. This study aims to investigate the risk factors of polymyxin B associated acute kidney injury (AKI) and to assess the relationship between polymyxin B plasma levels and its nephrotoxicity.

Methods

A retrospective study was performed in adult patients treated with polymyxin B. Risk factors associated with AKI and plasma trough concentrations of polymyxin B were identified via medical record review. A multivariate logistic regression model was established and the risk of polymyxin B‐associated AKI were predicted by a receiver operating characteristic curve, with maximal Youden index used to identify safety thresholds among the study population.

Results

Fifty‐four adult patients were included in the study. AKI was detected in 14 patients during polymyxin B treatment (25.9%, 14 out of 54). Cmin (odds ratio [OR] 2.071; 95% confidence interval [CI] 1.235–3.472) and baseline serum creatinine (OR 1.024; 95% CI 1.005–1.043) were significant independent risk factors for developing AKI. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was at maximum, the optimal cut‐off point was 6.678 of the ROC curve. When Cmin ≥ 3.13 mg/L, the probability of AKI was more than 50%.

Conclusion

In this study, when the calculated combined predictor value was >6.678, there was an increased risk of AKI. Maintaining a polymyxin B Cmin level below 3.13 mg/L may be helpful in reducing the incidence of polymyxin B associated nephrotoxicity.
Advances in treatment of elderly primary central nervous system lymphoma
Authors: Martinez‐Calle Nicolas , Isbell Lisa K. , Cwynarski Kate , Schorb Elisabeth
Published: August 2021

The management of older individuals (≥60 years) with primary central nervous system lymphoma remains a clinical challenge. Identification of optimal therapy and delivering adequate dose intensity are two of the major issues in treating elderly patients. Premorbid performance status and comorbidities influence individualised treatment approaches and geriatric assessment tools are increasingly utilised. Optimal induction treatment remains high‐dose methotrexate‐based immunochemotherapy, delivery is feasible in the majority of patients and the goal of treatment remains achieving complete remission. Consolidation strategies are also relevant in the elderly, aiming to maximise duration of response and quality of life (QoL). Potential options include high‐dose therapy with haematopoietic stem cell consolidation, non‐myeloablative chemotherapy and whole‐brain radiotherapy. Efficacy of novel agents, such as Bruton tyrosine kinase inhibitors and lenalidomide, have been reported; these represent an alternative for elderly patients unfit for chemotherapy. Prognosis remains poor, improvement of outcomes in this age group is urgently needed.
Holocene evolution of a proglacial lake in southern Kamchatka, Russian Far East
Authors: Nazarova Larisa , Sachse Dirk , Fuchs Harald G. E. , Dirksen Veronika , Dirksen Oleg , Syrykh Liudmila , Razjigaeva Nadezhda G. , Rach Oliver , Diekmann Bernhard
Published: August 2021

The Kamchatka Peninsula (Russian Far East) remains among the least studied regions of eastern Asia. Recent studies revealed a high degree of palaeoenvironmental variability between different parts of the peninsula. We investigated semi‐aquatic (chironomids) and terrestrial (leaf wax biomarkers) proxies from a sediment core collected from Lake Sokoch (southern Kamchatka) to provide reconstruction of the mean July air temperature and variations in limnic conditions. The lake formed after 10.0 cal. ka BP as a result of postglacial warming and was fed by glacial meltwaters from neighbouring glaciers. Our data show a later beginning of the Holocene thermal maximum (HTM) relative to more northern sites in Kamchatka, Siberia and Chukotka and support climate model experiments that suggest that the HTM was delayed in southern and central Kamchatka by about 2000 years compared with Alaska and NE Siberia. Warm conditions prevailed between 10.0 and 6.4 cal. ka BP with a short spell of cool and dry climate around 8.2 cal. ka BP that might be related to the 8.2 ka cooling event. The HTM took place between 6.5 and 3.4 cal. ka BP with the warmest phase from 6.0 to 5.0 cal. ka BP. An onset of Neoglacial cooling at 3.4 cal. ka BP is consistent with the strengthening of both the Siberian High and the Aleutian Low. Warming between 1.2 and 0.9 cal. ka BP can be attributed to the Mediaeval Climate Anomaly. The LIA cooling is related to another strengthening of the Siberian High and the Aleutian Low. The modern warming, though weakly traced in our record, is consistent with the recent meteorological observations. The presented palaeoenvironment record confirms the earlier findings of spatial differences within Kamchatka in timing and magnitude of the major Holocene climate fluctuations and contributes towards understanding the expression of Holocene climate change in Kamchatka.
DOC‐2/DAB2 interactive protein destabilizes c‐Myc to impair the growth and self‐renewal of colon tumor‐repopulating cells
Authors: Li Haiou , Zhou Yunjiao , Wang Meng , Wang Haizhou , Zhang Yangyang , Peng Ruyi , Zhang Ruike , Zhang Meng , Zhang Mengna , Qiu Peishan , Liu Lan , Zhao Qiu , Liu Jing
Published: August 2021

Colorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell‐like colon tumor‐repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c‐Myc is essential for maintaining cancer stem‐like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c‐Myc protein supported formation and growth of TRC spheroids. The tumor suppressor DOC‐2/DAB2 interactive protein (DAB2IP) suppressed c‐Myc expression to inhibit TRC expansion and self‐renewal. Particularly, DAB2IP disrupted c‐Myc stability through glycogen synthase kinase 3β/protein phosphatase 2A‐B56α‐mediated phosphorylation and dephosphorylation cascade on c‐Myc protein, leading to its eventual degradation through the ubiquitin‐proteasome pathway. The expression of DAB2IP was negatively correlated with c‐Myc in CRC specimens. Overall, our results improved mechanistic insight into how DAB2IP suppressed TRC growth and self‐renewal.
The EZH2 inhibitor tazemetostat upregulates the expression of CCL17/TARC in B‐cell lymphoma and enhances T‐cell recruitment
Authors: Yuan Hepei , Nishikori Momoko , Otsuka Yasuyuki , Arima Hiroshi , Kitawaki Toshio , Takaori‐Kondo Akifumi
Published: August 2021

An inhibitor of the histone methyltransferase enhancer of zeste homologue 2 (EZH2), tazemetostat, has been developed for the treatment of B‐cell lymphoma, but its mechanisms of action are not fully elucidated. We screened for genes targeted by tazemetostat in eleven B‐cell lymphoma cell lines and found that tazemetostat significantly increased the expression of chemokine (C‐C motif) ligand 17 (CCL17)/thymus‐ and activation‐regulated chemokine (TARC) in all, which codes for a chemokine that is a hallmark of Hodgkin/Reed‐Sternberg (H/RS) cells in Hodgkin lymphoma. Notably, gene set enrichment analysis demonstrated a positive correlation between the genes upregulated by tazemetostat in five follicular lymphoma (FL) cell lines and those reported to be overexpressed in H/RS cells. The CCL17 promoter region was enriched in repressive histone modification H3K27me3, and tazemetostat induced H3K27 demethylation and activated gene transcription. CCL17 protein secretion was also induced by EZH2 inhibition, which was further enhanced by concurrent CpG stimulation. In vitro transwell migration assay demonstrated that CCL17 produced by tazemetostat‐treated B cells enhanced the recruitment of T cells, which had the potential to exert antilymphoma response. Analysis of publicly available human lymphoma databases showed that CCL17 gene expression was inversely correlated with the EZH2 activation signature and significantly paralleled the CD4+ and CD8+ T‐cell–rich signature in FL and germinal center B‐cell–like diffuse large B‐cell lymphoma. Our findings indicate that tazemetostat can potentially activate antilymphoma response by upregulating CCL17 expression in B‐cell lymphoma cells and promote T‐cell recruitment, which provides a rationale for its combination with immunotherapy.
Trajectories of perinatal depressive symptoms in the context of the COVID‐19 pandemic
Authors: Gustafsson Hanna C. , Young Anna S. , Doyle Olivia , Nagel Bonnie J. , Mackiewicz Seghete Kristen , Nigg Joel T. , Sullivan Elinor L. , Graham Alice M.
Published: August 2021

This study sought to advance understanding of the potential long‐term consequences of the COVID‐19 pandemic for child development by characterizing trajectories of maternal perinatal depression, a common and significant risk factor for adverse child outcomes. Data came from 393 women (86% White, 8% Latina; mean age = 33.51 years) recruited during pregnancy (n = 247; mean gestational age = 22.94 weeks) or during the first year postpartum (n = 146; mean child age = 4.50 months; 55% female). Rates of depression appear elevated, relative to published reports and to a pre‐pandemic comparison group (N = 155). This study also provides evidence for subgroups of individuals who differ in their depressive symptom trajectories over the perinatal period. Subgroup membership was related to differences in maternal social support, but not to child birth outcomes.
Early life stress and behavior problems in early childhood: Investigating the contributions of child temperament and executive functions to resilience
Authors: de Maat Donna A. , Schuurmans Isabel K. , Jongerling Joran , Metcalf Stephen A. , Lucassen Nicole , Franken Ingmar H. A. , Prinzie Peter , Jansen Pauline W.
Published: August 2021

This preregistered study examined whether child temperament and executive functions moderated the longitudinal association between early life stress (ELS) and behavior problems. In a Dutch population‐based cohort (n = 2803), parents reported on multiple stressors (age 0–6 years), child temperament (age 5), and executive functions (age 4), and teachers rated child internalizing and externalizing problems (age 7). Results showed that greater ELS was related to higher levels of internalizing and externalizing problems, with betas reflecting small effects. Lower surgency buffered the positive association of ELS with externalizing problems, while better shifting capacities weakened the positive association between ELS and internalizing problems. Other child characteristics did not act as moderators. Findings underscore the importance of examining multiple protective factors simultaneously.
The cross‐talk between RAGE and DIAPH1 in neurological complications of diabetes: A review
Authors: Zglejc‐Waszak Kamila , Mukherjee Konark , Juranek Judyta Karolina
Published: August 2021

Neuropathy, or dysfunction of peripheral nerve, is one of the most common neurological manifestation in patients with diabetes mellitus (DM). DM is typically associated with a hyperglycaemic milieu, which promotes non‐enzymatic glycation of proteins. Proteins with advanced glycation are known to engage a cell‐surface receptor called the receptor for advanced glycation end products (RAGE). Thus, it is reasonable to assume that RAGE and its associated molecule‐mediated cellular signalling may contribute to DM‐induced symmetrical axonal (length‐dependent) neuropathy. Of particular interest is diaphanous related formin 1 (DIAPH1), a cytoskeletal organizing molecule, which interacts with the cytosolic domain of RAGE and whose dysfunction may precipitate axonopathy/neuropathy. Indeed, it has been demonstrated that both RAGE and DIAPH1 are expressed in the motor and sensory fibres of nerve harvested from DM animal models. Although the detailed molecular role of RAGE and DIAPH1 in diabetic neurological complications remains unclear, here we will discuss available evidence of their involvement in peripheral diabetic neuropathy. Specifically, we will discuss how a hyperglycaemic environment is not only likely to elevate advanced glycation end products (ligands of RAGE) and induce a pro‐inflammatory environment but also alter signalling via RAGE and DIAPH1. Further, hyperglycaemia may regulate epigenetic mechanisms that interacts with RAGE signalling. We suggest the cumulative effect of hyperglycaemia on RAGE–DIAPH1‐mediated signalling may be disruptive to axonal cytoskeletal organization and transport and is therefore likely to play a key role in pathogenesis of diabetic symmetrical axonal neuropathy.
Primary cilia in retinal pigment epithelium development and diseases
Authors: Sun Chunjiao , Zhou Jun , Meng Xiaoqian
Published: August 2021

Retinal pigment epithelium (RPE) is a highly polarized epithelial monolayer lying between the photoreceptor layer and the Bruch membrane. It is essential for vision through participating in many critical activities, including phagocytosis of photoreceptor outer segments, recycling the visual cycle‐related compounds, forming a barrier to control the transport of nutrients, ions, and water, and the removal of waste. Primary cilia are conservatively present in almost all the vertebrate cells and acts as a sensory organelle to control tissue development and homeostasis maintenance. Numerous studies reveal that abnormalities in RPE lead to various retinal diseases, such as age‐related macular degeneration and diabetic macular oedema, but the mechanism of primary cilia in these physiological and pathological activities remains to be elucidated. Herein, we summarize the functions of primary cilia in the RPE development and the mutations of ciliary genes identified in RPE‐related diseases. By highlighting the significance of primary cilia in regulating the physiological and pathological processes of RPE, we aim to provide novel insights for the treatment of RPE‐related retinal diseases.
Commonalities and evolutionary divergences of mandible shape ontogenies in rodents
Authors: Dubied Morgane , Montuire Sophie , Navarro Nicolas
Published: August 2021

In mammals, significant changes take place during postnatal growth, linked to changes in diet (from sucking to gnawing). During this period, mandible development is highly interconnected with muscle growth and the epigenetic interactions between muscle and bone control the spatialization of bone formation and remodelling in response to biomechanical strain. This mechanism contributes to postnatal developmental plasticity and may have influenced the course of evolutionary divergences between species and clades. We sought to model postnatal changes at a macroevolutionary scale by analysing ontogenetic trajectories of mandible shape across 16 species belonging mainly to two suborders of Rodents, Myomorpha and Hystricomorpha, which differ in muscle attachments, tooth growth and life‐history traits. Myomorpha species present a much stronger magnitude of changes over a shorter growth period. Among Hystricomorpha, part of the observed adult shape is set up prenatally, and most postnatal trajectories are genus‐specific, which agrees with nonlinear developmental trajectories over longer gestational periods. Beside divergence at large scale, we find some collinearities between evolutionary and developmental trajectories. A common developmental trend was also observed, leading to enlargement of the masseter fossa during postnatal growth. The tooth growth, especially hypselodonty, seems to be a major driver of divergences of postnatal trajectories. These muscle‐ and tooth‐related effects on postnatal trajectories suggest opportunities for developmental plasticity in the evolution of the mandible shape, opportunities that may have differed across Rodent clades.
Innovative approach for tear trough deformity correction using higher G prime fillers for safe, efficacious, and long‐lasting results: A prospective interventional study
Authors: Vadera Sapna , Shome Debraj , Kumar Vaibhav , Doshi Komal , Kapoor Rinky
Published: August 2021

Background

One of the most challenging areas for facial rejuvenation is the lower eyelid. Apart from the protruding orbital fat causing lower lid bags, a discrete entity called the “tear trough deformity” is distinguishable in this area.

Aim

The objective of this study is to compare and evaluate the standard technique of tear trough deformity correction with the lateral injection technique using a high G prime filler to establish a guideline for the safe and effective correction of tear trough deformity.

Methods

A prospective, double‐blind, study was carried out from Dec 2017 to 2019 including 30 participants in the age range of 35–60 years. The participants were divided into two groups of 15 patients each. In group A patients, conventional technique with a low G Prime filler was used, whereas in group B, lateral injection technique with a high G Prime filler was used.

Results

Marked improvement was seen in appearance and skin quality on both the sides in all the patients. As compared to our technique (lateral injections) where a mean of 0.5 ml of filler was used to lift the cheek and reduce the tear trough, the standard technique (Mauricio de Maio's 3‐point tear trough reshape technique) required a mean of 1.2 ml of filler for the same. Post‐procedure complications including bruising and Tyndall effect were much higher (statistically significant) using the standard medial technique for the correction tear trough.

Conclusion

Aesthetically satisfying results for the tear trough correction are possible, without actually injecting the tear trough directly, based on the knowledge of the underlying anatomy.
Chinese Adolescents’ Coping with COVID‐19: Relationships with Emotional Maladjustment and Parental Reactions to Negative Emotions
Authors: Shi Zeyi , Wang Qian
Published: August 2021

Two hundred and thirteen Chinese adolescents (103 females; mean age = 12.18 years) completed a survey one year before (Wave 1) and five months after the COVID‐19 outbreak (Wave 2). Path analysis revealed that after controlling for adolescents’ emotional maladjustment at Wave 1, perceived parental supportive reactions to adolescents’ negative emotions at Wave 1 predicted adolescents’ greater use of approach coping and less use of avoidance coping at Wave 2, which in turn, was associated with less emotional maladjustment at Wave 2; conversely, perceived parental nonsupportive reactions at Wave 1 predicted adolescents’ greater use of avoidance coping at Wave 2, which in turn, was associated with greater emotional maladjustment at Wave 2. The findings were similar for mothers and fathers.
Peer Connectedness and Pre‐Existing Social Reward Processing Predicts U.S. Adolescent Girls’ Suicidal Ideation During COVID‐19
Authors: Hutchinson Emily A. , Sequeira Stefanie L. , Silk Jennifer S. , Jones Neil P. , Oppenheimer Caroline , Scott Lori , Ladouceur Cecile D.
Published: August 2021

There is major concern about the impact of the COVID‐19 pandemic on adolescent suicidal ideation (SI) and peer relationships. We investigated (1) rates of SI and (2) the extent to which peer connectedness and pre‐existing neural activation to social reward predicted SI during the initial stay‐at‐home orders of the pandemic (April–May 2020) in a longitudinal sample of adolescent girls (N = 93; Mage = 15.06; 69% White non‐Hispanic). Daily diary and fMRI methods were used to assess peer connectedness and neural activation to social reward, respectively. Nearly 40% of girls endorsed SI during the initial stay‐at‐home orders. Greater peer connectedness and neural responsivity to anticipated social reward were associated with a reduced odds of SI during the pandemic among girls.
Longitudinal Changes in Adolescents’ School Bonding During the COVID‐19 Pandemic: Individual, Parenting, and Family Correlates
Authors: Maiya Sahitya , Dotterer Aryn M. , Whiteman Shawn D.
Published: August 2021

The current study examined changes in adolescents’ school bonding from before to during the COVID‐19 pandemic and its individual, parenting, and family‐level correlates. Participants were two adolescents (50% male; Mage = 14 years) and one parent (85% female; Mage = 45 years) from 682 families (N = 2046) from an ongoing longitudinal study. Adolescents reported on their school bonding, stress, and coping, while parents reported on their involvement in adolescents’ education and pandemic‐related financial need. A two‐wave latent change score model suggested that adolescents’ school bonding decreased from before to during the COVID‐19 pandemic. Stress and pandemic‐related financial need served as risk factors, whereas coping and parental involvement served as protective factors against declines in adolescents’ school bonding.
Adolescents' Longitudinal School Engagement and Burnout Before and During COVID‐19—The Role of Socio‐Emotional Skills
Authors: Salmela‐Aro Katariina , Upadyaya Katja , Vinni‐Laakso Janica , Hietajärvi Lauri
Published: August 2021

This longitudinal study examined school engagement and burnout profiles among early and middle adolescents before and during COVID‐19, and within‐class latent change and stability in students’ socio‐emotional skills the profiles. The longitudinal data were collected in fall 2019 and 2020 from 1381 5th to 6th, and 1374 7th to 8th grade students. Using repeated measures latent profile analyses based on school engagement and burnout we identified five study well‐being change profiles in both samples showing structural similarity: normative (53% sample 1; 69% sample 2), moderate‐decreasing (4%; 5%), high‐decreasing (17%; 10%), low‐increasing (6%;7%) and moderate‐increasing (20%; 10%) groups. The groups with increasing study well‐being showed simultaneous increase in intrapersonal socio‐emotional competencies but showed less changes in interpersonal outcomes.
Genomic signatures of inbreeding and mutation load in a threatened rattlesnake
Authors: Ochoa Alexander , Gibbs H. Lisle
Published: August 2021

Theory predicts that threatened species living in small populations will experience high levels of inbreeding that will increase their genetic load, but recent work suggests that the impact of load may be minimized by purging resulting from long‐term population bottlenecks. Empirical studies that examine this idea using genome‐wide estimates of inbreeding and genetic load in threatened species are limited. Here we use individual genome resequencing data to compare levels of inbreeding, levels of genetic load (estimated as mutation load) and population history in threatened Eastern massasauga rattlesnakes (Sistrurus catenatus), which exist in small isolated populations, and closely related yet outbred Western massasauga rattlesnakes (Sistrurus tergeminus). In terms of inbreeding, S. catenatus genomes had a greater number of runs of homozygosity of varying sizes, indicating sustained inbreeding through repeated bottlenecks when compared to S. tergeminus. At the species level, outbred S. tergeminus had higher genome‐wide levels of mutation load in the form of greater numbers of derived deleterious mutations compared to S. catenatus, presumably due to long‐term purging of deleterious mutations in S. catenatus. In contrast, mutations that escaped species‐level drift effects within S. catenatus populations were in general more frequent and more often found in homozygous genotypes than in S. tergeminus, suggesting a reduced efficiency of purifying selection in smaller S. catenatus populations for most mutations. Our results support an emerging idea that the historical demography of a threatened species has a significant impact on the type of genetic load present, which impacts implementation of conservation actions such as genetic rescue.