bluuebunny/crossref_metadata_2025 huggingface dataset:
Deformation characteristics of hydrogel products based on cross‐linked hyaluronic acid
Authors: Hong Gi‐Woong , Moon Hyoung Jin , Lee Hun Min , Kim Do Kyung , Lee Keyong Ho
Published: June 2023

Background

The cross‐linked hyaluronic acid (HA) fillers are the viscoelastic hydrogel with a dominant elasticity rather than a viscosity as a useful medical device in the soft tissue augmentation. These HA fillers undergo deformation to begin the biodegradation by the biochemical and physical environment of the body, and result of deformations are closely related to clinical performance.

Aims

The specific equation of molding index is newly generated and proved with Collin's equation, which is used for strong elastomers, for selecting optimal product in facial treatment.

Methods

In this study, the results of amplitude sweep test from five marketed HA fillers were mathematically demonstrated for the proper clinical application.

Results

The increment of loss modulus by deformation was evaluated as a useful factor for the maintenance of optimal shape molding performance and resistance to external deformation of the cross‐linked HA gel. From this study, the equation of molding index for weak viscoelastic hydrogels like HA products can be applied for choosing which products even in aesthetic plastic field. This molding index equation is compared to Collins' equation that index of deformation as elastomer like rubber and then found the positive correlation between two equations.

Conclusion

This study could provide a basic theory that achieve useful clinical performance according to characteristics among many types of medical devices based on the molding index.
Behavioral adjustment moderates the effect of neuroticism on brain volume relative to intracranial volume
Authors: Yu Qinggang , Schaefer Stacey M. , Davidson Richard J. , Kitayama Shinobu
Published: June 2023

Objective

The present study examined whether the effect of neuroticism on brain structure is moderated by behavioral adjustment.

Background

Neuroticism is widely thought to be harmful to health. However, recent work using proinflammatory biomarkers showed that this effect depends on behavioral adjustment, the willingness and ability to adjust and cope with environmental contingencies, such as different opinions of others or unpredictable life situations. Here, we sought to extend this observation to “brain health” by testing total brain volume (TBV).

Method

Using a community sample of 125 Americans, we examined structural magnetic resonance imaging of the brain and quantified TBV. We tested whether the effect of neuroticism on TBV was moderated by behavioral adjustment, net of intracranial volume, age, sex, educational achievement, and race.

Results

Behavioral adjustment significantly moderated the effect of neuroticism on TBV, such that neuroticism was associated with lower TBV only when behavioral adjustment was low. There was no such effect when behavioral adjustment was high.

Conclusion

The present findings suggest that neuroticism is not debilitating to those who constructively cope with stress. Implications are further discussed.
Self‐other agreement and criterion‐related validity of moral pride and hubris
Authors: Bai Feng , Lin Katrina Jia , Zhang Jessica
Published: June 2023

Objectives

This research investigates the moral implications of trait‐level moral pride and hubris, addressing prior limitations by gathering data from multiple sources. We raise two interrelated questions: (1) Do well‐acquainted peers agree with their friends on judgments of trait‐level moral pride and hubris? (2) Are moral pride and hubris related to divergent (im)moral outcomes, regardless of measurement sources?

Method

We collected data from a sample of university students and their friends (N = 173 dyads) in Hong Kong to examine self‐other agreement and criterion‐related validity of trait‐level moral pride and hubris.

Results

Our findings reveal a medium‐to‐large level of self‐other agreement for, as well as a moral divergence of, trait‐level moral pride and hubris. Notably, self‐reports of moral pride predict prosocial behavior, whereas self‐reports of moral hubris predict virtue‐signaling behavior, regardless of whether the outcomes are self‐ or other‐reported. Moreover, self‐reports trump other‐reports in predicting some outcomes, but the reverse is true for other outcomes.

Conclusions

Our findings suggest that individuals' proneness to experience morally specific pride and hubris constitutes “real” traits, evoking divergent (im)moral outcomes. Furthermore, self‐ and other‐reports each contain some unique trait‐relevant information, with their relative predictive power depending on the specific predictor and outcome.
Board political ideological diversity and information exposure as antecedents to value creation and value appropriation
Authors: Hudson Kerry , Morgan Robert E.
Published: June 2023

Strategic emphasis is a critical decision reflecting a firm's relative proclivity toward value creation versus value appropriation. Despite the increasing role of the board in setting the strategic priorities of firms, there is a dearth of research examining board‐level influences on strategic emphasis. Drawing on the cognitive perspective of corporate governance, we posit that exposure to external information via board interlocks provides competing incentives to pursue value creation and value appropriation strategies. We hypothesize that political ideological diversity among directors facilitates the utilization of external information for novel purposes, thus increasing firms' value creation focus. Combining data on directors' political ideologies with network analysis, we test these hypotheses in 584 large U.S. firms between 2000 and 2018. We find that political ideological diversity influences strategic emphasis both directly and in interaction with board interlock network centrality: politically ideological diverse boards exhibit a greater focus on value creation, and this effect is strengthened when the board is well connected to others. These results have implications for the director selection process, and for executives advocating for value creation strategies and the requisite R&D investments under differing conditions of board composition and information exposure.
Magnetic resonance imaging and neurologic characterization of combined osseous‐ and disc‐associated cervical spondylomyelopathy in dogs
Authors: Bonelli Marília de Albuquerque , da Costa Ronaldo Casimiro
Published: June 2023

Background

Although both disc‐ or osseous‐associated forms of cervical spondylomyelopathy (CSM) are observed in the same dogs, this combined form has not been thoroughly evaluated.

Objectives

To describe imaging characteristics of dogs with concurrent disc‐ and osseous CSM and investigate an association between findings on neurological examination and imaging.

Animals

Sixty dogs with disc and osseous‐associated CSM from 232 CSM‐affected dogs.

Methods

Retrospective study. Dogs diagnosed via high‐field MRI with a combination of intervertebral disc (IVD) protrusion and osseous proliferation of articular processes, dorsal lamina, or both were identified. Large and giant breed dogs were grouped according to whether combined compressions were at the same site or different sites. Statistical methods were used to investigate the association and relationship between variables.

Results

Thirty‐five out of 60 (58%) were large breeds and 22/60 (37%) were giant breeds. Mean and median age was 6.6 and 7 years respectively (range, 0.75‐11 years). Forty of the 60 dogs (67%) had concurrent osseous and disc‐associated spinal cord compression in the same location. This was considered the main compression site in 32/40 (80%) dogs. Dogs with osseous‐ and disc‐associated compressions at the same site were more likely to have a higher neurologic grade (P = .04).

Conclusions and Clinical Importance

A substantial percentage of dogs with CSM present with concomitant IVD protrusion and osseous proliferations, most at the same site. Characterizing this combined form is important in the management of dogs with CSM because it could affect treatment choices.
Hepatocellular organellar abnormalities following elimination of hepatitis C virus
Authors: Aoyagi Haruyo , Iijima Hiroko , Gaber Eman S. , Zaitsu Takuma , Matsuda Mami , Wakae Kosho , Watashi Koichi , Suzuki Ryosuke , Masaki Takahiro , Kahn Jeffrey , Saito Takeshi , El‐Kassas Mohamed , Shimada Noritomo , Kato Keizo , Enomoto Masaru , Hayashi Kazuhiko , Tsubota Akihito , Mimata Ayako , Sakamaki Yuriko , Ichinose Shizuko , Muramatsu Masamichi , Wake Kenjiro , Wakita Takaji , Aizaki Hideki
Published: June 2023

Background and aims

The future development of hepatocellular carcinoma (HCC) in patients after sustained virologic response (SVR) is an important issue. The purposes of this study were to investigate pathological alterations in organelle of the liver of SVR patients and to characterize organelle abnormalities that may be related to carcinogenesis after SVR.

Methods

The ultrastructure of liver biopsy specimens from patients with chronic hepatitis C (CHC) and SVR were compared to cell and mouse models and assessed semi‐quantitatively using transmission electron microscopy.

Results

Hepatocytes in patients with CHC showed abnormalities in the nucleus, mitochondria, endoplasmic reticulum, lipid droplet, and pericellular fibrosis, comparable to those seen in hepatitis C virus (HCV)‐infected mice and cells. DAA treatment significantly reduced organelle abnormalities such as the nucleus, mitochondria, and lipid droplet in the hepatocytes of patients and mice after SVR, and cured cells, but it did not change dilated/degranulated endoplasmic reticulum and pericellular fibrosis in patients and mice after SVR. Further, samples from patients with a post‐SVR period of >1 year had significantly larger numbers of abnormalities in the mitochondria and endoplasmic reticulum than those of <1 year. A possible cause of organelle abnormalities in patients after SVR could be oxidative stress of the endoplasmic reticulum and mitochondria associated with abnormalities of the vascular system due to fibrosis. Interestingly, abnormal endoplasmic reticulum was associated with patients with HCC for >1 year after SVR.

Conclusions

These results indicate that patients with SVR exhibit a persistent disease state and require long‐term follow‐up to detect early signs of carcinogenesis.
Nuclear translocation of YAP drives BMI‐associated hepatocarcinogenesis in hepatitis B virus infection
Authors: Luo Xufeng , Zhang Rui , Schefczyk Stefan , Liang Yaojie , Lin Shu S. , Liu Shi , Baba Hideo A. , Lange Christian M. , Wedemeyer Heiner , Lu Mengji , Broering Ruth
Published: June 2023

Background and Aims

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) development and progression. The aim of this study was to mechanistically investigate the involvement of Hippo signalling in HBV surface antigen (HBsAg)‐dependent neoplastic transformation.

Methods

Liver tissue and hepatocytes from HBsAg‐transgenic mice were examined for the Hippo cascade and proliferative events. Functional experiments in mouse hepatoma cells included knockdown, overexpression, luciferase reporter assays and chromatin immunoprecipitation. Results were validated in HBV‐related HCC biopsies.

Results

Hepatic expression signatures in HBsAg‐transgenic mice correlated with YAP responses, cell cycle control, DNA damage and spindle events. Polyploidy and aneuploidy occurred in HBsAg‐transgenic hepatocytes. Suppression and inactivation of MST1/2 led to the loss of YAP phosphorylation and the induction of BMI1 expression in vivo and in vitro. Increased BMI1 directly mediated cell proliferation associated with decreased level of p16INK4a, p19ARF, p53 and Caspase 3 as well as increased Cyclin D1 and γ‐H2AX expression. Chromatin immunoprecipitation and the analysis of mutated binding sites in dual‐luciferase reporter assays confirmed that the YAP/TEAD4 transcription factor complex bound and activated the Bmi1 promoter. In chronic hepatitis B patients, paired liver biopsies of non‐tumour and tumour tissue indicated a correlation between YAP expression and the abundance of BMI1. In a proof‐of‐concept, treatment of HBsAg‐transgenic mice with YAP inhibitor verteporfin directly suppressed the BMI1‐related cell cycle.

Conclusion

HBV‐associated proliferative HCC might be related to the HBsAg‐YAP‐BMI1 axis and offer a potential target for the development of new therapeutic approaches.
Tcf20 deficiency is associated with increased liver fibrogenesis and alterations in mitochondrial metabolism in mice and humans
Authors: Córdoba‐Jover Bernat , Ribera Jordi , Portolés Irene , Lecue Elena , Rodriguez‐Vita Juan , Pérez‐Sisqués Leticia , Mannara Francesco , Solsona‐Vilarrasa Estel , García‐Ruiz Carmen , Fernández‐Checa José C. , Casals Gregori , Rodríguez‐Revenga Laia , Álvarez‐Mora María Isabel , Arteche‐López Ana , Díaz de Bustamante Aranzazu , Calvo Rosa , Pujol Anna , Azkargorta Mikel , Elortza Felix , Malagelada Cristina , Pinyol Roser , Huguet‐Pradell Júlia , Melgar‐Lesmes Pedro , Jiménez Wladimiro , Morales‐Ruiz Manuel
Published: June 2023

Background & Aims

Transcription co‐activator factor 20 (TCF20) is a regulator of transcription factors involved in extracellular matrix remodelling. In addition, TCF20 genomic variants in humans have been associated with impaired intellectual disability. Therefore, we hypothesized that TCF20 has several functions beyond those described in neurogenesis, including the regulation of fibrogenesis.

Methods

Tcf20 knock‐out (Tcf20−/−) and Tcf20 heterozygous mice were generated by homologous recombination. TCF20 gene genotyping and expression was assessed in patients with pathogenic variants in the TCF20 gene. Neural development was investigated by immufluorescense. Mitochondrial metabolic activity was evaluated with the Seahorse analyser. The proteome analysis was carried out by gas chromatography mass‐spectrometry.

Results

Characterization of Tcf20−/− newborn mice showed impaired neural development and death after birth. In contrast, heterozygous mice were viable but showed higher CCl4‐induced liver fibrosis and a differential expression of genes involved in extracellular matrix homeostasis compared to wild‐type mice, along with abnormal behavioural patterns compatible with autism‐like phenotypes. Tcf20−/− embryonic livers and mouse embryonic fibroblast (MEF) cells revealed differential expression of structural proteins involved in the mitochondrial oxidative phosphorylation chain, increased rates of mitochondrial metabolic activity and alterations in metabolites of the citric acid cycle. These results parallel to those found in patients with TCF20 pathogenic variants, including alterations of the fibrosis scores (ELF and APRI) and the elevation of succinate concentration in plasma.

Conclusions

We demonstrated a new role of Tcf20 in fibrogenesis and mitochondria metabolism in mice and showed the association of TCF20 deficiency with fibrosis and metabolic biomarkers in humans.
Correlation of resistive index of prostatic capsular artery to clinical symptoms in men with chronic prostatitis/chronic pelvic pain syndrome
Authors: Yitgin Yasin , Karakose Ayhan
Published: June 2023

Objectives

To evaluate the relation between resistive index (RI) of prostatic capsular arteries by transrectal Doppler ultrasonography in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its correlation with lower urinary tract symptoms, erectile dysfunction and premature ejaculation parameters of CP/CPPS.

Methods

In total, we included 68 patients presenting with chronic prostatitis/chronic pelvic pain syndrome. We formed two groups, as Group 1 of 35 patients with a RI ≥ 0.7 and Group 2 of 33 patients with RI < 0.7. All patients were assessed with International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF‐5), premature ejaculation diagnostic tool (PEDT) and National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). In addition, the RI of the prostate capsular artery was measured in all patients using Doppler ultrasound. Statistical analyses were performed with SPSS version 18. A p value < .05 was considered significant.

Results

Demographic characteristics were similar in the two groups. IPSS was 11.3 ± 6 in Group 1 and 9.7 ± 5.3 in Group 2. IIEF‐5 was 18.6 ± 2 in Group 1 and 20.4 ± 2.3 in Group 2. PEDT was 12.4 ± 5.6 in Group 1 and 11.2 ± 4 in Group 2. CPSI (total) was 19.3 ± 12.3 in Group 1 and 10.6 ± 7.7 in Group 2. There was significant statistical difference in IPSS, IIEF‐5, and CPSI between the two groups (p < .001, p < .001, p < .001 respectively). However, we found no significant difference in PEDT between the two groups (p = .19).

Conclusions

There is a significant correlation between the lower urinary tract symptoms and erectile dysfunction parameters and the RI of the prostatic capsular artery in CP/CPPS and RI is an effective and noninvasive method to assess the severity of the disease.
His opportunity, her burden: A narrative critical review of why women decline academic opportunities
Authors: Monteiro Sandra , Chan Teresa M. , Kahlke Renate
Published: June 2023

Objectives

This paper stems from a desire to deepen our own understanding of why women might ‘say no’ when allies and sponsors offer or create opportunities for advancement, leadership or recognition. The resulting disparity between representation by men and women in leadership positions, invited keynote speakers and publication counts in academic medicine is a stubborn and wicked problem that requires a synthesis of knowledge across multidisciplinary literature. Acknowledging the complexity of this topic, we selected a narrative critical review methodology to explore reasons why one man's opportunity might be a woman's burden in academic medicine.

Methods

We engaged with an iterative process of identifying, reviewing and interpreting literature from Psychology (cognitive, industrial and educational), Sociology, Health Professions Education and Business, placing no restrictions on context or year of publication. Knowledge synthesis and interpretation were guided by our combined expertise, lived experience, consultations with experts outside the author team and these guiding questions: (1) Why might women have less time for career advancement opportunities? (2) Why do women have less time for research and leadership? (3) How are these disparities maintained?

Results

Turning down an opportunity may be a symptom of a much larger issue. The power of social expectations, culture and gender stereotypes remains a resistant force against calls for action. Consequently, women disproportionately take on other tasks that are not as well recognised. This disparity is maintained through social consequences for breaking with firmly entrenched stereotypes.

Conclusions

Popular strategies like ‘lean into opportunities’, ‘fake it till you make it’ and ‘overcome your imposter syndrome’ suggest that women are standing in their own way. Critically, these axioms ignore powerful systemic barriers that shape these choices and opportunities. We offer strategies that allies, sponsors and peers can implement to offset the power of stereotypes.
Gender Asymmetries in Cross‐National Couples
Authors: Esteve Albert , Elwert Annika , Batyra Ewa
Published: June 2023

We use census microdata for Spain and the United States to examine gender differences in cross‐national heterosexual couples (marriages and cohabitating unions involving natives and immigrant spouses). We examine whether native men and native women in cross‐national couples exhibit similar patterns regarding the country of birth, age, and educational attainment of their international partners. Countries are ranked by their level of the human development index (HDI). In both Spain and the United States, native men are slightly overrepresented in cross‐national couples. Native men are more likely to be married to individuals from low HDI countries than native women. On the contrary, native women are predominantly married to men born in countries with similar or higher levels of HDI. Unions of native men are characterized by large spousal age differences, which increase with the HDI gap; this pattern reverses among native women. These gender asymmetries do not extend to education level, with cross‐national couples, overall, involving highly educated individuals. These results point to the endurance of certain features of traditional marriage patterns in cross‐national couples, but the patterns differ starkly between native men and native women.
Local types of (Γ,G)$(\Gamma ,G)$‐bundles and parahoric group schemes
Authors: Damiolini Chiara , Hong Jiuzu
Published: June 2023

Let be a simple algebraic group over an algebraically closed field . Let be a finite group acting on . We classify and compute the local types of ‐bundles on a smooth projective ‐curve in terms of the first nonabelian group cohomology of the stabilizer groups at the tamely ramified points with coefficients in . When , we prove that any generically simply connected parahoric Bruhat–Tits group scheme can arise from a ‐bundle. We also prove a local version of this theorem, that is, parahoric group schemes over the formal disc arise from constant group schemes via tamely ramified coverings.
Cardiovascular perspectives of the TRP channel polycystin 2
Authors: Márquez‐Nogueras Karla M. , Kuo Ivana Y.
Published: June 2023

Calcium release from the endoplasmic reticulum (ER) is predominantly driven by two key ion channel receptors, inositol 1, 4, 5‐triphosphate receptor (InsP3R) in non‐excitable cells and ryanodine receptor (RyR) in excitable and muscle‐based cells. These calcium transients can be modified by other less‐studied ion channels, including polycystin 2 (PC2), a member of the transient receptor potential (TRP) family. PC2 is found in various cell types and is evolutionarily conserved with paralogues ranging from single‐cell organisms to yeasts and mammals. Interest in the mammalian form of PC2 stems from its disease relevance, as mutations in the PKD2 gene, which encodes PC2, result in autosomal dominant polycystic kidney disease (ADPKD). This disease is characterized by renal and liver cysts, and cardiovascular extrarenal manifestations. However, in contrast to the well‐defined roles of many TRP channels, the role of PC2 remains unknown, as it has different subcellular locations, and the functional understanding of the channel in each location is still unclear. Recent structural and functional studies have shed light on this channel. Moreover, studies on cardiovascular tissues have demonstrated a diverse role of PC2 in these tissues compared to that in the kidney. We highlight recent advances in understanding the role of this channel in the cardiovascular system and discuss the functional relevance of PC2 in non‐renal cells.

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Uptake of a Universal Sports Subsidy Program for School-Aged Children: A Population Data Analysis
Authors: Curtis Rachel G. , Crisp Michelle , Licari Simone , Virgara Rosa , Simpson Catherine E.M. , Maher Carol A.
Published: June 2023

Background: Around 40% of Australian children do not participate in sport. Cost is a major barrier to participation, particularly for children from low socioeconomic backgrounds. This study aimed to evaluate the uptake of a population-level children’s sports subsidy scheme, including sociodemographic differences in uptake. Methods: A state-wide cross-sectional analysis comparing sports voucher claimants (primary school-aged children with a valid Medicare or Australian visa number) from the 2019 financial year with population census data from South Australia. Chi-square was used to examine whether the percentage of eligible children who claimed a voucher differed based on age, sex, socioeconomic status (SES), and geographical remoteness. Subgroup analyses were conducted for the lowest 2 socioeconomic disadvantage deciles, split by gender. Scatterplots were used to compare sports between high and low SES children. Results: A total of 74,668 children claimed sports vouchers (45.5% of eligible children). Children who were relatively younger, female, from low socioeconomic backgrounds, and from major cities were least likely to claim the voucher. The 5 most common sports were Australian rules football (30.2%), netball (13.6%), soccer (13.1%), gymnastics (10.4%), and basketball (5.7%), with the popular sports similar for high and low SES children. Conclusions: Future work is needed to understand how Sports Voucher, and sport participation rates have changed over time, and to improve voucher uptake among girls, city dwellers, and low SES children.
Estimating Quadriceps and Hamstrings Strength Through Myoton Among Recreational Athletes
Authors: Gacto-Sánchez Mariano , Medina-Mirapeix Francesc , Benítez-Martínez Josep C. , Montilla-Herrador Joaquina , Palanca Ana , Agustín Rodrigo Martín-San
Published: June 2023

Context: The assessment of strength is one of the most usual practices among professionals involved in health care or sport. Quadriceps and hamstrings are the most commonly assessed muscle groups. Generally, the methods used to assess muscle strength are active and, therefore, alternative passive methods could be useful. Myoton provides measures on 3 mechanical properties of the muscle: tone, elasticity, and stiffness. Objective: This study aimed to analyze the association of Myoton, an easy-to-use tool not requiring voluntary stimulus from the subject, with strength values in quadriceps and hamstrings. Study Design: Experimental. Setting: University kinesiology laboratory. Participants: Thirty-eight recreational athletes were evaluated. Main Outcome Measures: Anthropometric and demographic data, Myoton-based measures of vastus lateralis, rectus femoris, vastus medialis, biceps femoris, and semitendinosus, and the maximum voluntary isometric contraction of quadriceps and hamstrings. Procedures: The association was examined using multiple regression models to estimate strength through Myoton-based parameters and different patient characteristics. The models encompassed either 2 or 3 independent variables. Results: The adjusted R2 values for predicting quadriceps strength were .666 for rectus femoris, .726 for vastus lateralis, and .667 for vastus medialis, while in regard to hamstrings, they were .617 for biceps femoris and .604 for semitendinosus. Conclusions: The main finding was that acceptable relationships were found between muscle strength and Myoton-based parameters when variables such as gender and/or age are considered. Our study reveals a new tool for estimating strength with outstanding advantages: it is easy, time-efficient, adaptable, and highly manageable through the feasible equations provided.
Not so smart? “Smart” drugs increase the level but decrease the quality of cognitive effort
Authors: Bowman Elizabeth , Coghill David , Murawski Carsten , Bossaerts Peter
Published: June 2023

The efficacy of pharmaceutical cognitive enhancers in everyday complex tasks remains to be established. Using the knapsack optimization problem as a stylized representation of difficulty in tasks encountered in daily life, we discover that methylphenidate, dextroamphetamine, and modafinil cause knapsack value attained in the task to diminish significantly compared to placebo, even if the chance of finding the optimal solution (~50%) is not reduced significantly. Effort (decision time and number of steps taken to find a solution) increases significantly, but productivity (quality of effort) decreases significantly. At the same time, productivity differences across participants decrease, even reverse, to the extent that above-average performers end up below average and vice versa. The latter can be attributed to increased randomness of solution strategies. Our findings suggest that “smart drugs” increase motivation, but a reduction in quality of effort, crucial to solve complex problems, annuls this effect.
Urchin-like ceria nanoparticles for enhanced gene therapy of osteoarthritis
Authors: Chen Haoyi , Ye Tianwen , Hu Fangqiong , Chen Kaizhe , Li Bin , Qiu Minglong , Chen Zhijie , Sun Yao , Ye Wenkai , Wang Han , Ni Dalong , Guo Lei
Published: June 2023

Osteoarthritis (OA) is the most common degenerative joint disease in the world. Gene therapy based on delivering microRNAs (miRNAs) into cells has potential for the treatment of OA. However, the effects of miRNAs are limited by the poor cellular uptake and stability. Here, we first identify a type of microRNA-224-5p (miR-224-5p) from clinical samples of patients with OA that can protect articular cartilage from degeneration and further synthesize urchin-like ceria nanoparticles (NPs) that can load miR-224-5p for enhanced gene therapy of OA. Compared with traditional sphere ceria NPs, the thorns of urchin-like ceria NPs can efficiently promote the transfection of miR-224-5p. In addition, urchin-like ceria NPs have excellent performance of scavenging reactive oxygen species (ROS), which can regulate the microenvironment of OA to further improve the gene treatment of OA. The combination of urchin-like ceria NPs and miR-224-5p not only exhibits favorable curative effect for OA but also provides a promising paradigm for translational medicine.
Coccolithophores and diatoms resilient to ocean alkalinity enhancement: A glimpse of hope?
Authors: Gately James A. , Kim Sylvia M. , Jin Benjamin , Brzezinski Mark A. , Iglesias-Rodriguez Maria D.
Published: June 2023

It is increasingly apparent that adequately mitigating anthropogenic climate interference will require ocean carbon dioxide removal (CDR) strategies. Ocean alkalinity enhancement (OAE) is an abiotic ocean CDR approach that aims to increase the ocean’s CO
2
uptake capacity through the dispersal of pulverized mineral or dissolved alkali into the surface ocean. However, OAE’s effect on marine biota is largely unexplored. Here, we investigate the impacts of moderate (~700 μmol kg
−1
) and high (~2700 μmol kg
−1
) limestone-inspired alkalinity additions on two biogeochemically and ecologically important phytoplankton functional group representatives:
Emiliania huxleyi
(calcium carbonate producer) and
Chaetoceros
sp. (silica producer). The growth rate and elemental ratios of both taxa showed a neutral response to limestone-inspired alkalinization. While our results are encouraging, we also observed abiotic mineral precipitation, which removed nutrients and alkalinity from solution. Our findings offer an evaluation of biogeochemical and physiological responses to OAE and provide evidence supporting the need for continued research into how OAE strategies affect marine ecosystems.
Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
Authors: Mittler Eva , Serris Alexandra , Esterman Emma S. , Florez Catalina , Polanco Laura C. , O’Brien Cecilia M. , Slough Megan M. , Tynell Janne , Gröning Remigius , Sun Yan , Abelson Dafna M. , Wec Anna Z. , Haslwanter Denise , Keller Markus , Ye Chunyan , Bakken Russel R. , Jangra Rohit K. , Dye John M. , Ahlm Clas , Rappazzo C. Garrett , Ulrich Rainer G. , Zeitlin Larry , Geoghegan James C. , Bradfute Steven B. , Sidoli Simone , Forsell Mattias N.E. , Strandin Tomas , Rey Felix A. , Herbert Andrew S. , Walker Laura M. , Chandran Kartik , Guardado-Calvo Pablo
Published: June 2023

Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus–experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb’s accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
Successful Use of Cefepime-Zidebactam (WCK 5222) as a Salvage Therapy for the Treatment of Disseminated Extensively Drug-Resistant New Delhi Metallo-β-Lactamase-Producing Pseudomonas aeruginosa Infection in an Adult Patient with Acute T-Cell Leukemia
Authors: Tirlangi Praveen Kumar , Wanve Bala Saheb , Dubbudu Ramakanth Reddy , Yadav Boorgula Sushma , Kumar L. Siva , Gupta Anand , Sree Racha Amarthya , Challa Hari Priya Reddy , Reddy P. Naveen
Published: June 2023

With limited and often toxic treatment options, carbapenem-resistant Gram-negative infections are associated with significant mortality. Cefepime-zidebactam is a promising antibiotic option undergoing a phase 3 trial that has activity against diverse antibiotic-resistant mechanisms in Gram-negative pathogens due to its β-lactam enhancer mechanism, mediating multiple PBP binding.
Cathelicidin CATH-B1 Inhibits Pseudorabies Virus Infection via Direct Interaction and TLR4/JNK/IRF3-Mediated Interferon Activation
Authors: Ye Chao , Wan Chao , Chen Jing , Li Gang , Li Yixuan , Wang Yue , Tao Qi , Peng Lianci , Fang Rendong
Published: June 2023

Although the antiviral activity of cathelicidins could be explained by direct interfering with the viral infection and regulating host antiviral response, the specific mechanism of cathelicidins regulating host antiviral response and interfering with pseudorabies virus (PRV) infection remains elusive. In this study, we investigated the multiple roles of cathelicidin CATH-B1 against PRV infection.
The evolution of infectious transmission promotes the persistence of
mcr-1
plasmids
Authors: Yang Jun , Wu Renjie , Xia Qiang , Yu Jingjing , Yi Ling-Xian , Huang Ying , Deng Meixin , He Wan-Yun , Bai Yuman , Lv Luchao , Burrus Vincent , Wang Chengzhen , Liu Jian-Hua
Published: June 2023

Conjugative plasmids play a vital role in bacterial evolution and promote the spread of antibiotic resistance. They usually cause fitness costs that diminish the growth rates of the host bacteria. Compensatory mutations are known as an effective evolutionary solution to reduce the fitness cost and improve plasmid persistence. However, whether the plasmid transmission by conjugation is sufficient to improve plasmid persistence is debated since it is an inherently costly process. Here, we experimentally evolved an unstable and costly
mcr-1
plasmid pHNSHP24 under laboratory conditions and assessed the effects of plasmid cost and transmission on the plasmid maintenance by the plasmid population dynamics model and a plasmid invasion experiment designed to measure the plasmid’s ability to invade a plasmid-free bacterial population. The persistence of pHNSHP24 improved after 36 days evolution due to the plasmid-borne mutation A51G in the 5′UTR of gene
traJ
. This mutation largely increased the infectious transmission of the evolved plasmid, presumably by impairing the inhibitory effect of FinP on the expression of
traJ
. We showed that increased conjugation rate of the evolved plasmid could compensate for the plasmid loss. Furthermore, we determined that the evolved high transmissibility had little effect on the
mcr-1
-deficient ancestral plasmid, implying that high conjugation transfer is vital for maintaining the
mcr-1
-bearing plasmid. Altogether, our findings emphasized that, besides compensatory evolution that reduces fitness costs, the evolution of infectious transmission can improve the persistence of antibiotic-resistant plasmids, indicating that inhibition of the conjugation process could be useful to combat the spread of antibiotic-resistant plasmids.

IMPORTANCE

Conjugative plasmids play a key role in the spread of antibiotic resistance, and they are well-adapted to the host bacteria. However, the evolutionary adaptation of plasmid-bacteria associations is not well understood. In this study, we experimentally evolved an unstable colistin resistance (
mcr-1
) plasmid under laboratory conditions and found that increased conjugation rate was crucial for the persistence of this plasmid. Interestingly, the evolved conjugation was caused by a single-base mutation, which could rescue the unstable plasmid from extinction in bacterial populations. Our findings imply that inhibition of the conjugation process could be necessary for combating the persistence of antibiotic-resistance plasmids.
Healing of acute anterior cruciate ligament rupture on MRI and outcomes following non-surgical management with the Cross Bracing Protocol
Authors: Filbay Stephanie R , Dowsett Matthew , Chaker Jomaa Mohammad , Rooney Jane , Sabharwal Rohan , Lucas Phil , Van Den Heever Andrew , Kazaglis James , Merlino Justin , Moran Mick , Allwright Maggie , Kuah Donald E K , Durie Ra , Roger Greg , Cross Mervyn , Cross Tom
Published: June 2023

Objective

Investigate MRI evidence of anterior cruciate ligament (ACL) healing, patient-reported outcomes and knee laxity in patients with acute ACL rupture managed non-surgically with the Cross Bracing Protocol (CBP).

Methods

Eighty consecutive patients within 4 weeks of ACL rupture were managed with CBP (knee immobilisation at 90° flexion in brace for 4 weeks, followed by progressive increases in range-of-motion until brace removal at 12 weeks, and physiotherapist-supervised goal-oriented rehabilitation). MRIs (3 months and 6 months) were graded using the ACL OsteoArthritis Score (ACLOAS) by three radiologists. Mann-Whitney U tests compared Lysholm Scale and ACL quality of life (ACLQOL) scores evaluated at median (IQR) of 12 months (7–16 months) post-injury, and χ2tests compared knee laxity (3-month Lachman’s test and 6-month Pivot-shift test), and return-to-sport at 12 months between groups (ACLOAS grades 0–1 (continuous±thickened ligament and/or high intraligamentous signal) versus ACLOAS grades 2–3 (continuous but thinned/elongated or complete discontinuity)).

Results

Participants were aged 26±10 years at injury, 39% were female, 49% had concomitant meniscal injury. At 3 months, 90% (n=72) had evidence of ACL healing (ACLOAS grade 1: 50%; grade 2: 40%; grade 3: 10%). Participants with ACLOAS grade 1 reported better Lysholm Scale (median (IQR): 98 (94–100) vs 94 (85–100)) and ACLQOL (89 (76–96) vs 70 (64–82)) scores, compared with ACLOAS grades 2–3. More participants with ACLOAS grade 1 had normal 3-month knee laxity (100% vs 40%) and returned to pre-injury sport (92% vs 64%), compared with participants with an ACLOAS grades 2–3. Eleven patients (14%) re-injured their ACL.

Conclusion

After management of acute ACL rupture with the CBP, 90% of patients had evidence of healing on 3-month MRI (continuity of the ACL). More ACL healing on 3-month MRI was associated with better outcomes. Longer-term follow-up and clinical trials are needed to inform clinical practice.
Effectiveness of GRACE risk score in patients admitted to hospital with non-ST elevation acute coronary syndrome (UKGRIS): parallel group cluster randomised controlled trial
Authors: Gale Chris P , Stocken Deborah D , Aktaa Suleman , Reynolds Catherine , Gilberts Rachael , Brieger David , Carruthers Kathryn , Chew Derek P , Goodman Shaun G , Fernandez Catherine , Sharples Linda D , Yan Andrew T , Fox Keith
Published: June 2023

Objective

To determine the effectiveness of risk stratification using the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) for patients presenting to hospital with suspected non-ST elevation acute coronary syndrome.

Design

Parallel group cluster randomised controlled trial.

Setting

Patients presenting with suspected non-ST elevation acute coronary syndrome to 42 hospitals in England between 9 March 2017 and 30 December 2019.

Participants

Patients aged ≥18 years with a minimum follow-up of 12 months.

Intervention

Hospitals were randomised (1:1) to patient management by standard care or according to the GRS and associated guidelines.

Main outcome measures

Primary outcome measures were use of guideline recommended management and time to the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospital admission, and readmission for cardiovascular event. Secondary measures included the duration of hospital stay, EQ-5D-5L (five domain, five level version of the EuroQoL index), and the composite endpoint components.

Results

3050 participants (1440 GRS, 1610 standard care) were recruited in 38 UK clusters (20 GRS, 18 standard care). The mean age was 65.7 years (standard deviation 12), 69% were male, and the mean baseline GRACE scores were 119.5 (standard deviation 31.4) and 125.7 (34.4) for GRS and standard care, respectively. The uptake of guideline recommended processes was 77.3% for GRS and 75.3% for standard care (odds ratio 1.16, 95% confidence interval 0.70 to 1.92, P=0.56). The time to the first composite cardiac event was not significantly improved by the GRS (hazard ratio 0.89, 95% confidence interval 0.68 to 1.16, P=0.37). Baseline adjusted EQ-5D-5L utility at 12 months (difference −0.01, 95% confidence interval −0.06 to 0.04) and the duration of hospital admission within 12 months (mean 11.2 days, standard deviation 18 days
v
11.8 days, 19 days) were similar for GRS and standard care.

Conclusions

In adults presenting to hospital with suspected non-ST elevation acute coronary syndrome, the GRS did not improve adherence to guideline recommended management or reduce cardiovascular events at 12 months.

Trial registration

ISRCTN 29731761
Effectiveness of a gamified digital intervention based on lifestyle modification (iGAME) in secondary prevention: a protocol for a randomised controlled trial
Authors: Cuesta-Vargas Antonio I , Biró Attila , Escriche-Escuder Adrian , Trinidad-Fernández Manuel , García-Conejo Celia , Roldan-Jimenez Cristina , Tang Wen , Salvatore Alfredo , Nikolova Borjanka , Muro-Culebras Antonio , Martín-Martín Jaime , González-Sánchez Manuel , Ruiz-Muñoz María , Mayoral Fermin
Published: June 2023

Introduction

Combating physical inactivity and reducing sitting time are one of the principal challenges proposed by public health systems. Gamification has been seen as an innovative, functional and motivating strategy to encourage patients to increase their physical activity (PA) and reduce sedentary lifestyles through behaviour change techniques (BCT). However, the effectiveness of these interventions is not usually studied before their use. The main objective of this study will be to analyse the effectiveness of a gamified mobile application (iGAME) developed in the context of promoting PA and reducing sitting time with the BCT approach, as an intervention of secondary prevention in sedentary patients.

Methods and analysis

A randomised clinical trial will be conducted among sedentary patients with one of these conditions: non-specific low back pain, cancer survivors and mild depression. The experimental group will receive a 12-week intervention based on a gamified mobile health application using BCT to promote PA and reduce sedentarism. Participants in the control group will be educated about the benefits of PA. The International Physical Activity Questionnaire will be considered the primary outcome. International Sedentary Assessment Tool, EuroQoL-5D, MEDRISK Instruments and consumption of Health System resources will be evaluated as secondary outcomes. Specific questionnaires will be administered depending on the clinical population. Outcomes will be assessed at baseline, at 6 weeks, at the end of the intervention (12 weeks), at 26 weeks and at 52 weeks.

Ethics and dissemination

The study has been approved by the Portal de Ética de la Investigación Biomédica de Andalucía Ethics Committee (RCT-iGAME 24092020). All participants will be informed about the purpose and content of the study and written informed consent will be completed. The results of this study will be published in a peer-reviewed journal and disseminated electronically and in print.

Trial registration number

NCT04019119
National and international programmatic perspective on facilitators and barriers for Sudan’s health sector response on female genital mutilation (2016–2018): a qualitative study
Authors: Ahmed Wisal , Adam Amira , Puttkammer Nancy , Gloyd Stephen , Farquhar Carey
Published: June 2023

Objectives

To explore the facilitators and barriers that affected the design and implementation of the first 3 years of Sudan’s largest health programme on female genital mutilation (FGM).

Design

We used a qualitative case study guided by the Consolidated Framework for Implementation Research to conduct in-depth interviews with programme managers and for thematic data analysis.

Setting

About 14 million girls and women in Sudan are affected by FGM, which is mainly performed by midwives (77%). Since 2016, Sudan has received substantial donor funding to develop and implement the largest global health programme to stop midwives’ involvement and improve the quality of FGM prevention and care services.

Participants

Eight Sudanese and two international programme managers representing governmental, international and national organisations and donor agencies participated in interviews. Their job positions required detailed involvement in planning, implementing and evaluating diverse health interventions in the areas of governance, building knowledge and skills of health workers, strengthening accountability, monitoring and evaluation and creating an enabling environment.

Results

Respondents identified funding availability and comprehensive plans, integration of FGM-related interventions within existing priority health intervention packages and presence of an evaluation and feedback culture within international organisations as implementation facilitators. The barriers were low health system functionality, low inter-organisational coordination culture, power asymmetries in decision-making during planning and implementation of nationally-funded and internationally-funded interventions, and non-supportive attitudes among health workers.

Conclusion

Understanding the factors affecting planning and implementation of Sudan’s health programme addressing FGM may potentially mitigate barriers and improve results. Interventions which change midwives’ supportive values and attitudes towards FGM, strengthen health system function and increase intersectoral and multisectoral coordination including equitable decision-making among relevant actors, may be needed to address the reported barriers. The impact of these interventions on the scale, effectiveness and sustainability of the health sector response merits further study.