bluuebunny/crossref_metadata_2025 huggingface dataset:
Postprandial glucose‐management strategies in type 1 diabetes: Current approaches and prospects with precision medicine and artificial intelligence
Authors: Jafar Adnan , Pasqua Melissa‐Rosina
Published: January 2024

Postprandial glucose control can be challenging for individuals with type 1 diabetes, and this can be attributed to many factors, including suboptimal therapy parameters (carbohydrate ratios, correction factors, basal doses) because of physiological changes, meal macronutrients and engagement in postprandial physical activity. This narrative review aims to examine the current postprandial glucose‐management strategies tested in clinical trials, including adjusting therapy settings, bolusing for meal macronutrients, adjusting pre‐exercise and postexercise meal boluses for postprandial physical activity, and other therapeutic options, for individuals on open‐loop and closed‐loop therapies. Then we discuss their challenges and future avenues. Despite advancements in insulin delivery devices such as closed‐loop systems and decision‐support systems, many individuals with type 1 diabetes still struggle to manage their glucose levels. The main challenge is the lack of personalized recommendations, causing suboptimal postprandial glucose control. We suggest that postprandial glucose control can be improved by (i) providing personalized recommendations for meal macronutrients and postprandial activity; (ii) including behavioural recommendations; (iii) using other personalized therapeutic approaches (e.g. glucagon‐like peptide‐1 receptor agonists, sodium‐glucose co‐transporter inhibitors, amylin analogues, inhaled insulin) in addition to insulin therapy; and (iv) integrating an interpretability report to explain to individuals about changes in treatment therapy and behavioural recommendations. In addition, we suggest a future avenue to implement precision recommendations for individuals with type 1 diabetes utilizing the potential of deep reinforcement learning and foundation models (such as GPT and BERT), employing different modalities of data including diabetes‐related and external background factors (i.e. behavioural, environmental, biological and abnormal events).
Multi‐modality imaging of the systemic right ventricle in congenital heart disease
Authors: Baroutidou Amalia , Ntiloudi Despoina , Kasinos Nearchos , Nyktari Evangelia , Giannakoulas George
Published: January 2024

A comprehensive and structured imaging approach in the evaluation of the systemic right ventricle (sRV) in patients with complete transposition of the great arteries (TGA) after atrial switch procedure and congenitally corrected transposition of the great arteries (ccTGA) is a key for their optimal lifelong surveillance. Despite the improvements in cardiovascular imaging of adults with congenital heart disease (ACHD), the imaging of sRV remains an ongoing challenge due to its complex morphology and the difficulty in applying the existing knowledge for the systemic left ventricle. While cardiac magnetic resonance (CMR) is considered the gold standard imaging method, echocardiographic evaluation is primarily preferred in everyday clinical setting. Although qualitative assessment of its systolic function is primarily used, the introduction of advanced echocardiographic techniques, such as speckle tracking echocardiography (STE) and three‐dimensional echocardiography (3DE), has provided new insights into the optimal assessment of the sRV. Standardized quantitative parameters remain to be elucidated, and morphometric and mechanistic studies are warranted to validate reference ranges for the sRV. This review highlights the challenges in the optimal evaluation of sRV and summarizes the available imaging tools.

Highlights

CMR is the gold standard imaging method of sRV.

Qualitative assessment of the systolic function of sRV is primarily used.

Advanced echocardiographic techniques (STE and 3DE) provide optimal sRV assessment.

Reference ranges for the sRV indices are warranted to be validated.
Predictors of therapeutic response following thalamic neuromodulation for drug‐resistant pediatric epilepsy: A systematic review and individual patient data meta‐analysis
Authors: Sharma Akshay , Parfyonov Maksim , Tiefenbach Jakov , Hogue Olivia , Nero Neil , Jehi Lara , Serletis Demitre , Bingaman William , Gupta Ajay , Rammo Richard
Published: January 2024

We sought to perform a systematic review and individual participant data meta‐analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug‐resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy‐four (84%) patients were implanted bilaterally. The median time to last follow‐up was 12 months (interquartile range = 6.75–26.25). Sixty‐nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option.
Happy parents, happy kids: Marital happiness, parenting styles, and children's behavioral outcomes in Chinese societies
Authors: Huang Ching‐Yu , Shen April Chiung‐Tao , Li Xuan , Feng Joyce Yen
Published: January 2024

Objective

We examine the impacts of parental marital happiness on child outcomes. We also examine the potential mediating role of parenting styles in the relationship between marital happiness and children's behavioral outcomes.

Background

Parents' marital happiness lays a crucial foundation for successful parenthood, which contributes to children's positive development. However, scant research has examined the relationship between parental marital happiness and child outcomes in Chinese populations.

Method

Data from a subsample of 3,258 parents of third‐grade children in Shanghai and Greater Taipei were analyzed (n = 1,285 from Shanghai; 1,973 from Greater Taipei). We conducted hierarchical multiple regression analyses to investigate whether marital happiness is a significant predictor of children's behavioral outcomes, adjusted for four covariates: parent gender, child gender, site, and subjective social status. We also conducted parallel mediation analyses to examine parenting styles as mediators.

Results

Our findings reveal that in both Shanghai and Greater Taipei, marital happiness was positively associated with authoritative parenting style and negatively associated with harsh parenting style. Moreover, marital happiness was significantly associated with children's behavioral outcomes, even after covariates were accounted for. Our parallel mediation analysis reveals that marital happiness had significant direct and indirect effects on children's behavioral outcomes through authoritative and harsh parenting styles.

Conclusion

Our findings demonstrate the pivotal importance of parental marital happiness in healthy child development.

Implications

Intervention programs promoting child welfare in Chinese communities should include interparental relations. Public resources should raise awareness of marital happiness and offer guidance and support for high‐quality relationships.
A review of extension programs serving military Veterans and their families
Authors: Younker Terasa , Radunovich Heidi Liss
Published: January 2024

To better understand the availability and quality of current Extension programming for Veterans and their families, the researchers reviewed the academic literature (yielding 12 publications) and conducted an online scan of Extension programs (yielding 112 resources). Programs discovered fell across nine areas: occupational training/support, mental health support, service to Veterans, family support, livelihood support, holistic support, life quality, healthcare access/quality, and community development. This study revealed that, while Extension programs exist for Veterans and their families, program coordination, needs assessments from Veteran populations, and better program evaluations are needed to maximize efficacy of Extension programs serving Veteran populations.
Fabrication and characterisation of Pickering emulsion‐based oleogel stabilised by citrus fibre and whey protein isolate colloidal complex: application in cookie formulation
Authors: Genc Ezgi , Karasu Salih , Akcicek Alican , Toker Omer Said
Published: January 2024

In this study, the oleogel was produced by Pickering emulsion‐based method by using citrus fibre (CF)‐whey protein isolate (WPI) colloidal complex. The obtained oleogels were characterised by rheological and textural properties, and then the oleogels were used in cookies as an alternative to palm oil. The four oleogels (1% to 5%) were fabricated using a CF‐10% WPI complex. Shear thinning rheological behaviour was observed in all emulsion and oleogel samples. The G values were greater than the G values, indicating that solid‐like behaviour dominated in all emulsion and oleogel samples. All oleogel samples had a higher than 90% oil‐holding capacity. The visual appearance of 3% CF‐10% WPI and 5% CF‐10% WPI showed no surface oil, and more integrity structure means that could well trap oil in a gel matrix. Increasing CF% concentration reduced oil droplets and created a more compact structure, particularly at 3% and 5% CF‐10% WPI. An increase in CF concentration from 2% to 5% led to an increase in the hardness value of the dried products and cookies that CF formed a 3D network structure with binds liquid oil. The oxidative stability showed that no significant changes were found between the 3% CF‐10% WPI and palm cookies (P < 0.05). Cookies containing oleogels with a 3% CF content exhibited a visual resemblance to this trait, suggesting a colour appearance that closely resembled cookies made with palm oil. The incorporation of oleogels into the cookie recipe proved to be an effective substitute for palm oil. CF‐10% WPI oleogels show promise for use in cookie preparation as a replacement for palm oil, offering potential as substitutes for saturated and trans fats in food products.
Comprehensive phenolic profiling of Australian‐grown Progrades™Desmanthus through LC‐ESI‐QTOF‐MS2 and determination of their antioxidant potential
Authors: Kang Xi , Guo Siwei , Xie Cundong , Gardiner Christopher , Kempe Nick , Suleria Hafiz A. R. , Dunshea Frank R.
Published: January 2024

Desmanthus is a Mimosaceae legume genus that is native to the Americas. Decades ago, the introduction of Desmanthus with impressive survival ability in semi‐clay soil filled the gap of no sown pasture legume adaptive to the northern Australian environment. In this study, the comprehensive phenolic profile of Progrades™ Desmanthus collected across northwestern Queensland was characterised by LC‐ESI‐QTOF‐MS2. Their antioxidant potential was evaluated by the in vitro antioxidant assays and correlatively analysed with the phenolic contents. As discovered, the phenolic contents varied significantly among geographical locations. Desmanthus collected from Armreynold showed the highest phenolic content mainly consisting of condensed tannins, whereas the Madison region sample displayed the highest flavonoid content. The mass spectrometry results identified 68 phenolic compounds, highlighting 21 phenolic acids and 36 flavonoids. This study provides academic evidence for the utilisation of Desmanthus in food and husbandry industries as an antioxidant ingredient or a potential source of phenolic compounds.
Therapy‐induced senescent cancer cells exhibit complement activation and increased complement regulatory protein expression
Authors: Abu‐Humaidan Anas HA , Ismail Mohammad A , Ahmad Fatima M , Al Shboul Sofian , Barham Raghad , Tadros Joud S , Alhesa Ahmad , El‐Sadoni Mohammed , Alotaibi Moureq R , Ababneh Nidaa A , Saleh Tareq
Published: January 2024

Therapy‐induced senescence (TIS) is a primary response to chemotherapy, contributing to untoward treatment outcomes such as evasion of immunosurveillance. Despite the established role of the complement system in the immune response to cancer, the role of complement in mediating the immune response against senescent tumor cells remains poorly understood. To explore this relationship, we exposed lung adenocarcinoma (A549), breast adenocarcinoma (MCF7) and pancreatic carcinoma (Panc‐1) cell lines to sublethal doses of either etoposide or doxorubicin to trigger TIS. Identification of TIS was based on morphological changes, upregulation of the senescence‐associated β‐galactosidase, p21Cip1 induction and lamin B1 downregulation. Using immunofluorescence microscopy, quantitative PCR, ELISA of conditioned media and in silico analysis, we investigated complement activation, complement protein expression, C3 levels in the conditioned media of senescent cells and secreted complement proteins as part of the senescence‐associated secretory phenotype (SASP), respectively. In cell lines undergoing TIS, complement‐related changes included (i) activation of the terminal pathway, evidenced by the deposition of C5b‐9 on senescent cells; (ii) an increase in the expression of CD59 and complement factor H and (iii) in A549 cells, an elevation in the expression of C3 with its secretion into the medium. In addition, increased C3 expression was observed in breast cancer samples expressing TIS hallmarks following exposure to neoadjuvant chemotherapy. In conclusion, TIS led to the activation of complement, upregulation of complement regulatory proteins and increased C3 expression. Complement appears to play a role in shaping the cancer microenvironment upon senescence induction.
Changing landscape of diabetes in Asia – What are the unmet needs?
Authors: Luk Andrea OY
Published: January 2024

The incidence rates of type 2 diabetes among adults in Asia have been stable, but the rates in youth and young adults have increased. In territory‐wide surveillance in Hong Kong, Special Administrative Region of People's Republic of China, all‐cause mortality rates among people with diabetes have exhibited a declining trend in the past 15 years, with a narrowing in the mortality gap between people with and without diabetes. At the same time, the improvement in survival resulted in a changing age structure and disease profile of people with diabetes, towards an increasing proportion of older people with long diabetes duration and multi‐morbidities. Reductions in event rates were not observed in the youngest age group who also had the least gains in risk factor control and uptake in organ protective drugs over time. A young age at diabetes diagnosis, associated with exposure to high glycemic burden from an early age, predicted higher risks of complications and premature mortality compared with later‐onset of diabetes. People presenting with type 2 diabetes below 40 years of age were 5‐fold more likely to die and their life expectancy was shortened by 8 years than age‐matched counterparts without diabetes. Analysis of population‐based data in Hong Kong Chinese identified hypertension followed by chronic kidney disease as the leading contributor to mortality in young people, indicating that efforts to optimize non‐glycemic risk factors and organ protection are as important in young individuals as it is in the older population.
Accuracy of an intraoral scanner with near‐infrared imaging feature in detection of interproximal caries of permanent teeth: An in vivo validation
Authors: Kanar Özlem , Tağtekin Dilek , Korkut Bora
Published: January 2024

Objective

This study aimed to evaluate the accuracy of an intraoral scanner with near‐infrared imaging (NIRI) feature in the diagnosis of interproximal caries and to compare it with the visual‐tactile method (VTM), bitewing radiography (BWR), and panoramic radiography (PR).

Materials and Methods

Six hundred thirty‐nine interproximal surfaces (mesial‐distal) of posterior teeth from 22 volunteers were examined. Results were scored by VTM, BWR, PR, and NIRI. Lesions were scored as 0 for no‐caries, 1 for early‐enamel lesion (EEL), and 2 for lesions involving dentino–enamel junction (DEJ). McNemar, Kappa, and Fleis Kappa tests were used to evaluate the agreement levels. Pearson's Chi‐square test was used to determine the matching rates after validation.

Results

A good level of agreement was observed between examination methods (Ƙ = 0.613; p < 0.001). In pairwise comparisons, a moderate agreement was seen between all the methods for lesions with DEJ involvement, while a statistically good agreement was observed between BWR and NIRI (Ƙ = 0.675; p < 0.001). As a result of validation, the accuracy of NIRI for molars was considered 85.2% and 75.7% for premolars in EELs, 85.2% for molars, and 70% for premolars regarding the lesions involving DEJ.

Conclusions

Intraoral scanners with the NIRI feature may be used for diagnosing interproximal caries, especially for permanent molars.

Clinical Significance

Early detection of proximal caries is one of the most essential topics forming the basis of preventive dentistry. This study investigates a caries diagnostic tool integrated into intraoral scanners to diagnose interproximal caries. A caries diagnostic tool integrated into an intraoral scanner may prevent the harmful effects of ionizing radiation in early caries diagnosis and may improve the patient's oral health status.
Happy Diamond Anniversary JMS! A Decade Analysis of the Journal of Management Studies
Authors: Krammer Sorin M. S. , Dahlin Peter , Doh Jonathan P. , Potočnik Kristina
Published: January 2024

The Journal of Management Studies, founded in 1963, is celebrating its 60th year. Clark et al. (2014) conducted a bibliometric analysis for its 50th anniversary assessing whether the journal had maintained its leading international ranking and sustained its mission to serve as a broad‐based management outlet. In this review, we build on and extend their findings by examining trends in the journal over the past decade (2012–22). We present a broader analysis of JMS by exploring its unique identity within the management journal ecosystem and examining its scope and breadth in terms of topics, methods, and author demographics to document JMS's evolution, impact, reach, and accessibility. We develop a new bibliometric framework that employs a mix of qualitative and quantitative analyses (including regression, text, and language analysis) to cover a broad range of considerations for a journal and its stakeholders. In so doing, we contribute to the bibliometric and review research areas by proposing new metrics (related to diversity, equity, and inclusion) and analysis tools to assess the relative position of an academic journal. Employing this framework, we conclude that JMS has retained and enhanced its position as a leading, cutting‐edge general management journal.
Different minimal alcohol consumption in male and female individuals with metabolic dysfunction‐associated fatty liver disease
Authors: Zhu Yixuan , Xu Xiaoming , Fan Zhiwen , Ma Xiaoyan , Rui Fajuan , Ni Wenjing , Hu Xinyu , Gu Qi , Shi Junping , Wu Chao , Yeo Yee Hui , Li Jie
Published: January 2024

Background and Aims

The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction‐associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all‐cause and cause‐specific mortality among MAFLD individuals of different genders.

Methods

Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all‐cause and cause‐specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all‐cause mortality.

Results

In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all‐cause and cause‐specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004–1.014; female, HRs: 1.032, 95% CIs: 1.022–1.042). In males with MAFLD, a linear association with all‐cause mortality was observed for weekly alcohol consumption (p for non‐linearity = .21). Conversely, in females with MAFLD, the risk of all‐cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non‐linearity < .05).

Conclusions

Our findings indicate that any increase in weekly alcohol consumption was associated with increased all‐cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female.
Secondary peristalsis and esophagogastric junction distensibility in symptomatic post‐fundoplication patients
Authors: Lu Michelle M. , Kahrilas Peter J. , Teitelbaum Ezra N. , Pandolfino John E. , Carlson Dustin A.
Published: January 2024

Background

The impact of esophageal dysmotility among patients with post‐fundoplication esophageal symptoms is not fully understood. This study aimed to investigate secondary peristalsis and esophagogastric junction (EGJ) opening biomechanics using functional lumen imaging probe (FLIP) panometry in symptomatic post‐fundoplication patients.

Methods

Eighty‐seven adult patients post‐fundoplication who completed FLIP for symptomatic esophageal evaluation were included. Secondary peristaltic contractile response (CR) patterns and EGJ opening metrics (EGJ distensibility index (EGJ‐DI) and maximum EGJ diameter) were evaluated on FLIP panometry and analyzed against high‐resolution manometry (HRM), patient‐reported outcomes, and fundoplication condition seen on esophagram and/or endoscopy.

Key Results

FLIP CR patterns included 14 (16%) normal CR, 30 (34%) borderline CR, 28 (32%) impaired/disordered CR, 13 (15%) absent CR, and 2 (2%) spastic reactive CR. Compared with normal and borderline CRs (i.e., CR patterns with distinct, antegrade peristalsis), patients with impaired/disordered and absent CRs demonstrated significantly greater time since fundoplication (2.4 (0.6–6.8) vs. 8.9 (2.6–14.5) years; p = 0.002), greater esophageal body width on esophagram (n = 50; 2.3 (2.0–2.8) vs. 2.9 (2.4–3.6) cm; p = 0.013), and lower EGJ‐DI (4.3 (2.7–5.4) vs. 2.6 (1.7–3.7) mm2/mmHg; p = 0.001). Intact fundoplications had significantly higher rates of normal CRs compared to anatomically abnormal (i.e., tight, disrupted, slipped, herniated) fundoplications (9 (28%) vs. 5 (9%); p = 0.032), but there were no differences in EGJ‐DI or EGJ maximum diameter.

Conclusions & Inferences

Symptomatic post‐fundoplication patients were characterized by frequent abnormal secondary peristalsis after fundoplication, potentially worsening with time after fundoplication or related to EGJ outflow resistance.
The SlGRAS9‐SlZHD17 transcriptional cascade regulates chlorophyll and carbohydrate metabolism contributing to fruit quality traits in tomato
Authors: Shi Yuan , Hu Guojian , Wang Yan , Liang Qin , Su Deding , Lu Wang , Deng Wei , Bouzayen Mondher , Liu Yudong , Li Zhengguo , Huang Baowen
Published: January 2024

Some essential components of fleshy fruits are dependent on photosynthetic activity and carbohydrate metabolism. Nevertheless, the regulatory mechanisms linking chlorophyll and carbohydrate metabolism remain partially understood.

Here, we uncovered the role of SlGRAS9 and SlZHD17 transcription factors in controlling chlorophyll and carbohydrate accumulation in tomato fruit. Knockout or knockdown of SlGRAS9 or SlZHD17 resulted in marked increase in chlorophyll content, reprogrammed chloroplast biogenesis and enhanced accumulation of starch and soluble sugars.

Combined genome‐wide transcriptomic profiling and promoter‐binding experiments unveiled a complex mechanism in which the SlGRAS9/SlZHD17 regulatory module modulates the expression of chloroplast and sugar metabolism either via a sequential transcriptional cascade or through binding of both TFs to the same gene promoters, or, alternatively, via parallel pathways where each of the TFs act on different target genes. For instance, the regulation of SlAGPaseS1 and SlSUS1 is mediated by SlZHD17 whereas that of SlVI and SlGLK1 occurs only through SlGRAS9 without the intervention of SlZHD17. Both SlGRAS9 and SlZHD17 can also directly bind the promoter of SlPOR‐B to regulate its expression.

Taken together, our findings uncover two important regulators acting synergistically to manipulate chlorophyll and carbohydrate accumulation and provide new potential breeding targets for improving fruit quality in fleshy fruits.
The global distribution of angiosperm genome size is shaped by climate
Authors: Bureš Petr , Elliott Tammy L. , Veselý Pavel , Šmarda Petr , Forest Félix , Leitch Ilia J. , Nic Lughadha Eimear , Soto Gomez Marybel , Pironon Samuel , Brown Matilda J. M. , Šmerda Jakub , Zedek František
Published: January 2024

Angiosperms, which inhabit diverse environments across all continents, exhibit significant variation in genome sizes, making them an excellent model system for examining hypotheses about the global distribution of genome size. These include the previously proposed large genome constraint, mutational hazard, polyploidy‐mediated, and climate‐mediated hypotheses.

We compiled the largest genome size dataset to date, encompassing 16 017 (> 5% of known) angiosperm species, and analyzed genome size distribution using a comprehensive geographic distribution dataset for all angiosperms.

We observed that angiosperms with large range sizes generally had small genomes, supporting the large genome constraint hypothesis. Climate was shown to exert a strong influence on genome size distribution along the global latitudinal gradient, while the frequency of polyploidy and the type of growth form had negligible effects. In contrast to the unimodal patterns along the global latitudinal gradient shown by plant size traits and polyploid proportions, the increase in angiosperm genome size from the equator to 40–50°N/S is probably mediated by different (mostly climatic) mechanisms than the decrease in genome sizes observed from 40 to 50°N northward.

Our analysis suggests that the global distribution of genome sizes in angiosperms is mainly shaped by climatically mediated purifying selection, genetic drift, relaxed selection, and environmental filtering.
Trait–environment relationships are timescale dependent
Authors: Cui Erqian
Published: January 2024

This article is a Commentary on Famiglietti et al. (2024), 241: 2423–2434.
Live dietary microbes and reduced prevalence of periodontitis: A cross‐sectional study
Authors: Lin Jie , Yang Hui , Lin Zhengshen , Xu Lingqiao
Published: January 2024

Objective

Investigate the link between live dietary microbe consumption and the prevalence of periodontitis.

Methods and Materials

National health and nutrition examination survey (2009–2014) data was used to assess the association among adults. Live dietary microbe intake was categorized as low or medium to high. Regression models were employed to assess this association, adjusting for demographic variables and other covariates. Examined dose–response relationship and conducted subgroup analyses by ethnicity, age and gender. Multiplicative interactions were evaluated using likelihood ratio tests.

Results

The analysis included 8574 participants. After adjusting for various factors including age, gender, ethnicity, dietary habits, dietary inflammatory index, alcohol consumption, smoking status, hypertension, diabetes mellitus and oral health behaviors, individuals with daily intake of medium to high levels of live dietary microbes showed a significantly reduced risk of periodontitis compared to those who did not consume such microbes with a dose–response trend (p for trend <0.0001, p < 0.01). Significant differences in the impact of live microbe intake on periodontitis were also observed across different age groups in all Models (p for interaction ≤0.05).

Conclusion

Medium to high live dietary microbe consumption independently correlates with lower periodontitis risk, irrespective of traditional risk factors and demographics.
Single operator experience, learning curve, outcomes, and insights gained with conduction system pacing
Authors: Marion William , Schanz John D. , Patel Sonali , Co Michael Lawrenz , Pavri Behzad B.
Published: January 2024

Background

Conduction system pacing (CSP) is increasingly utilized to prevent and correct dyssynchrony. Barriers to CSP adoption include limited training, methodologic variability, laboratory slot allocation, and few data on learning curves. We report learning curves/clinical outcomes from a single experienced electrophysiologist who was new to CSP, and share gained insights.

Methods

Retrospective analysis of all patients who underwent attempted CSP implantation (2016–2023). Patient characteristics, ECGs, echocardiograms, fluoroscopy/procedure times, lead data were recorded at implant and follow‐up.

Results

CSP leads were implanted successfully in 167/191(87.4%) patients with a follow‐up of 278 ± 378 days. His‐bundle pacing (HBP = 59) and left‐bundle‐area pacing (LBAP = 108) had similar procedure/fluoroscopy times, QRS duration decreases, and ejection fraction improvements (all p > NS). Eight HBP lead revisions were required for high capture thresholds LBAP demonstrated lower pacing thresholds, higher lead impedances, and greater R‐wave amplitudes at implant and follow‐up. After 25 HBP cases, implant pacing thresholds, fluoroscopy, procedural times did not decrease. After 25 LBAP cases, there were significant decreases in all these parameters (p < 0.05). A separate analysis in LBAP patients with recorded Purkinje signals showed no differences in paced ECG characteristics between patients with pre‐ QRS Purkinje signals versus patients with Purkinje signals post‐QRS onset.

Conclusions

Experienced implanters who are new to CSP can achieve steady‐state procedural/fluoroscopy times after a learning curve of 25 implants. LBAP showed lower capture thresholds and higher success rates. Adequate depth of lead deployment (as determined by published parameters) does not require Purkinje potential to be pre‐QRS. Operators new to CSP.can forego HBP and directly implement LBAP.
A short RP tachycardia in congenitally corrected transposition. What is the mechanism?
Authors: Bhargav Anish , Sukumaran Suresh Kumar , Balaguru Sridhar , Selvaraj Raja J.
Published: January 2024

A 51‐year‐old female with congenitally corrected transposition of great arteries (CCTGA), situs solitus, dextrocardia, atrial septal defect and persistent left superior vena cava underwent electrophysiology study for recurrent palpitations with documented narrow complex, short RP tachycardia. With a catheter in the region of the anterior mitral annulus, a His signal was recorded and HV interval was 35 msec. Tachycardia was induced with a ventricular extrastimulus. During the tachycardia there was 1:1 ventriculo‐atrial conduction and central atrial activation with a VA interval of 20 msec. The recorded His signal could be seen after the QRS. What is the mechanism of the tachycardia?
Protamine dosing and its impact in cardiac surgery transfusion practice—A retrospective bi‐institutional analysis
Authors: Mondal Samhati , Abuelkasem Ezeldeen , Vesselinov Roumen , Henderson Reney , Choi Seung , Mousa Ahmad , Zaza Khaled J. , Tanaka Kenichi A.
Published: January 2024

Background

Bleeding after cardiac surgery is common and continues to require 10–20% of the national blood supply. Transfusion of allogeneic blood is associated with increased morbidity and mortality. Excessive protamine in the absence of circulating heparin after weaning off CPB can cause anticoagulation and precipitate bleeding. Hence, adequate dose calculation of protamine is crucial yet under evaluated.

Study Design

Retrospective cohort study.

Methods

We conducted a retrospective bi‐institutional analysis of cardiac surgical patients who underwent cardiopulmonary bypass (CPB)‐assisted cardiac surgery to assess the impact of protamine dosing in transfusion practice. Total 762 patients were identified from two institutions using electronic medical records and the Society of Thoracic Surgery (STS) database who underwent cardiac surgery using CPB. Patients were similar in demographics and other baseline characteristics. We divided patients into two groups based on mg of protamine administered to neutralize each 100 U of unfractionated heparin (UFH)—low‐ratio group (Protamine: UFH ≤ 0.8) and high‐ratio group (Protamine: UFH > 0.8).

Results

We observed a higher rate of blood transfusion required in high‐ratio group (ratio >0.8) compared with low‐ratio group (ratio ≤0.8) (p < .001). The increased requirement was consistently demonstrated for intraoperative transfusions of red blood cells, plasma, platelets, and cryoprecipitate.

Conclusion

High protamine to heparin ratio may cause increased bleeding and transfusion in cardiac surgical patients. Protamine to heparin ratio of 0.8 or lower is sufficient to neutralize circulating heparin after weaning off cardiopulmonary bypass.
Phylogenetic relationships among horseshoe bats within the Rhinolophus ferrumequinum group (Mammalia, Chiroptera)
Authors: Uvizl Marek , Kotyková Varadínová Zuzana , Benda Petr
Published: January 2024

The horseshoe bats of the Rhinolophus ferrumequinum group form a well‐defined lineage within the Afro‐Palaearctic clade of the genus Rhinolophus. The group currently comprises four species widely distributed across the Palaearctic and Afrotropic regions: R. bocharicus (Central Asia), R. clivosus (from northern Africa and the Levant through Arabian Peninsula and eastern Africa to southern Africa), R. ferrumequinum (from western Europe and northern Africa through the Balkans and Middle East to Central Asia and India) and R. nippon (southern and central China, Korea, and Japan). The broad ranges and geographical variations within these species have led to the proposal of numerous subspecies. The phylogenetic relationships and intraspecific variation of the R. ferrumequinum group were investigated using a genetic approach. One mitochondrial marker and five nuclear markers were sequenced and supplemented with available sequences for all four species of the group. Our study revealed five major lineages within the R. ferrumequinum group, resulting in the recognition of four currently known species and identification of a new species. The prior name available for this lineage/species is R. acrotis. The relationships between the lineages varied depending on the chosen marker, leaving the interspecific relations within the ferrumequinum group unresolved. In addition, the results indicated that R. clivosus experienced historic introgression from northern Africa and the Levant, resulting in replacement of its mtDNA by that of R. ferrumequinum. Together, this study introduces a new Rhinolophus species, which increases the number of species in the ferrumequinum group to five.
Developing a Computational Model of Lungs for Patients With Acute Respiratory Distress Syndrome
Authors: Chavan Chinmay , Zainab Asma , Banerjee Debjyoti
Published: January 2024

Acute respiratory distress syndrome (ARDS) is a condition secondary to direct or indirect insult to lungs, leading to acute respiratory failure, and is associated with high mortality. Majority of the ARDS patients require mechanical ventilation, which acts as double-edged sword. Ventilator induced lung injury (VILI) is considered secondary to high inspiratory pressure and cyclical opening during inspiration, and collapse during expiration as suggested by ARDS network clinical trials. Other mechanism for VILI exist secondary to heterogeneous ventilation. To enumerate these mechanisms leading to VILI, a computational fluids dynamics (CFD) study was performed in this study to explore the flow patterns and the pressure distribution in a human tracheobronchial airway model from third to sixth generation branches. The authors validated the computational methodology and analyzed the results to obtain velocity profiles in the primary and secondary flow directions. The study investigated the role of various flow velocities corresponding to Reynolds number (Re) from 100 to 2000 on the pressure drops along branches and bifurcation zones. The identification of secondary flow patterns was critical in understanding the development of asymmetric velocity profiles in the triple bifurcation geometry. The observed patterns in pressure drops and velocity profiles over the laminar flow regime pave the path toward further development of a numerical model to aid treatment for patients with ARDS.
Degradation of GaN field emitter arrays induced by O2 exposure
Authors: Farsad Asadi Reza , Zheng Tao , Shih Pao-Chuan , Palacios Tomás , Akinwande Akintunde I. , Gnade Bruce
Published: January 2024

Field emitter arrays (FEAs) have the potential to operate at high frequencies and in harsh environments. However, they have been shown to degrade under oxidizing environments. Studying the effect of O2 on FEAs can help to understand the degradation mechanisms, identify the requirements for vacuum packaging, and estimate the lifetime of the device. In this work, the effect of O2 exposure on 100 × 100 gallium-nitride-field emitter arrays (GaN-FEAs) was studied. The GaN-FEAs were operated at 6 × 10−10 Torr with a 1000 V DC anode voltage and a 50 V DC gate voltage, where the anode current was 1 μA and the gate current was ≤4 nA. The devices were exposed to 10−7, 10−6, and 10−5 Torr of O2 for 100 000 L. The anode current dropped by 50% after 300 L and 98% after 100 000 L. It was observed that the degradation depends on the exposure dose, rather than pressure. The devices mostly degrade when they are ON, confirmed by exposing the device to O2 when the gate voltage was off, and also by the relation between the degradation and duty cycle when pulsing the gate. The results of O2 exposure were compared to Ar exposure to determine whether sputtering and changes in the surface geometry were the primary cause of degradation. The results suggest that changes in the work function and surface chemistry are the cause of emission degradation of GaN-FEA induced by O2.
Time-dependent effects of BRAF-V600E on cell cycling, metabolism, and function in engineered myocardium
Authors: Strash Nicholas , DeLuca Sophia , Janer Carattini Geovanni L. , Chen Yifan , Wu Tianyu , Helfer Abbigail , Scherba Jacob , Wang Isabella , Jain Mehul , Naseri Ramona , Bursac Nenad
Published: January 2024

Candidate cardiomyocyte (CM) mitogens such as those affecting the extracellular signal–regulated kinase (ERK) signaling pathway represent potential targets for functional heart regeneration. We explored whether activating ERK via a constitutively active mutant of B-raf proto-oncogene (BRAF),
BRAF-V600E
(caBRAF), can induce proproliferative effects in neonatal rat engineered cardiac tissues (ECTs). Sustained CM-specific caBRAF expression induced chronic ERK activation, substantial tissue growth, deficit in sarcomeres and contractile function, and tissue stiffening, all of which persisted for at least 4 weeks of culture. caBRAF-expressing CMs in ECTs exhibited broad transcriptomic changes, shift to glycolytic metabolism, loss of connexin-43, and a promigratory phenotype. Transient, doxycycline-controlled caBRAF expression revealed that the induction of CM cycling is rapid and precedes functional decline, and the effects are reversible only with short-lived ERK activation. Together, direct activation of the BRAF kinase is sufficient to modulate CM cycling and functional phenotype, offering mechanistic insights into roles of ERK signaling in the context of cardiac development and regeneration.
Molecular mechanisms and evolutionary robustness of a color switch in proteorhodopsins
Authors: Mao Jiafei , Jin Xinsheng , Shi Man , Heidenreich David , Brown Lynda J. , Brown Richard C. D. , Lelli Moreno , He Xiao , Glaubitz Clemens
Published: January 2024

Proteorhodopsins are widely distributed photoreceptors from marine bacteria. Their discovery revealed a high degree of evolutionary adaptation to ambient light, resulting in blue- and green-absorbing variants that correlate with a conserved glutamine/leucine at position 105. On the basis of an integrated approach combining sensitivity-enhanced solid-state nuclear magnetic resonance (ssNMR) spectroscopy and linear-scaling quantum mechanics/molecular mechanics (QM/MM) methods, this single residue is shown to be responsible for a variety of synergistically coupled structural and electrostatic changes along the retinal polyene chain, ionone ring, and within the binding pocket. They collectively explain the observed color shift. Furthermore, analysis of the differences in chemical shift between nuclei within the same residues in green and blue proteorhodopsins also reveals a correlation with the respective degree of conservation. Our data show that the highly conserved color change mainly affects other highly conserved residues, illustrating a high degree of robustness of the color phenotype to sequence variation.
Optimal trade-off control in machine learning–based library design, with application to adeno-associated virus (AAV) for gene therapy
Authors: Zhu Danqing , Brookes David H. , Busia Akosua , Carneiro Ana , Fannjiang Clara , Popova Galina , Shin David , Donohue Kevin C. , Lin Li F. , Miller Zachary M. , Williams Evan R. , Chang Edward F. , Nowakowski Tomasz J. , Listgarten Jennifer , Schaffer David V.
Published: January 2024

Adeno-associated viruses (AAVs) hold tremendous promise as delivery vectors for gene therapies. AAVs have been successfully engineered—for instance, for more efficient and/or cell-specific delivery to numerous tissues—by creating large, diverse starting libraries and selecting for desired properties. However, these starting libraries often contain a high proportion of variants unable to assemble or package their genomes, a prerequisite for any gene delivery goal. Here, we present and showcase a machine learning (ML) method for designing AAV peptide insertion libraries that achieve fivefold higher packaging fitness than the standard NNK library with negligible reduction in diversity. To demonstrate our ML-designed library’s utility for downstream engineering goals, we show that it yields approximately 10-fold more successful variants than the NNK library after selection for infection of human brain tissue, leading to a promising glial-specific variant. Moreover, our design approach can be applied to other types of libraries for AAV and beyond.
1.63-billion-year-old multicellular eukaryotes from the Chuanlinggou Formation in North China
Authors: Miao Lanyun , Yin Zongjun , Knoll Andrew H. , Qu Yuangao , Zhu Maoyan
Published: January 2024

Multicellularity is key to the functional and ecological success of the Eukarya, underpinning much of their modern diversity in both terrestrial and marine ecosystems. Despite the widespread occurrence of simple multicellular organisms among eukaryotes, when this innovation arose remains an open question. Here, we report cellularly preserved multicellular microfossils (
Qingshania magnifica
) from the ~1635-million-year-old Chuanlinggou Formation, North China. The fossils consist of large uniseriate, unbranched filaments with cell diameters up to 190 micrometers; spheroidal structures, possibly spores, occur within some cells. In combination with spectroscopic characteristics, the large size and morphological complexity of these fossils support their interpretation as eukaryotes, likely photosynthetic, based on comparisons with extant organisms. The occurrence of multicellular eukaryotes in Paleoproterozoic rocks not much younger than those containing the oldest unambiguous evidence of eukaryotes as a whole supports the hypothesis that simple multicellularity arose early in eukaryotic history, as much as a billion years before complex multicellular organisms diversified in the oceans.
Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome
Authors: Lana-Elola Eva , Aoidi Rifdat , Llorian Miriam , Gibbins Dorota , Buechsenschuetz Callan , Bussi Claudio , Flynn Helen , Gilmore Tegan , Watson-Scales Sheona , Haugsten Hansen Marie , Hayward Darryl , Song Ok-Ryul , Brault Véronique , Herault Yann , Deau Emmanuel , Meijer Laurent , Snijders Ambrosius P. , Gutierrez Maximiliano G. , Fisher Elizabeth M. C. , Tybulewicz Victor L. J.
Published: January 2024

Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21). DS is a gene dosage disorder that results in multiple phenotypes including congenital heart defects. This clinically important cardiac pathology is the result of a third copy of one or more of the approximately 230 genes on Hsa21, but the identity of the causative dosage–sensitive genes and hence mechanisms underlying this cardiac pathology remain unclear. Here, we show that hearts from human fetuses with DS and embryonic hearts from the Dp1Tyb mouse model of DS show reduced expression of mitochondrial respiration genes and cell proliferation genes. Using systematic genetic mapping, we determined that three copies of the dual-specificity tyrosine phosphorylation–regulated kinase 1A (Dyrk1a) gene, encoding a serine/threonine protein kinase, are associated with congenital heart disease pathology. In embryos from Dp1Tyb mice, reducingDyrk1agene copy number from three to two reversed defects in cellular proliferation and mitochondrial respiration in cardiomyocytes and rescued heart septation defects. Increased dosage of DYRK1A protein resulted in impairment of mitochondrial function and congenital heart disease pathology in mice with DS, suggesting that DYRK1A may be a useful therapeutic target for treating this common human condition.
Requirement of microtubules for secretion of a micronemal protein CpTSP4 in the invasive stage of the apicomplexan
Cryptosporidium parvum
Authors: Wang Dongqiang , Jiang Peng , Wu Xiaodong , Zhang Ying , Wang Chenchen , Li Meng , Liu Mingxiao , Yin Jigang , Zhu Guan
Published: January 2024

Cryptosporidium parvum
is a globally distributed apicomplexan parasite infecting humans and/or animals. Like other apicomplexans, it possesses specialized secretory organelles in the zoites, in which micronemes discharge molecules to facilitate the movement and invasion of zoites. Although past and recent studies have identified several proteins in cryptosporidial micronemes, our understanding of the composition, secretory pathways, and domain-ligand interactions of micronemal proteins remains limited. This study identifies a new micronemal protein, namely, CpTSP4, that is discharged during excystation, gliding, and invasion of
C. parvum
sporozoites. The CpTSP4 secretion depends on the intracellular trafficking on the two
Cryptosporidium
-unique microtubes that could be blocked by kinesin-5/Eg5 inhibitors. Additionally, a novel heparin-binding motif is identified and biochemically validated, which contributes to the nanomolar binding affinity of CpTSP4 to host cells. These findings indicate that kinesin-dependent microtubular trafficking is critical to CpTSP4 secretion, and heparin/heparan sulfate is one of the ligands for this micronemal protein.