bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omada: robust clustering of transcriptomes through multiple testing
Authors: Kariotis Sokratis , Tan Pei Fang , Lu Haiping , Rhodes Christopher J , Wilkins Martin R , Lawrie Allan , Wang Dennis 
Published: July 2024

Abstract

Background
Cohort studies increasingly collect biosamples for molecular profiling and are observing molecular heterogeneity. High-throughput RNA sequencing is providing large datasets capable of reflecting disease mechanisms. Clustering approaches have produced a number of tools to help dissect complex heterogeneous datasets, but selecting the appropriate method and parameters to perform exploratory clustering analysis of transcriptomic data requires deep understanding of machine learning and extensive computational experimentation. Tools that assist with such decisions without prior field knowledge are nonexistent. To address this, we have developed Omada, a suite of tools aiming to automate these processes and make robust unsupervised clustering of transcriptomic data more accessible through automated machine learning–based functions.

Findings
The efficiency of each tool was tested with 7 datasets characterized by different expression signal strengths to capture a wide spectrum of RNA expression datasets. Our toolkit’s decisions reflected the real number of stable partitions in datasets where the subgroups are discernible. Within datasets with less clear biological distinctions, our tools either formed stable subgroups with different expression profiles and robust clinical associations or revealed signs of problematic data such as biased measurements.

Conclusions
In conclusion, Omada successfully automates the robust unsupervised clustering of transcriptomic data, making advanced analysis accessible and reliable even for those without extensive machine learning expertise. Implementation of Omada is available at http://bioconductor.org/packages/omada/.
Tensions in Finland’s ex ante constitutional review: The interplay of politics, law, and media
Authors: Dahlberg Maija , Kantola Anu 
Published: July 2024

Abstract
Constitutional review has become increasingly subject to heated political debates and struggles. While the constitutionality of laws is often reviewed after the laws have entered into force (ex post), this article examines an ex ante constitutional review assessing the political tensions and struggles typical of it. We examine the Finnish experience, drawing on forty-nine semi-structured interviews among key actors involved in the work of the Constitutional Law Committee (CLC) of the Finnish Parliament, which controls the constitutionality of laws before they enter into force. We find that tensions between law and politics are an important element of the ex ante constitutional review and show how they emerge in the work of the CLC and how the key actors involved in the review seek to control and manage them. We also suggest that the political tensions surrounding the ex ante review have intensified in recent decades and find three main reasons for this development. First, as constitutional and human rights have found their way into an increasingly wide range of political matters, political tensions in constitutional assessment have been aggravated. Second, external legal experts have begun to play a more prominent and public role in the review process, adding to the public tensions relating to constitutional interpretation. Third, the media and journalists have become increasingly interested in constitutional questions, which further inflames tensions. As a result, we suggest that scholars should increasingly explore and make transparent these de facto practices in constitutional review.
Technological innovation structure and driving factors of China’s photovoltaic industry: based on patent innovation network
Authors: Guo Qing , Li Junyi 
Published: July 2024

Abstract
Photovoltaic (PV) industry is a strategic emerging industry in China, which provides risk resistance and autonomy for energy security by its technology innovation structure. The article conducts a comparative study on the technological innovation of PV industry between China and major PV powers to master the technological innovation structure of China’s PV industry. For this purpose, the article analyzes the relative evolution of the data above and profiles the structure of PV industry technological innovation by employing the social network analysis (SNA). Multiple linear regression was applied to analyze driving factors of the PV industry and its mechanism. The results show that: (i) Compared with other major economies, China’s PV industry is characterized by hysteresis, rapid advancement, and industry chain bias towards the midstream and downstream. (ii) The connection of the whole technological network gradually tends to be direct and diversified, but the tightness of the integral connection is decreasing. (iii) China’s siliceous resource retention is the biggest driving force for the development of PV industry, followed by the investment intensity of research and developement (R&D) in the corresponding industry. Based on the above findings, the article puts forward countermeasure recommendations.
Confronting Medical Diploma Mills: State Licensing Boards, Legislatures, and the Limits of Medical Authority in the 1920s
Authors: Appel Toby A 
Published: July 2024

Abstract
In the standard story of the rise of professional authority in medicine in the 1920s, state medical licensing boards were partners in a coalition, led by the American Medical Association, to radically improve medical education. Boards obtained state laws that limited admission to licensing examinations to graduates of schools approved by the AMA, thus bringing about the rapid demise of low-quality schools by about 1925. The reality at the state level was quite different, however. Medical examining boards containing homeopaths, eclectics, and sometimes osteopaths could be far from reliable partners. Passing laws to benefit the medical profession was exceedingly difficult and dependent on local medical politics. Through the lens of a major medical diploma mill scandal revealed by a journalist in 1923, this paper examines reform efforts in three states greatly affected by the scandal: Missouri, where the scandal originated, Connecticut, and Massachusetts. In each of these states, graduates of low-quality schools as well as fake doctors from diploma mills were able to take a state examination and practice. This paper argues that the AMA, far from being the major player in the elimination of inadequate schools, could set standards but had to stay on the sidelines.
Functional studies of McSTE24, McCYP305a1, and McJHEH, three essential genes act in cantharidin biosynthesis in the blister beetle (Coleoptera: Meloidae)
Authors: Huang Yi , Shen Ling , Du Fang , Wang Zhongkang , Yin Youping 
Published: July 2024

Abstract
Cantharidin is a toxic defensive substance secreted by most blister beetles when attacked. It has been used to treat many complex diseases since ancient times and has recently regained popularity as an anticancer agent. However, the detailed mechanism of the cantharidin biosynthesis has not been completely addressed. In this study, we cloned McSTE24 (encoding STE24 endopeptidase) from terpenoid backbone pathway, McCYP305a1 (encoding cytochrome P450, family 305) and McJHEH [encoding subfamily A, polypeptide 1 and juvenile hormone (JH) epoxide hydrolase] associated to JH synthesis/degradation in the blister beetle Mylabris cichorii (Linnaeus, 1758, Coleoptera: Meloidae). Expression pattern analyses across developmental stages in adult males revealed that the expressions of 3 transcripts were closely linked to cantharidin titer exclusively during the peak period of cantharidin synthesis (20–25 days old). In contrast, at other stages, these genes may primarily regulate different biological processes. When RNA interference with double-stranded RNA suppressed the expressions of the 3 genes individually, significant reductions in cantharidin production were observed in males and also in females following McJHEH knockdown, indicating that these 3 genes might primarily contribute to cantharidin biosynthesis in males, but not in females, while females could self-synthesis a small amount of cantharidin. These findings support the previously hypothesized sexual dimorphism in cantharidin biosynthesis during the adult phase. McCYP305a1 collaborates with its upstream gene McSTE24 in cantharidin biosynthesis, while McJHEH independently regulates cantharidin biosynthesis in males.
Mechanics Institutes in Mid-Nineteenth-Century Victoria: Racial Difference and Liberalism in the Settler Colony
Authors: Boucher Leigh 
Published: July 2024

ABSTRACT
In the second half of the nineteenth century, mechanics institutes proliferated across the Australian colonies at such a rate that, by 1900, they were more widespread, proportional to population, than in Britain. This article examines the first 30 years of their development in colonial Victoria to offer a new interpretation of their deep entanglement with settler colonial liberalism. As in Britain, the Victoria mechanics institutes largely failed to deliver technical education to working-class men. However, the men who propelled their proliferation had much wider hopes for their pedagogic function in the settler colony. This article examines how the twin forces of political liberalism and settler colonialism underwrote and shaped mechanics institutes in mid-nineteenth-century Victoria. Examining the ideas of colonial liberals who propelled their proliferation and the activities that took place within them, it becomes clear that these institutes were imagined to cultivate certain kinds of settler Britons, capable of bearing the freedoms of an emerging settler modernity. At the same time, moreover, they both legitimated and implemented a settler colonial project of dispossession and demographic replacement. Mechanics institutes, I argue, were thus agents of both settler colonial destruction and liberal cultivation.
Heroes and villains: opposing narrative roles engage neural synchronization in the inferior frontal gyrus
Authors: Ryu Hayoung , Kim M Justin 
Published: July 2024

Abstract
Neuroscientific studies have highlighted the role of the default mode network (DMN) in processing narrative information. Here, we examined whether the neural synchronization of the DMN tracked the appearances of protagonists and antagonists when viewing highly engaging, socially rich audiovisual narratives. Using inter-subject correlation analysis on two independent, publicly available movie-watching fMRI datasets, we computed whole-brain neural synchronization during the appearance of the protagonists and antagonists. Results showed that the inferior frontal gyrus (IFG) had higher ISC values during the appearance of the protagonists than the antagonists. Importantly, these findings were generalized in both datasets. We discuss the results in the context of information integration and emotional empathy, which are relevant to functions of the IFG. Our study presents generalizable evidence that the IFG show distinctive synchronization patterns due to differences in narrative roles.
Aging AdipoR2‐deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids
Authors: Ruiz Mario , Devkota Ranjan , Bergh Per‐Olof , Nik Ali Moussavi , Blid Sköldheden Sebastian , Mondejar‐Duran Jorge , Tufvesson‐Alm Maximilian , Bohlooly‐Y Mohammad , Sanchez Diego , Carlsson Peter , Henricsson Marcus , Jerlhag Elisabet , Borén Jan , Pilon Marc 
Published: July 2024

AbstractTo investigate how the fatty acid composition of brain phospholipids influences brain‐specific processes, we leveraged the AdipoR2 (adiponectin receptor 2) knockout mouse model in which the brain is enlarged, and cellular membranes are excessively rich in saturated fatty acids. Lipidomics analysis of brains at 2, 7, and 18 months of age showed that phosphatidylcholines, which make up about two‐thirds of all cerebrum membrane lipids, contain a gross excess of saturated fatty acids in AdipoR2 knockout mice, and that this is mostly attributed to an excess palmitic acid (C16:0) at the expense of oleic acid (C18:1), consistent with a defect in fatty acid desaturation and elongation in the mutant. Specifically, there was a ~12% increase in the overall saturated fatty acid content within phosphatidylcholines and a ~30% increase in phosphatidylcholines containing two palmitic acids. Phosphatidylethanolamines, sphingomyelins, ceramides, lactosylceramides, and dihydroceramides also showed an excess of saturated fatty acids in the AdipoR2 knockout mice while nervonic acid (C24:1) was enriched at the expense of shorter saturated fatty acids in glyceroceramides. Similar defects were found in the cerebellum and myelin sheaths. Histology showed that cell density is lower in the cerebrum of AdipoR2 knockout mice, but electron microscopy did not detect reproducible defects in the ultrastructure of cerebrum neurons, though proteomics analysis showed an enrichment of electron transport chain proteins in the cerebellum. Behavioral tests showed that older (33 weeks old) AdipoR2 knockout mice are hyperactive and anxious compared to control mice of a similar age. Also, in contrast to control mice, the AdipoR2 knockout mice do not gain weight in old age but do have normal lifespans. We conclude that an excess fatty acid saturation in brain phospholipids is accompanied by hyperactivity but seems otherwise well tolerated.
The detrimental role of galectin‐3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity
Authors: Jiménez‐González Sara , Delgado‐Valero Beatriz , Islas Fabian , Romero‐Miranda Ana , Luaces María , Ramchandani Bunty , Cuesta‐Corral María , Montoro‐Garrido Alejandro , Martínez‐Martínez Ernesto , Cachofeiro Victoria 
Published: July 2024

AbstractThe association between cardiac fibrosis and galectin‐3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin‐3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese‐infarcted rats. The inhibitor of galectin‐3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4‐phenylbutyric acid (4‐PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight‐obese patients who suffered a first MI showed higher circulating galectin‐3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal‐weight patients. A correlation was observed between galectin‐3 levels and extracellular volume. Obese‐infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin‐3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin‐3. Both MCP and 4‐PBA not only reduced cardiac fibrosis, oxidative stress, galectin‐3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin‐3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin‐3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.
Continuous Glucose Monitoring–Derived Differences in Pregnancies With and Without Adverse Perinatal Outcomes
Authors: Durnwald Celeste , Beck Roy W. , Li Zoey , Norton Elizabeth , Bergenstal Richard , Johnson Mary , Dunnigan Sean , Banfield Matthew , Krumwiede Katie , Sibayan Judy , Calhoun Peter , Carlson Anders L. 
Published: July 2024

OBJECTIVE:
To evaluate whether continuous glucose monitoring (CGM)–derived glycemic patterns observed throughout pregnancy were associated with adverse perinatal outcomes, specifically fetal growth disorders and hypertensive disorders of pregnancy (HDP).

METHODS:
We conducted a prospective observational study of individuals with viable singleton pregnancies and screening hemoglobin A1c levels less than 6.5%. Those with preexisting diabetes were excluded. Enrollment occurred at the earliest gestational age before 17 weeks. Participants wore blinded continuous glucose monitors consecutively as willing until delivery. Those with at least 14 days of CGM data were included in analysis. Rates of large-for-gestational-age (LGA) neonates, small-for-gestational age (SGA) neonates, and HDP were assessed. Continuous glucose monitoring–derived glycemic metrics were calculated, including mean glucose level and percent time above and below thresholds. Two-sample t tests were used to compare glycemic metrics between participants with and without adverse perinatal outcomes.

RESULTS:
Of 937 participants enrolled, 760 met inclusion criteria. Those delivering LGA neonates or who were diagnosed with HDP had higher mean glucose levels (102±9 vs 100±8, P=.01 and 103±8 vs 99±8, P<.001) and spent more time above 120 mg/dL (median 16% vs 12%, P=.006, and 16% vs 12%, P<.001, respectively) and above 140 mg/dL (median 3.9% vs 2.8%, P=.006, and 3.5% vs 2.8%, P<.001, respectively) throughout gestation than those without these outcomes. These findings were present regardless of gestational diabetes mellitus status. Participants with SGA neonates had lower mean glucose levels (97±7 vs 101±8, P=.01) and spent less time above 140 mg/dL (median 1.6% vs 2.3%, P=.01) and more time below 63 mg/dL (median 3.0% vs 2.3%, P=.02) than those without SGA neonates.

CONCLUSION:
Individuals with LGA neonates or HDP exhibit a slightly higher mean glucose levels and spend more time hyperglycemic in early pregnancy than those who do not experience these outcomes.
In vivo Assessment of AMP2, a Novel Ceramic-Binding BMP-2, in Ovine Lumbar Interbody Fusion
Authors: Christou Chris , Varcoe Tamara , Williams Georgia , Heil Todd , Leifeld Sarah , Park Hyeon , Peckham Steve , Stewart David , Greenbaum John , Wang Tian , Pelletier Matthew , Walsh William , Alvarez Luis 
Published: July 2024

Study Design.
Assessment of bone formation in an ovine interbody fusion study.

Objective.
To compare OsteoAdapt SP, which consists of AMP-2, a modified variant of recombinant human bone morphogenetic protein (rhBMP-2) bound to a tricalcium phosphate-containing carrier, to autologous iliac crest bone graft (ICBG) in a lumbar interbody fusion model.

Summary of Background Data.
Treatment of lumbar disk degeneration often involves spinal fusion to reduce pain and motion at the affected spinal segment by insertion of a cage containing bone graft material. Three graft materials were compared in this study—ICBG and OsteoAdapt SP (low or high dose).

Methods.
The sheep underwent lateral lumbar fusion surgery with PEEK or Titanium interbody cages packed with OsteoAdapt SP (low or high dose) or ICBG. Outcomes were evaluated at 8-, 16- and 26- weeks. Newly formed bone quality, bone mineralization, and fusion were assessed by manual palpation, qualitative and semi-quantitative histopathology, histomorphometry, computed tomography (CT), and micro-CT (mCT) analysis.

Results.
OsteoAdapt SP was implanted into 43 animals and ICBG into 21 animals (L3-L4). No group showed evidence of systemic toxicity by multiple assessments. All levels were fused by manual palpation at 26 weeks. Serial CT scans showed increasing fusion scores over time. Both doses of OsteoAdapt SP resulted in robust new bone formation and progression of fusion in the interbody cage. Range of motion tests for treatment groups was lower compared with ICBG at 8- and 16 weeks. Similarly, histology at eight weeks demonstrated more robust new bone formation for both OsteoAdapt SP groups compared to autograft.

Conclusion.
We have demonstrated the preclinical safety and efficacy of OsteoAdapt SP in a clinically relevant large animal model, supporting faster and more robust new bone formation within the interbody cage, comparable to or better than the gold standard, ICBG, in all measures.
Experts' Views on Children's Access to Community-Based Therapeutic and Education Services After Genomic Sequencing Results
Authors: Outram Simon M. , Brown Julia E. H. , Norstad Matthew , Zamora Astrid N. , Ackerman Sara L. 
Published: July 2024

ABSTRACT:

Objective:
To evaluate how community-based experts respond to families seeking therapeutic and educational support services after pediatric genomic sequencing for rare conditions.

Methods:
We interviewed 15 experts in the provision of community-based services for children with intellectual differences, developmental differences, or both, as part of a large study examining the utility of exome sequencing.

Results:
Interviewees highlighted the complexity of the overall referral and assessment system for therapeutic or educational needs, that genetic diagnoses are secondary to behavioral observations in respect to eligibility for the provision of services, and that social capital drives service acquisition. Although emphasizing that genetic results do not currently provide sufficient information for determining service eligibility, interviewees also highlighted their hopes that genetics would be increasingly relevant in the future.

Conclusion:
Genomic results do not usually provide information that directly impacts service provision. However, a positive genomic test result can strengthen evidence for behavioral diagnoses and the future trajectory of a child's condition and support needs. Interviewees' comments suggest a need to combine emerging genetic knowledge with existing forms of therapeutic and educational needs assessment, and for additional supports for families struggling to navigate social and therapeutic services.
The contribution of cumulative blood pressure load to dementia, cognitive function and mortality in older adults
Authors: Xu Xiaoyue , Catts Vibeke S. , Harris Katie , Wang Nelson , Numbers Katya , Trollor Julian , Brodaty Henry , Sachdev Perminder S. , Schutte Aletta E. 
Published: July 2024

Background:
Few studies evaluated the contribution of long-term elevated blood pressure (BP) towards dementia and deaths. We examined the association between cumulative BP (cBP) load and dementia, cognitive decline, all-cause and cardiovascular deaths in older Australians. We also explored whether seated versus standing BP were associated with these outcomes.

Methods:
The Sydney Memory and Aging Study included 1037 community-dwelling individuals aged 70–90 years, recruited from Sydney, Australia. Baseline data was collected in 2005–2007 and the cohort was followed for seven waves until 2021. cSBP load was calculated as the area under the curve (AUC) for SBP ≥140 mmHg divided by the AUC for all SBP values. Cumulative diastolic BP (cDBP) and pulse pressure (cPP) load were calculated using thresholds of 90 mmHg and 60 mmHg. Cox and mixed linear models were used to assess associations.

Results:
Of 527 participants with both seated and standing BP data (47.7% men, median age 77), 152 (28.8%) developed dementia over a mean follow-up of 10.5 years. Higher cPP load was associated with a higher risk of all-cause deaths, and cSBP load was associated with a higher risk of cardiovascular deaths in multivariate models (P for trend < 0.05). Associations between cPP load, dementia and cognitive decline lost statistical significance after adjustment for age. Differences between sitting and standing BP load were not associated with the outcomes.

Conclusion:
Long-term cPP load was associated with a higher risk of all-cause deaths and cSBP load associated with a higher risk of cardiovascular deaths in older Australians.