bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of severe nephrotic syndrome on thyroid function, nutrition and coagulation
Authors: Matyjek Anna , Niemczyk Stanisław , Literacki Sławomir , Fendler Wojciech , Rozmysłowicz Tomasz , Kronbichler Andreas
Published: September 2024

Background

Nephrotic syndrome (NS) is characterized by urinary loss of proteins, including hormones and their carrier proteins, potentially resulting in endocrine disorders. This study aimed to assess thyroid dysfunction frequency and potential implications in NS.

Methods

In this case–control study, patients with severe NS (serum albumin ≤2.5 g/dl) and controls without proteinuria were evaluated for thyroid, haemostatic and nutritional parameters, including body composition.

Results

A total of 42 nephrotic and 40 non-proteinuric patients were enrolled. The NS group showed higher thyroid-stimulating hormone and lower free hormones, corresponding to a higher frequency of both euthyroid sick syndrome {ESS; 36% versus 5%; odds ratio [OR] 10.6 [95% confidence interval (CI) 2.2–50.0]} and hypothyroidism [31% versus 5%; OR 8.5 (95% CI 1.8–40.7)] compared with the control group. Levothyroxine supplementation was required for 11 NS patients (26% of the NS group). In addition, compared with control individuals, NS patients exhibited lower lean tissue mass and a trend towards hypercoagulability, which was evidenced by higher levels of most coagulation factors and fibrinolysis inhibitors, and reduced endogenous anticoagulants activities. Furthermore, NS patients with ESS presented with a 10.4 kg (95% CI −18.68 to −2.12) lower lean tissue mass. Those with hypothyroidism had significantly reduced activity of coagulation factor X [by −30% (95% CI −47 to −13)] and protein S [by −27% (95% CI −41 to −13)] compared with euthyroid NS individuals.

Conclusions

Thyroid dysfunction is common in severe NS, often necessitating levothyroxine supplementation, which supports routine thyroid workup. A potential link between thyroid, nutritional and coagulation disorders in NS requires further investigation.
CuPCA: a web server for pan-cancer association analysis of large-scale cuproptosis-related genes
Authors: Xu Yishu , Ma Zhenshu , Wang Yajie , Zhang Long , Ye Jiaming , Chen Yuan , Yuan Zhengrong
Published: September 2024

Copper-induced cell death is a novel mechanism of cell death, which is defined as cuproptosis. The increasing level of copper can produce toxicity in cells and may cause the occurrence of cell death. Several previous studies have proved that cuproptosis has a tight association with various cancers. Thus, the discovery of relationships between cuproptosis-related genes (CRGs) and human cancers is of great importance. Pan-cancer analysis can efficiently help researchers find out the relationship between multiple cancers and target genes precisely and make various prognostic analyses on cancers and cancer patients. Pan-cancer web servers can provide researchers with direct results of pan-cancer prognostic analyses, which can greatly improve the efficiency of their work. However, to date, no web server provides pan-cancer analysis about CRGs. Therefore, we introduce the cuproptosis pan-cancer analysis database (CuPCA), the first database for various analysis results of CRGs through 33 cancer types. CuPCA is a user-friendly resource for cancer researchers to gain various prognostic analyses between cuproptosis and cancers. It provides single CRG pan-cancer analysis, multi-CRGs pan-cancer analysis, multi-CRlncRNA pan-cancer analysis, and mRNA–circRNA–lncRNA conjoint analysis. These analysis results can not only indicate the relationship between cancers and cuproptosis at both gene level and protein level, but also predict the conditions of different cancer patients, which include their clinical condition, survival condition, and their immunological condition. CuPCA procures the delivery of analyzed data to end users, which improves the efficiency of wide research as well as releases the value of data resources.

Database URL: http://cupca.cn/
Gene expression profiling of Cacopsylla pyricola (Hemiptera: Psyllidae) infected with Ca. Phytoplasma pyri (Acholeplasmatales: Acholeplasmataceae)
reveals candidate effectors and mechanisms of infection
Authors: Easterling Katherine A , Marshall Adrian T , Pitino Marco , Walker William B , Cooper W Rodney
Published: September 2024

Phytoplasmas can negatively or positively alter vector host fitness. “Candidatus Phytoplasma pyri,” is the causal agent of pear decline in commercial pear (Pyrus communis L.; Rosales: Rosaceae) and peach yellow leafroll in peach [Prunus persica (L.); Rosaceae]. This plant pathogen is transmitted by several species of pear psyllids (Cacopsylla spp. Hemiptera: Psyllidae). We sought to explore the relationship between the pear decline phytoplasma and its US vector, Cacopsylla pyricola (Förster), at the molecular genetic level through transcriptomic analysis using RNA-sequencing methodology. We also focused on phytoplasma and insect effectors, which are secreted proteins that can modulate interactions within a pathosystem. In this study, we identified 30 differentially expressed genes, 14 candidate insect effector genes, and 8 Ca. Phytoplasma pyri candidate effectors. Two strains of Ca. Phytoplasma pyri were identified based on immunodominant membrane protein sequence analysis from C. pyricola collected in the Pacific Northwest agricultural region. Here, we present a first genetic look at the pear decline pathosystem and report gene candidates for further exploration of infection mechanisms and potential tools for integrated pest management.
‘This Infamous, Scandalous, Headless Insurrection’: The Attack on William Laud and Lambeth Palace, May 1640, Revisited
Authors: Walter John
Published: September 2024

This article offers a re-evaluation of the attack on Lambeth Palace in May 1640. Reconstructing the full extent of crowd actions and placing them in the context of a tradition of self-activating street politics, it emphasises the political nature of the crowd’s actions and the evidence this provides of key concepts in popular political thinking. The crowd, with London apprentices at its core, articulated the popular belief in the role of parliament as the people’s protector and claimed a legitimate agency in seeking to remove evil counsel. The Lambeth attack was triggered by and in turn triggered a litter of libels. The libels—scribal in form, anonymously authored and publicly posted—asserted a popular right to defend the commonwealth. The apprentices’ role in urban life gave them a claim to a political identity and authority in the Lambeth attack which helps to explain the significant part they were to play, and to be invited to play by competing political parties, in print and on the streets, in the politics of the English revolution. The article emphasises (and then qualifies) the severity of the royal government’s revenge, explaining this discrepancy in terms of the balance of power between royal government and popular politics in London in 1640. Examining how political violence came close to the court and to the royal family, the article assesses the impact on Charles I’s kingship. It suggests that the Lambeth attack was of greater consequence than has hitherto been allowed for the fate of Charles I.
Digital analyses of Bolton tooth size ratios and their association to gender, angle class, and other occlusal traits: a study using a partially automated digital 3D model analysis
Authors: Vorloeper Julia , Coenen Franziska A , Lang Norbert A , Niederau Christian , Knaup Isabel , Craveiro Rogerio B , Wolf Michael
Published: September 2024

Background

This study aims to verify Bolton’s values for tooth size ratios and to evaluate possible relationships to different occlusal traits using precise digital measurement methods.

Materials and methods

Including 1000 consecutively selected patients from three study centres a digital, partially automated model analysis was performed utilizing the software OnyxCeph. The measurements comprised tooth width for calculation of anterior (AR) and overall ratio (OR) as a percentage, arch width, length, perimeter, overjet, overbite, space analysis in millimetre and the assessment of the angle classification.

Results

AR and OR were significantly increased compared to Bolton’s ratios of 77.2% (AR) and 91.3% (OR). In the gender comparison, male patients showed larger tooth size ratios, especially in the OR. Patients with Angle Class II/1 and II/2 had smaller tooth size ratios than patients with Angle Class III and I. Thus, patients with Angle Class II/1 had the largest tooth diameters in all maxillary teeth and with Angle Class II/2 the smallest tooth sizes in the mandible. The largest tooth widths in the lower jaw were observed in the Angle Class III patient group. Furthermore, a negative correlation from AR/OR to overjet, overbite, and available space in lower jaw as well as a positive correlation to available space in upper jaw was detected.

Conclusions

There is a clear correlation between the tooth size ratios and the present dysgnathia as well as other orthodontically relevant occlusal traits. This prior knowledge about our patients is extremely important to create an individualized treatment plan and enable sufficient occlusion. To achieve a functionally good occlusion with correct overjet and overbite, it is essential that the maxillary and mandibular teeth are proportional in size. Any deviation from the ideal patient in terms of tooth size, number, shape, or arch must be considered in the pre-therapeutic treatment plan in combination with the existing dysgnathia in order to be able to achieve a stable anterior and posterior occlusion with appropriate adjustments to the therapy post-therapeutically.
Plasma levels of polyols erythritol, mannitol, and sorbitol and incident coronary heart disease among women
Authors: Heianza Yoriko , Sun Qi , Wang Xuan , Tiwari Saumya , Watrous Jeramie D , Rexrode Kathryn M , Alotaibi Mona , Jain Mohit , Mora Samia , Willett Walter C , Qi Lu , Manson JoAnn E
Published: September 2024

Aims

Erythritol, a sugar alcohol (polyol), has recently been linked to the risk of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD).

Methods and results

This prospective nested case–control study included 762 incident cases of CHD and 762 controls from the Nurses’ Health Study. Plasma concentrations of polyols were measured at baseline (1989–90 or 2000–02). Associations of erythritol with cardiometabolic risk factors were also analysed in the Women’s Lifestyle Validation Study (n = 728; blood collected in 2010–12). Higher erythritol levels were related to more adverse cardiometabolic risk factor status. A relative risk (RR) for CHD per 1-SD increment was 1.15 [95% confidence interval (CI): 1.04, 1.28] for erythritol and 1.16 (95% CI: 1.05, 1.28) for mannitol/sorbitol, after adjusting for diet quality, lifestyles, and adiposity. Compared with women in the lowest quartile, those in the highest quartile (Q4) of erythritol had an RR of 1.55 (95% CI: 1.13, 2.14) for CHD. The RR in the Q4 of erythritol was 1.61 (95% CI: 1.15, 2.24; P = 0.006) when hypertension and dyslipidaemia were further added to the model; the RR was 1.21 (95% CI: 0.86, 1.70) after adjustment for diabetes. For mannitol/sorbitol, the RR in Q4 was 1.42 (95% CI: 1.05, 1.91; P = 0.022) for CHD in the multivariable-adjusted model including diabetes.

Conclusion

Higher levels of plasma erythritol and mannitol/sorbitol were related to elevated risks of CHD even after adjustment for diet, lifestyles, adiposity, and other risk factors. The unfavourable association of mannitol/sorbitol, but not of erythritol, with CHD risk remained significant independent of diabetes/hyperglycaemia.
Impacts of Acculturation on Depressive Symptoms and Activities of Daily Living of U.S. Older Chinese Immigrants
Authors: Jiang Yanping , Li Mengting , Kwon Soonhyung , Zhu Yuyang , Wu Bei , Tang Fengyan
Published: September 2024

Background and Objectives

Acculturation is a critical aspect of social experience for immigrants, including Asian immigrants. Existing literature has shown mixed findings on the health impacts of acculturation and largely relied on cross-sectional studies, preventing drawing definitive conclusions. This study aimed to examine the long-term effects of acculturation on depressive symptoms and activities of daily living (ADL) limitations in a large sample of older Chinese immigrants in the United States.

Research Design and Methods

Data were drawn from 2,811 older Chinese immigrants from the Population Study of Chinese Elderly in Chicago. Acculturation was assessed at baseline, and questionnaires on depressive symptoms and ADL limitations were completed at 4 assessments.

Results

Overall, results showed that acculturation was not associated with depressive symptoms at baseline but was associated with a faster decline in depressive symptoms over time. No associations were found between acculturation and ADL limitations. Stratified analyses showed that the significant relationship between acculturation and a faster decline in depressive symptoms was only evident among female participants. Also, acculturation was associated with a lower risk of reporting ADL limitations at baseline in female participants but a higher risk of reporting ADL limitations in male participants.

Discussion and Implications

This study indicates the long-term benefits of acculturation on mental health among older Chinese immigrants in the United States, particularly among females. Initiatives supporting the acculturation process need to consider sex disparities and individual preferences, aiming to foster sustained benefits for healthy aging in this population.
Classifying small earthquakes, explosions and collapses in the western United States using physics-based features and machine learning
Authors: Koper Keith D , Burlacu Relu , Armstrong Alysha D , Herrmann Robert B
Published: September 2024

Classifying the source type of small seismic events is a key task in seismology. A common goal is distinguishing tectonic earthquakes from explosions and human induced seismicity. To this end, we applied a spectral modelling workflow to Pg and Sg waves from ∼10 000 seismic events that occurred in or near Utah and were recorded by broadband seismometers in the western United States at distances of 10–300 km. The events were a mixture of tectonic earthquakes (EQ), industrial explosions (EX) and mining-induced seismicity (MIS, primarily collapses) and were mostly small (median magnitude of 1.34 MC). Our spectral modelling was successful for 54 per cent of the events, resulting in a new catalogue of M0 and fc values. We evaluated 13 physics-based features—including differential magnitudes, Pg/Sg spectral amplitude ratios, long-period/short-period spectral amplitude ratios and spectral misfit—as source classifiers. We found that Φ ≡ log10(M0) + 3log10(fc) was the most effective individual feature for distinguishing EQ from EX and MIS sources because EQ spectra are relatively enriched in high frequencies. We selected five less correlated features that spanned the feature space and used a naïve Bayes approach to create a three-way classification model. The model had 97.5 per cent accuracy when applied to an independent test data set. Model performance deteriorated when more than six features were combined. We conclude that models developed with a few physics-based waveform features can classify small seismic events with performance comparable to high-dimensional deep-learning models. Simple models that rely on physics-based features require less training data and make more interpretable decisions than deep-learning models, though they may require higher signal-to-noise ratios.
De novo gene integration into regulatory networks via interaction with conserved genes in peach
Authors: Cao Yunpeng , Hong Jiayi , Zhao Yun , Li Xiaoxu , Feng Xiaofeng , Wang Han , Zhang Lin , Lin Mengfei , Cai Yongping , Han Yuepeng
Published: September 2024

De novo genes can evolve “from scratch” from noncoding sequences, acquiring novel functions in organisms and integrating into regulatory networks during evolution to drive innovations in important phenotypes and traits. However, identifying de novo genes is challenging, as it requires high-quality genomes from closely related species. According to the comparison with nine closely related Prunus genomes, we determined at least 178 de novo genes in P. persica “baifeng”. The distinct differences were observed between de novo and conserved genes in gene characteristics and expression patterns. Gene ontology enrichment analysis suggested that Type I de novo genes originated from sequences related to plastid modification functions, while Type II genes were inferred to have derived from sequences related to reproductive functions. Finally, transcriptome sequencing across different tissues and developmental stages suggested that de novo genes have been evolutionarily recruited into existing regulatory networks, playing important roles in plant growth and development, which was also supported by WGCNA analysis and quantitative trait loci data. This study lays the groundwork for future research on the origins and functions of genes in Prunus and related taxa.
Knowledge-based approaches to the firm: an idea-driven perspective
Authors: Cohendet Patrick , Dupouët Olivier , Llerena Patrick , Naggar Raouf , Rampa Romain
Published: September 2024

The challenges of the 21st century imply reconsidering the knowledge-based approaches of the firm under idea-led perspectives. We propose to reexamine the limits of the knowledge-based approaches of the firm by integrating the management of ideas as a process into the analysis. Building on the differences between the notions of idea and knowledge, we reconsider in turn the raison d’être, boundaries, coordination and incentive mechanisms, and the role of the entrepreneur of the firm. We show that ideas as a process are central to a more actor-inclusive view of the firm, providing a more relevant explanation of how firms can create value and fit into the contemporary world.
Lipid production by robust Aspergillus oryzae BCC7051 and a mathematical model describing its growth and lipid phenotypic traits
Authors: Wannawilai Siwaporn , Palasak Thanaporn , Chamkhuy Warinthon , Khongto Bhimabol , Jeennor Sukanya , Laoteng Kobkul
Published: September 2024

Aims

To identify the promising oleaginous Aspergillus oryzae strain and leverage its lipid and biomass production through a mathematical model.

Methods and results

Comparative profiling of the cell growth and total fatty acid (TFA) content among 13 strains of A. oryzae was performed to explore the discrimination in their lipid productions. The oleaginicity of A. oryzae was found to be strain dependent, where the fungal strain BCC7051 exhibited superior performance in producing lipid-rich biomass by submerged fermentation. The TFA contents of the strain BCC7051 were comparable when cultivated at a range of pH values (pH 3.5–6.5) and temperatures (24–42°C). The mathematical model was generated, well describing and predicting the fungal growth and lipid phenotypic traits at various temperatures and carbon substrates.

Conclusion

The A. oryzae strain BCC7051 was a robust cell factory, acquiring economically feasible options for producing valuable lipid-based products.
Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: Bone Microarchitecture International Consortium (BoMIC) prospective cohorts
Authors: Sarfati Marine , Chapurlat Roland , Dufour Alyssa B , Sornay-Rendu Elisabeth , Merle Blandine , Boyd Steven K , Whittier Danielle E , Hanley David A , Goltzman David , Szulc Pawel , Wong Andy Kin On , Lespessailles Eric , Khosla Sundeep , Ferrari Serge , Biver Emmanuel , Ohlsson Claes , Lorentzon Mattias , Mellström Dan , Nethander Maria , Samelson Elizabeth J , Kiel Douglas P , Hannan Marian T , Bouxsein Mary L
Published: September 2024

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9 years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height, and weight, and then additionally adjusted for FN aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ −2.5, whereas 53% had T-scores between −1.0 and −2.5 and 37% had T-scores ≥−1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load (FL) was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, FL and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range.
The G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH signaling
Authors: Bian Fangzhou , Hansen Victoria , Feng Hong Colleen , He Jingyu , Chen Yanshi , Feng Kaining , Ebrahimi Brenda , Gray Ryan S , Chai Yang , Wu Chia-Lung , Liu Zhaoyang
Published: September 2024

The cartilage growth plate is essential for maintaining skeletal growth; however, the mechanisms governing postnatal growth plate homeostasis are still poorly understood. Using approaches of molecular mouse genetics and spatial transcriptomics applied to formalin-fixed, paraffin-embedded tissues, we show that ADGRG6/GPR126, a cartilage-enriched adhesion G protein-coupled receptor (GPCR), is essential for maintaining slow-cycling resting zone cells, appropriate chondrocyte proliferation and differentiation, and growth plate homeostasis in mice. Constitutive ablation of Adgrg6 in osteochondral progenitor cells with Col2a1Cre leads to a shortened resting zone, formation of cell clusters within the proliferative zone, and an elongated hypertrophic growth plate, marked by limited expression of parathyroid hormone-related protein (PTHrP) but increased Indian Hedgehog (IHH) signaling throughout the growth plate. Attenuation of smoothened-dependent hedgehog signaling restored the Adgrg6 deficiency-induced expansion of hypertrophic chondrocytes, confirming that IHH signaling can promote chondrocyte hypertrophy in a PTHrP-independent manner. In contrast, postnatal ablation of Adgrg6 in mature chondrocytes with AcanCreERT2, induced after the formation of the resting zone, does not affect PTHrP expression but causes an overall reduction of growth plate thickness marked by increased cell death specifically in the resting zone cells and a general reduction of chondrocyte proliferation and differentiation. Spatial transcriptomics reveals that ADGRG6 is essential for maintaining chondrocyte homeostasis by regulating osteogenic and catabolic genes in all the zones of the postnatal growth plates, potentially through positive regulation of SOX9 expression. Our findings elucidate the essential role of a cartilage-enriched adhesion GPCR in regulating cell proliferation and hypertrophic differentiation by regulation of PTHrP/IHH signaling, maintenance of slow-cycle resting zone chondrocytes, and safeguarding chondrocyte homeostasis in postnatal mouse growth plates.
Witnessing Ongwen
Authors: Atingo Jackline , Allen Tim , Macdonald Anna
Published: September 2024

The trial of Dominic Ongwen before the International Criminal Court (ICC) has been hailed as a milestone, especially because of his conviction for gender-based crimes, including forced marriage and forced pregnancy. Ongwen’s conviction for those crimes was linked to harrowing testimonies of a group of women who were given to him as so-called ‘wives’ during his time as a commander in the Lord’s Resistance Army rebel group. After a successful Article 56 application by the Office of the Prosecutor (OTP), special arrangements were made for these women to act as witnesses in advance of the trial in the Hague, and various assurances were provided to them. Based on ethnographic engagement and in-depth interviews with these witnesses, this article contributes to the literature on witnesses in international criminal trials, and the complexities of victimhood, describing their experiences of testifying, their views about justice, and their current lives. It notes the lack of adequate protection and benefits that have accrued to them. Interviews also occurred with ‘wives’ who testified for the Defence, whose accounts of their experiences are relatively more positive. Concerns are raised about the ICC’s capacity to fulfil basic expectations of victims of the sexual crimes it successfully prosecutes.
Imagelytics suite: deep learning-powered image classification for bioassessment in desktop and web environments
Authors: Milosavljević Aleksandar , Predić Bratislav , Milošević Djuradj
Published: September 2024

Bioassessment is the process of using living organisms to assess the ecological health of a particular ecosystem. It typically relies on identifying specific organisms that are sensitive to changes in environmental conditions. Benthic macroinvertebrates are widely used for examining the ecological status of freshwaters. However, a time-consuming process of species identification that requires high expertise represents one of the key obstacles to more precise bioassessment of aquatic ecosystems. Partial automation of this process using deep learning-based image classification is the goal of an ongoing project AIAQUAMI we are participating in. One of the project goals is to develop software support for image classification with visualization and reporting. For that purpose, we developed desktop and web applications that we open-sourced as Imagelytics Suite. Both desktop and web applications rely on a convolutional neural network (CNN) to classify images and the Grad-CAM algorithm to produce heatmaps of the image areas that mostly influenced the network decision. Along with the source code of the applications, we also open-sourced scripts that can be used to train CNN on an arbitrary dataset and produce required metadata, so it can be used with Imagelytics applications. In this article, we presented technical details regarding the design of the applications and the training method that will enable their general use for image classification tasks. As a part of the evaluation, we will show a use case related to species identification of non-biting midges (Diptera: Chironomidae).
Considerations on expanding criminal offender DNA databases with Y-STR profiles
Authors: Ralf Arwin , Zieger Martin , Kayser Manfred
Published: September 2024

Although national criminal offender DNA databases (NCODDs) including autosomal short tandem repeats (STRs) have been a successful tool to identify criminals for decades in many countries, yet there are many criminal cases they cannot solve. In cases with mixed male–female samples, particularly sexual assault, expanding NCODDs with Y-chromosomal STR (Y-STR) profiles allows database matching in the absence of autosomal STR profiles. Although Y-STR matches are not individual-specific, this can be largely overcome with rapidly mutating Y-STRs (RM Y-STR) allowing separation of paternally related men. Expanding NCODDs with Y-STR profiles is also beneficial for law enforcement in cases without known suspects via familial searching. Expanding NCODDs with Y-STR profiles may raise concerns about genetic privacy and fundamental human rights. A legal analysis of the European Convention on Human Rights revealed that when primarily for reidentifying convicted sex offenders, it would be in line with the case law of the European Court of Human Rights, while a generalized approach primarily for familial searching and involving all types of offenders may not. This paper aims to stimulate a debate among various stakeholders regarding the benefits and risks of expanding NCODDs with Y-STR profiles that in some countries has already been practically implemented.
Cultural shifts: an examination of cervical cancer stigma across age groups in the Caribbean
Authors: Song Gaole , Thomas-Purcell Kamilah , Sealy Diadrey-Anne , Bailey Althea , Ragin Camille , Ashing Kimlin
Published: September 2024

Background

Cervical cancer-related stigma is common but understudied in the Caribbean. This study aims to describe the age difference of cervical cancer stigma and to evaluate the influence on the prevention practices among the Caribbean nonpatient population in Jamaica, Grenada, and Trinidad and Tobago.

Methods

A cross-sectional study involving 1209 participants was conducted using a culturally trans-created Cancer Stigma Scale for the Caribbean context and supplemented with questions on cervical cancer and human papillomavirus (HPV) and HPV vaccine knowledge and beliefs. Descriptive analyses and χ2 tests were conducted.

Results

The χ2 tests showed age is statistically significantly related to participants’ response to stigma items such as “community members believe cervical cancer is viewed as shameful” (P = .0001); “women with cervical cancer are treated with less respect than usual by others” (P < .0001); “women with cervical cancer are rejected by family members” (P = .0007); “women with cervical cancer are rejected by intimate partners” (P < .0001); and “intimate partners blame women for having cervical cancer” (P = .0032). Additionally, age has statistically significant associations with endorsements of negative views of cervical cancer from the community (P < .0001) and family (P < .0001) as key barriers to cervical cancer care (item: “discourage women from seeking and obtaining screening and treatment”). Notably, younger respondents (18-25 years) are more sensitized to the unfair stigma and hold more stigma.

Conclusions

Among Caribbeans, age influences cervical cancer stigma. Younger persons acknowledged greater stigma within families and communities. This study can guide age-informed interventions and programs to reduce stigma and improve cervical cancer screening and care seeking to reduce cervical cancer burden and disparities.
Intra-osteal fixation of comminuted coronoid process fracture with mini plate for the treatment of complex elbow fracture
Authors: Wu Yuxuan , Wang Jianlan , Lian Xiaodong , Mu Jiang , Lu Ming , Zhang Shuang
Published: September 2024

Complex elbow fractures featuring a comminuted coronoid process are infrequent and pose considerable treatment challenges. The optimal strategy for maximizing recovery of elbow function through osteosynthesis remains a subject of ongoing debate among surgeons. We applied the principle of internal fixation by implementing intra-osteal fixation with a mini plate, which facilitated the successful restoration of exceptional elbow function in the patient. This approach adeptly managed the complexity of the coronoid process fracture, encompassing its fragmentation and associated injuries, thereby demonstrating its feasibility and efficacy in achieving favorable clinical outcomes. This article investigates the viability of this surgical technique for managing such complex fractures.
Production of flavor-active compounds and physiological impacts in immobilized Saccharomyces spp. cells during beer fermentation
Authors: de Araujo Thiago Machado , da Cunha Marcel Menezes Lyra , Barga Marcelo Calide , Della-Bianca Bianca Eli , Basso Thiago Olitta
Published: September 2024

Yeast immobilization in beer fermentation has recently regained attention, due to the expansion of the craft beer market and the diversification of styles and flavors. The aim of this study was to evaluate the physiological differences between immobilized and free yeast cells with a focus on flavor-active compounds formation. Three strains of Saccharomyces spp. (SY025, SY067, SY001) were evaluated in both free and immobilized (using a cellulose-based support, referred as ImoYeast) forms during static batch fermentations of 12 °P malt extract. Immobilized cells showed higher glycerol (SY025, 40%; SY067, 53%; SY001, 19%) and biomass (SY025, 67%; SY067, 78%; SY001, 56%) yields than free cells. Conversely, free cells presented higher ethanol yield (SY025, 9%; SY067, 9%; SY001, 13%). Flavor-active compounds production exhibited significant alterations between immobilized and free cells systems, for all strains tested. Finally, a central composite design with varying initial biomass (X0) and substrate (S0) concentrations was conducted using strain SY025, which can be helpful to modulate the formation of one or more flavor-active compounds. In conclusion, yeast immobilization in the evaluated support resulted in flavor alterations that can be exploited to produce different beer styles.
The EU Digital Services Act
Authors: Wilman Folkert , KalÄda Saulius Lukas , Loewenthal Paul-John
Published: September 2024

The EU Regulation on a Single Market for Digital Services (Digital Services Act, the ‘DSA’) is a comprehensive legal framework to regulate digital services and to tackle illegal activity online across the EU. The DSA represents one of the main pillars of the EU’s reform of the digital single market. It applies horizontally to online intermediaries operating in the EU, including online platforms such as social media, video-sharing platforms, online marketplaces, and search engines. This book serves as a reference work on the DSA, providing a comprehensive article-by-article analysis that will allow the reader to navigate the provisions of this new, complex legal act. While being novel, the DSA does not enter a completely unchartered territory: numerous provisions draw inspiration from, or are applied together with, the provisions of other Acts and areas of EU law. The book explores the jurisprudential origins of the provisions of the DSA and their articulation with other EU Acts, which will be essential for its interpretation and application. It strikes a balance between a practical commentary and an academic analysis, and it is aimed at legal practitioners, academics, and public authorities.
Liability of Providers of Intermediary Services
Authors: Wilman Folkert , Kalėda Saulius Lukas , Loewenthal Paul-John
Published: September 2024

This chapter examines how the Digital Services Act (DSA) handles the liability of providers of intermediary services. According to Article 3(g) DSA, intermediary services refer to covering mere conduit, caching, and hosting services. The chapter then discusses the provisions that contain conditional liability exemptions for providers of intermediary services. It explains the extent of liability exemptions that was inspired by the US law, which shielded providers of various online services from liability under copyright law for the third-party information they transmit or store. Moreover, the rules on liability interact with due diligence obligations to some extent.
Conclusion
Authors: Wilman Folkert , Kalėda Saulius Lukas , Loewenthal Paul-John
Published: September 2024

This chapter discusses the evolution of the Digital Services Act (DSA). It highlights the importance of striking a balance between conflicting rights, interests, and considerations that arise in regulating the provision of intermediary services. The way the DSA deals with tensions involved in platform regulations offers valuable perspectives when trying to understand the significance of the DSA. The chapter then provides an overview of the regulatory approach of the DSA. Regardless of the DSA's limits, providers of intermediary services continue to have considerable freedom to decide how they wish to provide their services in the EU. The chapter cites that the Commission is still in the process of adopting all necessary delegated and implementing acts and reinforcing its supervisory capabilities.
Deciphering prognostic indicators in non-HIV cryptococcal meningitis: Constructing and validating a predictive Nomogram model
Authors: Liang Feng , Li Runyang , Yao Make , Wang Jing , Li Yunhong , Lei Lijian , Guo Junhong , Chang Xueli
Published: September 2024

Cryptococcal meningitis (CM) is a well-recognized fungal infection, with substantial mortality in individuals infected with the human immunodeficiency virus (HIV). However, the incidence, risk factors, and outcomes in non-HIV adults remain poorly understood. This study aims to investigate the characteristics and prognostic indicators of CM in non-HIV adult patients, integrating a novel predictive model to guide clinical decision-making. A retrospective cohort of 64 non-HIV adult CM patients, including 51 patients from previous studies and 13 from the First Hospital of Shanxi Medical University, was analyzed. We assessed demographic features, underlying diseases, intracranial pressure, cerebrospinal fluid characteristics, and brain imaging. Using the least absolute shrinkage and selection operator (LASSO) method, and multivariate logistic regression, we identified significant variables and constructed a Nomogram prediction model. The model's calibration, discrimination, and clinical value were evaluated using the Bootstrap method, calibration curve, C index, goodness-of-fit test, receiver operating characteristic (ROC) analysis, and decision curve analysis. Age, brain imaging showing parenchymal involvement, meningeal and ventricular involvement, and previous use of immunosuppressive agents were identified as significant variables. The Nomogram prediction model displayed satisfactory performance with an akaike information criterion (AIC) value of 72.326, C index of 0.723 (0.592–0.854), and area under the curve (AUC) of 0.723, goodness-of-fit test P = 0.995. This study summarizes the clinical and imaging features of adult non-HIV CM and introduces a tailored Nomogram prediction model to aid in patient management. The identification of predictive factors and the development of the nomogram enhance our understanding and capacity to treat this patient population. The insights derived have potential clinical implications, contributing to personalized care and improved patient outcomes.
Patterns of Fitness and Gene Expression Epistasis Generated by Beneficial Mutations in the rho and rpoB Genes of Escherichia coli during High-Temperature Adaptation
Authors: González-González Andrea , Batarseh Tiffany N , Rodríguez-Verdugo Alejandra , Gaut Brandon S
Published: September 2024

Epistasis is caused by genetic interactions among mutations that affect fitness. To characterize properties and potential mechanisms of epistasis, we engineered eight double mutants that combined mutations from the rho and rpoB genes of Escherichia coli. The two genes encode essential functions for transcription, and the mutations in each gene were chosen because they were beneficial for adaptation to thermal stress (42.2 °C). The double mutants exhibited patterns of fitness epistasis that included diminishing returns epistasis at 42.2 °C, stronger diminishing returns between mutations with larger beneficial effects and both negative and positive (sign) epistasis across environments (20.0 °C and 37.0 °C). By assessing gene expression between single and double mutants, we detected hundreds of genes with gene expression epistasis. Previous work postulated that highly connected hub genes in coexpression networks have low epistasis, but we found the opposite: hub genes had high epistasis values in both coexpression and protein–protein interaction networks. We hypothesized that elevated epistasis in hub genes reflected that they were enriched for targets of Rho termination but that was not the case. Altogether, gene expression and coexpression analyses revealed that thermal adaptation occurred in modules, through modulation of ribonucleotide biosynthetic processes and ribosome assembly, the attenuation of expression in genes related to heat shock and stress responses, and with an overall trend toward restoring gene expression toward the unstressed state.
Efficacy and safety of febuxostat in Japanese paediatric patients with hyperuricaemia including gout: Phase 2, single arm, open‒label, multicentre studies
Authors: Ito Shuichi , Morita Yo , Nitami Makoto , Iwama Ryutaro , Nakajima Akihiro , Yamanaka Hisashi , Honda Masataka
Published: September 2024

Objectives

Urate-lowering efficacy and safety of febuxostat was evaluated in paediatric patients with hyperuricaemia including gout.

Methods

A Phase 2 study of febuxostat in paediatric patients aged 6–18 years with hyperuricaemia including gout was conducted. We evaluated the proportion of patients achieving serum uric acid (sUA) level ≤6.0 mg/dl at Week 26, and long-term safety and efficacy at Week 52. We also considered efficacy stratified by renal function.

Results

Thirty patients (10 at <40 kg and 20 at ≥40 kg) were enrolled. Twenty-four were males, 29 had asymptomatic hyperuricaemia, and 1 had gout. Age was 8 to 18 years. Of these, 63.3% (95% confidence interval 43.9–80.1%) achieved a sUA level of ≤6.0 mg/dl at Week 26. sUA level (mean ± standard deviation) was 5.55 ± 0.87 mg/dl, reduced from 9.01 ± 1.23 mg/dl at baseline. Febuxostat efficacy appeared similar for mild to moderate renal dysfunction and with normal renal function. There were no major safety issues.

Conclusions

In paediatric patients with hyperuricaemia including gout, febuxostat showed long-term, well-controlled urate-lowering efficacy with no major safety issues. Findings suggest that no dose adjustment is required for paediatric patients with mild to moderate renal dysfunction.
Advantage looping: Gene regulatory circuits between microRNAs and their target transcription factors in plants
Authors: Shankar Naveen , Nath Utpal
Published: September 2024

The 20 to 24 nucleotide microRNAs (miRNAs) and their target transcription factors (TF) have emerged as key regulators of diverse processes in plants, including organ development and environmental resilience. In several instances, the mature miRNAs degrade the TF-encoding transcripts, while their protein products in turn bind to the promoters of the respective miRNA-encoding genes and regulate their expression, thus forming feedback loops (FBLs) or feedforward loops (FFLs). Computational analysis suggested that such miRNA–TF loops are recurrent motifs in gene regulatory networks (GRNs) in plants as well as animals. In recent years, modeling and experimental studies have suggested that plant miRNA–TF loops in GRNs play critical roles in driving organ development and abiotic stress responses. Here, we discuss the miRNA–TF FBLs and FFLs that have been identified and studied in plants over the past decade. We then provide some insights into the possible roles of such motifs within GRNs. Lastly, we provide perspectives on future directions for dissecting the functions of miRNA-centric GRNs in plants.
A conserved protein family in mirid bug Riptortus pedestris plays dual roles in regulating plant immunity
Authors: Zhou Jiangxuan , Yin Zhiyuan , Shen Danyu , Zhang Qingsong , OYang Yujie , Li Xiaoxi , Ma Yurong , Ding Lanping , Pei Yong , Ai Gan , Dong Yumei , Yang Donglei , Wang Yuanchao , Dou Daolong , Xia Ai
Published: September 2024

The mirid bug (Riptortus pedestris), a major soybean pest, migrates into soybean fields during the pod filling stage and causes staygreen syndrome, which leads to substantial yield losses. The mechanism by which R. pedestris elicits soybean (Glycine max) defenses and counter-defenses remains largely unexplored. In this study, we characterized a protein family from R. pedestris, designated R.pedestris HAMP 1 (RPH1), and its putative paralogs (RPH1L1, 2, 3, 4, and 5), whose members exhibit dual roles in triggering and inhibiting plant immunity. RPH1 and RPH1L1 function as herbivore-associated molecular patterns (HAMPs), activating pattern-triggered immunity (PTI) in tobacco (Nicotiana benthamiana) and G. max. Furthermore, RPH1 stimulates jasmonic acid and ethylene biosynthesis in G. max, thereby enhancing its resistance to R. pedestris feeding. Additionally, RPH1 homologs are universally conserved across various herbivorous species, with many homologs also acting as HAMPs that trigger plant immunity. Interestingly, the remaining RPH1 putative paralogs (RPH1L2-5) serve as effectors that counteract RPH1-induced PTI, likely by disrupting the extracellular perception of RPH1. This research uncovers a HAMP whose homologs are conserved in both chewing and piercing-sucking insects. Moreover, it unveils an extracellular evasion mechanism utilized by herbivores to circumvent plant immunity using functionally differentiated paralogs.
COBRA-LIKE4 modulates cellulose synthase velocity and facilitates cellulose deposition in the secondary cell wall
Authors: Xue Jan Y , McNair Grant , Watanabe Yoichiro , Kaplen Madison V , Guevara-Rozo Sydne , Schuetz Mathias , Schneider Rene , Mansfield Shawn D , Samuels A Lacey
Published: September 2024

Cellulose is a critical component of secondary cell walls (CWs) and woody tissues of plants. Cellulose synthase (CESA) complexes (CSCs) produce cellulose as they move within the plasma membrane, extruding glucan chains into the CW that coalesce and often crystallize into cellulose fibrils. Here we examine COBRA-LIKE4 (COBL4), a GPI-anchored protein on the outer leaflet of the plasma membrane that is required for normal cellulose deposition in secondary CWs. Characterization of the Arabidopsis (Arabidopsis thaliana) cobl4 mutant alleles called irregular xylem6, irx6-2 and irx6-3, showed reduced α-cellulose content and lower crystallinity, supporting a role for COBL4 in maintaining cellulose quantity and quality. In live-cell imaging, mNeon Green-tagged CESA7 moved in the plasma membrane at higher speeds in the irx6-2 background compared to wild-type. To test conservation of COBL4 function between herbaceous and woody plants, poplar (Populus trichocarpa) COBL4 homologs PtCOBL4a and PtCOBL4b were transformed into, and rescued, the Arabidopsis irx6 mutants. Using the Arabidopsis secondary CW-inducible VND7-GR system to study poplar COBL4 dynamics, YFP-tagged PtCOBL4a localized to the plasma membrane in regions of high cellulose deposition in secondary CW bands. As predicted for a lipid-linked protein, COBL4 was more mobile in the plane of the plasma membrane than CESA7 or a control plasma membrane marker. Following programmed cell death, COBL4 anchored to the secondary CW bands. These data support a role for COBL4 as a modulator of cellulose organization in the secondary CW, influencing cellulose production, and CSC velocity at the plasma membrane.