bluuebunny/crossref_metadata_2025 huggingface dataset:
Contemporary Role of Testis Sparing Surgery: A Systematic Review
Authors: Russo Giorgio Ivan , Reale Giulio , Privitera Salvatore , Castelli Tommaso , Madonia Massimo , Cimino Sebastiano , Favilla Vincenzo , Morgia Giuseppe
Published: April 2023

Testis-sparing surgery (TSS) represents a therapeutic choice for testicular cancer (TC). However, international guidelines are very cautious about the use of the testis-sparing technique, namely due to the lack of certain indications and long-term oncological outcomes. The aim of this systematic-review is to illustrate current trends of what may today be the uses of organ-sparing surgery in TC, to evaluate the relationship between the organ-sparing safety and oncological features such as definitive histology, tumour size, and post-surgery oncological outcomes. This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. An electronic search of the Medline and Embase was undertaken until September 2014. The search was limited to English-Language articles. Current indications of TSS are synchronous bilateral testicular tumours, metachronous contralateral tumours, or tumour in a solitary testis with normal preoperative testosterone levels. Moreover, histological characteristics should not be taken into account when performing a TSS approach. TSS outcomes for germ cell tumours are encouraging and we reported high rates of disease-free survival and a few cases of patients receiving neoadjuvant chemotherapy or radiotherapy. In light of the examined, TSS could be considered a viable alternative to radical surgery of the testis but it should be performed in specialised centres with competence.
Holmium Laser Enucleation of the Prostate (HoLEP): Our Experience with the Learning Curve and the Development of the ‘En-Bloc No-Touch’ Technique
Authors: Scoffone Cesare Marco , Cracco Cecilia Maria
Published: April 2023

Background: Holmium laser enucleation of the prostate (HoLEP) is a safe and effective therapeuticoption in patients suffering from benign prostatic hyperplasia (BPH) of any size. In spite of its excellent and durable outcomes, HoLEP is gaining widespread acceptance very slowly, since it is perceived as requiring significant endoscopic skill and having a steep learning curve. Here we present our 4-year experience with this technique after more than 200 cases, describing our learning curve with the traditional three-lobe technique of Gilling, and its progressive modification into the so-called ‘en-bloc no-touch’ technique. Methods: From January 2011 to December 2014, 200 consecutive patients diagnosed with symptomatic and obstructive BPH underwent HoLEP in our department. Demographic and clinical data were prospectively collected. Age, total operating time, enucleation time and efficiency, morcellation time, energy employed, adenoma weight, hospital stay, and complications were recorded. Results: The HoLEP learning curve in our department included an initial 1-year experience with the traditional technique of Gilling, and its progressive modification with the development of the socalled ‘en-bloc no-touch’ approach, subsequently standardised step by step. At the beginning of the learning curve short time intervals between the procedures are relevant for faster learning. With time and experience, adenomas of all sizes are treated, with significantly shorter total operating and enucleation times, significantly increased enucleation efficiency, decreased use of energy (meaning fewer postoperative voiding symptoms), and fewer complications. Morcellation time is more devicedependent than surgeon-dependent, and is also influenced by the composition of the adenomatous tissue. Conclusion: The ‘en-bloc no-touch’ technique seems to simplify the procedure, making it easier to teach and to learn. HoLEP safety and efficacy are improved by increasing experience, as expected, but apparently also by the application of our modified and standardised procedure.
Non-knowledge in Medical Practices: Approaching the Uses of Social Media in Healthcare from an Epistemological Perspective
Authors: Sendra Anna , Torkkola Sinikka , Parviainen Jaana
Published: April 2023

Social media has transformed how individuals handle their illnesses. While many patients increasingly use these online platforms to understand embodied information surrounding their conditions, healthcare professionals often frame these practices as negative and do not consider the expertise that patients generate through social media. Through a combination of insights from social epistemology and ignorance studies, this paper problematizes the distinctive understandings of social media between patients and healthcare professionals from a different perspective. A total of four ideas are introduced: (1) healthcare professionals see embodied knowledge that arises from patients’ social media practices as uncomfortable knowledge; (2) healthcare professionals engage in several behaviours to preserve their authority and power in front of embodied knowledge created through these online platforms; (3) failing to consider embodied knowledge can have consequences not only in terms of trust between patients and healthcare professionals but also in connection with epistemological populism and the transition towards patient-centred care; and (4) media and digital health literacy could help healthcare professionals enhance the uses of social media in healthcare. Adopting this framework allows not only to offer valuable insights into how healthcare professionals manage patients’ social media practices, but also opens new avenues to improve healthcare digitisation.
Black and White Comedy: Trade and Race in Bredero's Moortje (1617)
Authors: Paijmans Marrigje
Published: April 2023

Moortje ( Little Moor, 1617) is an adaptation of Terence’s The Eunuch, in which the Dutch playwright Gerbrand Adriaensz Bredero replaced the castrate with a ‘Moor’. Scholars have demonstrated how Moortje renders an early modern discourse of race that, at the threshold of Dutch participation in colonial trade, facilitated the enslavement and trafficking of African people. This article aims to do justice to the polyphonic discussion on colonial trade in the seventeenth-century Republic, arguing that Moortje can also be read as a foreshadowing of postcolonial shame and ‘white innocence’. It does so through an analysis of race at the intersections with gender, focusing on the distinct processes through which two women in the play – one black and one white – are commodified on the market and appropriated by their new owner. It also analyses two paratexts in which Bredero compares the cultural appropriation of classical comedy to colonial appropriation. Together, the analyses indicate that racial thinking, although closely intertwined with the discourse on trade, does not in all respects facilitate the commodification and appropriation of the black woman. Rather blackness in Moortje represents the unknown, both in terms of colonial trade and its effects for the conscience of the white merchant.
‘A Final Solution for Humanity’? Modern Design and the Ambivalence of Redemption in Post-War West Germany
Authors: Scholz Natalie
Published: April 2023

During the Third Reich, a modern shape of everyday objects was propagated as realising a German nation defined as an organic and racial entity. What happened to this cultural nexus after 1945? Historical scholarship has emphasized above all that modern design went on to be successfully framed as a cultural good that redeemed West Germany from the Nazi past. This redeeming opposition between the political meanings of modern design before and after 1945, however, appears less clear-cut if one acknowledges the structure of denial in post-war discourses by focussing on the silences, omissions and discrepancies in various publications. Such an analysis exposes how the coding of modern design as ‘timeless’ together with its promotion in the context of the Marshall Plan made it possible to blur any historical understanding of how the underlying notions of everyday aesthetics had been intertwined with racially loaded ideas of the German people. This obscurity in the context of a not yet decolonized West facilitated the continuing influence of at least some aspects of modern design’s more troubling political legacies.
Sobrevida global y sobrevida libre de enfermedad a cinco y diez años en pacientes con cáncer de ovario
Authors: Navarrete Rengel Micaela Alejandra , Casares Tamayo Jimmy Ronald , Espinoza De Los Monteros Rommel
Published: April 2023

Introducción: La supervivencia del cáncer de ovario se aproxima al 50%, sin embargo, varía en función de los distintos factores pronósticos, siendo el principal la extensión de la enfermedad al diagnóstico. El objetivo del presente estudio fue establecer la supervivencia global y libre de enfermedad en un centro de referencia para el tratamiento de cáncer de ovario en Quito, Ecuador.
Métodos: El presente estudio longitudinal, se realizó en el Hospital Metropolitano de Quito, de enero del 2008 a diciembre del 2018. Se incluyeron mujeres con cáncer de ovario. Se registraron variables demográficas, número de embarazos, comorbilidades, diagnóstico histológico, tiempo de evolución, tratamiento recibido, estadío de la enfermedad, progresión, recaídas, período libre de enfermedad y mortalidad. La muestra fue no probabilística. Se realiza un análisis descriptivo y un análisis de supervivencia.
Resultados: Participaron 84 pacientes. La edad en 20 casos (23.8%) < 50 años, en 29 casos (34.5%) de 50 a 59 años y en 35 casos (41.7%) > 60 años. El 60.7 % con 1 a 3 embarazos, el 23.8% nunca se embarazo y el 15.5 % con > 4 embarazos, sin relación con la mortalidad. El tipo histológico más prevalente fue el carcinoma epitelial en 56 casos (66.6%). La media de tiempo de recaída fue 56.8 meses y de tiempo de sobrevida fue de 87.7 meses. La supervivencia a los 5 años fue del 62% y a los 10 años del 55%. La supervivencia fue menor en mayores de 60 años y con estadios IIB, IIC, IIIA y IIIC.
Conclusión: En este estudio la mortalidad se modificó por el estadío clínico, el tiempo de evolución y la edad de las pacientes con cáncer de ovario.
Celebrating in King Otto’s Greece
Authors: Kimourtzis Panayotis , Mandilara Anna
Published: April 2023

The heavy-handed regime of King Otto of Bavaria introduced the ritual of national celebrations in Greece in 1833. The monarchy instituted annual celebrations for occasions such as the apovatíria—the anniversary of Otto’s landing in Nafplio—and also organized festivities for some of the king’s other public appearances (departures, arrivals, inauguration of various institutions). The festivities were primarily based on the traditions of European royal courts and secondarily on the protocol of the Orthodox Church. The monarchy and its concomitant institutions, the church (with its religious ceremonies) and the army (with its hierarchy), offered a familiar and safe spectacle with their firmly established rites such as parades, processions, hymns, and chants. Given the scanty financial resources of the Greek state during Otto’s reign, sponsoring such celebrations required a delicate balance. Focusing on the example of the anniversary of the Greek War of Independence on March 25, 1838, this article emphasizes the regime’s effort to stage said celebrations in a manner befitting both the significance of each event and the king’s grandeur without provoking public sentiment with the high cost of the celebrations or with events that were unfamiliar to the inhabitants of the Greek capital, Athens.
A Review of Clinical Laboratory Education, Training and Progression: Historical Challenges, the Impact of COVID-19 and Future Considerations
Authors: Pearse Claudia , Scott Sheri
Published: April 2023

The COVID-19 pandemic had a wide global impact on society, including the clinical laboratory workforce. This historically underrepresented group of highly skilled professionals have now started to gain the attention they deserve. There had already been dramatic changes to laboratory training over the past 2 decades resulting from advances in technology, changes to service needs, and as a consequence of Pathology reform initiatives. The pandemic has had an additional impact. Higher education institutions and students adapted to emergency remote teaching. Clinical laboratories faced unprecedented challenges to meet COVID-19 testing demands and adjust to new ways of working whilst maintaining their usual high quality service provision. Training, assessment, and development arrangements had to convert to online platforms to maintain social distancing. The pandemic also had a global impact on mental health and wellbeing, further impacting learning/training. Despite these challenges, there have been many positive outcomes. This review highlights pre- and post-pandemic training and assessment for clinical laboratory professionals, with particular emphasis on Biomedical Scientists, outlining recent improvements among a history of challenges. There is increasing interest surrounding this vital workforce, accelerated thanks to the pandemic. This new public platform has emphasised the importance of quality diagnostic services in the patient pathway and in the response to national crises. The ability to maintain a quality service that is prepared for the future is grounded in the effective training and development of its staff. All of which can only be achieved with a workforce that is sustainable, invested in, and given a voice.
Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis
Authors: Choudhary Sumita , Kesavan Anup Kumar , Juneja Vijay , Thakur Sheetal
Published: April 2023

Computational prediction and protein structure modeling have come to the aid of various biological problems in determining the structure of proteins. These technologies have revolutionized the biological world of research, allowing scientists and researchers to gain insights into their biological questions and design experimental research much more efficiently. Pathogenic Mycobacterium spp. is known to stay alive within the macrophages of its host. Mycobacterium tuberculosis is an acid-fast bacterium that is the most common cause of tuberculosis and is considered to be the main cause of resistance of tuberculosis as a leading health issue. The genome of Mycobacterium tuberculosis contains more than 4,000 genes, of which the majority are of unknown function. An attempt has been made to computationally model and dock one of its proteins, Rv1250 (MTV006.22), which is considered as an apparent drug-transporter, integral membrane protein, and member of major facilitator superfamily (MFS). The most widely used techniques, i.e., homology modeling, molecular docking, and molecular dynamics (MD) simulation in the field of structural bioinformatics, have been used in the present work to study the behavior of Rv1250 protein from M. tuberculosis. The structure of unknown TB protein, i.e., Rv1250 was retrived using homology modeling with the help of I-TASSER server. Further, one of the sites responsible for infection was identified and docking was done by using the specific Isoniazid ligand which is an inhibitor of this protein. Finally, the stability of protein model and analysis of stable and static interaction between protein and ligand molecular dynamic simulation was performed at 100 ns The designing of novel Rv1250 enzyme inhibitors is likely achievable with the use of proposed predicted model, which could be helpful in preventing the pathogenesis caused by M. tuberculosis. Finally, the MD simulation was done to evaluate the stability of the ligand for the specific protein.
Gene length is a pivotal feature to explain disparities in transcript capture between single transcriptome techniques
Authors: Pavan Ricardo R. , Diniz Fabiola , El-Dahr Samir , Tortelote Giovane G.
Published: April 2023

The scale and capability of single-cell and single-nucleus RNA-sequencing technologies are rapidly growing, enabling key discoveries and large-scale cell mapping operations. However, studies directly comparing technical differences between single-cell and single-nucleus RNA sequencing are still lacking. Here, we compared three paired single-cell and single-nucleus transcriptomes from three different organs (Heart, Lung and Kidney). Differently from previous studies that focused on cell classification, we explored disparities in the transcriptome output of whole cells relative to the nucleus. We found that the major cell clusters could be recovered by either technique from matched samples, but at different proportions. In 2/3 datasets (kidney and lung) we detected clusters exclusively present with single-nucleus RNA sequencing. In all three organ groups, we found that genomic and gene structural characteristics such as gene length and exon content significantly differed between the two techniques. Genes recovered with the single-nucleus RNA sequencing technique had longer sequence lengths and larger exon counts, whereas single-cell RNA sequencing captured short genes at higher rates. Furthermore, we found that when compared to the whole host genome (mouse for kidney and lung datasets and human for the heart dataset), single transcriptomes obtained with either technique skewed from the expected proportions in several points: a) coding sequence length, b) transcript length and c) genomic span; and d) distribution of genes based on exons counts. Interestingly, the top-100 DEG between the two techniques returned distinctive GO terms. Hence, the type of single transcriptome technique used affected the outcome of downstream analysis. In summary, our data revealed both techniques present disparities in RNA capture. Moreover, the biased RNA capture affected the calculations of basic cellular parameters, raising pivotal points about the limitations and advantages of either single transcriptome techniques.
Biomaterial-assisted tumor therapy: A brief review of hydroxyapatite nanoparticles and its composites used in bone tumors therapy
Authors: Zhang Quan , Qiang Lei , Liu Yihao , Fan Minjie , Si Xinxin , Zheng Pengfei
Published: April 2023

Graphical Abstract
CRISPR screening in cardiovascular research
Authors: Shan Haihuan , Fei Teng
Published: April 2023

The recent advent and widespread application of CRISPR-based genome editing tools have revolutionized biomedical research and beyond. Taking advantage of high perturbation efficiency and scalability, CRISPR screening has been regarded as one of the most powerful technologies in functional genomics which allows investigation of different genetic subjects at a large scale in parallel. Significant progress has been made using various CRISPR screening tools especially in cancer research, however, fewer attempts and less success are reported in other contexts. In this mini-review, we discuss how CRISPR screening has been implemented in studies on cardiovascular research and related metabolic disorders, highlight the scientific progress utilizing CRISPR screening, and further envision how to fully unleash the power of this technique to expedite scientific discoveries in these fields.
Case report: Surgical repair for left main coronary artery to right atrium fistula with endocarditis
Authors: Zhang Weimin , Maimaitiaili Abdunabi , Xing Yan , Yan Fei , Huo Qiang
Published: April 2023

Coronary artery fistula (CAF) is a rare coronary anomaly defined as a communication between coronary artery and other heart chambers or vascular structures. In this case report, a 32-year-old woman with a giant left main coronary artery to the right atrium fistula with endocarditis was presented. CAF was diagnosed by transthoracic echocardiography and subsequently confirmed by cardiac computerized tomographic and coronary angiography. The patient received antibiotic treatment for infective endocarditis for 6 weeks preoperatively. The fistula was successfully treated with surgical repair. The patient is well now after 18 months of follow-up.
The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease
Authors: Tokiwa Hiroyuki , Ueda Kazutaka , Takimoto Eiki
Published: April 2023

Sexual dimorphism exists in the epidemiology of cardiovascular disease (CVD), which indicates the involvement of sexual hormones in the pathophysiology of CVD. In particular, ample evidence has demonstrated estrogen's protective effect on the cardiovascular system. While estrogen receptors, bound to estrogen, act as a transcription factor which regulates gene expressions by binding to the specific DNA sequence, a subpopulation of estrogen receptors localized at the plasma membrane induces activation of intracellular signaling, called “non-nuclear signaling” or “membrane-initiated steroid signaling of estrogen”. Although the precise molecular mechanism of non-nuclear signaling as well as its physiological impact was unclear for a long time, recent development of genetically modified animal models and pathway-selective estrogen receptor stimulant bring new insights into this pathway. We review the published experimental studies on non-nuclear signaling of estrogen, and summarize its role in cardiovascular system, especially focusing on: (1) the molecular mechanism of non-nuclear signaling; (2) the design of genetically modified animals and pathway-selective stimulant of estrogen receptor.
Association of myocardial iron deficiency based on T2* CMR with the risk of mild left ventricular dysfunction in HIV-1-infected patients
Authors: Yan Chengxi , Li Ruili , Zhang Jiannan , Zhang Li , Yang Minglei , Zhang Qiujuan , Li Hongjun
Published: April 2023

Objectives

This study sought to noninvasively determine myocardial iron levels in HIV-1-infected patients using CMR and explore the association between T2* values and mild left ventricular systolic dysfunction (LVSD).

Methods

This prospective study was conducted from June 2019 to July 2021. HIV-1-infected adults and healthy controls were consecutively enrolled for CMR exam. CMR exam included the assessment of myocardium iron content (T2*), cardiac function (cine), inflammation (T2), and fibrosis (through extracellular volume fraction [ECV] and late gadolinium enhancement [LGE]) measurements. Mild LVSD is defined as a left ventricular ejection fraction (LVEF) between 40% and 49%.

Results

Of 47 HIV-1-infected patients enrolled, 12 were diagnosed with mild LVSD (HIV-1+/LEVF+) and 35 were diagnosed with preserved LV function (HIV-1+/LEVF−). Compared with healthy controls, HIV-1-infected patients displayed higher T2*, T1, T2, ECV values and lower global circumferential strain (GCS) and global radial strain (GRS) (all P < 0.05). However, between patients with and without mild LVSD, only the T2* values and ECV (all P <0.05) were different. The association between increased T2* values (>26 ms) and mild LVSD remained significant after adjusting for the established univariate predictors (ECV >32.9%, T1 values >1336 ms) of mild LVSD (odds ratio [OR], 10.153; 95% confidence interval [CI] 1.565–65.878, P = 0.015).

Conclusions

Myocardial T2* values were elevated in HIV-1-infected patients, supporting the notion that ID was associated with mild LVSD. Our findings highlight the potential for ID in HIV-1-infected patients as an auxiliary biomarker to monitor the course of LVSD.
Examining the variability of rock glacier meltwater in space and time in high-elevation environments of Utah, United States
Authors: Munroe Jeffrey S. , Handwerger Alexander L.
Published: April 2023

Rock glaciers are common geomorphic features in alpine landscapes and comprise a potentially significant but poorly quantified water resource. This project focused on three complementary questions germane to rock glacier hydrology: 1) Does the composition of rock glacier meltwater vary from year to year? 2) How dependent is the composition of rock glacier meltwater on lithology? And 3) How does the presence of rock glaciers in a catchment change stream water chemistry? To address these questions, we deployed automated samplers to collect water from late June through mid-October 2022 in two rock-glacierized mountain ranges in Utah, United States characterized by different lithologies. In the Uinta Mountains of northern Utah, where bedrock is predominantly quartzite, water was collected at springs discharging from two rock glaciers previously shown to release water in late summer sourced from internal ice. In the La Sal Mountains of southeastern Utah, where trachyte bedrock is widespread, water was collected at a rock glacier spring, along the main stream in a watershed containing multiple rock glaciers, and from a stream in a watershed where rock glaciers are absent. Precipitation was also collected, and data loggers for water temperature and electric conductivity were deployed. Water samples were analyzed for stable isotopes with cavity ring-down spectroscopy and hydrochemistry with ICP-MS. Our data show that water discharging from rock glaciers in the Uinta Mountains exhibits a shift from a snowmelt source to an internal ice source over the course of the melt season that is consistent from year to year. We also found that the chemistry of rock glacier water in the two study areas is notably different in ways that can be linked back to their contrasting bedrock types. Finally, in the La Sal Mountains, the properties of water along the main stream in a rock-glacierized basin resemble the properties of water discharging from rock glaciers, and strongly contrast with the water in a catchment lacking rock glaciers. Collectively these results underscore the role of rock glaciers as an agent influencing the hydrochemistry of water in high-elevation stream systems.
The association of apolipoprotein B with chronic kidney disease in the Chinese population
Authors: Xu Yu , Liu Bo , Lin Lijin , Lei Fang , Sun Tao , Zhang Xingyuan , Song Xiaohui , Huang Xuewei , Zeng Qiang , Cai Jingjing , Wang Zhifang , Li Hongliang
Published: April 2023

Background

Whether serum apolipoprotein B (ApoB) is a risk factor for the development of Chronic kidney disease (CKD) has not been fully established in the general population. Therefore, our study evaluated the correlation between serum ApoB level and CKD to look for an alternative approach for CKD prevention and treatment in the general population.

Methods

There were 146,533 participants in this cross-sectional study. 3,325 participants with more than 2 measurements were enrolled in the retrospective longitudinal study with at least a 3-year follow-up. ApoB was measured by the immunoturbidimetric method in 6 centers. Our study defined CKD as an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2. The Spearman rank correlation analysis and the Random Forest algorithm were applied to rank the importance of variables determining the levels of eGFR. We used the logistic regression model to explain the correlation between serum ApoB and CKD. We used the Cox model to detect the correlation between baseline serum ApoB and the subsequent occurrence of CKD.

Results

Based on a cross-sectional study, 66.5% of the participants were males, with a median age of 49 (interquartile range [IQR] 43-55). Compared to the non-CKD group, the CKD group has higher levels of lipid profile and fasting glucose as well as the proportion of hypertension and hyperuricemia. The Spearman rank correlation analysis and the Random Forest algorithm revealed that ApoB has the highest correlation with eGFR decline among lipid profiles. The logistic regression analysis revealed that ApoB had a positive correlation with the prevalence of CKD after fully controlling confounders (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.02-1.11). Moreover, baseline ApoB level was correlated with a new-onset CKD in the longitudinal cohort after full adjustment for confounding factors (hazard ratio [HR], 1.61; 95% CI: 1.02-2.54). The correlation between ApoB level and the new-onset CKD was consistently observed in all sensitivity analyses.

Conclusion

Serum ApoB had the strongest correlation with CKD among all lipid variables. Moreover, high serum ApoB levels might precede the occurrence of CKD, suggesting that monitoring and reducing serum ApoB levels may provide an alternative method to prevent and treat CKD.
Blood glucose level affects prognosis of patients who received intravenous thrombolysis after acute ischemic stroke? A meta-analysis
Authors: Wang Yue , Jiang Guannan , Zhang Jie , Wang Jingfeng , You Wanchun , Zhu Juehua
Published: April 2023

Background and objectives

Intravenous recombinant tissue plasminogen activator (rtPA) thrombolysis is an effective treatment for acute ischemic stroke. Hyperglycemia is a major risk factor for the occurrence, development, and prognosis of ischemic stroke. This meta-analysis purposefully estimates the association between hyperglycemia and poor prognosis in acute ischemic stroke patients receiving intravenous rtPA thrombolytic therapy.

Materials and methods

According to the predefined inclusion criteria, we searched PubMed, Web of Science, and Cochrane Library databases. The association of high blood glucose(>140mg/dl) with symptomatic intracranial hemorrhage (sICH), poor clinical outcome and mortality at 90 days post-rtPA thrombolysis was studied using both a common effects model and a random effects model. Odds ratios (ORs) were plotted on forest plots.

Results

Of a total cohort of 2565 patients who received intravenous thrombolytic therapy, 721 had higher blood glucose. High glucose level significantly increased the odds of sICH (OR 1.80; 95% confidence interval(95%CI): 1.30- 2.50) and poor clinical outcome at 90 days (OR 1.82; 95%CI: 1.52-2.19), and all-cause mortality at 90 days (OR 2.51; 95%CI:1.65-3.82).

Conclusions

In our meta-analysis, high blood glucose was significantly associated with sICH, poor clinical outcome and higher mortality at 90 days.
Fatty liver mediates the association of hyperuricemia with prediabetes and diabetes: a weighting-based mediation analysis
Authors: Basnet Til Bahadur , Du Shanshan , Feng Ruimei , Gao Jie , Gong Jiamin , Ye Weimin
Published: April 2023

Background

Fatty liver, obesity, and dyslipidemia are associated with prediabetes or diabetes risk, and hyperuricemia co-exists. The present study evaluated the role of multiple mediators, namely, fatty liver, body mass index (BMI), and dyslipidemia, in the association between hyperuricemia and diabetes status.

Methods

Baseline data from the ongoing Fuqing cohort (5,336 participants) were analyzed to investigate the association of hyperuricemia with diabetes status using a multinomial logistic regression model. Furthermore, causal mediation analysis with the weighting-based approach was performed to estimate hyperuricemia’s total natural direct effect (tnde), total natural indirect effect (tnie), and total effect (te) on prediabetes and diabetes risk, mediating jointly via fatty liver, BMI, and dyslipidemia.

Results

In multinomial analysis without considering mediators’ effects, hyperuricemia was associated with a higher risk of prediabetes only (odds ratio: 1.25; 95% CI: 1.09–1.43; p < 0.001). When fatty liver, BMI, and dyslipidemia were considered as multiple mediators in the association, hyperuricemia was linked to both prediabetes [tnde: 1.11, 95% CI: 1.04–1.11; tnie: 1.07, 95% CI: 1.05–1.09; and overall proportion mediated (pm): 42%, 95% CI: 27%–73%] and diabetes risk (tnde: 0.96, 95% CI: 0.82–1.14; tnie: 1.25, 95% CI: 1.18–1.33; and pm: 100%, 95% CI: 57%–361%). Hyperuricemia showed significant tnde, te, and tnie, mediated by fatty liver jointly with dyslipidemia (pm = 17%) or BMI (pm = 35%), on prediabetes risk.

Conclusion

Hyperuricemia could increase prediabetes or diabetes risk, partially mediated by fatty liver, BMI, and dyslipidemia. Fatty liver is the crucial mediator in the association between hyperuricemia and prediabetes.
CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction
Authors: Hueso Luisa , Marques Patrice , Morant Brenda , Gonzalez-Navarro Herminia , Ortega Joaquin , Real José T. , Sanz María J , Piqueras Laura
Published: April 2023

Background/Aims

Chemokines are known to play critical roles mediating inflammation in many pathophysiological processes. The aim of this study was to investigate the role of chemokine receptor CCR4 and its ligands CCL17 and CCL22 in human morbid obesity.

Methods

Circulating levels of CCL17 and CCL22 were measured in 60 morbidly obese patients (mean age, 45 ± 1 years; body mass index/BMI, 44 ± 1 kg/m2) who had undergone bariatric bypass surgery, and 20 control subjects. Paired subcutaneous (SCAT) and visceral adipose tissue (VCAT) from patients were analysed to measure expression of CCR4 and its ligands by RT-PCR, western blot and immunohistochemical analysis. The effects of CCR4 neutralization ex vivo on leukocyte-endothelial cells were also evaluated.

Results

Compared with controls, morbidly obese patients presented higher circulating levels of CCL17 (p=0.029) and CCL22 (p<0.001) and this increase was positively correlated with BMI (p=0.013 and p=0.0016), and HOMA-IR Index (p=0.042 and p< 0.001). Upregulation of CCR4, CCL17 and CCL22 expression was detected in VCAT in comparison with SCAT (p<0.05). Using the parallel-plate flow chamber model, blockade of endothelial CCR4 function with the neutralizing antibody anti-CCR4 in morbidly obese patients significantly reduced leucocyte adhesiveness to dysfunctional endothelium, a key event in atherogenesis. Additionally, CCL17 and CCL22 increased activation of the ERK1/2 mitogen-activated protein kinase signalling pathway in human aortic endothelial cells, which was significantly reduced by CCR4 inhibition (p=0.016 and p<0.05).

Conclusion

Based on these findings, pharmacological modulation of the CCR4 axis could represent a new therapeutic approach to prevent adipose tissue dysfunction in obesity.
Anthropogenic noise events perturb acoustic communication networks
Authors: Kleist Nathan J. , Fristrup Kurt M. , Buxton Rachel T. , McKenna Megan F. , Job Jacob R. , Angeloni Lisa M. , Crooks Kevin , Wittemyer George
Published: April 2023

Anthropogenic noise sources impact ecological processes by altering wildlife behavior and interactions with cascading impacts on community structure. The distribution and magnitude of such noise has grown exponentially over the past century, and now inundates even remote areas. Here we investigate biological responses to prolific, anthropogenic noise sources associated with the physical presence of the source (vehicle noise and human voices) and disconnected from it (aircraft overflight). Bioacoustic responses to these noise sources were documented at 103 sites in 40 U. S. National Park units. The presence of bird sounds was noted in 10-s audio samples every 2 min, for 8 days at each site and related to the presence of human voices, vehicle noise, and aircraft noise in the same and preceding samples. Generalized additive models were used to fit smoothing splines to weight the influence of noise in past samples on the probability of detecting bird sounds in the present sample. We found that the probability of hearing birds increased immediately following noise events, and decreased about 2 h after the event. The negative effects were persistent more than 3 h after a noise event. The persistence of these responses – especially for noise from jets that were many kilometers distant – raises questions about the functional significance and ecological consequences of this altered activity, particularly in light of the widespread and diverse habitats in this study and ubiquity of the noise sources evaluated.
Distribution of six phenolic acids and soil nutrient relationships during litter decomposition in Rhododendron forests
Authors: Zhao Yumeng , Lin Jian , Quan Wenxuan , Li Chaochan
Published: April 2023

Litter decomposition is an essential process in nutrient cycling in terrestrial ecosystems. Phenolic acids have an allelopathic effect on the natural regeneration of rhododendron forests, which was recently observed in rhododendron forests in Southwest China. We investigated the distribution of phenolic acids and their relationship with soil nutrients during litter decomposition to provide a reference for the subsequent artificial management of rhododendron forests. High-performance liquid chromatography (HPLC) was used to analyze the contents of six phenolic acids in the litter layer, humus layer, and soil layer during litter decomposition. During the first 3 three months, the rapid decomposition of the litter from two early flowering rhododendron species released large amounts of phenolic acids, and the lower litter layer decomposed rapidly. In addition, the total phenolic acid content in the litter decreased by 257.60 μg/g (Rhododendron siderophyllum) and 53.12 μg/g (Rhododendron annae) in the first three 3 months. During subsequent litter decomposition, the protocatechuic acid content in the litters of Rhododendron siderophyllum ranged from 20.15 μg/g to 39.12 μg/g, and the ferulic acid content was 10.70 μg/g to –33.79 μg/g. The protocatechuic acid and ferulic acid contents in the litter of Rhododendron annae were in the ranges of 10.88—19.68 μg/g and 10.75—18.00 μg/g, respectively. The contents of these two phenolic acids and the trend of decomposition were different from those of gallic acid, chlorogenic acid, caffeic acid and syringic acid. The distribution of phenolic acids was influenced by soil organic matter (SOM), soil ammonium nitrogen (NH4+), soil nitrate nitrogen (NO3–) and soil available phosphorus (AP). The results indicate seasonal variations in phenolic acid release during litter decomposition. The amount of phenolic acid in the litter decreased after 18 months of decomposition, but it returned to the previous level in the soil and the humus after different trends. More research into the metabolism of phenolic acids is needed.
10 Years of GWAS in intraocular pressure
Authors: Gao Xiaoyi Raymond , Chiariglione Marion , Choquet Hélène , Arch Alexander J.
Published: April 2023

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, the leading cause of irreversible blindness worldwide. In this review, we summarize the findings of genome-wide association studies (GWASs) of IOP published in the past 10 years and prior to December 2022. Over 190 genetic loci and candidate genes associated with IOP have been uncovered through GWASs, although most of these studies were conducted in subjects of European and Asian ancestries. We also discuss how these common variants have been used to derive polygenic risk scores for predicting IOP and glaucoma, and to infer causal relationship with other traits and conditions through Mendelian randomization. Additionally, we summarize the findings from a recent large-scale exome-wide association study (ExWAS) that identified rare variants associated with IOP in 40 novel genes, six of which are drug targets for clinical treatment or are being evaluated in clinical trials. Finally, we discuss the need for future genetic studies of IOP to include individuals from understudied populations, including Latinos and Africans, in order to fully characterize the genetic architecture of IOP.
Blood cell traits and risk of glaucoma: A two-sample mendelian randomization study
Authors: Song De-Juan , Fan Bin , Li Guang-Yu
Published: April 2023

Importance: Glaucoma is the second leading cause of blindness in the world. The causal direction and magnitude of the association between blood cell traits and glaucoma is uncertain because of the susceptibility of observational studies to confounding and reverse causation.

Objective: To explore whether there is a causal relationship of blood cell traits including white blood cell (WBC) count (WBCC) and its subtypes [basophil cell count (BASO), monocyte cell count (MONO), lymphocyte cell count (LYMPH), eosinophil cell count (EOS), neutrophil cell count (NEUT)], red blood cell (RBC) count (RBCC), red blood distribution width (RDW), platelet count (PLT), and plateletcrit (PCT) on glaucoma risk.

Methods: A two-sample Mendelian randomization (MR) analysis was conducted. Genome-wide significant single nucleotide polymorphisms (SNPs) from published genome-wide association studies (GWAS) on human blood cell traits were utilized as exposure instruments and the dataset for outcome was from the GWAS summary data of glaucoma. In the univariable MR analysis, we examined the association between genetic evidence of blood cell traits and glaucoma. To further investigate the potential causal mechanisms underlying the observed association, we performed multivariable MR analysis with three models, taking into account the mediator effect of inflammation and oxidative stress. According to Bonferroni-corrected for the 10 exposures in 3 methods, the MR study yielded a statistically significant p-value of 0.0017.

Results: Genetically BASO, PCT, LYMPH, and PLT were potentially positively associated with glaucoma in the European ancestry [BASO: Odds ratio (OR) = 1.00122, 95% confidence interval (CI), 1.00003–1.00242, p = 0.045; PCT: OR = 1.00078, 95% CI, 1.00012–1.00143, p = 0.019; LYMPH: OR = 1.00076, 95% CI, 1.00002–1.00151, p = 0.045; PLT: OR = 1.00065, 95% CI, 1.00006–1.00123, p = 0.030], There was insufficient evidence to support a causal association of MONO, NEUT, EOS, WBCC, RBCC and RDW (MONO: OR = 1.00050, p = 0.098; NEUT: OR = 1.00028, p = 0.524; EOS: OR = 1.00020, p = 0.562; WBCC: OR = 1.00008, p = 0.830; RBCC: OR = 0.99996, p = 0.920; RDW: OR = 0.99987, p = 0.734) with glaucoma. The multivariable MR with model 1, 2, and 3 demonstrated that BASO, PCT, LYMPH, and PLT were still potentially genetically associated with the risk of glaucoma.

Conclusion: Our study reveals a genetic predisposition to higher LYMPH, BASO, PLT, and PCT are associated with a higher risk of glaucoma, whereas WBCC, MONO, EOS, NEUT, RBCC, and RDW are not associated with the occurrence of glaucoma. This finding also supports previous observational studies associating immune components with glaucoma, thus provide guidance on the predication and prevention for glaucoma.
Investigating the role of FADS family members in breast cancer based on bioinformatic analysis and experimental validation
Authors: Zhao Tingting , Gao Pingping , Li Yanling , Tian Hao , Ma Dandan , Sun Na , Chen Ceshi , Zhang Yi , Qi Xiaowei
Published: April 2023

Breast cancer (BC) is the most common malignant tumor in women worldwide. Emerging evidence indicates the significance of fatty acid metabolism in BC. Fatty acid desaturase (FADS) is closely associated with cancer occurrence and development. Here, bioinformatic analysis and experimental validation were applied to investigate the potential functions of FADS in BC. Several public databases, including TCGA, GEO, HPA, Kaplan–Meier plotter, STRING, DAVID, cBioPortal, TIMER, TRRUST, and LinkedOmics were used to determine mRNA/protein expression levels, prognostic significance, functional enrichment, genetic alterations, association with tumor-infiltrating immune cells, and related transcription factors and kinases. BC tissues showed higher and lower mRNA expression of FADS2/6/8 and FADS3/4/5, respectively. FADS1/2/6 and FADS3/4/5 showed higher and lower protein expression levels, respectively, in BC tissues. Moreover, FADS1/7 up- and FADS3/8 down-regulation predicted poor overall and recurrence-free survival, while FADS2/5 up- and FADS4 down-regulation were associated with poor recurrence-free survival. Receiver operating characteristic curves revealed that FADS2/3/4/8 were indicative diagnostic markers. FADS family members showing differential expression levels were associated with various clinical subtypes, clinical stages, lymph node metastasis status, copy number variants, DNA methylation, and miRNA regulation in BC. The mRNA expression level of FADS1/2/3/4/5/7/8 was observed to be significantly negatively correlated with DNA methylation. FADS1/2 upregulation was significantly correlated with clinical stages. FADS1/4 expression was obviously lower in BC patients with higher lymph node metastasis than lower lymph node metastasis, while FADS7/8 expression was obviously higher in BC patients with higher lymph node metastasis than lower lymph node metastasis. FADS family members showed varying degrees of genetic alterations, and Gene Ontology and KEGG pathway enrichment analyses suggested their involvement in lipid metabolism. Their expression level was correlated with immune cell infiltration levels. FADS2 was chosen for further validation analyses. We found FADS2 to be significantly over-expressed in clinical BC tissue samples. The proliferation, migration, and invasion abilities of MDA-MB-231 and BT474 cells were significantly reduced after FADS2 knockdown. Furthermore, FADS2 may promote the occurrence and development of BC cells via regulating the epithelial–mesenchymal transition (EMT) pathway. Altogether, our results suggest that FADS1/2/3/4 can serve as potential therapeutic targets, prognostic indicators, and diagnostic markers in patients with BC.
Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice
Authors: Martínez-Pérez Amparo , Diego-González Lara , Vilanova Manuel , Correia Alexandra , Simón-Vázquez Rosana , González-Fernández África
Published: April 2023

Purpose

The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V.

Experimental design

We tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer.

Results

Unexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response.

Conclusion

Our results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer.
Thieno[3,2-b]thiophene and triphenylamine-based hole transport materials for perovskite solar cells
Authors: Isci Recep , Unal Melis , Yesil Tamer , Ekici Alper , Sütay Berkay , Zafer Ceylan , Ozturk Turan
Published: April 2023

Heterocyclic compounds have played significant roles in achieving high performance as hole transport materials (HTMs) for perovskite solar cell (PSC) applications. Various studies have focused on the development of fused heterocyclic conjugated structures for hole transport materials. In this report, three novel π-extended conjugated materials (M1-M3), based on thieno[3,2-b]thiophene (TT) and 4,4′-dimethoxytriphenylamine [TPA(OMe)2], were designed and successfully synthesized via Palladium (0) catalyzed Suzuki coupling reaction. Their optical, electrochemical, and thermal properties were investigated by UV-Vis, fluorescence, cyclic voltammetry, and thermal analysis. The materials were utilized as hole transport materials in p-i-n architecture perovskite solar cells, which displayed performances of open-circuit voltage (Voc) as high as 1,050 mV, a maximum short-circuit current (Jsc) of 16,9 mA/cm2, a maximum fill factor (FF) of 29.3%, and a power conversion efficiency (PCE) of 5.20%. This work demonstrated that thieno[3,2-b]thiophene and TPA(OMe)2-based structures are promising cores for high-performance hole transport materials in perovskite solar cell architecture.