bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Frost Dilatometry Methodology and Critical Degree of Saturation of Brick Slices Versus Half Brick Samples
Authors: Lee Catherine
Published: February 2024

This study investigates the susceptibility of clay brick masonry to freeze‐thaw deterioration using the frost dilatometry methodology. Trends between the critical degree of saturation (Scrit) and varying sizes of clay bricks are examined to see if differences in material composition and pore structure impact the durability classification relative to freeze‐thaw damage. Previous research has investigated the Scrit for different sized clay brick masonry, however a disconnect exists between relating the specimen size to the resulting degree of frost damage. Therefore, a gap is present in the understanding of what size sample is most representative of a bricks durability as a whole and can sufficiently predict the performance of a brick in service. For this study, 2D and 3D frost dilatometry testing was conducted on brick slices and half brick samples from 14 historical bricks. Strain was measured along the x, y and z‐ axes to assess the resulting effect of frost decay. 

Results showed that the Scrit does appear to be impacted based on the size of the specimen being tested. Smaller sized samples (brick slices) typically resulted in a higher Scrit than larger samples (half bricks). For instance, samples U3, U4 and U5, which all originate from the same building had a projected Scrit of 88%, 89% and 88% respectively, when tested as brick slices. However, testing from the half bricks resulted in projected Scrits of 72%, 77% and 76% respectively. This shift in the projected Scrit was significant enough to alter the durability classification of each brick. Thus, it was found that out of a total 13 brick samples 11 (85%) were considered to be sufficiently durable, 2 (15%) questionably durable and none were deemed not durable, based on the data collected from testing brick slices. In comparison, to testing conducted on half bricks that found only 2 (15%) samples were considered sufficiently durable, 9 (69%) questionably durable and 2 (15%) were deemed not durable. These findings highlight the importance of standardizing a methodology for frost dilatometry testing to help ensure the durability performance of bricks are being assessed in a comparable manner.
The effect of excess cement on peri-implantitis: A literature review
Authors: Minim Pedro Rodrigues , Benavente Kevin Alexis Supa , Rischmoller Jackeline Eliana Aranda , Porto Vinicius Carvalho , Santiago Junior Joel Ferreira
Published: February 2024

Peri-implantitis (PI) is a major dental implantology challenge. Excess cement (EC) significantly impacts PI onset and progression. This review clarifies unremoved EC's effects on peri-implant tissue. A literature search from 2012 to 2024 was conducted. Eleven studies examining EC's impact on peri-implant health were included. Investigated parameters were cement type, implant diameter, EC duration, and oral microbiota-cement interaction. Studies show EC as a key PI risk, with better outcomes post-removal. Larger implant diameters correlated with higher EC risks. EC retention duration directly affected PI severity. Different cements, like methacrylate-based cement (MeC) and zinc oxide and eugenol-based cement (ZOEC), varied in affecting PI. ZOEC notably mitigated PI risks and lacked in EC cases. Early PI detection and prompt removal are crucial. Choosing ZOEC cement can significantly reduce PI risks. Dentists should use minimal cement for implant restorations. Developing standard research methods is key to validate findings and guide practice.
Density estimation of the globally threatened fishing cat Prionailurus viverrinus through a participatory science approach in the Chilika lagoon, eastern India
Authors: Adhya T , Banerjee S , Dey P , Nanda S , Santra S , Nesha I
Published: February 2024

The fishing catPrionailurus viverrinusis an Indo-Malayan wetland-dependent felid which is listed as Vulnerable on the IUCN Red List. Its main prey, fish, has low energetic demands and is abundant in productive aquatic habitats. This facilitates high piscivore densities and potentially alters expected scaling patterns that link population density to the body mass of small cats. With local community participation, we estimated the density of the fishing cat in Chilika, Asia’s largest brackish water lagoon, located in the state of Odisha, eastern India, with community participation. The study was carried out in 2 phases in different habitats during 2021 and 2022: a homogeneous marshy habitat and its buffer (Northern Block), and a heterogeneous matrix of different land-use types (Southern Block). We deployed a total of 144 camera traps across 4380 trap nights. Using spatially explicit capture-recapture (SECR), we estimated mean (±SE) fishing cat density to be 0.69 ± 0.1 ind. km-2in the Northern Block and 0.67 ± 0.33 ind. km-2in the Southern Block. The population abundance estimates for the Northern and the Southern Blocks were 159 ± 23 and 185 ± 91 respectively. In the former, SECR modelling indicated an effect of anthropogenic habitat modification upon the species’ home range extent. Our density estimates are amongst the highest reported for the species outside protected areas. The results imply that Chilika holds an abundant population of the fishing cat, the continued persistence of which requires mitigation of local and external threats to fish populations. Furthermore, our study, with its inclusive approach, sets a precedent for the use of camera trapping for obtaining robust density estimates of species with uniquely marked individuals in wetland habitats.
PSIKOLOGI BERMAIN ANAK USIA DINI DALAM MENSTIMULASI PERKEMBANGAN OTAK
Authors: Diananda Amita
Published: February 2024

In a psychological context, playing is an activity involving all psychological functions in a variety of situations. Playing in a child's world is a fun activity. Many things are gained in playing, such as new experiences, new skills, knowing various rules in the game, being able to discern various emotional conditions that may arise (such as pleasure, joy, tension, satisfaction, and maybe disappointment, too). Thus, psychologically, playing can help develop the potential that exists in children and help improve children's abilities in solving various known problems, as well as recognizing and obeying all existing rules. Besides that, it can also teach children to speak honestly, faithfully, and so on. All of these will be able to stimulate cognitive, social, emotional, motoric, and other intelligence development. The playground also plays a major role in increasing children's intelligence and caring. The results showed that children who were rarely stimulated by playing and be conscious of their environmentÂ  t play had their brain growth and development about 20 or 30 percent smaller than their normal size. As a result, brain dysfunction occurs which affects the intelligence and reactive ability of children to respond to everything that happens in their environment. The brain also requires adequate nutritional intake. Malnutrition in the brain results in a decrease in the brain's ability to receive, record, store, process, exercise, respond to, produce, and reconstruct information. In the brain, there is a part of brain cells that manage emotions called the amygdala which functions to store old memories related to emotions. This amygdala is related to human emotional behavior that can be changed and/or controlled for the better, such as from fear to being brave, from not caring to being attentive, and so on.
Pengaruh Pembelajaran Akidah Akhlak Terhadap Perilaku Siswa
Authors: Fitriani Aulia Rahma
Published: February 2024

This study aims to determine the effect of Akidah Akhlak Learning on the Behavior of Class VIII Students at MTs Nur As-Sholihat Lengkong Wetan, South Tangerang. This research uses quantitative research. The subjects of this research are class VIII students of MTs Nur As-Sholihat, totaling 203 students. The sample collection technique used is the Cluster Sampling technique. This study uses data collection techniques with observations, questionnaires, interviews, and documentation. Test the validity of the data using the Person Product Moment formula and test the reliability by paying attention to the value of the Cronbach alpha. In this study, the data analysis used a simple linear regression analysis technique. From the results of the hypothesis test, it was found that learning aqidah morals had a positive and significant effect on the behavior of class VIII students with an influence level of 2.2% while the rest was influenced by other factors not examined.
Pola Asuh Orang Tua Tunggal Dalam Membentuk Akhlak Terpuji Anak
Authors: Kaesuroh Dede , Budiana Irma
Published: February 2024

The purpose of this study was to find out how single parent parenting styles in shaping childrenâ€™s morals and to find out the morals of children raised by single parents. This research is qualitative field research. The research subjects were single parents in the helmet of 06 Kiara Payung Village. Data sources come from primary and secondary data. Data collection techniques are by observation, interview and documentation or archives. The data validity or validity tes technique used in this study is sources. Data analysis techniques used in this study are interactive data analysis techniques including the data collection stage, the data reduction stage, the data presentation stage and the conclusion drawing stage. The results showed the single parents parenting pattern in hamlet 06 of Kiara Payung Village used a democratic parenting pattern where single parents were good enough to take care of their childrenÂ  by conducting deliberation when making several choices. Parents also give freedom but not absolute control by parents and establish good communication and provide moral guidance. The character of the child is quite good but there are bad sides such as lying, fighting and others.
Peran Orang Tua Dalam Membentuk Kedisiplinan Anak Usia 5-6 Tahun
Authors: Sari Dewi Sekar , Alawiyah Neneng
Published: February 2024

Discipline is a character trait that every student requires. Failure to form this trait can result in students having difficulty in self-management. The purpose of this study was to find out the role of parents in shaping the discipline of their 5-6 years old children, both in the school environment and at home. This research used a descriptive approach with qualitative research methods (field research). The data was collected through observation, interviews, and documentation with a research time of one month. The research subjects were students between 5-6 years old in class B of the Cempaka Putri Curug Tangerang Kindergarten. The data acquired from the parents and students in the form of observations, teacher and parents interview, and documentation. Data analysis carried out inductively with data reduction, data presentation, conclusions, and verification. The data validated through triangulation technique. The result of the study indicate that parents have a critical role and tremendous influence in shaping the children's discipline.Â  Parents, assisted by teachers in school, has a clear impact in forming the children's discipline from their early age that will turn into a practice they will carry into their future.
PENGARUH VARIASI MENGAJAR GURU TERHADAP MINAT BELAJAR SISWA KELAS VI PADA MATA PELAJARAN AKIDAH AKHLAK
Authors: Fatihah Awwalina Restu , Juliastuti Juliastuti
Published: February 2024

This study was conducted to determine the positive and significant influence between the variations in teaching teachers on the learning interests of class VI students in the subject of Akidah Akhlak at MI Nurul Falah Suradita Cisauk, Tangerang Regency. The research uses survey research methods. And the population in this study was class VI students and the sample used a random sampling technique of 51 students. The research approach uses a causal approach and the type of research, namely quantitative research. Based on the acquisition of a simple linear regression analysis test with the equation Y = 35,509 + 0.484 X. Regression coefficient of the Teacher Teaching Variation variable (X) is 0.484 meaning that if the teacher's teaching variation increases by 1%, then the interest in learning has increased by 0.484% and the coefficient is positive, meaning that the teacher teaching variation variable contributes positively to student learning interest. Then obtained the R Square test explained the magnitude of the influence of the variable X on Y, which is 0.149 = 14.9%. That is, the magnitude of the influence of variable X (variation in teaching teachers) on Y (student interest in learning) is 14.9%, the remaining 85.1% is influenced by other factors such as family factors, physical factors, and psychological factors
Cancer risk in polycystic ovary syndrome patients: Common treatments and future perspectives
Authors:   Department of Pharmacy, East West University, Dhaka 1212, Bangladesh, Shahrin Alfi , Mele Mahmuda Akter ,   College of Science and Engineering, James Cook University, Townsville, Queensland 4811, Australia., Islam Mohammad Zahirul ,   Department of Food Science and Biotechnology, Gachon University, Seongnam 13120, Republic of Korea
Published: February 2024

In women of childbearing age, polycystic ovarian syndrome (PCOS) is the most common endocrine and metabolic condition. Ovulatory dysfunction, clinical symptoms of hyperandrogenism, and multiple cystic ovaries are the hallmarks of PCOS. Women who have PCOS may have irregular insulin activity in addition to other difficulties such as pattern hair loss, acne, obesity, infertility, and hirsutism. An unhealthy lifestyle, hereditary causes, androgen exposures, and neuroendocrine factors are frequently the causes of PCOS. This results in an unbalanced hormonal state, hyperandrogenism, high insulin, and inflammation. Due to the overlapping metabolic and endocrine issues, PCOS patients' cancer risk has been the subject of debate for decades.This review article examines the relationship between PCOS and various types of reproductive cancers, focusing on the possible reasons for cancer in PCOS patients.
Application of 3D printed titanium mesh and digital guide plate in the repair of mandibular defects using double-layer folded fibula combined with simultaneous implantation
Authors: Li Shangbo , Mi Lian , Bai Li , Liu Zijian , Li Li , Wu Yupeng , Chen Liqiang , Bai Na , Sun Jian , Liu Yanshan
Published: February 2024

Fibula transplantation plays an irreplaceable role in restoring the function and morphology of the defected mandible. However, the complex load-bearing environment of the mandible makes it urgent to accurately reconstruct the mandible, ensure the position of the condyle after surgery, and restore the patient’s occlusal function and contour. The intervention of digital design and three-dimensional (3D) printed titanium mesh provides a more efficient method and idea to solve this problem. Digital design guides the accurate positioning, osteotomy, and simultaneous implant placement during surgery, and 3D printed titanium mesh ensures stable condyle position after surgery, restoring good mandibular function. The double-layer folded fibula maintains the vertical height of the mandible and a good facial contour, and simultaneous implant placement can establish a good occlusal relationship. This study conducted a retrospective analysis of five patients with jaw defects who underwent digital fibula reconstruction over the past 3 years. It was found that the surgical protocol combining digital design, 3D printed intraoperative guides, 3D printed titanium mesh, free fibula flap, immediate implant, and occlusal reconstruction to repair jaw defects had more ideal facial appearance and biological function. It will provide a more reliable surgical protocol for clinical management of large mandibular defects.
Stemness properties of SSEA-4+ subpopulation isolated from heterogenous Wharton’s jelly mesenchymal stem/stromal cells
Authors: Smolinska Agnieszka , Chodkowska Magdalena , Kominek Agata , Janiec Jakub , Piwocka Katarzyna , Sulejczak Dorota , Sarnowska Anna
Published: February 2024

Background: High heterogeneity of mesenchymal stem/stromal cells (MSCs) due to different degrees of differentiation of cell subpopulations poses a considerable challenge in preclinical studies. The cells at a pluripotent-like stage represent a stem cell population of interest for many researchers worldwide, which is worthy of identification, isolation, and functional characterization. In the current study, we asked whether Wharton’s jelly-derived MSCs (WJ-MSCs) which express stage-specific embryonic antigen-4 (SSEA-4) can be considered as a pluripotent-like stem cell population.

Methods: SSEA-4 expression in different culture conditions was compared and the efficiency of two cell separation methods were assessed: Magnetic Activated Cell Sorting (MACS) and Fluorescence Activated Cell Sorting (FACS). After isolation, SSEA-4+ cells were analyzed for the following parameters: the maintenance of the SSEA-4 antigen expression after cell sorting, stem cell-related gene expression, proliferation potential, clonogenicity, secretome profiling, and the ability to form spheres under 3D culture conditions.

Results: FACS allowed for the enrichment of SSEA-4+ cell content in the population that lasted for six passages after sorting. Despite the elevated expression of stemness-related genes, SSEA-4+ cells neither differed in their proliferation and clonogenicity potential from initial and negative populations nor exhibited pluripotent differentiation repertoire. SSEA-4+ cells were observed to form smaller spheroids and exhibited increased survival under 3D conditions.

Conclusion: Despite the transient expression of stemness-related genes, our findings could not fully confirm the undifferentiated pluripotent-like nature of the SSEA-4+ WJ-MSC population cultured in vitro.
Virtual calcium removal in calcified coronary arteries with photon-counting detector CT—first in-vivo experience
Authors: Mergen Victor , Rusek Stéphane , Civaia Filippo , Rossi Philippe , Rajagopal Rengarajan , Bättig Eduardo , Manka Robert , Candreva Alessandro , Eberhard Matthias , Alkadhi Hatem
Published: February 2024

Purpose

To evaluate the feasibility and accuracy of quantification of calcified coronary stenoses using virtual non-calcium (VNCa) images in coronary CT angiography (CCTA) with photon-counting detector (PCD) CT compared with quantitative coronary angiography (QCA).

Materials and methods

This retrospective, institutional-review board approved study included consecutive patients with calcified coronary artery plaques undergoing CCTA with PCD-CT and invasive coronary angiography between July and December 2022. Virtual monoenergetic images (VMI) and VNCa images were reconstructed. Diameter stenoses were quantified on VMI and VNCa images by two readers. 3D-QCA served as the standard of reference. Measurements were compared using Bland-Altman analyses, Wilcoxon tests, and intraclass correlation coefficients (ICC).

Results

Thirty patients [mean age, 64 years ± 8 (standard deviation); 26 men] with 81 coronary stenoses from calcified plaques were included. Ten of the 81 stenoses (12%) had to be excluded because of erroneous plaque subtraction on VNCa images. Median diameter stenosis determined on 3D-QCA was 22% (interquartile range, 11%–35%; total range, 4%–88%). As compared with 3D-QCA, VMI overestimated diameter stenoses (mean differences −10%, p < .001, ICC: .87 and −7%, p < .001, ICC: .84 for reader 1 and 2, respectively), whereas VNCa images showed similar diameter stenoses (mean differences 0%, p = .68, ICC: .94 and 1%, p = .07, ICC: .93 for reader 1 and 2, respectively).

Conclusion

First experience in mainly minimal to moderate stenoses suggests that virtual calcium removal in CCTA with PCD-CT, when feasible, has the potential to improve the quantification of calcified stenoses.
Divergent electrophysiologic action of dapagliflozin and empagliflozin on ventricular and atrial tachyarrhythmias in isolated rabbit hearts
Authors: Wolfes Julian , Uphoff Jan , Kemena Sven , Wegner Felix , Rath Benjamin , Eckardt Lars , Frommeyer Gerrit , Ellermann Christian
Published: February 2024

Background

The use of SGLT-2 inhibitors has revolutionized heart failure therapy. Evidence suggests a reduced incidence of ventricular and atrial arrhythmias in patients with dapagliflozin or empagliflozin treatment. It is unclear to what extent the reduced arrhythmia burden is due to direct effects of the SGLT2 inhibitors or is solely a marker of improved cardiac function.

Methods

One hundred five rabbit hearts were allocated to eight groups and retrogradely perfused, employing a Langendorff setup. Action potential duration at 90% of repolarization (APD90), QT intervals, effective refractory periods, conduction velocity, and dispersion of repolarization were obtained with monophasic action potential catheters. A model for tachyarrhythmias was established with the IKr blocker erythromycin for QT prolongation associated proarrhythmia as well as the potassium channel opener pinacidil for a short-QT model. An atrial fibrillation (AF) model was created with isoproterenol and acetylcholine. With increasing concentrations of both SGLT2 inhibitors, reductions in QT intervals and APD90 were observed, accompanied by a slight increase in ventricular arrhythmia episodes. During drug-induced proarrhythmia, empagliflozin succeeded in decreasing QT intervals, APD90, and VT burden whereas dapagliflozin demonstrated no significant effects. In the presence of pinacidil induced arrhythmogenicity, neither SGLT2 inhibitor had a significant impact on cardiac electrophysiology. In the AF setting, perfusion with dapagliflozin showed significant suppression of AF in the course of restitution of electrophysiological parameters whereas empagliflozin showed no significant effect on atrial fibrillation incidence.

Conclusion

In this model, empagliflozin and dapagliflozin demonstrated opposite antiarrhythmic properties. Empagliflozin reduced ventricular tachyarrhythmias whereas dapagliflozin showed effective suppression of atrial arrhythmias.
The role of adiponectin in the association between abdominal obesity and type 2 diabetes: a mediation analysis among 232,438 Chinese participants
Authors: He Lingjie , Xuan Wenting , Liu Dixing , Zhong Jiana , Luo Huijin , Cui Han , Zhang Xiuwei , Chen Weikun
Published: February 2024

Background

Adiposity and adipokines are closely associated with obesity-related metabolic abnormalities, but little is known regarding whether abdominal obesity is linked to type 2 diabetes mellitus (T2DM) through circulating adiponectin levels. Thus, this large-population–based study was designed to investigate the mediating effect of adiponectin in the relationship between abdominal obesity and T2DM.

Methods

A total of 232,438 adults who lived in Dongguan, Guangdong Province, China, were enrolled in the present study. The circulating adiponectin concentrations were measured using latex-enhanced immunoturbidimetric assay. The association between circulating adiponectin and other clinical parameters was detected by Spearman’s correlation analysis. Restricted cubic spline (RCS) regression was also used to address the non-linearity of the relationship between waist circumference and diabetes. Mediation analyses of circulating adiponectin were conducted using linear and logistic regression.

Results

Subjects with abdominal obesity had lower levels of circulating adiponectin (P < 0.001). The circulating adiponectin value was inversely related to BMI (r = −0.370, P < 0.001), waist circumference (r = −0.361, P < 0.001), and fasting plasma glucose (r = −0.221, P < 0.001). The RCS plot showed a non-linear relation linking waist circumference with T2DM (P for non-linearity < 0.001). Patients with abdominal obesity presented 2.062 times higher odds of T2DM in comparison with those with non-abdominal obesity (odds ratio, 2.062; 95% confidence interval, 1.969–2.161) after adjusting for confounders. In the mediation analyses, the circulating adiponectin mediated the association between abdominal obesity and T2DM, with a mediation effect of 41.02% after adjustments. The above results were consistent in both men and women.

Conclusion

The relationship between abdominal obesity and T2DM is mediated through circulating adiponectin level in adults, suggesting that circulating adiponectin might be a potential predictor for controlling the adverse progression from adiposity to T2DM.
Effect of environmental factors on seminal microbiome and impact on sperm quality
Authors: Neto Filipe T. Lira , Viana Marina C. , Cariati Federica , Conforti Alessandro , Alviggi Carlo , Esteves Sandro C.
Published: February 2024

Objective

This review provides a comprehensive overview of the existing research on the seminal microbiome and its association with male infertility, while also highlighting areas that warrant further investigation.

Methods

A narrative review was conducted, encompassing all relevant studies published between 1980-2023 on the male reproductive tract microbiome in humans. This review considered studies utilizing culture-based, polymerase chain reaction (PCR)-based, and next-generation sequencing (NGS)-based methodologies to analyze the microbiome. Data extraction encompassed sample types (semen or testicular tissue), study designs, participant characteristics, employed techniques, and critical findings.

Results

We included 37 studies comprising 9,310 participants. Among these, 16 studies used culture-based methods, 16 utilized NGS, and five employed a combination of methods for microorganism identification. Notably, none of the studies assessed fungi or viruses. All NGS-based studies identified the presence of bacteria in all semen samples. Two notable characteristics of the seminal microbiome were observed: substantial variability in species composition among individuals and the formation of microbial communities with a dominant species. Studies examining the testicular microbiome revealed that the testicular compartment is not sterile. Interestingly, sexually active couples shared 56% of predominant genera, and among couples with positive cultures in both partners, 61% of them shared at least one genital pathogen. In couples with infertility of known causes, there was an overlap in bacterial composition between the seminal and vaginal microbiomes, featuring an increased prevalence of Staphylococcus and Streptococcus genera. Furthermore, the seminal microbiome had discernible effects on reproductive outcomes. However, bacteria in IVF culture media did not seem to impact pregnancy rates.

Conclusion

Existing literature underscores that various genera of bacteria colonize the male reproductive tract. These organisms do not exist independently; instead, they play a pivotal role in regulating functions and maintaining hemostasis. Future research should prioritize longitudinal and prospective studies and investigations into the influence of infertility causes and commonly prescribed medication to enhance our understanding of the seminal microbiota’s role in reproductive health.
A robust system model for the photovoltaic in industrial parks considering photovoltaic uncertainties and low-carbon demand response
Authors: Hong Juhua , Zhang Linyao , Hu Zhenda , Lin Weiwei , Zou Yichao
Published: February 2024

Against the backdrop of carbon peaking and carbon neutrality initiatives, industrial parks have the potential to mitigate external electricity procurement and reduce carbon emissions by incorporating photovoltaic and energy storage systems. However, the inherent unpredictability in photovoltaic power generation poses notable challenges to the optimal planning of industrial parks. In light of this, the present study proposes a robust planning model for the distribution of photovoltaic and energy storage systems within industrial estates, taking into account uncertainties in photovoltaic output and low-carbon demand response. The primary objective of the model is to minimize the yearly comprehensive cost of the industrial park. It is grounded in the carbon emission flow theory, utilizing dynamic carbon emission factors calculated throughout the year as the pricing basis for real-time electricity rates informed by demand response. Subsequently, historical photovoltaic output data are employed to formulate typical output scenarios and their probability distributions through scenario clustering. These norms and constraints serve to bind the associated uncertainty probabilities. Consequently, a two-stage distribution robust model for the photovoltaic and energy storage system is established, employing a data-driven methodology. The efficacy of the proposed model is substantiated through a case simulation of an industrial park utilizing the CPLEX commercial solver. This approach not only underscores the importance of addressing uncertainties in photovoltaic power generation for industrial park planning but also showcases a practical application of the developed model.
Improving ecosystem health in highly altered river basins: a generalized framework and its application to the Mississippi-Atchafalaya River Basin
Authors: McLellan Eileen L. , Suttles Kelly M. , Bouska Kristen L. , Ellis Jamelle H. , Flotemersch Joseph E. , Goff Madison , Golden Heather E. , Hill Ryan A. , Hohman Tara R. , Keerthi Shamitha , Keim Richard F. , Kleiss Barbara A. , Lark Tyler J. , Piazza Bryan P. , Renfro Alisha A. , Robertson Dale M. , Schilling Keith E. , Schmidt Travis S. , Waite Ian R.
Published: February 2024

Continued large-scale public investment in declining ecosystems depends on demonstrations of “success”. While the public conception of “success” often focuses on restoration to a pre-disturbance condition, the scientific community is more likely to measure success in terms of improved ecosystem health. Using a combination of literature review, workshops and expert solicitation we propose a generalized framework to improve ecosystem health in highly altered river basins by reducing ecosystem stressors, enhancing ecosystem processes and increasing ecosystem resilience. We illustrate the use of this framework in the Mississippi-Atchafalaya River Basin (MARB) of the central United States (U.S.), by (i) identifying key stressors related to human activities, and (ii) creating a conceptual ecosystem model relating those stressors to effects on ecosystem structure and processes. As a result of our analysis, we identify a set of landscape-level indicators of ecosystem health, emphasizing leading indicators of stressor removal (e.g., reduced anthropogenic nutrient inputs), increased ecosystem function (e.g., increased water storage in the landscape) and increased resilience (e.g., changes in the percentage of perennial vegetative cover). We suggest that by including these indicators, along with lagging indicators such as direct measurements of water quality, stakeholders will be better able to assess the effectiveness of management actions. For example, if both leading and lagging indicators show improvement over time, then management actions are on track to attain desired ecosystem condition. If, however, leading indicators are not improving or even declining, then fundamental challenges to ecosystem health remain to be addressed and failure to address these will ultimately lead to declines in lagging indicators such as water quality. Although our model and indicators are specific to the MARB, we believe that the generalized framework and the process of model and indicator development will be valuable in an array of altered river basins.
Detection of donor-derived cell-free DNA in the setting of multiple kidney transplantations
Authors: Pettersson Linnea , Frischknecht Lukas , Westerling Sofia , Ramezanali Hamid , Weidmann Lukas , Lopez Kai Castrezana , Schachtner Thomas , Nilsson Jakob
Published: February 2024

Background

The routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging.

Methods

We investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations.

Results

The assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%–0.6% and showed a fluctuation over time in patients where we analyzed sequential samples.

Conclusion

This is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making.
Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia
Authors: Gál Luca , Fóthi Ábel , Orosz Gergő , Nagy Sándor , Than Nándor Gábor , Orbán Tamás I.
Published: February 2024

Introduction

Preeclampsia (PE) is a severe obstetrical syndrome characterized by new-onset hypertension and proteinuria and it is often associated with fetal intrauterine growth restriction (IUGR). PE leads to long-term health complications, so early diagnosis would be crucial for timely prevention. There are multiple etiologies and subtypes of PE, and this heterogeneity has hindered accurate identification in the presymptomatic phase. Recent investigations have pointed to the potential role of small regulatory RNAs in PE, and these species, which travel in extracellular vesicles (EVs) in the circulation, have raised the possibility of non-invasive diagnostics. The aim of this study was to investigate the behavior of exosomal regulatory small RNAs in the most severe subtype of PE with IUGR.

Methods

We isolated exosomal EVs from first-trimester peripheral blood plasma samples of women who later developed preterm PE with IUGR (n=6) and gestational age-matched healthy controls (n=14). The small RNA content of EVs and their differential expression were determined by next-generation sequencing and further validated by quantitative real-time PCR. We also applied the rigorous exceRpt bioinformatics pipeline for small RNA identification, followed by target verification and Gene Ontology analysis.

Results

Overall, >2700 small RNAs were identified in all samples and, of interest, the majority belonged to the RNA interference (RNAi) pathways. Among the RNAi species, 16 differentially expressed microRNAs were up-regulated in PE, whereas up-regulated and down-regulated members were equally found among the six identified Piwi-associated RNAs. Gene ontology analysis of the predicted small RNA targets showed enrichment of genes in pathways related to immune processes involved in decidualization, placentation and embryonic development, indicating that dysregulation of the induced small RNAs is connected to the impairment of immune pathways in preeclampsia development. Finally, the subsequent validation experiments revealed that the hsa_piR_016658 piRNA is a promising biomarker candidate for preterm PE associated with IUGR.

Discussion

Our rigorously designed study in a homogeneous group of patients unraveled small RNAs in circulating maternal exosomes that act on physiological pathways dysregulated in preterm PE with IUGR. Therefore, our small RNA hits are not only suitable biomarker candidates, but the revealed biological pathways may further inform us about the complex pathology of this severe PE subtype.
Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment
Authors: Qiu Yue , Lu Guimei , Li Na , Hu Yanyan , Tan Hao , Jiang Chengyao
Published: February 2024

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of the gastric mucosa. The pathogenesis of GC is intricately linked to the tumor microenvironment within which the cancer cells reside. Tumor-associated macrophages (TAMs) primarily differentiate from peripheral blood monocytes and can be broadly categorized into M1 and M2 subtypes. M2-type TAMs have been shown to promote tumor growth, tissue remodeling, and angiogenesis. Furthermore, they can actively suppress acquired immunity, leading to a poorer prognosis and reduced tolerance to chemotherapy. Exosomes, which contain a myriad of biologically active molecules including lipids, proteins, mRNA, and noncoding RNAs, have emerged as key mediators of communication between tumor cells and TAMs. The exchange of these molecules via exosomes can markedly influence the tumor microenvironment and consequently impact tumor progression. Recent studies have elucidated a correlation between TAMs and various clinicopathological parameters of GC, such as tumor size, differentiation, infiltration depth, lymph node metastasis, and TNM staging, highlighting the pivotal role of TAMs in GC development and metastasis. In this review, we aim to comprehensively examine the bidirectional communication between GC cells and TAMs, the implications of alterations in the tumor microenvironment on immune escape, invasion, and metastasis in GC, targeted therapeutic approaches for GC, and the efficacy of potential GC drug resistance strategies.
Recent advances on CAR-T signaling pave the way for prolonged persistence and new modalities in clinic
Authors: Smirnov Sergei , Mateikovich Polina , Samochernykh Konstantin , Shlyakhto Evgeny
Published: February 2024

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies. The importance of the receptor costimulatory domain for long-term CAR-T cell engraftment and therapeutic efficacy was demonstrated with second-generation CAR-T cells. Fifth generation CAR-T cells are currently in preclinical trials. At the same time, the processes that orchestrate the activation and differentiation of CAR-T cells into a specific phenotype that predisposes them to long-term persistence are not fully understood. This review highlights ongoing research aimed at elucidating the role of CAR domains and T-cell signaling molecules involved in these processes.
Integrating clinical and cross-cohort metagenomic features: a stable and non-invasive colorectal cancer and adenoma diagnostic model
Authors: Zhou Dan , Chen Youli , Wang Zehao , Zhu Siran , Zhang Lei , Song Jun , Bai Tao , Hou Xiaohua
Published: February 2024

Background: Dysbiosis is associated with colorectal cancer (CRC) and adenomas (CRA). However, the robustness of diagnostic models based on microbial signatures in multiple cohorts remains unsatisfactory.

Materials and Methods: In this study, we used machine learning models to screen metagenomic signatures from the respective cross-cohort datasets of CRC and CRA (selected from CuratedMetagenomicData, each disease included 4 datasets). Then select a CRC and CRA data set from the CuratedMetagenomicData database and meet the requirements of having both metagenomic data and clinical data. This data set will be used to verify the inference that integrating clinical features can improve the performance of microbial disease prediction models.

Results: After repeated verification, we selected 20 metagenomic features that performed well and were stably expressed within cross-cohorts to represent the diagnostic role of bacterial communities in CRC/CRA. The performance of the selected cross-cohort metagenomic features was stable for multi-regional and multi-ethnic populations (CRC, AUC: 0.817–0.867; CRA, AUC: 0.766–0.833). After clinical feature combination, AUC of our integrated CRC diagnostic model reached 0.939 (95% CI: 0.932–0.947, NRI=30%), and that of the CRA integrated model reached 0.925 (95%CI: 0.917–0.935, NRI=18%).

Conclusion: In conclusion, the integrated model performed significantly better than single microbiome or clinical feature models in all cohorts. Integrating cross-cohort common discriminative microbial features with clinical features could help construct stable diagnostic models for early non-invasive screening for CRC and CRA.
Expression of HER2 in high-grade urothelial carcinoma based on Chinese expert consensus and the clinical effects of disitamab vedotin-tislelizumab combination therapy in the treatment of advanced patients
Authors: Zhu Kejia , Chang Yao , Zhao Delong , Guo Andong , Cao Jishuang , Wu Chenrui , Guan Yong , Ding Sentai
Published: February 2024

Background: A vast number of researchers have discovered high levels of human epidermal growth factor receptor-2 (HER2) expression in urothelial carcinoma (UC), but they do not use a uniform scoring system. Based on the 2021 edition of clinical pathological expert consensus on HER-2 testing in UC in China, we investigated the expression level and clinical significance of HER2 in high-grade UC. Furthermore, we looked at the prognosis of patients with locally advanced/metastatic UC after combining HER2 targeting antibody-drug conjugates (ADC) medication disitamab vedotin (DV) with programmed cell death protein 1 (PD-1) inhibitor tislelizumab.

Patients and methods: From 2019 to 2022, we collected paraffin specimens of UC from the Department of Urology at the Provincial Hospital Affiliated to Shandong First Medical University. HER2 expression-related factors were investigated. Patients with advanced UC who have failed systemic chemotherapy at least once and had received immune checkpoint inhibitor (ICI) medication during second-line treatment were selected and treated with DV in combination with tislelizumab. We assessed the therapy’s efficacy and safety.

Results: 185 patients with high-grade UC were included in this investigation. 127 patients (68.7%) were HER2 positive (IHC 2+/3+) according to the 2021 Clinical pathological expert consensus on HER2 testing in UC in China. The clinical stage of UC differed statistically significantly between the HER2-and HER2+ groups (p = 0.019). Sixteen advanced UC patients were treated with DV and tislelizumab for a median of 14 months. The disease control rate was 87.5%, while the objective response rate (ORR) was 62.5%. The ORR of HER2+ individuals was higher than that of HER2-individuals (70.0% vs. 50.0%). The median progression-free survival or overall survival was not reached. In this study, the incidence of treatment-related adverse events was 68.8% (11/16), with all of them being grade 1 or 2 adverse reactions.

Conclusion: HER2 protein expressed at a high percentage in UC, and 68.7% patients expressed HER2 positive (IHC 2+/3+). HER2+ expression is positively correlated with higher clinical stage of UC. HER2 targeted ADC drug disitamab vedotin combining with PD-1 inhibitor tislelizumab has shown efficacy, safety and controllable adverse reactions in the treatment of advanced UC.
Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies
Authors: Paranthaman Priyanga , Veerappapillai Shanthi
Published: February 2024

Introduction: Targeting tumor microenvironment is beneficial and present an ideal setting for the development of futuristic immunotherapy. Here, we make use of Nuclear prelamin A recognition factor (NARF), a protein linked to the coactivation of transcriptional regulators in human breast cancer stem cells (CSC) in our investigation.

Methods: In this study, we initially computed the epitope regions possessing the ability to stimulate both T and B cells within the NARF protein. These identified epitope areas were fused with an adjuvant such as RpfB and RpfE as well as linkers like AAY, GPGPG, KK, and EAAAK. The constructed vaccine was further characterized by assessing its physicochemical properties and population coverage. The potential interactions of the designed vaccine with different toll-like receptors were examined by a sequence of computational studies. Of note, docking study were employed to understand its mechanism of action. Molecular dynamics and immune simulation studies were conducted to comprehend more into their structural stability and immune responses. The resultant vaccine was back-translated, codon-optimised and introduced into pET-28 (+) vector.

Results and discussion: We hypothesize from the results that the designed NARF protein-based vaccine in our analysis could effectively provoke the immune responses in the target organism through TLR-7 binding and promotes MHC class-II mediated antigen presentation. Indeed, comprehensive evaluations conducted in both in vitro and in vivo settings are imperative to substantiate the safety and efficacy of the developed vaccine.
Effect of potassium fertilization on storage root number, yield, and appearance quality of sweet potato (Ipomoea batatas L.)
Authors: Liu Ben-kui , Xv Bing-jie , Si Cheng-cheng , Shi Wen-qing , Ding Guo-zheng , Tang Li-xue , Xv Ming , Shi Chun-yv , Liu Hong-jvan
Published: February 2024

Increasing storage root number is a pivotal approach to enhance both storage root (SR) yield and appearance quality of sweet potato. Here, 2-year field experiments were conducted to investigate the effect of 0 (K0), 120 (K1), 240 (K2), and 360 (K3) kg ha−1 potassium fertilizer (K2O) on lignin metabolism, root growth, storage root yield, and uniformity. The results demonstrated that potassium (K) application led to a decrease in the activities of key enzymes involved in lignin biosynthesis, including phenylalanine deaminase (PAL), 4-coumarate coenzyme A ligase (4-CL), cinnamic acid dehydrogenase (CAD), polyphenol oxidase (PPO), and peroxidase (POD). This resulted in a significant reduction in lignin and G-type lignin contents in potential SRs compared to K0 treatment within 10–30 days after planting (DAP). BJ553 exhibited a significant decrease in PAL activity, as well as lignin and G-type contents at 10 DAP, whereas YS25 showed delayed effects until 20 DAP. However, the number and distribution of secondary xylem conduits as well as the mid-column diameter area in roots were increased in K2 treatment. Interestingly, K2 treatment exhibited significantly larger potential SR diameter than other treatments at 15, 20, and 25 DAP. At harvest, K2 treatment increased the SR number, the single SR weight, and overall yield greatly compared with K0 treatment, with an average increase of 19.12%, 16.54%, and 16.92% respectively. The increase of SR number in BJ553 was higher than that of YS25. Furthermore, K2 treatment exhibited the lowest coefficient of variation for both SR length and diameter, indicating a higher yield of middle-sized SRs. In general, appropriate potassium application could effectively suppress lignin biosynthesis, leading to a reduction in the degree of pericycle lignification in potential SRs. This promotes an increase in the number of storage roots and ultimately enhances both yield and appearance quality of sweet potato. The effect of potassium fertilizer on lignin metabolism in BJ553 roots was earlier and resulted in a greater increase in the SR number compared to YS25.