bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating molecular epidemiology of carbapenem non-susceptible Klebsiella pneumoniae isolates with MLST, MALDI-TOF MS, PFGE
Authors: Ibik Yunus Emre , Ejder Nebahat , Sevim Elif , Rakici Erva , Tanriverdi Elif Seren , Copur Cicek Aysegül
Published: October 2023

Background

This study aimed to evaluate antibiotic resistance genes and virulence genes and the clonal relationship of the carbapenem-nonsusceptible Klebsiella pneumoniae strains by molecular methods which are isolated from various clinical specimens from patients treated in tertiary care hospital in Turkey.

Methods

Identification of 32 carbapenem non-susceptible K. pneumoniae were determined by VITEK-2 (BioMérieux, France) automated system. Thirteen colistin-resistant strains were tested with the broth microdilution method. Various antibiotic resistance genes and virulence genes frequently seen in carbapenem-resistant strains were screened by PCR. Immunochromatographic tests used in the rapid diagnosis of carbapenemases were compared with PCR results. In addition, PFGE, MLST and MALDI-TOF MS methods were used to determine the clonal relationship among these strains.

Results

PCR demonstrated that 31 of the strains carried at least one of the carbapenemase genes. In one strain, the coexistence of blaOXA−48+NDM was shown. The most common resistance genes were determined as blaSHV (84.3%), blaCTX−M−1 (46.8%), blaOXA−48 (40.6%), blaKPC (40.6%), blaTEM (31.2%), blaNDM (18.8%) respectively. Among the virulence genes; magA (68.7%) was the most common, followed by kpn (59.3%) and K2 (9.3%). Immunochromatographic tests were found to be 100% compatible with PCR results. All colistin-resistant isolates were also found to be resistant by colistin broth microdilution. In PFGE analysis, 25 different genotypes were determined and clustering isolates were collected in 5 different clusters and the clustering rate was 35.4%. In MLST analysis, ST101 type was determined as the most common ST type with a rate of 29%. ST101 is followed by ST16, ST307, ST14, ST147, ST309, ST377, ST395 and ST2096, respectively. The compatibility rate between MALDI-TOF MS and VITEK-2 was found 94.3%, in bacterial identification. In MALDI-TOF MS typing, the maximum similarity between the strains was less than 70% and clustering not shown.

Conclusion

In addition to OXA-48, which is endemic in our country, it has been determined that KPC, which is more common in the world, is becoming increasingly common in our region. ST101 type was determined as the most common type between the strains. To the best of our knowledge, this is the first study that compares these three methods in our country. There may be differences between bacterial identifications made with VITEK-2 and MALDI-TOF MS. In this study, it was observed that MALDI-TOF MS analyses were not compatible with the typing of strains according to PFGE and MLST analysis results.
Online interventions and virtual day centres for young people who use drugs: potential for harm reduction?
Authors: Sande Matej , Dekleva Bojan , Razpotnik Špela , Tadič Darja , Klemenčič Rozman Mija Marija , Rapuš Pavel Jana
Published: October 2023

Background

The methodological part of the large-scale study on the psychosocial distress of young people in Slovenia focused on vulnerable young people who use drugs and explored the potential of online interventions in harm reduction programmes. We looked at the needs of young people who, at the time of the research, were attending a virtual Discord day centre hosted by the DrogArt NGO or were involved in the organisation's other programmes. We explored young people's knowledge of online interventions, their satisfaction with them and the opportunities they offer for harm reduction programmes.

Methods

The study used a qualitative methodology with a combination of deductive and inductive coding, and relied on framework analysis, 18 young people who had used drugs or had stopped using participated in the study. The inclusion criterion was a maximum age of 25 years. In-depth interviews were conducted with the young people, which lasted on average between one and a half and two hours.

Results

The study showed the potential of online interventions, specifically the virtual day centre, which provide a safe and relaxed space for young people in the sample to meet and talk, which is accessible and where they feel welcome. Online interventions have also enabled some of the sample to engage in the ‘offline’ support types offered within the organisation. The main advantages of online interventions are seen by young people as being more ‘geographically’ accessible and more available during the COVID-19 epidemic. Online support suits some people because they can leave sessions more quickly and it is more informal, while others prefer it because of specific problems or difficulties, such as social anxiety.

Conclusions

The results show the relatively high potential of online interventions in harm reduction programmes, as well as more broadly for young people with various psychosocial difficulties and who, for example, do not use drugs. These types of support allow quick contact with a professional or peer and facilitate contact with a support programme. Young people are still poorly informed about the support programmes available in Slovenia and would like more information. Thus, in addition to developing and upgrading the network of programmes, we need to focus on providing information to young people through channels that are close to them and can reach them.
Prognostic role of body composition in peritoneal carcinomatosis patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy
Authors: Song Young , Bae Myung Il , Han Dong Woo , Park Eun Jung , Park Sujung , Ham Sung Yeon
Published: October 2023

Background

Bioelectric impedance analysis (BIA)-measured body composition and nutritional status have been used as prognostic indicators in various cancer cohorts. This study investigated whether BIA could provide information on prognosis in peritoneal carcinomatosis patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

We retrospectively analyzed the data of 99 patients with preoperative BIA data among those who underwent CRS and HIPEC. The association between BIA-derived parameters and intraoperative peritoneal cancer index (PCI) score was assessed. Predictive analysis for the occurrence of postoperative morbidities including major complications (Clavien–Dindo classification 3–4) and re-admission within 30 days after surgery as well as 1 year mortality was also performed.

Results

BIA-derived mineral (r = 0.224, p = 0.027), fat (r =  − 0.202, p = 0.048), and total body water (TBW)/fat-free mass (FFM) (r =  − 0.280, p = 0.005) showed significant associations with intraoperative PCI score. Lower TBW/FFM was an independent predictor of major postoperative complications (OR 0.047, 95% CI 0.003–0.749, p = 0.031) and re-admission (OR 0.094, 95% CI 0.014–0.657, p = 0.017) within 30 days after surgery. Higher fat mass was also independently associated with a higher risk of major postoperative complications (OR 1.120, 95% CI 1.006–1.248, p = 0.039) and re-admission (OR 1.123, 95% CI 1.024–1.230, p = 0.013). Intraoperative PCI score > 20 (OR 4.489, 95% CI 1.191–16.917, p = 0.027) and re-admission within 30 days after surgery (OR 5.269, 95% CI 1.288–21.547, p = 0.021) independently predicted postoperative 1-year mortality.

Conclusions

We demonstrate that preoperative BIA-derived TBW/FFM and fat mass were significantly correlated with metastatic extent, assessed by PCI score, in patients with peritoneal carcinomatosis. In addition, BIA-derived TBW/FFM and fat mass showed independent predictability for postoperative 30-day major complications and re-admission in patients undergoing CRS and HIPEC. Our findings suggest that assessment of BIA may improve discrete risk stratification in patients who are planned to receive CRS and HIPEC.
METTL3-regulated m6A modification impairs the decidualization of endometrial stromal cells by regulating YTHDF2-mediated degradation of FOXO1 mRNA in endometriosis-related infertility
Authors: Li Xiaoou , Jin Jie , Long Xuefeng , Weng Ruiwen , Xiong Wenqian , Liang Jiaxin , Liu Junjun , Sun Jingwen , Cai Xueqin , Zhang Ling , Liu Yi
Published: October 2023

Background

Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation.

Methods

We examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A.

Results

The expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein.

Conclusions

METTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.
Are motivational and self-regulation factors associated with 12 months’ weight regain prevention in the NoHoW study? An analysis of European adults
Authors: Palmeira António L. , Marques Marta M. , Sánchez-Oliva David , Encantado Jorge , Santos Inês , Duarte Cristiana , Matos Marcela , Carneiro-Barrera Almudena , Larsen Sofus C. , Horgan Graham , Sniehotta Falko F. , Teixeira Pedro J. , Stubbs R. James , Heitmann Berit L.
Published: October 2023

Purpose

Preventing weight regain can only be achieved by sustained changes in energy balance-related behaviors that are associated with weight, such as diet and physical activity. Changes in motivation and self-regulatory skills can support long-term behavioral changes in the context of weight loss maintenance. We propose that experiencing a supportive climate care is associated with enhanced satisfaction of basic psychological needs, intrinsic goals, and autonomous motivation. These factors are expected to be associate with the utilization of self-regulation skills, leading to more sustained behavior changes and ultimately preventing weight regain. This hypothesis was tested in this ancillary analysis of the NoHoW trial, where the study arms were pooled and followed for 12 months.

Methods

The NoHoW was a three-center, large-scale weight regain prevention full factorial trial. In this longitudinal study, data were collected in adults who lost > 5% weight in the past year (N = 870, complete data only, 68.7% female, 44.10 ± 11.86 years, 84.47 ± 17.03 kg) during their participation in a 12-month digital behavior change intervention. Weight and validated measures of motivational- and self-regulatory skills-related variables were collected at baseline, six- and 12 months. Change variables were used in Mplus’ path analytical models informed by NoHoW’s logic model.

Results

The bivariate correlations confirmed key mediators’ potential effect on weight outcomes in the expected causal direction. The primary analysis showed that a quarter of the variance (r2 = 23.5%) of weight regain prevention was achieved via the mechanisms of action predicted in the logic model. Specifically, our results show that supportive climate care is associated with needs satisfaction and intrinsic goal content leading to better weight regain prevention via improvements in self-regulatory skills and exercise-controlled motivation. The secondary analysis showed that more mechanisms of action are significant in participants who regained or maintained their weight.

Conclusions

These results contribute to a better understanding of the mechanisms of action leading to behavior change in weight regain prevention. The most successful participants used only a few intrinsic motivation-related mechanisms of action, suggesting that habits may have been learned. While developing a digital behavior change intervention, researchers and practitioners should consider creating supportive climate care to improve needs satisfaction and intrinsic goal contents.

Trial registration

ISRCTN, ISRCTN88405328, registered 12/22/2016.
Steering-by-leaning facilitates intuitive movement control and improved efficiency in manual wheelchairs
Authors: Togni Reto , Zemp Roland , Kirch Pleuni , Plüss Stefan , Vegter Riemer J. K. , Taylor William R.
Published: October 2023

Background

Manual wheelchair propulsion is widely accepted to be biomechanically inefficient, with a high prevalence of shoulder pain and injuries among users. Directional control during wheelchair movement is a major, yet largely overlooked source of energy loss: changing direction or maintaining straightforward motion on tilted surfaces requires unilateral braking. This study evaluates the efficiency of a novel steering-by-leaning mechanism that guides wheelchair turning through upper body leaning.

Methods

16 full-time wheelchair users and 15 able-bodied novices each completed 12 circuits of an adapted Illinois Agility Test-course that included tilted, straight, slalom, and 180° turning sections in a prototype wheelchair at a self-selected functional speed. Trials were alternated between conventional and steering-by-leaning modes while propulsion forces were recorded via instrumented wheelchair wheels. Time to completion, travelled distance, positive/negative power, and work done, were all calculated to allow comparison of the control modes using repeated measures analysis of variance.

Results

Substantial average energy reductions of 51% (able-bodied group) and 35% (wheelchair user group) to complete the task were observed when using the steering-by-leaning system. Simultaneously, able-bodied subjects were approximately 23% faster whereby completion times did not differ for wheelchair users. Participants in both groups wheeled some 10% further with the novel system. Differences were most pronounced during turning and on tilted surfaces where the steering-by-leaning system removed the need for braking for directional control.

Conclusions

Backrest-actuated steering systems on manual wheelchairs can make a meaningful contribution towards reducing shoulder usage while contributing to independent living. Optimisation of propulsion techniques could further improve functional outcomes.
A fatal case of neonatal viral sepsis caused by human parainfluenza virus type 3
Authors: Chen Xiangpeng , Wang Hong , Li Qi , Qi Yujie , Li Fei , He Wenwen , Wang Qiushi , Jin Fei , Guo Yanqing , Hei Mingyan , Xie Zhengde
Published: October 2023

Background

Sepsis is a systemic inflammatory response syndrome caused by severe infection in children, but cases of sepsis associated with human parainfluenza virus (HPIV) have been rarely reported in newborns.

Case presentation

We report a case of HPIV-3 positive full-term newborn admitted to the Neonatal Intensive Care Unit of Beijing Children’s Hospital due to hematuria, gloomy spirit, inactivity and loss of appetite for 6 h. He had septic shock when he arrived the Accident & Emergency Department requiring immediate intubation and mechanical ventilation. Intravenous antibiotics were started. He had completely negative response to all anti-shock treatments including fluid resuscitation and vasopressor supports, and died 14 h later. Viral nucleic acid detection and metagenomic next-generation sequencing (mNGS) analyses of nasopharyngeal aspirate and blood specimens verified an HPIV-3 infection, with negative bacterial culture results. The HPIV-3 strain detected in this patient was subtyped as HPIV C3a, and two unreported amino acid mutations were found in the HN protein region.

Conclusion

The patient had a severe infection associated with HPIV-3, which was the cause of sepsis and septic shock. This study showed the diagnostic value of mNGS in etiological diagnosis, especially in severe neonatal case.
Resurgence of SARS-CoV-2 Delta after Omicron variant superinfection in an immunocompromised pediatric patient
Authors: Alisoltani Arghavan , Simons Lacy M. , Agnes Maria Francesca Reyes , Heald-Sargent Taylor A. , Muller William J. , Kociolek Larry K. , Hultquist Judd F. , Lorenzo-Redondo Ramon , Ozer Egon A.
Published: October 2023

Background

Persistent SARS-CoV-2 infection in immunocompromised hosts is thought to contribute to viral evolution by facilitating long-term natural selection and viral recombination in cases of viral co-infection or superinfection. However, there are limited data on the longitudinal intra-host population dynamics of SARS-CoV-2 co-infection/superinfection, especially in pediatric populations. Here, we report a case of Delta-Omicron superinfection in a hospitalized, immunocompromised pediatric patient.

Methods

We conducted Illumina whole genome sequencing (WGS) for longitudinal specimens to investigate intra-host dynamics of SARS-CoV-2 strains. Topoisomerase PCR cloning of Spike open-reading frame and Sanger sequencing of samples was performed for four specimens to validate the findings. Analysis of publicly available SARS-CoV-2 sequence data was performed to investigate the co-circulation and persistence of SARS-CoV-2 variants.

Results

Results of WGS indicate the patient was initially infected with the SARS-CoV-2 Delta variant before developing a SARS-CoV-2 Omicron variant superinfection, which became predominant. Shortly thereafter, viral loads decreased below the level of detection before resurgence of the original Delta variant with no residual trace of Omicron. After 54 days of persistent infection, the patient tested negative for SARS-CoV-2 but ultimately succumbed to a COVID-19-related death. Despite protracted treatment with remdesivir, no antiviral resistance mutations emerged. These results indicate a unique case of persistent SARS-CoV-2 infection with the Delta variant interposed by a transient superinfection with the Omicron variant. Analysis of publicly available sequence data suggests the persistence and ongoing evolution of Delta subvariants despite the global predominance of Omicron, potentially indicative of continued transmission in an unknown population or niche.

Conclusion

A better understanding of SARS-CoV-2 intra-host population dynamics, persistence, and evolution during co-infections and/or superinfections will be required to continue optimizing patient care and to better predict the emergence of new variants of concern.
Untapped potential of non-conventional rubus species: bioactivity, nutrition, and livelihood opportunities
Authors: Bhatt Saurav Chandra , Naik Bindu , Kumar Vijay , Gupta Arun Kumar , Kumar Sanjay , Preet Manpreet Singh , Sharma Nitya , Rustagi Sarvesh
Published: October 2023

Rubusspecies holds promise as a valuable source of polyphenols and bioactive compounds, offering significant potential as functional food ingredients with both nutraceutical and pharmaceutical benefits. However, many edible species within this genus remain under-explored and their importance is largely unrecognized. This review aims to provide an overview of the nutritional and bioactive components of both explored and under-exploredRubusspecies, highlighting their potential health advantages, value addition, and recent advancements. The economic exploitation ofRubusis currently limited to a few cultivated species, while numerous non-conventional and wild edible species are overlooked. Recognizing the economic and nutritional significance of exploitedRubusspecies, it is imperative to explore the untapped potential of these underutilized plants. By doing so, these species can be preserved from endangerment and contribute to nutritional and livelihood security for communities having access to them. This review emphasizes the importance of understanding the exceptional characteristics ofRubusspecies as "superfoods" and encourages the promotion and cultivation of these unexplored species. By expanding the cultivation and utilization of under-exploredRubusspecies, we can unlock their full potential and support sustainable nutritional and economic benefits.
Safety outcomes and patients’ preferences for home-based intravenous enzyme replacement therapy (ERT) in pompe disease and mucopolysaccharidosis type I (MPS I) disorder: COVID-19 and beyond
Authors: Toscano Antonio , Musumeci Olimpia , Sacchini Michele , Ravaglia Sabrina , Siciliano Gabriele , Fiumara Agata , Verrecchia Elena , Maione Melania , Gentile Jennifer , Fischetto Rita , Crescimanno Grazia , Taurisano Roberta , Sechi Annalisa , Gasperini Serena , Cianci Vittoria , Maggi Lorenzo , Parini Rossella , Lupica Antonino , Scarpa Maurizio
Published: October 2023

Background

The Italian Medicines Agency (AIFA) demands precise information on benefit/risk profile of home-based enzyme replacement therapy (ERT) for the treatment of patients with Pompe disease and Mucopolysaccharidosis type I (MPS I). This passage is necessary to obtain the authorization for ERT home therapy, even after the coronavirus disease-19 (COVID-19) pandemic period. This research intends to evaluate the safety, treatment satisfaction, and compliance of MPS I patients treated with laronidase (Aldurazyme®) and Pompe Disease patients treated with alglucosidase alfa (Myozyme®) in a homecare setting.

Results

We report herein an early interim analysis of the HomERT (Home infusions of ERT) study, a multicenter, non-interventional, double-cohort study that retrospectively analyzed 38 patients from 14 sites in Italy: cohort A (Pompe disease − 32 patients) and cohort B (MPS I − 6 patients). Among the selected patients who started home therapy before enrollment, the average number of missed home-based infusions was 0.7 (1.3) in cohort A and 3.8 (6.4) in cohort B with no return to the hospital setting. Irrespective of the treatment location, 3 prior ADRs per cohort were reported. The majority of patients preferred home-based infusions (cohort A: 96.9%; cohort B: 100%): the main reason was attributed to treatment convenience (cohort A: 81.3%; cohort B: 83.3%). Despite the underlying conditions, most patients self-evaluated their health as “good” (cohort A: 50%; cohort B: 83.3%).

Conclusions

Evidence of favorable safety profile, improved treatment compliance and personal satisfaction validates the use of ERT with laronidase and alglucosidase alfa as a strong candidate for home therapy.
Construction of cascade circuits for dynamic temporal regulation and its application to PHB production
Authors: Li Xiaomeng , Qi Qingsheng , Liang Quanfeng
Published: October 2023

Background

To maximize the production capacity and yield of microbial cell factories, metabolic pathways are generally modified with dynamic regulatory strategies, which can effectively solve the problems of low biological yield, growth retardation and metabolic imbalance. However, the strategy of dynamic regulating multiple genes in different time and order is still not effectively solved. Based on the quorum-sensing (QS) system and the principle of cascade regulation, we studied the sequence and time interval of gene expression in metabolic pathways.

Results

We designed and constructed a self-induced dynamic temporal regulatory cascade circuit in Escherichia coli using the QS system and dual regulatory protein cascade and found that the time intervals of the cascade circuits based on the Tra, Las system and the Lux, Tra system reached 200 min and 150 min, respectively. Furthermore, a dynamic temporal regulatory cascade circuit library with time intervals ranging from 110 to 310 min was obtained based on this circuit using promoter engineering and ribosome binding site replacement, which can provide more selective synthetic biology universal components for metabolic applications. Finally, poly-β-hydroxybutyric acid (PHB) production was taken as an example to demonstrate the performance of the cascade circuit library. The content of PHB increased 1.5-fold. Moreover, circuits with different time intervals and different expression orders were found to have different potentials for application in PHB production, and the preferred time-interval circuit strain C2-max was identified by screening.

Conclusions

The self-induced dynamic temporal regulation cascade circuit library can enable the expression of target genes with sequential changes at different times, effectively solving the balance problem between cell growth and product synthesis in two-stage fermentation and expanding the application of dynamic regulatory strategies in the field of metabolic engineering.
First evidence of gonadal hybrid dysgenesis in Chagas disease vectors (Hemiptera, Triatominae): gonad atrophy prevents events of interspecific gene flow and introgression
Authors: Azevedo Luísa Martins Sensato , Cesaretto Natália Regina , de Oliveira Jader , Ravazi Amanda , dos Reis Yago Visinho , Tadini Samanta Cristina Antoniassi Fernand , da Silva Masarin Isabella , Borsatto Kelly Cristine , Galvão Cleber , da Rosa João Aristeu , de Azeredo-Oliveira Maria Tercília Vilela , Alevi Kaio Cesar Chaboli
Published: October 2023

Background

Hybridization events between Triatoma spp. have been observed under both natural and laboratory conditions. The ability to produce hybrids can influence different aspects of the parent species, and may even result in events of introgression, speciation and extinction. Hybrid sterility is caused by unviable gametes (due to errors in chromosomal pairing [meiosis]) or by gonadal dysgenesis (GD). All of the triatomine hybrids analyzed so far have not presented GD. We describe here for the first time GD events in triatomine hybrids and highlight these taxonomic and evolutionary implications of these events.

Methods

Reciprocal experimental crosses were performed between Triatoma longipennis and Triatoma mopan. Intercrosses were also performed between the hybrids, and backcrosses were performed between the hybrids and the parent species. In addition, morphological and cytological analyzes were performed on the atrophied gonads of the hybrids.

Results

Hybrids were obtained only for the crosses T. mopan♀ × T. longipennis♂. Intercrosses and backcrosses did not result in offspring. Morphological analyses of the male gonads of the hybrids confirmed that the phenomenon that resulted in sterility of the hybrid was bilateral GD (the gonads of the hybrids were completely atrophied). Cytological analyses of the testes of the hybrids also confirmed GD, with no germ cells observed (only somatic cells, which make up the peritoneal sheath).

Conclusions

The observations made during this study allowed us to characterize, for the first time, GD in triatomines and demonstrated that gametogenesis does not occur in atrophied gonads. The characterization of GD in male hybrids resulting from the crossing of T. mopan♀ × T. longipennis♂ highlights the importance of evaluating both the morphology and the cytology of the gonads to confirm which event resulted in the sterility of the hybrid: GD (which results in no gamete production) or meiotic errors (which results in non-viable gametes).

Graphical Abstract
A novel tetra-primer ARMS-PCR approach for the molecular karyotyping of chromosomal inversion 2Ru in the main malaria vectors Anopheles gambiae and Anopheles coluzzii
Authors: Pichler Verena , Sanou Antoine , Love R. Rebecca , Caputo Beniamino , Pombi Marco , Toe Kobie Hyacinth , Guelbeogo Moussa W. , Sagnon N’Fale , Ferguson Heather M. , Ranson Hilary , Torre Alessandra della , Besansky Nora J.
Published: October 2023

Background

Chromosomal inversion polymorphisms have been associated with adaptive behavioral, physiological, morphological and life history traits in the two main Afrotropical malaria vectors, Anopheles coluzzii and Anopheles gambiae. The understanding of the adaptive value of chromosomal inversion systems is constrained by the feasibility of cytological karyotyping. In recent years in silico and molecular approaches have been developed for the genotyping of most widespread inversions (2La, 2Rb and 2Rc). The 2Ru inversion, spanning roughly 8% of chromosome 2R, is commonly polymorphic in West African populations of An. coluzzii and An. gambiae and shows clear increases in frequency with increasing rainfall seasonally and geographically. The aim of this work was to overcome the constraints of currently available cytological and high-throughput molecular assays by developing a simple PCR assay for genotyping the 2Ru inversion in individual specimens of both mosquito species.

Methods

We designed tetra-primer amplification refractory mutation system (ARMS)-PCR assays based on five tag single-nucleotide polymorphisms (SNPs) previously shown to be strongly correlated with 2Ru inversion orientation. The most promising assay was validated against laboratory and field samples of An. coluzzii and An. gambiae karyotyped either cytogenetically or molecularly using a genotyping-in-thousands by sequencing (GT-seq) high-throughput approach that employs targeted sequencing of multiplexed PCR amplicons.

Results

A successful assay was designed based on the tag SNP at position 2R, 31710303, which is highly predictive of the 2Ru genotype. The assay, which requires only one PCR, and no additional post-PCR processing other than electrophoresis, produced a clear banding pattern for 98.5% of the 454 specimens tested, which is a 96.7% agreement with established karyotyping methods. Sequences were obtained for nine of the An. coluzzii specimens manifesting 2Ru genotype discrepancies with GT-seq. Possible sources of these discordances are discussed.

Conclusions

The tetra-primer ARMS-PCR assay represents an accurate, streamlined and cost-effective method for the molecular karyotyping of the 2Ru inversion in An. coluzzii and An. gambiae. Together with approaches already available for the other common polymorphic inversions, 2La, 2Rb and 2Rc, this assay will allow investigations of the adaptive value of the complex set of inversion systems observed in the two major malaria vectors in the Afrotropical region.

Graphical Abstract
Association of a history of gestational diabetes mellitus with osteoporosis, bone mineral density, and trabecular bone score in postmenopausal women
Authors: Lu Boqi , Zhang Liping
Published: October 2023

Background

Studies on the association of gestational diabetes mellitus (GDM) with osteoporosis, and bone mineral density (BMD) have been inconsistent. The aim of this study was to investigate the association of a history of GDM with osteoporosis, BMD, and trabecular bone score (TBS) in postmenopausal women.

Methods

Postmenopausal women from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2010, between 2013 and 2014, and between 2017 and 2018 were retrospectively included in this cross-sectional study. The logistic regression model was used to explore the relationship between GDM and osteoporosis, and a weighted linear regression model was applied to investigate the association between GDM and total femoral BMD, femoral neck BMD, and total TBS. Subgroup analysis of the association between GDM and osteoporosis was performed according to age, body mass index (BMI), and DM (yes or no).

Results

Of the 6732 women included, 253 women (3.76%) had GDM. No significant differences in total femoral BMD, femoral neck BMD, and total TBS were observed between postmenopausal women with and without a history of GDM. However, a history of GDM was associated with a higher risk of osteoporosis in postmenopausal women [odds ratio (OR): 11.18, 95% confidence intervals (CI): 3.64 to 34.27, P < 0.001]. There was no significant difference between a history of GDM and osteoporosis in postmenopausal women whom BMI is normal and overweight women. However, there was an association between a history of GDM and osteoporosis in postmenopausal obese women (OR: 26.57, 95% CI 10.23 to 68.98, P < 0.001).

Conclusion

A history of GDM was associated with a higher risk of osteoporosis in postmenopausal women, particularly in postmenopausal obese women.
DeepDelta: predicting ADMET improvements of molecular derivatives with deep learning
Authors: Fralish Zachary , Chen Ashley , Skaluba Paul , Reker Daniel
Published: October 2023

Established molecular machine learning models process individual molecules as inputs to predict their biological, chemical, or physical properties. However, such algorithms require large datasets and have not been optimized to predict property differences between molecules, limiting their ability to learn from smaller datasets and to directly compare the anticipated properties of two molecules. Many drug and material development tasks would benefit from an algorithm that can directly compare two molecules to guide molecular optimization and prioritization, especially for tasks with limited available data. Here, we develop DeepDelta, a pairwise deep learning approach that processes two molecules simultaneously and learns to predict property differences between two molecules from small datasets. On 10 ADMET benchmark tasks, our DeepDelta approach significantly outperforms two established molecular machine learning algorithms, the directed message passing neural network (D-MPNN) ChemProp and Random Forest using radial fingerprints, for 70% of benchmarks in terms of Pearson’s r, 60% of benchmarks in terms of mean absolute error (MAE), and all external test sets for both Pearson’s r and MAE. We further analyze our performance and find that DeepDelta is particularly outperforming established approaches at predicting large differences in molecular properties and can perform scaffold hopping. Furthermore, we derive mathematically fundamental computational tests of our models based on mathematical invariants and show that compliance to these tests correlates with overall model performance — providing an innovative, unsupervised, and easily computable measure of expected model performance and applicability. Taken together, DeepDelta provides an accurate approach to predict molecular property differences by directly training on molecular pairs and their property differences to further support fidelity and transparency in molecular optimization for drug development and the chemical sciences.
A new fixed-time stability of neural network to solve split convex feasibility problems
Authors: Zheng Jinlan , Gan Rulan , Ju Xingxing , Ou Xiaoqing
Published: October 2023

In this paper, we propose a novel neural network that achieves stability within the fixed time (NFxNN) based on projection to solve the split convex feasibility problems. Under the bounded linear regularity assumption, the NFxNN admits a solution of the split convex feasibility problem. We introduce the relationships between NFxNN and the corresponding neural networks. Additionally, we also prove the fixed-time stability of the NFxNN. The convergence time of the NFxNN is independent of the initial states. The effectiveness and superiority of the NFxNN are also demonstrated by numerical experiments compared with the other methods.
Development and validation of an individualized gene expression-based signature to predict overall survival of patients with high-grade serous ovarian carcinoma
Authors: Yuan Dandan , Zhu Hong , Wang Ting , Zhang Yang , Zheng Xin , Qu Yanjun
Published: October 2023

Background

High-grade serious ovarian carcinoma (HGSOC) is a subtype of ovarian cancer with a different prognosis attributable to genetic heterogeneity. The prognosis of patients with advanced HGSOC requires prediction by genetic markers. This study systematically analyzed gene expression profile data to establish a genetic marker for predicting HGSOC prognosis.

Methods

The RNA-seq data set and information on clinical follow-up of HGSOC were retrieved from Gene Expression Omnibus (GEO) database, and the data were standardized by DESeq2 as a training set. On the other hand, HGSOC RNA sequence data and information on clinical follow-up were retrieved from The Cancer Genome Atlas (TCGA) as a test set. Additionally, ovarian cancer microarray data set was obtained from GEO as the external validation set. Prognostic genes were screened from the training set, and characteristic selection was performed using the least absolute shrinkage and selection operator (LASSO) with 80% re-sampling for 5000 times. Genes with a frequency of more than 2000 were selected as robust biomarkers. Finally, a gene-related prognostic model was validated in both the test and GEO validation sets.

Results

A total of 148 genes were found to be significantly correlated with HGSOC prognosis. The expression profile of these genes could stratify HGSOC prognosis and they were enriched to multiple tumor-related regulatory pathways such as tyrosine metabolism and AMPK signaling pathway. AKR1B10 and ANGPT4 were obtained after 5000-time re-sampling by LASSO regression. AKR1B10 was associated with the metastasis and progression of several tumors. In this study, Cox regression analysis was performed to create a 2-gene signature as an independent prognostic factor for HGSOC, which has the ability to stratify risk samples in all three data sets (p < 0.05). The Gene Set Enrichment Analysis (GSEA) discovered abnormally active REGULATION_OF_AUTOPHAGY and OLFACTORY_TRANSDUCTION pathways in the high-risk group samples.

Conclusion

This study resulted in the creation of a 2-gene molecular prognostic classifier that distinguished clinical features and was a promising novel prognostic tool for assessing the prognosis of HGSOC. RiskScore was a novel prognostic model which might be effective in guiding accurate prognosis of HGSOC.
Multipoint surface electromyography measurement using bull’s-eye electrodes for wide-area topographic analysis
Authors: Shimura Megumi , Mizumoto Akihiko , Xia Yali , Shimomura Yoshihiro
Published: October 2023

Background

Surface electromyography (sEMG) is primarily used to analyze individual and neighboring muscle activity. However, using a broader approach can enable simultaneous measurement of multiple muscles, which is essential for understanding muscular coordination. Using the “bull’s-eye electrode,” which allows bipolar derivation without directional dependence, enables wide-area multipoint sEMG measurements. This study aims to establish a multipoint measurement system and demonstrate its effectiveness and evaluates forearm fatigue and created topographic maps during a grasping task.

Methods

Nine healthy adults with no recent arm injuries or illnesses participated in this study. They performed grasping tasks using their dominant hand, while bull’s-eye electrodes recorded their muscle activity. To validate the effectiveness of the system, we calculated the root mean squares of muscle activity and entropy, an indicator of muscle activity distribution, and compared them over time.

Results

The entropy analysis demonstrated a significant time-course effect with increased entropy over time, suggesting increased forearm muscle uniformity, which is possibly indicative of fatigue. Topographic maps visually displayed muscle activity, revealing notable intersubject variations.

Discussion

Bull’s-eye electrodes facilitated the capture of nine homogeneous muscle activity points, enabling the creation of topographic images. The entropy increased progressively, suggesting an adaptive muscle coordination response to fatigue. Despite some limitations, such as inadequate measurement of the forearm muscles’ belly, the system is an unconventional measurement method.

Conclusion

This study established a robust system for wide-area multipoint sEMG measurements using a bull’s-eye electrode setup. This system effectively evaluates muscle fatigue and provides a comprehensive topographic view of muscle activity. These results mark a significant step towards developing a future multichannel sEMG system with enhanced measurement points and improved wearability.

Trial registration

This study was approved by the Ethics Committee of Chiba University Graduate School of Engineering (acceptance number: R4-12, Acceptance date: November 04, 2022).
Virus diversity and activity is driven by snowmelt and host dynamics in a high-altitude watershed soil ecosystem
Authors: Coclet Clement , Sorensen Patrick O. , Karaoz Ulas , Wang Shi , Brodie Eoin L. , Eloe-Fadrosh Emiley A. , Roux Simon
Published: October 2023

Background

Viruses impact nearly all organisms on Earth, including microbial communities and their associated biogeochemical processes. In soils, highly diverse viral communities have been identified, with a global distribution seemingly driven by multiple biotic and abiotic factors, especially soil temperature and moisture. However, our current understanding of the stability of soil viral communities across time and their response to strong seasonal changes in environmental parameters remains limited. Here, we investigated the diversity and activity of environmental soil DNA and RNA viruses, focusing especially on bacteriophages, across dynamics’ seasonal changes in a snow-dominated mountainous watershed by examining paired metagenomes and metatranscriptomes.

Results

We identified a large number of DNA and RNA viruses taxonomically divergent from existing environmental viruses, including a significant proportion of fungal RNA viruses, and a large and unsuspected diversity of positive single-stranded RNA phages (Leviviricetes), highlighting the under-characterization of the global soil virosphere. Among these, we were able to distinguish subsets of active DNA and RNA phages that changed across seasons, consistent with a “seed-bank” viral community structure in which new phage activity, for example, replication and host lysis, is sequentially triggered by changes in environmental conditions. At the population level, we further identified virus-host dynamics matching two existing ecological models: “Kill-The-Winner” which proposes that lytic phages are actively infecting abundant bacteria, and “Piggyback-The-Persistent” which argues that when the host is growing slowly, it is more beneficial to remain in a dormant state. The former was associated with summer months of high and rapid microbial activity, and the latter with winter months of limited and slow host growth.

Conclusion

Taken together, these results suggest that the high diversity of viruses in soils is likely associated with a broad range of host interaction types each adapted to specific host ecological strategies and environmental conditions. As our understanding of how environmental and host factors drive viral activity in soil ecosystems progresses, integrating these viral impacts in complex natural microbiome models will be key to accurately predict ecosystem biogeochemistry.
Experimental investigation on stress distribution and migration of the overburden during the mining process in deep coal seam mining
Authors: Ma Shoulong , Zhang Mingwei , Ma Lu , Tian Zhuangcai , Li Xue , Su Zhenhao , Bian Sicheng
Published: October 2023

Coal mining has a significant impact on the movement of the overburden, leading to potential safety hazards in the working face. In this paper, a similarity simulation experiment was conducted to investigate the migration of overburden during the mining process of a specific working face in the Liuzhuang Coal Mine located in southern China. Sand and gravel were used to simulate the geological environment of each rock stratum. The deformation of the stratum was monitored using strain gauges, the fracture and displacement changes of the overburden stratum were recorded using cameras, and the characteristics of roof collapse was monitored using infrared thermal imager. The experimental model fully simulated the situation of the working face, and the actual working face size was obtained by enlarging the model by 100 times. The experiment found that during the initial stage of mining, there was no significant subsidence of the roof. In the course of the advancement of the working face, the primary roof intermittently fractured behind the working face, with subsequent propagation of upper cracks in an upward direction. The overburden rock layer above the goaf experienced continuous compaction, leading to the gradual closure of the separation layer. Simultaneously, new cracks constantly emerged in front of the working face, resulting in the progressive stabilization of the height of the crack zone. The stress measurements at each point exhibit a pattern of initial increased, followed by decrease, and ultimately stabilization. By considering the stress variation law of the overburden rock, the stress changes in key layers of the bedrock during mining could be categorized into four zones: the stress stable zone, stress increasing zone, stress reducing zone, and compaction stable zone. During the initial phase of coal seam mining, the presence of rock layers provided support, resulting in minimal subsidence of the overburden rock. However, as the mining operation progressed, the disturbance force and collapse of the overburden rock leaded to further downward subsidence. When the working face reached the stop line, the collapsed overburden rock gradually consolidates, resulting in a deceleration of energy release and the formation of a pressure relief zone. Consequently, the overburden rock above the working face underwent a slight additional subsidence, reaching its maximum level. A short cantilever rock beam structure was formed in the experiment. This study will provide valuable reference for future coal mining and serve as a vital theoretical basis for roof control in deep coal seam mining.