bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of two different concurrent training programs on specific performance, physiological and biochemical parameters in soccer players
Authors: Arslan Birgul , Pinar Salih , Ciloglu Figen
Published: December 2024

The study examined the effects of two concurrent training models, one being an eight-week High-Intensity Interval Training (HIIT) and the other, High-Intensity Functional Training (HIFT) both with additional strength training (S), on physiological parameters (blood lactate concentration and heart rate), athlete's performance (maximal strength, explosive power, aerobic endurance, 20 m sprint), and biochemical outputs. The study involved a total of 21 young males playing with amateur soccer licenses for at least 2 years divided into three groups. One group received S + HIIT training, second group received S + HIFT training and the control group continued their soccer-specific training. Both the experimental and the control groups underwent pre- and post-tests and while only the experimental groups underwent an eight-week training program. Pre- and post-tests of the all the participants included measurements of body composition, adaptation studies, trial measurements, biochemical blood, aerobic endurance measurements, sprint tests, and strength measurements. The Mixed Design ANOVA analysis was utilized to examine the performance, physiological, and biochemical data of the participants before and after the experiment. Concurrent training models were effective in increasing athletic performance (VO2max, CMJ, 1RM bench press and Yo-Yo test) and physiological outcomes during recovery (HR, blood lactate, Borg Scale) compared to the control group with traditional training. There was no significant difference between the biochemical changes in the S + HIIT, S + HIFT and control groups during the trial period. In summary, both concurrent training (CT) models had positive effects on sports performance and physiological outcomes, but not on biochemical outcomes.
Government Audit Announcements and Analysts’ Earning Forecasts: Evidence From China
Authors: Li Jia
Published: December 2024

This paper uses the difference-in-difference (DID) method to test the impact of government audits on analysts’ forecast accuracy. The empirical results show that after government audit announcements, analysts’ earning forecast accuracy of listed companies controlled by audited state-owned enterprises is significantly improved, while optimistic forecast bias and stock recommendation ratings are significantly lowered. Among them, the impact of operation and management issues on analysts’ forecast accuracy is more significant, while the impact of financial and accounting issues on analysts’ stock recommendation ratings is more significant. These indicate that government audit announcements have information effect and transmits companies’ incremental information to capital market. The conclusions pass the sensitivity tests and robustness tests. This paper not only enriches the literature on the relationship between government behavior and capital market, but also provides empirical support for the impact of government regulation on capital market efficiency.
Research on Driving Factors of Digital Innovation in the Tourism Industry
Authors: Chen Xuejun , Li Li , Ling Xiaopeng
Published: December 2024

Digital innovation has become a strategic choice to reshape the tourism industry ecosystem and promote its high-quality development. In the new environment of the digital economy, it is important to clarify the driving factors of digital innovation in the tourism industry and their relationship mechanism. On the basis of literature research, we construct an analytical framework or the driving factors of digital innovation in the tourism industry from seven aspects. Based on the collection of relevant research data from 31 provinces in China, and using 31 provinces in China (excluding Hong Kong, Macau, and Taiwan) as the subject of empirical research, the level of digital innovation development dynamics in each province was empirically investigated. The results show that the level of digital innovation development dynamics of the tourism industry in the 31 provinces of China shows great regional differences, and overall it can be divided into four echelons. Intra-industry upgrading, inter-industry competition, policy support, the technology innovation environment, economic level and the digital technology environment are the most important driving factors for digital innovation in China’s tourism industry. Market demand scale, e-commerce platforms, and internet facilities are more important driving factors for digital innovation in the industry. The degree of influence of market consumption structure, digital industry level and cultural industry level on digital innovation of the tourism industry is relatively small. The findings of the study make an important theoretical contribution to the understanding of the factors influencing innovation in the tourism industry in the new era. The article highlights the simultaneous approach of optimizing both endogenous and exogenous dynamics to enhance the innovative development of the global tourism industry.
Does Digital Economy Successfully Drive Down the Energy Intensity? Low-carbon Technology Innovation Perspective
Authors: Hou Jian , Wang Huiyu , Tian Tian , Zhang Sidan
Published: December 2024

Chinese government has been advocating a reduction in energy intensity in its efforts to meet peak carbon targets, particularly in the context of emerging economic growth and frequent technological breakthroughs. This study assesses China’s digital economy based on regional data experience and constructs a non-linear dynamic threshold model that incorporates heterogeneity thresholds for low-carbon technology innovation into the impact mechanism to explore whether the digital economy can effectively reduce regional energy intensity. It is found that China’s digital economy currently shows an overall upward trend with fluctuations in parts and a wide gap between the rich and the poor. Further, a significant heterogeneous threshold effect of low-carbon technology innovation exists in the effect of digital economy development on energy intensity: a lower level of low-carbon technology innovation is not advantageous to the decrease of energy intensity by digital economy development, while as the level of low-carbon technology innovation increases and exceeds the “threshold value,” the effect of digital economy development is effectively enhanced to a certain extent, thus promoting the reduction of energy intensity. As the level of low-carbon technology innovation raises and surpasses the “critical value,” the impact effect of digital economy development is heightened to a certain extent, thus promoting the decrease of energy intensity. The study replies the question of how to effectively use low-carbon technology innovation to accomplish digital economy development and help reduce regional energy intensity, which provides a reference for achieving the goal of carbon peak and accelerating green and high-quality economic development.
Mutations in AMBRA1 aggravate β-thalassemia by impairing autophagy-mediated clearance of free α-globin
Authors: Long Yong , Zhang Qianqian , Ling Ling , Zhuang Yuan , Wei Xiaolei , Huang Haoyang , Lu Zhanping , Huang Yushan , Chen Xianming , Ye Yuhua , Feng Xiaoqin , Zhang Haokun hao , Huang Binbin , Huang Yueyan , Liang Yidan , Fang Mingyan , Nakamura Yukio , Lin Bin , Zhang Xinhua , Lu Daru , Jin Xin , Xu Xiangmin
Published: December 2024

Accumulation of free α-globin is a critical factor in the pathogenesis of β-thalassemia. Autophagy plays a crucial role in clearing toxic free α-globin, thereby reducing disease severity. However, the impact of natural mutations in autophagy-related genes (ATGs) on the phenotypic variability of β-thalassemia remains unclear. In this study, we systematically investigated the relationship between variants in ATGs and disease phenotypes in a cohort of 1,022 patients with β-thalassemia, identifying four missense mutations in the autophagy and beclin 1 regulator 1 (AMBRA1) gene. Disruption of the Ambra1 gene in β-thalassemic mice was found to reduce autophagic clearance of α-globin in red blood cell precursors, exacerbating disease phenotypes. Functional characterization of the AMBRA1 gene and these mutations in patient-derived CD34+ cells, edited HUDEP-2 cells, and engineered HUDEP-2 β-thalassemic cells confirmed that AMBRA1 facilitates the autophagic clearance of free α-globin in human erythroid cells. Functional studies demonstrated that AMBRA1 missense mutants destabilize ULK1 protein, inhibit LC3 lipidation, and subsequently hinder autophagic flux, leading to increased α-globin deposition. Additionally, these mutations were associated with erythrotoxic effects in vitro, including increased intracellular reactive oxygen species levels, higher apoptosis rates, and impaired erythroid differentiation and maturation. This study sheds light on the molecular association between mutations in ATGs and the exacerbation of β-thalassemia, highlighting the potential role of the AMBRA1 gene as a promising diagnostic and therapeutic target for β-hemoglobinopathies.
High Pulmonary Hypertension Risk by Echocardiogram Shortens Survival in Polycythemia Vera
Authors: Gazda Alexander J , Pan Di , Erdos Katie , Abu-Zeinah Ghaith , Racanelli Alexandra , Horn Evelyn M , Scandura Joseph Michael
Published: December 2024

Pulmonary Hypertension (PH) is a known complication of myeloproliferative neoplasms (MPN) with estimated prevalence as high as 50%. Patients with Polycythemia Vera (PV) report a wide spectrum of symptoms that significantly overlap with those reported by patients with PH. Yet, it is not known how PH affects outcomes and survival in patients with PV. To address this gap, we investigated the impact of echocardiogram (ECHO) PH risk on survival of patients with PV from our large single center cohort. Of 637 patients with PV, 134 had at least one ECHO and were included for analysis. Overall survival (OS) did not differ between patients who had or did not have ECHO. PH risk was established based on tricuspid regurgitation jet velocity. Kaplan-Meier analysis showed that high PH risk is associated with shortened survival compared to mild PH risk (median survival 1.7 vs 3.7 years) or normal PH risk (median survival not yet reached). Cox Proportional Hazard Models found high PH risk was associated with >3-fold increased risk of death, independent of age and thrombosis history. Logistic regression identified age (odds ratio 6.9) and duration of PV diagnosis (odds ratio 5.4) as significant risks for PH. Based upon these results and receiver operator characteristic optimization, we recommend echocardiographic screening for patients with PV older than 70 years or with duration of PV longer than 8 years. Further studies inclusive of invasive hemodynamics, advanced CV imaging, and MPN-associated biomarkers are needed to best characterize this Group 5 PH patient population for therapeutic interventions.
Cumulative deficits frailty index and relationship status predict survival in multiple myeloma
Authors: Abdallah Nadine , Dizona Paul , Kumar Amanika , LaPlant Betsy , Menser Terri , Schaeferle Gavin , Aug Sarah , Weivoda Megan , Dispenzieri Angela , Buadi Francis K. , Warsame Rahma , Cook Joselle , Lacy Martha Q. , Hayman Suzanne , Gertz Morie A. , Rajkumar S. Vincent , Kumar Shaji K.
Published: December 2024

Several tools have been proposed for assessing frailty in multiple myeloma (MM), but most are based on clinical trial data sets. There are also limited data on the association between frailty and patient-reported outcomes and on the prognostic value of social determinants of health. This study evaluates the prognostic impact of frailty, based on the cumulative deficit frailty index (FI), and relationship and socioeconomic status (SES) in patients with newly diagnosed MM. This retrospective study included 515 patients with MM seen at Mayo Clinic (Rochester, MN) at diagnosis between 2005 and 2018. The FI was calculated using patient-reported data on activities of daily living and comorbidity data, with items scored as 0, 0.5, or 1, in which 1 indicated a deficit. The FI was calculated by dividing the total score by the number of nonmissing items. Frailty was defined as FI ≥0.15; 61% were nonfrail, and 39% were frail. Frailty and nonmarried/relationship status were associated with higher disease stage, decreased the likelihood of early transplantation, and independently associated with decreased survival. SES was not independently associated with survival. Frail patients reported worse scores for fatigue, pain, and quality of life. Approximately a quarter of patients had a deterioration in frailty status at 3 to 12 months, and <10% had improvement. In conclusion, a cumulative deficit FI was associated with higher symptom burden and decreased survival in a real-world cohort of patients with newly diagnosed MM. Frailty status is dynamic and should be reassessed during treatment. Social support has prognostic value and should be evaluated in clinical practice.
Efficacy of platelet-rich plasma in meniscal repair surgery: a systematic review of randomized controlled trials
Authors: Utrilla Giovanni Sergio , Degano Irene Roman , D’Ambrosi Riccardo
Published: December 2024

Purpose

This study’s primary objective was to evaluate the effectiveness of platelet-rich plasma (PRP) administration for meniscal injuries treated with meniscal repair procedures (sutures), using radiologic measures and clinical scales. The secondary objective was to identify potential bias-inducing elements in the analyzed studies.

Methods

In December 2023, a systematic search was conducted in PubMed, Cochrane, Embase, and Scopus for randomized controlled trials. This review compares PRP with placebo. Three studies were finally selected. The risk of bias was assessed using Cochrane's Risk of Bias Tool 2. Radiologic evaluation of meniscal healing was measured with magnetic resonance imaging (MRI) and arthroscopic studies, while clinical evaluation was performed using four scales [Knee Injury and Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS), International Knee Documentation Committee Subjective Knee Form (IKDC), and Western Ontario and McMaster Universities Index (WOMAC)] and by recording the incidence of complications.

Results

The three selected studies included 139 patients; of these, 76 (54.7%) were randomly assigned to the intervention group (PRP injection) and 63 (45.3%) to the control group (placebo). The mean age of the intervention group was 37.4 ± 7.5 years, while the mean age of the control group was 36.5 ± 9.2 years. There were 41 female patients (29.5%). The median follow-up duration was 27.58 ± 17.3 months. MRI evaluation did not show a significant improvement in the PRP group in any of the studies (p-value = 0.41–0.54). However, when assessed by the cumulative evaluation of MRI and arthroscopy, the cumulative failure rate was significantly better in the PRP group (p-value = 0.04–0.048). One study that evaluated isolated arthroscopy also showed significant improvement in the PRP group (p = 0.003). Regarding the VAS scale, no study demonstrated a significant difference, except for one study that showed significant improvement after 6 months and in the difference between the 3rd and 6th months. The KOOS scale yielded conflicting results; one study showed no significant difference, while the other two indicated significant improvement. The IKDC and WOMAC scales were evaluated in two studies, showing opposite results. All included studies reported no complications, and one study indicated no increased risk in the treatment group.

Conclusions

The results of this review indicate the necessity for further studies to make a definitive statement about the effectiveness of PRP administration in meniscal repair processes.

Level of evidence Systematic review and meta-analysis of articles of level 1.
Efficacy and safety of quadriceps tendon autograft versus bone–patellar tendon–bone and hamstring tendon autografts for anterior cruciate ligament reconstruction: a systematic review and meta-analysis
Authors: Zhang Xiao-Feng , Liu Pan , Huang Jun-Wu , He Yao-Hua
Published: December 2024

Background

Quadriceps tendon (QT), bone–patellar tendon–bone (BPTB), and hamstring tendon (HT) autografts are widely used for anterior cruciate ligament reconstruction (ACLR), but the optimal autograft choice remains controversial. This study assessed the treatment effects of QT versus BPTB and HT autografts for ACLR.

Methods

The PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies published from inception until July 2022. Effect estimates were presented as odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI) for categorical and continuous variables, respectively. All pooled analyses were performed using a random-effects model.

Results

Twenty-one studies (3 randomized controlled trials [RCTs], 3 prospective studies, and 15 retrospective studies) involving 2964 patients with ACLR were selected for meta-analysis. Compared with the HT autograft, the QT autograft was associated with a reduced risk of graft failure (OR: 0.46; 95% CI: 0.23–0.93; P = 0.031). Compared with the BPTB autograft, the QT autograft was associated with a reduced risk of donor site pain (OR: 0.16; 95% CI: 0.10–0.24; P < 0.001). Moreover, the QT autograft was associated with a lower side-to-side difference than that observed with the HT autograft (WMD: − 0.74; 95% CI: − 1.47 to − 0.01; P = 0.048). Finally, compared with the BPTB autograft, the QT autograft was associated with a reduced risk of moderate-to-severe kneecap symptoms during sports and work activities (OR: 0.14; 95% CI: 0.05–0.37; P < 0.001).

Conclusions

The findings of this study suggest that the QT autograft can be defined as a safe and effective alternative choice for ACLR, but its superiority is yet to be proven by RCTs and prospective studies.

Level of evidence

Level III.
Postoperative femoral head cartilage injury after hip arthroscopic treatment for femoroacetabular impingement syndrome and labral tear
Authors: Gao Guanying , Zhu Yichuan , Zhang Siqi , Ao Yingfang , Wang Jianquan , Xu Yan
Published: December 2024

Background

Postoperative femoral head cartilage injury (FHCI) is a rare condition that can be observed in a certain proportion of patients undergoing hip arthroscopy. However, the prevalence and associated factors of FHCI, and the effect of this condition on clinical outcomes still remain unknown.

Patients and methods

Consecutive patients who were diagnosed with femoroacetabular impingement syndrome (FAIS) and labral tear and underwent hip arthroscopic treatment in our institute between July 2020 and July 2021 were retrospectively evaluated. Supine anteroposterior hip radiographs, cross-table lateral radiographs, magnetic resonance imaging (MRI), and computed tomography (CT) were obtained preoperatively. Postoperative MRI, at least 6 months after arthroscopy, was performed. Postoperative FHCI was evaluated by two surgeons through MRI. Preoperative patient-reported outcomes (PROs) including visual analog scale (VAS) for pain, and modified Harris Hip Score (mHHS) before surgery and at final followup were obtained.

Results

A total of 196 patients were included. Postoperative FHCI was identified in 21 (10.7%) patients. The intraobserver reliability of the observer A and B for detecting postoperative FHCI using 3.0-T MRI was high (k = 0.929, and k = 0.947, respectively). The interobserver reliability between the two observers for detecting FHCI using 3.0-T MRI was high (k = 0.919). There was no significant difference in preoperative and postoperative mHHS, VAS, and percentage of patients who surpassed minimal clinically important difference (MCID) and achieved patient acceptable symptom state (PASS) between patients with and without postoperative FHCI (P > 0.05).

Conclusion

Although postoperative FHCI was observed in 10.7% of patients, which was associated with larger labrum, this condition did not result in inferior clinical outcomes.

Level of evidence IV, retrospective case series.

Trial registration The Chinese Clinical Trial Registry approved the registration (ChiCTR2200061166). The date of registration is 2022-06-15.
For many but not for all: the bikini incision direct anterior approach for total hip arthroplasty. A narrative review
Authors: Faldini Cesare , Traina Francesco , Pilla Federico , D’Agostino Claudio , Brunello Matteo , Morandi Guaitoli Manuele , Di Martino Alberto
Published: December 2024

Total hip arthroplasty (THA) has significantly improved the lives of patients with degenerative hip disorders. The direct anterior approach (DAA) is favored for its minimally invasive nature, leading to less postoperative pain and a faster recovery. The bikini incision (BI) approach was developed to enhance aesthetic outcomes while maintaining the clinical and functional benefits of the DAA. Despite its advantages, the BI technique presents challenges, controversies persist regarding its efficacy and safety, and there is no consensus within the medical community about its overall benefits. Incisions aligned with Langer’s lines, like the BI, promote better healing and minimal scarring. Studies indicate that BI patients report higher satisfaction with scar appearance and texture compared to traditional DAA patients. However, the BI carries a higher risk of lateral femoral cutaneous nerve (LFCN) injury, although most symptoms resolve within 6 months. For obese patients, the BI is associated with fewer complications, such as infections and delayed healing, compared to the conventional DAA, making it a safe and effective option. BI patients also experience better aesthetic outcomes and functional recovery, with reduced pain and itching. The BI technique in THA represents a significant advancement, offering improved aesthetic and wound-healing outcomes. The shift from the traditional DAA to the BI aligns with patient preferences for scars that are less visible and conspicuous. Despite the steep learning curve and risks, careful patient selection and refined surgical techniques can enhance the BI’s benefits. Future research should focus on long-term outcomes and comparative studies to further establish the BI’s efficacy and safety. As patient demand for aesthetically favorable surgeries grows, the BI is likely to become a preferred approach in THA.
Piikun: an information theoretic toolkit for analysis and visualization of species delimitation metric space
Authors: Sukumaran Jeet , Meila Marina
Published: December 2024

Background

Existing software for comparison of species delimitation models do not provide a (true) metric or distance functions between species delimitation models, nor a way to compare these models in terms of relative clustering differences along a lattice of partitions.

Results

is a Python package for analyzing and visualizing species delimitation models in an information theoretic framework that, in addition to classic measures of information such as the entropy and mutual information [1], provides for the calculation of the Variation of Information (VI) criterion [2], a true metric or distance function for species delimitation models that is aligned with the lattice of partitions.

Conclusions

is available under the MIT license from its public repository ( https://github.com/jeetsukumaran/piikun), and can be installed locally using the Python package manager ‘pip‘.
QTL mapping provides new insights into emamectin benzoate resistance in salmon lice, Lepeophtheirus salmonis
Authors: Sturm Armin , Carmona-Antoñanzas Greta , Humble Joseph L. , Croton Claudia , Boyd Sally , Mphuti Rapule , Taggart John B. , Bassett David I. , Houston Ross D. , Gharbi Karim , Bron James E. , Bekaert Michaël
Published: December 2024

Background

The salmon louse (Lepeophtheirus salmonis) is a parasite of wild and farmed salmonid fish, causing huge economic damage to the commercial farming of Atlantic salmon (Salmo salar) in the northern hemisphere. The avermectin emamectin benzoate (EMB) is widely used for salmon delousing. While resistance to EMB is widespread in Atlantic populations of L. salmonis, the molecular mechanisms of resistance remain to be elucidated. The aim of the present work was to obtain insights into potential EMB resistance mechanisms by identifying genetic and transcriptomic markers associated with EMB resistance.

Results

Crosses were performed between EMB-susceptible and -resistant L. salmonis, sourced from two parental strains isolated in Scotland, producing fully pedigreed families. The EMB susceptibility of individual parasites was characterised using time-to-response bioassays. Parasites of two families were subjected to double digest restriction site-associated DNA sequencing (ddRAD-seq) for simultaneous discovery of single nucleotide polymorphisms (SNPs) and genotyping. Data analysis revealed that EMB resistance is associated with one quantitative trait locus (QTL) region on L. salmonis chromosome 5. Marker-trait association was confirmed by genotyping assays for 7 SNPs in two additional families. Furthermore, the transcriptome of male parasites of the EMB-susceptible and -resistant L. salmonis parental strains was assessed. Among eighteen sequences showing higher transcript expression in EMB-resistant as compared to drug-susceptible lice, the most strongly up-regulated gene is located in the above QTL region and shows high homology to β spectrin, a cytoskeleton protein that has roles in neuron architecture and function. Further genes differentially regulated in EMB-resistant lice include a glutathione S-transferase (GST), and genes coding for proteins with predicted roles in mitochondrial function, intracellular signalling or transcription.

Conclusions

Major determinants of EMB resistance in L. salmonis are located on Chromosome 5. Resistance can be predicted using a limited number of genetic markers. Genes transcriptionally up-regulated in EMB resistant parasites include a β spectrin, a cytoskeletal protein with still incompletely understood roles in neuron structure and function, as well as glutathione S-transferase, an enzyme with potential roles in the biochemical defence against toxicants.
Candidate genes associated with fatty acid compositions in north American Atlantic salmon (Salmo salar)
Authors: Langille Barbara L. , Juárez Manuel , Prieto Nuria , Boison Solomon , Lim Panya Sae , Swift Bruce D. , Garber Amber F.
Published: December 2024

Fatty acids are a requirement for normal development, however, since humans are unable to de novo produce essential fatty acids, they must be obtained from diet. Atlantic salmon is a major dietary source of nutritious and digestible fatty acids. Here, we set out to uncover the genomic basis of individual fatty acids and indices (saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, n-3, and n-6) in 208 North American Atlantic salmon, to understand selection potential toward increasing relative quantities of essential fatty acids and to identify candidate genes for future research. Total n-6 (pro-inflammatory) was higher than total n-3 (anti-inflammatory) fatty acids with a ratio of 1 : 1.31 (n-3 : n-6). Heritability of fatty acids ranged from 0 to 0.99, however, most fatty acids and indices had moderate to high heritabilities (ranged from 0.20 to 0.88), implying that selection for improvement of traits could be possible. We found the same significant markers on chromosome 23 (based on false discovery rate thresholds of 2.0e-6 and suggestive significant thresholds of 2.0e-5 in Manhattan plots) in four fatty acids (γ-linoleic acid, stearidonic acid, dihimo-γ-linolenic acid, and eicosatrienoic acid), where three genes (sin3b, acbd6, and fads2) are known to be involved in lipid metabolism. These genes, fads2 in particular, would all make ideal candidates for future functional studies. In addition, there were four fatty acids with loci over the suggestive significant threshold with a variety of markers on different chromosomes (lauric acid, stearic acid, eicosatetraenoic acid (ETA), and docosadienoic acid), with associated genes that had relevant functions to fatty acids or adipose cells in general.
CGRclust: Chaos Game Representation for twin contrastive clustering of unlabelled DNA sequences
Authors: Alipour Fatemeh , Hill Kathleen A. , Kari Lila
Published: December 2024

Background

Traditional supervised learning methods applied to DNA sequence taxonomic classification rely on the labor-intensive and time-consuming step of labelling the primary DNA sequences. Additionally, standard DNA classification/clustering methods involve time-intensive multiple sequence alignments, which impacts their applicability to large genomic datasets or distantly related organisms. These limitations indicate a need for robust, efficient, and scalable unsupervised DNA sequence clustering methods that do not depend on sequence labels or alignment.

Results

This study proposes CGRclust, a novel combination of unsupervised twin contrastive clustering of Chaos Game Representations (CGR) of DNA sequences, with convolutional neural networks (CNNs). To the best of our knowledge, CGRclust is the first method to use unsupervised learning for image classification (herein applied to two-dimensional CGR images) for clustering datasets of DNA sequences. CGRclust overcomes the limitations of traditional sequence classification methods by leveraging unsupervised twin contrastive learning to detect distinctive sequence patterns, without requiring DNA sequence alignment or biological/taxonomic labels. CGRclust accurately clustered twenty-five diverse datasets, with sequence lengths ranging from 664 bp to 100 kbp, including mitochondrial genomes of fish, fungi, and protists, as well as viral whole genome assemblies and synthetic DNA sequences. Compared with three recent clustering methods for DNA sequences (DeLUCS, iDeLUCS, and MeShClust v3.0.), CGRclust is the only method that surpasses 81.70% accuracy across all four taxonomic levels tested for mitochondrial DNA genomes of fish. Moreover, CGRclust also consistently demonstrates superior performance across all the viral genomic datasets. The high clustering accuracy of CGRclust on these twenty-five datasets, which vary significantly in terms of sequence length, number of genomes, number of clusters, and level of taxonomy, demonstrates its robustness, scalability, and versatility.

Conclusion

CGRclust is a novel, scalable, alignment-free DNA sequence clustering method that uses CGR images of DNA sequences and CNNs for twin contrastive clustering of unlabelled primary DNA sequences, achieving superior or comparable accuracy and performance over current approaches. CGRclust demonstrated enhanced reliability, by consistently achieving over 80% accuracy in more than 90% of the datasets analyzed. In particular, CGRclust performed especially well in clustering viral DNA datasets, where it consistently outperformed all competing methods.
A PubMed search filter for efficiently retrieving exercise training studies
Authors: Yin Dawei , Engracia Mikaela V. , Edema Matthew K. , Clarke David C.
Published: December 2024

Background

A barrier to evidence-informed exercise programming is locating studies of exercise training programs. The purpose of this study was to create a search filter for studies of exercise training programs for the PubMed electronic bibliographic database.

Methods

Candidate search terms were identified from three sources: exercise-relevant MeSH terms and their corresponding Entry terms, word frequency analysis of articles in a gold-standard reference set curated from systematic reviews focused on exercise training, and retrospective searching of articles retrieved in the search filter development and testing steps. These terms were assembled into an exercise training search filter, and its performance was assessed against a basic search string applied to six case studies. Search string performance was measured as sensitivity (relative recall), precision, and number needed to read (NNR). We aimed to achieve relative recall ≥ 85%, and a NNR ≥ 2.

Results

The reference set consisted of 71 articles drawn from six systematic reviews. Sixty-one candidate search terms were evaluated for inclusion, 21 of which were included in the finalized exercise-training search filter. The relative recall of the search filter was 96% for the reference set and the precision mean ± SD was 54 ± 16% across the case studies, with the corresponding NNR = ~ 2. The exercise training search filter consistently outperformed the basic search string.

Conclusion

The exercise training search filter fosters more efficient searches for studies of exercise training programs in the PubMed electronic bibliographic database. This search string may therefore support evidence-informed practice in exercise programming.
TB treatment delays and associated risk factors in Dushanbe, Tajikistan, 2019–2021
Authors: Sharifov Radzhabali , Nabirova Dilyara , Tilloeva Zulfiya , Zikriyarova Sanam , Kishore Nishant , Jafarov Navruz , Yusufi Salomuddin , Horth Roberta
Published: December 2024

Background

In Tajikistan, where there are about 8,000 cases annually, many new cases are being diagnosed with severe disease, indicating a delay in receiving care. We aimed to estimate the proportion with delayed care and the main factors contributing to delayed care.

Methods

Using a retrospective cohort design, we conducted a study that included all people aged over 15 years who were newly diagnosed with pulmonary TB in Dushanbe from 2019 to 2021. We defined ‘patient delay’ as > 14 days from TB symptom onset to the first provider visit and ‘provider delay’ as > 3 days from the first visit to treatment initiation. Data was abstracted from medical records and participants were interviewed in-person. Multivariable negative binomial regression was used to estimate adjusted risk ratios (aRR) and 95% confidence intervals (CI).

Results

Of 472 participants, 49% were male, 65% had lung tissue cavitation, 33% had drug resistant TB, 11% had diabetes, 4% had HIV, and. Reported cases dropped from 196 in 2019 to 109 in 2020 and increased to 167 in 2021. The proportion of people experiencing patient delays was 82%, 72%, and 90% per year, respectively. The proportion of provider delays was 44%, 41% and 29% per year. Patient delay was associated with year (aRR: 1.09 [CI:1.02–1.18] in 2021 vs. 2019), age (aRR:0.91 [0.82–0.99] for 40–59-year-olds vs. 15–39-year-olds), having HIV (aRR:1.22 [1.08–1.38]), having blood in sputum (aRR:1.19 [1.10–1.28]), chest pain (aRR:1.32 [1.14–1.54]), having at least two structural barriers vs. none (aRR:1.52 [1.28–1.80]), having one of the following barriers: long wait lines (aRR:1.36 [1.03–1.80]), feeling that healthcare services were expensive (aRR:1.54 [1.28–1.85]), or having no time or too much work (aRR:1.54 [1.29–1.84]). Provider delay was associated with year (aRR: 0.67 [0.51–0.89] in 2021 vs. 2019), patients having to pay for X-ray services (aRR: 1.59 [1.22–2.07]) and lacking direct-observed-therapy (DOTS) in facility (aRR: 1.61 [1.03–2.52]).

Conclusions

Patient delay was high before the COVID-19 pandemic and increased in 2021, while provider delay decreased during this time. Addressing structural barriers to healthcare services, such as increased DOTS facilities, expanded hours, and zero fees, may decrease delays.
A spheroid whole mount drug testing pipeline with machine-learning based image analysis identifies cell-type specific differences in drug efficacy on a single-cell level
Authors: Vitacolonna Mario , Bruch Roman , Schneider Richard , Jabs Julia , Hafner Mathias , Reischl Markus , Rudolf Rüdiger
Published: December 2024

Background

The growth and drug response of tumors are influenced by their stromal composition, both in vivo and 3D-cell culture models. Cell-type inherent features as well as mutual relationships between the different cell types in a tumor might affect drug susceptibility of the tumor as a whole and/or of its cell populations. However, a lack of single-cell procedures with sufficient detail has hampered the automated observation of cell-type-specific effects in three-dimensional stroma-tumor cell co-cultures.

Methods

Here, we developed a high-content pipeline ranging from the setup of novel tumor-fibroblast spheroid co-cultures over optical tissue clearing, whole mount staining, and 3D confocal microscopy to optimized 3D-image segmentation and a 3D-deep-learning model to automate the analysis of a range of cell-type-specific processes, such as cell proliferation, apoptosis, necrosis, drug susceptibility, nuclear morphology, and cell density.

Results

This demonstrated that co-cultures of KP-4 tumor cells with CCD-1137Sk fibroblasts exhibited a growth advantage compared to tumor cell mono-cultures, resulting in higher cell counts following cytostatic treatments with paclitaxel and doxorubicin. However, cell-type-specific single-cell analysis revealed that this apparent benefit of co-cultures was due to a higher resilience of fibroblasts against the drugs and did not indicate a higher drug resistance of the KP-4 cancer cells during co-culture. Conversely, cancer cells were partially even more susceptible in the presence of fibroblasts than in mono-cultures.

Conclusion

In summary, this underlines that a novel cell-type-specific single-cell analysis method can reveal critical insights regarding the mechanism of action of drug substances in three-dimensional cell culture models.
Exploring autism spectrum disorder and co-occurring trait associations to elucidate multivariate genetic mechanisms and insights
Authors: Salenius Karoliina , Väljä Niina , Thusberg Sini , Iris Francois , Ladd-Acosta Christine , Roos Christophe , Nykter Matti , Fasano Alessio , Autio Reija , Lin Jake ,   the GEMMA study
Published: December 2024

Background

Autism spectrum disorder (ASD) is a partially heritable neurodevelopmental trait, and people with ASD may also have other co-occurring trait such as ADHD, anxiety disorders, depression, mental health issues, learning difficulty, physical health traits and communication challenges. The concomitant development of ASD and other neurological traits is assumed to result from a complex interplay between genetics and the environment. However, only a limited number of studies have performed multivariate genome-wide association studies (GWAS) for ASD.

Methods

We conducted to-date the largest multivariate GWAS on ASD and 8 ASD co-occurring traits (ADHD, ADHD childhood, anxiety stress (ASDR), bipolar (BIP), disruptive behaviour (DBD), educational attainment (EA), major depression, and schizophrenia (SCZ)) using summary statistics from leading studies. Multivariate associations and central traits were further identified. Subsequently, colocalization and Mendelian randomization (MR) analysis were performed on the associations identified with the central traits containing ASD. To further validate our findings, pathway and quantified trait loci (QTL) resources as well as independent datasets consisting of 112 (45 probands) whole genome sequence data from the GEMMA project were utilized.

Results

Multivariate GWAS resulted in 637 significant associations (p < 5e-8), among which 322 are reported for the first time for any trait. 37 SNPs were identified to contain ASD and one or more traits in their central trait set, including variants mapped to known SFARI ASD genes MAPT, CADPS and NEGR1 as well as novel ASD genes KANSL1, NSF and NTM, associated with immune response, synaptic transmission, and neurite growth respectively. Mendelian randomization analyses found that genetic liability for ADHD childhood, ASRD and DBT has causal effects on the risk of ASD while genetic liability for ASD has causal effects on the risk of ADHD, ADHD childhood, BIP, WA, MDD and SCZ. Frequency differences of SNPs found in NTM and CADPS genes, respectively associated with neurite growth and neural/endocrine calcium regulation, were found between GEMMA ASD probands and controls. Pathway, QTL and cell type enrichment implicated microbiome, enteric inflammation, and central nervous system enrichments.

Conclusions

Our study, combining multivariate GWAS with systematic decomposition, identified novel genetic associations related to ASD and ASD co-occurring driver traits. Statistical tests were applied to discern evidence for shared and interpretable liability between ASD and co-occurring traits. These findings expand upon the current understanding of the complex genetics regulating ASD and reveal insights of neuronal brain disruptions potentially driving development and manifestation.
Differential late-stage face processing in autism: a magnetoencephalographic study of fusiform gyrus activation
Authors: Sarovic Darko , Schneiderman Justin , Lundström Sebastian , Riaz Bushra , Orekhova Elena , Khan Sheraz , Gillberg Christopher
Published: December 2024

Background

Autism is associated with alterations of social communication, such as during face-to-face interactions. This study aimed to probe face processing in autistics with normal IQ utilizing magnetoencephalography to examine event-related fields within the fusiform gyrus during face perception.

Methods

A case–control cohort of 22 individuals diagnosed with autism and 20 age-matched controls (all male, age 29.3 ± 6.9 years) underwent magnetoencephalographic scanning during an active task while observing neutral faces, face-like pareidolic objects, and non-face objects. The fusiform face area was identified using a face localizer for each participant, and the cortical activation pattern was normalized onto an average brain for subsequent analysis.

Results

Early post-stimulus activation amplitudes (before 100–200 ms) indicated differentiation between stimuli containing fundamental facial features and non-face objects in both groups. In contrast, later activation (400–550 ms) differentiated real faces from both pareidolic and non-face objects across both groups and faces from objects in controls but not in autistics. There was no effect of autistic-like traits.

Conclusions

The absence of group differences in early activation suggest intact face detection in autistics possessing a normal IQ. Later activation captures a greater degree of the complexity and social information from actual faces. Although both groups distinguished faces from pareidolic and non-face objects, the control group exhibited a slightly heightened differentiation at this latency, indicating a potential disadvantage for autistics in real face processing. The subtle difference in late-stage face processing observed in autistic individuals may reflect specific cognitive mechanisms related to face perception in autism.
A cross-sectional study applying the PRECEDE model to explore factors influencing epidemic prevention behaviors among preschool educators
Authors: He Yi-Ying , Huang Wei-Hsiang , Tung Chen-Yin
Published: December 2024

Background

This study investigates the epidemic prevention behaviors of preschool educators and the factors influencing these behaviors, applying the PRECEDE model as a framework for analysis.

Methods

A cross-sectional survey was conducted among 190 preschool educators from public and private institutions in Taipei City and New Taipei City. A 64-item self-developed questionnaire was used to assess epidemic prevention behaviors and their determinants. The instrument’s reliability was supported by internal consistency (Cronbach’s α ranging from 0.85 to 0.92), while its validity was confirmed through expert review, item analysis, and confirmatory factor analysis (CFA). Statistical analyses included hierarchical regression to examine the influence of predisposing, reinforcing, and enabling factors on behavior.

Results

The model explained 54% of the variance in epidemic prevention behaviors. Enabling factors had the strongest influence (β = 0.46, p < 0.001), followed by reinforcing factors (β = 0.15, p < 0.05) and predisposing attitudes (β = 0.14, p < 0.05). Background variables, such as age (β = 0.23, p < 0.001) and years of service, collectively explained 14% of the variance.

Conclusion

The findings underscore the critical role of institutional support and professional training in enhancing epidemic prevention practices among preschool educators. Recommendations include integrating disease prevention training into professional development initiatives.
Occupational groups and risk of suicidal behavior in men: a Swedish national cohort study during 2002–2019
Authors: Nyberg Jenny , Wessman Catrin , Söderberg Mia , LaMontagne Anthony D. , Toren Kjell , Waern Margda , Åberg Maria
Published: December 2024

Introduction

The risk of suicide has been shown to vary by occupation. We aim to identify contemporary occupational groups at greatest risk for suicidal behaviour (fatal and non-fatal), in Swedish men of working-age.

Methods

A population-based cohort study of male conscripts without history of self-harm who enlisted during 1968–2001 and were followed-up during 2002–2019 (n = 1 542 665). Occupational groups and suicidal behaviours were identified using national registers. Incidence rate ratios (IRR) for suicidal behaviour at ages 25–65 were calculated among occupational groups, and compared to the incidence rate of the whole cohort.

Results

Major occupational groups with increased risk for suicidal behavior included elementary occupations, building and manufacturing, service, care and shop sale and mechanical manufacturing and transport. Subgroup analyses revealed particularly high risks for assistant nurses, other service workers not elsewhere classified, building frame and related trades workers and cleaners and helpers.

Conclusions

Men with elementary occupations as well as personal care and building and manufacturing workers were at greatest risk. This study provides a comprehensive description of risks for suicidal behaviour among occupational groups in men of working-age. These results suggest occupational groups that should be targeted for general suicide prevention intervention.
A multi-stage approach to support timely health policy decisions during crisis: the fast-track Delphi
Authors: Velarde Crézé Camille , Duperrex Olivier , Lebon Luc , Faivre Vincent , Pasche Myriam , Cornuz Jacques
Published: December 2024

Background

Scientists can play an important role in policymaking by providing evidence and consensual expert opinion on the state of scientific knowledge. Delphi surveys have been widely used to develop consensus on a topical issue, yet not compatible with public health crisis situations requiring rapid decisions. We developed a fast-track Delphi process, providing experts with a structured approach to rapidly develop and quantify consensus in support of informed policy decisions.

Methods

We identified key elements of consensus-building techniques through a literature review and derived methodological procedures that served as the basis for the elaboration of the new process. Selected methodological experts provided advice on necessary adjustments. The process was pilot tested using a real-world public health issue.

Results

The fast-track Delphi process is a hybrid approach between a conventional Delphi and the nominal group technique: one group session followed by two rounds of e-questionnaire, with predefined steps. We developed an ad hoc toolkit (REDCap templates, R code for analysis and production of reports, user guide) to overcome time constraints, which we pilot tested with experts. The feasibility test conducted in 18 days in the field of tobacco control demonstrated the applicability and usefulness of the process in real-world conditions.

Conclusions

We strongly believe that this fast-track Delphi process has the potential to help inform policy decisions in various types of crises, including emerging diseases or novel potentially harmful products.