bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the effects of resolving nautical bottlenecks on the Danube: a KPI-based conceptual framework
Authors: Duldner-Borca Bianca , van Hassel Edwin , Putz-Egger Lisa-Maria
Published: August 2023

Background

Shifting cargo from roads to eco-friendly inland waterway transport (IWT) is an important step towards reaching the decarbonization goals defined by the European Green Deal. The rehabilitation of nautical bottlenecks is essential to reach the fairway depth which is needed to allow a competitive transport on inland waterways.

Aim

The goal of this paper is to (1) identify key performance indicators (KPI) associated with nautical bottlenecks caused by insufficient maintenance, (2) understand the effects of resolving nautical bottlenecks on the identified KPIs and (3) develop a conceptual framework.

Methods

To develop the conceptual framework, we carried out a systematic literature review. We analysed the identified literature using qualitative content analysis and thus, derived relevant KPIs and their interdependencies.

Findings

Ten KPIs were identified, which could be clustered as being either IWT-related, market-related or location-related. One example for an IWT-related KPI is the vessel draft, while market-related KPIs are e.g., referring to the KPI modal share and location-related KPIs to other KPIs such as fairway depth.

Contribution

The conceptual framework visualizes the interdependencies between the KPIs and facilitates further research in this field, i.e., the development of a method for the evaluation of economic benefits of resolving nautical bottlenecks on inland waterways. A scientific method that allows the economic evaluation of resolving nautical bottlenecks it is essential to demonstrates the gain in quantitative net benefit if water levels are sufficient. A quantification of the net benefit serves as a motivator to intensify maintenance work on nautical bottlenecks and to facilitate decision-making regarding infrastructure projects.
Boosting variant-calling performance with multi-platform sequencing data using Clair3-MP
Authors: Yu Huijing , Zheng Zhenxian , Su Junhao , Lam Tak-Wah , Luo Ruibang
Published: August 2023

Background

With the continuous advances in third-generation sequencing technology and the increasing affordability of next-generation sequencing technology, sequencing data from different sequencing technology platforms is becoming more common. While numerous benchmarking studies have been conducted to compare variant-calling performance across different platforms and approaches, little attention has been paid to the potential of leveraging the strengths of different platforms to optimize overall performance, especially integrating Oxford Nanopore and Illumina sequencing data.

Results

We investigated the impact of multi-platform data on the performance of variant calling through carefully designed experiments with a deep learning-based variant caller named Clair3-MP (Multi-Platform). Through our research, we not only demonstrated the capability of ONT-Illumina data for improved variant calling, but also identified the optimal scenarios for utilizing ONT-Illumina data. In addition, we revealed that the improvement in variant calling using ONT-Illumina data comes from an improvement in difficult genomic regions, such as the large low-complexity regions and segmental and collapse duplication regions. Moreover, Clair3-MP can incorporate reference genome stratification information to achieve a small but measurable improvement in variant calling. Clair3-MP is accessible as an open-source project at: https://github.com/HKU-BAL/Clair3-MP.

Conclusions

These insights have important implications for researchers and practitioners alike, providing valuable guidance for improving the reliability and efficiency of genomic analysis in diverse applications.
Genetic architecture and key regulatory genes of fatty acid composition in Gushi chicken breast muscle determined by GWAS and WGCNA
Authors: Fan Shengxin , Yuan Pengtao , Li Shuaihao , Li Hongtai , Zhai Bin , Li Yuanfang , Zhang Hongyuan , Gu Jinxin , Li Hong , Tian Yadong , Kang Xiangtao , Zhang Yanhua , Li Guoxi
Published: August 2023

Background

Fatty acids composition in poultry muscle is directly related to its tenderness, flavour, and juiciness, whereas its genetic mechanisms have not been elucidated. In this study, the genetic structure and key regulatory genes of the breast muscle fatty acid composition of local Chinese chicken, Gushi-Anka F2 resource population by integrating genome-wide association study (GWAS) and weighted gene co-expression network analysis (WGCNA) strategies. GWAS was performed based on 323,306 single nucleotide polymorphisms (SNPs) obtained by genotyping by sequencing (GBS) method and 721 chickens from the Gushi-Anka F2 resource population with highly variable fatty acid composition traits in the breast muscle. And then, according to the transcriptome data of the candidate genes that were obtained and phenotypic data of fatty acid composition traits in breast muscle of Gushi chickens at 14, 22, and 30 weeks of age, we conducted a WGCNA.

Results

A total of 128 suggestive significantly associated SNPs for 11 fatty acid composition traits were identified and mapped on chromosomes (Chr) 2, 3, 4, 5, 13, 17, 21, and 27. Of these, the two most significant SNPs were Chr13:5,100,140 (P = 4.56423e-10) and Chr13:5,100,173 (P = 4.56423e-10), which explained 5.6% of the phenotypic variation in polyunsaturated fatty acids (PUFA). In addition, six fatty acid composition traits, including C20:1, C22:6, saturated fatty acid (SFA), unsaturated fatty acids (UFA), PUFA, and average chain length (ACL), were located in the same QTL intervals on Chr13. We obtained 505 genes by scanning the linkage disequilibrium (LD) regions of all significant SNPs and performed a WGCNA based on the transcriptome data of the above 505 genes. Combining two strategies, 9 hub genes (ENO1,ADH1, ASAH1, ADH1C, PIK3CD, WISP1, AKT1,PANK3, andC1QTNF2) were finally identified, which could be the potential candidate genes regulating fatty acid composition traits in chicken breast muscle.

Conclusion

The results of this study deepen our understanding of the genetic mechanisms underlying the regulation of fatty acid composition traits, which is helpful in the design of breeding strategies for the subsequent improvement of fatty acid composition in poultry muscle.
Characterization of a strain-specific CD-1 reference genome reveals potential inter- and intra-strain functional variability
Authors: Jung Yoon Hee , Wang Hsiao-Lin V. , Ali Samir , Corces Victor G. , Kremsky Isaac
Published: August 2023

Background

CD-1 is an outbred mouse stock that is frequently used in toxicology, pharmacology, and fundamental biomedical research. Although inbred strains are typically better suited for such studies due to minimal genetic variability, outbred stocks confer practical advantages over inbred strains, such as improved breeding performance and low cost. Knowledge of the full genetic variability of CD-1 would make it more useful in toxicology, pharmacology, and fundamental biomedical research.

Results

We performed deep genomic DNA sequencing of CD-1 mice and used the data to identify genome-wide SNPs, indels, and germline transposable elements relative to the mm10 reference genome. We used multiple genome-wide sequencing data types and previously published CD-1 SNPs to validate our called variants. We used the called variants to construct a strain-specific CD-1 reference genome, which we show can improve mappability and reduce experimental biases from genome-wide sequencing data derived from CD-1 mice. Based on previously published ChIP-seq and ATAC-seq data, we find evidence that genetic variation between CD-1 mice can lead to alterations in transcription factor binding. We also identified a number of variants in the coding region of genes which could have effects on translation of genes.

Conclusions

We have identified millions of previously unidentified CD-1 variants with the potential to confound studies involving CD-1. We used the identified variants to construct a CD-1-specific reference genome, which can improve accuracy and reduce bias when aligning genomics data derived from CD-1 mice.
The sleep patterns and their associations with mental health among nursing home residents: a latent profile approach
Authors: Mou Huanyu , Xu Dongjuan , Zhu Shanshan , Zhao Meng , Wang Yaqi , Wang Kefang
Published: August 2023

Background

Nursing home residents commonly experience poor sleep conditions. However, few studies have explored the potential sleep patterns among nursing home residents. This study aimed to identify the sleep patterns in nursing home residents, compare residents’ characteristics across sleep patterns, and examine the relationships between sleep patterns and residents’ mental health (i.e., depressive and anxiety symptoms).

Methods

This cross-sectional study was conducted in 27 nursing homes in Jinan, China, from March to June 2018. In total, 353 participants were recruited via convenience sampling, and of which, 326 completed the survey. A latent profile analysis was performed to identify sleep patterns based on the seven dimensions of the Pittsburgh Sleep Quality Index. Bivariate analyses were conducted to compare residents’ characteristics among the sleep patterns. Mixed-effects logistic regression analyses were adopted to investigate the relationships between sleep patterns and residents’ mental health.

Results

Three sleep patterns were identified, including ‘good sleepers’, ‘poor sleepers without hypnotic use’, and ‘poor sleepers with hypnotic use’. Residents’ gender, education, pain, instrumental activities of daily living, and number of chronic conditions were significantly differentiated across the sleep patterns. Compared with ‘good sleepers’, ‘poor sleepers without hypnotic use’ were significantly associated with more depressive symptoms (OR = 3.73, 95% CI = 2.09, 6.65, p < 0.001), but not with anxiety symptoms (OR = 2.04, 95% CI = 0.97, 4.29, p = 0.062); whereas ‘poor sleepers with hypnotic use’ had significantly more depressive (OR = 5.24, 95% CI = 2.54, 10.79, p < 0.001) and anxiety symptoms (OR = 5.02, 95% CI = 2.13, 11.83, p < 0.001).

Conclusions

This study reveals three distinct sleep patterns in nursing home residents and their significant associations with residents’ mental health. These findings can inform future research to develop appropriate and tailored intervention strategies for improving sleep and promoting mental health for nursing home residents.
Detection of Human cytomegalovirus UL55 Gene and IE/E Protein Expression in Colorectal Cancer Patients in Egypt
Authors: Raouf May , Sabry Ahmed A. , Ragab Mahinour A. , Achy Samar El , Amer Amira
Published: August 2023

Background

A possible relation between Human cytomegalovirus (HCMV) and colorectal cancer (CRC) has been widely explored with an unclear role yet speculated.

Aim

The study aimed at detecting HCMV UL55 gene, immediate early and early (IE/E) proteins in colorectal tumor tissues and adjacent non neoplastic tissues (ANNT). Also, it aimed to correlate HCMV presence with CRC clinicopathological features.

Subjects and methods

A prospective study of 50 HCMV seropositive patients with resectable CRC were enrolled in the study. Demographic, clinical, and radiological findings were recorded. Pathological assessment was done. Paired CRC tumorous and ANNT were examined for HCMV UL55 by PCR and for IE/ E proteins by immunohistochemistry (IHC).

Results

70% of CRC patients enrolled were females and 36% were elderly (> 60y). Adenocarcinoma was the prevalent histopathological type (92%) with Grade 2, higher stages, and nodal involvement accounting for (64%, 64% and 56%) respectively.

HCMV detection was significantly higher in tumoral tissue versus ANNT by PCR and IHC (P < 0.001, P < 0.008) respectively. Moderate agreement was found between the two techniques (κ = 0.572, P < 0.001).

Univariate analysis identified HCMV presence to be significantly higher in elderly patients, in tumors with higher stage and with nodal involvement (P = 0.041, P = 0.008, P = 0.018 respectively). In multivariate analysis, the latter two retained significance (P = 0.010, P = 0.008).

Conclusion

CRC tumor tissues are more infected by HCMV than ANNT. A significant association of HCMV presence with a higher CRC tumor stage and nodal involvement in an age-dependent manner was detected. HCMV oncomodulatory and a disease progression role is suspected.
Anatomical study of type classification and surface area of attachment sites for tibialis anterior tendon
Authors: Hirai Tomoki , Edama Mutsuaki , Togashi Ryoya , Osanami Haruki , Saito Rina , Kato Koyo , Shagawa Mayuu , Sekine Chie , Yokota Hirotake , Hirabayashi Ryo , Ishigaki Tomonobu , Akuzawa Hiroshi , Yamada Yuki , Toriumi Taku , Kageyama Ikuo
Published: August 2023

Background

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions.

Methods

We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner.

Results

Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1 MB), showing a significantly larger area for MCB than for 1 MB.

Conclusions

These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.
Successful surgical treatment of postmyomectomy uterine diverticulum: a case report
Authors: Kawatake Rina , Maebayashi Aki , Nishimaki Haruna , Nagaishi Masaji , Kawana Kei
Published: August 2023

Background

Uterine diverticulum is classified into congenital and acquired types. The acquired type is caused by caesarean scar syndrome, which occurs after caesarean section. There are no detailed reports on diverticulum after enucleation of uterine fibroids. Most cases are treated with hysteroscopy or laparoscopy, but a management consensus is lacking. We treated a patient with a uterine diverticulum that had formed after uterine fibroid enucleation by combining hysteroscopic and laparoscopic treatments.

Case presentation

The patient was a 37-year-old Japanese woman, G1P0. A previous doctor had performed abdominal uterine myomectomy for a pedunculated subserosal uterine fibroid on the right side of the posterior wall of the uterus near the internal cervical os. Menstruation resumed postoperatively, but a small amount of dark-red bleeding persisted. MRI two months after the myomectomy revealed a diverticulum-like structure 3 cm in diameter, communicating with the uterine lumen, on the right side of the posterior wall of the uterus. Under suspicion of uterine diverticulum after uterine fibroid enucleation, the patient sought treatment at our hospital approximately four months after the myomectomy. Through a flexible hysteroscope, a 5-mm-diameter fistula was observed in the posterior wall of the uterus, and a contrast-enhanced pocket, measuring approximately 3 cm, was located behind it. Uterine diverticulum following enucleation of a uterine fibroid was diagnosed, and surgery was thus deemed necessary. The portion entering the fistula on the internal cervical os side was resected employing a hysteroscope. Intra-abdominal findings included a 4-cm mass lesion on the posterior wall on the right side of the uterus. The mass was opened, and the cyst capsule was removed. A 5-mm fistula was detected and closed with sutures. Resuturing was not performed after dissection of the right round ligament due to tension. The postoperative course has been good to date, with no recurrence.

Conclusion

Uterine diverticula after myomectomy may be treated with a combined laparoscopic and hysteroscopic approach, similar to caesarean scar syndrome.
Validity evidence for a virtual multiple mini interview at a pharmacy program
Authors: Hammond Sarah , McLaughlin Jacqueline E. , Cox Wendy C.
Published: August 2023

Background

Numerous health professions schools have transitioned to virtual admissions interviews in recent years. While some research suggests that virtual multiple mini-interviews (vMMIs) are feasible, acceptable, and more affordable, there is a paucity of research concerning the validity of this approach. The purpose of this study was to examine the validity and reliability of vMMIs and explore differences in performance between vMMI and in-person MMIs.

Methods

Data were collected for two years of in-person MMIs and two years of vMMIs at a pharmacy program/school in the United States. An exploratory factor analysis (principal components analysis) with varimax rotation and Kaiser rule (i.e. retaining factors with eigenvalue > 1.0) was used to explore the construct validity of the vMMI data. Pearson correlation was used to examine correlations between vMMI stations and Cronbach alpha was used to determine the internal consistency of each station. Independent t-tests were used to examine differences between in-person MMI and vMMI scores. Cohen’s d was used to determine effect sizes.

Results

Four hundred and thirty-eight (42.69%) candidates completed an in-person MMI and 588 (57.31%) completed a vMMI. Factor analysis indicated that each vMMI station formed a single factor with loads ranging from 0.86 to 0.96. The vMMI stations accounted for most of the total variance, demonstrated weak to negligible intercorrelations, and high internal consistency. Significant differences between in-person and vMMI scores were found for the teamwork-giving, teamwork-receiving, and integrity stations. Medium effect sizes were found for teamwork-giving and teamwork-receiving and a small effect size was found for integrity.

Conclusions

Initial evidence suggests that the vMMI is a valid and reliable alternative to in-person MMIs. Additional research is needed to examine sources of differences in rating patterns between the two approaches and identify strategies that align with institutional priorities for recruitment and admissions.
Predicting delayed methotrexate elimination in pediatric acute lymphoblastic leukemia patients: an innovative web-based machine learning tool developed through a multicenter, retrospective analysis
Authors: Jian Chang , Chen Siqi , Wang Zhuangcheng , Zhou Yang , Zhang Yang , Li Ziyu , Jian Jie , Wang Tingting , Xiang Tianyu , Wang Xiao , Jia Yuntao , Wang Huilai , Gong Jun
Published: August 2023

Background

High-dose methotrexate (HD-MTX) is a potent chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). HD-MTX is known for cause delayed elimination and drug-related adverse events. Therefore, close monitoring of delayed MTX elimination in ALL patients is essential.

Objective

This study aimed to identify the risk factors associated with delayed MTX elimination and to develop a predictive tool for its occurrence.

Methods

Patients who received MTX chemotherapy during hospitalization were selected for inclusion in our study. Univariate and least absolute shrinkage and selection operator (LASSO) methods were used to screen for relevant features. Then four machine learning (ML) algorithms were used to construct prediction model in different sampling method. Furthermore, the performance of the model was evaluated using several indicators. Finally, the optimal model was deployed on a web page to create a visual prediction tool.

Results

The study included 329 patients with delayed MTX elimination and 1400 patients without delayed MTX elimination who met the inclusion criteria. Univariate and LASSO regression analysis identified eleven predictors, including age, weight, creatinine, uric acid, total bilirubin, albumin, white blood cell count, hemoglobin, prothrombin time, immunological classification, and co-medication with omeprazole. The XGBoost algorithm with SMOTE exhibited AUROC of 0.897, AUPR of 0.729, sensitivity of 0.808, specificity of 0.847, outperforming the other models. And had AUROC of 0.788 in external validation.

Conclusion

The XGBoost algorithm provides superior performance in predicting the delayed elimination of MTX. We have created a prediction tool to assist medical professionals in predicting MTX metabolic delay.
Plasma lipidic fingerprint associated with type 2 diabetes in patients with coronary heart disease: CORDIOPREV study
Authors: Villasanta-Gonzalez Alejandro , Mora-Ortiz Marina , Alcala-Diaz Juan F. , Rivas-Garcia Lorenzo , Torres-Peña Jose D. , Lopez-Bascon Asuncion , Calderon-Santiago Monica , Arenas-Larriva Antonio P. , Priego‑Capote Feliciano , Malagon Maria M. , Eichelmann Fabian , Perez-Martinez Pablo , Delgado-Lista Javier , Schulze Matthias B. , Camargo Antonio , Lopez-Miranda Jose
Published: August 2023

Objective

We aimed to identify a lipidic profile associated with type 2 diabetes mellitus (T2DM) development in coronary heart disease (CHD) patients, to provide a new, highly sensitive model which could be used in clinical practice to identify patients at T2DM risk.

Methods

This study considered the 462 patients of the CORDIOPREV study (CHD patients) who were not diabetic at the beginning of the intervention. In total, 107 of them developed T2DM after a median follow-up of 60 months. They were diagnosed using the American Diabetes Association criteria. A novel lipidomic methodology employing liquid chromatography (LC) separation followed by HESI, and detection by mass spectrometry (MS) was used to annotate the lipids at the isomer level. The patients were then classified into a Training and a Validation Set (60–40). Next, a Random Survival Forest (RSF) was carried out to detect the lipidic isomers with the lowest prediction error, these lipids were then used to build a Lipidomic Risk (LR) score which was evaluated through a Cox. Finally, a production model combining the clinical variables of interest, and the lipidic species was carried out.

Results

LC-tandem MS annotated 440 lipid species. From those, the RSF identified 15 lipid species with the lowest prediction error. These lipids were combined in an LR score which showed association with the development of T2DM. The LR hazard ratio per unit standard deviation was 2.87 and 1.43, in the Training and Validation Set respectively. Likewise, patients with higher LR Score values had lower insulin sensitivity (P = 0.006) and higher liver insulin resistance (P = 0.005). The receiver operating characteristic (ROC) curve obtained by combining clinical variables and the selected lipidic isomers using a generalised lineal model had an area under the curve (AUC) of 81.3%.

Conclusion

Our study showed the potential of comprehensive lipidomic analysis in identifying patients at risk of developing T2DM. In addition, the lipid species combined with clinical variables provided a new, highly sensitive model which can be used in clinical practice to identify patients at T2DM risk. Moreover, these results also indicate that we need to look closely at isomers to understand the role of this specific compound in T2DM development.

Trials registration NCT00924937.
Association of severe malaria with cognitive and behavioural outcomes in low- and middle-income countries: a meta-analysis and systematic review
Authors: Ssemata Andrew Sentoogo , Nakitende Ann Jacquelline , Kizito Simon , Thomas Melissa R. , Islam Sumaiya , Bangirana Paul , Nakasujja Noeline , Yang Ziyi , Yu Yunpeng , Tran Tuan M. , John Chandy C. , McHenry Megan S.
Published: August 2023

Background

Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs.

Methods

Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children < 18 years of age living in LMICs with active or past severe malaria infection and measured cognitive and/or behaviour outcomes. The quality of studies was assessed. Definitions of severe malaria included cerebral malaria, severe malarial anaemia, and author-defined severe malaria. Results from all studies were qualitatively summarized. For studies with relevant data on attention, learning, memory, language, internalizing behaviour and externalizing behaviour, results were pooled and a meta-analysis was performed. A random-effects model was used across included cohorts, yielding a standardized mean difference between the severe malaria group and control group.

Results

Out of 3,803 initial records meeting the search criteria, 24 studies were included in the review, with data from 14 studies eligible for meta-analysis inclusion. Studies across sub-Saharan Africa assessed 11 cohorts of children from pre-school to school age. Of all the studies, composite measures of cognition were the most affected areas of development. Overall, attention, memory, and behavioural problems were domains most commonly found to have lower scores in children with severe malaria. Meta-analysis revealed that children with severe malaria had worse scores compared to children without malaria in attention (standardized mean difference (SMD) −0.68, 95% CI −1.26 to −0.10), memory (SMD −0.52, 95% CI −0.99 to −0.06), and externalizing behavioural problems (SMD 0.45, 95% CI 0.13–0.78).

Conclusion

Severe malaria is associated with worse neuropsychological outcomes for children living in LMICs, specifically in attention, memory, and externalizing behaviours. More research is needed to identify the long-term implications of these findings. Further interventions are needed to prevent cognitive and behavioural problems after severe malaria infection.

Trial Registration: This systematic review was registered under PROSPERO: CRD42020154777.
Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses
Authors: Hu Yuanlong , Wang Xiaojie , Lin Lin , Huan Jiaming , Li Yuan , Zhang Lei , Li Yunlun
Published: August 2023

Background

Recent insights suggest that remnant cholesterol (RC) plays a role in cellular senescence, yet its specific contribution to frailty remains indeterminate. Through the integration of observational and mendelian randomization (MR) studies, this research explores the impact of elevated serum RC levels on frailty susceptibility.

Methods

A dual-method approach, combining an observational study with an MR study, was employed to investigate the connection between RC and frailty. The observational study included 11,838 participants from the National Health and Nutrition Examination Survey. Multivariable logistic regression and propensity score matching were employed to control for potential confounders. The non-linear relationship was assessed using restricted cubic splines. To circumvent observational study limitations, a two-sample MR analysis was conducted using the inverse-variance weighted method, leveraging genome-wide association studies (GWAS) data.

Results

After adjusting for potential confounding variables, the observational study identified a significant association between high serum RC levels and frailty in middle-aged and older adults (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.20 to 2.33, P = 0.003), exhibiting a non-linear dose–response correlation (non-linear P = 0.011). This association persisted after propensity score matching (OR = 1.53, 95% CI = 1.14 to 2.06, P = 0.005). The MR study echoed these results, demonstrating a causal association of RC with the frailty index (β = 0.059, 95% CI = 0.033 to 0.085, P = 1.05E-05), consistent with the observational findings (β = 0.017, 95% CI = 0.008 to 0.026, P = 4.51E-04).

Conclusion

This study provides evidence that higher RC levels amplify frailty risk in middle-aged and older adults, implying that the reduction of RC levels may present a promising strategy for frailty prevention and management.
Catheter navigation by intracardiac echocardiography enables zero-fluoroscopy linear lesion formation and bidirectional cavotricuspid isthmus block in patients with typical atrial flutter
Authors: Luani Blerim , Basho Maksim , Ismail Ammar , Rauwolf Thomas , Kaese Sven , Tobli Ndricim , Samol Alexander , Pankraz Katharina , Schmeisser Alexander , Wiemer Marcus , Braun-Dullaeus Rüdiger C. , Genz Conrad
Published: August 2023

Introduction

One of the most helpful aspects of intracardiac echocardiography (ICE) implementation in electrophysiological studies (EPS) is the real-time visualisation of catheters and cardiac structures. In this prospective study, we investigated ICE-guided zero-fluoroscopy catheter navigation during radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) in patients with typical atrial flutter (AFL).

Methods and results

Thirty consecutive patients (mean age 72.9 ± 11.4 years, 23 male) with ongoing (n = 23) or recent CTI-dependent AFL underwent an EPS, solely utilizing ICE for catheter navigation. Zero-fluoroscopy EPS could be successfully accomplished in all patients. Mean EPS duration was 41.4 ± 19.9 min, and mean ablation procedure duration was 20.8 ± 17.1 min. RF ablation was applied for 6.0 ± 3.1 min (50W, irrigated RF ablation). Echocardiographic parameters, such as CTI length, prominence of the Eustachian ridge (ER), and depth of the CTI pouch on the ablation plane, were assessed to analyse their correlation with EPS- or ablation procedure duration. The CTI pouch was shallower in patients with an ablation procedure duration above the median (4.8 ± 1.1 mm vs. 6.4 ± 0.9 mm, p = 0.04), suggesting a more lateral ablation plane in these patients, where the CTI musculature is stronger. CTI length or ER prominence above the respective median did not correlate with longer EPS duration.

Conclusions

Zero-fluoroscopy CTI ablation guided solely by intracardiac echocardiography in patients with CTI-dependent AFL is feasible and safe. ICE visualisation may help to localise the optimal ablation plane, detect and correct poor tissue contact of the catheter tip, and recognise early potential complications during the ablation procedure.

Graphical Abstract
Analysis of outcomes following loop electrosurgical excision and clinical features of patients with cervical high-grade squamous intraepithelial lesions with abnormal preoperative endocervical curettage
Authors: Feng Chunyang , Gu Liying , Wei Yingting , Niu Jiaxin , Yang Haima , Hong Zubei , Qiu Lihua
Published: August 2023

Objective

The purpose of this study was to identify the clinical characteristics of patients with high-grade squamous intraepithelial lesions (HSIL) with abnormal endocervical curettage (ECC) and to evaluate the efficacy of abnormal preoperative ECC in predicting recurrence after a loop electrosurgical excision procedure (LEEP).

Methods

We retrospectively analyzed a total of 210 cases of histological HSIL in female patients diagnosed using cervical biopsy and/or indiscriminating ECC, and these included 137 cases with normal ECC and 63 cases with abnormal ECC. We also collected preoperative information and data on postoperative human papillomavirus (HPV) and histological outcomes within 2 years.

Results

The additional detection rate of HSIL using indiscriminating ECC was 5%. Patients with abnormal ECC were older (P < 0.001), predominantly menopausal (P = 0.001), had high-grade cytology (P = 0.032), a type 3 transformation zone (P = 0.046), and a higher proportion of HPV type 16/18 infection (P = 0.023). Moreover, age (odds ratio [OR] = 1.078, 95% confidence interval [CI] = 1.0325–1.1333, P = 0.003) and HPV 16/18 infection (OR = 2.082, 95% CI = 1.042–4.2163, P = 0.038) were independent risk factors for abnormal ECC. With an observed residual lesion/recurrence rate of 9.5% over the 24-month follow-up, we noted a 9.3% higher rate in the abnormal ECC group when compared with the normal ECC group. Abnormal preoperative ECC (OR = 4.06, 95% CI = 1.09–15.14, P = 0.037) and positive HPV at the 12-month follow-up (OR = 16.55, 95% CI = 3.54–77.37, P = 0.000) were independent risk factors for residual disease/recurrence.

Conclusion

Preoperative ECC was one of the risk factors for post-LEEP residual/recurrent HSIL, and detecting abnormal ECC when managing older patients or patients with HPV 16/18 infection during colposcopy is critical.
Differential effects of SARS-CoV-2 variants on central nervous system cells and blood–brain barrier functions
Authors: Proust Alizé , Queval Christophe J. , Harvey Ruth , Adams Lorin , Bennett Michael , Wilkinson Robert J.
Published: August 2023

Background

Although mainly causing a respiratory syndrome, numerous neurological symptoms have been identified following of SARS-CoV-2 infection. However, how the virus affects the brain and how the mutations carried by the different variants modulate those neurological symptoms remain unclear.

Methods

We used primary human pericytes, foetal astrocytes, endothelial cells and a microglial cell line to investigate the effect of several SARS-CoV-2 variants of concern or interest on their functional activities. Cells and a 3D blood–brain barrier model were infected with the wild-type form of SARS-CoV-2, Alpha, Beta, Delta, Eta, or Omicron (BA.1) variants at various MOI. Cells and supernatant were used to evaluate cell susceptibility to the virus using a microscopic assay as well as effects of infection on (i) cell metabolic activity using a colorimetric MTS assay; (ii) viral cytopathogenicity using the xCELLigence system; (iii) extracellular glutamate concentration by fluorometric assay; and (iv) modulation of blood–brain barrier permeability.

Results

We demonstrate that productive infection of brain cells is SARS-CoV-2 variant dependent and that all the variants induce stress to CNS cells. The wild-type virus was cytopathic to all cell types except astrocytes, whilst Alpha and Beta variants were only cytopathic for pericytes, and the Omicron variant cytopathic for endothelial cells and pericytes. Lastly wild-type virus increases blood–brain barrier permeability and all variants, except Beta, modulate extracellular glutamate concentration, which can lead to excitotoxicity or altered neurotransmission.

Conclusions

These results suggest that SARS-CoV-2 is neurotropic, with deleterious consequences for the blood–brain barrier integrity and central nervous system cells, which could underlie neurological disorders following SARS-CoV-2 infection.
Feasibility of force myography for the direct control of an assistive robotic hand orthosis in non-impaired individuals
Authors: Gantenbein Jessica , Ahmadizadeh Chakaveh , Heeb Oliver , Lambercy Olivier , Menon Carlo
Published: August 2023

Background

Assistive robotic hand orthoses can support people with sensorimotor hand impairment in many activities of daily living and therefore help to regain independence. However, in order for the users to fully benefit from the functionalities of such devices, a safe and reliable way to detect their movement intention for device control is crucial. Gesture recognition based on force myography measuring volumetric changes in the muscles during contraction has been previously shown to be a viable and easy to implement strategy to control hand prostheses. Whether this approach could be efficiently applied to intuitively control an assistive robotic hand orthosis remains to be investigated.

Methods

In this work, we assessed the feasibility of using force myography measured from the forearm to control a robotic hand orthosis worn on the hand ipsilateral to the measurement site. In ten neurologically-intact participants wearing a robotic hand orthosis, we collected data for four gestures trained in nine arm configurations, i.e., seven static positions and two dynamic movements, corresponding to typical activities of daily living conditions. In an offline analysis, we determined classification accuracies for two binary classifiers (one for opening and one for closing) and further assessed the impact of individual training arm configurations on the overall performance.

Results

We achieved an overall classification accuracy of 92.9% (averaged over two binary classifiers, individual accuracies 95.5% and 90.3%, respectively) but found a large variation in performance between participants, ranging from 75.4 up to 100%. Averaged inference times per sample were measured below 0.15 ms. Further, we found that the number of training arm configurations could be reduced from nine to six without notably decreasing classification performance.

Conclusion

The results of this work support the general feasibility of using force myography as an intuitive intention detection strategy for a robotic hand orthosis. Further, the findings also generated valuable insights into challenges and potential ways to overcome them in view of applying such technologies for assisting people with sensorimotor hand impairment during activities of daily living.
Withania somnifera extracts induced attenuation of HIV-1: a mechanistic approach to restrict viral infection
Authors: Jadaun Pratiksha , Harshithkumar R , Gaikwad Shraddha Y , Seniya Chandrabhan , Borse Swapnil , Gawai Ashish A , Chavan-Gautam Preeti , Tillu Girish , Mukherjee Anupam
Published: August 2023

Background

Several anti-retroviral drugs are available against Human immunodeficiency virus type-1, but have multiple adverse side effects. Hence, there is an incessant compulsion for effectual anti-retroviral agents with minimal or no intricacy. Traditionally, natural products have been the most successful source for the development of new medications. Withania somnifera, also known as Ashwagandha, is the utmost treasured medicinal plant used in Ayurveda, which holds the potential to give adaptogenic, immunomodulatory, and antiviral effects. However, its effect on HIV-1 replication at the cellular level has never been explored. Herein, we focused on the anti-HIV-1 activity and the probable mechanism of action of hydroalcoholic and aqueous extracts of Withania somnifera roots and its phytomolecules.

Methods

The cytotoxicity of the extracts was determined through MTT assay, while the in vitro anti-HIV-1 activity was assessed in TZM-bl cells against the HIV-1 strains of X4 and R5 subtypes. Results were confirmed in peripheral blood mononuclear cells, using the HIV-1 p24 antigen assay. Additionally, the mechanism of action was determined through the Time of Addition assay, which was further validated through the series of enzymatic assays, i.e. HIV-1 Integrase, Reverse transcriptase, and Protease assays. To explore the role of the identified active metabolites of Withania somnifera in antiretroviral activity, molecular docking analyses were performed against these key HIV-1 replication enzymes.

Results

The hydroalcoholic and aqueous extracts of Withania somnifera roots were found to be safer at the sub-cytotoxic concentrations and exhibited their ability to inhibit replication of two primary isolates of HIV-1 through cell-associated and cell-free assays, in dose-dependent kinetics. Several active phytomolecules found in Withania somnifera successfully established hydrogens bonds in the active binding pocket site residues responsible for the catalytic activity of HIV replication and therefore, signifying their role in the attenuation of HIV-1 infection as implied through the in silico molecular docking studies.

Conclusions

Our research identified both the hydroalcoholic and aqueous extracts of Withania somnifera roots as potent inhibitors of HIV-1 infection. The in silico analyses also indicated the key components of Withania somnifera with the highest binding affinity against the HIV-1 Integrase by 12-Deoxywithastramonolide and 27-Hydroxywithanone, HIV-1 Protease by Ashwagandhanolide and Withacoagin, and HIV-1 Reverse transcriptase by Ashwagandhanolide and Withanolide B, thereby showing possible mechanisms of HIV-1 extenuation. Overall, this study classified the role of Withania somnifera extracts and their active compounds as potential agents against HIV-1 infection.
A nomogram model based on the combination of the systemic immune-inflammation index, body mass index, and neutrophil/lymphocyte ratio to predict the risk of preoperative deep venous thrombosis in elderly patients with intertrochanteric femoral fracture: a retrospective cohort study
Authors: Zeng Guowei , Li Xu , Li Wencai , Wen Zhijia , Wang Shenjie , Zheng Shaowei , Lin Xia , Zhong Haobo , Zheng Jianping , Sun Chunhan
Published: August 2023

Objectives

Deep vein thrombosis (DVT) has been considered as a frequent and serious consequence of intertrochanteric femoral fractures in the elderly. Several negative repercussions of DVT can be considerably mitigated by its timely recognition and treatment. The current work was aimed at exploring the factors independently predicting DVT among cases suffering from intertrochanteric femoral fractures and validate their predictive usefulness in diagnosing DVT.

Methods

Between April 2017 and July 2022, clinical information from 209 cases showing preoperative DVT for femoral intertrochanteric fractures were retrospectively evaluated. In patients with femoral intertrochanteric fractures, logistic regression analysis with a backward stepwise method was adopted for detecting independent predictors for the diagnosis of preoperative DVT. Using multivariate logistic regression, a nomogram prediction model was developed and verified with the testing group.

Results

According to multivariate logistic regression model, body mass index (BMI) (OR 0.79, 95% CI 0.63–0.99, P = 0.042), neutrophil/lymphocyte ratio (NLR) (OR 7.29, 95% CI 1.53, 34.64, P = 0.0012), and systemic immune-inflammation index (SII) (OR 6.61, 95% CI 2.35, 18.59, P = 0.001) were independent predictors for DVT before surgery among cases developing intertrochanteric femoral fracture. AUC values were 0.862 and 0.767 for training and testing groups, separately, while their mean errors in the calibration curve were 0.027 and 0.038 separately. Decision curve analysis (DCA) curve revealed a high value of clinical application for both groups.

Conclusion

Upon admission, BMI, NLR, and SII are independent predictors of DVT before surgery among cases developing intertrochanteric femoral fractures. Additionally, the nomogram based on the BMI, NLR, and SII can assist clinicians in determining if preventive and symptomatic therapies are required to improve DVT prognosis and reduce its associated mortality.
Chronic ACL-injured patients show increased medial and global anterior tibial subluxation measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction
Authors: Zhang Zhi-yu , Shi Wei-li , Bai Wen-bin , Meng Ling-yu , Meng Qing-yang , Wang Jian-quan , Wang Cheng
Published: August 2023

Background

The association between chronic anterior cruciate ligament (ACL) injury and inferior postoperative outcomes following ACL reconstruction (ACLR) has been highlighted in the literature. However, the inclusion of postoperative radiological assessments in previous studies has been limited. The aim of this study is to investigate whether chronic ACL injury is associated with an inferior tibiofemoral position measured on magnetic resonance (MR) images after primary ACLR.

Methods

A total of 62 patients that underwent primary ACLR were included in this study based on the time from injury to surgery, namely the acute ACL-injured group (within 6 weeks) and the chronic ACL-injured group (more than 1 year) and were matched 1:1 according to sex, age (± 2 years), and time from surgery to follow-up (± 3 months). Patient demographics, surgical records and follow-up data were retrieved and analyzed. The altered tibiofemoral position was measured quantitatively on preoperative and at least 1-year postoperative MR images and compared between the two groups, including the lateral, medial and global anterior tibial subluxation (LATS, MATS and GATS) and internal rotational tibial subluxation (IRTS).

Results

No significant differences in preoperative LATS, MATS, GATS or IRTS were identified between the acute and chronic ACL-injured groups. The chronic ACL-injured patients showed significantly increased postoperative MATS (p = 0.001) and GATS (p = 0.012), while no significant difference was identified in postoperative LATS or IRTS. Multivariate linear regression analyses showed that chronic ACL injury resulted in an estimated increase of 2.0 mm in postoperative MATS (p = 0.012) and 1.9 mm in postoperative GATS (p = 0.040). A significant improvement in postoperative LATS was observed in the acute ACL-injured group (p = 0.044) compared to preoperative LATS, while no improvements in these MRI measurements were observed in the chronic ACL-injured group.

Conclusion

Chronic ACL-injured patients showed increased MATS and GATS measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction, while no difference was identified in rotational tibiofemoral position. The acute ACL-injured group demonstrated a significant improvement in postoperative LATS, whereas no improvements were observed in the chronic ACL-injured group.

Level of evidence Level III.
A novel animal model of osteonecrosis of the femoral head based on 3D printing technology
Authors: Li Yiyang , Zhang Jiewen , Zhao Yiwei , Tian Run , Yang Pei
Published: August 2023

Background

Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic condition characterized by the disruption of blood supply to the femoral head, leading to ischemia of internal tissues, subchondral bone fractures, necrosis, and eventual collapse of the weight-bearing portion of the femoral head. This condition results in severe functional impairment, pain, and even disability of the hip joint. Existing animal models of ONFH have limitations in replicating the natural disease progression accurately. Thus, there is a critical need to develop a novel animal model capable of better simulating localized pressure on the human femoral head to facilitate ONFH-related research.

Methods

In this study, we present a novel approach for modeling ONFH, which involves integrating stress factors into the modeling process through the utilization of 3D printing technology and principles of biomechanics. A total of 36 animals were randomly assigned to six groups, where they received either the novel modeling technique or the traditional hormone induction method. Subsequently, an 8-week treatment period was implemented, followed by conducting micro-CT scans and histological evaluations to assess tissue outcomes.

Results

The study evaluated the cytotoxicity of the material used in the new model, and it was observed that the material did not exhibit any cytotoxic effects on cells. Additionally, the novel model successfully replicated the pathological features of ONFH, including femoral head collapse, along with a substantial presence of empty bone lacunae, cartilage defects, and subchondral bone fractures in the subchondral bone region.

Conclusion

In conclusion, our study provides evidence that the new model shows the ability to simulate the progression of the disease, making it a valuable tool for research in this field and can contribute to the development of better treatment strategies for this debilitating condition. It holds great promise for advancing our understanding of the pathogenesis of ONFH and the potential therapeutic interventions for this challenging clinical problem.