bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between transabdominal uterine artery Doppler and small-for-gestational-age: a systematic review and meta-analysis
Authors: Zhi Ruijuan , Tao Xiangping , Li Qingtao , Yu Ming , Li Honge
Published: September 2023

Background

The association between uterine artery Doppler (UtA) measurements and small for gestational age (SGA) has not been quantitatively analyzed throughout the whole pregnancy. This systematic review and meta-analysis aims to comprehensively explore the association between UtA measurements and SGA in the first, second, and third trimesters.

Methods

Studies were searched from Pubmed, Embase, Cochrane Library, and Web of Science. Weighted mean difference (WMD), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were used as the effect size. Heterogeneity of all effect sizes was tested and quantified using I2 statistics. Sensitivity analysis was conducted for all outcomes, and publication bias was evaluated using Begg’s test.

Results

A total of 41 studies were finally included in our meta-analysis. In the first trimester, mean PI was significantly higher in the SGA group than the non-SGA group (WMD: 0.31, 95%CI: 0.19–0.44). In the second trimester, odds of notch presence (OR: 2.54, 95%CI: 2.10–3.08), mean PI (WMD: 0.21, 95%CI: 0.12–0.30), and mean RI (WMD: 0.05, 95%CI: 0.05–0.06) were higher in the SGA group. Also, abnormal UtA measurements were associated with the increased odds of SGA (all P < 0.05). In the third trimester, PI z-score (WMD: 0.62, 95%CI: 0.33–0.91) and PI MoM (WMD: 0.08, 95%CI: 0.06–0.09) showed a significant increase in the SGA group. The odds of SGA were higher in the women with mean PI > 95% (OR: 6.03, 95%CI: 3.24–11.24).

Conclusions

Abnormal UtA measurements were associated with high odds of SGA, suggesting that UtA might be an adjunctive screening method for SGA in the whole pregnancy.
Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children
Authors: Shrestha Raj Kumar , Thapa Ashmita , Shrestha Dhruba , Pokhrel Sabi , Aryal Anubhav , Adhikari Rupika , Shrestha Nipun , Dhoubhadel Bhim Gopal , Parry Christopher M
Published: September 2023

Background

Transferrable mechanisms of quinolone resistance (TMQR) can lead to fluoroquinolone non-susceptibility in addition to chromosomal mechanisms. Some evidence suggests that fluoroquinolone resistance is increasing among the pediatric population. We sought to determine the occurrence of TMQR genes among quinolone-resistant E. coli and K. pneumoniae causing urinary tract infections among Nepalese outpatient children (< 18 years) and identify molecular characteristics of TMQR-harboring isolates.

Methods

We performed antimicrobial susceptibility testing, phenotypic extended-spectrum β-lactamase (ESBL) and modified carbapenem inactivation method tests, and investigated the presence of six TMQR genes (qnrA, qnrB, qnrS, aac(6’)-Ib-cr, oqxAB, qepA), three ESBL genes (blaCTX−M, blaTEM, blaSHV), and five carbapenemase genes (blaNDM, blaOXA−48, blaKPC, blaIMP, blaVIM). The quinolone resistance-determining region (QRDR) of gyrA and parC were sequenced for 35 TMQR-positive isolates.

Results

A total of 74/147 (50.3%) isolates were TMQR positive by multiplex PCR [aac(6’)-Ib-cr in 48 (32.7%), qnrB in 23 (15.7%), qnrS in 18 (12.3%), qnrA in 1 (0.7%), and oqxAB in 1 (0.7%) isolate]. The median ciprofloxacin minimum inhibitory concentration of TMQR-positive isolates (64 µg/mL) was two-fold higher than those without TMQR (32 µg/mL) (p = 0.004). Ser-83→Leu and Asp-87→Asn in GyrA and Ser-80→Ile in ParC were the most common QRDR mutations (23 of 35). In addition, there was a statistically significant association between TMQR and two β-lactamase genes; blaCTX−M (p = 0.037) and blaTEM (p = 0.000).

Conclusion

This study suggests a high prevalence of TMQR among the quinolone-resistant E. coli and K. pneumoniae isolates causing urinary tract infection in children in this area of Nepal and an association with the carriage of ESBL gene. This is a challenge for the management of urinary infections in children. Comprehensive prospective surveillance of antimicrobial resistance in these common pathogens will be necessary to devise strategies to mitigate the emergence of further resistance.
The relation between thrombus burden and early mortality risk in inpatients diagnosed with COVID-19-related acute pulmonary embolism: a retrospective cohort study
Authors: Ozden Sertcelik Umran , Ozkan Erdem , Sertcelik Ahmet , Karalezli Aysegul
Published: September 2023

Background

COVID-19-related acute pulmonary thromboembolism (APE) is associated with poor outcomes in patients with COVID-19. There are studies investigating the association between thrombus burden and high risk of early mortality in the pre-COVID-19 period. This study aimed to evaluate the relationship between clot burden and early mortality risk in COVID-19-related APE patients.

Methods

In this single-center retrospective cohort study, the data of hospitalized adult patients followed up for COVID-19-related APE between April 1, 2020, and April 1, 2021, were electronically collected. A radiologist evaluated the computed tomography (CT) findings and calculated the Mastora scores to determine clot burden. The early mortality risk group of each patient was determined using 2019 the European Society of Cardiology guidelines.

Results

Of the 87 patients included in the study, 58 (66.7%) were male, and the mean age was 62.5±16.2 years. There were 53 (60.9%) patients with a low risk of mortality, 18 (20.7%) with an intermediate-low risk, and 16(18.4%) with an intermediate-high/high risk. The median total simplified Mastora scores were 11.0, 18.5, and 31.5 in the low, the intermediate-low, and the intermediate-high/high-risk groups, respectively (p = 0.002). With the 80.61% ofpost-hocpower of the study, intermediate-high/high early mortality risk was associated statistically significantly with the total simplified Mastora score (adj OR = 1.06, 95%CI = 1.02–1.11,p = 0.009). Total simplified Mastora score was found to predict intermediate-high/high early mortality risk with a probability of 0.740 (95% CI = 0.603–0.877): At the optimal cut-off value of 18.5, it had 75.0% sensitivity, 66.2% specificity, 33.3% positive predictive value, and 92.2% negative predictive value.

Conclusions

The total simplified Mastora score was found to be positively associated with early mortality risk and could be useful as decision support for the risk assessment in hospitalized COVID-19 patients. Evaluation of thrombus burden on CT angiography performed for diagnostic purposes can accelerate the decision of close monitoring and thrombolytic treatment of patients with moderate/high risk of early mortality.
Increased difficulty and complications of delayed laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage in acute cholecystitis: a retrospective study
Authors: Liu Ya-qi , Cai Xuan , Zheng Zhi-xue , Xu Fang-jingwei , Bi Jing-tao
Published: September 2023

Background

Percutaneous transhepatic gallbladder drainage (PTGBD) is a relatively less invasive alternative treatment to cholecystostomy. However, the influence of the difficulty of delayed laparoscopic cholecystectomy (DLC) after PTGBD on clinical outcomes remains unknown. This study aimed to evaluate the clinical effects of DLC following PTGBD.

Methods

The clinical data of 113 patients diagnosed with moderate (grade II) acute cholecystitis according to the 2018 Tokyo Guidelines in the acute phase and who underwent DLC in our hospital from January 2018 to February 2022 were retrospectively collected and separated into two groups according to whether they received PTGBD treatment in the acute stage. The PTGBD group comprised 27 cases, and the no-PTGBD group included 86 cases. The TG18 difficulty score was used to evaluate every surgical procedure in the cases by reviewing the surgical videos. The clinical baseline characteristics and post-treatment outcomes were also evaluated.

Results

Both groups showed significant differences in length of postoperative stay, blood loss, operation time, and difficulty score. The PTGBD group showed a significantly longer postoperative stay and operation time, more blood loss, and a much higher difficulty score than the no-PTGBD group. Conversion rates did not differ. The morbidity rate in the PTGBD group was statistically higher.

Conclusions

PTGBD is an efficient way to relieve the symptoms of acute cholecystitis. However, it may increase the difficulty and complications of DLC.
Comparison of invisalign mandibular advancement and twin-block on upper airway and hyoid bone position improvements for skeletal class II children: a retrospective study
Authors: Yue Zheng , Yi Zian , Liu Xinyi , Chen Mengting , Yin Shuhui , Liu Qianqian , Chen Xuefeng , Hu Jiangtian
Published: September 2023

Background

This study is to evaluate and compare the improvement of upper airway morphology and hyoid bone position in children with Class II mandibular retrusion treated with Invisalign mandibular advancement (MA) and Twin-Block (TB) appliances, utilizing cone beam computed tomography (CBCT).

Methods

32 children aged between 8 and 11.5 years old were included in this study, with an average age of 10.2 years old. These children were divided into two groups, MA and TB, with 16 children in each group. Changes in upper airway morphology and hyoid bone position before and after treatment were analyzed using CBCT.

Results

(1) Changes in upper airway before and after treatment: the oropharynx volume (Or-V), the oropharynx minimum cross-sectional area (Or-mCSA), the hypopharynx volume (Hy-V), and the hypopharynx minimum cross-sectional area (Hy-mCSA) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05) compared to pre-treatment status. (2) Changes in hyoid bone position before and after treatment: The distances between H point and third cervical vertebra (H-C3), H point and pogonion (H-RGN), H point and mandibular plane (H-MP), H point and Frankfort horizontal plane (H-FH), H and S point (H-S), and H point and palatal plane (H-PP) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05).

Conclusion

Both MA and TB appliances effectively improved the structural narrowness of the upper airway and reduced respiratory resistance, thus improving breath quality. However, MA showed more effectiveness in improving the narrowest part of the hypopharynx compared to TB. Both appliances also promoted anterior downward movement of the hyoid bone, which opens the upper airway of the oropharynx and hypopharynx and helps the upper airway morphology return to normal range.
Volumetric reduction in large cystic jaw lesions postoperative enucleation: a longitudinal clinical study
Authors: Al-Qurmoti Sarah , Mahyoub Mueataz A. , Elhoumed Mohamed , Al-Moraissi Essam Ahmed , Tao Zhuo‑Ying , Hou Xiaoru , Li Jing , Bi Sisi , Wu Haiyan , Zhang Jing , Lv Huanhuan , Jiao Lina , Al-Karmati Sokina , Acharya Kiran , Hu Xiaoyi , Li Jinfeng
Published: September 2023

Background

Enucleation, a surgical procedure, is commonly used to treat large jaw cysts, unicystic ameloblastomas and keratocysts. However, it remains unclear to what extent the jaw bone regenerates after enucleation. We aimed to evaluate the percentage and the survival analysis of jaw bone regeneration, in terms of cavity volume residual (CVR), in patients who underwent enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts.

Methods

We collected data longitudinally from 75 patients who underwent jaw cystic lesions enucleation at the Stomatological Hospital of Xi’an Jiaotong University, between January 2015 and June 2021. All patients had both preoperative and postoperative cone-beam computed tomography (CBCT) imaging data. CBCT images were analyzed using Image J. Changes in the CVR were assessed at various follow-up time points, and the Kaplan-Meier method was utilized to evaluate the CVR over time.

Results

The patients had a mean age of 31.7 years (range: 5.5–72 years) with 58.66% of them being male. The postoperative CVR was 32.20% at three months, 21.10% at six months, 15.90% at 12 months, and 5.60% at 24 months. The percentage of CVR during follow-up periods for the initial size Quartile (Q)1 (212.54-1569.60 mm3) was substantially lower than those of Q2 and Q3 at and after seven months of follow-up and became statistically significant at the 12-month mark.

Conclusion

This study demonstrates that spontaneous bone regeneration can occur after enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts, even without the use of filler materials. The initial size of the lesion had a significant impact on the outcome of cystic lesion enucleation over time. To minimize the risks associated with radiation exposure and expenses, we recommend reducing the frequency of CT imaging follow-ups for patients with small initial cavity sizes (ranging from 212.54 to 1569.60 mm3).
A new scale assessing the stressors and rewards of children’s hospice work
Authors: Papworth Andrew , Bedendo Andre , Taylor Jo , Beresford Bryony , Mukherjee Suzanne , Fraser Lorna K , Ziegler Lucy
Published: September 2023

Background

There is a workforce shortage in the children’s hospice sector, but there has been little research on the specific challenges of working in this setting and on how these challenges might be alleviated. To identify appropriate interventions to improve staff wellbeing, the drivers of wellbeing in children’s hospices need to be known and measured. This paper reports on the development of two measures, one for work-related rewards and one for work-related stressors, for use in children’s hospice care teams.

Methods

A mixed-methods, four-stage study; the first three phases focused on the development of the scales, and the last stage focused on the validation of the scales. Participants of all stages were children’s hospice care team staff members in the UK. Stage 1: survey assessing the relevance and comprehensiveness of the original scale items (N = 60); Stages 2 (focus groups;N = 16) and 3 (cognitive interviews;N = 14) to assess content validity; Stage 4: UK-wide survey (N = 414) to validate the final version of the new, children’s hospice-specific scales using Rasch Analysis (RA) and Confirmatory Factor Analysis (CFA).

Results

Due to poor fitting indices shown in the results from the RA, five items (out of 36) were removed from the new rewards scale used in the UK-wide survey and 20 (out of 62) were removed from the new stressors scale. CFA also supported the removal of the items and showed a one-factor structure for the rewards scale and a three-factor structure for the stressors scale were adequate—the sub-scales for the stressors scale related to caring for an ill or dying child (“Child” sub-scale), working with parents and families (“Parent” sub-scale), and stressors related to organisational factors, such as team conflict and workload (“Organisation” sub-scale).

Conclusions

Both of the new scales showed good psychometric properties and can be useful in clinical settings and research to assess the perceived intensity of the work-related rewards and stressors for children’s hospice staff.
The dynamics of deltamethrin resistance evolution in Aedes albopictus has an impact on fitness and dengue virus type-2 vectorial capacity
Authors: Guo Yijia , Hu Ke , Zhou Jingni , Xie Zhensheng , Zhao Yijie , Zhao Siyu , Gu Jinbao , Zhou Xiaohong , Yan Guiyun , James Anthony A. , Chen Xiao-Guang
Published: September 2023

Background

Worldwide invasion and expansion of Aedes albopictus, an important vector of dengue, chikungunya, and Zika viruses, has become a serious concern in global public health. Chemical insecticides are the primary means currently available to control the mosquito populations. However, long-term and large-scale use of insecticides has selected for resistance in the mosquito that is accompanied by a genetic load that impacts fitness.

Results

A number of laboratory strains representing different resistance mechanisms were isolated and identified from laboratory-derived, deltamethrin-resistant Ae. albopictus recovered in previous work. Resistance levels and fitness costs of the strains were evaluated and compared to characterize the evolution of the resistance genotypes and phenotypes. The heterozygous F1534S mutation (1534F/S) in the voltage gated sodium channel (vgsc) gene product (VGSC), first detected in early stages of resistance evolution, not only confers high-level resistance, but also produces no significant fitness costs, leading to the rapid spread of resistance in the population. This is followed by the increase in frequency of homozygous F1534S (1534S/S) mosquitoes that have significant fitness disadvantages, prompting the emergence of an unlinked I1532T mutation with fewer side effects and a mating advantage better adapted to the selection and reproductive pressures imposed in the experiments. Metabolic resistance with no significant fitness cost and mediating a high-tolerance resistance phenotype may play a dominant role in the subsequent evolution of resistance. The different resistant strains had similar vector competence for dengue virus type-2 (DENV-2). Furthermore, a comparative analysis of vectorial capacity revealed that increased survival due to deltamethrin resistance balanced the negative fitness cost effects and contributed to the risk of dengue virus (DENV) transmission by resistant populations. The progressive evolution of resistance results in mosquitoes with both target-site insensitivity and metabolic resistance with lower fitness costs, which further leads to resistant populations with both high resistance levels and vectorial capacity.

Conclusions

This study reveals a possible mechanism for the evolution of deltamethrin resistance in Aedes albopictus. These findings will help guide practical strategies for insecticide use, resistance management and the prevention and control of mosquito-borne disease.
Economical synthesis of γ-cyclodextrin catalyzed by oriented cyclodextrin glycosyltransferase displayed on bacterial polyhydroxyalkanoate nanogranules
Authors: Duan Menglu , Wang Yan , Tan Dan , Yang Guowu , Deng Yuan , Ran Ganqiao , Li Jiao
Published: September 2023

Background

The advantages of γ-cyclodextrin (γ-CD) include its high solubility, ability to form inclusion complexes with various poorly water-soluble molecules, and favorable toxicological profile; thus, γ-CD is an attractive functional excipient widely used in many industrial settings. Unfortunately, the high cost of γ-CD caused by the low activity and stability of γ-cyclodextrin glycosyltransferase (γ-CGTase) has hampered large-scale production and application.

Results

This study reports the in vivo one-step production of immobilized γ-CGTase decorated on the surface of polyhydroxyalkanoate (PHA) nanogranules by the N-terminal fusion of γ-CGTase to PHA synthase via a designed linker. The immobilized γ-CGTase-PHA nanogranules showed outstanding cyclization activity of 61.25 ± 3.94 U/mg (γ-CGTase protein) and hydrolysis activity of 36,273.99 ± 1892.49 U/mg, 44.74% and 18.83% higher than that of free γ-CGTase, respectively. The nanogranules also exhibited wider optimal pH (cyclization activity 7.0–9.0, hydrolysis activity 10.0–11.0) and temperature (55–60 °C) ranges and remarkable thermo- and pH-stability, expanding its utility to adapt to wider and more severe reaction conditions than the free enzyme. A high yield of CDs (22.73%) converted from starch and a high ratio (90.86%) of γ-CD in the catalysate were achieved at pH 9.0 and 50 °C for 10 h with 1 mmol/L K+, Ca2+, and Mg2+ added to the reaction system. Moreover, γ-CGTase-PHA beads can be used at least eight times, retaining 82.04% of its initial hydrolysis activity and 75.73% of its initial cyclization activity.

Conclusions

This study provides a promising nanobiocatalyst for the cost-efficient production of γ-CD, which could greatly facilitate process control and economize the production cost.
Factors influencing drug switching and changes in low-density lipoprotein-cholesterol levels with atorvastatin: a real-world observational study
Authors: Lim Yu-Cheol , Lee Eui-Kyung , Park Mi-Hai
Published: September 2023

Background

Although generic drugs have been approved with the assurance of interchangeable applications with original drugs, some physicians, and patients still view their efficacy and interchangeability negatively. Using real-world data, we aimed to determine factors that impact switching between drugs that contain the same active ingredient, i.e., atorvastatin, and, in turn, whether this ‘switch’ could alter clinical outcomes.

Methods

Using the National Health Insurance Service senior cohort, a retrospective cohort study was conducted to assess patients who had newly started atorvastatin 10 mg and had at least two records of national health examinations from 2010 to 2014. Drug switching, which was defined as a change in the atorvastatin product administered 90 days before the first and second examinations, was assessed. Greedy propensity score matching (1:2) was performed between switchers and non-switchers to control for potential confounders. Factors influencing switching were analyzed using multivariate logistic regression to estimate odds ratios and 95% confidence intervals (CIs). Changes in low-density lipoprotein-cholesterol (LDL-C) levels attributable to drug switching were evaluated using difference-in-differences regression.

Results

A total of 1,588 patients were included, of whom 25.3% switched drugs (1,187 non-switchers and 401 switchers). Compared to patients taking generics before the first examination, those taking the original drugs had a lower odds ratio (0.31; 95% CI [0.21, 0.46]) for subsequent drug switching. A change in medical institution was associated with a significantly higher odds ratio (6.83; 95% CI [4.66, 10.02]). There were no significant differences in LDL-C alterations between switchers and non-switchers (0.42 mg/dL; 95% CI [-2.29, 3.13]).

Conclusion

The type of first-time drug administered and changes in medical institution can influence drug switching. No significant changes in LDL-C values were observed in the various switching scenarios between the original and generic drugs, suggesting their interchangeable application in real-world clinical practice.
EMG feedback improves grasping of compliant objects using a myoelectric prosthesis
Authors: Tchimino Jack , Dideriksen Jakob Lund , Dosen Strahinja
Published: September 2023

Background

Closing the control loop in myoelectric prostheses by providing artificial somatosensory feedback is recognized as an important goal. However, designing a feedback interface that is effective in realistic conditions is still a challenge. Namely, in some situations, feedback can be redundant, as the information it provides can be readily obtained through hearing or vision (e.g., grasping force estimated from the deformation of a compliant object). EMG feedback is a non-invasive method wherein the tactile stimulation conveys to the user the level of their own myoelectric signal, hence a measurement intrinsic to the interface, which cannot be accessed incidentally.

Methods

The present study investigated the efficacy of EMG feedback in prosthesis force control when 10 able-bodied participants and a person with transradial amputation used a myoelectric prosthesis to grasp compliant objects of different stiffness values. The performance with feedback was compared to that achieved when the participants relied solely on incidental cues.

Results

The main outcome measures were the task success rate and completion time. EMG feedback resulted in significantly higher success rates regardless of pin stiffness, indicating that the feedback enhanced the accuracy of force application despite the abundance of incidental cues. Contrary to expectations, there was no difference in the completion time between the two feedback conditions. Additionally, the data revealed that the participants could produce smoother control signals when they received EMG feedback as well as more consistent commands across trials, signifying better control of the system by the participants.

Conclusions

The results presented in this study further support the efficacy of EMG feedback when closing the prosthesis control loop by demonstrating its benefits in particularly challenging conditions which maximized the utility of intrinsic feedback sources.
The genetic variability of grapevine Pinot gris virus (GPGV) in Australia
Authors: Kaur Kamalpreet , Rinaldo Amy , Lovelock David , Rodoni Brendan , Constable Fiona
Published: September 2023

Grapevine Pinot gris virus (GPGV; genus Trichovirus in the family Betaflexiviridae) was detected in Australia in 2016, but its impact on the production of nursery material and fruit in Australia is still currently unknown. This study investigated the prevalence and genetic diversity of GPGV in Australia. GPGV was detected by reverse transcription-polymerase chain reaction (RT-PCR) in a range of rootstock, table and wine grape varieties from New South Wales, South Australia, and Victoria, with 473/2171 (21.8%) samples found to be infected. Genomes of 32 Australian GPGV isolates were sequenced and many of the isolates shared high nucleotide homology. Phylogenetic and haplotype analyses demonstrated that there were four distinct clades amongst the 32 Australian GPGV isolates and that there were likely to have been at least five separate introductions of the virus into Australia. Recombination and haplotype analysis indicate the emergence of new GPGV strains after introduction into Australia. When compared with 168 overseas GPGV isolates, the analyses suggest that the most likely origin of Australian GPGV isolates is from Europe. There was no correlation between specific GPGV genotypes and symptoms such as leaf mottling, leaf deformation, and shoot stunting, which were observed in some vineyards, and the virus was frequently found in symptomless grapevines.
Cerebral arterial flow dynamics during systole and diastole phases in young and older healthy adults
Authors: Owashi Kimi Piedad , Capel Cyrille , Balédent Olivier
Published: September 2023

Background

Since arterial flow is the leading actor in neuro-fluids flow dynamics, it might be interesting to assess whether it is meaningful to study the arterial flow waveform in more detail and whether this provides new important information. Few studies have focused on determining the influence of heart rate variation over time on the arterial flow curve. Therefore, this study aimed to evaluate cerebral arterial flow waveforms at extracranial and intracranial compartments in young and elderly healthy adults, also considering systole and diastole phases.

Methods

Cine phase-contrast magnetic resonance imaging (CINE-PC MRI) was performed on twenty-eight healthy young volunteers (HYV) and twenty healthy elderly volunteers (HEV) to measure arterial blood flows at the extracranial and intracranial planes. A semi-automated protocol using MATLAB scripts was implemented to identify the main representative points in the arterial flow waveforms. Representative arterial profiles were estimated for each group. Moreover, the effects of age and sex on flow times, amplitude-related parameters, and parameters related to systole and diastole phases were evaluated at the extracranial and intracranial compartments. Student’s t-test or Wilcoxon’s test (depending on the normality of the distribution) was used to detect significant differences.

Results

In HYVs, significant differences were observed between extracranial and intracranial levels in parameters related to the AP1 amplitude. Besides the detected differences in pulsatility index (extracranial: 0.92 ± 0.20 vs. 1.28 ± 0.33; intracranial: 0.79 ± 0.15 vs. 1.14 ± 0.18, p < .001) and average flow (715 ± 136 vs. 607 ± 125 ml/min, p = .008) between HYV and HEV, differences in the amplitude value of the arterial flow profile feature points were also noted. Contrary to systole duration (HYV: 360 ± 29 ms; HEV: 364 ± 47 ms), diastole duration presented higher inter-individual variability in both populations (HYV: 472 ± 145 ms; HEV: 456 ± 106 ms). Our results also showed that, with age, it is mainly the diastolic phase that changes. Although no significant differences in duration were observed between the two populations, the mean flow value in the diastolic phase was significantly lower in HEV (extracranial: 628 ± 128 vs. 457 ± 111 ml/min; intracranial: 599 ± 121 vs. 473 ± 100 ml/min, p < .001). No significant differences were observed in the arterial flow parameters evaluated between females and males in either HYV or HEV.

Conclusion

Our study provides a novel contribution on the influence of the cardiac cycle phases on cerebral arterial flow. The main contribution in this study concerns the identification of age-related alterations in cerebral blood flow, which occur mainly during the diastolic phase. Specifically, we observed that mean flow significantly decreases with age during diastole, whereas mean flow during systole is consistent.
Anterior cervical discectomy and fusion for the treatment of giant cervical disc herniation
Authors: Liang Weibin , Xiong Yu , Jia Yukun , Li Shaoqiang , Zhao Kaishuai , Peng Zhan , Wang Guangye
Published: September 2023

Objective

Giant cervical disc herniation (GCDH) was defined as a herniated intervertebral disc that accounted for more than 50% of the spinal canal. The purpose of this study was to analyse the feasibility of anterior cervical discectomy and fusion (ACDF) for the treatment of GCDH.

Methods

Patient demographic and imaging data, clinical results, and perioperative complications were analysed retrospectively.

Results

A total of 23 patients were included in the study. Spinal cord recovery pulsation was observed under a microscope in all cases. Postoperative magnetic resonance imaging showed complete decompression of the spinal cord and no residual intervertebral disc. The patients were followed up for 12 to 18 months. The average visual analogue scale score and Neck Disability Index decreased from 8.6 ± 0.5 and 86.0 ± 2.7% to 2.2 ± 0.2 and 26.7 ± 2.0%, respectively, three days after surgery. The average Japanese Orthopedic Association score increased from 6.9 ± 2.1 to 13.9 ± 1.1. The cervical spinal cord function improvement rate was 69.3%. No neurological complications after surgery were observed.

Conclusion

This study shows that ACDF is feasible for the treatment of GCDH disease. The results indicate that this approach can be used to safely remove herniated disc fragments, effectively relieve compression of the spinal cord, and improve neurological function.
Tafamidis decreased cardiac amyloidosis deposition in patients with Ala97Ser hereditary transthyretin cardiomyopathy: a 12-month follow-up cohort study
Authors: Tsai Cheng-Hsuan , Chao Chi-Chao , Hsieh Sung-Tsang , Yu An-Li , Wu Yuan-Kun , Cheng Mei-Fang , Lee Ming-Jen , Chou Chia-Hung , Shun Chia-Tung , Hsueh Hsueh-Wen , Jyh-Ming Juang Jimmy , Tseng Ping-Huei , Su Mao-Yuan , Lin Yen-Hung
Published: September 2023

Background

Transthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM.

Methods

We retrospectively analyzed a prospective cohort of ATTR-CM patients, including 14 with hereditary A97S ATTR-CM and 17 healthy controls with baseline CMR data. All ATTR-CM patients received tafamidis treatment and received CMR with extracellular volume (ECV) at baseline and after 1 year of follow-up.

Results

Baseline N-terminal pro-B-type natriuretic peptide, left ventricular (LV) mass, LV ejection fraction, global radial, circumferential and longitudinal strain, T1 mapping and ECV were significantly worse in the patients with ATTR-CM compared with the healthy controls. After 1 year of tafamidis treatment, ECV decreased from 51.5 ± 8.9% to 49.0 ± 9.4% (P = 0.041), however there were no significant changes in LV mass, LV ejection fraction, global radial strain, global circumferential strain, global longitudinal strain and T1 mapping.

Conclusions

After a one-year treatment period, tafamidis exhibited subtle but statistically significant reductions in ECV, potentially indicating a decrease in amyloid deposition among patients diagnosed with hereditary A97S ATTR-CM.
A robust deep learning workflow to predict CD8 + T-cell epitopes
Authors: Lee Chloe H. , Huh Jaesung , Buckley Paul R. , Jang Myeongjun , Pinho Mariana Pereira , Fernandes Ricardo A. , Antanaviciute Agne , Simmons Alison , Koohy Hashem
Published: September 2023

Background

T-cells play a crucial role in the adaptive immune system by triggering responses against cancer cells and pathogens, while maintaining tolerance against self-antigens, which has sparked interest in the development of various T-cell-focused immunotherapies. However, the identification of antigens recognised by T-cells is low-throughput and laborious. To overcome some of these limitations, computational methods for predicting CD8 + T-cell epitopes have emerged. Despite recent developments, most immunogenicity algorithms struggle to learn features of peptide immunogenicity from small datasets, suffer from HLA bias and are unable to reliably predict pathology-specific CD8 + T-cell epitopes.

Methods

We developed TRAP (T-cell recognition potential of HLA-I presented peptides), a robust deep learning workflow for predicting CD8 + T-cell epitopes from MHC-I presented pathogenic and self-peptides. TRAP uses transfer learning, deep learning architecture and MHC binding information to make context-specific predictions of CD8 + T-cell epitopes. TRAP also detects low-confidence predictions for peptides that differ significantly from those in the training datasets to abstain from making incorrect predictions. To estimate the immunogenicity of pathogenic peptides with low-confidence predictions, we further developed a novel metric, RSAT (relative similarity to autoantigens and tumour-associated antigens), as a complementary to ‘dissimilarity to self’ from cancer studies.

Results

TRAP was used to identify epitopes from glioblastoma patients as well as SARS-CoV-2 peptides, and it outperformed other algorithms in both cancer and pathogenic settings. TRAP was especially effective at extracting immunogenicity-associated properties from restricted data of emerging pathogens and translating them onto related species, as well as minimising the loss of likely epitopes in imbalanced datasets. We also demonstrated that the novel metric termed RSAT was able to estimate immunogenic of pathogenic peptides of various lengths and species. TRAP implementation is available at:https://github.com/ChloeHJ/TRAP.

Conclusions

This study presents a novel computational workflow for accurately predicting CD8 + T-cell epitopes to foster a better understanding of antigen-specific T-cell response and the development of effective clinical therapeutics.
The changing relationship between Cholera and interannual climate variables in Kolkata over the past century
Authors: Shackleton Debbie , Memon Fayyaz Ali , Chen Albert , Dutta Shanta , Kanungo Suman , Deb Alok
Published: September 2023

Background

In the Bengal Delta, research has shown that climate and cholera are linked. One demonstration of this is the relationship between interannual ocean-atmospheric oscillations such as the El Niño Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD). What remains unclear in the present literature is the nature of this relationship in the specific context of Kolkata, and how this relationship may have changed over time.

Results

In this study, we analyse the changing relationship between ENSO and IOD with cholera in Kolkata over recent (1999–2019) and historical (1897–1941) time intervals. Wavelet coherence analysis revealed significant non-stationary association at 2–4 year and 4–8 year periods between cholera and both interannual timeseries during both time intervals. However, coherence was notably weakened in the recent interval, particularly with regards to ENSO, a result supported by a complementary SARIMA analysis. Similar coherence patterns with temperature indicate it could be an important mediating factor in the relationship between cholera and oscillating climate phenomena in Kolkata.

Conclusions

This study reveals a shifting relationship between cholera and climate variables (ENSO and IOD) in Kolkata, suggesting a decoupling between environmental influences and cholera transmission in recent years. Our results therefore do not suggest that an intensification of ENSO is likely to significantly influence cholera in the region. We also find that the relationship between cholera and interannual climate variables is distinct to Kolkata, highlighting the spatial heterogeneity of the climate-cholera relationship even within the Bengal Delta.
Transient lateral rectus palsy associated with acute coronary syndrome treated with percutaneous coronary intervention: a case report
Authors: Farsavian Ali Asghar , Mobinikhaledi Mahya , Ghorbani Parastoo , Ghadirzadeh Erfan
Published: September 2023

Background

Patients who experience angina and acute myocardial infarction often receive diagnostic coronary angiography and percutaneous coronary intervention.

Case presentation

A 54-year-old Persian man with acute coronary syndrome was admitted to the hospital and underwent elective percutaneous coronary intervention. Two hours after the procedure, the patient experienced ophthalmoplegia and diplopia. The diagnosis was abducens nerve palsy resulting in transient lateral rectus palsy. The cause is presumed to have been an ischemic event affecting the unilateral abducens nerve. This could have occurred owing to the microembolism during the percutaneous coronary intervention, which resulted in left lateral rectus palsy. Within 1 month, the diplopia was relieved completely, and the physical examination was normal.

Conclusion

The occurrence of neuro-ophthalmic complications that may arise from percutaneous coronary intervention is extremely rare. To our knowledge, this is the second reported case of unilateral rectus palsy associated with percutaneous coronary intervention.
Biodistribution of mesenchymal stromal cell-derived extracellular vesicles administered during acute lung injury
Authors: Tieu Alvin , Stewart Duncan J. , Chwastek Damian , Lansdell Casey , Burger Dylan , Lalu Manoj M.
Published: September 2023

Background

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising cell-free therapy for acute lung injury (ALI). To date, no studies have investigated their biodistribution in ALI or discerned the timing of administration for maximal lung targeting, which are crucial considerations for clinical translation. Our study aimed to characterize a mouse model of ALI and establish the distribution kinetics and optimal timing of MSC-EV delivery during lung injury.

Methods

MSC-EVs were isolated by ultracentrifugation alone (U/C) or tangential flow filtration with ultracentrifugation (TFF-U/C) and characterized by nanoparticle tracking analysis and western blot. A lipopolysaccharide (LPS)-induced mouse model of ALI was established to study the inflammatory response over 72 h. ALI was assessed by histological lung injury score, bronchoalveolar lavage fluid cell count and inflammatory cytokines. For biodistribution studies, ALI mice were intravenously administered fluorescently labeled MSC-EVs to determine the optimal timing of administration and organ-specific biodistribution. Live in vivo and ex vivo fluorescence imaging was conducted at various timepoints post-EV injection.

Results

EVs isolated by either ultracentrifugation alone or TFF-U/C displayed comparable size distribution (~ 50–350 nm) and EV marker expression (CD63/81). TFF-U/C generated a 5.4-fold higher particle concentration and 3.9-fold higher total protein when compared to ultracentrifugation alone. From the inflammatory time-course study, cell count and IL-1β peaked in bronchoalveolar lavage fluid at 24 h after ALI induction. MSC-EVs delivered at 24 h (as opposed to 0.5 h, 5 h or 10 h) after disease induction resulted in a 2.7–4.4-fold higher lung uptake of EVs. Biodistribution studies comparing organ-specific MSC-EV uptake showed progressive lung accumulation up to 48 h post-delivery (threefold higher than the spleen/liver), with a decline at 72 h. Importantly, lung EV fluorescence at 48 h in ALI mice was significantly elevated as compared to control mice. The lung tropism of MSC-EVs was further validated as therapeutically inert EVs derived from HEK293T cells accumulated mainly to the spleen and liver with a 5.5-fold lower distribution to the lungs as compared to MSC-EVs.

Conclusion

MSC-EVs exhibit maximal lung accumulation when administered during heightened inflammation at 24 h after ALI induction. This lung tropism suggests that MSC-EVs may serve as a practical rescue treatment for acute inflammatory respiratory conditions.
Suprachoroidal spheroidal mesenchymal stem cell implantation in retinitis pigmentosa: clinical results of 6 months follow-up
Authors: Özkan Berna , Yılmaz Tuğan Büşra , Hemşinlioğlu Cansu , Sır Karakuş Gözde , Şahin Özlem , Ovalı Ercüment
Published: September 2023

Purpose

This prospective clinical case series aimed to evaluate the effect of suprachoroidal implantation of mesenchymal stem cells (MSCs) in the form of spheroids as a stem cell therapy for retinitis pigmentosa (RP) patients with relatively good visual acuity.

Methods

Fifteen eyes of 15 patients with RP who received suprachoroidal implantation of MSCs in the form of spheroids were included. Best-corrected visual acuity (BCVA), 10–2 and 30–2 visual field examination and multifocal electroretinography (mfERG) recordings were recorded at baseline, postoperative 1st, 3rd and 6th months during follow-up.

Results

Baseline median BCVA of RP patients was 1.30 (1.00–2.00) logMAR. BCVA has improved to 1.00 (0.50–1.30), 0.80 (0.40–1.30) and 0.80 (0.40–1.30) at the postoperative 1st, 3rd and 6th months, respectively. The improvements from baseline to the 3rd and 6th months were statistically significant (p = 0.03 and p < 0.001, respectively). In the 30–2 VF test, median MD was significantly improved at the 6th month compared to baseline (p = 0.030). In the 10–2 VF test, the median MD value was significantly different at the 6th month compared to the baseline (p = 0.043). The PSD value of the 10–2 VF test was significantly different at the 6th month compared to the 3rd month (p = 0.043). The amplitudes of P1 waves in < 2°, 5°–10° and 10°–15° rings improved significantly at the postoperative 6th month (p = 0.014, p = 0.018 and p = 0.017, respectively). There was also a statistically significant improvement in implicit times of P1 waves in 10°–15° ring at the postoperative 6th month (p = 0.004).

Conclusion

Suprachoroidal implantation of MSCs in the form of spheroids as a stem cell therapy for RP patients with relatively good visual acuity has an improving effect on BCVA, VF and mfERG recordings during the 6-month follow-up period. Spheroidal MSCs with enhanced effects may be more successful in preventing apoptosis and improving retinal tissue healing in RP patients.
Biomarkers for Duchenne muscular dystrophy progression: impact of age in the mdx tongue spared muscle
Authors: Lorena Marcelo dos Santos Voltani , Santos Estela Kato dos , Ferretti Renato , Nagana Gowda G. A. , Odom Guy L. , Chamberlain Jeffrey S. , Matsumura Cintia Yuri
Published: September 2023

Background

Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation, and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-α and TGF-β, are potential biomarkers for dystrophic muscle characterization.

Methods

To investigate disease progression and aging, we utilized young (1 month old) and old (21–25 months old) mdx and wild-type tongue muscles. Metabolite changes were analyzed using 1H nuclear magnetic resonance, while TNF-α and TGF-β were assessed using Western blotting to examine inflammation and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups.

Results

The histological analysis of the mid-belly tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild-type or mdx whole tongues of the same age. The metabolites alanine, methionine, and 3-methylhistidine were higher, and taurine and glycerol were lower in young tongues in both wild type and mdx (p < 0.001). The metabolites glycine (p < 0.001) and glutamic acid (p = 0.0018) were different only in the mdx groups, being higher in young mdx mice. Acetic acid, phosphocreatine, isoleucine, succinic acid, creatine, and the proteins TNF-α and TGF-β had no difference in the analysis between groups (p > 0.05).

Conclusions

Surprisingly, histological, metabolite, and protein analysis reveal that the tongue of old mdx remains partially spared from the severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes in the tongue muscle. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-α, and TGF-β do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging.
Energy efficiency maximization for UAV-enabled amplify-and-forward relaying via joint power and trajectory optimization
Authors: Guo Lili , Zhang Shibing , Ji Xiaodong , Shi Senyi
Published: September 2023

This paper investigates an optimization problem corresponding to energy efficiency maximization of an unmanned aerial vehicle (UAV)-enabled relaying system, where a fixed-wing UAV acts as an amplify-and-forward mobile relay to assist data transmission between a source node and a destination node. On the premise of satisfying the speed and acceleration constraints of the UAV, the energy efficiency (EE) of the relaying system is maximized by jointly optimizing the UAV’s trajectory and the individual transmit power levels of the source and the UAV relay. The initial joint optimization problem is non-convex and cannot be solved directly. Therefore, the joint optimization problem is decomposed into two sub-problems which are solved by applying the successive convex approximation technique and the Dinkelbach’s algorithm. On this basis, an efficient iterative algorithm is proposed to tackle the joint optimization problem through the block coordinate descent technique. Simulation results demonstrated that by conducting the proposed algorithm, the flight trajectory of the UAV and the individual transmit power levels of the nodes can be flexibly adjusted according to the system conditions, and the proposed algorithm contributes to the higher EE compared with the benchmark schemes.