bluuebunny/crossref_metadata_2025 huggingface dataset:
Starvar: symptom-based tool for automatic ranking of variants using evidence from literature and genomes
Authors: Kafkas Șenay , Abdelhakim Marwa , Uludag Mahmut , Althagafi Azza , Alghamdi Malak , Hoehndorf Robert
Published: July 2023

Background

Identifying variants associated with diseases is a challenging task in medical genetics research. Current studies that prioritize variants within individual genomes generally rely on known variants, evidence from literature and genomes, and patient symptoms and clinical signs. The functionalities of the existing tools, which rank variants based on given patient symptoms and clinical signs, are restricted to the coverage of ontologies such as the Human Phenotype Ontology (HPO). However, most clinicians do not limit themselves to HPO while describing patient symptoms/signs and their associated variants/genes. There is thus a need for an automated tool that can prioritize variants based on freely expressed patient symptoms and clinical signs.

Results

STARVar is a Symptom-based Tool for Automatic Ranking of Variants using evidence from literature and genomes. STARVar uses patient symptoms and clinical signs, either linked to HPO or expressed in free text format. It returns a ranked list of variants based on a combined score from two classifiers utilizing evidence from genomics and literature. STARVar improves over related tools on a set of synthetic patients. In addition, we demonstrated its distinct contribution to the domain on another synthetic dataset covering publicly available clinical genotype–phenotype associations by using symptoms and clinical signs expressed in free text format.

Conclusions

STARVar stands as a unique and efficient tool that has the advantage of ranking variants with flexibly expressed patient symptoms in free-form text. Therefore, STARVar can be easily integrated into bioinformatics workflows designed to analyze disease-associated genomes.

Availability

STARVar is freely available from https://github.com/bio-ontology-research-group/STARVar.
Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection
Authors: Rambaran Santhuri , Maseko Thando Glory , Lewis Lara , Hassan-Moosa Razia , Archary Derseree , Ngcapu Sinaye , Garrett Nigel , McKinnon Lyle R. , Padayatchi Nesri , Naidoo Kogieleum , Sivro Aida
Published: July 2023

Background

Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic differences in monocytes and dendritic cell populations using peripheral blood mononuclear cells from individuals with recurrent, active pulmonary tuberculosis with and without coexisting HIV infection (CAPRISA 011, Clinicaltrials.gov, NCT02114684, 29/01/2014) and compared them to samples from HIV positive individuals and healthy controls. Additionally, we assessed the associations between the frequency of monocyte and dendritic cell subsets and time to culture conversion and cavitary disease in patients with active TB using a cox proportional hazards and logistic regression models.

Results

Compared to healthy controls, the frequency of total monocytes (HLA-DR + CD14 +) was significantly higher in the TB/HIV and TB groups and the frequency of dendritic cells (HLA-DR + CD14-) was significantly higher in TB/HIV and HIV groups. We observed significant variation in the expression of CCR2, CD40, CD11b, CD86, CD163, CX3CR1 across different cell subsets in the four study groups. Increase in CCR2, CD11b and CD40 was associated with active TB infection, while decrease in CX3CR1 and increase in CD163 was associated with HIV infection. Expression of CX3CR1 (aHR 0.98, 95% CI 0.963 – 0.997, p = 0.019) on non-classical monocytes associated with longer time to TB culture conversion in the multivariable model correcting for randomization arm, age, sex, HIV status, lung cavitation, alcohol use, smoking and BMI. Higher surface expression of CD86 (aOR 1.017, 95% CI 1.001 – 1.032, p = 0.033) on intermediate monocytes associated with the presence of lung cavitation, while higher expression of transitional monocytes (aOR 0.944, 95% CI 0.892 – 0.999, p = 0.047) associated with the absence of lung cavitation in the multivariable model.

Conclusion

These data provide valuable insight into the heterogenous role of monocyte and dendritic cells in TB and HIV infections.
Trajectories of physical function and quality of life in people with osteoarthritis: results from a 10-year population-based cohort
Authors: Costa Daniela , Lopes David G. , Cruz Eduardo B. , Henriques Ana R. , Branco Jaime , Canhão Helena , Rodrigues Ana M.
Published: July 2023

Objective

To identify long-term trajectories of physical function and health-related quality of life (HRQoL) among people with hip and/or knee osteoarthritis (HKOA) and the sociodemographic, lifestyle, and clinical factors associated with different trajectories.

Methods

Participants with HKOA from the EpiDoC study, a 10-year follow-up (2011–2021) population-based cohort, were considered. Sociodemographic, lifestyle, and clinical variables were collected at baseline in a structured interview and clinical appointment. Physical function and HRQoL were evaluated with the Health Assessment Questionnaire (HAQ) and EuroQoL, respectively, at baseline and the three follow-ups. Group-based trajectory modeling identified physical function and HRQoL trajectories. Multinomial logistic regression analyzed the associations between the covariates of interest and trajectory assignment (p < 0.05).

Results

We included 983 participants with HKOA. We identified three trajectories for each outcome: “consistently low disability” (32.0%), “slightly worsening moderate disability” (47.0%), and “consistently high disability” (21.0%) for physical function; “consistently high HRQoL” (18.3%), “consistently moderate HRQoL” (48.4%) and “consistently low HRQoL” (33.4%) for HRQoL. Age ≥ 75 years, female sex, multimorbidity, and high baseline clinical severity were associated with higher risk of assignment to poorer physical function and HRQoL trajectories. Participants with high education level and with regular physical activity had a lower risk of assignment to a poor trajectory. Unmanageable pain levels increased the risk of assignment to the “consistently moderate HRQoL” trajectory.

Conclusion

Although the trajectories of physical function and HRQoL remained stable over 10 years, approximately 70% of people with HKOA maintained moderate or low physical function and HRQoL over this period. Modifiable risk factors like physical activity, multimorbidity and clinical severity were associated with poorer physical function and HRQoL trajectories. These risk factors may be considered in tailored healthcare interventions.
Effect of neuromuscular electrical stimulation combined with early rehabilitation therapy on mechanically ventilated patients: a prospective randomized controlled study
Authors: Liu Ying , Gong Yangyang , Zhang Chaofan , Meng Pingping , Gai Yubiao , Han Xiaoning , Yuan Zhiyong , Xing Jinyan , Dong Zehua
Published: July 2023

Background

This study aimed to investigate the effectiveness of neuromuscular electrical stimulation (NMES) blended with early rehabilitation on the diaphragm and skeletal muscle in sufferers on mechanical ventilation (MV).

Method

This is a prospective randomized controlled study. Eighty patients on MV for respiratory failure were divided into a study group (40 cases) and a control group (40 cases) randomly. The study group adopted a treatment method of NMES combined with early rehabilitation and the control group adopted the method of early rehabilitation only. The diaphragmatic excursion (DE), diaphragmatic thickening fraction (DTF), variation of thickness of intercostal muscles (TIM), variation of thickness of rectus abdominis (TRA), and variation of the cross-sectional area of rectus femoris (CSA-RF) were measured to evaluate the therapeutic effect by ultrasound before and after intervention at the first day of MV, the 3rd and 7th day of intervention and the day discharged from ICU.

Results

No significant difference was found in the general demographic information and ultrasound indicators between the two groups before treatment (all P > 0.05). After treatment, the variation of DTF (0.15 ± 0.05% vs. 0.12 ± 0.04%, P = 0.034) was significantly higher in the study group than that in the control group on the day discharged from ICU. The variation of TRA (0.05 ± 0.09% vs. 0.10 ± 0.11%, P = 0.029) and variation of CSA-RF (0.13 ± 0.07% vs. 0.19 ± 0.08%, P < 0.001) in the study group were significantly lower than that in the control group. The duration of MV in the study group was significantly shorter than that in the control group [109.5 (88.0, 213.0) hours vs. 189.5 (131.5, 343.5) hours, P = 0.023]. The study group had better muscle strength score than the control group at discharge (52.20 ± 11.70 vs. 44.10 ± 15.70, P = 0.011).

Conclusion

NMES combined with early rehabilitation therapy is beneficial in reducing muscle atrophy and improving muscle strength in mechanically ventilated patients. This treatment approach may provide a new option for patients to choose a rehabilitation program; however, more research is needed to fully evaluate the effectiveness of this treatment option.
Authentication of milk thistle commercial products using UHPLC-QTOF-ESI + MS metabolomics and DNA metabarcoding
Authors: Raclariu-Manolică Ancuța Cristina , Mauvisseau Quentin , Paranaiba Renato , De Boer Hugo J. , Socaciu Carmen
Published: July 2023

Background

Milk thistle is one of the most popular hepatoprotectants, and is often sold in combination with other ingredients. Botanical supplements are known to be vulnerable to contamination and adulteration, and emerging technologies show promise to improve their quality control.

Methods

Untargeted and semi-targeted metabolomics based on UHPLC-QTOF-ESI+MS techniques, UV spectrometry, and DNA metabarcoding using Illumina MiSeq were used to authenticate eighteen milk thistle botanical formulations (teas, capsules, tablets, emulsion).

Results

Untargeted metabolomics separated 217 molecules and by multivariate analysis the discrimination between the different preparations was established. The semi-targeted metabolomics focused on 63 phytochemicals, mainly silymarin flavonolignans and flavonoids, that may be considered as putative biomarkers of authenticity. All formulations contained molecules from silymarin complexes at different levels. The quantitative evaluation of silybins was done using in parallel UV spectrometry and UHPLC-QTOF-ESI+MS and their correlations were compared. DNA metabarcoding detected milk thistle in eleven out of sixteen retained preparations, whereas two others had incomplete evidence of milk thistle despite metabolomics validating specific metabolites, e.g., silymarin complex, identified and quantified in all samples. Meanwhile, the DNA metabarcoding provided insights into the total species composition allowing the interpretation of the results in a broad context.

Conclusion

Our study emphasizes that combining spectroscopic, chromatographic, and genetic techniques bring complementary information to guarantee the quality of the botanical formulations.
Can the performance of pyrethroid-chlorfenapyr nets be reduced when combined with pyrethroid-piperonyl butoxide (PBO) nets?
Authors: Syme Thomas , Nounagnon Judicaël , N’dombidjé Boris , Gbegbo Martial , Agbevo Abel , Ahoga Juniace , Ngufor Corine
Published: July 2023

Background

Pyrethroid-chlorfenapyr (CFP) and pyrethroid-piperonyl butoxide (PBO) nets are being scaled across endemic countries to improve control of malaria transmitted by pyrethroid-resistant mosquitoes. CFP is a pro-insecticide requiring activation by mosquito cytochrome P450 monooxygenase enzymes (P450s) while PBO improves pyrethroid potency by inhibiting the action of these enzymes in pyrethroid-resistant mosquitoes. The inhibitory action of PBO against P450s may thus reduce the efficacy of pyrethroid-CFP nets when applied inside the same household as pyrethroid-PBO nets.

Methods

Two experimental hut trials were performed to evaluate the entomological impact of two different types of pyrethroid-CFP ITN (Interceptor® G2, PermaNet® Dual) when applied alone and in combination with pyrethroid-PBO ITNs (DuraNet® Plus, PermaNet® 3.0) against a pyrethroid-resistant vector population in southern Benin. In both trials, all net types were tested as single and double net treatments. Bioassays were also performed to assess the resistance profile of the vector population at the hut site and investigate interactions between CFP and PBO.

Results

The vector population was susceptible to CFP but exhibited a high intensity of pyrethroid resistance that was overcame by PBO pre-exposure. Vector mortality was significantly lower in huts with combinations of pyrethroid-CFP nets plus pyrethroid-PBO nets compared to huts with two pyrethroid-CFP nets (74% vs. 85% for Interceptor® G2 and 57% vs. 83% for PermaNet® Dual, p < 0.001). PBO pre-exposure reduced the toxicity of CFP in bottle bioassays suggesting this effect may be partly attributable to antagonism between CFP and PBO. Higher levels of vector mortality were observed in huts with net combinations that included pyrethroid-CFP nets compared to those that did not and highest mortality was achieved when pyrethroid-CFP nets were applied alone as two nets together (83–85%).

Conclusions

This study shows evidence of a reduced performance of pyrethroid-CFP nets when combined with pyrethroid-PBO ITNs compared to when applied alone and higher efficacy with net combinations that included pyrethroid-CFP nets. These findings suggest that in similar contexts, prioritizing distribution of pyrethroid-CFP nets over other net types would maximize vector control impact.
Carbon nanoparticles localized clipped node dissection combined with sentinel lymph node biopsy with indocyanine green and methylene blue after neoadjuvant therapy in node positive breast cancer in China: initial results of a prospective study
Authors: Yang Xin , Li Yao , Ren Xiao-tian , Fan Lei , Hua Bin
Published: July 2023

Background

This study aimed to evaluate the feasibility of applying carbon nanoparticles (CNs) to visualize clip-marked metastatic nodes in combination with indocyanine green (ICG) and methylene blue (MB) as sentinel lymph node (SLN) tracers for targeted axillary dissection (TAD) after neoadjuvant therapy (NAT).

Methods

This feasibility trial enrolled 40 patients with node-positive breast cancer, and 38 patients completed NAT and surgery were included in the final analysis. Before NAT or surgery, clip-marked nodes were localized with CNs by ultrasonography. After NAT, the clip-marked nodes were removed under the guidance of carbon-tattooing and confirmed by radiography. SLNs were mapped with ICG and MB. Axillary lymph node dissection (ALND) was performed for all patients after TAD.

Results

The clip-marked nodes were retrieved in all patients. The SLN identification rate was 100%. 29 of 38 clipped-nodes were SLNs. The false-negative rate was 6.25% (2/32,95% CI:1.09% ~ 22.22%) for TAD nodes and 9.38% (3/32,95% CI 3.24%-24.22%) for SLNs, and 18.75% for clipped-nodes (6/32, 95% CI:7.86% ~ 37.04%). No adverse events were reported during clip placement, CNs localization, or the TAD procedure.

Conclusions

The TAD procedure with CNs to locate and visualize clipped nodes as well as SLN tracing with ICG and MB has good accessibility in China, and this technique could be easily mastered by experienced surgeons. The modified TAD technique has also demonstrated good predictive ability for residual axillary lesions after NAT, and is worth of further evaluation.
Interventions to prevent or reduce the incidence and severity of ovarian hyperstimulation syndrome: a systematic umbrella review of the best clinical evidence
Authors: Palomba Stefano , Costanzi Flavia , Nelson Scott M. , Caserta Donatella , Humaidan Peter
Published: July 2023

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threating iatrogenic complication of the early luteal phase and/or early pregnancy after in vitro fertilization (IVF) treatment. The aim of the current study was to identify the most effective methods for preventing of and reducing the incidence and severity of OHSS in IVF patients. A systematic review of systematic reviews of randomized controlled trials (RCTs) with meta-analysis was used to assess each potential intervention (PROSPERO website, CRD 268626) and only studies with the highest quality were included in the qualitative analysis. Primary outcomes included prevention and reduction of OHSS incidence and severity. Secondary outcomes were maternal death, incidence of hospital admission, days of hospitalization, and reproductive outcomes, such as incidence of live-births, clinical pregnancies, pregnancy rate, ongoing pregnancy, miscarriages, and oocytes retrieved. A total of specific interventions related to OHSS were analyzed in 28 systematic reviews of RCTs with meta-analyses. The quality assessment of the included studies was high, moderate, and low for 23, 2, and 3 studies, respectively. The certainty of evidence (CoE) for interventions was reported for 37 specific situations/populations and resulted high, moderate, and low-to-very low for one, 5, and 26 cases, respectively, while it was not reported in 5 cases. Considering the effective interventions without deleterious reproductive effects, GnRH-ant co-treatment (36 RCTs; OR 0.61, 95% C 0.51 to 0.72, n = 7,944; I2 = 31%) and GnRH agonist triggering (8 RCTs; OR 0.15, 95% CI 0.05 to 0.47, n = 989; I2 = 42%) emerged as the most effective interventions for preventing OHSS with a moderate CoE, even though elective embryo cryopreservation exhibited a low CoE. Furthermore, the use of mild ovarian stimulation (9 RCTs; RR 0.26, CI 0.14 to 0.49, n = 1,925; I2 = 0%), and dopaminergic agonists (10 RCTs; OR 0.32, 95% CI 0.23 to 0.44, n = 1,202; I2 = 13%) coadministration proved effective and safe with a moderate CoE. In conclusion, the current study demonstrates that only a few interventions currently can be considered effective to reduce the incidence of OHSS and its severity with high/moderate CoE despite the numerous published studies on the topic. Further well-designed RCTs are needed, particularly for GnRH-a down-regulated IVF cycles.
Alzheimer’s disease-associated complement gene variants influence plasma complement protein levels
Authors: Veteleanu Aurora , Stevenson-Hoare Joshua , Keat Samuel , Daskoulidou Nikoleta , Zetterberg Henrik , Heslegrave Amanda , Escott-Price Valentina , Williams Julie , Sims Rebecca , Zelek Wioleta M. , Carpanini Sarah M. , Morgan Bryan Paul
Published: July 2023

Background

Alzheimer’s disease (AD) has been associated with immune dysregulation in biomarker and genome-wide association studies (GWAS). GWAS hits include the genes encoding complement regulators clusterin (CLU) and complement receptor 1 (CR1), recognised as key players in AD pathology, and complement proteins have been proposed as biomarkers.

Main body

To address whether changes in plasma complement protein levels in AD relate to AD-associated complement gene variants we first measured relevant plasma complement proteins (clusterin, C1q, C1s, CR1, factor H) in a large cohort comprising early onset AD (EOAD; n = 912), late onset AD (LOAD; n = 492) and control (n = 504) donors. Clusterin and C1q were significantly increased (p < 0.001) and sCR1 and factor H reduced (p < 0.01) in AD plasma versus controls. ROC analyses were performed to assess utility of the measured complement biomarkers, alone or in combination with amyloid beta, in predicting AD. C1q was the most predictive single complement biomarker (AUC 0.655 LOAD, 0.601 EOAD); combining C1q with other complement or neurodegeneration makers through stepAIC-informed models improved predictive values slightly. Effects of GWS SNPs (rs6656401, rs6691117 in CR1; rs11136000, rs9331888 in CLU; rs3919533 in C1S) on protein concentrations were assessed by comparing protein levels in carriers of the minor vs major allele. To identify new associations between SNPs and changes in plasma protein levels, we performed a GWAS combining genotyping data in the cohort with complement protein levels as endophenotype. SNPs in CR1 (rs6656401), C1S (rs3919533) and CFH (rs6664877) reached significance and influenced plasma levels of the corresponding protein, whereas SNPs in CLU did not influence clusterin levels.

Conclusion

Complement dysregulation is evident in AD and may contribute to pathology. AD-associated SNPs in CR1, C1S and CFH impact plasma levels of the encoded proteins, suggesting a mechanism for impact on disease risk.
Mapping intron retention events contributing to complex traits using splice quantitative trait locus
Authors: Wang Siyuan , Wu Hongyu , Zhao Yongyan , Wang Luyao , Guan Xueying , Zhao Ting
Published: July 2023

Background

Alternative splicing (AS) of mRNA plays an important roles in transcriptome diversity, involving regulation of plant growth and stress response. Understanding the variation of AS events underlying GWAS loci in a crop population can provide insight into the molecular mechanisms of complex agronomic traits. To date, genome-wide association studies relating AS events to agronomic traits have rarely been conducted at the population level in crops.

Results

Here, a pipeline was constructed to identify candidate AS events related to complex traits. Firstly, ovule transcriptome data were used to characterize intron retention (IR), the predominant type of AS in plants, on a genome-wide scale. This was done in a natural population consisting of 279 upland cotton lines. Secondly, splice quantitative trait locus (sQTL) analysis was carried out, which yielded a total of 2295 sQTLs involving 1607 genes. Of these, 14.25% (n = 427) were cis-regulatory loci. Integration with expression quantitative trait loci (eQTL) revealed that 53 (21.4%) cis-sGenes were regulated by both cis-sQTLs and cis-eQTLs. Finally, co-localization analysis integrated with GWAS loci in this population showed 32 cis-QTLs to be co-located with genetic regulatory loci related to fiber yield and quality traits, indicating that sQTLs are likely to participate in regulating cotton fiber yield and quality. An in-depth evaluation confirmed that differences in the IR rates of sQTL-regulated candidate genes such as GhLRRK1 and GhGC1 are associated with lint percentage (LP), which has potential in breeding applications.

Conclusion

This study provides a clue that AS of mRNA has an impact on crop yield, along with functional sQTLs are new genetic resources for cotton precision breeding.
The relative value of Pre-Implementation stages for successful implementation of evidence-informed programs
Authors: Alley Zoe M. , Chapman Jason E. , Schaper Holle , Saldana Lisa
Published: July 2023

Background

Most implementations fail before the corresponding services are ever delivered. Measuring implementation process fidelity may reveal when and why these attempts fail. This knowledge is necessary to support the achievement of positive implementation milestones, such as delivering services to clients (program start-up) and competency in treatment delivery. The present study evaluates the extent to which implementation process fidelity at different implementation stages predicts achievement of those milestones.

Methods

Implementation process fidelity data—as measured by the Stages of Implementation Completion (SIC)—from 1287 implementing sites across 27 evidence-informed programs were examined in mixed effects regression models with sites nested within programs. Implementation process fidelity, as measured by the proportion of implementation activities completed during the three stages of the SIC Pre-Implementation phase and overall Pre-Implementation (Phase 1) and Implementation (Phase 2) proportion scores, was assessed as a predictor of sites achieving program start-up (i.e., delivering services) and competency in program delivery.

Results

The predicted probability of start-up across all sites was low at 35% (95% CI [33%, 38%]). When considering the evidence-informed program being implemented, that probability was nearly twice as high (64%; 95% CI [42%, 82%]), and 57% of the total variance in program start-up was attributable to the program. Implementation process fidelity was positively and significantly associated with achievement of program start-up and competency. The magnitude of this relationship varied significantly across programs for Pre-Implementation Stage 1 (i.e., Engagement) only. Compared to other stages, completing more Pre-Implementation Stage 3 (Readiness Planning) activities resulted in the most rapid gains in probability of achieving program start-up. The predicted probability of achieving competency was very low unless sites had high scores in both Pre-Implementation and Implementation phases.

Conclusions

Strong implementation process fidelity—as measured by SIC Pre-Implementation and Implementation phase proportion scores—was associated with sites’ achievement of program start-up and competency in program delivery, with early implementation process fidelity being especially potent. These findings highlight the importance of a rigorous Pre-Implementation process.
Validation of clinical exome sequencing in the diagnostic procedure of patients with intellectual disability in clinical practice
Authors: Ballesta-Martínez María Juliana , Pérez-Fernández Virginia , López-González Vanesa , Sánchez-Soler María José , Serrano-Antón Ana Teresa , Rodríguez-Peña Lidia Isolina , Barreda-Sánchez Maria , Armengol-Dulcet Lluís , Guillén-Navarro Encarna
Published: July 2023

Intellectual disability (ID) has a prevalence of 1–3% and aproximately 30–50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren’t clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.
New retinal findings in NLRP3-associated autoinflammatory disease
Authors: Wei Zhangwanyu , Yang Zhikun , Li Donghui , Zhang Xiao , Li Bing , Zhao Xufeng , Yan Wenyu , Wu Bingxuan , Wu Na , Wang Xuqian , Yu Weihong , Shen Min
Published: July 2023

Purpose

To determine whether the rare NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) is associated with retinal changes and to assess the ocular involvement.

Methods

A retrospective cohort study of 20 patients(40 eyes) diagnosed with rare NLRP3-AID at Peking Union Medical College Hospital, from April 2015 to August 2022. Patients underwent a comprehensive ophthalmological examination, including visual acuity, intraocular pressure examination, slit-lamp examination, fundus photography, optical coherence tomography(OCT), and fluorescence angiography (FA). Some patients also underwent optical coherence tomography angiography (OCTA).

Results

This study analyzed 40 eyes of 20 patients (11 [55.0%] male; median age, 25.0 years [range, 12–52 years]) and 13 patients (26 eyes, 65%) demonstrated ocular involvement. The most common ophthalmologic manifestation was conjunctivitis (22 eyes, 84.6%), followed by papilledema (14 eyes, 53.8%), retinopathy (10 eyes, 38.5%), optic atrophy (6 eyes, 23.1%), uveitis (4 eyes, 15.4%), reduced pupil light reflex (3 eyes, 11.5%) and cataracts (2 eyes, 7.7%). Ocular involvement was bilateral in 11 patients (55.0%). Five kinds of retinal lesions were seen in 5 patients (10 eyes, 25%) with NLRP3-AID, including peripheral retinal vascular leakage, microaneurysms, macular ischemia, macular epiretinal membrane formation and drusen.

Conclusions

Peripheral retinal vascular leakage, macular ischemia, microaneurysms and drusen are newly identified retinal findings in patients with NLRP3-AID, which suggests the importance of detailed retinal examination in these patients.
Optimising DTwP-containing vaccine infant immunisation schedules (OptImms) — a protocol for two parallel, open-label, randomised controlled trials
Authors: Kelly Sarah , Liu Xinxue , Theiss-Nyland Katherine , Voysey Merryn , Murphy Sarah , Li Grace , Nyantaro Mary , Gurung Meeru , Basnet Sudha , Pokhrel Bhishma , Bijukchhe Sanjeev M. , Eordogh Agnes , Gombe Ben , Kakande Ayoub , Kerridge Simon , Kimbugwe Geofrey , Kusemererwa Sylvia , Lubyayi Lawrence , Luzze Henry , Mazur Olga , Mujadidi Yama F. , Nabukenya Shamim , Nagumo Walter-Rodney , Nareeba Tryphena , Noristani Rabiullah , O’Reilly Peter , Roberts Andrew , Shah Ganesh , Shrestha Sonu , Shrestha Laxman P. , Thapa Surya B. , Kibengo Freddie M. , Sharma Arun K. , Elliott Alison , Shrestha Shrijana , Pollard Andrew J.
Published: July 2023

Background

Universal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines.

Methods

The OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety.

Discussion

These data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood.

Trial registrations

ISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).
Mmwave massive MIMO: one joint beam selection combining cuckoo search and ant colony optimization
Authors: Zhu Chunhua , Ji Qinwen , Guo Xinying , Zhang Jiankang
Published: July 2023

In order to degrade the inter-user interference caused by the same beam selected for different users in mmWave massive MIMO systems, this paper proposes a joint beam selection combining cuckoo search (CS) and ant colony optimization (ACO) (referred to as CSACO). Differently from the existing interference-aware beam selection, a candidate beam set (CBS) for all users is created according to the power distribution of the beamspace channel, thereby all users can be classified into non-interfering users (NIUs) and interfering users (IUs), and NIUs will be assigned the beams with large power directly, while for IUs, the beams are selected by the CSACO; in the proposed CSACO, all beams for IUs are regarded as an optimizable individual, which is continuously evolved towards the direction of sum-rate maximization. Simulation results verify that the proposed beam selection can obtain the higher sum-rate and energy efficiency compared with the existing ones.
Resource-efficient channel estimation for DCO-OFDM based VLC systems
Authors: Yu Zichen , Huang Nuo , Li Xu , Wang Wei , Gong Chen
Published: July 2023

We consider a resource-efficient pilot design for visible light
communication (VLC) system employing direct-current offset orthogonal
frequency division multiplexing (DCO-OFDM). Firstly, we experimentally
verify that the normalized channel gain vectors remain approximately
the same at different locations under a line-of-sight (LOS) path
between the transmitter and the receiver. Then, under the constant
normalized subcarrier gain assumption, it is proved that a single
pilot subcarrier is optimal to maximize the achievable rate without
signal clipping. The impact of power budget and statistical channel
characteristics is investigated regarding the optimal pilot position
and the related achievable rate. We extend the pilot position
optimization to a general case considering the light-emitting diode
(LED) and power amplifier (PA) with a limited linear dynamic range.
Assuming double-sided clipping, the impact of LED upper saturation
voltage and statistical channel characteristics on the optimal pilot
position and the achievable rate is investigated via the Bussgang
theorem. Finally, under constant normalized link gain assumption, we
propose a blind channel estimation approach based on the covariance of
frequency-domain outputs. The convergence of the proposed channel
estimation approaches based on constant normalized link gain is
verified experimentally.
Self super-resolution of optical coherence tomography images based on deep learning
Authors: Yuan Zhuoqun , Yang Di , Wang Weike , Zhao Jingzhu , Liang Yanmei
Published: July 2023

As a medical imaging modality, many researches have been devoted to improving the resolution of optical coherence tomography (OCT). We developed a deep-learning based OCT self super-resolution (OCT-SSR) pipeline to improve the axial resolution of OCT images based on the high-resolution and low-resolution spectral data collected by the OCT system. In this pipeline, the enhanced super-resolution asymmetric generative adversarial networks were built to improve the network outputs without increasing the complexity. The feasibility and effectiveness of the approach were demonstrated by experimental results on the images of the biological samples collected by the home-made spectral-domain OCT and swept-source OCT systems. More importantly, we found the sidelobes in the original images can be obviously suppressed while improving the resolution based on the OCT-SSR method, which can help to reduce pseudo-signal in OCT imaging when non-Gaussian spectra light source is used. We believe that the OCT-SSR method has broad prospects in breaking the limitation of the source bandwidth on the axial resolution of the OCT system.
Long-distance indoor optical camera communication using side-emitting fibers as distributed transmitters
Authors: Eöllős-Jarošíková Klára , Neuman Vojtěch , Jurado-Verdú Cristo Manuel , Teli Shivani Rajendra , Zvánovec Stanislav , Komanec Matěj
Published: July 2023

We present a design approach for a long-distance optical camera communication (OCC) system using side-emitting fibers as distributed transmitters. We demonstrate our approach feasibility by increasing the transmission distance by two orders up to 40 m compared to previous works. Furthermore, we explore the effect of the light-emitting diode (LED) modulation frequency and rolling shutter camera exposure time on inter-symbol interference and its effective mitigation. Our proposed OCC-fiber link meets the forward-error-correction (FEC) limit of 3.8 · 10−3 of bit error rate (BER) for up to 35 m (with BER= 3.35 · 10−3) and 40 m (with BER=1.13 · 10−3) using 2-mm and 3-mm diameter side-emitting fibers, respectively. Our results at on-off keying modulation frequencies of 3.54 kHz and 5.28 kHz pave the way to moderate-distance outdoor and long-distance indoor highly-reliable applications in the Internet of Things and OCC using side-emitting fiber-based distributed transmitters.
Antiresonant fiber structures based on swarm intelligence design
Authors: Zhenyu Gu , Tigang Ning , Li Pei , Jing Li , Jingjing Zheng , Wensheng Wang , Wei Jiang , Changzheng Ma , Yong Wang
Published: July 2023

In this work, we obtained a new, to the best of our knowledge, structure of anti-resonant fiber (ARF) by an adaptive particle swarm optimization (PSO) algorithm. Different from the prior method of stacking elemental parts and optimizing parameters through experience or algorithm, we decompose some classic structures into points and optimize the positions of these points through swarm intelligence. The fiber structure is reconstructed by interpolation, and some new structures with low confinement loss (CL) and high higher order mode extinction ratio (HOMER) are obtained. These novel ARFs exhibit similar structural characteristics, and are named as “the bulb-shaped ARFs”. Among these structures, the minimum achieved CL is 2.21 × 10−5dB/m at 1300 nm and the maximum achieved HOMER exceeds 14,000. This work provides a method with high degree of freedom in the design of non-uniform cross-section waveguides and helps to discover new fiber structures.
Improving sea surface floating matter identification from Sentinel-2 MSI imagery using optical radiative simulation of neighborhood difference
Authors: Zhu Xiaobo , Lu Yingcheng , Dou Changyong , Ju Weimin
Published: July 2023

The reflectance difference (ΔR) between a floating matter pixel and a nearby water reference pixel is a method of atmospheric radiation unmixing. This technique unveils target signals by referencing the background within the horizontal neighborhood. ΔR is effective for removing the mixed-pixel effect and partial atmospheric path radiance. However, other atmospheric interference sources in the difference pixel, including atmospheric extinction and sunglint, need to be clarified. To address these challenges, we combined in situ floating matter endmember spectra for simulation and Sentinel-2 Multispectral Instrument (MSI) sensors for validation. We focused on radiative transfer simulation of horizontal neighborhood and vertical atmospheric column, investigating the bilateral conversion of ΔR between bottom-of-atmosphere (BOA) and top-of-atmosphere (TOA) signals, and clarifying how the atmosphere affects the difference pixel (ΔR) and floating matter identification. Results showed that direct use of TOA ΔR works in discriminating algae from non-algae floating matters under weak sunglint, and is a suitable candidate for no bother with atmospheric correction, least uncertain, and wider coverage. And then, sunglint interference is also inevitable, whether serious or not.
SSEA-1 Correlates With the Invasive Phenotype in Breast Cancer
Authors: Kohler Katharina T. , Møller Hansen Anna A. , Kim Jiyoung , Villadsen René
Published: July 2023

The glycan moiety Lewis X (LeX) has been implicated in defining progenitor cells as well as playing a role in the progression of solid tumors, including breast cancer. Here, we used the original stage-specific embryonic antigen-1 (SSEA-1) antibody, MC-480, targeting the LeX motif to examine the expression pattern of this marker within the context of a differentiation hierarchy as well as functional properties of breast cancer cells. Immunohistochemical staining revealed the presence of SSEA-1 in a progenitor zone in the normal breast gland. In breast cancer, 81 of 220 carcinomas (37%) were positive for SSEA-1 and a distinct pattern could be correlated to major subtypes. Specifically, estrogen receptor alpha (ERα)-negative tumors showed a higher frequency of SSEA-1 expression compared to ERα-positive tumors, which are generally considered more differentiated (56% vs 29%, p<0.005). Functional assays performed on two representative breast cancer cell lines demonstrated that SSEA-1-expressing cells exhibited cancer stem cell properties as well as having more invasive potential, regardless of ERα status. A potential role of SSEA-1 in metastasis was confirmed by pairwise staining of primary- and corresponding lymph node tumors. Altogether, our data suggest that expression of SSEA-1 in breast cancer contributes to the malignant phenotype:
Chagas disease is related to structural changes of the gut microbiota in adults with chronic infection (TRIPOBIOME Study)
Authors: Pérez-Molina José A. , Crespillo-Andújar Clara , Trigo Elena , Chamorro Sandra , Arsuaga Marta , Olavarrieta Leticia , Navia Beatriz , Martín Oihane , Monge-Maillo Begoña , Norman Francesca F. , Lanza Val F. , Serrano-Villar Sergio
Published: July 2023

Background

The implications of the gut microbial communities in the immune response against parasites and gut motility could explain the differences in clinical manifestations and treatment responses found in patients with chronic Chagas disease.

Methodology/Principal findings

In this pilot prospective cross-sectional study, we included 80 participants: 29 with indeterminate CD (ICD), 16 with cardiac CD (CCD), 15 with digestive CD (DCD), and 20 controls without CD. Stool was collected at the baseline visit and faecal microbial community structure DNA was analyzed by whole genome sequencing. We also performed a comprehensive dietary analysis. Ninety per cent (72/80) of subjects were of Bolivian origin with a median age of 47 years (IQR 39–54) and 48.3% (29/60) had received benznidazole treatment. There were no substantial differences in dietary habits between patients with CD and controls. We identified that the presence or absence of CD explained 5% of the observed microbiota variability. Subjects with CD exhibited consistent enrichment of Parabacteroides spp, while for Enterococcus hirae, Lactobacillus buchneri and Megamonas spp, the effect was less clear once excluded the outliers values. Sex, type of visceral involvement and previous treatment with benznidazole did not appear to have a confounding effect on gut microbiota structure. We also found that patients with DCD showed consistent Prevotella spp enrichment.

Conclusions

We found a detectable effect of Chagas disease on overall microbiota structure with several potential disease biomarkers, which warrants further research in this field. The analysis of bacterial diversity could prove to be a viable target to improve the prognosis of this prevalent and neglected disease.
Exposure to long wavelength light that improves aged mitochondrial function shifts acute cytokine expression in serum and the retina
Authors: Shinhmar Harpreet , Hogg Chris , Jeffery Glen
Published: July 2023

Aged mitochondrial function can be improved with long wavelength light exposure. This reduces cellular markers of inflammation and can improve system function from fly through to human. We have previously shown that with age there are increases in cytokine expression in mouse serum. Here, we ask what impact 670nm light has on this expression using a 40 cytokine array in blood serum and retina in C57Bl6 mice. 670nm exposure was delivered daily for a week in 12 month old mice. This shifted patterns of cytokine expression in both serum and retina inducing a selective increase. In serum examples of significant increases were found in IL (interleukins) 1α, IL-7, 10, 16, 17 along with TNF-α and CXCL (chemokines) 9 and 10. In retina the increases were again mainly in some IL’s and CXCL’s. A few cytokines were reduced by light exposure. Changes in serum cytokines implies that long wavelengths impact systemically even to unexposed tissues deep in the body. In the context of wider literature, increased cytokine expression may be protective. However, their upregulation by light merits further analysis as cytokines upregulation can also be negative and there are probably complex patterns of interaction in the dynamics of their expression.
Influence of cutting velocity on surface roughness during the ultra-precision cutting of titanium alloys based on a comparison between simulation and experiment
Authors: Lou Yonggou , Chen Lei , Wu Hongbing , To Sandy
Published: July 2023

The Ti-6Al-4V titanium alloy is a kind of light alloy material with high specific strength, corrosion resistance and heat resistance. Because of its excellent performance, it has become an important material in aerospace industry. However, this kind of alloy has very poor machinability, and rapid tool wear is a very serious problem in titanium alloy processing. At present, it is difficult to guarantee the ultra-precision machining quality of titanium alloy materials, which limits its application in high-tech fields. In order to solve this problem, the influence of cutting speed on ultra-precision cutting process of titanium alloy was analyzed comprehensively. and it was found that better surface quality could be obtained at lower cutting speed. In order to study the influence of cutting speed in ultra-precision cutting of titanium alloys, cutting experiments have been carried out. Additionally, a finite element model was established to analyze the ultra-precision cutting process. Also, the constitutive model, damage model, friction model, and heat transfer in the modeling process were discussed. The chip morphology, cutting temperature, cutting force, and surface morphology under different cutting velocities are analyzed by simulation. Then, the simulation results were compared with the experimental results. The findings show that cutting speed has great influence on the ultra-precision turning of the Ti-6Al-4V alloy and the surface roughness obtained by ultra-precision cutting of titanium alloy can be lower than 20 nm at a lower cutting speed.