bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous Monoculture Alters the Fungal Community and Accumulates Potential Pathogenic Strains in the Rhizosphere of Codonopsis pilosula
Authors: Zhao Xia , Liu Yang , Yue Liang , Tian Yuan , Zhou Qin , Wang Yun , Liu Shaofang , Guo Zhihong , Zhang Yubao , Wang Ruoyu
Published: December 2023

Codonopsis pilosula (known as dangshen) is experiencing a serious replant disease caused by continuous monoculture in its main and endemic cultivation region in Dingxi, China. In this study, changes in physicochemical properties, fungal microbiomes, and isolated strains were investigated in the rhizosphere soil of 1-, 2-, 3-, and 5-year continuous monoculture natural fields. It was observed that wilted seedlings and a variety of root rot diseases occurred after the third year of continuous monoculture in the field. The soil-available potassium content and the pH value decreased significantly in the 3- and 5-year fields. Using Illumina sequencing, it was demonstrated that the 3- and 5-year fields had a higher diversity of fungal communities compared with the 1- and 2-year fields. At the genus level, abundance of some potentially pathogenic fungal taxa also increased. A total of 33 isolated strains belonging to the Fusarium species complexes Plectosphaerella cucumerina, Paraphoma ledniceana, Alternaria alstroemeriae, Mucor hiemalis, and Clonostachys rosea were obtained from the roots in 3- and 5-year fields. The correlation analysis revealed that the abundance of the fungal community at the genus level was positively correlated with the available phosphorus, total nitrogen, and soil organic matter. The results revealed that continuous monoculture has a negative impact on the fungal community and enriches potential pathogenic fungi in the rhizosphere of C. pilosula.
DNase aggravates intestinal microvascular injury in IBD patients by releasing NET‐related proteins
Authors: Shao Yiming , Li Linbin , Yang Yunxi , Ye Yulan , Guo Zaiwen , Liu Lu , Huang Jiamin , Chen Yi , Gao Xi , Sun Bingwei
Published: December 2023

Neutrophils accumulate in the inflammatory mucosa of patients with inflammatory bowel disease (IBD), and excessive release of NETs (neutrophil extracellular traps may be one of the important factors that cause IBD progression. However, the specific mechanism underlying vascular injury caused by NETs remains unclear. Immunofluorescence, ELISA, and flow cytometry were used in this study to detect the expression of NETs and DNase in the tissue and peripheral blood samples of patients with IBD. DSS mouse model was used to detect colon injury and vascular permeability. We found that NETs and DNase levels increased in the colon of patients with IBD. We found an increase in the activity of NET‐related MPO released by DNase. DNase released NET‐related proteins and damaged vascular endothelial cells in vitro. In DSS mouse model, the synchronous increase of DNase and NETs in the colon leads to an increase in vascular injury markers (CD44, sTM). DNase aggravated colon injury and increased vascular permeability in vivo, which was inhibited by gentamicin sulfate (GS). GS does not reduce the expression of DNase, but rather reduces the release of NET‐related proteins to protect vascular endothelium by inhibiting DNase activity. MPO and histones synergistically damaged the vascular endothelium, and vascular injury can be improved by their active inhibitors. We further found that H2O2 is an important substrate for MPO induced vascular damage. In conclusion, in IBD, DNase, and NET levels increased synchronously in the lesion area and released NET‐related proteins to damage the vascular endothelium. Therefore, targeting DNase may be beneficial for the treatment of IBD.
Evaluation of the Ask-Inform-Manage-Encourage-Refer Intervention and Its Implementation Targeting the Provision of Mental Wellbeing Support Within the Audiology Setting
Authors: Bennett Rebecca J. , Bucks Romola S. , Saulsman Lisa , Pachana Nancy A. , Eikelboom Robert H. , Meyer Carly J.
Published: December 2023

Objectives:

The ask, inform, manage, encourage, refer (AIMER) program is a behavior change intervention designed to increase the frequency with which hearing healthcare clinicians (HHCs) ask about and provide information regarding mental wellbeing within adult audiology services. The objective of this study was to systematically evaluate the first iteration of the AIMER program to determine whether the intervention achieved the changes in HHC behaviors anticipated and to evaluate feasibility of implementing the AIMER program based on the implementation protocol.

Design:

The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to guide this evaluation. Data were collected from October 2020 to February 2022 and included both quantitative and qualitative measures (i.e., observation reports, staff surveys, clinical diaries, clinical file audits, and interviews).

Results:

Comparison between pre- and post-implementation data showed that the AIMER intervention successfully increased: (i) HHC’s skills and confidence for discussing mental wellbeing; (ii) how often HHCs ask about mental wellbeing within audiology consultations; (iii) how often HHCs provide personalized information and support regarding mental wellbeing within audiology consultations; and (iv) how often HHCs use mental wellbeing terms within clinical case notes and general practitioner reports. The factors affecting feasibility of implementing the AIMER program within the clinical setting could be classified into three major categories: (i) the AIMER program itself and its way of delivery to clinical staff; (ii) people working with the AIMER program; and (iii) contextual factors. Key recommendations to improve future implementation of the AIMER program were provided by the participants.

Conclusions:

The AIMER program was shown to be effective at increasing the frequency with which HHCs ask about and provide information regarding mental wellbeing within routine audiological service delivery. Implementation of the AIMER program was feasible but leaves room for improvement. Use of the reach, effectiveness, adoption, implementation, and maintenance framework facilitated systematic evaluation of multiple indicators providing a broad evaluation of the AIMER program. Our analysis helps to better understand the optimal levels of training and facilitation and provides recommendations to improve future scale-up of the AIMER program. The findings of this study will be used to further adapt and improve the AIMER program and to enhance program implementation strategies before its further dissemination.
Partial DMEK Donor Removal as a Successful Treatment of Donor-Related Fungal Keratitis
Authors: Yalamanchili Siri P. , Cleary Sean M. , Sell Shawn S. , Eden Robert A. , Schultze Robert L.
Published: December 2023

An 84-year-old woman with Fuchs dystrophy underwent uncomplicated Descemet membrane endothelial keratoplasty in her right eye (OD). Donor rim culture returned positive for Candida albicans with no signs of clinical infection until postoperative week (POW) 14 when the patient noted new eye pain and photosensitivity in the OD. Examination revealed 3+ cells without hypopyon and 2 infiltrates localized to a small peripheral area of previously noted clinically insignificant inferior donor graft scrolling. Anterior chamber tap of the OD was performed, which showed no fungal growth. The patient was administered topical fortified voriconazole 1% 6 times a day and oral voriconazole 200 mg twice a day. On day 3, the infiltrate enlarged, and intracameral amphotericin (0.15 mg/mL, 0.1 cc) was injected. On day 6 with progression of the infiltrate, a partial donor descemetorhexis to remove the infiltrate and intracameral injection of voriconazole (0.25 mg/mL, 0.1 cc) were performed. Culture from the partially removed graft was positive for C. albicans. Vision improved to logMAR 0.18 (Snellen 20/30) with no evidence of recurrence to postoperative month 10. To the best of our knowledge, this is the first case of late-onset Candida interface keratitis successfully treated with a partial descemetorhexis.
Decreased platelet activation predicts hepatic decompensation and mortality in patients with cirrhosis
Authors: Hofer Benedikt S. , Brusilovskaya Ksenia , Simbrunner Benedikt , Balcar Lorenz , Eichelberger Beate , Lee Silvia , Hartl Lukas , Schwabl Philipp , Mandorfer Mattias , Panzer Simon , Reiberger Thomas , Gremmel Thomas
Published: December 2023

Background and Aims:

Patients with cirrhosis show alterations in primary hemostasis, yet prognostic implications of changes in platelet activation remain controversial, and assay validity is often limited by thrombocytopenia. We aimed to study the prognostic role of platelet activation in cirrhosis, focusing on bleeding/thromboembolic events, decompensation, and mortality.

Approach and Results:

We prospectively included 107 patients with cirrhosis undergoing a same-day hepatic venous pressure gradient (HVPG) and platelet activation measurement. Platelet activation was assessed using flow cytometry after protease-activated receptor (PAR)-1, PAR-4, or epinephrine stimulation. Over a follow-up of 25.3 (IQR: 15.7–31.2) months, first/further decompensation occurred in 29 patients and 17 died. More pronounced platelet activation was associated with an improved prognosis, even after adjusting for systemic inflammation, HVPG, and disease severity. Specifically, higher PAR-4–inducible platelet activation was independently linked to a lower decompensation risk [adjusted HR per 100 MFI (median fluorescence intensity): 0.95 (95% CI: 0.90–0.99); p=0.036] and higher PAR-1-inducible platelet activation was independently linked to longer survival [adjusted HR per 100 MFI: 0.93 (95% CI: 0.87–0.99); p=0.040]. Thromboembolic events occurred in eight patients (75% nontumoral portal vein thrombosis [PVT]). Higher epinephrine-inducible platelet activation was associated with an increased risk of thrombosis [HR per 10 MFI: 1.07 (95% CI: 1.02–1.12); p=0.007] and PVT [HR per 10 MFI: 1.08 (95% CI: 1.02–1.14); p=0.004]. In contrast, of the 11 major bleedings that occurred, 9 were portal hypertension related, and HVPG thus emerged as the primary risk factor.

Conclusions:

Preserved PAR-1- and PAR-4–inducible platelet activation was linked to a lower risk of decompensation and death. In contrast, higher epinephrine-inducible platelet activation was a risk factor for thromboembolism and PVT.
HYDROXYCHLOROQUINE CAN BE RESUMED WITH CLOSE MONITORING AFTER RETINOPATHY HAS DEVELOPED, WITHOUT MAJOR VISUAL LOSS: CASE REPORT
Authors: Sunness Janet S. , Sunness Rivka Hadassah , Hellmann David B.
Published: December 2023

Purpose:

The aim of this study was to present a patient with systemic lupus erythematosus on longstanding hydroxychloroquine (HCQ) use for whom HCQ was stopped because of signs of toxicity and then resumed four years later because of dire systemic need.

Methods:

This is a long-term retrospective study. Humphrey visual fields (10-2 and 24-2), fundus autofluorescence imaging, and spectral domain optical coherence tomography (OCT) were used to follow progression over time.

Results:

The patient was on HCQ for 26 years, with a cumulative dose over 3,000 g. HCQ was stopped in 2011 because of macular toxicity. She remained off HCQ for four years, during which time she developed type 1 diabetes due to an immunologic attack on the pancreas and then JC (John Cunningham) viremia after a period of treatment with mycophenolate, which put her at risk for progressive multifocal leukoencephalopathy. Mycophenolate was discontinued, and HCQ was resumed with careful follow-up over the next 7 years. The toxic maculopathy showed only mild slow progression since HCQ was resumed.

Conclusion:

Careful annual monitoring using Humphrey visual field 10-2 and spectral domain OCT imaging remains the standard of care for the patients on HCQ. However, it may be possible with close monitoring when there is compelling systemic need to resume HCQ after it has been stopped, with only slow progression of the retinopathy. This allowed the patient to have an improved quality of life and reduced the risk of severe morbidity and mortality.
The application of cardiac magnetic resonance imaging (CMR) in myocarditis after COVID-19 vaccines : Case series from single medical center in Taiwan
Authors: Wang Yu-Hsiang , Lu Ya-Wen , Chan Si-Wa , Kuo Ling , Chen Shih-Ann
Published: December 2023

During the coronavirus disease 2019 (COVID-19) pandemic, reports of vaccine-induced myocarditis, particularly messenger ribonucleic acid (mRNA)-based myocarditis, were widely spread. This case series describes various cases of COVID-19 vaccine-induced myocarditis confirmed by cardiac magnetic resonance imaging (MRI), including those who were administered rare protein-based vaccines. Eleven patients comprising eight males and three females with suspected myocarditis underwent cardiac MRI at Taichung Veterans General Hospital between October 2021 and May 2022. The median age of the patients was 33.5 years old (range: 22-57 years). The onset of myocarditis was mainly observed following mRNA vaccine inoculation. One patient received the MVC-COV1901 vaccine, a unique protein-based COVID-19 vaccine in Taiwan, and met the 2018 Lake Louise Criteria for the diagnosis of myocarditis, confirmed by cardiac MRI. Most patients reported chest discomfort after receiving various vaccine types. Among four patients with reduced left ventricular ejection fraction (LVEF), two showed LVEF restoration during the follow-up period, and the other two were lost to follow-up. Cardiac MRI characterizes myocardial features such as edema, inflammation, and fibrosis, and has been proven to diagnose myocarditis accurately with a sensitivity of 87.5% and a specificity of 96.2% according to the 2018 Lake Louise criteria. This diagnosis was achieved without invasive procedures such as endomyocardial biopsy or coronary angiography.
Self-Measured Blood Pressure Monitoring During the COVID-19 Pandemic: Perspectives From Community Health Center Clinicians
Authors: Meador Margaret , Sachdev Neha , Anderson Eboni , Roy Debosree , Bay R. Curtis , Becker Lauren H. , Lewis Joy H.
Published: December 2023

The early period of the COVID-19 pandemic necessitated a rapid increase in out-of-office care. To capture the impact from COVID-19 on care for patients with hypertension, a questionnaire was disseminated to community health center clinicians. The extent, types, and causes of care delays and disruptions were assessed along with adaptations and innovations used to address them. Clinician attitudinal changes and perspectives on future hypertension care were also assessed. Of the 65 respondents, most (90.8%) reported their patients with hypertension experienced care delays or disruptions, including lack of follow-up, lack of blood pressure assessment, and missed medication refills or orders. To address care delays and disruptions for patients with hypertension, respondents indicated that their health center increased the use of telehealth or other technology, made home blood pressure devices available to patients, expanded outreach and care coordination, provided medication refills for longer periods of time, and used new care delivery options. The use of self-measured blood pressure monitoring (58.5%) and telehealth (43.1%) was identified as the top adaptations that should be sustained to increase access to and patient engagement with hypertension care; however, barriers to both remain. Policy and system level changes are needed to support value-based care models that include self-measured blood pressure and telehealth.
Youth Preseason Performance on the Sport Concussion Assessment Tool 5 Across Multiple Sports
Authors: Leggett Benjamin , Eliason Paul , Sick Stacy , Burma Joel S. , Wong Sophie K. , Laperrière David , Goulet Claude , Fremont Pierre , Russell Kelly , Schneider Kathryn J. , Emery Carolyn A.
Published: December 2023

Objective:

To examine preseason Sport Concussion Assessment Tool 5 (SCAT5) performance of adolescent sport participants by environment (in-person/virtual), sex, age, concussion history, collision/noncollision sport participation, and self-reported medical diagnoses.

Design:

Cross-sectional.

Setting:

Canadian community and high-school sport settings.

Participants:

Three thousand eight hundred five adolescent (2493 male, 1275 female, and 37 did not disclose; 11- to 19-year-old) sport participants.

Assessment of Risk Factors:

Sport Concussion Assessment Tool 5 administration method (in-person/virtual), sex (male/female/unreported), age (years), concussion history (0/1/2/3+), collision/noncollision sport participant, and self-reported medical diagnoses [attention deficit disorder or attention-deficit/hyperactivity disorder, headache/migraine, learning disability, and psychiatric disorder (ie, anxiety/depression/other)].

Outcome Measures:

Preseason SCAT5 outcomes including total number of symptoms (TNS; /22), symptom severity score (SSS; /132), Standardized Assessment of Concussion (SAC; /50), and modified Balance Error Scoring System (mBESS; /30).

Results:

Multiple multilevel linear or Poisson regression complete case analyses adjusting for clustering and robust standard errors, with β-coefficients (95% CI) back-transformed to indicate an increase/decrease in SCAT5 subdomains when relevant for clinical interpretation. Virtual (V) performance was associated with fewer symptoms reported [TNSDifference V-IP= −1.53 (95% CI, −2.22 to −0.85)], lower SSS [−2.49 (95% CI, −4.41 to −0.58)], and fewer mBESS errors (IP) [−0.52 (95% CI, −0.77 to −0.27)] compared with in-person. For every one-year increase in age, more symptoms [TNS = 0.22 (95% CI, 0.01-0.44)], higher SSS [0.52 (95% CI, 0.01-1.06)], higher SAC [0.27 (95% CI, 0.15-0.38), and poorer balance [mBESS = −0.19 (−0.28 to −0.09)] were observed. Differences between males and females were also seen across all SCAT5 outcomes. Individuals reporting any medical diagnosis or 3+ concussion history also reported more symptoms (TNS) and higher SSS than those who did not.

Conclusions:

Administration environment, sex, age, concussion history, and medical diagnoses were associated with SCAT5 subdomains and are important considerations when interpreting the SCAT5 results.
Comparison of the Utility of PI-RADS 2.1, ADC Values, and Combined Use of Both, for the Diagnosis of Transition Zone Prostate Cancers
Authors: Liu Xinghua , Xiong Qiuxia , Zeng Wenbing , Yang Ran , Wen Yun , Li Xiang
Published: December 2023

Objective

To assess the performance of apparent diffusion coefficient (ADC; values or category) alone, Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) scoring alone, and the two in combination, to diagnose transition zone prostate cancers (PCas).

Methods

This retrospective study included 222 patients who underwent multiparametric magnetic resonance imaging of the prostate between May 2020 and December 2022 and who had pathologically confirmed PCa or benign prostatic hyperplasia (BPH). Prostate Imaging Reporting and Data System version 2.1 and ADC (values or category) were used in the assessment of suspicious findings identified in the transition zone. The interobserver agreements for region-of-interest measurements were calculated by intraclass correlation coefficients. Logistic regression analyses were used to determine the performance of PI-RADS v2.1 alone and in combination with ADC (values or category) to diagnose PCa. Receiver operating characteristic curve and DeLong test were used to evaluate the diagnostic performance of the quantitative parameters.

Results

A total of 152 patients had BPH, and 70 patients had PCa. For BPH versus PCa, the ADC values of PCa (0.64 × 10−3 ± 0.16 × 10−3 mm2/s) were significantly lower than BPH (1.06 ± 0.18 × 10−3 mm2/s; P < 0.001). The PI-RADS scores for PCa (5 [interquartile range, 5–5]) were significantly higher than BPH (2 [interquartile range, 2–3]; P < 0.001). For all patients who had PI-RADS 1–5, the combined use of ADC (values or category) together with PI-RADS v2.1 did not perform significantly better than the use of PI-RADS v2.1 alone. The receiver operating characteristic of ADC category in combination with PI-RADS v2.1 score, 0.756 (95% confidence interval, 0.646–0.846), was significantly higher than that for PI-RADS 2.1 alone, 0.631 (95% confidence interval, 0.514–0.738), in PI-RADS 3–4 lesions (P = 0.047).

Conclusion

The ADC category can help to improve the diagnostic performance of PI-RADS v2.1 category 3–4 lesions in diagnosing PCa.
Distinct Molecular Processes Mediate Donor-derived Cell-free DNA Release From Kidney Transplants in Different Disease States
Authors: Gauthier Patrick T. , Madill-Thomsen Katelynn S. , Demko Zachary , Prewett Adam , Gauthier Philippe , Halloran Philip F. ,   the Trifecta-Kidney Investigators
Published: December 2023

Background.

Among all biopsies in the Trifecta-Kidney Study (ClinicalTrials.gov NCT04239703), elevated plasma donor-derived cell-free DNA (dd-cfDNA) correlated most strongly with molecular antibody–mediated rejection (AMR) but was also elevated in other states: T cell–mediated rejection (TCMR), acute kidney injury (AKI), and some apparently normal biopsies. The present study aimed to define the molecular correlates of plasma dd-cfDNA within specific states.

Methods.

Dd-cfDNA was measured by the Prospera test. Molecular rejection and injury states were defined using the Molecular Microscope system. We studied the correlation between dd-cfDNA and the expression of genes, transcript sets, and classifier scores within specific disease states, and compared AMR, TCMR, and AKI to biopsies classified as normal and no injury (NRNI).

Results.

In all 604 biopsies, dd-cfDNA was elevated in AMR, TCMR, and AKI. Within AMR biopsies, dd-cfDNA correlated with AMR activity and stage. Within AKI, the correlations reflected acute parenchymal injury, including cell cycling. Within biopsies classified as MMDx Normal and archetypal No injury (NRNI), dd-cfDNA still correlated significantly with rejection- and injury-related genes. TCMR activity (eg, the TCMRProb classifier) correlated with dd-cfDNA, but within TCMR biopsies, top gene correlations were complex and not the top TCMR-selective genes.

Conclusions.

In kidney transplants, elevated plasma dd-cfDNA is associated with 3 distinct molecular states in the donor tissue: AMR, recent parenchymal injury (including cell cycling), and TCMR, potentially complicated by parenchymal disruption. Moreover, subtle rejection- and injury-related changes in the donor tissue can contribute to dd-cfDNA elevations in transplants considered to have no rejection or injury.
Target-enhanced whole-genome sequencing (TE-WGS) shows clinical validity equivalent to commercially available targeted oncology panel
Authors: Lee Sangmoon , Roh Jin , Park Jun Sung , Tuncay Islam Oguz , Lee Wonchul , Kim Jung-Ah , Oh Brian Baek-Lok , Shin Jong-Yeon , Lee Jeong Seok , Ju Young Seok , Kim Ryul , Park Seongyeol , Koo Jaemo , Park Hansol , Lim Joonoh , Connolly-Strong Erin , Kim Tae-Hwan , Choi Yong Won , Ahn Mi Sun , Lee Hyun Woo , Kim Seokhwi , Kim Jang-Hee , Kwon Minsuk
Published: December 2023

Cancer poses a significant global health challenge, with increasing incidence rates demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the potential medical application of WGS.

Methods

This study evaluates the power of target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. A cohort of forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches currently used in the clinic.

Results

TE-WGS methods detected all the variants reported from TSO500 (100%, 498/498). A high correlation in the detection of variant allele fractions (VAF) was observed between the TE-WGS and TSO500 methodologies (r=0.977). Notably, within the pool of 498 variants commonly detected by both approaches, 223 variants (44.8%) were discerned within peripheral blood samples exclusively through the TE-WGS technique, suggesting their presence as constitutional variants inherent to the germline. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS method, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion-genes, MSI- and homologous-recombination deficiency (HRD) scores, which were essential for clinical decision making.

Conclusion

TE-WGS proves to be a comprehensive approach in personalized oncology, matching the key biomarker detection capabilities of the established TSO500 panel. Additionally, TE-WGS uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness further underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.
Anemia in Pregnant Women as a Cultural Phenomenon: A Literature Review
Authors: Aden Christine , Pandin Moses Glorino Rumambo , Nursalam Nursalam
Published: December 2023

Background

Explores how restrictions on food intake during pregnancy, due to cultural taboos, can lead to anemia. The study aims to provide an overview of prohibited food types, the supportive environment, the impact on pregnancy, and interventions that can be implemented to overcome anemia.

Method

The authors conducted a literature review by searching for articles on five databases, namely Science Direct, Springer Link, Pubmed, Sage, and Scopus. They also searched for suitable articles from other references, mainly journal articles published in the last five years (2019-2023).

Results

In total, there were 20 reviewed explaining the types of food prohibited during pregnancy and the reasons for this as well as support from family, religious figures, mothers, and in-laws. Overcoming anemia in pregnant women with a cultural approach resulted in meaningful results, with the intervention carried out for around three months. The use of picture books that are appropriate to the cultural context and local wisdom increases information about the importance of iron for pregnant women, increases the frequency of eating, the number of iron tablet intakes, the amount of food intake containing iron each day, and increases the baby’s birth weight.

Conclusion

Anemia caused by cultural taboos on certain foods during pregnancy can be prevented and treated with local wisdom intervention approaches.
State-of-the-RNArt: benchmarking current methods for RNA 3D structure prediction
Authors: Bernard Clément , Postic Guillaume , Ghannay Sahar , Tahi Fariza
Published: December 2023

RNAs are essential molecules involved in numerous biological functions. Understanding RNA functions requires the knowledge of their 3D structures. Computational methods have been developed for over two decades to predict the 3D conformations from RNA sequences. These computational methods have been widely used and are usually categorised as eitherab initioor template-based. The performances remain to be improved. Recently, the rise of deep learning has changed the sight of novel approaches. Deep learning methods are promising, but their adaptation to RNA 3D structure prediction remains difficult. In this paper, we give a brief review of theab initio, template-based and novel deep learning approaches. We highlight the different available tools and provide a benchmark on nine methods using the RNA-Puzzles dataset. We provide an online dashboard that shows the predictions made by benchmarked methods, freely available on the EvryRNA platform:https://evryrna.ibisc.univ-evry.fr/evryrna/state_of_the_rnart/
Recent cross-sectional prevalence studies in sub-Saharan Africa for communicable, maternal, neonatal, and nutritional diseases and conditions: a scoping review
Authors: Dolley S , Miller C , Quach P , Norman T
Published: December 2023

Background

Cross-sectional prevalence studies provide benefits to policymakers, epidemiologists, trialists, and the future health of target and general populations. Too few of these studies are performed in hotspots of traditional global health disease burden. This results in a lack of recent, local, accurate prevalence estimates to inform policy, epidemiology, and the design of interventional randomized controlled trials that may be conducted in these regions.

Objective

This scoping review aims to establish a novel dataset usable as an observational baseline. The topic being analyzed is the set of characteristics describing recently published prospective cross-sectional prevalence studies in sub-Saharan Africa for humans affected with communicable, maternal, neonatal, and nutritional diseases and conditions.

Methods

This scoping review conducted a systematic literature search of PubMed. The search identified publications in the last four years describing completed cross-sectional prevalence studies in sub-Saharan Africa. Title and abstract screening was completed. Data extraction was performed on a random sample of the final dataset.

Results

This scoping review identified 868 titles and abstracts through our systematic search. Through our screening process, 394 of these were candidates eligible for inclusion in our dataset. Ultimately, 363 were in the final dataset. Of the 38 studies in the random sample, this scoping review found a large portion of the studies completed with no funding. Malaria was the predominant disease studied, followed by parasitic intestinal infection and malnutrition. Studies with funding were slower, from data collection to submission to a journal, than studies with no funding. Studies that use a national ethical review process tend to take longer than those using hospital or university institutional review boards.

Conclusions

Cross-sectional prevalence studies are happening in sub-Saharan Africa for many communicable, maternal, neonatal, and nutritional diseases and conditions. This healthy research ecosystem is filled with variety. A variety of data collection methods, sources of funding, types of study sites, and target populations exist. Many studies are self-funded by the principal investigator. These studies are rarely conducted for the explicit purpose of informing the designs of future randomized trials. Some trends might be observable in the data that point to causal factors for study speed or sample size.
Pathogenesis of Multiple Sclerosis: Genetic, Environmental, and Random Mechanisms
Authors: Goodin Douglas S.
Published: December 2023

BACKGROUND

MS-pathogenesis requires both genetic factors and environmental events. The question remains, however, whether these factors and eventscompletelydescribe the MS disease-process. This question was addressed using the Canadian MS-data, which includes 29,478 individuals, representing 65-83% of all Canadian MS-patients.

METHODS

The “genetically-susceptible” subset of the population, (G), includeseveryonewho hasany non-zerolife-time chance of developing MS, undersomeenvironmental-conditions. A “sufficient” environmental-exposure, forany“genetically-susceptible” individual, includeseveryset of environmental conditions, each of which issufficient, by itself, tocauseMS in that person. This analysis incorporates several differentepidemiologic-parameters, involved in MS-pathogenesis, only some of which are directly-observable, and establishes “plausible-value-ranges”for each parameter. Thoseparameter-valuecombinations (solutions) that fall within theseplausible-rangesare then determined.

RESULTS

Only a fraction of the population can possibly be “genetically-susceptible”. Thus, many individuals haveno possibilityof developing MS underanyenvironmental conditions. Moreover,some“genetically-susceptible” individuals, despite their experiencing a “sufficient” environmental-exposure,will neverdevelop disease.

CONCLUSIONS

This analysisexplicitly includesall of those genetic factors and environmental events (including interactions), which are necessary for MS-pathogenesis, regardless of whether these are known, suspected, or as yet unrecognized. Nevertheless, in addition, “true” randomness seems to play a critical role in disease-pathogenesis. This observation provides empirical evidence that undermines the widely-held deterministic view of nature. Moreover, both sexes seem to have a similar genetic and environmental disease-basis. If so, this indicates that this random element is primarily responsible for the currently-observed differences in disease-expression betweensusceptible-womenandsusceptible-men.
Characterization and Mitigation of a Simultaneous Multi-Slice fMRI Artifact: Multiband Artifact Regression in Simultaneous Slices
Authors: Tubiolo Philip N. , Williams John C. , Van Snellenberg Jared X.
Published: December 2023

Simultaneous multi-slice (multiband) acceleration in fMRI has become widespread, but may be affected by novel forms of signal artifact. Here, we demonstrate a previously unreported artifact manifesting as a shared signal between simultaneously acquired slices in all resting-state and task-based multiband fMRI datasets we investigated, including publicly available consortium data from the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) Study. We propose Multiband Artifact Regression in Simultaneous Slices (MARSS), a regression-based detection and correction technique that successfully mitigates this shared signal in unprocessed data. We demonstrate that the signal isolated by MARSS correction is likely non-neural, appearing stronger in neurovasculature than grey matter. Additionally, we evaluate MARSS both against and in tandem with sICA+FIX denoising, which is implemented in HCP resting-state data, to show that MARSS mitigates residual artifact signal that is not modeled by sICA+FIX. MARSS correction leads to study-wide increases in signal-to-noise ratio, decreases in cortical coefficient of variation, and mitigation of systematic artefactual spatial patterns in participant-level task betas. Finally, MARSS correction has substantive effects on second-level t-statistics in analyses of task-evoked activation. We recommend that investigators apply MARSS to multiband fMRI datasets with moderate or higher acceleration factors, in combination with established denoising methods.
Effects of Probiotics, Glucose Oxidase and its Combination on Immune Function, Antioxidant Status, Serum Biochemical Incides and Toxin Residue in Sheep when Challenged with Aflatoxin B1
Authors: Zhang Yu , Lu Henan , Erdene-Khas  , Zhang Caixia , Wang Hairong
Published: December 2023

The objective of this study was to investigate the ability of a mixed mycotoxins detoxification agent (probiotics, Glucose oxidase (GOD) and its combination) to alleviate the toxicity of aflatoxin B1 (AFB1) by assessing growth performance, serum toxin residue, immune function, antioxidant status and serum biochemical indices of sheep. Twenty 8-month-old Mongolian sheep were randomly assigned to 1-5 diet treatment groups: 1) the control (CON) group: basal diet; 2) the AFB1 (A) group: CON + 0.2 mg/kg AFB1; 3) the AFB1 and probiotics (AP) group: A + 0.5% probiotics; 4) the AFB1 and GOD (AG) group: A + 0.5% GOD; 5) the AFB1, probiotics, and GOD (APG) group: A + 0.5% probiotics + 0.5% GOD. Results showed that treatment A adversely affected the health and performance of sheep. However, the treatments AP, AG, or APG exerted a positive effect on health, performance and other indications. In conclusion, probiotics, GOD, and its combination induced injury of Mongolian sheep by alleviating the negative effects of AFB1 on the production performance, immune indexes, antioxidant indexes, and serum biochemical indexes and effectively reducing serum toxin residue.

Key Contribution

The study investigated the effects of probiotics, Glucose oxidase and its combination on serum detoxification of AFB1 by assessing growth performance, serum toxin residue, immune function, antioxidant status and blood biochemical indices of sheep. AFB1 - contaminated diets supplemented with probiotics and GOD were effective in improving growth performance, immunity, antioxidant function, liver function, and decreasing serum AFB1 residue of sheep.
Generating single-cell gene expression profiles for high-resolution spatial transcriptomics based on cell boundary images
Authors: Zhang Bohan , Li Mei , Kang Qiang , Deng Zhonghan , Qin Hua , Su Kui , Feng Xiuwen , Chen Lichuan , Liu Huanlin , Fang Shuangsang , Zhang Yong , Li Yuxiang , Brix Susanne , Xu Xun
Published: December 2023

Stereo-seq is a cutting-edge technique for spatially resolved transcriptomics that combines subcellular resolution with centimeter-level field-of-view, serving as a technical foundation for analyzing large tissues at the single-cell level. Our previous work presents the first one-stop software that utilizes cell nuclei staining images and statistical methods to generate high-confidence single-cell spatial gene expression profiles for Stereo-seq data. With recent advancements in Stereo-seq technology, it is possible to acquire cell boundary information, such as cell membrane/wall staining images. To take advantage of this progress, we update our software to a new version, named STCellbin, which utilizes the cell nuclei staining images as a bridge to align cell membrane/wall staining images with spatial gene expression maps. By employing an advanced cell segmentation technique, accurate cell boundaries can be obtained, leading to more reliable single-cell spatial gene expression profiles. Experimental results verify that STCellbin can be applied on the mouse liver (cell membranes) andArabidopsisseed (cell walls) datasets and outperforms other competitive methods. The improved capability of capturing single cell gene expression profiles by this update results in a deeper understanding of the contribution of single cell phenotypes to tissue biology.

Availability & Implementation

The source code of STCellbin is available athttps://github.com/STOmics/STCellbin.
Portable Multi-focal Visual Evoked Potential Diagnostics for Multiple Sclerosis/Optic Neuritis patients
Authors: Banijamali S. Mohammad Ali , Versek Craig , Babinski Kristen , Kamarthi Sagar , Green-LaRoche Deborah , Sridhar Srinivas
Published: December 2023

Purpose

Multiple Sclerosis (MS) is a neuro-inflammatory disease of the Central Nervous System (CNS) in which the body’s immune system attacks and destroys myelin sheath that protects nerve fibers and causes disruption in axonal signal transmission. Demyelinating Optic Neuritis (ON) is often a manifestation of MS and involves inflammation of the optic nerve. ON can cause vision loss, pain and discomfort in the eyes, and difficulties in color perception.

In this study, we developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from near the O1, Oz, O2, O9 and O10 locations on the scalp (extended 10-20 system) using custom electroencephalography (EEG) electrodes.

Methods

Each test session is constituted by a short 2.5-minute full-field visual evoked potentials (ffVEP) test, followed by a 12.5-minute multifocal VEP (mfVEP) test. The ffVEP test evaluates the integrity of the visual pathway by analyzing the P1 (also known as P100) component of responses from each eye, while the mfVEP test evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEP responses. The results of the ffVEP test for patients were evaluated against normative data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification.

Results

20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging (MRI) and Optical Coherence Tomography (OCT) findings.

Conclusion

This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.
Optimal distance metrics for single-cell RNA-seq populations
Authors: Ji Yuge , Green Tessa D. , Peidli Stefan , Bahrami Mojtaba , Liu Meiqi , Zappia Luke , Hrovatin Karin , Sander Chris , Theis Fabian J.
Published: December 2023

In single-cell data workflows and modeling, distance metrics are commonly used in loss functions, model evaluation, and subpopulation analysis. However, these metrics behave differently depending on the source of variation, conditions and subpopulations in single-cell expression profiles due to data sparsity and high dimensionality. Thus, the metrics used for downstream tasks in this domain should be carefully selected. We establish a set of benchmarks with three evaluation measures, capturing desirable facets of absolute and relative distance behavior. Based on seven datasets using perturbation as ground truth, we evaluated 16 distance metrics applied to scRNA-seq data and demonstrated their application to three use cases. We find that linear metrics such as mean squared error (MSE) performed best across our three evaluation criteria. Therefore, we recommend the use of MSE for comparing single-cell RNA-seq populations and evaluating gene expression prediction models.
Highly multiplexed, image-based pooled screens in primary cells and tissues with PerturbView
Authors: Kudo Takamasa , Meireles Ana M. , Moncada Reuben , Chen Yushu , Wu Ping , Gould Joshua , Hu Xiaoyu , Kornfeld Opher , Jesudason Rajiv , Foo Conrad , Höckendorf Burkhard , Bravo Hector Corrada , Town Jason P. , Wei Runmin , Rios Antonio , Chandrasekar Vineethkrishna , Heinlein Melanie , Cai Shuangyi , Lu Cherry Sakura , Celen Cemre , Kljavin Noelyn , Jiang Jian , Hleap Jose Sergio , Kayagaki Nobuhiko , de Sousa e Melo Felipe , McGinnis Lisa , Li Bo , Singh Avtar , Garraway Levi , Rozenblatt-Rosen Orit , Regev Aviv , Lubeck Eric
Published: December 2023

Optical pooled screening (OPS) is a highly scalable method for linking image-based phenotypes with cellular perturbations. However, it has thus far been restricted to relatively low-plex phenotypic readouts in cancer cell lines in culture, due to limitations associated within situsequencing (ISS) of perturbation barcodes. Here, we developed PerturbView, an OPS technology that leveragesin vitrotranscription (IVT) to amplify barcodes prior to ISS, enabling screens with highly multiplexed phenotypic readouts across diverse systems, including primary cells and tissues. We demonstrate PerturbView in iPSC-derived neurons, primary immune cells, and tumor tissue sections from animal models. In a screen of immune signaling pathways in primary bone marrow-derived macrophages, PerturbView uncovered both known and novel regulators of NFκB signaling. Furthermore, we combined PerturbView with spatial transcriptomics in tissue sections from a mouse xenograft model, paving the way toin vivoscreens with rich optical and transcriptomic phenotypes. PerturbView broadens the scope of OPS to a wide range of models and applications.
The Anti-inflammatory Drug Leflunomide Inhibits NS2B3 Cluster Formation During Dengue Viral Infection as Revealed by Single Molecule Imaging
Authors: Varghese Jiby Mary , Aravinth S , Pant Neeraj , Mondal Partha Pratim
Published: December 2023

A prerequisite for Dengue viral infection is the clustering of NS2B3 viral protein in the infected cell. This calls for drugs capable of reversing the biological processes leading to the declustering of NS2B3 viral complex. In this work, we report a new drug (leflunomide) that shows reversal of NS2B3 clustering, post 24 hours of cell transfection with a recombinant probe (Dendra2-NS2B3) containing the viral complex of interest (NS2B3). To study, we constructed a photoactivable recombinant plasmid for visualizing the activity of the target protein-of-interest (Dendra2-NS2B3). This enabled a better understanding of the underlying biological processes involved in Dengue and the role of NS2B3. The study was performed in a cellular system by transfecting the cell (NIH3T3 -mouse fibroblast cell line), followed by drug treatment studies. A range of physiologically relevant concentrations (250nM −10μM) of the FDA-approved drug (leflunomide) was used. The single molecule super-resolution microscopy (scanSM LM) study showed declustering of NS2B3 clusters for concentrations>250nMand near complete disappearance of clusters at concentrations>5μM. Moreover, the associated critical biophysical parameters suggest a substantial decrease in clustered molecules (from 53.2±1.77% for control to 14.89±4.80% at 250nM, and further reduction to 10.55±2.91% at 500nM). Moreover, the number of clusters reduced from 46±15 to 13±4, and the number of molecules per cluster decreased from 133±29 to 62±3, with a depletion in large clusters (from 24 to 12). The parameters collectively indicate the clustering nature of NS2B3 viral protein during the infection process at a cellular level and the effect of leflunomide in declustering. The results supported by statistical analysis suggest strong declustering promoted by leflunomide, which holds the promise to contain/treat dengue viral infection.

Statement of Significance

The fact that there is no approved antiviral approach for Dengue makes it life-threatening and calls for ways to tackle viral infection. Hence, understanding Dengue biology at a single molecule level plays a vital role. In the present super-resolution study, we noted the formation of key viral protein (NS2B3) clusters post 24 hours of transfection in a cellular system. We identified a repurposed FDA-approved drug (Leflunomide) that inhibits the clustering process and promotes declustering at higher drug concentrations. This may become the basis of future studies, which may have therapeutic potential against Dengue.