bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence–Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice
Authors: Lan Wei-Zhong , Tang He , Wen Long-Bo , Chen Zhao , Zhou Yong-li , Dai Wei-wei , Wang Mao , Li Xiao-ning , Wang Wei-Jia , Tang Fan , Yang Zhi-kuan , Tang Yong
Published: May 2024

Objectives:

To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses.

Methods:

Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians.

Results:

The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P<0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P<0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 (P=0.864).

Conclusions:

AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.
Prevalence of Dry Eye Disease in Laser-Assisted In Situ Keratomileusis Candidates
Authors: Cartes Cristian , Aravena Camila , Monsalve Alejandro , Segovia Christian , Romero Cristobal , Quidel Daniela , Cid Fernanda , Monsalve Rudy , Navarro Luis , Araya Daniela , Araneda Daniela , Sepulveda Maylyn
Published: May 2024

Objective:

To evaluate the prevalence of dry eye disease (DED) in laser-assisted in situ keratomileusis (LASIK) candidates.

Methods:

A chart review of consecutive LASIK candidates who underwent full ocular surface work-up was performed, including ocular surface disease index (OSDI), noninvasive tests (noninvasive tear breakup time [ni-TBUT], tear meniscus height, lipid layer thickness, and meibography), and invasive tests (Schirmer test I, fluorescein TBUT, corneal staining, and meibomian gland [MG] expressibility). The prevalence of DED was calculated according to the Dry Eye Workshop II (DEWS II), and Japanese and Asia Dry Eye Society (JDES/ADES) criteria.

Results:

In total, 135 patients (270 eyes) were evaluated. The mean age was 32.6±8.3 years, and 62.9% were women (n=85); 19 patients (15.4%) wore contact lenses, and 31 patients (23.8%) used artificial tears. The mean OSDI was 18.2±16.9, which was abnormal in 54.1% (n=62). Inferior lid MG dropout was the sign with the highest percentage of abnormal results (61.5%; n=83). There were no differences between men and women in any test except for ni-TBUT (6.3±0.3 and 7.2±0.2, respectively; P=0.002). Dry eye disease prevalence was 25.9% and 53.3%, according to JDES/ADES and DEWS II criteria, respectively. The only significant risk factor for DED was artificial tear use for both DEWS II (odds ratio [OR]=3.5, confidence interval [CI] [1.35–9.39]) and JDES/ADES (OR=2.58, CI [1.03–6.48]).

Conclusions:

This study found a high prevalence of DED and abnormalities in LASIK candidates and highlights the importance of ocular surface evaluation before photorefractive surgery.
Investigating the topographic effect of epithelium in myopic eyes with subtle topographic preoperative abnormalities
Authors: Salah-Mabed Imene , Saad Alain , Gatinel Damien
Published: May 2024

Purpose:

To explore the topographic effect of the epithelium in keratoconus suspected (KCS) and in normal Placido classified corneas.

Setting:

Rothschild Foundation, Paris, France.

Design:

Prospective interventional case series.

Methods:

Anterior corneal specular Placido topography using OPD-Scan II was performed in 97 eyes of 67 patients undergoing photorefractive keratectomy for myopia, before and after epithelium removal. The differences in axial keratometry, asphericity, and astigmatism were computed.

Results:

After epithelial peeling, some Placido-normal classified corneas became KCS. Therefore, we have subdivided this group into 2 groups: one of normal classified corneas which stayed normal after epithelium removal (Group NN) and another of corneas that became KCS classified (Group NK). The mean difference in axial mean keratometry in the third central millimeter rings was +0.50 ± 0.24 diopters (D), 0.69 ± 0.31 D, and 0.49 ± 0.35 D and the mean difference in the magnitude of epithelial-induced astigmatism in the first central millimeter ring was 0.37 D × 89 degrees (positive cylinder), 0.54 D 86 degrees, and 0.52 D 86 degrees, respectively, in Group NN, NK, and KK (KCS corneas that stayed KCS). These differences were significant (P < .0001). Preoperative keratometry was the only predictive factor differentiating Group NN from NK (P < .001).

Conclusions:

The epithelial layer tended to reduce the magnitude of the Bowman layer's astigmatism, prolateness, and keratometry, more importantly in Group NK. In the KK group, we found a similar trend as in normal eyes (Group NN). The epithelium would be able to mask Bowman layer's irregularities until a certain degree of severity.
The CLABSI Playbook: Design and Implementation of a Multipronged Approach to Decrease CLABSIs
Authors: Bohan Christian O. , Mlinarich Joseph , Hahn Donna , Shelly Mark , Dang Navneet
Published: May 2024

Central line–associated blood stream infections (CLABSIs) are a quality marker for the critical care environment. They have become an area of particular interest because they cost the healthcare system close to a billion dollars per year and have a significant impact on patient safety. Through a preliminary analysis of our system's CLABSI rates, we found significantly higher rates than the national average, prompting further investigation. We decreased our CLABSI rate by over 40% from 2021 (1.6 per 1,000 line days) to the fourth quarter of 2022 (0.91) and kept the rate below or around the national rate (0.86) for the last three quarters of 2022. Through looking at current outcome data, identifying key stakeholders, developing dedicated committees, conducting root cause analyses, monitoring progress, adjusting procedures, scaling to the system, and continuously monitoring and reporting results, we have shown the efficacy of this kind of quality improvement structure and strive to reduce our hospital system's impact on avoidable healthcare-associated patient harm.
When is a Reverse Shoulder Arthroplasty Indicated for a Rotator Cuff Tear?
Authors: St. Pierre Patrick
Published: May 2024

Rotator cuff tears are the most frequent shoulder injury in patients over 50 years old. Treatment of rotator cuff tears is individualized based on the age, demands, and symptoms of the patient. Nonoperative treatment may often be effective, especially in lower-demand or elderly patients. Surgical repair is indicated after failure of nonoperative treatment or in patients whose high-demand lifestyle requires full strength and function of the shoulder. In older patients, larger tears are less likely to heal and rotator cuff repair may not reliable. In cases of failed previous rotator cuff repair, there may not be enough viable tissue for complete repair. If there is underlying arthritis, a rotator cuff repair is unlikely to resolve all symptoms, and treatment to care for the arthritis and rotator cuff tear is indicated. Reverse shoulder arthroplasty provides the surgical answer for these scenarios and is now being used for numerous indications of shoulder pathology.
A Scoping Review of Complementary and Alternative Medicine for Human Papillomavirus Infections and Cervical Dysplasia
Authors: Walsh Caroline J. , Friedman Julie C. , Piper Christi , Conageski Christine
Published: May 2024

Objective

The goal of this scoping review is to synthesize clinically relevant scientific literature on current complementary and alternative medications that address human papillomavirus (HPV) infections and cervical dysplasia.

Materials and Methods

A systematic search of published studies was performed December 2021 for the following concepts: human papilloma virus, cervical dysplasia, and complementary and alternative medicine (CAM). Relevant publications were identified by searching Ovid MEDLINE ALL, Embase, Cochrane Library, AMED, and MEDLINE databases, in addition to clinical trial databases. Data were extracted based on specific study selection criteria and analyzed by 3 authors independently using Covidence software.

Results

A total of 2324 studies were identified of which 56 met inclusion criteria. Treatment outcomes measured regression of HPV, improvement of cervical cytology, and/or regression of histopathology with varied definitions of success across all studies. The CAM therapies found to have the most clinical benefit and best supporting data via randomized control trials were topical mushroom (Coriolus versicolor) gel, oral and topical selenium therapies, and oral indol-3-carbinol. Adverse events were reported in only 28/56 (50%) of included studies.

Conclusions

The evidence for treating HPV and cervical dysplasia with CAM is of low quality because of lack of standardized, clinically relevant treatment outcomes, lack of standardization of products, and minimal reporting on adverse and long-term effects. Future large, randomized control trials are needed to further assess efficacy and safety of CAM therapies to address HPV and cervical dysplasia.
Time Differences From Abnormal Cervical Cancer Screening to Colposcopy Between Insurance Statuses
Authors: Khurana Sonia , Smolar Isaiah , Warren Leslie , Velasquez Jessica , Kaplowitz Elianna , Rios Jeanette , Pero Adriana , Roberts Harley , Mitchell Mackenzie , Oner Ceyda , Abraham Cynthia
Published: May 2024

Objective

Screening and diagnostic follow-up to prevent cervical cancer are influenced by socioeconomic and systemic factors. This study sought to characterize intervals from abnormal cervical cancer screening to colposcopy between practices differing by insurance status at a large, urban academic center.

Materials and Methods

This retrospective cohort study included patients aged 21–65 who presented for colposcopy between January 1, 2021, and January 1, 2022, at the resident and faculty gynecology practices of a single large urban academic medical center. Patient characteristics were compared using t tests or Wilcoxon rank sum tests for continuous measures and χ2 or Fisher exact tests for categorical measures. Intervals from abnormal cervical cancer screening to colposcopy were compared using the Wilcoxon rank sum test and linear regression analysis with multivariable models adjusted for age, cervical cytology result, human papillomavirus result, and HIV status.

Results

Resident practice patients were publicly insured and more likely to be Black or Hispanic (p < .0001); rates of high-risk human papillomavirus and smoking were similar. Resident practice patients had longer intervals from abnormal cervical cancer screening to colposcopy compared with faculty practice patients (median 79.5 vs 34 d, p < .0001). On adjusted analysis, resident practice patients faced a 95% longer interval (p < .0001).

Conclusions

Publicly insured patients of a resident-based practice faced significantly longer intervals from abnormal cervical cancer screening to colposcopy than faculty practice patients at a single urban academic center. Effort to address these differences may be an area of focus in improving health disparities.
Psychosocial Factors Associated With Vulvodynia
Authors: Queiroz Janice F. , Aquino Antonio C.Q. , Sarmento Ayane C.A. , Siqueira Beatriz B. , Medeiros Heitor D. , Falsetta Megan L. , Maurer Tracey , Gonçalves Ana Katherine
Published: May 2024

Objectives

We set out to identify the psychosocial factors associated with vulvodynia and the effects on sexuality, mental health, and quality of life.

Materials and Methods

PubMed, LILACS, Embase, CINAHL, Web of Science, Scopus, and PsycINFO were searched in August 2023. Two authors selected and extracted the data independently. The risk of bias was assessed using the Newcastle-Ottawa Scale for Observational Studies. To rank the strength of evidence, the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) approach was utilized.

Results

A total of 3,182 articles were identified. Twenty-two observational studies (8 cohorts and 14 case-controls) met the eligibility criteria and were included, comprising 2,624 patients. Vulvodynia has been associated with psychological factors (anxiety and depression) and social factors (childhood exposure to physical and sexual abuse, posttraumatic stress, and domestic abuse). Concerning sexual function, the most frequent outcomes were dyspareunia and sexual dysfunction. Only one study assessed quality of life, which showed that women with chronic vulvar pain had greater difficulty performing physical activities and experienced negative moods and feelings. The assessment of the risk of bias showed that the average quality of studies was good to excellent. However, the studies failed to select the nonexposed cohort or control group to describe the results, and often, the study population was rather small, which made it impossible to carry out a meta-analysis.

Conclusions

The certainty of evidence for the associations between anxiety and depression, vulvodynia, and sexual functioning suggests that combating these factors could improve overall quality of life in vulvodynia patients.
Aryl Hydrocarbon Receptor Knockout Accelerates PanIN Formation and Fibro-Inflammation in a Mutant Kras-Driven Pancreatic Cancer Model
Authors: Walcheck Morgan T. , Schwartz Patrick B. , Carrillo Noah D. , Matkowskyj Kristina A. , Nukaya Manabu , Bradfield Christopher A. , Ronnekleiv-Kelly Sean M.
Published: May 2024

Objectives

The pathogenesis of pancreas cancer (PDAC) remains poorly understood, hindering efforts to develop a more effective therapy for PDAC. Recent discoveries show the aryl hydrocarbon receptor (AHR) plays a crucial role in the development of several cancers and can be targeted for therapeutic effect. However, its involvement in the pathogenesis of PDAC remains unclear. To address this gap, we evaluated the role of AHR in the development of PDAC precancerous lesions in vivo.

Materials and Methods

We created a global AHR-null, mutant Kras-driven PDAC mouse model (A−/−KC) and evaluated the changes in PDAC precursor lesion formation (PanIN‐1, 2, and 3) and associated fibro-inflammation between KC and A−/−KC at 5 months of age. We then examined the changes in the immune microenvironment followed by single-cell RNA-sequencing analysis to evaluate concomitant transcriptomic changes.

Results

We identified a significant increase in PanIN-1 lesion formation and PanIN-1 associated fibro-inflammatory infiltrate in A−/−KC versus KC mice. This was associated with significant changes in the adaptive immune system, particularly a decrease in the CD4+/CD8+ T-cell ratio, as well as a decrease in the T-regulatory/Th17 T-cell ratio suggesting unregulated inflammation.

Conclusions

These findings show the loss of AHR results in heightened Kras-induced PanIN formation, through modulation of immune cells within the pancreatic tumor microenvironment.
Expression and Prognosis of Differential Gene Troponin T1 Between Right and Left Colon Cancers
Authors: Wu Yue , Zhang Yijun , Xu Fanfan , Zhang Ziyan , Wang Yinzhong
Published: May 2024

Colorectal cancer (CRC) is one of the most common digestive tract tumors in humans. At present, many scholars believe that the primary site of the tumor has a direct and profound impact on its curative effect. There are significant differences in the expression of many genes, tumor microenvironment, and prognosis between the left and right colon. However, there is a lack of detailed studies on whether the differentially expressed genes in the left and right colon significantly impact the prognosis of patients with CRC. Troponin T1 (TNNT1) is an important gene that affects the prognosis difference between left and right colon cancer screening from “The Cancer Genome Atlas” database. By analyzing the differential gene expression data and clinical data of the left and right hemicolons in the database, the online prognostic database was used to screen the key molecules that significantly affect the tumor immune microenvironment and patient prognosis and to predict their functions and pathways. Quantitative reverse transcription–polymerase chain reaction was used to verify the expression difference of TNNT1 in CRC cell lines SW480 and HCT116, and normal human colorectal epithelial cell line FHC. The relationship between TNNT1 expression in 88 pairs of CRC samples and clinical information and pathologic parameters of patients with CRC was analyzed to judge the impact of TNNT1 expression on patient survival. Database analysis showed that TNNT1 was significantly overexpressed in CRC, and TNNT1 was one of the main differential genes between left colon cancer (LCC) and right colon cancer (RCC). The expression of TNNT1 was significantly increased in RCC, which could lead to poor prognosis of patients. Quantitative reverse transcription–polymerase chain reaction indicated that the expression of TNNT1 was significantly up-regulated in CRC cell lines SW480 and HCT116. Eighty-eight immunohistochemistry (IHC) of CRC tissues and adjacent tissues suggested that the expression of TNNT1 in CRC was significantly higher than that in normal adjacent tissues. By analyzing the clinical information and pathologic indicators matched with these clinical samples, we found that high TNNT1 expression in the primary tumor location (right colon) and high N stage (N2, N3) were unfavorable factors affecting the prognosis of patients with CRC. Multivariate Cox regression analysis suggested that high expression of TNNT1 may be an independent risk factor for the prognosis of patients with CRC. As one of the main differential genes between LCC and RCC, TNNT1 is representative to some extent. Its high expression may be one of the reasons why the prognosis of patients with RCC is worse than that of patients with LCC.
Dynamic Prediction of Mortality Using Longitudinally Measured Pediatric Sequential Organ Failure Assessment Scores: A Joint Modeling Approach*
Authors: Akhondi-Asl Alireza , Geva Alon , Burns Jeffrey P. , Mehta Nilesh M.
Published: May 2024

OBJECTIVES:

The pediatric Sequential Organ Failure Assessment (pSOFA) score was designed to track illness severity and predict mortality in critically ill children. Most commonly, pSOFA at a point in time is used to assess a static patient condition. However, this approach has a significant drawback because it fails to consider any changes in a patients’ condition during their PICU stay and, especially, their response to initial critical care treatment. We aimed to evaluate the performance of longitudinal pSOFA scores for predicting mortality.

DESIGN:

Single-center, retrospective cohort study.

SETTING:

Quaternary 40-bed PICU.

PATIENTS:

All patients admitted to the PICU between 2015 and 2021 with at least 24 hours of ICU stay.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We calculated daily pSOFA scores up to 30 days, or until death or discharge from the PICU, if earlier. We used the joint longitudinal and time-to-event data model for the dynamic prediction of 30-day in-hospital mortality. The dataset, which included 9146 patients with a 30-day in-hospital mortality of 2.6%, was divided randomly into training (75%) and validation (25%) subsets, and subjected to 40 repeated stratified cross-validations. We used dynamic area under the curve (AUC) to evaluate the discriminative performance of the model. Compared with the admission-day pSOFA score, AUC for predicting mortality between days 5 and 30 was improved on average by 6.4% (95% CI, 6.3–6.6%) using longitudinal pSOFA scores from the first 3 days and 9.2% (95% CI, 9.0–9.5%) using scores from the first 5 days.

CONCLUSIONS:

Compared with admission-day pSOFA score, longitudinal pSOFA scores improved the accuracy of mortality prediction in PICU patients at a single center. The pSOFA score has the potential to be used dynamically for the evaluation of patient conditions.
Measuring Physical Function in the PICU: Development and Testing of a Children’s Version (Age 2–18 yr) of the Chelsea Critical Care Physical Assessment Tool
Authors: Ferguson Alexandra H. , Stockton Kellie A. , Wright Sarah E. , George Joanne M. , Fulton Tessa J. , Stocker Christian , Long Debbie A.
Published: May 2024

OBJECTIVES:

To adapt and develop a reliable and easily administered outcome measure of physical and respiratory function in critically ill children in the PICU.

DESIGN:

Modified Delphi study to adapt the Chelsea Critical Care Physical Assessment (CPAx) tool for use in children 2–18 years old, with subsequent prospective testing in a single-center cohort.

SETTING:

Single-center tertiary PICU.

SUBJECTS:

Delphi process in 27 panelists (including physiotherapists, occupational therapists, and pediatric intensivists from seven countries from January 2018 to March 2018). Cohort study in 54 patients admitted to PICU for greater than 24 hours over a 3-month period (April 2018 to June 2018), with median age 5.5 years (interquartile range [IQR], 3–12.75 yr), 33 of 54 male, and 38 of 54 invasively ventilated.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Three Delphi iterations were required to reach greater than or equal to 80% consensus in all the children’s CPAx (cCPAx) items. In the subsequent cohort study, six physiotherapists used the cCPAx tool and scored 54 participants, with a total 106 observations. The median cCPAx tool score was 14.50 (IQR, 3–25) out of a possible total of 50. Inter-rater reliability for 30 randomly selected participants was excellent (intraclass correlation coefficient, 0.998). Completion rate of cCPAx in the 54 patients occurred in 78 of 106 occasions (74%).

CONCLUSIONS:

The cCPAx tool content that was developed using Delphi methodology provided a feasible and clinically relevant tool for use in assessing physical morbidity in PICU patients 2–18 years old. Overall, the cCPAx scores were low, demonstrating low levels of physical function and high levels of immobility during PICU care.
Pre–Coronary Artery Bypass Grafting Computed Tomography–Based Fractional Flow Reserve Predicts Graft Failure: Implications for Planning Invasive Treatment of Coronary Artery Disease
Authors: Wardziak Łukasz , Kruk Mariusz , Demkow Marcin , Kępka Cezary
Published: May 2024

Objective

The aim of the study is to evaluate whether a pre–coronary artery bypass grafting (CABG) coronary computed tomography-based fractional flow reserve (FFR-CT) result at the site of a future anastomosis would predict the graft failure in patients undergoing CABG.

Methods

In 43 patients who had coronary computed tomography angiography (CCTA) prior to the CABG, follow-up CCTA were acquired >12 months post-CABG procedure. The FFR-CT values were simulated on the basis of the pre-CABG CCTA. Based on follow-up CCTA, the anastomosis sites and the graft patency were determined. The graft failure was defined as either its stenosis >50% or occlusion.

Results

Ninety eight (44 saphenous, 54 left or right internal mammary artery) grafts were assessed. Eighteen grafts from 16 patients were dysfunctional on follow-up CCTA. The FFR-CT values at the location of future anastomosis were higher in dysfunctional than in normal grafts (0.77 [0.71–0.81] vs 0.60 [0.56–0.66], respectively, P = 0.0007). Pre-CABG FFR-CT (hazard ratio = 1.1; 95% CI: 1.012–1.1, P = 0.0230), and bypass graft to right coronary artery (hazard ratio = 3.7; 95% CI: 1.4–9.3 vs left anterior descending artery) were independent predictors of graft dysfunction during follow-up. The optimal threshold of FFR-CT to predict graft failure was >0.68 (sensitivity 88.9% (95% CI: 65.3–98.6), specificity 63.7% (95% CI: 52.2–74.2), positive predictive value 35.6% (95% CI: 28.3%–43.5%), negative predictive value 96.2% (95% CI: 87.2%–99.0%)).

Conclusions

Pre-CABG functional FFR-CT predicts future coronary bypass graft failure. This shows utility of FFR-CT for guiding coronary revascularization and also suggests significance of physiological assessment prior to CABG.
Hepatic PSMA-Avid Postradiation Inflammation
Authors: Silveira Patrick , Razmaria Aria , Yeh Randy
Published: May 2024

A 62-year-old man with de novo large volume metastatic prostate cancer to the bone, liver, and nodes status post multiple lines of therapy including external beam radiation to T12–L2 approximately 13 months prior underwent 68Ga-PSMA PET/CT to determine eligibility for 177Lu-PSMA therapy. 68Ga-PSMA PET/CT demonstrated tracer-avid osseous and nodal lesions consistent with metastases. In addition, regional geographic tracer avidity was seen in the midline left hepatic lobe associated with capsular retraction and demonstrated no FDG avidity on subsequent imaging, probably inflammatory related to prior radiation to T12–L2.
Effects of passive ankle exoskeletons on neuromuscular function during exaggerated standing sway
Authors: Farris Dominic J. , Po Jemima C. N. , Yee Jordan , Williamson James L. , Dick Taylor J. M.
Published: May 2024

Wearable robotic exoskeletons designed to assist human movement should integrate with the neuromusculoskeletal system. This means assisting movement while not perturbing motor control. We sought to test if passive ankle exoskeletons, which have been shown to successfully assist human gait, affect neuromuscular control of an exaggerated anterior–posterior standing sway task. Participants actively swayed while wearing an ankle exoskeleton that provided 0, 42 or 85 Nm rad
−1
of additional stiffness to the ankle joint in resistance to dorsiflexion. Sway amplitude was controlled via biofeedback to elicit similar ankle angle displacements across conditions. With greater exoskeleton stiffness, participants swayed at lower sway-cycle frequencies and slower centre of pressure speeds. Furthermore, increasing exoskeleton stiffness resulted in longer operating lengths of the medial gastrocnemius and overall reduced plantar flexor muscle activation. For the soleus, there was also a temporal shift in the cross-correlation of its electromyogram with the centre of pressure displacement, meaning that muscle activation peaked later than anterior sway displacement. Together, these data suggest that assistive ankle exoskeletons influence neuromuscular control of ankle-based sway tasks. Changes in fascicle lengths could influence afferent feedback signals and the short-range stiffness of ankle muscles, while shifts in muscle activation timing suggest changes in neural control. The observed neuromuscular adaptations to exoskeleton assistance demonstrate the potential implications for standing balance and overall movement control, prompting future investigations.
Luteibacter mycovicinus sp. nov., a yellow-pigmented gammaproteobacterium found as an endohyphal symbiont of endophytic Ascomycota
Authors: Baltrus David A. , Carter Morgan , Clark Meara , Smith Caitlin , Spraker Joseph , Inderbitzin Patrik , Arnold A. Elizabeth
Published: May 2024

We isolated and described a yellow-pigmented strain of bacteria (strain 9143T), originally characterized as an endohyphal inhabitant of an endophytic fungus in the Ascomycota. Although the full-length sequence of its 16S rRNA gene displays 99 % similarity to Luteibacter pinisoli, genomic hybridization demonstrated <30 % genomic similarity between 9143T and its closest named relatives, further supported by average nucleotide identity results. This and related endohyphal strains form a well-supported clade separate from L. pinisoli and other validly named species including the most closely related Luteibacter rhizovicinus. The name Luteibacter mycovicinus sp. nov. is proposed, with type strain 9143T (isolate DBL433), for which a genome has been sequenced and is publicly available from the American Type Culture Collection (ATCC TSD-257T) and from the Leibniz Institute DSMZ (DSM 112764T). The type strain reliably forms yellow colonies across diverse media and growth conditions (lysogeny broth agar, King’s Medium B, potato dextrose agar, trypticase soy agar and Reasoner's 2A (R2A) agar). It forms colonies readily at 27 °C on agar with a pH of 6–8, and on salt (NaCl) concentrations up to 2 %. It lacks the ability to utilize sulphate as a sulphur source and thus only forms colonies on minimal media if supplemented with alternative sulphur sources. It is catalase-positive and oxidase-negative. Although it exhibits a single polar flagellum, motility was only clearly visible on R2A agar. Its host range and close relatives, which share the endohyphal lifestyle, are discussed.
Streptomyces albipurpureus sp. nov., a novel actinobacterium with antimicrobial activity isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don
Authors: Jiang Xiao , Tang Yun , Yang You , Tang Jin , Hou Mingyan , Liu Ruiling , Dong Qian , Ma Zhaoxu
Published: May 2024

A novel actinobacterium, designated strain CWNU-1T, was isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don and examined using a polyphasic taxonomic approach. The organism developed pale blue aerial mycelia that was simply branched and terminated in open or closed coils of three or more volutions on International Streptomyces Project 3 agar. Spores were ellipsoidal to cylindrical with wrinkled surfaces. The strain showed high 16S rRNA gene sequence similarity to Streptomyces kurssanovii NBRC 13192T (98.8 %), Streptomyces xantholiticus NBRC 13354T (98.7 %) and Streptomyces peucetius JCM 9920T (98.6 %). The phylogenetic result based on 16S rRNA gene and genome sequences clearly demonstrated that strain CWNU-1T formed an independent phylogenetic lineage. On the basis of orthologous average nucleotide identity, CWNU-1T was most closely related to Streptomyces inusitatus NBRC 13601T with 79.3 % identity. The results of the digital DNA–DNA hybridization analysis also indicated low levels of relatedness with other species, as the highest value was observed with S. inusitatus NBRC 13601T (25.3 %). With reference to phenotypic characteristics, phylogenetic data, orthologous average nucleotide identity and digital DNA–DNA hybridization results, strain CWNU-1T was readily distinguished from its most closely related strains and classified as representing a novel species, for which the name Streptomyces albipurpureus sp. nov. is proposed. The type strain is CWNU-1T (=CGMCC 4.7758T=MCCC 1K07402T=JCM 35391T).
Effect of Microbubble Size, Composition and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening
Authors: Martinez Payton J. , Song Jane J. , Castillo Jair , DeSisto John , Song Kang-Ho , Green Adam L. , Borden Mark
Published: May 2024

Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubble (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB+FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNAseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 µm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 µm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter’s poorin vivostability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.
A Tip Optofluidic Immunoassay System for COVID-19 Immuno-protection Evaluation Using Fingertip Blood
Authors: Li Ruihan , Zhang Binmao , Li Hao , An Lixiang , Zhu Tianen , Hu Shi , Yang Fan , Wu Weishu , Fan Xudong , Chai Yujuan , Yang Hui , Tan Xiaotian
Published: May 2024

Infectious diseases such as COVID-19 continue posing significant global health challenges, with recurrent re-infections contributing to long-term symptoms such as cardiac issues and anosmia. Effective management of re-infections relies heavily on maintaining high levels of circulating binding and neutralizing antibodies. Traditional methods for antibody quantification, such as ELISA, face significant challenges, including narrow dynamic ranges and complex sample preparation procedures, which hinder their applications in rapid and routine diagnosis. This study introduces a novel optofluidic biosensing technology, tip optofluidic immunoassay (TOI), that addresses these limitations by enabling the quantitative analysis of binding IgG against multiple SARS-CoV-2 strains from only 1 μL of fingertip blood. The proposed TOI system, featuring industrial-grade micro-fabricated immuno-reactors and a portable chemiluminescent imaging station, can provide test results within 12 minutes. For IgG binding assays, TOI possesses a lower limit of detection of 0.1 ng/mL, a dynamic range of 3-4 orders of magnitude, along with a high signal-to-noise ratio (approximately 10,000). This technology not only simplifies the antibody quantification process but also enhances patient compliance and facilitates decentralized testing, which is crucial for infectious disease management. By enabling precise and rapid antibody assessment, this system can support the optimization of vaccination strategies and broader public health responses to COVID-19 and other infectious diseases.
Diagnostic utility of plasma ptau217, ptau181, GFAP for Alzheimer disease in a heterogeneous younger onset dementia clinical cohort
Authors: Eratne Dhamidhu , Li Qiao-Xin , Lewis Courtney , Dang Christa , Kang Matthew JY , Grewal Jasleen , Loi Samantha , Walterfang Mark , Evans Andrew H , Malpas Charles B , Pedrini Steve , Martins Ralph , Chatterjee Pratishtha , Zetterberg Henrik , Blennow Kaj , Berkovic Samuel F , Santillo Alexander F , Collins Steven , Masters Colin L , Velakoulis Dennis ,   The MiND Study Group
Published: May 2024

Objective

We investigated diagnostic utility of phosphorylated tau 217 and 181 (ptau217, ptau181), glial fibrillary acidic protein (GFAP), amyloid beta 42 and 40 (Aβ42, Aβ40), neurofilament light (NfL) to distinguish AD from non-AD conditions, in a heterogenous clinical cohort of younger people.

Methods

Plasma biomarkers were analysed using ultrasensitive technology, and compared in patients with CSF Alzheimer disease profiles (A+T+) to other profiles (OtherAT).

Results

Seventy-nine patients were included, median age 60.8 years: 16 A+T+, 63 OtherAT. Ptau217, ptau181, GFAP were significantly elevated in A+T+ compared to OtherAT (3.67 vs 1.12pg/mL, 3.87 vs 1.79pg/mL, 189 vs 80pg/mL, respectively). ptau217 distinguished AD from OtherAT with 90% accuracy (88% specificity, 100% sensitivity)

Conclusions

Plasma ptau217 has strong diagnostic utility to diagnose AD in a clinically relevant, younger cohort of people with symptoms, adding further weight for a simple diagnostic blood test for AD as a cause of a patient’s symptoms.
Auricular Vagus Nerve Stimulation Mitigates Inflammation and Vasospasm in Subarachnoid Hemorrhage: A Randomized Trial
Authors: Huguenard Anna L , Tan Gansheng , Rivet Dennis J , Gao Feng , Johnson Gabrielle W , Adamek Markus , Coxon Andrew T , Kummer Terrance T , Osbun Joshua W , Vellimana Ananth K , Limbrick David D , Zipfel Gregory J , Brunner Peter , Leuthardt Eric C
Published: May 2024

Background

Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). Transauricular vagus nerve stimulation (taVNS) offers a noninvasive approach to target the inflammatory response following SAH.

Methods

In this prospective, triple-blinded, randomized, controlled trial, twenty-seven patients were randomized to taVNS or sham stimulation. Blood and cerebrospinal fluid (CSF) were collected to quantify inflammatory markers. Cerebral vasospasm severity and functional outcomes (modified Rankin Scale, mRS) were analyzed.

Results

No adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than sham (p < 0.001). In the taVNS group, TNF-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); IL-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%), with significant improvement from admission to first follow-up (p = 0.014), unlike the sham group (p = 0.18). The taVNS group had a significantly lower rate of discharge to skilled nursing facility or hospice (p = 0.04).

Conclusion

taVNS is a non-invasive method of neuro- and systemic immunomodulation. This trial supports that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04557618
Dopaminergic inhibition of the inwardly rectifying potassium current in direct pathway medium spiny neurons in normal and parkinsonian striatum
Authors: Wang Qian , Wang Yuhan , Liao Francesca-Fang , Zhou Fu-Ming
Published: May 2024

Despite the profound behavioral effects of the striatal dopamine (DA) activity and the inwardly rectifying potassium channel (Kir) being a key determinant of striatal medium spiny neuron (MSN) activity that also profoundly affects behavior, previously reported DA regulations of Kir are conflicting and incompatible with MSN function in behavior. Here we show that in normal mice with an intact striatal DA system, the predominant effect of DA activation of D1Rs in D1-MSNs is to cause a modest depolarization and increase in input resistance by inhibiting Kir, thus moderately increasing the spike outputs from behavior-promoting D1-MSNs. In parkinsonian (DA-depleted) striatum, DA increases D1-MSN intrinsic excitability more strongly than in normal striatum, consequently strongly increasing D1-MSN spike firing that is behavior-promoting; this DA excitation of D1-MSNs is stronger when the DA depletion is more severe. The DA inhibition of Kir is occluded by the Kir blocker barium chloride (BaCl2). In behaving parkinsonian mice, BaCl2microinjection into the dorsal striatum stimulates movement but occludes the motor stimulation of D1R agonism. Taken together, our results resolve the long-standing question about what D1R agonism does to D1-MSN excitability in normal and parkinsonian striatum and strongly indicate that D1R inhibition of Kir is a key ion channel mechanism that mediates D1R agonistic behavioral stimulation in normal and parkinsonian animals.
Solutions of ferrous salts protect liposomes from UV damage: implications for Life Origin
Authors: Turner Ben , Fiksel Gennady , Subbotin Vladimir
Published: May 2024

Previously, we presented a hypothesis on the Darwinian evolution of liposomes that relies only on natural and ever-present phenomena: solar UV radiation, day/night cycle, gravity, and the formation of amphiphiles, e.g., fatty acids and phospholipids, in aqueous media. The hypothesis further suggests that liposomes, formed at the air-water interface, will be inevitably destroyed by Sun UV unless they are submerged and shielded by primordial water. The hypothesis makes two testable predictions. First, certain ingredients of the Archean waters, e.g., ferric salts, can completely attenuate UV; and second, such ferric salts solution can protect the submerged liposomes from the solar UV damage. In our previous experiments (Subbotin and Fiksel 2023a), we tested the prediction of UV attenuation by ferrous salt solutions. We have demonstrated that out of several tested iron salt solutions, two salts demonstrated very strong UV attenuation: at a concentration of 2.5 g/L of (NH4)5[Fe(C6H4O7)2] and FeCl3, the UV intensity drops by a factor of 1000 at a submersion depth of 7.4 mm and 6.3 mm, respectively. In the present study, we tested the second prediction: we investigated whether the above ferrous salt solutions can protect UV-sensitive liposomes from UV damage. The results demonstrated that 10 mm of solutions, the ferric ammonium citrate or iron trichoride, completely protected UV-sensitive liposomes from UV damage. These results supplement and reinforce the proposed hypothesis.
Segmental regulation of intestinal motility by colitis and the adaptive immune system in the ileum and colon
Authors: Bris Raquel Gómez , Rodríguez-Rodríguez Pilar , Zapero Marina Ortega , Ruvira Santiago , Saez Angela , Arribas Silvia Magdalena , Granado Jose Maria Gonzalez
Published: May 2024

Gastrointestinal motility disturbances are common in inflammatory bowel disease (IBD); however, their exact causes remain elusive.

This study explores the motility of various intestinal segments in both healthy and IBD states, focusing on the role of the adaptive immune system. Using a dextran sulfate sodium (DSS)-induced colitis model in mice lacking B and T lymphocytes, we evaluated motility in the ileum and colon using an organ bath system.

In healthy mice, absence of adaptive lymphocytes in the ileum reduces muscarinic receptor sensitivity or increase cholinesterase activity. Colitis increases motility, intensifying the intensity and frequency of spontaneous contractions while decreasing responsiveness to cholinergic stimuli.

In the proximal colon, healthy mice lacking adaptive immune system exhibit increased contractile capacity and frequency, along with reduced muscarinic receptor sensitivity or increased cholinesterase activity. Conversely, colitis diminishes contractile capacity regardless of genotype, while recovery increases frequency of spontaneous contractions.

In the mid-colon during colitis, healthy mice lacking adaptive immune system exhibit reduced muscarinic receptor sensitivity or increased cholinesterase activity, while the absence of adaptive lymphocytes during colitis exacerbates both spontaneous and stimuli-induced contractions. Finally, in the distal colon, the adaptive immune system enhances stimuli-induced contractility in health and reduces contractility and enhances muscarinic responses during colitis.

Overall, intestinal motility in both the ileum and colon is finely regulated, with the adaptive immune system playing a crucial role. These findings contribute to our understanding of IBD pathology, emphasizing the importance of investigating gastrointestinal motility in IBD research.
Fast feature- and category-related parafoveal previewing support natural visual exploration
Authors: Fakche Camille , Hickey Clayton , Jensen Ole
Published: May 2024

Studies on vision tend to prevent or control eye movements, while humans naturally saccade every ∼250 ms. As the oculomotor system takes ∼100 ms to initiate and execute a saccade, this leaves only ∼150 ms to identify the fixated object and select the next saccade goal. This is very little time, suggesting that vision relies on parafoveal processing before and after the eye movement. However, evidence of high-level parafoveal access is sparse. The purpose of our study was to use magnetoencephalography (MEG) combined with eye-tracking and multivariate pattern analysis to identify the neuronal dynamics of parafoveal processing which support natural visual exploration. We demonstrated that future saccade goals in the parafovea could be decoded at the feature and category level peaking at ∼90 ms and ∼160 ms respectively. Simultaneously, decoding of fixated objects at the feature and category level peaked at ∼70 ms and ∼145 ms respectively. Also decoding feature and category specific neuronal information related to past parafoveal objects were sustained for ∼230 ms after saccading away from them. The feature and category of objects in the parafovea could only be decoded if they were in the saccade goal. In sum, we provide insight on the neuronal mechanism of pre-saccadic attention by demonstrating that feature and category specific information of foveal and parafoveal objects can be extracted in succession within a ∼150 ms time-interval and may serve to plan the next saccade. This information is maintained also after fixations and may support integration across the full visual scene. Our study provides novel insight on the temporal dynamics of foveal and parafoveal processing at the feature and semantic levels during natural visual exploration.
SLC35G1: A highly chloride-sensitive transporter responsible for the basolateral membrane transport in intestinal citrate absorption
Authors: Mimura Yoshihisa , Yasujima Tomoya , Inoue Katsuhisa , Akino Shogo , Namba Chitaka , Kusuhara Hiroyuki , Sekiguchi Yutaro , Ohta Kinya , Yamashiro Takahiro , Yuasa Hiroaki
Published: May 2024

The intestinal absorption of essential nutrients, especially those not readily biosynthesized, is a critical physiological process for maintaining homeostasis. Numerous studies have indicated that intestinal absorption is mediated by various membrane transporters. Citrate, a crucial bioactive compound produced as an intermediate in the Krebs cycle, is absorbed in the small intestine through carrier-mediated systems because of its high hydrophilicity. While the luminal absorption of citrate is mediated by Na+-dicarboxylate cotransporter 1 (NaDC1/SLC13A2), the mechanism governing the release of the transported citrate into the bloodstream remains unknown. Here, we explored the transporters responsible for intestinal citrate absorption at the basolateral membrane, focusing on highly expressed orphan transporters in the small intestine as candidates. Consequently, SLC35G1, originally identified as a partner of stromal interaction molecule 1, a cell surface transmembrane glycoprotein, was found to play a role in the intestinal absorption of citrate at the basolateral membrane. Furthermore, our results revealed that SLC35G1-mediated citrate transport was diminished by chloride ions at physiologically relevant extracellular concentrations. This suggests that SLC35G1, to our best knowledge, is the first transporter identified to be extremely sensitive to chloride ions among those functioning on the basolateral membrane of intestinal epithelial cells. This study provides valuable insights into the intestinal absorption of citrate and significantly contributes to elucidating the poorly understood molecular basis of the intestinal absorption system.