bluuebunny/crossref_metadata_2025 huggingface dataset:
Graded supplemental choline chloride fed throughout the grow and finish periods elicited minimal influence on growth performance and carcass characteristics of pigs in a commercial setting
Authors: Sommer Kaitlyn M , Burris Elli S , Jespersen Julianna C , Estes Kari , Dilger Anna C , Dilger Ryan N
Published: December 2024

Choline is vital in a variety of physiological processes that influence brain development, growth, and carcass characteristics in birds and mammals. In this study, we investigated the influence of graded supplemental choline chloride on growth performance, carcass quality, and liver characteristics in grow-finish pigs. Pigs (672 barrows and 588 gilts) were obtained from a commercial nursery facility at 8 weeks of age and assigned to treatment based on body weight and sex, with 21 same-sex pigs comprising a replicate pen. Each dietary treatment was provided to 15 replicate pens, with 8 pens of barrows and 7 pens of gilts per each of 4 dietary treatments, which included: 1) C0, basal diet containing 0% of supplemental choline chloride; 2) C300, C0 + 0.06% supplemental choline chloride, to provide 300 mg/kg of choline ions; 3) C600, C0 + 0.12% supplemental choline chloride, to provide 600 mg/kg of choline ions; and 4) C900, C0 + 0.17% supplemental choline chloride, to provide 900 mg/kg of choline ions. Feed and water were provided ad libitum throughout the study, and pigs were managed using standard commercial practices. Data were analyzed by two-way ANOVA using the MIXED procedure of SAS, with factors including dietary treatment and sex. There was no dietary impact (P > 0.05) on growth performance. Pigs receiving intermediate levels of supplemental choline had higher (P < 0.05) tenderloin weights compared with other dietary treatments. Furthermore, and as expected, sex differences were denoted in both growth performance and carcass characteristics. Overall, graded supplementation of choline chloride did not significantly alter growth performance or carcass characteristics of pigs raised in a commercial setting.
Black fly diversity and molecular detection of blood parasites in Simulium khelangense (Diptera, Simuliidae) from Laos
Authors: Gomontean Bhuvadol , Jumpato Waraporn , Namtaku San , Wannasingha Wannachai , Wongpakam Komgrit , Thanee Isara , Inkhavilay Khamla , Malavong Banchai , Pramual Pairot
Published: December 2024

Black flies (Diptera: Simuliidae) are significant pests and vectors transmitting pathogens to humans and other animals. However, knowledge of species diversity as well as their role as pests and vectors in Laos is limited, despite the country having abundant suitable lotic habitats, that is, running water. In this study, we collected wild adult black fly specimens from Laos. Both morphology and genetic data supported that they were Simulium khelangense Takaoka, Srisuka and Saeung, and therefore, a new distribution record for this species. Screening of the blood protozoa from 106 females detected Leucocytozoon (n = 7) and Trypanosoma (n = 9). Identifications of Leucocytozoon based on cytochrome b sequences in MalAvi database indicated that 5 specimens had identical sequences to those of 4 lineages (GALLUS17 [n = 2], GALLUS35 [n = 1], GALLUS37 [n = 1], and GALLUS41 [n = 1]) of unidentified species (i.e., Leucocytozoon sp.). The remaining 2 had no identical sequences but were very similar (99%) to GALLUS34 and GALLUS41 lineages. Identifications of Trypanosoma based on the small subunit rRNA indicated that all were T. avium. The results presented here further support the role of S. khelangense as a potential vector of Leucocytozoon and Trypanosoma as well as being a possible pest of domestic avian species.
Experimental and computational investigations of RNA duplexes containing N7-regioisomers of adenosine and LNA-adenosine
Authors: Yildirim Ilyas , Andralojc Witold , Taghavi Amirhossein , Baranowski Daniel , Gdaniec Zofia , Kierzek Ryszard , Kierzek Elzbieta
Published: December 2024

Although glycosidic bonds in purines typically involve the N9 position, the chemical synthesis of adenosine produces N7-ribofuranosyladenine (7A) as a kinetically favorable ribosylation product. Similarly, in the synthesis of LNA-adenosine (AL), a minor product, N7-LNA-adenosine (7AL), is observed. While extensive research has focused on investigating the properties of N9-regioisomers of adenosine, 7A has been largely overlooked and considered as a side-product. In this study, we conducted comprehensive experimental and computational investigations to elucidate the structural and thermodynamic properties of 7A and 7AL. Our results reveal that 7A and 7AL primarily enhance the thermodynamic stability of 1 × 1 mismatches when paired with purines but decrease stability when paired with pyrimidines. Utilizing nuclear magnetic resonance and computational techniques, we discovered that 1 × 1 7A:A and 7AL:A prefer anti-anti conformations, while 1 × 1 7A:G and 7AL:G prefer syn-anti orientations, both forming two hydrogen bond states, resulting in enhanced duplex stabilities. Altogether, these findings underscore the unique properties of 7A and 7AL when incorporated in RNA, which could advance structure-based RNA studies and potentially be utilized to modulate binding affinity, selectivity and biostability of RNA molecules.
Association Between Vitamin D and COVID-19–Related Outcomes: An Umbrella Review of Meta-Analyses
Authors: Yang Jia-ming , Li Ze-qin , Zhong Yan-biao , Xie Hui-yong , Luo Yun , Xiao Li , Liao Jing-hai , Wang Mao-yuan
Published: December 2024

Context

COVID-19 remains globally pandemic, and although several meta-analyses have explored the association between vitamin D and COVID-19 relative to clinical outcomes, a unified view has not yet emerged.

Objective

To summarize the evidence for associations between vitamin D levels and COVID-19–related clinical outcomes and to assess the strength and validity of these associations.

Data Sources

PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews databases were searched from January 1, 2020, to June 15, 2024.

Data Extraction

Two reviewers independently extracted data and assessed study quality.

Data Analysis

Low vitamin D levels increased the risk of infection by 1.26- to 2.18-fold, the risk of severe illness by 1.50- to 5.57-fold, the risk of intensive care unit (ICU) admission by more than 2-fold, and the risk of death by 1.22- to 4.15-fold. In addition, patients with vitamin D deficiency had an average increase in length of hospital stay of 0.54 days compared with patients with high vitamin D levels. Overall, vitamin D supplementation may reduce severity (eg, ICU admissions, need for mechanical ventilation) and shorter length of hospital stay but has a nonsignificant effect on infection and mortality rates. In addition, there were significant differences in vitamin D levels between individuals testing positive for COVID-19 and those testing negative (mean difference [MD] = –3.22 ng mL–1; 95% CI, –5.18 to –1.25), those with severe cases and those with mild cases (MD = –4.60 ng mL–1; 95% CI, –5.49 to –3.71), and nonsurvivors and survivors of COVID-19 infection (MD = –6.59 ng mL–1; 95% CI: –8.94 to –4.24).

Conclusions

Low vitamin D levels are associated with higher infection rates, more severe disease, and higher mortality rates among individuals with COVID-19, whereas vitamin D supplementation may reduce patients’ disease severity. The beneficial effects on infection rates and mortality remain to be further explored, however, in higher-quality, randomized controlled studies. Nonetheless, caution is warranted because the methodological quality of most meta-analyses and the level of evidence for most outcomes are very low.

Systematic review registration

PROSPERO registration No. CRD42022385036.
Canopy elastic turbulence: Insights and analogies to canopy inertial turbulence
Authors: Lopez de la Cruz Ricardo Arturo , Haward Simon J , Shen Amy Q
Published: December 2024

Canopy flows occur when a moving fluid encounters a matrix of free-standing obstacles and are found in diverse systems, from forests and marine ecology to urban landscapes and biology (e.g. cilia arrays). In large-scale systems, involving Newtonian fluids (like water or air), canopy flows typically exhibit inertial turbulence due to high Reynolds numbers (Re). However, in small-scale systems like cilia, where Re is low, but the fluid can be viscoelastic (like mucus), the relevant control parameter is the Weissenberg number (Wi), quantifying elastic stresses in the flow. Here, we investigate the flow of a viscoelastic polymer solution over a microscopic canopy within a microfluidic device. As the Weissenberg number increases, the flow undergoes distinct transitions, eventually becoming unstable beyond a critical Wi. At high Wi, we observe the emergence of elastic turbulence (ET), a chaotic flow regime that, despite differing underlying mechanisms, exhibits striking similarities to large-scale canopy inertial turbulence. Similar to canopy inertial turbulence, ET within the canopy can be spatially divided into distinct regions: a porous layer within the canopy, a mixing layer at the canopy tips, a transitional region just above the canopy, and a Poiseuille-like flow further up. The separation of the flow into different regions reveals a new analogy between inertial turbulence and ET, providing a fresh insight into ET flows and expanding their potential for innovative microfluidic designs and real-world applications.
Comparative analysis of sleep physiology using qualitative and quantitative criteria for insomnia symptoms
Authors: Lee Ruda , Larson Olivia , Dhaliwal Sammy , Moon Kibum , Gerardy Bethany , de Chazal Philip , Cistulli Peter A , Chen Ning-Hung , Han Fang , Li Qing Yun , Maislin Greg , McArdle Nigel , Penzel Thomas , Schwab Richard J , Tufik Sergio , Magalang Ulysses J , Singh Bhajan , Gislason Thorarinn , Pack Allan I , Keenan Brendan T , Younes Magdy , Gehrman Philip
Published: December 2024

Despite decades of research, defining insomnia remains challenging due to its complex and variable nature. Various diagnostic systems emphasize the chronic nature of insomnia and its impact on daily functioning, relying heavily on patient self-reporting due to limitations in objective measures such as polysomnography (PSG). Discrepancies between subjective experiences and objective PSG results highlight the need for more nuanced approaches, such as electroencephalogram (EEG) spectral analysis, which reveals distinct patterns of high-frequency activity in individuals with insomnia. This study explores EEG markers of insomnia by integrating subjective reports with objective physiological markers, specifically ORP (Odds-Ratio-Product) and spectral features, to address inconsistencies found in previous research and clinical settings. Qualitative and quantitative definitions of insomnia are contrasted to highlight differences in sleep architecture and EEG characteristics. The research aims to determine whether groups defined by weekly frequency and daily duration of symptoms have different distribution patterns and which physiological characteristics best distinguish insomnia patients from controls. Our findings suggest that ORP, as a dependent variable, captures the most significant differences in the independent variables across the model. Elevated beta power in insomnia patients indicates increased cortical arousal, supporting the perspective of insomnia as a hyperarousal disorder. Future research should focus on using ORP to enhance the understanding of sleep disturbances in insomnia. Comprehensive evaluation of insomnia requires integrating qualitative, quantitative, and neurophysiological data to fully understand its impact on sleep architecture and quality.
Effects of low acid-binding capacity specialty soy protein sources on nursery pig performance in a commercial environment
Authors: Stas Ethan B , Warner Alan J , Post Zach B , Hastad Chad W , Faccin Jamil E G , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Goodband Robert D , Gebhardt Jordan T
Published: December 2024

Two experiments were conducted to determine the effects of low acid-binding capacity (ABC) specialty soy protein sources on weanling pig performance. In experiment 1, 2,260 pigs, initially weighed 6.7 kg, were used to determine the effects of low ABC soy proteins as a replacement to poultry meal (PM) or spray-dried blood plasma (SDBP). Treatments were arranged in a 2 × 2 factorial plus a control diet fed in two phases. There were 20 or 21 pigs per pen with 22 replications (pens) per treatment. The control diet contained PM (AV-E Digest, XFE Products, Des Moines, IA) and SDBP (Appetein, APC Inc., Ankeny, IA). Specialty soy protein concentrate (SSPC; AX3 Digest, Protekta, Newport Beach, CA) and microbial-enhanced soybean meal (MESBM; MEPRO; Prairie Aquatech, Brookings, SD) were used to replace PM or PM and SDBP on a standardized ileal digestible Lys basis. From d 0 to 21 and d 0 to 42, pigs fed either soy protein source replacing PM had greater (P ≤ 0.016) average daily gain (ADG) and average daily feed intake than pigs fed PM. From d 0 to 21, pigs fed SSPC had increased (P < 0.001) G:F compared with pigs fed MESBM and those fed either soy protein source replacing SDBP had increased (P = 0.044) G:F compared with pigs fed SDBP. In experiment 2, 1,057 pigs, initially weighed 6.2 kg, were used to determine the effects of diet ABC at a pH of 4 (ABC-4) with specialty soy proteins with or without pharmacological levels of Zn from ZnO. Experimental diets were fed in two phases with 22 pigs per pen and 12 replications per treatment. Dietary treatments were arranged in a 2 × 2 factorial with main effects of ABC-4 (low or high) and pharmacological levels of Zn from ZnO (105 or 2,000 mg/kg). The low ABC-4 diet without ZnO was formulated to 150 and 200 meq/kg using SSPC in phases 1 and 2, respectively. The high ABC-4 diet used enzymatically treated soybean meal (HP 300, Hamlet Protein, Findlay, OH) which increased the ABC-4 by 127 and 104 meq/kg in phases 1 and 2, respectively. From d 0 to 21 and d 0 to 42, there was an ABC-4 × ZnO interaction (P ≤ 0.026) observed where pigs fed low ABC-4 diets had greater (P < 0.05) ADG and G:F than pigs fed high ABC-4 diets without ZnO, but when diets contained added ZnO, there were no differences based on ABC-4. In conclusion, low ABC specialty soy proteins can be used to achieve low dietary ABC-4 levels to improve the performance of weanling pigs and provide a similar response to those fed pharmacological levels of Zn.
Impact of sub-lethal Aclonifen intoxication on biochemical and stress markers on Oncorhynchus mykiss: an integrative assessment of multi-biomarker responses
Authors: Horani Reham Al , Dogan Demet
Published: December 2024

Aclonifen is a diphenyl ether herbicide being included in the list of priority substances. Nevertheless, the data related to its sublethal effects on fish are limited. Therefore, the present study has been carried out to investigate the toxic effects of aclonifen in juvenile Oncorhynchus mykiss following 24, 48, 72 and 96 hours of application to sublethal concentrations of 12.7, 63.5 and 127 μg/L. The application resulted in altered blood biochemistry appearing as hyperglycemia, decreased cholesterol and induced activities of transaminases of ALT and AST. The inhibition of AChE in brain, gill and liver was unimportant revealing its weak potential as anticholinesterase. The induction recorded for SOD, CAT, GPx and GST activities was accompanied with sustained elevation in TBARS and PC levels. It demonstrates both the pro-oxidant potential of aclonifen and oxidation of lipid and proteins resulting in the loss of membrane integrity and protein function. Hyperglycemic condition and decreased protein levels in gill and liver might be proposed as general adaptive responses to compensate increased energy demand. The integrative assessment of multi-biomarker responses shows concentration and duration related rise in calculated indexes. CAT, PC and SOD achieved the maximum scores for brain, gill and liver, respectively. Considering the results, oxidative stress inducing potential and weak anticholinesterase activity along with its disturbing impact on blood biochemistry were evidenced. Moreover, adverse affects observed after short term application on O. mykiss, present the potential risk aclonifen may cause at population level in aquatic ecosystems emphasizing the importance of pesticide regulations to avoid adverse impacts on non-target species.
Molecular epidemiology, evolution, and transmission dynamics of raccoon rabies virus in Connecticut
Authors: Veytsel Gabriella , Desiato Julia , Chung Hyunjung , Tan Swan , Risatti Guillermo R , Helal Zeinab H , Jang Sungmin , Lee Dong-Hun , Bahl Justin
Published: December 2024

In North America, raccoon rabies virus (RRV) is a public health concern due to its potential for rapid spread, maintenance in wildlife, and impact on human and domesticated animal health. RRV is an endemic zoonotic pathogen throughout the eastern USA. In 1991, an outbreak of RRV in Fairfield County, Connecticut, spread through the state and eventually throughout the Northeast and into Canada. Factors that contribute to, or curb, RRV transmission should be explored and quantified to guide targeted rabies control efforts, including the size and location of buffer zones of vaccinated animals. However, population dynamics and potential underlying determinants of rabies virus diversity and circulation in Connecticut have not been fully studied. In this study, we aim to (i) investigate RRV source–sink dynamics between Connecticut and surrounding states and provinces, (ii) explore the impact of the Connecticut River as a natural barrier to transmission, and (iii) characterize the genomic diversity and transmission dynamics in Connecticut. Using RRV whole-genome sequences collected from various host species between 1990 and 2020, we performed comparative genetic and Bayesian phylodynamic analyses at multiple spatial scales. We analyzed 71 whole-genome sequences from Connecticut, including 21 recent RRV specimens collected at the Connecticut Veterinary Medical Diagnostic Laboratory that we sequenced for this study. Our analyses revealed evidence of RRV incursions over the US–Canada border, including bidirectional spread between Quebec and Vermont. Additionally, we highlighted the importance of Connecticut and New York in seeding RRV transmission in eastern North America, including two introduction events from New York to Connecticut that resulted in sustained local transmission. While RRV transmission does occur across the Housatonic and Connecticut Rivers, we demonstrated the distinct presence of spatial structuring in the phylogenetic trees and characterized the directionality of RRV migration. The significantly higher mean transition rates from locations east to west of the Connecticut River, compared to west to east, may be leveraged in directing interventions to fortify these natural barriers. Ultimately, the findings of these international, regional, and state analyses can inform targeted control programs, vaccination efforts, and enhanced surveillance at borders of key viral sources and sinks.
Weight-bearing CT and Advances in the Diagnosis of Syndesmotic Instability
Authors: Ranganathan Noopur , Guss Daniel , Ashkani-Esfahani Soheil
Published: December 2024

Detection and treatment of syndesmotic instability are imperative to optimize clinical outcomes and prevent future disabilities, chronic pain, and osteoarthritis. Assessing syndesmosis under physiological conditions has been reported to play an important role in recognition of instability, particularly if subtle. Weightbearing computed tomography (WBCT) has emerged as a novel, more accurate imaging modality that can assess the ankle syndesmosis under physiological load in a 3-dimensional manner. In this article, we briefly reviewed recent advances, various measurements and interpretation techniques for the diagnosis of syndesmotic instability using WBCT. Level of Evidence: Diagnostic; level V.
Follow-up Adherence After Teleretinal Screening for Diabetic Retinopathy
Authors: Chamberlain Paul D. , Date Rishabh C. , Shen Kevin L. , Campagna Giovanni A. , Piller Linda B. , Chu Yvonne I. , Weng Christina Y.
Published: December 2024

Aim:

Determine the follow-up rate for patients referred following an abnormal teleretinal imaging (TRI) screening and examine patient characteristics predictive of follow-up nonadherence.

Materials and Methods:

A cross-sectional study of patients screened between August 2014 and July 2016 in the Harris Health System (HHS) in Houston, TX. All diabetic patients referred for in-person examination, who had data for all study variables, and who did not have established ophthalmic care in the HHS within the previous 2 years were included. Data collected included TRI findings, clinic location, age, race, gender, hemoglobin A1C (HbA1c), and insulin use. The primary outcome was whether or not a patient attended an in-person follow-up visit. Attendance was the dependent variable in a multivariable logistic regression with the aforementioned exposures used as independent variables.

Results:

There were 1695 patients included in the study. The follow-up rate (ie, the percentage of patients who went for an in-person examination with an ophthalmologist following a positive screening test and referral) was 54.9%. TRI findings of proliferative diabetic retinopathy (PDR) + referable diabetic macular edema (DME) predicted poorer compliance with follow-up recommendations compared to patients with PDR alone (OR 0.64, 95% CI 0.42-0.99; P=0.046). Age, race, gender, glycemic control, and insulin use did not predict compliance.

Conclusion:

Age, race, gender, glycemic control, and insulin use were not found to be predictive of follow-up compliance rates; the most severe disease (PDR + DME) predicted noncompliance. Diabetic retinopathy screening programs may consider more aggressive measures in emphasizing compliance in patients with the worst disease as these patients are more likely to miss follow-up appointments. More studies are needed to characterize risk factors for noncompliance.
The Safety of Recently Approved Therapeutics in Age-Related Macular Degeneration
Authors: Khanani Ibrahim , Aziz Aamir A. , Khanani Zoha A. , Khan Hannah , Mojumder Ohidul , Sulahria Humza , Ali Haaziq , Khan Huma , Rahimzadeh Tyler S. , Vannavong Jordyn , Gahn Greggory M. , Khanani Arshad M.
Published: December 2024

Recent developments in treatments for both forms of advanced age-related macular degeneration (AMD) have led to the approval of multiple agents and modalities within the last few years. Five new medications for both neovascular AMD (nAMD) and geographic atrophy (GA) secondary to nonexudative AMD (neAMD) have been FDA-approved within the last 5 years, along with a new device designed for sustained drug delivery for nAMD. In nAMD, the newest agents approved by the FDA are brolucizumab (Novartis Pharmaceuticals, Basel, Switzerland), faricimab (F. Hoffman-La Roche, Basel, Switzerland), aflibercept 8 mg (Regeneron Pharmaceuticals, Tarrytown, NY, USA), and a new device in the port delivery system with ranibizumab (Genentech, San Francisco, CA, USA). The first agents FDA-approved for GA secondary to neAMD are pegcetacoplan (Apellis Pharmaceuticals, Waltham, MA, USA) and avacincaptad pegol (Iveric Bio, Parsippany, NJ, USA). Evaluation of safety in both clinical trials and the real-world has been of paramount importance after the approval of these newest agents to understand their effects in real patients. Real-world data, as demonstrated in both registrational studies along with retrospective chart review studies, has shown to be an important factor in the implementation of newer drugs, along with the treatment decisions that physicians choose to make regarding their dosing and follow-up. This review article discusses the safety of the most recently approved FDA as seen in both clinical trials and real-world studies.
Retropupillary Iris Clip Intraocular Lenses: A Case Series of 57 Eyes
Authors: Mallick Pauline , Fung Adrian T.
Published: December 2024

Purpose:

To report visual and refractive outcomes and intraoperative and postoperative complications after pars plana vitrectomy (PPV) with retropupillary implantation of an iris clip intraocular lens (IOL).

Methods:

This is a retrospective case series of patients who underwent secondary retropupillary intraocular lens insertion combined with pars plana vitrectomy to treat aphakia secondary to a dislocated nucleus lens (group A); or IOL dislocation (group B). Patient demographics, preoperative visual and refractive outcomes, intraoperative factors, postoperative visual and refractive outcomes, and complications within the follow-up period ranging from 6 months up to 3 years postoperative, were recorded.

Results:

In total, 57 eyes of 50 patients were included with a follow-up range of 6 months to 3 years. The overall mean age was 77.0 years (range 28 to 99 years), with 26/50 (52%) of patients being male. There were 13/57 (22.8%) patients in group A and 44/57 (77.2%) patients in group B. The single most common identifiable cause for lens dislocation was pseudoexfoliation, which was seen in 13/57 (22.8%) of eyes. The mean improvement in visual acuity (baseline and final follow) was 0.72 logMAR (1.09 logMAR to 0.37 logMAR) in all patients, 1.12 logMAR (1.64 logMAR to 0.52 logMAR) in group A, and 0.60 logMAR (0.91 logMAR to 0.31 logMAR) in group B. In 46 eyes (80.7%), postoperative refractive errors were within ±1.00 dioptres (D) of the target refraction, with a mean difference of 0.36D from target refraction. Complications included corneal edema (35.1%), hyphema (26.3%), anterior chamber inflammation (26.3%), vitreous hemorrhage (14%), elevated intraocular pressure (IOP, 12.3%) and cystoid macular edema (CME, 5.3%). All these complications were managed with topical medical therapy and did not require further surgical intervention. One eye from group A was the only eye that developed retinal detachment (RD) or endophthalmitis. No patients had IOL dislocation in the postoperative follow-up period, which ranged from 6 months to 3 years.

Conclusions:

Retropupillary implantation of an iris clip IOL with pars plana vitrectomy is an efficient, predictable, and stable surgical option for aphakic eyes without capsular support. Postoperative corneal edema, hyphema, and anterior chamber inflammation are common but usually resolve without the need for further surgical intervention.
Retinal Microstructural and Microvascular Changes in Alzheimer Disease: A Review
Authors: Olivares Ordoñez Marco Antonio , Smith Rebekah Cossette , Yiu Glenn , Liu Yin Allison
Published: December 2024

“The eyes are a window to the brain,” prompting the investigation of whether retinal biomarkers can indicate Alzheimer disease (AD) and cognitive impairment. AD is a neurodegenerative condition with a lengthy preclinical phase where pathologic changes in the central nervous system (CNS) occur before clinical symptoms. Mild cognitive impairment (MCI) often precedes AD. As part of the CNS, the retina exhibits similar pathologic changes related to AD as those seen in the brains of patients with MCI. Noninvasive imaging technologies such as optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) allow high-resolution visualization of the retina, providing an opportunity to screen and monitor AD noninvasively. In this review, we summarize the relationship between AD and retinal pathology detected by OCT and OCTA. The most common findings in patients with AD include peripapillary retinal nerve fiber layer thinning, decreased macular thickness, an enlarged foveal avascular zone, and decreased vascular densities in the superficial and deep capillary plexuses. These retinal changes correlate with magnetic resonance imaging (MRI) findings of cerebral atrophy, positron emission tomography (PET) findings of increased amyloid load, and neuropsychological testing results suggesting cognitive dysfunction. We conclude that retinal microstructural and microvascular abnormalities may serve as biomarkers for the early detection and clinical monitoring of AD and as tools for evaluating potential treatment effects. Future studies should focus on standardizing protocols for in vivo ophthalmic imaging to measure retinal pathology in AD and MCI.
Tyrosine Kinase Inhibitors: The Next Chapter in Reducing Treatment Burden for Exudative Retinal Diseases?
Authors: Ravichandran Pranesh , Canizela Cecilia , Sayed Abrahem , Hussain Rehan M.
Published: December 2024

Tyrosine kinase inhibitors (TKIs) serve to inhibit the phosphorylation cascade that usually leads to abnormal processes such as vascular leakage and tumorigenesis. Within retinal diseases specifically, dysregulation of the vascular endothelial growth factor receptor tyrosine kinases can lead to age-related macular degeneration and diabetic macular edema. These diseases have a growing prevalence and are leading causes of vision loss. The current standard of care requires repeated administration of anti–vascular endothelial growth factor injections, which poses a significant burden on patients. Novel TKIs provide an opportunity to reduce injection frequency by targeting a broader range of molecules involved in angiogenesis and exudation. This review will cover TKIs in development and how their use of different technologies and targets may enhance visual and anatomic outcomes for patients with exudative retinal disease.
Reprogramming patient-induced pluripotent stem cell-specific retinal organoids for deciphering epigenetic modifications of RNA methylation
Authors: Chien Yueh , Yang Yi-Ping , Lin Tai-Chi , Chiou Guang-Yuh , Yarmishyn Aliaksandr A. , Wang Chia-Hao , Ching Lo-Jei , Lin Yi-Ying , Chen Shih-Jen , Hwang De-Kuang , Hsu Chih-Chien
Published: December 2024

Background:

Induced pluripotent stem cell (iPSC) technology has emerged as a powerful tool for disease modeling, providing an innovative platform for investigating disease mechanisms. iPSC-derived organoids, including retinal organoids, offer patient-specific models that closely replicate in vivo cellular environments, making them ideal for studying retinal neurodegenerative diseases where retinal ganglion cells (RGCs) are impacted. N6-methyladenosine (m6A), a prevalent internal modification in eukaryotic mRNAs, plays a critical role in RNA metabolic processes such as splicing, stability, translation, and transport. Given the high energy demands of RGCs, mitochondrial dysfunction, which leads to impaired adenosine triphosphate (ATP) production and increased reactive oxygen species (ROS) levels, is often central to the progression of retinal neurodegenerative disorders. However, the epigenetic mechanisms underlying m6A modification and their contributions to these conditions remain unclear.

Methods:

Patient-specific iPSCs were generated from individuals with Leber hereditary optic neuropathy (LHON) and differentiated into RGCs within retinal organoids. To analyze m6A methylation, we used quantitative polymerase chain reaction (PCR) and focused on differential expression of key m6A-modifying enzymes.

Results:

iPSC-derived retinal organoids are adaptable for studying and investigating the epigenetic mechanisms of retinal neurodegenerative diseases. Our data demonstrated the profiling of global m6A-related gene expression levels in LHON patient-derived iPSC-RGCs compared with controls, highlighting specific disruptions in m6A modification pathways.

Conclusion:

These findings suggest that differential m6A modifications may play pivotal roles in the pathogenesis of retinal neurodegenerative diseases and affect the progression of the disease in affected individuals.
Long-term results of laparoscopic Heller-Dor for esophageal-gastric junction outflow obstruction: a prospective comparative study
Authors: Salvador Renato , Forattini Francesca , Provenzano Luca , Costantini Andrea , Vittori Arianna , Santangelo Matteo , Capovilla Giovanni , Costantini Mario , Moletta Lucia , Nezi Giulia , Nicoletti Loredana , Valmasoni Michele
Published: December 2024

Background:

The aim of this prospective, controlled study was to assess the 5-year follow-up of laparoscopic Heller-Dor (LHD) in patients with esophago-gastric junction outflow obstruction (EGJOO), compared with achalasia patients (ACH). The management of EGJOO reflects the experience gained with esophageal achalasia, for which LHD has been proven to be an effective long-term treatment. Prospective long-term results of LHD in EGJOO patients are still lacking.

Materials and methods:

Patients with diagnosis of idiopathic EGJOO referred for dysphagia or food-regurgitation, treated with LHD, were enrolled and then followed prospectively for 5 years. During the follow-up, patients were evaluated with Eckardt score (ES), Barium-swallow X-ray, high-resolution manometry (HRM), 24-hour pH-monitoring and endoscopy. Primary outcome was therapeutic success (ES ≤ 3 or no additional treatment).

Results:

The study involved 150 patients: 25 in the EGJOO group and 125 in the ACH group. After 5 years, there was no significant difference in success rate: 90.5% in the EGJOO group, 87.5% in ACH stage I – pattern I, 91.6% in ACH stage I – pattern II and pattern III (P = 0.94). The ES and all the HRM parameters were similar in all groups. Moreover, the screening endoscopy and the 24-hour pH-monitoring showed a similar postoperative acid exposure in all groups.

Conclusion:

This is the first study based on prospective data to assess the long-term outcome of LHD in patients with EGJOO. After at least 5 years of follow-up, LHD has a comparable success rate in both EGJOO and achalasia patients and can be proposed as a safe and effective treatment for EGJOO patients.
Invasive or non-invasive vagus nerve stimulation modulation of brain function and remodeling after stroke: a review
Authors: Zhang Jun , Zhou Fengyuan , Roberts Neil , Yuan Qiang , Wang Meihua , Wu Gang , Yang Weijian , Fu Pengfei , Wang Meiyun , Hu Jin
Published: December 2024

Background:

The main reason restricting stroke patients from reintegrating into society is neurological deficits. Of particular interest is the potential vagus nerve stimulation (VNS) potentially offers for sustaining improvement in neurological deficits. The goal of the present study is to provide a summary of the findings from research that has been carried out to elucidate the mechanisms and demonstrate the efficacy and safety of the clinical application of VNS, as well as to identify research gaps in the field, in order to offer references for subsequent further research and application.

Methods:

A systematic search was conducted in the PubMed, Web of Science, Embase, and Ovid MEDLINE databases (1866 publications). An initial screening of abstracts and titles was performed, followed by a thorough review and assessment of the full texts of 253 relevant papers.

Results:

Ultimately, 62 studies that met the eligibility criteria were included. VNS may be performed either invasively or non-invasively. The modulation of brain function that is produced by VNS may improve cerebral function by one or more of the following means, namely stimulating the pathway that regulates synaptic plasticity, inhibiting inflammatory response, promoting vascular regeneration or protecting the blood–brain barrier. Application of invasive VNS has produced promising results in the treatment of moderate/severe upper limb dyskinesia in patients with ischemic stroke and has gradually entered clinical practice. Furthermore, transcutaneous auricular VNS has also demonstrated potential therapeutic effects (standardized mean differences 1.16, 95% CI = 0.02–2.30). However, further developments are required in many aspects, including preventing indications of dysfunction, optimization of parameters, timing and duration of stimulation and site of application.

Conclusions:

The VNS as a promising therapeutic approach for stroke rehabilitation. The application of VNS in the treatment of hemorrhagic stroke is still unexplored and warrants attention in future studies.
An artificial intelligence-driven revolution in orthopedic surgery and sports medicine
Authors: Guan Jiekai , Li Zuhao , Sheng Shihao , Lin Qiushui , Wang Sicheng , Wang Dongliang , Chen Xiao , Su Jiacan
Published: December 2024

With the advancement of population aging, the incidence of orthopedic diseases increases annually. The early diagnosis and precise treatment of many orthopedic diseases still require advancements in technology to address effectively. With the rapid development of artificial intelligence (AI), this technology is expected to achieve early diagnosis and improved treatment of many diseases, providing revolutionary changes in clinical. However, the integration of AI in orthopedics is still in its infancy, and its existing intelligent algorithms have been clinically applied models and their advantages need to be further summarized to pave the way for future development and exploration. The review provides a concise overview of the basic concepts and mechanisms of AI in orthopedics, and summarizes orthopedic surgery and sports medicine in four areas of application and development, specifically, developing precision diagnostics, assisting treatment, monitoring assisted during rehabilitation, and enhancing educational research and data analysis. In this section, the main focus is on each aspect of the AI programs that are now used in clinical applications, and also comparing them to the purely manual results. In conclusion, the continued application and development of AI are anticipated to enhance our understanding of the diagnosis, progression, and prognosis of orthopedic diseases, ultimately laying the groundwork for more effective clinical applications.
Alterations of oscillatory activity and cognitive function after aneurysmal subarachnoid hemorrhage
Authors: Liu Peng , Han Chuanliang , Zhang Tongyu , Xu Yueqiao , Yang Kun , Li Yuxia , Ye Zhennan , Wang Changming , Zhang Hongqi
Published: December 2024

Background:

Aneurysmal subarachnoid hemorrhage (aSAH) can lead to cognitive impairment (CI), but underlying neural mechanisms remain to be elucidated.

Materials and methods:

To predict long-term CI after aSAH, resting electroencephalography (EEG) was measured in 112 patients hospitalized with a diagnosis of aSAH (n = 66) or unruptured intracranial aneurysms (controls) (n = 46). A neuropsychological battery was administered 8–24 months after discharge.

Results:

Power spectrum analysis in the parietal-occipital lobe showed significantly higher power theta vs. alpha oscillations in patients with CI after aSAH. The power of theta and alpha oscillations were significantly correlated with multiple cognitive scale scores on the neuropsychological battery. A neural model was established, which showed that connectivity between inhibitory and excitatory neurons in neural circuits contributed to changes in theta and alpha oscillations and CI in aSAH.

Conclusion:

The data collection, analysis, and computational model established in this study can serve as a new paradigm for other clinical studies investigating CI.
ChatGPT Can Often Respond Adequately to Common Patient Questions Regarding Femoroacetabular Impingement
Authors: Adelstein Jeremy M. , Sinkler Margaret A. , Li Lambert T. , Fortier Luc M. , Vakharia Ajit M. , Salata Michael J.
Published: December 2024

Objective:

This study aims to analyze the ability of ChatGPT to answer frequently asked questions (FAQs) regarding FAI. We hypothesize that ChatGPT can provide accurate and thorough responses when presented with FAQs regarding FAI.

Design:

Ten FAQs regarding FAI were presented to ChatGPT 3.5 and initial responses were recorded and analyzed against evidence-based literature. Responses were rated as “excellent response requiring no further clarification,” “satisfactory response requiring minimal clarification,” “satisfactory response requiring moderate clarification,” or “unsatisfactory response requiring substantial clarification.”

Setting:

Institutional.

Independent Variables:

Frequently asked questions regarding femoroacetabular impingement.

Main Outcome Measures:

Accuracy and thoroughness of ChatGPT responses to FAQs. Hypothesis was formulated before data collection.

Results:

Most responses from ChatGPT were rated as satisfactory and required only minimal clarification. Two responses received an excellent rating and required no further clarification, while only 1 response from ChatGPT was rated unsatisfactory and required substantial clarification.

Conclusions:

ChatGPT provided largely accurate and thorough responses to FAQs regarding FAI while appropriately reiterating the importance of always consulting a medical professional.
Respiratory syncytial virus pulmonary infections in adults – disease burden and prevention
Authors: Waterer Grant W. , Metersky Mark
Published: December 2024

Purpose of review

We highlight the evolving understanding of the burden of respiratory syncytial virus (RSV) in older adults and recent data on the three new vaccines.

Recent findings

As well as a greater recognition of the amount of RSV infection in adults, and especially over 60 years of age, there has been a significant amount of study detailing the postacute burden including excess cardiovascular disease and loss of physical and cognitive functioning. Three new RSV vaccines now have published data for two seasons, and while direct comparison is not possible due to differences in the timing, methodology and populations studies, all show good efficacy with no serious side effects of concern.

RSV causes a substantial amount of morbidity and mortality in older adults with both acute and longer term impacts. With effective vaccines now available clinicians should be advocating with their patients to prevent RSV infection.
Clinical Analysis of Pediatric Acute Leukemias of Ambiguous Lineage: A Single Institution Retrospective Review
Authors: Xia Chen , Xiaoli Chen , Xiaofan Zhu
Published: December 2024

Acute leukemias of ambiguous lineage (ALAL) is a rare type of acute leukemia, referring to a group of disorders characterized by a combination of myeloid, lymphoid, or more lineages, whose incidence is significantly lower in children than adults. Here, we summarized the clinical features and outcomes of 36 pediatric ALAL patients in past 16 years. The patients diagnosed as ALAL based on the criteria of EGIL scoring system in 1998 (EGIL 1998) and/or the 2016 revisions to the WHO classification (WHO 2016) from January 1, 2005 to December 1, 2021 were included, respectively. During follow-up for a median 22 months, the median leukemia-free survival (LFS) was 18 months (0 to 172 mo) and the median overall survival (OS) was 22 months (1 to 173 mo), with a 5-year LFS rate of 67.3±9.2% and a 5-year OS rate of 66.0±10.7%. Patients who sustained negative minimal residual disease after 2 courses of standardized chemotherapy contributed to better 5-year OS (100% vs. 37.2±22.0%, P=0.028) and LFS (100% vs. 46.7±16.6%, P=0.028).
Congenital diaphragmatic hernia presenting as tension hydropneumothorax: surgical dilemma
Authors: Aihole Jayalaxmi Shripati
Published: December 2024

Introduction:

Congenital diaphragmatic hernia (CDH) most commonly seen on the left side, presenting usually in neonates and infants with respiratory distress.

Importance:

CDH presenting as tension hydropneumothorax requiring urgent intercostal chest tube drainage (ICD) and subsequently inducing the injury to the herniated bowel and lung, is not an uncommon event, rarely reported in toddlers as well as its management.

Case presentation:

Two such rare cases of CDH presenting with tension hydropneumothorax requiring ICD insertion and their consequences have been discussed here.

Clinical discussion:

CDH can present later in life due to consequent recurrent bronchopneumonia and failure to thrive.

Conclusion:

Clinical history and clinical judgement can only aid the surgeon in avoiding such confusing clinical scenarios.
The Impact of a Couple-Based Intervention on One-Year Viral Suppression Among Pregnant Women Living With HIV and Their Male Partners in Malawi: A Randomized Controlled Trial
Authors: Rosenberg Nora E. , Graybill Lauren A. , Mtande Tiwonge , McGrath Nuala , Maman Suzanne , Nthani Tiyamike , Krysiak Robert , Thengolose Isaac , Hoffman Irving F. , Miller William C. , Hosseinipour Mina
Published: December 2024

Introduction:

Couple-based behavioral interventions (CBIs) have been associated with improved HIV virological outcomes for pregnant women and their male partners living with HIV in observational settings, but have never been tested in a randomized controlled trial (RCT).

Setting:

Bwaila District Hospital Antenatal Clinic (Lilongwe, Malawi).

Methods:

An RCT was conducted among 500 pregnant women living with HIV (index clients) randomized 1:1 to the standard of care (SOC) or CBI and followed for 1 year. The CBI offered an initial session for index clients, HIV-assisted partner notification, 2 enhanced couple counseling and testing sessions, illustrated materials, and antiretroviral therapy pickup for either couple member at the antenatal clinic. At 12 months, viral load among index clients and male partners with HIV was measured. Risk differences (RD) and 95% confidence intervals (CIs) compared viral suppression (<1000 copies/mL) between arms.

Results:

The mean index client age was 26.6 years; most were married or cohabiting (93.3%). Index client viral suppression was 6.5% higher in the CBI arm (88.0%) than in the SOC arm (81.6%). Male partner viral suppression was 16.2% higher in the CBI arm (73.6%) than the SOC arm (57.4%). Overall, couple viral suppression was 7.8% higher (CI: 0.5% to 15.1%, P = 0.04) in the CBI arm (84%) than in the SOC arm (76.0%). Social harms were rare (3.6%) and comparable between arms (P = 0.8).

Conclusions:

This CBI had a positive impact on couple viral suppression. Scaling this CBI to antenatal clients with HIV and their male partners could improve HIV outcomes among expecting families.
Fumarate Hydratase–Deficient Renal Cell Carcinoma With Paraganglioma Detected on 18F-FDG PET/CT
Authors: Deng Yan , He Limeng , Wu Ji , Zhang Wei
Published: December 2024

We report FDG PET/CT findings of fumarate hydratase–deficient renal cell carcinoma coincidence with para-aortic paraganglioma in a 27-year-old man. He presented with painless gross hematuria for 3 days. CT identified an enhancing lesion in the left kidney, suggestive of a tumor. 18F-FDG PET/CT imaging showed the mass with high FDG uptake. An adjacent FDG-avid nodule was also noted. Postoperative pathology supported a diagnosis of fumarate hydratase–deficient renal cell carcinoma of the left kidney mass, and the adjacent nodule was paraganglioma.
Anatomy-based Filler Injection: Diagnosis to Treatment Techniques for the Glabellar Region
Authors: Hong Gi-Woong , Kim Soo-Bin , Yoon Song Eun , Wan Jovian , Park Hyun Jin , Yi Kyu-Ho
Published: December 2024

Glabellar filler injections are a popular non-surgical approach to address depressions and wrinkles caused by aging, muscle activity, and soft tissue loss. An anatomy-based technique emphasizes understanding the complex structure of the glabellar region, including the corrugator supercilii and procerus muscles, and the superficial vascular pathways, such as the supratrochlear and supraorbital arteries. Effective treatment involves precise filler placement, often combined with botulinum toxin to address both volume loss and dynamic wrinkles. Injection techniques like the fern leaf and duck walk methods are preferred to minimize the risk of vascular complications and achieve a smooth, natural appearance. The choice of injection depth and technique is crucial to avoid damaging vital structures and to enhance aesthetic outcomes. Understanding individual anatomic variations and selecting appropriate treatment combinations can significantly improve the safety and effectiveness of glabellar filler injections, providing a rejuvenated and balanced facial appearance.