bluuebunny/crossref_metadata_2025 huggingface dataset:
Mini-Invasive Harvesting of Quadriceps Tendon Graft With Patellar Bone Block for ACL Reconstruction Using a Dedicated Harvester
Authors: Vittone Giulio , Valcarenghi Jérôme , Mouton Caroline , Seil Romain
Published: October 2023

Background:

The selection of the type of graft used to reconstruct the anterior cruciate ligament (ACL) remains a matter of debate. In the past, the quadriceps tendon (QT) was associated with considerable morbidity and less favorable outcomes than other grafts. Improvements in harvesting methods have decreased morbidity of the surgical procedure and led to an increase in the use of QT in recent years.

Indications:

The QT graft with patellar bone block is a viable option for all patients with closed physis undergoing ACL reconstruction. It is especially suitable for young and active patients who practice activities that require kneeling or athletes in which hamstrings preservation is advisable.

Technique Description:

A vertical mini-invasive longitudinal incision starts 1 cm proximal to the middle of the patellar pole. After dissection, the bone block is marked and detached with an oscillating saw. A drill hole is performed in the bone block to serve for the passage of a traction suture. The bone block is lifted with the help of the traction suture, and the graft is trimmed to the desired diameter. The layer between tendon and capsule is separated by blunt dissection to spare the capsule of the suprapatellar pouch. Harvesting is achieved using a dedicated QT harvester. Usually, a graft length of 8 cm is harvested. The defect in the QT is closed using a suture passer at the proximal end. Finally, the graft is prepared and calibrated according to the planned technique for ACL reconstruction.

Results:

There was no major intraoperative complication in the senior author's series (more than 50 patients) using the dedicated QT harvester. On rare occasions (<10% of the cases), the device opened the suprapatellar joint capsule, creating the additional need for capsular repair during defect closure. On two occasions, the graft was shorter than expected, which may have been caused by insufficient dissection or improper use of the harvester.

Discussion/Conclusion:

ACL reconstruction with minimally invasive QT graft harvesting methods has shown very good clinical outcomes with few complications. It can be recommended for primary and revision ACL reconstruction.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Lithofacies, stratigraphy and depositional history of Middle Muschelkalk evaporites (Zeglingen Formation) in northern Switzerland
Authors: Pietsch Johannes S. , Wetzel Andreas , Deplazes Gaudenz , Filipponi Marco
Published: October 2023

In northern Switzerland, Middle Muschelkalk evaporites (Zeglingen Formation) were deposited under arid conditions in the southernmost part of the epicontinental Central European Basin during times of reduced inflow of sea water from the Tethyan realm. Because of their marginal position in the basin, direct and detailed correlation of Muschelkalk sediments of northern Switzerland with equivalent strata in interior parts of the basin is not straightforward. Based on detailed sedimentological logging of 640 m of drill cores from ten wells in northern Switzerland, 22 lithofacies and 10 lithofacies associations were distinguished for the Middle Muschelkalk evaporites. High-resolution regional correlations of gamma-ray logs record substantial thickness variation of the evaporites. Locally, dissolution was recognized by visual core examination that could be dated to Middle Triassic times and that was likely related to subsurface fluid flow along deeper seated faults. In combination with the regional thickness variation, the dissolution phenomena suggest a tectonically active depositional setting in the Middle Triassic. Middle Muschelkalk evaporites consist of nine types of mainly auto-cyclic shallowing- or brining-upward mini-cycles which form a correlatable succession of five distinct 4th order cycle-sets. Despite the tectonically active depositional environment, most lithofacies encountered appear to have nearly flat bounding surfaces. Thus, marine transgressions flooded wide areas nearly simultaneously. The corresponding deposits serve as reference levels to tie the peripheral facies of northern Switzerland into the supra-regional context.
A comparison of Oxford nanopore library strategies for bacterial genomics
Authors: Sauvage Thomas , Cormier Alexandre , Delphine Passerini
Published: October 2023

Background

Oxford nanopore Technologies (ONT) provides three main library preparation strategies to sequence bacterial genomes. These include tagmentation (TAG), ligation (LIG) and amplification (PCR). Despite ONT’s recommendations, making an informed decision for preparation choice remains difficult without a side-by-side comparison. Here, we sequenced 12 bacterial strains to examine the overall output of these strategies, including sequencing noise, barcoding efficiency and assembly quality based on mapping to curated genomes established herein.

Results

Average read length ranged closely for TAG and LIG (> 5,000 bp), while being drastically smaller for PCR (< 1,100 bp). LIG produced the largest output with 33.62 Gbp vs. 11.72 Gbp for TAG and 4.79 Gbp for PCR. PCR produced the most sequencing noise with only 22.7% of reads mappable to the curated genomes, vs. 92.9% for LIG and 87.3% for TAG. Output per channel was most homogenous in LIG and most variable in PCR, while intermediate in TAG. Artifactual tandem content was most abundant in PCR (22.5%) and least in LIG and TAG (0.9% and 2.2%). Basecalling and demultiplexing of barcoded libraries resulted in ~ 20% data loss as unclassified reads and 1.5% read leakage.

Conclusion

The output of LIG was best (low noise, high read numbers of long lengths), intermediate in TAG (some noise, moderate read numbers of long lengths) and less desirable in PCR (high noise, high read numbers of short lengths). Overall, users should not accept assembly results at face value without careful replicon verification, including the detection of plasmids assembled from leaked reads.
An investigation of psychoactive polypharmacy and related gender-differences in older adults with dementia: a retrospective cohort study
Authors: Trenaman Shanna C , Quach Jack , Bowles Susan K , Kirkland Susan , Andrew Melissa K
Published: October 2023

Background

Older adults living with dementia may express challenging responsive behaviours. One management strategy is pharmacologic treatment though these options often have limited benefit, which may lead to multiple treatments being prescribed.

Methods

The aim of the present study was to describe psychoactive medication polypharmacy and explore factors associated with psychoactive polypharmacy in a cohort of older adults living with dementia in Nova Scotia, Canada, including a gender-stratified analysis. This was a retrospective cohort study of those aged 65 years or older with a recorded diagnosis of dementia between 2005 and 2015. Medication dispensation data was collected from April 1, 2010, or dementia diagnosis (cohort entry) to either death or March 31, 2015 (cohort exit). Psychoactive medication claims were captured. Psychoactive medication polypharmacy was defined as presence of three or more psychoactive prescription medications dispensed to one subject and overlapping for more than 30 days. Psychoactive polypharmacy episodes were described in duration, quantity, and implicated medications. Regression analysis examined factors associated with experience and frequency of psychoactive polypharmacy. All analysis were stratified by gender.

Results

The cohort included 15,819 adults living with dementia (mean age 80.7 years; 70.0% female), with 99.4% (n = 15,728) receiving at least one psychoactive medication over the period of follow-up. Psychoactive polypharmacy was present in 19.3% of the cohort. The gender specific logistic regressions demonstrated that for both men and women a younger age was associated with an increased risk of psychoactive polypharmacy (women: OR 0.97, 95%CI[0.96, 0.98], men: OR 0.96, 95%CI[0.95, 0.97]). Men were less likely to experience psychoactive polypharmacy if their location of residence was urban (OR 0.86, 95%CI[0.74, 0.99]). There was no significant association between location of residence (urban or rural) and psychoactive polypharmacy for women living with dementia. Antidepressants were the most dispensed medication class, while quetiapine was the most dispensed medication.

Conclusions

This study suggests that of adults living with dementia those of younger ages were more likely to experience psychoactive polypharmacy and that men living with dementia in rural locations may benefit from increased access to non-pharmacological options for dementia management.
Identifying the impact of social isolation and loneliness on psychological well-being among the elderly in old-age homes of India: the mediating role of gender, marital status, and education
Authors: Mishra Bijeta , Pradhan Jalandhar , Dhaka Suman
Published: October 2023

Background

Social isolation and loneliness can be detrimental to the overall functioning of the older adults. The study examines the impact of social isolation and loneliness on the psychological well-being of older adults residing in various old-age homes in India and investigates the mediating role of gender, marital status, and education level in the way social isolation and loneliness affect psychological well-being.

Methods

Data has been collected from 320 individuals aged sixty years or above. Data were collected using standardized measures like Lubben Social Network Scale- 6, revised UCLA Loneliness Scale, and shortened version of psychological well-being scale by Ryff & Keyes (1995). Multivariate and mediation analysis were performed to understand the associations of social isolation and loneliness with psychological well-being.

Results

A statistically significant MANOVA effect was obtained for social isolation (F = 3.836, p < .01), and loneliness (F = 3.782, p < .01). Gender and education as independent factors were significantly associated with the psychological well-being of individuals. However, both gender and education did not mediate the impact of social isolation and loneliness on the psychological well-being of older adults. Further, marital status had a partial mediating effect on the relationship between social isolation, loneliness, and psychological well-being.

Conclusions

The findings of the study can be incorporated into measures aiming at alleviation of feelings of social isolation and loneliness among the elderly. Further, the findings can be used to design various intervention strategies aimed at the reduction of social isolation and loneliness among older adults and the restoration of their psychological well-being.
Study protocol for prospective multi-institutional phase III trial of standard of care therapy with or without stereotactic ablative radiation therapy for recurrent ovarian cancer (SABR-ROC)
Authors: Kim Yong Bae , Byun Hwa Kyung , Wee Chan Woo , Kim Hojin , Kim Seyoung , Yang Gowoon , Kim Jina , Park Sang Joon , Lee Jung-Yun
Published: October 2023

Background

Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision.

Methods

The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0–1; 0–3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16–45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews.

Discussion

SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients.

Trial registration

This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022.
Heavy metal deposition and parameter change of soft contact lenses by exposure to particulate matter
Authors: Jung Won Young , Kim Jin Woo , Kim So Ra , Park Mijung
Published: October 2023

Background

Particulate matter (PM) is known to contain heavy metals and be harmful to the tissues and organs of the human body including the eyes. As such, in this study, the deposition of heavy metals from PM on soft contact lenses was examined, and changes in the lens parameters were further investigated.

Methods

Six types of soft contact lenses were exposed to captured PM10 for eight hours. The central thickness, water content, refractive power, and oxygen transmissibility of each contact lens were measured after analyzing the amounts of six heavy metals adsorbed on the contact lenses.

Results

Lead, manganese, barium, arsenic, vanadium, and cadmium were detected in the captured PM, and only lead was adsorbed on all soft contact lenses except senofilcon C. The largest deposition was 23.21 ± 0.70 (10− 3)µg/lens of the lead on lotrafilcon B. The oxygen transmissibility of nelfilcon A exhibited statistically significant changes, however, it was within the ISO standard tolerance. Nevertheless, changes in the central thickness, water content, and refractive power of each soft contact lens were not statistically significant.

Conclusions

This study revealed that a considerable amount of lead in PM10 was adsorbed on soft contact lenses. Amongst lens parameters, only oxygen transmissibility changed significantly. Thus, wearing soft contact lenses under high PM10 concentration might affect the physiology of the eyes.
Vision degrading myodesopsia assessed with optos ultra-widefield scanning laser ophthalmoscope
Authors: Lin Tiezhu , Shi Cheng , Wu Bing , Pazo Emmanuel Eric , Shen Lijun
Published: October 2023

Background

To investigate the diagnostic sensitivity of Optos imaging for vision degrading myodesopsia (VDM).

Methods

A total of 420 eyes from 345 patients with VDM were collected in this cross-sectional study. All eyes were classified as having posterior vitreous detachment (PVD) or not having PVD. The sensitivity of Optos imaging for the visibility of vitreous floaters was evaluated. The associated factors with the visibility of vitreous floaters on Optos images were analyzed in univariate and multivariate logistic regression analyses.

Results

The mean age of all patients was 56.19 ± 13.89 years old, and 66.67% of patients were female. The vitreous floaters were visible on the ultrasound B scan in all eyes, but only in 47.62% of Optos images (55.29% in eyes with PVD and 15% in eyes without PVD). In the multiple binary logistic regression analysis, age (OR = 1.094, 95%CI = 1.063–1.125, P < 0.001), spherical equivalent (OR = 0.869, 95%CI = 0.791–0.955, P = 0.004) and the distance of the floaters from the retina (OR = 1.191, 95%CI = 1.059–1.339, P = 0.003) were significantly correlated with the visibility of vitreous floaters on Optos images. On Optos images, 25.71% of VDM eyes presented additional retinal abnormalities.

Conclusions

Optos imaging has a low sensitivity for vitreous floaters, particularly in eyes without PVD. On Optos imaging, floaters were more visible in older patients, eyes with greater myopia, and floaters that were further from the retina.
Relationship between adiponectin and blood pressure in obese Latino adolescent boys with a family history of type 2 diabetes
Authors: Hijazin Kristin , Smith Brandon , Garrett Coleby , Knox Allan , Kelly Louise A.
Published: October 2023

introduction

Adipokines are associated with several pathological states including, metabolic syndrome, obesity, insulin resistance and type 2 diabetes. One of these adipokines, adiponectin is of particular interest as it has been shown to have numerous anti-inflammatory effects, However, the association between adiponectin and blood pressure remains inconclusive especially in the Latino adolescent with obesity.

Purpose

To investigate the relationship between plasma adiponectin and blood pressure in Latino adolescents’ boys with obesity and a with a family history of Type 2 diabetes.

Methods

Thirty two Latino adolescent males with obesity aged 14–17 years with a family history of type 2 diabetes underwent a frequently sampled glucose tolerance test (FSIVGTT) to measure insulin sensitivity. Body composition was assessed using dual energy x-ray absorptiometry. Obesity was defined as having a BMI percentile ≥95. Blood pressure was assessed using the Dinamap automated blood pressure monitor, and the average of three readings was used in the analysis. Fasting plasma adiponectin was determined using radioimmunoassay.

Results

There were moderate positive significant correlations for adiponectin and Systolic blood pressure(SBP) (rho = 0.436, p < 0.027) and Diastolic blood pressure(DBP) (rho = 0.41,p < 0.028). A multivariate liner regression showed that plasma adiponectin could significantly detect 19% of the variance in SBP (p = 0.017, and 33% for DBP (p = 0.017). In a simple linear regression adiponectin was not related to any of our variables (p < 0.05).

Conclusion

In conclusion, adiponectin was positively and significantly correlated to blood pressure in Latino adolescent with obesity. Future studies should investigate this relationship in a large sample of Latino adolescent youth.
A cross-sectional survey exploring HIV and HCV prevalence among men who purchase sex in Dnipro, Ukraine
Authors: Lazarus Lisa , Herpai Nicole , Pavlova Daria , Gill Amaanat , Cholette François , McClarty Leigh M. , Isac Shajy , Lopatenko Anna , Pickles Michael , Mishra Sharmistha , Shaw Souradet Y. , Lorway Robert , McKinnon Lyle R. , Sandstrom Paul , Blanchard James , Balakireva Olga , Becker Marissa L. ,   on behalf of the Dynamics Study Team, Aral Sevgi , Bondar Tetiana , Cheuk Eve , Daniuk Christina , Forget Evelyn , Lee Emma , Ma Huiting , Moses Stephen , Murney Maureen , Nguien Nam-Mykhailo , Shakarishvili Ani , Tarasova Tatiana
Published: October 2023

Background

HIV programming in Ukraine largely targets “key population” groups. Men who purchase sex are not directly reached. The aim of our study was to explore the prevalence of sexually transmitted and blood-borne infections (STBBIs) among men who purchase sex from female sex workers.

Methods

Following geographic mapping and population size estimation at each “hotspot”, we conducted a cross-sectional bio-behavioural survey with men who purchase sex between September 2017 and March 2018 in Dnipro, Ukraine. Eligibility criteria included purchasing sex services at a “hotspot” and being ≥ 18 years. Participants completed a structured questionnaire, followed by HIV/HCV rapid testing and a dried blood spot (DBS) sample collection for confirmatory serology.

Results

The study enrolled 370 participants. The median age was 32 (interquartile range [IQR] = 27–38) and the median age of first purchase of sexual services was 22 (IQR = 19–27). Over half (56%) of participants reported ever testing for HIV; four participants (2%, N = 206) reported having tested positive for HIV, with three out of the four reporting being on ART. Forty percent of participants had ever tested for HCV, with three (2%, N = 142) having ever tested positive for HCV. In DBS testing, nine participants (2.4%) tested positive for HIV and 24 (6.5%) tested positive for ever having an HCV infection.

Conclusion

Prevalence of HIV and HCV in this population was high. Given high rates of study enrolment and testing, efforts should be made to reach men who purchase sex with expanded STBBI programming.
Phytochemical analysis, in vitro and in silico effects from Alstonia boonei De Wild stem bark on selected digestive enzymes and adipogenesis in 3T3-L1 preadipocytes
Authors: Anyanwu Gabriel O. , Ejike Uju D. , Gyebi Gideon A. , Rauf Khalid , Nisar-Ur-Rehman  , Iqbal Jamshed , Zaib Sumera , Usunobun Usunomena , Onyeneke Eusebius C. , Alotaibi Badriyah S. , Batiha Gaber El-Saber
Published: October 2023

Background

Obesity is a global health issue arising from the unhealthy accumulation of fat. Medicinal plants such as Alstonia boonei stem bark has been reported to possess body weight reducing effect in obese rats. Thus, this study sought to investigate the in vitro and in silico effects of fractions from Alstonia boonei stem bark on selected obesity-related digestive enzymes and adipogenesis in 3T3-L1 preadipocytes.

Method

Two fractions were prepared from A. boonei: crude alkaloid fraction (CAF) and crude saponin fraction (CSF), and their phytochemical compounds were profiled using Liquid chromatography with tandem mass spectrometry (LCMS/MS). The fractions were assayed for inhibitory activity against lipase, α-amylase and α-glucosidase, likewise their antiadipogenic effect in 3T3-L1 adipocytes. The binding properties with the 3 enzymes were also assessed using in silico tools.

Results

Eleven alkaloids and six saponin phytochemical compounds were identified in the CAF and CSF using LCMS/MS. The CAF and CSF revealed good inhibitory activity against pancreatic lipase enzyme, but weak and good activity against amylase respectively while only CSF had inhibitory activity against α-glucosidase. Both fractions showed antiadipogenic effect in the clearance of adipocytes and reduction of lipid content in 3T3-L1 adipocytes. The LCMS/MS identified compounds (41) from both fractions demonstrated good binding properties with the 3 enzymes, with at least the top ten compounds having higher binding energies than the reference inhibitors (acarbose and orlistat). The best two docked compounds to the three enzymes were firmly anchored in the substrate binding pockets of the enzymes. In a similar binding pattern as the reference acarbose, Estradiol-17-phenylpropionate (-11.0 kcal/mol) and 3α-O-trans-Feruloyl-2 α -hydroxy-12-ursen-28-oic acid (-10.0 kcal/mol) interacted with Asp197 a catalytic nucleophile of pancreatic amylase. Estradiol-17-phenylpropionate (-10.8 kcal/mol) and 10-Hydroxyyohimbine (-10.4 kcal/mol) interacted with the catalytic triad (Ser152-Asp176-His263) of pancreatic lipase while Estradiol-17-phenylpropionate (-10.1 kcal/mol) and 10-Hydroxyyohimbine (-9.9 kcal/mol) interacted with Asp616 and Asp518 the acid/base and nucleophilic residues of modelled α-glucosidase.

Conclusion

The antiobesity effect of A. boonei was displayed by both the alkaloid and saponin fractions of the plant via inhibition of pancreatic lipase and adipogenesis.
A qualitative investigation of uninsured patient and primary care provider perspectives on specialty care eConsults
Authors: Bifulco Lauren , Grzejszczak Lynsey , Velez Idiana , Angelocci Tracy , Anderson Daren
Published: October 2023

Background

Uninsured and underinsured patients face specialty care access disparities that prevent them from obtaining the care they need and negatively impact their health and well-being. We aimed to understand how making specialty care electronic consultations (eConsults) available at a multi-site Federally Qualified Health Center (FQHC) in central Texas affected uninsured patients’ care-seeking experiences and impacted their ability to receive the needed care.

Methods

We used concepts from Ecological Systems Theory to examine individual, interpersonal, organization-level, social, and health policy environment factors that impacted patients’ access to specialty care and the use of eConsults. We conducted thematic analysis of semi-structured, qualitative interviews with patients about seeking specialty care while uninsured and with uninsured patients and FQHC PCPs about their experience using eConsults to obtain specialists’ recommendations.

Results

Patients and PCPs identified out-of-pocket cost, stigma, a paucity of local specialists willing to see uninsured patients, time and difficulty associated with travel and transportation to specialty visits, and health policy limitations as barriers to obtaining specialty care. Benefits of using eConsults for uninsured patients included minimizing/avoiding financial stress, expanding access to care, expanding scope of primary care, and expediting access to specialists. Concerns about the model included patients’ limited understanding of eConsults, concern about cost, and worry whether eConsults could appropriately meet their specialty needs.

Conclusions

Findings suggest that eConsults delivered in a primary care FQHC addressed uninsured patients’ specialty care access concerns. They helped to address financial and geographic barriers, provided time and cost savings to patients, expanded FQHC PCPs’ knowledge and care provision options, and allowed patients to receive more care in primary care.
Single-nucleus transcriptome inventory of giant panda reveals cellular basis for fitness optimization under low metabolism
Authors: Yang Shangchen , Lan Tianming , Wei Rongping , Zhang Ling , Lin Lin , Du Hanyu , Huang Yunting , Zhang Guiquan , Huang Shan , Shi Minhui , Wang Chengdong , Wang Qing , Li Rengui , Han Lei , Tang Dan , Li Haimeng , Zhang Hemin , Cui Jie , Lu Haorong , Huang Jinrong , Luo Yonglun , Li Desheng , Wan Qiu-Hong , Liu Huan , Fang Sheng-Guo
Published: October 2023

Background

Energy homeostasis is essential for the adaptation of animals to their environment and some wild animals keep low metabolism adaptive to their low-nutrient dietary supply. Giant panda is such a typical low-metabolic mammal exhibiting species specialization of extremely low daily energy expenditure. It has low levels of basal metabolic rate, thyroid hormone, and physical activities, whereas the cellular bases of its low metabolic adaptation remain rarely explored.

Results

In this study, we generate a single-nucleus transcriptome atlas of 21 organs/tissues from a female giant panda. We focused on the central metabolic organ (liver) and dissected cellular metabolic status by cross-species comparison. Adaptive expression mode (i.e., AMPK related) was prominently displayed in the hepatocyte of giant panda. In the highest energy-consuming organ, the heart, we found a possibly optimized utilization of fatty acid. Detailed cell subtype annotation of endothelial cells showed the uterine-specific deficiency of blood vascular subclasses, indicating a potential adaptation for a low reproductive energy expenditure.

Conclusions

Our findings shed light on the possible cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas and helped to understand physiological adaptation response to nutrient stress.
Expression and splicing mediate distinct biological signals
Authors: Dam Søren Helweg , Olsen Lars Rønn , Vitting-Seerup Kristoffer
Published: October 2023

Background

Through alternative splicing, most human genes produce multiple isoforms in a cell-, tissue-, and disease-specific manner. Numerous studies show that alternative splicing is essential for development, diseases, and their treatments. Despite these important examples, the extent and biological relevance of splicing are currently unknown.

Results

To solve this problem, we developed pairedGSEA and used it to profile transcriptional changes in 100 representative RNA-seq datasets. Our systematic analysis demonstrates that changes in splicing, on average, contribute to 48.1% of the biological signal in expression analyses. Gene-set enrichment analysis furthermore indicates that expression and splicing both convey shared and distinct biological signals.

Conclusions

These findings establish alternative splicing as a major regulator of the human condition and suggest that most contemporary RNA-seq studies likely miss out on critical biological insights. We anticipate our results will contribute to the transition from a gene-centric to an isoform-centric research paradigm.
The BAF chromatin remodeling complex licenses planarian stem cells access to ectodermal and mesodermal cell fates
Authors: Wiggans Mallory , Zhu Shu Jun , Molinaro Alyssa M. , Pearson Bret J.
Published: October 2023

Background

The flatworm planarian, Schmidtea mediterranea, has a large population of adult stem cells (ASCs) that replace any cell type during tissue turnover or regeneration. How planarian ASCs (called neoblasts) manage self-renewal with the ability to produce daughter cells of different cell lineages (multipotency) is not well understood. Chromatin remodeling complexes ultimately control access to DNA regions of chromosomes and together with specific transcription factors determine whether a gene is transcribed in a given cell type. Previous work in planarians determined that RNAi of core components of the BAF chromatin remodeling complex, brg1 and smarcc2, caused increased ASCs and failed regeneration, but how these cellular defects arise at the level of gene regulation in neoblasts is unknown.

Results

Here, we perform ATAC and RNA sequencing on purified neoblasts, deficient for the BAF complex subunits brg-1 and smarcc2. The data demonstrate that the BAF complex promotes chromatin accessibility and facilitates transcription at target loci, as in other systems. Interestingly, we find that the BAF complex enables access to genes known to be required for the generation of mesoderm- and ectoderm-derived lineages, including muscle, parenchymal cathepsin, neural, and epithelial lineages. BAF complex knockdowns result in disrupted differentiation into these cell lineages and functional consequences on planarian regeneration and tissue turnover. Notably, we did not detect a role for the BAF complex in neoblasts making endodermal lineages.

Conclusions

Our study provides functional insights into how the BAF complex contributes to cell fate decisions in planarian ASCs in vivo.
Simple analysis of gel images with IOCBIO Gel
Authors: Kütt Jaak , Margus Georg , Kask Lauri , Rätsepso Triinu , Soodla Kärol , Bernasconi Romain , Birkedal Rikke , Järv Priit , Laasmaa Martin , Vendelin Marko
Published: October 2023

Background

Current solutions for the analysis of Western Blot images lack either transparency and reproducibility or can be tedious to use if one has to ensure the reproducibility of the analysis.

Results

Here, we present an open-source gel image analysis program, IOCBIO Gel. It is designed to simplify image analysis and link the analysis results with the metadata describing the measurements. The software runs on all major desktop operating systems. It allows one to use it in either a single-researcher environment with local storage of the data or in a multiple-researcher environment using a central database to facilitate data sharing within the research team and beyond. By recording the original image and all operations performed on it, such as image cropping, subtraction of background, sample lane selection, and integration boundaries, the software ensures the reproducibility of the analysis and simplifies making corrections at any stage of the research. The analysis results are available either through direct access to the database used to store it or through the export of the relevant data.

Conclusions

The software is not only limited to Western Blot image analysis and can be used to analyze images obtained as a part of many other widely used biochemical techniques such as isoelectric focusing. By recording the original data and all the analysis steps, the program improves reproducibility in the analysis and contributes to the implementation of FAIR principles in the related fields.
Multi-system diseases and death trajectory of metabolic dysfunction-associated fatty liver disease: findings from the UK Biobank
Authors: Jia Yu , Li Dongze , You Yi , Yu Jing , Jiang Wenli , Liu Yi , Zeng Rui , Wan Zhi , Lei Yi , Liao Xiaoyang
Published: October 2023

Background

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification.

Methods

After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections.

Results

Participants aged 59 (51–64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid–base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results.

Conclusions

Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD.
Factors affecting haemoglobin dynamics in African children with acute uncomplicated Plasmodium falciparum malaria treated with single low-dose primaquine or placebo
Authors: Onyamboko Marie A. , Olupot-Olupot Peter , Were Winifred , Namayanja Cate , Onyas Peter , Titin Harriet , Baseke Joy , Muhindo Rita , Kayembe Daddy K. , Ndjowo Pauline O. , Basara Benjamin B. , Okalebo Charles B. , Williams Thomas N. , Uyoga Sophie , Taya Chiraporn , Bamisaiye Adeola , Fanello Caterina , Maitland Kathryn , Day Nicholas P. J. , Taylor Walter R. J. , Mukaka Mavuto
Published: October 2023

Background

Single low-dose primaquine (SLDPQ) effectively blocks the transmission of Plasmodium falciparum malaria, but anxiety remains regarding its haemolytic potential in patients with glucose-6-phopshate dehydrogenase (G6PD) deficiency. We, therefore, examined the independent effects of several factors on haemoglobin (Hb) dynamics in falciparum-infected children with a particular interest in SLDPQ and G6PD status.

Methods

This randomised, double-blind, placebo-controlled, safety trial was conducted in Congolese and Ugandan children aged 6 months–11 years with acute uncomplicated P. falciparum and day (D) 0 Hbs ≥ 6 g/dL who were treated with age-dosed SLDPQ/placebo and weight-dosed artemether lumefantrine (AL) or dihydroartemisinin piperaquine (DHAPP). Genotyping defined G6PD (G6PD c.202T allele), haemoglobin S (HbS), and α-thalassaemia status.

Multivariable linear and logistic regression assessed factor independence for continuous Hb parameters and Hb recovery (D42 Hb > D0 Hb), respectively.

Results

One thousand one hundred thirty-seven children, whose median age was 5 years, were randomised to receive: AL + SLDPQ (n = 286), AL + placebo (286), DHAPP + SLDPQ (283), and DHAPP + placebo (282). By G6PD status, 284 were G6PD deficient (239 hemizygous males, 45 homozygous females), 119 were heterozygous females, 418 and 299 were normal males and females, respectively, and 17 were of unknown status.

The mean D0 Hb was 10.6 (SD 1.6) g/dL and was lower in younger children with longer illnesses, lower mid-upper arm circumferences, splenomegaly, and α-thalassaemia trait, who were either G6PDd or heterozygous females. The initial fractional fall in Hb was greater in younger children with higher D0 Hbs and D0 parasitaemias and longer illnesses but less in sickle cell trait. Older G6PDd children with lower starting Hbs and greater factional falls were more likely to achieve Hb recovery, whilst lower D42 Hb concentrations were associated with younger G6PD normal children with lower fractional falls, sickle cell disease, α-thalassaemia silent carrier and trait, and late treatment failures. Ten blood transfusions were given in the first week (5 SLDPQ, 5 placebo).

Conclusions

In these falciparum-infected African children, posttreatment Hb changes were unaffected by SLDPQ, and G6PDd patients had favourable posttreatment Hb changes and a higher probability of Hb recovery. These reassuring findings support SLDPQ deployment without G6PD screening in Africa.

Trial registration

The trial is registered at ISRCTN 11594437.
Cardiovascular outcomes between COVID-19 and non-COVID-19 pneumonia: a nationwide cohort study
Authors: Lee Min-Taek , Baek Moon Seong , Kim Tae Wan , Jung Sun-Young , Kim Won-Young
Published: October 2023

Background

Previous studies that assessed the risk of cardiovascular outcomes in survivors of coronavirus disease 2019 (COVID-19) were likely limited by lack of generalizability and selection of controls nonrepresentative of a counterfactual situation regarding COVID-19-related hospitalization. This study determined whether COVID-19 hospitalization was associated with incident cardiovascular outcomes compared to non-COVID-19 pneumonia hospitalization.

Methods

Nationwide population-based study conducted using the Korean National Health Insurance Service database. A cohort of 132,784 inpatients with COVID-19 (October 8, 2020–September 30, 2021) and a cohort of 31,173 inpatients with non-COVID-19 pneumonia (January 1–December 31, 2019) were included. The primary outcome was the major adverse cardiovascular event (MACE; a composite of myocardial infarction and stroke). Hazard ratios (HRs) with 95% confidence intervals (CIs) of all outcomes of interest were estimated between inverse probability of treatment-weighted patients with COVID-19 and non-COVID-19 pneumonia.

Results

After weighting, the COVID-19 and non-COVID-19 pneumonia groups included 125,810 (mean [SD] age, 47.2 [17.6] years; men, 49.3%) and 28,492 patients (mean [SD] age, 48.6 [18.4] years; men, 47.2%), respectively. COVID-19 hospitalization was not associated with an increased risk of the MACE (HR, 0.84; 95% CI 0.69–1.03). However, the MACE (HR, 7.30; 95% CI 3.29–16.21), dysrhythmia (HR, 1.88; 95% CI 1.04–3.42), acute myocarditis (HR, 11.33; 95% CI 2.97–43.20), myocardial infarction (HR, 6.78; 95% CI 3.03–15.15), congestive heart failure (HR, 1.95; 95% CI 1.37–2.77), and thrombotic disease (HR, 8.26; 95% CI 4.06–16.83) risks were significantly higher in patients with COVID-19 aged 18–39 years. The findings were consistent after adjustment for preexisting cardiovascular disease. COVID-19 hospitalization conferred a higher risk of acute myocarditis (HR, 6.47; 95% CI 2.53–16.52) or deep vein thrombosis (HR, 1.97; 95% CI 1.38–2.80), regardless of vaccination status.

Conclusions

Hospitalized patients with COVID-19 were not at an increased risk of cardiovascular outcomes compared to patients with non-COVID-19 pneumonia. Further studies are needed to evaluate whether the increased risk of cardiovascular outcomes is confined to younger patients.
Screening for atypical porcine pestivirus in Swedish boar semen used for artificial insemination and a characterisation of the seminal RNA microbiome including the virome
Authors: Stenberg Hedvig , Malmberg Maja , Hayer Juliette
Published: October 2023

Background

This study aimed to characterise the RNA microbiome, including the virome of extended semen from Swedish breeding boars, with particular focus on Atypical porcine pestivirus (APPV). This neurotropic virus, associated with congenital tremor type A-II in piglets, was recently demonstrated to induce the disease through insemination with semen from infected boars.

Results

From 124 Artificial Insemination (AI) doses from Swedish breeding boars, APPV was detected in one dose in addition to a sparse seminal RNA virome, characterised by retroviruses, phages, and some fecal-associated contaminants. The detected seminal microbiome was large and characterized by Gram-negative bacteria from the phylum Proteobacteria, mainly consisting of apathogenic or opportunistic bacteria. The proportion of bacteria with a pathogenic potential was low, and no antimicrobial resistance genes (ARGs) were detected in the datasets.

Conclusion

Overall, the results indicate a good health status among Swedish breeding boars. The detection of APPV in semen raises the question of whether routine screening for APPV in breeding boars should be instigated.
Caproate production from Enset fiber in one-pot two-step fermentation using anaerobic fungi (Neocallimastix cameroonii strain G341) and Clostridium kluyveri DSM 555
Authors: Seid Nebyat , Ochsenreither Katrin , Neumann Anke
Published: October 2023

Background

Lignocellulosic biomass plays a crucial role in creating a circular bioeconomy and minimizing environmental impact. Enset biomass is a byproduct of traditional Ethiopian Enset food processing that is thrown away in huge quantities. This study aimed to produce caproate from Enset fiber using Neocallimastix cameroonii strain G341 and Clostridium kluyveri DSM 555 in one-pot two-step fermentation.

Results

The process started by growing N. cameroonii on Enset fiber as a carbon source for 7 days. Subsequently, the fungal culture was inoculated with active C. kluyveri preculture and further incubated. The results showed that N. cameroonii grew on 0.25 g untreated Enset fiber as the sole carbon source and produced 1.16 mmol acetate, 0.51 mmol hydrogen, and 1.34 mmol formate. In addition, lactate, succinate, and ethanol were detected in small amounts, 0.17 mmol, 0.08 mmol, and 0.7 mmol, respectively. After inoculating with C. kluyveri, 0.3 mmol of caproate and 0.48 mmol of butyrate were produced, and hydrogen production also increased to 0.95 mmol compared to sole N. cameroonii fermentation. Moreover, after the culture was supplemented with 2.18 mmol of ethanol during C. kluyveri inoculation, caproate, and hydrogen production was further increased to 1.2 and 1.36 mmol, respectively, and the consumption of acetate also increased.

Conclusion

A novel microbial cell factory was developed to convert untreated lignocellulosic Enset fiber into the medium chain carboxylic acid caproate and H2 by a co-culture of the anaerobic fungi N. cameroonii and C. kluyveri. This opens a new value chain for Enset farmers, as the process requires only locally available raw materials and low-price fermenters. As the caproate production was mainly limited by the available ethanol, the addition of locally produced ethanol-containing fermentation broth (“beer”) would further increase the titer.

Graphical Abstract
Comparison of COVID-19 vaccine policies and their effectiveness in Korea, Japan, and Singapore
Authors: Ma Mengyuan , Shi Leiyu , Liu Meiheng , Yang Junyan , Xie Wanzhen , Sun Gang
Published: October 2023

Background

This study aimed to analyze coronavirus disease 2019 (COVID-19)vaccine policies and effectiveness in Korea, Japan, and Singapore, thereby providing empirical experience for vaccination and response to similar public health emergencies.

Methods

The study systematically summarized the COVID-19 vaccine policies in Korea, Japan, and Singapore through public information from the Our World in Data website and the official websites of the Ministries of Health in these three countries.Total vaccinations, COVID-19 vaccination rates, rates of fully vaccinated, rates of boostervaccinated, and total confifirmed cases were selected for cross-sectional comparison of COVID-19 vaccination in these three countries. Combining the basic characteristics of these three countries, daily cases per million, daily deaths per million, and the effective reproduction rate were calculated to measure the effectiveness of COVID-19 vaccine policies implementation in each of these three countries

Results

The countermeasures against the COVID-19 in Korea, Japan, and Singapore, although seemingly different on the surface, have all taken an aggressive approach. There are large similarities in the timing of the start of COVID-19 vaccination, the type of vaccine, how vaccine appointments are made, and whether vaccination are free, and all had high vaccination rates. A systematic comparison of the anti-epidemic practices in the three East Asian countries revealed that all three countries experienced more than one outbreak spike due to the spread of new mutant strains after the start of mass vaccination with COVID-19 vaccination, but that vaccination played a positive role in reducing the number of deaths and stabilizing the effective reproduction rate.

Conclusions

This study comparatively analyzed the COVID-19 vaccine policies and their effects in South Korea, Japan, and Singapore, and found that there is a common set of logical combinations behind the seemingly different strategies of these three countries. Therefore, in the process of combating COVID-19, countries can learn from the successful experience of combating the epidemic and continue to strengthen the implementation of vaccination programs, as well as adjusting public perceptions to reduce the level of vaccine hesitancy, enhance the motivation for vaccination, and improve the coverage of COVID-19 vaccine based on different cultural factors, which remains the direction for future development.