bluuebunny/crossref_metadata_2025 huggingface dataset:
ProQ-associated small RNAs control motility in Vibrio cholerae
Authors: Ghandour Rabea , Devlitsarov Daniel , Popp Phillip , Melamed Sahar , Huber Michaela , Siemers Malte , Krüger Thomas , Kniemeyer Olaf , Klingl Andreas , Brakhage Axel A , Erhardt Marc , Papenfort Kai
Published: December 2024

Gene regulation at the post-transcriptional level is prevalent in all domains of life. In bacteria, ProQ-like proteins have emerged as important RNA chaperones facilitating RNA stability and RNA duplex formation. In the major human pathogen Vibrio cholerae, post-transcriptional gene regulation is key for virulence, biofilm formation, and antibiotic resistance, yet the role of ProQ has not been studied. Here, we show that ProQ interacts with hundreds of transcripts in V. cholerae, including the highly abundant FlaX small RNA (sRNA). Global analyses of RNA duplex formation using RIL-Seq (RNA interaction by ligation and sequencing) revealed a vast network of ProQ-assisted interactions and identified a role for FlaX in motility regulation. Specifically, FlaX base-pairs with multiple sites on the flaB flagellin mRNA, preventing 30S ribosome binding and translation initiation. V. cholerae cells lacking flaX display impaired motility gene expression, altered flagella composition and reduced swimming in liquid environments. Our results provide a global view on ProQ-associated RNA duplex formation and pinpoint the mechanistic and phenotypic consequences associated with ProQ-associated sRNAs in V. cholerae.
The case for neurons: a no-go theorem for consciousness on a chip
Authors: Kleiner Johannes , Ludwig Tim
Published: December 2024

We apply the methodology of no-go theorems as developed in physics to the question of artificial consciousness. The result is a no-go theorem which shows that under a general assumption, called dynamical relevance, Artificial Intelligence (AI) systems that run on contemporary computer chips cannot be conscious. Consciousness is dynamically relevant, simply put, if, according to a theory of consciousness, it is relevant for the temporal evolution of a system’s states. The no-go theorem rests on facts about semiconductor development: that AI systems run on central processing units, graphics processing units, tensor processing units, or other processors which have been designed and verified to adhere to computational dynamics that systematically preclude or suppress deviations. Whether our result resolves the question of AI consciousness on contemporary processors depends on the truth of the theorem’s main assumption, dynamical relevance, which this paper does not establish.
Effects on Multimodal Connectivity Patterns in Female Schizophrenia During 8 Weeks of Antipsychotic Treatment
Authors: Gao Shuzhan , Sun Yunkai , Wu Fan , Jiang Jing , Peng Ting , Zhang Rongrong , Ling Chenxi , Han Yanlin , Xu Qing , Zou Lulu , Liao Yanhui , Liang Chuang , Zhang Daoqiang , Qi Shile , Tang Jinsong , Xu Xijia
Published: December 2024

Background and Hypothesis

Respective abnormal structural connectivity (SC) and functional connectivity (FC) have been reported in individuals with schizophrenia. However, transmodal associations between SC and FC following antipsychotic treatment, especially in female schizophrenia, remain unclear. We hypothesized that increased SC-FC coupling may be found in female schizophrenia, and could be normalized after antipsychotic treatment.

Study Design

Sixty-four female drug-naïve patients with first-diagnosed schizophrenia treated with antipsychotic drugs for 8 weeks, and 55 female healthy controls (HCs) were enrolled. Magnetic resonance imaging (MRI) data were collected from HCs at baseline and from patients at baseline and after treatment. SC and FC were analyzed by network-based statistics, calculating nonzero SC-FC coupling of the whole brain and altered connectivity following treatment. Finally, an Elastic-net logistic regression analysis was employed to establish a predictive model for evaluating the clinical efficacy treatment.

Study Results

At baseline, female schizophrenia patients exhibited abnormal SC in cortico-cortical, frontal-limbic, frontal-striatal, limbic-striatal, and limbic-cerebellar connectivity compared to HCs, while FC showed no abnormalities. Following treatment, cortico-cortical, frontal-limbic, frontal-striatal, limbic-striatal, temporal-cerebellar, and limbic-cerebellar connectivity were altered in both SC and FC. Additionally, SC-FC coupling of altered connectivity was higher in patients at baseline than in HC, trending toward normalization after treatment. Furthermore, identified FC or/and SC predicted changes in psychopathological symptoms and cognitive impairment among female schizophrenia following treatment.

Conclusions

SC-FC coupling may be a potential predictive biomarker of treatment response. Cortico-cortical, frontal-limbic, frontal-striatal, limbic-striatal, temporal-cerebellar, and limbic-cerebellar could represent major targets for antipsychotic drugs in female schizophrenia.
The performance of ejection fraction as a predictor of mortality and morbidity in acute aluminium phosphide poisoning
Authors: Zaghary Meray Medhat Shokry , Ali Hasnaa Ahmed Ahmed , Ahmed Asmaa Mohammed Khalaf
Published: December 2024

Aluminium phosphide poison become an alarming, well-known, effective suicidal poison with a high mortality rate. There is a need for a simple tool that can triage patients with bad prognosis. The study aimed to assess the accuracy of ejection fraction as a predictor of mortality and morbidity in acute aluminium phosphide toxicity cases. The study involved 70 cases of acutely aluminium phosphide-poisoned patients in our hospital from January 2021 to January 2024. The study found that 54.3% of the cases were males and 45.7% were females, with a mean age of 22.4 ± 11.8 years old. The oral route was the route of administration of all cases, and the intention of poisoning was intentional in 84.3% of cases. Regarding the outcome of patients, 62.9% of the cases recovered, and 37.1% died. The Receiver Operating Characteristic Curve found that the ejection fraction below 37.5% had an accuracy rate of 96.8% with excellent discrimination for mortality, sensitivity of 100%, specificity of 93.2%, positive predictive value of 89.6%, and negative predictive value of 100%. The ejection fraction below 52.5% had an accuracy rate of 89% with good discrimination for complications, sensitivity of 83.3%, specificity of 96.8%, positive predictive value of 90.9%, and negative predictive value of 93.7%. So, the ejection fraction plays an essential tool in predicting mortality and complications in acute aluminium phosphide toxicity and should be assessed on every patient in the first 24 h of admission to facilitate the triage of these patients.
Isolation and identification of six newly recorded wheat Fusarium crown rot associated Fusarium species
Authors: Ma Guoping , Qi Kai , Zhang Yueli , Zhang Bo , Jiang Hang , Ma Li-Guo , Qi Jun-shan
Published: December 2024

Fusarium crown rot (FCR) has become one of the most serious diseases affecting wheat production worldwide. To date, many Fusarium species associated with wheat FCR disease have been reported. To gain a deeper understanding of Fusarium species diversity associated with wheat FCR, extensive research was conducted to identify different Fusarium species. A total of 194 diseased wheat samples were collected from Dezhou, Heze, Jining, Linyi, Qingdao, Rizhao, Weihai, and Zaozhuang cities of Shandong province, China. A total of 1512 Fusarium isolates were obtained from collected samples and identified using sequence analysis of the translation elongation factor-1α (TEF-1α), RNA polymerase II largest subunit (RPB1), and RNA polymerase II second largest subunit (RPB2) gene sequences. Of these Fusarium isolates, 1082 were identified as Fusarium pseudograminearum, and the remaining isolates were identified as F. graminearum (n = 338), F. asiaticum (n = 41), F. proliferatum (n = 17), F. sinensis (n = 8), F. oxysporum (n = 7), F. acuminatum (n = 6), F. verticillioides (n = 5), F. nanum (n = 3), F. sulawesiense (n = 2), F. fujikuroi (n = 1), F. odoratissimum (n = 1), and F. reticulatum (n = 1). Among the 13 Fusarium species, F. verticillioides, F. nanum, F. sulawesiense, F. fujikuroi, F. odoratissimum, and F. reticulatum were obtained from wheat FCR samples for the first time and were considered six new record species. Pathogenicity tests of all the six newly recorded Fusarium species on the major wheat cultivar ‘Jimai 22’ revealed that all the tested isolates caused FCR disease. This is the first report of F. fujikuroi, F. nanum, F. odoratissimum, F. reticulatum, F. sulawesiense, and F. verticillioides causing wheat FCR worldwide.
An evaluation of pruning programs to manage shoot blight, caused by the bacterium Erwinia amylovora
Authors: Yannuzzi Isabella Magna , Cox Kerik
Published: December 2024

Fire blight is an economically devastating disease caused by the bacterium Erwinia amylovora. Infections lead can shoot blight and, when unmanaged, become systemic and can quickly cause tree death and spread through an orchard via active infections sites producing bacterial ooze. With climate change, increasingly popular high-density training systems, and the susceptibility of many consumers desired apple cultivars, shoot blight management has become exceptionally challenging despite the diverse management tactics available. To better understand pruning as a management practice, we evaluated ten pruning programs in two different orchards over the course of two years. The pruning programs in this study encompass extension recommendations and grower preferences and include a variety of supplemental chemical applications and sanitation practices to answer three primary questions: (i) How do the impacts of pruning on the management of shoot blight compare between a vertical-axis orchard with mature trees and a high-density planting with young trees? (ii) Do sanitation and ancillary chemical management have a significant impact on shoot blight control achieved through pruning? (iii) How do a variety of pruning programs, including those preferred by researchers, growers, and extension agents compare in terms of shoot blight management? The impacts of pruning programs were more pronounced in the vertical-axis orchard in terms of reducing infection spread and overall shoot blight incidence. However, in the high-density plantings pruning programs were mostly ineffective and fire blight spread quickly throughout the trees and planting. Overall, the most aggressive pruning programs, which removed tissue of several seasons of growth, had the greatest impact on fire blight in both plantings. In line with the findings of many previous studies, sanitation and chemical management supplementation were not found to be necessarily beneficial.
Rehabilitation for Physical Frailty in Lung Transplant Candidates: A Systematic Review
Authors: McGarrigle Laura , Norman Gill , Hurst Helen , Gillespie Loraine , Todd Chris
Published: December 2024

Purpose:

Physical frailty is prevalent in lung transplant (LTx) candidates and is linked to adverse outcomes preoperatively and postoperatively. Exercise is beneficial in optimizing exercise capacity and quality of life in candidates, but its impact on physical frailty is unknown.

Methods:

We prospectively registered and published a protocol (PROSPERO CRD42022363730) before undertaking a systematic review. We searched 4 databases plus trial registries from 1980 to February 2024 for studies of exercise interventions in adults awaiting LTx. Outcomes were measures or surrogate markers of physical frailty. An NIH assessment tool was used to assess study quality, and certainty of evidence was assessed using GRADE.

Results:

Fifteen studies (664 patients) were included. Interventions were in-person pulmonary rehabilitation, home exercise, and telerehabilitation. Studies included aerobic, resistance, balance, and breathing training. Only 2 studies assessed frailty using a phenotypic measure. Studies demonstrated improvement in some surrogate frailty outcomes including the Short Physical Performance Battery, 5 times sit-to-stand test, and handgrip or muscle strength measures. The study quality was fair or poor; evidence was low or very low certainty for all outcomes due to imprecision and high risk of bias. Uncontrolled study designs and heterogeneity of interventions and outcomes limit conclusions on effectiveness.

Conclusions:

Exercise training appears beneficial in modifying surrogate markers of physical frailty before LTx, but conclusions are limited by low or very low certainty evidence. High quality randomized trials are needed to determine the impact of exercise interventions on physical frailty and to develop guidelines for LTx prehabilitation.
Audit of a Novel Nurse-Led Program for Non-Antibiotic Management of Acute Uncomplicated Diverticulitis
Authors: Alibrahim Huseen , Pinto Jessica , Sabboobeh Sarah , Boukhili Neyla , Demian Marie , Vasilevsky Carol-Ann , Boutros Marylise
Published: December 2024

BACKGROUND:

Non-antibiotic outpatient treatment of acute uncomplicated diverticulitis is safe; however, uptake remains low.

OBJECTIVE:

To assess the success of non-antibiotic management of uncomplicated diverticulitis through a nurse clinician-led outpatient program.

DESIGN:

Retrospective audit from June 2022-March 2024.

SETTINGS:

Nurse clinician-led outpatient program for non-antibiotic management of acute uncomplicated diverticulitis at a university-affiliated hospital.

PATIENTS:

Immunocompetent adults with CT-proven acute uncomplicated diverticulitis and C-reactive protein <150 mg/L. Eligible patients not referred to the program but treated in the Emergency Department during the same time period were also reviewed.

INTERVENTIONS:

This program included education, diet modification, analgesia, clinic visit, and telephone follow-ups by a nurse-clinician.

MAIN OUTCOME MEASURES:

Primary outcome was success of the program, defined as the proportion not requiring an Emergency Department visit, admissions within 60 days of diagnosis or need for antibiotics.

RESULTS:

Of 236 patients referred to the program, 84 met inclusion criteria, of which 43 (51.2%) were started on antibiotics before referral but were treated by the program. Forty-one (48.8%) completed the non-antibiotic protocol (48.8%, n = 41), with 97.6% success. Concurrently, 219 eligible patients were treated in the Emergency Department but not referred to the program. There was no difference in the number of Emergency Department visits between the 2 groups [program: n = 7 (8.3%) vs Emergency Department: n = 27 (12.3%)] within 60 days of diagnosis. Two patients (2.3%) treated in the program required admission, while 7 (3.2%) patients in the Emergency Department group were admitted. Overall, antibiotics were started before referral in 51.2% of patients in the program compared to 92.2% in the Emergency Department (p < 0.005).

LIMITATIONS:

Modest sample size, single institutional data and retrospective design.

CONCLUSIONS:

Implementation of non-antibiotic treatment for mild acute uncomplicated diverticulitis can be successful using an outpatient nurse-clinician led program with referrals from the Emergency Department and community. See Video Abstract.
Guideline Concordant Extended Pharmacologic Venous Thromboembolism Prophylaxis Utilization After Colorectal Cancer Resection Is Low Regardless of Patient Factors or Hospital Characteristics
Authors: Donahue Colleen , Brinton Daniel , Booth Alexander , Westfal Maggie , George Virgilio , Maxwell Pinckney Johnstone , Simpson Kit , Curran Thomas
Published: December 2024

BACKGROUND:

Venous thromboembolism after colorectal cancer resection is common and highly morbid. Extended pharmacologic venous thromboembolism prophylaxis after cancer surgery lowers venous thromboembolism risk and is recommended by major professional societies. Adherence is low in contemporary local and regional studies.

OBJECTIVE:

Assess patient and hospital factors associated with receipt of prophylaxis after colorectal cancer surgery in a national data set.

DESIGN:

Retrospective cohort study.

SETTINGS:

Surveillance, epidemiology, and end results Medicare dataset.

PATIENTS:

Patients over age 64 undergoing resection for colorectal cancer between 2016 and 2017.

MAIN OUTCOME MEASURES:

Primary outcome was receipt of prophylaxis within 7 days of discharge. Patient and hospital factors associated with receiving prophylaxis were identified using multivariable logistic regression. Secondary outcomes included 30- and 90-day venous thromboembolism.

RESULTS:

Of 23,527 patients, 4.7% received prophylaxis. Utilization increased from 2016 to 2017 (3.9% vs. 5.5%; p < 0.001). Patients treated at National Cancer Institute designated hospitals received prophylaxis more frequently than teaching, non-National Cancer Institute hospitals and non-teaching, non-National Cancer Institute hospitals (10.2% vs. 5.6% vs. 1.7%; p < 0.001). Patients receiving care at larger hospitals by bed size quartile were more likely to receive prophylaxis compared to those at smaller hospitals (9.0% vs. 4.0% vs. 3.4% vs. 2.2%; p < 0.01). On multivariable regression, National Cancer Institute status, larger bed size, White race (compared to other), rectal tumor location and more recent year of treatment were independently associated with prophylaxis utilization. Venous thromboembolism events at 30- and 90-days were 1.87% and 2.63%, respectively. Prophylaxis was associated with decreased 30-day venous thromboembolism (1.26% vs. 1.9%; p = 0.1211).

LIMITATIONS:

Retrospective, large database study.

CONCLUSIONS:

Utilization of prophylaxis after colorectal cancer surgery remains limited even in large, specialized hospitals. Further work is needed to understand this departure from guideline concordant care. See Video Abstract.
Jazz dancing for improving cardiorespiratory fitness, body composition, muscle strength, and sleep quality in postmenopausal women: a randomized clinical trial with 6- and 12-month follow-ups
Authors: Bocchi Martins Julia Beatriz , Fausto Danielly Yani , Sonza Anelise , Coutinho de Azevedo Guimarães Adriana
Published: December 2024

Objective

The aim of the study was to analyze the effects of 16 weeks of Jazz Dance training compared to a control group in postmenopausal women, postintervention, and at the 6- and 12-month follow-ups, on cardiorespiratory fitness, body composition, muscle strength, and sleep quality.

Methods

Two-arm randomized clinical trial with a total of 47 women (jazz dance intervention group [JDIG] [n = 23] and control group (CG) [n = 24]) with a mean age of 53.41 ± 2.8 y. Data collection was carried out at four times, baseline, postintervention, and 6- and 12-month follow-ups using the 6-minute walk test (cardiorespiratory fitness); bioimpedance (body composition); isokinetic dynamometry (muscle strength); and the Pittsburgh Sleep Quality Index (sleep quality).

Results

In the intention-to-treat analysis, the results showed positive differences for the JDIG in cardiorespiratory fitness at all time points (P = 0.034) and in the group x time interaction (P = <0.001). Lower limb muscle strength showed differences from baseline to postintervention and from baseline to the 12-month follow-up for the concentric force ratio (P = 0.021; P = 0.009). However, for peak extension and flexion, the results were not positive for the JDIG. There was a short-term improvement in sleep duration for the JDIG (P = 0.001) and significant intergroup differences in subjective sleep quality, where the JDIG showed better results compared to the CG (P = 0.041).

Conclusions

Jazz Dance is effective for improving cardiorespiratory fitness (in the short, medium, and long term) and sleep quality (in the short and medium term); however, it does not seem to have presented sufficient intensity and duration for facilitating changes in body composition or increasing lower limb muscle strength in postmenopausal women.
Emotional Distress in Younger (<55 Years) and Older (≥55) Patients After a First-Time Myocardial Infarction and Its Prospective Associations With Working Status and Secondary Preventive Goals Among the Younger Cohort
Authors: Almén Niclas , Leissner Philip , Hambraeus Kristina , Borg Sabina , Norlund Fredrika , Henriksson Catrin , Johansson Pelle , Olsson Erik M.G.
Published: December 2024

Background

Research has shown that younger patients who have had a myocardial infarction (MI) experience more emotional distress than their older counterparts.

Objective

In this study, we aimed to compare emotional distress 2 months post-MI (follow-up 1) between younger (<55) vs older (≥55) patients in Sweden, and investigate its impact on working status and 4 secondary preventive goals 1 year after MI (follow-up 2).

Methods

Data (N = 50 213) from the SWEDEHEART National Quality Registers for Cardiac Care, which covers approximately 90% of all MIs in Sweden, were used.

Results

After adjusting for confounders, logistic regression analyses showed that younger patients who had experienced an MI had higher odds of experiencing emotional distress than older patients at follow-up 1 (adjusted odds ratio [AOR], 1.59; 95% confidence interval [CI], 1.52–1.67) and follow-up 2 (AOR, 1.47; 95% CI, 1.40–1.55). Emotional distress at follow-up 1 was associated with lower odds of working (AOR, 0.60; 95% CI, 0.53–0.67) and achieving smoking and physical activity goals (AOR, 0.76; 95% CI, 0.67–0.86; AOR, 0.83; 95% CI, 0.76–0.91) at follow-up 2. However, emotional distress was not associated with achieving goals for low-density lipoproteins or systolic blood pressure at follow-up 2.

Conclusions

Younger patients experienced emotional distress more often after a first-time MI than their older counterparts, and their distress predicted long-term lower levels of returning to work and achievement of smoking and physical activity goals. The results highlight the importance of identifying younger patients who have had an MI and are experiencing emotional distress, and offering them interventions targeting distress.
Development and validation of an interpretable machine learning model to predict major adverse cardiovascular events after noncardiac surgery in geriatric patients: a prospective study
Authors: Yu Jiayu , Peng Xiran , Zhou Ruihao , Zhu Tao , Hao Xuechao
Published: December 2024

Background:

Major adverse cardiovascular events (MACEs) within 30 days following noncardiac surgery are prognostically relevant. Accurate prediction of risk and modifiable risk factors for postoperative MACEs is critical for surgical planning and patient outcomes. We aimed to develop and validate an accurate and easy-to-use machine learning model for predicting postoperative MACEs in geriatric patients undergoing noncardiac surgery.

Materials and methods:

The cohort study was conducted at an academic medical center between June 2019 and February 2023. The outcome was postoperative MACEs within 30 days after surgery. Significant predictors were selected using permutation-shuffling. Ten machine learning models were established and compared with the Revised Cardiac Risk Index (RCRI). The SHapley Additive exPlanations algorithm was used to interpret the models.

Results:

Of the 18,395 patients included, 354 (1.92%) experienced postoperative MACEs. Eighteen predictors were included in model development. The AutoGluon model outperformed other models and the RCRI with an AUROC of 0.884 (95% CI: 0.878–0.890), an accuracy of 0.976 (95% CI: 0.973–0.978), and a Brier score of 0.023 (95% CI: 0.020–0.026). In interpretability analyses, the hemoglobin level was the most important predictor. We identified the relationships between predictors and postoperative MACEs and interaction effects between some predictors. The AutoGluon model has been deployed as a web-based tool for further external validation (https://huggingface.co/spaces/MDC2J/Predicting_postoperative_MACEs).

Conclusion:

In this prospective study, the AutoGluon model could accurately predict MACEs after noncardiac surgery in geriatric patients, outperforming existing models and the RCRI. Subsequent interpretability analysis can provide insight into how our model works and help personalize surgical strategies.
Verbal Deescalation Training
Authors: Thompson Lara , Conklin Anna , Holcomb Brittni , Moore Courtney , Staton Lindsey , Zhang Xiaoxi
Published: December 2024

Verbal deescalation training is lacking in nurse residency programs. This results in inability to mediate violent events, increased staff injury, and decreased job satisfaction. Training in verbal deescalation promotes confidence, satisfaction, and safety. Nurses participated in didactic and simulated verbal deescalation training resulting in an increase in verbal deescalation confidence of 1.6 on a 1–10 Likert scale. Meaningful verbal deescalation training increases confidence and could reduce workplace violence as well as improve workplace safety and job satisfaction.
Positioning of the Inferior Alveolar Nerve and Surgical Implications
Authors: Charoenvicha Chirakan , Sirikul Wachiranun , Thaweethanasit Ditsayanin , Kongmebhol Pailin , Madla Chakri , Wongtriratanachai Puttan
Published: December 2024

Background

The inferior alveolar nerve (IAN), a crucial branch of the trigeminal nerve, innervates the mandible. Precise knowledge of IAN positioning ensures surgical safety.

Methods

This cross-sectional study analyzed head and neck computed tomography scans from Maharaj Nakorn Chiang Mai Hospital. Inclusion criteria comprised dentate adults. Exclusion criteria included mandibular trauma/pathology or prior surgery. The study aimed to determine IAN positioning relative to key surgical landmarks: the first molar, lingula, and mental foramen.

Results

A total of 450 Thai mandibles (900 hemimandibles) with a mean age of 36 years (58.2% male) were included. No significant differences were observed in IAN positioning relative to the first molar between the left and right sides in superior and inferior landmarks. However, the buccal distance was significantly closer on the left. The lingula distance was higher on the left, whereas that to the mental foramen was lower.

Conclusion

Surgical implications suggest maintaining a 15-mm distance from the lower mandibular border during osteotomy and upper plate placement, restricting horizontal cuts within this 15-mm range from the lingula, and ensuring screws do not extend more than 7 mm from the buccal surface. This study provides valuable guidance for minimizing the risk of iatrogenic injury to the IAN.
Assessing the Reliability of YouTube Content for Plastic Surgery Patient Information in Africa With the Modified DISCERN and JAMA Scores
Authors: Alice Umutoni , Dadson Shirley S. , Edeh Emmanuel , Ndudi Mbonu G. , Kuol Piel P. , Barasa Theophilus , Ojamah Okojie S. , Nkansah-Poku Kwadwo A.B. , Nyarko Emmanuel B. , Majata Ebenisha Choonya , Kanmounye Ulrick Sidney
Published: December 2024

Introduction

YouTube has become a popular source of health information, including plastic surgery. Given the platform's wide reach and potential influence on patient decisions, this study aimed to assess the quality of information available on YouTube for African audiences seeking plastic surgery procedures.

Methods

This cross-sectional study extracted data from YouTube videos on plastic surgery relevant to Africa. A search strategy identified videos in English using keywords. The first 50 results for each term were included, with duplicates removed. Next, the metadata of videos published from inception to June 9, 2024, were extracted. Two reviewers independently assessed videos using standardized tools to evaluate reliability (modified DISCERN and JAMA criteria) and engagement (likes-to-views ratio [LVR] and comments-to-views ratio [CVR]). The Mann-Whitney U test was used for unadjusted bivariable comparisons. Then ordinal logistic and beta regression analyses were used to evaluate the primary (modified DISCERN and JAMA scores) and secondary (LVR and CVR) outcomes, with a statistical significance level set at 0.05.

Results

Eight hundred ninety-seven plastic surgery videos were analyzed, and 3.9% were published by African entities. Large subscriber count (coefficient = −6.9e-8, 95% confidence interval [CI] [−1.13e-7, −2.9e-8], P = 0.001), African-authored (coefficient = −0.85, 95% CI [−1.44, −0.25], P = 0.005), and advertising (coefficient = −1.01, 95% CI [−1.63, −0.57], P < 0.001) videos had lower modified DISCERN scores. Advertising videos equally had lower JAMA scores (coefficient = −1.29, 95% CI [−1.83, −0.74], P < 0.001). Academic videos had lower LVR (coefficient = −0.48, 95% CI [−0.66, −0.30], P < 0.001), whereas independent videos had higher LVR (coefficient = 0.40, 95% CI [0.26, 0.54], P < 0.001). Academic videos had lower CVR (coefficient = −0.40, 95% CI [−0.67, −0.13], P = 0.003), whereas videos with other purposes had higher CVR (coefficient = 0.37, 95% CI [0.10, 0.64], P = 0.007).

Conclusions

This study underscores a potential disparity in the quality of online plastic surgery information based on video sources and purposes.
Comparison of Self-repair Disparities in Articular Cartilage Defect Models With Various Load-bearing Sites
Authors: Tan Zhen-Wei , Duan Xin , Ti Shi-Tong , Yu Xi-Jie
Published: December 2024

This study aimed to explore the construction of experimental animal models replicating cartilage defects across diverse load-bearing sites, compare self-repair conditions, and examine the role of mechanical stimulation in cartilage self-repair. Experimental animal models were established in rabbits to simulate full-thickness cartilage defects without penetrating the subchondral bone, at various load-bearing sites, including the posterior femoral condyle, anterior femoral condyle and femoral trochlear of knee joint, and the humerus of the shoulder joint. The successful exposure and construction of cartilage defects at the anterior femoral condyle, femoral trochlear, and posterior femoral condyle through the medial extension of surgical incision. In addition, a fully non-loaded articular cartilage defect could be constructed in the shoulder joint of the upper limb using a specific surgical approach. No mortality or disability was observed in the experimental animals after the surgeries. At the 8-week sampling period postsurgery, the defect sites showed the growth of hyaline tissues. The repair effects were ranked in the following order from good to poor; posterior femoral condyle, anterior femoral condyle, femoral trochlear, and humerus. The application of suitable compressive loads under normal load-bearing conditions has been found to positively impact the repair of articular cartilage.
Enhanced Osseointegration of Titanium Alloy Bone Implants Coated With Carob-calcium Hydroxide Nanoparticles: A Comparative Study
Authors: AlNatheer Yaser , Alghamdi Osama G. , Devanesan Sandhanasamy , AlSalhi Mohamad S. , Alshawakir Yasser A. , Khounganian Rita M. , Alrahlah Ali , Seif Sameh A.
Published: December 2024

Objectives:

This study aimed to evaluate the osseointegration properties of titanium bone implants coated with carob-mediated calcium hydroxide nanoparticles biomechanically, radiographically, and histologically on rabbit tibias.

Material and Methods:

Forty coated and forty uncoated titanium alloy bone implants were inserted into 20 New Zealand rabbits; each tibia received 2 implants. The rabbits were sacrificed after 4 or 8 weeks, and samples were retrieved for biomechanical evaluation through removal torque test to assess the bond between implant and bone, radiographic evaluation through microcomputed tomography analysis to compare the bone-to-implant contact percentage and bone volume of the peri-implant area, scanning electron microscopic and histologic evaluation through hematoxylin and eosin stain. Statistical analyses between pairs of means were conducted using the independent t test. Multiple comparisons between the study groups across time intervals were performed using a 2-way analysis of variance. P-values ≤0.05 were considered statistically significant.

Results:

Higher removal torque values (P<0.01) were needed to remove the coated implants when biomechanically tested. In addition, the microcomputed tomography evaluation revealed a higher bone-to-implant contact percentage (P<0.05) in favor of coated implants. In addition, the 4-week healing interval of the coated implants showed no significant difference when compared with the 8-week healing interval of the uncoated implants biomechanically and radiographically, suggesting early osseointegration.

Conclusions:

The findings of this study imply that coating titanium implants with carob-mediated calcium hydroxide nanoparticles improved and fastened osseointegration and bone ingrowth, resulting in early osteogenesis and shortening the treatment time.
Rethinking cancer drug synergy prediction: a call for standardization in machine learning applications
Authors: Wong Alexandra M. , Crawford Lorin
Published: December 2024

Drug resistance poses a significant challenge to cancer treatment, often caused by intratumor heterogeneity. Combination therapies have been shown to be an effective strategy to prevent resistant cancer cells from escaping single-drug treatments. However, discovering new drug combinations through traditional molecular assays can be costly and time-consuming.In silicoapproaches can overcome this limitation by exploring many candidate combinations at scale. This study systematically evaluates the utility of various machine learning algorithms, input features, and drug synergy prediction tasks. Our findings indicate a pressing need for establishing a standardized framework to measure and develop algorithms capable of predicting synergy.
The Ulcerative Colitis-Associated Gene NXPE1 Catalyzes Glycan Modifications on Colonic Mucin
Authors: Humeidi Ranad , Rapley Noriko , Gu Xiebin , An Joon Soo , Ananthakrishnan Ashwin N. , Creasey Elizabeth A. , Daly Mark J. , Schreiber Stuart L. , Graham Daniel B. , Seyedsayamdost Mohammad R. , Xavier Ramnik J.
Published: December 2024

Colonic mucus forms a first line of defense against bacterial invasion while providing nutrition to support coinhabiting microbes in the gut. Mucus is composed of polymeric networks of mucin proteins, which are heavily modified post-translationally. The full compendium of enzymes responsible for these modifications and their roles in health and disease remain incompletely understood. Herein we determine the biochemical function of NXPE1, a gene implicated in ulcerative colitis (UC), and demonstrate that it encodes an acetyltransferase that modifies mucin glycans. Specifically, NXPE1 utilizes acetyl-CoA to regioselectively modify the mucus sialic acid, 5-N-acetylneuraminic acid (Neu5Ac), at the 9-OH group to generate 9-O-acetylated Neu5Ac (Neu5,9Ac2). We further demonstrate that colonic organoids derived from donors harboring the missense variant NXPE1 G353R, which is protective against UC, exhibit severely impaired acetylation of Neu5Ac on mucins. Together, our findings support a model in which NXPE1 masks the alcohols of mucus sialoglycans via acetylation, which is important for modulating mucus barrier properties that limit interactions with commensal microbes.
A somatic multiple myeloma mutation unravels a mechanism of oligomerization-mediated product inhibition in GGPPS
Authors: Yehia Ruba , Portašiková Jasmína Mária , Mor Yosef Rut , Da’adoosh Benny , Kádek Alan , Man Petr , Giladi Moshe , Haitin Yoni
Published: December 2024

Protein prenylation regulates the cellular localization of small GTPases and is pivotal for multiple myeloma (MM) pathology. Geranylgeranyl diphosphate synthase (GGPPS), synthesizing a prenylation moiety, exhibits dimeric or hexameric stoichiometry in different species. However, the functional significance of this divergence remains elusive. Focusing on the hexameric human paralog, formed by trimer-of-dimers, we uncover that GGPPSR235C, expressed in an MM cell line, localizes to the active site lid region at the inter-dimeric interface. Using crystallography and mass spectrometry (MS), we show that GGPPSR235Cretains its hexameric stoichiometry but exhibits destabilized inter-dimer interactions. Unexpectedly, this results in increased apparent substrate affinity and product release kinetics. These functional effects are further enhanced in a dimeric mutant, GGPPSY246D. Combining MS and fluorescence spectroscopy, we exposed that reduced lid dynamics and increased active site occupancy by the product are intertwined. Together, our results expose product inhibition as a regulatory mechanism in GGPPS, driven by hexamerization.
ChromBPNet: bias factorized, base-resolution deep learning models of chromatin accessibility reveal cis-regulatory sequence syntax, transcription factor footprints and regulatory variants
Authors: Pampari Anusri , Shcherbina Anna , Kvon Evgeny Z. , Kosicki Michael , Nair Surag , Kundu Soumya , Kathiria Arwa S. , Risca Viviana I. , Kuningas Kristiina , Alasoo Kaur , Greenleaf William James , Pennacchio Len A. , Kundaje Anshul
Published: December 2024

Despite extensive mapping of cis-regulatory elements (cREs) across cellular contexts with chromatin accessibility assays, the sequence syntax and genetic variants that regulate transcription factor (TF) binding and chromatin accessibility at context-specific cREs remain elusive. We introduce ChromBPNet, a deep learning DNA sequence model of base-resolution accessibility profiles that detects, learns and deconvolves assay-specific enzyme biases from regulatory sequence determinants of accessibility, enabling robust discovery of compact TF motif lexicons, cooperative motif syntax and precision footprints across assays and sequencing depths. Extensive benchmarks show that ChromBPNet, despite its lightweight design, is competitive with much larger contemporary models at predicting variant effects on chromatin accessibility, pioneer TF binding and reporter activity across assays, cell contexts and ancestry, while providing interpretation of disrupted regulatory syntax. ChromBPNet also helps prioritize and interpret regulatory variants that influence complex traits and rare diseases, thereby providing a powerful lens to decode regulatory DNA and genetic variation.
Accuratede novodesign of a voltage-gated anion channel
Authors: Zhou Chen , Li Huican , Wang Jiaxing , Chu Zhilin , Sun Shijin , Sun Ke , Zhu Aiqin , Wang Jiawei , Jin Xueqin , Yang Fan , Gamal El-Din Tamer M. , Wu Kun , Lu Peilong
Published: December 2024

Ion channels gated by environmental cues play key roles in fundamental biological processes. Designing ion channels with tailored gating mechanisms remains a significant challenge due to the complexities involved in designing conformational changes in proteins. Here we report the accuratede novodesign of a voltage-gated anion channel, namely VGAC. VGAC adopts a 15-helix pentameric structure featuring a constriction composed of five arginine residues within the transmembrane span. In patch-clamp experiments, VGAC showed strictly voltage-dependent currents and demonstrated selectivity for chloride anions over iodide anions. Our data suggests that the arginine constriction undergoes voltage-induced conformational changes, serving as both the voltage sensor and selectivity filter. A 2.9-Å-resolution cryo-electron microscopy structure of VGAC closely aligns with the design model. The ability to design ion channels with custom-designed conformational changes provides new insights into our understanding of the fundamental principles of membrane biophysics and unveils a wide range of potential applications.
Differentiating BOLD and non-BOLD signals in fMRI time series using cross-cortical depth delay patterns
Authors: Chen Jingyuan E. , Blazejewska Anna I. , Fan Jiawen , Fultz Nina E. , Rosen Bruce R. , Lewis Laura D. , Polimeni Jonathan R.
Published: December 2024

Over the past two decades, rapid advancements in magnetic resonance technology have significantly enhanced the imaging resolution of functional Magnetic Resonance Imaging (fMRI), far surpassing its initial capabilities. Beyond mapping brain functional architecture at unprecedented scales, high-spatial-resolution acquisitions have also inspired and enabled several novel analytical strategies that can potentially improve the sensitivity and neuronal specificity of fMRI. With small voxels, one can sample from different levels of the vascular hierarchy within the cerebral cortex and resolve the temporal progression of hemodynamic changes from parenchymal to pial vessels. We propose that this characteristic pattern of temporal progression across cortical depths can aid in distinguishing neurogenic blood-oxygenation-level-dependent (BOLD) signals from typical nuisance factors arising from non-BOLD origins, such as head motion and pulsatility. In this study, we examine the feasibility of applying cross-cortical depth temporal delay patterns to automatically categorize BOLD and non-BOLD signal components in modern-resolution BOLD-fMRI data. We construct an independent component analysis (ICA)-based framework for fMRI de-noising, analogous to previously proposed multi-echo (ME) ICA, except that here we explore the across-depth instead of across-echo dependence to distinguish BOLD and non-BOLD components. The efficacy of this framework is demonstrated using visual task data at three graded spatiotemporal resolutions (voxel sizes = 1.1, 1.5, and 2.0 mm isotropic at temporal intervals = 1700, 1120, and 928 ms). The proposed framework leverages prior knowledge of the spatiotemporal properties of BOLD-fMRI and serves as an alternative to ME-ICA for cleaning moderate- and high-spatial-resolution fMRI data when multi-echo acquisitions are not available.
Histone H3.3 ensures cell proliferation and genomic stability during myeloid cell development
Authors: Chauhan Sakshi , Dey Anup , Macfarlan Todd , Ozato Keiko
Published: December 2024

Variant histone H3.3 is thought to be critical for survival of many cells, since it is deposited in expressed genes, a feature different from core histones. For example, H3.3 deletion leads to embryonic lethality in mice. However, requirement of H3.3 in later stage of development has remained unclear. The aim of this work was to elucidate the role of H3.3 for development of myeloid lineage, important for innate immunity. We conditionally knocked out (cKO) the H3.3 genes in myeloid progenitor cells differentiating into bone marrow derived macrophages (BMDMs). Progenitor cells lacking H3.3 were defective in replication, suffered from extensive DNA damage, and underwent apoptosis. SurvivingH3.3cKO cells expressed many interferon stimulated genes (ISGs) throughout differentiation. Further,H3.3cKO BMDMs possessed chromatin accessible sites, and histone posttranslational modifications consistent with the gene expression profiles, Accordingly,H3.3cKO BMDMs retained general nucleosomal structure genome wide. In summary, H3.3 is required for proliferation of myeloid progenitor cells, but is in large part dispensable for differentiation of BMDMs.
PrecisionTrack: Reliable Tracking of Large Groups of Animals Interacting in Complex Environments Over Extended Periods
Authors: Coulombe Vincent , Roussel David-Alexandre , Monfared Mohamad Sadegh , Leboulleux Quentin , Peralta Modesto R. , Aghel Khadijeh , Gosselin Benoit , Labonté Benoit
Published: December 2024

Mice living in complex social groups within ethological environments exhibit a wide range of adaptive behaviors, including individual and group dynamics, often undetected in standard behavioral studies. To better understand the coping and adaptive strategies employed by each member of a social colony, it is necessary to develop tools that enable accurate, long-term monitoring of large groups of animals in a fully automated and unbiased manner. In this work, we introduce PrecisionTrack, a practical solution to the multi-animal pose tracking problem. This solution enables an accurate and reliable tracking of large groups of animal socially interacting within complex environments, even over prolonged periods. Our algorithm builds on a Transformer-CNN hybrid neural network for cross-species classification, detection, and pose estimation, leveraging pose-based matching AI-driven ArUco identification for fast and accurate re-identification. PrecisionTrack demonstrates superior performance in tracking accuracy and latency compared to current gold standards, while sustaining these capabilities over extended periods when tracking large groups of animals in complex environments. Furthermore, we trained PrecisionTrack to identify and monitor over 30 animal species. Overall, PrecisionTrack represents a reliable, accessible step toward adopting more ethological methodologies in behavioral research.
A General Strategy to Endow Dyes with Genic Fluorescence for Wash-Free Imaging of Proteins in Living Cells
Authors: Zhou Xuelian , Miao Lu , Xu Ning , Chen Yonghui , Shi Jinjing , Zhou Jinhua , Wang Guangying , Qiao Qinglong , Xu Zhaochao
Published: December 2024

Fluorescent dyes are the main fluorophore for protein labeling and fluorescent imaging in living cells. However, due to the inevitable nonspecific binding of the dye to non-targets within the cell, background signals are generated, which severely affect the imaging quality. Here, we endow the dye with genic fluorescence by introducing a fluorescent proteins FRET pair, such that only the dye bound to the target protein emits fluorescence (λex= FPs, λem= Dyes), while nonspecifically bound dye remains non-fluorescent. This significantly improves the signal-to-noise ratio (SNR) in wash-free imaging. This strategy is achieved by fusing the Halo-tag to fluorescent proteins (sfGFP, mCherry) that can generate FRET with Halo dyesO-RhoandSi-Rho. The FPs serve as the donor, and the FRET mechanism imparts genic fluorescence property toO-RhoandSi-Rho. Since the excitation wavelength of the donor (λex= FPs) cannot excite the unspecifically dye fluorescence, background fluorescence interference is reduced. We further improved the SNR by increasing the FRET efficiency between the FPs and dyes. The system was used for four-color super-resolution imaging of target proteins and dynamic SIM tracking of mitochondria. In addition, the genic FRET fluorophore constructed with the ultra-stable mStayGold showed significant photobleaching resistance and can be used for long-term dynamic super-resolution imaging. Theoretically, by selecting appropriate FRET pairs, this method can improve the SNR of any fluorophore, providing a new labeling strategy for live-cell wash-free imaging.