bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gearing Effect in Clockwise Rotational Orthognathic Surgery
Authors: Woo Soo Hyun , Kim Young Chul , Lee Jang Yeol , Choi Jong Woo 
Published: September 2023

Background:
The standard procedure for managing skeletal class III malocclusion is maxillary advancement with mandibular setback. Occlusal plane–altering orthognathic surgery, such as jaw rotation, is useful as well. Although clockwise jaw rotation is a common procedure, its mechanism has not been well investigated. With this study, the authors aim to introduce the gearing effect to correct class III malocclusion in Asians by maxillary posterior impaction using clockwise rotation without advancing the maxilla.

Methods:
Patients with class III correction with clockwise rotation of the maxillomandibular complex without maxillary advancement were included; those who underwent genioplasty were excluded. Various facial skeletal cephalometric landmarks were measured using artificial intelligence–based cephalometric analysis software. The gearing effect was determined by dividing the lower anterior facial height (LAFH) in relatively short and long groups compared with those in the anterior nasal spine to posterior nasal spine length.

Results:
In a total of 29 patients, the amount of menton setback between group 1 (n = 15; short LAFH) and group 2 (n = 14; long LAFH) was 1.67 ± 0.66 and 2.74 ± 0.99 mm per 1 mm of posterior nasal spine impaction, respectively (P = 0.002), and 1.58 (interquartile range, 0.78) and 1.95 (interquartile range, 1.05) mm per 1 degree of clockwise rotation of the palatal angle, respectively (P = 0.007). The convexity of the A point was improved without any significant change in the sella-nasion–A point angle before and after surgery.

Conclusions:
This article addresses the scientific evidence regarding the impact of clockwise rotational orthognathic surgery based on the gearing effect. The mandibular setback turned out to be more effective in patients with a long LAFH.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Irradiation Affects Adipose-Derived Stem Cells and Wound Healing Depending on Radiation Dose and Frequency
Authors: Asahi Rintaro , Sunaga Ataru , Shirado Takako , Saito Natsumi , Mori Masanori , Yamamoto Yoshihiro , Wu Yunyan , Yoshimura Kotaro 
Published: September 2023

Background:
Radiation therapies are often associated with permanent devitalization in the surrounding tissue. The authors hypothesized that stem cells are damaged depending on each irradiation dose and frequency of fractionated radiotherapies, which results in impaired tissue function, including wound-healing capacity.

Methods:
Susceptibility of human adipose-derived stem cells (ASCs) to a single irradiation (0 to 10 Gy) was assessed in vitro. In vivo chronic radiation effects were also assessed on mouse dorsal skin (n = 4 to 5) for 6 months after a total of 40 Gy irradiation (0 Gy as control) using 1 of 3 fractionated protocols (2 Gy daily for 20 days, 10 Gy weekly for 4 weeks, or 10 Gy monthly for 4 months). Oxygen partial pressure, oxygen saturation of hemoglobin, and dorsal skin viscoelasticity were measured periodically, and wound healing and tissue immunohistology were compared at 6 months.

Results:
A single irradiation of cultured human ASCs resulted in a dose-dependent increase in cell death up to 2 Gy but with no further increases between 2 and 10 Gy. Most of the apoptotic ASCs were in the proliferation phase. Among the 3 in vivo irradiation protocols, the 2 Gy×20 group had the most severe chronic tissue damage (ie, skin dysfunction, subcutaneous atrophy, depletion of CD34+ stem cells) 6 months after the irradiation. Wound healing was also impaired most significantly in the 2 Gy×20 group.

Conclusion:
These results have important clinical implications for surgeons and radiotherapists in the timing of surgical interventions and the optimization of fractionation protocols.

Clinical Relevance Statement:
Irradiation damages stem cells depending on the radiation dose and frequency. Using the ultimately optimized protocol, surgeons can minimize the long-term functional deficits of radiated tissue without losing the anticancer efficacy of radiation therapy.
Nifuroxazide Suppresses PD-L1 Expression and Enhances the Efficacy of Radiotherapy in Hepatocellular Carcinoma
Authors: Zhao Tiesuo , Wei Pengkun , Zhang Congli , Zhou Shijie , Liang Lirui , Guo Shuoshuo , Yin Zhinan , Cheng Sichang , Gan Zerui , Xia Yuanling , Zhang Yongxi , Guo Sheng , Zhong Jiateng , Yang Zishan , Tu Fei , Wang Qianqing , Bai Jin , Ren Feng , Feng Zhiwei , Jia Huijie 
Published: September 2023

AbstractRadiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosisin vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.
IMPACT OF THE COVID-19 PANDEMIC ON ROUTINE HIV CARE AND ANTIRETROVIRAL TREATMENT OUTCOMES IN KENYA: A NATIONALLY REPRESENTATIVE ANALYSIS
Authors: Kimanga Davies O. , Makory Valeria N.B. , Hassan Amin S. , Ngari Faith , Ndisha Margaret M. , Muthoka Kennedy J. , Odero Lydia , Omoro Gonza O. , Aoko Appolonia , Ng’ang’a Lucy 
Published: September 2023

ABSTRACTBackgroundThe COVID-19 pandemic adversely disrupted global health service delivery. We aimed to assess impact of the pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and initial virologic non-suppression (VnS) among individuals starting antiretroviral therapy (ART) in Kenya.MethodsIndividual-level longitudinal service delivery data were analysed. Random sampling of individuals aged >15 years starting ART between April 2018 – March 2021 was done. Date of ART initiation was stratified into pre-COVID-19 (April 2018 – March 2019 and April 2019 – March 2020) and COVID-19 (April 2020 – March 2021) periods. Mixed effects generalised linear, survival and logistic regression models were used to determine the effect of COVID-19 pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and VnS, respectively.ResultsOf 7,046 individuals sampled, 35.5%, 36.0% and 28.4% started ART during April 2018 – March 2019, April 2019 – March 2020 and April 2020 – March 2021, respectively. Compared to the pre-COVID-19 period, the COVID-19 period had higher same-day HIV diagnosis/ART initiation (adjusted risk ratio [95% CI]: 1.09 [1.04–1.13], p<0.001) and lower six-months non-retention (adjusted hazard ratio [95% CI]: 0.66 [0.58–0.74], p<0.001). Of those sampled, 3,296 (46.8%) had a viral load test done at a median 6.2 (IQR, 5.3–7.3) months after ART initiation. Compared to the pre-COVID-19 period, there was no significant difference in VnS during the COVID-19 period (adjusted odds ratio [95% CI]: 0.79 [95%% CI: 0.52–1.20], p=0.264).ConclusionsIn the short term, the COVID-19 pandemic did not have an adverse impact on HIV care and treatment outcomes in Kenya. Timely, strategic and sustained COVID-19 response may have played a critical role in mitigating adverse effects of the pandemic and point towards maturity, versatility and resilience of the HIV program in Kenya. Continued monitoring to assess long-term impact of the COVID-19 pandemic on HIV care and treatment program in Kenya is warranted.
Abundance of Northern Hemisphere tree species declines in the warm and arid regions of their climatic niches
Authors: Astigarraga Julen , Esquivel-Muelbert Adriane , Ruiz-Benito Paloma , Rodríguez-Sánchez Francisco , Zavala Miguel A. , Vilà-Cabrera Albert , Schelhaas Mart-Jan , Kunstler Georges , Woodall Christopher W. , Cienciala Emil , Dahlgren Jonas , Govaere Leen , König Louis A. , Lehtonen Aleksi , Talarczyk Andrzej , Pugh Thomas A. M. 
Published: September 2023

AbstractClimate change is expected to drive species towards colder and wetter regions of their distribution with alternative processes such as forest management having the potential to alter species displacements. Here, using data from more than two million monitored trees from 73 widely-distributed species, we quantify changes in tree species abundance across Northern Hemisphere forests and find a widespread decline in abundance across the whole of species’ climatic niches. Yet, our analysis revealed that this decline is heavily influenced by alterations at the stand-level and consequent stand development. Remarkably, when accounting for stand development, our findings show a consistent trend of species abundance optimum shifting towards cold and wet regions within their climatic niches. We provide species-specific information on the direction and magnitude of climate-driven changes in abundance that should be taken into account when designing conservation, management and restoration plans in an era of unprecedented human-caused environmental change.
Harmonized decay classification for dead wood in Nordic national forest inventories
Authors: Aakala Tuomas , Heikkinen Juha 
Published: September 2023

AbstractDead wood quality is recorded as a biodiversity indicator and in estimating forest ecosystem carbon storage, using decay classification systems. In large-scale national forest inventories (NFIs), these systems are typically slightly different among countries, but harmonizing them would allows analyses over much broader scales and the use of larger data sets. Here, we developed a harmonized decay classification for the NFIs of Finland, Norway, and Sweden, using wood density as the harmonizing criterion. We sampled 441 pine, spruce, birch and aspen in different conditions and decay classes, measured their density and developed the harmonized classification for each species and dead wood type (standing and fallen dead wood). The assignments relied on minimizing within-class variance in wood density in the harmonized classes. Assigned into three (standing dead wood) and four (fallen dead wood) classes, the harmonization led to some losses of information, especially in the advanced decay stages in Finnish and Norwegian classifications. Importantly, the harmonized classes included slightly different decay classes from the national classifications, depending on the tree species and type. This is an advantage over the expert assessment that typically treat all species and types of dead wood the same way despite clear differences in decomposition pathways.
Poor Generalization by Current Deep Learning Models for Predicting Binding Affinities of Kinase Inhibitors
Authors: Ong Wern Juin Gabriel , Kirubakaran Palani , Karanicolas John 
Published: September 2023

AbstractThe extreme surge of interest over the past decade surrounding the use of neural networks has inspired many groups to deploy them for predicting binding affinities of drug-like molecules to their receptors. A model that can accurately make such predictions has the potential to screen large chemical libraries and help streamline the drug discovery process. However, despite reports of models that accurately predict quantitative inhibition using protein kinase sequences and inhibitors’ SMILES strings, it is still unclear whether these models can generalize to previously unseen data. Here, we build a Convolutional Neural Network (CNN) analogous to those previously reported and evaluate the model over four datasets commonly used for inhibitor/kinase predictions. We find that the model performs comparably to those previously reported, provided that the individual data points are randomly split between the training set and the test set. However, model performance is dramatically deteriorated when all data for a given inhibitor is placed together in the same training/testing fold, implying that information leakage underlies the models’ performance. Through comparison to simple models in which the SMILES strings are tokenized, or in which test set predictions are simply copied from the closest training set data points, we demonstrate that there is essentially no generalization whatsoever in this model. In other words, the model has not learned anything about molecular interactions, and does not provide any benefit over much simpler and more transparent models. These observations strongly point to the need for richer structure-based encodings, to obtain useful prospective predictions of not-yet-synthesized candidate inhibitors.
Harnessing Raman spectroscopy and Multimodal Imaging of Cartilage for Osteoarthritis Diagnosis
Authors: Crisford Anna , Cook Hiroki , Bourdakos Konstantinos , Venkateswaran Seshasailam , Dunlop Douglas , Oreffo Richard OC , Mahajan Sumeet 
Published: September 2023

AbstractOsteoarthritis (OA) is a complex disease of cartilage characterised by chronic joint pain, limitations in mobility and function leading to reduced quality of life. Current methods to diagnose OA, such as X- ray, MRI and the invasive synovial fluid analysis lack molecular specificity and are limited to detection of the late stages of the disease. A rapid minimally invasive and non-destructive approach for early diagnosis of OA is a critical unmet need. Label-free techniques such as Raman Spectroscopy (RS), Coherent anti-Stokes Raman scattering (CARS), Second Harmonic Generation (SHG) and Two Photon Fluorescence (TPF) are increasingly being explored to characterise cartilage tissue. However, current studies are based on whole tissue analysis and do not take into account the different and structurally distinct layers in cartilage. In this work, we used Raman spectroscopy to obtain signatures from superficial and deep layers of healthy and osteoarthritic cartilage obtained from a total of 64 patients (45 OA and 19 controls). Spectra were acquired both in the ‘fingerprint’ region from 700 to 1720 cm-1and high-frequency stretching region from 2500 to 3300 cm-1. Principal component and linear discriminant analysis was used to identify the peaks that contributed the most to classification of the different samples. The most pronounced differences were observed at the proline (855 cm-1and 921 cm-1) and hydroxyproline (877 cm-1and 938 cm-1), sulphated glycosaminoglycan (sGAG) (1064 cm-1and 1380 cm-1) for both control and OA as well as the 1245 cm-1and 1272 cm-1, 1320 cm- 1and 1345 cm-1, 1451 collagen modes in OA samples, consistent with expected collagen structural changes. Classification accuracy based on Raman fingerprint spectral analysis of superficial and deep layer cartilage for controls was found to be 94% and 96%, respectively. OA diseased cartilage was classified with 80% and 87% accuracy based on analysis of the superficial and the deep layers, respectively. Raman spectra from the C-H stretching region (2500-3300 cm-1) did not result in high classification accuracies for OA diseased cartilage. Intriguingly, relatively less differences were found with gender in healthy cartilage indicating that OA brings about significant chemical changes across both genders in both layers. On the other hand, we found significant differences in superficial and deep layer cartilage signatures with age (under 60 and over 60 years). Preliminary images of different layers of cartilage using CARS, SHG and TPF showed Cell clustering in OA, and differences in pericellular matrix and collagen structure in the superficial and the deep layers. The current study demonstrates the potential of Raman Spectroscopy together with multimodal imaging as a potential tool that provides insight into the chemical and structural composition of different layers of cartilage to improve OA diagnosis.
Integrative single-cell analysis of epigenomic and transcriptomic states in patients with systemic sclerosis-associated interstitial lung disease
Authors: Li Shifang , Gong Meijiao 
Published: September 2023

AbstractInterstitial lung disease is the primary cause of death in individuals who have systemic sclerosis, one of the autoimmune connective tissue diseases. Understanding the pathophysiology of the disease is crucial to developing treatment options. Here, we performed a single-cell multi-omic analysis on lung tissue samples from patients with systemic sclerosis-associated interstitial lung disease (SSC-ILD), profiling chromatin accessibility and gene expression in the same samples and discovering significant cellular heterogeneity. Systemic-venous endothelial cells (ECs) have been shown to be pro-inflammatory and highly active. In addition, it was shown that the transcription factor FOSL2 targets the genes involved in response to unfolded proteins in systemic-venous ECs. Furthermore, we prioritized functional risk variants for systemic sclerosis using a genome-wide association study. Ligand-receptor analysis revealed that ECs significantly increased interaction with B cells via CXCL10-CXCR3 in patients with SSC-ILD. Overall, our analysis emphasizes epigenetic and transcriptional patterns in systemic-venous ECs, which might be beneficial in understanding the pathogenesis of SSC-ILD.
Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study
Authors: Achaiah Andrew , Fraser Emily , Saunders Peter , Hoyles Rachel , Benamore Rachel , Ho Ling-Pei 
Published: September 2023

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Clinical studies have demonstrated association between different blood leukocytes and mortality and FVC decline. Here we question which blood leukocyte levels are specifically associated with progression of fibrosis, measured by accumulation of fibrosis on CT scan using a standardised automated method.MethodsUsing the CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) CT algorithm, we determined the correlation between different blood leukocytes (<4 months from CT) and total lung fibrosis (TLF) scores, pulmonary vessel volume (PVV), FVC% and TLCO% at baseline (n=171) and with progression of fibrosis (n=71), the latter using multivariate Cox regression.ResultsNeutrophils (but not monocyte or lymphocytes) correlated with extent of lung fibrosis (TLF/litre) (r=0.208, p=0.007), PVV (r=0.259, p=0.001), FVC% (r=-0.127, p=0.029) at baseline. For the 71 cases with repeat CT; median interval between CTs was 25.9 (16.8-39.9) months. Neutrophil but not monocyte levels are associated with increase in TLF/litre [HR 2.66, 95%CI, 1.35-5.25, p=0.005].ConclusionOur study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.Key messagesWHAT IS ALREADY KNOWN ON THIS TOPICIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic condition. Recently, several human studies have implicated blood leukocyte levels (monocyte, neutrophil and lymphocyte) with FVC decline and mortality. However, direct association between leukocytes and progression of fibrosis using quantitative CT analysis has not been explored.WHAT THIS STUDY ADDSThis study explored the association between blood monocytes, neutrophils and lymphocytes against increase in fibrosis over time, measured using a quantitative CT algorithm, CALIPER. We show that levels of blood neutrophil and lymphocytes but not monocytes were associated with greater risk of progression of fibrosis.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE AND/OR POLICYOur study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.
Social support and ideal cardiovascular health in urban Jamaica: a cross-sectional study
Authors: Blake Alphanso L. , Bennett Nadia R. , McKenzie Joette A. , Tulloch-Reid Marshall K. , Govia Ishtar , McFarlane Shelly R. , Walters Renee , Francis Damian K. , Wilks Rainford J. , Williams David R. , Younger-Coleman Novie O. , Ferguson Trevor S. 
Published: September 2023

ABSTRACTRecent studies have suggested that high levels of social support can encourage better health behaviours and result in improved cardiovascular health. In this study we evaluated the association between social support and ideal cardiovascular health among urban Jamaicans. We conducted a cross-sectional study among urban residents in Jamaica’s south-east health region. Socio-demographic data and information on cigarette smoking, physical activity, dietary practices, blood pressure, body size, cholesterol, and glucose, were collected by trained personnel. The outcome variable, ideal cardiovascular health, was defined as having optimal levels of ≥5 of these characteristics (ICH-5) according to the American Heart Association definitions. Social support exposure variables included number of friends (network size), number of friends willing to provide loans (instrumental support) and number of friends providing advice (informational support). Principal component analysis was used to create a social support score using these three variables. Survey-weighted logistic regression models were used to evaluate the association between ICH-5 and social support score.Analyses included 841 participants (279 males, 562 females) with mean age of 47.6 ± 18.42 years. ICH-5 prevalence was 26.6% (95%CI 22.3, 31.0) with no significant sex difference (male 27.5%, female 25.7%). In sex-specific, multivariable logistic regression models, social support score, was inversely associated with ICH-5 among males (OR 0.67 [95%CI 0.51, 0.89], p=0.006) but directly associated among females (OR 1.26 [95%CI 1.04, 1.53], p=0.020) after adjusting for age and community SES. Living in poorer communities was also significantly associated with higher odds of ICH-5 among males, while living communities with high property value was associated with higher odds of ICH among females.In this study, higher level of social support was associated with better cardiovascular health among women, but poorer cardiovascular health among men in urban Jamaica. Further research should explore these associations and identify appropriate interventions to promote cardiovascular health.