bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prion Basis of Progressive Neurodegenerative Disorders
Authors: Joshi Tvisha , Ahuja Nidhi
Published: February 2023

The discovery of proteinaceous infectious agents by Prusiner in 1982 was sensational. All previously known pathogens contained nucleic acids, the code of life, that enabled them to reproduce. In contrast, the proteinaceous agents of disease, called prion proteins (PrP), lacked nucleic acids and propagated by binding to the functional, endogenous form of cellular prion protein (referred to as PrPC) and altering its conformation to produce the infectious disease-causing misfolded protein (referred to as PrPSc). The accumulation and aggregation of these infectious prion proteins within the brain cause destruction of neural tissue and lead to fatal spongiform encephalopathies. In this review, we present the molecular pathology of prion-based diseases. These insights are of particular importance since the principles of prion pathogenesis apply to other neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Collectively, the global prevalence of these diseases is rapidly increasing while effective therapies against them are still lacking. Thus, the need to understand their etiology and pathogenesis is urgent, and it holds profound implications for societal health.
Mini‐αA Upregulates the miR‐155‐5p Target Gene CDK2 and Plays an Antiapoptotic Role in Retinal Pigment Epithelial Cells during Oxidative Stress
Authors: Chen Qianyin , Lin Huimin , Li Shengnan , Deng Xuan , Zhang Jinglin
Published: February 2023

Background. Age‐related macular degeneration (AMD) is the leading cause of serious vision loss in the elderly. Regulating microRNA (miRNA) gene expression offers exciting new avenues for treating AMD. This study aimed to investigate whether miRNAs and their target genes play an antiapoptotic role during oxidative stress‐induced apoptosis of retinal pigment epithelial (RPE) cells via mini‐αA. Methods. ARPE‐19 cells were treated with 3.5 mM NaIO3 for 48 h to establish a retinal degeneration model. Cells were treated with mini‐αA (10, 15, and 20 μM) for 4 h. miR‐155‐5p was knocked down and overexpressed. Cell viability and apoptosis were measured using the Cell Counting Kit‐8 assay and flow cytometry, respectively. The reactive oxygen species level was detected by flow cytometry. miR‐155‐5p target genes were predicted via bioinformatics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for miR‐155‐5p target genes. A quantitative real‐time polymerase chain reaction was performed to detect miRNAs and cell cycle‐related target genes. Western blotting was performed to measure the levels of apoptotic pathway genes encoding Bcl‐2, Bax, cleaved caspase‐3, and cyclin‐dependent kinase 2 (CDK2). Dual‐luciferase reporter gene assay was performed to verify the targeted binding relationship between miR‐155‐5p and CDK2. Results. NaIO3 can induce oxidative damage and promote apoptosis. Conversely, mini‐αA had inhibitory effects and could reverse the oxidative damage and apoptosis triggered by NaIO3 in the retinal degeneration model. The expression of miR‐155‐5p was upregulated in cells treated with NaIO3 and was downregulated after mini‐αA treatment. Furthermore, miR‐155‐5p can target the following cell cycle‐related and proliferation‐related genes: CDK2, CDK4, CCND1, and CCND2. Moreover, our study indicated that miR‐155‐5p was involved in the antioxidative damage and antiapoptotic effects of mini‐αA via CDK2 regulation. Conclusions. miR‐155‐5p promotes the antioxidative damage and antiapoptotic effects of mini‐αA during oxidative stress‐induced apoptosis of RPE cells via CDK2 regulation. This study provides a new therapeutic target for AMD.
Misdiagnosis of Psychosis and Obsessive-Compulsive Disorder in a Young Patient with Autism Spectrum Disorder
Authors: Ying Jiangbo , Zhang Melvyn Weibin , Sajith Sreedharan Geetha , Tan Giles Ming-Yee , Wei Ker-Chiah
Published: February 2023

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and the presence of restricted and repetitive patterns of behavior. Making a first diagnosis of ASD in adults has certain difficulties, including inaccurate recall of developmental history and overlapping behaviors with other psychiatric conditions. This case study presents a young man who was assessed to have no major mental illness during his first visit to emergency services in a psychiatric hospital. During his second visit, he was initially assessed to have first episode psychosis, due to his possible delusional beliefs related to the insurance payout, social withdrawal, and strange behaviors, and then later he was assessed to have obsessive-compulsive disorder (OCD) instead of psychosis, because of his recurrent and intrusive thoughts. Eventually, his diagnosis was revised to ASD during outpatient follow-up after more comprehensive assessment. It is not easy to differentiate ASD from psychosis among some adult patients, even for expert psychiatrists. Cognitive rigidity in ASD may be similar to delusions in psychosis. Unusual behaviors in ASD can be confused with disorganized behaviors in psychosis. Differentiating ASD from OCD can be a complicated task as well, due to similarities between ASD and OCD. Restricted interests and repetitive behaviors in ASD may be perceived as obsessions and compulsions in OCD. Overall, diagnosis of ASD in adults requires comprehensive evaluation. Distinguishing symptoms of OCD and psychosis from autistic traits is critical for accurate diagnosis and optimal treatment. Although research in adult ASD has expanded alongside increased prevalence statistics over the past few years, more efforts to enhance the diagnostic processes in adult ASD are needed to reduce the challenges in this field.
Optimization Studies on Methyl Orange (MO) Dye Adsorption using Activated Carbon Nanoadsorbent of Ocimum basilicum Linn Leaves
Authors: Aruna Janani V. , Gokul D. , Dhivya N. , Nesarani A. , Mukilan K. , Suresh Kumar A. , Vignesh Kumar M.
Published: February 2023

This study is focused on the application of activated carbon nanoadsorbent derived from Ocimum basilicum Linn (sweet basil) leaves for the removal of methyl orange dye from an aqueous solution. The Ocimum basilicum Linn leaves are dried, powdered, cured with H2SO4, and thermally treated to form an activated carbon biosorbent. Sorbent characterization studies like scanning electron microscope (SEM) and Fourier transform infrared (FTIR) spectroscopy have revealed the adsorption of the methyl orange dye from their aqueous solution in the batch mode process. The biosorbent has shown a maximum adsorption capacity of 1.54 mg g−1 at 10 mg l−1 concentration, 1.2 g sorbent dosage, pH of 3, contact time of 180 min, and pHpzc at 3.9. Experimental results are analyzed using equilibrium models and it is found that the Langmuir isotherm model and kinetic model fit well and also the results have corresponded well with pseudo-first order. The intraparticle diffusion (IPD) mechanism has shown that pore diffusion occurs at a slower rate. The Elovich model has displayed that adsorption is affected by film diffusion. From the statistical optimization studies, it is demonstrated that Box–Behnken model can correlate the good agreement between experimental and predicted values. The highest adsorption capacity for the nanoadsorbent was found using quadrate models and optimizing the variables at a time of 237 min, initial dye concentration of 5.31 mg l−1, adsorbent dose of 1.22 g, and pH of 4.23.
Prediction of Response to Lenvatinib Monotherapy for Unresectable Hepatocellular Carcinoma by Machine Learning Radiomics: A Multicenter Cohort Study
Authors: Bo Zhiyuan , Chen Bo , Zhao Zhengxiao , He Qikuan , Mao Yicheng , Yang Yunjun , Yao Fei , Yang Yi , Chen Ziyan , Yang Jinhuan , Yu Haitao , Ma Jun , Wu Lijun , Chen Kaiyu , Wang Luhui , Wang Mingxun , Shi Zhehao , Yao Xinfei , Dong Yulong , Shi Xintong , Shan Yunfeng , Yu Zhengping , Wang Yi , Chen Gang
Published: February 2023

Purpose:

We aimed to construct machine learning (ML) radiomics models to predict response to lenvatinib monotherapy for unresectable hepatocellular carcinoma (HCC).

Experimental Design:

Patients with HCC receiving lenvatinib monotherapy at three institutions were retrospectively identified and assigned to training and external validation cohorts. Tumor response after initiation of lenvatinib was evaluated. Radiomics features were extracted from contrast-enhanced CT images. The K-means clustering algorithm was used to distinguish radiomics-based subtypes. Ten ML radiomics models were constructed and internally validated by 10-fold cross-validation. These models were subsequently verified in an external validation cohort.

Results:

A total of 109 patients were identified for analysis, namely, 74 in the training cohort and 35 in the external validation cohort. Thirty-two patients showed partial response, 33 showed stable disease, and 44 showed progressive disease. The overall response rate (ORR) was 29.4%, and the disease control rate was 59.6%. A total of 224 radiomics features were extracted, and 25 significant features were identified for further analysis. Two distant radiomics-based subtypes were identified by K-means clustering, and subtype 1 was associated with a higher ORR and longer progression-free survival (PFS). Among the 10 ML algorithms, AutoGluon displayed the highest predictive performance (AUC = 0.97), which was relatively stable in the validation cohort (AUC = 0.93). Kaplan–Meier analysis showed that responders had a better overall survival [HR = 0.21; 95% confidence interval (CI): 0.12–0.36; P < 0.001] and PFS (HR = 0.14; 95% CI: 0.09–0.22; P < 0.001) than nonresponders.

Conclusions:

Valuable ML radiomics models were constructed, with favorable performance in predicting the response to lenvatinib monotherapy for unresectable HCC.
Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: Longer Term Follow-Up from the Phase 3 KEYNOTE-240 Trial
Authors: Merle Philippe , Kudo Masatoshi , Edeline Julien , Bouattour Mohamed , Cheng Ann-Lii , Chan Stephen Lam , Yau Thomas , Garrido Marcelo , Knox Jennifer , Daniele Bruno , Breder Valeriy , Lim Ho Yeong , Ogasawara Sadahisa , Cattan Stéphane , Chao Yee , Siegel Abby B. , Martinez-Forero Iván , Wei Ziwen , Liu Chih-Chin , Finn Richard S.
Published: February 2023

Introduction: KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported. Methods: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo. Dual primary endpoints were OS and PFS assessed per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included objective response rate (ORR), assessed per RECIST v1.1 by BICR, and safety. Results: 413 patients were randomized (pembrolizumab, n = 278; placebo, n = 135). As of July 13, 2020, median (range) time from randomization to data cutoff was 39.6 (31.7–48.8) months for pembrolizumab and 39.8 (31.7–47.8) months for placebo. Estimated OS rates (95% CI) were 17.7% (13.4–22.5%) for pembrolizumab and 11.7% (6.8–17.9%) for placebo at 36 months. The estimated PFS rate (95% CI) for pembrolizumab was 8.9% (5.3–13.6%) and 0% for placebo at 36 months. ORR (95% CI) was 18.3% (14.0–23.4%) for pembrolizumab and 4.4% (1.6–9.4%) for placebo. Immune-mediated hepatitis events did not increase with follow-up. No viral hepatitis flare events were reported. Conclusion: With extended follow-up, pembrolizumab continued to maintain improvement in OS and PFS and was associated with a consistent adverse event profile compared with placebo in patients with sorafenib-treated advanced HCC. Although KEYNOTE-240 did not meet prespecified statistical significance criteria at the final analysis, these results together with the antitumor activity of second-line pembrolizumab observed in KEYNOTE-224 and the statistically significant and clinically meaningful OS and PFS benefits of second-line pembrolizumab in patients from Asia observed in KEYNOTE-394 reinforce the clinical activity of pembrolizumab in previously treated patients with advanced HCC.
Efficacy and Safety of Belimumab in Lupus Nephritis Patients: A Real-World Observational Study in China
Authors: Tan Meng , Xu Jing , Tan Ying , Qu Zhen , Yu Feng , Zhao Minghui
Published: February 2023

Background: This study aimed to describe disease activity, clinical outcome, and overall patterns of lupus nephritis care in patients who received belimumab in a real-world clinical setting in China. Materials and Methods: This observational cohort study included lupus nephritis patients who received belimumab as adjunct therapy. We deeply investigated the characteristics of those patients including clinical response to belimumab and safety. Results: All 61 lupus nephritis patients were included with a median follow-up period of 9 months (6, 19). Prevalence of proteinuria (52.5–24.6%) and hematuria (33.3–9.8%) was decreased with a stable level of eGFR at last visit. The percentage of patients achieved complete or partial renal response increased from 47.5% to 78.7% and the proportion of complete or partial renal response in patients with proliferative lupus nephritis was higher than those with membranous lupus nephritis (75 vs. 50%) at last visit. The median SLEDAI score decreased from 6 to 2, and there was an increase in patient of LLDAS from 17 to 33 at last visit. A notable dose reduction was seen for glucocorticosteroid dose, with a median change from 10 to 5 mg/d. The proportion of patients receiving >7.5 mg/d steroids reduced from 52.5% at baseline to 23.0% at last visit. The discontinuation of belimumab was rare (3/61) for drug-induced fever, hyperthyroidism, and uveitis. Conclusions: Lupus nephritis patients with belimumab demonstrated improvements in clinical response and a reduction in glucocorticosteroids, which provided evidence of effectiveness and safety in real-world clinical practice in China.
Considerations for Advanced Heart Failure Consultation in Individuals With Fontan Circulation: Recommendations From ACTION
Authors: Lubert Adam M. , Cedars Ari , Almond Christopher S. , Amdani Shahnawaz , Conway Jennifer , Friedland-Little Joshua M. , Gajarski Robert J. , Kindel Steven J. , Lorts Angela , Morales David L.S. , O’Connor Matthew J. , Peng David M. , Rosenthal David N. , Smyth Lauren , Sutcliffe David L. , Schumacher Kurt R.
Published: February 2023

Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Fontan Committee has developed recommended thresholds for advanced heart failure referral to guide primary cardiologists. These recommendations are divided into 4 categories of clinical Fontan circulatory dysfunction including (1) cardiac/systemic ventricular dysfunction, (2) Fontan pathway dysfunction, (3) lymphatic dysfunction, and (4) extracardiac dysfunction.
2. Education and Ideology (Or Is It the Other Way Around?)
Authors: Gomendio Montserrat , Wert José Ignacio
Published: February 2023

Chapter 2 contains an analysis of the impact of ideology on education. The authors explore the main issues defended by right- and left-wing political parties, and the extent to which they have become polarised in different countries, making consensus impossible. While parties on the left of the spectrum focus on equity, those on the right focus on parental choice and quality. This is followed by a more detailed investigation of ideological divides on specific issues: the role of the state versus private providers, the right of parents to choose, quality versus equity, education system architecture, teachers (skills, training, salaries), curriculum, student assessments and funding.
4. ILSAs
Authors: Gomendio Montserrat , Wert José Ignacio
Published: February 2023

In Chapter 4 we analyse in detail the findings from International Large Scale Assessments (ILSAs). We describe the magnitude of differences in different countries’ student performance, and explain the main geographical differences, as well as trends over time. Despite huge disparities between countries in terms of student performance—which generated an expectation that education systems could improve rapidly by learning good practices from top performers—according to PISA, in most countries no improvements have taken place in almost two decades. The explanation could be that governments have not adopted the right education policies, that PISA policy recommendations are wrong, or a combination of both. We closely investigate the available evidence and the conclusions drawn by PISA, and suggest that policy recommendations related to the lack of impact of investment are solid, others are strongly context-dependent, and those related to equity are not based on robust evidence and are therefore debatable.
5. Does the Evidence Count?
Authors: Gomendio Montserrat , Wert José Ignacio
Published: February 2023

In Chapter 5, we analyse in detail features of education systems in top-performing countries, low-performing countries and those that have improved over time. We find that a very strong narrative has been built around the success of Finland and the shock experienced by Germany in the first PISA cycle. This narrative basically supports comprehensive systems, school autonomy and trust in teachers. We question why no clear narrative has been created from looking at the real top performers: countries in East Asia where levels of school autonomy tend to be low, where some countries such as Singapore have early tracking and prioritise high teaching standards and a rigorous teaching profession. We argue that borrowing education policy from egalitarian societies (such as Finland) and importing it to countries with high levels of inequity (such as Latin American countries) leads to the worst outcomes in terms of equity. Finally, we find no evidence that countries experiencing the ‘PISA shock’ have improved their education systems.
6. Spain
Authors: Gomendio Montserrat , Wert José Ignacio
Published: February 2023

In Chapter 6 we describe our experience as policymakers in the Spanish Government, the political costs associated with approving and implementing an education reform at the peak of the financial crisis, and the goals and achievements of such a reform. We describe the underlying conflicts of interest for a broad range of stakeholders, and how these were obscured in the wider public debate. We discuss in detail why PISA’s conclusion that the Spanish education system has sacrificed excellence for the sake of equity is wrong, how it is used to justify mediocre results, and the consequences of such policy recommendations in terms of facilitating the reversal of reforms. We also raise the issue that PISA 2018 data for Spain was initially withdrawn and then released months later. We argue that PISA should be held accountable to countries demanding explanations and develop a hypothesis as to why changes in the methodology may have led to unreliable results.
7. Education Reforms
Authors: Gomendio Montserrat , Wert José Ignacio
Published: February 2023

In Chapter 7, we analyse the interactions between ideology, governance, conflicts of interest and the evidence provided by ILSAs. We argue that the evidence can be split into three main categories. The first category includes strong evidence which has no impact on policy. The most robust evidence suggests that is reduced impact for greater levels of investment, i.e. decreases in class size and increases in teacher salaries, does not work in education. The reason why this approach has had no influence is because it generates a head-on conflict between the vested interests of unions and those of most stakeholders who strongly oppose them, because they are recommending a decrease in the amount of resources received from public funds. The second category includes variables that are strongly context-dependent (such as enhanced school autonomy), which may be difficult for policymakers to interpret. Furthermore, policy recommendations often ignore this fact and recommend such policies universally with dire consequences. Finally, the third category includes variables that attempt to measure equity, which tend to be inconclusive and partial, meaning that the policy recommendations have been heavily influenced by ideology. This has led to a universal recommendation to apply comprehensive policies and avoid those that are regarded as ‘discriminatory’ (such as ability grouping and early tracking). Such policies lead to the worst outcomes in terms of equity among non-egalitarian societies.
Contrasting Vertical Circulation between Severe and Light Air Pollution inside a Deep Basin: Results from the Collaborative Experiment of 3D Boundary-Layer Meteorology and Pollution at the Sichuan Basin (BLMP-SCB)
Authors: Zhao Suping , He Jianjun , Dong Longxiang , Qi Shaofeng , Yin Daiying , Chen Jinbei , Yu Ye
Published: February 2023

The study of air pollution in a valley is a classic research subject. Compared with flat terrain, the formation and development of haze pollution are more complicated and unique within a deep basin. How a basin or valley plays a role in the horizontal and vertical distribution of air pollutants is poorly understood in highly industrialized deep basins in China due to scarce field observations. We conducted a collaborative experiment of three-dimensional (3D) boundary layer meteorology and pollution at the western Sichuan Basin (SCB) close to the Tibetan Plateau (TP). Generally, the concentrations of PM1 (particulate matter smaller than 1.0 μm), NO, and NO2 largely decline with elevation, while O3 shows a slight increasing trend inside the SCB. Three different types of pollutant profiles and the formation mechanisms are described below. The high PM1 near the surface layer corresponds to the vertical clockwise circulation, i.e., a wind shift with increasing altitude in a clockwise direction. The air pollutants at the central and eastern SCB can be transported to the eastern foothills of the TP by southeasterly winds and then are trapped within the western SCB by a strong surface temperature inversion. The pollutants over the eastern TP also can be dispersed to above the SCB by westerly winds. More aerosol particles are concentrated at about 2.0 km MSL by jointly ascending and descending motion below and above the layer over the valley. The relative uniform PM1 in the vertical direction correlates to the counterclockwise circulation. The trapped pollutants in the western SCB can be transported to the eastern region by westerly winds and then are dispersed to the upper air by unstable stratification.
Efficacy and Feasibility of the CO-OP Approach in Parkinson's Disease: RCT Study Protocol
Authors: Davies Sarah J. , Gullo Hannah L. , Doig Emmah
Published: February 2023

Background. Parkinson's disease (PD) leads to cognitive dysfunction which limits participation and occupational performance. Cognitive Orientation to Daily Occupational Performance (CO-OP) approach is effective in other adult neurological populations and warrants investigation in PD. Purpose. To describe a study protocol evaluating the preliminary efficacy and feasibility of CO-OP approach in PD. Method. A randomised controlled trial (RCT) with adults with PD was assigned to either: CO-OP training-intensive (CO-OP-I, 20 sessions) or waitlist control (WLC) followed by CO-OP-standard (CO-OP-S, 10 sessions). Outcomes. Occupational performance and satisfaction of adults with PD in chosen goals. Measures will be obtained at baseline, post-intervention, and 3-month follow-up. Implications. As the first RCT focused on CO-OP in PD, this trial will provide evidence for the potential of this approach in PD and lay the groundwork for future large-scale trials. Trial Registration. Australian New Zealand Clinical Trials registry, ACTRN12621001483842. Registered November 1, 2021; retrospectively registered 3 months after commencement.
Identification of Facebook posts on nephrology-related terms that benefit patient outreach
Authors: Abdullah Rafidah , Zakaria Nor Fadhlina , Mushahar Lily , Yakob Suryati
Published: February 2023

Objective:

The impact of social media on public health has been examined in various studies. However, none have explored user engagement based on the type of Facebook posts related to renal disease. Therefore, the present study sought to determine which type of nephrology-related posts have greater user engagement.

Setting:

Facebook pages.

Methods:

The posts on a specific Facebook page curated by a team of nephrologists in Malaysia were examined in this cross-sectional study. The type of post, likes, comments, shares of a post and reach of a post were used for data analysis. Analysis of variance was used to quantify the relative contribution of each independent variable to the odds of the post being highly liked or shared. The Kruskal–Wallis test was used to compare links, photos, shared videos, status and videos for parameters such as reach, the number of times a specific piece of content has been displayed on a screen (impressions), and user engagement.

Results:

Shared videos and photos received the highest median reach of 5,862 and 5,880, respectively. People who ‘liked’ the page in 2019, 2020 and 2021 numbered 193, 4,196 and 2,835, respectively. Among the types of content on the Facebook page, photos and shared videos received the highest median lifetime reach of the post compared to links, status and videos in terms of ‘people who liked the page’.

Conclusion:

The study findings suggest that posting a video or photo maximises the chance of engagement and meaningfully impacts public health outcomes.
Higher Association of Pelvis-Knee-Ankle Angle Compared With Hip-Knee-Ankle Angle With Knee Adduction Moment and Patient-Reported Outcomes After High Tibial Osteotomy
Authors: Iwasaki Koji , Ohkoshi Yasumitsu , Hosokawa Yoshiaki , Chida Shuya , Ukishiro Kengo , Kawakami Kensaku , Suzuki Sho’ji , Maeda Tatsunori , Onodera Tomohiro , Kondo Eiji , Iwasaki Norimasa
Published: February 2023

Background:

High tibial osteotomy (HTO) reduces the load distribution of the medial compartment by modifying leg alignment. Knee adduction moment (KAM), a surrogate measure of dynamic loading in the knee joint, decreases after HTO. However, leg alignment does not fully account for KAM.

Purpose:

To assess the association between the pelvis-knee-ankle angle (PKA), a novel radiographic parameter reflecting leg alignment and pelvic width, and KAM and patient-reported outcomes after HTO.

Study Design:

Cross sectional study; Level of evidence, 3.

Methods:

PKA is the angle between the line from the midpoint of the anterior superior iliac spine to the center of the knee joint and the mechanical axis of the tibia. In this study, 54 patients with medial compartment knee osteoarthritis and varus alignment who underwent 3-dimensional gait analysis preoperatively and 2 years after medial open-wedge HTO were evaluated. The primary outcomes were hip-knee-ankle angle (HKA), PKA, KAM peaks, and Knee Society Score (KSS). Single and multivariate regression analysis including PKA and KAM peaks as well as other demographic and radiologic factors was performed.

Results:

HKA was weakly correlated with the first peak KAM ( r = −0.33; P < .01) and second peak KAM ( r = −0.27; P = .01) before HTO, but not significantly correlated after HTO. PKA was moderately correlated with the first peak KAM ( r = 0.45; P < .01) and second peak KAM ( r = 0.45; P < .01) before HTO and with the first peak KAM ( r = 0.51; P < .01) and second peak KAM ( r = 0.56; P < .01) after HTO. Multivariate linear regression revealed that postoperative PKA was still associated with the KAM peaks after HTO. Only postoperative PKA was correlated with the KSS satisfaction subscale ( r = −0.30; P = .03).

Conclusion:

Although HKA was not correlated with KAM peaks after HTO, PKA was significantly correlated with KAM peaks in patients with varus knee osteoarthritis after HTO.
Transoral Approach Used to Remove a Giant Sialolith
Authors: Butt Fawzia
Published: February 2023

Study Design: Case Report.Objective: Sialoliths are a cause of Sialolithiasis affecting an estimated 12 in 1000 adult population. The patient’s presentation vary from being asymptomatic to pain with swelling and purulent discharge if accompanied with a infection. Giant sialoliths greater than 15 mm are rare. The purpose of the article is to document and educate clinicians on the management of giant sialoliths with possible sparing of the salivary gland.Methods: This report documents a patient with a sialolith measuring 45 mm in the widest diameter removed using a trans-oral approach.Results: The patient presented with an intra-oral sialolith which was asymptomatic except for the hard swelling felt cervically. Clinical examination and radiographic imaging was adequate for a diagnosis and the fact that there was no tenderness over the glandular area a decision to spare the gland was made.Conclusion: There are few reports of giant sialoliths and majority present with sialadenitis. In this case it was rare for the stone to have reached this size with hardly any symptoms. In patients where the gland has not been affected clinicians may consider sparing it and remove only the sialolith to reduce the morbidity and risks associated with glandular excision.
Selective homing of CAR-CIK cells to the bone marrow niche enhances control of the Acute Myeloid Leukemia burden
Authors: Biondi Marta , Tettamanti Sarah , Galimberti Stefania , Cerina Beatrice , Tomasoni Chiara , Piazza Rocco , Donsante Samantha , Bido Simone , Perriello Vincenzo Maria , Broccoli Vania , Doni Andrea , Dazzi Francesco , Mantovani Alberto , Dotti Gianpietro , Biondi Andrea , Pievani Alice , Serafini Marta
Published: February 2023

Acute myeloid leukemia (AML) is a hematological malignancy derived from neoplastic myeloid progenitor cells characterized by abnormal clonal proliferation and differentiation. Although novel therapeutic strategies have recently been introduced, the prognosis of AML remains unsatisfactory. So far, the efficacy of chimeric antigen receptor (CAR)-T therapy in AML has been hampered by several factors including the poor accumulation of the blood-injected cells in the leukemia bone marrow (BM) niche, where chemotherapy-resistant leukemic stem cells reside. Thus, we hypothesized that overexpression of CXCR4, whose ligand CXCL12 is highly expressed by BM stromal cells within the niche, could improve T cell homing to the BM and consequently enhance their intimate contact with BM-resident AML cells facilitating disease eradication. Specifically, we engineered conventional CD33.CAR-cytokine induced killer cells (CIKs) with the wild-type CXCR4 and the variant CXCR4R334X, responsible for leukocyte sequestration in the BM of WHIM syndrome patients. Overexpression of both CXCR4wt and CXCR4mut in CD33.CAR-CIKs resulted in significant improvement of chemotaxis toward recombinant CXCL12 or BM stromal cell conditioned medium with no observed impairment of cytotoxic potential in vitro. Moreover, CXCR4-overexpressing CD33.CAR-CIKs showed enhanced in vivo BM homing, associated with a prolonged retention for the CXCR4R334X variant. However, only CD33.CAR-CIKs co-expressing CXCR4wt but not CXCR4mut exerted a more sustained in vivo antileukemic activity and extended animal survival, suggesting a non-canonical role for CXCR4 in modulating CAR-CIK functions independent of BM homing. Taken together, these data suggest that arming CAR-CIKs with CXCR4 may represent a promising strategy for increasing their therapeutic potential for AML.
Evaluation of a decided sample size in machine learning applications
Authors: Rajput Daniyal , Wang Wei-Jen , Chen Chun-Chuan
Published: February 2023

Background

An appropriate sample size is essential for obtaining a precise and reliable outcome of a study. In machine learning (ML), studies with inadequate samples suffer from overfitting of data and have a lower probability of producing true effects, while the increment in sample size increases the accuracy of prediction but may not cause a significant change after a certain sample size. Existing statistical approaches using standardized mean difference, effect size, and statistical power for determining sample size are potentially biased due to miscalculations or lack of experimental details. This study aims to design criteria for evaluating sample size in ML studies. We examined the average and grand effect sizes and the performance of five ML methods using simulated datasets and three real datasets to derive the criteria for sample size. We systematically increase the sample size, starting from 16, by randomly sampling and examine the impact of sample size on classifiers’ performance and both effect sizes. Tenfold cross-validation was used to quantify the accuracy.

Results

The results demonstrate that the effect sizes and the classification accuracies increase while the variances in effect sizes shrink with the increment of samples when the datasets have a good discriminative power between two classes. By contrast, indeterminate datasets had poor effect sizes and classification accuracies, which did not improve by increasing sample size in both simulated and real datasets. A good dataset exhibited a significant difference in average and grand effect sizes. We derived two criteria based on the above findings to assess a decided sample size by combining the effect size and the ML accuracy. The sample size is considered suitable when it has appropriate effect sizes (≥ 0.5) and ML accuracy (≥ 80%). After an appropriate sample size, the increment in samples will not benefit as it will not significantly change the effect size and accuracy, thereby resulting in a good cost-benefit ratio.

Conclusion

We believe that these practical criteria can be used as a reference for both the authors and editors to evaluate whether the selected sample size is adequate for a study.
Impact of postoperative intravenous iron therapy on postoperative infections in older patients with severe anaemia after hip fracture surgery
Authors: Hansen Lene T. , Riis Johannes , Kragholm Kristian H. , Larsen Lis K. , Cavallius Christian , Mørch Marianne M. , Clemmensen Silas Z. , Krogager Maria L. , Melgaard Dorte
Published: February 2023

Background

Anaemia is common following hip fracture in ortho-geriatric patients and is associated with postoperative infections.. This study investigated whether intravenous iron supplements reduced the rate of postoperative infections within 30 days postoperatively in older adults after hip fracture surgery.

Methods

This observational study included 198 ortho-geriatric patients July 2018—May 2020. In May 2019 a local guideline was implemented and recommended II therapy on the 3rdpostoperative day if haemoglobin concentration was < 6.5 mmol/L after hip fracture surgery.

Results

The patients were divided into four treatment groups: blood transfusion (n = 44), IV iron (n = 69), blood transfusion + IV iron (n = 35) and no treatment (n = 50). The number of patients who had an infection within 30 days was similar in the two time periods (38.8% before vs. 38.9% after systematic I.V. iron supplementation,P = 1.00) and no significant difference according to risk of infection was found between treatment groups.

Conclusion

This study documents no effect of intravenous iron supplements on postoperative infections in older adults after hip fracture surgery.

Trial registration

The study was registered with the Danish Data Protection Authority (2008–58-0028) the 2thof September 2019.
The effect of distance nurse-led fatigue management on fatigue, sleep quality, and self-efficacy in patients with multiple sclerosis: a quasi-experimental study
Authors: Qomi Mahla , Rakhshan Mahnaz , Ebrahimi Monfared Mohsen , Khademian Zahra
Published: February 2023

Background

Fatigue is one of the most common problems in patients with multiple sclerosis (MS) and has adverse effects on their sleep status and self-efficacy. This study aimed to determine the effect of distance nurse-led fatigue management on fatigue, sleep quality, and self-efficacy in patients with MS.

Methods

This quasi-experimental study was performed on 60 patients with MS in Arak, Iran. Subjects were randomly assigned into intervention and control groups. The intervention group received eight sessions of nurse-led fatigue management training through the Skyroom platform. The control group received only the usual programs. Data were collected before and two months after the intervention using the Fatigue Severity Scale, the Pittsburgh Sleep Quality Index, and the Multiple Sclerosis Self-Efficacy Scale. The significance level in this study was determined 0.05.

Results

After the intervention, the mean score of fatigue severity in the intervention group was significantly lower than the control group (2.52 ± 0.40 vs 5.65 ± 0.52) (P < 0.001). Also, after the intervention, the mean score of self-efficacy in the intervention group was significantly higher than the control group (49.37 ± 3.25 vs 24.43 ± 2.52) (P < 0.001). Furthermore, after the intervention the mean score of sleep quality was lower in intervention group (11.92 ± 2.01) than the control group (15.46 ± 1.40) (P < 0.001).

Conclusion

Distance nurse-led fatigue management improved fatigue, sleep quality, and self-efficacy in patients with MS. We recommend the use of these courses as an important step toward improving fatigue, sleep quality, and self-efficacy among these patients.
Putting non-communicable disease data to work in Vietnam: an investigation of community health surveillance capacity
Authors: Nguyen Thu Nam T. , Nguyen Thi Tho T. , Tran Bao Quoc , Pham Cong Tuan , Perry Kelly E. , Haregu Tilahun , Oldenburg Brian , Kowal Paul
Published: February 2023

Introduction

Despite the public health system’s critical role in non-communicable disease (NCD) surveillance in Vietnam, limited evidence exists on the implementation of NCD surveillance activities within these systems and the need for capacity building across different system levels to meet expected NCD surveillance goals. This study aimed to evaluate the status of and describe factors affecting the implementation of NCD surveillance activities and to identify the NCD surveillance capacity building needs of the public health system in Vietnam.

Methods

We used a mixed-methods approach in four provinces, conducting self-completed surveys of staff from six Preventive Medicine Institutes (PHI), 53 Centres for Disease Control (CDC) and 148 commune health stations (CHS), as well as 14 in-depth interviews and 22 focus group discussions at four PHI, four CDC, and eight district health centres and CHS.

Results

Study findings highlighted that although Vietnam has a well-functioning NCD surveillance system, a number of quality issues related to NCD surveillance data were salient. Multifactorial reasons were identified for incomplete, unconfirmed, and inaccurate mortality data and current disease surveillance data. Data on NCD management and treatment were reported to be of better quality than data for screening, targeted treatment, and counselling communication. Main factors affected the effective implementation of NCD surveillance, namely lack of complete and specific guidelines for NCD surveillance, limitations in human resource capacity within NCD departments, and shortage of funding for NCD surveillance activities.

Conclusion

Study findings provide practical strategies for strengthening health system capacity for NCD surveillance through developing policies, guidelines, and standardised tools to guide NCD surveillance and a road map for integrated NCD surveillance, developing training packages and manuals for all levels of the health system, and conducting utilisation-focused surveillance training programs.
SARS-CoV-2 spread and area economic disadvantage in the italian three-tier restrictions: a multilevel approach
Authors: Dei Bardi Luca , Acampora Anna , Cacciani Laura , Di Martino Mirko , Agabiti Nera , Davoli Marina , Cesaroni Giulia
Published: February 2023

Background

To face the second wave of COVID-19, Italy implemented a tiered restriction system with different limitation levels (yellow = medium; orange = medium-high, red = high) at the beginning of November 2020. The restrictions systematically reduced the transmission of SARS-CoV-2 with increasing strength for increasing tier. However, it is unknown whether the effect of limitations was equal between provinces with different socioeconomic levels. Therefore, we investigated the association between the province’s socioeconomic level and SARS-CoV-2 infection daily reproduction number in each restriction level.

Methods

We measured the province’s socioeconomic level as the percentage of individuals whose 2019 total yearly income was lower than 10,000€, using the measure as a proxy of economic disadvantage. We estimated the daily reproduction number (Rt) at the province level using the SARS-CoV-2 daily incidence data from November 2020 to May 2021. We then used multilevel linear regression models with random intercepts stratified by restriction level to estimate the association between economic disadvantage and Rt. We also adjusted the analyses for potential confounders of the association between the province’s economic disadvantage and the Rt: the percentage of people with 0–5 years, the quartiles of population density, and the geographical repartition.

Results

Overall, we found increasing Rt in yellow (+ 0.004 p < 0.01, from Rt = 0.99 to 1.08 in three weeks) and containing effects for the orange (-0.005 p < 0.01, from Rt = 1.03 to 0.93) and the red tier (-0.014 p < 0.01, from Rt = 1.05 to 0.76). More economically disadvantaged provinces had higher Rt levels in every tier, although non-significantly in the yellow level (yellow = 0.001 p = 0.19; orange = 0.002 p = 0.02; red = 0.004 p < 0.01). The results showed that the association between economic disadvantage and Rt differed by level of restriction. The number of days into the restriction and the economic disadvantage had statistically significant interactions in every adjusted model. Compared to better off, more economically disadvantaged provinces had slower increasing trends in yellow and steeper Rt reductions in orange, but they showed slower Rt reductions in the highest tier.

Conclusion

Lower tiers were more effective in more economically disadvantaged provinces, while the highest restriction level had milder effects. These results underline the importance of accounting for socioeconomic level when implementing public health measures.
mDIXON-Quant technique diagnostic accuracy for assessing bone mineral density in male adult population
Authors: Tang Rui , Tang Guangyu , Hua Ting , Tu Yun , Ji Rui , Zhu Jingqi
Published: February 2023

Background

To investigate the diagnostic efficacy of mDIXON-Quant technique for prediction of bone loss in male adults.

Methods

One hundred thirty-eight male adults were divided into normal, osteopenia, and osteoporosis groups based on DXA and QCT for the lumbar spine. Differences in mDIXON-Quant parameters [fat fraction (FF) and T2*value] among three groups, as well as the correlation of mDIXON-Quant parameters and bone mineral density (BMD) were analyzed. The areas under the curves (AUCs) for mDIXON-Quant parameters for prediction of low bone mass were calculated.

Results

According to DXA standard, FF and T2*value were significantly increased in osteoporosis group compared with normal group (P = 0.012 andP < 0.001). According to QCT standard, FF was significantly increased in osteopenia and osteoporosis groups compared with normal group (bothP < 0.001). T2*values were significantly different among three groups (allP < 0.05). After correction for age and body mass index, FF was negatively correlated with areal BMD and volumetric BMD (r = -0.205 and -0.604, respectively; bothP < 0.05), and so was T2*value (r = -0.324 and -0.444, respectively; bothP < 0.05). The AUCs for predicting low bone mass according to DXA and QCT standards were 0.642 and 0.898 for FF, 0.648 and 0.740 for T2*value, and 0.677 and 0.920 for both combined, respectively.

Conclusions

FF combined with T2*value has a better diagnostic efficacy than FF or T2*value alone in prediction of low bone mass in male adults, which is expected to be a promising MRI method for the screening of bone quality.

Trial registration

ChiCTR1900024511 (Registered 13–07-2019).
Uptight responses between clenching and forearm raising with factors of visual feedback and maintenance effort in healthy young women: An experimental study on factorial design
Authors: Zhou Lijuan , Li Baoyong , Zheng Xianyu , Guo Shaoxiong , Zhang Yuan , Chen Changsheng , Wang Kelun , Wang Meiqing
Published: February 2023

Background

To achieve different central preset force levels requires various fine-tuning efforts and may elicit different uptight responses. The mandibular lever system has a distinct regularity in the fine-tuning function of the upper limbs. The purpose of the present study was to detect whether the uptight responses elicited from motivating clenching differ from those induced by motivating forearm raising at different force levels.

Methods

Twenty-five healthy females were enrolled in this study. The target was low, medium, and maximum force levels with or without visual feedback and/or maintenance effort. Surface electromyographic (SEMG) activity was recorded from the bilateral anterior temporalis and masseter or left biceps brachii muscle (BicL), and the T-Scan III System synchronously recorded the sensitive force values. The uptight responses and task difficulties were recorded for occlusal and left forearm lifting tasks using a unique visual analogue scale.

Results

The highest uptight response value was achieved at a low clenching force level with visual feedback requiring no maintenance effort but at a maximum forearm-raising force level with visual feedback and maintenance effort. The SEMG activities of both jaw-closing muscles and BicL were associated with the central preset force level (P < 0.001). However, the maintenance effort only increased the jaw-closing muscles’ SEMG activity at the maximal force level (P < 0.001).

Conclusions

Clenching at the central preset lower force level with visual feedback is prone to elicit a higher degree of uptight response. The constant need for a low-intensity bite can have a negative effect on an individual's mood.