bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal time for the addition of non-corticosteroid immunosuppressants in myasthenia gravis: a single-center retrospective study in China
Authors: Ma Jiaojiao , Chen Dan , Yi Fangfang , Song Jie , Luo Sushan , Zhong Huahua , Xi Jianying , Wu Zongtai , Li Zunbo , Zhao Chongbo
Published: November 2024

Introduction

Patients with myasthenia gravis (MG) display strong treatment heterogeneity. Recent studies have indicated that low-dose steroids or immunosuppressants are effective. However, factors affecting the add-on of non-corticosteroid immunosuppressants to corticosteroids remain unknown.

Method

Consecutive patients with MG were retrospectively reviewed from May 15, 2015, to December 29, 2020. We included one group of patients with steroid treatment alone and another group who transitioned to non-steroid immunosuppressant therapy. Clinical features of the included patients were analyzed. Univariate and multivariate Cox regression models were used to identify potential influential factors.

Results

A total of 107 patients with MG were analyzed, including 66 receiving corticosteroid treatment alone and 41 who subsequently also received non-corticosteroid immunosuppressant therapy. Eight potential factors were primarily selected in univariate analysis (Ps < 0.1). Achieving minimal symptom expression (MSE) within 6 months (HR: 4.424, 95%CI: 2.102–11.865), body mass index (BMI) (HR: 0.385, 95% CI: 0.186–0.797), quantitative MG (QMG) bulbar muscle score (HR: 1.553, 95% CI: 1.140–2.118), disease duration (HR: 0.987, 95% CI: 0.977–0.997) and relapse (HR: 2.638, 95% CI: 1.031–6.750) were finally identified as potential influencing factors.

Discussion

We found multifactorial clinical factors were highly associated with the add-on of non-steroid immunosuppressants after steroid treatment in patients with MG. Achieving MSE within 6 months, BMI, QMG bulbar muscle score at baseline before steroid treatment, disease duration, and disease relapse may represent crucial influencing factors, which should be considered to improve the long-term prognosis for patients with MG in future studies and practice.
A comparison of natalizumab’s effects on SDMT between pediatric-onset and adult-onset multiple sclerosis patients
Authors: Puthenparampil Marco , Scialpi Graziana , Gaggiola Marta , Zanotelli Giovanni , Miscioscia Alessandro , Berardi Angela , Riccardi Alice , Nosadini Margherita , Sartori Stefano , Perini Paola , Rinaldi Francesca , Gallo Paolo
Published: November 2024

Background

Pediatric-onset multiple sclerosis (POMS) patients often exhibit a wide range of cognitive deficits. Therefore, therapeutic approaches should aim not only to prevent cognitive decline but also to promote cognitive improvement.

Objective

This study aimed to explore the effects of natalizumab (NTZ) on cognitive function, as measured by the Symbol Digit Modalities Test (SDMT), in both POMS and adult-onset multiple sclerosis (AOMS) patients.

Method

A total of 63 patients (34 AOMS and 29 POMS) were enrolled in this retrospective, single-center study. Patients were clinically and radiologically assessed every 6 months, and they completed the SDMT at baseline and after at least 24 months of follow-up. SDMT values were reported as corrected values (cSDMT) and z-scores (zSDMT). Annualized cSDMT and zSDMT scores were calculated by dividing the change in scores by the length of the follow-up period (expressed in years).

Results

Both POMS and AOMS groups showed improvement in annualized cSDMT and zSDMT scores, but the improvement was significantly greater in the POMS group compared to the AOMS group (+3.85 ± 4.32 vs. +1.76 ± 2.80, p = 0.010 for cSDMT; 0.41 ± 0.40 vs. 0.25 ± 0.34, p = 0.026 for zSDMT). After re-baselining at 6 months, 93% of POMS patients (27 patients) and 85.3% of AOMS patients (29 patients, p = 0.84) achieved NEDA-3 (no evidence of disease activity). The NEDA-3 status, along with clinical and demographic parameters at baseline, did not account for the observed SDMT improvement.

Conclusion

The favorable clinical, radiological, and neuropsychological outcomes observed in this study support the use of natalizumab as a viable treatment option in POMS.
Dose, exposure, and treatment regimen of intravenous immunoglobulin G in multifocal motor neuropathy
Authors: Li Zhaoyang , Roepcke Stefan , Franke Ryan , Yel Leman
Published: November 2024

Introduction

Intravenous immunoglobulin (IVIG) is the only approved treatment for multifocal motor neuropathy (MMN), a rare, chronic, immune-mediated demyelinating neuropathy. There is a significant gap in understanding of the role of serum immunoglobulin G (IgG) levels in the efficacy of IVIG in affected patients. We aimed to characterize the interplay between dose and exposure of IVIG and the effects of patient factors on individual variabilities.

Methods

Serum IgG trough concentration data from a phase 3, randomized, double-blind, placebo-controlled, crossover trial of IVIG 10% in 44 patients with MMN (NCT00666263) were analyzed using fit-for-purpose population PK modeling. Patient factors were tested as covariates, and IgG PK profiles following various dosing regimens were simulated.

Results

Serum IgG levels, with significant inter-patient variability, correlated with dose and treatment interruptions at the individual patient level. Simulated data for various dosing regimens (0.4–2 g/kg once every 1–4 weeks [Q1–4W]) revealed that more frequent dosing provided more stable IgG levels than less frequent dosing, and dose splitting over multiple days had no significant effects on PK.

Discussion

In patients with MMN, stable dosing and consistent serum IgG levels are crucial to avoid negative responses owing to treatment interruptions. Dosing intervals more frequent than Q4W may alleviate periodic symptom deterioration. Dose splitting potentially offers flexibility for patients requiring large volumes of IVIG without negatively affecting serum IgG PK, while maintaining treatment efficacy. Variability in serum IgG levels between patients suggests that individualizing IVIG treatment regimens and target IgG levels may play a key role in managing MMN.
Intra- and inter-network connectivity abnormalities associated with surgical outcomes in degenerative cervical myelopathy patients: a resting-state fMRI study
Authors: Ge Yuqi , Song Jiajun , Zhao Rui , Guo Xing , Chu Xu , Zhou Jiaming , Xue Yuan
Published: November 2024

Resting-state functional MRI (fMRI) has revealed functional changes at the cortical level in degenerative cervical myelopathy (DCM) patients. The aim of this study was to systematically integrate static and dynamic functional connectivity (FC) to unveil abnormalities of functional networks of DCM patients and to analyze the prognostic value of these abnormalities for patients using resting-state fMRI. In this study, we collected clinical data and fMRI data from 44 DCM patients and 39 healthy controls (HC). Independent component analysis (ICA) was performed to investigate the group differences of intra-network FC. Subsequently, both static and dynamic FC were calculated to investigate the inter-network FC alterations in DCM patients. k-means clustering was conducted to assess temporal properties for comparison between groups. Finally, the support vector machine (SVM) approach was performed to predict the prognosis of DCM patients based on static FC, dynamic FC, and fusion of these two metrics. Relative to HC, DCM patients exhibited lower intra-network FC and higher inter-network FC. DCM patients spent more time than HC in the state in which both patients and HC were characterized by strong inter-network FC. Both static and dynamic FC could successfully classify DCM patients with different surgical outcomes. The classification accuracy further improved after fusing the dynamic and static FC for model training. In conclusion, our findings provide valuable insights into the brain mechanisms underlying DCM neuropathology on the network level.
Novel bias-reduced coherence measure for EEG-based speech tracking in listeners with hearing impairment
Authors: Keding Oskar , Alickovic Emina , Skoglund Martin A. , Sandsten Maria
Published: November 2024

In the literature, auditory attention is explored through neural speech tracking, primarily entailing modeling and analyzing electroencephalography (EEG) responses to natural speech via linear filtering. Our study takes a novel approach, introducing an enhanced coherence estimation technique to assess the strength of neural speech tracking. This enables effective discrimination between attended and ignored speech. To mitigate the impact of colored noise in EEG, we address two biases–overall coherence-level bias and spectral peak-shifting bias. In a listening study involving 32 participants with hearing impairment, tasked with attending to competing talkers in background noise, our coherence-based method effectively discerns EEG representations of attended and ignored speech. We comprehensively analyze frequency bands, individual frequencies, and EEG channels. Frequency bands of importance are shown to be delta, theta and alpha, and the important EEG channels are the central. Lastly, we showcase coherence differences across different noise reduction settings implemented in hearing aids (HAs), underscoring our method's potential to objectively assess auditory attention and enhance HA efficacy.
Neurofeedback to enhance sleep quality and insomnia: a systematic review and meta-analysis of randomized clinical trials
Authors: Recio-Rodriguez Jose I. , Fernandez-Crespo Mei , Sanchez-Aguadero Natalia , Gonzalez-Sanchez Jesús , Garcia-Yu Irene A. , Alonso-Dominguez Rosario , Chiu Hsiao-Yean , Tsai Pei-Shan , Lee Hsin-Chien , Rihuete-Galve Maria I.
Published: November 2024

Objective

This systematic review and meta-analysis of randomized-clinical trials aims to analyze the effect of interventions incorporating surface neurofeedback techniques on self-perceived sleep quality and insomnia in patients with or without sleep disturbances.

Methods

The review was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and was deposited in the Prospero international prospective registry of systematic reviews (CRD42024528401). Seven clinical trials with different main outcomes but with pre-post intervention records of self-perceived sleep quality or insomnia symptoms assessed by questionnaires met our inclusion criteria, including a publication date within the last 10 years. Five trials investigated sleep quality through scores on the Pittsburgh sleep quality Index (PSQI) and three trials signs of insomnia severity assessed with validated scales. The methodological quality of the included studies was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias and showed a high quality of them.

Results

A total of 5 studies that evaluated sleep quality with the PSQI total score were included in the meta-analysis. The results revealed that control conditions succeeded in improving PSQI-assessed sleep quality more than the analyzed Neurofeedback interventions (PSQI total score 0.57; 95% CI 0.13 to 1.01; p = 0.01). On the other hand, a total of 3 studies that evaluated insomnia severity with various insomnia scales were included in the meta-analysis The results revealed that neither the NF interventions nor the control conditions show a favorable outcome relative to each other (−0.13; 95% CI −0.44 to 0.18; p = 0.41).

Conclusion

The interventions studied mostly apply a neurofeedback training protocol based on maintaining alpha waves in a range between 8 and 12 Hz, with electrode positioning in the frontal area or in the sensorimotor cortex and with a number of neurofeedback sessions ranging from 8 to 20 sessions. The meta-analysis showed that interventions incorporating surface neurofeedback do not produce additional benefits in self-perception of sleep quality or insomnia compared to a wide variety of control conditions including cognitive behavioral treatment or other biofeedback modalities.

Systematic review registration

PROSPERO – International prospective register of systematic reviews – CRD42024528401 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=528401.
The potential role of CGRP in synuclein-associated neurodegenerative disorders
Authors: Alexoudi Athanasia , Donadio Vincenzo , Karageorgiou Elissaios
Published: November 2024

In this hypothesis article, the potential clinicopathological associations of Calcitonin Gene Related Peptide (CGRP) with the development of synuclein-associated neurodegenerative disorders (SAND) are discussed. The presence of α-syn and CGRP in the CNS and the ENS and the intricate role of CGRP and its related pathways in inflammation, apoptosis, metabolism, neuromodulation, and brain-gut communication are analyzed. Since this hypothesis is confirmed, modulating CGRP-potential related pathways may lead to novel disease-modifying therapies.
Reward processing deficits arise early in familial frontotemporal dementia
Authors: Cryns Noah G. , Hardy Emily G. , Roy Ashlin R. K. , Datta Samir , Sokolowski Andrzej , Sturm Virginia E. , Kramer Joel H. , Boxer Adam L. , Miller Bruce L. , Rosen Howard J. , Perry David C.
Published: November 2024

Reward processing involves evaluation of stimuli to inform what an individual works to pursue or avoid. Patients with behavioral variant frontotemporal dementia (bvFTD) often display reward processing changes, including insensitivity to aversive stimuli. It is unknown how early in the disease course reward changes are detectable. We recruited mutation positive (symptomatic and asymptomatic) and negative members of families with known mutations in progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72). The sample included 4 groups: asymptomatic non-carriers (n = 34), asymptomatic carriers [Clinical Dementia Rating (CDR) 0, n = 16], mildly symptomatic carriers (CDR 0.5, n = 10) and bvFTD (sporadic and genetic, n = 45). A series of tasks utilized pleasant, unpleasant, and neutral olfactants to probe reward consumption and effort to obtain reward. A group by valence interaction showed unpleasant scent ratings were more positive in groups with greater disease severity [χ2(6) = 87.983, p < 0.001]. Mildly symptomatic carriers showed a small difference in ratings of pleasant and unpleasant stimuli, similar to bvFTD. In an effort task, where participants chose to avoid or receive scents, mildly symptomatic carriers and bvFTD chose to smell unpleasant scents more frequently than asymptomatic groups, with mildly symptomatic carriers exceeding bvFTD in their frequency of choosing to smell unpleasant scents. In this same task, motivated effort, determined by rate of button press, determined success at obtaining or avoiding scents. Success rate, calculated based on the number of responses where participants’ button presses exceeded an individual threshold set in a practice trial, differed across groups (p = 0.048), driven by mildly symptomatic carriers, who were consistently unsuccessful. There was a group difference in variability in button press rate across trials (p = 0.007), driven by mildly symptomatic carriers who showed less varied effort between scents. These findings suggest alterations to reward functioning can be detected early in bvFTD, even before meeting diagnostic criteria. These results may aid in identifying distinctive, initial reward changes in bvFTD that can facilitate early and accurate diagnosis and inspire efforts to identify anatomic underpinnings of early symptomatic changes.
Effect of school feeding program on dietary folate intake among school adolescent girls in Sidama region, southern Ethiopia
Authors: Bolka Amelo , Bosha Tafese , Gebremedhin Samson
Published: November 2024

Background

Ethiopia recently initiated a school feeding program (SFP) that provides nutritious meals to vulnerable students during school to combat malnutrition and improve their nutrition. However, there is limited evidence regarding the program’s impact on dietary folate intake among adolescent girls. Improving folate status in adolescent girls is important to prevent neural tube defect and anemia This study was aimed at assessing the effect of the SFP on dietary folate intake among school adolescent girls in the Sidama Region, Southern Ethiopia.

Methods

This school-based cross-sectional study compared dietary folate intake among adolescent girls enrolled in schools with (n = 290) and without (n = 290) SFP. Multistage sampling method was used to select adolescent girls from 12 schools. The multiple pass 24-h dietary recall method was used to estimate the dietary intake of adolescent girls. Dietary diversity in the preceding day of the survey was assessed with the standard nine-food group score. Nutrient inadequacy was defined as a proportion of adolescents with dietary value of nutrient intake less than the recommended daily allowance (RDA). The dietary folate intake was compared between two groups using multilevel mixed effects linear regression model adjusted for potential confounders.

Results

The result showed significantly higher mean (±SD) dietary folate intake in SFP beneficiaries (421.12 ± 78.60 μg/day) than the non-beneficiaries (393.26 ± 74.57 μg/day; β = 27.19, p < 0.001). SFP beneficiary girls had a significantly higher mean (±SD) dietary diversity score (5.24 ± 1.35) compared to non-beneficiary girls (4.83 ± 1.54; β = 0.40, p = 0.001). The prevalence of inadequate folate intake was significantly higher among no-beneficiaries (47.4%) compared to beneficiaries (36.9%; p = 0.01).

Conclusion

The SFP in Sidama region improved folate intake and dietary diversity of adolescent girls. The evidence from this study supports the expansion of the program to enhance dietary intake of nutrients of adolescent girls in the region.
Oat polar lipids and sunflower lecithin similarly improve cardiometabolic risk markers and appetite controlling hormone responses after breakfast and a subsequent lunch. A randomized crossover study in healthy adults
Authors: Hossain Mohammad Mukul , Tovar Juscelino , Cloetens Lieselotte , de Kam Soraya , Nilsson Anne
Published: November 2024

Introduction

The alarming global increase in lifestyle-related disorders such as obesity and type 2 diabetes mellitus (T2DM) has increased during the last several decades. Poor dietary choices significantly contribute to this increase and prevention measures are urgently needed. Dietary intake of bioactive compounds found in foods are linked to a decrease likelihood of these disorders. For this purpose, a randomized crossover meal study was performed to compare the postprandial metabolic effects of lecithin and oat polar lipids in healthy subjects.

Materials and methods

Eighteen young healthy subjects ingested test meals enriched with lecithin, oat polar lipids (PLs) or rapeseed oil. There were four test meals (i) 15 g oat polar lipids: OPL, (ii) 18 g sunflower lecithin (of which 15 g were polar lipids): LPL, (iii) 18 g rapeseed oil: RSO, and (iv) reference white wheat bread: WWB. Lipid-enriched test meals contained equivalent amounts of total fat (18 g), and all breakfast meals contained 50 g available carbohydrates. The meals were served as breakfast followed by a standardised lunch (white wheat bread and meat balls) after 3.5 h. Test variables were measured at fasting and repeatedly during 5.5 h after ingestion of the breakfast.

Results

Our study demonstrated that both LPL and OPL had beneficial effects on postprandial glucose and insulin responses, and appetite regulating gut hormones, as compared to RSO and WWB. Significant increase in GLP-1, GIP, and PYY concentrations were seen after consuming breakfast meals with LPL and OPL, and ghrelin concentration was reduced compared to meals with RSO and WWB (p < 0.05). Furthermore, triglycerides (TG) concentration was significantly reduced after OPL compared to RSO (p < 0.05). Our data show that there were no significant variations in glycaemic and insulin responses, TG, and gut hormone concentrations between LPL and OPL during breakfast (0–210 min) or over the whole study period (0–330 min).

Conclusion

Our study revealed that the consumption of both lecithin and oat PLs included in breakfast meal may similarly enhance postprandial glucose tolerance, reduce TG, and enhance the secretion of incretins and appetite regulating hormones in healthy young adults.

Clinical trial registration

ClinicalTrials.gov, identifier NCT05139355.
Analysis of risk factors and establishment of early warning model for recent postoperative complications of colorectal cancer
Authors: Ou Yang , Yang Yang , Yang Weimin , Pan Yulin , Tian Wu , Wang Zejun , Yu Xianzhe , Luo Jihang , Wang Leibo
Published: November 2024

Objective

This study aimed to analyze factors associated with recent complications after colorectal cancer surgery, constructing a nomogram to aid gastrointestinal surgeons in preoperative decision-making for patients at risk of such complications.

Methods

In this retrospective study, clinical data were collected from patients undergoing radical colorectal cancer surgery at the Department of Gastrointestinal Surgery of the Affiliated Cancer Hospital of Guizhou Medical University and the Second People’s Hospital of Chengdu from November 1, 2021, to January 26, 2024. Univariable and multivariable logistic regression analyses were conducted to assess risk factors for recent postoperative complications and develop a prediction model. External validation was performed using data from 48 postoperative colorectal cancer patients in the Second People’s Hospital of Chengdu City from January 1, 2023, to May 30, 2023. Evaluation included receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis using R4.2.2 statistical software.

Results

A total of 324 patients who underwent radical colorectal cancer surgery were enrolled. The training cohort (n=176) identified four independent risk factors for recent complications: PNI ≥45 (OR=4.17, P<0.001), Albumin <40 g/L (OR=3.9, P<0.001), ASA score III-IV (OR=6.29, P<0.001), and Tumor diameter ≥5 cm (OR=4.24, P<0.001). A nomogram was constructed incorporating these factors. The AUC of the nomogram model in the training cohort was 0.835, with subsequent internal and external validation cohort AUCs of 0.815 and 0.819, respectively, indicating strong discriminatory ability. The calibration curve demonstrated good consistency, and decision curve analysis indicated high clinical utility.

Conclusion

PNI ≥45, Albumin <40 g/L, ASA score III-IV, and Tumor diameter ≥5 cm emerged as independent risk factors for recent complications following colorectal cancer surgery. We developed a nomogram model for these complications, potentially aiding gastrointestinal surgeons in preoperative patient evaluation and treatment planning for colorectal cancer surgery.
A new nomogram for predicting extraurothelial recurrence in patients with upper urinary tract urothelial carcinoma following radical nephroureterectomy
Authors: Wu Hao , Jia Dan , Dai Xianyu , Cao Hongliang , Wang Fulin , Yang Tong , Wang Lei , Xu Tao , Gao Baoshan
Published: November 2024

Purpose

We sought to develop and validate a nomogram for predicting extra-urinary recurrence (EUR) following radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC).

Methods

Data from 556 UTUC patients post-RNU at the First Hospital of Jilin University were retrospectively analyzed. These patients were categorized into a training group (n=389) and a validation group (n=167). Variables significantly associated with prognosis were identified using univariate Cox regression and most minor absolute shrinkage and selection operator (LASSO) analysis. These independent predictors were incorporated into the nomogram to estimate extra-urinary recurrence-free survival (EURFS). Validation of the nomogram involved ROC curves, calibration plots, and decision curve analysis (DCA). Patients were stratified into two risk categories based on their nomogram scores to compare EURFS using the Kaplan-Meier method.

Results

Eight predictors were identified: T-stage, N-stage, tumor grade, local and nerve invasion, preoperative hemoglobin level, neutrophil-to-lymphocyte ratio (NLR), and creatinine, all proving to be independent predictors of EUR. A nomogram was created based on these eight factors, and using the ROC, calibration curves, and DCA, good prediction results were shown in both the training and validation groups. The training and validation groups also showed reliable predictive performance. In particular, there was a significant difference in survival between the high-risk and low-risk groups (P<0.0001). We have also built a network calculator that calculates patient survival time. The URL is https://haowu24.shinyapps.io/dynnomapp.

Conclusion

A nomogram for predicting distant metastases in UTUC patients was successfully developed, and its accuracy, reliability, and clinical value were demonstrated. This new tool helps to improve the clinical management of UTUC cases.
Case report: High grade serous fallopian tube carcinoma with rare NRG1 gene fusion presenting as widespread peritoneal carcinomatosis
Authors: Crymes Anthony , Evans Mark G. , Adeyelu Tolulope , Reid Jack , Ibe Ifegwu O. , Oberley Matthew J. , Tseng Jill H.
Published: November 2024

The discovery of gene fusions involving Neuregulin-1 (NRG1) within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. NRG1 fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed MYH10::NRG1 fusion. Moreover, we queried the whole transcriptome sequencing results of neoplasms analyzed by a commercial laboratory (Caris Life Sciences) to determine the overall incidence of NRG1 fusions in carcinomas of the ovary, fallopian tube, and peritoneum (0.18%). Twenty-five additional tumors were found to demonstrate NRG1 fusions, including 20 new genes partners that had not been previously identified in gynecologic carcinomas. Overall, NRG1 fusion events are rare in ovarian, fallopian tube, and primary peritoneal carcinomas, but they may carry diagnostic significance in the context of borderline/low grade serous tumors, which demonstrated exclusively CLU::NRG1 fusions, and could have important predictive implications for response to ERBB/ERBB2/ERBB3-directed therapies.
Risk factors associated with lymph node metastasis in papillary thyroid cancer: a retrospective analysis based on 2,428 cases
Authors: Yu Kejie , Wu Xianjiang , Dai Lei , Le Qi , Xie Yue , Wang Yingchun , Zhang Weidong
Published: November 2024

Background

Papillary thyroid cancer (PTC) with lymph node metastasis (LNM) is associated with an increased risk of postoperative recurrence. Understanding the clinical characteristics of PTC patients can help surgeons assess the likelihood of LNM. This study aims to identify risk factors for LNM in PTC patients.

Methods

We retrospectively analyzed clinical data from 2,428 patients diagnosed with PTC who underwent initial thyroid surgery in our single center. Risk factors related to central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), and skip metastasis were investigated by univariate and multivariate binary logistic regression analyses.

Results

Univariate analysis revealed that the following factors were associated with an increased likelihood of CLNM (P<0.05): male gender, age < 45 years, maximal axial diameter (MAD) > 1 cm, body mass index (BMI) ≥ 28 kg/m² and multifocality. Univariate analysis also revealed that patients with age < 45 years, MAD > 1 cm, BMI ≥ 28 kg/m², multifocality, and CLNM demonstrated a higher propensity for LLNM (P<0.05). Lower pole tumors were more likely to have CLNM than upper pole tumors, while upper pole tumors were more prone to present LLNM (P<0.05) and skip metastasis (P<0.05). Multivariable binary logistic regression analysis identified that gender (odds ratio [OR], 1.732; 95% CI, 2.113–2.577; P < 0.001), age (OR, 1.905; 95% CI, 1.596–2.273; P < 0.001), MAD (OR, 4.639; 95% CI, 3.639–5.913; P < 0.001), and multifocality (OR, 1.860; 95% CI, 1.453–2.381; P < 0.001) were independent risk factors for CLNM and MAD (OR, 5.289; 95% CI, 3.777–7.404; P<0.001), multifocality (OR, 1.858; 95% CI, 1.248–2.766; P=0.002), and CLNM (OR, 5.030; 95% CI, 3.347–7.561; P<0.001) for LLNM.

Conclusion

Despite the overall postoperative recurrence rate in PTC patients is low, identifying risk factors such as male gender, age < 45 years, MAD > 1 cm, multifocality, and CLNM can help predict LNM. In specific cases, selective lymphadenectomy in the central or lateral neck area may be warranted.
Statin prescription disparities in patients with breast cancer and diabetes for primary cardiovascular disease prevention
Authors: Yang Alicia B. , Mhango Grace , Kong Chung Yin , Lin Jenny J. , Wisnivesky Juan P. , Leiter Amanda
Published: November 2024

Background

This brief report examines statin prescription trends for primary cardiovascular disease (CVD) prevention in breast cancer (BC) survivors with diabetes, a large population at particularly high CVD risk.

Methods

A population-based, retrospective cohort study was conducted using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims. We identified women with preexisting diabetes who were diagnosed with stage 0–III primary BC between 2008 and 2017 without preexisting CVD. We assessed statin prescription rates over time and also examined differences in statin prescription rates according to patient sociodemographic characteristics. Using a multivariate logistic regression adjusted for sociodemographic and clinical variables, independent predictors of statin prescription were identified.

Results

Of 8,423 BC patients with diabetes without preexisting CVD, 5,698 (68%) had a statin prescription. Statin prescriptions increased over time (BC diagnosis year 2008–2009: 65%, 2010–2011: 67%, 2012–2013: 66%, 2014–2015: 69%, 2016–2017: 70%; p = 0.01) and differed by age (66–69: 66%, 70–74: 70%, 75–79: 69%, ≥80: 65%; p < 0.01) and race (White: 68%, Black: 62%, Latina: 66%, Other: 72%; p < 0.01). In a multivariate analysis, race (Black vs. White: OR 0.80, 95% CI: 0.68–0.95) remained a predictor of statin prescription.

Conclusion

In older early-stage BC survivors, statin prescriptions increased over time and varied by age, race, and BC stage. These findings can potentially inform strategies to improve guideline-concordant statin prescriptions in a group at high risk for CVD and reduce disparities.
Factors influencing participation of elderly population in mass drug administration for lymphatic filariasis: a cross-sectional study
Authors: Jabir Muhammed , Balakrishnan Vijayakumar , Krishnamoorthy Kaliannagounder , Kumar Ashwani , Abraham Philip Raj
Published: November 2024

Background

The success of mass drug administration (MDA) for lymphatic filariasis (LF) elimination relies on achieving a participation rate of at least 65% within the endemic community. However, participation of sub-population in the community varies and a significant treatment gap among the elderly population, remains to be addressed. The present study explores the factors influencing the elderly participation in MDA and propose possible solutions to bridge the gap.

Methods

A cross-sectional study of individuals aged 60 years and above was conducted from August to December 2023 in Yadgiri district of Karnataka, which is endemic for LF. The participants were interviewed using a structured questionnaire, focusing on the perception about LF and MDA and drug consumption behaviours. STATA 14 software was used to analyse the data. We used a logistic regression model to determine the factors influencing drug consumption.

Results

The study included 315 elderly individuals with a mean age (SD) of 67.4 (6.2) years. Although, 58.4% of them received the drugs during the last round of MDA in 2023, only 40.6% consumed it. The drug refusal rate was 19.4%. Fear of side effects (22.9%) was cited as the primary reason for not accepting the drugs. Weak perception of LF transmission risk (25.7%) and mistrust of drug safety (42.5%) were reported as reasons for non-compliance. Logistic regression identified significant associations, including residence (peri-urban: OR = 6.80), chronic disease (diabetes: OR = 2.89), trust on drug safety (OR = 16.27), and opinion of neighbours (OR = 5.35).

Conclusion

Participation of elderly population in MDA was suboptimal (40.6%). Tailored interventions to improve consumption such as addressing misconceptions, building trust in MDA and effective monitoring and management of adverse events are vital to enhance their participation. The National Programme should have specific guidelines and strategies to address this issue to improve their participation in MDA for elimination of LF.
Structure-guided drug repurposing identifies aristospan as a potential inhibitor of β-lactamase: insights from virtual screening and molecular dynamics simulations
Authors: Shahwan Moyad , Khan Mohd Shahnawaz , Zuberi Azna , Altwaijry Nojood , Shamsi Anas
Published: November 2024

The rise of β-Lactamase mediated antibiotic resistance is a major concern for public health; hence, there is an urgent need to find new treatment approaches. Structure-guided drug repurposing offers a promising approach to swiftly deliver essential therapeutics in the fight against escalating antibiotic resistance. Here, a structure-guided virtual screening approach was used involving drug profiling, molecular docking, and molecular dynamics (MD) simulation to identify existing drugs against β-Lactamase-associated drug resistance. We exploited a large panel of FDA-approved drugs to an extensive in silico analysis to ascertain their ability to inhibit β-Lactamase. First, molecular docking investigations were performed to assess the binding affinities and interactions of screened molecules with the active site of β-Lactamase enzymes. Out of all the screened candidates, Aristospan was identified to possess promising characteristics, which include appropriate drug profiles, high binding specificity, and efficiency towards the binding pocket of β-Lactamase. Further analysis showed that Aristospan possesses several desirable biological characteristics and tends to bind to the β-Lactamase binding site. To explore the interactions further, the best docking pose of Aristospan was selected for MD simulations to assess the thermodynamic stability of the drug-enzyme complex and its conformational changes over 500 ns. The MD simulations in independent replica runs demonstrated that the β-Lactamase-Aristospan complex was stable in the 500 ns trajectory. These enlightening results suggest that Aristospan may harbor the potential for further evolution into a possible β-Lactamase inhibitor, with potential applications in overcoming antibiotic resistance in both Gram-positive and Gram-negative bacteria.
Yigu decoction regulates plasma miRNA in postmenopausal osteoporosis patients: a randomized controlled trial
Authors: Chen Haifeng , Zhang Ruikun , Li Guijin , Yan Kun , Wu Ziqi , Zhang Yang , Chen Zhineng , Yao Xinmiao
Published: November 2024

Background

Postmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD.

Methods

In this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism.

Results

Compared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P < 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins.

Conclusion

This study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner.
Recent advances in extracellular matrix manipulation for kidney organoid research
Authors: Wang Ren , Sui Yufei , Liu Qiuyan , Xiong Yucui , Li Shanshan , Guo Wu , Xu Yiwei , Zhang Sheng
Published: November 2024

The kidney plays a crucial role in maintaining the body’s microenvironment homeostasis. However, current treatment options and therapeutic agents for chronic kidney disease (CKD) are limited. Fortunately, the advent of kidney organoids has introduced a novel in vitro model for studying kidney diseases and drug screening. Despite significant efforts has been leveraged to mimic the spatial-temporal dynamics of fetal renal development in various types of kidney organoids, there is still a discrepancy in cell types and maturity compared to native kidney tissue. The extracellular matrix (ECM) plays a crucial role in regulating cellular signaling, which ultimately affects cell fate decision. As a result, ECM can refine the microenvironment of organoids, promoting their efficient differentiation and maturation. This review examines the existing techniques for culturing kidney organoids, evaluates the strengths and weaknesses of various types of kidney organoids, and assesses the advancements and limitations associated with the utilization of the ECM in kidney organoid culture. Additionally, it presents a discussion on constructing specific physiological and pathological microenvironments using decellularized extracellular matrix during certain developmental stages or disease occurrences, aiding the development of kidney organoids and disease models.
Multi-omics analysis provides insights into the mechanism underlying fruit color formation in Capsicum
Authors: Song Zhao , Xu Xiaowan , Chen Xiao , Chang Jingjing , Li Jing , Cheng Jiaowen , Zhang Baige
Published: November 2024

Fruit color is a crucial attribute of fruit quality in peppers (Capsicum spp.). However, few studies have focused on the mechanism of color formation in immature pepper fruits. In this study, the light-yellow color observed in immature CSJ009 fruits compared to CSJ010 could be attributed to decreased chlorophyll and carotenoid pigments. Through integrated analysis of the transcriptome and metabolome of CSJ009 and CSJ010, we identified 23,930 differentially expressed genes (DEGs) and 345 differentially accumulated metabolites (DAMs). Furthermore, integrated analysis revealed a strong correlation between the HCT-like gene and metabolite MWS0178 (chlorogenic acid). Paraffin section assay revealed that the epidermal cells of immature CSJ010 fruits exhibited a more compact arrangement with significantly greater length than those of CSJ009. Quantitative determination of carotenoids showed that lutein emerged as the predominant carotenoid in immature pepper fruits. Additionally, missense mutation of LCYB2 is likely to lead to a decrease in β-carotene content in immature CSJ009 fruits, whereas CCS may directly catalyze the conversion of lycopene to β-carotene in mature fruits. The null mutation in CCS promoted the biosynthesis of β,ϵ-branch carotenoids leading to lutein being the most abundant carotenoid found in orange CSJ010 fruits. These findings provide important insights into the mechanism underlying color formation in pepper fruits and establish a foundation for the further exploration of color-related genes.
Improving seed germination: effect of stratification and dormancy-release priming in Lonicera insularis Nakai
Authors: Lee Jihun , Park Kyungtae , Lee Hamin , Jang Bo-Kook , Cho Ju-Sung
Published: November 2024

Lonicera insularis Nakai is endemic plant predominantly distributed along the coastlines of Ulleung-do and Dok-do in South Korea, and is significant for medicinal and ornamental uses. However, previous studies reported that L. insularis seeds exhibit morphological dormancy (MD), causing them to germinate only at specific temperatures. Therefore, this study aimed to classify the dormancy type of L. insularis seeds, expand the germination temperature range, and confirm the industrial applicability through dormancy-release (DR) priming. The seeds of L. insularis exhibited no inhibition of water absorption by the seed coat, with 85.0% germination observed at 15°C, similar to the viability (84.0%). Initially, the initial seeds of L. insularis exhibited an embryo-to-seed (E:S) ratio of 0.24 during dispersal, which increased to 0.81 by day 18 at 15°C, indicating that the seeds exhibit MD with underdeveloped embryos. Treatments with GA3 and GA4 + 7 to overcome MD and expand the germination temperature range did not significantly enhance germination. However, seeds that grew embryos through stratification for 2 weeks at 15°C effectively expanded the germination temperature range. Additionally, DR-primed seeds maintained the expanded germination temperature range even after redrying, confirming the commercial potential of DR-primed seeds. Therefore, this study represents the first application of a novel approach to alleviate dormancy in L. insularis seeds through the integration of stratification and priming techniques, termed dormancy-release priming. This approach resulted in a significant increase in germination and expanded the effective temperature range for seed germination. These findings suggest that dormancy-release priming could be a valuable method for producing non-dormant seeds, enhancing the potential for L. insularis distribution and industrial applications.
Beyond the 9-to-5 grind: workaholism and its potential influence on human health and disease
Authors: Aziz Shahnaz , Covington Ciara
Published: November 2024

Workaholism is often considered a conventional word in the general population to portray those individuals who continuously work and find it challenging not to work. It is usually described as a work addiction and operationalized as a compulsive need to work excessively hard. However, the concept of workaholism remains poorly understood. The first objective of this review is to define workaholism, followed by its related concepts, and how it is assessed. Notably, we distinguish workaholism from work addiction and work engagement. Next, we review the current research literature, largely from the last two decades, to suggest that workaholism contributes toward a wide range of health outcomes, ranging from sleep to stress. In particular, we focus on evidence suggesting that workaholism may be associated with differing risk factors for cardiovascular diseases and potentially other related metabolic abnormalities. Finally, we discuss potential limitations of the existing literature on workaholism, and we provide future directions for this emerging field. Specifically, we underscore the need to link workaholism with more biomarkers of metabolic diseases, such as those related to inflammation, the gut microbiome, and glucose homeostasis. In addition, we highlight the importance of establishing causality between workaholism and poor health outcomes, such as cardiovascular diseases and type 2 diabetes.
Parental education, Family Health Climate and accelerometer-based measured physical activity and sedentary behavior of primary school-aged children
Authors: Ziegeldorf Alexandra , Hottenrott Nina , Moritz Johanna , Wagner Petra , Wulff Hagen
Published: November 2024

Introduction

Sociodemographic factors such as parental education level (ED) influence the physical activity (PA) and sedentary behavior (SED) of primary school-aged children. In this context, family factors, such as the physical activity-related Family Health Climate (FHCPA), are relevant. However, the effect of FHCPA on the interaction between ED and children’s activity behavior has not yet been investigated. Therefore, this study aimed to analyze the mediating effect of FHCPA on the relation between parental ED and children’s device-based measured PA and SED.

Methods

A total of 94 children and their parents participated in the study. Questionnaires were used to assess parental ED and FHCPA. Children’s moderate to vigorous physical activity (MVPA) and SED were measured using accelerometers. Bivariate correlations were conducted to investigate associations between parental ED and MVPA/SED/FHCPA. Mediation analyses were used to investigate the role of FHCPA in the association between maternal and paternal ED and children’s MVPA/SED. Results indicate a small correlation between maternal ED and FHCPA for the total sample (ρ = 0.318, p < 0.001) and a medium correlation for girls only (ρ = 0.570, p < 0.001). Mediation analyses showed no significant mediation effect. However, there was a significant direct association when considering FHCPA in the relation between higher maternal ED and SED in girls compared to lower ED.

Discussion

Future research should examine more complex models to further develop and refine to facilitate the derivation of more effective recommendations for health prevention programs, particularly for mothers and girls.