bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of Cardiovascular disease risk prediction model for patients with Chronic kidney disease stage 3-5 within 5 years
Authors: Liu Huixia , Li Yujuan , Xiong Jing
Published: July 2024

Background and aims: Cardiovascular disease (CVD) is the leading reason for death in patients who are with chronic kidney disease (CKD). However, with progress of CKD, the ability of traditional CVD risk factors to predict clinical outcomes weakens, and non-traditional risk factors play a key role in the pathogenesis of CVD. Previous prediction models based only on traditional CVD risk show limitations and inaccuracies. Our study aims to develop and validate a prediction model for CVD risk including traditional and non-traditional risk factors in stage 3-5 CKD patients within 5 years in China.
Methods: 301 patients with CKD stage 3-5 were recruited from January 2010 to January 2022 and followed up till July 2022. Lasso regression and multivariate logistic regression were used to identify baseline predictors for model development, regression modeling was performed using logistic regression and internally validated using tenfold cross-validation. Discrimination and calibration of resulting prediction models were assessed using c-statistic and P-value of the Hosmer-Lemeshow test. Decision curve analysis was performed to assess clinical effectiveness.
Results: During follow-up, 169 developed first CVD events within 5 years. The median time of occurrence was 10 months. Of 29 clinical parameters, 11 variables were finally identified as significant predictors and included in the prediction model. 4 prediction models were created in a derivation cohort: original, inflammation, imaging and full model. Full model had the lowest AIC of 311.531 and P-value of 0.3319 of the Hosmer-Lemeshow test.
Conclusions: A nomogram was constructed to predict the risk of CVD for CKD patients.
Factors affecting postoperative nasal morphology after Le FortⅠosteotomy on multiple regression analysis
Authors: TOMOMATSU NOBUYOSHI , Nakamura Taishi , Matsumoto Shin , Takahara Namiaki , Nakakuki Koichi , YODA Tetsuya
Published: July 2024

External nasal morphology changes after LeFort I osteotomy, and various techniques including alar cinch suture, and subspinal osteotomy have been devised to accommodate these changes. However, despite various modifications, external nasal morphology may vary unexpectedly on an individual basis. Considering that the patient's external nasal morphology may be a contributing factor, this paper reports a retrospective study of the surgical technique and direction of maxillary movement in addition to the measurement of factors that comprise the external nasal morphology. Multiple regression analysis identified the patient's preoperative nasal width as a factor that increased the alar base width of the nose, in addition to the incision (oral vestibular incision) and the amount of anterior and superior movements at point A of the maxilla. The factors that caused the nasal apex to turn upward were the amount of anterior and superior movements at point A and the absence of subspinal osteotomy. The direction of surgical maxillary movement was influenced not only by anterior movement, but also by superior movement and surgical technique. Furthermore, the patient's preoperative nasal morphology was taken into consideration in determining the preoperative mode of movement.
The significance of cirrhosis in cases with intra-hepatic cholangiocarcinoma: A SEER-based retrospective cohort study
Authors: Wang Wen-Hui , Lin Hong-Jun , Lu Qing
Published: July 2024

Objective
To systematically evaluate the significance of cirrhosis in cases of intrahepatic cholangiocarcinoma (IHCC) concerning short and long-term outcomes.
Methods
Cases diagnosed with IHCC from 2000 to 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Comparative analyses were conducted between cases with cirrhosis and those without cirrhosis.
Results
A total of 644 cases with sufficient staging information and cirrhosis data were ultimately included. Comparative analyses indicated that cirrhosis was more prevalent among male cases (72.3% vs 50.6%, P < 0.001). Similar tumor differentiation status was observed between the two groups (P = 0.510). Cases without cirrhosis exhibited a higher incidence of T3-T4 disease (19.3% vs 12.2%, P = 0.025). Radiotherapy (3.3% vs 7.9%, P = 0.024), chemotherapy (45.5% vs 56.8%, P = 0.007), and surgery (37.1% vs 47.1%, P = 0.016) were more frequently performed among cases without cirrhosis. Cirrhosis was identified as a risk factor with minimal impact on survival but was not a prognostic factor. Even after matching, cases with cirrhosis still demonstrated a comparable long-term prognosis compared to those without cirrhosis.
Conclusion
Cirrhosis represents a risk factor rather than a prognostic factor for IHCC cases. While cirrhotic cases may have a lower resectability rate, their overall prognosis is similar to that of non-cirrhotic cases.
Safety and pharmacokinetics of subcutaneous administration of broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed, uninfected neonates and infants: study protocol for a phase I trial Acronym: PedMAb1
Authors: Goga Ameena , Ramraj Trisha , Naidoo Logashvari , Daniels Brodie , Matlou Masefetsane , Chetty Terusha , Dassaye Reshmi , Ngandu Nobubelo , Galli Laura , Reddy Tarylee , Seocharan Ishen , Ndlangamandla Qondeni , September Qholokazi , Ngcobo Nokwanda , Reddy Mayuri , Cafun-Naidoo Tamon , Woeber Kubashni , Jeenarain Nitesha , Imamdin Rabia , Keshnee Maharajh , Ramjeth Ashmintha , Bhengu Thobile , Clarence Emma , de perre Philippe van , Tylleskar Thorkild , Nagot Nicolas , Moles Jean-Pierre , Moore Penny L. , Mkhize Nonhlanhla N. , Gama Lucio , Dispinseri Stefania , Biswas Priscilla , Scarlatti Gabriella
Published: July 2024

Background:
The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV.
Methods:
Two bNAbs, CAP256V2LS and VRC07-523LS, will be assessed in a sequential and randomized phase I, single-site, single-blind, dose-finding trial. We aim to investigate the 28-day safety and pharmacokinetics (PK) profile of incrementally higher doses of these bNAbs in breastfeeding HIV-1 exposed born without HIV neonates alongside standard of care antiretroviral (ARV) medication to prevent (infants) or treat (mothers) HIV infection.
The trial design includes 3 steps and 7 arms (1, 2, 3, 4, 5, 6 and 6b) with 8 infants in each arm. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single subcutaneous (SC) administration at increasing mg/kg body weight doses within 96 hours of birth: arms 1, 2 and 3 at doses of 5, 10, and 20 mg/kg of CAP256V2LS, respectively; arms 4 and 5 at doses of 20 and 30 mg/kg of VRC07-523LS, respectively. Step two will evaluate the safety and PK profile of a combination of the two bNAbs administered SC at fixed doses within 96 hours of birth. Step three will evaluate the safety and PK profile of the two bNAbs administered SC in combination at fixed doses, after 3 months. Arms 1 and 6 will follow sequential recruitment, whereas randomization will occur sequentially between arms (a) 2 & 4 and (b) 3 & 5. Before each randomization, a safety pause will allow review of safety data of the preceding arms.
Discussion: The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV.
Protocol Version: Version 4.0 dated 15 March 2024.
Trial Registration:
Pan African Clinical Trial Registry (PACTR): PACTR202205715278722, 21 April 2022; South African National Clinical Trial Registry (SANCTR): DOH-27-062022-6058.
Effect of aortic valve replacement on myocardial perfusion and exercise capacity in patients with severe aortic stenosis
Authors: Aslam Saadia , Dattani Abhishek , Alfuhied Aseel , Gulsin Gaurav S. , Arnold Jayanth R. , Steadman Christopher D. , Jerosch-Herold Michael , Xue Hui , Kellman Peter , McCann Gerry P. , Singh Anvesha
Published: July 2024

Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6–12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63m/s, aortic valve area index 0.45 ± 0.13cm2/m2). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO2). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p < 0.001), with a corresponding 15% increase in myocardial perfusion reserve (MPR) (2.04 ± 0.57 to 2.34 ± 0.68; p = 0.004). Increasing severity of AS, presence of late gadolinium enhancement, lower baseline stress MBF and MPR were associated with a greater improvement in MPR post-AVR. On multivariable analysis low baseline MPR was independently associated with increased MPR post-AVR. There was no significant change in peak VO2 post-AVR, but a significant increase in exercise duration. Change in MPR was associated with change in peak VO2 post AVR (r = 0.346, p = 0.045). Those with the most impaired stress MBF and MPR at baseline demonstrate the greatest improvements in these parameters following AVR and the magnitude of change in MPR correlated with improvement in peak VO2, the gold standard measure of aerobic exercise capacity.
Association of First-trimester Remnant Cholesterol and Gestational Diabetes Mellitus: a retrospective cohort study
Authors: Guo Xueke , Wang Ruifang , Xiang Junmiao , Jiang Feina , Zhang Jie , Peng Xuting , Zheng Xiuying , Dai Yuanyuan , Cai Zhuhua
Published: July 2024

Background
LACK of research on the correlation between first trimester levels of remnant cholesterol (RC) and Gestational Diabetes Mellitus (GDM), and no studies have investigated the association between RC and complement.
Method & outcome measures:
This study is a retrospective cohort study conducted at the Third Affiliated Hospital of Wenzhou Medical University from May 2018 to December 2022. Baseline characteristics and laboratory test results were collected from all participants. The widely used formula for calculating RC is detailed as RC (mmol/L) = TC (mmol/L) - HDL-c (mmol/L) - LDL-c (mmol/L). Logistic regression and subgroup analysis were utilized to evaluate the risk impact of RC on GDM. Additionally, a correlation matrix was constructed to assess the relationship between RC and its associated factors.
Results
The study involved 830 participants, with a median RC of 0.4 mmol/L. Among them, 121 pregnant women (14.6%) were ultimately diagnosed with GDM. Multivariate adjusted logistic regression analysis revealed a positive correlation between RC and GDM risk (OR = 1.81, 95% CI 1.09–2.99). Subsequent subgroup analysis indicated no significant interaction between the groups (P > 0.05). The study also observed the strongest correlations between RC and age (r = 0.11), RC and BMI (r = 0.09), RC and C1q (r = 0.14), RC and GLU (r = 0.08).
Conclusion
The serum RC level at 4–8 weeks of pregnancy is positively correlated with the risk of GDM in pregnant women. First-trimester RC serves as an early warning indicator for GDM in pregnant women. This study may contribute to optimizing GDM prevention and early intervention in pregnant women.
Association between sugar-sweetened beverages intake and myopia: results from the National Health and Nutrition Examination Survey 2001-2008
Authors: Hao Zhuang , Jiang Mengqi , Ma Jiyuan , Wu Tong , Liu Yan , Zhou Jian
Published: July 2024

Objective: To investigate the relationship between sugar-sweetened beverages （SSBs）intake and myopia in a large population-based sample.
Study design: A cross-sectional study.
Methods: The data from population under 40 years were collected from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2008. Multivariable logistic regression analyses were performed to investigate the association between the SSBs intake and myopia. Additionally, the relationship between SSBs intake and myopia was further explored using propensity score matching (PSM). The generalized variance inflation factor (GVIF) was calculated to detect the potential for multicollinearity. Furthermore, restricted cubic spline (RCS) analysis was conducted to assess any potential non-linear relationship between SSBs intake and myopia.
Results: Of 11,851 participants under 40 years of age, 3,769 had myopia. The average consumption of SSBs was 664.28±18.43 grams/d in the emmetropia group and 605.35±20.01 grams/d in the myopia group before PSM, but no significant difference was detected after PSM(emmetropia group: 623.83±17.99 grams/d; myopia group:605.35±20.01 grams/d; P = 0.43). Multivariable logistics regression analysis showed SSBs intake was not associated with the risk of myopia before and after PSM, and the presence of multicollinearity was unlikely among all covariates. RCS analysis revealed a nonlinear relationship between SSBs intake and the risk of myopia before PSM (P for non-linear = 0.0244). However, after matching, no significant nonlinear associations were observed between SSBs intake and the risk of myopia (P for non-linear = 0.2434).
Conclusion: Our study provides initial evidence that consuming SSBs may not be a risk factor for myopia in a large-scale population. Future longitudinal and experimental studies can shed more light on the relationship between dietary factors and myopia, which can inform public health recommendations and interventions.
Automatic infant 2D pose estimation from videos: comparing seven deep neural network methods
Authors: Gama Filipe , Mísař Matěj , Navara Lukáš , Popescu Sergiu T. , Hoffmann Matej
Published: July 2024

Automatic markerless estimation of infant posture and motion from ordinary videos carries great potential for movement studies “in the wild”, facilitating understanding of motor development and massively increasing the chances of early diagnosis of disorders. There is rapid development of human pose estimation methods in computer vision thanks to advances in deep learning and machine learning. However, these methods are trained on datasets featuring adults in different contexts. This work tests and compares seven popular methods (AlphaPose, DeepLabCut/DeeperCut, Detectron2, HRNet, MediaPipe/BlazePose, OpenPose, and ViTPose) on videos of infants in supine position. Surprisingly, all methods except DeepLabCut and MediaPipe have competitive performance without additional finetuning, with ViTPose performing best. Next to standard performance metrics (object keypoint similarity, average precision and recall), we introduce errors expressed in the neck-mid-hip ratio and additionally study missed and redundant detections and the reliability of the internal confidence ratings of the different methods, which are relevant for downstream tasks. Among the networks with competitive performance, only AlphaPose could run close to real time (27 fps) on our machine. We provide documented Docker containers or instructions for all the methods we used, our analysis scripts, and processed data at https://hub.docker.com/u/humanoidsctu and https://osf.io/x465b/.
Modified trochanteric flip osteotomy in varus intertrochanteric osteotomy for treatment of Legg-Calvé-Perthes disease
Authors: Laufer Andrea , Antfang Carina , Gosheger Georg , Frommer Adrien , Toporowski Gregor , Tretow Henning , Roedl Robert , Vogt Bjoern
Published: July 2024

Background
Legg-Calvé-Perthes disease (LCPD) presents challenges in treatment due to its varied course and unclear etiology. This study aimed to evaluate the efficacy of combining proximal femoral varus osteotomy (PFVO) with a modified trochanteric flip osteotomy to address biomechanical consequences and improve hip abductor muscle strength.
Methods
We present a modified approach combining PFVO with a trochanteric flip osteotomy. In this technique the greater trochanter in compound with its muscular insertions is separated from the femur and attached distally using a varization blade plate. Eight patients (nine hips) with LCPD were treated using this technique. Clinical examination findings and radiographic evaluations were retrospectively analyzed. The median follow-up was 28 months.
Results
At the last follow-up, two patients exhibited Trendelenburg gait, but hip abduction was improved in all patients. Radiographically, consolidation at the osteotomy site was observed in all cases, with no delayed union or non-union. The mean CE angle improved by 7.6°, while the mean CCD decreased by 19.5°. The mean MPFA decreased by 17.5° resulting in a mean of 81°.
Conclusion
Combining PFVO with a modified trochanteric flip osteotomy addresses biomechanical issues associated with PFVO, potentially improving hip containment and abductor muscle strength. This approach may offer advantages over traditional osteotomy techniques in treating LCPD. Despite satisfactory radiological outcomes in most cases, further research is needed to assess long-term effectiveness and address challenges such as femoral head enlargement and persistent gait abnormalities.
Zero-inflation in the Multivariate Poisson Lognormal Family
Authors: Chiquet Julien , Gindraud François , Mariadassou Mahendra , Batardière Bastien
Published: July 2024

Analyzing high-dimensional count data is a challenge and statistical model-based approaches provide an adequate and efficient framework thatpreserves explainability. The (multivariate) Poisson-Log-Normal (PLN) modelis one such model: it assumes count data are driven by an underlying structuredlatent Gaussian variable, so that the dependencies between counts solely stems from the latent dependencies.However PLN doesn't account for zero-inflation, a feature frequentlyobserved in real-world datasets. Here we introducethe Zero-Inflated PLN (ZIPLN) model, adding a multivariate zero-inflated component to themodel, as an additional Bernoulli latent variable. The Zero-Inflation can befixed, site-specific, feature-specific or depends on covariates. We estimatemodel parameters using variational inference that scales up to datasets with a few thousands variables and compare two approximations:(i) independent Gaussian and Bernoulli variational distributions or (ii)Gaussian variational distribution conditioned on the Bernoulli one. The method is assessedon synthetic data and the efficiency of ZIPLN is established even when zero-inflation concerns up to 90\% of the observed counts.We then apply both ZIPLN and PLN to a cow microbiome dataset, containing 90.6\% ofzeroes. Accounting for zero-inflation significantly increases log-likelihood and reduces dispersion in the latent space, thus leading to improved group discrimination.
Biohydrogen production potential from the organic fraction of municipal solid waste in co- digestion with sewage sludge through high-solids dark fermentation
Authors: Silva-Martínez Rodolfo Daniel , Aguilar-Juárez Oscar , Díaz-Jiménez Lourdes , Valdez-Guzmán Blanca Estela , Aranda-Jaramillo Brenda , Carlos-Hernández Salvador
Published: July 2024

Background
Biohydrogen production from the organic fraction of municipal solid waste (OFMSW) in co-digestion with sewage sludge (SS) through dark fermentation (DF) is emerging as an alternative route for efficient waste treatment and biofuel production. Notwithstanding, there is little experience with a high-solid approach, where practical conditions are created to further develop feasible industrial-scale projects. This study conducted a biochemical hydrogen potential test using a 7L batch reactor at 35°C for 39 days. Parameters such as pH, redox potential, temperature, alkalinity, total solids, and substrate/inoculum ratio were adjusted and monitored. Biogas composition was analyzed by gas chromatography. The microbial characterization of SS and post-reaction percolate liquids was determined through metagenomics analyses.
Results
Results demonstrate an initial biohydrogen yield of 38.4 Nml/gVS OFMSW, which forms ~ 60% of the produced biogas. Aeration was proven as an efficient inoculum pretreatment method, mainly to decrease the levels of methanogenic archaea and metabolic competition, and at the same time maintain the required total solid (TS) contents for high-solid conditions. The microbial community analysis shows that the biohydrogen production was carried out by specific anaerobic and aerobic bacteria and dominated by the phylum Firmicutes such as the genus Bacillus, Clostridium, Romboutsia; and the phylum Proteobacteria with the genus Proteus.
Conclusion
These results aid in setting the base ground to further develop the technology and design a larger bioreactor for DF of OFMSW in co-digestion with SS, considering diverse parameters, the manufacturing process, and instrumentation. Thus, this research provides an alternative solution for OFMSW treatment and biohydrogen production and expects to serve as a basis for future research, which may intend to improve biochemical conditions to increase the amount of hydrogen produced, optimize biodegradation and, at the same time, develop an industrial high-solid dark fermentation system that is technically and economically viable.
Impact of diabetes mellitus on oncologic outcomes in patients receiving robot- assisted radical cystectomy for bladder cancer
Authors: Tuderti Gabriele , Chiacchio Giuseppe , Mastroianni Riccardo , Anceschi Umberto , Bove Alfredo Maria , Brassetti Aldo , D'Annunzio Simone , Ferriero Mariaconsiglia , Misuraca Leonardo , Proietti Flavia , Flammia Rocco Simone , Guaglianone Salvatore , Lombardo Riccardo , Anselmi Marianna , Zampa Ashanti , Nunzio CosimoDe , Pastore Antonio Luigi , Galosi⁴ Andrea Benedetto , Leonardo Costantino , Gallucci Michele , Simone Giuseppe
Published: July 2024

Purpose
Aim of this study is to investigate the association between DM and oncological outcomes among patients with muscle-invasive (MI) or high-risk non-muscle invasive (NMI) bladder cancer (BC) who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion (RARC)
Methods
An IRB approved multi-institutional BC database was queried, including patients underwent RARC between January 2013 and June 2023. Patients were divided into two groups according to DM status. Baseline, clinical, perioperative, pathologic data were compared. Chi-square and Student t tests were performed to compare categorical and continuous variables, respectively. Kaplan-Meier method and Cox regression analyses were performed to assess the association between DM and oncologic outcomes.
Results
Out of 547 consecutive patients, 97 (17.7%) had DM. The two cohorts showed similar preoperative features, except for ASA score (p=0.01) and Hypertension rates (p<0.001). No differences were detected for perioperative complications, pT stage, pN stages and surgical margins status (all p>0.12). DM patients displayed significantly lower 5-yr disease-free survival (DFS) (44.6% vs 63.3%, p=0.007), 5-yr cancer-specific survival (CSS) (45.1% vs 70.1%, p=0.001) and 5-yr Overall survival (OS) (39.9% vs 63.8%, p=0.001). At Multivariable Cox-regression analyses DM status was identified as independent predictor of worse cancer-specific survival (CSS) (HR 2.1; p=0.001) and overall survival (OS) (HR 2.05; p<0.001).
Conclusion
Among BC patients who underwent RARC, DM patients showed worse oncologic outcomes than the non-DM patients, with DM status playing an independent negative predicting role in CSS and OS. Future prospective studies are awaited, stimulating basic and translational research to identify possible mechanisms of interaction between DM and BC.
Atypical left-ventricular hypertrophy with apical aneurysm in Leopard Syndrome.
Authors: Fernandez-Sanchez Jose Antonio , Cobarro-Galvez Lucia , Bermudez-Jimenez Francisco Jose , Macias-Ruiz Rosa , Oyonarte-Ramirez Jose Manuel , Jimenez-Jaimez Juan
Published: July 2024

Noonan Syndrome with Multiple Lentigines (NSML-formerly known as LEOPARD syndrome) is a rare autosomal dominant condition that usually exhibits cardiac involvement with hypertrophic cardiomyopathy (HCM). Here we present a case of a NSML patient with an unusual and patchy cardiac hypertrophy distribution.
Pro-MA: Progressively Margin-based Attribution in Pre-trained Vision-Language Models
Authors: You Sisi , Li Jiachang
Published: July 2024

Knowledge attribution is focused on analyzing the internal knowledge architecture of neural networks, aiming to accurately identify the factual knowledge stored within a model. Existing knowledge attribution methods concentrate on Pre-trained Language Models (PLMs), with limited exploration in Pre-trained Vision-Language Models (VLMs). However, the knowledge attribution methods of PLMs cannot be directly utilized on VLMs due to different decision-making processes and unstable integral gradients. Specifically, VLMs involve extra knowledge-irrelevant steps like localization and show high variance in gradient distributions along the attribution paths. To address the above challenges, we propose Progressive Margin-based Attribution (Pro-MA) to achieve more accurate attribute knowledge attribution in VLMs. Firstly, we employ cross-attribute comparison to identify and eliminate irrelevant knowledge by constructing high-similarity negative samples. Secondly, we utilize progressive attribution scoring that quantifies the contribution of neurons to the output by the margin of the attribute-value loss function along the path of active neurons. Evaluation on the OVAD and VAW datasets shows that Pro-MA outperforms the state-of-the-art knowledge attribution methods.
Human Dental Mesenchymal Stem Cells Restorate Immune Response in Sera of Pemphigus Vulgaris Patients
Authors: Ozgen Zuleyha , Duran Yazgul , Ergun Tulin , Göker Kamil , Senem Sabriye , AKKOÇ Tunç
Published: July 2024

Pemphigus is an IgG-mediated autoimmune condition characterized by autoantibodies targeting desmogleins, leading to acantholysis. Current treatments, including systemic corticosteroids and immunosuppressive drugs, are associated with significant adverse effects. Mesenchymal stem cells (MSCs) offer a promising alternative due to their immunomodulatory properties and low immunogenicity. This study evaluates the immunomodulatory effects of Dental Follicle Mesenchymal Stem Cells (DF-MSCs) on Pemphigus Vulgaris (PV) patients and healthy controls by examining T-cell proliferation, apoptosis, cytokine levels, and anti-desmoglein 1/3 IgG profiles. Twenty-one symptomatic PV patients and eleven healthy volunteers were included. DF-MSCs were isolated, characterized, and differentiated into osteocytes, adipocytes, and chondrocytes. Peripheral Blood Mononuclear Cells (PBMCs) were co-cultured with DF-MSCs, and various assays were conducted to evaluate T-cell proliferation, apoptosis, regulatory T cells, cytokine expression, and autoantibody levels. Results showed that DF-MSC co-cultures significantly reduced lymphocyte proliferation (43.58–16.27%), IL-4 (38.06 ng/L to 32.26 ng/L), TNF-α (32.45 ng/L to 29.41 ng/L), and DSG1 (3.29 ng/ml to 3.00 ng/ml) and DSG3 (262.40 ng/ml to 245.08 ng/ml) levels in PV patients. An increase in regulatory T cells (1.22–3.75%), IL-10 (47.46 pg/ml to 54.94 pg/ml), and IFN-γ (12.39 ng/ml to 19.70 ng/ml) was also observed. No significant changes were noted in healthy controls. These findings suggest that DF-MSCs could potentially offer a curative approach for treating pemphigus by restoring immune balance. However, further clinical trials are necessary to confirm their efficacy.
Inferring causal associations in hydrological systems: A comparison of methods
Authors: Liang Hanxu , Wang Wensheng , Chen Bin , Guo Li , Liu Hu , Yu Siyi , Zhang Dan
Published: July 2024

Many research issues in hydrological systems are intrinsically causal, aiming to determine whether and how one factor affects another. Although causal inference methods have been applied more or less in hydrology, there still remains a lack of systematic comparison between different methods. Here, four popular methods in the causal inference community, including the cross-correlation function (CCF), convergent cross mapping (CCM), transfer entropy (TE), and a causal network learning algorithm (PCMCI+) were selected, with a detailed explanation of their basic principles and underlying assumptions. Next, the performances of these methods were evaluated in large sample tests and sensitivity analysis using synthetic time series generated by a conceptual hydrological model with two predesigned causal structures. Then, the four methods were applied in two real-world cases to further understand their characteristics. The findings show the superior performance of the PCMCI + method in synthetic cases and a commendable level of interpretability in real cases, thus warranting its broader application in hydrological systems. The limitations of the other three methods, especially in effectively addressing confounding and mediating factors, led to several unreasonable causal links. Furthermore, the emergence of conflicting results among different methods in real-world applications underscores the necessity for a multifaceted understanding based on their particular assumptions and constraints. A comprehensive application of diverse methods according to the specific issue is encouraged for the robustness of conclusions, with their assumptions clearly stated in advance. Overall, our research reveals the potential and limitations of different causal inference methods in comprehension of complex interactions within hydrological systems, serving as a useful guide for their further prosperity in hydrology.
Cost-effectiveness of RefluxStop compared to proton pump inhibitors and Nissen fundoplication for management of persistent gastroesophageal reflux disease in Norway
Authors: Harper Sam , Kartha Muralikrishnan , Mealing Stuart , Eftang Lars , Gaupset Robin
Published: July 2024

Background Heartburn, chest pain, and regurgitation are characteristics of gastroesophageal reflux disease. The standard treatment in Norway is proton pump inhibitors (PPIs), but surgical alternatives such as Nissen fundoplication are pursued when medical management proves ineffective. RefluxStop is an implantable device presenting a new approach to restoration of the antireflux barrier. The aim of this study is to evaluate the cost-effectiveness of RefluxStop, Nissen fundoplication, and PPI-based medical management (MM) in Norway.Methods A Markov model was adapted from a published cost-effectiveness analysis developed for the UK NHS assessing the cost-effectiveness of RefluxStop in comparison with PPI-based MM and Nissen fundoplication. The perspective of the Norwegian healthcare payer, lifetime horizon, one-month cycle length, and a 4% annual discount rate for costs and health-benefits were used. Health states included in the model were initial MM, MM relapse, follow-on surgery, reoperations, MM with a higher dose, Barrett’s esophagus, esophageal cancer, and death. Adverse events related to MM and surgeries were included with benefits measured in quality-adjusted life-years (QALYs). Norwegian diagnostic-related group tariffs and literature were used as sources for unit costs. Clinical efficacy data for RefluxStop was based on an ongoing clinical study and comparator treatments were informed by published studies. Deterministic and probabilistic sensitivity analyses were used to address uncertainty of the parameter estimates.Results Compared to PPI-based MM and Nissen fundoplication, the base case incremental cost-effectiveness ratios (ICERs) of RefluxStop were NOK 68,262 and NOK 79,543 per QALY gained, respectively. The results of the model were robust to variation in individual inputs with exception of monthly failure rate of RefluxStop relative to Nissen fundoplication. RefluxStop demonstrated a significantly high probability of cost-effectiveness at the cost-effectiveness threshold of NOK 275,000 per QALY gained, with probabilities of 100% and 92% against PPI-based MM and Nissen fundoplication, respectively.Conclusion The RefluxStop device is highly likely to be cost-effective compared to PPI-based MM and Nissen fundoplication in Norway. Further study is required to assess the real-world long-term safety and efficacy of this novel device.
Exploring the Prevalence and Determinants of Substance Use Among Drug Addicts in Pakistan
Authors: Siddiqui Sonia , Khalid Farhia , Khalid Muhammad Farooq , Towheed Aetesam , Ahmed Shoaib , Paracha Hafsa , Naqvi Talheen Ali , Hassan Tania , Owais Ayesha
Published: July 2024

Objectives
To investigate the underlying causes that lead to the initiation of drug usage among drug addicts in Pakistan and to assess the prevalence of drug abuse and its association with influential factors.
Methods
This cross-sectional study involved 598 adult males and 2 females. Participants were recruited from different psychiatric rehabilitation centres using the standard scoring scale of substance use according to The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. An additional questionnaire was used to assess the socio-demographic details.
Results
The mean age of participants was 29.54 ± 6.76 years. The mean score of DSM-5 level 2 was 16.55. The logistic regression analysis shows a significant association between peer pressure (OR = 24.98, 95% CI: 14.208–43.945; p < 0.0005) and curiosity (OR = 0.027, 95% CI: 0.11 − 0.068; p < 0.0005) with the severity of substance use. Sex (6.7%), relationship problems (6.7%), stress (5.3%), and strict family (6.7%) were also significantly associated with the severity of substance use. All polydrug users in this study were significantly associated with the severity of the drug. Marijuana (69%) was the most commonly used by the participants followed by heroin (56.9%) and methamphetamine (52.5%). It was found that substance use was significantly associated with memory impairment and violence. The majority of the participants (95%) have tried to stop using drugs. Age, marital status, and education are not associated with the severity of drug use.
Conclusion
The findings emphasize the urgency of tailored interventions and support strategies to combat substance addiction effectively.
Isolation and identification of the rare actinomycete, Amycolatopsis roodepoortensis strain EA7 from the agricultural soils of northern Iran and identification of their biological products
Authors: Amiri Elham , Mirpour Mirsasan , Issazadeh Khosro , Rasti Behnam
Published: July 2024

This paper delves into the antimicrobial activity and identification of bioactive compounds of Amycolatopsis roodepoortensis strain EA7. Biochemical and molecular methods were utilized for the identification of actinomycetes. One strain displaying superior antimicrobial activity was chosen for the identification of bioactive compounds. The antimicrobial activity was thoroughly investigated. The analysis of the 16S rRNA gene revealed that strain EA7 belonged to the Amycolatopsis roodepoortensis specie with 99.63% confidence. The ethyl acetate extract exhibited the largest zone of inhibition against gram-positive pathogenic bacteria (25mm) using the disc diffusion method. In the MIC method, the ethyl acetate extract displayed the lowest MIC values ranging from 312.5 µg/mL (S. aureus PTCC 1112) to 1250 µg/mL (P. aeruginosa clinical and standard strain). However, the methanolic extract showed lower antimicrobial activity. In the GC-MS analysis, compounds were identified based on their percentage of area, retention time, molecular formula, molecular weight, and quality in the strain EA7 extract, with acetic acid, 2-methylpropyl ester (15.8%) being the major compound. In the LC-MS analysis, nine major compounds with anticancer and antimicrobial activity were identified. Among these, tetrangomycin, amycolactam, dihydroxybenzamide, and dipyrimycin A are compounds with potential anticancer activity, while tetracycline exhibits potential antimicrobial activity.
Atezolizumab- and bevacizumab -induced encephalitis in a patient with advanced hepatocellular carcinoma: a case report and literature review
Authors: Sagong Min , Kim Keun Tae , Jang Byoung Kuk
Published: July 2024

Treatment with atezolizumab and bevacizumab is the first-line therapy for unresectable hepatocellular carcinoma. Although immune checkpoint inhibitors are novel and effective treatments, they can induce immune-related adverse events. However, neurological immune-related adverse events have rarely been reported. We report the case of a man in his 40s with hepatocellular carcinoma who developed life-threatening encephalitis after atezolizumab plus bevacizumab was administered. The patient presented with fever, headache, altered mentality, and general epileptic seizures, ten days after administration. Cerebrospinal fluid analysis showed elevated white blood cells and elevated protein levels, but revealed no infection or malignancy. Brain magnetic resonance imaging showed diffuse leptomeningeal enhancement in both the cerebrum and cerebellum. As immune checkpoint inhibitor-induced encephalitis was strongly suspected, steroid pulse therapy was initiated and neurological symptoms quickly improved. The patient was discharged after 66 days of hospitalization, and administration of sorafenib and radiotherapy was started for the hepatocellular carcinoma on an outpatient basis. This case demonstrates the importance of recognizing neurological immune-related adverse events following atezolizumab and bevacizumab treatment for early intervention. We discuss this case in comparison to available literature and previous two cases of Atezolizumab- and bevacizumab- induced encephalitis in hepatocellular carcinoma.
Adaptive significance of age- and light-related variation in needle structure, photochemistry, and pigments in evergreen coniferous trees
Authors: Oluborode James , Chadzinikolau Tamara , Formela-Luboińska Magda , Ye Zi-Piao , Robakowski Piotr
Published: July 2024

Evergreen conifers thrive in challenging environments by maintaining multiple sets of needles, optimizing photosynthesis even under harsh conditions. This study aimed to investigate the relationships between needle structure, photosynthetic parameters, and age along the light gradient in the crowns of Abies alba, Taxus baccata, and Picea abies. We hypothesized that: (1) Needle structure, photochemical parameters, and photosynthetic pigment content would correlate with needle age and light levels in tree crowns. (2) The photosynthetic capacity of ageing needles would decline and adjust to the increasing self-shading of branches. Our results revealed a non-linear increase in the leaf mass-to-area ratio. The maximum quantum yield of photosystem II photochemistry decreased linearly with needle age without reaching levels indicative of photoinhibition. Decreased maximum electron transport rates (ETRmax) were linked to declining values of saturation photosynthetic photon flux and increasing non-photochemical quenching of fluorescence (NPQ), indicating energy losses as heat. The chlorophyll a to chlorophyll b ratio linearly decreased, suggesting older needles sustain high light capture efficiency. These findings offer new insights into the combined effects of needle ageing and self-shading on photochemistry and pigment content. This functional needle balance highlights the trade-off between the costs of long-term needle retention and the benefits of efficient resource utilization. In environments where air temperature is less of a constraint on photosynthesis due to climate warming, evergreen coniferous trees could sustain or enhance their photosynthetic capacity. They can achieve this by shortening needle lifespan and retaining fewer cohorts of needles with higher ETRmax and lower NPQ compared to older needles.
Iron-Dependent KDM4D Activity Controls the Quiescence-Activity Balance of MSCs via the PI3K-Akt-Foxo1 Pathway
Authors: Xie Zhongyu , Che Yunshu , Huang Guo , Su Zepeng , Lin Jiajie , Zheng Guan , Ye Guiwen , Yu Wenhui , Li Jinteng , Wu Yanfeng , Shen Huiyong
Published: July 2024

Iron deficiency is a prevalent nutritional deficit associated with organ damage and dysfunction. Recent research increasingly associates iron deficiency with bone metabolism dysfunction, although the precise underlying mechanisms remain unclear. Some studies have proposed that iron-dependent methylation-erasing enzyme activity regulates cell proliferation and differentiation under physiological or pathological conditions. However, it remains uncertain whether iron deficiency inhibits the activation of quiescent mesenchymal stem cells (MSCs) by affecting histone demethylase activity. In our study, we identified KDM4D as a key player in the activation of quiescent MSCs. Under conditions of iron deficiency, the H3K9me3 demethylase activity of KDM4D significantly decreased. This alteration resulted in increased heterochromatin with H3K9me3 near the PIK3R3 promoter, suppressing PIK3R3 expression and subsequently inhibiting the activation of quiescent MSCs via the PI3K-Akt-Foxo1 pathway. Iron-deficient mice displayed significantly impaired bone marrow MSCs activation and decreased bone mass compared to normal mice. Modulating the PI3K-Akt-Foxo1 pathway could reverse iron deficiency-induced bone loss.
Mechanistic insights from the atomic-level quaternary structure of short-lived GPCR oligomers in live cells
Authors: Raicu Valerica , Stoneman Michael , Yokoi Koki , Biener Gabriel , Killeen Thomas , Adhikari Dhruba , Rahman Sadia , Harikumar Kaleeckal , Miller Laurence
Published: July 2024

The functional significance of the interactions between proteins in living cells to form short-lived quaternary structures cannot be overemphasized. Yet, quaternary structure information is not captured by current methods, neither can those methods determine structure within living cells. The dynamic versatility, abundance, and functional diversity of G protein-coupled receptors (GPCRs) pose myriad challenges to existing technologies but also present these proteins as the ideal testbed for new technologies to investigate the complex inter-regulation of receptor-ligand, receptor-receptor, and receptor-downstream effector interfaces in living cells. Here, we present development and use of a novel method capable of overcoming existing challenges by combining distributions (or spectrograms) of FRET efficiencies from populations of fluorescently tagged proteins associating into oligomeric complexes in live cells with diffusion-like trajectories of FRET donors and acceptors obtained from molecular dynamics (MD) simulations. Our approach provides an atom-level picture of the binding interfaces within oligomers of the human secretin receptor (hSecR) in live cells and allows for extraction of mechanistic insights into the function of GPCRs oligomerization. This FRET-MD spectrometry approach is a robust platform for investigating protein-protein binding mechanisms and opens a new avenue for investigating stable as well as fleeting quaternary structures of any membrane proteins in living cells.
Continuous multivariate conversion processes for stabilized anode in aqueous zinc-ion battery
Authors: Ma Tianyi , Zhuang Changlei , Yang Jinzhang , Yin Bosi , Zhu Lingfeng , Sun Ying , Li Hui , Zhang Siwen , Li Jiazhuo , Feng Xinyu , Zhang Lei , Meng Fanbo , Duan Xiaoguang , Su Dawei
Published: July 2024

The performance of aqueous zinc-ion batteries (AZIBs) is often hindered by issues at the electrode/electrolyte interface, such as dendrite growth and unwanted byproducts. In this study, we applied pyridoxine (PN) electrolyte and used in situ UV‒vis spectroscopy to observe its multistep transformation. The pristine protonated pyridoxine (PN+) gradually lost a proton connecting to the N atom and became PN due to the applying voltage bias. Then PN kept lost a proton that connected to the O atom, changing to a higher electronegativity variant named PN-. The final variant maintained its state and possibly coordinated with zinc ion, and bonded to H+. Relying on the continuous multivariate conversion processes, these transformed PN variants can release H+ ions to maintain pH balance at the interface and interact strongly with zinc ions, improving the zinc ion solvation structure and reducing hydrogen evolution reaction (HER). Additionally, as-generated higher electronegativity variants formed an electrostatic shielding layer on the Zn electrode, promoting uniform zinc deposition and enhancing the plating/stripping process. As proof of continuous multivariate conversion processes, Zn||Zn symmetric batteries operated stably for 7000 hours at 1 mA cm–2 and 1 mAh cm–2, and Zn||NH4V4O10 (NVO) full batteries showed excellent stability over 1500 cycles. These results significantly outperformed those using the standard ZnSO4 (ZS) electrolyte and previously reported systems. This work suggests a promising approach for advancing various metal batteries towards commercialization, not limited to AZIBs.
Reducing Aluminum Toxicity in Food Packaging Using Bio- Polymer
Authors: Kumar Neeta Shiva , Dhivyapriya R , Spoorthi B R , Soratur Spoorti
Published: July 2024

In the era of modern food industry, food packaging has gained a lot of interest that helps in protecting food from environmental factors and in maintaining the integrity of food. Aluminum, being widely used material in food packaging has been used as containers, foils and pouches in packaging of hot foods, snacks and beverages. Many studies have been conducted which show that there is an increase in Aluminum content in brains of patients with Parkinson’s and Alzheimer’s diseases. It has been suspected that leaching of Aluminum content from the food packaging is one of the main reasons. Hence in this work, a biopolymer barrier has been used in reduction of Aluminum leaching into food. Chitosan, being a biopolymer, is non-toxic and biodegradable which has film forming and antimicrobial properties can be used as a barrier in order to prevent the leaching of Aluminum into the food. Hot rice (approx. 60°C) was used as sample for the experiment. Hot rice was wrapped in Aluminum foil and chitosan coated Aluminum foil for 90 minutes. Aluminum content was detected using inductively coupled plasma- optical emission spectrometer (ICP-OES) for only rice; rice in Aluminum foil and rice in chitosan coated Aluminum foil and found to be 2.81ppm, 3.29ppm and 2.87ppm respectively. The result obtained implied that chitosan acts as a barrier thereby inferring that chitosan coated Aluminum foil can be used to reduce leaching of Aluminum to the food and hence minimise the ill effects of Aluminum intake to the body.