bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoblastoma: present scenario and future challenges
Authors: Byroju Vishnu Vardhan , Nadukkandy Aisha Shigna , Cordani Marco , Kumar Lekha Dinesh 
Published: September 2023

AbstractWith an average incidence of 1 in every 18,000 live births, retinoblastoma is a rare type of intraocular tumour found to affect patients during their early childhood. It is curable if diagnosed at earlier stages but can become life-threateningly malignant if not treated timely. With no racial or gender predisposition, or even environmental factors known to have been involved in the incidence of the disease, retinoblastoma is often considered a clinical success story in pediatric oncology. The survival rate in highly developed countries is higher than 95% and they have achieved this because of the advancement in the development of diagnostics and treatment techniques. This includes developing the already existing techniques like chemotherapy and embarking on new strategies like enucleation, thermotherapy, cryotherapy, etc. Early diagnosis, studies on the etiopathogenesis and genetics of the disease are the need of the hour for improving the survival rates. According to the Knudson hypothesis, also known as the two hit hypothesis, two hits on the retinoblastoma susceptibility (RB) gene is often considered as the initiating event in the development of the disease. Studies on the molecular basis of the disease have also led to deciphering the downstream events and thus in the discovery of biomarkers and related targeted therapies. Furthermore, improvements in molecular biology techniques enhanced the development of efficient methods for early diagnosis, genetic counseling, and prevention of the disease. In this review, we discuss the genetic and molecular features of retinoblastoma with a special emphasis on the mutation leading to the dysregulation of key signaling pathways involved in cell proliferation, DNA repair, and cellular plasticity. Also, we describe the classification, clinical and epidemiological relevance of the disease, with an emphasis on both the traditional and innovative treatments to tackle retinoblastoma.
Investigating the potential of oncolytic viruses for cancer treatment via MSC delivery
Authors: Ghaleh Hadi Esmaeili Gouvarchin , Vakilzadeh Gazal , Zahiri Ali , Farzanehpour Mahdieh 
Published: September 2023

AbstractMesenchymal stem cells (MSCs) have attracted considerable interest as a promising approach for cancer treatment due to their ability to undergo tumor-trophic migration. MSCs possess the unique ability to selectively migrate to tumors, making them an excellent candidate for targeted delivery of oncolytic viruses (OVs) to treat isolated tumors and metastatic malignancies. OVs have attracted attention as a potential treatment for cancer due to their ability to selectively infect and destroy tumor cells while sparing normal cells. In addition, OVs can induce immunogenic cell death and contain curative transgenes in their genome, making them an attractive candidate for cancer treatment in combination with immunotherapies. In combination with MSCs, OVs can modulate the tumor microenvironment and trigger anti-tumor immune responses, making MSC-releasing OVs a promising approach for cancer treatment. This study reviews researches on the use of MSC-released OVs as a novel method for treating cancer.
Graphical Abstract
Educational inequalities in metabolic syndrome prevalence, timing, and duration amongst adults over the life course: a microsimulation analysis based on the lifelines cohort study
Authors: Hoveling Liza A. , Lepe Alexander , Boissonneault Michael , de Beer Joop A. A. , Smidt Nynke , de Kroon Marlou L. A. , Liefbroer Aart C. 
Published: September 2023

Abstract
Background
Educational inequalities in metabolic syndrome (MetS) are a growing public health concern. Intervening on modifiable factors may help reduce these inequalities, but there is a need for evidence on the long-term impact of intervening on these factors. Thus, we simulate the development of educational inequalities in MetS across the life course and assess the impact of intervening on the modifiable factors that contribute to these inequalities.

Methods
We used data from the prospective multigenerational Dutch Lifelines Cohort Study to estimate the required input for a continuous-time microsimulation. The microsimulation projects the development of educational inequalities in MetS between ages 18 and 65, and assesses the potential benefit of intervening on smoking, alcohol use, diet quality, and health literacy.

Findings
The likelihood of ever experiencing MetS between ages 18 and 65 varies from 32.5% among high educated women to 71.5% among low educated men. On average, 27.6% more individuals with low education will ever experience MetS between ages 18 and 65 compared to those with high education. Additionally, individuals with low education generally will develop MetS 2.3 years earlier, and will spend an extra 2.6 years with MetS, compared to individuals with high education. Changes to smoking behaviours in individuals with low education produced the largest effect; it would reduce inequalities in prevalence, timing and duration by an average of 7.5%, 9.5%, and 6.9%, respectively.

Conclusions
Interventions targeting the modifiable factors included in this study, especially smoking, could help reduce the estimated educational inequalities in MetS over the life course.
Gender differences in the distribution of children’s physical activity: evidence from nine countries
Authors: Kretschmer Luke , Salali Gul Deniz , Andersen Lars Bo , Hallal Pedro C. , Northstone Kate , Sardinha Luís B. , Dyble Mark , Bann David ,   International Children’s Accelerometry Database (ICAD) Collaborators, Andersen L. B. , Anderssen S. , Cardon G. , Davey R. , Jago R. , Janz K. F. , Kriemler S. , Møller N. , Northstone K. , Pate R. , Puder J. J. , Reilly J. , Salmon J. , Sardinha L. B. , van Sluijs E. M. F. 
Published: September 2023

Abstract
Background
Physical activity in childhood is thought to influences health and development. Previous studies have found that boys are typically more active than girls, yet the focus has largely been on differences in average levels or proportions above a threshold rather than the full distribution of activity across all intensities. We thus examined differences in the distribution of physical activity between girls and boys in a multi-national sample of children.

Methods
We used the harmonised International Children Accelerometry Database (ICAD), including waist-worn accelerometry data from 15,461 individuals (Boys: 48.3%) from 9 countries. Employing Generalised Additive Models of Location, Shape, and Scale (GAMLSS) we investigated gender differences in the distribution of individuals, including comparisons of variability (SD) and average physical activity levels (mean and median) and skewness. We conducted this analysis for each activity intensity (Sedentary, Light, and Moderate-to-Vigorous (MVPA)) and a summary measure (counts per minute (CPM)).

Results
Sizable gender differences in the distribution of activity were found for moderate to vigorous activity and counts per minute, with boys having higher average levels (38% higher mean volumes of MVPA, 20% higher CPM), yet substantially more between-person variability (30% higher standard deviation (SD) for MVPA, 17% higher SD for CPM); boys’ distributions were less positively skewed than girls. Conversely, there was little to no difference between girls and boys in the distribution of sedentary or light-intensity activity.

Conclusions
Inequality in activity between girls and boys was driven by MVPA. The higher mean volumes of MVPA in boys occurred alongside greater variability. This suggests a need to consider the underlying distribution of activity in future research; for example, interventions which target gender inequality in MVPA may inadvertently lead to increased inequality within girls.
Temporal trends, sex differences, and age-related disease influence in Neutrophil, Lymphocyte count and Neutrophil to Lymphocyte-ratio: results from InCHIANTI follow-up study
Authors: Pellegrino Raffaello , Paganelli Roberto , Di Iorio Angelo , Bandinelli Stefania , Moretti Antimo , Iolascon Giovanni , Sparvieri Eleonora , Tarantino Domiziano , Ferrucci Luigi 
Published: September 2023

Abstract
Background
Neutrophils and lymphocytes represent the larger percentage of all white blood cells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of several clinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years’ follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population.

Methods
The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session.

Results
The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value = 0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants.

Conclusion
NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases.
Generating synthetic gait patterns based on benchmark datasets for controlling prosthetic legs
Authors: Kim Minjae , Hargrove Levi J. 
Published: September 2023

Abstract
Background
Prosthetic legs help individuals with an amputation regain locomotion. Recently, deep neural network (DNN)-based control methods, which take advantage of the end-to-end learning capability of the network, have been proposed. One prominent challenge for these learning-based approaches is obtaining data for the training, particularly for the training of a mid-level controller. In this study, we propose a method for generating synthetic gait patterns (vertical load and lower limb joint angles) using a generative adversarial network (GAN). This approach enables a mid-level controller to execute ambulation modes that are not included in the training datasets.

Methods
The conditional GAN is trained on benchmark datasets that contain the gait data of individuals without amputation; synthetic gait patterns are generated from the user input. Further, a DNN-based controller for the generation of impedance parameters is trained using the synthetic gait pattern and the corresponding synthetic stiffness and damping coefficients.

Results
The trained GAN generated synthetic gait patterns with a coefficient of determination of 0.97 and a structural similarity index of 0.94 relative to benchmark data that were not included in the training datasets. We trained a DNN-based controller using the GAN-generated synthetic gait patterns for level-ground walking, standing-to-sitting motion, and sitting-to-standing motion. Four individuals without amputation participated in bypass testing and demonstrated the ambulation modes. The model successfully generated control parameters for the knee and ankle based on thigh angle and vertical load.

Conclusions
This study demonstrates that synthetic gait patterns can be used to train DNN models for impedance control. We believe a conditional GAN trained on benchmark datasets can provide reliable gait data for ambulation modes that are not included in its training datasets. Thus, designing gait data using a conditional GAN could facilitate the efficient and effective training of controllers for prosthetic legs.
Minimally invasive medial femoral approach to total knee arthroplasty improves short-term outcomes compared to the standard medial parapatellar approach: a systematic review and meta-analysis
Authors: Yang Xin , Cheng Qing-hao , Yang Yong-ze , Zhang An-ren , Fan Hua , Guo Hong-zhang 
Published: September 2023

Abstract
Objective
The aim of this study is to conduct a comprehensive evaluation of the effectiveness of the medial parapatellar approach via the vastus medialis obliquus muscle in comparison with the standard medial parapatellar approach for total knee arthroplasty, using a systematic approach.

Methods
A computer search was conducted on PubMed, EMBASE, Medline, Cochrane libraries, and Web of Science databases to comprehensively collect randomized controlled studies on minimally invasive (MMV) approaches for knee arthroplasty, specifically the vastus and medial parapatellar (MP) approaches. Two authors independently screened the literature based on inclusion and exclusion criteria, evaluated the quality of the included studies using the Cochrane systematic review method, and performed a meta-analysis using RevMan 5.3 software.

Results
A total of twelve randomized controlled studies were ultimately included, comprising 788 knees. The small incision medial femoral muscle approach (MMV) group consisted of 398 cases, while the traditional parapatellar approach (MP) group consisted of 390 cases. Data analysis showed that in the comparison of KSS, VAS, and ROM score at 3 months after surgery, MMV approach was superior to MP approach [MD = 2.89, 95%CI (0.33, 5.46), P = 0.03], [MD = − 0.22, 95%CI (− 0.36, − 0.09), P = 0.001], and [MD = 1.08, 95%CI (0.04, 2.12), P = 0.04]. However, there was no significant difference in the postoperative KSS, VAS, and ROM score between the MMV and MP approaches at 6 and 12 months after surgery. The operation time of the MMV group was longer than that of the MP group [MD = 8.98, 95%CI (4.64, 13.32), P < 0.0001], and the number of days of straight leg raising after surgery was shorter in the MMV group than in the MP group [MD = − 1.91, 95%CI (− 3.45, − 0.37), P = 0.01], with statistically significant differences. There was no significant difference in the lateral support band release rate [OR = 0.72, 95%CI (0.23, 2.28), P = 0.58], length of hospital stay [MD = 0.07, 95%CI (− 0.18, 0.31), P = 0.58], postoperative complications [MD = 0.62, 95%CI (0.33, 1.18), P = 0.15], and intraoperative blood loss [MD = 70.50, 95%CI (− 57.51, 198.72), P = 0.28].

Conclusion
Most of the approaches have similar length of stay and incidence of complications compared to standard approaches. However, the minimally invasive midvastus approach has shown potential to improve short-term outcomes.
Study registration: PROSPERO registration number CRD42023410583.
Short-term clinical efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion versus minimally invasive transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: a systematic review and meta-analysis
Authors: Han Hao , Song Yifan , Li Yiming , Zhou Hengcai , Fu Yufei , Li Jie 
Published: September 2023

Abstract
Background
The aim of this study was to comprehensively evaluate the short-term clinical efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) versus minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of lumbar degenerative diseases by meta-analysis.

Methods
A computer-based search of PubMed, Embase, Web of Science, Cochrane Database, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Science and Technology Journal Database (VIP) was conducted from the inception of the each database to April 2023. The searched literature was then screened according to strict inclusion and exclusion criteria. The critical data were extracted and analyzed using Review Manager software5.4.1. Pooled effects were calculated on the basis of data attributes by mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). The Newcastle–Ottawa Scale was used to assess the quality of the studies.

Results
A total of 13 studies and 949 patients met the inclusion criteria for this meta-analysis, 445 in the UBE-LIF group and 504 in the MIS-TLIF group. UBE-TLIF was superior to MIS-TLIF in terms of intraoperative blood flow, postoperative drainage flow, duration of hospital stay, VAS score for low back pain and ODI score, but the operative time was longer than MIS-TLIF group. There were no significant differences between the two groups in terms of total complication rate, modified Macnab grading criteria, fusion rate, VAS score of leg pain, lumbar lordosis, intervertebral disk height.

Conclusion
Both UBE-TLIF and MIS-TLIF are effective surgical modalities for the treatment of degenerative lumbar spine diseases. They have similar treatment outcomes, but UBE-TLIF has the advantages of less intraoperative blood loss, shorter postoperative hospital stay, and faster recovery.
Trial registration: This study has been registered at INPLASY.COM (No. INPLASY202320087).
Clinical, biochemical and molecular analysis in a cohort of individuals with gyrate atrophy
Authors: Palmer Eleanor , Stepien Karolina M. , Campbell Christopher , Barton Stephanie , Iosifidis Christos , Ghosh Arunabha , Broomfield Alexander , Woodall Alison , Wilcox Gisela , Sergouniotis Panagiotis I. , Black Graeme C. 
Published: September 2023

Abstract
Background
Gyrate atrophy of the choroid and retina is a rare autosomal recessive metabolic disorder caused by biallelic variants in the OAT gene, encoding the enzyme ornithine δ-aminotransferase. Impaired enzymatic activity leads to systemic hyperornithinaemia, which in turn underlies progressive chorioretinal degeneration. In this study, we describe the clinical and molecular findings in a cohort of individuals with gyrate atrophy.

Methods
Study participants were recruited through a tertiary UK clinical ophthalmic genetic service. All cases had a biochemical and molecular diagnosis of gyrate atrophy. Retrospective phenotypic and biochemical data were collected using electronic healthcare records.

Results
18 affected individuals from 12 families (8 male, 10 female) met the study inclusion criteria. The median age at diagnosis was 8 years (range 10 months – 33 years) and all cases had hyperornithinaemia (median: 800 micromoles/L; range: 458–1244 micromoles/L). Common features at presentation included high myopia (10/18) and nyctalopia (5/18). Ophthalmic findings were present in all study participants who were above the age of 6 years. One third of patients had co-existing macular oedema and two thirds developed pre-senile cataracts. Compliance with dietary modifications was suboptimal in most cases. A subset of participants had extraocular features including a trend towards reduced fat-free mass and developmental delay.

Conclusions
Our findings highlight the importance of multidisciplinary care in families with gyrate atrophy. Secondary ophthalmic complications such as macular oedema and cataract formation are common. Management of affected individuals remains challenging due to the highly restrictive nature of the recommended diet and the limited evidence-base for current strategies.
Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1
Authors: Schoch Kelly , McConkie-Rosell Allyn , Walley Nicole , Bhambhani Vikas , Feyma Timothy ,   Undiagnosed Diseases Network, Pizoli Carolyn E. , Smith Edward C. , Tan Queenie K.-G. , Shashi Vandana 
Published: September 2023

Abstract
Background
A recurrent de novo variant (c.892C>T) in NACC1 causes a neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM). An unusual and consistently reported feature is episodic extreme irritability and inconsolability. We now characterize these episodes, their impact on the family, and ascertain treatments that may be effective. Parents of 14 affected individuals provided narratives describing the irritability episodes, including triggers, behavioral and physiological changes, and treatments. Simultaneously, parents of 15 children completed the Non-communicating Children’s Pain Checklist-Revised (NCCPC-R), a measure to assess pain in non-verbal children.

Results
The episodes of extreme irritability include a prodromal, peak, and resolving phase, with normal periods in between. The children were rated to have extreme pain-related behaviors on the NCCPC-R scale, although it is unknown whether the physiologic changes described by parents are caused by pain. Attempted treatments included various classes of medications, with psychotropic and sedative medications being most effective (7/15). Nearly all families (13/14) describe how the episodes have a profound impact on their lives.

Conclusions
NECFM caused by the recurrent variant c.892C>T is associated with a universal feature of incapacitating episodic irritability of unclear etiology. Further understanding of the pathophysiology can lead to more effective therapeutic strategies.