bluuebunny/crossref_metadata_2025_split huggingface dataset:
Easily misdiagnosed X-linked adrenoleukodystrophy
Authors: Wang Qiu-Hong , Wang Yang-Yang , Wang Jing , Liu Li-Ying , Gao Jing , Hao Guo-Zhen , Chen Chen , Lu Qian , Dun Shuo , Zhang Qi , Zou Li-Ping 
Published: July 2024

Abstract
Background
Addison’s disease and X-linked adrenoleukodystrophy (X-ALD) (Addison’s-only) are two diseases that need to be identified. Addison’s disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison’s-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison’s disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD.

Methods
We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics.

Results
Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison’s disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394–2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison’s-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum.

Conclusions
Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison’s disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison’s-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.
Successful treatment of cortical visual impairment in children using anti-amblyopia treatment despite the absence of amblyopia: a case report
Authors: Sica Attilio , Michieletto Paola , Pensiero Stefano , Barbi Egidio 
Published: July 2024

Abstract
Background
Cortical visual impairment (CVI) is a verifiable visual dysfunction that cannot be attributed to disorders of the anterior visual pathways or any potentially co-occurring ocular impairment. Given the limited knowledge on the most effective interventions for visual impairment resulting from CVI, this case report provides valuable insights into an example of successful implementation of anti-amblyopia therapy in a patient with CVI.

Case presentation
This case report presents a 5-year-old girl with CVI secondary to hypoxic-ischemic injury, resulting in visual impairment, dyspraxia, and abnormal visual evoked potential testing. The girl did not suffer from amblyopia, there was no evidence of relevant refractive errors or strabismus, so visual pathway damage was the cause of her visual deficit. Nevertheless, the patient underwent anti-amblyopia therapy and showed significant improvement in visual acuity after 12 months of treatment. The improvement, resulting from visual stimulation, was due to a good functional recovery by a better usage of the damaged visual pathways. The therapy included prescribing corrective glasses and implementing secondary occlusion of the better eye for 4 months, which was protracted for another 4 months, leading to further improvements in visual acuity.

Conclusions
The case report shows that addressing even minor refractive errors and implementing anti-amblyopia therapy can significantly improve vision in children with CVI, even without co-existing amblyopia. It also highlights the importance of early intervention and multidisciplinary rehabilitation in children with CVI, focusing on motor and cognitive skills. Additionally, it emphasizes the need for further research to establish evidence-based practice standards for improving vision in children with CVI.
Comparison of D2 vs D3 lymph node dissection for RIght COloN cancer (RICON): study protocol for an international multicenter open-label randomized controlled trial
Authors: Balaban Vladimir , Mutyk Mikhail , Bondarenko Nikolay , Zolotukhin Stanislav , Sovpel Oleg , Sovpel Igor , Zykov Dmitriy , Rublevskiy Igor , Klochkov Mikhail , Prado Alfredo Ponce , He Mingze , Tsarkov Petr 
Published: July 2024

Abstract
Background
Colon cancer is a global health concern, ranking fifth in both new diagnoses and deaths among tumors worldwide. Surgical intervention remains the primary treatment for localized cases, with a historical evolution marked by a focus on short-term outcomes. While Japan pioneered radical tumor removal with a systematic categorization of lymph nodes (D1, D2, D3), the dissemination of Japanese practices to the West was delayed until 90th of last century. Discrepancies between Japanese D3 dissection and the CME with CVL principle persist, with variations in longitudinal margins and recommended procedures. Non-randomized trials indicate the superiority of D3 over D2, but a consensus is lacking.

Methods
This prospective, international, multicenter, randomized controlled trial employs a two-arm, parallel-group, open-label design to rigorously compare the 5-year overall survival outcomes between D2 and D3 lymph node dissection in stage II-III right colon cancer. Building on prior studies, the trial aims to address existing knowledge gaps and provide a comprehensive evaluation of the outcomes associated with D3 dissection. The study population comprises patients with right colon cancer, ensuring a focused investigation into the specific context of this disease. The trial design emphasizes its global scope and collaboration across multiple centers, enhancing the generalizability of the findings.

Discussion
This study’s primary objective is to elucidate the potential superiority in 5-year overall survival benefits of D3 lymph node dissection compared to the conventional D2 approach in patients with stage II-III right colon cancer. By examining this specific subset of patients, the research aims to contribute valuable insights into optimizing surgical strategies for improved long-term outcomes. The trial’s international and multicenter nature enhances its applicability across diverse populations. The outcomes of this study may inform future guidelines and contribute to the ongoing discourse surrounding the standardization of colon cancer surgery, particularly in the context of right colon cancer.

Trial registration
ClinicalTrials.gov NCT03200834. Registered on June 27, 2017.
Case report: two novel PPARG pathogenic variants associated with type 3 familial partial lipodystrophy in Brazil
Authors: da Silva Monique Alvares , Soares Reivla Marques Vasconcelos , de Oliveira Filho Antônio Fernandes , Campos Leonardo René Santos , de Lima Josivan Gomes , de Melo Campos Julliane Tamara Araújo 
Published: July 2024

Abstract
Introduction and aim
Type 3 Familial Partial Lipodystrophy (FPLD3) is a rare metabolic disease related to pathogenic PPARG gene variants. FPLD3 is characterized by a loss of fatty tissue in the upper and lower limbs, hips, and face. FPLD3 pathophysiology is usually associated with metabolic comorbidities such as type 2 diabetes, insulin resistance, hypertriglyceridemia, and liver dysfunction. Here, we clinically and molecularly characterized FPLD3 patients harboring novel PPARG pathogenic variants.

Materials and methods
Lipodystrophy-suspected patients were recruited by clinicians from an Endocrinology Reference Center. Clinical evaluation was performed, biological samples were collected for biochemical analysis, and DNA sequencing was performed to define the pathogenic variants associated with the lipodystrophic phenotype found in our clinically diagnosed FPLD subjects. Bioinformatics predictions were conducted to characterize the novel mutated PPARγ proteins.

Results
We clinically described FPLD patients harboring two novel heterozygous PPARG variants in Brazil. Case 1 had the c.533T > C variant, which promotes the substitution of leucine to proline in position 178 (p.Leu178Pro), and cases 2 and 3 had the c.641 C > T variant, which results in the substitution of proline to leucine in the position 214 (p.Pro214Leu) at the PPARγ2 protein. These variants result in substantial conformational changes in the PPARγ2 protein.

Conclusion
Two novel PPARG pathogenic variants related to FPLD3 were identified in a Brazilian FPLD cohort. These data will provide new epidemiologic data concerning FPLD3 and help understand the genotype-phenotype relationships related to the PPARG gene.
No beneficial effect of aerobic whole-body electromyostimulation on lower limbs strength and power – a randomized controlled trial
Authors: Krause Anne , Centner Christoph , Walther Moritz , Memmert Daniel , Walser Nicolas , Ritzmann Ramona 
Published: July 2024

Abstract
Background
Applying whole-body electromyostimulation (wbEMS) to voluntary activation of the muscle is known to impact motor unit recruitment. Thus, wbEMS as an additional training stimulus enhances force-related capacities. This study aimed to evaluate the mono- and multiarticular strength adaptations to a running intervention with wbEMS compared to running without wbEMS.

Methods
In a randomized controlled trial (RCT), 59 healthy participants (32 female/ 27 male, 41 ± 7 years) with minor running experience conducted an eight-week running intervention (2x/ week à 20 min) with a wbEMS suit (EG) or without wbEMS (control group, CG). Maximal isokinetic knee extensor and flexor strength and jump height during countermovement jumps were recorded prior and after the intervention to assess maximal strength and power.

Results
Following eight weeks of running, maximal isokinetic knee extension torque decreased significantly over time for both interventions (EG $$\Delta$$
Δ
-4%, CG $$\Delta$$
Δ
-4%; F(1, 44.14) = 5.96, p = 0.02, $${\upeta }$$
η
= 0.12). No changes were observed for flexion torque (F(1, 43.20) = 3.93, p = 0.05, $${\upeta }$$
η
= 0.08) or jump height (F(1, 43.04) = 0.32, p = 0.57, $${\upeta }$$
η
= 0.01).

Conclusions
The outcomes indicate that there is no additional effect over neuromuscular function adaptations with the inclusion of wbEMS during running training. Knee extensor strength is even slightly reduced which supports the principle of training specificity in regards to strength adaptation. We conclude that strength improvements cannot be achieved by running with wbEMS.

Trial registration
German Clinical Trials Register, ID DRKS00026827, date 10/26/21.
Quantitative assessment of preoperative brain development in pediatric congenital heart disease patients by synthetic MRI
Authors: Xu Shengfang , Ma Zihan , Zhang Jinlong , Wang Shaoyu , Ge Xin , Yue Songhong , Li Xinyi , Qian Jifang , Zhu Dalin , Liu Guangyao , Zhang Jing 
Published: July 2024

Abstract
Objectives
This study investigated the quantitative assessment and application of Synthetic MRI (SyMRI) for preoperative brain development in children with congenital heart disease (CHD).

Methods
Forty-three CHD patients aged 2–24 months were prospectively included in the observation group, and 43 healthy infants were included in the control group. The SyMRI scans were processed by postprocessing software to obtain T1, T2, and PD maps. The values of T1, T2, and PD in different brain regions were compared with the scores of the five ability areas of the Gesell Development Scale by Pearson correlation analysis.

Results
In the observation group, the T1 values of the posterior limb of the internal capsule (PLIC), Optic radiation (PTR), cerebral peduncle, centrum semiovale, occipital white matter, temporal white matter, and dentate nucleus were greater than those in the control group. In the observation group, the T2 values of the PLIC, PTR, frontal white matter, occipital white matter, temporal white matter, and dentate nucleus were greater than those in the control group. Pearson correlation analysis revealed that the observation group had significantly lower Development Scale scores. In the observation group, the T2 value of the splenium of the corpus callosum was significantly positively correlated with the personal social behavior score. The AUCs for diagnosing preoperative brain developmental abnormalities in children with CHD using T1 values of the temporal white matter and dentate nucleus were both greater than 0.60.

Conclusions
Quantitative assessment using SyMRI can aid in the early detection of preoperative brain development abnormalities in children with CHD.

Critical relevance statement
T1 and T2 relaxation values from SyMRI can be considered as a quantitative imaging marker to detect abnormalities, allowing for early clinical evaluation and timely intervention, thereby reducing neurodevelopmental disorders in these children.

Key Points

T1 and T2 relaxation values by SyMRI are related to myelin development.

Evaluated development quotient markers were lower in the observation compared to the control group.

SyMRI can act as a reference indicator for brain development in CHD children.

Graphical Abstract
Research progress and prospects of benefit-risk assessment methods for umbilical cord mesenchymal stem cell transplantation in the clinical treatment of spinal cord injury
Authors: Shen Ruoqi , Lu Yubao , Cai Chaoyang , Wang Ziming , Zhao Jiayu , Wu Yingjie , Zhang Yinian , Yang Yang 
Published: July 2024

AbstractOver the past decade, we have witnessed the development of cell transplantation as a new strategy for repairing spinal cord injury (SCI). However, due to the complexity of the central nervous system (CNS), achieving successful clinical translation remains a significant challenge. Human umbilical cord mesenchymal stem cells (hUMSCs) possess distinct advantages, such as easy collection, lack of ethical concerns, high self-renewal ability, multilineage differentiation potential, and immunomodulatory properties. hUMSCs are promising for regenerating the injured spinal cord to a significant extent. At the same time, for advancing SCI treatment, the appropriate benefit and risk evaluation methods play a pivotal role in determining the clinical applicability of treatment plans. Hence, this study discusses the advantages and risks of hUMSCs in SCI treatment across four dimensions—comprehensive evaluation of motor and sensory function, imaging, electrophysiology, and autonomic nervous system (ANS) function—aiming to improve the rationality of relevant clinical research and the feasibility of clinical translation.
Clinical exome analysis and targeted gene repair of the c.1354dupT variant in iPSC lines from patients with PROM1-related retinopathies exhibiting diverse phenotypes
Authors: Puertas-Neyra Kevin , Coco-Martin Rosa M. , Hernandez-Rodriguez Leticia A. , Gobelli Dino , Garcia-Ferrer Yenisey , Palma-Vecino Raicel , Tellería Juan José , Simarro Maria , de la Fuente Miguel A. , Fernandez-Bueno Ivan 
Published: July 2024

Abstract
Background
Inherited retinal dystrophies (IRD) are one of the main causes of incurable blindness worldwide. IRD are caused by mutations in genes that encode essential proteins for the retina, leading to photoreceptor degeneration and loss of visual function. IRD generates an enormous global financial burden due to the lack of understanding of a significant part of its pathophysiology, molecular diagnosis, and the near absence of non-palliative treatment options. Patient-derived induced pluripotent stem cells (iPSC) for IRD seem to be an excellent option for addressing these questions, serving as exceptional tools for in-depth studies of IRD pathophysiology and testing new therapeutic approaches.

Methods
From a cohort of 8 patients with PROM1-related IRD, we identified 3 patients carrying the same variant (c.1354dupT) but expressing three different IRD phenotypes: Cone and rod dystrophy (CORD), Retinitis pigmentosa (RP), and Stargardt disease type 4 (STGD4). These three target patients, along with one healthy relative from each, underwent comprehensive ophthalmic examinations and their genetic panel study was expanded through clinical exome sequencing (CES). Subsequently, non-integrative patient-derived iPSC were generated and fully characterized. Correction of the c.1354dupT mutation was performed using CRISPR/Cas9, and the genetic restoration of the PROM1 gene was confirmed through flow cytometry and western blotting in the patient-derived iPSC lines.

Results
CES revealed that 2 target patients with the c.1354dupT mutation presented monoallelic variants in genes associated with the complement system or photoreceptor differentiation and peroxisome biogenesis disorders, respectively. The pluripotency and functionality of the patient-derived iPSC lines were confirmed, and the correction of the target mutation fully restored the capability of encoding Prominin-1 (CD133) in the genetically repaired patient-derived iPSC lines.

Conclusions
The c.1354dupT mutation in the PROM1 gene is associated to three distinct AR phenotypes of IRD. This pleotropic effect might be related to the influence of monoallelic variants in other genes associated with retinal dystrophies. However, further evidence needs to be provided. Future experiments should include gene-edited patient-derived iPSC due to its potential as disease modelling tools to elucidate this matter in question.

Graphical Abstract
Impact of a family support intervention on hospitalization costs and hospital readmissions among ICU patients at high risk of death or severe functional impairment
Authors: Andersen Sarah K. , Chang Chung-Chou H. , Arnold Robert M. , Pidro Caroline , Darby Joseph M. , Angus Derek C. , White Douglas B. ,   the Pairing Re-engineered Intensive Care Teams with Nurse-driven Emotional Support, Relationship building (PARTNER) Investigators
Published: July 2024

Abstract
Background
Patients with advanced critical illness often receive more intensive treatment than they would choose for themselves, which contributes to high health care costs near the end of life. The purpose of this study was to determine whether a family support intervention delivered by the interprofessional ICU team decreases hospitalization costs and hospital readmissions among critically ill patients at high risk of death or severe functional impairment.

Results
We examined index hospitalization costs as well as post-discharge utilization of acute care hospitals, rehabilitation and skilled nursing facilities, and hospice services for the PARTNER trial, a multicenter, stepped-wedge, cluster randomized trial of an interprofessional ICU family support intervention. We determined patients’ total controllable and direct variable costs using a computerized accounting system. We determined post-discharge resource utilization (as defined above) by structured telephone interview at 6-month follow-up. We used multiple variable regression modelling to compare outcomes between groups. Compared to usual care, the PARTNER intervention resulted in significantly lower total controllable costs (geometric mean: $26,529 vs $32,105; log-linear coefficient: − 0.30; 95% CI − 0.49, − 0.11) and direct variable costs ($3912 vs $6034; − 0.33; 95% CI − 0.56, − 0.10). A larger cost reduction occurred for decedents ($20,304 vs. $26,610; − 0.66; 95% CI − 1.01, − 0.31) compared to survivors ($31,353 vs. $35,015; − 0.15; 95% CI − 0.35,0.05). A lower proportion in the intervention arm were re-admitted to an acute care hospital (34.9% vs 45.1%; 0.66; 95% CI 0.56, 0.77) or skilled nursing facility (25.3% vs 31.6%; 0.63; 95% CI 0.47, 0.84).

Conclusions
A family support intervention delivered by the interprofessional ICU team significantly decreased index hospitalization costs and readmission rates over 6-month follow-up.
Trial registration Trial registration number: NCT01844492
Asymptotic stability and bifurcations of a perturbed McMillan map
Authors: Qian Lili , Lu Qiuying , Deng Guifeng 
Published: July 2024

AbstractThis paper presents various bifurcations of the McMillan map under perturbations of its coefficients, such as period-doubling, pitchfork, and hysteresis bifurcation. The associated existence regions are located. Using the quasi-Lyapunov function method, the existence of asymptotically stable fixed point is also demonstrated.
Profiles of child labour: prevalence, activities, contexts, and children’s harm extent in Raya-Kobo and Angot Districts, Ethiopia
Authors: Weldeyesus Mengistu Abate , Alemu Bamlaku Alamirew 
Published: July 2024

AbstractUsing a mixed research design, the overall objective of this study is to investigate the profiles of child labour in Ethiopia’s districts of Raya-Kobo and Angot. The study’s specific objectives are to examine types of activities and prevalence of child labour, to identify the children’s working contexts, and to evaluate the extent of harm children face in workplaces. The study hypothesizes the existence of significant variations in the profiles of child labour (activity types, prevalence rates, settings, and level of harm to children) as a result of several circumstances. While survey methodology was used to collect primary data from 431 randomly selected respondents, desk review and document analysis were also used to gather secondary data. The sampling procedures used include multi-stage purposive and systematic random sampling. Descriptive and inferential (Ordered Probit Regression model) methods of data analysis are utilized to analyze the data. The results of the descriptive analysis demonstrate a high incidence and magnitude of child labour, as well as children’s early entry to work. The regression analysis reveals children’s exposure to high levels of harm at work, which is directly exacerbated by household age, income diversification, land fragmentation, livestock number, shocks, and the predicted value of remittances. Contrarily, access to rural transportation, household heads’ education level, cart ownership, and family size reduce children’s harm extent while working. The study highlights the need to design strategies for age-appropriate work to protect children from hazardous and high-intensity activities, undertake community awareness campaigns about the impact of child labour on children, and strengthen local stakeholders’ capacity. Additionally, connecting rural areas and farmers’ croplands to towns or major routes via repaired or new roads would be beneficial.