bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late-onset Renal involvement presenting with TMA and tubular injury in cobalamin C disease: a report of three cases and review of the literature
Authors: Bao Daorina , Yang Hong-yu , Yin Yan-qi , Wang Su-xia , Li Yang , Zhang Xin , Su Tao , Xu Rong , Li Chun-yue , Zhou Fu-de 
Published: October 2023

Abstract

Background: Mutation of methylmalonic aciduria type C and homocystinuria (MMACHC) gene causes inherited cobalamin C disease (cblC), an inborn error of cobalamin metabolism, which presents with methylmalonic aciduria (MMA) and homocystinuriain clinical. Renal complications may also be present in patients with this inborn deficiency. The most common histological change is presented with thrombotic microangiopathy (TMA). However, to our acknowledge, renal tubular injury in the late-onset presentation of cblC is rarely been reported.This study provides a detailed description of the characteristics of kidney disease in cblC deficiency, aiming to improve the early recognition of this treatable disease for clinical nephrologists.
Case presentation: Here we described three teenage patients who presented with hematuria, proteinuria, and hypertension in clinical. They were diagnosed with renal involvement due to cblC deficiency after laboratory tests revealed elevated serum and urine homocysteine, renal biopsy showed TMA and tubular injury, along with genetic testing showing a heterogeneous compound mutation of MMACHC. Hydroxocobalamin, betaine, and L-carnitine were administered to these patients. All of them improved, with decreased homocysteine, controlled blood pressure, and kidney outcomes recovered, ranging from recovery of kidney function to kidney failure.
Conclusions: The clinical diagnosis of cblC disease associated with kidney injury should be considered in patients with unclear TMA accompanied by a high concentration of serum homocysteine, even in teenagers or adults. Early diagnosis and timely intervention are vital to improving the prognosis of cobalamin C disease.
Prediction of hamstring graft diameter based on anthropometric variables in anterior cruciate ligament reconstruction
Authors: Thapa Sushil , Panta Sunil , Upadhyay Hari Prasad , Pokharel Jhapindra 
Published: October 2023

Abstract

Background: The diameter of the graft is an important determinant of successful anterior cruciate ligament (ACL) reconstruction. If the diameter of hamstring graft can be predicted accurately, we can determine whether this graft is suitable or we need to harvest a different one. There is no published literature in the Nepali population on the ability to accurately predict the diameter of hamstring grafts using anthropometric variables in ACL reconstruction.
Hypothesis: We can accurately predict the hamstring autograft diameter using some anthropometric variables.
Study Design: Cross-sectional, Descriptive
Methods: An analytical cross-sectional study was conducted among seventy-four patients from January 2021 to December 2022 who underwent ACL reconstruction using a hamstring autograft in Department of Orthopaedics of Bharatpur Hospital. Several anthropometric variables recorded were; (1) Age (2) Gender (3) BMI (4) Height (5) Weight and (6) Thigh length. The hamstring grafts (semitendinosus and gracilis) were either quadrupled or pentapled and the diameter was measured with a cylindrical sizer. Pearson correlation coefficients (r) and bivariate analysis were used to identify the relationship between the predictor variables (age, gender, BMI, height, weight and thigh length) and outcome variable (hamstring graft diameter).
Results: There were 19 females and 55 males. There was statistically significant association between diameter with gender (p-value=0.004), BMI(p-value=0.048), height (p-value=0.005), weight(p-value=0.005), thigh length (p-value=0.037). Age was found to have a negative correlation with graft diameter (p-value =0.401). An equation has been formulated to predict the graft diameter in relation to the height of an individual.
Conclusion: Out of all the variables, height was the strongest predictor of hamstring graft diameter. Patients taller than 160 cm, weighing more than 65 kg, with BMI more than 25 kg/m2 and thigh length more than 37 cm had graft diameter 8mm or more. The graft diameter was found to be inversely related to age, with individuals older than 40 years having graft sizes less than 8 mm.
The Anthro-Thumb: A Biomimetic Soft Robotic CarpoMetaCarpal (CMC) Saddle Joint for the Thumb
Authors: Symes Declan , Sardinha Emanuel David Nunez , Jafari Aghil , Hussain Javeed , Etoundi Appolinaire 
Published: October 2023

Abstract

Robotic hand design is multifaceted, with the design of robotic thumbs often oversimplified for ease of manufacture, control, and reliability. While soft robotics presents a plethora of design possibilities, this paper delves into the conception, evolution, and evaluation of a unique bio-inspired soft thumb. By harnessing the biologically accurate mechanisms of the CMC joint, this research seeks to enhance the functionality of tendon-driven robotic hands. The introduced Anthro-Thumb is a biomimetic soft robotic thumb, providing a comprehensive range of motion at the thumb’s base, all the while ensuring cost-efficiency and reduced mechanical intricacy. A holistic overview of thumb bio-mechanics is presented, extracting relevant biological data and juxtaposing it with the prevailing trends in robotic thumb systems. When subjected to the Kapandji physiotherapy test, the design secured a commendable score of 9. The findings affirm that employing biomimetic soft structured robotic CMC saddle joints is a promising strategy to navigate the intricacies associated with robotic thumb development in robotic hands.
A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+ breast cancer cells
Authors: Melvin Adam , Quesada Braulio Ortega , Cuccia Jonathan , Coates Rachael , Nassar Blake , Littlefield Ethan , Martin Elizabeth 
Published: October 2023

Abstract
Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to therapy. It is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer; however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause this. In this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress (FSS) found in human vasculature was designed and fabricated. This device provides a platform to evaluate the effects of FSS on MCF-7 cell line, a receptor positive (ER+) breast cancer cell line, during circulation in the vessels. Elucidation of the effects of FSS on MCF-7 cells was carried out utilizing two approaches: single cell analysis and bulk analysis. For single cell analysis, cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device (on-chip). Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting (off-chip). It was found that cells exposed to an FSS magnitude of 10 dyn/cm2 with a residence time of 60 seconds enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell level. To understand possible mechanisms for enhanced Ki67 expression, on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK, AKT, and JAK/STAT. Results demonstrated that after shearing the cells phosphorylation of p-AKT, p-mTOR, and p-STAT3 were observed. However, there was no change in p-ERK1/2. AKT is a mediator of ER rapid signaling, analysis of phosphorylated ERα was carried out and no significant differences between sheared and non-sheared populations were observed. Taken together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer cells. These findings provide additional information that may help inform why cancer cells located at metastatic sites are usually more aggressive than primary breast cancer cells.
Extremal Growth of Multiple Toeplitz Operators and Implications for Numerical Stability of Approximation Schemes
Authors: Rastogi Yash 
Published: October 2023

Abstract
This paper pioneers the application of reproducing kernel spaces in proving the stability of numerical methods for approximating linear differential equations. We analyze families of products of Hardy space Toeplitz operators that do not fall into a well-understood class of operators through explicit techniques, many of which are based upon exploiting the reproducing kernel Hilbert space structure of the Hardy space on the unit disk and properties of Toeplitz operators. This results in bounds that would not be feasible through more general functional analytic techniques. In particular, for these operators, we relate the power bound and a resolvent condition of Kreiss-Ritt type since it is well-known that such a relationship implies the stability of certain methods for the numerical solution of linear differential equations. Our methods apply \textit{mutatis mutandis} to operators of the form $T_{g(z)}^{-1}T_{f(z)}T_{g(z)}$ where $f(z)$ is a polynomial in $z$ and $\overline{z}$ and $g(z)$ is a polynomial in $z$, which arise frequently in the numerical solution of the Cauchy problem for linear ordinary, partial, and delay differential equations used as models for processes in science and engineering.
MSC Classification: 46E22, 47B35, 65M12, 65L20
Pyridostigmine attenuates hypertension by inhibiting activation of the renin-angiotensin system in the hypothalamic paraventricular nucleus
Authors: Lu Yi , Wang Yi-dong , Xu Tian-qi , Zhao Xu-he , Zhou Jun , Jin Lian-hai , Liu Jin-jun 
Published: October 2023

Abstract
Purpose
Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension. Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension.
Methods
2K1C rats received pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated.
Results
Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression.
Conclusions
Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.
Harnessing Ceramic Hydroxyapatite as an Effective Polishing Strategy to Remove Product- and Process-related Impurities in Bispecific Antibody Purification
Authors: Zhang Wei , Ingavat Nattha , Xinhui Wang , Min Liew Jia , Mahfut Farouq Bin , Pui But Ka , Jiun Kok Yee , Bi Xuezhi , Yang Yuansheng , Shintaro Kobayashi , Maria Tsoumpra 
Published: October 2023

Abstract
Bispecific antibody (bsAb), a novel therapeutic modality, provides excellent treatment efficacy, yet poses numerous challenges to downstream process development, which are mainly due to high diversity and complexity of bsAb structures and impurity profiles. The mixed-mode medium, ceramic hydroxyapatite (CHT), allows proteins to interact with its calcium sites (C-sites) through metal affinity and/or its phosphate sites (P-sites) through cation exchange interactions. This dual binding capability potentially offers unique bind and elute behaviours for different proteins of interest, resulting in optimal product purity when suitable elution conditions are employed. In this study, the effectiveness of CHT as a polishing step for bsAb purification was investigated across three model molecules and benchmarked against the traditional cation exchange chromatography (CEX). For both asymmetric and symmetric IgG-like bsAb post Protein A eluates, at least 97% product purity was achieved after CHT polishing. CHT delivered a superior aggregate clearance to CEX, resulting in low high molecular weight (HMW) impurities (0.5%) and low process-related impurities in the product pools. CHT also yielded significantly less “chromatography-induced aggregation” for all aggregation-prone bsAb molecules. Developability of CHT for more efficient low molecular weight (LMW) impurity removal was further demonstrated via post-load-wash (PLW) optimization with the selected bsAbs, resulting in up to 48% additional LMW reduction. Furthermore, possible mechanistic explanation about CHT performance on both process- and product-related impurity removal in bsAb polishing was proposed. Positive CHT C-site cooperation mediated effective impurity removal and mitigated “chromatography-induced aggregation”, and domain composition and size of bsAbs molecules may determine the effectiveness of such C-site cooperation.
Association of oxidative stress in mild patchy alopecia areata: a case- control study
Authors: Kakşi Sümeyye Altıntaş , Ülfer Gözde , Çakıter Alkım , Özen Tunç , Yiğitbaşı Türkan , Özdemir Mustafa 
Published: October 2023

Abstract
Background
Alopecia areata (AA) is a chronic immune-mediated disease characterized by sudden-onset, sharply circumscribed alopecic patches that can occur in any part of the body, mostly on the scalp. Its etiology has not yet been fully clarified. Recently, increasing data regarding the relationship between oxidative stress and AA are available in the literature.
Objectives
To evaluate the effect of oxidative stress with ischemia-associated albumin (IMA) and conventional methods together with total oxidant state (TOS), total antioxidant state (TAS) and oxidative stress index (OSI) in patients with new-onset mild AA.
Methods
The study was conducted as a single-center, prospective, case-control study and included 36 patients with AA and 34 healthy volunteers. Serum TAS, TOS, OSI and IMA levels were compared between the two groups.
Results
The TOS and OSI levels were found to be significantly higher and the TAS level was significantly lower in the AA group. Although the IMA level was higher in the AA group, it did not significantly differ from the control group.
Conclusions
This study supports the presence of a relationship between oxidative stress and AA. Antioxidant defense mechanisms may be delayed to compensate for the high oxidant levels in mild acute AA. Oxidative damage can also be caused by non-ischemic pathways, and IMA levels may become more pronounced in more chronic and severe cases. We consider that there is a need to investigate individual oxidative causes in larger and different subgroup populations of AA and re-evaluate related markers after antioxidant treatment.
Differentiation of benign and metastatic lymph nodes in soft tissue sarcoma
Authors: Burkhard-Meier Anton , Jurinovic Vindi , Berclaz Luc M. , Albertsmeier Markus , Dürr Hans Roland , Klein Alexander , Knösel Thomas , Gioia Dorit Di , Unterrainer Lena M. , Schmidt-Hegemann Nina-Sophie , Ricke Jens , Bergwelt-Baildon Michael , Kunz Wolfgang G. , Lindner Lars H. 
Published: October 2023

Abstract
Introduction:
Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes in staging imaging are a frequent matter of discussion in multidisciplinary tumor boards. Predictive markers are needed to enable stratification and improve treatment of STS patients.
Materials and Methods
In this study, 56 STS patients with radiologically suspicious and subsequently histologically examined lymph nodes (LN) were reviewed. Patients with benign (n = 26) and metastatic (n = 30) LN were analyzed with regard to clinical, laboratory and radiological parameters.
Results
Short axis diameter (SAD) and long axis diameter (LAD) of LN were significantly larger in patients with LNM (median 22.5 vs. 14mm, p < 0.001 and median 29.5 vs. 21mm, p = 0.003, respectively). In addition, presence of central necrosis and high maximal standardized uptake value (SUVmax) in FDG-PET-CT scan were significantly associated with LNM (60 vs. 11.5% of patients, p < 0.001 and median 8.59 vs. 3.96, p = 0.013, respectively). With systemic therapy, a slight median size regression per time was observed in both metastatic and benign LN. Serum LDH and CRP levels were significantly higher in patients with LNM (median 247 vs. 187.5U/l, p = 0.005 and 1.5 vs. 0.55mg/dl, p = 0.039, respectively).
Conclusion
This study shows significant associations between LNM and imaging features as well as laboratory parameters of STS patients. The largest SAD, SUVmax in FDG-PET-CT scan, the presence of central necrosis, and high serum LDH level are the most important parameters to distinguish benign from metastatic LNs.
Attractiveness and gender dynamics in surgical specialties: A comparative analysis of French medical graduates (2017-2022)
Authors: Saadé Saadé , Delafontaine Arnaud , Cattan Johann , Celanie Doris , Saiydoun Gabriel 
Published: October 2023

Abstract
Background: This study aims to describe the attractiveness of surgical specialties and the evolution of the male-female distribution among French medical graduates (FMG) from 2017 to 2022.
Methods: Our database included the candidates’ ranking, sex and choice of specialty from 2017 to 2022. It included all French medical graduates from 2017 to 2022 and all French medical schools. A linear regression was performed to predict future trends. Dependent variables were median and mean rankings and the percentage of women. The independent variable was year of application. A Pearson correlation was performed to examine any relationship with mean workweek.
Results: A total number of 5,270 residents chose a surgical programme between 2017 and 2022. The number of residents who were assigned their desired surgical programme held stable at 878±10 surgical residents per year. Plastic and reconstructive surgery remained the most frequently chosen surgical programme. Thoracic and cardiovascular surgery was the least frequently chosen surgical programme between 2017 and 2022. The mean ranking for a candidate choosing a surgical programme rose significantly by 9% from 2017 to 2022 (p<0.01). Neurosurgery exhibited the greatest fall as a surgical specialty as its rankings increased by 163.66% (p=0.003). Maxillo-facial surgery was the only specialty with a statistically significant fall in its ranking by -35.82% (p=0.03). The overall proportion of women was 51.13%. Obstetrics-and-gynaecology was the highest represented specialty among female candidates, being composed of 83.88% of women on average. Orthopaedic surgery was the lowest represented, being composed of 28.65% of women on average. The number of female surgical residents increased significantly over the six-year period, by 7.6% (p<0.01).
Conclusions:More and more medical school graduates decide not to choose surgery for their residency programme. Some specialties continue to be attractive while many are losing their appeal. While there does appear to be progress towards gender equity, further investigation is necessary to assess its actual implementation.
Predicting molecular events underlying rare diseases using variant annotation, aberrant gene expression events, and human phenotype ontology
Authors: Yepez Vicente , Smith Nicholas H. , Scheller Ines , Gagneur Julien , Mertes Christian 
Published: October 2023

Abstract

Rare genetic diseases often pose significant challenges for diagnosis. Over the past years, RNA sequencing and other omics modalities have emerged as complementary strategies to DNA sequencing to enhance diagnostic success. In the 6th round of the Critical Assessment of Genome Interpretation (CAGI), the SickKids clinical genomes and transcriptomes challenge aimed to evaluate the diagnostic potential of multi-omics approaches in identifying and resolving undiagnosed genetic disorders. Here, we present our participation in that challenge, where we leveraged genomic, transcriptomic, and clinical data from 79 children with diverse suspected Mendelian disorders to develop a model predicting the causal gene. We employed a machine learning model trained on a cohort of 93 solved mitochondrial disease samples to prioritize candidate genes. In our analysis of the SickKids cohort, we successfully prioritized the causal genes in 2 out of the 3 diagnosed individuals exhibiting abnormalities at the RNA-seq level and 6 cases out of the 12 where no effect on RNA was seen making our solution one of the winning ones. The challenge and our approach highlight the invaluable contributions of an integrative analysis of genetic, transcriptomic, and clinical data to pinpoint the disease-causing gene.
The challenge was evaluated using three previously diagnosed individuals in which RNA-seq data proved helpful for diagnostics together with twelve individuals diagnosed solely through DNA analysis. Some of those cases were reported after the challenge by Deshwar et al. Our model was able to prioritize 2 out of the 3 RNA-seq supported cases on the top 3 ranks (Table 1), while reaching a recall of over 50% under the top 100 genes across all 15 cases (Fig. 4).