bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure analysis of cement-biochar composites
Authors: Lorenzoni Renata , Cunningham Patrick , Fritsch Tobias , Schmidt Wolfram , Kruschwitz Sabine , Bruno Giovanni
Published: October 2023

The use of biochar, as a concrete constituent has been proposed to reduce the massive carbon footprint of concrete. Due to the low density and complex porosity of biochar, microstructural analysis of Portland cement-biochar composites is challenging. This causes challenges to the improvement of micro-scale understanding of biochar composite behavior. This work advances the microstructural understanding of Portland cement composites with 0, 5, and 25 volume percent (vol%) of cement replaced with wood biochar by applying common characterization techniques of mercury intrusion porosimetry (MIP), gas sorption, scanning electron microscopy (SEM), and isothermal heat flow calorimetry (HFC) in conjunction with 1H nuclear magnetic resonance (NMR) and micro-X-ray computed tomography (XCT) analysis techniques. The combination of these techniques allows a multi-scale investigation of the effect of biochar on the microstructure of cement paste. NMR and XCT techniques allow the observation and quantification of the pore space. HFC and MIP confirmed that biochar absorbs moisture and reduces the effective water-cement ratio. Gas sorption, MIP, and NMR shows that 5 vol% replacement does not significantly affect the gel and capillary pore structures. Results from XCT (supported by MIP and NMR) show that biochar can reduce the formation of larger pores. Importantly, XCT results suggest that biochar can act as a flaw in the microstructure which could explain reductions in the mechanical properties. Overall, the mechanical properties already analyzed in the literature are consistent with the microstructural changes observed, and these results highlight the need to carefully tailor the volume fraction of biochar to control its effect on the paste microstructure.
Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: A phase I/II randomized study
Authors: Noronha Vanita , Patil Vijay , Menon Nandini , Kalra Devanshi , Singh Ajaykumar , Shah Minit , Goud Supriya , Jobanputra Kunal , Nawale Kavita , Shah Srushti , Chowdhury Oindrila Roy , Mathrudev Vijayalakshmi , Jogdhankar Shweta , Singh Madhu , Singh Ashish , Adak Supriya , Sandesh Mayuri , R Arunkumar , Ankathi Sumankumar , Mahajan Abhishek , Prabhash Kumar
Published: October 2023

Background:
Pantoprazole decreases acidity of the tumor-microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy.
Methods:
We conducted a phase I/II RCT in adult head and neck squamous cell carcinoma(HNSCC) patients planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy +/- Intravenous Pantoprazole. Primary endpoint in phase I was to determine the maximum safe dose of Intravenous Pantoprazole whereas it was progression free survival(PFS) in phase II.
Results:
The dose of IV Pantoprazole established in phase I was 240mg. Between Nov’18 and Oct’20, we recruited 120 patients in phase II, 59 on Pantoprazole and 61 on Standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was Intravenous Cisplatin in 22% and Oral-Metronomic-Chemotherapy(OMC) in 78%. Addition of Pantoprazole did not prolong PFS, 2.2months (95%CI, 2.07-3.19) in the Pantoprazole arm and 2.5months (95%CI, 2.04-3.81, HR, 1.14; 95%CI 0.78-1.66; P=0.48) in the standard arm. Response rates were similar; Pantoprazole arm 8.5%, standard arm 6.6%; P=0.175. OS was also similar; 5.6months (95%CI, 4.47-8.51) in the Pantoprazole arm and 5.4months (95%CI, 3.48-8.54, HR 1.06; 95%CI 0.72-1.57; P=0.75) in the standard arm. Grade >3 toxicities were similar.
Conclusion:
Intravenous Pantoprazole 240mg added to systemic therapy does not improve outcomes in patients with advanced HNSCC.
Nonequilibrium phase transition of a one dimensional system reaches the absorbing state by two different ways
Authors: Saif M. Ali
Published: October 2023

We study the nonequilibrium phase transitions from the absorbing phase to the active phase for the model of disease spreading (Susceptible-Infected-Refractory-Susceptible (SIRS)) on a regular one dimensional lattice. In this model, particles of three species (S, I and R) on a lattice react as follows: S + I → 2I with probability λ, I → R after infection time τI and R → I after recovery time τR. In the case of τR > τI , this model has been found to has two critical thresholds separate the active phase from absorbing phases [51]. The first critical threshold λc1 is corresponding to a low infection probability and second critical threshold λc2 is corresponding to a high infection probability. At the first critical threshold λc1, our Monte Carlo simulations of this model suggest the phase transition to be of directed percolation class (DP). However, at the second critical threshold λc2 we observe that, the system becomes so sensitive to initial values conditions which suggests the phase transition to be discontinuous transition. We confirm this result using order parameter quasistationary probability distribution and finite-size analysis for this model at λc2. Additionally, the typical space-time evolution of this model at λc2 shows that, the spreading of active particles are compact in a behavior which remind us the spreading behavior in the compact directed percolation.
Comparison of conventional MRI analysis versus MRI-based radiomics to predict the circumferential margin resection involvement of rectal cancer
Authors: Liang Hong , Ma Yanqing , Hang Yuan , Guan Zheng , Zhang Yang , Wei Yuguo , Wang Peng , Zhang Ming
Published: October 2023

Objectives: To compare the application of conventional MRI analysis and MRI-based radiomics to identify the circumferential resection margin (CRM) status of rectal cancer (RC).
Methods: A cohort of 301 RC patients were enrolled in this retrospective study. Conventional MRI characteristics included gender, age, diameter, distance to anus, MRI-based T/N phase, CEA, and CA 19-9, then the relevant logistic model (Logistic-cMRI) was built. MRI-based radiomics of rectal cancer and mesorectal fascia were calculated after volume of interest segmentation, and the logistic model of rectal cancer radiomics (Logistic-rcRadio) and mesorectal fascia radiomics (Logistic-mfRadio) were constructed. And the combined nomogram (nomo-cMRI/rcRadio/mfRadio) containing conventional MRI characteristics, radiomics of rectal cancer and mesorectal fascia was developed. The receiver operator characteristic curve (ROC) was delineated and the area under curve (AUC) was calculated the efficiency of models.
Results: The AUC of Logistic-cMRI was 0.864 (95%CI, 0.820 to 0.901). The AUC of Logistic-rcRadio was 0.883 (95%CI, 0.832 to 0.928) in the training set and was 0.725 (95%CI, 0.616 to 0.826) in the testing set. The AUCs of Logistic-mfRadio was 0.891 (95%CI, 0.838 to 0.936) in the training set and was 0.820 (95%CI, 0.725 to 0.905) in the testing set. The AUCs of nomo-cMRI/rcRadio/mfRadio were the highest in both the training set of 0.942 (95%CI, 0.901 to 0.969) and the testing set of 0.909 (95%CI, 0.830 to 0.959).
Conclusions: MRI-based radiomics of rectal cancer and mesorectal fascia showed similar efficacy in predicting the CRM status of RC. The combined nomogram performed better in assessment.
Autologous adipose-derived vascular stromal component injection offers a safe and effective method for treating knee osteoarthritis: A one-year double-blind, randomized controlled clinical trial
Authors: Lu Junyue , Xu Biaoping , Hu Jiaxuan , yu Jin , Kang Jiliang , Yu Yan , Wang Ying , Wen Youliang
Published: October 2023

Background: Currently, conservative treatment for knee osteoarthritis (KOA) has limited efficacy, and autologous adipose-derived stromal vascular fraction (SVF) knee injections as a novel treatment approach are receiving widespread attention. Our study aimed to explore the efficacy and safety of SVF treatment for KOA patients.
Methods: This double-blind, randomized controlled trial recruited unilateral KOA patients from the Rehabilitation Departments of the First, Second, and Third Affiliated Hospitals of Gannan Medical University. Sixty-six unilateral KOA participants were randomly divided into three groups for conventional treatment, SVF treatment, and a combination of SVF and conventional treatment. We compared the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Visual Analogue Scale (VAS) scores, range of motion (ROM) of the knee, cartilage degeneration situation, and the incidence, nature, and severity of adverse events after treatment at 7 days, 1 month, 6 months, and 12 months.
Results:A total of 62 patients completed the follow-up. There were no significant baseline differences among the groups. Our results demonstrated that, compared to baseline values, average VAS and WOMAC scores significantly decreased, while ROM significantly increased in the SVF and combination treatment groups during the 12-month follow-up, with a significant difference when compared to the control group (P< 0.05). Cartilage regeneration was observed in the combination treatment group at the 12-month follow-up (P < 0.05). No serious adverse events were observed during the 12-month follow-up, and no significant difference was noted in the incidence of complications among the three groups (P > 0.05).
Conclusion:A single SVF injection demonstrates good safety, no serious adverse reactions, and can achieve better therapeutic effects when combined with conventional treatment, which is worth further investigation and promotion in clinical practice.
Trial registration Chinese Clinical Trial Registry (ChiCTR2300074894). First trial registration in the format 18/08/2023
Boron nitride whiskers and nano alumina synergistically enhancing the vertical thermal conductivity of epoxy-cellulose aerogel nanocomposites
Authors: Li Zhaoyang , Pan Duo , Han Ziyuan , Kumar D. Jaya Prasanna , Ren Juanna , Hou Hua , El-Bahy Zeinhom M. , Mersal Gaber A. M. , Xu Ben Bin , Liu Yongzhi , Liu Chuntai , Ibrahim Mohamed M.
Published: October 2023

With the continuous innovation of electronic information technology, thermal interface materials, which mainly play the role of heat dissipation in microelectronic devices, will face great challenges. In this work, the boron nitride whiskers (BNWK)@Al2O3/cellulose aerogels (CA) obtained by electrostatic self-assembly one-dimensional BNWK and zero-dimensional nano-Al2O3 combined with directional freezing of CA. The obtained BNWK@Al2O3/CA not only has a unique vertical network structure, but also exhibits exceptional compressive mechanical strength, especially when the mass ratio of BNWK/nano-Al2O3 is 1:7, the compressive strength of BNWK@Al2O3(1:7)/CA reaches 97 kPa, based on the flexibility of the CA and the support of the rigid hybrid filler BNWK@Al2O3, the theoretical relaxation time of the composite is also as high as 25327 s. Furthermore, the thermal conductivity of the epoxy-based composite (BNWK@Al2O3/CA/EP) with a filler loading of 8.6 wt% is about 1.92 W/(m·K), which is 9.6 times that of pure EP, the excellent thermally conductive property is due to the accelerated phonon transport by the vertically arranged BNWK@Al2O3 network structure. Hence, this work provides a new idea for developing a new generation of thermal interface materials.
Non-equilibrium critical scaling and universality in a quantum simulator
Authors: De Arinjoy , Cook Patrick , Collins Katherine , Morong Will , Paz Daniel , Titum Paraj , Pagano Guido , Gorshkov Alexey , Maghrebi Mohammad , Monroe Christopher
Published: October 2023

Universality and scaling laws are hallmarks of equilibrium phase transitions and critical phenomena1-3. However, extending these concepts to non-equilibrium systems is an outstanding challenge. Despite recent progress in the study of dynamical phases4,5, the universality classes and scaling laws for non-equilibrium phenomena are far less understood than those in equilibrium6. In this work, using a trapped-ion quantum simulator with single-ion resolution, we investigate the non-equilibrium nature of critical fluctuations following a quantum quench to the critical point. We probe the scaling of spin fluctuations after a series of quenches to the critical Hamiltonian of a long-range Ising model. With systems of up to 50 spins, we show that the amplitude and timescale of the post-quench fluctuations scale with system size with distinct universal critical exponents. While a generic quench can lead to thermal critical behaviour, we find that a second quench from one critical state to another (i.e. a double quench) results in critical behaviour that does not have an equilibrium counterpart. Our results demonstrate the ability of quantum simulators to explore universal scaling beyond the equilibrium paradigm.
How to make some complications predictable consequences in Interventional Radiology
Authors: Ierardi Anna Maria , Ascenti Velio , Lanza Carolina , Carriero Serena , Amato Gaetano , Pellegrino Giuseppe , Giurazza Francesco , Torcia Pierluca , Carrafiello Gianpaolo
Published: October 2023

The aim of the article is to introduce a new term in post-procedural events related to the procedure itself. All the Societies and Councils report these events as complications and they are divided in mild, moderate and severe or immediate and delayed. On the other hand the term error is known as the application of a wrong plan, or strategy to achieve a goal. For the first time, we are trying to introduce the term “consequence”; assuming that the procedure is the only available and the best fit to clinical indication, a consequence should be seen as an expected and unavoidable occurrence of an "adverse event" despite correct technical execution.
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

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

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

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

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

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

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

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

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

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

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

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).
Soil-transmitted helminth infections: prevalence, incidence, post-treatment infection rate, and associated factors among children and young adults living in rural areas of Gabon
Authors: EDOA Jean Ronald , Adégbitè Bayodé Roméo , Honkpéhèdji Yabo Josiane , Zinsou Jeannot Fréjus , Boussougou-Sambe Stravensky Térence , Woldearegai Tamirat Gebru , Mordmüller Benjamin , Adegnika Ayola Akim , Dejon-Agobé Jean Claude
Published: October 2023

Background
Soil-transmitted helminth (STH) infections are of public health concern in endemic areas. For efficient control, the epidemiology of the disease needs to be updated. This report assesses the prevalence, incidence, post-treatment infection (PTI) rate, and risk factors of STH infections in two rural areas of Gabon.
Method
In this longitudinal and prospective study, participants aged six to 30 years from Lambaréné and vicinity were included and followed in two consecutive periods of six and nine months. Stool samples were obtained at the beginning and at the end of each follow-up phase (FUP). The Kato Katz technique was used for the detection of STH eggs while harada-mori technique and coproculture were used for the detection of larvae. Prevalence was determined at the three main time points of the study, incidence was assessed during the two study phases, and PTI was defined as an infection detected nine months post-treatment.
Results
A total of 262 participants were included. The overall prevalence of STH infections was 42% (95%CI: 34–50) and 44% (95%CI: 37–51) at baseline of both FUPs, respectively. Trichuris trichiura was the most prevalent species at each time point of assessment. The cumulative incidence at six- and nine-months follow-up of STH was 18% (95%CI: 12–27) and 35% (95%CI: 27–43), respectively, while the incidence rate was 41 (95%CI: 28–55) and 56 (95%CI: 46–67) per 100 person-years, respectively. The PTI rate at nine-months follow-up for T. trichiura, hookworm, and Ascaris lumbricoides was 58% (95%CI: 41–74), 31% (95%CI: 11–59) and 18% (95%CI: 5–40), respectively. The STH infection intensity was generally light.
Conclusion
The prevalence level of STH infection is moderate in the vicinity of Lambaréné, with T. trichiura being the most prevalent species. Our results reveal a rapid spread of the disease in the population mainly following intervention and particularly for trichuriasis, and therefore call for the full implementation of the World Health Organisation’s recommendations in the area, particularly adequate sanitation and hygiene activities.
Trial registration:
clinicaltrials.gov Identifier NCT02769013. Registered 21 April 2016, https://clinicaltrials.gov/study/NCT02769013
Mothers working to prevent early stillbirth study (MiNESS 20-28): Case Control Study Protocol
Authors: Heazell Alexander EP , Wilkinson Jack D , Morris Rachel K , Simpson Nigel AB , Smith Lucy K , Stacey Tomasina , Storey Claire , Higgins Lucy E
Published: October 2023

Background: An estimated 1,600 babies die every year before, during or immediately after birth between 20-28 weeks’ gestation in the United Kingdom. Baby loss at this stage of pregnancy has similar impact on parental physical and psychological wellbeing to late stillbirth (>28 weeks gestation). Further, peri-viable (20-22 week) births with signs of life are inconsistently reported as miscarriages or neonatal deaths. Therefore, in this study these legally disparate baby deaths are considered together (“Early Stillbirth”). Observational studies have improved understanding of previously unrecognised potentially modifiable risk factors for late stillbirth (including supine going to sleep position) and have influenced international clinical practice. Evidence is lacking regarding how previously identified and novel exposures may relate to early stillbirth risk.
Methods: This study aims to identify modifiable risk factors for early stillbirth that are amenable to public health campaigns or adaptation of antenatal care. The study design will be a case-control study of non-anomalous singleton baby loss 20+0 – 27+6 (n=316) and randomly-selected control pregnancies (2:1 ratio; n=632) at group-matched gestations, based on the local historic gestation distribution of cases. Data will be collected by participant recall via researcher-administered questionnaire and extraction from contemporaneous medical records. Unadjusted and confounder-adjusted odds ratios will be calculated using logistic regression. Exposures associated with early stillbirth at OR ≥1.5 will be detectable (p<0.05, β>0.80) assuming exposure prevalence of 30-60%.
Discussion: Dissemination of information about modifiable risk factors for stillbirth in late pregnancy (including #sidetosleep) may be responsible for recent reductions in late stillbirths in the UK. Critically, there has been no reduction in early stillbirth (~40% of UK baby losses). Information about modifiable factors associated with early stillbirth is now urgently required to inform clinical practice, to assist expectant mothers/parents to reduce their baby’s risk of early stillbirth, and to help address inequalities in pregnancy outcome. This study will focus on what portion of early stillbirth risk may be mitigated by facilitating positive health exposures among expectant mothers/parents and their partners, or by adaptation of their environment or healthcare provision. Information obtained from this study will enable development of antenatal care and education to reduce risk of early stillbirth.
Trial registration: NCT06005272
Supportive Relationships with Parents, Teachers, and Peers and Student’s Subjective and Objective Stress Levels
Authors: Hoferichter Frances , Lohilahti Jonne , Hufenbach Miriam , Grabe Hans Jörgen , Hageman Geja , Raufelder Diana
Published: October 2023

During adolescence, students increasingly report suffering from stress and school burnout, which poses a risk to students’ healthy development. However, social support may counteract perceived stress according to the Buffering Hypothesis and the Conservation of Resources Theory. In search of factors that would support healthy student development, studies have primarily focused on self-report data and neglected biophysiological processes. Addressing this research desideratum, this study examined whether perceived social support buffers the interplay of self-reported stress considering biophysiological markers (i.e., cortisol, alpha-amylase, oxidative stress, and telomere length). 83 secondary school students (Mage = 13.72, SD = 0.67; 48% girls) from Germany participated in a questionnaire study and biophysiological testing. Moderation analyses in R revealed that support from parents moderated the relationships between psychological stress as well as cynicism and inadequacy at school linked to alpha-amylase. Whereas teacher support buffered against the increase of oxidative stress related to cynicism and inadequacy.
Adaptive Quadtree Splitting Parallelization (AQSP) algorithm for the VVC standard
Authors: González-Ruiz Alberto , Díaz-Honrubia Antonio Jesús , Tapia-Fernández Santiago , García-Lucas David , Cebrián-Márquez Gabriel , Mengual-Galán Luis
Published: October 2023

The Versatile Video Coding (VVC) standard, also known as H.266, was released in 2020 as the natural successor to the High Efficiency Video Coding (HEVC) standard. Among its innovative coding tools, VVC extended the concept of Quadtree (QT) splitting to the Multi-Type Tree (MTT) structure, introducing binary and ternary partitions to enhance HEVC's coding efficiency. While this brought significant compression improvements, it also resulted in a substantial increase in encoding time, primarily due to VVC's larger Coding Tree Unit (CTU) size of 128×128 pixels. To mitigate this, this work introduces a flexible parallel approach for the QT traversal and splitting scheme of the VVC encoder, called Adaptive Quadtree Splitting Parallelization (AQSP) algorithm. This approach is based on the distribution of Coding Units (CUs) among different threads using the current depth level of the QT as a basis to minimize the number of broken dependencies. In this way, the algorithm achieves a good trade-off between time savings and coding efficiency. Experimental results show that, when compared with the original VVC encoder, AQSP achieves an acceleration factor of 1.70$\times$ with 4 threads at the expense of a negligible impact in terms of BD-rate. These outcomes position AQSP competitively in comparison to other state-of-the-art approaches.
Environmental tobacco smoke exposure exaggerates bleomycin- induced collagen overexpression during pulmonary fibrogenesis
Authors: Wang Qixin , Goracci Chiara , Sundar Isaac Kirubakaran , Rahman Irfan
Published: October 2023

Environmental tobacco smoke (ETS) is known to cause lung inflammatory and injurious responses. Smoke exposure is associated with the pathobiology related to lung fibrosis, whereas the mechanism by which ETS exposure augments lung fibrogenesis is unclear. We hypothesized that ETS exposure could exacerbate fibrotic responses via collagen dynamic dysregulation and complement activation. C57BL/6J and p16-3MR mice were exposed to ETS followed by bleomycin administration. ETS exposure exacerbated bleomycin-induced collagen and lysyl oxidase overexpression in the fibrotic lesion. ETS exposure also led to augmented bleomycin-induced upregulation of C3 and C3AR, which are pro-fibrotic markers. Moreover, overexpressed collagens and C3 levels were highly significant in males than females. The old mice (17 months old) were exposed to ETS and treated with bleomycin to induce fibrogenesis, since fibrogenesis is an aging-associated disease. Fewer gene and protein dysregulations trends were identified between ETS exposure with the bleomycin group and the bleomycin alone group in old mice. Based on our findings, we suggested that ETS exposure increases the risk of developing severe lung fibrotic responses via collagen overexpression and lysyl oxidase-mediated collagen stabilization in the fibrotic lesion. ETS exposure also potentially affected the complement system activation induced by bleomycin. Further, male mice were more susceptible than females during fibrogenesis exacerbation.
Rudolf Wolf to Alfred Wolfer: The Transfer of the Reference Observer in the International Sunspot Number Series (1876–1893)
Authors: Bhattacharya Shreya , Lefevre Laure , Chatzistergos Theodosios , Hayakawa Hisashi , Jansen Maarten
Published: October 2023

In 1876, Alfred Wolfer started observing the Sun and recording properties of sunspots alongside Rudolf Wolf. Their observations became the basis for the construction of the Sunspot Number series. After Wolf’s death in 1893, Wolfer became the primary observer for the Sunspot Number series. Even though the observations of Wolf and Wolfer had an overlap of almost 17 years (1876–1893), this shift of primary observer from Wolf to Wolfer seems to have led to inconsistencies in the Sunspot Number series primarily due to inhomogeneities in Wolf’s observations. To address this issue, we digitise Mittheilungen (Wolf’s Journals) and analyze their tabulated datasets. These journals include the raw sunspot data from various observers that the Zürich Observatory used to compile the Sunspot Number (SNV1). These datasets have been used as source data for the construction of the first version of the Sunspot Number (SNV1) series, but they were not digitally accessible for a recalibration of the Sunspot Number series until recently. We have also acquired external datasets from recent archival investigations for contemporaneous sunspot observations. In this study, we use the Mittheilungen dataset to produce a new recalibration of the sunspot number series covering 1816–1944, using four major observers (Tevel, Schwabe, Weber, and Wolfer) as backbones. The availability of the raw data allows us to identify issues in the determination of the scaling factors or k-factors between the records of different observers, but also the use of modern techniques for cross-calibrations. Our reconstruction for the years 1816–1944 is done with a novel method inspired by Chatzistergos et al.(2017, A&A, 602, A69), allowing to eliminate inconsistencies that resulted from the application of erroneous k-factors.