bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular IFN-γ and IL-4 levels of CD4 + and CD8 + T cells in the peripheral blood of naturally infected (Leishmania infantum) symptomatic dogs before and following a 4-week treatment with miltefosine and allopurinol: a double-blinded, controlled and cross-sectional study
Authors: Matralis Dimitrios T. , Koutinas Alexander F. , Papadogiannaki Ioanna E. , Papadopoulos Elias G. , Papadogiannakis Emmanouil I. 
Published: January 2023

Abstract
Background
Canine leishmaniosis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum with a wide spectrum of clinical signs, with cutaneous, ocular, renal and lymphoreactive conditions prevailing in the clinical setting. The immune system plays a pivotal role in the evolution of Leishmania infection and its response to antileishmanial treatment. Cytokines are important immune response mediators that are released by activated lymphocytes and less so by other immunocytes. In dogs with leishmaniosis, IFN-γ and IL-4 have been recognized as the main activators of cellular and humoral immunity, respectively. The objective of this study was to investigate intracellular IL-4 and IFN-γ expression by CD4 + and CD8 + lymphocytes in the peripheral blood of symptomatic dogs before and after combined antileishmanial treatment with miltefosine and allopurinol.

Results
Postantileishmanial treatment CD4 + IL-4 + and CD8 + IL-4 + cell counts were significantly decreased, although no similar changes were observed in the comparisons made between the pre- and posttreatment CD4 + IFN-γ + and CD8 + IFN-γ + counts and ratios.

Conclusion
The findings indicate that IL-4 production by T cells may facilitate the symptomatic phase of CanL, whereas IFN-γ production by CD4 + and CD8 + cells may indicate its negligible role in the evolution of natural CanL and perhaps the equivocal positive influence of antileishmanial treatment.
The synergistic and enhancive effects of IL-6 and M-CSF to expand and differentiate functional dendritic cells from human monocytes under serum-free condition
Authors: Yao Chao-Ling , Tseng Tsung-Yu 
Published: January 2023

Abstract
Background
Dendritic cells (DCs) are differentiated from monocytes, and have a strong ability to perform phagocytosis, present antigens and activate T cell immune response. Therefore, DCs are one of the key factors in fighting cancer in immunotherapy, and it is an important issue to develop a serum-free system for DC differentiation and expansion in vitro for clinical application.

Results
In this study, IL-6 and M-CSF were determined and a concentration combination of cytokines was optimized to develop an optimal DC serum-free differentiation medium (SF-DC Optimal) that can effectively differentiate CD14+ monocytes into CD40+CD209+ DCs. After differentiation, the morphology, growth kinetics, surface antigen expression, phagocytosis ability, cytokine secretion, mixed lymphocyte reaction and stimulation for maturation of the differentiated DCs were checked and confirmed. Importantly, this research is the first report finding that the addition an extra low concentration of IL-6 and M-CSF exhibited a synergistic effect with GM-CSF and IL-4 to generate higher numbers and more fully functional DCs than the addition of GM-CSF and IL-4 only under serum-free condition.

Conclusion
A large number of functional DCs can be generated by using SF-DC Optimal medium and provide an alternative source of DCs for related basic research and clinical applications.
Aβ42 treatment of the brain side reduced the level of flotillin from endothelial cells on the blood side via FGF-2 signaling in a blood–brain barrier model
Authors: Nakamura Tomohisa , Hashita Tadahiro , Chen Yuxin , Gao Yuan , Sun Yang , Islam Sadequl , Sato Hiroyuki , Shibuya Yasuyuki , Zou Kun , Matsunaga Tamihide , Michikawa Makoto 
Published: January 2023

AbstractOur previous study showed that the flotillin level is decreased in the blood of patients with Alzheimer’s disease (AD) when compared to that of patients with non-AD and vascular dementia; however, the molecular mechanism remains to be determined. In this study, to elucidate whether Aβ accumulation in the brain has an effect on the blood flotillin level, we used our previously established blood–brain barrier (BBB) culture model using microvascular endothelial cells obtained from human induced pluripotent stem cells (iBMECs) and astrocytes prepared from rat cortex. In this BBB model with iBMECs plated on the upper compartment (blood side) and astrocytes plated on the lower compartment (brain side), the trans-endothelial electrical resistance values are high (over 1500 Ωm2) and stable during experiments. We found that the addition of Aβ42 (0.5 and 2 µM) to the brain side significantly reduced the level of flotillin secreted by iBMECs on the blood side. The level of basic fibroblast growth factor (FGF-2) in the brain side was significantly reduced by Aβ42 treatment, and was accompanied by a reduction in the level of phosphorylation of the fibroblast growth factor receptor in iBMECs. The brain-side Aβ42 treatment-induced reduction of flotillin secretion into the blood side was restored in a dose-dependent manner by the addition of FGF-2 into the brain side. These results indicated that Aβ accumulation in the brain side reduced FGF-2 release from astrocytes, which attenuated FGF-2-mediated iBMECs signaling via the FGF-2 receptor, and thereby reduced flotillin secretion from iBMECs on the blood side. Our findings revealed a novel signaling pathway crossing the BBB from the brain side to the blood side, which is different from the classical intramural periarterial drainage or lymphatic-system-to-blood pathway.
Association of physical activity with physical function and quality of life in people with hip and knee osteoarthritis: longitudinal analysis of a population-based cohort
Authors: Lopes David G. , Costa Daniela , Cruz Eduardo B. , Mendonça Nuno , Henriques Ana Rita , Branco Jaime , Canhão Helena , Rodrigues Ana M. 
Published: January 2023

AbstractHip and knee osteoarthritis (HKOA) is a chronic disease characterized by joint pain that leads to reduced physical function and health-related quality of life (HRQoL). At present, no cure is available. Clinical trials indicate that people with HKOA benefit from physical activity in several health-related outcomes. However, few studies have evaluated the long-term positive effect of regular physical activity. This study analyzed participants with HKOA from a nationwide population-based cohort (EpiDoC Cohort) to assess the impact of physical activity on patients’ physical function and HRQoL over a long-term follow-up. The regular weekly frequency of intentional physical activity was self-reported as non-frequent (0 times/week), frequent (1–2 times/week), or very frequent (≥ 3 times/week). This study followed 1086 participants over a mean period of 4.7 ± 3.4 years, during which 6.3% and 14.9% of participants reported frequent and very frequent physical activity, respectively. Using linear mixed models, we found that frequent (β =  − 0.101 [− 0.187, − 0.016]; β = 0.039 [− 0.002, 0.080]) and very frequent physical activity (β =  − 0.061 [− 0.118, − 0.004]; β = 0.057 [0.029, 0.084]) were associated with improved physical function and HRQoL over time, respectively, when compared with non-frequent exercise, adjusting for years to baseline, sex, age, years of education, body mass index, multimorbidity, hospitalizations, clinical severity, and unmanageable pain levels. These findings raise awareness of the importance of maintaining exercise/physical activity long term to optimize HRQoL and physical function. Further studies must address barriers and facilitators to improve the adoption of regular physical activity among citizens with HKOA.
Development and validation of a four-dimensional registration technique for DCE breast MRI
Authors: Mattusch Chiara , Bick Ulrich , Michallek Florian 
Published: January 2023

Abstract
Background
Patient motion can degrade image quality of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) due to subtraction artifacts. By objectively and subjectively assessing the impact of principal component analysis (PCA)-based registration on pretreatment DCE-MRIs of breast cancer patients, we aim to validate four-dimensional registration for DCE breast MRI.

Results
After applying a four-dimensional, PCA-based registration algorithm to 154 pretreatment DCE-MRIs of histopathologically well-described breast cancer patients, we quantitatively determined image quality in unregistered and registered images. For subjective assessment, we ranked motion severity in a clinical reading setting according to four motion categories (0: no motion, 1: mild motion, 2: moderate motion, 3: severe motion with nondiagnostic image quality). The median of images with either moderate or severe motion (median category 2, IQR 0) was reassigned to motion category 1 (IQR 0) after registration. Motion category and motion reduction by registration were correlated (Spearman’s rho: 0.83, p < 0.001). For objective assessment, we performed perfusion model fitting using the extended Tofts model and calculated its volume transfer coefficient Ktrans as surrogate parameter for motion artifacts. Mean Ktrans decreased from 0.103 (± 0.077) before registration to 0.097 (± 0.070) after registration (p < 0.001). Uncertainty in perfusion quantification was reduced by 7.4% after registration (± 15.5, p < 0.001).

Conclusions
Four-dimensional, PCA-based image registration improves image quality of breast DCE-MRI by correcting for motion artifacts in subtraction images and reduces uncertainty in quantitative perfusion modeling. The improvement is most pronounced when moderate-to-severe motion artifacts are present.
The association between acute brucellosis with a Guillain–Barré syndrome-like presentation: a case report
Authors: Doya Leen Jamel , Haidar Ibrahim , Sakkour Souad 
Published: January 2023

Abstract
Background
Brucellosis is a zoonotic disease caused by Gram-negative bacteria. It has variable manifestations (gastrointestinal, hepatobiliary, skeletal). Neurobrucellosis may develop at any stage of the disease (acute, subacute, and chronic phases) and affects the central and peripheral nervous systems. Acute peripheral neuropathy mimicking Guillain–Barré syndrome caused by brucellosis is rarely reported: only four cases in children were found in the literature review.

Case presentation
We report a case of a 4-year-old Syrian boy who presented with fever, weakness of lower limbs, backache, and fatigue. The patient lived in a brucellosis endemic area. A physical examination including a neurological examination showed mild paresthesia and muscle weakness. He had a stiff neck with Kernig’s sign with an absence of deep tendon reflexes in the lower extremities. Proprioception in the lower extremities was impaired, but he did not have any sensory problems. Abdominal cutaneous reflexes were absent. Brucellosis and Guillain–Barré syndrome were found in laboratory investigations and on electroneurogram (ENG). The patient was treated with sulfamethoxazole + trimethoprim, rifampicin, gentamicin, and dexamethasone, with an improvement.

Conclusion
This case demonstrates a rare case of brucellosis neurologic manifestation. Brucellosis should be kept in mind in all patients with acute paralysis, especially in those who live in endemic areas.
DHAV 3CD targets IRF7 and RIG-I proteins to block the type I interferon upstream signaling pathway
Authors: Xia Xiaoyan , Cheng Anchun , Wang Mingshu , Ou Xumin , Sun Di , Zhang Shaqiu , Mao Sai , Yang Qiao , Tian Bin , Wu Ying , Huang Juan , Gao Qun , Jia Renyong , Chen Shun , Liu Mafeng , Zhao Xin-Xin , Zhu Dekang , Yu Yanling , Zhang Ling 
Published: January 2023

AbstractDuck hepatitis A virus type 1 (DHAV-1) is an acute, highly lethal infectious agent that infects ducklings and causes up to 95% mortality in ducklings up to 1 week of age, posing a significant economic threat to the duck farming industry. Previous studies have found that the proteolytic enzyme 3 C encoded by DHAV-1 can inhibit the IRF7 protein from blocking the upstream signaling pathway of the type I interferon to promote viral replication. However, there are still few studies on the mechanism of DHAV-1 in immune evasion. Here, we demonstrate that the DHAV-1 3CD protein can interact with IRF7 protein and reduce IRF7 protein expression without directly affecting IRF7 protein nuclear translocation. Further studies showed that the 3CD protein could reduce the expression of RIG-I protein without affecting its transcription level. Furthermore, we found that the 3CD protein interacted with the N-terminal structural domain of RIG-I protein, interfered with the interaction between RIG-I and MAVS, and degraded RIG-I protein through the proteasomal degradation pathway, thereby inhibiting its mediated antiviral innate immunity to promote DHAV-1 replication. These data suggest a novel immune evasion mechanism of DHAV-1 mediated by the 3CD protein, and the results of this experiment are expected to improve the understanding of the biological functions of the viral precursor protein and provide scientific data to elucidate the mechanism of DHAV-1 infection and pathogenesis.
Stability of some generalized fractional differential equations in the sense of Ulam–Hyers–Rassias
Authors: Makhlouf Abdellatif Ben , El-hady El-sayed , Arfaoui Hassen , Boulaaras Salah , Mchiri Lassaad 
Published: January 2023

AbstractIn this paper, we investigate the existence and uniqueness of fractional differential equations (FDEs) by using the fixed-point theory (FPT). We discuss also the Ulam–Hyers–Rassias (UHR) stability of some generalized FDEs according to some classical mathematical techniques and the FPT. Finally, two illustrative examples are presented to show the validity of our results.
Optimizing the use of temporal artery biopsy: A retrospective study
Authors: Villeneuve Etienne , Lacroix Jean-Michel , Brisebois Simon 
Published: January 2023

Background Giant cell arteritis is an inflammatory disease of the large- and medium-sized vessels. It is the most common primary vasculitis, with lifetime incidences of 0.5% and 1% in men and women, respectively. Its diagnosis is based upon clinical criteria, which may include temporal artery biopsy. Expected positivity rates of temporal artery biopsies and patient selection remain controversial topics in the literature. Methods A cross-sectional retrospective study of 127 patients referred for temporal artery biopsy with a diagnosis of suspected giant cell arteritis between January 2014 and December 2018 was performed. The primary outcome was the positivity rate. The relationships between positivity rates, symptoms, clinical suspicion, biopsy delay, biopsy length and corticosteroid treatment were also studied. Results A positivity rate of 23.7% (16.6–32.6%) was shown, along with a significant association between jaw claudication and specimen positivity (odds ratio 8.1, p < 0.05). Moreover, there were significant associations between a high initial clinical suspicion of disease and specimen positivity ( p < 0.05), as well as a high initial clinical suspicion of disease and pursuit of corticosteroid treatment following biopsy results, regardless of positivity ( p < 0.05). The duration of corticosteroid treatment prior to biopsy was not associated with a change in positivity rate. Conclusions The positivity rate of temporal artery biopsy was 23.7%. Treatment of patients with negative temporal artery biopsy was associated with maintenance of corticosteroid treatment when the initial clinical suspicion of arteritis was high. Therefore, temporal artery biopsy may not be necessary for patients with a high initial clinical suspicion of giant cell arteritis. Graphical Abstract
Molecular signatures of inherited and acquired sporadic late onset nemaline myopathies
Authors: Nicolau Stefan , Dasgupta Aneesha , Dasari Surendra , Charlesworth M. Cristine , Johnson Kenneth L. , Pandey Akhilesh , Doles Jason D. , Milone Margherita 
Published: January 2023

AbstractAcquired sporadic late onset nemaline myopathy (SLONM) and inherited nemaline myopathy (iNM) both feature accumulation of nemaline rods in muscle fibers. Unlike iNM, SLONM is amenable to therapy. The distinction between these disorders is therefore crucial when the diagnosis remains ambiguous after initial investigations. We sought to identify biomarkers facilitating this distinction and to investigate the pathophysiology of nemaline rod formation in these different disorders. Twenty-two muscle samples from patients affected by SLONM or iNM underwent quantitative histological analysis, laser capture microdissection for proteomic analysis of nemaline rod areas and rod-free areas, and transcriptomic analysis. In all iNM samples, nemaline rods were found in subsarcolemmal or central aggregates, whereas they were diffusely distributed within muscle fibers in most SLONM samples. In SLONM, muscle fibers harboring nemaline rods were smaller than those without rods. Necrotic fibers, increased endomysial connective tissue, and atrophic fibers filled with nemaline rods were more common in SLONM. Proteomic analysis detected differentially expressed proteins between nemaline rod areas and rod-free areas, as well as between SLONM and iNM. These differentially expressed proteins implicated immune, structural, metabolic, and cellular processes in disease pathophysiology. Notably, immunoglobulin overexpression with accumulation in nemaline rod areas was detected in SLONM. Transcriptomic analysis corroborated proteomic findings and further revealed substantial gene expression differences between SLONM and iNM. Overall, we identified unique pathological and molecular signatures associated with SLONM and iNM, suggesting distinct underlying pathophysiological mechanisms. These findings represent a step towards enhanced diagnostic tools and towards development of treatments for SLONM.
The influence of anisotropic electrical resistivity on surface magnetotelluric responses and the design of two new anisotropic inversions
Authors: Thongyoy Wisart , Siripunvaraporn Weerachai , Rung-Arunwan Tawat , Amatyakul Puwis 
Published: January 2023

AbstractUsing the 3-D axial anisotropy, the dipping anisotropy, and the azimuthal anisotropy as case studies, we investigated the influence of each anisotropic resistivity element on the magnetotelluric surface responses. To justify the strong and weak influence and edge effect, we have introduced the influence indices for the impedance components, and the edge effect indices for the tipper components. Interestingly, for decoupled modes, we found that $${\rho }_{xx}$$

ρ

xx

has a strong influence on Zxy, Zyy, and Ty, while $${\rho }_{yy}$$

ρ

yy

strongly affects Zyx, Zxx, and Tx. The three elements $${\rho }_{zz}$$

ρ

zz

, $${\rho }_{xz}$$

ρ

xz

, and $${\rho }_{yz}$$

ρ

yz

have only a very weak influence on all types of responses. For the coupled mode, $${\rho }_{xx}$$

ρ

xx

, $${\rho }_{yy}$$

ρ

yy

, and $${\rho }_{xy}$$

ρ

xy

display a strong influence on all responses. Based on our studies on the influence of the anisotropic resistivity elements, we design and propose two practical processes to replace the conventional axial, dipping, azimuthal, and general anisotropic inversions. First, the axial or dipping inversion can be approximately decoupled into $${\rho }_{x}$$

ρ
x

-mode and $${\rho }_{y}$$

ρ
y

-mode inversions. The decoupled mode inversions can be performed either independently and in parallel, or as a joint inversion. Second, since the three resistivity elements always show a weak influence, the general anisotropic inversion can be simplified to just the reduced coupled azimuthal anisotropic inversion with only three resistivity elements as outputs. Both proposed techniques can save a lot of the computational resources. Criteria to choose either the decoupled or coupled modes depend greatly on the magnitudes and distributions of the Zxx and/or Zyy, and Tx and/or Ty responses.
Graphical Abstract
In situ repair of segmental loss posterior lateral meniscal root tears outperforms meniscofemoral ligament imbrication in the ACL reconstructed knee
Authors: Seiter Max , Douglass Brenton W. , Brady Alex W. , Dornan Grant J. , Brown Justin R. , Hackett Thomas R. 
Published: January 2023

AbstractPurposeThe purpose of this study was to compare the biomechanical effect of in‐situ repair of posterior lateral meniscal root (PLMR) tear with segmental meniscal loss, with and without meniscofemoral ligament (MFL) imbrication, on anterior cruciate ligament (ACL) graft force and knee joint kinematics.MethodsTen fresh‐frozen cadaveric knee specimens underwent kinematic evaluation in five states: 1) Native, 2) ACLR, 3) Segmental PLMR loss, 4) In‐situ PLMR repair, and 5) MFL augmentation. Kinematic evaluation consisted of five tests, each performed at full extension and at 30° of flexion: 1) Anterior drawer, 2) Internal Rotation, 3) External Rotation, 4) Varus, and 5) Valgus. Additionally, a simulated pivot shift test was performed. Knee kinematics and ACL graft force were measured.ResultsPLMR tear did not significantly increase ACL graft force in any test. However, PLMR repair significantly reduced ACL graft force compared to the ACLR alone (over constraint ‐26.6 N, p = 0.001). PLMR tear significantly increased ATT during the pivot shift test (+ 2.7 mm, p = 0.0001), and PLMR repair restored native laxity. MFL augmentation did not improve the mechanics.ConclusionsIn‐situ PLMR repair eliminated pivot shift laxity through ATT and reduced force on the ACL graft, indicating that this procedure may be ACL graft‐protective. MFL augmentation was not shown to have any effect on graft force or knee kinematics and untreated PLMR tears may place an ACL graft at higher risk. This study suggests concomitant repair to minimize additional forces on the ACL graft.
A case of mesenteric venous thrombosis complicating appendiceal diverticulitis
Authors: Ichikawa Jun , Toda Kosuke , Fujita Haruku , Hirai Kenjiro , Ohe Hidenori , Yamamoto Hidekazu 
Published: January 2023

Abstract
Background
Mesenteric venous thrombosis (MVT) and appendiceal diverticulitis are rare diseases. There has been no previous report on MVT complicating appendiceal diverticulitis. Herein, we report the first case of MVT complicating appendiceal diverticulitis.

Case presentation
A 70-year-old male patient with right lower abdominal pain presented to our hospital. Abdominal contrast-enhanced computed tomography (CT) suggested MVT complicating appendiceal diverticulitis. Initially, we started conservative treatment with antibacterial drugs, but on the 2nd hospital day his general condition deteriorated due to sepsis that seemed to be caused by appendiceal diverticulitis. Therefore, we performed laparoscopic appendectomy. Histopathological findings of the specimen showed appendiceal diverticulitis. After the operation, he gradually improved. He was discharged on the 30th hospital day.

Conclusions
We report a successfully treated case of MVT complicating appendiceal diverticulitis by surgical intervention. This is the first case of MVT complicating appendiceal diverticulitis.