bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning approaches to predicting the risk of in-ward cardiac arrest of cardiac patients in teaching hospital Karapitiya, Sri Lanka
Authors: Rajapaksha Lahiru T. W. , Vidanagamachchi Sugandima M. , Gunawardena Sampath
Published: July 2022

Background Cardiac arrest is an instantaneous loss of cardiac function in a person who may or may not be diagnosed with heart disease, and it has a significant impact on a patient’s well-being and can also pose a threat to their life. This retrospective cohort study evaluates patients who were admitted to the Teaching Hospital Karapitiya (THK) from the 13th of August 2018 to the 6th of February 2020. It includes 112 patients who were transferred from the Emergency Treatment Unit to the Cardiac Medical Ward.MethodsA Deep-Learning Cardiac Arrest Prediction Model (DCPAM) was developed to predict the risk of cardiac arrest and to determine whether the patient would develop a cardiac arrest or not. A recurrent neural network (RNN) and a decision tree classification model were employed for this model. A total of nineteen commonly recorded medical details in the bed head tickets (BHT) of all cardiac patients were used in developing this model. As a comparative measure with existing early warning systems, we used the area under the receiver operating characteristic curve (AUROC). ResultsThe Deep-Learning Cardiac Arrest Prediction Model developed using the RNN model significantly outperformed the aforementioned existing early warning systems by achieving 96% accuracy whereas the decision tree model showed 80% accuracy. Furthermore, the RNN model showed 95.83% of sensitivity with a confidence interval of 95.37% to 96.25% and specificity of 93.42% with a confidence interval of 92.07 to 94.61%.Conclusion Our proposed deep learning approach was developed in an environment that had no electronic medical recording systems in use. Nonetheless, it demonstrated higher sensitivity and specificity than traditional early warning systems. Thus, it can be seen as an effective approach to identifying the risk of cardiac arrests in in-ward cardiac patients. Through this study, we analyze the feasibility of implementing an early warning system within the current health care setup in Sri Lanka.
Characterization of mitochondrial alterations in Aicardi-Goutières patients mutated in RNASEH2A and RNASEH2B genes
Authors: Dragoni Francesca , Garau Jessica , Sproviero Daisy , Orcesi Simona , Varesio Costanza , De Siervi Silvia , Gagliardi Stella , Cereda Cristina , Pansarasa Orietta
Published: July 2022

BackgroundAicardi-Goutières Syndrome (AGS) is a rare encephalopathy characterized by neurological and immunological features. Mitochondrial dysfunctions may lead to mitochondrial DNA (mtDNA) release and consequent immune system activation. We investigated the role of mitochondria and mtDNA in AGS pathogenesis by studying patients mutated in RNASEH2B and RNASEH2A genes.MethodsLymphoblastoid cell lines (LCLs) from RNASEH2A and RNASEH2B mutated patients and healthy control were used. Transmission Electron Microscopy (TEM) and flow cytometry were used to assess morphological alterations, reactive oxygen species (ROS) production and mitochondrial membrane potential variations. Seahorse Analyzer was used to investigate metabolic alterations and mtDNA oxidation and VDAC1 oligomerization were assessed by immunofluorescence. Western Blot and RT-qPCR were used to quantify mtTFA protein and mtDNA release. ResultsMorphological alterations of mitochondria were observed in both mutated LCLs and loss of physiological membrane potential was mainly identified in RNASEH2A LCLs. ROS production and 8-oxoGuanine levels were increased in RNASEH2B LCLs. Also VDAC1 signal was increased, suggesting a mitochondrial pore formation possibly determining mtDNA release. Indeed, higher cytoplasmic mtDNA levels were found in RNASEH2B LCLs. Metabolic alterations confirmed mitochondrial damage in both LCLs. ConclusionData highlighted mitochondrial alterations in AGS patients’ LCLs suggesting a pivotal role in AGS pathogenesis.
Photothermal Properties of Fe3O4 Nanoparticles Coated With Turmeric Extract
Authors: Alvarado-Noguez Margarita Lizeth , Matías-Reyes Ana Eunice , Cruz-Burelo Hugo Arturo De La , Domínguez-Pacheco Flavio Arturo , Cruz-Orea Alfredo , Santoyo-Salazar Jaime , Hernández-Aguilar Claudia
Published: July 2022

Magnetite (Fe3O4) nanoparticles (MNPs) below 30 nm are considered addressable magnetic cores which can be stimulated by an external AC magnetic field. In this study, MNPs were covered directly with Curcuma longa extract from a modified coprecipitation route as an organic base. The particle size distribution ranging from 9 to 18 nm according to transmission electron microscopy (TEM) and dynamic light scattering (DLS). Two main particle size populations were found associated with particle aggregation in the samples. In addition, their thermal features were determined using photothermal techniques to obtain their thermal diffusivity, effusivity, conductivity, and heat capacity per unit volume. The thermal diffusivity and effusivity values of the MNPs were obtained using a thermal wave resonator cavity (TWRC) and inverse photopyroelectric (IPPE) photothermal techniques, respectively. The obtained thermal parameters were similar to the water thermal values because the MNPs were measured in aqueous solutions. The main goal of this study was to define the thermal response, by obtaining the thermal characterization, of MNPs in suspensions related to superparamagnetic cores and Curcuma longa coatings.
Castleman disease with plasmacytoma transformation: a case report
Authors: Li Xiang , Wang Jigang , Wang Wei
Published: July 2022

Background: Castleman disease is a rare lymphoproliferative disorder that shares similar symptoms, signs, and pathological features with malignant lymphoma. Diagnosis of CD primarily depends on pathological examinations, and CD can be histopathologically classified into hyaline vascular, plasma cell, or mixed types. The hyaline vascular type of unicentric CD is the most common, accounting for 80%-90% of cases.[3] Treatment of Castleman's disease includes surgical resection, simple chemotherapy, surgery combined with chemotherapy, or chemotherapy combined with radiotherapy, etc. Case Presentation : Here, we report the case of a 68-year-old man with bilateral cervical lymphadenopathy who was pathologically diagnosed with multicentric Castleman disease(mixed type) with plasmacytoma. He underwent a bilateral cervical lymphadenectomy, which resulted in a promising prognosis. Conclusions: Castleman disease with plasmacytoma occurs only rarely, and its pathological features are very special. To date, it has been rarely reported worldwide, and its clinical characteristics are still unclear.
Effects of low tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer
Authors: Qian Xiao-Long , Xia Xiao-Qing , Li Ya-Qing , Jia Yu-Mian , Sun Yuan-Yuan , Song Yuan-Ming , Xue Hui-Qin , Hao Yan-Fei , Wang Jin , Wang Xiao-Zi , Liu Chen-Ying , Zhang Xin-Min , Zhang Li-Na , Guo Xiao-Jing
Published: July 2022

Purpose: High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. Methods: The study included breast cancers from 991 patients who received NACT. ROC curve was used to analyze the predictive value of TILs for tpCR and NR in breast cancer with different molecular subtypes. Multivariate logistic regression was used to assess the association of various factors, particularly the TILs, with the possibility of tpCR and NR. Spearman’s rank correlation coefficient was used to analyze the relationship between TILs and routine pathological indices.Results: ROC curve analysis confirmed that TILs showed significant predictive value for NR of HR + HER2 - and TNBC. When TILs at a cutoff of 10% and 17.5%, the sum of sensitivity and specificity reaches the maximum in HR + HER2- and TNBC respectively. Among HR+HER2− breast cancer, TILs≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥17.5% was an independent predictor for low NR rate. Conclusions: The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. The study is also suggestive that patients with HR+HER2− cancer with low TILs infiltration may benefit more from other neoadjuvant regimes such as endocrine therapy. Further studies are required to validate these findings.
A multiscale modelling framework to study the interdependence of brain, behavior and pandemic
Authors: Kumar Spandan , Sharma Bhanu , Singh Vikram
Published: July 2022

A major constraint of the behavioral epidemiological models is the underlying assumption that human behavior is static, however, it is known to be highly dynamic, especially in changing and vulnerable situations during a pandemic. To incorporate the dynamicity of human nature in the existing epidemiological models, in this work, we propose a population-wide multi-time-scale theoretical framework that assimilates neuronal plasticity as the basis of altering human emotions and behavior. For that, variable connection weights between different brain regions and their firing frequencies are coupled with a compartmental SIR model to estimate the contact rate. As an illustration, a model of fear conditioning in conjunction with awareness campaigns is developed and simulated. Results indicate that in the presence of fear conditioning there exists an optimum duration of daily broadcast time during which awareness campaigns are most effective in mitigating the pandemic. Further, global sensitivity analysis using the Morris method highlighted that learning rate and firing frequency of the unconditioned circuit are the key regulators in modulating the emergent pandemic waves. The present study makes a case for incorporating neuronal dynamics as a basis of behavioral immune response and has further implications in designing future awareness campaigns.
MRSA increases risk of epiphyseal acute osteomyelitis in children: a case-control study
Authors: jia haiting , sun lihua , Wang Chunhua
Published: July 2022

Background: To explore clinical characteristics of epiphyseal acute osteomyelitis in children by comparing with metaphyseal acute osteomyelitis.Methods: A retrospective single-center case-control study of children with acute osteomyelitis of long bone, with positive pus culture, between November 2017 and January 2021 was performed. Medical records, laboratory results, and magnetic resonance imaging(MRI) were reviewed. According to infection location on MRI, observation group comprised patients with epiphysis involvement, and patients with metaphysis involvement constituted control group. All patients were treated with antibiotics combined with fenestration of metaphyseal cortex. Body temperature, inflammatory index, pus culture, number of operations, length of stay, and complications were compared.Results: Forty-three patients were included, 12 in observation group and 31 in control group. Maximum body temperature (39.59±0.67℃ vs. 39.11±0.73℃, p>0.05), leukocyte (16.37±5.50×109/L vs. 18.99±5.57×109/L, p>0.05), neutrophil (10.99±4.39×109/L vs. 12.28±4.02×109/L, p>0.05), C-reactive protein (116.45±66.02mg/L vs. 93.05±60.29 mg/L, p>0.05), ESR (76.17±28.26mm/h vs. 61.48±24.43mg/L, p>0.05), number of operations (3.25±1.71 vs. 2.77±0.76, p>0.05), and length of stay (33.25±8.24 days vs. 32.10±9.24 days, p>0.05) were with no statistical differences. The methicillin-resistant Staphylococcus aureus(MRSA) positive proportion of pus culture in observation group was 50.0% compared with 16.1% in control group (6/12 vs. 5/31, p<0.05). No complication occurred in observation group, while one patient developed knee joint contracture in control group.Conclusions: In pus culture-positive acute osteomyelitis of long bone in children, no significant difference in clinical features between epiphysis and metaphysis involvement. MRSA increased risk of epiphyseal acute osteomyelitis in children.
RepSox and Mesenchymal stem cells - conditional medium ameliorate synergistically EMT by further inhibiting TGF-β/Smad signaling pathway in NRK-52E fibrosis
Authors: Zeng Lianlin , Liu Xia , Li Tao , Zhang Wei , Li Wenying , Wu Peichen , Lv Yangping , Zhou Zhengli , Wu Chunling , Chen Bo
Published: July 2022

Background
TGF-β1 has been recognized as the core driver of renal fibrosis and involved in the pathophysiological process from chronic kidney disease (CKD) to end-stage renal disease (ESRD). RepSox is an effective and selective inhibitor of TGFβR-1/ALK5. Mesenchymal stem cells (MSCs) have been proved to have significant anti-fibrotic effects in vitro and in vivo. This study aimed to explore whether RepSox and MSCs could synergistically inhibit the classical TGF-β/Smad signaling pathway and ameliorate epithelial-interstitial transdifferentiation (EMT).
Methods
NRK-52E was divided into nine groups, including normal group, DMSO group, RepSox group, TGF-β1 + RepSox group, TGF-β1 + RepSox + MSCs-conditional medium (MSCs-cm) group, TGF-β1 group, TGF-β1 + MSCs-cm group, MSCs-cm group, and RepSox + MSCs-cm group. RepSox was added 2 h before modeling until the fibrosis model was established with TGF-β1 treatment for 48 h, and the followed by MSCs-cm treatment for 48 h. The remaining groups performed the synchronization. EMT and TGF-β1/Smad signaling pathway were detected by immunofluorescence and western blot.
Results
TGF-β1 increased significantly the expressions of α-SMA, fibronectin (FN), collagen type I, TGF-β1, KIM-1, Snail, and the ratios of TIMP1/MMP9 and p-Smad2/3/Smad2/3, and obviously reduced E-Cadherin expression. TGF-β1 + RepSox group, TGF-β1 + MSCs-cm group, and RepSox + TGF-β1 + MSCs-cm all inhibited ECM, Snail, KIM-1, TGF-β/Smad pathway, and up-regulated E-cadherin expression. However, the anti-fibrotic effect of RepSox + TGF-β1 + MSCS-cm was more effective than other groups.
Conclusion
RepSox and MSCs-cm could synergistically ameliorate EMT by further inhibiting classic TGF-β/Smad signaling pathway in NRK-52E fibrosis.
Reciprocal Facilitation Between Mental And Visuomotor Rotations
Authors: Guo Jianfei , Song Joo-Hyun
Published: July 2022

Humans exhibit remarkably complex cognitive abilities and adaptive behavior in daily life. Cognitive operation in the "mental workspace," such as mentally rotating an additional piece of luggage to fit into fixed trunk space, helps us maintain and manipulate information moment-to-moment basis. Skill acquisition in the "sensorimotor workspace," such as learning a new mapping between the magnitude of new vehicle movement and wheel turn, allows us to adjust our behavior to changing environmental or internal demands to maintain appropriate motor performance. While this cognitive and sensorimotor synergy is at the root of adaptive behavior in the real world, their interplay has been understudied due to a divide-and-conquer approach. We evaluated whether a separate domain-specific or common domain-general operation drives mental and sensorimotor rotational transformations. We observed that participants performed visual mental rotation faster after the visuomotor rotation training, and their learning rate for visuomotor adaptation improved after their mental rotation training. Such bidirectional transfer achieved through the two widely different tasks demonstrated remarkable reciprocal plasticity and supported a common transformation mechanism between two intertwined workspaces. It also urges the necessity of an explicitly integrated approach to enhance our understanding of the dynamic interdependence between cognitive and sensorimotor mechanisms.
Intracardiac paraganglioma with cough as the first symptom: a case report
Authors: cao jingyi , Yang Fan , Yang Qingqing , Cai Chengliang , Xue Qing , Lu Fanglin
Published: July 2022

Background Cardiac paraganglioma is clinically rare, and its main symptoms are hypertension and metabolic changes. According to the medical history and clinical manifestations, combined with routine laboratory examinations and imaging examinations, the diagnosis can be made, and pathological examination is required for the final diagnosis.Case presentation The authors present a 31-year-old male patient with a left atrial mass. The initial symptom was cough. Cardiac enlargement was found during the chest X-ray. The follow-up imaging examination showed that the left atrial occupying, and the possibility of malignant occupying was not ruled out. The patient underwent surgical resection of the mass. The final pathological result showed paraganglioma. Thoracic CT review two months after the operation showed that the original occupying had disappeared and no new occupying was found.Conclusions Pheochromocytoma and paraganglioma (PPGL) are a kind of neuroendocrine tumors. PPGL can cause secondary hypertension, and lead to a series of clinical syndromes, including myocardial injury, metabolic changes, and so on. The tumor should be surgically removed as soon as possible after the diagnosis. However, squeezing the tumor during the operation can lead to the release of catecholamine, which may cause a hypertensive crisis, arrhythmia, and moderate stroke. Due to the drastic reduction of catecholamine after the operation, it may cause peripheral vasodilation, leading to persistent hypotension and even death. Therefore, multidisciplinary cooperation before, during, and after the operation is extremely important.
Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross- sectional analysis of baseline data from the PR-IAH study
Authors: Sakane Naoki , Kato Ken , Hata Sonyun , Nishimura Erika , Araki Rika , Kouyama Kunichi , Hatao Masako , Matoba Yuka , Matsushita Yuichi , Domichi Masayuki , Suganuma Akiko , Sakane Seiko , Murata Takashi , Wu Fei Ling
Published: July 2022

Background
Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D.
Methods
This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected.
Results
The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13–5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22–0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37–0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups.
Conclusions
We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia.
Trial registration:
University hospital Medical Information Network (UMIN) Center: UMIN000039475)、Approval date 13 February 2020
Lower HLA-G levels in Extravillous Trophoblasts of Human Term Placenta in Gestational Diabetes Mellitus than in normal controls
Authors: Knabl Julia , Hüttenbrenner Rebecca , Mahner Sven , Kainer Franz , Desoye Gernot , Jeschke Udo
Published: July 2022

The non-classical HLA (human leucocyte antigen) class I molecule HLA-G is widely known to play a major role in feto-maternal tolerance. We tested the hypothesis that HLA-G expression is altered in placentas of women with gestational diabetes mellitus (GDM) in a specific pattern depending on fetal sex.HLA-G expression was analysed in a total of eighty placentas (40 GDM/ 40 controls) by immunohistochemistry using the semi-quantitative immunoreactive score (IRS). Double-immunofluorescence staining identified the cells expressing HLA-G in the decidua and to evaluate the expression pattern. We found a significant (p<0.001) reduction of HLA-G expression in extravillous cytotrophoblasts in GDM as compared to controls. We could demonstrate that this downregulation is not due to a loss of cell number, but to a loss of expression intensity. We found a special change in cell pattern in extravillous trophoblastic cells: They show an obvious rarefication on HLAG expression on EVT cell surface. No significant differences according to fetal sex were found.These data show that GDM alters HLA-G expression in EVT cells and provide new insights in altered placental function in diabetic placenta.
Examining bidirectional associations between perceived social support and psychological symptoms in the context of stressful event exposure: A prospective, longitudinal study
Authors: Thomas Sarah , Kanske Philipp , Schäfer Judith , Hummel Katrin Veronika , Trautmann Sebastian
Published: July 2022

BackgroundAfter stressful event exposure, higher perceived social support is a well-established correlate of decreased risk for psychological symptoms, including depressive, anxiety and posttraumatic stress (PTS) symptoms. However, longitudinal data on the direction of this association and the stability of perceived social support are scarce and have yielded mixed results, with a particular lack of prospective studies. We aimed to investigate changes in perceived social support and bidirectional associations between perceived social support and psychological symptoms in a prospective, longitudinal study.MethodsA sample of German soldiers was assessed before and after deployment to Afghanistan. Group-based trajectory modelling was used to investigate the stability of perceived social support and to identify possible distinguishable trajectories of perceived social support. Bidirectional associations between perceived social support (general and workplace) and psychological symptoms (depressive, anxiety and PTS) were examined using gamma regressions.ResultsAverage levels of perceived general social support did not change, while perceived workplace social support increased slightly (t(344) = 5.51, p < .001). There were no distinguishable trajectories of perceived social support. Higher perceived general (Mean ratio (MR) = 0.84, 95% CI = [0.74, 0.95]) and workplace social support (MR = 0.82, 95% CI = [0.72, 0.92]) predicted lower depressive symptoms, but not anxiety or PTS symptoms. Only higher PTS (MR = 0.95, 95% CI = [0.91, 0.99]) and higher depressive symptoms (MR = 0.96, 95% CI = [0.93, 0.99]) predicted lower perceived general social support.ConclusionsPerceived social support can remain relatively stable under exposure to environmental stressors such as military deployment. Higher perceived social support could protect against depressive symptoms via a stress-buffering mechanism, while support may need to be more tailored to individual needs for a protection against PTS symptoms. Individuals with elevated depressive and PTS symptoms might have impaired abilities or opportunities to access social support after stressful event exposure. Future studies could investigate distressing social emotions and associated maladaptive social cognitions as possible mechanisms in the association between symptoms and lower perceived social support. Especially with respect to PTS symptoms, future studies could focus on conditions that enable individuals to benefit from social support.
Increased MET Copy Number and its Differing Prognostic Values in Schistosomal and Non-Schistosomal Colorectal Cancers
Authors: Pan Weiyu , Luan Lijuan , Huang Jie , Wang Weixia , Huang Sinian , Bu Dacheng , Yao Junxia , Hou Yingyong
Published: July 2022

Objective: To compare the prognostic role regarding gene copy number alteration of MET in schistosomal colorectal cancer (SCRC) and non-schistosomal colorectal cancer (NSCRC).Methods: This retrospective study included 131 SCRC and 207 NSCRC patients, MET status was evaluated by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in tissue microarray sections.Results: No significant differences were found in terms of clinical characteristics for SCRC patients and NSCRC patients except for age, where significantly more patients over 60 years old presented SCRC than NSCRC (P < 0.001). 10.0% of cases were MET FISH-positive (mean ≥ 3 copies/cell). MET protein expression was positive in 60.3% of cases, but was not associated with MET FISH-positive (P = 0.574). All patients were followed, and the median time was 51.3 months (range, 1.0 – 134.4 months). The prognostic significance of MET FISH-positive was different between SCRC and NSCRC. In SCRC, patients that were MET FISH-positive had significantly shorter survival compared to those that were MET FISH-negative (P = 0.014). In NSCRC, the overall survival shows a slight trend toward favorable prognosis in association with MET FISH-positive for stage I-II patients (P = 0.138), yet MET FISH-positive were significantly correlated to adverse survival for stage III-IV patients (P = 0.015). Conclusions: Increased MET copy number acts as a negative prognostic factor for SCRC, which has bidirectional prognostic significance in NSCRC.
Management linked to ecological intensification supports pollinator abundance in Iberian wood-pastures
Authors: Pardo Adara , Rolo Víctor , Carrascosa Alejandro , Gonzalez-Bornay Guillermo , Moreno Gerardo
Published: July 2022

Context
Iberian wood-pastures (dehesas) constitute important habitats for flower-visiting insects, thus supporting the delivery of essential ecosystem services. However, dehesas have been experiencing increasing degradation either by farming intensification or abandonment.
Objectives
We assess if alternative management strategies linked to ecological intensification, designed to maximize productivity in Iberian dehesas, are also favorable for biodiversity, specifically pollinators.
Methods
We carried surveys in nine dehesas located across western and southwestern Spain. Each site comprised five paddocks under different management: conventional grazing, alternative systems linked to ecological intensification (rotational grazing, legume-enriched young and old pastures) and abandonment. We surveyed bees and hoverflies along fixed transects, together with flower cover and botanical composition, and we assessed landscape configuration.
Results
Results showed that rotational grazing, legume-enriched and abandonment enhanced pollinator abundance compared to conventional management, but practices linked to ecological intensification were more beneficial. Flower cover, together with plant diversity and landscape composition, were important drivers of pollinator abundance, richness and diversity. These patterns varied among pollinator groups, e.g., hoverflies were less impacted by management than bees, while being more affected by plant diversity.
Conclusions
Our findings suggest that alternative management linked to ecological intensification has potential in low-input farming systems such as Iberian dehesas. These measures can help to maximize productivity, whilst preserving biodiversity and essential ecosystem services such as pollination. Complementary measures, including the preservation or restoration of marginal landscape elements and semi-natural habitats, which ensure abundant feeding and nesting resources, also appear to be crucial for effectively safeguarding pollinating insects in this High Nature Value farming system.
Parasitic strongyle nemabiome communities in wild ruminants in Sweden
Authors: Halvarsson Peter , Baltrušis Paulius , Kjellander Petter , Höglund Johan
Published: July 2022

Background
Wildlife hosts may serve as reservoirs for strongyles which can be transmitted to domestic livestock. Therefore, we aimed to assess the risk for transmission of important nematode pathogens to domestic sheep in Sweden. The main aim of the study was to assess the risk for transmission of important pathogens from four wildlife hosts to domestic sheep.
Methods
First, fecal samples were collected from roe deer (n = 125), fallow deer (n = 106), red deer (n = 18) and mouflon (n = 13) in south central Sweden during the hunting season in 2019. Second, after fecal examination samples were cultured and the larvae were harvested, followed by DNA extractions. Third, all samples were then barcoded and processed for sequence analysis on the PacBio platform. Finally, bioinformatic sequence analysis was conducted with DADA2, while species diversity and richness as well as interactions between the different hosts were calculated and analyzed in R.
Results
Nematode ITS2 sequences were found in 225 of 262 (86%) samples. In total 31 taxa were identified amongst which 26 (86%) to the species level These were found in different combinations, amongst which 24 (77%) occurred in roe deer, 19 (61%) in fallow deer, 20 (65%) in red deer, and 10 (32%) in mouflon. Only five species are known to be associated with livestock (Chabertia ovina, Haemonchus contortus, Oesophagostomum venulosum, Teladorsagia circumcincta and Trichostrongylus axei). However, in the present study the relative abundance and prevalence of most of these species were low. The most striking exception was T. axei which was relatively abundant in all wildlife hosts. In addition, a wide range of wildlife specific nematodes such as Ostertagia leptospicularis and Spiculopteragia spp. were identified including the invasive nematode Spiculopteragia houdemeri which was found for the first time in red deer, fallow deer, and mouflon in Sweden. The difference in the number of shared species between mouflon and all cervids (n = 6) was less than between all three cervids (n = 8).
Conclusion
In contrast to our previous study with sheep, the relative abundance and prevalence of T. axei was generally much higher in wildlife than both H. contortus, and T. circumcincta which were negligible. Although the risk for cross-infections of nematodes between the studied wildlife hosts and sheep in Sweden cannot be ruled out, our findings indicate that the transmission potential appear to be relatively low for H. contortus and T. circumcincta, which are the two most pathogenic species in sheep.
Limitations of Calculating Theoretical Solutions for Closed BCMP Queueing Networks and Verification of Alternative Theoretical Values by Parallel Simulation
Authors: Mizuno Shinya
Published: July 2022

The global spread of the new coronavirus has caused people to rethink their ideas about waiting. In terms of building design, facilities must consider infection control measures and whether evaluations can be performed using queueing theory. Flexible definitions of queueing networks, such as Baskett, Chandy, Muntz and Palacios (BCMP) queueing networks, must be applied to large-scale models that exist in the real world, to evaluate congestion levels. This study applied a closed BCMP queueing network to a real-world model and examined the limitations of the theoretical solution calculation and the possibility of substituting theoretical values by parallel simulation. Parallel computing was applied to the mean value analysis method. Calculations were performed in a large-scale computing environment, enabling calculations on a much larger scale than with conventional models. The results also showed the computation time and required computing resources for the calculation. Since a larger customer class places a greater burden on computational resources, we conducted simulations on models for which a theoretical solution is required and assessed the accuracy of these simulations to confirm that they are sufficiently accurate as an alternative method to the theoretical solution. We proposed a process to calculate performance evaluation indices such as the average number of people in the system in parallel simulations and confirmed that the performance evaluation indices are sufficiently accurate for models with large customer classes. The study findings contribute to both social practicality and academic significance by making it possible to conduct mathematically supported congestion assessments in real-world models and to propose application scenarios for queueing theory.
NCX1 disturbs calcium homeostasis, and promotes RANKL-induced osteoclast differentiation by regulating JNK/c-Fos/NFATc1 signaling pathway in multiple myeloma
Authors: Li Tingting , Qiu Dongbiao , Chen Qingjiao , Yang Apeng , Chen Junmin , Addresses Zhiyong
Published: July 2022

Although several types of calcium channels abnormalities have been shown to promote myeloma bone disease (MBD), the relationship between Na+/Ca2+ exchanger 1 (NCX1) and MBD remains unexplored. Here, we examined the role of NCX1 in the development of multiple myeloma (MM), with a special focus on the underlying effects involved osteoclast differentiation. Firstly, we detected NCX1 protein was highly expressed in BM tissues of MM patients, and its expression was positively correlated with serum calcium and the percentage of BM CD138+ cells. In vitro, NCX1 suppression with the inhibitor KB-R7943 reduced cell viability of MM cells and caused apoptosis. Extracellular high Ca2+ environment increased the level of intracellular Ca2+ in MM cells through gating the calcium influx, with subsequent promoting the expression of NCX1 and osteoclastogenesis related genes (receptor activator of nuclear factor-κB (RANKL), nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and proto-oncogene Fos (c-Fos)). This phenomenon could be reversed by KB-R7943 or calcium chelation. Furthermore, NCX1 overexpression in MM cells accelerated osteoclastogenesis, while NCX1 knockdown or suppression resulted in the opposite effect. Mechanistically, we further investigated the related mechanisms of NCX1 regulating osteoclast differentiation using RNA sequencing, western blotting and Enzyme linked immunosorbent assay, and found that NCX1 modulates osteoclast differentiation in MM though JNK/c-Fos/NFATc1 signaling pathway. In conclusion, the Ca2+/NCX1-mediated signaling participates in the osteoclasts-myeloma cells interactions, which represents a promising target for future therapeutic intervention in MBD.
Expression of Satb2 in adult brain of key non-mammalian vertebrates: insights from evolution
Authors: Lozano Daniel , López Jesús M. , Morona Ruth , Jiménez Sara , Moreno Nerea
Published: July 2022

Satb2 is a transcription factor with functional and regulatory mechanisms, and post-translational modifications highly conserved in mammals. However, although its distribution has been analyzed in the mouse brain, there are few data in other non-mammal models. Therefore, in the present study we have analyzed the immunolocalization of Satb2 in the brain of adult specimens of different models at key evolutionary points of vertebrate diversification, including representative species of sarcopterygians and actinopterygians. In addition, we used other neuronal markers of highly conserved populations in the vertebrate brain, such as catecholaminergic, serotonergic and Otp populations, involved in the specificity of certain brain areas. The neuroanatomical pattern of Satb2, interpreted according to the current prosomeric model, serves to identify brain regions and compare them among the studied species, and with previous reported data, mainly for amniotes. We identified that Satb2 expressions have similar topologies in the subpallium of models studied, whereas striking differences were found in the pallium between sarcopterygian and actinopterygian vertebrates. Only the turtle showed expression in the dorsal derivatives of the pallium, specifically in the dorsal cortex, only scattered in Xenopus, whereas the lateral derivatives of the pallium expressed Satb2 in sarcopterygians, but not in actinopterygians. In the medial amygdala, or homologous structures, all models expressed Satb2, but only tetrapods also co-expressed Otp, probably originating from the paraventricular hypothalamic region, since only in those models a minor population of Satb2/Otp cells was also detected. In the caudal telencephalon, all models showed significant expression in the preoptic area, including the acroterminal domain of this region, where Satb2-expressing cells were dopaminergic. In the alar hypothalamus, all models showed Satb2 in the subparaventricular area, whereas in the basal hypothalamus only sarcopterygians showed a significant population in the tuberal hypothalamus, doubly labeled with Otp only in lungfish. The diencephalon of sarcopterygians showed Satb2 labeling in the prethalamus, and only turtles and lungfish showed expression in the thalamus. At midbrain levels, the optic tectum housed scattered Satb2 cells exclusively in turtles, while the expression along the rostrocaudal reticular formation and parabrachial nucleus was a conserved feature of sarcopterygians. The neuroanatomical pattern of Satb2 revealed important differences between sarcopterygians and actinopterygians, and these divergences may be related to the distinct functional involvement of Satb2 in the acquisition of various neural phenotypes and in the establishment of connectivity of these cells.
Characterization of reading errors in languages with different orthographic regularity: an Italian-English comparison
Authors: Marinelli Chiara Valeria , Romani Cristina , McGowan Victoria A. , Giustizieri Simona , Zoccolotti Pierluigi
Published: July 2022

The study examined whether a classification of errors based on Hendriks and Kolk’s (1997) proposal would effectively characterize the reading profile of children learning two orthographies varying for regularity, such as Italian and English. The study considered both an age-match and a school-match comparisons. Offline analysis of error production was carried out for two lists of stimuli: List 1 including regular words varying for frequency and matched non-words) and List 2 including low-frequency words varying for regularity. In List 1, Italian made mostly multiple attempts characterized by a slow and progressive approach to the target (sounding-out behavior) while English children showed a prevalence of word substitutions and non-word lexicalizations. As for List 2, Italian children again made more multiple attempts and progressive approach to the target (with more sounding-out behaviors and syllabications), while the English children made more phonological-visual errors, word substitutions, morphological, and semantic errors. Both groups showed a high proportion of phonological-visual and regularization errors (stress assignment in the case of Italian children). Overall, the use of an error coding system specifically tuned to the characteristics of the orthographies investigated allowed a more comprehensive identification of reading difficulties which made emerge more clearly the different strategies used by children of different language in reaching orthographic proficiency (more reliance on the sub-lexical routine in Italian and on lexical routines in English). These results call for more attention to error patterns in the identification of reading difficulties in children of different languages including those learning a transparent orthography where error analyses have largely been ignored.
Exponential and polynomial decay results for a swelling porous elastic system with a single nonlinear variable exponent damping: Theory and numerics
Authors: Soufyane Abdelaziz , Al-Mahdi Adel M. , Al-Gharabli Mohammed M. , Kissami Imad , Zahri Mostafa
Published: July 2022

We consider a swelling porous-elastic system with a single nonlinear variable exponent damping. We prove that the system is stable under a natural condition on the parameters of the system and the variable exponent. We obtain exponential and polynomial decay results by using the Multiplier method and these results generalize the existing results in the literature. In addition, we end our paper with some numerical illustrations.AMS Subject Classifications: 93D20; 35B40.
The geographic distribution of pharmacies in Canada
Authors: Grootendorst Paul
Published: July 2022

Background
Pharmacists are assuming an increasingly important role in the provision of primary care services. This raises questions about access to pharmacy services among those with medical needs. There is evidence on proximity of residents of Ontario and Nova Scotia to community pharmacies. There is little evidence for the rest of Canada.
Methods
We investigated availability of pharmacist services, both the number of community pharmacies and their hours of operation, at both the provincial and sub-provincial (Forward Sortation Area, FSA) level in Canada. We estimated regression models to assess associations of FSA-level service availability and medical need as measured using the share of residents aged 65 + and median household income.
Results
There are between 2.0 and 3.3 community pharmacies per 10,000 population, depending on the province. There are also provincial variations in the number of hours that pharmacies are open. Quebec pharmacies were open a median of 75 hours a week. In Manitoba, pharmacies were open a median of 53 hours a week. The per capita number of pharmacies and their total hours of operation at the FSA level tend to be higher in less affluent regions and in which the share of residents is aged 65 or older. Provincial differences in pharmacy availability were still evident after controlling for medical need.
Conclusion
Community pharmacies in Canada tend to locate where health needs (as measured using advance age and low income) are greatest. The impact on patient health outcomes of these pharmacy locational patterns remains an area for future research.
Magnetic separation accompanied by the phase transition for the purification of nematic liquid crystal
Authors: Meng Xiangshen , Li Jian , Lin Yueqiang , Liu Xiaodong , Li Decai , He Zhenghong
Published: July 2022

Free ions are generally unfavorable in liquid crystal (LC) displays, and LC purification technologies are critically important. The colloidal γ-Fe2O3 magnetic nanoparticles (MNPs) have a high ratio of surface to volume, which may adsorb more free ions and are uniform in the LC at room temperature. The precipitation and separation of the doped colloidal γ-Fe2O3 MNPs resulting from the magnetic field accompanied by an isotropic-nematic phase transition are more efficient than in the single case of the phase transition or the magnetic field. The residual ion concentrations have decreased distinctly using the low gradient magnetic field (∇B ~ 2 T/m) with the phase transition. In addition, the higher the concentration of the doped colloidal γ-Fe2O3 MNPs, the lower the concentrations of the residual ions and γ-Fe2O3 MNPs. As a result, the commercial nematic LC can be purified by this approach based on nanotechnology in our study.
Biodistribution of Sotrovimab, a SARS-CoV-2 monoclonal antibody, using PET imaging in cynomolgus monkey
Authors: Aweda Tolulope A , Cheng Shih-Hsun , Lenhard Stephen , Sepp Armin , Skedzielewski Tinamarie , Hsu Chih-Yang , Marshall Shelly , Haag Heather , Kehler Jonathan , Jagdale Prabhas , Peter Alessia , Schmid Michael A , Gehman Andrew , Doan Minh , Mayer Andrew , Gorycki Peter , Fanget Marie , Colas Christophe , Smith Brenda , Maier Cuirtis C , Alsaid Hasan
Published: July 2022

Purpose
Sotrovimab (VIR-7831), a human IgG1κ monoclonal antibody (mAb), binds to a conserved epitope on the SARS-CoV-2 spike protein receptor binding domain (RBD). The Fc region of VIR-7831 contains an LS modification to promote neonatal Fc-receptor (FcRn)-mediated recycling and extend its serum half-life. Here, we aimed to evaluate the impact of the LS modification on tissue biodistribution, by comparing VIR-7831 to its non-LS modified equivalent, VIR-7831-WT in cynomolgus monkeys.
Methods
89Zr-based PET/CT imaging of VIR-7831 and VIR-7831-WT was performed up to 14 days post injection. All major organs were analyzed for absolute concentration as well as tissue:blood ratios, with the focus on respiratory tract, and a physiologically-based pharmacokinetics (PBPK) model was used to evaluate the tissue biodistribution kinetics. Radiomics features were also extracted from the PET images and SUV values.
Results
SUVmean uptake in the pulmonary bronchi for 89Zr-VIR-7831 was statistically higher than 89Zr-VIR-7831-WT at Days 6 (3.43 ± 0.55 and 2.59 ± 0.38, respectively), and 10 (2.66 ± 0.32 and 2.15 ± 0.18, respectively), while the reverse was observed in the liver at Days 6 (5.14 ± 0.80 and 8.63 ± 0.89, respectively), 10 (4.52 ± 0.59 and 7.73 ± 0.66, respectively), and 14 (4.95 ± 0.65 and 7.94 ± 0.54, respectively). Though the calculated terminal half-life was 21.3 ± 3.0 days for VIR-7831 and 16.5 ± 1.1 days for VIR-7831-WT, no consistent differences were observed in the tissue:blood ratios between the antibodies except in the liver. While the lung:blood SUVmean uptake ratio for both mAbs was 0.25 on Day 3, the PBPK model predicted the total lung tissue and the interstitial space to serum ratio to be 0.31, 0.55, respectively. Radiomics analysis showed VIR-7831 had mean centralized PET SUV distribution in lung and liver, indicating more uniform uptake than VIR-7831-WT.
Conclusion
The half-life extended VIR-7831 remained in circulation longer than VIR-7831-WT, consistent with enhanced FcRn binding, while the tissue:blood concentration ratios in most tissues for both drugs remained statistically indistinguishable throughout the course of the experiment. In the bronchiolar region, a higher concentration of 89Zr-VIR-7831 was detected. The data also allow unparalleled insight into tissue distribution and elimination kinetics of mAbs that can guide future biologic drug discovery efforts, while the residualizing nature of the 89Zr label sheds light on the sites of antibody catabolism.
Functional traits related to competition for light influence tree diameter increments in a biodiversity manipulation experiment
Authors: Melis Raimondo , Morillas Lourdes , Roales Javier , Costa-Saura Jose Maria , Cascio Mauro Lo , Spano Donatella , Mereu Simone
Published: July 2022

Understanding how functional traits and diversity modulate plant interactions within forests is becoming a widespread research goal in ecology. We applied neighbourhood analysis to a Mediterranean biodiversity manipulation experiment (IDENT-Macomer) to assess the importance of functional traits in predicting tree diameter increments (DI) in a mixed forest. We used tree functional traits to weigh the neighbourhood competition index (NCI) and functional dispersion (FDis), which is a functional diversity metric. We found that functional traits affect competitive performance across species within a mixed forest and that resource acquisition is based primarily on trait hierarchy. We also found that traits related to competition for light, such as maximum plant height (Hmax), are the best predictors of DI. Our results reveal that NCI is a more reliable predictor than FDis, but the combination of both effects helps to better explain differences in DI. Finally, our findings show that gathering functional trait data is a practise that should be prioritised in mixed forest management due to the predictive importance of NCI and FDis in experiments with high density and species diversity.