bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania
Authors: Topazian Hillary M. , Moser Kara A. , Ngasala Billy , Oluoch Peter O. , Forconi Catherine S. , Mhamilawa Lwidiko E. , Aydemir Ozkan , Kharabora Oksana , Deutsch-Feldman Molly , Read Andrew F. , Denton Madeline , Lorenzo Antonio , Mideo Nicole , Ogutu Bernhards , Moormann Ann M. , Mårtensson Andreas , Odwar Boaz , Bailey Jeffrey A. , Akala Hoseah , Ong'echa John Michael , Juliano Jonathan J.
Published: June 2022

Background

Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat to malaria elimination. ACT-resistance in Asia raises concerns for emergence of resistance in Africa. While most data show high efficacy of ACT regimens in Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times.

Methods

Three hundred children aged 2–10 years with uncomplicated P. falciparum infection were enrolled in Kenya and Tanzania after receiving treatment with artemether-lumefantrine. Blood samples were taken at 0, 24, 48, and 72 h, and weekly thereafter until 28 days post-treatment. Parasite and host genetics were assessed, as well as clinical, behavioral, and environmental characteristics, and host anti-malarial serologic response.

Results

While there was a broad range of clearance rates at both sites, 85% and 96% of Kenyan and Tanzanian samples, respectively, were qPCR-positive but microscopy-negative at 72 h post-treatment. A greater complexity of infection (COI) was negatively associated with qPCR-detectable parasitemia at 72 h (OR: 0.70, 95% CI: 0.53–0.94), and a greater baseline parasitemia was marginally associated with qPCR-detectable parasitemia (1,000 parasites/uL change, OR: 1.02, 95% CI: 1.01–1.03). Demographic, serological, and host genotyping characteristics showed no association with qPCR-detectable parasitemia at 72 h. Parasite haplotype-specific clearance slopes were grouped around the mean with no association detected between specific haplotypes and slower clearance rates.

Conclusions

Identifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa.
Prevalence and Risk Factors of Preterm Birth Among Pregnant Women Admitted at the Labor Ward of the Komfo Anokye Teaching Hospital, Ghana
Authors: Anto Enoch Odame , Ofori Boadu Wina Ivy , Opoku Stephen , Senu Ebenezer , Tamakloe Valentine Christian Kodzo Tsatsu , Tawiah Augustine , Ankobea Frank , Acheampong Emmanuel , Anto Agartha Odame , Appiah Michael , Wiafe Yaw Amo , Annani-Akollor Max Efui , Obirikorang Christian , Addai-Mensah Otchere
Published: June 2022

Preterm birth is a global epidemic and a leading cause of neonatal mortality in Sub-Saharan Africa. We evaluated the prevalence and risk factors of preterm birth among women attending the labor ward for delivery at a tertiary hospital in Ghana. This comparative cross-sectional study was conducted among a cohort of 209 pregnant women admitted to the labor ward of the Komfo Anokye Teaching Hospital (KATH). Pregnant women who delivered between 28 and 36 completed weeks of gestation were classified as preterm delivery whereas those who delivered after 37–42 completed weeks were described as term. Sociodemographic, clinical, and obstetric data were collected from patient's folder and hospital archives. Categorical variables were analyzed and expressed as frequencies and proportions. We determined the association between obstetric factors and preterm delivery with multiple logistic regressions. Significance level of the strength of association was determined at p-value < 0.05. of the 209 participants, the prevalence of preterm birth was 37.3% (78/209) whereas 62.7% (131/209) delivered at Term. Intrauterine growth restriction (IUGR) [aOR = 2.15, 95% CI = (1.819.55), p = 0.0390], HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome [aOR = 3.94, 95% CI = (1.64–9.48), p = 0.0020], early gestational obesity [aOR = 2.11, 95% CI = (1.31–11.92), p = 0.0480] and preeclampsia [aOR = 4.56, 95% CI = (1.63–12.76), p = 0.004] were identified as independent risk factors of preterm birth. Prevalence of preterm birth was high among women attending labor admission at the Komfo Anokye Teaching Hospital and this was independently influenced by IUGR, HELLP syndrome, early gestational obesity, and preeclampsia. Identifying early signs of adverse pregnancy outcomes would inform the need for management policy to prevent high prevalence of preterm births.
Membranous Nephropathy Secondary to Graves’ Disease: A Case Report
Authors: Neves Precil Diego Miranda de Menezes , Muniz Monique Pereira Rêgo , Morgantetti Giuliano Ferreira , Cutrim Érico Murilo Monteiro , Macieira Carlos de Andrade , Salgado-Filho Natalino , Lages Joyce Santos , Brito Dyego José de Araújo , Cunha Kaile de Araújo , Gatto Giuseppe Cesare , Silva Gyl Eanes Barros
Published: June 2022

Membranous nephropathy (MN) is a form of kidney disease that is idiopathic in 70%–80% of cases. Glomerular involvement in autoimmune thyroiditis can occur in 10%–30% of patients, and MN manifests in association with Hashimoto thyroiditis in up to 20% of the cases with glomerular involvement. Reports of MN associated with Graves’ disease (GD) are extremely rare in the current literature. Herein, we report the case of a 46-year-old man admitted to the hospital with nephrotic syndrome and symptomatic hyperthyroidism due to GD. Kidney biopsy revealed a secondary MN pattern. Immunohistochemical staining for PLA2R was negative, and thyroglobulin showed weak and segmental staining along the glomerular capillary. Anti-thyroid peroxidase (TPO) antibody test was not performed. The patient was treated for GD with methimazole and prednisone, and despite reaching clinical improvement after 8 months, proteinuria remained close to nephrotic levels. In this scenario, the patient was submitted to radioactive iodine, and there was a dramatic reduction in proteinuria levels after treatment. In conclusion, GD association with MN is rare, and when present, diagnosis using PLA2R and immunohistochemistry can be useful in determining association. In addition, radioactive iodine therapy can be an effective treatment modality when preceded with immunosuppressive corticosteroid therapy.
CD317-Positive Immune Stromal Cells in Human “Mesenchymal Stem Cell” Populations
Authors: Kay Alasdair G. , Fox James M. , Hewitson James P. , Stone Andrew P. , Robertson Sophie , James Sally , Wang Xiao-nong , Kapasa Elizabeth , Yang Xuebin B. , Genever Paul G.
Published: June 2022

Heterogeneity of bone marrow mesenchymal stromal cells (MSCs, frequently referred to as “mesenchymal stem cells”) clouds biological understanding and hampers their clinical development. In MSC cultures most commonly used in research and therapy, we have identified an MSC subtype characterized by CD317 expression (CD317pos(29.77 ± 3.00% of the total MSC population), comprising CD317dim(28.10 ± 4.60%) and CD317bright(1.67 ± 0.58%) MSCs) and a constitutive interferon signature linked to human disease. We demonstrate that CD317posMSCs induced cutaneous tissue damage when applied a skin explant model of inflammation, whereas CD317negMSCs had no effect. Only CD317negMSCs were able to suppress proliferative cycles of activated human T cellsin vitro, whilst CD317posMSCs increased polarization towards pro-inflammatory Th1 cells and CD317negcell lines did not. Using anin vivoperitonitis model, we found that CD317negand CD317posMSCs suppressed leukocyte recruitment but only CD317negMSCs suppressed macrophage numbers. Using MSC-loaded scaffolds implanted subcutaneously in immunocompromised mice we were able to observe tissue generation and blood vessel formation with CD317negMSC lines, but not CD317posMSC lines. Our evidence is consistent with the identification of an immune stromal cell, which is likely to contribute to specific physiological and pathological functions and influence clinical outcome of therapeutic MSCs.
Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study
Authors: Gao Ning , Kong Minjian , Li Xuebiao , Wei Dongdong , Zhu Xian , Hong Ze , Ni Ming , Wang Yifan , Dong Aiqiang
Published: June 2022

Background

Previous studies have shown that patients with systemic lupus erythematosus (SLE) tend to have a higher risk of cardiovascular disease (CVD), but the potential causal relationship between genetic susceptibility to SLE and CVD risk is not clear. This study systematically investigated the potential association between genetically determined SLE and the risk of CVD.

Methods

The genetic tools were obtained from genome-wide association studies of SLE and CVD, with no overlap between their participating populations. Mendelian randomization (MR) analysis was performed using inverse variance weighting as the primary method. Simultaneously, a series of repeated analyses, sensitivity analyses, and instrumental variable strength evaluations were performed to verify the reliability of our results.

Results

MR analysis showed that genetic susceptibility to SLE was associated with a higher risk of heart failure (OR=1.025, 95% CI [1.009-1.041], P=0.002), ischemic stroke (OR=1.020, 95% CI [1.005-1.034], P=0.009), and venous thromboembolism (OR=1.001, 95% CI [1.000-1.002], P=0.014). However, genetic susceptibility to SLE was negatively correlated with the risk of type 2 diabetes (OR=0.968, 95% CI [0.947-0.990], P=0.004). Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity.

Conclusion

Our MR study explored the causal role of SLE in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of SLE and provide comprehensive CVD assessment and treatment for SLE patients.
Seagrass Connectivity on the West Coast of Africa Supports the Hypothesis of Grazer-Mediated Seed Dispersal
Authors: Tavares Ana I. , Assis Jorge , Patrício A. R. , Ferreira Rogério , Cheikh Mohamed Ahmed Sidi , Bandeira Salomão , Regalla Aissa , Santos Iderlindo , Potouroglou Maria , Nicolau Suzana , Teodósio Maria Alexandra , Almada Carmen , Santos Rui , Pearson Gareth A. , Serrao Ester A.
Published: June 2022

Population connectivity influences the distribution of genetic diversity and divergence along a species range, as the likelihood of extinction or differentiation increases in isolated populations. However, there is still poor understanding of the processes mediating inter-population dispersal in marine species that are sessile and lack planktonic life stages. One such case is the seagrass speciesHalodule wrightii, which produces basal seeds, although detached plants can drift. Along the tropical western coast of Africa, this species occurs in distant discontinuous habitats, raising the question of how interpopulation dispersal is mediated. The species is a key source of ecosystem functions including feeding large migratory grazers. This study aims to infer whether genetic differentiation of the seagrassH. wrightiialong the western coast of Africa supports a hypothesis of predominant transportation of rafting seagrass by ocean currents, versus the hypothesis of biotic vectors of dispersal. Additional hypotheses were addressed concerning range-wide clonality and genetic diversity, assessed with microsatellite markers on populations of the west coast of Africa from Mauritania to Angola. Population genetic diversity and structure were compared with predictions from biophysical models of dispersal by oceanographic currents. The genetic data revealed low divergence among most populations, in strong contrast with predictions of very low probability of connectivity mediated by currents along the western African coastline. Moderate to high genotypic diversity showed important seed recruitment, but genetic and genotypic diversities were lower at range edges. Populations north and south of the equator were differentiated, and remarkably, so were neighboring equatorial populations despite their proximity. These results reveal independent sources of colonization of meadows in these islands, which are major habitat for migratory grazing green turtles, also supporting the hypothesis of biotically mediated seed transport. The importance of seagrass for conservation of endangered macrofauna has been widely reported; here we report evidence supporting the reciprocal role, that macrofauna protection can also plays a role in long-term survival and reproductive success of seagrass.
Prediction of Pan-Arctic Sea Ice Using Attention-Based LSTM Neural Networks
Authors: Wei Jianfen , Hang Renlong , Luo Jing-Jia
Published: June 2022

Within the rapidly changing Arctic region, accurate sea ice forecasts are of crucial importance for navigation activities, such as the planning of shipping routes. Numerical climate models have been widely used to generate Arctic sea ice forecasts at different time scales, but they are highly dependent on the initial conditions and are computationally expensive. Recently, with the increasing availability of geoscience data and the advances in deep learning algorithms, the use of artificial intelligence (AI)-based sea ice prediction methods has gained significant attention. In this study, we propose a supervised deep learning approach, namely attention-based long short-term memory networks (LSTMs), to forecast pan-Arctic sea ice at monthly time scales. Our method makes use of historical sea ice concentration (SIC) observations during 1979–2020, from passive microwave brightness temperatures. Based on the persistence of SIC anomalies, which is known as one of the dominant sources of sea ice predictability, our approach exploits the temporal relationships of sea ice conditions across different time windows of the training period. We demonstrate that the attention-based LSTM is able to learn the variations of the Arctic sea ice and can skillfully forecast pan-Arctic SIC on monthly time scale. By designing the loss function and utilizing the attention mechanism, our approach generally improves the accuracy of sea ice forecasts compared to traditional LSTM networks. Moreover, it outperforms forecasts with the climatology and persistence based empirical models, as well as two dynamical models from the Copernicus Climate Change Service (C3S) datastore. This approach shows great promise in enhancing forecasts of Arctic sea ice using AI methods.
Haploid Helps Phaeocystis Globosa Distribute to Deeper Dim Water, as Evidenced by Growth and Photosynthetic Physiology
Authors: Zhuang Junlian , Lu Jiachang , Cao Kun-Fang , Li Jie
Published: June 2022

Phaeocystis globosa has a haplo-diplontic alternative life cycle and is an important causative species of harmful algal blooms. Diploid solitary cells of Phaeocystis can form colonies and bloom in the surface water. However, haploid cells are abundant in deep water rather than surface water. We hypothesize that the haploid cells of Phaeocystis globosa could better adapt to deep dim water than its diploid cells. Haploid and diploid solitary cells of P. globosa were cultured with eutrophic medium (f/2) under moderately low (15 µmol photons m-2 s-1), extremely low (5 µmol photons m-2 s-1) and normal (60 µmol photons m-2 s-1) irradiance conditions. The results showed that irradiances used in this study did not induce reactive oxygen species (ROS) damage in either haploid or diploid cells. Both haploid and diploid solitary cells grew faster at higher irradiance during the initial exponential growth phase. However, the haploid abundances under moderately and extremely low irradiances were higher than that under normal irradiance after the exponential growth phase, but diploid cells formed more colonies at higher irradiances. An increase in the photosynthetic pigments (PSC) ratio combined with a reduction in photoprotective pigments (PPC) ratio were found in both ploidies with decreasing irradiance, but the ratios of PSC and PPC and xanthophyll cycle pigments were significantly higher in haploid cells than in diploid cells. For haploids, the highest potential photochemistry efficiency of photosystems П was found under extremely low irradiance, but for diploids, it was observed under moderately low irradiance. The results suggest that both haploid and diploid solitary cells of P. globosa in eutrophic water can survive under low-light conditions, but haploid cells have an advantage in extremely low irradiance.
Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation
Authors: Betjes Michiel G. H. , Roelen Dave L. , van Agteren Madelon , Kal-van Gestel Judith
Published: June 2022

Background

Biopsy-proven causes of graft loss many years after kidney transplantation are scarcely documented.

Methods

Patients transplanted between 1995 and 2005 (n = 737) in a single center were followed on a regular basis until 2021. The recipients were divided according to age at transplantation into 3 groups; 18–39 years (young), 40–55 years (middle age), and older than 55 years (elderly). For cause biopsies of renal transplants were clustered into the categories, rejection, IFTA, return original disease, and diagnosis of de novo kidney disease.

Results

Rejection was the main cause of graft failure censored for death at every time period after transplantation. The incidence of T cell-mediated rejection (TCMR) became rare 6 years after transplantation while the cumulative incidence of antibody-mediated rejection (ABMR) increased over time (1.1% per year). ABMR was not diagnosed anymore beyond 15 years of follow-up in recipients without pre-transplant donor-specific antibodies (DSA). An episode of TCMR was associated with an increased incidence of ABMR diagnosis in the short-term but did not increase the overall incidence of AMBR not in the long-term. Death as a cause of graft failure was an important competitive risk factor long after transplantation and resulted in a significantly lower frequency of rejection-related graft loss in the elderly group (11 vs. 23% in the young group at 15 year follow-up).

Conclusion

Rejection is a major cause of graft loss but recipient’s age, time after transplantation, and the presence of DSA before transplantation determine the relative contribution to overall graft loss and the type of rejection involved.
ACE2 Promoted by STAT3 Activation Has a Protective Role in Early-Stage Acute Kidney Injury of Murine Sepsis
Authors: Chen Tianxin , Fang Zhendong , Zhu Jianfen , Lv Yinqiu , Li Duo , Pan Jingye
Published: June 2022

Sepsis-induced AKI (SIAKI) is the most common complication with unacceptable mortality in hospitalized and critically ill patients. The pathophysiology of the development of SIAKI is still poorly understood. Our recent work has demonstrated the role of signal transducer and activator of transcription 3 (STAT3) pathways in regulating inflammation and coagulation in sepsis. We hypothesized that STAT3 activation has a critical role in early-stage SIAKI. The early-stage SIAKI model was established in cecal ligation and puncture (CLP) mice, which recapitulates the clinical and renal pathological features of early-stage AKI patients. Brush border loss (BBL) was the specific pathological feature of acute tubular injury in early-stage AKI. The role of STAT3 signaling and angiotension system in early-stage SIAKI was evaluated. The STAT3 activation (increased pSTAT3) and increased angiotensin-converting enzyme 2 (ACE2) expressions were observed in CLP mice. The low responsive expressions of pSTAT3 and ACE2 to septic inflammation in CLP AKI mice were associated with BBL. Correlation analysis of proteins' expressions showed pSTAT3 expression was significantly positively related to ACE2 expression in CLP mice. Reduced pSTAT3 after S3I201 intervention, which blocked STAT3 phosphorylation, decreased ACE2 expression, and exacerbated tubular injury in early-stage SIAKI. Our data indicate that endogenous increase of ACE2 expression upregulated by STAT3 activation in early-stage SIAKI play protective role against acute tubular injury.
Soil Microbial Communities Affect the Growth and Secondary Metabolite Accumulation in Bletilla striata (Thunb.) Rchb. f.
Authors: Xiao Chenghong , Xu Chunyun , Zhang Jinqiang , Jiang Weike , Zhang Xinqing , Yang Changgui , Xu Jiao , Zhang Yongping , Zhou Tao
Published: June 2022

Bletilla striata (Thunb.) Rchb.f. is a perennial herb belonging to the Orchidaceae family. Its tubers are used in traditional Chinese medicine to treat gastric ulcers, inflammation, silicosis tuberculosis, and pneumogastric hemorrhage. It has been reported that different soil types can affect the growth of B. striata and the accumulation of secondary metabolites in its tubers, but the biological mechanisms underlying these effects remain unclear. In this study, we compared agronomic traits and the accumulation of secondary metabolites (extractum, polysaccharide, total phenol, militarine) in B. striata grown in sandy loam or sandy clay soil. In addition, we compared physicochemical properties and microbial communities between the two soil types. In pot experiments, we tested how irradiating soil or transplanting microbiota from clay or loam into soil affected B. striata growth and accumulation of secondary metabolites. The results showed that sandy loam and sandy clay soils differed significantly in their physicochemical properties as well as in the structure and composition of their microbial communities. Sandy loam soil had higher pH, SOM, SOC, T-Ca, T-N, T-Mg, T-Mn, T-Zn, A-Ca, A-Mn, and A-Cu than sandy clay soil, but significantly lower T-P, T-K, T-Fe, and A-P content. Sandy loam soil showed 7.32% less bacterial diversity based on the Shannon index, 19.59% less based on the Ace index, and 24.55% less based on the Chao index. The first two components of the PCoA explained 74.43% of the variation in the bacterial community (PC1 = 64.92%, PC2 = 9.51%). Similarly, the first two components of the PCoA explained 58.48% of the variation in the fungal community (PC1 = 43.67%, PC2 = 14.81%). The microbiome associated with sandy clay soil can promote the accumulation of militarine in B. striata tubers, but it inhibits the growth of B. striata. The accumulation of secondary metabolites such as militarine in B. striata was significantly higher in sandy clay than in sandy loam soil. Conversely, B. striata grew better in sandy loam soil. The microbiome associated with sandy loam soil can promote the growth of B. striata, but it reduces the accumulation of militarine in B. striata tubers. Pot experiment results further confirmed that the accumulation of secondary metabolites such as militarine was higher in soil transplanted with loam microbiota than in soil transplanted with clay microbiota. These results may help guide efforts to improve B. striata yield and its accumulation of specific secondary metabolites.
Spatial Distribution and Hierarchical Clustering of β-Amyloid and Glucose Metabolism in Alzheimer’s Disease
Authors: Zhou Da-An , Xu Kai , Zhao Xiaobin , Chen Qian , Sang Feng , Fan Di , Su Li , Zhang Zhanjun , Ai Lin , Chen Yaojing
Published: June 2022

Increased amyloid burden and decreased glucose metabolism are important characteristics of Alzheimer’s disease (AD), but their spatial distribution and hierarchical clustering organization are still poorly understood. In this study, we explored the distribution and clustering organization of amyloid and glucose metabolism based on18F-florbetapir and18F-fluorodeoxyglucose PET data from 68 AD patients and 20 cognitively normal individuals. We found that: (i) cortical regions with highest florbetapir binding were the regions with high glucose metabolism; (ii) the percentage changes of amyloid deposition were greatest in the frontal and temporal areas, and the hypometabolism was greatest in the parietal and temporal areas; (iii) brain areas can be divided into three hierarchical clusters by amyloid and into five clusters by metabolism using a hierarchical clustering approach, indicating that adjacent regions are more likely to be grouped into one sub-network; and (iv) there was a significant positive correlation in any pair of amyloid-amyloid and metabolism-metabolism sub-networks, and a significant negative correlation in amyloid-metabolism sub-networks. This may suggest that the influence forms and brain regions of AD on different pathological markers may not be synchronous, but they are closely related.
A Subset of Oligodendrocyte Lineage Cells Interact With the Developing Dorsal Root Entry Zone During Its Genesis
Authors: Green Lauren A. , Gallant Robert M. , Brandt Jacob P. , Nichols Ev L. , Smith Cody J.
Published: June 2022

Oligodendrocytes are the myelinating cell of the CNS and are critical for the functionality of the nervous system. In the packed CNS, we know distinct profiles of oligodendrocytes are present. Here, we used intravital imaging in zebrafish to identify a distinct oligodendrocyte lineage cell (OLC) that resides on the dorsal root ganglia sensory neurons in the spinal cord. Our profiling of OLC cellular dynamics revealed a distinct cell cluster that interacts with peripheral sensory neurons at the dorsal root entry zone (DREZ). With pharmacological, physical and genetic manipulations, we show that the entry of dorsal root ganglia pioneer axons across the DREZ is important to produce sensory located oligodendrocyte lineage cells. These oligodendrocyte lineage cells on peripherally derived sensory neurons display distinct processes that are stable and do not express mbpa. Upon their removal, sensory behavior related to the DRG neurons is abolished. Together, these data support the hypothesis that peripheral neurons at the DREZ can also impact oligodendrocyte development.
Clinical Features, Diagnosis, and Treatment of Primary Intraventricular Lymphoma: Insights From a Monocentric Case Series
Authors: Cheng Lidong , Zhu Hongtao , Wang Jing , Wang Guanghui , Ma Xiaoyu , Zhao Kai , Wang Junwen , Shu Kai
Published: June 2022

Objective

Primary ventricular lymphoma (PVL) is an extremely rare and commonly misdiagnosed disease. Previous studies were predominantly case reports, and literature regarding the diagnosis and treatment of PVL is limited. Therefore, this study aimed to evaluate the characteristics of patients with PVL.

Methods

The data of patients with pathologically confirmed PVL were assessed. Epidemiological data, imaging findings, surgery, pathological results, and prognosis were retrospectively analyzed. A systematic review of relevant literature was also conducted.

Results

A total of eight patients with PVL were identified. The main symptom was increased intracranial pressure. Radiographically, five patients had single lesion and three had multiple lesions; typical findings on magnetic resonance imaging included hypointensity on T1- and T2-weighted imaging, adjacent brain edema, and homogeneous enhancement on contrast-enhanced T1-weighted images. Preoperatively, six cases were misdiagnosed and two cases did not get a definite diagnosis. Craniotomy was performed on all patients, and four achieved gross total resection. Hydrocephalus was relieved after surgical resection in four patients. Pathology revealed diffuse large B-cell lymphoma in all patients. Only one patient had a severe complication. A total of three patients received concomitant adjuvant treatment, whereas five patients refused any adjuvant therapy. At the time of follow-up, the median survival time of patients was 15 months.

Conclusion

Primary ventricular lymphoma mainly presented with symptoms of increased intracranial pressure and had several imaging characteristics for the diagnosis, but the condition still tends to be misdiagnosed. Surgical resection is a feasible treatment for patients with isolated nodules, especially those with acute obstructive hydrocephalus.
Association of Recent and Long-Term Supplement Intakes With Laboratory Indices in Patients With COVID-19 in Tehran, Iran, During 2020
Authors: Hashemi Rezvan , Montazer Mohsen , Salehi Zahra , Azadbakht Leila
Published: June 2022

Background

Although previous studies observed the relationship between individual dietary supplements and enhancing body resistance against viruses, few studies have been conducted regarding the role of different supplements in treatment of COVID-19. This article aims to determine the association of recent and long-term supplement consumption on the biochemical indices and impatient duration among patients with COVID-19.

Methods

In this cross-sectional study on 300 adult men and women with COVID-19, recent and long-term supplement intakes were investigated by using a questionnaire. In addition, lifestyle was also assessed in aspects of fruits and vegetable consumption, physical activity, sleeping duration, fluid intake, and smoking status. Furthermore, the laboratory and paraclinical parameters were obtained from medical records. The relationship between supplement intake with the length of hospitalization and clinical laboratory tests was investigated by one-way analysis of variance (ANOVA).

Results

Those patients with supplement intake in the last 2 months had a significantly lower amount of blood urea nitrogen (BUN) (31.31 ± 13.87 vs. 37.57 ± 19.77 mg/dL, P: 0.002) and higher serum 25(OH)D (28.13 ± 14.09 vs. 23.81 ± 13.55 ng/mL, P: 0.03). Subjects with long-term supplement intake had a significantly lower invasive oxygen support (0.00 vs 5.10 %, P: 0.05), lactate dehydrogenase (LDH) (498.11 ± 221.43 vs. 576.21 ± 239.84 U/L, P: 0.02), fewer days of fever (0.49 ± 3.54 vs. 2.64 ± 9.21, P: 0.02), and higher serum 25(OH)D (31.03 ± 13.20 vs. 22.29± 13.42 ng/mL, P < 0.001). The length of hospital stay was practically the same between groups who received and did not receive supplementation during the 2 months prior to hospitalization (6.36 ± 3.32 vs. 6.71 ± 4.33 days, P: 0.004). Similarly, people who took supplements during the past year had practically similar hospitalization lengths (6.29 ± 4.13 vs. 6.74 ± 3.55 days, P: 0.004).

Conclusion

In conclusion, although practically the length of hospital stay was the same in both groups of supplement consumers and others, immune-boosting supplements were associated with improved several laboratory indices. However, due to the cross-sectional nature of our study, further longitudinal studies seem to be essential.
MRI-Based Radiomics for Preoperative Prediction of Lymphovascular Invasion in Patients With Invasive Breast Cancer
Authors: Nijiati Mayidili , Aihaiti Diliaremu , Huojia Aisikaerjiang , Abulizi Abudukeyoumujiang , Mutailifu Sailidan , Rouzi Nueramina , Dai Guozhao , Maimaiti Patiman
Published: June 2022

Objective

Preoperative identification of lymphovascular invasion (LVI) in patients with invasive breast cancer is challenging due to absence of reliable biomarkers or tools in clinical settings. We aimed to establish and validate multiparametric magnetic resonance imaging (MRI)-based radiomic models to predict the risk of lymphovascular invasion (LVI) in patients with invasive breast cancer.

Methods

This retrospective study included a total of 175 patients with confirmed invasive breast cancer who had known LVI status and preoperative MRI from two tertiary centers. The patients from center 1 was randomly divided into a training set (n=99) and a validation set (n = 26), while the patients from center 2 was used as a test set (n=50). A total of 1409 radiomic features were extracted from the T2-weighted imaging (T2WI), dynamic contrast-enhanced (DCE) imaging, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC), respectively. A three-step feature selection including SelectKBest, interclass correlation coefficients (ICC), and least absolute shrinkage and selection operator (LASSO) was performed to identify the features most associated with LVI. Subsequently, a Support Vector Machine (SVM) classifier was trained to develop single-layer radiomic models and fusion radiomic models. Model performance was evaluated and compared by the area under the curve (AUC), sensitivity, and specificity.

Results

Based on one feature of wavelet-HLH_gldm_GrayLevelVariance, the ADC radiomic model achieved an AUC of 0.87 (95% confidence interval [CI]: 0.80–0.94) in the training set, 0.87 (0.70-1.00) in the validation set, and 0.77 (95%CI: 0.64-0.86) in the test set. However, the combination of radiomic features derived from other MR sequences failed to yield incremental value.

Conclusions

ADC-based radiomic model demonstrated a favorable performance in predicting LVI prior to surgery in patients with invasive breast cancer. Such model holds the potential for improving clinical decision-making regarding treatment for breast cancer.
Gene Mutations Related to Glucocorticoid Resistance in Pediatric Acute Lymphoblastic Leukemia
Authors: Zhang JinFang , Zeng LingJi , Wang YuLian , Pan JianWei , Li XingDong , Feng Bei , Yang Quan
Published: June 2022

Objective

To investigate the correlation between gene mutations and glucocorticoid resistance in pediatric acute lymphoblastic leukemia (ALL).

Methods

A total of 71 children with ALL admitted to our center between September 2019 and September 2021 were enrolled. DNA obtained from bone marrow or peripheral blood samples at initial diagnosis was used for genetic testing via whole exome sequencing. Meanwhile, patient clinical information was collected. Subsequently, the correlations of gene mutations with clinical features and glucocorticoid resistance were analyzed.

Results

Of the 71 children enrolled, 61 (85.9%) had B-cell ALL (B-ALL) and 10 (14.1%) had T-cell ALL (T-ALL). The five genes with the highest mutation frequency in B-ALL were TTN (24.4%), FLT3 (14.6%), TP53 (14.6%), MUC16 (9.8%), and EPPK1 (9.8%). In contrast, those with the highest frequency in T-ALL were NOTCH1 (54.5%), FBXW7 (27.3%), TTN (27.3%), MUC16 (27.3%), and PHF6 (18.2%). Upon statistical analysis, TTN and NOTCH1 mutations were found to be associated with prednisone resistance. Further, TTN and MUC16 mutations were associated with a lower age at diagnosis, and NOTCH1 mutations were associated with T-ALL in female patients. Leukocyte counts and LDH levels did not differ based on the presence of any common gene mutation, and no association between these gene mutations and overall survival was observed.

Conclusions

Our study is the first to demonstrate the association between TTN mutation and glucocorticoid resistance in ALL. Our findings could guide strategies for overcoming drug resistance and aid in the development of drug targets.
Indole-3-Carbinol (I3C) Protects the Heart From Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Cellular Apoptosis in Mice
Authors: Li Qi , Xia Boyu , Wu Jingjing , Yuan Xiaomei , Lu Xu , Huang Chao , Gu Hongcheng , Zheng Koulong , You Qingsheng , Liu Kun
Published: June 2022

Strategies for treating myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and inflammation, which in turn leads to apoptosis and necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of indole-3-carbinol (I3C), a phytochemical found in most cruciferous vegetables, in a mouse model of myocardial ischemia/reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in infarct size and serum creatine kinase (CK) and lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic proteins, including Bax, caspase-3, and caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC) and glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic, antioxidant, and anti-inflammatory effects.
An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent Molecule Reveals Zn2+ Micro-Dynamics During Drug-Induced Organelle Ionic Disorder
Authors: Fang Hongbao , Li Yaheng , Yao Shankun , Geng Shanshan , Chen Yuncong , Guo Zijian , He Weijiang
Published: June 2022

The endoplasmic reticulum (ER) is the main storage site of Zn2+, and Zn2+ plays an important role in regulating ER homeostasis. Therefore, we designed and synthesized a ratiometric fluorescent Zn2+ probe ER-Zn targeting ER stress. The probe displayed a specific Zn2+ induced blue shift at the spectral maximum values of excitation (80 nm) and emission (30 nm). The ratio imaging capability of Zn2+ under dual excitation mode can be applied not only to quantitative and reversible detection of exogenous Zn2+, but also the observation of the Zn2+ level change under ER stress, elucidating the different behaviors of Zn2+ release in ER stimulated by tunicamycin and thapsigargin. Additionally, the NIR imaging capability of ER-Zn provides an important basis for further research on animal models and is expected to realize the visualization and treatment of ER stress-related diseases through the regulation of ER stress by Zn2+. We envision that this probe can be applied to screen drugs for diseases related to ER stress regulation.
The Mechanical Properties of in Situ Canine Skeletal Muscle
Authors: Allen P. D. , Barclay J. K.
Published: June 2022

This study was undertaken to determine if fiber arrangement was responsible for differences in the whole muscle mechanical properties. Experiments were carried out in situ in blood perfused dog skeletal muscles at approximately normal body temperature between 36° and 38°C. The following mechanical relationships were studied using a pneumatic muscle lever to measure Tension (P), length (L) and dP/dt: and dL/dt with a high frequency oscillograph (500–1000 Hz): 1.) Length:Tension; 2.) Force:Velocity; and 3.) Stress:Strain of Series Elastic. Electron microscopy and fiber typing were done as adjunctive studies. Muscles were stimulated by direct nerve stimulation with 0.1msec stimuli at a rate of 1 impulse per second for twitch contractions, or in 200 msec bursts of 100 Hz 0.1 msec stimuli for brief tetanic contractions. The pennate short fibered gastrocnemius plantaris developed 1.0 kg/g of tension during brief tetanic stimulation, at optimal length (Lo) with full stimulus voltage, while the parallel long fibered semitendinosus developed 0.5 kg/g under the same conditions. The Length:Tension relationship for these two muscles was qualitatively similar but quantitatively different. The Force:Velocity relationship (ΔL/L0 vs. P/P0) for both muscles were also qualitatively similar and could be described by the previously proposed rectangular hyperbola but a better predicted fit to the observed data could be produced by adding a descending exponential function to the rectangular hyperbola. Unlike previous studies, the Stress:Strain properties of the series elastic component measured by quick release (ΔL/Li vs. ΔP/Po) were linear and gastrocnemius was 25 per cent higher than the semitendinosus. Overall, both muscles were found to have mechanical properties that differed little from the previously reported literature for amphibian, cardiac and small mammalian muscles studied by others in vitro. The major differences that we found were in the shapes of the force:velocity curve of the contractile component, and the Stress:Strain curve of series elastic component. Equations and explanations for these differences are devised and presented.
Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino
Authors: Beñaldo Felipe A. , Araya-Quijada Claudio , Ebensperger Germán , Herrera Emilio A. , Reyes Roberto V. , Moraga Fernando A. , Riquelme Alexander , Gónzalez-Candia Alejandro , Castillo-Galán Sebastián , Valenzuela Guillermo J. , Serón-Ferré María , Llanos Aníbal J.
Published: June 2022

Neonatal pulmonary hypertension (NPHT) is produced by sustained pulmonary vasoconstriction and increased vascular remodeling. Soluble guanylyl cyclase (sGC) participates in signaling pathways that induce vascular vasodilation and reduce vascular remodeling. However, when sGC is oxidized and/or loses its heme group, it does not respond to nitric oxide (NO), losing its vasodilating effects. sGC protein expression and function is reduced in hypertensive neonatal lambs. Currently, NPHT is treated with NO inhalation therapy; however, new treatments are needed for improved outcomes. We used Cinaciguat (BAY-582667), which activates oxidized and/or without heme group sGC in pulmonary hypertensive lambs studied at 3,600 m. Our study included 6 Cinaciguat-treated (35 ug kg−1 day−1x 7 days) and 6 Control neonates. We measured acute and chronic basal cardiovascular variables in pulmonary and systemic circulation, cardiovascular variables during a superimposed episode of acute hypoxia, remodeling of pulmonary arteries and changes in the right ventricle weight, vasoactive functions in small pulmonary arteries, and expression of NO-sGC-cGMP signaling pathway proteins involved in vasodilation. We observed a decrease in pulmonary arterial pressure and vascular resistance during the acute treatment. In contrast, the pulmonary pressure did not change in the chronic study due to increased cardiac output, resulting in lower pulmonary vascular resistance in the last 2 days of chronic study. The latter may have had a role in decreasing right ventricular hypertrophy, although the direct effect of Cinaciguat on the heart should also be considered. During acute hypoxia, the pulmonary vascular resistance remained low compared to the Control lambs. We observed a higher lung artery density, accompanied by reduced smooth muscle and adventitia layers in the pulmonary arteries. Additionally, vasodilator function was increased, and vasoconstrictor function was decreased, with modifications in the expression of proteins linked to pulmonary vasodilation, consistent with low pulmonary vascular resistance. In summary, Cinaciguat, an activator of sGC, induces cardiopulmonary modifications in chronically hypoxic and pulmonary hypertensive newborn lambs. Therefore, Cinaciguat is a potential therapeutic tool for reducing pulmonary vascular remodeling and/or right ventricular hypertrophy in pulmonary arterial hypertension syndrome.
The Effects of Maternal Intake of EPA and DHA Enriched Diet During Pregnancy and Lactation on Offspring’s Muscle Development and Energy Homeostasis
Authors: Ghnaimawi Saeed , Zhang Shilei , Baum Jamie I. , Huang Yan
Published: June 2022

EPA and DHA are n-3 long-chain polyunsaturated fatty acids with a diversity of health benefits on offspring. The objective of this study was to test the in vivo effect of maternal ingestion of EPA and DHA on fetal and offspring muscle development and energy balance. Two groups of female C57BL/6 mice were fed EPA and DHA enriched diet (FA) and diet devoid of EPA and DHA (CON) respectively throughout the entire period of gestation and lactation. Embryos at E13 and offspring at age of D1 and D21 were selected for sample collection and processing. No change in birth number and body weight were observed between groups at D1 and D21. Transient increase in the expression levels of myogenesis regulating genes was detected at D1 (p < 0.05) in FA group. Most of the expression of muscle protein synthesis regulating genes were comparable (p > 0.05) between FA and CON groups at D1 and D21. The significant increase in MHC4, and IGF-1 was not linked to increased muscle mass. A persistent increase in ISR expression (p < 0.05) but not in GLUT-4 (p > 0.05) was detected in offspring. Up-regulation of adipogenesis regulating genes was accompanied by increasing intramuscular fat accumulation in the offspring of FA group. Considerable increase in transcripts of genes regulating lipid catabolism and thermogenesis in liver (p < 0.05) was noticed in FA group at D21; whereas, only the levels of carnitine palmitoyl transferase 1A (Cpt1α) and Enoyl-CoA Hydratase And 3-Hydroxyacyl CoA Dehydrogenase (Ehhadh) increased at D1. Similarly, genes regulating lipolysis were highly expressed at D21 in FA group. EPA and DHA treatment promoted BAT development and activity by increasing the expression of BAT signature genes (p < 0.05). Also, maternal intake of EPA and DHA enriched diet enhanced browning of sWAT. Taken together, maternal ingestion of EPA/DHA may be suggested as a therapeutic option to improve body composition and counteract childhood obesity- related metabolic disorders and confer lifelong positive metabolic impact on offspring.
Leadless Left Bundle Branch Area Pacing in Cardiac Resynchronisation Therapy: Advances, Challenges and Future Directions
Authors: Wijesuriya Nadeev , Elliott Mark K. , Mehta Vishal , Sidhu Baldeep S. , Strocchi Marina , Behar Jonathan M. , Niederer Steven , Rinaldi Christopher A.
Published: June 2022

Leadless left bundle branch area pacing (LBBAP) represents the merger of two rapidly progressing areas in the field of cardiac resynchronisation therapy (CRT). It combines the attractive concepts of pacing the native conduction system to allow more physiological activation of the myocardium than conventional biventricular pacing, with the potential added benefits of avoiding long-term complications associated with transvenous leads via leadless left ventricular endocardial pacing. This perspective article will first review the evidence for the efficacy of leadless pacing in CRT. We then summarise the procedural steps and pilot data for leadless LBBAP, followed by a discussion of the safety and efficacy of this novel technique. Finally, we will examine how further mechanistic evidence may shed light to which patients may benefit most from leadless LBBAP, and how improvements in current experience and technology could promote widespread uptake and expand current clinical indications.