bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Marrow Multiparametric Magnetic Resonance Imaging with Texture Analysis for Follow-up of Advanced Stage Myelofibrosis after Transplantation
Authors: Gambella Massimiliano , Zaottini Federico , Bregante Stefania , Picasso Riccardo , Barabino Emanuele , Martinoli Carlo , Angelucci Emanuele
Published: February 2021

Introduction

Hematopoietic cell transplantation (HCT) is a potentially curative treatment in myelofibrosis (MF). Nevertheless, in at least one-third of patients, a reliable parameter for disease response is lacking due to the absence of a molecular marker (in triple-negative MF) or the suboptimal sensitivity for CALR and MPL monitoring with routinely used PCR methods. Trephine biopsy provides a limited histological description, as it does not represent the fibrosis and/or blast eradication status of the entire bone marrow.

The aim of this study is to identify magnetic resonance imaging (MRI) biomarkers that reflect response to transplant and may serve as predictors of transplant efficacy.

Methods

We report the case of a 45-year-old man diagnosed with triple-negative MF who was eligible for HCT following progression after a previous procedure. A pre-transplant trephine biopsy showed grade III fibrosis, according to the WHO 2016 classification. CD34+ cells were found to comprise 10%-15% of cells. He underwent MRI 8 days before bone marrow transplantation from a haploidentical donor. A second, comparative MRI was performed 6 months after HCT; concurrent chimerism was estimated through Short Tandem Repeats (STRs) analysis. A multiparametric protocol was applied, including intravoxel incoherent motion (IVIM) diffusion-weighted imaging, Dixon GRE with fat fraction calculation, and Turbo Spin Echo T1 and STIR sequences. MRI examination was performed on a 3 Tesla MRI machine and included lumbar segments L4 and L5, pelvis, sacral bone, and coccyx. A phased-array surface coil was applied to optimize signal-to-noise ratio. Finally, radiomics and texture analysis were performed on ADC sequences using specific image software post-analysis (Slicer 3D v.4.10.2).

Results

The selected MRI parameters showed substantial modifications between the first and second exams. T1 and STIR sequences demonstrated a decrease in bone marrow fibrosis (Figure 1). ADC values increased at pre-specified target points (iliac crest, pre-transplant: 0.762, post-transplant: 0.901; femur, pre-transplant: 0.77, post-transplant: 0.808). Moreover, among 300 features analyzed (Figure 2), 20 presented changes potentially related with bone marrow restoration. Concomitant STRs analysis showed a full donor chimerism status.

Conclusions

To the best of our knowledge, this is the first case of functional, textural analysis-based MRI employed in transplanted MF. Multiparametric MRI data, including anatomical and functional sequences (particularly IVIM with texture analysis of ADC values and Dixon with fat fraction calculation) may represent valuable biomarkers for accurate detection of bone marrow engraftment and chimerism.

Disclosures

No relevant conflicts of interest to declare.
Construction of a Novel CD34+ Hematopoietic Stem Cell Derived Xenograft Model of Human Hyperleukocytic Acute Myeloid Leukemia
Authors: Jin Yanxia , Chen Yanling , Zheng Yujia , Zhou Fuling
Published: February 2021

Acute myeloid leukemia (AML) is an abnormal clonal proliferative disease of hematopoietic progenitors in the bone marrow, which is the most common malignant disease in the blood system. Hyperleukocytic leukemia (HLL) is one of the high-risk types and commonly defined as peripheral blood leukocyte counts exceeding 50-100×109/l. The patients with hyperleukocytic acute myeloid leukemia (HL-AML) usually suffer from poor prognosis due to low responsiveness to initial chemotherapeutic agents, so these patients have higher mortality with life-threatening complication than those without hyperleukocytosis. However, there is no available patient derived xenograft model (PDX) in HL-AML, especially the CD34+ hematopoietic stem cell derived xenograft model of human HL-AML.

In this study, firstly, the primary HL-AML cells were collected and separated from the patients who underwent leukapheresis by using Fresenius COM.TEC machine, and the CD34+ hematopoietic stem cells were isolated from primary HL-AML cells using magnetic beads. Then, the NOD-SCID-IL2rγnull (B-NSG) mice were treated with 1.5 Gy χ-ray for total body irradiation at day 0, and intravenously injected with isolated 1.5 × 107 HLL cells or 1.5 × 106 CD34+ cells mixed with G-CSF within 24 h of irradiation. After inoculation, the blood smear, bone marrow smear, immunophenotyping and histopathology were used to test whether the model was successfully constructed.

For construction of hematopoietic stem cell derived xenograft model in HL-AML, at day 9, the immunophenotypes of hCD45+ and hCD34+ cells were found and had higher ratios in CD34+ group than HLL group in peripheral blood, which suggested the model was successfully established. The body weight of mice in CD34+ group were decreased faster than the HLL group due to severe tumor load and the leukocyte counts were increased higher than the correspondent HLL group after cell inoculation. In CD34+ group, the blood routine examination had changed, especially the WBC counts and PLT counts. On the 25th day, leukemic cells were found by the blood smears analysis and detected by flow cytometry, and which were more obviously found in bone marrow, and the immunophenotypes ratio of hCD45+ and hCD34+ were increased in CD34+ group. A lot of CD34+ cells were infiltrated into bone marrow, liver and spleen tissues on the 25th day that detected by histopathological analysis, which indicated that the more obviously model construction using hematopoietic stem cell derived leukemic cell.

In a conclusion, we successfully constructed a novel CD34+ hematopoietic stem cells derived animal model of human hyperleukocytic AML, which is available for mechanism research and drug treatment.

Disclosures

No relevant conflicts of interest to declare.
Novel 2 Marker Sandwich Immunoassay for the Detection of Precursor- and Mature Granulocyte-Derived Exosomes in Peripheral Blood: A Preliminary Case Study
Authors: Chong Esther G , Nguyen Anthony Loc , Mitsuhash Masato , Cao Huynh
Published: February 2021

Introduction:

In order to assess hematopoietic precursor cells, bone marrow biopsies are routinely conducted, which is painful for the patient and is not applicable for frequent testing. However, precursor, maturating, and matured cells are known to produce exosomes, which are released into peripheral blood. By analyzing these exosomes in plasma, bone marrow condition may be assessed noninvasively.

Myeloid precursor cells express different surface markers than when they have matured. It is reasonable to speculate that these markers would be incorporated into exosomes. In this study, we developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) by using a combination of monoclonal antibodies against 2 different leukocyte antigens, to account for the number of exosomes in plasma.

Methods

In 6 patients undergoing chemotherapy, venous blood was drawn at regular intervals before, during, and after respective chemotherapies was given. Various clones of monoclonal antibodies against CD11b, CD33, CD34, CD35, CD81, and CD117 were obtained, and antibodies were biotinylated by EZ link Sulfo-NHS-LC-Biotin. Anti-brain antibodies were switched with anti-leukocyte antibodies, and exosome activity was trended.

Results

CD11b+ and CD 117+ plates showed small changes during chemotherapy (within +/- 50% of the initial value), while plasma WBC count showed a dramatic decrease during chemotherapy.

In the recovery phase of WBC after chemotherapy, CD11b+ and CD16+showed a greater than 2-fold increase, with the up-trend taking place earlier than its plasma WBC counterparts. CD 117+ CD33+ also showed an up-trend, but was slower than their CD11b+ and CD16+ counterpart.

Finally, each exosome value was divided by other markers to calculate the ratio, and compared between pre and post chemotherapy blood. In half of the cases, there was not a difference, versus an almost double premature/mature ratio in post-chemotherapy blood in the other half of patients.

Conclusion

From data collected from pre-chemotherapy studies, the lack of correlation between ELISA data compared to plasma WBC data, indicates that plasma exosome analysis might not be suitable for the monitoring of acute bone marrow suppression.

Additionally, in the recovery phase, surface markers correlation with WBC was present in only some of the markers, indicating that the assay sensitivity is dependent on the marker combinations.

Overall, both myeloid precursor- and mature granulocyte-derived exosomes were increased during the recovery from chemotherapy in 3 out of 5 patients, and exosome profiles were different after chemotherapy in 2 out of 5 patients.

Disclosures

Mitsuhash: NanoSomiX:Current Employment.
Covid-19 Disease Is Not Associated with Venous Thromboembolism in a Cohort of Patients in Jeddah, Saudi Arabia
Authors: Kamel Fatemah , Magadmi Rania , Alqutub Sulafa , Badawi Maha A. , Al-Sayes Fatin , Badawi Mazen , Madani Tariq , Adam Soheir
Published: February 2021

Background: Coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS2), is associated with significant morbidity and mortality. The aim of this study is to characterize risk factors and clinical features of COVID-19 disease in an adult cohort in Jeddah, Saudi Arabia.

Methods: A retrospective case control study was conducted at King Abdulaziz University hospital (KAUH) in Jeddah, Saudi Arabia. Clinical and demographic data on patients presenting at KAUH with concern for COVID-19 disease between March 18 and May 18, 2020 were collected and analyzed.

Results: Electronic medical records on 297 patients presenting at KAUH were reviewed. Of these, 175 (59%) tested positive for COVID-19 by polymerase chain reaction (PCR) and 122 (41%) tested negative. COVID-19 positive patients were more likely to be males (OR=1.59; 95% CI=1.22-2.07), and non-health care workers (OR=1.53; 95% CI=1.13-2.08). Hypertension (10%), diabetes (10%), and two or more concurrent co-morbid conditions (54.4%), were more prevalent among COVID-19 positive patients. Patients presenting with fever, cough, and loss of sense of taste or smell were more likely to test positive for COVID-19 (p=0.001, 0.008, 0.008, respectively. Radiological evidence of pneumonia was associated with confirmed COVID-19 disease. Dyspnea, cough and gastrointestinal symptoms were not associated with risk of COVID-19 at presentation. On admission, white blood cells, neutrophils, lymphocytes, eosinophils, basophils, and platelets were significantly lower among COVID-19 positive patients compared to controls. Surprisingly, D-dimer levels were lower among COVID-19 positive patients. Furthermore, only two patients developed thrombosis; one with pulmonary embolism and one with coronary artery thrombosis.

Conclusion: Male gender, hypertension and diabetes were associated with risk of COVID-19 disease in this study population. D-dimer levels were not elevated in COVID-19 patients, and venous thromboembolism was not prevalent in cases, compared to controls. This is in contrast to previous reports on the association of COVID-19 disease with venous thromboembolism in other populations. Thus, individual and environmental risk factors may play an important role in the pathophysiology of thrombosis in COVID-19 disease.

Disclosures

No relevant conflicts of interest to declare.
Optical Mapping Uncovers Multiple Novel Genomic Structural Variants in Patient Leukemias
Authors: Finlay Darren , Murad Rabi , Hong Karl , Lee Joyce , Pang Andy , Lai Chi-Yu , Burian Carol , Mason James R. , Hastie Alex , Yin Jun , Vuori Kristiina
Published: February 2021

Leukemias are a diverse collection of hematopoietic cancers with limited chemotherapeutic treatment options. Patients unsuitable or unable for bone marrow transplantation have a dismal prognosis. Although previous studies have shown that there are only a limited number of potential driver mutations (3-8) per leukemia, there is an extensive heterogeneity of subtypes of disease. Using optical mapping with the Saphyr genome imaging system we confirm what other laboratories have found; that leukemias have additionally approximately 30-70 genomic structural variants per patient. This suggests that these SVs could ascribe the observed heterogeneity and could be responsible for individual pathogenesis of disease. Furthermore, we show that of many these SVs involve genes with functions associated with cellular processes relevant to cancer. Whilst known SVs, such asBCR-ABLtranslocations, are readily detected, multiple novel variants are also uncovered by Saphyr. Here we demonstrate the utility of this technique to uncover potential driver SV events and provide examples of such, some of which are associated with sensitivity and resistance to chemotherapeutics, including the standard of care drug Idarubicin (Idamycin). Finally, optical genome mapping shows 100% concordance with extant cytogenetic analyses, yet with a more streamlined methodology, a greater resolution, and higher sensitivity of detection.

Figure

Disclosures

Hong: Bionano Genomics:Current Employment.Lee:Bionano Genomics, San Diego:Current Employment.Pang:Bionano Genomics:Current Employment.Lai:Bionano Genomics:Current Employment.Hastie:Bionano Genomics:Current Employment.Vuori:Bionano Genomics:Membership on an entity's Board of Directors or advisory committees.
Molecular coevolution of coagulation factor VIII and von Willebrand factor
Authors: Zakas Philip M. , Coyle Christopher W. , Brehm Anja , Bayer Marion , Solecka-Witulska Barbara , Radford Caelan E. , Brown Christine , Nesbitt Kate , Dwyer Courtney , Kannicht Christoph , Spencer H. Trent , Gaucher Eric A. , Doering Christopher B. , Lillicrap David
Published: February 2021

Ancestral sequence reconstruction provides a unique platform for investigating the molecular evolution of single gene products and recently has shown success in engineering advanced biological therapeutics. To date, the coevolution of proteins within complexes and protein–protein interactions is mostly investigated in silico via proteomics and/or within single-celled systems. Herein, ancestral sequence reconstruction is used to investigate the molecular evolution of 2 proteins linked not only by stabilizing association in circulation but also by their independent roles within the primary and secondary hemostatic systems of mammals. Using sequence analysis and biochemical characterization of recombinant ancestral von Willebrand factor (VWF) and coagulation factor VIII (FVIII), we investigated the evolution of the essential macromolecular FVIII/VWF complex. Our data support the hypothesis that these coagulation proteins coevolved throughout mammalian diversification, maintaining strong binding affinities while modulating independent and distinct hemostatic activities in diverse lineages.
Highlights from the Respiratory Failure and Mechanical Ventilation 2020 Conference
Authors: Withers Adelaide , Ching Man Tiffany Choi , D'Cruz Rebecca , de Vries Heder , Fisser Christoph , Ribeiro Carla , Shah Neeraj , Van Hollebecke Marine , Vosse Bettine A.H. , Heunks Leo , Patout Maxime
Published: February 2021

The Respiratory Intensive Care Assembly of the European Respiratory Society organised the first Respiratory Failure and Mechanical Ventilation Conference in Berlin in February 2020. The conference covered acute and chronic respiratory failure in both adults and children. During this 3-day conference, patient selection, diagnostic strategies and treatment options were discussed by international experts. Lectures delivered during the event have been summarised by Early Career Members of the Assembly and take-home messages highlighted.
CiliarMove: new software for evaluating ciliary beat frequency helps find novel mutations by a Portuguese multidisciplinary team on primary ciliary dyskinesia
Authors: Sampaio Pedro , da Silva Mónica Ferro , Vale Inês , Roxo-Rosa Mónica , Pinto Andreia , Constant Carolina , Pereira Luisa , Quintão Carla M. , Lopes Susana S.
Published: February 2021

Evaluation of ciliary beat frequency (CBF) performed by high-speed videomicroscopy analysis (HVMA) is one of the techniques required for the correct diagnosis of primary ciliary dyskinesia (PCD). Currently, due to lack of open-source software, this technique is widely performed by visually counting the ciliary beatings per a given time-window. Our aim was to generate open-source, fast and intuitive software for evaluating CBF, validated in Portuguese PCD patients and healthy volunteers.

Nasal brushings collected from 17 adult healthy volunteers and 34 PCD-referred subjects were recorded using HVMA. Evaluation of CBF was compared by two different methodologies: the new semi-automated computer software CiliarMove and the manual observation method using slow-motion movies. Clinical history, nasal nitric oxide and transmission electron microscopy were performed for diagnosis of PCD in the patient group. Genetic analysis was performed in a subset (n=8) of suspected PCD patients.

The correlation coefficient between the two methods was R2=0.9895. The interval of CBF values obtained from the healthy control group (n=17) was 6.18–9.17 Hz at 25°C. In the PCD-excluded group (n=16), CBF ranged from 6.84 to 10.93 Hz and in the PCD group (n=18), CBF ranged from 0 to 14.30 Hz.

We offer an automated open-source programme named CiliarMove, validated by the manual observation method in a healthy volunteer control group, a PCD-excluded group and a PCD-confirmed group. In our hands, comparisons between CBF intervals alone could discern between healthy and PCD groups in 78% of the cases.
Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine
Authors: Ament Michael , Day Kathleen , Stauffer Virginia L , Skljarevski Vladimir , Rettiganti Mallikarjuna , Pearlman Eric , Aurora Sheena K.
Published: February 2021

Background

Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine.

Methods

The episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4–14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18–65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed.

Results

Galcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days.

Conclusions

Galcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine.

Trial registration

NCT,NCT02614183(EVOLVE-1), registered 25 November 2015; NCT,NCT02614196, (EVOLVE-2), registered 25 November 2015; NCT,NCT02614261(REGAIN), registered 25 November 2015.
Structure Investigations of Islands with Atomic-Scale Boron–Carbon Bilayers in Heavily Boron-Doped Diamond Single Crystal: Origin of Stepwise Tensile Stress
Authors: Polyakov S. N. , Denisov V. N. , Denisov V. V. , Zholudev S. I. , Lomov A. A. , Moskalenko V. A. , Molchanov S. P. , Martyushov S. Yu. , Terentiev S. A. , Blank V. D.
Published: February 2021

The detailed studies of the surface structure of synthetic boron-doped diamond single crystals using both conventional X-ray and synchrotron nano- and microbeam diffraction, as well as atomic force microscopy and micro-Raman spectroscopy, were carried out to clarify the recently discovered features in them. The arbitrary shaped islands towering above the (111) diamond surface are formed at the final stage of the crystal growth. Their lateral dimensions are from several to tens of microns and their height is from 0.5 to 3 μm. The highly nonequilibrium conditions of crystal growth enhance the boron solubility and, therefore, lead to an increase of the boron concentrations in the islands on the surface up to 1022 cm−3, eventually generating significant stresses in them. The stress in the islands is found to be the volumetric tensile stress. This conclusion is based on the stepwise shift of the diamond Raman peak toward lower frequencies from 1328 to 1300 cm−1 in various islands and on the observation of the shift of three low-intensity reflections at 2-theta Bragg angles of 41.468°, 41.940° and 42.413° in the X-ray diffractogram to the left relative to the (111) diamond reflection at 2theta = 43.93°. We believe that the origin of the stepwise tensile stress is a discrete change in the distances between boron–carbon layers with the step of 6.18 Å. This supposition explains also the stepwise (step of 5 cm−1) behavior of the diamond Raman peak shift. Two approaches based on the combined application of Raman scattering and X-ray diffraction data allowed determination of the values of stresses both in lateral and normal directions. The maximum tensile stress in the direction normal to the surface reaches 63.6 GPa, close to the fracture limit of diamond, equal to 90 GPa along the [111] crystallographic direction. The presented experimental results unambiguously confirm our previously proposed structural model of the boron-doped diamond containing two-dimensional boron–carbon nanosheets and bilayers.
A nanograting-based flexible and stretchable waveguide for tactile sensing
Authors: Peng Wang , Liao Qingxi , Song Han
Published: February 2021

Based on the related characteristics of optical waveguide and flexible optical materials, a flexible and stretchable optical waveguide structure oriented to tactile perception is proposed. The sensing principle of optical waveguide is based on mechanical deformation caused by output light loss. It overcomes the shortcomings of traditional optical waveguide devices, which are unable to conform to irregular surface. The flexible and stretchable optical waveguide is fabricated with nanoreplica molding method, and it has been applied to the measurement of pressure and strain in the field of tactile sensing. The flexible and stretchable optical waveguide had a strain detection range of 0 to 12.5%, and the external force detection range is from 0 to 23 × 10–3 N.
Quantitative proteomics analysis of lysine 2-hydroxyisobutyrylation in IgA nephropathy
Authors: Huang Shaoying , Zheng Fengping , Lin Hua , Zhou Xianqing , Xu Huixuan , Zhang Cantong , Dai Weier , Hocher Berthold , Zhang Xinzhou , Tang Donge , Dai Yong
Published: February 2021

Background

Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions.

Methods

In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry.

Results

Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins.

Conclusions

Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.
Influence of 200 years of water resource management on a typical central European river. Does industrialization straighten a river?
Authors: Wolf Stefanie , Esser Verena , Schüttrumpf Holger , Lehmkuhl Frank
Published: February 2021

Background

Over the last 200 years, the courses of most European rivers have experienced significant irreversible changes. These changes are connected to different kinds of anthropogenic river use and exploitation, which have varied from running water mills and rafting to large-scale hydroelectric power plants, industrial water withdrawal and flood protection measures. Today, in most developed countries, water quality and ecological river development are important factors in water management. The aim of this study is to evaluate the specific impacts of different time periods during the last 200 years on river courses and their effects on current river management using the example of the 165-km-long German Rur River (North Rhine-Westphalia). The Rur River is a typical central European upland-to-lowland river whose catchment has been affected by various phases of industrial development.

Methods

In this study, a range of morphological changes over the last 200 years are determined based on historic maps and up-to-date orthophotos. River length, sinuosity, oxbow structures, sidearms and the number of islands are used to investigate human impact. The results are correlated with historic time periods.

Results

This analysis shows that river straightening increases, especially during the Industrial Revolution, even without direct hydraulic channelization. The period and grade of river straightening have a direct morphodynamic impact on today’s river restorations. Since the Rur River is a typical upland-to-lowland river, the results show an additional impact by geofactors, such as landform configurations.

Conclusions

Morphodynamic development is correlated with five historic periods of industrial development between 1801 and 2019 up to the introduction of the EU—Water Framework Directive (EU-WFD). Each period shows a different influence on the watercourse, which is connected with human intervention. Even if worldwide comparisons show that the five historical phases differ slightly in their timing between regions, they are applicable to other study areas.
The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain
Authors: Dong Yan , Li Chong-Yang , Zhang Xiao-Min , Liu Ya-Nan , Yang Shuang , Li Meng-Nan , Xu Shi-Lian
Published: February 2021

Our previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.
A 44-kb deleted-type copy number variation is associated with decreasing complement component activity and calf mortality in Japanese Black cattle
Authors: Sasaki Shinji , Miki Youko , Ibi Takayuki , Wakaguri Hiroyuki , Yoshida Yuichi , Sugimoto Yoshikazu , Suzuki Yutaka
Published: February 2021

Background

Calf mortality generally occurs in calves prior to weaning, which is a serious problem in cattle breeding. Several causative variants of monogenic Mendelian disorders in calf mortality have been identified, whereas genetic factors affecting the susceptibility of calves to death are not well known. To identify variants associated with calf mortality in Japanese Black cattle, we evaluated calf mortality as a categorical trait with a threshold model and performed a genome-wide copy number variation (CNV) association study on calf mortality.

Results

We identified a 44-kb deleted-type CNV ranging from 103,317,687 to 103,361,802 bp on chromosome 5, which was associated with the mortality of 1–180-day-old calves. The CNV harbored C1RL, a pseudogene, and an IncRNA localized in the C1R and C1S gene cluster, which is a component of the classical complement activation pathway for immune complexes for infectious pathogens. The average complement activity in CNVR_221 homozygotes at postnatal day 7 was significantly lower than that of wild-type animals and heterozygotes. The frequency of the risk allele in dead calves suffering from diarrhea and pneumonia and in healthy cows was 0.35 and 0.28, respectively (odds ratio = 2.2, P = 0.016), suggesting that CNVR_221 was associated with the mortality of Japanese Black calves suffering from an infectious disease.

Conclusions

This study identified a deleted-type CNV associated with the mortality of 1–180-day-old calves. The complement activity in CNVR_221 homozygotes was significantly lower than that in heterozygotes and wild type animals. The frequency of the risk allele was higher in dead calves suffering from an infectious disease than in healthy cows. These results suggest that the existence of CNVR_221 in calves could be attributed to a reduction in complement activity, which in turn leads to susceptibility to infections. Thus, the risk allele could serve as a useful marker to reduce the mortality of infected Japanese Black calves.
TMT-based quantitative proteomic analysis reveals defense mechanism of wheat against the crown rot pathogen Fusarium pseudograminearum
Authors: Qiao Fangfang , Yang Xiwen , Xu Fengdan , Huang Yuan , Zhang Jiemei , Song Miao , Zhou Sumei , Zhang Meng , He Dexian
Published: February 2021

Background

Fusarium crown rot is major disease in wheat. However, the wheat defense mechanisms against this disease remain poorly understood.

Results

Using tandem mass tag (TMT) quantitative proteomics, we evaluated a disease-susceptible (UC1110) and a disease-tolerant (PI610750) wheat cultivar inoculated with Fusarium pseudograminearum WZ-8A. The morphological and physiological results showed that the average root diameter and malondialdehyde content in the roots of PI610750 decreased 3 days post-inoculation (dpi), while the average number of root tips increased. Root vigor was significantly increased in both cultivars, indicating that the morphological, physiological, and biochemical responses of the roots to disease differed between the two cultivars. TMT analysis showed that 366 differentially expressed proteins (DEPs) were identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment in the two comparison groups, UC1110_3dpi/UC1110_0dpi (163) and PI610750_3dpi/PI610750_0dpi (203). It may be concluded that phenylpropanoid biosynthesis (8), secondary metabolite biosynthesis (12), linolenic acid metabolites (5), glutathione metabolism (8), plant hormone signal transduction (3), MAPK signaling pathway-plant (4), and photosynthesis (12) contributed to the defense mechanisms in wheat. Protein-protein interaction network analysis showed that the DEPs interacted in both sugar metabolism and photosynthesis pathways. Sixteen genes were validated by real-time quantitative polymerase chain reaction and were found to be consistent with the proteomics data.

Conclusion

The results provided insight into the molecular mechanisms of the interaction between wheat and F. pseudograminearum.
Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study
Authors: Xu Fenghua , Li Ning , Wang Chun , Xing Hanyang , Chen Dongfeng , Wei Yanling
Published: February 2021

Background

Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated.

Methods

In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy.

Results

Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none.

Conclusions

This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO.

Trial registry

This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).
Renal dysfunction and prognosis of COVID-19 patients: a hospital-based retrospective cohort study
Authors: Xiang Hui-Xian , Fei Jun , Xiang Ying , Xu Zheng , Zheng Ling , Li Xiu-Yong , Fu Lin , Zhao Hui
Published: February 2021

Introduction

Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure.

Materials and methods

All 154 patients with COVID-19 were recruited from the Second People’s Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study.

Results

There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge.

Conclusion

Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.
Maternal obesity influences birth weight more than gestational diabetes
Authors: Alfadhli Eman M
Published: February 2021

Background

Maternal obesity and gestational diabetes (GDM) are commonly encountered during pregnancy. Both conditions are independently associated with unfavorable pregnancy consequences. The objective of this study was to compare the effects of obesity and GDM on birth weight, macrosomia, and other adverse pregnancy outcomes.

Methods

This cohort study involved 531 women with a singleton pregnancy attending the Maternity and Children’s Hospital, Medina, Saudi Arabia, between June 2014 and June 2015. Participants underwent a 75-g oral glucose tolerance test between 24 and 28 weeks. The International Association of Diabetes and Pregnancy Study Groups criteria were used for GDM diagnosis. BMI was assessed at the first antenatal visit, and obesity was defined as a BMI ≥30.0 kg/m2. All women were followed up until delivery. Women were divided into 4 groups: non-GDM nonobese (reference group), GDM nonobese, obese non-GDM, and obese GDM. Clinical characteristics and adverse pregnancy outcomes were compared.

Results

The mean age and BMI of the participants were 30.5 years and 29.3 kg/m2, respectively. GDM was diagnosed in 50.2% of the participants, and obesity was diagnosed in 47.8% of the participants. Obese women with GDM were the oldest and heaviest among all women. The mean birth weight increased in order among the four groups; it was highest in the infants in the obese GDM group, followed by those in the obese non-GDM, GDM nonobese and reference groups. Obesity and GDM alone or in combination were associated with higher rates of macrosomia and cesarean deliveries than the reference group. Neonatal intensive care unit (NICU) admission was higher in infants in the GDM nonobese and obese GDM groups. The frequency of low Apgar score was significantly higher in infants in the obese GDM group than in infants in the reference group.

Conclusions

Maternal obesity seems to influence birth weight more than GDM, while GDM is associated with a greater risk of admission to the NICU. The combination of both conditions is associated with the greatest risk of adverse pregnancy outcomes.
A validation of the Postpartum Specific Anxiety Scale 12-item research short-form for use during global crises with five translations
Authors: Silverio Sergio A. , Davies Siân M. , Christiansen Paul , Aparicio-García Marta E. , Bramante Alessandra , Chen Ping , Costas-Ramón Natalia , de Weerth Carolina , Della Vedova Anna M. , Infante Gil Lilliam , Lustermans Hellen , Wendland Jaqueline , Xu Jihong , Halford Jason C. G. , Harrold Joanne A. , Fallon Victoria
Published: February 2021

Background

Global crises inevitably increase levels of anxiety in postpartum populations. Effective and efficient measurement is therefore essential. This study aimed to create a 12-item research short form of the 51-item Postpartum Specific Anxiety Scale [PSAS] and validate it for use in rapid response research at a time of global crises [PSAS-RSF-C]. We also present the same 12-items, in five other languages (Italian, French, Chinese, Spanish, Dutch) to increase global accessibility of a psychometric tool to assess maternal mental health.

Methods

Twelve items from the PSAS were selected on the basis of a review of their factor loadings. An on-line sample of UK mothers (N = 710) of infants up to 12 weeks old completed the PSAS-RSF-C during COVID-19 ‘lockdown’.

Results

Principal component analyses on a randomly split sample (n = 344) revealed four factors, identical in nature to the original PSAS, which in combination explained 75% of the total variance. Confirmatory factor analyses (n = 366) demonstrated the four-factor model fit the data well. Reliability of the overall scale and of the underlying factors in both samples proved excellent.

Conclusions

Findings suggest the PSAS-RSF-C may prove useful as a clinical screening tool and is the first postpartum-specific psychometric scale to be validated during the COVID-19 pandemic. This offers psychometrically sound assessment of postpartum anxiety. By increasing the accessibility of the PSAS, we aim to enable researchers the opportunity to measure maternal anxiety, rapidly, at times of global crisis.
Novel immune-related genes in the tumor microenvironment with prognostic value in breast cancer
Authors: Tan Wen , Liu Maomao , Wang Liangshan , Guo Yang , Wei Changsheng , Zhang Shuqi , Luo Chengyu , Liu Nan
Published: February 2021

Background

Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical.

Methods

The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas (TCGA) were employed to comprehensively evaluate the TME. Then, TME characteristics were assessed, overlapping genes of the top 3 Gene Ontology (GO) terms and upregulated differentially expressed genes (DEGs) were analyzed. Finally, through combined analyses of overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network, novel immune related genes with good prognosis were screened and validated in both TCGA and GEO database.

Results

Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on GO functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. The top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.

Conclusions

High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.
An assessment of nutrition information on front of pack labels and healthiness of foods in the United Kingdom retail market
Authors: Ogundijo D. A. , Tas A. A. , Onarinde B. A.
Published: February 2021

Background

Front of pack nutrition labelling is part of United Kingdom government’s programme of activities aiming to tackle diet-related diseases. There are several front of pack labelling formats available and they differ in the information they deliver. This study assessed the frequency of usage of front of pack food labelling systems on food products in the United Kingdom grocery market. It also measured the healthiness of some foods in the online market by categorising them according to their nutrient contents.

Methods

Five hundred food products in five categories [(1) cereals and cereal products, (2) dairy products, (3) beverages, (4) packaged meats and meat products, and (5) pre-packaged fruits and vegetables] from three main United Kingdom retail websites were investigated. A simple random sampling method was used for product selection according to the categories on the retailers’ websites. The healthiness of foods was also assessed by categorising them into ‘healthier’, ‘moderately healthy’ and ‘least healthy’ based on fat, saturated fat, salt and sugar contents.

Results

The total number of label types assessed comprises 19.6% of Guideline Daily Amounts or Reference Intakes and 43.8% had a combination of Traffic Light and Reference Intakes (hybrid label). Slightly over a quarter (27.4%) of products included nutritional information in a grid or table, 3.4% of the foods had two of any of the following: Health Logo, Reference Intakes and Traffic Light labels, and 5.8% did not have any Reference Intakes, Traffic Light, Health Logo or Hybrid label. Most of the foods assessed were manufactured in the United Kingdom with only 30.8% imported from 32 countries across four continents.

Conclusions

Traffic Light and Guideline Daily Amounts were the most used front of pack labelling formats on the assessed food product. A higher number of assessed products belonged to the “moderately healthy” and “healthier” categories than the “least healthy”. The imported foods that were found in the United Kingdom retail market showed that food choices could be made from the diverse food types.