Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE cell-mediated food allergy characterized by repetitive vomiting and other gastrointestinal symptoms. Although little is known about FPIES pathophysiology, some cytokines have been reported to be involved. Since one of the main symptoms is vomiting, which is common to other diseases, it is difficult to distinguish acute FPIES from other conditions such as infectious enterocolitis. Thus, specific biomarkers are required for differential diagnosis. We aimed to identify potential biomarkers distinguishing acute FPIES from infectious enterocolitis and IgE-mediated anaphylaxis, which also cause vomiting. Methods: Seven patients with acute FPIES, nine with IgE-mediated anaphylaxis, and six with infectious enterocolitis were enrolled. The serum concentrations of interleukins (IL)-2, -4, -6, -8, -10, interferon-γ, and tumor necrosis factor-α were measured and compared among the three groups of patients. The serum concentrations of IL-2 and IL-10 were also compared between the symptomatic and asymptomatic stages. Alterations in serum cytokine levels were evaluated in acute FPIES during an oral food challenge test. Results: Serum IL-2 and IL-10 levels were significantly higher in acute FPIES patients than in patients with infectious enterocolitis and IgE-mediated anaphylaxis, whereas no significant differences were detectable in the serum levels of the other cytokines. The IL-2 and IL-10 elevation was only observed in the symptomatic stage of acute FPIES. Conclusion: The elevation in serum levels of IL-2 and IL-10 was specifically observed in symptomatic acute FPIES cases, suggesting that the measurement of IL-2 and IL-10 could be employed for differential diagnosis.

Background: Allergen immunotherapy(AIT) is the only disease-modifying treatment with long-term effects in patients with seasonal allergic rhinoconjunctivitis(SAR). Its efficacy depends on the precise identification of the pollen triggering symptoms. However, a diagnostic approach based on retrospective clinical history and sensitization to extracts often does not lead to unequivocal results. Objectives: To assess the usability and impact of a recently established algorithm for a potential clinical decision support system (@IT.2020-DSS) for pollen allergy and its diagnostic steps (including anamnesis, SPT, component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary) on doctor’s AIT prescription decisions. Methods: After a concise educational training on the @IT.2020-DSS algorithm, 46 doctors (18allergy specialists, AS, and 28general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the support algorithm. The usability and perceived impact of the algorithm on individual clinical performance were evaluated. Results: The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p<.01). AIT prescription based on anamnesis and SPT were heterogeneous but converged towards a consensus after the integration of CRD and eDiary information. Doctors considered the algorithm useful and recognized its potential in enhancing traditional diagnostics. Conclusions: The implementation of CRD and eDiary in the @IT2020-DSS algorithm improved consensus on hypothetical AIT prescription for SAR among AS and GP. The hypothesis, that a CDSS for etiological SAR diagnosis and AIT prescription may be useful in real-life clinical practice deserves further investigations.

Wind erosion is the main form of soil erosion in arid and semi-arid areas. It leads to soil loss and land degradation, which aggravates ecosystem vulnerability and threatens regional sustainable development. The assessment of wind erosion and the study of its driving factors can reduce soil wind erosion and provide decision-making assistance to solve environmental problems. Southern Africa is affected by severe soil erosion, which has brought a series of development problems, such as food crises and poverty. This study used meteorological and remote sensing data, and the revised wind erosion equation model to explore the temporal and spatial dynamics of soil erosion in southern Africa from 1991 to 2015. The impact of climate dynamics on soil wind erosion was also analyzed. The results showed that wind erosion fluctuated during the study period, and it first showed a downward trend and then stabilized at a relatively low level after 2010. Soil wind erosion across 66.65% of the study area significantly decreased (p < 0.05) and near-surface wind speed was the most important factor. The change in wind speed had a positive impact on soil wind erosion across 68.18% of the area. Temperature and precipitation were significantly related to soil wind erosion over 18.96% and 24.63% of the area, respectively. Both can also indirectly affect soil wind erosion through their effects on vegetation cover. This study will help decision-makers to evaluate areas that are at high-risk from soil erosion in southern Africa and enable them to effectively protect fragile ecosystems.

No abstract - Ist paragraph of the article A species’ ecological significance remains same whether it is found inside or outside a protected area (PA) then why the PAs are obligatory guarantor to maintain the biodiversity within their boundaries (Gascon et al. 2015)? Despite an increase in the number of PAs, connectivity is generally poor between and amongst the PAs, over 60% of PAs are too small to support major ecologically important and migratory species and eventually biodiversity is falling across the board (Coad et al. 2019). The PA approach, which was developed in the 20th century has been widely recognised as one of the most important strategies for achieving conservation goals (Shafer 2015). However, in the 21st century, it appears that PA based conservation approach has almost reached its practical and political limits (Coad et al. 2019; Shafer 2015) . Over the previous 1.5 century, the role of PAs was explored and expanded and both success and failures have been spectacular(Shafer 2015; Kalamandeen & Gillson 2007; Butchart et al. 2010; Watson et al. 2014). Most of the PAs were established for the primary goal of conservation and later sustainable growth have now stretched to contribute towards livelihood, poverty reduction and national development (Shafer 2015). Over 202,000 PAs worldwide, cover almost 15% of planet’s surface under some practice of protection (Terraube et al. 2020). Moreover, substantial wildlife exists outside the PAs, where exact estimates are not available due to insufficient monitoring efforts (Cox & Underwood 2011; McCleery et al. 2020).

Background Pulmonary artery hypertension (PAH) is a life-threatening and deteriorating disease with no promising therapy available currently due to its diversity and complexity. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism of PAH. Angiotensin-converting enzyme 2 (ACE2), which catalyzes the hydrolysis of the vasoconstrictor angiotensin (Ang) II into the vasodilator Ang-(1-7), has been shown to be an important regulator of blood pressure and cardiovascular diseases. Herein we hypothesized diminazene aceturate (DIZE), an ACE2 activator, could ameliorate the development of PAH and pulmonary vascular remodeling. Methods A murine model of PAH was established using left pneumonectomy (PNx) on day 0 followed by injection of a single dose of the VEGF receptor-2 inhibitor SU5416 (25mg/kg) subcutaneously on day 1. All hemodynamic and biochemical measurements were done at the end of the study on day 42. Animals were divided into 4 groups (n= 6/group): (1) sham-operated group, (2) vehicle-treatment group (SuPNx42), (3) early treatment group (SuPNx42/DIZE1-42) with DIZE at 15 mg/kg/day, subcutaneously from day 1 to day 42, and (4) late treatment group (SuPNx42/DIZE29-42) with DIZE from day 29-42. Results In both the early and late treatment groups, DIZE significantly attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, and right ventricle brain natriuretic peptide (BNP), as well as reversed the overexpression of ACE while up-regulating the expression of Ang-(1-7) when compared with the vehicle-treatment group. In addition, the early treatment group also significantly decreased plasma BNP and increased the expression of eNOS. Conclusions ACE2 activator has therapeutic potentials for preventing and attenuating the development of PAH in an animal model of left pneumonectomy combined with VEGF inhibition. Activation of ACE2 may thus be a useful therapeutic strategy for the treatment of human PAH.

Von Willebrand disease (VWD), the most prevalent congenital bleeding disorder, arises from a deficiency in von Willebrand factor (VWF), which has crucial roles in hemostasis. The present study investigated functional consequences and underlying pathomolecular mechanisms of several VWF propeptide (VWFpp) variants detected in our cohort of VWD patients for the first time. Transient expression experiments in HEK293T cells demonstrated that four out of the six investigated variants (p.Gly55Glu, p.Val86Glu, p.Trp191Arg, and p.Cys608Trp) severely impaired secretion. Their co-transfections with the wt partly corrected VWF secretion, displaying loss of large/intermediate multimers. Immunostaining of the transfected HEK293 cells illustrated the retention of the VWF variants in the endoplasmic reticulum (ER). Docking of the COP I and COP II cargo recruitment proteins, ADP-ribosylation factor 1 and Sec24, onto the N-terminal VWF model (D1D2D´D3) revealed that these variants occur at VWFpp putative interfaces, which can hinder VWF loading at the ER exit quality control. Furthermore, quantitative and automated morphometric exploration of the 3-dimensional immunofluorescence images showed changes in the number/size of the VWF storage organelles, Weibel-Palade body (WPB)-like vesicles. The result of this study highlighted the significance of the VWFpp variants on anterograde ER-Golgi trafficking of VWF as well as the biogenesis of WPB-like vesicles.

Tissue damage associated with trauma might release a sufficient autoantigen substrate to break immune tolerance. In a previous study, we showed that the leukopenia observed following severe inflammation is related to adenosine A1-receptor (A1R) desensitization and A2AR upregulation. We hypothesized that, under destructive pathological conditions this mechanism is beneficial in reducing prevalence of autoimmunity. In this study, we aim to evaluate the protective role of A1R and A2AR in prevention of autoimmune diseases. We used two murine models of autoimmune diseases: type 1 diabetes (T1D) induced by low-dose streptozotocin and pristane-induced lupus (PIL) and on neutrophils we studied NETosis regulation by adenosine. In both the T1D and PIL models, A1R-KO mice were predisposed to the development of autoimmunity. In the PIL model, in WT mice, parallel to the decline of A1R mRNA levels, lymphocytes number dropped (-85%) 6h after pristane injection. WT mice remained without any sign of disease at 36 weeks. In contrast, following pristane 43% of A1R-KO mice suffered from lupus-like disease. Compared to A1R-KO, in WT mice at 10 days A2AR mRNA levels were significantly higher. Similar to PIL, in T1D model the presence of A1R and A2AR was protective. In addition, we found that A1R increases and A2AR suppresses NETosis. We suggest that adenosine-dependent immune suppression and reduction in neutrophil extracellular traps (NETs) limits the reactive T-cells and development of anti-double strand DNA (dsDNA) antibodies that promote autoimmunity.

Objective To develop a survey evaluating women’s experience of outpatient hysteroscopy (OPH) to generate data for benchmarking services in the UK Design Quality improvement project and national survey. Setting 77 hospitals with OPH services collected data over two-months. Population 5151 women Methods The OPH-Patient Satisfaction Survey (OPH-PSS) was developed using a multi-disciplinary approach. Good practice guidance in hysteroscopy and existing survey’s provided content for the survey. Pilot testing identified aspects of the women’s OPH journey that contributed to a final survey that was rolled out nationally. Main outcome variable Adequacy of OPH services reflected in women’s experience of their OPH journey and the quality of care being delivered. Results The majority (3193, 76%) of hysteroscopic procedures were diagnostic. Most women (4485, 87%) received adequate information regarding OPH with 4581 (89%) agreeing that analgesia was discussed. 5033 (97%) felt involved in their care. Women commonly reported pain (4490, 87%), but >50% regarded this as slight. 1 in 10 women felt anxious. 1217 (26%) women experienced feeling faint. Overall, >90% (4,867) of women considered the OPH service good. The mean score rating for overall level of care was considerably high (9.7/10). Comparative pain scores for OPH vs the worst pain felt during a menstrual period showed OPH to be less painful, except for endometrial ablation (P=<0.001). Conclusion This novel survey, evaluating women’s experience of OPH (OPH-PSS), provides a useful tool for benchmarking OPH services. Overall, the information provided to women and their subsequent experience of OPH is good, but pain is common.

Population size is a central parameter for conservation, however monitoring abundance is often problematic for threatened marine species. Despite substantial investment in research, many marine species remain data-poor resulting in uncertain population forecasts and restricting the evaluation of past and present conservation actions. Such is the case for the white shark (Carcharodon carcharias), a highly mobile apex predator for whom population monitoring is a conservation priority following substantial declines recorded through the 20th century. Here, we estimate the effective number of breeders that successfully contribute offspring in one reproductive cycle (Nb) providing a snapshot of recent reproductive effort in an east-Australian New Zealand population of white shark. Nb was estimated over four consecutive age cohorts (2010, 2011, 2012, 2013) using two genetic estimators (linkage-disequilibrium; LD and sibship assignment; SA) based on genetic data derived from two types of genetic markers (single-nucleotide-polymorphisms; SNPs and microsatellite loci). While estimates of Nb using different marker types produced comparable estimates, microsatellite loci were the least precise. The LD and SA estimates of Nb within cohorts using SNPs were comparable, for example the 2013 age-cohort Nb(SA) was 289 (95%CI 200-461) and Nb(LD) was 208.5 (95%CI 116.4-712.7). We show that over the time period studied Nb was stable and ranged between 206.1(±45.9) and 252.0(±46.7) per year using a combined estimate of Nb(SA+LD) from SNP loci, and a simulation approach showed that in this population effective population size (Ne) per generation can be expected to be larger than Nb per reproductive cycle. This study demonstrates how breeding population size can be monitored over time to provide insight into the effectiveness of recovery and conservation measures for the white shark, where the methods described here may be applicable to other data-poor species of conservation concern.

Despite the wealth of knowledge available on the diversity of methicillin resistant Staphylococcus aureus (MRSA) strains that belonged to different clones, there have been no reports that analyzed such diversity on isolates belonging to the same clone. This study aimed to determine the diversity of ST239-MRSA strains, the predominant MRSA clone in worldwide, and to illustrate the correlation between the toxin genes, antimicrobial resistances and the genetic background of these strains. The molecular epidemiology of ST239-MRSA clone was analyzed by phenotypic antibiotyping, various genotypic assays. We found that coa-RFLP showed the highest discriminatory power in opposition to agr typing that had the lowest discriminatory power. The majority of our isolates (80%) were MDR, belonged to SCCmec III, agr I, coa genotype I and harbored sea and pvl genes. Our study demonstrated an overall negative correlation between the antimicrobial resistance and the toxin gene profiles. Meanwhile, there was no significant correlation between the toxin profiles and genetic background. The high diversity of ST239-MRSA strains might be among the contributors to the reported difficulties in control and prevention of MRSA infection in Egypt. With such diversity, it is assumed that these strains may have undergone different evolutionary processes.

1. Toxin resistance in all taxa is important for their survival. Resistance to bufadienolide toxin is mediated by molecular changes to the sodium-potassium-pump. As for toads themselves, the parotid is consisted of extremely high concentration of bufadienolide toxin, it indicates toads need stronger resistance for self-protection than any other species involved in toad predation. Thus, besides the widespread convergence of Na+/K+-ATPase, toads may develop a unique self-resistance way for their accumulated bufadienolide toxin. 2. Our studies on invasive cane toads from Australia and common asiatic toads from China showed that toads store defensive venom in parotid as a combinatorial library composed of low-toxic protoxin (conjugated bufadienolides), which is characterized by two building blocks, i.e. high-toxic toxin (free bufadienolide) and the argininyl side chain contributed to toxin absorption promotion. This protoxin could be hydrolyzed to high-toxic toxin for defense immediately as it is discharged from parotid at the time when toad is attacked or stimulated by predators. 3. Our results revealed that toads indeed develop a unique protoxin self-resistance way to their own extremely high concentration of bufadienolide toxin for self-protection besides the widespread convergence of Na+/K+-ATPase. The revelation of this protoxin self-resistance way highlights the importance and ecological multifunctionality of the sophisticated combinatorial chemistry of nature and may partly account for the strong adaptability of toad as infamous ailing invaders. It completes the picture of self-resistance mechanism to their own bufadienolide toxin for toad or may even for many other venomous animals.

Fetal Akinesia Deformation Sequence (FADS) is a hereditary disease with a very low incidence, which mainly involves the abnormal development of the musculoskeletal system. we detected a novel compound heterozygous mutation in MuSK related to FADS, which may help to provide more information to the affected couples

This paper is devoted to the study of a nonlinear pseudoparabolic equation in an annular with Robin-Dirichlet conditions. At first, by applying the standard Faedo-Galerkin method, we prove existence and uniqueness results. Next, using concavity method, we prove blow-up results for solutions when the initial energy is nonnegative or negative, then we also establish the lifespan for the equation via finding the upper bound and the lower bound for the blow-up times. Finally, we give a sufficient condition for the global existence and decay of weak solutions.

Objectives: To explore the safety and efficacy of total thoracoscopic repair of ventricular septal defects (VSD). We compared clinical outcomes of VSD via a total thoracoscopic approach with those of mini-sternotomy. Methods: We retrospectively reviewed clinical data from patients with VSD from 2012 to January 2019. According to the surgical pattern, they were divided into two groups: the total thoracoscopic surgery group (36 patients, 27 females, aged 29.08 ± 9.52 years), and a mini-sternotomy group (31 patients, 12 females, aged 28.39 ± 8.67 years). Results: There were no deaths in either group. In the thoracoscopic group, cardiopulmonary bypass (CPB) time and aortic cross-clamping (ACC) time were significantly longer than those of the mini-sternotomy group (CPB time: 111.78 ± 23.16 min vs 77.58 ± 37.90 min, respectively, p < 0.001; ACC time: 111.78 ± 23.16 min vs 77.58 ± 37.90 min, respectively, p < 0.001). Tracheal intubation time (6.42 ± 3.85 hours vs 28.55 ± 123.18 hours, p = 0.325), intensive care unit (ICU) stay time (20.47 ± 9.52 hours vs 49.65 ± 163.72 hours, p = 0.330), postoperative hospital stay time (5.11 ± 2.48 days vs 5.90 ± 6.27 days, p = 0.488) and chest drainage (139.86 ± 111.71 ml vs 196.13 ± 147.34 ml, p = 0.081) tended to be lower in the thoracoscopy group, although there was no significant difference. No residual shunt or tricuspid regurgitation was found at follow-up. Conclusions: Total thoracoscopic repair is safe and effective in patients with VSD, with or without tricuspid regurgitation.

We report the case of a 62-year-old male patient, admitted for aortic valve replacement. Bilateral common carotid artery occlusion and bilateral internal carotid artery occlusion have been reported, as well as right vertebral artery occlusion. Aortic valve replacement was performed in the standard fashion using the cardiopulmonary bypass. No neurological deficit was apparent on emergence from anesthesia. Keywords: bilateral carotid occlusion, the vertebral artery occlusion, cardiac surgery

A persistent left superior vena cava is relatively common venous anomaly. But, the presence of persistent left superior vena cava with the atresia of the right superior vena cava is a much rarer situation. The association of these anomalies with the drainage of the left hepatic vein into the right atrium is an extremely rare situation. Here we present one such case in the situs solitus and normocardia.

Objectives: The optimal treatment for stage T1 glottis squamous cell carcinoma remains controversial. We compared the oncological and vocal outcomes of patients who received endoscopic surgery with radiofrequency ablation (RFA) or open surgery. Design&Setting&Participants: Data were retrospectively collected for 93 patients who received primary treatment by RFA (n = 65) or open surgery (n = 28) from 2008 to 2014. Main outcome measures:Their characteristics were compared using the chi-square test. The 5-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Prognostic factors were assessed by univariate analysis using the log-rank test and by multivariate analysis using Cox models. Subjective vocal outcomes were evaluated by Voice Handicap Index-30 (VHI-30) questionnaire. The VHI scores of the two groups were compared using Mann-Whitney U test. Results and Conclusions:The 5-year DFS was 72.3%(47 / 65) for the RFA group and 92.9% (26 / 28) for open surgery group The open surgery group and a significantly better 5-year DFS (P=0.03), but the two groups had comparable OS (RFA: 86.2%; open surgery: 78.6%; P=0.26). Open surgery led to significantly worse voice quality (P<0.001). Among patients who received open surgery, those with involvement of the anterior commissure had higher total VHI scores (P=0.02).RFA and open surgery were both effective surgical treatments for stage T1 glottis squamous cell cancer. Open surgery was associated with a lower local recurrence rate but a worse VHI score. Among patients receiving open surgery, those with tumors involving the anterior commissure had poorer vocal outcomes.

This paper is concerned a novel spreading dynamical model for Echinococcosis with stochastic parameter perturbation. we show that there exist a unique positive solution of the stochastic model. Sufficient conditions for the stationary distribution which is ergodic is established by appropriate Lyapunov functions. Furthermore, we obtain the conditions on which the system will extinct. Finally, we illustrate our results by numerical simulation.

Olfactory and gustatory dysfunctions (OGD) have been reported as relevant symptoms that may predict presence of coronavirus disease 2019 (COVID-19) in adults, associated with mild or moderate disease1, 2, 3. However, published data on OGD in children are scant, likely due to several factors specific to the pediatric population such as a lower incidence of infection, the tendency of COVID-19 to be asymptomatic4, 5, and the difficulty of studying childhood OGD with objective methods. Two case reports have been published to date: one with 3 adolescents6, and the other describing a 17-year-old girl with beta-thalassemia who presented total loss of smell and taste for 8 days7 . Current data on the prevalence of OGD are based on only 2 small cohorts of COVID-19–positive children8, 9. In a related study, Mannheim et al.10 describe that 19 (30%) of 64 infected children (0–17 years old) presented nasal congestion, rhinorrhea, and total loss of smell, though providing no data on the exact number of patients with olfactory dysfunction exclusively.

Background/Objectives: Pupil size and reactivity have been studied in adult and pediatric populations to objectively measure pain which showed that pupillometry is a promising biomarker for pain measurement. Vaso-occlusive crisis, is a common complication of sickle cell disease (SCD) and better assessment tools are needed. The objective of this study is to establish normative values for pupil size and reactivity in pediatric patients with SCD with the hope that pupillometry can be used as a tool to objectively measure pain and response to treatment. Design/Methods: Institutional review board (IRB) approved prospective study enrolled 82 patients with SCD. Readings were performed using a NeurOptics PLR-2000 pupillometer. The following measures were collected: resting pupil size, % change in pupil size, pupil constriction velocity, and pupil dilation velocity. Results: Forty-four males and 38 females, all black, were studied. Median age was 11 years (range:2-21). The mean minimum and maximum pupil sizes were 3.52mm and 5.08mm, respectively. The mean dilation velocity and maximum constriction velocity were 1.03mm/s and -4.48mm/s, respectively. When comparing our participants with white participants in a previously published pediatric study, there was a significant difference in maximum constriction velocity, maximum pupil size, and minimum pupil size.1 There was no significant difference when comparing means for these parameters. Conclusion: There was no significant difference in pupil size and reactivity between patients with SCD and black patients without the disease. Further investigation of pupillometry within the black population during vaso-occlusive crisis and in the “well state” is warranted in pediatric patients with SCD.

We evaluated filtration behavior and virus removal capability for a mAb and plasma IgG under constant flow rate directly following flow-through column chromatography in an integrated process. For mAb solution with quantified host cell protein (HCP) content processed in flow-through mode on in-series mixed-mode AEX and modified CEX columns connected to the Planova BioEX filter (pool-less), HCP logarithmic reduction value (LRV) of 2.3 and 93.9% protein recovery were achieved for the process. Filtration behavior for 5 to 15 mg/mL plasma IgG run at flux of 10 to 100 LMH to 100 L/m2 throughput on Planova BioEX filters showed similar behavior across the protein concentrations tested although filtration pressure increased with throughput at 50 LMH and above, indicating the suitability of lower flux processes for continuous processing. Comparing both plasma IgG and mAb filtration behavior to four clogging models showed little difference in fit among the models, but with slightly better fit to the cake filtration model. Viral clearance tested by in-line spiking X-MuLV or MVM into purified plasma IgG showed robust removal at low flux. Integrating the Planova BioEX filter into continuous processes with column chromatography can achieve efficient downstream processing with reduced footprint and process time.

Virus filtration is a critical process in the production of biotherapeutics and drug products derived by plasma fractionation. The filterability of process solutions on virus removal filters is largely dependent on preceding downstream process steps, and column chromatography can have a particularly large impact on the throughput and flux of virus filtration. Filterability (throughput and flux) on Planova BioEX was greatly reduced for mAb and plasma IgG spiked with aggregate, and filterability improvement achieved by processing with chromatography resins (modified CEX, mixed-mode AEX and normal AEX column) was specific to protein solution. The various protein solutions spiked with aggregate showed distinct solution characteristics and by using the resulting filtration volume and flow rate, experimental and calculated filtration parameters were compared and evaluated with four clogging models: cake filtration, intermediate blocking, standard blocking and complete blocking. Effective purification of feed solutions by column chromatography has the capability to improve virus filtration processes. Further, the application of filtration parameters to the appropriate clogging model makes it possible to extrapolate filtration behavior to larger processing volumes.

Abstract: Background. Doxorubicin chemotherapy drug , use is limited by it’s potential to cause cardiotoxicity. In resource poor settings, like Malawi, monitoring of doxorubicin cardiotoxicity is not routinely conducted in cancer patients and the incidence of doxorubicin cardiotoxicity is not known. Methods. Children aged 3 months to 18 years with cancer were prospectively enrolled from the paediatric oncology ward and followed up from January 2016 to June 2019. Transthoracic echocardiographic monitoring of left ventricular ejection fraction (LVEF) was done at baseline, one month, six months and a year after completion of therapy. Cardiotoxicity was defined as a decline in LVEF of ≥10% to a final value of <50%, and an overall incidence risk of developing cardiotoxicity was estimated. A one-way analysis of variance was conducted to compare baseline LVEF with that measured during follow up intervals. Findings. A total of 91 children were enrolled into the study, 74% (68/91) were male, and 67% (62/91) were aged 5 months to 14 years. Burkitt lymphoma was diagnosed in 41% (38/91) of the children. No one experienced cardiotoxicity during the study period. However, of 77 children who had at least one follow up, five children 6·54% (95% CI: 2.1-14.5) experienced a reduction in LVEF of >10%, though not to a final value of <50%. No deterioration of systolic function was found among 20 children who had completed follow up. (F= 2·43, p-value=0·07). Interpretation. In this cohort, there were no observed cardiotoxic events associated with doxorubicin administration as per pre-defined criterion

Human histone H1 subtypes interaction networks was constructed to show a spectrum of their activities realized through the protein-protein interactions. Histone H1 subtypes participate in over half a thousand interactions with nuclear and cytosolic proteins engaged in the enzymatic activity and binding of nucleic acids and proteins. Small scale networks created by H1 subtypes are similar in their topological parameters (p > 0.05) but hub proteins of the networks formed with subtype H1.1 and H1.4 differ from those of subtype H1.3 and H1.5 in the closeness centrality, clustering coefficient and neighborhood connectivity (p < 0.05). Molecular function and biological process of the networks hubs is related to RNA binding and ribosome biogenesis (subtype H1.1 and H1.4), cell cycle and cell division (subtype H1.3 and H1.5) and protein ubiquitination and degradation (subtype H1.2). Such a disparity between H1 subtypes is also manifested by enriched GO terms of their interacting proteins. The residue propensity and secondary structures of interacting surfaces as well as a value of equilibrium dissociation constant indicate that a type of H1 subtypes interactions is transient in term of the stability and medium-strong in relation to the strength of binding. Histone H1 subtypes bind interacting partners in the intrinsic disorder–dependent mode, according to the coupled folding and binding and mutual synergistic folding mechanism. These results evidence that multifunctional H1 subtypes operate via protein interactions in the networks of crucial cellular processes and, therefore, confirm a new histone H1 paradigm relating to its functioning in the protein-protein interaction networks.