Background: During the 2022-23 season, three autonomous communities recommended influenza vaccination for all children between 6 and 59 months. The objective is to evaluate the adverse effects associated with the administered influenza vaccines in the Region of Murcia, as well as their influence on the recommendation of the same to acquaintances or repetition in future seasons. Material and methods: Cross-sectional descriptive study with an online questionnaire sent to the parents of vaccinated minors of 6-23 months of age receiving inactivated intramuscular vaccine (IIV) or 24-59 months of age receiving live-attenuated intranasal vaccine (LAIV). Results: among 4,971 surveys received the most common adverse effect for LAIV and IIV were runny nose (40.90%) and local pain (31.94%) respectively. Sixty percent of adverse effects lasted ≤1 day, and around 10% lasted ≥3 days. The interference of adverse effects with the minor’s daily life was very infrequent (3.32%), as was the need for visiting the medical office (2.68%). Overall, 96.44% of parents would recommend influenza vaccination to friends and relatives after the experience. Only 3.56% would not recommend it, while 1.68% would not vaccinate their child against influenza again. The most frequently cited reason being adverse effects. Conclusions: Our study shows the safety of influenza vaccines. Despite the low impact of adverse effects, they influence some parents in their intention to continue vaccinating or recommending it to acquaintances, which remarks the need to reinforce the information given to parents so that this fact does not influence.

Venetoclax use in Patient with Ataxia Telangiectasia and Early-T-Cell Precursor Acute Lymphoblastic LeukemiaShaikha Alqahtani1, Ramya Ramakrishnan1, Shuyu E2 , Sa A. Wang2, Cesar Nunez1, David McCall1, Miriam B., Garcia1, Michael E. Roth1, Branko Cuglievan1, Amber Gibson1Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, Division of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

The recognition of constipation as a possible non-Immunoglobulin E (IgE) mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow’s milk allergy and constipation as a primary symptom, have found that between 28-78% of children improve on a cow’s milk elimination diet. Due to the paucity of data and a focus on IgE mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow’s milk allergy guidelines available in English language. The Exploring Non- IgE Mediated Allergy(ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper has used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data is insufficient to support a systematic review.

During mammalian terrestrial locomotion, body flexibility facilitated by the vertebral column is correlated with observed modes of locomotion, known as gait (e.g., sprawl, trot, hop, bound, gallop). In small-to-medium sized mammals (average weight up to 5 kg), the relationship between locomotive mode and vertebral morphology is largely unexplored. Here we studied the vertebral column from 46 small-to-medium sized mammals. Nine vertebrae across cervical, thoracic, and lumbar region were chosen to represent the whole vertebral column. Vertebra shape was analysed using three-dimensional geometric morphometrics with phylogenetic comparative method. We also applied the multi-block method, which can consider all vertebrae as a single structure for analysis. We calculated morphological disparity, phylogenetic signal, and evaluated the effects of allometry and gait on vertebral shape. We also investigated pattern of integration in the column. We found the cervical vertebrae show the highest degree of morphological disparity, and the first thoracic vertebra shows the highest phylogenetic signal. A significant effect of gait type on vertebrae shape was found, with the lumbar vertebrae having the strongest correlation; but this effect was not significant after taking phylogeny into account. On the other hand, allometry has a significant effect on all vertebrae regardless of the contribution from phylogeny. The regions showed differing degrees of integration, with cervical vertebrae most strongly correlated. With these results, we have revealed novel information that cannot be captured from study of a single vertebra alone: although the lumbar vertebrae are the most correlated with gait, the cervical vertebrae are more morphologically diverse and more drive the diversity among species when considering whole column shape.

Aim: This study evaluated the use of machine learning in leveraging drug ADME data to develop a novel anticholinergic burden (AB) scale and compared its performance to previously published scales. Methods: Experimental and in silico ADME data were collected for antimuscarinic activity, blood-brain barrier penetration, bioavailability, chemical structure and P-gp substrate profile. These five ADME properties were used to train an unsupervised model to assign anticholinergic burden scores to drugs. The performance of the model was evaluated through 10-fold cross-validation and compared with the clinical ACB scale and non-clinical ATS scale which is based primarily on muscarinic binding affinity. Results: In silico software (ADMET predictor ®) used for screening drugs for their blood-brain barrier (BBB) penetration correctly identified some drugs that do not cross the BBB. The mean AUC for the unsupervised and ACB scale based on five selected features was 0.76 and 0.64 respectively. The unsupervised model agreed with the ACB scale on the classification of more than half of the drugs (n=49 of m=88) and agreed on the classification of less than half the drugs in the ATS scale (n=12/25). Conclusion: Our findings suggest that the commonly used ACB scale may misclassify certain drugs due to their inability to cross the BBB. On the other hand, the ATS scale would misclassify drugs solely depending on muscarinic binding affinity without considering ADME properties. Machine learning models can be trained on these features to build classification models that are easy to update and have greater generalizability.

Synechococcus elongatus PCC 11801 is a fast-growing cyanobacterium, exhibiting high tolerance to environmental stresses. We have earlier characterized its genome and analysed its transcriptome and proteome. However, to deploy it as a potential cell factory, it is necessary to expand its synthetic biology toolbox, including promoter elements and ribosome binding sites (RBSs). Here, based on the global transcriptome analysis, 48 native promoters of the genes with high transcript count were characterized using a fluorescent reporter system. P cpcB, P psbA1, P 11770 promoters exhibited consistently higher fluorescence under all the cultivation conditions. Similarly, from the genome data and proteome analysis, 534 operons were identified. Fifteen intergenic regions exhibiting higher protein expression from the downstream gene were systematically characterized for RBSs, using an operon construct comprising of fluorescent protein genes eyfp and mTurq under P cpcB (P cpcB: eyfp:RBS: mTurq:T rrnB). Overall, the work presents promoter and RBS sequence libraries, with varying strengths, to expedite bioengineering of PCC 11801.

Post-transplant lymphoproliferative disorder (PTLD) is a significant complication of solid organ transplantation due to the lifelong immunosuppression (IS), ranging from non-malignant lymphoproliferations to lymphomas. Plasmablastic lymphoma (PBL), a rare and aggressive lymphoma, usually presenting in immunocompromised individuals has been rarely reported in the post-transplant setting. Here we summarize the clinical and pathological features of two children with PBL and history of solid organ transplant.

ABSTRACT.Squamous cell carcinoma (SCC) of the bladder is a rare urologic malignancy, estimated to affect 3% to 5% of the bladder. Squamous cell carcinoma (SCC) of the bladder remains the most common subtype throughout Africa. Most literatures focused on management of Transitional cell carcinoma(TCC) with fewer discussion in SCC management. TCC typically presents with painless hematuria, whereas SCC presents with painful hematuria, bladder mass, and necroturia. SCC is mostly radioresistant and does not respond to chemotherapy. The mainstay treatment is Partial Cystectomy or radical cystectomy, which can be performed through open surgery, laparoscopic or robot-assisted approach, all techniques with acceptable results. We report a case with favourable outcome following partial cystectomy which was managed by open surgery. In a 12months follow up the patient remained asymptomatic with good surgical outcome.

A document by Lingyu Fu. Click on the document to view its contents.

Issues surrounding gender equality are – and should be - front and centre in the water resources community, and other STEM fields. Very necessarily, the focus tends to remain on recruitment and inclusivity offering support for students and early career academics. The leaky pipeline concept used to describe the incremental loss of women from STEM fields with career duration results in a disproportionate loss of women, creating a parallel problem where highly qualified, top tier academics are disproportionately lost from the system after significant financial and personnel investment by institutions is made. Ultimately, the leaky pipeline undermines the extensive investment of the hydrology and other STEM communities in equity, diversity, inclusion, and accessibility (EDIA) recruitment and retention programs by cutting short career ambitions and the trajectories of diverse top performing individuals, resulting in no net benefit of EDIA policy investments. Addressing this critical gender gap requires the attention and support of the hydrology community of practice with specific focus on generating opportunities for advancement, confronting systemic and structural biases, and improving education around allyship. Institutions and professional organizations need to consciously grow diversity in leadership and recognize and outwardly manage the perception of academic excellence around slow research and education that attracts increased diversity. Supporting allyship, reducing competitiveness among community members, and reinforcing collaboration will not only attract, but retain, a higher proportion of diversity in the hydrology community, academia, and STEM professions in general. It is time for the water resources (and other STEM) communities to demand broader accountability and recognition of the barriers to women, implement and reward more diverse definitions of research excellence, and offer allyship training to the community of practice at large.

Recent advances in genomic technology, including the rapid development of long-read sequencing technology and single-cell RNA-sequencing methods, are poised to significantly expand the kinds of studies that are feasible in ecological genomics. In this perspective, we review these new technologies and discuss their potential impact on gene expression studies in non-model organisms. Although traditional RNA-sequencing methods have been an extraordinarily powerful tool to apply functional genomics in an ecological context, bulk RNA-seq approaches often rely on de novo transcriptome assembly, and cannot capture expression changes in rare cell populations or distinguish shifts in cell type abundance. Advancements in genome assembly technology, particularly long-read sequencing, and improvements in the scalability of single-cell RNA-sequencing (scRNA-seq), offer unprecedented resolution in understanding cellular heterogeneity and gene regulation. We discuss the potential of these technologies enable disentangling differential gene regulation from cell type composition differences and uncovering subtle expression patterns masked by bulk RNA-seq. The integration of these approaches provides a more nuanced understanding of the ecological and evolutionary dynamics of gene expression, paving the way for refined models and deeper insights into the generation of biodiversity.

Background. Food allergy (FA) is associated with poor quality of life and high levels of psychological distress. Psychological support is therefore extremely important but is not always available. As part of the Global Access to Psychological Services for Food Allergy (GAPS) Study, we aimed to assess distress and use of psychological services for adults with food allergy. Methods. Participants (n=1329 adults with FA) from >20 countries were recruited through patient organisations, social media adverts and online survey panels to complete an online survey. Surveys were offered in six languages. Results. A total of 67.7% of adults reported they had experienced FA-related psychological distress with the biggest issue being anxiety about having an allergic reaction (64.1%). Only 19.4% had been assessed for FA-related psychological distress; 22.9% had seen a mental health professional for treatment for their FA-related distress. There were significant differences across countries for levels of distress, screening for distress, seeing a mental health professional and being diagnosed with a FA-related mental health disorder (all p<0.001). The UK and Brazil had the highest number of adults reporting distress. The biggest barriers to seeing a mental health professional were cost, lack of insurance coverage, failure to provide a referral, and lack of practitioner in the area. Conclusions. FA-related distress is common in adults. Few have accessed the psychological care and support they need and there is significant variability across countries. Clinicians should consider routine assessment of adults for distress and easily accessible resources are needed to help support adult patients.

The 2022 Cochrane Lecture challenged Cochrane and its community to enhance their equity efforts and presented specific issues needing attention. We have created an actionable plan to address these challenges. These include: 1. Setting priorities for reviews based on health equity and global burden of disease 2. Advocate and support initiatives to promote equity, diversity, and inclusion in Cochrane 3. Actively seek global representation in the governance of the Campbell and Cochrane Health Equity Thematic Group We advocate for the inclusion of health equity considerations in all Cochrane systematic reviews. To achieve this, we need the cooperation of all those involved, such as journal editors, funders, and researchers. We invite the global community to work with us to address these equity gaps in research and practice.

Alzheimer’s disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. The canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology. Fluctuation of the levels of ovarian sex hormones during perimenopause is associated with changes in glucose metabolism, as a possible window of opportunity to further understand the roles of sex steroid hormones and their associated receptors in the pathophysiology of AD. We review these dimensions, emphasizing the potential of estrogen receptors (ER) to reveal mitochondrial functions in the search for further research and therapeutic strategies for AD pharmacotherapy. Understanding and addressing the intricate interactions of mitochondrial dysfunction and estrogen receptors potentially pave the way for more effective approaches to AD therapy.

Background: Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT assessing their specificity and sensitivity in diagnosing peanut allergy. Methods: Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. Results: On the eleven studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients was studied as well with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). Conclusion: BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanut. More investigations on the potential for MATs diagnostic methods are warranted.

The goal was to evaluate the hysteresis performance of segmented buckling resistant braces with low yield point steel LYP160, the monotonic tensile and cyclic loading tests of LYP160 were conducted and the corresponding laws have been obtained. According to the load-displacement curves of the specimen, the low yield point steel was characterized by good ductility and energy absorption ability. With the consideration of Chaboche model on the materials, the cyclic loading was simulated by ABAQUS and the cyclic hardening parameters of low yield point steel were obtained. On this basis, the hysteretic properties of buckling resistant braces under cyclic loads were simulated and analyzed. After the analysis and comparison of buckling resistant braces specimens with isotropic core plate and segmented variable section core plate, it can be found that: When the buckling resistant braces with isotropic core plate was loaded to L/100, the lateral deformation of BRB would reach 17mm and the seriously squeezed would observe on lateral constraint members. The buckling resistant braces would fail due to the accumulation of deformation on lateral constraint members at both ends of BRB. When the segmented buckling resistant braces was applied, the core plate with variable section would yield first in the middle part, other parts could still continue to consume energy due to the action of the limit plate. It would avoid the phenomenon that other parts could not continue to consume energy after the core plate failed at one point first. Under the action of cyclic loads, the stiffness of the segmented buckling resistant brace was constant and the better ability to consume energy was reflected.

LETTER

Fleas are small wingless hematophagous insect that are frequently infesting on rodents and other small mammals while acting as vectors of many zoonotic diseases including plague, a disease challenging public health in many part of the world including Tanzania. 291 rodents from nine species were captured with Sherman traps in farm land, peridomestic areas, bush and forest buffer zone across wet and dry season in plague and non-plague foci villages. Captured rodents were anaesthetized and 190 fleas comprising four species were collected and morphologically identified with available dichotomous key. Dinopsyllus lypusus were (46.32%) , Ctenophthalmus spp (26.84%), Xenopsylla brasiliensis (16.32%) and Xenopsylla cheopis (10.53%). 38.42% of fleas were collected from Mastomy natalensis, 22.63% from Lemniscomys striatus and 18.42% from Rattus rattus. Highest flea infestation prevalence was found on R.rattus and was strongly associated with X.cheopis and X.brasiliensis. Specific flea index of X.cheopis on R.rattus was (01) in plague foci and (<0.5) in non-plague foci. Result of GLM final model indicated that flea abundance was significant influenced by rodent species ( p < .001), season ( p= .031), habitats ( p= .02), rodent weight ( p < .001), rodent sex ( p < .001) and plague locations ( p= .02). There was significance difference in variation of flea abundance between rodent sexes (W = 9158.5, p = .009) and weak positive correlation between rodent’s weight and fleas abundance ( R= 0.17, p< 0.05). Despite that, specific flea index of X.cheopis on rats in both plague foci and non-plague foci villages were not indicating alarming condition that would require urgent control of fleas, still society should consistently adhere to rodent and fleas control methods especially in farm land and peridomestic areas where flea abundance is high and human activities are customarily implemented.