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Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as well as kidney transplant patients with cytomegalovirus (CMV) and polyomavirus (BKV) infections. Using an antibody-based assay, we quantified ~ 350 cell surface markers, cytokines, and chemokines involved in inflammation and immunity. Unique protein signatures were identified specific to the acute phase of infection irrespective of the pathogen type, with significant changes during convalescence. In addition, tumor necrosis factor receptor superfamily member 6 (TNR6), C-C Motif Chemokine Receptor 7 (CCR7), and C-C motif chemokine ligand-1 (CCL1) were increased in the acute and convalescent phases across all viral, bacterial, and protozoan compared to blood from healthy donors. Furthermore, despite the differences between pathogens, proteins were enriched in common biological pathways such as cell surface receptor signaling pathway and response to external stimulus. In conclusion, we demonstrated that irrespective of the pathogen type, there are common immunoregulatory and proinflammatory signals.

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

Aysha Aloqab,1,2 Valmore A Semidey,1 Gorka Sesma,3 Abdulmalik AlYahya,1 Khaled Al Malki,1 Abdulrahman Al Yahya,4 Rawa Mosaed Alohali,4 Mozon AlShareef,5 Hassan A Al-Dhibi1 1Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2Ophthalmology, Bahrain Defence Force Hospital, Riffa, Bahrain; 3Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 4Fellowship and Residency Training Program, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 5Medicine Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi ArabiaCorrespondence: Valmore A Semidey, King Khaled Eye Specialist Hospital, Al Urubah Road, Riyadh, 12329, Kingdom of Saudi Arabia, Tel +96614281234 ext. 2665, Fax +966114821234 ext. 3773, Email asemidey@hotmail.comPurpose: This study aimed to describe the functional and anatomical outcomes of post-cataract surgery fungal endophthalmitis at King Khaled Eye Specialist Hospital (KKESH).Patients and Methods: A retrospective analysis of clinical data from a single institution was performed. This study included 29 patients with post-cataract surgery endophthalmitis with suspected or confirmed fungal etiology who presented between January 1, 2017, and December 31, 2022. We evaluated demographics, clinical features, microbiological assessments, and treatment strategies. The effects of various treatments on outcomes were analyzed. The need for additional treatment and functional and anatomical outcomes was also investigated.Results: The mean time from surgery to the onset of ocular symptoms was 52.1 (SD ± 59.9; range, 3– 210) days, and the mean time from surgery to the first visit to KKESH was 81.4 (SD ± 103.5; range, 2– 510) days. Low culture positivity was noted in four samples, with two revealing Aspergillus sp. and two revealing Cladosporium sp. Of the 29 patients, 6 underwent pars plana vitrectomy (PPV) and received intravitreal antimicrobial/antibiotic injections. Two of the six patients also underwent simultaneous intraocular lens removal. The average number of additional treatments, regardless of visual acuity, was lower in the PPV group than in the conservative group (0.5 [SD ± 1.1; range, 0– 3] and 1.48 [SD ± 1.47; range, 0– 6], respectively). In the PPV group, 50% (n=3) of the eyes achieved functional success and 83.3% (n=5) of the eyes achieved anatomical success. In contrast, in the conservative group, 43.5% (n=10) of the eyes achieved functional success and 69.6% (n=16) of the eyes achieved anatomical success.Conclusion: For post-cataract surgery fungal endophthalmitis, a high index of suspicion and prompt PPV with empirical administration of intravitreal antifungal agents are required to achieve a favorable prognosis.Keywords: endophthalmitis, fungal, exogenous, pars plana vitrectomy, intraocular lens removal

Mawaddah Sabr,1,&ast; Valmore A Semidey,2 Marcos J Rubio-Caso,2 Renad Aljuhani Jnr,3 Gorka Sesma1,&ast; 1Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 3Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Gorka Sesma, Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Al Urubah Branche Road, West Building 2nd Floor, Riyadh, 11462, Saudi Arabia, Tel +966114849700, Fax +966114821908, Email gsesma@kkesh.med.saBackground: Retinal detachment is a major postsurgical threat in pediatric cataract surgery; however, the effect of axial length remains unclear. This study aimed to assess the relationship between axial length and detachment risk in vulnerable patients.Methods: This retrospective cohort study analyzed 132 eyes of 84 pediatric cataract surgery patients aged < 20 years old. Axial length was measured preoperatively, and the incidence of retinal detachment was recorded over a median follow-up of 4 years. Logistic regression analysis was used to examine the axial length-detachment relationship.Results: Twenty eyes had postoperative retinal detachments. The median axial length was longer in the detachment group (23.6 mm) than in the non-detachment group (21.6 mm). Eyes with axial length ≤ 23.4 mm had 0.55-fold decreased odds of detachment compared to longer eyes. Preexisting myopia and glaucoma confer heightened risk. Approximately half of the patients retained some detachment risk eight years postoperatively.Conclusion: Shorter eyes (axial length ≤ 23.4 mm) appear to be protected against pediatric retinal detachment after cataract surgery, whereas myopia, glaucoma, and axial elongation > 23.4 mm elevate the postoperative risk. Understanding these anatomical risk profiles requires surgical planning and follow-up care of children undergoing lensectomy.Plain language Summary: This study investigated the protective role of a shorter axial length in preventing retinal detachment after pediatric cataract surgery. This highlights the correlation between smaller eye sizes and reduced detachment risk, emphasizing the need for careful consideration of anatomical factors in surgical planning and patient monitoring, particularly for patients with preexisting myopia or postoperative glaucoma. Keywords: pediatric cataract surgery, axial length, retinal detachment, myopia, congenital glaucoma, congenital cataract

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

Pronunciation has been historically excluded from the language skills and sub-skills taught in the language classroom (Isaacs, 2009). Several factors or limitations such as a lack of training and time, and not being an English native speaker, among others, contribute to teachers' feelings of insecurity when teaching this language sub-skill (Derwing & Munro, 2015). Nevertheless, nowadays, the use of technology opens new possibilities for English as a foreign language (EFL) teachers and students to benefit from online resources specifically designed to teach pronunciation while using animated, authentic, and appealing materials in their lessons (Hismanoglu, 2010). In this respect, the present study aimed at exploring EFL teachers' attitudes toward using technology to teach pronunciation, the online resources they mostly use for this purpose, and their opinion of the resources' benefits and limitations. Participants were ten EFL teachers from the School of Languages of a Mexican university. The research adopted a qualitative approach under a constructivist paradigm. The method for data collection consisted of a semi-structured interview analyzed using inductive analysis. The results revealed that teachers have a positive attitude towards using technology to teach pronunciation. Their awareness of the benefits technology offers to students facilitates the teaching of segmental and suprasegmental features. However, the study discovered that some teachers neglect pronunciation teaching with or without technology, and most of them only use the repetition drill technique in face-to-face classes. Besides, teachers' lack of experience in using pronunciation software and time constraints point to the need for teachers' professional development program that helps them develop technological skills and awakens their interest in this language area. Finally, among other factors, the study identified those factors that specifically affect the teaching of pronunciation with technology.

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Abstract Purpose To evaluate the accuracy of magnetic resonance imaging (MRI) for jawbone assessment compared to reference-standard measurements in the literature. Materials and methods An electronic database search was conducted in PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library in June 2022, and updated in August 2023. Studies evaluating the accuracy of MRI for jawbone assessment compared with reference-standard measurements (histology, physical measurements, or computed tomography) were included. The outcome measures included bone histomorphometry and linear measurements. The risk of bias was assessed by the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). The review was registered in the PROSPERO database (CRD42022342697). Results From 63 studies selected for full-text analysis, nine manuscripts were considered eligible for this review. The studies included assessments of 54 participants, 35 cadavers, and one phantom. A linear measurement error ranging from 0.03 to 3.11 mm was shown. The accuracy of bone histomorphometry varies among studies. Limitations of the evidence included heterogeneity of MRI protocols and the methodology of the included studies. Conclusion Few studies have suggested the feasibility of MRI for jawbone assessment, as MRI provides comparable results to those of standard reference tests. However, further advancements and optimizations are needed to increase the applicability, validate the efficacy, and establish clinical utility of these methods.

El siguiente artículo lleva a cabo un análisis sobre la construcción discursiva del concepto de hábitat rural y de qué manera esos discursos han impactado en los abordajes territoriales en materia habitacional, en la región noroeste de la provincia de Córdoba, Argentina. Se parte de considerar que el análisis del discurso proporciona las claves para comprender cuáles son los focos de poder, qué estrategias componen y cómo se cristaliza esto en las formaciones discursivas relacionadas con el hábitat rural. Para ello se toman tres escenarios discursivos considerados fundamentales en esta construcción: el Estado, los medios masivos de comunicación y los discursos socioterritoriales. Durante el análisis, se toma como eje el Plan de Sustitución de Viviendas Precarias y Erradicación de Mal de Chagas como ejemplo para observar el despliegue de estos discursos construyendo modos determinados de abordar estos territorios. A partir de considerar algunos elementos ofrecidos por M. Foucault, el artículo muestra claves que permitan un abordaje amplio e integral de los territorios rurales, que tengan en consideración las prácticas domésticas, productivas y comunitarias propias de la ruralidad campesina local.

Importance: Understanding the pathophysiology of the macula in amblyopic eyes is an active research area. Objective: To correlate macular retinal vascular density changes with best-corrected visual acuity changes following occlusion therapy for amblyopia in children. Design: A prospective cohort study of children visiting the Pediatric Ophthalmology Division of our institution between January 2020 and January 2022 was conducted. Setting: A specialist eye hospital in Saudi Arabia. Participants: Thirty children with unilateral amblyopia. Exposure: Occlusion therapy for amblyopia.Main Outcome and Measures: Best corrected visual acuity (logMAR) before and at each of the four optical coherence tomographic angiographies was compared in amblyopic and fellow eyes. The effect of pretreatment determinants on the correlation between best-corrected visual acuity and retinal vascular density changes was reviewed. Results: In this cohort of 30 amblyopic and 30 fellow eyes from 30 children (mean age 8.7 ± 1.4 years; male: female 18:12. The best-corrected visual acuity improved from a median of 0.6 (interquartile range 0.5; 1.1) pretreatment to a median of 0.4 (interquartile range 0.2; 0.6) posttreatment in amblyopic eyes, and from a median of 0.1 to 0.05 in the fellow eyes. The total percentage change in retinal vascular density in the amblyopic eye was significantly higher than that in the fellow eye (Z = −1.92, P = 0.05). The change in best-corrected visual acuity in the amblyopic eye after a median of 98 months (interquartile range, 69–126 months) of intervention was significantly correlated with the refraction-adjusted change in retinal vascular density (B = −0.03, 95 % confidence interval −0.04, −0.02, P

BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.FundingNIH.

Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

Abstract Introduction Primary congenital glaucoma causes vision loss if intraocular pressure is uncontrolled. Nonpenetrating deep sclerectomy is effective in treating primary congenital glaucoma. However, the effects of inadvertent trabeculodescemetic window perforation remain unclear. Methods This retrospective cohort study included patients with primary congenital glaucoma who underwent nonpenetrating deep sclerectomy between 2014 and 2021. The perforation group had intraoperative trabeculodescemetic window perforations; the non-perforation group did not. The primary outcome was intraocular pressure between the groups over 15 months. The secondary outcomes included surgical success and complications. Results The study included 74 eyes of 44 patients. The cohort comprised 31 perforated and 43 non-perforated eyes. Both groups showed significant intraocular pressure reduction without significant between-group differences in complete (68 vs. 77%), qualified (19 vs. 9%), or failed (13 vs. 14%) treatments. The median intraocular pressure decreased from 39 to 14 mmHg in the perforation group and 35 to 12 mmHg in the non-perforation group. Of the 74 treated eyes, 68 (92%) showed no complications. Conclusions An inadvertent trabeculodescemetic window perforation during nonpenetrating deep sclerectomy for primary congenital glaucoma did not significantly affect intraocular pressure outcomes compared to non-perforated cases over 15 months. Nonpenetrating deep sclerectomy reduced intraocular pressure regardless of intraoperative perforation in patients with primary congenital glaucoma. Perforation of the trabeculodescemetic window was associated with a low incidence of postoperative complications.

Gorka Sesma,1 Tasnim Al Mairi,2 Heba Fareed Khashoggi,1 Shorog Ibrahim AlDhahi,1 Fahad Aljohar,3 Rajiv Khandekar,4 Abdulaziz Awad1 1Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2Emergency Department, Almoosa Specialist Hospital, Al Mubarraz, Saudi Arabia; 3Diagnostic and Imaging Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 4Department of Vision Science, University of British Columbia, Vancouver, CanadaCorrespondence: Gorka Sesma, Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Al Urubah Branche Road, West Building 2nd Floor, Riyadh, 11462, Saudi Arabia, Tel +966 11 4849700, Fax +966 11 4821908, Email gsesma@kkesh.med.saPurpose: Optical coherence tomography angiography (OCTA) noninvasively images retinal microvasculature. Foveal avascular zone (FAZ) biomarkers can act as indicators of various forms of amblyopia, making them valuable tools for clinicians. The purpose of this study was to assess the effect of amblyopia therapy on the FAZ using OCTA to determine FAZ size in children with untreated amblyopia.Patients and Methods: This two-arm cohort study enrolled 23 children with untreated strabismic or anisometropic amblyopia who underwent OCTA between 2021– 2022. Each arm had 23 eyes, with one arm having amblyopic eyes and the other having normal eyes. FAZ area, perimeter, and circularity index were measured before and quarterly during 1 year of occlusion therapy. Differences in avascular zone biomarkers between amblyopic and fellow eyes were compared and linked to demographic and ocular factors.Results: Similar FAZ areas were found in the amblyopic (0.3 mm2) and nonamblyopic eyes (0.28 mm2) (P = 0.83), with no significant change in either group (P = 0.93). Amblyopic eyes showed a larger FAZ perimeter reduction (0.12 mm2) than fellow eyes (0.02 mm2), but the difference was not statistically significant (P = 0.09). The circularity index in amblyopic eyes matched with fellow eyes (0.67 mm2), P = 0.38. Initial visual acuity and strabismus correlated with changes in the follow-up FAZ area.Conclusion: Amblyopia treatment did not significantly alter FAZ area in this cohort. Perimeter variations between amblyopic and fellow eyes require further study. The conclusions were limited by the sample size and lack of randomization.Plain Language Summary: Amblyopia is a common vision problem in children in which one eye does not see the fellow eye. This can occur if the eyes are not lined up right or if their prescriptions are different. Amblyopia is treated by placing a patch over the stronger eye to help the weaker eye better see.Researchers have used a technique called optical coherence tomography angiography (OCTA) to compare the foveal avascular zone (FAZ) before and after treatment in children with amblyopia. The FAZ is a spot on the back of the eye where there are no blood vessels or light-sensitive cells. Changes in the FAZ may indicate the severity of amblyopia.The study included 23 children with untreated amblyopia. Over the course of more than a year, measurements of FAZ area, perimeter, and roundness were taken before and during occlusion therapy. The size of the FAZ was also compared between the eyes with and without amblyopia.At the start of the study and after treatment, there were no significant differences between the FAZs of amblyopic eyes and other eyes. There were some differences in the size of the FAZ between eyes. Changes in the FAZ area were linked to the initial state of vision and misalignment.Overall, this study found that occlusion therapy did not change FAZ area in children with amblyopia. More research is needed to determine why the FAZ perimeter can differ between the eyes. Larger randomized studies would provide more information about how the FAZ changes when treating amblyopia.Keywords: amblyopia, optical coherence tomography angiography, foveal avascular zone, occlusion therapy, biomarkers

Reducing hot cracking is essential for ensuring seamless production of nickel superalloys, which are extensively used in welded structures for aircraft engines. The prevalence of hot cracking in precipitation-strengthened alloy 718 is primarily governed by two factors: firstly, the chemical composition and the coarse microstructure formed during solidification, and secondly, the activation of hot cracking mechanisms, which is particularly critical in mushroom-shaped welding morphologies. In this study, different nickel-based superalloys welded using laser beam welding (LBW), more specifically bead on plate welding (BoP), specimens are compared. The cracking susceptibility of both wrought and two investment casting 718 alloys with tailored chemical compositions is examined through the application of both continuous and pulsed LBW. Additionally, various pre-weld treatments, including with and without Pre-HIP (hot isostatic pressing), are analyzed. The influences of chemical composition, LBW parameters and pre- and post-welding treatments on both internal and external cracks determined by conventional and advanced non-destructive tests are studied. A clear reduction of hot cracking susceptibility and overall welding quality improvement was observed in a tailored 718 alloy with relatively high Ni (55.6% wt) and Co (1.11% wt) contents.

El mito de origen de la matrilinealidad macua conecta las relaciones sexuales y el intercambio económico entre mujeres y hombres. El objetivo de este artículo es analizar las continuidades en las concepciones sobre sexualidad y agencia por parte de las mujeres macua a través del mito. Este artículo se basa en la investigación etnográfica realizada por la primera autora durante 12 meses (2018-2019). Los resultados muestran una actualización de este mito a la realidad macua, sumergida en la economía global, que sirve como instrumento para redefinir y renegociar las relaciones de género.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64–3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18–3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05–1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815–1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.

The tetravalent dengue vaccine candidate, TAK-003, induces a functional antibody response, but the titers of antibodies against the four serotypes of the dengue virus (DENV) can vary. Here, through a transcriptomic analysis on whole blood collected from recipients of a two-dose schedule of TAK-003, we examine gene expression, splicing, and transcript isoform-level changes for both protein-coding and noncoding genes to broaden our understanding of the immune response. Our analysis reveals a dynamic pattern of vaccine-associated regulation of long noncoding RNAs (lncRNAs), differential splicing of interferon-stimulated gene exons, and gene expression changes related to multiple signaling pathways that detect viral infection. Co-expression networks isolate immune cell-type-related and interferon-response modules that represent specific biological processes that correlate with more robust antibody responses. These data provide insights into the early determinants of the variable immune response to the vaccine, highlighting the significance of splicing and isoform-level gene regulatory mechanisms in defining vaccine immunogenicity.

Body temperature must be monitored in patients receiving Hospital-at-Home (HaH) care for COVID-19 and other infectious diseases. Continuous temperature telemonitoring (CTT) detects fever and patient deterioration early, facilitating decision-making. We performed a validation clinical study assessing the safety, comfort, and impact on healthcare practice of Viture®, a CTT system, compared with a standard digital axillary thermometer in 208 patients with COVID-19 and other infectious diseases treated in HaH at the Navarra University Hospital (HUN). Overall, 3258 pairs of measurements showed a clinical bias of −0.02 °C with limits of agreement of −0.96/+0.92 °C, a 95% acceptance rate, and a mean absolute deviation of 0.36 (SD 0.30) °C. Viture® detected 3 times more febrile episodes and revealed fever in 50% more patients compared with spot measurements. Febrile episodes were detected 7.23 h (mean) earlier and modified the diagnostic and/or therapeutic approach in 43.2% of patients. Viture® was validated for use in a clinical setting and was more effective in detecting febrile episodes than conventional methods.

Abstract Higgs coupling deviations from Standard Model predictions contain information about two scales of Nature: that of new physics responsible for the deviation, and the scale where new bosons must appear. The two can coincide, but they do not have to. The scale of new bosons can be calculated by going beyond an effective field theory description of the coupling deviation. We compute model-independent upper bounds on the scale of new bosons for deviations in Higgs to WW and ZZ couplings, finding that any measured deviation at present or future colliders requires the existence of new bosons within experimental reach. This has potentially interesting implications for naturalness.

Ghaida Alahmadi,1 Azza MY Maktabi,2 Gorka Sesma,1 Saleh Almesfer1 1Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2Pathology and Laboratory Medicine Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi ArabiaCorrespondence: Gorka Sesma, Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Al Urubah Branche Road, West Building 2 nd Floor, Riyadh, 11462, Saudi Arabia, Tel +966114849700, Fax +966114821908, Email gsesma@kkesh.med.saPurpose: To evaluate the efficacy of intravitreal chemotherapy for vitreous seeding in patients with retinoblastoma (Rb).Design: Retrospective, single-arm cohort study.Methods: This study was conducted at a tertiary eye center. Between 2013 and 2021, 27 patients (27 eyes) with vitreous Rb receiving adjuvant intravitreal melphalan (IVM) as secondary/salvage treatment in one eye were included. Patients who were unable to follow-up or treated elsewhere were excluded. Survival analysis was performed to assess the incidence of enucleation in the melphalan-treated group, as well as in bilateral cases with eyes receiving melphalan and those receiving standard treatment, consisting of chemotherapy, thermotherapy, and enucleation according to the disease stage.Results: The median (interquartile range) follow-up time was 65 months (range, 34– 83 months). Seventeen patients (63%) had bilateral disease. Sixteen eyes (59%) were saved. The Kaplan–Meier survival estimates for eyes receiving melphalan were 100% at 1 year (95% confidence interval [CI]:11.2– 14.3), 75% (95% CI:14.2– 48.9) at 3 years, and 50% at 5 years. Melphalan-treated patients with bilateral disease showed a significantly higher number of saved eyes than the standard treatment group (P=0.002). Tumor recurrence was the primary cause of enucleation, accounting for 36% of the cases. In the vitreous hemorrhage group, the odds of enucleation were 13 times higher (95% CI:1.04– 165.28) than in the group without this condition.Conclusion: IVM is an effective treatment option for vitreous seeds. After 3 years of follow-up, the estimated survival rate for saved eyes decreased, and vitreous hemorrhage significantly increased the likelihood of enucleation. Further studies are required to determine the precise effects of IVM.Graphical Abstract: Keywords: retinoblastoma, melphalan, intravitreal chemotherapy, ocular oncology, intraocular tumors

Objective. To assess the association between early postoperative choroidal detachment and intraocular pressure (IOP) following nonpenetrating deep sclerectomy in pediatric primary congenital glaucoma. Design. Retrospective double-arm cohort study. Setting. Single center in Saudi Arabia. Patients. Seventy-two eyes of 45 patients were evaluated. Primary congenital glaucoma patients aged 0–3 years undergoing nonpenetrating deep sclerectomy as the first procedure from 2014 to 2021 were divided into groups with (n = 20) and without (n = 52) postoperative choroidal detachment. Main Outcome Measures. The primary outcome was complete surgical success, defined as an intraocular pressure below 21 mmHg without medication or additional surgery at 24 months. The intraocular pressure was evaluated in the first 72 hours after surgery and at 1, 3, 6, 12, 18, and 24 months. Kaplan–Meier survival analysis over 24 months was used to evaluate this outcome in both cohorts. The secondary outcome was the time to choroidal detachment resolution. Results. There was no significant difference in surgical success between choroidal detachment and nonchoroidal detachment groups (P=0.12). Preoperative and 2-year postoperative intraocular pressure was similar between groups, with a significant decrease in intraocular pressure from baseline (P

Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.

IntroductionThe declaration of the end of the Public Health Emergency for COVID-19 on May 11th, 2023, has shifted the global focus led by WHO and CDC towards monitoring the evolution of SARS-CoV-2. Augmenting these international endeavors with local initiatives becomes crucial to not only track the emergence of new variants but also to understand their spread. We present a cost-effective digital PCR-based pooled sample testing methodology tailored for early variant surveillance.MethodsUsing 1200 retrospective SARS-CoV-2 positive samples, either negative or positive for Delta or Omicron, we assessed the sensitivity and specificity of our detection strategy employing commercial TaqMan variant probes in a 1:9 ratio of variant-positive to variant-negative samples.ResultsThe study achieved 100% sensitivity and 99% specificity in 10-sample pools, with an Area Under the Curve (AUC) exceeding 0.998 in ROC curves, using distinct commercial TaqMan variant probes.DiscussionThe employment of two separate TaqMan probes for both Delta and Omicron establishes dual validation routes, emphasizing the method’s robustness. Although we used known samples to model realistic emergence scenarios of the Delta and Omicron variants, our main objective is to demonstrate the versatility of this strategy to identify future variant appearances. The utilization of two divergent variants and distinct probes for each confirms the method’s independence from specific variants and probes. This flexibility ensures it can be tailored to recognize any subsequent variant emergence, given the availability of its sequence and a specific probe. Consequently, our approach stands as a robust tool for tracking and managing any new variant outbreak, reinforcing our global readiness against possible future SARS-CoV-2 waves.

The IMmunoPhenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective longitudinal study designed to enroll 1000 hospitalized patients with COVID-19 (NCT04378777). IMPACC collects detailed clinical, laboratory and radiographic data along with longitudinal biologic sampling of blood and respiratory secretions for in depth testing. Clinical and lab data are integrated to identify immunologic, virologic, proteomic, metabolomic and genomic features of COVID-19-related susceptibility, severity and disease progression. The goals of IMPACC are to better understand the contributions of pathogen dynamics and host immune responses to the severity and course of COVID-19 and to generate hypotheses for identification of biomarkers and effective therapeutics, including optimal timing of such interventions. In this report we summarize the IMPACC study design and protocols including clinical criteria and recruitment, multi-site standardized sample collection and processing, virologic and immunologic assays, harmonization of assay protocols, high-level analyses and the data sharing plans.

Omar Abdallah Khan, Gorka Sesma, Abeer Alawi, Manal AlWazae Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi ArabiaCorrespondence: Gorka Sesma, Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, Tel +966114849700, Fax +966114821908, Email gsesma@kkesh.med.saPurpose: To compare the outcomes of non-penetrating deep sclerectomy (NPDS) for primary congenital glaucoma (PCG) performed by experienced vs trainee surgeons.Patients and Methods: This retrospective cohort study was conducted in 2022 in Saudi Arabia. Consultants (Gr-1) and trainee pediatric ophthalmologists (Gr-2) performed NPDS on pediatric patients with PCG. Success was defined as an intraocular pressure (IOP) less than 21 mmHg at 6 months after surgery. Complications, glaucoma medications, and additional procedures were also observed in the two groups.Results: Gr-1 and Gr-2 operated on 14 and 39 eyes with PCG, respectively. The absolute success rates were 90.9% (95% confidence interval [CI]: 73.9, 100) in Gr-1 and 96.7% (95% CI: 90.2, 100) in Gr-2 (odds Ratio=1.1; 95% CI: 0.87, 1.3; P=0.54). Survival analysis suggested that the failure rate in the first 6 months after NPDS was not significantly different between the two groups (hazard ratio=1.45; 95% CI: 0.13, 16.0; P=0.767). The complications included hypotony (2 cases), vitreous hemorrhage (1 case), and total flap penetration (1 case). Only one eye in Gr-2 needed glaucoma medication after surgery. There was no significant difference in the success rates of one surgeon before and after training (P=0.43). The age (P=0.59) and sex (P=0.77) of patients, type of surgeon (P=0.94), and preoperative IOP (P=0.59) were not significant predictors of a stable IOP at 6 months after NPDS.Conclusion: At 6 months after NPDS surgery performed by experienced and trainee pediatric ophthalmologists, the outcomes (stabilization of IOP) were similar between the two groups.Graphical Abstract: Keywords: pediatric glaucoma, learning curve, medical education, surgical training, intraocular pressure, glaucoma surgery

In this work, we will explore the effects of non-commutativity in fractional classical and quantum schemes using the flat Friedmann–Robertson–Walker (FRW) cosmological model coupled to a scalar field in the K-essence formalism. In previous work, we have obtained the commutative solutions in both regimes in the fractional framework. Here, we introduce non-commutative variables, considering that all minisuperspace variables qnci do not commute, so the symplectic structure was modified. In the quantum regime, the probability density presents a new structure in the scalar field corresponding to the value of the non-commutative parameter, in the sense that this probability density undergoes a shift back to the direction of the scale factor, causing classical evolution to arise earlier than in the commutative world.

IntroductionPostpartum depression (PPD) is a prevalent mental health condition affecting women globally within the first year following childbirth. Substance use during pregnancy has been associated with an increased risk of developing PPD, but the evidence remains inconclusive. This meta-analysis aims to comprehensively assess the effects of different substances on PPD risk, exploring potential modifiers and confounding factors.ObjectivesTo examine the proportion of PPD among substance users during pregnancy, compared to non-users, and investigate the specific risk associated with different substances (tobacco, alcohol, and non-specified substance use/multiple substance use).MethodsA systematic literature search was conducted from inception to November 2022 using the Web of Science database (Clarivate Analytics), incorporating Web of Science Core Collection, the BIOSIS Citation Index, the KCI-Korean Journal Database, MEDLINE®, the Russian Science Citation Index, the SciELO Citation Index, and the Cochrane Central Register of Reviews, and Ovid/PsycINFO databases. Inclusion criteria comprised original studies with pregnant women, using validated depression scales and substance use reporting.ResultsAmong the 26 included studies, encompassing 514,441 women, the pooled prevalence of PPD among substance users during pregnancy was 29% (95% CI 25–33). Meta-analyzes revealed an overall odds ratio (OR) of 3.67 (95% CI 2.31–5.85, p

The cerambycid beetle Rosalia alpinais associated with temperate, broadleaved (mainly beech) forests containing dead or decaying wood. This species is protected under the Habitats Directive of the European Union. Given its narrow ecological niche and limited dispersal abilities, habitat fragmentation is a conservation concern for populations of R. alpina. In order to maximise the effectiveness of habitat restoration, a scientifically sound procedure for patch selection is needed. In Gipuzkoa (N Spain), we used Light Detection and Ranging (LiDAR) images to search for 20x20-m cells matching the parameterisation of a predictive and local habitat model for R. alpinaat the tree level. The cells selected under quantitative criteria were clustered to identify potential habitat patches. Conefor Sensinode software was used to estimate the importance of each of those patches in terms of the connectivity of the population, based on dispersal distances of R. alpinaand the probabilities of dispersing events among patches. We identified 380 potential habitat patches, mostly in the south-eastern sector of the study area, which were classified into “core areas” and “connecting areas”. The performance of the model was tested in the field (61% of correct assignations), although the actual occurrence of R. alpinawithin the habitat patches should be assessed in the future. This model represents a step forward in guiding the cost-effective implementation of conservation activities, through a strict preservation of the current core habitat patches and an increase in the size of connecting patches.Therefore, we show that connectivity models combining remote sensing data and local habitat selection can be an aid in conservation planning and restoration actions, probably outperforming less efficient strategies, such as random or expert selection. RESUMEN: El escarabajo cerambícido Rosalia alpinaestá asociado a los bosques templados de frondosas (principalmente hayas) que albergan madera muerta o en descomposición. La especie está protegida bajo la Directiva de Hábitats de la Unión Europea. Dado su estrecho nicho ecológico y su limitada capacidad de dispersión, la fragmentación de su hábitat es un problema de conservación para las poblaciones de R. alpina. Para maximizar la efectividad de la restauración del hábitat, se necesita un procedimiento científicamente sólido para la selección de parches forestales sobre los que intervenir. En Gipuzkoa (norte de España) utilizamos imágenes LiDAR para buscar celdas de 20x20 m que se ajustaran a la parametrización de un modelo predictivo local de hábitat para R. alpinaa nivel de árbol. Las celdas seleccionadas bajo criterios cuantitativos fueron agrupadas para identificar parches de hábitat potencial. Se utilizó el software Conefor Sensinode para estimar la importancia de cada uno de estos parches en términos de conectividad para la población, con base en las distancias de dispersión de R. alpinay la probabilidad de eventos de dispersión entre parches. Se identificaron 380 parches de hábitat potencial, mayoritariamente en el sector sureste del área de estudio, que fueron clasificados como “áreas centrales” o “áreas de conexión”. La ejecutoria del modelo fue testada en campo (61 % de asignaciones correctas), si bien la presencia real de R. alpinaen los parches de hábitat debería ser confirmada en el futuro. Este modelo constituye un avance para guiar la implementación de actividades de conservación de manera eficiente, mediante la protección estricta de “áreas centrales” y el incremento del tamaño de las “áreas de conexión”. Por lo tanto, mostramos que los modelos de conectividad que combinan datos de detección remota y selección local del hábitat pueden asistir en la planificación de la conservación y en las acciones de restauración específicas, seguramente mejorando los resultados de estrategias menos eficientes, como la selección al azar o basada en criterio experto.

Como parte de la transformación de la educación, se ha considerado el uso de la tecnología para elevar la calidad en el aprendizaje. Este estudio evalúa un programa experimental que gira en torno a la implementación de podcasts como material de apoyo fuera del aula, con énfasis a favorecer el aprendizaje del vocabulario y la pronunciación del idioma inglés. La investigación con enfoque mixto, utilizó los métodos Audiolingual y el Enfoque Natural bajo un criterio humanista. Participaron cincuenta y dos estudiantes mexicanos de primer grado de una escuela primaria pública estatal, con edades de seis y siete años, divididos de forma natural en un grupo experimental y otro de control. Para recopilar datos cuantitativos y cualitativos se aplicaron varias técnicas: pretest, postest, notas de diario y grupos focales. Los resultados revelaron una mejora significativa en la pronunciación y la adquisición de vocabulario en los alumnos del grupo experimental, superando de manera significativa a los alumnos del grupo de control. Entre otros hallazgos relevantes, destacan el aumento de las habilidades de los niños y las niñas para trabajar con tecnología, el desarrollo de la autonomía y las actitudes positivas de los alumnos por participar en actividades utilizando podcasts para aprender inglés.

Abstract Background Elimination disorders are highly prevalent in childhood and often associated with clinically relevant comorbid psychological disorders. The aim of this study is to determine if, and to what extent, children with elimination disorders show higher internalizing and externalizing problems than their healthy peers. Methods A multistep literature search was performed from database inception until May 1st, 2022. PRISMA/MOOSE‐compliant systematic review (PROSPERO: CRD42022303555) were used to identify studies reporting on internalizing and/or externalizing symptoms in children with an elimination disorder and a healthy control (HC) group. First, a systematic review was provided. Second, where data allowed for it, a quantitative meta‐analysis with random effects model was conducted to analyze the differences between the elimination disorder and the HC groups for internalizing and externalizing symptoms. Effect size was standardized mean difference. Meta‐regression analyses were conducted to examine the effect of sex, age, and study quality. Funnel plots were used to detect a publication bias. Where found, the trim and fill method was used to correct it. Results 36 articles were included, 32 of them reporting on enuresis (n = 3244; mean age = 9.4; SD = 3.4; 43.84% female) and 7 of them on encopresis (n = 214; mean age = 8.6; SD = 2.3; 36.24% female). Children with an elimination disorder presented significantly lower self‐concept (ES:0.42; 95%CI [0.08; 9.76]; p = 0.017) and higher symptom scores for thought problems (ES:−0.26; 95%CI: −0.43;−0.09]; p = 0.003), externalizing symptoms (ES: −0.20; 95%CI [−0.37;−0.03]; p = 0.020), attention problems (ES:−0.37; 95%CI [−0.51;−0.22]; p = 0.0001), aggressive behavior (ES:−0.33; 95%CI [−0.62;−0.04]; p = 0.025) and social problems (ES:−0.39; 95%CI [−0.58;−0.21]; p = 0.0001). Significant publication biases were found across several of the studied domains. No significant effect of sex, age or quality of the study score was found. Conclusions Children with an elimination disorder may have significant internalizing and externalizing problems, as well as impaired self‐concept. It is recommendable to screen for them in children with enuresis or encopresis and provide appropriate interventions.