Search

We investigate the contrasting realities of the pandemic on psychosocial experiences and ways of coping among American Voices Project respondent surveys (N = 720) and interviews (N = 172). Despite similar levels of distress early in the pandemic, by late 2020 clear differences across education, race and ethnicity, and gender emerged, both quantitatively and qualitatively. Those with structural advantages reported greater gains from the pandemic, including self-improvement opportunities like therapy and time outdoors. In contrast, respondents without college degrees, Black and Hispanic individuals, and women reported experiencing greater psychosocial shocks into the later months of 2020 and feeling disproportionately undervalued, socially disconnected, and stressed, respectively. The former two groups also systematically differed in their coping strategies, which included hard work, emotion suppression, and faith.

Atmospheric effects, such as turbulence and background thermal noise, inhibit the propagation of light used in ON–OFF keying (OOK) free-space optical (FSO) communication. Here we present and experimentally validate a convolutional neural network (CNN) to reduce the bit error rate of FSO communication in post-processing that is significantly simpler and cheaper than existing solutions based on advanced optics. Our approach consists of two neural networks, the first determining the presence of bit sequences in thermal noise and turbulence and the second demodulating the bit sequences. All data used for training and testing our network is obtained experimentally by generating OOK bit streams, combining these with thermal light, and passing the resultant light through a turbulent water tank which we have verified mimics turbulence in the air to a high degree of accuracy. Our CNN improves detection accuracy over threshold classification schemes and has the capability to be integrated with current demodulation and error correction schemes.

Abstract This study explores carbon sequestration in South Korea’s riverine wetlands, focusing on the four major rivers: Han, Yeongsan, Geum, and Nakdong. Field data from the Yeongsan River wetland, including 3D topography surveys, grainsize analyses, and loss-on-ignition measurements, were used to assess carbon stocks and their environmental drivers. The Yeongsan River was selected as a representative site due to its geomorphological, hydrological, and climatic similarities with the other three major rivers, which influence sediment transport and carbon dynamics. Carbon stocks of 3.31 megagrams (Mg) per hectare, observed in the Dam-Yang Stream Wetland, suggest that the four major rivers collectively have the potential to store approximately 23.42 million metric tons of carbon annually, accounting for 3.9% of South Korea’s carbon budget. Geomorphological features at different elevations significantly influence soil carbon storage, with finer sediments contributing to higher carbon retention in low-energy environments. Seasonal variations in stream geomorphology, driven by floods and tropical cyclones, are dominant factors regulating sediment transport and organic matter deposition. Our findings suggest that controlled discharge events could enhance sediment and organic material retention, boosting carbon sequestration across riverine wetlands. This study highlights the critical role of geomorphological and hydrological processes in enhancing wetland carbon storage and mitigating carbon emissions.

Abstract Objective To systematically evaluate which lesion‐based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets. Methods We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N1 = 109, N2 = 638, N3 = 794) to statistically predict acute stroke severity (NIHSS) based on lesion volume, lesion location, and structural and functional disconnection with the lesion location using normative connectomes. Results We found that prediction models trained on small single‐center datasets could perform well using within‐dataset cross‐validation, but results did not generalize to independent datasets (median R2N1 = 0.2%). Performance across independent datasets improved using large single‐center training data (R2N2 = 15.8%) and improved further using multicenter training data (R2N3 = 24.4%). These results were consistent across lesion attributes and prediction models. Including either structural or functional disconnection in the models outperformed prediction based on volume or location alone (P

Abstract Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study’s objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106–107 days), control late pre-term (127 days), and EXTEND lambs who were born pre-term and supported on EXTEND until late pre-term age (125–128 days). Bioinformatic analysis determined differential gene expression among the three cohorts and across four different brain tissue sections: basal ganglia, cerebellum, hippocampus, and motor cortex. There were no clinically relevant histological differences between the control late pre-term and EXTEND ovine brain tissues. RNA-sequencing demonstrated that there was greater differential gene expression between the control pre-term lambs and EXTEND lambs than between the control late pre-term lambs and EXTEND lambs (Supplemental Figs. 1 and 2). Our study demonstrates that the use of EXTEND to support pre-term lambs until they reach late pre-term gestational age results in brain tissue gene expression that more closely resembles that of the lambs who reached late pre-term gestation within their maternal sheep’s womb than that of the lambs who were born prematurely.

Abstract Variably Protease Sensitive Prionopathy (VPSPr) is a rare human prion disease that, like Creutzfeldt-Jakob disease (CJD), results in the deposition of abnormally folded prion protein aggregates in the brain and is ultimately fatal. Neuropathology and clinical features of VPSPr are heterogeneous. However, the key discriminating feature is the relative sensitivity of the pathological prion protein to proteinase digestion compared to that typically seen in other human prion cases. Three major fragments of 23, 17 and 7 kDa are characteristic of the disease following digestion with proteinase K. We recently reported the utility of the highly adaptive and reproducible ProteinSimple™ capillary electrophoresis (CE) system to perform protein separation of PK digested prion protein in CJD. Consequently, we explored capillary-based electrophoresis (CE) technology as a sensitive method to detect and characterize VPSPr in a cohort of 29 cases. The unique 7 kDa fragment has high intensity, particularly in cases with the codon 129 VV genotype, but can be missed by regular Western blotting due to the small size. However, this fragment is readily detected by CE in all cases. In addition, the flexibility of CE produced highly reproducible, semi-quantitative data for determining relative proteinase K sensitivity and epitope mapping of representative cases from each codon 129 genotype (VV, MV and MM).

Objective: The study aims to capture the emotional challenges faced by international students due to the changes in U.S. visa regulations during the COVID-19 outbreak. Participants: 165 international students from University of Florida participated in the study. Methods: We conducted a cross-sectional online survey using previously validated questionnaire tools (PHQ-9 and GAD-7). The collected data was quantitatively analyzed through different statistical approaches, including ANOVA, Independent Sample t-Test, and Binary Logistic Regression. Results: 18.8% of our study sample had a moderately severe to severe depressive status, and 20.6% of the study sample had severe anxiety. Additionally, there was a statistically significant difference in the depression and anxiety scores based on gender. Conclusions: Our findings addressed the importance of taking serious measures when emotionally impactful political issues arise to prevent the development of mental illnesses among international students at U.S. institutions of higher education.

Within psychology, efforts to address racial-ethnic disparities in students' academic outcomes have focused primarily on students themselves. But there is another important person in classrooms: the teacher. In the United States, most racial-ethnically minoritized students are taught by White teachers. Drawing on research on cross-race interactions, we argue that for White teachers--especially those new to the profession--this dynamic is likely to elicit psychological threat, which then undermines their relationships with students, their well-being, and their effectiveness as an instructor. We hypothesized that values affirmation, a technique to mitigate threat and stress, could improve these outcomes. We randomly assigned White public school teachers (N = 109) at schools serving predominantly minoritized students to complete a values affirmation exercise or a matched control exercise in the fall of their first year of teaching. Five months later, affirmed teachers reported greater well-being and better teacher-student relationships than their control counterparts, and their classrooms were rated as more rigorous and more supportive of students' academic growth by trained observers.

One strategy to encourage college students to meet physical activity and public health guidelines is the Exercise is Medicine on Campus Initiative (EIM-OC), whose goal is to promote physical activity as a vital health sign within universities. To develop, implement, and evaluate the EIM-OC Initiative, it is critical to understand the mechanics of the program via a logic model. Objective: The objective is to present a conceptual logic model for EIM-OC Initiative implementation. Methods: Using an activities-approach framework, a logic model was developed using inputs, activities, outputs, and outcomes. Results: This logic model serves as a guide for the conceptual relationships within the EIM-OC Initiative. It was hypothesized that the EIM-OC Initiative would have an overarching outcome of improving physical activity levels in the university setting to promote overall community wellness and health. Conclusion: The authors anticipate this logic model will serve as a framework for other universities implementing EIM-OC.

Abstract. Introduction:. Accurate assessment of pain severity is important for caring for patients with sickle cell disease (SCD). The Brief Pain Inventory was developed to address limitations of previous pain-rating metrics and is available in a short form (BPI-SF). However, the BPI-SF is a self-report scale dependent on patient comprehension and interpretation of items. Objective:. To examine patterns in how patients completed the BPI-SF and determine whether incorrectly completing the BPI-SF was related to cognitive functioning or education. Methods:. A secondary analysis was completed using data from a study examining brain aging and cognitive impairment in SCD. T-tests were performed to examine whether neurocognitive function (immediate and delayed memory, visuospatial skills, attention, and language), word reading, and years of education differed based on correct BPI-SF completion. Results:. The sample (n = 71) was 43.7% male, 98.6% African American or mixed race. Of that, 53.5% had sickle cell anemia, and the mean years of education was 13.6. Overall, 21.1% of participants (n = 15) incorrectly completed the BPI-SF pain severity items, and 57.7% completed the body map item incorrectly. Those who completed the severity items incorrectly had statistically significant differences in education. Group differences in neurocognitive function were no longer significant after familywise error rates were controlled for. Literacy was not associated with error rates. Conclusion:. Education level may influence patients' ability to correctly complete the BPI-SF. Findings suggest that careful consideration is warranted for use of the BPI in patients with SCD. Recommended revisions to the BPI include simplifying the language, shortening sentence length, and clearly specifying the timeframes.

Creutzfeldt-Jakob disease (CJD) is a rare, fatal, rapidly progressive neurodegenerative disease resulting from an accumulation of misfolded prion proteins (PrP). CJD affects 1–2 new individuals per million each year, and the sporadic type accounts for 90% of those cases. Though the median age at onset and disease duration vary depending on the subtype of sporadic CJD (sCJD), the disease typically affects middle-aged to elderly individuals with a median survival of 4–6 months. sCJD in younger individuals is extremely rare. Here, we present a 21-year-old female who died with a sporadic prion disease. She presented with psychiatric symptoms followed by a rapidly progressive neurocognitive and motor decline. EEG was negative for periodic sharp wave complexes; however, brain MRI was suggestive of prion disease. The cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) assay was indeterminate. Neuropathologic examination at autopsy revealed severe neuronal loss and gliosis with secondary white matter degeneration but minimal spongiform changes and PrP deposits in the cerebellum and neocortex by immunohistochemistry. Absence of pathogenic mutations and methionine/valine heterozygosity at codon 129 of the prion protein gene (PRNP), atypical type 1 protease-resistant PrP that lacks or shows underrepresentation of the diglycosylated PrP isoform by western blot analysis, and no acquired prion disease risk factors resulted in a final diagnosis of atypical sCJD. Very young onset sCJD often has atypical clinical presentations and disease progression, neuropathological examination results, and/or laboratory test results that may confound diagnosis. It is critical to perform thorough, comprehensive evaluations to make an accurate diagnosis, which includes autopsy confirmation with histology, prion protein typing and prion gene sequencing.

Rationale & Objective: In the general population, neighborhood socioeconomic status (SES) has been found to be associated with cardiovascular risk, but this relationship has not been well studied among patients with chronic kidney disease (CKD). This study seeked to evaluate the association between neighborhood SES and cardiovascular outcomes in a CKD cohort. Study Design: Multicenter prospective cohort. Setting & Participants: In total, 3,197 participants in the Chronic Renal Insufficiency Cohort Study without cardiovascular disease at baseline. Exposure: Neighborhood SES quartiles using a validated neighborhood-level SES summary measure for 6 census-derived variables. Outcome: Incident heart failure, myocardial infarction, and all-cause death. Analytical Approach: Cox proportional hazards. Results: During median follow-up of 8.8 years, there were 465 incident heart failure events, 297 myocardial infarctions, and 891 deaths. In a fully adjusted model, among individuals with estimated glomerular filtration rate ≥45 mL/min/1.73 m2, lowest neighborhood SES quartile was associated with higher risk of heart failure (HR, 1.96 [95% CI, 1.04-3.67]) compared with the highest quartile. This association was not significant among those with estimated glomerular filtration rate

Typically 20–40 extreme cyclone events (sometimes called ‘weather bombs’) occur in the Arctic North Atlantic per winter season, with an increasing trend of 6 events/decade over 1979–2015, according to 6 hourly station data from Ny-Ålesund. This increased frequency of extreme cyclones is consistent with observed significant winter warming, indicating that the meridional heat and moisture transport they bring is a factor in rising temperatures in the region. The winter trend in extreme cyclones is dominated by a positive monthly trend of about 3–4 events/decade in November–December, due mainly to an increasing persistence of extreme cyclone events. A negative trend in January opposes this, while there is no significant trend in February. We relate the regional patterns of the trend in extreme cyclones to anomalously low sea-ice conditions in recent years, together with associated large-scale atmospheric circulation changes such as ‘blockinglike’ circulation patterns (e.g. Scandinavian blocking in December and Ural blocking during January–February).

Abstract Background Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients. Methods TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained. Results 525 patients (71.4% Crohn’s disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18–39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P

Abstract Background Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood. Methods Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor’s evolution at subclonal resolution. Results The most unique, previously unreported aspect of the tumor’s evolution that we observed in this patient was the presence of “subclone incubators,” defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient’s metastases for effective clinical intervention. Conclusions Our analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.

Background: Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient's head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes. Objective: However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice. To this end, we develop a computational framework based on diverse clinical data sets. Methods: We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) that included changes in tissue conductivity due to local electrical current flow. These “adaptive” models simulate ECT both during therapeutic stimulation using high current (∼1 A) and when dynamic impedance is measured, as well as prior to stimulation when low current (∼1 mA) is used to measure static impedance. We modeled two scalp layers: a superficial scalp layer with adaptive conductivity that increases with electric field up to a subject-specific maximum (σSS¯), and a deep scalp layer with a subject-specific fixed conductivity (σDS). Results: We demonstrated that variation in these scalp parameters may explain clinical data on subject-specific static impedance and dynamic impedance, their imperfect correlation across subjects, their relationships to seizure threshold, and the role of head anatomy. Adaptive tES models demonstrated that current flow changes local tissue conductivity which in turn shapes current delivery to the brain in a manner not accounted for in fixed tissue conductivity models. Conclusions: Our predictions that variation in individual skin properties, rather than other aspects of anatomy, largely govern the relationship between static impedance, dynamic impedance, and ECT current delivery to the brain, themselves depend on assumptions about tissue properties. Broadly, our novel modeling pipeline opens the door to explore how adaptive-scalp conductivity may impact transcutaneous electrical stimulation (tES).

High-grade serous ovarian cancer (HGSOC) is prone to developing resistance to treatment. Here, the authors use single-cell RNA-seq and an analysis of archetypes, and find that shifts in metabolism and proliferation are associated with the response to treatment and clonal heterogeneity in HGSOC.

Introduction: The COVID-19 pandemic has compelled a majority of hospital systems to reduce surgical and procedural volumes in an attempt to preserve resources. Elective surgery and procedures resumption has proven to be a calculated risk between COVID-19 exposure and resource depletion and patient morbidity and mortality from surgical deferral. Methods: Within a few days of halting elective surgery and procedures, our 7-hospital (2427 in-patient beds, 26,647 inpatient surgeries) healthcare system developed a multidisciplinary Pivot Plan with the primary outcome of a phased resumption of elective surgery and procedures. The plan entailed the integration of our electronic medical record, order entry automatization, perioperative staff utilization, partnering with primary care providers, and a stepwise COVID-19 testing algorithm based on a predetermined hierarchy of case acuity and timeliness of patient care. Results: The Pivot Plan was instituted on May 10, 2020. Since then, 22,624 patients have been tested for COVID-19 in anticipation of an elective surgery and procedures; 140 (0.62%) tested positive for COVID-19 and had their procedure deferred. As our testing capability has increased, we have been able to increase our added elective surgery and procedures capacity from 13 cases per day to 531 cases per day. In turn, we have seen the case volume increase by 52%. Conclusion: Our academic healthcare system located in one of the initial COVID-19 hotspots in the United States has successfully resumed elective surgery and procedures in part due to a receptive and supportive culture based upon nimbleness, agility, and rapid integration of multiple resources from a cohort of diverse disciplines applied to the perioperative services workflow.

We developed and tested strategies for using spatial representations to help students understand core probability concepts, including the multiplication rule for computing a joint probability from a marginal and conditional probability, interpreting an odds value as the ratio of two probabilities, and Bayesian inference. The general goal of these strategies is to promote active learning by introducing concepts in an intuitive spatial format and then encouraging students to try to discover the explicit equations associated with the spatial representations. We assessed the viability of the proposed active-learning approach with two exercises that tested undergraduates’ ability to specify mathematical equations after learning to use the spatial solution method. A majority of students succeeded in independently discovering fundamental mathematical concepts underlying probabilistic reasoning. For example, in the second exercise, 76% of students correctly multiplied marginal and conditional probabilities to find joint probabilities, 86% correctly divided joint probabilities to get an odds value, and 69% did both to achieve full Bayesian inference. Thus, we conclude that the spatial method is an effective way to promote active learning of probability equations.

Generating photonic cluster states using a single non-heralded source and a single entangling gate would optimise scalability and reduce resource overhead. Here, the authors generate up to 4-photon cluster states using a quantum dot coupled to a fibre loop, with a fourfold generation rate of 10 Hz.

Abstract Background The number of cases from the coronavirus disease 2019 (COVID-19) global pandemic has overwhelmed existing medical facilities and forced clinicians, patients, and families to make pivotal decisions with limited time and information. Main body While machine learning (ML) methods have been previously used to augment clinical decisions, there is now a demand for “Emergency ML.” Throughout the patient care pathway, there are opportunities for ML-supported decisions based on collected vitals, laboratory results, medication orders, and comorbidities. With rapidly growing datasets, there also remain important considerations when developing and validating ML models. Conclusion This perspective highlights the utility of evidence-based prediction tools in a number of clinical settings, and how similar models can be deployed during the COVID-19 pandemic to guide hospital frontlines and healthcare administrators to make informed decisions about patient care and managing hospital volume.

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star–black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc^{−3} yr^{−1} and the neutron star–black hole merger rate to be between 7.8 and 140 Gpc^{−3} yr^{−1}, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc^{-3} yr^{-1} at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)^{κ} with κ=2.9_{-1.8}^{+1.7} for z≲1. Using both binary neutron star and neutron star–black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2_{-0.2}^{+0.1} to 2.0_{-0.3}^{+0.3}M_{⊙}. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3_{-0.5}^{+0.3} and 27.9_{-1.8}^{+1.9}M_{⊙}. While we continue to find that the mass distribution of a binary’s more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M_{⊙}, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χ_{i}≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum.

Newly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a substantial proportion of treated patients does not respond. CD4+FOXP3+ regulatory T cells (Tregs), a suppressive subset of T cells, can impair anti-tumor responses and reduce the efficacy of currently available immunotherapies. An alternative view that has emerged over the last decade proposes to tackle this immune brake by targeting the suppressive action of Tregs on the anti-tumoral response. It was recently demonstrated that the tumor necrosis factor alpha (TNF-α) tumor necrosis factor receptor 2 (TNFR2) is critical for the phenotypic stabilization and suppressive function of human and mouse Tregs. The broad non-specific effects of TNF-α infusion in patients initially led clinicians to abandon this signaling pathway as first-line therapy against neoplasms. Previously unrecognized, TNFR2 has emerged recently as a legitimate target for anti-cancer immune checkpoint therapy. Considering the accumulation of pre-clinical data on the role of TNFR2 and clinical reports of TNFR2+ Tregs and tumor cells in cancer patients, it is now clear that a TNFR2-centered approach could be a viable strategy, once again making the TNF-α pathway a promising anti-cancer target. Here, we review the role of the TNFR2 signaling pathway in tolerance and the equilibrium of T cell responses and its connections with oncogenesis. We analyze recent discoveries concerning the targeting of TNFR2 in cancer, as well as the advantages, limitations, and perspectives of such a strategy.

Abstract Conjunctival melanoma is a rare malignant condition of the ocular surface. It is potentially lethal, with regional lymph node spread often preceding distant solid-organ metastasis. Due to its rarity and the long latency between treatment and local recurrence or the development of metastases, it is difficult to study. The literature is composed entirely of case series of varying quality, and there is significant variability in the management of this condition. This commentary attempts to distil the evidence base to provide practical management tips for the clinician.

Abstract Background Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder that can present as a severe, infantile form also known as Wolman disease. We sought to determine the outcomes and clinical needs of infants diagnosed with LAL-D, treated with enzyme replacement therapy (ERT). Methods A chart review was conducted on two infantile-onset LAL-D patients to determine clinical outcomes based on laboratory results, abdominal imaging, growth and dietary records, cardiology, endocrinology, ophthalmology, hematology, and neurocognitive evaluations. Results Two patients, both diagnosed and treated before 6 months old, demonstrated clinical improvement following weekly ERT. They required dosage increases to optimize growth and symptomatology. Both received a formula low in long chain triglycerides and high in medium chain triglycerides, an intervention that allowed significant catch-up growth. Patient 1 required treatment for partial adrenal insufficiency and hypothyroidism. Both patients demonstrated reduction in liver and spleen size and varying degrees of improved liver function. Neither experienced serious adverse reactions to ERT. Conclusion ERT has led to longer and healthier survival of affected infants. It is imperative that dietary interventions and systemic clinical care become integral to the management. Continued evidence of survival and clinical improvement in this population, coupled with available mass spectrometry enzyme assay from dried blood spots, raises the question of this rare and possibly underdiagnosed disorder’s candidacy for newborn screening.

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper "Th1-Th17" profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19.