Incubation Period and Serial Interval of Mpox in 2022 Global Outbreak Compared with Historical Estimates.

Understanding changes in the transmission dynamics of mpox requires comparing recent estimates of key epidemiologic parameters with historical data. We derived historical estimates for the incubation period and serial interval for mpox and contrasted them with pooled estimates from the 2022 outbreak. Our findings show the pooled mean infection-to-onset incubation period was 8.1 days for the 2022 outbreak and 8.2 days historically, indicating the incubation periods remained relatively consistent over time, despite a shift in the major mode of transmission. However, we estimated the onset-to-onset serial interval at 8.7 days using 2022 data, compared with 14.2 days using historical data. Although the reason for this shortening of the serial interval is unclear, it may be because of increased public health interventions or a shift in the mode of transmission. Recognizing such temporal shifts is essential for informed response strategies, and public health measures remain crucial for controlling mpox and similar future outbreaks.

Reconstruction and analysis of the transmission network of African swine fever in People's Republic of China, August 2018-September 2019.

Introduction of African swine fever (ASF) to China in mid-2018 and the subsequent transboundary spread across Asia devastated regional swine production, affecting live pig and pork product-related markets worldwide. To explore the spatiotemporal spread of ASF in China, we reconstructed possible ASF transmission networks using nearest neighbour, exponential function, equal probability, and spatiotemporal case-distribution algorithms. From these networks, we estimated the reproduction numbers, serial intervals, and transmission distances of the outbreak. The mean serial interval between paired units was around 29 days for all algorithms, while the mean transmission distance ranged 332 -456 km. The reproduction numbers for each algorithm peaked during the first two weeks and steadily declined through the end of 2018 before hovering around the epidemic threshold value of 1 with sporadic increases during 2019. These results suggest that 1) swine husbandry practices and production systems that lend themselves to long-range transmission drove ASF spread; 2) outbreaks went undetected by the surveillance system. Efforts by China and other affected countries to control ASF within their jurisdictions may be aided by the reconstructed spatiotemporal model. Continued support for strict implementation of biosecurity standards and improvements to ASF surveillance is essential for halting transmission in China and spread across Asia.

Outcomes and prognostic factors in angioimmunoblastic T-cell lymphoma: final report from the international T-cell Project.

Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma (PTCL) with distinct clinicopathologic features and poor prognosis. We performed a subset analysis of 282 patients with AITL enrolled between 2006 and 2018 in the international prospective T-cell Project (NCT01142674). The primary and secondary end points were 5-year overall survival (OS) and progression-free survival (PFS), respectively. We analyzed the prognostic impact of clinical covariates and progression of disease within 24 months (POD24) and developed a novel prognostic score. The median age was 64 years, and 90% of patients had advanced-stage disease. Eighty-one percent received anthracycline-based regimens, and 13% underwent consolidative autologous stem cell transplant (ASCT) in first complete remission (CR1). Five-year OS and PFS estimates were 44% and 32%, respectively, with improved outcomes for patients who underwent ASCT in CR1. In multivariate analysis, age ≥60 years, Eastern Cooperative Oncology Group performance status >2, elevated C-reactive protein, and elevated ß2 microglobulin were associated with inferior outcomes. A novel prognostic score (AITL score) combining these factors defined low-, intermediate-, and high-risk subgroups with 5-year OS estimates of 63%, 54%, and 21%, respectively, with greater discriminant power than established prognostic indices. Finally, POD24 was a powerful prognostic factor with 5-year OS of 63% for patients without POD24 compared with only 6% for patients with POD24 (P < .0001). These data will require validation in a prospective cohort of homogeneously treated patients. Optimal treatment of AITL continues to be an unmet need, and novel therapeutic approaches are required.

Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study.

Peripheral T-cell lymphomas (PTCLs) are uniquely vulnerable to epigenetic modifiers. We demonstrated in vitro synergism between histone deacetylase inhibitors and DNA methyltransferase inhibitors in preclinical models of T-cell lymphoma. In a phase 1 trial, we found oral 5-azacytidine and romidepsin to be safe and effective, with lineage-selective activity among patients with relapsed/refractory (R/R) PTCL. Patients who were treatment naïve or who had R/R PTCL received azacytidine 300 mg once per day on days 1 to 14, and romidepsin 14 mg/m2 on days 8, 15, and 22 every 35 days. The primary objective was overall response rate (ORR). Targeted next-generation sequencing was performed on tumor samples to correlate mutational profiles and response. Among 25 enrolled patients, the ORR and complete response rates were 61% and 48%, respectively. However, patients with T-follicular helper cell (tTFH) phenotype exhibited higher ORR (80%) and complete remission rate (67%). The most frequent grade 3 to 4 adverse events were thrombocytopenia (48%), neutropenia (40%), lymphopenia (32%), and anemia (16%). At a median follow-up of 13.5 months, the median progression-free survival, duration of response, and overall survival were 8.0 months, 20.3 months, and not reached, respectively. The median progression-free survival and overall survival were 8.0 months and 20.6 months, respectively, in patients with R/R disease. Patients with tTFH enjoyed a particularly long median survival (median not reached). Responders harbored a higher average number of mutations in genes involved in DNA methylation and histone deacetylation. Combined azacytidine and romidepsin are highly active in PTCL patients and could serve as a platform for novel regimens in this disease. This trial was registered at www.clinicaltrials.gov as #NCT01998035.

Implicit and explicit learning of socio-emotional information in a dynamic interaction with a virtual avatar.

Implicit learning (IL) deals with the non-conscious acquisition of structural regularities from the environment. IL is often deemed essential for acquiring regularities followed by social stimuli (e.g., other persons' behavior), hence is hypothesized to play a role in typical social functioning. However, our understanding of how this process might operate in social contexts is limited for two main reasons. First, while IL is highly sensitive to the characteristics of the surface stimuli upon which it operates, most IL studies have used surface stimuli with limited social validity (e.g., letters, symbols, etc.). Second, while the social environment is dynamic (i.e., our behaviors and reactions influence those of our social partners and vice-versa), the bulk of IL research employed noninteractive paradigms. Using a novel task, we examine whether IL is involved in the acquisition of regularities from a dynamic interaction with a realistic real-life-like agent. Participants (N = 115) interacted with a cinematic avatar that displayed different facial expressions. Their task was to regulate the avatar's expression to a specified level. Unbeknownst to them, an equation mediated the relationship between their responses and the avatar's expressions. Learning occurred in the task, as participants gradually increased their ability to bring the avatar in the target state. Subjective measures of awareness revealed that participants acquired both implicit and explicit knowledge from the task. This is the first study to show that IL operates in interactive situations upon socially relevant surface stimuli, facilitating future investigations of the role that IL plays in (a)typical social functioning.

Effect of Health Insurance Status and Visitation Restrictions on Virtual Visitation Technology in the Neonatal Intensive Care Unit.

OBJECTIVE: This study aimed to examine the relationship between virtual technology system utilization and insurance status or type of visitation restrictions in a single-center neonatal intensive care unit. STUDY DESIGN: Prospective cohort study with separate analyses performed based on insurance status (public vs. nonpublic) and "in effect" unit visitation restrictions. The three study epochs based on patient visitation restrictions were Epoch 1 (July to October 2019) with standard visitation restrictions, Epoch 2 (November 2019 to February 2020) with respiratory syncytial virus/influenza visitation restrictions, and Epoch 3 (March to June 2020) with coronavirus disease 2019 (COVID-19) visitation restrictions, respectively. RESULTS: Families of 357 infants used web-based cameras through most of the infant's hospitalization (median: 86.05%, Q3: 97.9%) with 165,795 total camera logins, indicating consistent utilization. There was a trend for fewer logins per infant and significantly longer time to consent (p = 0.03) in the Public Insurance group. Unit visitation restrictions impacted the time to consent, the shortest being in Epoch 3 during the COVID-19 pandemic (p = 0.03). CONCLUSION: Virtual visitation technology is well embraced by neonatal instensive care unit families; however, gaps in access and use among subgroups signals a form of social inequality that needs to be explored further. KEY POINTS: · Virtual visitation technology can bridge the distance gap for families of hospitalized infants.. · Utilization of virtual technology is affected by socioeconomic factors and seasonal unit visitation restrictions.. · Factors influencing disparities in access and utilization of virtual technology need to be investigated further..

Nanoscale Ion-Exchange Materials: From Analytical Chemistry to Industrial and Biomedical Applications.

Nano-sized ion exchangers (NIEs) combine the properties of common bulk ion-exchange polymers with the unique advantages of downsizing into nanoparticulate matter. In particular, being by nature milti-charged ions exchangers, NIEs possess high reactivity and stability in suspensions. This brief review provides an introduction to the emerging landscape of various NIE materials and summarizes their actual and potential applications. Special attention is paid to the different methods of NIE fabrication and studying their ion-exchange behavior. Critically discussed are different examples of using NIEs in chemical analysis, e.g., as solid-phase extraction materials, ion chromatography separating phases, modifiers for capillary electrophoresis, etc., and in industry (fuel cells, catalysis, water softening). Also brought into focus is the potential of NIEs for controlled drug and contrast agent delivery.

Analysis of Engineered Nanoparticles in Seawater Using ICP-MS-Based Technology: From Negative to Positive Samples.

A growing global emission of engineered nanoparticles (ENPs) into the aquatic environment has become an emerging safety concern that requires methods capable of identifying the occurrence and possibly determining the amounts of ENPs. In this study, we employed sector-field inductively coupled mass spectrometry to assess the presence of ENPs in coastal seawater samples collected from the Black Sea in regions suffering different anthropogenic impacts. Ultrafiltration through commercial 3 kDa membrane filters was shown to be feasible to separate the ENPs from the bulk seawater, and the subsequent ultrasound-mediated acidic dissolution makes the metals constituting the ENPs amenable to analysis. This procedure allowed the ENPs bearing Cu, Zn, V, Mo, and Sn to be for the first time quantitated in seashore surface water, their concentration ranging from 0.1 to 1.0 µg L-1 (as metal) and related to the presence of industry and/or urban stress. While these levels are decreased by natural dilution and possible sedimentation, the monitored ENPs remain measurable at a distance of 2 km from the coast. This can be attributed not only to local emission sources but also to some natural backgrounds.

Transmission Dynamics and Effectiveness of Control Measures during COVID-19 Surge, Taiwan, April-August 2021.

An unprecedented surge of COVID-19 cases in Taiwan in May 2021 led the government to implement strict nationwide control measures beginning May 15. During the surge, the government was able to bring the epidemic under control without a complete lockdown despite the cumulative case count reaching >14,400 and >780 deaths. We investigated the effectiveness of the public health and social measures instituted by the Taiwan government by quantifying the change in the effective reproduction number, which is a summary measure of the ability of the pathogen to spread through the population. The control measures that were instituted reduced the effective reproduction number from 2.0-3.3 to 0.6-0.7. This decrease was correlated with changes in mobility patterns in Taiwan, demonstrating that public compliance, active case finding, and contact tracing were effective measures in preventing further spread of the disease.

Cerebrospinal fluid flow cytometry and risk of central nervous system relapse after hyperCVAD in adults with acute lymphoblastic leukemia.

BACKGROUND: Potential involvement of the central nervous system (CNS) by acute lymphoblastic leukemia is typically evaluated by a conventional cytospin (CC) of cerebrospinal fluid (CSF). Multiparameter flow cytometry (MFC) is generally more sensitive and specific than morphology, but data to guide its use versus CC are limited. METHODS: This study identified 92 patients who had MFC performed on their initial CSF specimen and received at least 4 cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine (hyperCVAD) as their initial treatment. RESULTS: Eighteen (20%) were CSF+ by MFC at the baseline, and only 6 of these patients were positive by CC. In contrast, 0 of 51 patients who were negative by MFC and had CC available were positive by CC. Despite the receipt of significantly more intra-CSF chemotherapy (P < .001), the cumulative incidence of CNS relapse by MFC was 22% among CSF+ patients versus 5% among those who were CSF- (P = .044). No such association was observed between CNS relapse and CC results (P = .42). None of the 74 CSF- patients became CSF+ during their initial treatment despite being tested a median of 5 times (range, 2-10). CSF positivity by MFC was the factor most strongly associated with CNS relapse in a series of univariate Cox models (hazard ratio, 3.7; P = .067). The initial CSF status by MFC had no significant impact on overall or event-free survival. CONCLUSIONS: MFC of CSF is superior to CC of CSF in identifying adults at high risk for CNS relapse after treatment with hyperCVAD. Surveillance of CSF by MFC has limited utility.

Current and emerging mass spectrometry methods for the preclinical development of metal-based drugs: a critical appraisal.

This Trends article highlights the multiple ways in which the state-of-the-art molecular mass spectrometry can support the preclinical development of novel metal-based anticancer drugs. Examples from the recent literature-beyond routine characterization applications-are presented to illustrate what analytical and experimental design challenges are to be addressed to facilitate the translation of promising drug candidates to clinical practice.

Impact of a Standardized Nutrition Bundle Including Donor Human Milk on Hospital Outcomes in Very Low Birth-Weight (VLBW) Infants in a Safety-Net Hospital.

BACKGROUND: Standardized protocols have been shown to reduce clinical practice variation and improve patient outcomes. PURPOSE: To measure the impact of a standardized nutrition bundle inclusive of donor human milk (DHM) on hospital outcomes of very low birth-weight (VLBW) infants in a safety-net hospital. METHODS: The study used the Model for Improvement methodology to drive improvement in practice. Outcome measures consisted of necrotizing enterocolitis (NEC), mortality, growth at 36 weeks' postmenstrual age and discharge, as well as volume and type of milk consumption during hospitalization. FINDINGS: NEC rate decreased from 16.67% in the control group to 6.78% in the standardized nutrition bundle group (P = .07). Similarly, there was significant reduction in mortality with the bundled intervention (15.6% in the control group vs 1.6% in the nutrition bundle group; P = .006). Time to first (15 vs 27.5 hours of life; P < .001) and full-volume enteral feeding (8.5 vs 10 days; P = .086) were reduced in the standardized nutrition bundle group compared with the control group. The human milk volume almost doubled with the intervention. IMPLICATIONS FOR PRACTICE: Our standardized nutrition bundle protocol inclusive of DHM resulted in lower NEC rates and reduced mortality. The implementation of the DHM program proved to be cost-effective and saved lives. Our findings may help guide development of a structured approach to nutrition protocols inclusive of DHM that can be adapted by other units located in safety-net hospitals. IMPLICATIONS FOR RESEARCH: Future research on ethnic and racial barriers to access and affordability of DHM is warranted and much needed.

Protein-Mediated Transformations of Superparamagnetic Nanoparticles Evidenced by Single-Particle Inductively Coupled Plasma Tandem Mass Spectrometry: A Disaggregation Phenomenon.

Progress toward translating superparamagnetic iron oxide nanoparticles (SPIONs) with specific diagnostic and therapeutic properties for clinical applications depends on developing and implementing appropriate methodologies that would allow in-depth characterizations of their behavior in a real biological environment. Herein, we report a versatile approach for studying interactions between SPIONs and proteins using single-particle inductively coupled plasma tandem mass spectrometry. By monitoring the changes in the size distribution upon exposure to human serum, the formation of stable protein corona is revealed, accompanied by particle disaggregation.

Metal-Specific Response of High-Resolution ICP-MS for Proteins Binding to Gold Nanoparticles in Human Serum.

Metalloproteins have many different functions such as storage and transport of proteins, enzymes, signal transduction proteins, etc. Herein, for a selection of gold nanoparticles differing in shape, size, charge, and surface modification, the binding behavior in human serum was assessed with respect to metal-containing proteins. Our results based on sector-field ICP-MS measurements and a simple calculation algorithm indicate the possible involvement of proteins, incorporating Cu and Fe, in the formation of the biomolecular layer around the particle surface. Given that such binding encompasses a substantial amount of copper and iron within the serum proteome (>50%) at a calculated nanoparticle dose, it may result in depleting their biological functions and should be taken into account when selecting lead candidates with an improved biocompatibility.

Oral 5-azacytidine and romidepsin exhibit marked activity in patients with PTCL: a multicenter phase 1 study.

The peripheral T-cell lymphomas (PTCLs) are uniquely sensitive to epigenetic modifiers. Based on the synergism between histone deacetylase inhibitors and hypomethylating agents that we established in preclinical PTCL models, we conducted a phase 1 study of oral 5-azacytidine (AZA) and romidepsin (ROMI) in patients with advanced lymphoid malignancies, with emphasis on PTCL. According to a 3 + 3 design, patients were assigned to 1 of 7 cohorts with AZA doses ranging from 100 mg daily on days 1 to 14 to 300 mg daily on days 1 to 21, ROMI doses ranging from 10 mg/m2 on days 8 and 15 to 14 mg/m2 on days 8, 15, and 22, with cycles of 21 to 35 days. Coprimary end points included maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). We treated a total of 31 patients. The MTD was AZA 300 mg on days 1 to 14 and ROMI 14 mg/m2 on days 8, 15, and 22 on a 35-day cycle. DLTs included grade 4 thrombocytopenia, prolonged grade 3 thrombocytopenia, grade 4 neutropenia, and pleural effusion. There were no treatment-related deaths. The combination was substantially more active in patients with PTCL than in those with non-T-cell lymphoma. The overall response rate in all, non-T-cell, and T-cell lymphoma patients was 32%, 10%, and 73%, respectively, and the complete response rates were 23%, 5%, and 55%, respectively. We did not find an association between response and level of demethylation or tumor mutational profile. This study establishes that combined epigenetic modifiers are potently active in PTCL patients. This trial was registered at www.clinicaltrials.gov as NCT01998035.

Estimation of delay-adjusted all-cause excess mortality in the USA: March-December 2020.

We estimate the delay-adjusted all-cause excess deaths across 53 US jurisdictions. Using provisional data collected from September through December 2020, we first identify a common mean reporting delay of 2.8 weeks, whereas four jurisdictions have prolonged reporting delays compared to the others: Connecticut (mean 5.8 weeks), North Carolina (mean 10.4 weeks), Puerto Rico (mean 4.7 weeks) and West Virginia (mean 5.5 weeks). After adjusting for reporting delays, we estimate the percent change in all-cause excess mortality from March to December 2020 with range from 0.2 to 3.6 in Hawaii to 58.4 to 62.4 in New York City. Comparing the March-December with September-December 2020 periods, the highest increases in excess mortality are observed in South Dakota (36.9-54.0), North Dakota (33.9-50.7) and Missouri (27.8-33.9). Our findings indicate that analysis of provisional data requires caution in interpreting the death counts in recent weeks, while one needs also to account for heterogeneity in reporting delays of excess deaths among US jurisdictions.

Profiling of selenium and other trace elements in breads from rice and maize cultivated in a seleniferous area of Punjab (India).

The objective of the study was to assess selenium and other elements levels in Indian Roti bread from Se-rich maize and rice using inductively coupled plasma mass-spectrometry. Se levels in Roti bread from Se-rich maize and rice exceeded those in the control samples by a factor of more than 594 and 156, respectively. Using Se-enriched maize increased bread Co, Cr, Mn, Mo, and Zn content, whereas Fe and I levels were reduced. In Se-rich rice-based bread a decrease in Co, Cr, Cu, Fe, I, Mo, and Zn contents was observed. Daily consumption of Se-rich maize and rice bread (100 g) could account for 5.665% and 4.309% from recommended dietary allowance, also exceeding the upper tolerable levels by a factor of 7.8 and 5.9, respectively. Therefore, Roti bread from both Se-rich maize and rice may be considered as an additional source of selenium. At the same time, regular intake of Se-rich grains and its products including breads may cause adverse health effects even after a few days and should be regularly monitored in order to prevent Se overload and toxicity.

Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas.

This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30+ peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.

An ICP-MS-based assay for characterization of gold nanoparticles with potential biomedical use.

Most of potential diagnostic and therapeutic nanoparticles fail to reach clinical trials because assessment of their 'drug-like' properties is often overlooked during the discovery stage. This compromises the results of cell culture and animal experiments, making them insufficient to evaluate the lead candidates for testing on patients. In this study, we demonstrate the potential of high-resolution inductively coupled plasma mass spectrometry (ICP-MS) as a nanoparticle qualification tool. Using novel gold nanoparticles stabilized by N-heterocyclic carbenes as test nanoparticles, it was shown that important prerequisites for biomedical applications, such as resistance to the action of human serum milieu or reactivity toward serum biomolecules, can be reliably assessed by recording the signals of gold or sulfur isotopes. Implemented during the screening stage, the method would provide benefits in shortening timelines and reducing cost for selection and initial testing of medicinal nanoparticle candidates.

How well can we characterize human serum transformations of magnetic nanoparticles?

This mini-review summarizes analytical methods in use to uncover biochemical transformations that magnetic nanoparticles (MNPs) are possibly undergoing while residing in human blood. Examples from the recent literature are presented to illustrate what analytical challenges are to be addressed to shed light on this important issue of biomedical application of MNPs.