MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID.

Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture the new host immune response to accurately diagnose acute primary and breakthrough infections when known SARS2 virus or proteins are present. It is also positive after vaccination when spike proteins elicit an acute immune response. Applying the same principles for long-COVID patients, MENSA is positive for SARS2 in 40% of PASC vs none of the COVID recovered (CR) patients without any sequelae demonstrating ongoing SARS2 viral inflammation only in PASC. Additionally, in PASC patients, MENSAs are also positive for Epstein-Barr Virus (EBV) in 37%, Human Cytomegalovirus (CMV) in 23%, and herpes simplex virus 2 (HSV2) in 15% compared to 17%, 4%, and 4% in CR controls respectively. Combined, a total of 60% of PASC patients have a positive MENSA for SARS2, EBV, CMV, and/or HSV2. MENSA offers a unique antibody snapshot to reveal the underlying viral drivers in long-COVID thus demonstrating the persistence of SARS2 and reactivation of viral herpes in 60% of PASC patients.

Clinical Epidemiological Characteristics and Risk Factors for Severity of SARS-CoV-2 Pneumonia in Pediatric Patients: A Hospital-Based Study in Vietnam.

Introduction Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which can cause organ failure in several organs, cardiac problems, or acute respiratory distress syndrome (ARDS). Identifying clinical epidemiological characteristics and risk factors for complications of COVID-19 allows clinicians to diagnose and treat promptly. Objectives This study aims to describe the clinical epidemiological characteristics of COVID-19 and assess risk factors for the severity of SARS-CoV-2 pneumonia in children treated at Haiphong Children's Hospital. Methods A descriptive cross-sectional study was conducted in Haiphong Children's Hospital, Haiphong, Vietnam, for one year, from January 1, 2022, to December 31, 2022. Results In our study, 540 children were evaluated; the male-to-female ratio was 1.48/1; the median age was 23 months (IQR=6-74); Children aged under one year accounted for the highest proportion (n=202; 37.4%); 40 (7.4%) children had underlying illnesses. The number of admitted patients diagnosed with COVID-19 peaked in February 2022. Regarding severity, 380 (70.4%) cases were mild, 136 (25.2%) were moderate, only 24 (4.4%) cases were severe, and no children died. Common symptoms were fever in 483 (89.4%), coughing in 399 (73.9%), and tachypnea in 163 (30.2%) children. Laboratory features: white blood cell count, platelet count, serum CRP, and coagulation test showed little change. Around 116 (21.5%) had lymphopenia and 148 (27.4%) had pneumonia. Patients under one year were approximately 1.64 times more likely to experience pneumonia complications from COVID-19 than those without such a history (OR=1.64, 95%CI = 1.12 - 2.41, p=0.0112). Patients with underlying conditions were approximately 2.08 times more likely to experience pneumonia complications from COVID-19 compared to those without such conditions (OR=2.08, 95%CI =1.08 - 4.02, p=0.0289). Conclusion In COVID-19 pediatric patients, the severity of the disease was mild to moderate without any mortality. Children aged under one year accounted for the highest proportion of all COVID-19 patients. This study found that age under one year and underlying illnesses are related to pneumonia in COVID-19 pediatric patients.

Genomic analysis reveals deep population divergence in the water snake Trimerodytes percarinatus (Serpentes, Natricidae).

Although several phylogeographic studies of Asian snakes have been conducted, most have focused on pitvipers, with non-venomous snakes, such as colubrids or natricids, remaining poorly studied. The Chinese keelback water snake (Trimerodytes percarinatus Boulenger) is a widespread, semiaquatic, non-venomous species occurring in China and southeastern Asia. Based on mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) data, we explored the population genetic structure, genetic diversity, and evolutionary history of this species. MtDNA-based phylogenetic analysis showed that T. percarinatus was composed of five highly supported and geographically structured lineages. SNP-based phylogenetic analysis, principal component analysis, and population structure analysis consistently revealed four distinct, geographically non-overlapping lineages, which was different from the mtDNA-based analysis in topology. Estimation of divergence dates and ancestral area of origin suggest that T. percarinatus originated ~12.68 million years ago (95% highest posterior density: 10.36-15.96 Mya) in a region covering southwestern China and Vietnam. Intraspecific divergence may have been triggered by the Qinghai-Xizang Plateau uplift. Population demographics and ecological niche modeling indicated that the effective population size fluctuated during 0.5 Mya and 0.002 Mya. Based on the data collected here, we also comment on the intraspecific taxonomy of T. percarinatus and question the validity of the subspecies T. p. suriki.

Mechanical thrombectomy treatment of basilar artery occlusion within 24 hours of symptom onset: A Single-Center Experience.

Background: To evaluate the efficacy, safety, and predictive factors for clinical outcomes of mechanical thrombectomy (MT) performed within 24 hours of stroke onset in patients with basilar artery occlusion (BAO). Method: A prospective, single-center study collected clinical and imaging data from 49 patients with BAO treated with MT within 24 hours of stroke symptom onset. Direct suction using the Penumbra system and thrombus retrieval by Solitaire stent were the primary endovascular techniques used to restore basilar artery flow. Outcomes included angiographic recanalization success, improvement National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) at discharge and after 3 months, and occurrence of symptomatic intracerebral hemorrhage (sICH) complications. Results: The mean age was 67.6 ± 10.4 years (range, 47-88 years). The mean NIHSS and Glasgow Coma Scale (GCS) on admission were 22.9 ± 11.2 (range, 6-40) and 10.4 ± 3.1 (range, 5-15), respectively. The major etiologic risk factors were large artery atherosclerosis (83.7%), followed by cardioembolism (16.3%). Successful recanalization (thrombolysis in cerebral infarction [TICI] ≥ 2b) was achieved in all patients (100%), and TICI 3 was achieved in 93.9% of patients. Of the total sample, 6.1% (3/49) of patients showed NIHSS improve-ments of 0 points at discharge, and 24.9% (12/49) of patients showed NIHSS improvements of 10 points at discharge. After 3 months, 22 patients (44.9%) had favorable clinical outcomes (mRS 0-2), whereas 7 (14.3%) had poor outcomes (mRS 3-5); overall mortality was 40.8% (20/49). Complications of sICH were documented in 15.6% of patients. Univariate analysis identified atrial fibrillation (P = 0.016), NIHSS on admission < 15 (P = 0.032), and GCS on admission > 8 (P = 0.010) as predictive factors for favorable outcomes. Conclusions: The current study suggests that MT treatment of BAO has high recanalization rates and good outcomes.

Use of point-of-care ultrasound in the diagnosis and treatment of pulmonary oedema in an infant.

This case demonstrates the value of perioperative point-of-care ultrasound for rapid bedside evaluation and treatment of pulmonary oedema in an infant. A nine-week-old male infant undergoing cleft lip repair received significant intravenous fluid resuscitation for intraoperative hypotension. After uneventful extubation, he developed increased work of breathing and a gradual decline in oxygen saturation despite supplemental oxygen by way of a facemask. Lung point-of-care ultrasound revealed confluent B-lines in multiple lung fields, consistent with pulmonary oedema, likely from fluid overload. He was treated with furosemide resulting in clinical improvement within 30 minutes.

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19.

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam.

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.

Super-resolution for Medical Image via Sparse Representation and Adaptive M-estimator.

OBJECTIVE: The goal of super-resolution is to generate high-resolution images from low-resolution input images. METHODS: In this paper, a combined method based on sparse signal representation and adaptive M-estimator is proposed for single-image super-resolution. With the sparse signal representation, the correlation between the sparse representation of high-resolution patches and that of low-resolution patches for the identical image is learned as a set of joint dictionaries and a set of high-resolution patches is obtained for high- and low-resolution patches. Then the dictionaries and high-resolution patches are used to produce the high-resolution image for a low-resolution single image. RESULTS: At the post-processing phase, the adaptive M-estimator, combining the advantages of traditional L1 and L2 norms, is used to give further processing for the resultant high-resolution image, to reduce the artefact by learning and reconstitution, and improve the performance. CONCLUSION: Three experimental results show the performance improvement of the proposed algorithm over other methods.

Surface and contour-preserving origamic architecture paper pop-ups.

Origamic architecture (OA) is a form of papercraft that involves cutting and folding a single sheet of paper to produce a 3D pop-up, and is commonly used to depict architectural structures. Because of the strict geometric and physical constraints, OA design requires considerable skill and effort. In this paper, we present a method to automatically generate an OA design that closely depicts an input 3D model. Our algorithm is guided by a novel set of geometric conditions to guarantee the foldability and stability of the generated pop-ups. The generality of the conditions allows our algorithm to generate valid pop-up structures that are previously not accounted for by other algorithms. Our method takes a novel image-domain approach to convert the input model to an OA design. It performs surface segmentation of the input model in the image domain, and carefully represents each surface with a set of parallel patches. Patches are then modified to make the entire structure foldable and stable. Visual and quantitative comparisons of results have shown our algorithm to be significantly better than the existing methods in the preservation of contours, surfaces, and volume. The designs have also been shown to more closely resemble those created by real artists.

Automatic paper sliceform design from 3D solid models.

A paper sliceform or lattice-style pop-up is a form of papercraft that uses two sets of parallel paper patches slotted together to make a foldable structure. The structure can be folded flat, as well as fully opened (popped-up) to make the two sets of patches orthogonal to each other. Automatic design of paper sliceforms is still not supported by existing computational models and remains a challenge. We propose novel geometric formulations of valid paper sliceform designs that consider the stability, flat-foldability and physical realizability of the designs. Based on a set of sufficient construction conditions, we also present an automatic algorithm for generating valid sliceform designs that closely depict the given 3D solid models. By approximating the input models using a set of generalized cylinders, our method significantly reduces the search space for stable and flat-foldable sliceforms. To ensure the physical realizability of the designs, the algorithm automatically generates slots or slits on the patches such that no two cycles embedded in two different patches are interlocking each other. This guarantees local pairwise assembility between patches, which is empirically shown to lead to global assembility. Our method has been demonstrated on a number of example models, and the output designs have been successfully made into real paper sliceforms.

Biomimetic peptide nanosensors.

The development of a miniaturized sensing platform tailored for sensitive and selective detection of a variety of biochemical analytes could offer transformative fundamental and technological opportunities. Due to their high surface-to-volume ratios, nanoscale materials are extremely sensitive sensors. Likewise, peptides represent robust substrates for selective recognition due to the potential for broad chemical diversity within their relatively compact size. Here we explore the possibilities of linking peptides to nanosensors for the selective detection of biochemical targets. Such systems raise a number of interesting fundamental challenges: What are the peptide sequences, and how can rational design be used to derive selective binders? What nanomaterials should be used, and what are some strategies for assembling hybrid nanosensors? What role does molecular modeling play in elucidating response mechanisms? What is the resulting performance of these sensors, in terms of sensitivity, selectivity, and response time? What are some potential applications? This Account will highlight our early attempts to address these research challenges. Specifically, we use natural peptide sequences or sequences identified from phage display as capture elements. The sensors are based on a variety of nanomaterials including nanowires, graphene, and carbon nanotubes. We couple peptides to the nanomaterial surfaces via traditional surface functionalization methods or self-assembly. Molecular modeling provides detailed insights into the hybrid nanostructure, as well as the sensor detection mechanisms. The peptide nanosensors can distinguish chemically camouflaged mixtures of vapors and detect chemical warfare agents with sensitivities as low as parts-per-billion levels. Finally, we anticipate future uses of this technology in biomedicine: for example, devices based on these sensors could detect disease from the molecular components in human breath. Overall, these results provide a novel platform for the development of highly sensitive and selective "nanoelectronic noses".

Biofunctionalized zinc oxide field effect transistors for selective sensing of riboflavin with current modulation.

Zinc oxide field effect transistors (ZnO-FET), covalently functionalized with single stranded DNA aptamers, provide a highly selective platform for label-free small molecule sensing. The nanostructured surface morphology of ZnO provides high sensitivity and room temperature deposition allows for a wide array of substrate types. Herein we demonstrate the selective detection of riboflavin down to the pM level in aqueous solution using the negative electrical current response of the ZnO-FET by covalently attaching a riboflavin binding aptamer to the surface. The response of the biofunctionalized ZnO-FET was tuned by attaching a redox tag (ferrocene) to the 3' terminus of the aptamer, resulting in positive current modulation upon exposure to riboflavin down to pM levels.

Hand eczema among Hong Kong nurses: a self-report questionnaire survey conducted in a regional hospital.

BACKGROUND: Hand eczema is common in the nursing profession, and has been reported widely in various parts of the world. OBJECTIVES: The aim of this study was to determine the prevalence and severity of hand eczema among nurses working in a regional hospital in Hong Kong, as well as its psychosocial impact and any possible associated risk factors. PATIENTS/MATERIALS/METHODS: The study took the form of a self-report questionnaire survey; 1240 nurses in a regional hospital were asked to participate in the survey by completing the questionnaire and returning it anonymously within 2 weeks. RESULTS: Seven hundred and twenty-four nurses returned the questionnaire (a response rate of 59%). The prevalence of hand eczema among the respondents was 22.1% (160/724). More than 90% had moderate to severe hand eczema. Itchiness and dryness were the most common symptoms. Occupational work, housework, mood, social activities and sleep were particularly affected. Multinomial logistic regressions showed that a personal or family history of atopy and a hand washing frequency of >20 times per day were independent risk factors for hand eczema. CONCLUSIONS: Hand eczema is common and severe among Hong Kong nurses. The results of this study suggest that hand eczema is an important problem for nurses and that preventive measures should be emphasized.

Preferential binding of peptides to graphene edges and planes.

Peptides identified from combinatorial peptide libraries have been shown to bind to a variety of abiotic surfaces. Biotic-abiotic interactions can be exploited to create hybrid materials with interesting electronic, optical, or catalytic properties. Here we show that peptides identified from a combinatorial phage display peptide library assemble preferentially to the edge or planar surface of graphene and can affect the electronic properties of graphene. Molecular dynamics simulations and experiments provide insight into the mechanism of peptide binding to the graphene edge.

Prevalence and risk factors for sexually transmitted infections in a high-risk occupational group: the case of fishermen along Lake Victoria in Kisumu, Kenya.

The aim of this study was to assess prevalence and risk factors for sexually transmitted infections (STIs) among fishermen along Lake Victoria, Kenya. This cross-sectional study surveyed 250 fishermen from beaches in Kisumu District using proportional-to-size sampling based on the number of registered boats per beach. Participants provided demographic and sexual behaviour information, blood for HIV-1 herpes simplex virus type 2 (HSV-2) and syphilis serological tests urine for transcription-mediated amplification assays for Neisseria gonorrhoeae and Chlamydia trachomatis and penile and scrotal swabs for human papillomavirus (HPV) DNA assay. Consistent condom use with the three most recent sexual partners was reported by 30%; 38% reported concurrent sexual partnerships and 65% reported ever having transactional sex. HIV seroprevalence was 26%, HSV-2 seroprevalence by Western blot assay was 58% and 9.5% were rapid plasma reagin and Treponema pallidum particle agglutination assay positive. Genital HPV DNA of any type was detected in 57.2% with 74% of these having two or more HPV types. C. trachomatis and N. gonorrhoeae were detected in 3.2% and 1.2% respectively. Risk factors for syphilis seropositivity included working on multiple beaches during the past year (adjusted odds ratio [AOR] 3.81; 95% confidence interval [CI] 1.29-11.28). HPV infection was associated with owning a radio which is a marker for higher socioeconomic status (AOR 6.33; 95% CI 2.94-7.14) and reporting transactional sex with the most recent sexual partner (AOR 3.03; 95% CI 1.23-7.69). In conclusion, 90% of fishermen had evidence of one or more STIs. This exceptionally high-risk occupational group represents a high priority for preventive interventions.

Chemical functionalization of graphene enabled by phage displayed peptides.

The development of a general approach for the nondestructive chemical and biological functionalization of graphene could expand opportunities for graphene in both fundamental studies and a variety of device platforms. Graphene is a delicate single-layer, two-dimensional network of carbon atoms whose properties can be affected by covalent modification. One method for functionalizing materials without fundamentally changing their inherent structure is using biorecognition moieties. In particular, oligopeptides are molecules containing a broad chemical diversity that can be achieved within a relatively compact size. Phage display is a dominant method for identifying peptides that possess enhanced selectivity toward a particular target. Here, we demonstrate a powerful yet benign approach for chemical functionalization of graphene via comprehensively screened phage displayed peptides. Our results show that graphene can be selectively recognized even in nanometer-defined strips. Further, modification of graphene with bifunctional peptides reveals both the ability to impart selective recognition of gold nanoparticles and the development of an ultrasensitive graphene-based TNT sensor. We anticipate that these results could open exciting opportunities in the use of graphene in fundamental biochemical recognition studies, as well as applications ranging from sensors to energy storage devices.

Genital hygiene practices of fishermen targeted for a topical microbicide intervention against sexually transmitted infections in Kisumu, Kenya.

Research on hygiene has been relatively limited in the current era of rigorous observational studies and clinical trials. We set out to investigate the perception and practices of genital hygiene among fishermen working on the beaches along Lake Victoria, targeted for a topical male microbicide hygiene intervention. We conducted 12 focus group discussions involving fishermen (n = 130), recording the discussions in Dholuo (the local language) and transcribing them verbatim before translating into English. Transcripts were double-coded and analysed using constant comparative analysis. Despite easy access to lake water and recognition of a link that may exist between poor genital hygiene and the risk of penile infection and poor sexual relationships, few fishermen regularly washed their genitalia due to fear/embarrassment from cleaning their genitalia in public, traditional Luo beliefs such as that washing with soap would reduce the fish catch, lack of time because of their busy schedules, laziness and lack of responsibility, and excessive consumption of alcohol and illicit drugs. Hygiene practices of the fishermen were poor and could contribute to genital infections including sexually transmitted infections. Given the fishermen's poor genital hygiene practices, they may benefit from hygiene intervention, including that provided by penile microbicides, which can be applied in the privacy of their bedrooms.

Biomimetic chemosensor: designing peptide recognition elements for surface functionalization of carbon nanotube field effect transistors.

Single-wall carbon nanotube field effect transistors (SWNT-FETs) are ideal candidates for fabricating sensors due to their unique electronic properties and have been widely investigated for chemical and biological sensing applications. The lack of selectivity of SWNT-FETs has prompted extensive research on developing ligands that exhibit specific binding as selective surface coating for SWNTs. Herein we describe the rational design of a peptide recognition element (PRE) that is capable of noncovalently attaching to SWNTs as well as binding to trinitrotoluene (TNT). The PRE contains two domains, a TNT binding domain derived from the binding pocket of the honeybee odor binding protein ASP1, and a SWNT binding domain previously identified from the phage peptide display library. The PRE structure in the presence of SWNT was investigated by performing classical all-atom molecular dynamics simulations, circular dichroism spectroscopy, and atomic force microscopy. Both computational and experimental analyses demonstrate that the peptide retains two functional domains for SWNT and TNT binding. The binding motif of the peptide to SWNT and to TNT was revealed from interaction energy calculations by molecular dynamics simulations. The potential application of the peptide for the detection of TNT is theoretically predicted and experimentally validated using a SWNT-FET sensor functionalized with a designer PRE. Results from this study demonstrate the creation of chemosensors using designed PRE as selective surface coatings for targeted analytes.

Chemoresponsiveness associated with canonical molecular changes in colorectal adenocarcinomas.

BACKGROUND: The canonical molecular changes in colorectal tumorigenesis were assessed for correlation with response to chemotherapy, in order to identify candidate markers. PATIENTS AND METHODS: In total, 156 patients received adjuvant postoperative fluoropyrimidine-based chemotherapy and 32 patients received oxaliplatin- or irinotecan-based chemotherapy following palliative surgery or for metastatic or recurrent colorectal tumors. Representative molecular changes in tumor tissues, including adenomatous polyposis coli (APC) gene, wingless-type MMTV integration site family (Wnt), mismatch repair (MMR), RAF, transforming growth factor (TGF)-beta, bone morphogenetic protein, and p53, had been previously determined, with an additional 42 patients included in this analysis. RESULTS: The disease-free survival period (mean+/-SEM) was significantly longer after fluoropyrimidine-based adjuvant chemotherapy in tumors with TGF-beta2 expression (42+/-1.4 vs. 21+/-4.7 months; p=0.005) and D18S46 loss of heterozygosity or microsatellite instability (45.7+/-1.5 vs. 40.5+/-1.4 months; p=0.048). In the metastatic settings, the high disease-control rate of oxaliplatin and irinotecan regimens correlated significantly with wild-type APC and intact MMR, respectively, relative to mutant APC and defective MMR (p=0.013, respectively). Interestingly, specific molecular steps of tumorigenensis were closely associated with particular toxicities. CONCLUSION: A subset of molecular changes occurring during colorectal tumorigenesis showed significant associations with therapeutic responses and toxicities to chemotherapy regimens, suggesting that these changes may be candidate predictors of chemoresponsiveness with further validation.