Bone marrow findings post allogeneic transplant for myeloproliferative neoplasms and chronic myelomonocytic leukemia with increased fibrosis.

BACKGROUND: Allogeneic hematopoietic stem cell transplant for myeloid neoplasms with increased fibrosis is uncommon; morphologic features posttransplant can be concerning for persistent disease. METHODS: In this retrospective study, we identified 22 patients transplanted for myeloproliferative neoplasms or chronic myelomonocytic leukemia with fibrosis at our institution, and reviewed slides from pretransplant and posttransplant bone marrow biopsies. Clinical features and results of molecular, chimerism, and cytogenetic studies were retrieved from the medical record. RESULTS: Pretransplant bone marrow biopsies commonly exhibited hypercellularity, atypical megakaryocytes, and reticulin fibrosis. At day 100, 36% of biopsies had reticulin grade >MF1 and 33% of those tested had positive molecular studies, with no significant associations between day 100 marrow characteristics and molecular profile or peripheral count recovery times. In the 1 year posttransplant biopsies (n = 12), 7 of 9 had negative molecular studies; of these, none had reticulin grade >MF1, 1 had trichrome 1+, 2 had atypical megakaryocytes, and 1 was hypercellular. CONCLUSIONS: Supporting recent literature, our study indicates that persistent day 100 reticulin fibrosis/collagen deposition does not show an association with day 100 molecular status. Our study additionally provides data for 12 patients with 1 year posttransplant marrow biopsies, with the majority of those lacking either increased fibrosis or molecular evidence of persistent disease.

ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress.

Mesenchymal stem cells (MSCs) are known to facilitate angiogenesis and promote neo-vascularization via secretion of trophic factors. Here, we explored the molecular mechanism adopted by ADAMTS13 in modulating the expression of some key angiogenic markers in human umbilical cord-derived MSCs under serum-deprivation stress. Wharton's jelly MSCs (WJ-MSCs) were isolated from the perivascular region of human umbilical cords by explant culture. ADAMTS13 was upregulated at both mRNA and protein levels in WJ-MSCs under serum-deprivation stress. Correspondingly, some key angiogenic markers were also seen to be upregulated. By screening signaling pathways, p38 and JNK pathways were identified as negative and positive regulators for expression of ADAMTS13, and the angiogenic markers, respectively. Our results also indicated the Notch pathway and p53 as other probable partners modulating the expression of ADAMTS13 and the angiogenic markers. Knockdown of ADAMTS13 using siRNA led to reversal in the expression of these angiogenic markers. Further, ADAMTS13 was shown to act via the EphrinB2/EphB4 axis followed by ERK signaling to control expression of the angiogenic markers. Interestingly, stronger expression levels were noted for ADAMTS13, VEGF and PDGF under a more stringent nutrient stress condition. Thus, we highlight a novel role of ADAMTS13 in WJ-MSCs under nutrient stress condition.

Sex and blood group determination from hair using ATR-FTIR spectroscopy and chemometrics.

Examination of hair with its intact root is commonly used for DNA profiling of the donor. However, its use for gathering other types of information is less explored. Using attenuated total reflectance-Fourier transform infrared spectroscopy, the present study aims to explore other relevant aspects in a non-destructive manner for forensics. Determining the sex and blood group of human hair samples were the major goals of the study. Sex determination was accomplished by analyzing the differential vibrational intensities and stretching of various chemical groups associated with hair and its proteins. Statistical inference of spectral data was performed using chemometric algorithms such as PCA and PLS-DA. The PLS-DA model determined sex with 100% accuracy and blood grouping with an average accuracy of 95%. The present study is the first of its kind to determine sex and blood grouping from human scalp hair shafts, as far as the author knows. By acting as a preliminary screening test, this study could have significant implications for forensic analysis of crime scene samples. Human and synthetic hair were used in validation studies, resulting in 100% accuracy, specificity, and sensitivity, with 0% false positives and false negatives. The technique ATR FTIR spectroscopy could complement the currently used methods of hair analysis such as physical examination and mitochondrial or genomic DNA analysis.

Efficacy of intertruncal and corner-pocket approaches of ultrasound-guided supraclavicular block in terms of ulnar nerve blockade: A randomised controlled study.

Background and Aims: The incidence of ulnar nerve sparing has declined with the corner-pocket approach of the supraclavicular block (SCB), however, it continues to persist. A recent technique of SCB, the intertruncal approach, separately blocks each trunk of the brachial plexus. Thus, we hypothesised that the intertruncal approach results in a complete ulnar nerve blockade. Methods: Eighty-eight patients were randomised to undergo SCB using an ultrasound (USG)-guided corner-pocket or intertruncal approach and were compared primarily regarding the complete sensory and motor blockade of the ulnar nerve and all four nerves (ulnar, radial, median and musculocutaneous nerves) at 15 min. Secondary objectives included time required for block performance, patient discomfort score, time to readiness for surgery and duration of sensory blockade of the ulnar nerve. Continous data were compared using an independent t-test, and categorical data were compared using the Chi-square test. Results: The proportion of participants with complete sensory (30/44 vs. 14/44, P < 0.001) and complete motor (22/44 vs. 7/44, P < 0.001) blocks in the ulnar nerve and all four nerves at 15 min was significantly higher in the intertruncal group. Block performance time and patient discomfort score were higher in the intertruncal group (P < 0.001). The total duration of sensory blockade in the ulnar nerve was more in the corner-pocket group (P < 0.001). Conclusion: USG-guided intertruncal approach is superior to the corner-pocket approach of SCB regarding a complete ulnar nerve blockade.

Enzyme-free isolation of mesenchymal stem cells from decidua basalis of the human placenta.

Mesenchymal stem cells (MSCs), also referred to as "medicinal signaling cells," have gained prominence as candidates for cell-based therapy and in clinical trials owing to their regenerative and therapeutic properties. Here, we present a protocol for isolating MSCs from the decidua basalis layer of human placenta using an explant culture approach. We describe steps for collecting, disinfecting, and plating placental tissue. We then detail procedures for characterizing the isolated MSCs through flow cytometry and in vitro differentiation.

Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection.

Host:pathogen interactions dictate the outcome of infection, yet the limitations of current approaches leave large regions of this interface unexplored. Here, we develop a novel fitness-based screen that queries factors important during the middle to late stages of infection. This is achieved by engineering influenza virus to direct the screen by programming dCas9 to modulate host gene expression. Our genome-wide screen for pro-viral factors identifies the cytoplasmic DNA exonuclease TREX1. TREX1 degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self-DNA. We reveal that this same process aids influenza virus replication. Infection triggers release of mitochondrial DNA into the cytoplasm, activating antiviral signaling via cGAS and STING. TREX1 metabolizes the DNA, preventing its sensing. Collectively, these data show that self-DNA is deployed to amplify innate immunity, a process tempered by TREX1. Moreover, they demonstrate the power and generality of pathogen-driven fitness-based screens to pinpoint key host regulators of infection.

Understanding the Effect of Single Atom Cationic Defect Sites in an Al2O3 (012) Surface on Altering Selenate and Sulfate Adsorption: An Ab Initio Study.

Adsorption is a promising under-the-sink selenate remediation technique for distributed water systems. Recently it was shown that adsorption induced water network re-arraignment control adsorption energetics on the α-Al2O3 (012) surface. Here, we aim to elucidate the relative importance of the water network effects and surface cation identity on controlling selenate and sulfate adsorption energy using density functional theory calculations. Density functional theory (DFT) calculations predicted the adsorption energies of selenate and sulfate on nine transition metal cations (Sc-Cu) and two alkali metal cations (Ga and In) in the α-Al2O3 (012) surface under simulated acidic and neutral pH conditions. We find that the water network effects had larger impact on the adsorption energy than the cationic identity. However, cation identity secondarily controlled adsorption. Most cations decreased the adsorption energy weakening the overall performance, the larger Sc and In cations enabled inner-sphere adsorption in acidic conditions because they relaxed outward from the surface providing more space for adsorption. Additionally, only Ti induced Se selectivity over S by reducing the adsorbing selenate to selenite but not reducing the sulfate. Overall, this study indicates that tuning water network structure will likely have a larger impact than tuning cation-selenate interactions for increasing adsorbate effectiveness.

Classic Hodgkin lymphoma in young people.

Classic Hodgkin lymphoma (CHL) is a unique form of lymphoid cancer featuring a heterogeneous tumor microenvironment and a relative paucity of malignant Hodgkin and Reed-Sternberg (HRS) cells with characteristic phenotype. Younger individuals (children, adolescents and young adults) are affected as often as the elderly, producing a peculiar bimodal age-incidence profile that has generated immense interest in this disease and its origins. Decades of epidemiological investigations have documented the populations most susceptible and identified multiple risk factors that can be broadly categorized as either biological or environmental in nature. Most risk factors result in overt immunodeficiency or confer more subtle alterations to baseline health, physiology or immune function. Epstein Barr virus, however, is both a risk factor and well-established driver of lymphomagenesis in a significant subset of cases. Epigenetic changes, along with the accumulation of somatic driver mutations and cytogenetic abnormalities are required for the malignant transformation of germinal center-experienced HRS cell precursors. Chromosomal instability and the influence of endogenous mutational processes are critical in this regard, by impacting genes involved in key signaling pathways that promote the survival and proliferation of HRS cells and their escape from immune destruction. Here we review the principal features, known risk factors and lymphomagenic mechanisms relevant to newly diagnosed CHL, with an emphasis on those most applicable to young people.

Contrasting Capability of Single Atom Palladium for Thermocatalytic versus Electrocatalytic Nitrate Reduction Reaction.

The occurrence of high concentrations of nitrate in various water resources is a significant environmental and human health threat, demanding effective removal technologies. Single atom alloys (SAAs) have emerged as a promising bimetallic material architecture in various thermocatalytic and electrocatalytic schemes including nitrate reduction reaction (NRR). This study suggests that there exists a stark contrast between thermocatalytic (T-NRR) and electrocatalytic (E-NRR) pathways that resulted in dramatic differences in SAA performances. Among Pd/Cu nanoalloys with varying Pd-Cu ratios from 1:100 to 100:1, Pd/Cu(1:100) SAA exhibited the greatest activity (TOFPd = 2 min-1) and highest N2 selectivity (94%) for E-NRR, while the same SAA performed poorly for T-NRR as compared to other nanoalloy counterparts. DFT calculations demonstrate that the improved performance and N2 selectivity of Pd/Cu(1:100) in E-NRR compared to T-NRR originate from the higher stability of NO3* in electrocatalysis and a lower N2 formation barrier than NH due to localized pH effects and the ability to extract protons from water. This study establishes the performance and mechanistic differences of SAA and nanoalloys for T-NRR versus E-NRR.

Diagnostic Discrepancies in Small-volume Biopsy for the Initial Diagnosis, Recurrence, and Transformation of Follicular Lymphoma: A Multi-Institutional Collaborative Study.

Small-volume biopsies (SVBs) including fine-needle aspiration (FNA), cell block, and needle core biopsies (NCB) are increasingly utilized to diagnose and guide the clinical management of lymphoma. We established a multi-institutional interdisciplinary collaboration of cytopathologists, hematopathologists, and oncologists focused on the role of SVB in the management of patients with follicular lymphoma (FL). To assess the performance characteristics of SVB in this setting, we evaluated all consecutive SVBs performed for clinical indications of initial diagnosis, recurrence, or transformation of FL over a 5-year period and focused on the 182 that had at least one subsequent biopsy within 3 months as part of the same clinical work-up. The most common outcome of a subsequent biopsy as part of the same clinical work-up was a more specific diagnosis usually assigning the pathologic grade (111/182, 61%), followed by a complete agreement with the SVB (24/182, 13%), and change from nondiagnostic on initial biopsy to diagnostic on subsequent biopsy (21/182, 12%). A minority resulted in a diagnostic change from benign to lymphoma (17/182, 9%), a change in FL grade (5/182, 3%), or change in the lymphoma diagnostic category (4/182, 2%). There were no cases where an initial diagnosis of lymphoma was overturned. The distribution of discrepancies was similar across initial SVB types (FNA, FNA + cell block, NCB with or without FNA). Tissue limitations were noted in a minority of cases (53/182, 29%) and were enriched among initially nondiagnostic biopsies (16/21, 76%). Flow cytometry immunophenotyping was performed in the majority of cases both at the first and last biopsy (147/182, 81%). SVB can be a powerful method to detect FL in various clinical indications, with discrepant cases mostly resulting from a refinement in the initial diagnosis.

Malignant undifferentiated and rhabdoid tumors of the gastroesophageal junction and esophagus with SMARCA4 loss: a case series.

Undifferentiated SMARCA4-deficient carcinoma of the esophagus and gastroesophageal junction is a rare, highly aggressive, and diagnostically challenging malignancy. Here we present a case series of high-grade undifferentiated malignant neoplasms of the esophagus and gastroesophageal junction that share SMARCA4 loss by immunohistochemistry and demonstrate a rhabdoid phenotype. Five cases are presented, including 4 men and 1 woman with an age range of 48-79 years. Interestingly, only one case showed intestinal metaplasia (Barrett's esophagus) and no cases demonstrated glandular dysplasia or glandular differentiation. In all, the lesional cells were immunoreactive with antibodies to keratins (3/5), CD34 (2/4), and CD138 (4/5). SMARCA4 expression was diffusely lost in all cases, whereas SMARCB1 expression was intact. OncoScan™ assay demonstrated loss of SMARCA4 in all cases analyzed. Additional OncoScan™ findings included abnormalities of CDKN2A in 2 of 3 cases, abnormalities of TP53 in 2 of 3 cases, and abnormalities of PTPRD in 2 of 3 cases, among other abnormalities.

Small volume biopsy diagnostic yield at initial diagnosis versus recurrence/transformation of follicular lymphoma: A retrospective Cyto-Heme Interinstitutional Collaborative study.

BACKGROUND: Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL). METHODS: The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial FL diagnosis and suspected recurrence or transformation of FL. A total of 676 workups beginning with SVB were assessed for the mean number of biopsies per workup, the proportion of workups requiring multiple biopsies, and the proportion with a complete diagnosis including grade, on initial biopsy. RESULTS: Compared to workups performed for question transformation/recurrence, those done for initial FL diagnosis were significantly more likely to require multiple biopsies (p < .01), had a higher mean number of biopsies per workup (1.7 vs. 1.1, absolute standardized difference = 1.1), and a lower complete diagnosis rate at initial biopsy (39% vs. 56%). At initial FL diagnosis, NCB +/- FNA was associated with fewer biopsies per workup compared to FNA +/- CB (1.2 vs. 1.9), fewer workups requiring multiple biopsies (23% vs. 83%), and a higher complete diagnosis rate (71% vs. 18%). In contrast, during assessment for transformation/recurrence, NCB and FNA showed a similar mean number of biopsies per workup (1.2 vs. 1.2) and few workups required multiple biopsies (6% vs. 19%). CONCLUSIONS: SVB at initial FL diagnosis often required additional biopsies to establish a complete diagnosis. In contrast, when assessing for transformed/recurrent FL, additional biopsies were generally not obtained regardless of SVB type, suggesting that in these clinical settings SVB may be sufficient for clinical decision-making.

Testicular cavernous hemangioma masquerading as testicular malignancy.

Cavernous hemangiomas are benign tumors of vascular origin that can develop in any part of the body. However, its occurrence in the testis is rare. To the best of our knowledge, we are reporting the first case of a patient with cavernous hemangioma with concern for an extracapsular extension on ultrasound imaging.

Fractal Dimension and Radiomorphometric analysis of Orthopanoramic radiographs in patients with tobacco and areca nut associated oral mucosal lesions: A pilot in-vivo study in a North Indian cohort.

OBJECTIVE: The aim of this study was to determine the fractal dimension (FD) and radiomorphometric indices (RMIs) in the mandible from orthopantomographic radiographs in patients with oral lesions associated with smokeless/smoking tobacco (SLT/ST) and areca nut habits in a North Indian cohort. STUDY DESIGN: A prospective, cross-sectional, observational pilot study was conducted of 120 subjects, including controls and 3 study groups of 30 patients each with oral submucous fibrosis, tobacco pouch keratosis, and oral leukoplakia (OL). Two observers calculated FD and the RMIs of mandibular cortical thickness (MCT), panoramic mandibular index (PMI), and mandibular cortical index (MCI). RESULTS: Mean FD was significantly reduced compared to controls with all oral lesions (P < .05) and with all habits in 3 of 4 regions of interest (P < .05). MCT was significantly reduced with OL (P < .005) and in ST users (P < .05). PMI did not differ regarding lesion status or habits. Compared to the controls, MCI C2 type was significantly more common in all oral lesions (P ≤ .005) and all types of habit (P < .005). Inter- and intraobserver agreement was strong to excellent. CONCLUSIONS: FD and RMI values were significantly altered compared to controls in oral lesions associated with tobacco and areca nut habits and in the dominant type of habit.

Anti-membrane Antibodies Persist at Least One Year and Discriminate Between Past Coronavirus Disease 2019 Infection and Vaccination.

BACKGROUND: The consequences of past coronavirus disease 2019 (COVID-19) infection for personal and population health are emerging, but accurately identifying distant infection is a challenge. Anti-spike antibodies rise after both vaccination and infection and anti-nucleocapsid antibodies rapidly decline. METHODS: We evaluated anti-membrane antibodies in COVID-19 naive, vaccinated, and convalescent subjects to determine if they persist and accurately detect distant infection. RESULTS: We found that anti-membrane antibodies persist for at least 1 year and are a sensitive and specific marker of past COVID-19 infection. CONCLUSIONS: Thus, anti-membrane and anti-spike antibodies together can differentiate between COVID-19 convalescent, vaccinated, and naive states to advance public health and research.

Efficient conversion of low-concentration nitrate sources into ammonia on a Ru-dispersed Cu nanowire electrocatalyst.

Electrochemically converting nitrate ions, a widely distributed nitrogen source in industrial wastewater and polluted groundwater, into ammonia represents a sustainable route for both wastewater treatment and ammonia generation. However, it is currently hindered by low catalytic activities, especially under low nitrate concentrations. Here we report a high-performance Ru-dispersed Cu nanowire catalyst that delivers an industrial-relevant nitrate reduction current of 1 A cm-2 while maintaining a high NH3 Faradaic efficiency of 93%. More importantly, this high nitrate-reduction catalytic activity enables over a 99% nitrate conversion into ammonia, from an industrial wastewater level of 2,000 ppm to a drinkable water level <50 ppm, while still maintaining an over 90% Faradaic efficiency. Coupling the nitrate reduction effluent stream with an air stripping process, we successfully obtained high purity solid NH4Cl and liquid NH3 solution products, which suggests a practical approach to convert wastewater nitrate into valuable ammonia products. Density functional theory calculations reveal that the highly dispersed Ru atoms provide active nitrate reduction sites and the surrounding Cu sites can suppress the main side reaction, the hydrogen evolution reaction.