Miracle-dz/UniFAR-FTUs huggingface dataset:
SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity

Objectives Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation. Methods Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls. Results All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response. Conclusions The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.
Clinical Mortality Review of COVID-19 Patients at Sukraraj Tropical and Infectious Disease Hospital, Nepal; A Retrospective Study

Coronavirus Disease 2019 (COVID-19) has challenged the health system worldwide, including the low and middle income countries like Nepal. In view of the rising number of infections and prediction of multiple waves of this disease, mortalities due to COVID-19 need to be critically analyzed so that every possible effort could be made to prevent COVID-19 related mortalities in future. Main aim of this research was to study about the mortalities due to COVID-19 at a tertiary level hospital, in Nepal. This was a retrospective, observational study that included all inpatients from Sukraraj Tropical and Infectious Disease Hospital, who were reverse transcriptase polymerase chain reaction positive for SARS-COV-2 and died during hospital stay from January 2020 till January 2021. Medical records of the patients were evaluated. Out of 860 total admissions in a year, there were 50 mortalities in the study center. Out of 50 mortalities, majority were males (76%) with male to female ratio of 3.17:1. Most were above 65 years of age (72%) and had two or more comorbidities (64%). The most common comorbidities among the patients who had died during hospital stay were hypertension (58%) followed by diabetes mellitus (50%) and chronic obstructive airway disease (24%). The median duration from the symptom onset to death was 18 days, ranged from the minimum of 2 days till maximum of 39 days. D-dimer was found to be >1 mg/L in 58% cases and ferritin was >500 ng/ml in 42% patients at presentation. A total of 42% patients had thrombocytopenia, 80% patients had lymphocytopenia and 60% had Neutrophil to Lymphocyte ratio >11.75 with the mean NLR of 18.38. Of total mortalities, 16% patients also showed microbiological evidence of secondary infection; Male gender, age more than 65 years, multiple comorbidities with lymphocytopenia, elevated Neutrophil lymphocyte ratio and elevated inflammatory markers were risk factors found in majority of mortalities in our study. These findings could be utilized for early triage and risk assessment in COVID-19 patients so that aggressive treatment strategies could be employed at the earliest to reduce mortalities due to COVID-19 in future.
The Effect of Ocular Perfusion Pressure on Retinal Thickness in Young People with Presumed Systemic Hypotension

Low ocular perfusion pressure (OPP) may increase the risk of optic neuropathy. This study investigated the effects of OPP on the ganglion cell complex (GCC) and optic nerve head-retinal nerve fibre layer (ONH-RNFL) thickness in presumed systemic hypotensives (PSH). Fifteen participants with PSH and 14 controls underwent automated sphygmomanometry and Icare tonometry to calculate OPP: mean OPP (MOPP), systolic OPP (SOPP), and diastolic OPP (DOPP). ONH-RNFL and macula GCC thickness were evaluated using the Optovue iVue optical coherence tomographer. Statistical analysis comprised independent t-tests, the Mann–Whitney U test and binary logistic regression analysis. There was no significant difference when comparing ONH-RNFL and macula GCC thickness between both groups. Increased MOPP (OR = 0.51; 95% CI: 0.27–0.97; p = 0.039) and SOPP (OR = 0.79; 95% CI: 0.64–0.98; p = 0.035) were significantly associated with a decreased risk of reductions in GCC total thickness. Increased SOPP (OR = 0.11; 95% CI: 0.01–0.89; p = 0.027) was significantly associated with a decreased risk of reductions in the average ONH-RNFL thickness. The study found no significant retinal thickness changes in PSH’s, in comparison to the controls. The study established that, by increasing MOPP and SOPP, there was a decreased risk of reductions in the total GCC thickness and average ONH-RNFL thickness. Higher SOPP may decrease the possibility of retinal thinning of the GCC and ONH-RNFL. However, higher MOPP may decrease the odds of thinning of the GCC before ONH-RNFL changes.
A Multistep Workflow to Evaluate Newly Generated iPSCs and Their Ability to Generate Different Cell Types

Induced pluripotent stem cells (iPSCs) derived from human somatic cells have created new opportunities to generate disease-relevant cells. Thus, as the use of patient-derived stem cells has become more widespread, having a workflow to monitor each line is critical. This ensures iPSCs pass a suite of quality-control measures, promoting reproducibility across experiments and between labs. With this in mind, we established a multistep workflow to assess our newly generated iPSCs. Our workflow tests four benchmarks: cell growth, genomic stability, pluripotency, and the ability to form the three germline layers. We also outline a simple test for assessing cell growth and highlight the need to compare different growth media. Genomic integrity in the human iPSCs is analyzed by G-band karyotyping and a qPCR-based test for the detection of common karyotypic abnormalities. Finally, we confirm that the iPSC lines can differentiate into a given cell type, using a trilineage assay, and later confirm that each iPSC can be differentiated into one cell type of interest, with a focus on the generation of cortical neurons. Taken together, we present a multistep quality-control workflow to evaluate newly generated iPSCs and detail the findings on these lines as they are tested within the workflow.
Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6–35 Months of Age

Supplemental Digital Content is available in the text. Background: This phase 2 observer-blind, randomized, multicenter, dose-ranging study evaluated immunogenicity and safety of different formulations of an AS03-adjuvanted H5N1 influenza vaccine in children 6–35 months of age. Methods: One hundred eighty-five children randomized into 5 groups [1.9 µg hemagglutinin (HA)/AS03B, 0.9 µg HA/AS03C, 1.9 µg HA/AS03C, 3.75 µg HA/AS03C or 3.75 µg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03B the highest amount. One year later, all subjects were to receive unadjuvanted 3.75 µg HA as antigen challenge. Immunogenicity was assessed 21 days after primary vaccination (day 42) and 7 days after antigen challenge (day 392). Immunogenicity-fever index, based on hemagglutination inhibition and microneutralization antibody titers at day 42 and fever 7 days after each vaccination, was used to guide the selection of an acceptable formulation. Results: After primary vaccination, formulations elicited strong homologous immune responses with all subjects’ hemagglutination inhibition titers ≥1:40 post-vaccination. Immunogenicity-fever index based on hemagglutination inhibition and microneutralization assays showed that 1.9 µg HA/AS03B ranked the highest. Antibody levels persisted >4 times above baseline 12 months after primary vaccination with all formulations (day 385). Antibodies increased >4-fold after antigen challenge (day 392/day 385) with 1.9 µg HA/AS03B, 0.9 µg HA/AS03C and 1.9 µg HA/AS03C formulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 µg HA/AS03D) to 60.5% (1.9 µg HA/AS03B). Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 µg HA/AS03B providing the most favorable balance of immunogenicity versus reactogenicity for use in children 6–35 months of age.
Validation of a Circulating Tumor DNA‐Based Next‐Generation Sequencing Assay in a Cohort of Patients with Solid tumors: A Proposed Solution for Decentralized Plasma Testing

Abstract Background Characterization of circulating tumor DNA (ctDNA) has been integrated into clinical practice. Although labs have standardized validation procedures to develop single locus tests, the efficacy of on‐site plasma‐based next‐generation sequencing (NGS) assays still needs to be proved. Materials and Methods In this retrospective study, we profiled DNA from matched tissue and plasma samples from 75 patients with cancer. We applied an NGS test that detects clinically relevant alterations in 33 genes and microsatellite instability (MSI) to analyze plasma cell‐free DNA (cfDNA). Results The concordance between alterations detected in both tissue and plasma samples was higher in patients with metastatic disease. The NGS test detected 77% of sequence alterations, amplifications, and fusions that were found in metastatic samples compared with 45% of those alterations found in the primary tumor samples (p = .00005). There was 87% agreement on MSI status between the NGS test and tumor tissue results. In three patients, MSI‐high ctDNA correlated with response to immunotherapy. In addition, the NGS test revealed an FGFR2 amplification that was not detected in tumor tissue from a patient with metastatic gastric cancer, emphasizing the importance of profiling plasma samples in patients with advanced cancer. Conclusion Our validation experience of a plasma‐based NGS assay advances current knowledge about translating cfDNA testing into clinical practice and supports the application of plasma assays in the management of oncology patients with metastatic disease. With an in‐house method that minimizes the need for invasive procedures, on‐site cfDNA testing supplements tissue biopsy to guide precision therapy and is entitled to become a routine practice. Implications for Practice This study proposes a solution for decentralized liquid biopsy testing based on validation of a next‐generation sequencing (NGS) test that detects four classes of genomic alterations in blood: sequence mutations (single nucleotide substitutions or insertions and deletions), fusions, amplifications, and microsatellite instability (MSI). Although there are reference labs that perform single‐site comprehensive liquid biopsy testing, the targeted assay this study validated can be established locally in any lab with capacity to offer clinical molecular pathology assays. To the authors' knowledge, this is the first report that validates evaluating an on‐site plasma‐based NGS test that detects the MSI status along with common sequence alterations encountered in solid tumors.
Differences in menopausal symptoms and female sexual function by region and ethnicity in West Texas and Central Arizona: a cross-sectional survey

Supplemental Digital Content is available in the text Abstract Objective: To evaluate menopausal symptoms and sexual problems in Hispanic and non-Hispanic women in two Southwest areas. Methods: An anonymous survey including the Green Climacteric Scale (GCS), Female Sexual Function Index (FSFI), and demographics was distributed to English and Spanish-speaking women age 40 to 60 in Scottsdale, Arizona, and West Texas. FSFI for sexually active women and GCS scores for the Hispanic and non-Hispanic women in Texas were analyzed with multivariable analysis and compared between Texas and Arizona for Non-Hispanic participants. Results: Predominantly non-Hispanic women (70%), average age 51.5 (SD = 7.25) completed questionnaires (199 West Texas, 163 Scottsdale). A majority of sexually active women (88%) were found to be at risk of sexual dysfunction. Within the Texas cohort, GCS score was estimated to be 3.49 points lower (less symptoms) in Hispanic versus non-Hispanic participants [95% CI −6.58 to −0.40, P = 0.03], and FSFI score was estimated to be 2.31 points lower (more symptoms) in Hispanic versus non-Hispanic participants [95% CI −4.49 to −0.14, P = 0.04]. Among non-Hispanic women, GCS scores were lower (less symptoms) in Texas versus Arizona by 10.25 points [95% CI −14.83 to −5.66, P < 0.01], while FSFI scores were higher overall (less symptoms) in Texas by 3.65 points [95% CI 0.53-6.77), P = 0.02]. All FSFI and GCS scores were adjusted for multiple variables. Conclusions: In a group of menopausal women from the Southwest, most reported symptoms were consistent with FSD, and the degree of sexual problems appeared to be greater in the Hispanic participants from Texas. Video Summary:http://links.lww. com/MENO/A781.
Participatory and Transdisciplinary Studies of Brucella Infection in Humans and Animals in Yunnan Province, China—Lessons Learned

Brucellosis is an important zoonosis occurring globally. In addition to the risk for disease in humans, the disease causes production losses, since the disease in livestock is characterized by abortion and other reproductive failures. The disease is a public health concern in China, but no information is available on knowledge, perception and awareness of potential risk groups such as farmers, butchers and animal health workers; yet successful control requires compliance of those affected groups to be effective. Following the principles of the Ecohealth approach, emphasis was given to participation of all relevant stakeholders, use of qualitative and quantitative tools, and cross-sectorial collaboration. Data collection included on-farm questionnaires (N = 192) and collection of bulk milk samples of goat (N = 40), cattle (N = 45) and buffalo (N = 41) from farms, as well as serum samples (N = 228) from humans. Milk samples were tested with an ELISA for presence of antibodies, while a serum agglutination test was used for human samples. Qualitative work included 17 focus group discussion (FGD) with villagers and 47 in-depth interviews (IDI) with village animal health workers, doctors, and butchers, focused on knowledge, perception and awareness on zoonoses including brucellosis. Results from questionnaires indicate that abortions are a common problem; cattle with abortion history are kept for further insemination and the milk still consumed or sold. Antibodies against Brucella were detected in cows’ (5/45) and goats’ (1/40) milk samples, and in human samples (5/126) in Yiliang, while in Mangshi, all buffalo (N = 41) and humans (N = 102) were negative. FGD and IDI results showed an alarmingly low knowledge and awareness on zoonoses; particularly, low awareness about brucellosis was noted, even among the professional groups. Collaboration between village animal health workers and doctors was uncommon. No confirmed brucellosis cases were found in retrospective investigation of hospital and veterinary stations. This study demonstrates the presence of brucellosis in livestock and humans in Yunnan, indicating a non-negligible risk for humans. It is also made apparent that there is a need for increased awareness among both farmers and professionals in order to reduce the risk of zoonotic transmissions.
Improving Readiness to Manage Intimate Partner Violence in Family Medicine Clinics by Collaboration With a Community Organization.

Background and Objectives Primary care clinicians are in a unique position to address intimate partner violence (IPV) in routine clinical practice. The purpose of this study was to improve clinician readiness to identify and manage IPV in four family medicine residency practice sites on the west side of Chicago by partnering with a local domestic violence organization. Methods Practice sites included three federally qualified health centers and one hospital-based office. Eligible clinicians included resident and faculty physicians, nurse practitioners, and certified nurse midwives. We assessed readiness using the validated Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS). We used initial survey results (n=53, 73%) to develop a targeted clinician educational intervention by a community organization. We administered the PREMIS tool postintervention at 1 and 6 months, measuring perceived and actual knowledge, preparedness, and practice issues. We performed comparison statistics to assess aggregate change. Results PREMIS response rates were n=53 (72%), n=32 (47%), and n=36 (49%), for preintervention, 1, and 6 months postintervention, respectively. Mean clinician preparedness score improved significantly at 1 and 6 months (P<.001, P<.009). Mean self-perceived knowledge score improved significantly at 1 month (P<.001) and trended toward improvement at 6 months (P=.07). Actual knowledge trended toward improvement at 1 month (P=.07) and after 6 months (P=.05). Mean practice issues scores did not improve significantly. Conclusions Participation in a 45-minute targeted educational intervention improved clinician readiness to manage IPV. Collaborating with a community partner builds a relationship for further referrals and advocacy for patients.
Straightforward ARGET ATRP for the Synthesis of Primary Amine Polymethacrylate with Improved Chain-End Functionality under Mild Reaction Conditions

Activators regeneration by electron transfer atom transfer radical polymerization (ARGET ATRP) of 2-aminoethyl methacrylate hydrochloride (AMA) was successfully performed for the first time. The polymerizations were conducted at 35 °C in isopropanol (IPA)/water mixtures or pure water, using CuBr2/TPMA (TPMA: tris(2-pyridylmethyl)amine) as a metal catalyst complex with slow feeding of ascorbic acid (AscA) to allow regeneration of the activator species. The reactions showed first-order kinetics with monomer conversion and high monomer conversion (>90%), and controlled polymers (Đ ≈ 1.3) were obtained using optimized conditions. For the first time, as a result of the PAMA’s high chain-end functionality, it was possible to extend the polymer and synthesize a well-defined block copolymer (PAMA-b-POEOMA) (OEOMA: oligo(ethylene oxide) methyl ether methacrylate) by ATRP techniques, using AMA as the first block. PAMA-based nanogels, with potential biomedical applications, were prepared by ARGET ATRP in inverse min.
Peripheral blood transcriptome heterogeneity and prognostic potential in lung cancer revealed by RNA‐Seq

Understanding of the complex interaction between the peripheral immune system and lung cancer (LC) remains incomplete, limiting patient benefit. Here, we aimed to characterize the host peripheral immune response to LC and investigate its potential prognostic value. Bulk RNA‐sequencing data of peripheral blood leucocytes (PBLs) from healthy volunteers and LC patients (n = 142) were analysed for characterization of host systemic immunity in LC. We observed broad blood transcriptome perturbations in LC patients that were heterogeneous, as two new subtypes were established independent of histology. Functionally, the heterogeneity between the two subtypes included dysregulation of diverse biological processes, such as the cell cycle, blood coagulation and inflammatory signalling pathways, together with the abundance and activity of blood cells, particularly lymphocytes and neutrophils, ultimately manifesting as differences in antitumour immune status. Based on these findings, a prognostic model composed of ten genes dysregulated in one LC subtype with relatively poor immune status was developed and validated in a Gene Expression Omnibus (GEO) data set (n = 108), helping to generate a prognostic nomogram. Collectively, our study provides novel and comprehensive insight into the heterogeneity of the host peripheral immune response to LC. The expression heterogeneity–based predictive model may help guide prognostic management for LC patients.
Examining the Relationship Between Gastroschisis and Placental Fetal Vascular Malperfusion

Introduction Gastroschisis is a congenital malformation characterized by intestinal herniation through an abdominal wall defect. Despite its unknown pathogenesis, known risk factors include maternal smoking, alcohol use, and young maternal age. Previous work has shown that gastroschisis is associated with placental delayed villous maturation, and the goal of this study was to assess for additional associated placental pathologies that may help clarify the pathogenesis of gastroschisis. Methods We conducted a retrospective slide review of 29 placentas of neonates with gastroschisis. Additionally, we reviewed pathology reports from one control group of 30 placentas with other congenital malformations. Gross and histological data were collected based on a standardized rubric. Results Gastroschisis was associated with increased placental fetal vascular malperfusion (FVM) in 62% of cases (versus 0% of controls, p < 0.0001). It was also associated with increased placental villous maldevelopment in 76% of cases (versus 3% of controls, p < 0.0001). Conclusion Our study demonstrates an association between gastroschisis and FVM. While FVM could be the consequence of vascular disruption due to the ventral location of gastroschisis, it could also reflect estrogen-induced thrombosis in early pregnancy. Further research is needed to separate these possibilities and determine the cause of the placental FVM observed in gastroschisis.