Miracle-dz/UniFAR-FTUs huggingface dataset:
Enzymatic Synthesis of Chemical Nuclease Triplex-Forming Oligonucleotides with Gene-Silencing Applications

Abstract Triplex-forming oligonucleotides (TFOs) are short, single-stranded oligomers that hybridise to a specific sequence of duplex DNA. TFOs can block transcription and thereby inhibit protein production, making them highly appealing in the field of antigene therapeutics. In this work, a primer extension protocol was developed to enzymatically prepare chemical nuclease TFO hybrid constructs, with gene-silencing applications. Click chemistry was employed to generate novel artificial metallo-nuclease (AMN)-dNTPs, which were selectively incorporated into the TFO strand by a DNA polymerase. This purely enzymatic protocol was then extended to facilitate the construction of 5-methylcytosine (5mC) modified TFOs that displayed increased thermal stability. The utility of the enzymatically synthesised di-(2-picolyl)amine (DPA)-TFOs was assessed and compared to a specifically prepared solid-phase synthesis counterpart through gel electrophoresis, quantitative PCR, and Sanger sequencing, which revealed similar recognition and damage properties to target genes. The specificity was then enhanced through coordinated designer intercalators—DPQ and DPPZ—and high-precision DNA cleavage was achieved. To our knowledge, this is the first example of the enzymatic production of an AMN-TFO hybrid and is the largest base modification incorporated using this method. These results indicate how chemical nuclease-TFOs may overcome limitations associated with non-molecularly targeted metallodrugs and open new avenues for artificial gene-editing technology.
GPR174 signals via Gαs to control a CD86-containing gene expression program in B cells

Significance Modeling immune responses in vitro is critical for studying many facets of the B cell response. We show that during culture without stimulation, mouse B cells undergo massive changes in gene expression. Many of these changes are promoted by GPR174 signaling via Gαs. GPR174 and Gαs also contribute to reduced B cell viability during culture. We suggest that GPR174 antagonists may be useful to reduce the shift in gene expression and to augment B cell survival during culture. We also provide evidence that ligand engagement of GPR174 can activate this pathway in vivo. Variants in the GPR174 locus have been associated with autoimmune diseases. Our findings provide knowledge for understanding how alterations in GPR174 expression may contribute to disease.
Prevention of Neisseria gonorrhoeae with meningococcal B vaccine: a matched cohort study in Southern California.

BACKGROUND Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea. METHODS We conducted a matched cohort study from 2016-2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non-OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, Y ("MenACWY") who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome. RESULTS The study included 6,641 recipients of 4CMenB matched to 26,471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% CI) were 2.0 (1.3-2.8) for recipients of 4CMenB and 5.2 (4.6-5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (HR [95% CI] 0.54 [0.34-0.86]), but chlamydia rates were similar between vaccine groups (HR [95% CI] 0.98 [0.82-1.17]). CONCLUSIONS These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.
Phycoerythrin: a pink pigment from red sources (rhodophyta) for a greener biorefining approach to food applications

Abstract Phycoerythrin (PE) is a photosensitive red pigment from phycobiliprotein family predominantly present in the red algae. The concentration of PE depends on photon flux density (PFD) and the quality of light absorbed by the algae tissue. This necessitates robust techniques to extract PE from the embedded cell-wall matrix of the algal frond. Similarly, PE is sensitive to various factors which influence its stability and purity of PE. The PE is extracted from Red algae through different extraction techniques. This review explores an integrative approach of fractionating PE for the scaling-up process and commercialization. The mechanism for stabilizing PE pigment in food was critically evaluated for further retaining this pigment within the food system. The challenges and possibilities of employing efficient extraction for industrial adoption are meticulously estimated. The techniques involved in the sustainable way of extracting PE pigments improved at a laboratory scale in the past decade. Although, the complexity of industrial-scale biorefining was found to be a bottleneck. The extraction of PE using benign chemicals would be safe for food applications to promote health benefits. The precise selection of encapsulation technique with enhanced sensitivity and selectivity of the membrane would bring better stability of PE in the food matrix. Graphical Abtsract
Assessment of clinical trial protocols for pathology content using the SPIRIT‐Path guidelines highlights areas for improvement

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement provides evidence‐based recommendations for the minimum content of clinical trial protocols. The Cellular Molecular Pathology Initiative, hosted by the UK National Cancer Research Institute, developed an extension, SPIRIT‐Path, describing how to effectively incorporate pathology support into clinical trial protocols. The current study assessed the inclusion of SPIRIT‐Path items in protocols of active clinical trials. Publicly available clinical trial protocols were identified for assessment against the new guidelines using a single UK hospital as the ‘test site’. One hundred and ninety interventional clinical trials were identified as receiving support from the pathology department. However, only 38 had publicly available full trial protocols (20%) and following application of the inclusion/exclusion criteria, 19 were assessed against the SPIRIT‐Path guidelines. The reviewed clinical trial protocols showed some areas of compliance and highlighted other items that were inadequately described. The latter lacked information about the individuals responsible for the pathology content of the trial protocol, how pathology activities and roles were organised in the trial, where the laboratory work would be carried out, and the accreditation status of the laboratory. Only one trial had information specific to digital pathology, a technology certain to become more prevalent in the future. Adoption of the SPIRIT‐Path checklist will facilitate comprehensive trial protocols that address all the key cellular and molecular pathology aspects of interventional clinical trials. This study highlights once again the lack of public availability of trial protocols. Full trial protocols should be available for scrutiny by the scientific community and the public who participate in the studies, increasing the transparency of clinical trial activity and improving quality.
BIOMECHANICAL ASSESSMENT OF CHANGE OF DIRECTION PERFORMANCE IN MALE UNIVERSITY SOCCER PLAYERS

The purpose of this study was to identify biomechanical variables that distinguish change of direction performance in an athletic population. Twenty varsity men’s soccer athletes were recruited. Motion capture and force plate data were collected simultaneously during the plant phase of a 505 agility test. The median time to complete the agility task was used to distinguish a “fast” group (n=10) and a “slow” group (n=10). An ANOVA (0.05 alpha level = was used to compare groups‘ kinematic and kinetic variables. Several differences were found between groups including: contact time, transition, relative horizontal to vertical ground reaction force, center of mass height, torso lean, pelvis rotation, spine rotation, hip adduction/abduction. The findings suggest that fast and slow change of direction performance adopt different technical strategies.
An Evaluation of Prehospital Adenosine Use

Abstract Background Adenosine has been safely used by paramedics for the treatment of stable supraventricular tachycardia since the mid-1990s. However, there continues to be variability in paramedics’ ability to identify appropriate indications for adenosine administration. As the first of a planned series of studies aimed at improving the accuracy of SVT diagnosis and successful administration of adenosine by paramedics, this study details the current usage patterns of adenosine by paramedics. Methods This cross-sectional retrospective study investigated adenosine use within a large northeast EMS region from January 1, 2019, through September 30, 2021. Excluding pediatric and duplicate case reports, we created a dataset containing patient age, sex, and vital signs before, during, and after adenosine administration; intravenous line location; and coded medical history from paramedic narrative documentation, including a history of atrial fibrillation, suspected arrhythmia diagnosis, and effect of adenosine. In cases with available prehospital electrocardiograms (EKGs) for review, two physicians independently coded the arrhythmia diagnosis and outcome of adenosine administration. Statistical analysis included interrater reliability with Cohen’s kappa statistic. Results One hundred eighty-three cases were included for final analysis, 84 did not have a documented EKG for review. Categorization of presenting rhythms in these cases occurred by a physician reviewing EMS narrative and documentation. Forty of these 84 cases (48%) were adjudicated as SVT likely, 32 (38%) as SVT unlikely and 12 (14%) as uncategorized due to lack of supporting documentation. Of the 99 cases with EKGs available to review, there was substantial agreement of arrhythmia diagnosis interpretation between physician reviewers (Cohen’s kappa 0.77–1.0); 54 cases were adjudicated as SVT by two physician reviewers. Other identified cardiac rhythms included atrial fibrillation (16), sinus tachycardia (11), and ventricular tachycardia (2). Adenosine cardioversion occurred in 47 of the 99 cases with EKGs available for physician review (47.5%). Adenosine cardioversion was also deemed to occur in 87% (47/54) of cases when the EKG rhythm was physician adjudicated SVT. Conclusions This study supports the use of adenosine as a prehospital treatment for SVT while highlighting the need for continued efforts to improve paramedics’ identification and management of tachyarrhythmias.
Hospital inpatient admissions of children of mothers with severe mental illness: A Western Australian cohort study

Background: Children of parents with mental illness face a number of adversities, potentially contributing to poor health. Aim: The aim of this study was to quantify the association between maternal severe mental illness and children’s hospital admissions. Method: Record linkage cohort study of 467,945 children born in Western Australia between 1 January 1980 and 31 December 2001. Follow-up was from age 28 days until fifth birthday. Linked registers captured information on potential confounders. Rate ratios and adjusted rate ratios measured relative change in the numbers of admissions and total days of stay, while rate differences measured absolute change in outcomes. Cause-specific increases were calculated for ICD-9 chapters and for ‘potentially preventable’ conditions. Results: After adjusting for potential confounders, children of mothers with severe mental illness had a 46% relative increased rate in hospital admissions (95% confidence interval = [38%, 54%]) and an absolute increase in 0.69 extra days in hospital per child, per year (95% confidence interval = [0.67, 0.70]). The relative increase in admissions was greatest in the child’s first year of life (adjusted rate ratio = 1.76, 95% confidence interval = [1.64, 1.88]; rate difference = 0.32, 95% confidence interval = [0.30, 0.34]). Rates of admissions were increased for a range of causes, particularly injuries, infections and respiratory disease, and for conditions classified as ‘potentially preventable’. Conclusion: Children of mothers with severe mental illness have a substantial excess in hospital use compared to children of well mothers. This vulnerable group should be targeted with interventions to avert preventable morbidity and premature mortality in later life.
Quality of Life Measurement for Adolescent Patients with Sinonasal Symptoms

To validate each of the sino‐nasal outcome test (SNOT‐22) and the sinus and nasal quality of life (SN5) surveys for the adolescent population defined as 12 to 18 years old, and to determine if they correlate in regard to reports of sinonasal symptoms and quality of life.
Recovery of mental health parameters after ablation in patients with premature ventricular complex induced cardiomyopathy.

OBJECTIVE The diagnosis of premature ventricular complex-induced cardiomyopathy (PVC-CMP) is based on the presence of common PVCs associated with cardiomyopathy without a reasonable etiology for the cardiomyopathy. The treatment strategies for PVCs include radiofrequency catheter ablation (RFCA) and drug therapy. In addition to physiological symptoms, PVCs also cause psychological symptoms. Impaired quality of life and sleep quality parameters have been observed in these patients. The aim of the study was to investigate the effects of RFCA treatment on cardiac function and psychiatric health parameters. PATIENTS AND METHODS A total of 60 consecutive patients undergoing catheter ablation for cardiomyopathy-associated idiopathic PVCs were included in this study. Each patient underwent a three-lead ECG recording over a 24-hour period during normal daily ambulatory activities at a screening visit before and 3 months after RFCA. The Beck Depression Inventory Index (BDI-I), Beck Anxiety Inventory Index (BAI-I), and Global Pittsburgh Sleep Quality Index (GPSQI) were assessed before and after RFCA. RESULTS PVC frequency decreased from 21.99±6.10 to 1.2% after RFCA. Left ventricular ejection fraction (LVEF) increased from 0.41±0.05 to 0.50±0.06 after RFCA (p<0.001). GPSQI (4.90±1.99 to 3.80±1.75, p <0.001), BDI-I (14.12±7.05 to 8.67±5.13, p<0.001), BAI-I (15.12±6.89 to 9.40±5.11, p<0.001) values decreased after RFCA. We found a moderate negative correlation between GPSQI, BDI-I, BAI-I and LVEF (rs=-0.56; p <0.001, rs=-0.55; p<0.001 and rs=-0.62; p<0.001). CONCLUSIONS In addition to the recovery of systolic and diastolic cardiac functions, mental and psychiatric health parameters also showed great improvement.
Time course changes to structural, mechanical and material properties of bone in rats after complete spinal cord injury

Abstract Objective: Characterise the spatiotemporal trabecular and cortical bone responses to complete spinal cord injury (SCI) in young rats. Methods: 8-week-old male Wistar rats received T9-transection SCI and were euthanised 2-, 6-, 10- or 16-weeks post-surgery. Outcome measures were assessed using micro-computed tomography, mechanical testing, serum markers and Fourier-transform infrared spectroscopy. Results: The trabecular and cortical bone responses to SCI are site-specific. Metaphyseal trabecular BV/TV was 59% lower, characterised by fewer and thinner trabeculae at 2-weeks post-SCI, while epiphyseal BV/TV was 23% lower with maintained connectivity. At later-time points, metaphyseal BV/TV remained unchanged, while epiphyseal BV/TV increased. The total area of metaphyseal and mid-diaphyseal cortical bone were lower from 2-weeks and between 6- and 10-weeks post-SCI, respectively. This suggested that SCI-induced bone changes observed in the rat model were not solely attributable to bone loss, but also to suppressed bone growth. No tissue mineral density differences were observed at any time-point, suggesting that decreased whole-bone mechanical properties were primarily the result of changes to the spatial distribution of bone. Conclusion: Young SCI rat trabecular bone changes resemble those observed clinically in adult and paediatric SCI, while cortical bone changes resemble paediatric SCI only.
Mini tomato production in organic system under greenhouse with partial control of meteorological elements

The objective of this research was to evaluate the meteorological elements of the environments and the production components of mini tomato crop in organic system in different forms of cultivation, biofertilizer doses and technological levels of protected environments. The research was conducted in completely randomized design in a 3 x 2 x 5 factorial scheme, corresponding to three greenhouses (A - climatized, B - mobile screen and C - fixed screen), two forms of cultivation (pots and beds) and five doses of a commercial biofertilizer (0, 50, 100, 150 and 200% of dose indicated), with five replicates. The treatments affected the analyzed variables, except for biofertilizer doses and interaction of treatments. Air temperature was unchanged among the environments and the mean and minimum relative humidity were within the control range in the climatized greenhouse. The greenhouse with mobile screen showed the best production results for the cultivation in beds and the biofertilizer doses were indifferent for all treatments.
Quantifying preference for social stimuli in young children using two tasks on a mobile platform

Children typically prefer to attend to social stimuli (e.g. faces, smiles) over non-social stimuli (e.g. natural scene, household objects). This preference for social stimuli is believed to be an essential building block for later social skills and healthy social development. Preference for social stimuli are typically measured using either passive viewing or instrumental choice paradigms, but not both. Since these paradigms likely tap into different mechanisms, the current study addresses this gap by administering both of these paradigms on an overlapping sample. In this study, we use a preferential looking task and an instrumental choice task to measure preference for social stimuli in 3–9 year old typically developing children. Children spent longer looking at social stimuli in the preferential looking task but did not show a similar preference for social rewards on the instrumental choice task. Task performance in these two paradigms were not correlated. Social skills were found to be positively related to the preference for social rewards on the choice task. This study points to putatively different mechanisms underlying the preference for social stimuli, and highlights the importance of choice of paradigms in measuring this construct.
Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine

Abstract Objectives To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). Methods A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies—NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose. Results Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P < 0.001), NAb positivity (5.5 vs 83.5%, P < 0.001) and geometric mean titre (29.5 vs 215.8 AU/ml, P < 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after a fourth dose were more frequently under rituximab (P = 0.001). Negative NAb was associated with older age (P = 0.015), RA (P = 0.002), SSc (P = 0.026), LEF (P = 0.016) and rituximab use (P = 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; P = 0.047), LEF (OR = 0.32, P = 0.036) and rituximab use (OR = 0.19, P = 0.022) were independently associated with negative NAb after the fourth vaccine dose. Conclusions This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #NCT04754698.
The Effects of Graded Levels of Calorie Restriction: XVIII.Tissue-Specific Changes in Cell Size and Number in Response to Calorie Restriction

Abstract Calorie restriction (CR) without malnutrition increases the health and life span of diverse taxa. The mechanism(s) behind CR are debated but may be directly linked to body composition changes that maintain energy balance. During a deficit, energy is primarily obtained from white adipose tissue (WAT; utilized) while other tissues remain unchanged (protected) or grow (invested) relative to body mass. The changes in mass of 6 tissues from 48 male C57BL/6 mice following 3-month graded (10%, 20%, 30%, or 40%) CR or fed ad libitum for 12 or 24 hours a day were related to cell size (hypo/hypertrophy) and/or number (hypo/hyperplasia). Tissues studied were retroperitoneal and subcutaneous WAT, brown adipose tissue (BAT; utilized), lungs (protected), and stomach and cecum (invested). Methodology was based on number of nuclei/tissue equaling the number of cells. Extracted DNA was quantified and used to estimate cell numbers (total DNA/DNA per diploid nucleus) and size (tissue mass/nuclei number). WAT utilization was caused solely by hypotrophy whereas BAT utilization resulted from reduced cell number and size. WAT cell size positively correlated with circulating hormones related to energy balance, and BAT cell number and size positively correlated with body temperature. No changes were found in the lungs, consistent with their protected status, whereas hyperplasia appeared to be the dominant mechanism for invested alimentary-tract tissues. These findings indicate the pattern of change of cell size and number across increasing levels of short-term CR is tissue-specific.