Efficient removal and recovery of phosphorus from industrial wastewater in the form of vivianite.

With the shortage of phosphorus resources, the concept of phosphorus recovery from wastewater is generally proposed. Recently, phosphorus recovery from wastewater in the form of vivianite has been widely reported, which could be used as a slow-release fertilizer as well as the production of lithium iron phosphate for Li-ion batteries. In this study, chemical precipitation thermodynamic modeling was applied to evaluate the effect of solution factors on vivianite crystallization with actual phosphorus containing industrial wastewater. The modeling results showed that the solution pH influences the concentration of diverse ions, and the initial Fe2+ concentration affects the formation area of vivianite. The saturation index (SI) of vivianite increased with the initial Fe2+ concentration and Fe:P molar ratio. pH 7.0, initial Fe2+ concentration 500 mg/L and Fe:P molar ratio 1.50 were the optimal conditions for phosphorus recovery. Mineral Liberation Analyzer (MLA) accurately determined the purity of vivianite was 24.13%, indicating the feasibility of recovering vivianite from industrial wastewater. In addition, the cost analysis showed that the cost of recovering phosphorus by the vivianite process was 0.925 USD/kg P, which can produce high-value vivianite products and realize "turn waste into treasure".

Highly multiplexed oligonucleotide probe-ligation testing enables efficient extraction-free SARS-CoV-2 detection and viral genotyping.

There is an urgent and unprecedented need for sensitive and high-throughput molecular diagnostic tests to combat the SARS-CoV-2 pandemic. Here we present a generalized version of the RNA-mediated oligonucleotide Annealing Selection and Ligation with next generation DNA sequencing (RASL-seq) assay, called "capture RASL-seq" (cRASL-seq), which enables highly sensitive (down to ~1-100 pfu/ml or cfu/ml) and highly multiplexed (up to ~10,000 target sequences) detection of pathogens. Importantly, cRASL-seq analysis of COVID-19 patient nasopharyngeal (NP) swab specimens does not involve nucleic acid purification or reverse transcription, steps that have introduced supply bottlenecks into standard assay workflows. Our simplified protocol additionally enables the direct and efficient genotyping of selected, informative SARS-CoV-2 polymorphisms across the entire genome, which can be used for enhanced characterization of transmission chains at population scale and detection of viral clades with higher or lower virulence. Given its extremely low per-sample cost, simple and automatable protocol and analytics, probe panel modularity, and massive scalability, we propose that cRASL-seq testing is a powerful new technology with the potential to help mitigate the current pandemic and prevent similar public health crises.

Advanced treatment of phosphorus-containing tail water by Fe-Mg-Zr layered double hydroxide beads: Performance and mechanism.

The adsorption process for low concentration phosphorus wastewater treatment has advantages of simple convenience, stable performance and less sludge, while most of current adsorbents fail to be separated for reuse. Meanwhile, few people pay attention to the removal of low concentration phosphorus from tail water by adsorbents. In this study, a newly efficient Fe-Mg-Zr layered double hydroxide beads were prepared by simple in-situ crosslinking method and applied for low concentration phosphorus adsorption from real tail water. The maximum adsorption capacity of Fe-Mg-Zr beads was 21.61 mg/g, showing more practical application value for phosphorus removal. Fixed bed experiments showed that 5.0 g adsorbent could removed 2.12 mg phosphorus from tail wastewater containing 1.03 mg/L phosphorus. The beads adsorbent can be reused with excellent adsorption performance even after five cycles of adsorption-desorption operation. After detailed analyses, it was found that ligand exchange and ion exchange were the dominant mechanisms for phosphorus adsorption by this beads. Overall, the material has the advantages of simple preparation, good adsorption performance, easy separation and recycle, indicating a great potential for low concentration phosphorus wastewater treatment.

Effect of hydraulic retention time on effluent pH in anammox bioreactors: Characteristics of effluent pH and pH as an indicator of reactor performance.

In order to assess the performance of anaerobic ammonium oxidation (anammox) bioreactors, it is necessary to study the stoichiometry of the anammox reaction and pH. This study focused on the effect of the hydraulic retention time (HRT) on the effluent pH in anammox-upflow anaerobic sludge blanket (UASB) bioreactors. Anammox-UASB bioreactors with and without a recirculation system were used to investigate the effluent pH and bioreactor performance. It was concluded that under varying HRT conditions, the decrease in effluent pH did not indicate the deterioration of nitrogen removal, but did indicate that the nitrogen removal efficiency was reduced owing to a sudden increase in the nitrogen loading rate resulting from the decrease in HRT. Moreover, the results showed that the HRT directly affected the concentration of OH-, which affected the increase/decrease in effluent pH. This study demonstrated that effluent pH is a more powerful tool than previous techniques used to assess bioreactor performance. We suggest that the effluent pH could be used for preliminary assessment.

Smoking behaviors, physical activities, pulmonary diseases and COVID-19 severity: A Mendelian randomization study.

Smoking behaviors, physical activities, and pulmonary diseases have been revealed to be associated with COVID-19 severity through observational research. The possible causative effect remains undetermined. To investigate this, we thus carried out a Mendelian randomization (MR) analysis. We chose genetic variants from genome-wide association studies that are strongly linked to 5 exposures related to smoking, 1 exposure related to drinking, 3 levels of physical activity, and 3 pulmonary diseases. The COVID-19 Host Genetics Initiative provided summary-level data for severe COVID-19 (13,769 cases and 1,072,442 noncases), hospitalized COVID-19 (32,519 cases and 2,062,805 noncases), and COVID-19 susceptibility (122,616 cases and 2,475,240 noncases). Univariate and multivariate MR analyses were carried out. Significant associations were found between severe COVID-19 and cigarette smoking per day (OR = 1.357, 95% CI: 1.087-1.694), lifetime smoking index (OR = 2.277, 95% CI: 1.602-3.325), and interstitial lung disease (OR = 1.23, 95% CI: 1.112-1.362), hospitalized COVID-19 and lifetime smoking index (OR = 2.199, 95% CI: 1.738-2.781), smoking initiation (OR = 1.419, 95% CI: 1.230-1.637), and interstitial lung disease (OR = 1.146, 95% CI: 1.082-1.214), as well as COVID-19 susceptibility and lifetime smoking index (OR = 1.39, 95% CI: 1.252-1.543), smoking initiation (OR = 1.235, 95% CI: 1.163-1.311), and duration of vigorous activity per day (OR = 0.733, 95% CI: 0.574-0.935). Duration of vigorous activity per day was suggestively inversely linked to hospitalized COVID-19 (OR = 0.434, 95% CI: 0.221-0.853) and severe COVID-19 (OR = 0.323, 95% CI: 0.123-0.850). The association for lifetime smoking index remained consistent with severe COVID-19, hospitalized COVID-19, and COVID-19 susceptibility in multivariable MR analysis. Genetic liability to lifetime smoking index mediated the interstitial lung disease effects on severe COVID-19 risk (21.0%) and hospitalized COVID-19 risk (14.4%). This study identified several smoking behaviors, duration of vigorous activity per day, and interstitial lung disease that may be causally related to COVID-19 severity.

Hemostatic Interventions and All-Cause Mortality in Hemodynamically Unstable Pelvic Fractures: A Systematic Review and Meta-Analysis.

Objective: To conduct a systematic review and meta-analysis of the all-cause mortality associated with the most commonly used hemostatic treatments in patients with hemodynamically unstable pelvic fractures. Methods: Up to April 30, 2023, we searched PubMed, Embase, Web of Science, and Cochrane, including the references to qualified papers. A meta-analysis was performed on studies that reported odds ratios (ORs) or the number of events needed to calculate them. The PROSPERO registration number was CRD42023421137. Results: Of the 3452 titles identified in our original search, 29 met our criteria. Extraperitoneal packing (EPP) (OR = 0.626 and 95% CI = 0.413-0.949), external fixation (EF) (OR = 0.649 and 95% CI = 0.518-0.814), and arterial embolism (AE) (OR = 0.459 and 95% CI = 0.291-0.724) were associated with decreased mortality. Resuscitative endovascular balloon occlusion of the aorta (REBOA) (OR = 2.824 and 95% CI = 1.594-5.005) was associated with increased mortality. A random effect model meta-analysis of eight articles showed no difference in mortality between patients with AE and patients with EPP for the initial treatments for controlling blood loss (OR = 0.910 and 95% CI = 0.623-1.328). Conclusion: This meta-analysis collectively suggested EF, AE, or EPP as life-saving procedures for patients with hemodynamically unstable pelvic fractures.

Central Retinal Artery Occlusion: Visual Outcomes from a Large Northern California Cohort.

PURPOSE: To assess visual acuity (VA) outcomes in a large cohort of patients diagnosed with nonarteritic central retinal artery occlusion (CRAO), and to ascertain whether time from symptom onset to presentation, presenting VA, or conservative treatment delivery (anterior chamber paracentesis, ocular massage, intraocular pressure lowering drugs, hyperventilation, or some combination of those) impacted ultimate VA outcomes. DESIGN: Retrospective cohort study. SUBJECTS: The study included 794 patients who presented with CRAO between 2011 and 2020. Within this cohort, 484 individuals presented within 30 days of symptom onset and had comprehensive documentation regarding the details of their presentation, management, and follow-up ≥ 90 days postdiagnosis. METHODS: Retrospective chart review was conducted for all patients with a diagnosis of CRAO initially identified via International Classification of Diseases coding, followed by confirmation of diagnosis by 2 retina specialists. Cases of arteritic CRAO were excluded. MAIN OUTCOME MEASURES: Visual acuity recovery, defined as improvement from ≤ 20/200 or worse at presentation to ≥ 20/100 ≥ 90 days after diagnosis. RESULTS: Of the 794 identified patients, 712 (89.7%) presented with VA of ≤ 20/200. Similarly, 447 (92.4%) of the 484-patient subset that presented within 30 days and had comprehensive documentation presented with VA ≤ 20/200. Of the 441 of those patients with documented follow-up, 380 (86.2%) remained at that level. Of the 244 patients who presented within 4.5 hours of symptom onset, 227 (93%) presented ≤ 20/200 and 201 (92.6%) of the 217 of those with follow-up data did not improve beyond that threshold. There was no significant difference (P < 0.05) in final VA between patients presenting before versus after 4.5 hours from time of vision loss. There was also no significant difference (P < 0.05) in VA outcomes between patients who did or did not receive conservative treatment. CONCLUSIONS: This large retrospective study further highlights the poor visual prognosis for patients with CRAO. Earlier time to presentation did not seem to impact final VA outcome, nor did conservative treatment efforts. Efficacious evidence-based treatment options are needed for this patient population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Genetic associations between gut microbiota and allergic rhinitis: an LDSC and MR analysis.

Background: Several studies have suggested a potential link between allergic rhinitis (AR) and gut microbiota. In response, we conducted a meta-analysis of Linkage Disequilibrium Score Regression (LDSC) and Mendelian randomization (MR) to detect their genetic associations. Methods: Summary statistics for 211 gut microbiota taxa were gathered from the MiBioGen study, while data for AR were sourced from the Pan-UKB, the FinnGen, and the Genetic Epidemiology Research on Aging (GERA). The genetic correlation between gut microbiota and AR was assessed using LDSC. The principal estimate of causality was determined using the Inverse-Variance Weighted (IVW) method. To assess the robustness of these findings, sensitivity analyses were conducted employing methods such as the weighted median, MR-Egger, and MR-PRESSO. The summary effect estimates of LDSC, forward MR and reverse MR were combined using meta-analysis for AR from different data resources. Results: Our study indicated a significant genetic correlation between genus Sellimonas (Rg = -0.64, p = 3.64 × 10-5, Adjust_P = 3.64 × 10-5) and AR, and a suggestive genetic correlation between seven bacterial taxa and AR. Moreover, the forward MR analysis identified genus Gordonibacter, genus Coprococcus2, genus LachnospiraceaeUCG010, genus Methanobrevibacter, and family Victivallaceae as being suggestively associated with an increased risk of AR. The reverse MR analysis indicated that AR was suggestively linked to an increased risk for genus Coprococcus2 and genus RuminococcaceaeUCG011. Conclusion: Our findings indicate a causal relationship between specific gut microbiomes and AR. This enhances our understanding of the gut microbiota's contribution to the pathophysiology of AR and lays the groundwork for innovative approaches and theoretical models for future prevention and treatment strategies in this patient population.

Genetic associations between gut microbiota and type 2 diabetes mediated by plasma metabolites: a Mendelian randomization study.

Background: Numerous research studies have indicated a possible association between type 2 diabetes (T2DM) and gut microbiota. To explore specific metabolic pathways connecting gut microbiota and T2DM, we employed Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) techniques. Methods: This research utilized data from genome-wide association studies (GWAS) that are publicly accessible. We evaluated the genetic correlation between gut microbiota and T2DM using LDSC. Causality was primarily determined through the inverse variance weighted (IVW) method. To verify the robustness of our results, we conducted sensitivity analyses using several approaches, including the weighted median, MR-Egger, and MR-PRESSO. We integrated summary effect estimates from LDSC, along with forward and reverse MR, into a meta-analysis for T2DM using various data sources. Additionally, mediation analysis was performed to explore the impact of plasma metabolites on the relationship between gut microbiota and T2DM. Results: Our study indicated a significant genetic correlation between genus RuminococcaceaeUCG005 (Rg = -0.26, Rg_P = 2.07×10-4) and T2DM. Moreover, the forward MR analysis identified genus RuminococcaceaeUCG010 (OR = 0.857, 95% CI 0.795, 0.924; P = 6.33×10-5) and order Clostridiales (OR = 0.936, 95% CI 0.878, 0.997; P = 0.039) as being significantly associated with a decreased risk of T2DM. The analysis also highlighted several plasma metabolites as significant mediators in these relationships, with metabolites like octadecadienedioate (C18:2-DC) and branched chain 14:0 dicarboxylic acid being notably involved. Conclusion: The findings demonstrate a significant impact of gut microbiota on T2DM via plasma metabolites, suggesting potential metabolic pathways for therapeutic targeting. This study enhances our understanding of the microbiota's role in T2DM pathogenesis and supports the development of microbiota-based interventions.

In-Hospital Amantadine Does Not Improve Outcomes After Severe Traumatic Brain Injury: An 11-Year Propensity-Matched Retrospective Analysis.

BACKGROUND: Disruption of dopamine neurotransmission is associated with functional impairment after severe traumatic brain injury (sTBI). This has prompted the study of dopamine agonists, such as amantadine, to assist recovery of consciousness. Randomized trials have mostly addressed the posthospital setting, with inconsistent findings. Therefore, we evaluated the efficacy of early amantadine administration on recovery of consciousness after sTBI. METHODS: We searched the medical records of all patients with sTBI admitted to our hospital between 2010 and 2021 who survived 10 days postinjury. We identified all patients receiving amantadine and compared them with all patients not receiving amantadine and a propensity score-matched nonamantadine group. Primary outcome measures included discharge Glasgow Coma Scale, Glasgow Outcome Scale-Extended score, length of stay, mortality, recovery of command-following (CF), and days to CF. RESULTS: In our study population, 60 patients received amantadine and 344 did not. Compared with the propensity score-matched nonamantadine group, the amantadine group had no difference in mortality (86.67% vs. 88.33%, P = 0.783), rates of CF (73.33% vs. 76.67%, P = 0.673), or percentage of patients with severe (3-8) discharge Glasgow Coma Scale scores (11.11% vs. 12.28%, P = 0.434). In addition, the amantadine group was less likely to have a favorable recovery (discharge Glasgow Outcome Scale-Extended score 5-8) (14.53% vs. 16.67%, P < 0.001), had a longer length of stay (40.5 vs. 21.0 days, P < 0.001), and had a longer time to CF (11.5 vs. 6.0 days, P = 0.011). No difference in adverse events existed between groups. CONCLUSIONS: Our findings do not support the early administration of amantadine for sTBI. Larger inpatient randomized trials are necessary to further investigate amantadine treatment for sTBI.

Predicting traumatic brain injury outcomes using a posterior dominant rhythm.

OBJECTIVE: Predicting severe traumatic brain injury (sTBI) outcomes is challenging, and existing models have limited applicability to individual patients. This study aimed to identify metrics that could predict recovery following sTBI. The researchers strived to demonstrate that a posterior dominant rhythm on electroencephalography is strongly associated with positive outcomes and to develop a novel machine learning-based model that accurately forecasts the return of consciousness. METHODS: In this retrospective study, the authors assessed all intubated adults admitted with sTBI (Glasgow Coma Scale [GCS] score ≤ 8) from 2010 to 2021, who underwent EEG recording < 30 days from sTBI (n = 195). Seventy-three clinical, radiographic, and EEG variables were collected. Based on the presence of a PDR within 30 days of injury, two cohorts were created-those with a PDR (PDR[+] cohort, n = 51) and those without (PDR[-] cohort, n = 144)-to assess differences in presentation and four outcomes: in-hospital survival, recovery of command following, Glasgow Outcome Scale-Extended (GOS-E) score at discharge, and GOS-E score at 6 months post discharge. AutoScore, a machine learning-based clinical score generator that selects and assigns weights to important predictive variables, was used to create a prognostic model that predicts in-hospital survival and recovery of command following. Lastly, the MRC-CRASH and IMPACT traumatic brain injury predictive models were used to compare expected patient outcomes with true outcomes. RESULTS: At presentation, the PDR(-) cohort had a lower mean GCS motor subscore (1.97 vs 2.45, p = 0.048). Despite no difference in predicted outcomes (via MRC-CRASH and IMPACT), the PDR(+) cohort had superior rates of in-hospital survival (84.3% vs 63.9%, p = 0.007), recovery of command following (76.5% vs 53.5%, p = 0.004), and mean discharge GOS-E score (3.00 vs 2.39, p = 0.006). There was no difference in the 6-month GOS-E score. AutoScore was then used to identify the 7 following variables that were highly predictive of in-hospital survival and recovery of command: age, body mass index, systolic blood pressure, pupil reactivity, blood glucose, and hemoglobin (all at presentation), and a PDR on EEG. This model had excellent discrimination for predicting in-hospital survival (area under the curve [AUC] 0.815) and recovery of command following (AUC 0.700). CONCLUSIONS: A PDR on EEG in sTBI patients predicts favorable outcomes. The authors' prognostic model has strong accuracy in predicting these outcomes, and performed better than previously reported models. The authors' model can be valuable in clinical decision-making as well as counseling families following these types of injuries.

[Promoting Nitrogen Removal in ANAMMOX Biofilm Reactor by Fe2+ Under Low Nitrogen Concentration].

The feasibility for nitrogen removal in a two-stage ANAMMOX biofilm reactor promoted by Fe2+ under low nitrogen concentration was investigated. The results showed that the ANAMMOX reaction could be effectively promoted by a ρ(Fe2+) of 5, 10, and 15 mg·L-1. A ρ(Fe2+) of 10 mg·L-1 presented the highest promotion for the ANAMMOX reaction, with the highest nitrogen removal efficiency (NRE) of 81.71% under a ρ(TN) of 150 mg·L-1and a nitrogen loading rate (NLR) of 0.62 kg·(m3·d)-1. Fe2+ promoted the secretion of extracellular polymeric substance (EPS) and the synthesis of heme c in the ANAMMOX system. Batch test results further verified the positive effects by Fe2+on the activity of anaerobic ammonium oxidizing bacteria (AnAOB). The specific ANAMMOX activity (SAA) of 10 mg·L-1 ρ(Fe2+) was 3.6 times as high as that of the control group[ρ(Fe2+)=0 mg·L-1], whereas the activity of AnAOB was significantly inhibited with ρ(Fe2+) increased to 20 mg·L-1. High-throughput sequencing results showed that the addition of Fe2+ increased the abundance of Candidatus_Kuenenia. When ρ(Fe2+) was 10 mg·L-1, the relative abundance of Candidatus_Kuenenia in reactor 1 and reactor 2 increased to 16.18% and 4.22%, respectively. The stable operation of the two-stage ANAMMOX biofilm process promoted by Fe2+provides an alternative technology for low-strength nitrogen wastewater.

Unbiased discovery of autoantibodies associated with severe COVID-19 via genome-scale self-assembled DNA-barcoded protein libraries.

Pathogenic autoreactive antibodies that may be associated with life-threatening coronavirus disease 2019 (COVID-19) remain to be identified. Here, we show that self-assembled genome-scale libraries of full-length proteins covalently coupled to unique DNA barcodes for analysis by sequencing can be used for the unbiased identification of autoreactive antibodies in plasma samples. By screening 11,076 DNA-barcoded proteins expressed from a sequence-verified human ORFeome library, the method, which we named MIPSA (for Molecular Indexing of Proteins by Self-Assembly), allowed us to detect circulating neutralizing type-I and type-III interferon (IFN) autoantibodies in five plasma samples from 55 patients with life-threatening COVID-19. In addition to identifying neutralizing type-I IFN-α and IFN-ω autoantibodies and other previously known autoreactive antibodies in patient plasma, MIPSA enabled the detection of as yet unidentified neutralizing type-III anti-IFN-λ3 autoantibodies that were not seen in healthy plasma samples or in convalescent plasma from ten non-hospitalized individuals with COVID-19. The low cost and simple workflow of MIPSA will facilitate unbiased high-throughput analyses of protein-antibody, protein-protein and protein-small-molecule interactions.

Neutralizing IFNL3 Autoantibodies in Severe COVID-19 Identified Using Molecular Indexing of Proteins by Self-Assembly.

Unbiased antibody profiling can identify the targets of an immune reaction. A number of likely pathogenic autoreactive antibodies have been associated with life-threatening SARS-CoV-2 infection; yet, many additional autoantibodies likely remain unknown. Here we present Molecular Indexing of Proteins by Self Assembly (MIPSA), a technique that produces ORFeome-scale libraries of proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing. We used MIPSA to profile circulating autoantibodies from 55 patients with severe COVID-19 against 11,076 DNA-barcoded proteins of the human ORFeome library. MIPSA identified previously known autoreactivities, and also detected undescribed neutralizing interferon lambda 3 (IFN-λ3) autoantibodies. At-risk individuals with anti- IFN-λ3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation.

Nitrite accumulation stability evaluation for low-strength ammonium wastewater by adsorption and biological desorption of zeolite under different operational temperature.

How to achieve stable nitrite accumulation was still a huge challenge for low-carbon and energy-saving biological nitrogen removal of low-strength ammonium wastewater. This study proposed a new way to solve this problem with zeolite biological fixed bed (ZBFB) by cycle operation of adsorption and biological desorption. In order to evaluate nitritation performance of this reactor, the influence of operational temperature on nitrite accumulation stability was investigated by 126 cycles operation in four parallel ZBFB reactors for low-strength ammonium wastewater (50 mg/L NH4+-N). It was found that higher operational temperature (i.e., 36.0 °C), rather than other temperature (i.e., 27.0 °C, 30.0 °C, 33.0 °C), could maintain stable nitrite accumulation with nitrite production rate of 0.312 kg NO2--N·m-3 zeolite·day-1 and nitrite accumulation ratio higher than 95.0% after biological desorption. High-throughput sequencing analysis results showed that bacterial structure significantly changed in ZBFB under different operational temperature, and obvious enrichment of genus Nitrosomonas (AOB) and gradually enhanced free ammonia (FA) inhibition on genus Nitrospira and Nitrobacter (NOB) were found by elevation of operational temperature, leading to different nitrite accumulation performance in ZBFB reactors. The mechanism for stable nitrite accumulation performance by ZBFB might be attributed to overwhelming growth rate of AOB than NOB, faster ammonium desorption and enhanced FA inhibition on NOB under operational temperature (i.e., 36.0 °C). All in all, keeping high temperature for biological desorption step should be extremely crucial for stable nitrite accumulation by ZBFB, which could facilitate further low-carbon and energy-saving biological nitrogen removal for low-strength ammonium wastewater treatment.

Efficacy and safety of sotagliflozin adjuvant therapy for type 1 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the efficacy and safety of sotagliflozin (SOTA) adjuvant therapy for type 1 diabetes mellitus (T1DM). METHODS: Through April 2019, the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure databases were electronically searched to identify randomized controlled trials exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluations of the obtained literature were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using Revman 5.3 software. RESULTS: A total of 7 randomized controlled trials were included. The meta-analysis results showed that compared with the patients in the placebo group, the patients in the SOTA group had a lower hemoglobin A1c (mean difference [MD] = -0.28, 95% confidence interval [CI] [-0.34, -0.22], P < .01), lower total daily insulin use (MD = -8.89, 95% CI [-11.64, -6.13], P < .01), faster weight loss (MD = -3.03, 95% CI [-3.79, -2.26], P < .01), better fasting blood glucose and 2-hour postprandial blood glucose control (MD = -0.75, 95% CI [-1.04, -0.45], P < .01; MD = -2.42, 95% CI [-3.17, -1.67], P < .01), and a higher rate of well-controlled glucose levels (relative risk = 1.75, 95% CI [1.55, 1.99], P < .01), while no significant difference in the incidence of severe hypoglycemic events was found between the SOTA and placebo groups (risk difference [RD] = -0.01, 95% CI [-0.02, 0.00], P = .13). The incidence of diabetic ketoacidosis was higher in the SOTA group than in the placebo group (RD = 0.03, 95% CI [0.02, 0.04], P < .01). The incidence of genital mycotic infection was higher in the SOTA group than in the placebo group (RD = 0.06, 95% CI [0.05, 0.08], P < .01). No significant difference in the incidence of urinary tract infections was detected between the SOTA group and the placebo group (RD = 0.00, 95% CI [-0.01, 0.01], P = 0.97). CONCLUSIONS: SOTA is a potential drug for the treatment of T1DM and is effective for controlling blood sugar. The main adverse reactions to SOTA are genital mycotic infections and diabetic ketoacidosis. We must further assess the severity of diabetic ketoacidosis caused by SOTA.

Ultra-efficient sequencing of T Cell receptor repertoires reveals shared responses in muscle from patients with Myositis.

BACKGROUND: Myositis, or idiopathic inflammatory myopathy (IIM), is a group disorders of unknown etiology characterized by the inflammation of skeletal muscle. The role of T cells and their antigenic targets in IIM initiation and progression is poorly understood. T cell receptor (TCR) repertoire sequencing is a powerful approach for characterizing complex T cell responses. However, current TCR sequencing methodologies are complex, expensive, or both, greatly limiting the scale of feasible studies. METHODS: Here we present Framework Region 3 AmplifiKation sequencing ("FR3AK-seq"), a simplified multiplex PCR-based approach for the ultra-efficient and quantitative analysis of TCR complementarity determining region 3 (CDR3) repertoires. By using minimal primer sets targeting a conserved region immediately upstream of CDR3, undistorted amplicons are analyzed via short read, single-end sequencing. We also introduce the novel algorithm Inferring Sequences via Efficiency Projection and Primer Incorporation ("ISEPPI") for linking CDR3s to their associated variable genes. FINDINGS: We find that FR3AK-seq is sensitive and quantitative, performing comparably to two different industry standards. FR3AK-seq and ISEPPI were used to efficiently and inexpensively characterize the T cell infiltrates of surgical muscle biopsies obtained from 145 patients with IIM and controls. A cluster of closely related TCRs was identified in samples from patients with sporadic inclusion body myositis (IBM). INTERPRETATION: The ease and minimal cost of FR3AK-seq removes critical barriers to routine, large-scale TCR CDR3 repertoire analyses, thereby democratizing the quantitative assessment of human TCR repertoires in disease-relevant target tissues. Importantly, discovery of closely related TCRs in muscle from patients with IBM provides evidence for a shared antigen-driven T cell response in this disease of unknown pathogenesis. FUNDING: This work was supported by NIH grant U24AI118633 and a Prostate Cancer Foundation Young Investigator Award.

Highly multiplexed oligonucleotide probe-ligation testing enables efficient extraction-free SARS-CoV-2 detection and viral genotyping.

The emergence of SARS-CoV-2 has caused the current COVID-19 pandemic with catastrophic societal impact. Because many individuals shed virus for days before symptom onset, and many show mild or no symptoms, an emergent and unprecedented need exists for development and deployment of sensitive and high throughput molecular diagnostic tests. RNA-mediated oligonucleotide Annealing Selection and Ligation with next generation DNA sequencing (RASL-seq) is a highly multiplexed technology for targeted analysis of polyadenylated mRNA, which incorporates sample barcoding for massively parallel analyses. Here we present a more generalized method, capture RASL-seq ("cRASL-seq"), which enables analysis of any targeted pathogen- (and/or host-) associated RNA molecules. cRASL-seq enables highly sensitive (down to ~1-100 pfu/ml or cfu/ml) and highly multiplexed (up to ~10,000 target sequences) detection of pathogens. Importantly, cRASL-seq analysis of COVID-19 patient nasopharyngeal (NP) swab specimens does not involve nucleic acid extraction or reverse transcription, steps that have caused testing bottlenecks associated with other assays. Our simplified workflow additionally enables the direct and efficient genotyping of selected, informative SARS-CoV-2 polymorphisms across the entire genome, which can be used for enhanced characterization of transmission chains at population scale and detection of viral clades with higher or lower virulence. Given its extremely low per-sample cost, simple and automatable protocol and analytics, probe panel modularity, and massive scalability, we propose that cRASL-seq testing is a powerful new surveillance technology with the potential to help mitigate the current pandemic and prevent similar public health crises.

Effectiveness and safety of hypotensive resuscitation in traumatic hemorrhagic shock: A protocol for meta-analysis.

BACKGROUND: Hypotensive resuscitation is an old study. But its benefits and losses are still controversial. In clinic, the method of fluid resuscitation needs more reliable experimental evidence. This study's objective is to systematically evaluate the efficacy of hypotensive resuscitation in patients with traumatic hemorrhagic shock. METHODS AND ANALYSIS: Through October 2019, Web of Science, PubMed, the Cochrane Library, EMBASE, and Clinical Trials will be systematically searched to identify randomized controlled trials exploring the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock. Strict screening and quality evaluation will be independently performed on the obtained literature by 2 researchers; outcome indexes will be extracted, and a meta-analysis will be performed on the data using Revman 5.3 software. ETHICS AND DISSEMINATION: The stronger evidence about the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock will be provided for clinicians. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133169. STRENGTHS OF THIS STUDY: This study is not only a simple combination of data, but also to verify and discuss the reliability of the results, and provide more convincing evidence for clinicians. LIMITATIONS OF THIS STUDY: Firstly, according to the previous literature researching, it is found that the number of relevant randomized controlled trials is small and the quality level of the literature is uneven. Secondly, the efficacy of hypotensive resuscitation is discussed for a long time, different trials may take place at different times. Comparability between different trials is reduced.

Effectiveness and safety of sotagliflozin adjuvant therapy for type 1 diabetes mellitus: A protocol for Systematic review and Meta-analysis.

BACKGROUND: Type 1 Diabetes Mellitus (T1DM) has long required insulin treatment. Sotagliflflozin (SOTA), as a dual SGLT-1/2 inhibitor, has the potential to be the first oral antidiabetic drug (OAD) to be approved for T1DM in the US market. It is important to evaluate the effectiveness of SOTA for T1DM. METHODS: Web of Science, PubMed datebase, Cochrane Library, Embase, Clinical Trials, and CNKI will be searched to identify randomized controlled trials (RCTs) exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluation will be performed on the obtained literature independently by 2 researchers; outcome indexes will be extracted. The bias risk of the included studies will be evaluated based on Cochrane assessment tool. Meta-analysis will be performed on the data using Revman 5.3 software. RESULT: We will provide practical and targeted results assessing the efficacy and safety of SOTA for T1DM patients, to provide reference for clinical use of SOTA. CONCLUSION: The stronger evidence about the efficacy and safety of SOTA for T1DM patients will be provided for clinicians. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133099.