UNASSIGNED: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India.
UNASSIGNED: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC.
UNASSIGNED: Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response.
UNASSIGNED: AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.

Tripterygium glycosides tablets (TGT) are the commonly used preparation for rheumatoid arthritis (RA). However, the changes in TGT on RA are still unclear at the metabolic level. This study aimed to reveal the biological processes of TGT in collagen-induced arthritis (CIA) rats through integrated metabolomics and network analysis. First, the CIA model in rats was established, and the CIA rats were given three doses of TGT. Then, the endogenous metabolites in the serum from normal rats, CIA rats, and CIA rats treated with varying doses of TGT were detected by UHPLC-QTOF-MS/MS. Next, univariate and multivariate statistical analyses were performed to find the differential metabolites. Finally, differential metabolites, metabolic pathways, and hub genes were analyzed integrally to reveal the biological processes of TGT in CIA rats. The paw diameter, arthritis score, immunoglobulin G (IgG) concentration, CT image, and histological assay showed that TGT had evident therapeutic effects on CIA rats. Untargeted metabolomics revealed that TGT could ameliorate the down-regulation of lipid levels in CIA rats. Four key differential metabolites were found including LysoP(18:0), LysoPA(20:4), LysoPA(18:2), and PS(O-20:0/17:1). The glycerophospholipid metabolic pathway was perturbed in treating CIA with TGT. A total of 24 genes, including PLD1, LPCAT4, AGPAT1, and PLA2G4A, were found to be the hub genes of TGT in CIA rats. In conclusion, the integrated analysis provided a novel and holistic perspective on the biological processes of TGT in CIA rats, which could give helpful guidance for further TGT on RA. Future studies based on human samples are necessary.

UNASSIGNED: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren\'s disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren\'s disease.
UNASSIGNED: To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren\'s disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland.
UNASSIGNED: In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren\'s disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time.
UNASSIGNED: Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

This review reports the recent advances in surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) platforms for the diagnosis of infectious diseases. As observed through the recent infection outbreaks of COVID-19 worldwide, a timely diagnosis of the disease is critical for preventing the spread of a disease and to ensure epidemic preparedness. In this regard, an innovative point-of-care diagnostic method is essential. Recently, SERS-based assay platforms have received increasing attention in medical communities owing to their high sensitivity and multiplex detection capability. In contrast, LFAs provide a user-friendly and easily accessible sensing platform. Thus, the combination of LFAs with a SERS detection system provides a new diagnostic modality for accurate and rapid diagnoses of infectious diseases. In this context, we briefly discuss the recent application of LFA platforms for the POC diagnosis of SARS-CoV-2. Thereafter, we focus on the recent advances in SERS-based LFA platforms for the early diagnosis of infectious diseases and their applicability for the rapid diagnosis of SARS-CoV-2. Finally, the key issues that need to be addressed to accelerate the clinical translation of SERS-based LFA platforms from the research laboratory to the bedside are discussed.

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UNASSIGNED: Several COVID-19 vaccination rollout strategies are implemented. Real-world data from the large-scale, government-mandated Central Vaccination Center (CVC), Thailand, could be used for comparing the breakthrough infection, across all available COVID-19 vaccination profiles.
UNASSIGNED: This prospective cohort study combined the vaccine profiles from the CVC registry with three nationally validated outcome datasets to assess the breakthrough COVID-19 infection, hospitalization, and death among Thais individuals who received at least one dose of the COVID-19 vaccine. The outcomes were analyzed by comparing vaccine profiles to investigate the shot effect and homologous effect.
UNASSIGNED: Of 2,407,315 Thais who had at least one dose of COVID-19 vaccine, 63,469 (2.75%) had breakthrough infection, 42,001 (1.79%) had been hospitalized, and 431 (0.02%) died. Per one vaccination shot added, there was an 18% risk reduction of breakthrough infection (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.80-0.82), a 25% risk reduction of hospitalization (HR 0.75, 95% CI 0.73-0.76), and a 96% risk reduction of mortality (HR 0.04, 95% CI 0.03-0.06). The heterologous two-shot vaccine profiles had a higher protective effect against infection, hospitalization, and mortality compared to the homologous counterparts.
UNASSIGNED: COVID-19 breakthrough infection, hospitalization, and death differ across vaccination profiles that had a different number of shots and types of vaccines.
UNASSIGNED: This study did not involve any funding.

\"Pediatric acute-onset neuropsychiatric syndrome\", or PANS, is a rare syndrome characterized by an acute onset of obsessive-compulsive disorder (OCD), and/or severely restricted food intake accompanied by a variety of neuropsychiatric symptoms. To our knowledge, this is the first case report of twin adolescents with COVID-19-associated PANS. Dizygotic twin sisters in late teens, with abrupt and acute onset of severely restrictive food intake, weight loss, OCD, anxiety with intermittent auditory and visual hallucinations, depression, attention deficit, and sleep disturbances, simultaneously accompanied by milder neurologic symptoms such as hand tremor, tinnitus, dizziness, headache, and weakness of proximal muscles, were applied to child and adolescent psychiatry clinic. The only relevant agent underlying those neuropsychiatric and somatic complaints was COVID-19, and it was validated with laboratory testing, such as positive IgG titers of SARS-CoV-2 and negative biomarkers for other possible bacterial or viral agents. Generalized epileptic anomaly and a vermian/folial atrophy in the cerebellum were detected in further evaluations. Treatment options consisted of psychotropic agents, antibiotics, antiepileptic, and intravenous immunoglobulin transfusion finely treated the neuropsychiatric symptoms. Clinicians should consider SARS-CoV-2 as a potential agent, when a child presents with abrupt onset, dramatic neuropsychiatric symptoms also consisting of PANS, even in asymptomatic patients or with mild respiratory symptoms.

Gallic acid (GA) is a natural polyphenolic compound with many health benefits. To assess the potential risk of long-term consumption of GA to gut health, healthy dogs were fed a basal diet supplemented with GA (0%, 0.02%, 0.04%, and 0.08%) for 45 d, and fecal microbiota and metabolomics were evaluated. This study demonstrated that GA supplementation regulated serum lipid metabolism by reducing serum triglyceride, fat digestibility, and Bacteroidetes/Firmicutes ratio. In addition, the relative abundance of Parasutterella was significantly lower, and the SCFAs-producing bacteria were increased along with fecal acetate and total SCFAs contents accumulation in the 0.08% GA group. Metabolomics data further elucidated that 0.08% GA significantly affected carbohydrate metabolism by downregulating succinic acid in fece, thereby alleviating inflammation and oxidative stress. Overall, this study confirmed the beneficial effects of long-term consumption of GA on lipid metabolism and gut health, and the optimal level of GA supplementation was 0.08%.

UNASSIGNED: To assess clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT) we performed sub-group analyses on a completed randomised control trial (RCT) on CPT in severe COVID-19.
UNASSIGNED: A series of subclass analyses were performed on the previously published outcome data and accompanying clinical metadata from a completed RCT (Clinical Trial Registry of India, No. CTRI/2020/05/025209).
UNASSIGNED: The subclass analyses were performed on the outcome data and accompanying clinical metadata from a completed randomized control trial. Data on the plasma abundance of a large panel of cytokines from the same cohort of patients were also utilised to characterize the heterogeneity of the putative anti-inflammatory function of convalescent plasma (CP) in addition to passively providing neutralizing antibodies.
UNASSIGNED: While across all age-groups primary clinical outcomes were not significantly different in the RCT, significant immediate mitigation of hypoxia, reduction in hospital stay as well as significant survival benefit were registered in younger (<67 years in our cohort) severe COVID-19 patients with ARDS on receiving CPT. In addition to neutralizing antibody content of convalescent plasma, its anti-inflammatory proteome on attenuation of systemic cytokine deluge, significantly contributed to the clinical benefits of CPT.
UNASSIGNED: The sub-group analyses revealed that clinical benefit of CPT in severe COVID-19 is linked to the anti-inflammatory protein content of CP, apart from the anti-SARS-CoV-2 neutralizing antibody content.

UNASSIGNED: Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean Red Ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus.
UNASSIGNED: A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2.
UNASSIGNED: The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect.
UNASSIGNED: The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.