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Rifampicin (RIF) is one of the most effective anti-tuberculosis first-line drugs prescribed along with isoniazid. However, the emergence of RIF resistance Mycobacterium tuberculosis (MTB) isolates is a major issue towards tuberculosis (TB) control program in high MDR TB-burdened countries including Pakistan. Molecular data behind phenotypic resistance is essential for better management of RIF resistance which has been linked with mutations in rpoB gene. Since molecular studies on RIF resistance is limited in Pakistan, the current study was aimed to investigate the molecular data of mutations in rpoB gene behind phenotypic RIF resistance isolates in Pakistan.

A total of 322 phenotypically RIF-resistant isolates were randomly selected from National TB Reference Laboratory, Pakistan for sequencing while 380 RIF resistance whole-genome sequencing (WGS) of Pakistani isolates (BioProject PRJEB25972), were also analyzed for rpoB mutations.

Among the 702 RIF resistance samples, 675 (96.1%) isolates harbored mutlecular detection of drug resistance is a faster and better approach than phenotypic drug susceptibility testing to reduce the time for transmission of RIF resistance strains in population. Such insights will inform the deployment of anti-TB drug regimens and disease control tools and strategies in high burden settings, such as Pakistan.

Evaluating the national burdens across multiple vaccine-preventable diseases (VPDs) can be informative to identify the areas for improvements in the national immunization program.

The annual burden of diseases from 2008 to 2020 in Japan were calculated with the incidence- and pathogen-based approach for the 15 VPDs (hepatitis B virus infection, human papillomavirus (HPV), influenza, invasive pneumococcal disease, invasive Haemophilus influenzae type b (Hib) disease, invasive meningococcal disease, Japanese encephalitis, measles, mumps, pertussis, rotavirus, rubella, tetanus, tuberculosis and varicella), using disability-adjusted life year (DALY).

The average annual burden between 2008 and 2020 is the highest in influenza (114,129 DALY/year), followed by HPV infection, hepatitis B virus infection, tuberculosis and mumps (109,782, 69,883, 23,855 and 5693 DALY/year). In the pre-COVID-19 period (2008-2019), the decreasing trend of burden was observed in hepatitis B virus infection, invasive pneumococcal disease, invasive Hib disease, tuberculosis and varicella. HPV infection is the only VPD which had more than 100,000 DALY/year for all years during the study period. In 2020, the estimated annual burdens are decreased in influenza (71%), invasive pneumococcal disease (51%), invasive Hib diseases (54%), invasive meningococcal disease (64%), measles (98%), mumps (47%) pertussis (83%), rotavirus infection (95%), rubella (94%) and varicella (35%) compared with those in 2019.

The study demonstrated decreasing trends of burdens for some VPDs, while a persistently high burden has been observed for other VPDs, including HPV infection. The COVID-19 pandemic has caused dramatic reductions in the burdens of many VPDs in 2020.

The study demonstrated decreasing trends of burdens for some VPDs, while a persistently high burden has been observed for other VPDs, including HPV infection. The COVID-19 pandemic has caused dramatic reductions in the burdens of many VPDs in 2020.

We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy.

Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin×Lymphocyte)/(CRP×10

). Patients with a CALLY index ≥5 (n=200) were compared to those with an index <5 (n=184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort).

The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p=0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5 71% vs. <5 46%; p<0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p<0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort.

The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.

The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.

In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer.

Nine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L 1%-9%; Median/M 10%-79%; High/H 80%-100%) and PR level (Low/L 0%-19%; High/H 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and log rank test.

Four hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). Phycocyanobilin manufacturer While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P=.22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P=.074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P=.024) in all patients and 0.14 (95%CI, 0.02-1.02, P=.053) in patients receiving anti-HER2 therapy.

ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.Research demonstrating improved outcomes with third-generation ankle replacement implants has resulted in increasing utilization of total ankle arthroplasty over the past 3 decades. The purpose of this study was to examine the quality and trends of clinical outcomes research being published on third-generation total ankle arthroplasty implants. Two fellowship-trained foot and ankle surgeons reviewed all peer-reviewed, Medline-indexed English-language clinical outcomes studies evaluating total ankle arthroplasty published between 2006 and 2019. Articles were assessed for study design and indicators of study quality. A total of 694 published articles were reviewed and 231 met all inclusion criteria. The majority (78%) of studies were retrospective, most of which were case series (54%) or cohorts (32%). Ten percent (10%) of studies were funded by industry and 28% did not disclose funding sources. Thirty-eight percent (38%) of studies reported a conflict of interest and 6% did not disclose whether or not there were conflicts. The average patient follow-up time across studies was 72 months. We found that although the study of outcomes with third-generation total ankle arthroplasty prostheses is steadily increasing, most studies are Level IV, retrospective case series. Some studies have disclosed industry funding and/or a conflict of interest, and a considerable number did not disclose potential funding and/or financial conflicts. Future investigators should strive to design studies with the highest quality methodology possible.

a) To analyze the relationship of known and emerging biomarkers/indicators for early risk identification of cardiometabolic health risk; b) to identify early risk markers to be used in both clinical and nonclinical settings; and c) to propose a definition of early risk identification in terms of pre-metabolic syndrome (PreMetSyn).

Pubmed/Medline, Web of Science, Embase, and Cochrane were searched for Systematic Reviews and Meta-analysis. Selected studies were evaluated, and relevant data were extracted and synthesized.

Serum uric acid is a good predictive biomarker of metabolic syndrome (MetSyn) and has been associated with non-alcoholic liver fat disease (NAFLD) and type 2 diabetes. NAFLD emerges as an early risk indicator of PreMetSyn by itself. Muscle strength should also be included as an early risk marker of cardiometabolic health. High serum triglycerides and waist circumference confirm their predictive value regarding MetSyn. Indicators related to an inflammatory/pro-inflammatory status usually lrum triglycerides and waist circumference confirm their predictive value regarding MetSyn. Indicators related to an inflammatory/pro-inflammatory status usually linked to MetSyn showed limited evidence as robust biomarkers for PreMetSyn. Authors suggest defining PreMetSyn related to cardiometabolic risk. It is also necessary to determine how close people are to the cut-off point of MetSyn components, including emerging indicators proposed by our review. Some biomarkers could be used as indicators of PreMetSyn, before any of the MetSyn components appear, allowing early health interventions to prevent its development. Defining a PreMetSyn status might consider both emerging indicators and those variables already included in the definition of MetSyn. New indicators should be considered to create a new risk score specifically meant for PreMetSyn.

Increasing evidence suggests that major psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ) share biological, neuropsychological and clinical features, despite the criteria for their respective diagnoses being different. Neuroimaging studies have shown disrupted 'static' neural connectivity in these disorders. However, the changes in brain dynamics across the three psychiatric disorders remain unknown.

We aim to examine the connections and divergencies of the dynamic amplitude of low-frequency fluctuation (dALFF) in MDD, BD and SZ. In total, 901 participants [MDD, 229; BD, 146; SZ, 142; and healthy controls (HCs), 384] received resting-state functional magnetic resonance imaging. The dALFF was calculated using sliding-window analysis and compared across three psychiatric disorders.

We found significant increases of dALFF in the right fusiform, right hippocampus, right parahippocampal in participants with MDD, BD and SZ compared to HC. We also found specific increased dALFF changes in caudate and left thalamus for SZ and BD and decreased dALFF changes in calcarine and lingual for SZ and MDD.