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The COVID-19 pandemic has led to an "infodemic", of false and true information circulating on social media platforms. This phenomenon has posed various challenges in implementing disaster management programs to mitigate the effects of the pandemic, both globally and specifically in Indonesia. This study seeks to investigate the public's perception of social media discourse during the COVID-19 infodemic in Indonesia. Both primary and secondary data were collected to gain a comprehensive understanding of the issue. The primary data was collected through a focused group discussion (FGD) method. Meanwhile, secondary data sources were gathered using a literature review of scholarly articles. Approximately 60 articles were selected from sources such as Google Scholar and PubMed, published between 2019 and 2022. The articles were selected based on their relevance of the topic discussion. The study used Critical Discourse Analysis by Fairclough and Wodak (1997) to analyze the data. Both of the data were then synthesized to glimpse how the infodemic has impacted various disaster management efforts across various parts of the country. The results revealed that the infodemic has worsened public perceptions of how the Indonesian government handles COVID-19 as well as disrupting various disaster management processes. The study finds that the infodemic's impact on the public's perception has resulted in misinformation hampering effective pandemic management efforts. By recognizing the severity of the infodemic and working to combat it, Indonesia can more effectively manage the COVID-19 pandemic and minimize its negative impact on the public.

The 2022 earthquake in Cianjur Regency has claimed many lives, caused damage and large material losses. In addition, there are findings of new active faults in the Cugenang area that can potentially threaten the safety of the population. Therefore, it is necessary for the Government to reduce physical and material losses and reduce the number of casualties if a similar incident occurs again. BNPB is the leading sector in disaster management in Indonesia, one of which is disaster risk reduction efforts. This study aimed to analyze the role of BNPB in the efforts of nonstructural mitigation activities in the Cugenang Fault area of Cianjur Regency. The research method used was qualitative with an exploratory design. The data in this study were obtained from interviews, documentation, and observation in Cugenang District. The results of this study showed that BNPB's role in nonstructural mitigation efforts was carried out through activities: Policy Recommendation for post-disaster spatial plan of Cianjur 2022, Dissemination of information about the risk of natural disasters in Cugenang, Preparation of disaster risk assessment 2023. Conclusion The Cugenang Fault is an active fault that is prone to earthquake threats. Therefore, the government is obliged to protect the community from the threat of earthquakes through nonstructural mitigation activities. The research suggestion is for the local government to make a RTRW policy to protect the community from earthquakes through nonstructural mitigation activities.

Indonesia dengan wilayah geografi yang relatif sama dengan Jepang dan sangat dipengaruhi oleh pergerakan lempeng tektonik menyebabkan Indonesia rawan terhadap gempa tektonik, terlebih Serpong Kota Tangerang Selatan lokasi Reaktor Serba Guna - G.A. Siwabessy (RSG-GAS) berada tercatat dalam buku Katalog Gempabumi Signifikan dan Merusak Tahun 1821-2018, sebagai wilayah berisiko terdampak gempa. Berdasarkan hal tersebut, penelitian ini mengidentifikasi dan menganalisis upaya mitigasi yang dilakukan untuk mengurangi risiko ancaman bencana akibat kegagalan teknologi di RSG-GAS. Metode penelitian yang digunakan kualitatif dengan desain penelitian deskriptif eksploratif, mengeksplorasi fenomena baru dan mendeskripsikan sesuai pengamatan langsung dari data primer yang diperoleh melalui wawancara dengan narasumber, dan data sekunder melalui studi dokumen milik narasumber dan studi pustaka. Validasi data dilakukan dengan teknik triangulasi dengan melakukan investigasi data dari berbagai sumber yang di analisis sesuai dengan kerangka penelitian. Tindakan mitigasi sudah dilakukan sebelum desain disusun, tepatnya pada penentuan calon tapak sampai pada saat ini tahap operasi. Pemutakhiran evaluasi tapak reaktor dilakukan pada aspek kejadian eksternal (aspek kegempaan, kegunungapian, geoteknik, meteorologi dan hidrologi, ulah manusia, serta dispersi zat radioaktif). Pemutakhiran evaluasi tapak dari aspek kejadian eksternal menjadi pertimbangan dalam desain RSG-GAS berbasis mitigasi, termasuk simulasi station balckout yang telah dilakukan di RSG-GAS, untuk mengetahui kapasitas dan kerentanan RSG-GAS terhadap bahaya eksternal yang terjadi seperti di Fukushima Daiichi. Peraturan Perundang-undangan terkait desain mempertimbangkan bahaya eksternal seperti gempabumi dan bahaya lainnya juga sudah diundangkan. Untuk memperkuat kapasitas pemerintah dan pemangku kepentingan perlu dilakukan revisi Peraturan Pemerintah untuk mengatur tanggung jawab dan kewenangannya dalam penanggulangan kedaruratan nuklir untuk menjamin keselamatan masyarakat guna tercipta keamanan nasional.

In early breast cancer (EBC) patients, local disease relapse occurs at the site of the original primary tumor in 90% of cases and the addition of external beam radiotherapy (EBRT) after surgery is necessary to reduce recurrence rate. This observation suggested that surgery itself could represent a perturbing factor, possibly by altering the local microenvironment by inducing a wound healing response. Recent evidences indicate that, in selected EBC patients, 5 weeks of EBRT can be successfully replaced by a single dose of Targeted Intraoperative Radiotherapy (TARGIT). Interestingly, TARGIT acts not only affecting tumor cell survival itself, but is also able to alter the tumor microenvironment, by modifying cytokines secretion and activation of several intracellular pathways in breast cancer cells. In order to understand the significance of these modifications in breast tumor microenvironment after exposure to TARGIT we set up a mouse model of TARGIT treatment. Our results highlighted that the act of surgery alone strongly stimulates breast cancer cell growth and the addition of local irradiation completely reverses the surgery-induced breast cancer cell growth. Moreover, we evaluated the impact of TARGIT by analyzing microRNA (miR) expression both in our mouse model and in human specimens. To this aim, we collected paired specimens of peri-tumoral mammary tissues from 30 early breast cancer (EBC) patients, before and after treatment with TARGIT. Microarray approach followed by qRT-PCR validation revealed the presence of specific TARGIT-regulated miRs. Among the others, miR-223 was the most highly and significantly modified. In silico analyses indicated that epidermal growth factor (EGF) is a potential candidate of mR-223 regulation. In vitro experiments, using both normal and tumor derived cell lines validated the bioinformatic prediction, demonstrating that the 3' UTR of EGF is a target of miR-223 and this binding results in the control of EGF production by the cells. Importantly, miR-223 overexpression was able to impair, at least in part, the wound-induced growth of normal and tumor derived breast-cancer cells, eventually influencing breast cancer cell proliferation and survival. Our results suggest that the effects of radiotherapy in the wounded tissue go far beyond the mere killing of residual tumor cells and is able to balance the negative effects of the wound healing process, both in human and mouse breast tissue. TARGIT-induced microenvironment modifications, in particular miR-223 up-regulation, significantly impair breast cancer response to surgery-induced inflammation eventually resulting in recurrence control. Our experimental findings strongly support the notion that the timely application of radiotherapy to the tumor bed, immediately after tumor removal, is critical to counteract the effects of surgery and wound healing process on residual breast cancer cells and normal peri-tumoral breast tissue. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug-resistant (MDR) Mtb strains. Herein, we design and synthesize 35 novel b enzo[c] p henanthridine d erivatives (BPDs). The two most potent compounds, BPD-6 and BPD-9, accumulated within the bacterial cell and exhibited strong inhibitory activity (MIC 90 ~2 to 10 µM) against multiple Mycobacterium strains while remaining inactive against a range of other Gram-negative and Gram-positive bacteria. BPD-6 and BPD-9 were also effective in reducing Mtb survival within infected macrophages, and BPD-9 reduced the burden of Mycobacterium bovis BCG in the lungs of infected mice. The two BPD compounds displayed comparable efficacy to rifampicin (RIF) against non-replicating Mtb (NR-Mtb). Importantly, BPD-6 and BPD-9 inhibited the growth of multiple MDR Mtb clinical isolates. Generation of BPD-9-resistant mutants identified the involvement of the Mmr efflux pump as an indirect resistance mechanism. The unique specificity of BPDs to Mycobacterium spp. and their efficacy against MDR Mtb isolates suggest a potential novel mechanism of action. The discovery of BPDs provides novel chemical scaffolds for anti-TB drug discovery.IMPORTANCEThe emergence of drug-resistant tuberculosis (TB) is a serious global health threat. There remains an urgent need to discover new antibiotics with unique mechanisms of action that are effective against drug-resistant Mycobacterium tuberculosis (Mtb). This study shows that novel semi-synthetic compounds can be derived from natural compounds to produce potent activity against Mtb. Importantly, the identified compounds have narrow spectrum activity against Mycobacterium species, including clinical multidrug-resistant (MDR) strains, are effective in infected macrophages and against non-replicating Mtb (NR-Mtb), and show anti-mycobacterial activity in mice. These new compounds provide promising chemical scaffolds to develop potent anti-Mtb drugs of the future., Competing Interests: The authors declare no conflict of interest.

Mycobacterium tuberculosis (Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their potential to shorten treatment and reduce the development of antibiotic resistance. Previously, we described a modular biomimetic strategy to identify SMIP-30 , targeting PPM1A (IC 50 = 1.19 μM), a metal-dependent phosphatase exploited by Mtb to survive intracellularly. SMIP-30 restricted the survival of Mtb in macrophages and lungs of infected mice. Herein, we redesigned SMIP-30 to create SMIP-031 , which is a more potent inhibitor for PPM1A (IC 50 = 180 nM). SMIP-031 efficiently increased the level of phosphorylation of S403-p62 and the expression of LC3B-II to activate autophagy, resulting in the dose-dependent clearance of Mtb in infected macrophages. SMIP-031 possesses a good pharmacokinetic profile and oral bioavailability ( F = 74%). In vivo, SMIP-031 is well tolerated up to 50 mg/kg and significantly reduces the bacteria burden in the spleens of infected mice.

The differentiation and activation of macrophages are critical regulatory programs that are central to host inflammation and pathogen defense. However, the transcriptional regulatory pathways involved in these programs are not well understood. Herein, we demonstrate that the activity and expression of the transcription factor ATF2 is precisely regulated during primary human monocyte-to-macrophage differentiation and that its activation is linked to M1 polarization and antibacterial responses. Genetic perturbation experiments demonstrated that deletion of ATF2 (THP-ΔATF2) resulted in irregular and abnormal macrophage morphology, whereas macrophages overexpressing ATF2 (THP-ATF2) developed round and pancake-like morphology, resembling classically activated (M1) macrophages. Mechanistically, we show that ATF2 binds to the core promoter of PPM1A, a phosphatase that regulates monocyte-to-macrophage differentiation, to regulate its expression. Functionally, overexpression of ATF2 sensitized macrophages to M1 polarization, resulting in increased production of major histocompatibility complex class II, IL-1β, and IP-10; improved phagocytic capacity; and enhanced control of the intracellular pathogen Mycobacterium tuberculosis. Gene expression profiling revealed that overexpression of ATF2 reprogramed macrophages to promote antibacterial pathways enriched in chemokine signaling, metabolism, and antigen presentation. Consistent with pathways analysis, metabolic profiling revealed that genetic overexpression or stimuli-induced activation of ATF2 alters the metabolic capacity of macrophages and primes these cells for glycolytic metabolism during M1 polarization or bacterial infection. Our findings reveal that ATF2 plays a central role during macrophage differentiation and M1 polarization to enhance the functional capacities of macrophages., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Tuberculosis, a deadly infectious lung disease caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of bacterial disease-related deaths worldwide. Mtb reprograms and disables key antibacterial response pathways, many of which are regulated by epigenetic mechanisms that control the accessibility of chromatin to the transcriptional machinery. Recent reports suggest that host phosphatases, such as PPM1A, contribute to regulating chromatin accessibility during bacterial infections. However, changes in genome-wide chromatin accessibility during Mtb infection and whether PPM1A plays a role in this process remains unknown. Herein, we use combinatorial chromatin accessibility (ATAC-seq) and transcriptomic (RNA-seq) profiling of wild-type, PPM1A knockout and PPM1A overexpressing macrophages to demonstrate that Mtb infection induces global chromatin remodelling consistent with changes in gene expression. The strongest concordant changes to chromatin accessibility and gene expression triggered by Mtb infection were enriched for genes involved in type I interferon (IFN) signalling pathways. A panel of 15 genes with the strongest concordant changes in chromatin accessibility and gene expression were validated to be significantly upregulated in Mtb-infected human monocyte-derived macrophages. PPM1A expression affects chromatin accessibility profiles during Mtb infection that are reflected in the total number, chromosome location, and directionality of change. Transcription factor binding motif analysis revealed enrichment for transcription factors involved in the type I IFN pathway during Mtb infection, including members of the IRF, MEF2, and AP-1 families. Our study shows that altered type I IFN responses in Mtb-infected macrophages occur due to genome-wide changes in chromatin accessibility, and that PPM1A could influence a subset of these signatures., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)