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Lysosomes must maintain the integrity of their limiting membrane to ensure efficient fusion with incoming organelles and degradation of substrates within their lumen. Pancreatic cancer cells upregulate lysosomal biogenesis to enhance nutrient recycling and stress resistance, but it is unknown whether dedicated programmes for maintaining the integrity of the lysosome membrane facilitate pancreatic cancer growth. Using proteomic-based organelle profiling, we identify the Ferlin family plasma membrane repair factor Myoferlin as selectively and highly enriched on the membrane of pancreatic cancer lysosomes. Mechanistically, lysosomal localization of Myoferlin is necessary and sufficient for the maintenance of lysosome health and provides an early acting protective system against membrane damage that is independent of the endosomal sorting complex required for transport (ESCRT)-mediated repair network. Myoferlin is upregulated in human pancreatic cancer, predicts poor survival and its ablation severely impairs lysosome function and tumour growth in vivo. Thus, retargeting of plasma membrane repair factors enhances the pro-oncogenic activities of the lysosome. Gupta et al. show that the membrane repair factor Myoferlin protects against membrane damage of pancreatic cancer lysosomes to sustain enhanced lysosomal function and promote tumour growth.

Pancreatic ductal adenocarcinoma (PDA) is a heterogeneous disease comprised of a basal-like subtype with mesenchymal gene signatures, undifferentiated histopathology and worse prognosis compared to the classical subtype. Despite their prognostic and therapeutic value, the key drivers that establish and control subtype identity remain unknown. Here, we demonstrate that PDA subtypes are not permanently encoded, and identify the GLI2 transcription factor as a master regulator of subtype inter-conversion. GLI2 is elevated in basal-like PDA lines and patient specimens, and forced GLI2 activation is sufficient to convert classical PDA cells to basal-like. Mechanistically, GLI2 upregulates expression of the pro-tumorigenic secreted protein, Osteopontin (OPN), which is especially critical for metastatic growth in vivo and adaptation to oncogenic KRAS ablation. Accordingly, elevated GLI2 and OPN levels predict shortened overall survival of PDA patients. Thus, the GLI2-OPN circuit is a driver of PDA cell plasticity that establishes and maintains an aggressive variant of this disease.

Abstract Lysosomes must maintain integrity of their limiting membrane to ensure efficient fusion with incoming organelles and degradation of substrates within their lumen. Pancreatic cancer cells upregulate lysosomal biogenesis to enhance nutrient recycling and stress resistance, but whether dedicated programs for maintaining lysosomal membrane integrity facilitate pancreatic cancer growth is unknown. Using proteomic-based organelle profiling, we identify the Ferlin family plasma membrane repair factor, Myoferlin, as selectively and highly enriched on the membrane of pancreatic cancer lysosomes. Mechanistically, lysosome localization of Myoferlin is necessary and sufficient for maintenance of lysosome health and provides an early-acting protective system against membrane damage that is independent from the endosomal sorting complex required for transport (ESCRT)-mediated repair network. Myoferlin is upregulated in human pancreatic cancer, predicts poor survival, and its ablation severely impairs lysosome function and tumour growth in vivo. Thus, retargeting of plasma membrane repair factors enhances pro-oncogenic activities of the lysosome. Competing Interest Statement The authors have declared no competing interest.

This study examined the growth patterns of the spotted catfish, Arius maculatus (Thunberg, 1792) in the Thanlwin River Estuary throughout the analysis of standard lengths obtained from observed otolith data and back‐calculated data. Between April 2023 and January 2024, 516 fish ranging in standard lengths from 8.3 to 33 cm were collected. The annual deposition of annuli in otoliths was confirmed using the marginal increment ratio, with ages ranging from 2 to 9 years. The Dahl‐Lea back‐calculation method expanded the length at age data to 2472 records for ages 1–9 years. Growth was characterized using Von Bertalanffy growth curves, revealing the significant differences between the observed data (asymptotic length L∞ = 25.34 cm, growth coefficient K = 0.257 year−1 and growth performance index ϕ′ = 2.02) and the back‐calculated data (L∞ = 36.23 cm, K = 0.087 year−1 and ϕ′ = 2.21). The findings of the study suggested that the back‐calculated otolith data were more dependable for determining growth parameters compared to the observed otolith data. A. maculatus appears to exhibit slow growth characteristics, suggesting that the environmental conditions in the Thanlwin River Estuary may be deficient for this species. The insights gleaned from this research are crucial for guiding and shaping fishery management policies through informed advice and recommendations. The annual rings of otolith was verified by the marginal increment ratio. The sample ranged in age from 2 to 9 years old. Back‐calculated length of this species were evaluated and the results are more reliable than the observed length to estimate the growth parameters in the study. All in all, the species grows fairly slowly in research area.

Objective This study aims to estimate the cost of clinical management of COVID-19 infected patients based on their severity by exploring the resources used in health care provision in Myanmar. Methods A multicenter retrospective cost analysis of COVID-19 patients was performed using the micro-costing approach from the perspective of the health system. It covered two cost components, namely direct and indirect cost of treating a patient. Input data and their quantities were obtained from COVID-19 Standard Treatment Guidelines of Ministry of Health and Sports, and administrative and financial records of resource utilization of three designated health facilities in Yangon Region. Valuation of these resources was based on the price list from the Procurement Section of the Ministry. Results This study estimated the unit cost of clinical management of COVID-19 infected patients with no symptom to be 953,552 MMK(717 USD) , with mild-moderate symptoms to be 1,155,222 MMK(869 USD) and with severe-critically ill conditions to be 5,705,052 MMK(4290 USD) . Average cost for a patient par day was 86,687 MMK(65 USD) for asymptomatic patients, 105,020 MMK(79 USD) for mild-moderate patients and 283,252 MMK(214 USD) for severe-critically ill patients. Since the first case detected till December 31, 2020, COVID-19 clinical management cost was accounted for 139 Billion MMK (104 Million USD) for total 124,630 confirmed cases. Conclusions COVID-19 pandemic has caused health systems to incur the significant health care expenses. Timely implementation of the sustainable, affordable and efficient policy for COVID-19 responses is of utmost important for every nation especially in the face of a pandemic. This study provides the fundamental inputs for strategic planning, for future economic evaluations of different policy interventions, and policy recommendations for health systems to remain resilient during and after the COVID-19 pandemic in Myanmar.

Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting. To understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not differ significantly among virus serotypes, infection status (primary versus secondary) and disease severity. Based on the phylogenetic analysis, we identified DENV-1 genotype-1, DENV-4 genotype-1 and DENV-3 genotype-3 and genotype-1 which was detected for the first time. Next-generation sequencing analysis revealed greater frequencies of nonsynonymous and synonymous mutations per gene in the nonstructural genes. Moreover, mutation rates were also higher among DENV-1. In conclusion, there was an increasing trend of DENV-3 cases during DENV endemic season in 2018 with the first detection of the genotype 1. However, DENV-1 has remained the predominant serotype in this study area since 2013, and we identified stop codon mutations in the DENV-1 genome. This report is the first to feature a complete genome analysis of the strains of DENV-3 and DENV-4 circulating among pediatric patients in Myanmar. This study highlighted the importance of annual surveillance for a better understanding of the molecular epidemiology of DENVs.

The two neighboring late prehistoric/protohistoric sites of Aw Gyi and Maliwan, located in the southernmost part of Myanmar in the Isthmus of Kra, yielded large quantities of glass beads and wastes. The measurement of 61 glass compositions from these sites using laser ablation-inductively coupled plasma-mass spectrometry has revealed two different patterns. At Aw Gyi, a combination of potash and m-Na-Ca-Al glasses, also noticed at Arikamedu, India (1st c. BC and onward), and Phu Khao Thong, Thailand (2nd c. BC–4th c. AD), two ports facing the Bay of Bengal, suggests the existence of a “Bay of Bengal” network, active from the 2nd–1st c. BC. At Maliwan, the glass types are more diversified with some of them found generally during the 4th to 2nd c. BC period. This is in line with the radiocarbon dating of the site that shows an occupation from the 4th to the 1st c. BC. However, Maliwan has little in common in terms of glass typology with other early and contemporary sites along the Isthmus of Kra indicating that they were not part of the same network. At Aw Gyi and Maliwan, evidence would suggest bead making, but the craft areas where such an activity would have taken place remains to be found. Despite this caveat, the difference in glass composition and typology between these close-by sites draws perhaps a more complex economic and political situation than expected with different networks at early periods on the east and west side of the Isthmus of Kra.

Background Amputation is still the most common therapy for patients suffering from osteosarcoma in Myanmar, despite the fact that limb salvage surgery e.g. Borggreve–Van Nes-Winkelmann rotationplasty for malignant tumors located within the distal femur or proximal tibia is the current state-of-the-art reconstructive procedure. A safe and reliable operation technique is crucial in order to perform a complex surgical procedure like the rotationplasty in lower-middle income economies with limited infrastructure and resources. The authors present seven cases of patients with osteosarcomas that received a Borggreve–Van Nes-Winkelmann rotationplasty with an evaluation of the procedures focusing on safety and sustainability. Methods From 2019 until 2020, seven young patients with osteosarcomas of the distal femur or proximal tibia were treated with Borggreve–Van Nes-Winkelmann rotationplasties in the Orthopaedic Hospital in Mandalay, Myanmar. As modification of the standard procedure the dissection and subsequent clamping of the femoral artery in order to minimize blood loss as well as the formation of an adipocutaneous flap that minimizes swelling and decreases the pressure on the vessels were successfully performed. This modified procedure resembles a safe and simplified surgical technique that is feasible under the circumstances of lower-middle income economies with good outcomes. Results All patients showed good functional and aesthetic results. One of the seven patients needed secondary wound closure due to wound dehiscence. Conclusions A simplified and safe operation technique for the performance of the Van Nes-Borggreve rotationplasty was adapted to the given constraints in lower-middle income economies and proved to be successful. Trial registration All patients approved to participate in the study and have given consent to publication.

The community-based MDR-TB care (CBMDR-TBC) project was implemented in 2015 by The Union in collaboration with national TB programme (NTP) in 33 townships of upper Myanmar to improve treatment outcomes among patients with MDR-TB registered under NTP. They received community-based support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each project township had a project nurse exclusively for MDR-TB and a community volunteer who provided evening directly observed therapy (in addition to morning directly observed therapy by NTP). To determine the effect of CBMDR-TBC project on death and unfavourable outcomes during the intensive phase of MDR-TB treatment. In this cohort study involving record review, all patients diagnosed with MDR-TB between January 2015 and June 2016 in project townships and initiated on treatment till 31 Dec 2016 were included. CBMDR-TBC status was categorized as \"receiving support\" if project initiation in patient's township was before treatment initiation, \"receiving partial support\" if project initiation was after treatment initiation, and \"not receiving support\" if project initiation was after intensive phase treatment outcome declaration. Time to event analysis (censored on 10 April 2017) and cox regression was done. Of 261 patients initiated on treatment, death and unfavourable outcomes were accounted for 13% and 21% among \"receiving support (n = 163)\", 3% and 24% among \"receiving partial support (n = 75)\" and 13% and 26% among \"not receiving support (n = 23)\" respectively. After adjusting for other potential confounders, the association between CBMDR-TBC and unfavourable outcomes was not statistically significant. However, when compared to \"not receiving support\", those \"receiving support\" and \"receiving partial support\" had 20% [aHR (0.95 CI: 0.8 (0.2-3.1)] and 90% lower hazard [aHR (0.95 CI: 0.1 (0.02-0.9)] of death, respectively. This was intriguing. Implementation of CBMDR-TBC coincided with implementation of decentralized MDR-TB centers at district level. Hence, patients that would have generally not accessed MDR-TB treatment before decentralization also started receiving treatment and were also included under CBMDR-TBC \"received support\" group. These patients could possibly be expected to sicker at treatment initiation than patients in other CBMDR-TBC groups. This could be the possible reason for nullifying the effect of CBMDR-TBC in \"receiving support\" group and therefore similar survival was found when compared to \"not receiving support\". CBMDR-TBC may prevent early deaths and has a scope for expansion to other townships of Myanmar and implications for NTPs globally. However, future studies should consider including data on extent of sickness at treatment initiation and patient level support received under CBMDR-TBC.

This article presents the results of the first excavations at Maliwan and Maliwan, the earliest port-settlements from southern Myanmar in the Isthmus of Kra, showing their involvement in extensive networks as far as the West and China during the last centuries BC.