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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study—a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed. Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14–28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00–0·48]) compared with infection with wild-type virus only. The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines. National Medical Research Council Singapore.

An antibiotic biosynthesis monooxygenase (Abm) has been identified in the rice blast fungus Magnaporthe oryzae that converts jasmonic acid into hydroxylated JA, which contributes to pathogenicity through the evasion of host immune response. Distinct modifications fine-tune the activity of jasmonic acid (JA) in regulating plant growth and immunity. Hydroxylated JA (12OH-JA) promotes flower and tuber development but prevents induction of JA signaling, plant defense or both. However, biosynthesis of 12OH-JA has remained elusive. We report here an antibiotic biosynthesis monooxygenase (Abm) that converts endogenous free JA into 12OH-JA in the model rice blast fungus Magnaporthe oryzae . Such fungal 12OH-JA is secreted during host penetration and helps evade the defense response. Loss of Abm in M. oryzae led to accumulation of methyl JA (MeJA), which induces host defense and blocks invasive growth. Exogenously added 12OH-JA markedly attenuated abm Δ-induced immunity in rice. Notably, Abm itself is secreted after invasion and most likely converts plant JA into 12OH-JA to facilitate host colonization. This study sheds light on the chemical arms race during plant-pathogen interaction, reveals Abm as an antifungal target and outlines a synthetic strategy for transformation of a versatile small-molecule phytohormone.

Background Species within the genus Dibothriocephalus / Diphyllobothrium are notable for being among the largest cestodes capable of human infection. Historically, Dibothriocephalus latus (previously Diphyllobothrium latus ) is considered the more prevalent species (in Europe and Patagonia). However, Dibothriocephalus nihonkaiensis (previously Diphyllobothrium nihonkaiensis ) is commonly found in East Asian countries, particularly Japan, where diets frequently include raw salmons. The increasing globalization and adoption of diverse dietary practices have led to the detection of tapeworm infections like D. nihonkaiensis outside their traditionally endemic areas, potentially making them more common than previously thought, as exemplified by the present case in Singapore. Case presentation A 35-year-old Chinese female presented with chronic abdominal distension, loose stools and unintentional weight loss. 3 months prior to her symptom onset, she had travelled extensively throughout Asia (Thailand, Vietnam, Laos, Malaysia and China) and Mexico and had consumed raw salmon throughout her travels. A full blood count revealed eosinophilia, and a worm was passed during bowel preparation. Molecular sequencing identified it as D. nihonkaiensis . She was treated successfully with praziquantel. Conclusion Increased globalization, cross-cultural dietary exchange, and greater salmon consumption have expanded the geographic distribution of D. nihonkaiensis infections beyond previously endemic regions. Consequently, clinicians worldwide must maintain a high index of suspicion for this parasitic infection, even in non-endemic areas. A thorough patient history, with particular attention to dietary habits and travel, is paramount for accurate and timely diagnosis, thereby enabling appropriate treatment and preventing potential complications. Increased awareness, reporting, and molecular identification of Dibothriocephalus are crucial for determining infection sources and guiding food safety surveillance.

Abstract Background The performance of real-time reverse transcription polymerase chain reaction (rRT-PCR) for SARS-CoV-2 varies with sampling site(s), illness stage, and infection site. Methods Unilateral nasopharyngeal, nasal midturbinate, throat swabs, and saliva were simultaneously sampled for SARS-CoV-2 rRT-PCR from suspected or confirmed cases of COVID-19. True positives were defined as patients with at least 1 SARS-CoV-2 detected by rRT-PCR from any site on the evaluation day or at any time point thereafter, until discharge. Diagnostic performance was assessed and extrapolated for site combinations. Results We evaluated 105 patients; 73 had active SARS-CoV-2 infection. Overall, nasopharyngeal specimens had the highest clinical sensitivity at 85%, followed by throat, 80%, midturbinate, 62%, and saliva, 38%–52%. Clinical sensitivity for nasopharyngeal, throat, midturbinate, and saliva was 95%, 88%, 72%, and 44%–56%, respectively, if taken ≤7 days from onset of illness, and 70%, 67%, 47%, 28%–44% if >7 days of illness. Comparing patients with upper respiratory tract infection (URTI) vs pneumonia, clinical sensitivity for nasopharyngeal, throat, midturbinate, and saliva was 92% vs 70%, 88% vs 61%, 70% vs 44%, 43%–54% vs 26%–45%, respectively. A combination of nasopharyngeal plus throat or midturbinate plus throat specimen afforded overall clinical sensitivities of 89%–92%; this rose to 96% for persons with URTI and 98% for persons ≤7 days from illness onset. Conclusions Nasopharyngeal specimens, followed by throat specimens, offer the highest clinical sensitivity for COVID-19 diagnosis in early illness. Clinical sensitivity improves and is similar when either midturbinate or nasopharyngeal specimens are combined with throat specimens. Upper respiratory specimens perform poorly if taken after the first week of illness or if there is pneumonia.

Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness ( p  = 0.01, χ 2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2. Here, the authors sample air and surfaces in hospital rooms of COVID-19 patients, detect SARS-CoV-2 RNA in air samples of two of three tested airborne infection isolation rooms, and find surface contamination in 66.7% of tested rooms during the first week of illness and 20% beyond the first week of illness.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are used to treat BRCA-mutated (BRCAm) cancer patients; however, resistance has been observed. Therefore, biomarkers to indicate PARPi resistance and combination therapy to overcome that are urgently needed. We identified a high prevalence of activated FGF receptor 3 (FGFR3) in BRCAm triple-negative breast cancer (TNBC) cells with intrinsic and acquired PARPi resistance. FGFR3 phosphorylated PARP1 at tyrosine 158 (Y158) to recruit BRG1 and prolong chromatin-loaded MRE11, thus promoting homologous recombination (HR) to enhance PARPi resistance. FGFR inhibition prolonged PARP trapping and synergized with PARPi in vitro and in vivo. High-level PARP1 Y158 phosphorylation (p-Y158) positively correlated with PARPi resistance in TNBC patient-derived xenograft models, and in PARPi-resistant TNBC patient tumors. These findings reveal that PARP1 p-Y158 facilitates BRG1-mediated HR to resolve the PARP-DNA complex, and PARP1 p-Y158 may indicate PARPi resistance that can be relieved by combining FGFR inhibitors (FGFRis) with PARPis. In summary, we show that FGFRi restores PARP trapping and PARPi antitumor efficacy in PARPi-resistant breast cancer by decreasing HR through the PARP1 p-Y158/BRG1/MER11 axis, suggesting that PARP1 p-Y158 is a biomarker for PARPi resistance that can be overcome by combining FGFRis with PARPis.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are used to treat BRCA-mutated (BRCAm) cancer patients; however, resistance has been observed. Therefore, biomarkers to indicate PARPi resistance and combination therapy to overcome that are urgently needed. We identified a high prevalence of activated FGF receptor 3 (FGFR3) in BRCAm triple-negative breast cancer (TNBC) cells with intrinsic and acquired PARPi resistance. FGFR3 phosphorylated PARP1 at tyrosine 158 (Y158) to recruit BRG1 and prolong chromatin-loaded MRE11, thus promoting homologous recombination (HR) to enhance PARPi resistance. FGFR inhibition prolonged PARP trapping and synergized with PARPi in vitro and in vivo. High-level PARP1 Y158 phosphorylation (p-Y158) positively correlated with PARPi resistance in TNBC patient-derived xenograft models, and in PARPi-resistant TNBC patient tumors. These findings reveal that PARP1 p-Y158 facilitates BRG1-mediated HR to resolve the PARP-DNA complex, and PARP1 p-Y158 may indicate PARPi resistance that can be relieved by combining FGFR inhibitors (FGFRis) with PARPis. In summary, we show that FGFRi restores PARP trapping and PARPi antitumor efficacy in PARPi- resistant breast cancer by decreasing HR through the PARP1 p-Y158/BRG1/MER11 axis, suggesting that PARP1 p-Y158 is a biomarker for PARPi resistance that can be overcome by combining FGFRis with PARPis.