Peptide P2 targeting Vibrio parahaemolyticus PirB toxins blocks the cytotoxic effects to shrimp Litopenaeus vannamei by Xin Zhang, Ting Chen, Chunhua Ren, Yanhong Wang, Xiao Jiang, Jiasheng Huang, Bo Ma, Boxiang Zhu, Jiayue Yin, Chaoqun Hu, Peng Luo

“…PirB is the main virulence factor of acute hepatopancreatic necrosis disease (AHPND) which induced the sloughing of hepatopancreatic cells and shrimp death. In addition, Litopenaeus vannamei aminopeptidase N (Lv-APN) is reported to be a functional receptor that mediates the pathogenicity by VpAHPND. …”
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Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections by Emily Lydon, Christina M. Osborne, Brandie D. Wagner, Lilliam Ambroggio, J. Kirk Harris, Ron Reeder, Todd C. Carpenter, Aline B. Maddux, Matthew K. Leroue, Nadir Yehya, Joseph L. DeRisi, Mark W. Hall, Athena F. Zuppa, Joseph Carcillo, Kathleen Meert, Anil Sapru, Murray M. Pollack, Patrick McQuillen, Daniel A. Notterman, Charles R. Langelier, Peter M. Mourani

“…ABSTRACT Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. …”
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Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors by Alfred Zippelius, Petra Herzig, Pratiksha Gulati, Christian Klein, Marta Trüb, Kirsten D Mertz, Robert Rosenberg, Viola Heinzelmann-Schwarz, Mark Wiese, Didier Lardinois, Pablo Umana, Marina Natoli, Klas Hatje, Fabian Junker, Zhiwen Jiang, Iakov I Davydov, Markus Germann, Daniel Marbach, Adrian Zwick, Patrick Weber, Stefan Seeber, Lothar Tietze, Laura Codarri-Deak, Henry Kao

“…Similarly, little is known on the differential effects of dual, compared with single, checkpoint inhibition.Methods We here performed in-depth characterization, including multicolor flow cytometry, single cell RNA sequencing and multiplex supernatant analysis, using tumor single cell suspensions from patients with cancer treated ex vivo with novel bispecific antibodies targeting programmed cell death protein 1 (PD-1) and TIM-3 (PD1-TIM3), PD-1 and LAG-3 (PD1-LAG3), or with anti-PD-1.Results We identified patient samples which were responsive to PD1-TIM3, PD1-LAG3 or anti-PD-1 using an in vitro approach, validated by the analysis of 659 soluble proteins and enrichment for an anti-PD-1 responder signature. …”
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IFNβ drives ferroptosis through elevating TRIM22 and promotes the cytotoxicity of RSL3 by Huiyue Dong, Huiyue Dong, Ling Zhu, Ling Zhu, Jingjing Sun, Jingjing Sun, Qiuyan Chen, Qiuyan Chen, Pengyang Liu, Pengyang Liu, Wei Zhang, Huajing Zeng, Rong Lin, Rong Lin, Zongyang Yu, Zongyang Yu, Jun Lu, Jun Lu, Jun Lu, Jun Lu

“…The production of this pathway, interferon-β (IFNβ), could suppress the growth of tumor cells, yet it is unclear whether ferroptosis is involved in IFNβ-induced cell death.MethodsThe effects of IFNβ on ferroptosis were analyzed in HT1080, 4T1, HCT116 and 786-O cells. …”
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Noninvasive respiratory support following extubation in critically ill adults with obesity: a systematic review and network meta-analysisResearch in context by Joris Pensier, Arthur Naudet-Lasserre, Clément Monet, Mathieu Capdevila, Yassir Aarab, Inès Lakbar, Gérald Chanques, Nicolas Molinari, Audrey De Jong, Samir Jaber

“…The number needed to treat with NIV or NIV + HFNC to avoid one death was 15. These findings support the application of NIV to mitigate extubation failure in critically ill adults with obesity. …”
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Editorial by Jörg Tremmel, Markus Rutsche

“…All experts agree: If mankind had failed to develop vaccines against SARS-CoV-2, the death toll would have been much higher. This issue seeks to explore what could be described as a “generational approach to vaccinations”. …”
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Defining neonatal status epilepticus: A scoping review from the ILAE neonatal task force by Magda L. Nunes, Elissa G. Yozawitz, Courtney J. Wusthoff, Renée A. Shellhaas, Efraín Olivas‐Peña, Jo M. Wilmshurst, Ronit M. Pressler, Chahnez C. Triki, Hans Hartmann, Terrie Inder, Geraldine B. Boylan, Kette Valente, Solomon L. Moshe, Eli M. Mizrahi, Nicholas S. Abend

“…Plain Language Summary Prolonged seizures are a neurologic emergency, if untreated, can lead to permanent injury or death. In adults and children, seizures lasting longer than 30 min are believed to cause brain damage. …”
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Treatment Inertia and Symptom Burden in Anemia of CKD: Insights from the SATISFY Survey in the Middle East, South Africa, and Türkiye by Arici M, Al-Ghamdi SMG, Assounga AG, El-Koraie AF, McMillan A, Camidge LJ, Sumarsono B, Blogg M, Ng DB, Lansang EP

“…Improved awareness of this disagreement may help facilitate physician–patient dialogue to improve patient experience.Plain Language Summary: A survey to understand the experiences of people living with anemia and kidney disease in the Middle East, South Africa, and TürkiyeBackgroundPeople living with kidney disease can have a low number of red blood cells (anemia).This can cause heart problems, make kidney disease worse, and lead to death.Not much is known about the experiences of people living with kidney disease and anemia in the Middle East, South Africa, and Türkiye.For example, what symptoms do they experience, and which treatments do they receive for their anemia?…”
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Characterisation of <i>Staphylococcus aureus</i> Strains and Their Prophages That Carry Horse-Specific Leukocidin Genes <i>lukP/Q</i> by Stefan Monecke, Sindy Burgold-Voigt, Andrea T. Feßler, Martina Krapf, Igor Loncaric, Elisabeth M. Liebler-Tenorio, Sascha D. Braun, Celia Diezel, Elke Müller, Martin Reinicke, Annett Reissig, Adriana Cabal Rosel, Werner Ruppitsch, Helmut Hotzel, Dennis Hanke, Christiane Cuny, Wolfgang Witte, Stefan Schwarz, Ralf Ehricht

“…<i>aureus</i> are bicomponent toxins that form polymeric pores in host leukocyte membranes, leading to cell death and/or triggering apoptosis. Some of these toxin genes are located on prophages and are associated with specific hosts. …”
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Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy by Yu Chen, Xuan Wang, Jie Dai, Li Zhou, Xuefeng Xia, Jun Guo, Xue Bai, Lu Si, Bixia Tang, Chuanliang Cui, Xiaoting Wei, Xinan Sheng, Siming Li, Zhihong Chi, Lili Mao, Bin Lian, Xieqiao Yan, Yan Kong, Caili Li, Xuan Gao, Lirui Tang, Linzi Sun, Zhonghui Qi, Zelong Xu

“…In this study, we retrospectively analyzed the efficacy of anti-programmed death (PD)-1 in patients with PMME and explored its molecular basis.Methods The response and survival of patients with PMME and NEMM under anti-PD-1 monotherapy were retrospectively analyzed. …”
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Modulation of myeloid and T cells in vivo by Bruton’s tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma by Li Zhang, Matthew Crocker, Lawrence Fong, Lisa M Coussens, Charles D Lopez, Shamilene Sivagnanam, Meenal Sinha, Brandon Chen, Jaqueline Marquez, Alexander Cheung, Whitney Tamaki, Jacob Stultz, Kendra Todd, Courtney Betts, Madeline J Griffith, Isabelle Solman, Eric Liu, Denise Pener, Anne Fahlman, Erin Taber, Kimberly Lerner, Brindha Rajagopalan, Clarisha Ware, Mark Bridge, Johnson Vo, Hannah Dragomanovich, Julie Sudduth-Klinger, Gina Vaccaro, Margaret Tempero

“…Monotherapy also led to a trend in increased mature CD208+dendritic cell density, increased late effector (programmed cell death protein 1 (PD-1–) eomesodermin (EOMES+)) CD8+ T-cell frequency, with a concomitantly decreased dysfunctional (PD-1+ EOMES+) CD8+ T-cell frequency. …”
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Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy by James Dooley, Bart Neyns, Elizabeth Allen, Frank Tacke, Louis Boon, Damya Laoui, Julia Katharina Schwarze, Helena Van Damme, Bruno Dombrecht, Máté Kiss, Heleen Roose, Eva Van Overmeire, Daliya Kancheva, Liesbet Martens, Aleksandar Murgaski, Pauline Madeleine Rachel Bardet, Gillian Blancke, Maude Jans, Evangelia Bolli, Maria Solange Martins, Yvon Elkrim, Kiavash Movahedi, Niels Vandamme, Sebahat Ocak, Isabelle Scheyltjens, Lars Vereecke, Frank Aboubakar Nana, Pascal Merchiers, Jo Agnes Van Ginderachter

“…The therapeutic use of these Nb-Fc fusion proteins was evaluated, either as monotherapy or as combination therapy with anti-programmed cell death protein-1 (anti-PD-1), in both the LLC-OVA and MC38 mouse models.Results We were able to discern two ti-Treg populations, one of which is characterized by the unique expression of Ccr8 in conjunction with Treg activation markers. …”
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Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084 by Sinead Delany‐Moretlwe, Brett Hanscom, Xu Guo, Clemensia Nkabiito, Patricia Mandima, Patricia Ntege Nahirya, Juliet Mpendo, Muchaneta Bhondai‐Mhuri, Nyaradzo Mgodi, Rebecca Berhanu, Jennifer Farrior, Estelle Piwowar‐Manning, Susan L. Ford, Craig W. Hendrix, Alex R. Rinehart, James F. Rooney, Adeola Adeyeye, Raphael J. Landovitz, Myron S. Cohen, Mina C. Hosseinipour, Mark A. Marzinke, the HPTN 084 Study Team

“…Pregnancy incidence, maternal adverse event (AE) incidence, pregnancy outcomes (including composite outcome of spontaneous abortion <20 weeks, intrauterine foetal death or stillbirth ≥20 weeks, premature birth <37 weeks, or small for gestational age) were assessed. …”
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Development and interpretation of a pathomics-driven ensemble model for predicting the response to immunotherapy in gastric cancer by Jing Wang, Zhe Li, Wei Wang, Md Tauhidul Islam, Xiaoyan Wang, Zhen Han, Zihan Li, Guoxin Li, Yuming Jiang, Taojun Zhang, Wenjun Xiong, Zepang Sun, Lequan Yu, Zhicheng Zhang, Xianqi Yang, Shengtian Sang, Alyssa A Guo

“…The univariate Cox regression analysis revealed that the prediction signature of pathomics-driven ensemble model was a prognostic factor for progression-free survival in patients with gastric cancer who underwent immunotherapy (p&lt;0.001, HR 0.35 (95% CI 0.24 to 0.50)), and remained an independent predictor after multivariable Cox regression adjusted for clinicopathological variables, (including sex, age, carcinoembryonic antigen, carbohydrate antigen 19-9, therapy regime, line of therapy, differentiation, location and programmed death ligand 1 (PD-L1) expression in all patients (p&lt;0.001, HR 0.34 (95% CI 0.24 to 0.50)). …”
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COVID-19 – if the cure is worse than the disease. The Italian chaos by Giuseppe FERRARI

“…More than 90% of the official deaths caused by COVID -19 are above 60s and 82% above 70s. …”

Dynamic Challenges of Active Tuberculosis: Prevalence and Risk Factors of Co-Infection in Clinical and Microbiological Characteristics at King Abdulaziz University Hospital, Jeddah... by Mokhtar JA, Attallah DM, Jiman-Fatani AA, Al-Rabia MW, Alqarni MA, Saleh BH, Amboon MM, Altorki TA, Alkuwaity KK, Abujamel T, Kaki R, Albarakati TN, Daghistani H, Ismail MA, Alharbi O, Abu ITM, Alfadil A, Ibrahem K, Mufrrih M, Sait AM

“…Effective strategies, targeted interventions, and future research are vital for reducing mortality.This study examines the stability of tuberculosis (TB) disease presentation using dynamic models among patients treated at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia.Key findings include:This is the first study to analyze TB disease stability across different demographic groups.Males, elderly individuals, cancer patients, and those with pulmonary disease or other comorbidities were found to have a higher risk of death from TB.The results emphasize the need for healthcare practices to adopt the “equilibrium state” method for hazard assessment. …”
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Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders by Jeffrey A Meyerhardt, Sunil Kumar, Jessica A Zerillo, Aparna Parikh, James M Cleary, Scott Rodig, Benjamin Schlechter, Kimmie Ng, Stephanie K Dougan, Nora Horick, Glenn J Hanna, Andrew L Coveler, Anuj K Patel, Nadine J McCleary, Douglas A Rubinson, Jeffrey W Clark, Kent Mouw, Kathleen Pfaff, Thomas A Abrams, Matthew B Yurgelun, Eliezer M Van Allen, S Jennifer Wang, Leah H Biller, Harshabad Singh, Emma L Welsh, Brandon M Huffman, Lestat R Ali, Megan T Hoffman, Katherine A Metayer, Shayla Murray, Alexandra Bird, Jennifer A Chan, Wolfram Goessling, Jeffrey S Wisch, Brendan Reardon, Robert J Mayer, Catherine Del Vecchio Fitz, Charlotte Kuperwasser

“…Background Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed.Methods This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). …”
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Oncolytic virus OH2 extends survival in patients with PD-1 pretreated melanoma: phase Ia/Ib trial results and biomarker insights by Juan Li, Xuan Wang, Li Zhou, Jun Guo, Lu Si, Bixia Tang, Chuanliang Cui, Xiaoting Wei, Xinan Sheng, Siming Li, Zhihong Chi, Lili Mao, Bin Lian, Xieqiao Yan, Yan Kong, Caili Li, Xiangyong Gu, Binlei Liu, Hui Tian, Han Hu

“…OH2 was well tolerated without serious adverse events (AEs) or deaths reported. No Grade 3 or higher treatment-related AEs occurred. …”
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Assessment of platelet-to-white blood cell ratio on short-term mortality events in patients hospitalized with acute decompensated heart failure: evidence from a cohort study from J... by Xin Huang, Xin Huang, Xin Huang, Xin Huang, Maobin Kuang, Maobin Kuang, Maobin Kuang, Maobin Kuang, Jiajun Qiu, Jiajun Qiu, Jiajun Qiu, Jiajun Qiu, Chao Wang, Chao Wang, Chao Wang, Chao Wang, Guotai Sheng, Guotai Sheng, Yang Zou, Guobo Xie

“…Based on the threshold analysis findings, patients with ADHF and a PWR below 15.88 had a significantly higher risk of death within 30 days.…”
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Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia by Mary Kay Koenig, Vincenzo Leuzzi, Riadh Gouider, Riadh Gouider, Eppie M. Yiu, Eppie M. Yiu, Barbara Pietrucha, Asbjørg Stray-Pedersen, Susan L. Perlman, Steve Wu, Trudy Burgers, Rupam Borgohain, Rukmini Mridula Kandadai, Isabelle Meyts, Giorgia Bucciol, Anaita Udwadia-Hegde, Ravi Yadav, Donna Roberts, Aaron Dane, Maureen Roden, Dirk Thye, Biljana Horn, Howard M. Lederman, William P. Whitehouse

“…Treatment-emergent adverse events (TEAE), reported in 67 (99%) out of 68 patients, were typically mild and did not cause discontinuation of treatment or death. Treatment-related TEAE were noted in 48 (71%) patients. …”
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