Medicine, Research & Experimental

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Article Biochemistry & Molecular Biology

Heterologous AD5-nCOV plus CoronaVac versus homologous CoronaVac vaccination: a randomized phase 4 trial

Jingxin Li, Lihua Hou, Xiling Guo, Pengfei Jin, Shipo Wu, Jiahong Zhu, Hongxing Pan, Xue Wang, Zhizhou Song, Jingxuan Wan, Lunbiao Cui, Junqiang Li, Yin Chen, Xuewen Wang, Lairun Jin, Jingxian Liu, Fengjuan Shi, Xiaoyu Xu, Tao Zhu, Wei Chen, Fengcai Zhu

Summary: The study suggests that additional COVID-19 vaccine doses may be needed for individuals who initially received CoronaVac. Heterologous boosting with Convidecia, a recombinant adenovirus type 5 (AD5)-vectored vaccine, was found to be safe and more immunogenic than homologous boosting with CoronaVac in adults previously vaccinated with CoronaVac.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Intratumoral oncolytic herpes virus G47 increment for residual or recurrent glioblastoma: a phase 2 trial

Tomoki Todo, Hirotaka Ito, Yasushi Ino, Hiroshi Ohtsu, Yasunori Ota, Junji Shibahara, Minoru Tanaka

Summary: A crucial clinical trial demonstrates that repeated tumor-administration of oncolytic herpes virus G47 Increment in residual or recurrent glioblastoma leads to improved survival rates and a safe profile.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Performance of plasma phosphorylated tau 181 and 217 in the community

Michelle M. Mielke, Jeffrey L. Dage, Ryan D. Frank, Alicia Algeciras-Schimnich, David S. Knopman, Val J. Lowe, Guojun Bu, Prashanthi Vemuri, Jonathan Graff-Radford, Clifford R. Jack, Ronald C. Petersen

Summary: Plasma phosphorylated tau 181 (P-tau181) and 217 (P-tau217) can predict abnormal amyloid and tau pathology in community-based populations, but their predictive abilities vary across different brain regions, and are influenced by multiple comorbidities.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial

Sattva S. Neelapu, Michael Dickinson, Javier Munoz, Matthew L. Ulrickson, Catherine Thieblemont, Olalekan O. Oluwole, Alex F. Herrera, Chaitra S. Ujjani, Yi Lin, Peter A. Riedell, Natasha Kekre, Sven de Vos, Christine Lui, Francesca Milletti, Jinghui Dong, Hairong Xu, Julio C. Chavez

Summary: In a phase 2 trial, axicabtagene ciloleucel demonstrated high complete response rate and manageable safety profile as first-line treatment for high-risk large B-cell lymphoma.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial

John A. Spertus, Mary C. Birmingham, Michael Nassif, C. Damaraju, Antonio Abbate, Javed Butler, David E. Lanfear, Ildiko Lingvay, Mikhail N. Kosiborod, James L. Januzzi

Summary: Large traditional clinical trials have shown that sodium-glucose co-transporter 2 inhibitors can improve symptoms in heart failure patients. In a new trial conducted remotely (CHIEF-HF trial), canagliflozin was found to significantly improve symptoms in heart failure patients, regardless of ejection fraction or diabetes status.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

Sarthak Sinha, Nicole L. Rosin, Rohit Arora, Elodie Labit, Arzina Jaffer, Leslie Cao, Raquel Farias, Angela P. Nguyen, Luiz G. N. de Almeida, Antoine Dufour, Amy Bromley, Braedon McDonald, Mark R. Gillrie, Marvin J. Fritzler, Bryan G. Yipp, Jeff Biernaskie

Summary: New findings illuminate the molecular mechanisms of dexamethasone action in severe COVID-19 patients, highlighting the expansion of distinct neutrophil states and altered immune dynamics. These results pave the way for the development of targeted immunotherapies for severe COVID-19 by defining COVID-19-enriched neutrophil states and the molecular mechanisms of dexamethasone action.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER

Pardeep S. Jhund, Toru Kondo, Jawad H. Butt, Kieran F. Docherty, Brian L. Claggett, Akshay S. Desai, Muthiah Vaduganathan, Samvel B. Gasparyan, Olof Bengtsson, Daniel Lindholm, Magnus Petersson, Anna Maria Langkilde, Rudolf A. de Boer, David DeMets, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Lars Kober, Carolyn S. P. Lam, Felipe A. Martinez, Marc S. Sabatine, Sanjiv J. Shah, Scott D. Solomon, John J. V. McMurray

Summary: A patient-level pooled meta-analysis of two trials showed that the sodium-glucose cotransporter 2 inhibitor dapagliflozin can reduce the risk of cardiovascular-associated deaths and hospital admissions for heart failure in patients with heart failure, regardless of ejection fraction.

NATURE MEDICINE (2022)

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Review Medicine, Research & Experimental

mRNA Vaccines in the COVID-19 Pandemic and Beyond

Michael J. Hogan, Norbert Pardi

Summary: This review provides a detailed overview of the development of mRNA vaccines for SARS-CoV-2, discusses and compares preclinical and clinical data, gives a mechanistic overview of immune responses generated by mRNA vaccination, and speculates on the challenges and promising future of this emergent vaccine platform.

ANNUAL REVIEW OF MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge

Wouter Bulten, Kimmo Kartasalo, Po-Hsuan Cameron Chen, Peter Strom, Hans Pinckaers, Kunal Nagpal, Yuannan Cai, David F. Steiner, Hester van Boven, Robert Vink, Christina Hulsbergen-van de Kaa, Jeroen van der Laak, Mahul B. Amin, Andrew J. Evans, Theodorus van der Kwast, Robert Allan, Peter A. Humphrey, Henrik Gronberg, Hemamali Samaratunga, Brett Delahunt, Toyonori Tsuzuki, Tomi Hakkinen, Lars Egevad, Maggie Demkin, Sohier Dane, Fraser Tan, Masi Valkonen, Greg S. Corrado, Lily Peng, Craig H. Mermel, Pekka Ruusuvuori, Geert Litjens, Martin Eklund

Summary: The PANDA challenge is the largest histopathology competition to date, aiming to catalyze the development of reproducible AI algorithms for Gleason grading in prostate cancer. The submitted algorithms achieved pathologist-level performance and their diversity and generalization were validated through cross-continental cohorts.

NATURE MEDICINE (2022)

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Review Medicine, Research & Experimental

Blood-based biomarkers for Alzheimer's disease

Antoine Leuzy, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Shorena Janelidze, Jeffrey L. Dage, Oskar Hansson

Summary: Blood-based biomarkers are playing an increasing role in the diagnosis and research of neurodegenerative disorders like Alzheimer's disease. Biomarkers such as plasma P-tau and NfL show promising potential for detection and monitoring of these diseases.

EMBO MOLECULAR MEDICINE (2022)

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Review Nanoscience & Nanotechnology

Strategies for sustained drug release from electrospun multi-layer nanostructures

Deng-Guang Yu, Menglong Wang, Ruiliang Ge

Summary: This review discusses the history and trends of the combination of electrospinning technology and sustained drug release (SDR), introducing 15 strategies for providing SDR profiles through multi-chamber core-shell nanostructures. Electrospun multi-chamber nanostructures are considered to be helpful in promoting the development of sustained drug release formulations.

WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY (2022)

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Article Medical Laboratory Technology

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury

David A. Schwartz, Elyzabeth Avvad-Portari, Pavel Babal, Marcella Baldewijns, Marie Blomberg, Amine Bouachba, Jessica Camacho, Sophie Collardeau-Frachon, Arthur Colson, Isabelle Dehaene, Joan Carles Ferreres, Brendan Fitzgerald, Marta Garrido-Pontnou, Hazem Gergis, Beata Hargitai, A. Cecilia Helguera-Repetto, Sandra Holmstrom, Claudine Liliane Irles, Asa Leijonhfvud, Sasha Libbrecht, Tamas Marton, Noel McEntagart, James T. Molina, Raffaella Morotti, Alfons Nadal, Alexandra Navarro, Maria Nelander, Angelica Oviedo, Andre Ricardo Oyamada Otani, Nikos Papadogiannakis, Astrid C. Petersen, Drucilla J. Roberts, Ali G. Saad, Anna Sand, Sam Schoenmakers, Jennifer K. Sehn, Preston R. Simpson, Kristen Thomas, M. Yolotzin Valdespino-Vazquez, Lotte E. van der Meeren, Jo Van Dorpe, Robert M. Verdijk, Jaclyn C. Watkins, Mehreen Zaigham

Summary: This study evaluated the mechanism of stillbirth and neonatal death following maternal infection with COVID-19. The findings suggest that placental abnormalities caused by SARS-CoV-2 infection result in placental malperfusion and insufficiency, leading to fetal hypoxic-ischemic injury and perinatal death.

ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE (2022)

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Review Medicine, Research & Experimental

Recent advances in nanomedicines for photodynamic therapy (PDT)-driven cancer immunotherapy

Bin Ji, Minjie Wei, Bin Yang

Summary: Cancer immunotherapy has shown great progress in advanced-stage malignancies, but low response rates and immunosuppressive tumor microenvironments limit its effectiveness. Photodynamic therapy (PDT) can induce immunogenic cell death and enhance immune responses. Recent nanomedicine-based strategies have improved the efficiency of PDT and immunotherapy, and synergistic nanotherapeutics have been used to amplify immune responses. Challenges and future expectations in PDT-driven cancer immunotherapy are discussed.

THERANOSTICS (2022)

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Article Biochemistry & Molecular Biology

Delivering precision oncology to patients with cancer

Joaquin Mateo, Lotte Steuten, Philippe Aftimos, Fabrice Andre, Mark Davies, Elena Garralda, Jan Geissler, Don Husereau, Iciar Martinez-Lopez, Nicola Normanno, Jorge S. Reis-Filho, Stephen Stefani, David M. Thomas, C. Benedikt Westphalen, Emile Voest

Summary: Precision medicine is reshaping cancer care, but accessibility to all patients remains a challenge. This Perspective highlights the importance of addressing the challenges in implementing precision oncology, including equal access to genomics tests, robust evidence for new drugs and technologies, interpretation of genomics data by physicians, and empowering patients in shared decision-making.

NATURE MEDICINE (2022)

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Article Immunology

Global COVID-19 Vaccine Acceptance: A Systematic Review of Associated Social and Behavioral Factors

Choudhary Sobhan Shakeel, Amenah Abdul Mujeeb, Muhammad Shaheer Mirza, Beenish Chaudhry, Saad Jawaid Khan

Summary: This systematic review examined COVID-19 vaccine acceptance and hesitancy rates across different countries and continents. The analysis of 81 peer-reviewed publications showed global variations in vaccine acceptance, with the highest rates found in Ecuador, Malaysia, and Indonesia, and the lowest rates in Lebanon. Healthcare workers in China and nurses in Italy had the highest acceptance rates, while healthcare workers in the Democratic Republic of Congo had the lowest acceptance. The reasons behind vaccine hesitancy and acceptance were found to be similar across different regions, including low levels of education and awareness, inefficient government efforts, and misinformation on social media.

VACCINES (2022)

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Article Biochemistry & Molecular Biology

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial

Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Angelika Martina Starzer, Heidrun Forstner, Beate Rottenmanner, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegul Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Christian F. Singer, Ansgar Weltermann, Rainer Puhr, Matthias Preusser

Summary: The TUXEDO-1 trial demonstrates the efficacy of trastuzumab deruxtecan, an antibody-drug conjugate, in treating brain metastases in patients with HER2-positive breast cancer. The study showed a high intracranial response rate and maintained quality of life and cognitive functioning in the patients.

NATURE MEDICINE (2022)

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Review Biochemistry & Molecular Biology

Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis

Ioannis P. Trougakos, Evangelos Terpos, Harry Alexopoulos, Marianna Politou, Dimitrios Paraskevis, Andreas Scorilas, Efstathios Kastritis, Evangelos Andreakos, Meletios A. Dimopoulos

Summary: Vaccination is crucial in controlling the COVID-19 pandemic, and mRNA vaccines are particularly effective. However, adverse effects following vaccination have been observed, which may be related to the vaccine formulation and the inflammatory effects of the antigens produced. It is important to conduct further research on the cellular and molecular basis of these adverse effects to ensure vaccine safety.

TRENDS IN MOLECULAR MEDICINE (2022)

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Article Cell Biology

A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection

Panpan Zhou, Meng Yuan, Ge Song, Nathan Beutler, Namir Shaabani, Deli Huang, Wan-Ting He, Xueyong Zhu, Sean Callaghan, Peter Yong, Fabio Anzanello, Linghang Peng, James Ricketts, Mara Parren, Elijah Garcia, Stephen A. Rawlings, Davey M. Smith, David Nemazee, John R. Teijaro, Thomas F. Rogers, Ian A. Wilson, Dennis R. Burton, Raiees Andrabi

Summary: This study describes a broadly neutralizing antibody CC40.8 that targets the spike fusion machinery of coronaviruses and demonstrates its protective efficacy against SARS-CoV-2 in animal models, indicating its potential for the development of pan-coronavirus vaccines.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Medicine, General & Internal

Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies

Takuya Tada, Hao Zhou, Belinda M. Dcosta, Marie I. Samanovic, Vidya Chivukula, Ramin S. Herati, Stevan R. Hubbard, Mark J. Mulligan, Nathaniel R. Landau

Summary: This study found that the Omicron variant has significantly reduced sensitivity to neutralization by vaccines and vaccine-elicited antibodies. However, a booster immunization can enhance the neutralizing effect against Omicron. In addition, individuals with a history of prior SARS-CoV-2 infection showed increased neutralizing activity against Omicron. Different monoclonal antibodies showed varying effectiveness against the Omicron variant.

EBIOMEDICINE (2022)

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Article Biochemistry & Molecular Biology

Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis

Vladislav A. Korobeynikov, Alexander K. Lyashchenko, Beatriz Blanco-Redondo, Paymaan Jafar-Nejad, Neil A. Shneider

Summary: This study demonstrates that an antisense oligonucleotide can effectively lower the levels of FUS protein in mice and in a patient with FUS-dependent ALS. The research provides evidence that the insolubility of FUS and related RNA-binding proteins contribute to neurodegeneration in ALS-FTD. Silencing FUS using a non-allele-specific antisense oligonucleotide delays motor neuron degeneration in a disease-relevant mouse model and reduces the burden of FUS aggregates in ALS patients.

NATURE MEDICINE (2022)

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