tbuckley/cabot-search huggingface dataset:
Early Tecovirimat Treatment for Mpox Disease Among People With HIV
Authors: Bruce Aldred, Robert H. Lyles, Jane Y. Scott, Daniel J. Gromer, Amalia Aldredge, Kimberly A. Workowski, Zanthia Wiley, Boghuma K. Titanji, Brittany Szabo, Anandi N. Sheth, Paulina A. Rebolledo, Minh Ly Nguyen, Vincent C. Marconi, Colleen F. Kelley, Sheetal Kandiah, Aley Kalapila, Jesse T. Jacob, Betsy Hall, Jonathan A. Colasanti, Emily J. Cartwright, Valeria D. Cantos
Journal: JAMA Internal Medicine (2024)

Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly PWH with low CD4+ T-cell counts or severe mpox clinical manifestations.
Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial
Authors: Maria Ubals, Patricia Nadal-Baron, Maider Arando, Ángel Rivero, Adrià Mendoza, Vicent Descalzo Jorro, Dan Ouchi, Clara Pérez-Mañá, Marlene Álvarez, Andrea Alemany, Yannick Hoyos-Mallecot, Ethan Nunley, Nicole A P Lieberman, Alexander L Greninger, Cristina Galván-Casas, Clara Suñer, Camila G-Beiras, Roger Paredes, Alicia Rodríguez-Gascón, Andrés Canut, Vicente García-Patos, Magí Farré, Michael Marks, Lorenzo Giacani, Martí Vall-Mayans, Oriol Mitjà
Journal: The Lancet Infectious Diseases (2024)

Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Immune responses following BNT162b2 XBB.1.5 vaccination in patients on haemodialysis in Germany
Authors: Anne Cossmann, Markus Hoffmann, Metodi V Stankov, Karsten Lürken, Gema Morillas Ramos, Amy Kempf, Inga Nehlmeier, Stefan Pöhlmann, Georg M N Behrens, Alexandra Dopfer-Jablonka
Journal: The Lancet Infectious Diseases (2024)
Climate finance and conflict: adaptation amid instability
Authors: Clionadh Raleigh, Andrew Linke, Sam Barrett, Elham Kazemi
Journal: The Lancet Planetary Health (2024)

Conflict and climate change might be present in the same areas and expose communities that struggle with these dual risks, but they do not co-occur in consistent or predictable ways. We question how to effectively adapt to climate change in areas experiencing violence. Conflict can make adaptation to climate change more difficult, but when local conflict patterns are better understood it is possible to introduce climate adaptation measures that are effective and responsive to the needs of the population. Further, we argue that conflict mitigation is not a climate adaptation. Even in conflict zones, the most effective climate adaptations focus on climate-centred technical solutions and poverty reduction, local governance legitimacy, and community-led efforts to cooperate in periods of climate stress. We outline some of these possibilities.
Hydrophobic surface induced pro-metastatic cancer cells for in vitro extravasation models
Authors: Minseok Lee, Seunggyu Kim, Sun Young Lee, Jin Gyeong Son, Joonha Park, Seonghyeon Park, Jemin Yeun, Tae Geol Lee, Sung Gap Im, Jessie S. Jeon
Journal: Bioactive Materials (2024)

vascularized cancer models utilizing microfluidics have emerged as a promising tool for mechanism study and drug screening. However, the lack of consideration and preparation methods for cancer cellular sources that are capable of adequately replicating the metastatic features of circulating tumor cells contributed to low relevancy with
Polyploid tubular cells: a shortcut to stress adaptation
Authors: Letizia De Chiara, Elena Lazzeri, Paola Romagnani
Journal: Kidney International (2024)

Tubular epithelial cells (TC) compose the majority of kidney parenchyma and play fundamental roles in maintaining homeostasis. Like other tissues, mostly immature TC with progenitor capabilities are able to replace TC lost during injury via clonal expansion and differentiation. In contrast, differentiated TC lack this capacity. However, as the kidney is frequently exposed to toxic injuries, evolution positively selected a response program that endows differentiated TC to maintain residual kidney function during kidney injury. Recently, we and others have described polyploidization of differentiated TC, a mechanism to augment the function of remnant TC after an injury by rapid hypertrophy. Polyploidy is a condition characterized by more than two complete sets of chromosomes. Polyploid cells often display an increased functional capacity and are generally more resilient to stress as evidenced by being conserved across many plants and eukaryote species from flies to mammals. Here, we discuss the occurrence of TC polyploidy in different contexts and conditions and how this integrates into existing concepts of kidney cell responses to injury. Collectively, we aim at stimulating the acquisition of novel knowledge in the kidney field as well as accelerating the translation of this basic response mechanism to the clinical sphere.
Clinical outcomes and management of JAK inhibitor-associated acne in patients with moderate-to-severe atopic dermatitis undergoing upadacitinib: A multicenter retrospective study
Authors: Gianluca Avallone, Luca Mastorino, Gianluca Tavoletti, Nicole Macagno, Francesca Barei, Donatella Schena, Mariateresa Rossi, Elisabetta Magnaterra, Flaminia Antonelli, Graziella Babino, Riccardo Viola, Luigi Gargiulo, Claudio Conforti, Luca Rapparini, Enzo Errichetti, Cataldo Patruno, Pasqualina Ruggiero, Gabriele Roccuzzo, Carlo A. Maronese, Giampiero Girolomoni, Massimo Gola, Andrea Chiricozzi, Anna Balato, Francesca Ambrogio, Alessandra Narcisi, Iris Zalaudek, Carlotta Gurioli, Maddalena Napolitano, Angelo V. Marzano, Caterina Foti, Antonio Costanzo, Bianca M. Piraccini, Silvia M. Ferrucci, Michela Ortoncelli, Pietro Quaglino, Simone Ribero
Journal: Journal of the American Academy of Dermatology (2024)
Linked-color imaging with or without artificial intelligence for adenoma detection: a randomized trial
Authors: Kazuya Miyaguchi, Yoshikazu Tsuzuki, Nobutaka Hirooka, Hisashi Matsumoto, Hideki Ohgo, Hidetomo Nakamoto, Hiroyuki Imaeda
Journal: Endoscopy (2024)

Abstract Background Adenoma detection rate (ADR) is an important indicator of colonoscopy quality and colorectal cancer incidence. Both linked-color imaging (LCI) with artificial intelligence (LCA) and LCI alone increase adenoma detection during colonoscopy, although it remains unclear whether one modality is superior. This study compared ADR between LCA and LCI alone, including according to endoscopists’ experience (experts and trainees) and polyp size. Methods Patients undergoing colonoscopy for positive fecal immunochemical tests, follow-up of colon polyps, and abdominal symptoms at a single institution were randomly assigned to the LCA or LCI group. ADR, adenoma per colonoscopy (APC), cecal intubation time, withdrawal time, number of adenomas per location, and adenoma size were compared. Results The LCA (n=400) and LCI (n=400) groups showed comparable cecal intubation and withdrawal times. The LCA group showed a significantly higher ADR (58.8% vs. 43.5%; P&lt;0.001) and mean (95%CI) APC (1.31 [1.15 to 1.47] vs. 0.94 [0.80 to 1.07]; P&lt;0.001), particularly in the ascending colon (0.30 [0.24 to 0.36] vs. 0.20 [0.15 to 0.25]; P=0.02). Total number of nonpolypoid-type adenomas was also significantly higher in the LCA group (0.15 [0.09 to 0.20] vs. 0.08 [0.05 to 0.10]; P=0.02). Small polyps (≤5, 6–9mm) were detected significantly more frequently in the LCA group (0.75 [0.64 to 0.86] vs. 0.48 [0.40 to 0.57], P&lt;0.001 and 0.34 [0.26 to 0.41] vs. 0.24 [0.18 to 0.29], P=0.04, respectively). In both groups, ADR was not significantly different between experts and trainees. Conclusions LCA was significantly superior to LCI alone in terms of ADR.
Effect of an E-learning resource on endoscopists’ proximal serrated polyp detection rate: a randomized controlled trial
Authors: David E. F. W. M. van Toledo, Joep E. G. IJspeert, Arne G. C. Bleijenberg, Anne Depla, Nahid S. M. Montazeri, Evelien Dekker
Journal: Endoscopy (2024)

Abstract Background Recent studies demonstrated that a higher proximal serrated polyp detection rate (PSPDR) among endoscopists is associated with a lower risk of post-colonoscopy colorectal cancer (PCCRC) incidence and death for their patients. Our objective was to evaluate the effect of an e-learning resource on PSPDR. Methods We performed a multicenter randomized controlled trial within the Dutch fecal immunochemical test-based colorectal cancer screening program. Endoscopists were randomized using block randomization per center to either receive a 60-minute e-learning resource on serrated polyp detection or not. PSPDR was calculated based on all colonoscopies performed during a 27-month pre-intervention and a 17-month post-intervention period. The primary end point was difference in PSPDR between intervention and control arms (intention to treat) using mixed effect logistic regression modeling, with time (pre-intervention/post-intervention) and interaction between time and arm (intervention/control) as fixed effects, and endoscopists as random effects. Results 116 endoscopists (57 intervention, 59 controls) were included, and performed 27494 and 33888 colonoscopies, respectively. Median PSPDR pre-intervention was 13.6% (95%CI 13.0–14.1) in the intervention arm and 13.8% (95%CI 13.3–14.3) in controls. Post-intervention PSPDR was significantly higher over time in the intervention arm than in controls (17.1% vs. 15.4%, P=0.01). Conclusion In an era of increased awareness and increasing PSPDRs, endoscopists who undertook a one-time e-learning course significantly accelerated the increase in PSPDR compared with endoscopists who did not undertake the e-learning. Widespread implementation might reduce PCCRC incidence.
Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control
Authors: Qian Shi, Hamza Malik, Rachel M Crawford, Jennifer Streeter, Jinxi Wang, Ran Huo, Jean C Shih, Biyi Chen, Duane Hall, E Dale Abel, Long-Sheng Song, Ethan J Anderson
Journal: Cardiovascular Research (2024)

Abstract Aims A mechanistic link between depression and risk of arrhythmias could be attributed to altered catecholamine metabolism in the heart. Monoamine oxidase-A (MAO-A), a key enzyme involved in catecholamine metabolism and longstanding antidepressant target, is highly expressed in the myocardium. The present study aimed to elucidate the functional significance and underlying mechanisms of cardiac MAO-A in arrhythmogenesis. Methods and results Analysis of the TriNetX database revealed that depressed patients treated with MAO inhibitors had a lower risk of arrhythmias compared with those treated with selective serotonin reuptake inhibitors. This effect was phenocopied in mice with cardiomyocyte-specific MAO-A deficiency (cMAO-Adef), which showed a significant reduction in both incidence and duration of catecholamine stress-induced ventricular tachycardia compared with wild-type mice. Additionally, cMAO-Adef cardiomyocytes exhibited altered Ca2+ handling under catecholamine stimulation, with increased diastolic Ca2+ reuptake, reduced diastolic Ca2+ leak, and diminished systolic Ca2+ release. Mechanistically, cMAO-Adef hearts had reduced catecholamine levels under sympathetic stress, along with reduced levels of reactive oxygen species and protein carbonylation, leading to decreased oxidation of Type II PKA and CaMKII. These changes potentiated phospholamban (PLB) phosphorylation, thereby enhancing diastolic Ca2+ reuptake, while reducing ryanodine receptor 2 (RyR2) phosphorylation to decrease diastolic Ca2+ leak. Consequently, cMAO-Adef hearts exhibited lower diastolic Ca2+ levels and fewer arrhythmogenic Ca2+ waves during sympathetic overstimulation. Conclusion Cardiac MAO-A inhibition exerts an anti-arrhythmic effect by enhancing diastolic Ca2+ handling under catecholamine stress.
Treating Opioid Use Disorder in General Practice — Diagnosis, Harm Reduction, and Medications
Authors: Sarah Bagley, Je’Mal Barnes, Barbara Blunt, Jennifer Foreman, Scott Hadland, Sandra Mayen, Raina McMahan, L.J. Punch, Darren Taichman
Journal: New England Journal of Medicine (2024)

In this Double Take video from the New England Journal of Medicine and NEJM Knowledge+, L.J. Punch (the T St. Louis, a harm-reduction program), Sarah Bagley (Boston Medical Center), Jennifer Foreman (Randolph Health Medical Group), and Scott Hadland (Massachusetts General Hospital for Children) review how primary care providers can best care for patients with opioid use disorder. They guide clinicians on how to diagnose the disorder, build trust with patients, offer counseling on harm reduction, and use medications to treat addiction and withdrawal symptoms. They also emphasize the importance of reducing stigma to improve therapeutic alliances with this patient population. To learn more about the latest practices for assessing and managing acute and chronic pain, current guidelines for the appropriate use of opioids for pain management, and evidence-based strategies for recognizing and treating opioid use disorder, participate in a free NEJM Knowledge+ Pain Management and Opioids program, available at https://knowledgeplusoffers.nejm.org/oud-double-take/. For further reading on stigma reduction, review the following articles: Stigma Reduction to Combat the Addiction Crisis — Developing an Evidence Base (McGinty and Barry, in the April 2, 2020, issue), and Stigma as a Fundamental Hindrance to the United States Opioid Overdose Crisis Response (Tsai et al., in the November 26, 2019, issue of PLOS Medicine). For further reading on alternative dosing of buprenorphine and naloxone, review the following articles: Low-Dose Initiation of Buprenorphine in Hospitalized Patients on Full Agonist Opioid Therapy: A Retrospective Observational Study (Schult et al, in the November 12, 2023, issue of the Journal of Addiction Medicine), and Microinduction of Buprenorphine/Naloxone: A Review of the Literature (Ahmed et al., in the December 30, 2020, issue of the American Journal on Addictions).
Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy
Authors: Pratibha Dwarkanath, Alfa Muhihi, Christopher R Sudfeld, Blair J Wylie, Molin Wang, Nandita Perumal, Tinku Thomas, Shabani M Kinyogoli, Mohamed Bakari, Ryan Fernandez, John-Michael Raj, Ndeniria O Swai, Nirmala Buggi, Rani Shobha, Mary M Sando, Christopher P Duggan, Honorati M Masanja, Anura V Kurpad, Andrea B Pembe, Wafaie W Fawzi
Journal: New England Journal of Medicine (2024)

The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers.
Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy
Authors: Julian D. Gillmore, Daniel P. Judge, Francesco Cappelli, Marianna Fontana, Pablo Garcia-Pavia, Simon Gibbs, Martha Grogan, Mazen Hanna, James Hoffman, Ahmad Masri, Mathew S. Maurer, Jose Nativi-Nicolau, Laura Obici, Steen Hvitfeldt Poulsen, Frank Rockhold, Keyur B. Shah, Prem Soman, Jyotsna Garg, Karen Chiswell, Haolin Xu, Xiaofan Cao, Ted Lystig, Uma Sinha, Jonathan C. Fox
Journal: New England Journal of Medicine (2024)

Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo.
A Phase 3 Study of Pembrolizumab versus Placebo for Previously Treated Patients from Asia with Hepatocellular Carcinoma: Health-Related Quality of Life Analysis from KEYNOTE-394
Authors: Shukui Qin, Weijia Fang, Zhenggang Ren, Shuangyan Ou, Ho Yeong Lim, Feng Zhang, Kin Chung Lee, Hye Jin Choi, Jiandong Tong, Min Tao, Aibing Xu, Ashley Cheng, Chang-Hsien Lu, Chang-Fang Chiu, Mohamed Ibrahim Abdul Wahid, Shital Kamble, Josephine M Norquist, Wenyan Zhong, Chen Li, Zhendong Chen
Journal: Liver Cancer (2024)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. &lt;i&gt;p&lt;/i&gt; values were one-sided and nominal without adjustment for multiplicity. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The HRQoL population included patients randomly assigned to pembrolizumab (&lt;i&gt;n =&lt;/i&gt; 298) and placebo (&lt;i&gt;n =&lt;/i&gt; 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, −8.4; 95% CI: −11.7 to −5.1) versus pembrolizumab (−4.0; 95% CI: −6.4 to −1.6; difference vs. placebo: 4.4; 95% CI: 0.5–8.4; nominal &lt;i&gt;p&lt;/i&gt; = 0.0142). Similarly, a greater decline in the EQ-5D-3L visual analog scale score was observed with placebo (−6.9; 95% CI: −9.4 to −4.5) versus pembrolizumab (−2.7; 95% CI: −4.5 to −1.0; difference vs. placebo: 4.2; 95% CI: 1.2–7.2; nominal &lt;i&gt;p&lt;/i&gt; = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58–1.25; nominal &lt;i&gt;p&lt;/i&gt; = 0.1993). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Patients receiving placebo showed a greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.
Papular–Purpuric “Gloves and Socks” Syndrome in Parvovirus B19 Infection
Authors: Jetanat Chantrapitak, Mati Chuamanochan
Journal: New England Journal of Medicine (2024)

A 26-year-old man with a 1-week history of a rash on his hands and feet and fever had scattered, partially blanchable macules that had merged into erythematous patches on his hands and feet.
Yukiko Gotoh: I am fascinated by the beauty of science
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2024)

Yukiko Gotoh is a professor in the Department of Pharmaceutical Sciences at the University of Tokyo. Her lab studies the mechanisms that underlie the regulation of neural stem/progenitor cell fate during brain development and homeostasis. They are particularly interested in the underlying genetic and epigenetic mechanisms that control cell fate and neuronal maturation, as well as the relevance of neural stem/progenitor cell dysregulation in neurodevelopmental disorders. We recently spoke to Yukiko about her current work, the joys of teamwork, and her passion for helping other scientists in Japan.
CD8 cis-targeted IL-2 drives potent antiviral activity against hepatitis B virus
Authors: Francesco Andreata, Kelly D. Moynihan, Valeria Fumagalli, Pietro Di Lucia, Danielle C. Pappas, Keigo Kawashima, Irene Ni, Paul H. Bessette, Chiara Perucchini, Elisa Bono, Leonardo Giustini, Henry C. Nguyen, S. Michael Chin, Yik Andy Yeung, Craig S. Gibbs, Ivana Djuretic, Matteo Iannacone
Journal: Science Translational Medicine (2024)

CD8 + T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying CD8 + T cell dysfunction showed that interleukin-2 (IL-2)–based treatment, unlike programmed cell death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential against HBV. However, IL-2’s effectiveness is hindered by its pleiotropic nature, because its receptor is found on various immune cells, including regulatory T (T reg ) cells and natural killer (NK) cells, which can counteract antiviral responses or contribute to toxicity, respectively. To address this, we developed a cis-targeted CD8-IL2 fusion protein, aiming to selectively stimulate dysfunctional CD8 + T cells in chronic HBV. In a mouse model, CD8-IL2 boosted the number of HBV-reactive CD8 + T cells in the liver without substantially altering T reg or NK cell counts. These expanded CD8 + T cells exhibited increased interferon-γ and granzyme B production, demonstrating enhanced functionality. CD8-IL2 treatment resulted in substantial antiviral effects, evidenced by marked reductions in viremia and antigenemia and HBV core antigen–positive hepatocytes. In contrast, an untargeted CTRL-IL2 led to predominant NK cell expansion, minimal CD8 + T cell expansion, negligible changes in effector molecules, and minimal antiviral activity. Human CD8-IL2 trials in cynomolgus monkeys mirrored these results, achieving a roughly 20-fold increase in peripheral blood CD8 + T cells without affecting NK or T reg cell numbers. These data support the development of CD8-IL2 as a therapy for chronic HBV infection.
Impact of Interventricular Interaction on Ventricular Function
Authors: Michael I. Brener, Manreet K. Kanwar, Matthew M. Lander, Nadira B. Hamid, Amresh Raina, Sanjum S. Sethi, Matthew T. Finn, Justin A. Fried, Jayant Raikhelkar, Amirali Masoumi, Hannah R. Rosenblum, Mathew S. Maurer, Gabriel Sayer, Daniel Burkhoff, Nir Uriel
Journal: JACC Heart Failure (2024)