tbuckley/cabot-search huggingface dataset:
Complete closure of large rectal wound and perforation using a novel through-the-scope twin clip
Authors: Ding Peng, Yinglin Niu, Ziyu Liu, Linchao Li, Rui Wang, Guangwei Qiu, Huihong Zhai
Journal: Endoscopy (2024)

Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique used to resect large or early cancerous rectal lesions. However, severe fibrosis or large size of lesion significantly increases the difficulty and risk of the procedure. In particular, postoperative perforation and closure of large wounds remain major clinical challenges. For small perforations, endoscopic closure with through-the-scope (TTS) and over-the-scope (OTS) clips is commonly used [1]. However, larger wounds or complex perforations may require specialized suturing devices or surgical repair. Previous reports have documented the use of the TTS twin clip (TTS-TC; Micro-Tech, Nanjing, China) for closing gastric or duodenal wounds [2]. This report presents a case of successful closure using TTS-TCs of a large rectal wound with perforation. This technique not only offers ease of operation but also excels in closing large wound areas, providing a new therapeutic option, and our report offers practical evidence for similar cases.
Let’s appose our hands together and anastomose the digestive tract – that’s our destiny
Authors: Geoffroy Vanbiervliet
Journal: Endoscopy (2024)

What can be learned in 10 years? A period of 10 years represents the typical time frame for a newborn to reach the age of adolescence, and for an adolescent to become an adult. A decade was the interval during which endoscopists began to treat functional diseases via the orificial route. It was the interval where the fine-needle aspiration technique for endoscopic ultrasound (EUS) sampling gradually ceased to be used in favor of biopsy needles, which offered higher histological precision. Ten years was the (short) time taken for luminal apposition to move from a concept to an indispensable technique, from a new means of draining paradigestive collections to a means of performing digestive anastomoses under remarkably safe conditions.
Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53‐deficient myeloma cells
Authors: Romane Durand, Céline Bellanger, Géraldine Descamps, Christelle Dousset, Sophie Maïga, Jennifer Derrien, Laura Thirouard, Louise Bouard, Hélène Asnagli, Philip Beer, Andrew Parker, Patricia Gomez‐Bougie, Marie‐Claire Devilder, Philippe Moreau, Cyrille Touzeau, Agnès Moreau‐Aubry, David Chiron, Catherine Pellat‐Deceunynck
Journal: HemaSphere (2024)

In multiple myeloma, as in B-cell malignancies, mono- and especially bi-allelic
A preoperative window-of-opportunity study of oral SERD, imlunestrant, in newly diagnosed ER-positive, HER2-negative early breast cancer: Results from EMBER-2 Study.
Authors: Patrick Neven, Nicole Stahl, Maria Vidal, Miguel Martín, Peter A. Kaufman, Nadia Harbeck, Kelly K. Hunt, Stacey Carter, Francois-Clement Bidard, Peter A. Fasching, Philippe Aftimos, Duncan Wheatley, Erika Hamilton, Rebecca Aft, Swati Kulkarni, Peter Schmid, Manali Bhave, Roohi Ismail-Khan, Claudia Karacsonyi, Shawn T. Estrem, Bastien Nguyen, Umut Ozbek, Eunice Yuen, Vanessa Rodrik-Outmezguine, Eva Ciruelos
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer. Pharmacodynamic (PD) biomarker data can optimize drug dosing; in this study, we present PD data from the EMBER-2 study. Patients and Methods: Postmenopausal women with untreated, operable estrogen receptor (ER)–positive, HER2-negative early breast cancer were randomized to 400 versus 800 mg of imlunestrant daily for ∼2 weeks before surgery. A single arm study tested a daily dose of 200 mg. PD biomarker changes (ER, progesterone receptor, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired tumor samples (pre-/posttreatment). Safety and pharmacokinetics were also assessed. Results: Among evaluable paired samples (n = 75), PD profiles demonstrated consistent ER targeting between 400- and 800-mg doses, with less toxicity at the 400-mg dose. Although inducing the lowest rate of complete cell-cycle arrest, PD and pharmacokinetic results were similar for the 200-mg dose. Conclusions: EMBER-2 combined with existing phase I data has identified 400 mg as the optimal imlunestrant dose.
The Evolutionary Forest of Pancreatic Cancer
Authors: Katelyn M. Mullen, Jungeui Hong, Marc A. Attiyeh, Akimasa Hayashi, Hitomi Sakamoto, Zachary A. Kohutek, Caitlin A. McIntyre, Haochen Zhang, Alvin P. Makohon-Moore, Amanda Zucker, Laura D. Wood, Matthew A. Myers, Brian J. Arnold, Simone Zaccaria, Joanne F. Chou, Marinela Capanu, Nicholas D. Socci, Benjamin J. Raphael, Christine A. Iacobuzio-Donahue
Journal: Cancer Discovery (2024)

Although the pancreatic cancer genome has been described, it has not been explored with respect to stages of diagnosis or treatment bottlenecks. We now describe and quantify the genomic features of PDAC in the context of evolutionary metrics and in doing so have identified a novel prognostic biomarker.
FDA Approval Summary: Capecitabine Labeling Update under Project Renewal
Authors: Sundeep Agrawal, Clara Lee, William F. Pierce, Elizabeth Everhart, Adriene King-Ducre, Melanie Royce, Christy L. Osgood, Laleh Amiri-Kordestani, Haw-Jyh Chiu, Tiffany K. Ricks, Lili Pan, Jeanne Fourie Zirkelbach, Rosane Charlab, Michael Pacanowski, Tamy Kim, Richard Pazdur, Paul G. Kluetz, Jennifer J. Gao
Journal: Clinical Cancer Research (2024)

On December 14, 2022, the U.S. Food and Drug Administration (FDA) approved revisions to the United States Prescribing Information (USPI) for capecitabine that revised existing indications and dosage regimens, added new indications and their recommended dosage regimens, revised safety information, updated the description of the risk of capecitabine in patients with dihydropyrimidine dehydrogenase (DPD) deficiency, and edited other sections of the USPI to conform with FDA's current labeling guidance. These supplements were reviewed and approved under Project Renewal, a public health initiative established by the FDA's Oncology Center of Excellence that aims to update the prescribing information of certain older oncology drugs to ensure information is clinically meaningful and scientifically up to date. This article summarizes the FDA approach that supported revisions to the capecitabine USPI within the context of Project Renewal.
Achieving Nepal's clean cooking ambitions: an open source and geospatial cost–benefit analysis
Authors: Camilo Ramirez, Babak Khavari, Alicia Oberholzer, Bhoj Raj Ghimire, Bhogendra Mishra, Santiago Sinclair-Lecaros, Dimitris Mentis, Anobha Gurung, Dilip Khatiwada, Francesco Fuso Nerini
Journal: The Lancet Planetary Health (2024)
Effect of heat stress in the first 1000 days of life on fetal and infant growth: a secondary analysis of the ENID randomised controlled trial
Authors: Ana Bonell, Ana M Vicedo-Cabrera, Giovenale Moirano, Bakary Sonko, David Jeffries, Sophie E Moore, Andy Haines, Andrew M Prentice, Kris A Murray
Journal: The Lancet Planetary Health (2024)

The intersecting crises of climate change, food insecurity, and undernutrition disproportionately affect children. Understanding the effect of heat on growth from conception to 2 years of age is important because of mortality and morbidity implications in the near term and over the life course.
Malaria vector control in sub-Saharan Africa: complex trade-offs to combat the growing threat of insecticide resistance
Authors: Richard M Oxborough, Karen L Figueroa Chilito, Filemon Tokponnon, Louisa A Messenger
Journal: The Lancet Planetary Health (2024)

Mass distribution of insecticide-treated nets (ITNs) has been a key factor in reducing malaria cases and deaths in sub-Saharan Africa. A shortcoming has been the over-reliance on pyrethroid insecticides, with more than 2·13 billion pyrethroid ITNs (PY ITNs) distributed in the past two decades, leading to widespread pyrethroid resistance. Progressive changes are occurring, with increased deployment of more effective pyrethroid-chlorfenapyr (PY-CFP) or pyrethroid-piperonyl butoxide (PY-PBO) ITNs in areas of pyrethroid resistance. In 2023, PY-PBO ITNs accounted for 58% of all ITNs shipped to sub-Saharan Africa. PY-PBO and PY-CFP ITNs are 30-37% more expensive than standard PY ITNs, equating to an additional US$132-159 million required per year in sub-Saharan Africa to fund the shift to more effective ITNs. Several countries are withdrawing or scaling back indoor residual spraying (IRS) programmes to cover the shortfall, which is reflected by the number of structures sprayed by the US President's Malaria Initiative decreasing by 30% from 5·67 million (2021) to 3·96 million (2023). Benin, located in West Africa, is a prime example of a country that ceased IRS in 2021 after 14 years of annual spraying. Our economic evaluation indicates that IRS in Benin cost $3·50 per person protected per year, around five times more per person protected per year compared with PY-PBO ($0·73) or PY-CFP ITNs ($0·76). Although costly to implement, a major advantage of IRS is the portfolio of at least three chemical classes for prospective resistance management. With loss of synergy to PBO developing rapidly, there is the danger of over-reliance on PY-CFP ITNs. As gains in global malaria control continue to reverse each year, current WHO projections estimate that key 2030 malaria incidence milestones will be missed by a staggering 89%. This Personal View explores contemporary malaria vector control trends in sub-Saharan Africa and cost implications for improved disease control and resistance management.
Evaluating progress and accountability for achieving COP26 Health Programme international ambitions for sustainable, low-carbon, resilient health-care systems
Authors: Iris Martine Blom, Fawzia N Rasheed, Hardeep Singh, Matthew J Eckelman, Meghnath Dhimal, Martin Hensher, Renzo R Guinto, Alice McGushin, Xuejuan Ning, Poornima Prabhakaran, Marina Romanello, Dana van Alphen, Nick Watts, Jessica C Yu, Carol Zavaleta-Cortijo, Andrea J MacNeill, Jodi D Sherman
Journal: The Lancet Planetary Health (2024)
Unbiased temperature-related mortality estimates using weekly and monthly health data: a new method for environmental epidemiology and climate impact studies
Authors: Xavier Basagaña, Joan Ballester
Journal: The Lancet Planetary Health (2024)

Exposure to environmental factors has a high burden on human health, with millions of premature annual deaths associated with the short-term health effects of ambient temperatures and air pollution. However, direct estimations of exposure-related mortality from real data are still not available in most parts of the world, especially in low-resource settings, due to the unavailability of daily health records to calibrate epidemiological models.
Projecting future excess deaths associated with extreme precipitation events in China under changing climate: an integrated modelling study
Authors: Jie Ban, Kailai Lu, Yuanyuan Liu, Jiawei Zang, Zhen Zhou, Can Zhang, Zhao Liu, Jianbin Huang, Yidan Chen, Xuejie Gao, Ying Xu, Can Wang, Wenjia Cai, Peng Gong, Yong Luo, Tiantian Li
Journal: The Lancet Planetary Health (2024)
The co-benefits of active travel interventions beyond physical activity: a systematic review
Authors: Ding Ding, Mengyun Luo, Maria Florencia Petrelli Infante, Lucy Gunn, Deborah Salvo, Belen Zapata-Diomedi, Ben Smith, William Bellew, Adrian Bauman, Tracy Nau, Binh Nguyen
Journal: The Lancet Planetary Health (2024)
Walking the line
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2024)

Our history of industrialisation and current consumer economy are using up the Earth's resources faster than they can be replenished and putting pressure on natural systems beyond their capacity to absorb and adapt. The danger of permanently destabilizing the natural systems that support human life and wreaking untold harm to human populations are of course recognised in international treaties, such as the Paris Agreement and the Kunming-Montreal Global Biodiversity Protocol, that commit to collectively reduce our impacts and avoid dangerous tipping points.
Two pandemics, a shared lesson
Authors: Emma Starbuck
Journal: The Lancet Infectious Diseases (2024)

Viral times: reflections on the COVID-19 and HIV pandemics explores how the COVID-19 pandemic can shape our understanding of the HIV pandemic, and vice versa. The book is a compilation of 16 papers written by 28 authors, and includes case studies from eleven different countries. The book was edited by Jaime García-Iglesias, Maurice Nagington, and Peter Aggleton, and it is targeted towards a range of specialist backgrounds, as well as the general reader.
The regulation of neurotechnology: the neurorights bill in Mexico
Authors: Karen Herrera-Ferrá, José M Muñoz, Anahiby Becerril, Eric García-López, José Ángel Marinaro, Luis Ricardo Sánchez Hernández, Jesús Alejandro Alonso Olamendi, Alejandra Lagunes Soto Ruiz
Journal: The Lancet Psychiatry (2024)
Global burden of oral cancer in 2022 attributable to smokeless tobacco and areca nut consumption: a population attributable fraction analysis
Authors: Harriet Rumgay, Suzanne T Nethan, Richa Shah, Jérôme Vignat, Olalekan Ayo-Yusuf, Pankaj Chaturvedi, Eliete N S Guerra, Prakash C Gupta, Ruchika Gupta, Shiwei Liu, Cecilia Magnusson, Mark Parascandola, Yvette C Paulino, Negar Rezaei, Kamran Siddiqi, Saman Warnakulasuriya, Beatrice Lauby-Secretan, Isabelle Soerjomataram
Journal: The Lancet Oncology (2024)
Activated sympathetic nerve post stroke downregulates Toll-like receptor 5 and disrupts the gut mucosal barrier
Authors: Huidi Wang, Jie Li, Guangyan Wu, Xiaofei Lin, Jiaying Chen, Jingru Liang, Jiahui Zhang, Xiaoxia Luo, Hongyun Mao, Jiahui Xie, Zhuang Li, Hongwei Zhou, Kaiyu Xu, Jia Yin, Yan He
Journal: Cell Reports Medicine (2024)

Highlights•The gut mucosal barrier is impaired with flagellated bacteria invasion at 2 h post stroke•The bacterial invasion is due to reduced downstream products of TLR5•Activated sympathetic nerve decreases intestinal TLR5 expression•Biomarkers for gut permeability can predict prognosis in patients with strokeSummaryThe gut permeability significantly increases after ischemic stroke, partly due to disrupted mucosal barrier, but the mechanism remains elusive. Here, we found that the mucus disruption starts at 2 h post stroke, whereas goblet cell functions remain intact. Meanwhile, the flagellated bacteria Helicobacter thrives and penetrates in the mucus layer. Elimination of the mucosal microbiota or transplantation of Helicobacter in germ-free mice reveals an important role of the mucosal microbiota in mucus disruption. The bacterial invasion is due to downregulated Toll-like receptor 5 (TLR5) and its downstream products flagellin-specific IgA and antimicrobial peptides. Knockdown of intestinal TLR5 increases the abundance of flagellated bacteria and exacerbates mucus injury. Intestinal TLR5 is downregulated by the activation of sympathetic nerve. Serum noradrenaline level is positively associated with flagellin level in patients with stroke and patients' prognosis. These findings reveal a neural pathway in which the sympathetic nerve disrupts the mucosal barrier, providing potential therapeutic targets for stroke injury.Graphical abstract
Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights
Authors: Eishani K Sokolowski, Romy Kursawe, Vijay Selvam, Redwan M Bhuiyan, Asa Thibodeau, Chi Zhao, Cassandra N Spracklen, Duygu Ucar, Michael L Stitzel
Journal: Cell Metabolism (2024)

Endoplasmic reticulum (ER) and inflammatory stress responses contribute to islet dysfunction in type 2 diabetes (T2D). Comprehensive genomic understanding of these human islet stress responses and whether T2D-associated genetic variants modulate them is lacking. Here, comparative transcriptome and epigenome analyses of human islets exposed ex vivo to these stressors revealed 30% of expressed genes and 14% of islet cis-regulatory elements (CREs) as stress responsive, modulated largely in an ER- or cytokine-specific fashion. T2D variants overlapped 86 stress-responsive CREs, including 21 induced by ER stress. We linked the rs6917676-T T2D risk allele to increased islet ER-stress-responsive CRE accessibility and allele-specific β cell nuclear factor binding. MAP3K5, the ER-stress-responsive putative rs6917676 T2D effector gene, promoted stress-induced β cell apoptosis. Supporting its pro-diabetogenic role, MAP3K5 expression correlated inversely with human islet β cell abundance and was elevated in T2D β cells. This study provides genome-wide insights into human islet stress responses and context-specific T2D variant effects.
Clinical pain management: Current practice and recent innovations in research
Authors: Jing Wang, Lisa V. Doan
Journal: Cell Reports Medicine (2024)

SummaryChronic pain affects one in five adults. It is not only a major cause of disability for individual patients but also a driver of costs for entire healthcare systems. Treatment of pain remains a challenge, and the use of opioids has further led to a concurrent opioid epidemic. In this review, we discuss current standard treatment options for chronic pain, including pharmacological, behavioral, and interventional treatments. In addition, we review ongoing research in different areas that will potentially unlock new therapies.Graphical abstract
Failure of metabolic checkpoint control during late-stage granulopoiesis drives neutropenia in reticular dysgenesis
Authors: Wenqing Wang, Martin Arreola, Thomas Mathews, Andrew W DeVilbiss, Zhiyu Zhao, Misty Martin-Sandoval, Abdulvasey Mohammed, Giorgia Benegiamo, Avni Awani, Ludger J. E. Goeminne, Daniel Patrick Dever, Yusuke Nakauchi, Matthew H Porteus, Mara Pavel-Dinu, Waleed Al Herz, Johan Auwerx, Sean J. Morrison, Katja G. Weinacht
Journal: Blood (2024)
Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity
Authors: Christine H. Andreassen, Rune Holt, Li Juel Mortensen, Nadia Krarup Knudsen, John E. Nielsen, Nadia Nicholine Poulsen, Sam K. Yahyavi, Ida M. Boisen, Zhihui Cui, Luisina Ongaro, Jasmin P. Hjerresen, Birgitte G. Toft, Thomas Hasselager, Niklas R. Jørgensen, Daniel J. Bernard, Anders Juul, Charles O’Brien, Anne Jørgensen, Martin Blomberg Jensen
Journal: Cell Reports Medicine (2024)

Highlights•RANKL in Sertoli cells signals to RANK in germ cells and is inhibited by denosumab•Denosumab increases sperm count in mice and germ cell proliferation ex vivo in men•Denosumab suppresses the high RANKL levels in seminal fluid of infertile men•Denosumab increases sperm concentration in infertile men with high serum AMHSummarySperm production depends on proper Sertoli-germ cell interaction, and we hypothesized that receptor activator of nuclear factor κB ligand (RANKL) activity in Sertoli cells may influence spermatogenesis. Treatment with the RANKL inhibitor denosumab, normally used to treat osteoporosis, increased testicular weight, inhibin B, and germ cell proliferation in ex vivo testis cultures and in vivo in a humanized RANKL mouse. The effect on germ cell proliferation was positively associated with baseline serum concentrations of anti-müllerian hormone (AMH). In accordance, denosumab increased germ cell proliferation in ex vivo human testis cultures with low/moderate but not severe impairment of Sertoli cell function. In a placebo-controlled randomized clinical trial, denosumab had no effect on semen quality but increased sperm concentration in a subgroup of infertile men with serum AMH ≥38 pmol/L at baseline. In conclusion, high serum AMH may increase the probability of a beneficial response to denosumab treatment in infertile men, thus suggesting a possible venue for precision medicine in male infertility.Graphical abstract
Strategies and tactics to reduce the impact of healthcare on climate change: systematic review
Authors: Jeffrey Braithwaite, Carolynn L Smith, Elle Leask, Shalini Wijekulasuriya, Kalissa Brooke-Cowden, Georgia Fisher, Romika Patel, Lisa Pagano, Hania Rahimi-Ardabili, Samantha Spanos, Christina Rojas, Andrew Partington, Ella McQuillan, Genevieve Dammery, Ann Carrigan, Lauren Ehrenfeld, Enrico Coiera, Johanna Westbrook, Yvonne Zurynski
Journal: BMJ (2024)

To review the international literature and assess the ways healthcare systems are mitigating and can mitigate their carbon footprint, which is currently estimated to be more than 4.4% of global emissions.
Drug treatments to prevent first decompensation in cirrhosis
Authors: Camille A. Kezer, Annalisa Berzigotti, Brett E. Fortune, Douglas A. Simonetto
Journal: Hepatology (2024)

Cirrhosis is a prevalent condition affecting more than 100 million people globally and carrying significant morbidity and mortality related to the development of portal hypertension and hepatic decompensation. Current treatment is primarily targeted at identifying chronic liver disease early and preventing the progression of fibrosis by treating the underlying etiology of liver disease. Treatment options for patients with advanced fibrosis are limited, and the only drug class approved for the prevention of hepatic decompensation remains non-selective beta blockers. There are several pharmacological therapies being developed in both preclinical and clinical trials to explore their efficacy in preventing first hepatic decompensation. Most studies evaluate primary endpoints reflective of disease severity and portal hypertension, such as change in hepatic venous pressure gradient or fibrosis stage based on histology or imaging. While many drugs are being investigated, much work is still needed to identify treatment targets with effective outcomes in order to move the needle in the field of cirrhosis management. This narrative review will address the current state of cirrhosis therapies including potential new therapeutic targets as well as provide direction on future advancements that will improve our current treatment paradigm and lead to better outcomes for those burdened with cirrhosis.