tbuckley/cabot-search huggingface dataset:
Cause or consequence?
Authors: Fernando Madalena Volpe
Journal: European Respiratory Journal (2022)

The SABINA III study results reported by Bateman et al . [1] indicate an association between higher prescription of short-acting β2-agonists (SABAs) and rates of severe asthma exacerbations. Cross-sectional studies are not adequate for making causal inferences <https://bit.ly/3IKSdQm>
Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies
Authors: Adam D. Cohen, Samir Parekh, Bianca D. Santomasso, Jaime Gállego Pérez-Larraya, Niels W. C. J. van de Donk, Bertrand Arnulf, Maria-Victoria Mateos, Nikoletta Lendvai, Carolyn C. Jackson, Kevin C. De Braganca, Jordan M. Schecter, Loreta Marquez, Erin Lee, Ingrid Cornax, Enrique Zudaire, Claire Li, Yunsi Olyslager, Deepu Madduri, Helen Varsos, Lida Pacaud, Muhammad Akram, Dong Geng, Andrzej Jakubowiak, Hermann Einsele, Sundar Jagannath
Journal: Blood Cancer Journal (2022)

Abstract Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to &lt;1% across the cilta-cel program, supporting its favorable benefit–risk profile for treatment of MM.
Changes in Physical Activity and the Risk of Dementia in Patients With New-Onset Type 2 Diabetes: A Nationwide Cohort Study
Authors: Jung Eun Yoo, Kyungdo Han, Bongseong Kim, Sang-Hyun Park, Seon Mee Kim, Hye Soon Park, Ga Eun Nam
Journal: Diabetes Care (2022)

OBJECTIVE We investigated the association between interval changes in physical activity (PA) and dementia risk among patients with new-onset type 2 diabetes. RESEARCH DESIGN AND METHODS We identified 133,751 participants newly diagnosed with type 2 diabetes in a health screening (2009–2012), with a follow-up health screening within 2 years (2010–2015). PA level changes were categorized into continuous lack of PA, decreaser, increaser, and continuous PA groups. Dementia was determined using dementia diagnosis codes and antidementia drug prescriptions. RESULTS During the median follow-up of 4.8 years, 3,240 new cases of all-cause dementia developed. Regular PA was associated with lower risks of all-cause dementia (adjusted hazard ratio [aHR] 0.82; 95% CI 0.75–0.90), Alzheimer disease (AD) (aHR 0.85; 95% CI 0.77–0.95), and vascular dementia (VaD) (aHR 0.78; 95% CI 0.61–0.99). Increasers who started to engage in regular PA had a lower risk of all-cause dementia (aHR 0.86; 95% CI 0.77–0.96). Moreover, the risk was further reduced among those with continuous regular PA: all-cause dementia (aHR 0.73; 95% CI 0.62–0.85), AD (aHR 0.74; 95% CI 0.62–0.88), and VaD (aHR 0.62; 95% CI 0.40–0.94). Consistent results were noted in various subgroup analyses. CONCLUSIONS Regular PA was independently associated with lower risks of all-cause dementia, AD, and VaD among individuals with new-onset type 2 diabetes. Those with continuous regular PA and, to a lesser extent, those who started to engage in regular PA had a lower risk of dementia. Regular PA should be encouraged to prevent dementia in high-risk populations and those with new-onset type 2 diabetes.
How to embed quality improvement into medical training
Authors: Peter Davey, Shobhan Thakore, Vicki Tully
Journal: BMJ (2022)

What you need to know• From the start, medical training should involve identifying problems, analysing why they happen, and testing change • Enable interprofessional learning by focusing on problems identified by multiprofessional clinical teams • Support requires clinical and educational leadership, and individual support such as coaching PRACTICE
T lymphocytes as dynamic regulators of glioma pathobiology
Authors: Elizabeth C Cordell, Mahmoud S Alghamri, Maria G Castro, David H Gutmann
Journal: Neuro-Oncology (2022)

Abstract The brain tumor microenvironment contains numerous distinct types of nonneoplastic cells, which each serve a diverse set of roles relevant to the formation, maintenance, and progression of these central nervous system cancers. While varying in frequencies, monocytes (macrophages, microglia, and myeloid-derived suppressor cells), dendritic cells, natural killer cells, and T lymphocytes represent the most common nonneoplastic cellular constituents in low- and high-grade gliomas (astrocytomas). Although T cells are conventionally thought to target and eliminate neoplastic cells, T cells also exist in other states, characterized by tolerance, ignorance, anergy, and exhaustion. In addition, T cells can function as drivers of brain cancer growth, especially in low-grade gliomas. Since T cells originate in the blood and bone marrow sinuses, their capacity to function as both positive and negative regulators of glioma growth has ignited renewed interest in their deployment as immunotherapeutic agents. In this review, we discuss the roles of T cells in low- and high-grade glioma formation and progression, as well as the potential uses of modified T lymphocytes for brain cancer therapeutics.
Increased cytotoxic T-cells in the airways of adults with former bronchopulmonary dysplasia
Authors: Petra Um-Bergström, Melvin Pourbazargan, Bettina Brundin, Marika Ström, Monika Ezerskyte, Jing Gao, Eva Berggren Broström, Erik Melén, Åsa M. Wheelock, Anders Lindén, C. Magnus Sköld
Journal: European Respiratory Journal (2022)

Rationale Bronchopulmonary dysplasia (BPD) in preterm-born infants is a risk factor for chronic airway obstruction in adulthood. Cytotoxic T-cells are implicated in COPD, but their involvement in BPD is not known. Objectives To characterise the distribution of airway T-cell subsets in adults with a history of BPD. Methods Young adults with former BPD (n=22; median age 19.6 years), age-matched adults born preterm (n=22), patients with allergic asthma born at term (n=22) and healthy control subjects born at term (n=24) underwent bronchoalveolar lavage (BAL). T-cell subsets in BAL were analysed using flow cytometry. Results The total number of cells and the differential cell counts in BAL were similar among the study groups. The percentage of CD3 + CD8 + T-cells was higher (p=0.005) and the proportion of CD3 + CD4 + T-cells was reduced (p=0.01) in the BPD group, resulting in a lower CD4/CD8 ratio (p=0.007) compared to the healthy controls (median 2.2 versus 5.3). In BPD and preterm-born study subjects, both CD3 + CD4 + T-cells (r s =0.38, p=0.03) and CD4/CD8 ratio (r s =0.44, p=0.01) correlated positively with forced expiratory volume in 1 s (FEV 1 ). Furthermore, CD3 + CD8 + T-cells were negatively correlated with both FEV 1 and FEV 1 /forced vital capacity (r s = −0.44, p=0.09 and r s = −0.41, p=0.01, respectively). Conclusions Young adults with former BPD have a T-cell subset pattern in the airways resembling features of COPD. Our findings are compatible with the hypothesis that CD3 + CD8 + T-cells are involved in mechanisms behind chronic airway obstruction in these patients.
Utility of the rapid antigen detection BinaxNOW A&amp;B test for detection of novel influenza A (H1N1) virus
Authors: Loreto Fuenzalida, Silvia Blanco, Cristina Prat, Marta Vivancos, MÂª JesÃºs Dominguez, Josep Maria MÃ²dol, Carlos Rodrigo, Vicente Ausina
Journal: Clinical Microbiology and Infection (2009)
Improvements in Parental Sleep, Fear of Hypoglycemia, and Diabetes Distress With Use of an Advanced Hybrid Closed-Loop System
Authors: Erin C. Cobry, Alessandro Bisio, R. Paul Wadwa, Marc D. Breton
Journal: Diabetes Care (2022)

OBJECTIVE Parental sleep quality may contribute to glycemic control in youth with type 1 diabetes. In this article we present sleep analysis from a multicenter, randomized trial of children ages 6–13 years with type 1 diabetes evaluating the Tandem Control-IQ (CIQ) hybrid closed-loop (HCL) system. RESEARCH DESIGN AND METHODS Pittsburgh Sleep Quality Index (PSQI) scores were assessed at baseline to identify parents as “poor” sleepers (PSQI &amp;gt;5). Glycemic and psycho-behavioral outcomes before and after CIQ use were analyzed in poor sleepers (n = 49) and their children. RESULTS Nocturnal time in range (P &amp;lt; 0.001) and time hyperglycemic (P &amp;lt; 0.001), Hypoglycemia Fear Survey for Parents score (P &amp;lt; 0.001), Problem Areas in Diabetes scale score (P &amp;lt; 0.001), PSQI score (P &amp;lt; 0.001), and Hypoglycemia Fear Survey for Children score (P = 0.025) significantly improved. Of poor sleepers, 27 became good sleepers (PSQI score &amp;lt;5). CONCLUSIONS Use of CIQ in youth with type 1 diabetes ages 6–13 years significantly improved sleep and psychosocial measures in parent poor sleepers, coinciding with improvements in child nocturnal glycemia, highlighting the relationship between HCL systems and parent sleep quality.
The spatiotemporal neural dynamics of object location representations in the human brain
Authors: Monika Graumann, Caterina Ciuffi, Kshitij Dwivedi, Gemma Roig, Radoslaw M. Cichy
Journal: Nature Human Behaviour (2022)

Abstract To interact with objects in complex environments, we must know what they are and where they are in spite of challenging viewing conditions. Here, we investigated where, how and when representations of object location and category emerge in the human brain when objects appear on cluttered natural scene images using a combination of functional magnetic resonance imaging, electroencephalography and computational models. We found location representations to emerge along the ventral visual stream towards lateral occipital complex, mirrored by gradual emergence in deep neural networks. Time-resolved analysis suggested that computing object location representations involves recurrent processing in high-level visual cortex. Object category representations also emerged gradually along the ventral visual stream, with evidence for recurrent computations. These results resolve the spatiotemporal dynamics of the ventral visual stream that give rise to representations of where and what objects are present in a scene under challenging viewing conditions.
Transcription Factors Evolve Faster Than Their Structural Gene Targets in the Flavonoid Pigment Pathway
Authors: Lucas C Wheeler, Joseph F Walker, Julienne Ng, Rocío Deanna, Amy Dunbar-Wallis, Alice Backes, Pedro H Pezzi, M Virginia Palchetti, Holly M Robertson, Andrew Monaghan, Loreta Brandão de Freitas, Gloria E Barboza, Edwige Moyroud, Stacey D Smith
Journal: Molecular Biology and Evolution (2022)

Abstract Dissecting the relationship between gene function and substitution rates is key to understanding genome-wide patterns of molecular evolution. Biochemical pathways provide powerful systems for investigating this relationship because the functional role of each gene is often well characterized. Here, we investigate the evolution of the flavonoid pigment pathway in the colorful Petunieae clade of the tomato family (Solanaceae). This pathway is broadly conserved in plants, both in terms of its structural elements and its MYB, basic helix–loop–helix, and WD40 transcriptional regulators, and its function has been extensively studied, particularly in model species of petunia. We built a phylotranscriptomic data set for 69 species of Petunieae to infer patterns of molecular evolution across pathway genes and across lineages. We found that transcription factors exhibit faster rates of molecular evolution (dN/dS) than their targets, with the highly specialized MYB genes evolving fastest. Using the largest comparative data set to date, we recovered little support for the hypothesis that upstream enzymes evolve slower than those occupying more downstream positions, although expression levels do predict molecular evolutionary rates. Although shifts in floral pigmentation were only weakly related to changes affecting coding regions, we found a strong relationship with the presence/absence patterns of MYB transcripts. Intensely pigmented species express all three main MYB anthocyanin activators in petals, whereas pale or white species express few or none. Our findings reinforce the notion that pathway regulators have a dynamic history, involving higher rates of molecular evolution than structural components, along with frequent changes in expression during color transitions.
Residual Adrenal Function After Multivisceral Resection With Adrenalectomy in Adult Patients
Authors: Marco Fiore, Marco Baia, Lorenzo Conti, Federico Piccioni, Luigi Mariani, Sandro Pasquali, Ettore Seregni, Gabriele Maltese, Mauro Galizia, Stefano Radaelli, Alessandro Maria Villa, Franco Valenza, Alessandro Gronchi
Journal: JAMA Surgery (2022)

<h3>Importance</h3> The risk of developing adrenal insufficiency (AI) following adrenalectomy has been insufficiently studied in the context of multivisceral resection (MVR). <h3>Objective</h3> To evaluate the incidence of AI in patients undergoing MVR with en bloc adrenalectomy. <h3>Design, Setting, and Participants</h3> Prospective observational longitudinal study in a single referral center including 56 consecutive adult patients undergoing retroperitoneal sarcoma surgery from June 2019 to August 2020. Those who were candidates for MVR with en bloc adrenalectomy and had no preexisting adrenal impairment were considered eligible. Of these, 4 individuals were excluded because they did not receive adrenalectomy at the time of surgery and 2 because they were not considered evaluable for the main end point. Follow-up was set at 4 months after surgery, and 49 patients completed follow-up. Data were analyzed from October 2020 to September 2021. <h3>Exposures</h3> Diagnosis of AI was determined by low-dose (1 μg) adrenocorticotropic hormone (ACTH) stimulation test with a threshold of 20 μg/dL in blood samples retrieved 30 and 60 minutes after stimulation. ACTH test was repeated on postoperative days 1 and 10 and at 4 months' follow-up. <h3>Main Outcome and Measures</h3> The primary end point was incidence and relevance of AI after MVR. Secondary end points were associations with patient- and tumor-related factors, impact on perioperative hemodynamic management, and association with postoperative morbidity and mortality. <h3>Results</h3> Fifty patients (26 female; median [IQR] age, 59 [46-67] years) were evaluable. Incidence of AI was 64% (32 of 50 patients) in the early postoperative period and 38.5% (15 of 39 patients) at follow-up. Patients with AI showed lower postoperative cortisol values. Factors associated with risk of AI at univariate analysis were high American Society of Anesthesiologists score (odds ratio [OR], 0.31; 95% CI, 0.14-0.48) and high malignancy grade (OR, 0.35; 95% CI, 0.24-0.46). Clinical outcomes not associated with AI included morbidity, mortality, reoperation rate, admission to intensive care unit, length of intensive care unit stay, total hospital stay, and long-term quality of life. <h3>Conclusions and Relevance</h3> In this study, AI after MVR with en bloc adrenalectomy was frequent, even in patients with adequate preoperative adrenal function. Despite this, adrenalectomy can be safely performed. Patients at risk should be monitored in the long term to exclude underrated impairment of adrenal function.
Yolk sac steps up to the plate
Authors: Hanna K.A. Mikkola
Journal: The Journal of Experimental Medicine (2022)

Atkins et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20211924) create a PSC differentiation model for human yolk sac hematopoiesis and discover multipotent progenitors with erythro-myeloid and T lymphoid potential. The multipotent progenitors emerge via hemogenic endothelium and share origin with primitive erythroid wave in KDR+CD235a/b+ mesoderm.
Derivation and Validation of a Score Using Prehospital Data to Identify Adults With Trauma Requiring Early Laparotomy
Authors: Adam Gutierrez, Kazuhide Matsushima, Areg Grigorian, Morgan Schellenberg, Kenji Inaba
Journal: JAMA Network Open (2022)

<h3>Importance</h3> A scoring tool to identify which adults with traumatic injury will require early laparotomy could help improve prehospital triage and system readiness. <h3>Objective</h3> To develop and validate a prediction model using prehospital information for early laparotomy following trauma. <h3>Design, Setting, and Participants</h3> This retrospective cohort study analyzed data from the 2017 version of the American College of Surgeons Trauma Quality Improvement Program database. All adult patients with traumatic injury aged 18 years or older who were admitted to a US trauma center in 2017 were included. Patients were randomly assigned to a derivation or validation cohort. Data were collected and analyzed between July 2020 and September 2020. <h3>Main Outcomes and Measures</h3> The primary outcome was laparotomy within 2 hours of hospital arrival. A scoring system was developed to predict early laparotomy using a logistic regression model in the derivation cohort. This was validated in the validation cohort using the area under the receiver operating characteristic curve. <h3>Results</h3> A total of 379 890 US adults with traumatic injury were included; 190 264 patients were in the derivation cohort and 189 626 patients were in the validation cohort. The cohorts had the same proportion of laparotomy within 2 hours of hospital arrival (1.1%). The median (IQR) age was 32 (25-46) years in the early laparotomy group and 54 (33-72) years in the group with no early laparotomy. The early laparotomy group contained 113 776 of 188 211 (60.5%) male patients, while the group with no early laparotomy contained 1702 of 2053 (82.9%) male patients. The variable most strongly associated with early laparotomy was penetrating injury to the head, neck, torso, or extremities proximal to the elbow or knee (odds ratio, 13.47; 95% CI, 12.22-14.86) with a point value of 10 (maximum overall score 20). Other variables included in the scoring system were the male sex, a systolic blood pressure less than 90 mm Hg, a Glasgow Coma Scale of less than or equal to 13, having chest wall instability or deformity, pelvic fracture, and high-risk blunt mechanism. In the validation cohort, the C statistic of the scoring system was 0.78 (95% CI, 0.77-0.79). <h3>Conclusions and Relevance</h3> In this study, a novel scoring tool using prehospital information was derived and validated to identify which adults with traumatic injury will require laparotomy within 2 hours of hospital arrival. This tool may help trauma professionals allocate operative team resources before patient arrival.
OCEAN BATHING.
Authors: PHILIP MARVEL
Journal: JAMA (1905)

In considering some of the advantages and disadvantages of sea bathing, one must not lose sight of the fact that it is impossible to separate them from the influences of other agencies, such as temperature and the physical conditions of the atmosphere. And, again, it is no less true that the physical and mental condition of the individual at the time of the bath may greatly modify or influence the effect. Sea water being composed of minerals such as chlorid of sodium, magnesium, bromin and iodin, is truly a mineral water, and an ocean bath, therefore, may be properly classified as a mineral bath. Since temperature is one of the agencies to be considered, we must not regard its presence or absence, beyond a relative degree, other than a definite quantity of either the water or the body. In nature's operations, heat and cold are as necessary as they are
L'Hérédité musicale.
Journal: JAMA (1927)

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Combination of BMI1 and MAPK/ERK inhibitors is effective in medulloblastoma
Authors: Sara Badodi, Nicola Pomella, Yau Mun Lim, Sebastian Brandner, Gillian Morrison, Steven M Pollard, Xinyu Zhang, Nicolae Radu Zabet, Silvia Marino
Journal: Neuro-Oncology (2022)

Abstract Background Epigenetic changes play a key role in the pathogenesis of medulloblastoma (MB), the most common malignant pediatric brain tumor. Methods We explore the therapeutic potential of BMI1 and MAPK/ERK inhibition in BMI1High;CHD7Low MB cells and in a preclinical xenograft model. Results We identify a synergistic vulnerability of BMI1High;CHD7Low MB cells to a combination treatment with BMI1 and MAPK/ERK inhibitors. Mechanistically, CHD7-dependent binding of BMI1 to MAPK-regulated genes underpins the CHD7-BMI1-MAPK regulatory axis responsible of the antitumour effect of the inhibitors in vitro and in a preclinical mouse model. Increased ERK1 and ERK2 phosphorylation activity is found in BMI1High;CHD7Low G4 MB patients, raising the possibility that they could be amenable to a similar therapy. Conclusions The molecular dissection of the CHD7-BMI1-MAPK regulatory axis in BMI1High;CHD7Low MB identifies this signature as a proxy to predict MAPK functional activation, which can be effectively drugged in preclinical models, and paves the way for further exploration of combined BMI1 and MAPK targeting in G4 MB patients.
MEF2C promotes M1 macrophage polarization and Th1 responses
Authors: Xibao Zhao, Qianqian Di, Han Liu, Jiazheng Quan, Jing Ling, Zizhao Zhao, Yue Xiao, Han Wu, Zherui Wu, Wengang Song, Huazhang An, Weilin Chen
Journal: Cellular and Molecular Immunology (2022)
Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer
Authors: Namrata S. Patil, Barzin Y. Nabet, Sören Müller, Hartmut Koeppen, Wei Zou, Jennifer Giltnane, Amelia Au-Yeung, Shyam Srivats, Jason H. Cheng, Chikara Takahashi, Patricia E. de Almeida, Avantika S. Chitre, Jane L. Grogan, Linda Rangell, Sangeeta Jayakar, Maureen Peterson, Allison W. Hsia, William E. O’Gorman, Marcus Ballinger, Romain Banchereau, David S. Shames
Journal: Cancer Cell (2022)