tbuckley/cabot-search huggingface dataset:
Gut Microbiota–Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling
Authors: Makoto Matsushita, Kazutoshi Fujita, Takuji Hayashi, Hisako Kayama, Daisuke Motooka, Hiroaki Hase, Kentaro Jingushi, Gaku Yamamichi, Satoru Yumiba, Eisuke Tomiyama, Yoko Koh, Yujiro Hayashi, Kosuke Nakano, Cong Wang, Yu Ishizuya, Taigo Kato, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Motohide Uemura, Ryoichi Imamura, Maria D.C. Rodriguez Pena, Jennifer B. Gordetsky, George J. Netto, Kazutake Tsujikawa, Shota Nakamura, Kiyoshi Takeda, Norio Nonomura
Journal: Cancer Research (2021)

Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer. Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific Pten knockout mice as a prostate cancer model to investigate whether there is a gut microbiota-mediated connection between animal fat intake and prostate cancer. Oral administration of an antibiotic mixture (Abx) in prostate cancer-bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including Rikenellaceae and Clostridiales, inhibited prostate cancer cell proliferation, and reduced prostate Igf1 expression and circulating insulin-like growth factor-1 (IGF1) levels. In prostate cancer tissue, MAPK and PI3K activities, both downstream of the IGF1 receptor, were suppressed by Abx administration. IGF1 directly promoted the proliferation of prostate cancer cell lines DU145 and 22Rv1 in vitro. Abx administration also reduced fecal levels of short-chain fatty acids (SCFA) produced by intestinal bacteria. Supplementation with SCFAs promoted tumor growth by increasing IGF1 levels. In humans, IGF1 was found to be highly expressed in prostate cancer tissue from obese patients. In conclusion, IGF1 production stimulated by SCFAs from gut microbes influences the growth of prostate cancer via activating local prostate MAPK and PI3K signaling, indicating the existence of a gut microbiota-IGF1-prostate axis. Disrupting this axis by modulating the gut microbiota may aid in prostate cancer prevention and treatment. SIGNIFICANCE: These results suggest that intestinal bacteria, acting through short-chain fatty acids, regulate systemic and local prostate IGF1 in the host, which can promote proliferation of prostate cancer cells.
Association of Sex With Risk of 2-Year Revision Among Patients Undergoing Total Hip Arthroplasty
Authors: Amanda Chen, Liz Paxton, Xinyan Zheng, Raquel Peat, Jialin Mao, Alexander Liebeskind, Laura E. Gressler, Danica Marinac-Dabic, Vincent Devlin, Terri Cornelison, Art Sedrakyan
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The worldwide population is aging and includes more female individuals than male individuals, with higher rates of total hip arthroplasty (THA) among female individuals. Although research on this topic has been limited to date, several studies are currently under way. <h3>Objectives</h3> To evaluate the association between sex and 2-year revision after THA. <h3>Design, Setting, and Participants</h3> This cohort study used data from statewide databases in New York and California between October 1, 2015, and December 31, 2018. Patients 18 years or older with osteoarthritis who underwent THA and had sex recorded in the database were included in the analysis. <h3>Exposure</h3> Total hip arthroplasty. <h3>Main Outcomes and Measures</h3> The outcome of interest was the difference in early, all-cause revision surgery rates after primary THA between women and men. The association of sex with the revision rate was examined using Cox proportional hazards regression analysis. <h3>Results</h3> Of 132 826 patients included in the study, 74 002 (55.7%) were women; the mean (SD) age was 65.9 (11.0) years, and the median follow-up time was 1.3 years (range, 0.0-3.0 years). The 2-year revision rate was 2.5% (95% CI, 2.4%-2.6%) among women and 2.1% (95% CI, 2.0%-2.2%) among men. After adjusting for demographic characteristics, comorbidities, and facility volume, a minimal clinically meaningful difference was observed in revision rates despite women having a higher risk of all-cause revision compared with men (hazard ratio, 1.16; 95% CI, 1.07-1.26;<i>P</i> &lt; .001). The risk of revision was increased among women compared with men in the subgroup of patients who were younger than 55 years (hazard ratio, 1.47; 95% CI, 1.20-1.81;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this cohort study, no clinically meaningful difference in all-cause revision rates after primary THA was found between men and women at 2-year follow-up. The modest difference in the risk of revision between men and women in a small subgroup of patients younger than 55 years suggests that the risk of revision in this population should be studied further.
British Association of Dermatologists guidelines for the management of adults with basal cell carcinoma 2021*
Authors: I. Nasr, E.J. McGrath, C.A. Harwood, J. Botting, P. Buckley, P.G. Budny, P. Fairbrother, K. Fife, G. Gupta, M. Hashme, S. Hoey, J.T. Lear, R. Mallipeddi, E. Mallon, R.J. Motley, C. Newlands, J. Newman, E.V. Pynn, N. Shroff, D.N. Slater, L.S. Exton, M.F. Mohd Mustapa, M.C. Ezejimofor
Journal: British Journal of Dermatology (2021)

Linked Comment: M.D. Moncrieff and J.P. Nobes. Br J Dermatol 2021; 185:877. Plain language summary available online
Capturing dynamic biological signals via bio-mimicking hydrogel for precise remodeling of soft tissue
Authors: Zhengwei Cai, Qimanguli Saiding, Liang Cheng, Liucheng Zhang, Zhen Wang, Fei Wang, Xinliang Chen, Gang Chen, Lianfu Deng, Wenguo Cui
Journal: Bioactive Materials (2021)

Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior. However, capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes. Here, a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation, and the chemical signals provided with chemokine and natural adhesion sites, which guaranteed the precise soft tissue remodeling. This bio-mimicking hydrogel efficiently facilitated cell anchoring, migration, and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors. Besides, the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1α dependent signal pathway. Furthermore, the early polarization of macrophages, collagen deposition and angiogenesis in rat acute wound model, and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve, myocardium, and even bone.
AB0497 IMPACT OF COXITIS ON THE BONE MINERAL DENSITY OF THE HIP IN ANKYLOSING SPONDYLITIS
Authors: A. Feki, I. Sellami, R. Akrout, S. Ben Jemaa, Z. Gassara, M. Ezzeddine, M. H. Kallel, H. Fourati, S. Baklouti
Journal: Annals of the Rheumatic Diseases (2021)

Background: Ankylosing spondylitis (AS) is an inflammatory disease, with new bone formation and ossification of the ligamentous apparatus as the primary pathological changes. The osteoporosis is coexisting with new bone formation. It is well known a common complication of this chronic disease. Hip involvement is common in AS [1]. Objectives: The objective of this work is to assess the impact of chronic inflammation of the hip (coxitis) on the bone density at this site. Methods: This is a cross-sectional study of patients who fulfil the modified New York criteria for AS. These patients had not medical history of osteoporosis or other condition that may affect bone metabolism. Hip involvement was appreciated by physical examination and pelvic x-ray. The functional hip gene was assessed by Lequesne Algofunctional Index (LFI). Bone mineral density at the femoral site was measured using Lunar Prodigy dual-energy X-ray absorptiometry. Osteoporosis is defined when T score is ≤ -2.5 DS (standards deviations). Osteopenia is defined when T score is ≤ -1 DS but more than -2.5 DS. A p value &lt;0.05 was considered significant. Results: Forty-seven AS patients were collected, 12 women and 35 men with a mean age of 43.8 ± 13.4 years. Smoking was noted in 25% of cases. AS clinical form was axial in 33 cases (70.2%) and mixed (axial and peripheral) in 14 cases (29.8%). The mean duration of AS was 15 ± 10.9 years. Nineteen patients (40.4%) were on DMARD at the time of the study. Coxitis was present in 31 patients (66%). It was bilateral in 13 cases (42.5%). The mean of the LFI was 7.1 ± 6.5 with extremes of 0 to 18. Coxitis form was early in 18 cases (40.9%), synostosis in 15 cases (34.1%) and destructive in 11 cases (25%). Twenty-nine patients (61.7%) had normal femoral bone densitometry, 13 patients (27.7%) had osteopenia and 4 patients (8.5%) had osteoporosis. The mean T-score value at femoral neck site was -0.5 SD ± 1.303 [-3– -2]. Patients with coxitis had a significantly lower T score at the femoral site compared to those without coxitis (-0.77 ± 1.31 DS versus 0.07 ± 1.11 DS respectively with p = 0.036). Conclusion: Our study confirms the role of chronic inflammation in the genesis of bone loss in AS. Given the risks of developing secondary complications as a result of low bone density, early management of AS should be recommended in order to control the inflammatory process and prevent the onset of osteoporosis. References: [1]Toussirot E, Wendling D. Bone mass in ankylosing spondylitis. Clin Exp Rheumatol 2000:16–20. Disclosure of Interests: None declared.
HIV pre-exposure prophylaxis: scaling up for impact now and in the future
Authors: Benjamin R Bavinton, Andrew E Grulich
Journal: The Lancet Public Health (2021)

More than a decade after the first efficacy evidence for oral HIV pre-exposure prophylaxis (PrEP) was reported, PrEP uptake globally has been inadequate and global HIV prevention targets have been missed. Access to PrEP is still highly concentrated in a fairly small number of countries and, even within countries with widespread PrEP access, inequalities have emerged. More ambitious, high-priority global targets for PrEP uptake are required and could accelerate the HIV prevention response in a similar way to the success of the 90-90-90 testing and treatment targets. Health systems must be PrEP-friendly and allow PrEP to be prescribed in settings already attended by large numbers of HIV-negative individuals who are at risk. Several models have been advanced for the greater demedicalisation of PrEP. Individual-level barriers to PrEP uptake and persistence have been characterised, such as low awareness, low willingness to use PrEP, and the gap between self-perceived and actual HIV risk. Overcoming these barriers will require further efforts to understand and address them first. New PrEP modalities are emerging; as more options become available, we need to develop a greater understanding of the long-term patterns of PrEP use in different populations and to develop models of such use that can accommodate people alternating through periods of use and non-use, as well as switching between dosing regimens or modalities as they become available. Scaling up PrEP is crucial to achieving the UNAIDS prevention targets for 2030. Simply getting more people onto PrEP cannot be the only goal: the big-picture definition of success for PrEP programmes must be their impact on the HIV epidemic.
Corrections to “SPARC expression in resected pancreatic cancer patients treated with Gemcitabine: results from the CONKO-001 study”
Authors: M. Sinn, B.V. Sinn, J.K. Striefler, J.L. Lindner, J.M. Stieler, P. Lohneis, S. Bischoff, H. Bläker, U. Pelzer, M. Bahra, M. Dietel, B. Dörken, H. Oettle, H. Riess, C. Denkert
Journal: Annals of Oncology (2016)
AB0393 PRE-EXISTING MORBIDITY AS A RISK FACTORS FOR MORTALITY IN IgA VASCULITIS
Authors: J. Nossent, D. Preen, W. Raymond, H. Keen, C. Inderjeeth
Journal: Annals of the Rheumatic Diseases (2021)

Background: IgA vasculitis is generally considered to be a self-limiting condition, but this is at odds with the increased mortality observed in adult patients with IgA vasculitis (1). Objectives: With sparse data on prognostic factors in IgAV, we investigated whether pre-existing conditions are risk factors for mortality in adult IgAV patients. Methods: Observational population-based cohort study using state-wide linked longitudinal health data for adults with IgAV (n=267) and matched controls (n=1080) between 1980-2015. Charlson comorbidity index (CCI) and serious infections (SI) were recorded over an extensive lookback period prior to diagnosis. Date and causes of death were extracted from the WA Death Registry. Mortality rate (deaths/1000 person-years) ratios (MRR) and time dependent survival analysis assessed the risk of death. Age and gender specific mortality rate data were obtained from the Australian Bureau of Statistics. Results: During 9.9 (±9.8) years lookback IgAV patients accrued higher CCI scores (2.60 vs1.50 p&lt;0.001) and had higher risk of SI (OR 8.4, p&lt;0.001), not fully explained by CCI scores. During 19 years follow-up, the risk of death in IgAV patients (n=137) was higher than in controls (n=397) (MRR 2.06, CI 1.70-2.50, p&lt;0.01) and the general population (SMRR 5.64, CI 4.25, 7.53, p&lt;0.001). Survival in IgAV was reduced at five (72.7 vs. 89.7 %) and twenty years (45.2% vs. 65.6 %) (both p&lt;0.05). CCI (HR1.88, CI:1.25 - 2.73, p=0.001), renal failure (HR 1.48, CI: 1.04 - 2.22, p=0.03) and prior SI (HR 1.48, CI:1.01 – 2.16, p=0.04) were independent risk factors. Death from infections (5.8 vs 1.8%, p=0.02) was significantly more frequent in IgAV patients. Conclusion: Premorbid accrual of comorbidity is increased and predicts premature death in IgAV patients. However, comorbidity does not fully explain the increased risk of serious infections prior to diagnosis or the increased mortality due to infections in IgAV. References: [1]Villatoro-Villar M, Crowson CS, Warrington KJ, Makol A, Ytterberg SR, Koster MJ. Clinical Characteristics of Biopsy-Proven IgA Vasculitis in Children and Adults: A Retrospective Cohort Study. Mayo Clin Proc. 2019;94(9):1769-80. Acknowledgements: The authors would like to acknowledge the support of the Arthritis Foundation of WA and acknowledge the Western Australian Data Linkage Branch, the Western Australian Department of Health, and the data custodians of, the Hospital and Morbidity Data Collection, the Emergency Department Data Collection the WA Cancer Register and the WA Death Register for their assistance with the study. Disclosure of Interests: None declared
Evaluation Tools for Outcomes Assessment in Hepato-Pancreato-Biliary Surgery
Authors: Yuman Fong
Journal: JAMA Surgery (2021)

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Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection
Authors: Laura Montefusco, Moufida Ben Nasr, Francesca D’Addio, Cristian Loretelli, Antonio Rossi, Ida Pastore, Giuseppe Daniele, Ahmed Abdelsalam, Anna Maestroni, Marco Dell’Acqua, Elio Ippolito, Emma Assi, Vera Usuelli, Andy Joe Seelam, Roberta Maria Fiorina, Enrica Chebat, Paola Morpurgo, Maria Elena Lunati, Andrea Mario Bolla, Giovanna Finzi, Reza Abdi, Joseph V. Bonventre, Stefano Rusconi, Agostino Riva, Domenico Corradi, Pierachille Santus, Manuela Nebuloni, Franco Folli, Gian Vincenzo Zuccotti, Massimo Galli, Paolo Fiorina
Journal: Nature Metabolism (2021)
AB0641 EFFECT OF AGE ON PARATHYROID HORMONE RESPONSE TO VITAMIN D INSUFFICIENCY IN PRIMARY HYPERPARATHYROIDISM
Authors: V. Deshani, M. Khalid, K. Jadoon
Journal: Annals of the Rheumatic Diseases (2021)

Background: Primary hyperparathyroidism (PHPT) is a common endocrine condition, commonly seen with increasing age. In vast majority, it is diagnosed incidentally and causes no particular symptoms. Symptoms are usually related to acute hypercalcaemia or the complications of chronically elevated serum calcium level. Vitamin D deficiency is common among general population and in patients with PHPT. Studies in secondary hyperparathyroidism (SHPT) have shown that parathyroid hormone (PTH) response is affected by age, with those over 80 showing greater rise in PTH levels. We wanted to see if age has a similar impact on PTH response to vitamin D in those with PHPT. Objectives: To evaluate the impact of age on PTH response to vitamin D insufficiency in those with PHPT. Methods: Patients with primary hyperparathyroidism (PHPT), attending general endocrine clinic of a district general hospital, were divided into two groups based on age; less than 70 (n=73) and 70 and above (n=61).Each group was subdivided into vitamin D insufficient (VDI) and vitamin D sufficient (VDS) subgroups. We compared calcium and parathyroid hormone levels and forearm BMD (presented as T score) in VDI and VDS subgroups in the two age groups, at the time of diagnosis. Data were analyzed using unpaired t-test and presented as mean ± SEM, using Graphpad Prism 9.0.1. Results: There was significant difference in Vitamin D levels in VDI and VDS subgroups, in both age groups (&lt;70; mean vitamin D 27.98 vs. 68.44, p&lt;0.0001; ≥70; mean vitamin D 34.44 vs. 75.74, p&lt;0.0001). The two groups were significantly different in terms of age (mean age 58 vs. 76, p&lt;0.0001). Although there was no difference in calcium and forearm BMD in VDI and VDS, in both age groups, those under 70 showed a greater PTH response to vitamin D insufficiency (mean PTH 19.29 vs. 12.91 respectively, p&lt;0.001). Conclusion: While in SHPT, those with increasing age show greater rise in PTH levels, our data show that in PHPT, younger patients show a greater PTH rise in response to vitamin D insufficiency. Further work is needed to elucidate the underlying mechanisms. References: [1]Wyskida et al., Parathyroid hormone response to different vitamin D levels in population-based old and very-old Polish cohorts, Experimental Gerontology, Volume 127, 2019, 110735, ISSN 0531-5565, https://doi.org/10.1016/j.exger.2019.110735 . [2]Malik M Z, Latiwesh O B, Nouh F, et al. (August 15, 2020) Response of Parathyroid Hormone to Vitamin D Deficiency in Otherwise Healthy Individuals. Cureus 12(8): e9764. doi:10.7759/cureus.9764 Disclosure of Interests: None declared.
Characterization of Clinical Symptoms by Race Among Women With Early-Stage, Hormone Receptor–Positive Breast Cancer Before Starting Chemotherapy
Authors: Xin Hu, Puneet K. Chehal, Cameron Kaplan, Rebecca A. Krukowski, Roy H. Lan, Edward Stepanski, Lee Schwartzberg, Gregory Vidal, Ilana Graetz
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Race disparities persist in breast cancer mortality rates. One factor associated with these disparities may be differences in symptom burden, which may reduce chemotherapy tolerance and increase early treatment discontinuation. <h3>Objectives</h3> To compare symptom burden by race among women with early-stage breast cancer before starting chemotherapy and quantify symptom differences explained by baseline characteristics. <h3>Design, Setting, and Participants</h3> A cross-sectional analysis of symptom burden differences by race among Black and White women with a diagnosis of stage I to III, hormone receptor–positive breast cancer who had a symptom report collected before chemotherapy initiation in a large cancer center in the southern region of the US from January 1, 2007, through December 31, 2015. Analyses were conducted from November 1, 2019, to March 31, 2021. Blinder-Oaxaca decomposition was used, adjusting for baseline sociodemographic and clinical characteristics. <h3>Main Outcomes and Measures</h3> Four symptom composite scores with a mean (SD) of 50 (10) were reported before starting chemotherapy (baseline) and were derived from symptom items: general physical symptoms (11 items), treatment adverse effects (8 items), acute distress (4 items), and despair (7 items). Patients rated the severity of each symptom they experienced in the past week on a scale of 0 to 10 (where 0 indicates not a problem and 10 indicates as bad as possible). <h3>Results</h3> A total of 1338 women (mean [SD] age, 54.6 [11.6] years; 420 Black women [31.4%] and 918 White women [68.6%]) were included in the study. Before starting chemotherapy, Black women reported a statistically significantly higher (ie, worse) symptom composite score than White women for adverse effects (44.5 vs 43.8) but a lower acute distress score (48.5 vs 51.0). Decomposition analyses showed that Black patients' characteristics were associated with higher symptom burden across all 4 scores. However, these differences were offset by relatively greater, statistically significant, unexplained physical, distress, and despair symptom reporting by White patients. <h3>Conclusions and Relevance</h3> In this study, before starting chemotherapy, Black patients with early-stage breast cancer reported significantly higher burden for symptoms that may be exacerbated with chemotherapy and lower distress symptoms compared with White patients. Future studies should explore how symptoms change before and after treatment and differ by racial/ethnic groups and how they are associated with treatment adherence and mortality disparities.