tbuckley/cabot-search huggingface dataset:
Perceptions, knowledge, and perceived competencies of South African speech-language pathologists to render transgender voice and communication training
Authors: Johan Jacobus Maasz, Jeannie van der Linde, Carmen Milton, Marien Alet Graham, Maria Neethling du Toit
Journal: International Journal of Transgender Health (2024)

Background Speech-language pathologists (SLPs) receive extensive education and training on voice and voice disorders. Therefore, they are integral in rendering transgender voice and communication training (TVCT), as part of their scope of practice. Research has, however, identified a lack of confidence in SLPs to render this service due to a perceived lack of education, knowledge, and clinical exposure.
Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis
Authors: Huei-Kai Huang, Albert Tzu-Ming Chuang, Tzu-Chi Liao, Shih-Chieh Shao, Peter Pin-Sung Liu, Yu-Kang Tu, Edward Chia-Cheng Lai
Journal: JAMA Network Open (2024)

Importance Denosumab, a humanized monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is a widely used antiresorptive medication for osteoporosis treatment. Recent preclinical studies indicate that inhibition of RANKL signaling improves insulin sensitivity, glucose tolerance, and β-cell proliferation, suggesting that denosumab may improve glucose homeostasis; however, whether denosumab reduces the risk of incident diabetes remains unclear. Objective To evaluate whether denosumab use is associated with a lower risk of developing diabetes in patients with osteoporosis. Design, Setting, and Participants This nationwide, propensity score–matched cohort study used administrative data from Taiwan’s National Health Insurance Research Database. Adult patients who received denosumab for osteoporosis therapy in Taiwan between 2012 and 2019 were included. To eliminate the inherent bias from confounding by indication, the patients were categorized into a treatment group (34 255 patients who initiated denosumab treatment and adhered to it) and a comparison group (34 255 patients who initiated denosumab treatment but discontinued it after the initial dose) according to the administration status of the second dose of denosumab. Propensity score matching was performed to balance patient characteristics and to control for confounders. Exposure Treatment with denosumab. Main Outcomes and Measures The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. A Cox proportional hazards model was used to estimate the hazard ratio (HR) for incident diabetes. Data were analyzed from January 1 to November 30, 2023. Results After propensity score matching, 68 510 patients were included (mean [SD] age, 77.7 [9.8] years; 57 762 [84.3%] female). During a mean (SD) follow-up of 1.9 (1.6) years, 2016 patients developed diabetes in the treatment group and 3220 developed diabetes in the comparison group (incidence rate, 35.9 vs 43.6 per 1000 person-years). Compared with the comparison group, denosumab treatment was associated with a lower risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90). Several sensitivity analyses also demonstrated similar results of lower diabetes risk associated with denosumab treatment. Conclusions and relevance The results from this cohort study indicating that denosumab treatment was associated with lower risk of incident diabetes may help physicians choose an appropriate antiosteoporosis medication for patients with osteoporosis while also considering the risk of diabetes.
Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease
Authors: Chen-Pei Lin, Irene Frigerio, John G. J. M. Bol, Maud M. A. Bouwman, Alex J. Wesseling, Martin J. Dahl, Annemieke J. M. Rozemuller, Ysbrand D. van der Werf, Petra J. W. Pouwels, Wilma D. J. van de Berg, Laura E. Jonkman
Journal: Translational Neurodegeneration (2024)

Abstract Background Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Diffusion magnetic resonance imaging (MRI) has the potential to evaluate the integrity of the LC noradrenergic system. The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD. Methods Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD, 14 PD, and 8 control brain donors. Fractional anisotropy (FA) and mean diffusivity were derived from the LC, and from tracts between the LC and the anterior cingulate cortex, the dorsolateral prefrontal cortex (DLPFC), the primary motor cortex (M1) or the hippocampus. Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase (DBH) to quantify noradrenergic cell density and fiber load. Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations. Results The AD and PD cases showed loss of LC noradrenergic cells and fibers. In the cortex, the AD cases showed increased DBH + immunoreactivity in the DLPFC compared to PD cases and controls, while PD cases showed reduced DBH + immunoreactivity in the M1 compared to controls. Higher FA within the LC was found for AD, which was correlated with loss of noradrenergic cells and fibers in the LC. Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group, whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group. The tract alterations were not correlated with cortical DBH + immunoreactivity. Conclusions In AD and PD, the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC, rather than noradrenergic changes in the cortex.
Integrating skin color assessments into clinical practice and research: A review of current approaches
Authors: Valerie M. Harvey, Andrew Alexis, Chidubem A.V. Okeke, Lynn McKinley-Grant, Susan C. Taylor, Seemal R. Desai, Tarannum Jaleel, Candrice R. Heath, Sewon Kang, Neelam Vashi, Jenna Lester, Rebecca Vasquez, Michelle Rodrigues, Nada Elbuluk, Iltefat Hamzavi, Shawn G. Kwatra, Hema Sundaram, Caryn Cobb, Stafford G. Brown, Indermeet Kohli, Valerie D. Callender
Journal: Journal of the American Academy of Dermatology (2024)
Global, regional and national epidemiology of alopecia areata: a systematic review and modelling study
Authors: Jae Joon Jeon, Seung-Won Jung, You Hyun Kim, Rosa Parisi, Ju Yeong Lee, Myung Ha Kim, Won-Soo Lee, Solam Lee
Journal: British Journal of Dermatology (2024)

Alopecia areata (AA) is a chronic autoimmune disease that leads to a high psychiatric, economic and systemic disease burden. A comprehensive understanding of AA epidemiology is essential for evaluating healthcare source utilization; however, a systematic approach to summarizing epidemiological data on AA is lacking.
Sequestosome 1 (p62) mitigates hypoxia-induced cardiac dysfunction by stabilizing hypoxia-inducible factor 1α and nuclear factor erythroid 2-related factor 2
Authors: Rajeshwary Ghosh, Amir Nima Fatahian, Omid M T Rouzbehani, Marissa A Hathaway, Tariq Mosleh, Vishaka Vinod, Sidney Vowles, Sophie L Stephens, Siu-Lai Desmond Chung, Isaac D Cao, Anila Jonnavithula, J David Symons, Sihem Boudina
Journal: Cardiovascular Research (2024)

Abstract Aims Heart failure due to ischaemic heart disease (IHD) is a leading cause of mortality worldwide. A major contributing factor to IHD-induced cardiac damage is hypoxia. Sequestosome 1 (p62) is a multi-functional adaptor protein with pleiotropic roles in autophagy, proteostasis, inflammation, and cancer. Despite abundant expression in cardiomyocytes, the role of p62 in cardiac physiology is not well understood. We hypothesized that cardiomyocyte-specific p62 deletion evokes hypoxia-induced cardiac pathology by impairing hypoxia-inducible factor 1α (Hif-1α) and nuclear factor erythroid 2-related factor 2 (Nrf2) signalling. Methods and results Adult mice with germline deletion of cardiomyocyte p62 exhibited mild cardiac dysfunction under normoxic conditions. Transcriptomic analyses revealed a selective impairment in Nrf2 target genes in the hearts from these mice. Demonstrating the functional importance of this adaptor protein, adult mice with inducible depletion of cardiomyocyte p62 displayed hypoxia-induced contractile dysfunction, oxidative stress, and cell death. Mechanistically, p62-depleted hearts exhibit impaired Hif-1α and Nrf2 transcriptional activity. Because findings from these two murine models suggested a cardioprotective role for p62, mechanisms were evaluated using H9c2 cardiomyoblasts. Loss of p62 in H9c2 cells exposed to hypoxia reduced Hif-1α and Nrf2 protein levels. Further, the lack of p62 decreased Nrf2 protein expression, nuclear translocation, and transcriptional activity. Repressed Nrf2 activity associated with heightened Nrf2-Keap1 co-localization in p62-deficient cells, which was concurrent with increased Nrf2 ubiquitination facilitated by the E3 ligase Cullin 3, followed by proteasomal-mediated degradation. Substantiating our results, a gain of p62 in H9c2 cells stabilized Nrf2 and increased the transcriptional activity of Nrf2 downstream targets. Conclusion Cardiac p62 mitigates hypoxia-induced cardiac dysfunction by stabilizing Hif-1α and Nrf2.
Repeated ( <i>S</i> )-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota–brain axis
Authors: Yubin Jiang, Xingming Wang, Jiawei Chen, Yibao Zhang, Kenji Hashimoto, Jian-Jun Yang, Zhiqiang Zhou
Journal: Gut Microbes (2024)

Chronic pain is commonly linked with diminished working memory. This study explores the impact of the anesthetic (S)-ketamine on spatial working memory in a chronic constriction injury (CCI) mouse model, focusing on gut microbiome. We found that multiple doses of (S)-ketamine, unlike a single dose, counteracted the reduced spontaneous alteration percentage (%SA) in the Y-maze spatial working memory test, without affecting mechanical or thermal pain sensitivity. Additionally, repeated (S)-ketamine treatments improved the abnormal composition of the gut microbiome (β-diversity), as indicated by fecal 16S rRNA analysis, and increased levels of butyrate, a key gut – brain axis mediator. Protein analysis showed that these treatments also corrected the upregulated histone deacetylase 2 (HDAC2) and downregulated brain-derived neurotrophic factor (BDNF) in the hippocampi of CCI mice. Remarkably, fecal microbiota transplantation from mice treated repeatedly with (S)-ketamine to CCI mice restored %SA and hippocampal BDNF levels in CCI mice. Butyrate supplementation alone also improved %SA, BDNF, and HDAC2 levels in CCI mice. Furthermore, the TrkB receptor antagonist ANA-12 negated the beneficial effects of repeated (S)-ketamine on spatial working memory impairment in CCI mice. These results indicate that repeated (S)-ketamine administration ameliorates spatial working memory impairment in CCI mice, mediated by a gut microbiota – brain axis, primarily through the enhancement of hippocampal BDNF – TrkB signaling by butyrate.
Treatment for central centrifugal cicatricial alopecia—Delphi consensus recommendations
Authors: Tiaranesha Jackson, Yacine Sow, Jewell Dinkins, Crystal Aguh, Katherine Omueti Ayoade, Victoria Barbosa, Cheryl Burgess, Valerie Callender, George Cotsarelis, Pearl Grimes, Valerie Harvey, Chesahna Kindred, Jenna Lester, Kristen Lo Sicco, Tiffany Mayo, Amy McMichael, Michelle Oboite, Temitayo Ogunleye, Elise Olsen, Achiamah Osei-Tutu, Melissa Piliang, Maryanne Senna, Jerry Shapiro, Antonella Tosti, Cheri Frey, Prince Adotama, Susan C. Taylor
Journal: Journal of the American Academy of Dermatology (2024)
Associations between dermatologic immune-related adverse event morphologies and systemic immunomodulatory/immunosuppressive treatment: A large retrospective cohort study
Authors: Rachel M. Reardon, Katherine L. Perlman, Maria S. Asdourian, Nishi Shah, Ted V. Jacoby, Leah L. Thompson, Kerry L. Reynolds, Yevgeniy R. Semenov, Steven T. Chen
Journal: Journal of the American Academy of Dermatology (2024)
Foxp1 Is Required for Renal Intercalated Cell Differentiation and Acid–Base Regulation
Authors: Shi-Ting Wu, Yu Feng, Renhua Song, Yanmiao Qi, Lin Li, Dongbo Lu, Yixuan Wang, Wenrun Wu, Angela Morgan, Xiaohong Wang, Yin Xia, Renjing Liu, Stephen I. Alexander, Justin Wong, Yuzhen Zhang, Xiangjian Zheng
Journal: Journal of the American Society of Nephrology (2024)

Key Points Foxp1 is a key transcriptional factor for the differentiation of intercalated cells in collecting ducts. Dmrt2 and Hmx2 act downstream of Foxp1 to control the differentiation of type A and type B intercalated cells, respectively. Foxp1 and Dmrt2 are essential for body acid–base balance regulation. Background Kidney collecting ducts comprise principal cells and intercalated cells, with intercalated cells playing a crucial role in kidney acid–base regulation through H + and HCO 3 − secretion. Despite its significance, the molecular mechanisms controlling intercalated cell development remain incompletely understood. Methods To investigate the specific role of Foxp1 in kidney tubular system, we specifically deleted Foxp1 expression in kidney distal nephrons and collecting ducts. We examined the effects of Foxp1 on intercalated cell differentiation and urine acidification. RNA sequencing and Chip-seq were used to identify Foxp1 target genes. To dissect the genetic network that regulates intercalated cell differentiation, Dmrt2 -deficient mice were generated to determine the role of Dmrt2 in intercalated cell differentiation. Foxp1 -deficient mice were crossed with Notch2 -deficient mice to dissect the relation between Foxp1 and Notch signaling. Results Foxp1 was selectively expressed in intercalated cells in collecting ducts. The absence of Foxp1 in kidney tubules led to the abolishment of intercalated cell differentiation in the collecting ducts, resulting in distal renal tubular acidosis. Foxp1 regulates the expression of Dmrt2 and Hmx2 , two genes encoding transcription factors specifically expressed in type A and type B intercalated cell cells, respectively. Further genetic analysis revealed that Dmrt2 was essential for type A intercalated cell differentiation, and Foxp1 was necessary downstream of Notch for the regulation of intercalated cell differentiation. Conclusions Foxp1 is required for the renal intercalated cell differentiation and participated in acid–base regulation. Foxp1 regulated downstream transcriptional factors, Dmrt2 and Hmx2, which were involved in the specification of distinct subsets of intercalated cells.
Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms—a Danish longitudinal study
Authors: Morten Kranker Larsen, Vibe Skov, Lasse Kjær, Christina Schjellerup Eickhardt-Dalbøge, Trine Alma Knudsen, Marie Hvelplund Kristiansen, Anders Lindholm Sørensen, Troels Wienecke, Morten Andersen, Johnny T. Ottesen, Johanne Gudmand-Høyer, Jordan Andrew Snyder, Mikkel Porsborg Andersen, Christian Torp-Pedersen, Henrik Enghusen Poulsen, Thomas Stiehl, Hans Carl Hasselbalch, Christina Ellervik
Journal: Blood Cancer Journal (2024)

Abstract The neutrophil-to-lymphocyte ratio(NLR) is increased in chronic inflammation and myeloproliferative neoplasms (MPN). We hypothesize that NLR is associated with all-cause mortality and mortality by comorbidity burden in the general population and individuals with MPN. We included 835,430 individuals from The Danish General Suburban Population Study, general practitioners, and outpatient clinics. We investigated NLR on mortality stratified by prevalent and incident MPN, essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), comorbidity burden (CCI-score), and the Triple-A risk score using hazard ratio (HR) and 95% confidence interval (95%CI). NLR 1–1.9 was the reference level. During a median follow-up of 11.2 years, 197,802 deaths were recorded. All-cause mortality increased for a stepwise increasing NLR with a HR (95%CI) for NLR ≥ 6 of 2.06(2.03–2.09) for the whole population and 2.93(2.44–3.50) in prevalent MPN. ET, PV, and MF had a HR (95%CI) for NLR ≥ 2 of 2.14(1.71–2.69), 2.19(1.89–2.54), and 2.31(1.91–2.80). Results were similar for incident MPN. Mortality was higher for stepwise increasing NLR and CCI-score( p interaction &lt; 2×10 –16 ), with a HR for NLR ≥ 6 of 2.23(2.17–2.29), 4.10(4.01–4.20), and 7.69(7.50–7.89), for CCI-score 0, 1–2, or ≥3. The Triple-A risk score demonstrated alignment with NLR. Increasing NLR and comorbidity burden were associated with lower survival in individuals without MPN but were even worse in prevalent and incident MPN, ET, PV, and MF.
Circulating tumor cells in Waldenström macroglobulinemia
Authors: Clémentine Boccon-Gibod, Elise Sourdeau, Pierre Morel, Elise Chapiro, Florence Nguyen-Khac, Clotilde Bravetti, Frédéric Davi, Véronique Morel, Nicolas Gauthier, Adrien Grenier, Inès Boussen, Sylvain Choquet, Véronique Leblond, Magali Le Garff-Tavernier, Marine Baron, Damien Roos-Weil
Journal: Leukemia (2024)
Periodic Lamellae‐Based Nanofibers for Precise Immunomodulation to Treat Inflammatory Bone Loss in Periodontitis
Authors: Ze He, Yao Liu, Zi‐Li Zheng, Jia‐Cheng Lv, Shi‐Bo Liu, Ju Zhang, Hang‐Hang Liu, Jia‐Zhuang Xu, Zhong‐Ming Li, En Luo
Journal: Advanced Healthcare Materials (2024)

Periodontitis is a common oral disease accompanied by inflammatory bone loss. The pathological characteristics of periodontitis usually accompany an imbalance in the periodontal immune microenvironment, leading to difficulty in bone regeneration. Therefore, effective treatment strategies are needed to modulate the immune environment in order to treat periodontitis. Here, highly-oriented periodic lamellae poly(ε-caprolactone) electrospun nanofibers (PLN) are developed by surface-directed epitaxial crystallization. The in vitro result shows that the PLN can precisely modulate macrophage polarization toward the M2 phenotype. Macrophages polarized by PLN significantly enhance the migration and osteogenic differentiation of Bone marrow stromal cells. Notably, results suggest that the topographical cues presented by PLN can modulate macrophage polarization by activating YAP, which reciprocally inhibits the NF-κB signaling pathway. The in vivo results indicate that PLN can inhibit inflammatory bone loss and facilitate bone regeneration in periodontitis. The authors' findings suggest that topographical nanofibers with periodic lamellae is a promising strategy for modulating immune environment to treat inflammatory bone loss in periodontitis.
Expression of concern: Excess mortality attributed to heat and cold: a health impact assessment study in 854 cities in Europe
Authors: None The Lancet Planetary Health Editors
Journal: The Lancet Planetary Health (2024)

On March 16, 2023, The Lancet Planetary Health published an article entitled “Excess mortality attributed to heat and cold: a health impact assessment study in 854 cities in Europe”. In July, 2023, the first author contacted the editorial office to alert us that the author team had found a coding error. This error does not invalidate the paper's major findings, in particular regarding the spatial distribution of excess mortality linked to heat and cold, and the conclusions of the article remain the same. However, correcting this error does result in many changes to the numbers throughout the text as well as changes to the tables and figures, and the overall effect is to reduce the magnitude of the estimates, consistently for heat and cold and across locations. Since being alerted, the Editors have been working with the Authors on how best to correct the record. While we resolve this issue, we wish to alert readers to these concerns, and will provide an update when available. Excess mortality attributed to heat and cold: a health impact assessment study in 854 cities in EuropeMaps of mortality risks and excess deaths indicate geographical differences, such as a north–south gradient and increased vulnerability in eastern Europe, as well as local variations due to urban characteristics. The modelling framework and results are crucial for the design of national and local health and climate policies and for projecting the effects of cold and heat under future climatic and socioeconomic scenarios. Full-Text PDF Open Access
Reducing transfusion utilization for children with sickle cell anemia in sub‐Saharan Africa with hydroxyurea: Analysis from the phase <scp>I</scp>/<scp>II REACH</scp> trial
Authors: Alexandra Power‐Hays, George A. Tomlinson, Leon Tshilolo, Brígida Santos, Thomas N. Williams, Peter Olupot‐Olupot, Luke R. Smart, Banu Aygun, Adam Lane, Susan E. Stuber, Teresa Latham, Russell E. Ware
Journal: American Journal of Hematology (2024)

Abstract Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two‐month pre‐treatment screening period followed by 6 months of fixed‐dose hydroxyurea (15–20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios (IRR) across treatment periods were calculated. Among 635 enrolled children with 4124 person‐years of observation, 258 participants (40.4%) received 545 transfusions. The transfusion rate per 100 person‐years was 43.2 before hydroxyurea, 21.7 on fixed‐dose, 14.5 during dose escalation, and 10.8 on MTD. During MTD, transfusion incidence was reduced by 75% compared to pre‐treatment (IRR 0.25, 95% confidence interval [CI] 0.18–0.35, p &lt; .0001), and by 50% compared to fixed dose (IRR 0.50, 95% CI 0.39–0.63, p &lt; .0001). Hydroxyurea at MTD decreases transfusion utilization in African children with SCA. If widely implemented, universal testing and hydroxyurea treatment at MTD could potentially prevent 21% of all pediatric transfusions administered in sub‐Saharan Africa. Increasing hydroxyurea access for SCA should decrease the transfusion burden and increase the overall blood supply.
Global burden of vaccine-associated alopecia, 1979–2023: a comprehensive analysis of the international pharmacovigilance database
Authors: Seoyeon Kyung, Selin Woo, Minji Kim, Hayeon Lee, Jiseung Kang, Masoud Rahmati, Dong Keon Yon
Journal: British Journal of Dermatology (2024)

While global concern over vaccine-associated alopecia has been gradually increasing, it has also been reported that alopecia, classified as an autoimmune disease, can manifest as an immune-related side-effect caused by vaccinations. However, comprehensive research on vaccine-associated alopecia has been limited. Therefore, we carried out a comprehensive analysis using information from VigiBase (1979–2023) from more than 156 countries, managed by the WHO and the Uppsala Monitoring Centre. Thus, this global pharmacovigilance study of vaccine-associated alopecia, encompassing all age and sex groups, provides international and comprehensive evidence that substantiates the overall real-world impact of vaccines.
Corrigendum to “On-site fabrication of bi-layered adhesive mesenchymal stromal cell dressings for the treatment of heart failure” [Biomaterials 209 (2019) 41–53]
Authors: Kazuya Kobayashi, Yuki Ichihara, Nobuhiko Sato, Nobuyoshi Umeda, Laura Fields, Masafumi Fukumitsu, Yoshiyuki Tago, Tomoya Ito, Satoshi Kainuma, Mihai Podaru, Fiona Lewis-McDougall, Kenichi Yamahara, Rakesh Uppal, Ken Suzuki
Journal: Biomaterials (2024)