Recent Publications

Sci Rep. 2024 Feb 27;14(1):4738. doi: 10.1038/s41598-024-55443-5.

ABSTRACT

This study focuses on the importance of early and regular Antenatal Care (ANC) visits in reducing maternal and child mortality rates in Bangladesh, a country where such health indicators are a concern. The research utilized data from the Bangladesh Demographic and Health Survey (BDHS) conducted in 2017-18 and employed the Cox proportional hazard model to identify factors influencing women's intention of ANC services. The results revealed that 40.4% of women engaged in at least one ANC activity during the first trimester, which, although higher than in other countries, falls below the global average. Notably, women between the aged of 25 and 29 years took 15% less time for their first ANC visit compared to their younger counterparts, suggesting higher awareness and preparedness in this age group. Education, both for women and their partners, had a significant influence on the intention to visit ANC early. Women in the poor wealth quantile exhibited lower odds of seeking timely ANC, whereas those with a planned pregnancy were more likely to do so. Moreover, access to mass media decreased the timing of ANC visits by 26% compared to women who were not exposed. Moreover, living in rural areas was linked to a 17% delay in the timing of the first ANC visit compared to urban areas. These findings underscore the importance of addressing these determinants to improve the timeliness and accessibility of ANC services, thereby enhancing maternal and child health outcomes in Bangladesh.

PMID:38413798 | DOI:10.1038/s41598-024-55443-5

Br J Oral Maxillofac Surg. 2023 Dec 29:S0266-4356(23)00608-3. doi: 10.1016/j.bjoms.2023.12.013. Online ahead of print.

ABSTRACT

This prospective cohort study examined the changes in airway area and soft tissue parameters following interpositional arthroplasty for temporomandibular joint (TMJ) ankylosis. Ten patients with TMJ ankylosis underwent surgery, and preoperative and postoperative skeletal and soft tissue measurements were obtained. A significant rise in soft tissue parameters was observed following surgery, although only minor changes in skeletal parameters were seen. The nasoropharyngeal area, oral area, soft palate area, and tongue area were examined. After the surgery, increases in values were observed in the nasoropharyngeal area (from 3482.4 mm2 to 3618.7 mm2), the oral area (from 2731.8 mm2 to 2840.8 mm2), the soft palate area (from 204.9 mm2 to 217.3 mm2), and the tongue area (from 2577.5 mm2 to 2600.8 mm2). These findings suggest that interpositional arthroplasty can improve airway area and soft tissue dimensions, affecting the stomatognathic system's aesthetic and functional aspects. Further research is needed to validate these results and assess long-term stability.

PMID:38413292 | DOI:10.1016/j.bjoms.2023.12.013

Tob Induc Dis. 2024 Feb 26;22. doi: 10.18332/tid/184053. eCollection 2024.

ABSTRACT

INTRODUCTION: JUUL is a high-nicotine pod-based vaping device that is popular among adolescents and young adults. On 23 June 2022, the US Food and Drug Administration (FDA) denied authorization to market JUUL, and ordered JUUL Labs to remove products from the US market. The next day, a US federal appeals court temporarily suspended the ban. The mixed public discourse surrounding the FDA ban warrants further investigation.

METHODS: This study examined Twitter data to describe public reaction to these announcements. Posts containing terms 'JUUL' and/or '#JUUL' (N=97548 unique tweets) were collected from 23 June to 3 July 2022, from Twitter's Streaming Application Programming Interface (API). After removing retweets, we used an inductive approach to become familiar with the data, generated a codebook, and conducted a content analysis on a random sample of n=4000 tweets.

RESULTS: A total of 2755 (68.9%) tweets discussed JUUL in the context of the FDA ban. News (n=1425/2755; 51.7%) about the JUUL ban, government distrust (n=588; 21.3%), and individual rights (n=253; 9.2%) were the most prevalent themes. Less commonly discussed themes included inconsistencies between policies (n=174; 6.3%), mentions of switching to other products (n=162; 5.9%), smoking cessation (n=99; 3.6%), and craving for JUUL (n=94; 3.4%). Sentiment analysis of JUUL ban-related posts (n=2755) demonstrated that 1989 (72.2%) tweets were categorized as neutral, while anti-ban posts (n=566; 20.5%) were more prevalent than pro-ban posts (n=200; 7.3%).

CONCLUSIONS: Besides straightforward announcements of the JUUL ban and its suspension, Twitter posts discussed government distrust, individual rights, and policy inconsistencies. While most posts conveyed neutral sentiments, anti-ban posts were almost three times more prevalent than pro-ban posts. Our findings suggest that text-based social media platforms like Twitter may be an effective instrument to understand opinions, attitudes, and beliefs regarding the FDA's JUUL ban.

PMID:38410122 | PMC:PMC10895646 | DOI:10.18332/tid/184053

Spine (Phila Pa 1976). 2024 Feb 26. doi: 10.1097/BRS.0000000000004971. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective analysis of prospectively collected data.

OBJECTIVE: To identify the best definition of primary anteverted pelvis in the setting of adult spine deformity (ASD), and to investigate whether this is a pathologic setting that requires surgical correction.

SUMMARY OF BACKGROUND DATA: While pelvic retroversion has been thoroughly investigated, pelvic anteversion (AP) is a far lesser discussed topic. Four different AP definitions have been proposed, and AP has been described as a normal or pathologic entity by different authors.

METHODS: All patients consulting for ASD at the five participating sites were included. Firstly, the four definitions of AP were compared with descriptive statistics (anatomic method - Pelvic Tilt <0°; Relative Pelvic Version method - RPV >5°; Roussouly method - Pelvic Incidence (PI)<50° and Sacral Slope (SS)>35°); low PT method - PT/PI <25th percentile). Secondly a subgroup analysis among operated AP patients with a two-year follow-up was performed. Complication rate, radiographic parameters and clinical scores (ODI, SF-36) were compared in a multivariate analysis between patients who did and did not maintain an AP at the 2-year follow-up.

RESULTS: 1163 patients were available for the first analysis. The RPV method appeared to be the most appropriate to define AP in ASD patient. For the second analysis, data on 410 subjects were available, and most of them were young adults with idiopathic scoliosis that did not require pelvic fixation. AP patients who maintained an AP after ASD surgery presented comparable radiographic and clinical outcomes to the patients who presented a normo/retroverted pelvis after surgery.

CONCLUSIONS: According to the results of the presented study, the RPV method is the most appropriate to define primary AP, which is not a pathologic condition and is most often observed in young adults with idiopathic scoliosis. Anteverted pelvis does not require direct surgical correction in this patient group.

PMID:38407226 | DOI:10.1097/BRS.0000000000004971

Med Oncol. 2024 Feb 23;41(3):77. doi: 10.1007/s12032-024-02304-w.

NO ABSTRACT

PMID:38393647 | DOI:10.1007/s12032-024-02304-w

J Biomech. 2024 Feb 15:111990. doi: 10.1016/j.jbiomech.2024.111990. Online ahead of print.

ABSTRACT

Nucleus replacement devices (NRDs) have potential to treat degenerated or herniated intervertebral discs (IVDs). However, IVD height loss is a post-treatment complication. IVD height recovery involves the nucleus pulposus (NP), but the mechanism of this in response to physiological loads is not fully elucidated. This study aimed to characterise the non-linear recovery behaviour of the IVD in intact, post-nuclectomy, and post-NRD treatment states, under physiological loading. 36 bovine IVDs (12 intact, 12 post-nuclectomy, 12 post-treatment) underwent creep-recovery protocols simulating Sitting, Walking or Running, followed by 12 h of recovery. A rheological model decoupled the fluid-independent (elastic, fast) and fluid-dependent (slow) recovery phases. In post-nuclectomy and post-treatment groups, nuclectomy efficiency (ratio of NP removed to remaining NP) was quantified following post-test sectioning. Relative to intact, post-nuclectomy recovery significantly decreased in Sitting (-0.3 ± 0.4 mm, p < 0.05) and Walking (-0.6 ± 0.3 mm, p < 0.001) coupled with significant decreases to the slow response (p < 0.05). Post-nuclectomy, the fast and slow responses negatively correlated with nuclectomy efficiency (p < 0.05). In all protocols, the post-treatment group performed significantly worse in recovery (-0.5 ± 0.3 mm, p < 0.01) and the slow response (p < 0.05). Results suggest the NP mainly facilitates slow-phase recovery, linearly dependent on the amount of NP present. Failure of this NRD to recover is attributed to poor fluid imbibition. Additionally, unconfined NRD performance cannot be extrapolated to the in vitro response. This knowledge informs NRD design criteria to provide high osmotic pressure, and encourages testing standards to incorporate long-term recovery protocols.

PMID:38383232 | DOI:10.1016/j.jbiomech.2024.111990

Sci Adv. 2024 Feb 23;10(8):eadj3582. doi: 10.1126/sciadv.adj3582. Epub 2024 Feb 21.

ABSTRACT

The cellular helical structure is well known for its crucial role in development and disease. Nevertheless, the underlying mechanism governing this phenomenon remains largely unexplored, particularly in recapitulating it in well-controlled engineering systems. Leveraging advanced microfluidics, we present compelling evidence of the spontaneous emergence of helical endothelial tubes exhibiting robust right-handedness governed by inherent cell chirality. To strengthen our findings, we identify a consistent bias toward the same chirality in mouse vascular tissues. Manipulating endothelial cell chirality using small-molecule drugs produces a dose-dependent reversal of the handedness in engineered vessels, accompanied by non-monotonic changes in vascular permeability. Moreover, our three-dimensional cell vertex model provides biomechanical insights into the chiral morphogenesis process, highlighting the role of cellular torque and tissue fluidity in its regulation. Our study unravels an intriguing mechanism underlying vascular chiral morphogenesis, shedding light on the broader implications and distinctive perspectives of tubulogenesis within biological systems.

PMID:38381835 | DOI:10.1126/sciadv.adj3582

Sci Adv. 2024 Feb 23;10(8):eadj0758. doi: 10.1126/sciadv.adj0758. Epub 2024 Feb 21.

ABSTRACT

Isotope effects have received increasing attention in materials science and engineering because altering isotopes directly affects phonons, which can affect both thermal properties and optoelectronic properties of conventional semiconductors. However, how isotopic mass affects the optoelectronic properties in 2D semiconductors remains unclear because of measurement uncertainties resulting from sample heterogeneities. Here, we report an anomalous optical bandgap energy red shift of 13 (±7) milli-electron volts as mass of Mo isotopes is increased in laterally structured 100MoS2-92MoS2 monolayers grown by a two-step chemical vapor deposition that mitigates the effects of heterogeneities. This trend, which is opposite to that observed in conventional semiconductors, is explained by many-body perturbation and time-dependent density functional theories that reveal unusually large exciton binding energy renormalizations exceeding the ground-state renormalization energy due to strong coupling between confined excitons and phonons. The isotope effect on the optical bandgap reported here provides perspective on the important role of exciton-phonon coupling in the physical properties of two-dimensional materials.

PMID:38381831 | DOI:10.1126/sciadv.adj0758

Mol Pain. 2024 Jan-Dec;20:17448069241230420. doi: 10.1177/17448069241230420.

ABSTRACT

Ca2+ imaging is frequently used in the investigation of sensory neuronal function and nociception. In vitro imaging of acutely dissociated sensory neurons using membrane-permeant fluorescent Ca2+ indicators remains the most common approach to study Ca2+ signalling in sensory neurons. Fluo4 is a popular choice of single-wavelength indicator due to its brightness, high affinity for Ca2+ and ease of use. However, unlike ratiometric indicators, the emission intensity from single-wavelength indicators can be affected by indicator concentration, optical path length, excitation intensity and detector efficiency. As such, without careful calibration, it can be difficult to draw inferences from differences in the magnitude of Ca2+ transients recorded using Fluo4. Here, we show that a method scarcely used in sensory neurophysiology - first proposed by Maravall and colleagues (2000) - can provide reliable estimates of absolute cytosolic Ca2+ concentration ([Ca2+]cyt) in acutely dissociated sensory neurons using Fluo4. This method is straightforward to implement; is applicable to any high-affinity single-wavelength Ca2+ indicator with a large dynamic range; and provides estimates of [Ca2+]cyt in line with other methods, including ratiometric imaging. Use of this method will improve the granularity of sensory neuron Ca2+ imaging data obtained with Fluo4.

PMID:38379503 | DOI:10.1177/17448069241230420

Int J Cardiol Heart Vasc. 2024 Feb 9;51:101339. doi: 10.1016/j.ijcha.2024.101339. eCollection 2024 Apr.

ABSTRACT

BACKGROUND: Cardiac magnetic resonance imaging (CMR) based T1 mapping and extracellular volume fraction (ECV) are powerful tools for identifying myocardial fibrosis. This systematic review and meta-analysis aims to characterize the utility of native T1 mapping and ECV in patients with non-ischemic cardiomyopathy (NICM) and to clarify the prognostic significance of elevated values.

METHODS: A literature search was conducted for studies reporting on use of CMR-based native T1 mapping and ECV measurement in NICM patients and their association with major adverse cardiac events (MACE), ventricular arrhythmias (VAs), and left ventricular reverse remodeling (LVRR). Databases searched included: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status.

RESULTS: Native T1 and ECV were significantly higher in NICM patients compared to controls (MD 78.80, 95 % CI 50.00, 107.59; p < 0.01; MD 5.86, 95 % CI 4.55, 7.16; p < 0.01). NICM patients who experienced MACE had higher native T1 and ECV (MD 52.87, 95 % CI 26.59, 79.15; p < 0.01; MD 6.03, 95 % CI 3.79, 8.26; p < 0.01). There was a non-statistically significant trend toward higher native T1 time in NICM patients who experienced VAs. NICM patients who were poor treatment responders had higher baseline native T1 and ECV (MD 40.58, 95 % CI 12.90, 68.25; p < 0.01; MD 3.29, 95 % CI 2.25, 4.33; p < 0.01).

CONCLUSIONS: CMR-based native T1 and ECV quantification may be useful tools for risk stratification of patients with NICM. They may provide additional diagnostic utility in combination with LGE, which poorly characterizes fibrosis in patients with diffuse myocardial involvement.

PMID:38371310 | PMC:PMC10873728 | DOI:10.1016/j.ijcha.2024.101339

Transpl Int. 2024 Feb 2;36:11792. doi: 10.3389/ti.2023.11792. eCollection 2023.

ABSTRACT

90% of the UK diabetic population are classified as T2DM. This study aims to compare outcomes after SPK transplant between recipients with T1DM or T2DM. Data on all UK SPK transplants from 2003-2019 were obtained from the NHSBT Registry (n = 2,236). Current SPK transplant selection criteria for T2DM requires insulin treatment and recipient BMI < 30 kg/m2. After exclusions (re-transplants/ambiguous type of diabetes) we had a cohort of n = 2,154. Graft (GS) and patient (PS) survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Complications were compared using chi-squared analyses. 95.6% of SPK transplants were performed in recipients with T1DM (n = 2,060). Univariate analysis showed comparable outcomes for pancreas GS at 1 year (p = 0.120), 3 years (p = 0.237), and 10 years (p = 0.196) and kidney GS at 1 year (p = 0.438), 3 years (p = 0.548), and 10 years (p = 0.947). PS was comparable at 1 year (p = 0.886) and 3 years (p = 0.237) and at 10 years (p = 0.161). Multi-variate analysis showed comparable outcomes in pancreas GS (p = 0.564, HR 1.221, 95% CI 0.619, 2.406) and PS(p = 0.556, HR 1.280, 95% CI 0.563, 2.911). Comparable rates of common complications were demonstrated. This is the largest series outside of the US evaluating outcomes after SPK transplants and shows similar outcomes between T1DM and T2DM recipients. It is hoped dissemination of this data will lead to increased referral rates and assessment of T2DM patients who could benefit from SPK transplantation.

PMID:38370534 | PMC:PMC10869449 | DOI:10.3389/ti.2023.11792

Br J Surg. 2024 Jan 31;111(2):znae020. doi: 10.1093/bjs/znae020.

NO ABSTRACT

PMID:38364060 | DOI:10.1093/bjs/znae020

JMIR Form Res. 2024 Feb 16;8:e44717. doi: 10.2196/44717.

ABSTRACT

BACKGROUND: Respiratory rate is a crucial indicator of disease severity yet is the most neglected vital sign. Subtle changes in respiratory rate may be the first sign of clinical deterioration in a variety of disease states. Current methods of respiratory rate monitoring are labor-intensive and sensitive to motion artifacts, which often leads to inaccurate readings or underreporting; therefore, new methods of respiratory monitoring are needed. The PulsON 440 (P440; TSDR Ultra Wideband Radios and Radars) radar module is a contactless sensor that uses an ultrawideband impulse radar to detect respiratory rate. It has previously demonstrated accuracy in a laboratory setting and may be a useful alternative for contactless respiratory monitoring in clinical settings; however, it has not yet been validated in a clinical setting.

OBJECTIVE: The goal of this study was to (1) compare the P440 radar module to gold standard manual respiratory rate monitoring and standard of care telemetry respiratory monitoring through transthoracic impedance plethysmography and (2) compare the P440 radar to gold standard measurements of respiratory rate in subgroups based on sex and disease state.

METHODS: This was a pilot study of adults aged 18 years or older being monitored in the emergency department. Participants were monitored with the P440 radar module for 2 hours and had gold standard (manual respiratory counting) and standard of care (telemetry) respiratory rates recorded at 15-minute intervals during that time. Respiratory rates between the P440, gold standard, and standard telemetry were compared using Bland-Altman plots and intraclass correlation coefficients.

RESULTS: A total of 14 participants were enrolled in the study. The P440 and gold standard Bland-Altman analysis showed a bias of -0.76 (-11.16 to 9.65) and an intraclass correlation coefficient of 0.38 (95% CI 0.06-0.60). The P440 and gold standard had the best agreement at normal physiologic respiratory rates. There was no change in agreement between the P440 and the gold standard when grouped by admitting diagnosis or sex.

CONCLUSIONS: Although the P440 did not have statistically significant agreement with gold standard respiratory rate monitoring, it did show a trend of increased agreement in the normal physiologic range, overestimating at low respiratory rates, and underestimating at high respiratory rates. This trend is important for adjusting future models to be able to accurately detect respiratory rates. Once validated, the contactless respiratory monitor provides a unique solution for monitoring patients in a variety of settings.

PMID:38363588 | DOI:10.2196/44717

Eur J Med Res. 2024 Feb 15;29(1):124. doi: 10.1186/s40001-024-01711-z.

ABSTRACT

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs.

PMID:38360737 | DOI:10.1186/s40001-024-01711-z

Am J Transplant. 2024 Feb 13:S1600-6135(24)00134-5. doi: 10.1016/j.ajt.2024.02.008. Online ahead of print.

ABSTRACT

Time to arrest in donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischaemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following DCD SPK transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated by a Cox proportional hazards model. Adjusted restricted cubic spline (RCS) models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (aHR 0.98, 95% CI 0.68-1.41, P=0.901). Increasing asystolic time worsened graft survival (aHR 2.51, 95% CI 1.16-5.43, P=0.020). RCS modelling revealed a non-linear relationship was demonstrated between asystolic time and graft survival, and no relationship between TTD and graft survival. We found no evidence that TTD impacts on pancreas graft survival after DCD SPK transplantation, however increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimise asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

PMID:38360185 | DOI:10.1016/j.ajt.2024.02.008

EClinicalMedicine. 2024 Feb 7;69:102465. doi: 10.1016/j.eclinm.2024.102465. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established.

METHODS: For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD).

FINDINGS: A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n = 3362) and 29.1% (n = 2624), respectively. 35.9% (n = 3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n = 204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40-62), compared to 73 years (IQR 64-80) in the general population (p < 0.0001).

INTERPRETATION: The ENLSR represents the first comprehensive national registry of PV carriers in England and one of the largest cohorts of MMR PV carriers worldwide. The establishment of a secure, centralised infrastructure and mechanism for routine registration of newly identified carriers ensures sustainability of the data resource.

FUNDING: This work was funded by the Wellcome Trust, Cancer Research UK and Bowel Cancer UK. The funder of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

PMID:38356732 | PMC:PMC10864212 | DOI:10.1016/j.eclinm.2024.102465

Nat Commun. 2024 Feb 13;15(1):1334. doi: 10.1038/s41467-024-45680-7.

ABSTRACT

G protein-coupled receptors (GPCRs) bind to different G protein α-subtypes with varying degrees of selectivity. The mechanism by which GPCRs achieve this selectivity is still unclear. Using 13C methyl methionine and 19F NMR, we investigate the agonist-bound active state of β1AR and its ternary complexes with different G proteins in solution. We find the receptor in the ternary complexes adopts very similar conformations. In contrast, the full agonist-bound receptor active state assumes a conformation differing from previously characterised activation intermediates or from β1AR in ternary complexes. Assessing the kinetics of binding for the agonist-bound receptor with different G proteins, we find the increased affinity of β1AR for Gs results from its much faster association with the receptor. Consequently, we suggest a kinetic-driven selectivity gate between canonical and secondary coupling which arises from differential favourability of G protein binding to the agonist-bound receptor active state.

PMID:38351103 | DOI:10.1038/s41467-024-45680-7

J Public Health Res. 2024 Feb 8;13(1):22799036241231544. doi: 10.1177/22799036241231544. eCollection 2024 Jan.

ABSTRACT

Terrorism has emerged as an increasingly pressing global issue, giving rise to escalating casualties and devastating implications for peace and security. The low- and middle-income countries (LMICs), already grappling with inadequate healthcare services and an estimated annual mortality toll ranging from 5.7 to 8.4 million, face further setbacks as terrorism exacerbates their prevailing healthcare deficiencies. Among the aspects of how terrorism affects healthcare in LMICs are high morbidity, mortality, and treatment wait times. The four principal areas of reverberation encompass amplified vulnerabilities in healthcare systems, financial shortfalls in LMIC healthcare systems, worsened personnel shortages in healthcare, and the devastating impact on healthcare facilities. In response to these challenges, international organizations and countries have played a pivotal role in mitigating the impact of terrorism on healthcare systems. Additionally, to improve healthcare in these regions, investing in infrastructure, supporting healthcare workers, and ensuring safety are paramount. Implementing mobile health interventions, traditional medicine, and mobile laboratories may enhance healthcare accessibility. Further, employing blockchain technology for data security and supply chain management may strengthen healthcare systems in these areas.

PMID:38343397 | PMC:PMC10854384 | DOI:10.1177/22799036241231544

Cancer Res Commun. 2024 Feb 9. doi: 10.1158/2767-9764.CRC-23-0244. Online ahead of print.

ABSTRACT

Estrogen receptor-positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy. In this study, we investigated ESR1 mutations as novel targets for breast cancer immunotherapy. Using machine learning algorithms, we identified ESR1-derived peptides predicted to form stable complexes with HLA-A *0201. We then validated the binding affinity and stability of the top predicted peptides through in-vitro binding and dissociation assays and showed that these peptides bind HLA-A*0201 with high affinity and stability. Using tetramer assays, we confirmed the presence and expansion potential of antigen-specific cytotoxic T lymphocytes (CTLs) from healthy female donors. Lastly, using in-vitro cytotoxicity assays, we showed the lysis of peptide-pulsed targets and breast cancer cells expressing common ESR1 mutations by expanded antigen-specific CTLs. Ultimately, we identified five peptides derived from the three most common ESR1 mutations (D538G, Y537S, and E380Q) and their associated wild-type peptides, which were the most immunogenic. Overall, these data confirm the immunogenicity of epitopes derived from ESR1 and highlight the potential of these peptides to be targeted by novel immunotherapy strategies.

PMID:38335301 | DOI:10.1158/2767-9764.CRC-23-0244

Front Cardiovasc Med. 2024 Jan 25;11:1284562. doi: 10.3389/fcvm.2024.1284562. eCollection 2024.

ABSTRACT

Dyslipidemia is a leading contributor to atherosclerotic cardiovascular disease (ASCVD). There has been a significant improvement in the treatment of dyslipidemia in the past 10 years with the development of new pharmacotherapies. The intent of this review is help enhance clinicians understanding of non-statin lipid lowering therapies in accordance with the 2022 American College of Cardiology Expert Consensus Clinical Decision Pathway on the Role of Non-statin Therapies for LDL-Cholesterol Lowering. We also present a single-center experience implementing a systematic inpatient protocol for lipid lowering therapy for secondary prevention of ASCVD.

PMID:38333418 | PMC:PMC10851935 | DOI:10.3389/fcvm.2024.1284562