Tag: nevin manimala

Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2414009121. doi: 10.1073/pnas.2414009121. Epub 2024 Dec 30.

ABSTRACT

Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order. We analyze the deformations induced by the cells in the extracellular matrix and find broadly distributed strain bands with a prevalence of compression. A model of active nematic hydrodynamics is able to describe several statistical features of the experimentally observed flow, suggesting that collective cancer cell invasion can be interpreted as a nematic active fluid in the turbulent regime. Our results help elucidate the migration patterns of cancer cells in vivo and provide quantitative guidance for the development of realistic in vitro and in silico models for collective cell migration.

PMID:39793073 | DOI:10.1073/pnas.2414009121

Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2422543121. doi: 10.1073/pnas.2422543121. Epub 2024 Dec 30.

ABSTRACT

Among the most pressing problems societies face today are economic inequality and the erosion of democratic norms and institutions. In fact the two problems-inequality and democratic erosion-are linked. In a large cross-national statistical study of risk factors for democratic erosion, we establish that economic inequality is one of the strongest predictors of where and when democracy erodes. Even wealthy and longstanding democracies are vulnerable if they are highly unequal (though national wealth might provide some resiliency). The association between inequality and risk of democratic backsliding is robust, and holds under different measures and structures of both income inequality and wealth inequality. The association is unlikely to be a case of reverse causation. For concerned citizens seeking to understand why so many democracies are eroding and how to stop this process, our study indicates that policies for ameliorating inequality are a promising path forward.

PMID:39793070 | DOI:10.1073/pnas.2422543121

Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2411348121. doi: 10.1073/pnas.2411348121. Epub 2024 Dec 30.

ABSTRACT

Collaborative management partnerships (CMPs) between state wildlife authorities and nonprofit conservation organizations to manage protected areas (PAs) have been used increasingly across Sub-Saharan Africa since the 2000s. They aim to attract funding, build capacity, and increase the environmental effectiveness of PAs. Our study documents the rise of CMPs, examines their current extent, and measures their effectiveness in protecting habitats. We combine statistical matching and Before-After-Control-Intervention regressions to quantify the impact of CMPs, using tree cover loss as a proxy. We identify 127 CMPs located in 16 countries. CMPs are more often located in remote PAs, with habitats that are least threatened by human activity. Our results indicate that, on average, each year in a CMP results in an annual decrease in tree cover loss of about 55% compared to PAs without CMPs. Where initial anthropogenic pressure was low, we measure no effect. Where it was high, we see a 66% decrease in tree cover loss. This highly heterogeneous effect illustrates the importance of moving beyond average effect size when assessing conservation interventions, as well as the need for policy makers to invest public funds to protect the areas the most at risk.

PMID:39793059 | DOI:10.1073/pnas.2411348121

J Med Internet Res. 2025 Jan 10;27:e55066. doi: 10.2196/55066.

ABSTRACT

BACKGROUND: Objective structured clinical examinations (OSCEs) are a widely recognized and accepted method to assess clinical competencies but are often resource-intensive.

OBJECTIVE: This study aimed to evaluate the feasibility and effectiveness of a virtual reality (VR)-based station (VRS) compared with a traditional physical station (PHS) in an already established curricular OSCE.

METHODS: Fifth-year medical students participated in an OSCE consisting of 10 stations. One of the stations, emergency medicine, was offered in 2 modalities: VRS and PHS. Students were randomly assigned to 1 of the 2 modalities. We used 2 distinct scenarios to prevent content leakage among participants. Student performance and item characteristics were analyzed, comparing the VRS with PHS as well as with 5 other case-based stations. Student perceptions of the VRS were collected through a quantitative and qualitative postexamination online survey, which included a 5-point Likert scale ranging from 1 (minimum) to 5 (maximum), to evaluate the acceptance and usability of the VR system. Organizational and technical feasibility as well as cost-effectiveness were also evaluated.

RESULTS: Following randomization and exclusions of invalid data sets, 57 and 66 participants were assessed for the VRS and PHS, respectively. The feasibility evaluation demonstrated smooth implementation of both VR scenarios (septic and anaphylactic shock) with 93% (53/57) of students using the VR technology without issues. The difficulty levels of the VRS scenarios (septic shock: P=.67; anaphylactic shock: P=.58) were comparable to the average difficulty of all stations (P=.68) and fell within the reference range (0.4-0.8). In contrast, VRS demonstrated above-average values for item discrimination (septic shock: r’=0.40; anaphylactic shock: r’=0.33; overall r’=0.30; with values >0.3 considered good) and discrimination index (septic shock: D=0.25; anaphylactic shock: D=0.26; overall D=0.16, with 0.2-0.3 considered mediocre and <0.2 considered poor). Apart from some hesitancy toward its broader application in future practical assessments (mean 3.07, SD 1.37 for VRS vs mean 3.65, SD 1.18 for PHS; P=.03), there were no other differences in perceptions between VRS and PHS. Thematic analysis highlighted the realistic portrayal of medical emergencies and fair assessment conditions provided by the VRS. Regarding cost-effectiveness, initial development of the VRS can be offset by long-term savings in recurring expenses like standardized patients and consumables.

CONCLUSIONS: Integration of the VRS into the current OSCE framework proved feasible both technically and organizationally, even within the strict constraints of short examination phases and schedules. The VRS was accepted and positively received by students across various levels of technological proficiency, including those with no prior VR experience. Notably, the VRS demonstrated comparable or even superior item characteristics, particularly in terms of discrimination power. Although challenges remain, such as technical reliability and some acceptance concerns, VR remains promising in applications of clinical competence assessment.

PMID:39793025 | DOI:10.2196/55066

J Neurosurg. 2025 Jan 10:1-10. doi: 10.3171/2024.7.JNS24310. Online ahead of print.

ABSTRACT

OBJECTIVE: This study focuses on epidermal growth factor receptor-mutated lung adenocarcinoma, known for frequent brain metastasis. It aimed to compare the clinical outcomes and cost-effectiveness of combining Gamma Knife radiosurgery (GKRS) with tyrosine kinase inhibitors (TKIs) (GKRS+TKI group) versus TKIs alone (TKI group) for the treatment of patients with newly diagnosed brain metastasis in this condition.

METHODS: Study characteristics of the two groups were matched using inverse probability of treatment weighting (IPTW). In the incremental cost-utility ratio (ICUR) model, a healthcare provider perspective, a 1-month cycle length, a 5-year time horizon, and a discount rate of 2% per year for both effectiveness and costs were adopted. Probabilistic and one-way sensitivity analyses were also conducted to demonstrate the robustness of the findings. Statistical analysis was performed using IBM SPSS version 23.0, and cost-effectiveness analysis was conducted using TreeAge Pro software.

RESULTS: After applying IPTW, the GKRS+TKI group included 205 patients, and the TKI group consisted of 102 patients, with no statistically significant differences in whole confounders. The GKRS+TKI group demonstrated significantly prolonged median progression-free survival (37.5 months vs 10.6 months, p < 0.001) and median overall survival (55.1 months vs 30.8 months, p < 0.001) compared with the TKI group. The GKRS plus TKI strategy achieved an ICUR of $30,532.25 per quality-adjusted life year relative to the TKIs at the willingness-to-pay threshold of US$33,059 (Taiwan’s per capita gross domestic product).

CONCLUSIONS: The use of GKRS plus TKIs not only reduces disease recurrence and improves prognosis but also demonstrates a higher level of cost-effectiveness. These findings offer valuable guidelines for clinicians and inform healthcare authorities in optimizing resource allocation for improved medical care.

PMID:39793022 | DOI:10.3171/2024.7.JNS24310

JMIR Res Protoc. 2025 Jan 10;14:e58531. doi: 10.2196/58531.

ABSTRACT

BACKGROUND: Due to advances in treatment, HIV is now a chronic condition with near-normal life expectancy. However, people with HIV continue to have a higher burden of mental and physical health conditions and are impacted by wider socioeconomic issues. Positive Voices is a nationally representative series of surveys of people with HIV in the United Kingdom. It monitors the physical, mental, and social health, well-being, and needs of this population so that they can be addressed.

OBJECTIVE: This paper aimed to describe the methodology, recruitment strategies, and key sociodemographic features of participants recruited for the second national round of Positive Voices (PV2022).

METHODS: PV2022 was a national, cross-sectional questionnaire study that included people attending HIV care at 101 of the 178 clinics in the United Kingdom between April 2022 and March 2023. Data from the HIV and AIDS reporting system (HARS), a national surveillance database of people with HIV and attending care that is held at the UK Health Security Agency (UKHSA), was used as a sampling frame. The information collected in PV2022 included demographic and socioeconomic factors, HIV diagnoses and treatment, mental and physical health, health service use and satisfaction, social care and support, met and unmet needs, stigma and discrimination, quality of life, lifestyle factors, and additional challenges experienced due to the COVID-19 pandemic. Data linkage to HARS enabled the extraction of clinical information on antiretroviral therapy (ART), HIV viral load, and CD4 lymphocyte counts. Probabilistic sampling was used to provide a randomly selected, representative sample of people attending HIV care who could be invited to complete a paper or online questionnaire ‘on the web’ to online. At the start of 2023, the study was underrecruiting, mainly due to the mpox outbreak, and a separate sequential recruitment strategy was initiated in 14 of the largest and most demographically diverse clinics to increase participant numbers.

RESULTS: Of the 4622 participants who completed the questionnaire, 3692 were recruited through probabilistic recruitment and 930 through sequential recruitment. The overall response rate (measured as the number of people who completed a questionnaire of those who either accepted or declined) was 50%. Survey respondents represented approximately 1 in 20 people diagnosed with HIV in England, Wales, and Scotland. The median age of participants was 52 years, 3428 of participants were male, 2991 were of White ethnicity, and 1121 were of Black ethnicity.

CONCLUSIONS: PV2022 is currently the largest survey of people with HIV in the United Kingdom (as of September 2024). The PV2022 findings will be used to explore the health and well-being of the HIV population and examine associations with demographic, socioeconomic, lifestyle, and other HIV-related factors.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/58531.

PMID:39793018 | DOI:10.2196/58531

J Neurosurg Pediatr. 2025 Jan 10:1-6. doi: 10.3171/2024.10.PEDS24242. Online ahead of print.

ABSTRACT

OBJECTIVE: While the association of a syrinx with a tethered spinal cord in the context of VACTERL (vertebral defects [V], imperforate anus or anal atresia [A], cardiac malformations [C], tracheoesophageal defects [T] with or without esophageal atresia [E], renal anomalies [R], and limb defects [L]) association is known, the incidence of idiopathic syrinxes among these patients has not previously been reported. The authors aimed to characterize the incidence of syrinxes and the pattern of congenital anomalies in pediatric patients with VACTERL association, with a specific focus on the presence of idiopathic syrinxes in this population.

METHODS: An institutional database was retrospectively queried for all pediatric patients with VACTERL association. Patients were assessed for the presence of a syrinx. Those with no accompanying lesion to which the syrinx could be ascribed were designated idiopathic. Descriptive statistics and qualitative analyses characterized the clinical presentation and outcomes of this population.

RESULTS: The authors retrospectively identified 186 patients between 1993 and 2023 with VACTERL association. Of these 186 patients, 141 (75.8%) had a tethered spinal cord and 44 (23.7%) had a syrinx. Most syrinxes could be ascribed to the presence of a tethered spinal cord and/or Chiari malformation; however, 4 (9.1%) of the 44 appeared idiopathic, suggesting the incidence of idiopathic syrinxes in this patient population may be as high as 2.2% (4/186). Most patients remained asymptomatic aside from a single patient who presented with mild gait dysfunction that resolved over time. All syrinxes were managed conservatively, and all but one decreased or remained stable in size on follow-up imaging.

CONCLUSIONS: Although limited, current estimates suggest the general incidence of an idiopathic syrinx is between 5.6 and 8.4 per 100,000 people; these findings in a pediatric cohort with VACTERL association suggest an incidence of 2200 per 100,000 (i.e., 2.2%). Thus, an idiopathic syrinx may be 200-400 times as prevalent in the pediatric VACTERL population.

PMID:39793014 | DOI:10.3171/2024.10.PEDS24242

J Neurosurg. 2025 Jan 10:1-12. doi: 10.3171/2024.8.JNS241180. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective was to comprehensively investigate the clinical, molecular, and imaging characteristics and outcomes of H3 K27-altered diffuse midline glioma (DMG) in adults.

METHODS: Retrospective chart and imaging reviews were performed in 111 adult patients with H3 K27-altered DMG from two tertiary institutions. Clinical, molecular, imaging, and survival characteristics were analyzed. Characteristics were compared between adult and 365 pediatric patients from a previous multicenter meta-analysis dataset. Cox analyses were performed to determine predictors of overall survival (OS) in adult patients.

RESULTS: The median (range) age of adult patients was 40 (18-75) years, and 64 males and 47 females were included. Adults had a higher male proportion (57.7% vs 45.3%, p = 0.023), lower proportion of histological grade 4 (41.4% vs 74.0%, p < 0.001), and different tumor locations (p < 0.001) compared with pediatric patients; adults commonly showed a thalamus location (41.5%) followed by the spinal cord (27.0%), whereas pediatric patients predominantly showed a pons location (64.9%). The OS of adults was longer than that of pediatric patients (30.3 vs 12.0 months, p < 0.001, log-rank test). Older age at diagnosis (HR 0.96, p = 0.001), histologically lower grade (HR 0.25, p = 0.003), and gross-total resection of nonenhancing tumor (HR 0.15, p = 0.003) were independent favorable prognostic factors.

CONCLUSIONS: Adult patients with H3 K27-altered DMG showed distinct clinical, histological, and imaging characteristics compared to pediatric counterparts, with a significantly better prognosis. The authors’ results suggest that aggressive surgery should be pursued when deemed feasible for better survival outcomes.

PMID:39793011 | DOI:10.3171/2024.8.JNS241180

JMIR Hum Factors. 2025 Jan 10;12:e53969. doi: 10.2196/53969.

ABSTRACT

BACKGROUND: Bangladesh and West Bengal, India, are 2 densely populated South Asian neighboring regions with many socioeconomic and cultural similarities. In dealing with breast cancer (BC)-related issues, statistics show that people from these regions are having similar problems and fates. According to the Global Cancer Statistics 2020 and 2012 reports, for BC (particularly female BC), the age-standardized incidence rate is approximately 22 to 25 per 100,000 people, and the age-standardized mortality rate is approximately 11 to 13 per 100,000 for these areas. In Bangladesh, approximately 90% of patients are at stages III or IV, compared with 60% in India. For the broader South Asian population, this figure is 16%, while it is 11% in the United States and the United Kingdom. These statistics highlight the need for an urgent investigation into the reasons behind these regions’ late diagnoses and treatment.

OBJECTIVE: Early detection is essential for managing BC and reducing its impact on individuals. However, raising awareness in diverse societies is challenging due to differing cultural norms and socioeconomic conditions. We aimed to interview residents to identify barriers to BC awareness in specific regions.

METHODS: We conducted semistructured interviews with 17 participants from West Bengal and Bangladesh through Zoom (Zoom Video Communications). These were later transcribed and translated into English for qualitative data analysis. All our participants were older than 18 years, primarily identified as female, and most were married.

RESULTS: We have identified 20 significant barriers to effective BC care across 5 levels-individual, family, local society, health care system, and country or region. Key obstacles include neglect of early symptoms, reluctance to communicate, societal stigma, financial fears, uncertainty about treatment costs, inadequate mental health support, and lack of comprehensive health insurance. To address these issues, we recommend context-specific solutions such as integrating BC education into middle and high-school curricula, providing updates through media channels like talk shows and podcasts, promoting family health budgeting, enhancing communication at cultural events and religious gatherings, offering installment payment plans from health care providers, encouraging regular self-examination, and organizing statewide awareness campaigns. In addition, social media can be a powerful tool for raising mass awareness while respecting cultural and socioeconomic norms.

CONCLUSIONS: Fighting BC or any fatal disease is challenging and requires support from various dimensions. However, studies show that raising mass awareness is crucial for the early detection of BC. By adopting a sensitive and well-informed approach, we aim to improve the early detection of BC and help reduce its impact on South Asian communities.

PMID:39793010 | DOI:10.2196/53969

Otol Neurotol. 2025 Feb 1;46(2):229-236. doi: 10.1097/MAO.0000000000004396. Epub 2024 Dec 11.

ABSTRACT

OBJECTIVE: The physician-scientist workforce is shrinking in the United States. Academic otologists/neurotologists face a diverse set of barriers to successful careers. We aimed to characterize the factors affecting contemporary otology/neurotology surgeon-scientists.

STUDY DESIGN: An electronic survey was distributed to faculty members of the American Neurotology Society and the American Otological Society in 2021. The survey queried demographics, practice setting, compensation, and barriers to conducting research for respondents in academic practice.

RESULTS: One hundred fifty-seven otologists/neurotologists responded to the survey, corresponding to an overall response rate of 25%. Of the respondents, 94 were in academic practice. The median protected research time was 0.5 days/wk, whereas the mode was zero. Across academic rank, salary compensation was lower for academic surgeons with active research funding and for female academic surgeons as compared with their male counterparts. Grant-funded female academic surgeons had significantly worse compensation compared with rank-matched male surgeons with similar protected time. No grant-funded female earned more than the 30th percentile for their rank. Identified barriers to research were pressure to maintain clinical productivity, insufficient protected time, and personal/family demands. Respondents highlighted several areas for improvement: compensation for research activity, administrative support, and improved grant funding mechanisms for clinician-scientists.

CONCLUSIONS: Otology/neurotology surgeon-scientists face barriers to research, including limited protected time, poor administrative support, increasingly competitive funding environments, and misaligned compensation models. New initiatives by the National Institute on Deafness and other Communication Disorders aim to increase the surgeon-scientist workforce, but their success may depend upon removing identified barriers at the level of academic institutions.

PMID:39792984 | DOI:10.1097/MAO.0000000000004396