Category: Nevin Manimala

Opt Lett. 2025 Aug 15;50(16):5181-5184. doi: 10.1364/OL.569137.

ABSTRACT

Fourier ptychographic microscopy (FPM) enhances the spatial-bandwidth product of imaging systems, but its extension to color imaging remains challenging. Existing channel-split methods incur long acquisition times, while multiplexed-illumination approaches suffer from color leakage and require complex post-processing. In this work, we introduce a novel, to the best of our knowledge, color-faithful FPM framework under multiplexed illumination by integrating a physically interpretable color constraint into a differentiable FPM model. Unlike prior works, our method enforces color fidelity during optimization by constraining the first- and second-order moment of RGB channels, effectively preserving the true color tone in reconstructions. This statistical constraint not only improves color accuracy but also offers broad compatibility with existing differentiable FPM models. Numerical simulations and optical experiments show that our method ensures high color fidelity, providing a practical full-color FPM solution.

PMID:40815770 | DOI:10.1364/OL.569137

Opt Lett. 2025 Aug 15;50(16):5041-5044. doi: 10.1364/OL.566313.

ABSTRACT

Statistical estimation methods for localization microscopy (LM) estimate emitter locations using a parameterized statistical model presumed for the data, enabling derivations of estimators and theoretical accuracy bounds. The most widely used performance bound is the Cramér-Rao lower bound (CRLB), which provides a lower bound on the error covariance of any unbiased estimator of the model parameters (i.e., emitter locations) and characterizes the asymptotic performance of the maximum likelihood estimator (MLE). In practice, however, the presumed model is almost always mismatched to the true model that generates the data due to experimental uncertainties stemming from aberrations, calibration errors, and misalignment. As a result, the CRLB no longer provides an accurate lower bound on achievable localization accuracy, and a different performance bound called the Misspecified Cramér-Rao Bound (MCRB) must be considered. In this Letter, we derive the MCRB in different LM setups, with different Poisson statistics, and analyze the behavior of the derived MCRBs. Our analysis provides a quantitative framework for understanding how experimental imperfections affect the limits of achievable localization accuracy.

PMID:40815735 | DOI:10.1364/OL.566313

Sci Immunol. 2025 Aug 15;10(110):eadt3955. doi: 10.1126/sciimmunol.adt3955. Epub 2025 Aug 15.

ABSTRACT

Peripheral helper T (T_PH) cells can play pathogenic roles in human autoimmune diseases. T_PH cells are proposed to be the major B cell helpers in inflamed joints in rheumatoid arthritis (RA), but whether and how T_PH cells are engaged in tissue inflammation remains unclear. We demonstrate that T_PH cells comprise two subsets in RA: stem-like T_PH (S-T_PH) and effector T_PH (E-T_PH) cells. These two subsets differed in transcriptome, epigenome, B cell helper capacity, spatial localization, and cell interactions. S-T_PH cells displayed self-renewal capacity and were mainly found within tertiary lymphoid structures (TLSs) in synovial tissue together with B cells. S-T_PH cells potently induced B cells to produce immunoglobulins. By contrast, E-T_PH cells expressed effector molecules and colocalized with proinflammatory macrophages and CD8⁺ T cells outside TLSs. S-T_PH cells could differentiate into E-T_PH cells upon TCR stimulation and coculture with B cells. Collectively, our study shows that S-T_PH cells play a central role in promoting T_PH responses by undergoing self-renewal and seeding E-T_PH cells.

PMID:40815671 | DOI:10.1126/sciimmunol.adt3955

Postgrad Med J. 2025 Aug 15:qgaf113. doi: 10.1093/postmj/qgaf113. Online ahead of print.

ABSTRACT

BACKGROUND: Regional anesthetic techniques are applied in cardiac surgery to improve postoperative pain and accelerate recovery. Pecto-intercostal fascial block (PIFB) combined with rectus sheath block (RSB) has been proved to provide ideal analgesia for cardiac surgery, but the effects of combing regional anesthetic techniques on postoperative recovery are uncertain.

METHODS: This is a prospective and randomized controlled trial at Fuwai Hospital from 1 June 2024 to 3 July 2024. Eighty patients undergoing elective cardiac surgery via cardiopulmonary bypass were randomized at a 1:1 ratio to be allocated in the intervention group (PIFB combined with RSB) or control group (without regional blocks). The primary outcome was the global score of the 15-item quality of recovery (QoR-15) questionnaire at 24 h after surgery. Secondary outcomes included QoR-15 at 72 h, postoperative pain scores, time to extubation, length of stay, medical expenses in hospital and postoperative morbidities.

RESULTS: The QoR-15 global score at 24 h after cardiac surgery was 122.35 ± 6.71 in the intervention group vs 115.30 ± 5.90 in the control group (P < .001). The proportion of patients experiencing better quality of recovery (Qor-15 ≥ 118) was higher in the intervention group (77.5% vs 55%, P = .033). Postoperative pain scores were 1.90 ± 0.18 in the intervention group compared to 2.95 ± 0.99 in the control group (P = .027) at 24 h. Time to extubation was earlier in the intervention group (274.40 ± 98.36 vs 741.28 ± 93.82 min, P < .001). There were no statistically differences in Qor-15 at 72 h and other recovery outcomes.

CONCLUSION: The administration of PIFB combined with RSB could improve quality of recovery and relieve postoperative pain for patients following cardiac surgery. Key message What is already known on this topic Previous studies have demonstrated that ultrasound-guided nerve blocks effectively reduce postoperative pain in cardiac surgery patients. However, whether these techniques further enhance overall postoperative recovery remained unclear. What this study adds This trial revealed that ultrasound-guided nerve blocks improved postoperative QoR-15 scores, and combined regional techniques further improved recovery without compromising analgesia. How this study might affect research, practice, or policy The findings support applying combined nerve blocks into enhanced recovery protocols for cardiac surgery, offering evidence to optimize postoperative analgesia strategies.

PMID:40815622 | DOI:10.1093/postmj/qgaf113

PLoS One. 2025 Aug 15;20(8):e0322845. doi: 10.1371/journal.pone.0322845. eCollection 2025.

ABSTRACT

Primary Sjögren’s syndrome (pSS) is an autoimmune disorder characterized by dry eyes and mouth, often with systemic involvement. This study aimed to investigate the clinical manifestations and laboratory features in pSS patients, particularly focusing on those with anti-centromere antibodies (ACA) and anti-SSA/Ro antibodies. We conducted a retrospective analysis of 152 patients diagnosed with pSS at Ningbo Medical Center Lihuili Hospital from 2018 to 2023, using the 2016 ACR/EULAR criteria. Additionally, 105 age- and sex-matched healthy controls were included to establish a comparative baseline for laboratory parameters. Clinical data were obtained from medical records, and patients were categorized into ACA-positive and SSA-positive groups based on their autoantibody profiles. Appropriate statistical analyses, including ANOVA, chi-square tests, correlation analysis, and multivariate regression analysis, were used to compare clinical and laboratory parameters in pSS patients. ACA-positive patients were significantly older and exhibited a higher prevalence of Raynaud’s phenomenon and left ventricular diastolic dysfunction, while SSA-positive patients presented with more marked hematological abnormalities. ACA-positive patients have a more prevalent occurrence of positive antinuclear antibodies (ANA) and anti-mitochondrial M2 antibodies (AMA-M2), as well as significantly higher levels of left ventricular end-diastolic diameter (LVEDD), IgM, and lactate dehydrogenase (LDH). In addition, SSA-positive patients exhibited elevated levels of globulins (GLB), IgG, IgA, and rheumatoid factor (RF), accompanied by decreased albumin (ALB) levels. ACA-positive patients had abnormal proportions of CD4+ and CD8+ T cells and had reduced counts of NK cells (CD16+CD56+), CD3+ T cells, and CD8+ T cells. Correlation and multivariate regression analyses revealed a significant association between NK cell and levels of IgG, IgM, GLB, and LDH. Furthermore, SSA-positive patients showed abnormal proportions of CD19+ B cells and NK cells, with reduced counts of CD3+ T cells (including CD4+ and CD8+ T cells) and NK cells. Correlation and multivariate regression analyses indicated a significant correlation between CD4+ T cell and levels of IgG, ALB, and GLB. Overall, T cell-mediated immunity plays a significant role in SSA-positive patients; NK cells are shown to be critically involved in the pathogenesis of ACA-positive pSS.

PMID:40815617 | DOI:10.1371/journal.pone.0322845

Cochlear Implants Int. 2025 Aug 15:1-10. doi: 10.1080/14670100.2025.2542049. Online ahead of print.

ABSTRACT

PURPOSE: A real-world study of the Ultra cochlear implant was completed in 2022, aiming to compare preoperative and postoperative performance. The use of two different electrode arrays and their ability to preserve residual hearing were also investigated.

METHODS: A TOTAL OF: 78 subjects were enrolled in this study. All participants completed the preoperative baseline assessment and postoperative speech and hearing tests. Subjective questionnaires were administered to participants under 6 years old. The development of impedance and M-levels over time was also analysed. For participants older than 6 years of age, pure tone audiometry was performed to evaluate hearing preservation.

RESULTS: The postoperative average aided hearing threshold and speech test results showed a statistically significant improvement compared to preoperative results (p < 0.05). No significant difference was observed between the two electrode arrays (p > 0.05). Overall, impedance and M-levels showed typical trends of progression. Most participants obtained good hearing preservation, while no significant difference in hearing deterioration was reported between the two electrodes (p = 0.20).

CONCLUSION: The Ultra implant can significantly improve hearing and speech abilities. No significant difference was observed in speech perception between the two arrays. Results confirmed that the Ultra implant is safe and effective for both paediatric and adult populations.

PMID:40815546 | DOI:10.1080/14670100.2025.2542049

JAMA Health Forum. 2025 Aug 1;6(8):e252043. doi: 10.1001/jamahealthforum.2025.2043.

ABSTRACT

IMPORTANCE: Little is known about how the prices and affordability of medicines included on the World Health Organization’s Model List of Essential Medicines vary across the globe.

OBJECTIVE: To compare the list prices and affordability of essential medicines across high-, middle-, and low-income markets.

DESIGN AND SETTING: This cross-sectional study examined data from 2022 on list prices and volumes of 549 essential medicines in 72 high-, middle-, and low-income markets (covering 87 countries). These data were obtained from IQVIA. The statistical analyses were performed between August 2024 and March 2025.

MAIN OUTCOMES AND MEASURES: Laspeyres price indices were used to compare average drug prices across countries, both in nominal and purchasing power parity-adjusted terms. The affordability of 8 essential medicines, used to treat major causes of death and disability globally, was assessed by calculating how many days of minimum wage would be required to pay for 1 month of treatment.

RESULTS: The availability of essential medicines ranged from 225 (41%) in Kuwait to 438 (80%) in Germany (base country). After accounting for purchasing power parities, prices of essential medicines in Lebanon were, on average, 18.1% of those in Germany (Lebanon price index, 18.1 vs Germany price index, 100), while average prices in the US were 3.0 times higher than in Germany (US price index, 298.2). A positive association was observed between countries’ gross domestic product per capita (expressed in logarithmic terms) and nominal drug prices (R = 0.30; P = .01), indicating that richer countries generally had higher drug prices. However, when adjusting for the purchasing power of different currencies, an inverse association was observed (R = -0.35; P = .003), suggesting that richer countries had lower real prices. Drug affordability, as measured by the number of days’ minimum wage needed to purchase a month’s treatment, varied widely, with median affordability highest in Europe and the Western Pacific, and lowest in Africa and Southeast Asia.

CONCLUSIONS AND RELEVANCE: The results of this cross-sectional analysis showed significant variation in the prices and affordability of 549 essential medicines across 72 markets in 2022. Strategies to promote equitable drug prices and improve drug affordability are urgently needed.

PMID:40815523 | DOI:10.1001/jamahealthforum.2025.2043

JAMA Health Forum. 2025 Aug 1;6(8):e252465. doi: 10.1001/jamahealthforum.2025.2465.

ABSTRACT

IMPORTANCE: The number of physicians and advanced practitioners (APs) whose care is concentrated in nursing homes (often referred to as nursing home or skilled nursing facility specialists [SNFists]) has increased rapidly. Therefore, whether these clinicians provide better care is important.

OBJECTIVE: To examine the association between SNFist care and outcomes of long-stay nursing home (NH) residents with Alzheimer disease and related dementias (ADRD).

DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study of 417 378 residents with ADRD in US NHs, claims for a 20% national sample of Medicare fee-for-service beneficiaries between 2013 and 2019 were analyzed. Adjusted estimates were based on a machine learning approach that incorporated a doubly robust procedure using a generalized estimating equation with inverse probability treatment weighting. Three secondary analyses were conducted: (1) stratified analyses for physicians and APs, (2) inclusion of physicians of any specialty and APs, and (3) use of proxy outcomes for in-place deaths. Data were analyzed from June 1, 2024, to May 3, 2025.

INTERVENTION: Receipt of care from a SNFist; SNFists included generalist physicians and APs.

MAIN OUTCOMES AND MEASURES: Hospitalizations and emergency department (ED) visits for ambulatory care-sensitive (ACS) conditions. Death without an ACS hospitalization and death without any hospitalization were used in secondary analyses.

RESULTS: Of the total 417 378 residents, 242 540 received care from SNFists (mean [SD] age, 83.5 [8.7] years), and 174 838 never received care from SNFists (mean [SD] age, 84.8 [8.5] years). Compared with the residents who never received care from SNFists, the residents who received care from SNFists were more likely to be Black (12.6% vs 9.4%; P < .001), dually eligible (77.5% vs 73.1%; P < .001), and have more chronic conditions (eg, anemia, 60.9% vs 57.6%). Compared with non-SNFist clinicians, the SNFist clinicians were more likely to be female (physicians, 37.1% vs 23.3%; APs, 88.1% vs 85.1%), practice at more facilities (mean [SD] number of facilities, 9.4 [8.7] for SNFist physicians vs 6.4 [6.1] for non-SNFist physicians; 8.6 [8.1] for SNFist APs vs 7.1 [6.8] for non-SNFist APs), and less likely to practice in rural areas (physicians, 9.3% vs 25.4%; APs, 8.1% vs 20.2%). In adjusted analyses, receiving care from a SNFist vs non-SNFist was associated with 7% lower odds of an ACS hospitalization (odds ratio [OR], 0.93; 95% CI, 0.90-0.96) and 7% lower odds of an ACS ED visit (OR, 0.93; 95% CI, 0.90-0.96). In stratified analyses, receiving care from a SNFist physician vs a non-SNFist physician was associated with 13% lower odds (OR, 0.87; 95% CI, 0.83-0.90) of an ACS hospitalization and 7% lowers odds of an ACS ED visit (OR, 0.93, 95% CI, 0.88-0.97); comparisons of SNFist APs vs non-SNFist APs were not statistically significant. Estimates from the analysis including physicians of any specialty and APs were consistent with the primary results. SNFist care was associated with increased odds of in-place death.

CONCLUSIONS AND RELEVANCE: Findings of this cohort study suggest that the use of SNFists by NHs may enhance the quality of care for residents with ADRD.

PMID:40815522 | DOI:10.1001/jamahealthforum.2025.2465

Protein Sci. 2025 Sep;34(9):e70250. doi: 10.1002/pro.70250.

ABSTRACT

Intrinsically disordered proteins (IDPs) play key roles in various biological processes; they are associated with liquid-liquid phase separation and are targets in disorder-based drug design. Efforts to identify their structural propensities-that can be linked to molecular recognition, malfunction, targeting-still lead to ambiguous results. Secondary structure is routinely assessed by NMR spectroscopy by calculating the secondary chemical shifts (SCSs). Focusing on a given environment in the polypeptide backbone, SCSs highlight the deviation from the “random coil” state. However, the analysis is dependent on which of the numerous random coil chemical shift (RCCS) predictors is applied in the calculations, resulting in an especially pronounced ambiguity for IDPs. To overcome this, we introduce two novel statistical tools that enable the sound identification of structural propensities. We propose the chemical shift discordance ratio (DR) for prefiltering RCCS predictors based on self-consistency. Further on, we introduce the Structural Propensity Identification by t-statistics (SPIT) approach for extracting maximum information from SCS data by using multiple RCCS predictors simultaneously. This way SCS patterns indicating structural propensities can be clearly distinguished from the “noise”. The applicability of these methods is demonstrated for four proteins of varying degrees of disorder. Ubiquitin and α-synuclein are used as respective benchmarks for a globular and a disordered protein, while two proline-rich IDPs are included as especially challenging molecules in secondary structure analysis.

PMID:40815493 | DOI:10.1002/pro.70250

Mol Biol Rep. 2025 Aug 15;52(1):829. doi: 10.1007/s11033-025-10931-3.

ABSTRACT

BACKGROUND: Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne disease caused by a virus belonging to the Orthonairovirus genus. Mononuclear phagocytic cells, hepatocytes and endothelial cells are known to be the primary targets of the CCHF virus during the infection. Epitranscriptomes refers to all chemical modifications of RNA within a cell. The most common among these-and the focus of this study- is N6-methyladenosine (m6A) methylation.

METHODS AND RESULTS: In this study, for the first time, we investigated the expression profiles of ALKBH5, FTO and YTHDF2 genes using quantitative real-time polymerase chain reaction (qPCR) in CCHF patients. The case group consisted of individuals diognosed with CCHF, while the control group comprised healthy individuals with no active infections. The patient group was further classified into mild and severe cases based on clinical presentation. The expression of the ALKBH5 and YTHDF2 genes was statistically significantly upregulated in fatals (p < 0.001). In addition, ALKBH5 genes were differentially expressed in fatals compared to nonfatal case (p = 0.005). Furthermore, we found that FTO gene was significantly upregulated in severe CCHF patients (p = 0.03). We also compared gene expression levels in patients grouped by clinical parameters that above or within normal limits. FTO expression was found to be significantly decreased in patient with elevated ALT and AST levels (p = 0.043 and p = 0.048, respectively).

CONCLUSION: We suggest that upregulated expression of these genes may be associated with CCHF prognosis. These genes may also serve as potential molecular biomarker for diseaase progression.

PMID:40815491 | DOI:10.1007/s11033-025-10931-3