bluuebunny/crossref_metadata_2025 huggingface dataset:
Psilocybin-assisted psychotherapy for Parkinson's disease without depression: A case-report
Authors: Fleury Vanessa , Tomkova Emilie , Catalano Chiuvé Sabina , Penzenstadler Louise
Published: February 2025

Background

Psychedelic assisted psychotherapy (PAP) can improve treatment-resistant depression. Its usefulness in Parkinson's disease (PD) is unknown. PD patients may have problems adjusting to their chronic progressive neurological disease. A change from emotional avoidance to acceptance has been reported following psilocybin administration in patients with treatment-resistant depression.

Objective

To report for the first time the effect of psilocybin in a PD patient.

Methods

A non-depressed 43-year-old female with a 2-year history of PD presented with difficulty adjusting to PD, anxious ruminations and pessimism. The patient declined an increase in dopaminergic medication or the introduction of an anxiolytic. Therapeutic patient education was not beneficial. The patient received four sessions of high-dose PAP within one year. Neurological and psychiatric assessments were performed before and at one year follow-up using qualitative interviews and quantitative assessment of motor status, dispositional optimism, depression, anxiety, apathy, and well-being.

Results

PAP was well tolerated. It significantly improved the patient's overall pessimistic outlook on her future and decreased her anxious ruminations and worries about potential handicap due to PD. Her general well-being improved, as well as all psychometric scores except for the apathy scale. Motor status remained unchanged. Better acceptance of PD allowed her to accept pharmacological treatment adjustment.

Conclusions

PAP could be a safe and useful treatment for PD patients with dispositional pessimism and difficulties accepting their disease by promoting profound decentration from habitual thoughts and emotions, improving mood and PD acceptance. Randomized, controlled studies are needed to confirm this result.
Are ICU Bedspaces Based in Evidence, and Do They Support Patient Sleep? A Narrative Review
Authors: Tronstad Oystein , Szollosi Irene , Flaws Dylan , Zangerl Barbara , Fraser John F
Published: February 2025

Objective: This narrative review summarizes some of the evidence guiding current intensive care unit (ICU) design, focussing on environmental factors impacting on sleep, and compares available evidence and recommendations to current ICU designs and builds. Background: The importance of sleep for recovery after illness is well known. However, hospitalized patients frequently experience poor and disrupted sleep. This is especially true for patients admitted to the ICU. There are many factors negatively impacting on ICU patients’ ability to sleep. Some relate to their illness or pre-existing sleep problems; others relate to patient care activities. While the ICU bedspace may facilitate 24h care, there is growing awareness of the detrimental impact the bedspace environment (especially suboptimal lighting and excessive sound/noise) has on sleep quality, and important questions raised regarding how this may impact on recovery and health outcomes. Multiple guidelines and recommendations exist to guide ICU bedspace design. However, questions have been raised whether contemporary ICUs are evidence-based, and whether the available evidence is effectively translated into the built ICU. Methods: A comprehensive literature review was conducted, exploring the evidence supporting current ICU bedspace design and the impact of ICU design and environmental factors on patient sleep. Results and conclusion: This review summarizes the impact of the ICU bedspace environment on patient outcomes and describes features of the ICU bedspace design that may not adhere to best evidence and contribute to poor sleep. Suggestions on how ICU bedspaces can be improved to optimize sleep are provided.
Catastrophic Severe Injuries and Medical Conditions in Girls’ and Women’s Softball: An 8-Year Epidemiologic Study
Authors: Martin Chelsea , Osterhout Kathryn , Shore Erin , Delong Randi , Mihalik Johna , Kucera Kristen
Published: February 2025

Background:

Research on catastrophic injuries and medical conditions among majority girls’ and women’s sports are underrepresented. In this study, we describe the incidence, characteristics, and mechanisms of severe softball injuries/medical conditions between 2014 and 2021.

Hypothesis:

Catastrophic injury and illness patterns will be observed with a higher incidence rate at the collegiate level.

Study Design:

Descriptive epidemiologic study.

Level of Evidence:

Level 3.

Methods:

Events from the National Center for Catastrophic Sport Injury Research (NCCSIR) and National Electronic Injury Surveillance System (NEISS) were included. NCCSIR included catastrophic injuries during participation in high school (HS) or college sponsored girls’/women’s softball resulting in death, temporary or permanent disability, or life-threatening injury. NEISS included severe girls’/women’s softball injuries (product code 5034) among 13- to 17- and 18- to 24-year-olds among severe dispositions. National estimates were derived using a weighted sample for NEISS. Counts (%) and incidence rates (IR) per 100,000 participants overall and by age level, injury/medical event, and outcome were reported.

Results:

NCCSIR captured 0.3 events per 100,000 participants (95% confidence interval, 0.1-0.5), and incidence was higher in college (IR, 2.5; 0.9-6.6) compared with HS (IR, 0.1; 0.1-0.4). Sudden cardiac arrest was the most common event (5, 63%), and 2 (25%) fatalities were reported. NEISS captured 10.2 events per 100,000 participants (9.7-10.8). Incidence was higher in 18- to 24-year-olds (IR, 8.9; 8.3-9.6) compared with 13- to 17-year-olds (IR, 4.2; 3.8-4.6), and no fatalities were captured.

Conclusion:

Collegiate and 18- to 24-year-old athletes demonstrated a higher incidence of severe injuries than HS and 13- to 17-year-old athletes across both surveillance systems. NEISS captured a higher incidence of catastrophic events than NCCSIR. NCCSIR observed more cardiac events, whereas NEISS observed more head/face injuries.

Clinical Relevance:

Continued monitoring of severe injuries and medical events in softball is necessary to support response and prevention measures.
Management of mycosis fungoides and Sézary syndrome with mogamulizumab in combination with psoralen plus UVA: two case reports
Authors: Bernardelli Andrea , Visco Carlo
Published: February 2025

This report describes the cases of two patients with mycosis fungoides and Sézary syndrome (MF/SS) who achieved clinical benefit with mogamulizumab combination therapies. Case 1 is a 56-year-old male with stage IIIB (T4NxM0B1) MF, which later progressed into SS, with ongoing skin symptoms (erythema, lichenified skin, and pruritis) and axillary and inguinal lymphadenomegaly. Skin-directed and systemic therapies failed to achieve a long-lasting response in this patient. Mogamulizumab (1 mg/kg once weekly for 4 weeks; once every 2 weeks thereafter) yielded temporary improvement in skin symptoms, but progression in the skin was confirmed after ~2 months. Subsequently, the combination of mogamulizumab with psoralen plus ultraviolet light A (PUVA) yielded a partial response; however, PUVA was discontinued due to phototoxicity and mogamulizumab was continued as monotherapy. At the latest evaluation, clinical improvement in the skin and reduced lymphadenomegaly were evident with ongoing mogamulizumab monotherapy; the patient is awaiting allogeneic hematopoietic stem cell transplantation. Case 2 is an 80-year-old male with stage IIIB (T4NxM0B1) granulomatous variant MF who presented with diffuse erythema with desquamation, ectropion, and inguinal lymphadenopathy. Treatment with oral prednisone and bexarotene failed to achieve adequate, long-lasting responses. Mogamulizumab (1 mg/kg once weekly for 4 weeks; once every 2 weeks thereafter) monotherapy yielded an initial improvement, characterized by less intense erythema, but the improvement was not sustained. Mogamulizumab was supplemented with oral prednisone and then PUVA; this combination resulted in improvement in the skin. PUVA was stopped due to unavailability, and methotrexate (10 mg once weekly) was initiated alongside continued mogamulizumab; this led to improvement in erythema. The patient continued mogamulizumab plus methotrexate with improving clinical status, prior to their death, which was deemed to be unlikely to be related to treatment. Our experience suggests that, in principle, mogamulizumab can be used in combination with other therapies; however, further research is needed.
Tacrolimus toxicity management in a pregnant kidney transplant recipient with newly diagnosed human immunodeficiency virus: A case report
Authors: Matarneh Ahmad , chokshi Ravi , Sardar Sundus , Salmeron Dinia , O’brien James , Khalil Fareeha , Trivedi Naman , Ghahramani Nasrollah , Shah Vaqar
Published: February 2025

Managing kidney transplant recipients during pregnancy presents significant challenges, particularly in balancing the interactions and safety concerns of immunosuppressive medications such as mycophenolate mofetil and tacrolimus. Pregnancy can affect tacrolimus levels, and its safety profile during pregnancy remains underexplored. When the patient also hasa human immunodeficiency virus, management becomes even more complicated due to potential interactions between antiretrovirals and immunosuppressants. Notably, tacrolimus is highly susceptible to drug-drug interactions. Even minor adjustments in highly active antiretroviral therapy can result in significant fluctuations in tacrolimus levels, potentially leading to subtherapeutic concentrations (increasing the risk of rejection) or supratherapeutic levels with toxicity. Tacrolimus toxicity is often managed by administering cytochrome P450 enzyme inducers, with the choice of agent depending on factors such as the degree of enzyme induction. Agents such as isoniazid or rifampicin are typically considered. In this case report, we described the treatment of tacrolimus toxicity with rifampicin in a pregnant kidney transplant recipient with a newly diagnosed human immunodeficiency virus infection.
Prostaglandin Intracameral Implants for Ocular Hypertension and Open-Angle Glaucoma
Authors: Cheng Christine M. , Rehmani Cameron , Chin Jordan
Published: February 2025

Background: Sustained-release prostaglandin intracameral implants are new targeted treatment options for open-angle glaucoma or ocular hypertension that lower intraocular pressure (IOP) and reduce or eliminate the need for topical eye drops. Objective: To summarize evidence supporting prostaglandin intracameral implants for treatment of ocular hypertension or open angle glaucoma and identify patient populations most likely to benefit from these treatments. Data sources: A PubMed search (1/1/2016 to 10/1/2024) was conducted to identify randomized, controlled clinical trials for bimatoprost 10-μg and travoprost 75-μg intracameral implants. Manufacturer prescribing information, formulary dossiers, Food and Drug Administration (FDA) clinical reviews and glaucoma clinical treatment guidelines were also reviewed. Study selection and data extraction: English-language randomized controlled trials involving bimatoprost 10-μg or travoprost 75-μg intracameral implants were included. Data synthesis: Bimatoprost and travoprost intracameral implants demonstrated noninferior IOP reduction compared to timolol eye drops in phase 3 trials, with sustained effects up to 12 and 36 months, respectively. The FDA-approved implants are limited to a single administration to the affected eye to minimize corneal risks. The travoprost implant contains a titanium reservoir and requires surgical placement, while the bimatoprost implant is biodegradable and can be placed in a clinic setting. There are no studies directly comparing the safety and efficacy of the two intracameral implants. Conclusions: Prostaglandin intracameral implants are a novel approach to reducing medication burden while delivering sustained IOP reducing effects. Pharmacists should be aware of efficacy and safety considerations of these implants relative to available topical treatments for ocular hypertension or open angle glaucoma.
Detection of AdeAB, TetA, and TetB efflux pump genes in clinical isolates of tetracycline-resistant Acinetobacter baumannii from patients of Suez Canal University Hospitals
Authors: Azab Hasnaa , Askar Aya Mohamed , El-Fadeal Noha M. Abd , Othman Amira A. A. , Rayan Amal H. , Khattab Sally
Published: February 2025

Background

Acinetobacter baumannii is an opportunistic bacteria associated primarily with hospital-acquired infections. Its tendency to acquire or donate resistance genes to neighboring bacteria is a major concern. Tetracyclines have shown promise in treating A. baumannii infections, but tetracycline resistance is growing globally in A. baumannii isolates.

Objectives

The study aimed to study (1) the prevalence of multidrug-resistant (MDR) A. baumannii infections at Suez Canal University Hospitals, (2) the distribution of efflux pump genes AdeA &B, TetA, and TetB, and (3) the effect of efflux pump inhibitor (CCCP) on tetracycline-resistant isolates.

Methods

Clinical samples (457) were collected (blood, urine, sputum, ETA, pus, and pleural fluid), followed by A. baumannii isolation and identification, PCR detection of efflux pump genes, and detection of tetracycline susceptibility and its MIC before and after treatment with the efflux pump inhibitor (CCCP).

Results

A total of 31 A. baumannii isolates were recovered (6.78%). The highest rate of isolation was from the ICU (48.3%) from the ET aspirate samples (48.3%). The efflux system AdeA and TetB genes were distributed in 100% of isolates, whereas AdeB was found in 93.5% of isolates and the TetA gene in 87.1% of isolates. All A. baumannii isolates were MDR showing resistance to three or more classes of antibiotics. 45% of the isolates showed a 4-fold reduction of MIC and 12.9% showed a 2-fold reduction in the MIC.

Conclusions

Efflux pump is an important mechanism for tetracycline resistance among A. baumannii isolates.
Continuing exposure to disadvantageous material and perceived economic factors on self-rated health in different life stages: fixed effects analyses with data from the German Socioeconomic Panel
Authors: Rähse Tobias , Richter Matthias , Knöchelmann Anja
Published: February 2025

Background

Life course epidemiology explores health disparities over time. The accumulation thesis thereby suggests an add-up of disadvantages, while the adaptation model assumes an adjustment to disadvantageous conditions. Examining the relevance of these accumulation and adaptation processes, the present study analyses continuing exposure to various material and perceived economic factors on self-rated health (SRH) across different life stages.

Methods

All analyses are based on longitudinal data from the German Socio-Economic Panel (SOEP) from 1994 to 2017. Exposure variables, including loan burdens, housing status and quality (material factors) as well as financial and occupational worries, housing and income satisfaction (perceived economic factors), were analyzed dichotomously. Exposure duration was calculated as observed years in exposure for each of the factors, taking only continuous exposure years into account. The analyses were carried out separately for sex and life stages (emerging, early middle & later middle, late adulthood) using fixed effects models to adjust for time-varying covariates.

Results

The analyses showed accumulation processes associated with housing status, financial worries and income satisfaction impacting SRH across most life stages. The effects of continuing exposure to occupational worries, housing satisfaction, housing quality, and loan burdens were more variable, indicating accumulation processes in certain life stages and sex-specific variations.

Conclusions

While predominantly accumulation effects were found for certain factors, others showed more varied patterns. Future research should explore the mechanisms underlying these effects to develop well-timed measures that mitigate the negative health implications of continuing exposures to disadvantageous factors, emphasizing the importance of multiple exposures and later life health effects that may impede healthy ageing.
South Asian women’s lived experiences of health care after disclosure of family violence: a qualitative meta-synthesis review
Authors: Baloch Surriya , McLindon Elizabeth , Hameed Mohajer , Hegarty Kelsey
Published: February 2025

Introduction

Given the high prevalence of family violence (FV) amongst South Asian women, the experiences and expectations of addressing FV within healthcare, is of policy, practice and research interest. Whilst FV is shaped and influenced by various interconnected sociodemographic and cultural factors, it can be addressed in healthcare settings through identification and response.

Objective

To explore South Asian women's lived experiences and expectations about identifying and responding to FV within healthcare.

Methods

This review utilised a systematic methodology; nine databases were searched up to June 2024. A total of 8,217 records were screened by two reviewers independently based on a priori inclusion and exclusion criteria. A thematic analytical approach guided the integration of findings from 14 qualitative studies.

Results

Thematic synthesis of the articles generated three themes (1) I was afraid to share, (2) They just walk away, (3) Understand and listen to my pain. These themes represented the perspectives, feelings, and expectations of both local and migrant South Asian women survivor participants. Cultural factors and social obstacles may prevent South Asian women from seeking and using appropriate support services. Additional barriers may include healthcare providers’ reluctance to address FV with South Asian women because of a lack of cultural knowledge and/or appropriate methods to address FV. South Asian women participants reflected that they want healthcare providers to understand them, acknowledge their discomfort, and provide culturally appropriate strategies and solutions.

Conclusion

It is highly recommended that policymakers and health-care providers continue to be mindful of the social and cultural challenges faced by South Asian women who experience FV.
Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses
Authors: Nguyen Thai-Duong , Khanal Shristi , Lee Eunhee , Choi Jinsol , Bohara Ganesh , Rimal Nikesh , Choi Dong-Young , Park Soyeun
Published: February 2025

Parkinson’s disease is a neurodegenerative disorder characterized by cardinal motor symptoms resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta. Although current medications may alleviate its symptoms, Parkinson’s disease remains incurable. Astaxanthin is an antioxidant and anti-inflammatory agent; however, its high susceptibility to oxidative degradation and low aqueous solubility limit its therapeutic efficacy. This study aimed to improve the pharmaceutical properties and neuroprotective effects of astaxanthin for Parkinson’s disease treatment by using lactoferrin-conjugated astaxanthin-loaded liposomes (Lf-ASX-LPs). We successfully formulated Lf-ASX-LPs with high encapsulation efficiency (97.6%) and favorable physical characteristics (diameter: 109.8 ± 1.1 nm; polydispersity index: 0.18 ± 0.01; zeta potential: − 9.5 ± 1.1 mV). Lf-functionalized liposomes demonstrated enhanced cellular uptake and permeation in a Transwell® study, showing a 16.7-fold higher internalization in SH-SY5Y cells over 24 h than those without Lf conjugation. Additionally, Lf functionalization enhanced brain penetration ability, as demonstrated by a biodistribution study using nude mice, compared to LPs without Lf conjugation. In vitro, Lf-ASX-LPs reduced cell loss by 20.1% and oxygen species by 30.0%, ameliorated the reduction in mitochondrial membrane potential under 1-methyl-4-phenylpyridinium-induced toxicity by 40.1%, and reduced extracellular nitric oxide levels under lipopolysaccharide-induced toxicity by 32.0%, indicating cytoprotective and antioxidant effects. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model, treatment with Lf-ASX-LPs resulted in 5.0-, 3.1-, and 5.6-fold increases in dopamine levels, TH+ fiber density, and TH+ neurons, respectively, restoring dopaminergic neuron damage. The developed formulation also alleviated behavioral impairment and neuroinflammation, reducing astrocyte and microglial activation in the striatum and substantia nigra of the MPTP-treated animals. Thus, our formulation of Lf-ASX-LPs represents a promising strategy for providing neuroprotection and retarding Parkinson’s disease progression.

Graphical abstract
Cytoplasmic SALL4-A isoform expression as a diagnostic marker of less aggressive tumor behavior in gastric cancer
Authors: Rahmani Saeed , Babajani Amirhesam , Abolhasani Maryam , Ghods Roya , Kalantari Elham , Madjd Zahra
Published: February 2025

Background

Gastric cancer (GC) poses significant challenges globally, ranking fifth in incidence and fourth in cancer-related mortality. SALL4, a stem cell transcription factor with multiple isoforms, includes SALL4-A as its full-length form. This study aims to evaluate the diagnostic potential of SALL4-A isoform expression in GC and its clinical significance.

Method

Immunohistochemical (IHC) analysis was conducted on Tissue Micro Array (TMA) slides from 167 GC patients. Clinicopathological parameters were correlated with SALL4-A expression, and survival analysis was performed. Diagnostic performance was assessed using metrics such as sensitivity, specificity, and area under the curve (AUC).

Results

SALL4-A exhibited distinct cytoplasmic expression in GC, correlating with lower histological grade (p = 0.003) and TNM stage (p = 0.003), particularly in the intestinal subtype. Diagnostic evaluation showed an AUC of 0.803 for cytoplasmic expression, demonstrating high diagnostic potential. However, SALL4-A expression did not show significant prognostic value.

Conclusion

Cytoplasmic SALL4-A expression in GC is associated with less aggressive tumor phenotypes and shows promise as a diagnostic marker. Further research is warranted to elucidate its mechanistic role and potential integration into clinical practice.
Advanced NGS analysis of cell-free tumor DNA supports clonal relation to primary high-grade B-cell lymphoma lesion and CNS relapse despite MRI negativity
Authors: Navrkalova Veronika , Mareckova Andrea , Porc Jakub , Hricko Samuel , Hrabcakova Viera , Kissova Jarmila , Kundova Sona , Jarosova Marie , Pospisilova Sarka , Kotaskova Jana , Janikova Andrea
Published: February 2025

High-grade B-cell lymphomas (HGBCLs) are aggressive blood cancers with a severe disease course, especially when the central nervous system (CNS) is involved. Standard histological examination depends on tissue availability and is currently supplemented with molecular tests, as the status of MYC, BCL2, or BCL6 gene rearrangements is required for proper lymphoma classification. This case report demonstrates the relevance of cerebrospinal fluid (CSF) cell-free DNA testing by integrative next-generation sequencing (NGS) panel. The benefit of this approach resided in tumor genotyping alongside the proof of CNS progression despite MRI negativity, revealing a clonal relationship with the primary tumor lesion. In addition, our strategy allowed us to classify the tumor as DLBCL/HGBL-MYC/BCL2 entity. In clinical practice, such a minimally invasive approach provides a more sensitive tool than standard imaging and cell analyzing techniques, enabling more accurate disease monitoring and relapse prediction in particular cases.
Analysis of the efficacy of multidisciplinary integration based on 3D reconstruction technology for the treatment of gout stone
Authors: Zhou Shizhe , Zhang Zengxiao , Liu Tian , Xu Yijun , Pan Yuehai , Chen Ying
Published: February 2025

Objective

This study investigates the efficacy of multidisciplinary fusion therapy based on 3D reconstruction technology for the treatment of gouty stone by comparing the efficacy of multidisciplinary fusion therapy with pharmacologic therapy.

Methods

This study is a cohort study.Patients who underwent gout stone surgery at the Affiliated Hospital of Qingdao University from November 2020 to November 2022 were included in this study, totaling 85 to form the MDT surgery group, and matched among gout stone patients in the outpatient clinic during the same period to form the medication group. Patients in the 2 groups were followed up for 6 months to compare baseline and follow-up data.

Results

Both groups experienced a decrease in uric acid levels and an increase in SF-36 scores during follow-up. After adjusting for confounders, multifactorial logistic regression showed that the uric acid attainment rate of patients in the MDT surgery group was 4.011 times higher than that of the drug group (OR: 4.011, 95% CI: 1.595, 10.086, P = 0.003); the proportion of patients with an increase in SF-36 in the MDT surgery group was 4.976 times higher than that of the drug group (OR: 4.976, 95% CI: 2.243, 11.040, P < 0.001); the proportion of patients treated with high-dose medication in the MDT surgery group was 1.8% of that of patients in the drug group (OR: 0.018, 95% CI: 0.002, 0.148, P < 0.001); and the proportion of patients in the MDT surgery group who developed frequent gout was 2.8% of that in the drug group (OR: 0.028 95% CI: 0.003, 0.2398, P = 0.001). the proportion of patients in the MDT surgery group who developed abnormal liver function was 0.317 times higher than that in the drug group (OR: 0.317, 95% CI: 0.121, 0.831, P = 0.019).

Conclusion

The multidisciplinary integration of 3D reconstructive techniques for gout stone treatment resulted in an increase in uric acid compliance, a decrease in the frequency of gout and the appearance of liver impairment; and a greater benefit in terms of improvement in the quality of life of the patients after treatment.
Long-term outcomes of drainless anatomical lung resection surgery for pulmonary malignancies
Authors: Kuo Ting-Fang , Lin Mong-Wei , Chen Ke-Cheng , Kuo Shuenn-Wen , Huang Pei-Ming , Lee Jang-Ming
Published: February 2025

Objective

Drainless minimally invasive anatomical lung resection surgery for pulmonary malignancies is safe and feasible in terms of early postoperative outcomes. However, the quality of surgery in the long term remains uncertain. This study aimed to investigate the perioperative outcomes, 3-year overall, and disease-free survival rates of patients who underwent minimally invasive anatomical lung resection surgery with the drainless technique for pulmonary malignancies.

Methods

Fifty-eight patients who underwent drainless minimally invasive anatomical lung resection surgery for pulmonary malignancies (36 -lobectomy; 22 -segmentectomy) between November 2017 and June 2022 by a single surgeon were enrolled. Patients’ characteristics and perioperative, early postoperative, and long-term data were collected. The lymph node dissection stations and number, resection margin, 3-year overall and disease-free survival rates were assessed.

Results

The median age was 64 years. Forty-four patients were females (76%) and forty-seven patients were non-smokers (81%). The median five-factor modified frailty index was 1. Most patients had primary lung cancer; four (7%), 43 (74%), seven (12%), and three (5%) had stage 0, I, II, and III, respectively. The median lymph node dissection stations was four, and the number was 17. The resection margin was free in 98% of the cases. The 3-year overall survival rate was 98.3% in all patients, and 97.2% and 100% in the lobectomy and segmentectomy subgroups, respectively. The 3-year disease-free survival rate was 85.3% in all patients and 80.5% and 92.9% in the lobectomy and segmentectomy subgroups, respectively.

Conclusion

The drainless technique is safe and feasible for minimally invasive anatomical lung resection surgery for pulmonary malignancies in terms of early postoperative and long-term outcomes. However, further randomized controlled studies are warranted.
Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD
Authors: Wang Shaowei , Li Boyang , Li Jie , Cai Zhiheng , Hugo Cristelle , Sun Yi , Qian Lu , TCW Julia , Chui Helena C. , Dikeman Dante , Asante Isaac , Louie Stan G. , Bennett David A. , Arvanitakis Zoe , Remaley Alan T. , Kerman Bilal E. , Yassine Hussein N.
Published: February 2025

Background

Cellular senescence, a hallmark of aging, has been implicated in Alzheimer’s disease (AD) pathogenesis. Cholesterol accumulation is known to drive cellular senescence; however, its underlying mechanisms are not fully understood. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis, and its expression and trafficking are altered in APOE4 and AD models. However, the role of ABCA1 trafficking in cellular senescence associated with APOE4 and AD remains unclear.

Methods

We examined the association between cellular senescence and ABCA1 expression in human postmortem brain samples using transcriptomic, histological, and biochemical analyses. Unbiased proteomic screening was performed to identify the proteins that mediate cellular ABCA1 trafficking. We created ABCA1 knock out cell lines and mouse models to validate the role of ABCA1 in cholesterol-induced mTORC1 activation and senescence. Additionally, we used APOE4-TR mice and induced pluripotent stem cell (iPSC) models to explore cholesterol-ABCA1-senescence pathways.

Results

Transcriptomic profiling of the human dorsolateral prefrontal cortex from the Religious Order Study/Memory Aging Project (ROSMAP) cohort revealed the upregulation of cellular senescence transcriptome signatures in AD, which correlated with ABCA1 expression and oxysterol levels. Immunofluorescence and immunoblotting analyses confirmed increased lipofuscin-stained lipids and ABCA1 expression in AD brains and an association with mTOR phosphorylation. Discovery proteomics identified caveolin-1, a sensor of cellular cholesterol accumulation, as a key promoter of ABCA1 endolysosomal trafficking. Greater caveolin-1 expression was observed in APOE4-TR mouse models and AD human brains. Oxysterol induced mTORC1 activation and senescence were regulated by ABCA1 lysosomal trapping. Treatment of APOE4-TR mice with cyclodextrin reduced brain oxysterol levels, ABCA1 lysosome trapping, mTORC1 activation, and attenuated senescence and neuroinflammation markers. In human iPSC-derived astrocytes, the reduction of cholesterol by cyclodextrin attenuated inflammatory responses.

Conclusions

Oxysterol accumulation in APOE4 and AD induced ABCA1 and caveolin-1 expression, contributing to lysosomal dysfunction and increased cellular senescence markers. This study provides novel insights into how cholesterol metabolism accelerates features of brain cellular senescence pathway and identifies therapeutic targets to mitigate these processes.
Prothrombin complex concentrate for reversal of oral anticoagulants in patients with oral anticoagulation-related critical bleeding: a systematic review of randomised clinical trials
Authors: Ovesen Christian , Purrucker Jan , Grundtvig Josefine , Mikkelsen Theis Bech , Gluud Christian , Jakobsen Janus Christian , Christensen Hanne , Steiner Thorsten
Published: February 2025

Background

Swift reversal of oral anticoagulation is deemed essential for the outcome of patients with anticoagulation-related critical bleeding. The aim of this systematic review was to evaluate the benefits and harms of prothrombin complex concentrate (PCC) in patients with oral anticoagulants-related critical bleeding.

Methods

For this systematic review CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Web of Science, and clinical trial registries were systematically searched. Clinical study reports were also requested from competent authorities. Eligible for inclusion were randomised clinical trials comparing PCC versus no intervention, placebo, or other reversal interventions in participants with critical bleeding related to ongoing treatment with vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC). Pre-specified primary outcomes were all-cause mortality, health-related quality of life, and serious adverse events for which meta-analyses, Trial Sequential Analysis, and GRADE assessments were conducted.

Results

Three trials, randomising a total of 291 participants, evaluated PCC against two different active comparators in participants with VKA-related critical bleeding, and two trials, randomising a total of 534 participants, evaluated PCC against two different active comparators in participants with factor Xa-related critical bleeding. Among participants with VKA-related critical bleeding, meta-analyses showed no evidence of a difference between PCC versus fresh frozen plasma (FFP) when assessing all-cause mortality (risk ratio [RR] 1.05; 95% confidence interval (CI) 0.27 to 4.05; low certainty), health-related quality of life (mean difference 1.04; 95% CI − 0.94 to 3.02; very low certainty), and serious adverse events (RR 1.33; 95% CI 0.94 to 1.88; very low certainty), but information is currently sparse. Among participants with factor Xa-related critical bleeding, PCC could not be shown superior or inferior to other reversal strategies (FFP or andexanet alfa) on any patient-relevant outcome, but information is currently sparse.

Conclusion

Among participants with VKA or DOAC-related critical bleeding, evidence from randomised clinical trials is currently insufficient to establish if PCC is superior or inferior versus other interventions in decreasing the risk of undesirable patient-relevant outcomes or improving health-related quality of life.
Implementation of prehospital point-of-care ultrasound using a novel continuous feedback approach in a UK helicopter emergency medical service
Authors: Naeem Salman , Aziz Shadman , Hirst Thomas , Strobel Johannes , Mulvey Jamin M. , Lang Ailidh , Patel Jankee , Smith Alexander , Cheng Ka Jun , Palmer Michael , Schlautmann Jonas , Christian Michael D. , Nevin Daniel
Published: February 2025

Background

There has been increased use of prehospital point-of-care ultrasound (PoCUS) by helicopter emergency medical services (HEMS) in recent years. Lack of governance structure and evidence of benefit have been described as major barriers to its implementation. This paper describes a novel approach to implementation of prehospital PoCUS and clinical governance framework in a UK HEMS.

Methods

A retrospective database review was undertaken at London’s Air Ambulance (LAA) from 1st September 2021 to 31st March 2023. All patients who had PoCUS examination were included. Scans were archived in a cloud-based server and reviewed weekly by expert clinicians. They were graded in adequacy, agreement between reviewer and clinician was recorded and fed back to the clinicians allowing continuous feedback learning. In-hospital diagnosis was sought for patients having the full Pump, Pleura and Pouring blood (PPPB) protocol. Cohen’s Kappa (ƙ) was calculated for inter-rater reliability. Sensitivity and specificity analysis was performed using 2 × 2 tables.

Results

LAA attended 3,068 missions. Our reviewers identified 701 PoCUS scanning encounters and 628 were included in the final analysis. Clinicians performed 420 scans for pneumothorax, 308 for free fluid and 305 pericardial effusions respectively. Majority of the population were male (85%) who sustained traumatic (93.5%) thoracic injuries (65%). Paramedics performed 29% of the scans. Reviewers deemed 83% of the scans of adequate quality. Inter-rater reliability between clinicians and reviewers was 0.6 for pericardial effusion, 0.67 for pneumothorax and 0.71 for free fluid respectively. A full PPPB protocol was performed in 52 patients out of which 46 were included. The sensitivity and specificity of PPPB protocol for diagnosis life-threatening injuries was 0.5 and 0.9 respectively.

Conclusion

Introduction of prehospital PoCUS in a HEM service utilizing high quality training, user-friendly workflow and image archiving system, robust governance framework and continuous feedback may be feasible allowing high quality ultrasound examinations. The bespoke PPPB protocol in prehospital may improve diagnosis of life-threatening injuries.
“The NET effect”: Neutrophil extracellular traps—a potential key component of the dysregulated host immune response in sepsis
Authors: Retter Andrew , Singer Mervyn , Annane Djillali
Published: February 2025

Neutrophils release neutrophil extracellular traps (NETs) as part of a healthy host immune response. NETs physically trap and kill pathogens as well as activating and facilitating crosstalk between immune cells and complement. Excessive or inadequately resolved NETs are implicated in the underlying pathophysiology of sepsis and other inflammatory diseases, including amplification of the inflammatory response and inducing thrombotic complications. Here, we review the growing evidence implicating neutrophils and NETs as central players in the dysregulated host immune response. We discuss potential strategies for modifying NETs to improve patient outcomes and the need for careful patient selection.
Enterococcus and Eggerthella species are enriched in the gut microbiomes of COVID-19 cases in Uganda
Authors: Agudelo Carolina , Kateete David Patrick , Nasinghe Emmanuel , Kamulegeya Rogers , Lubega Christopher , Mbabazi Monica , Baker Noah , Lin Kathryn Y. , Liu Chang C. , Kasambula Arthur Shem , Kigozi Edgar , Komakech Kevin , Mukisa John , Mulumba Kassim , Mwachan Patricia , Nakalanda Brenda Sharon , Nalubega Gloria Patricia , Nsubuga Julius , Sitenda Diana , Ssenfuka Henry , Cirolia Giana T. , Gustafson Jeshua T. , Wang Ruohong , Nsubuga Moses Luutu , Yiga Fahim , Stanley Sarah A. , Bagaya Bernard Ssentalo , Elliott Alison , Joloba Moses , Wolf Ashley R.
Published: February 2025

Background

Infection with the COVID-19-causing pathogen SARS-CoV-2 is associated with disruption in the human gut microbiome. The gut microbiome enables protection against diverse pathogens and exhibits dysbiosis during infectious and autoimmune disease. Studies based in the United States and China have found that severe COVID-19 cases have altered gut microbiome composition when compared to mild COVID-19 cases. We present the first study to investigate the gut microbiome composition of COVID-19 cases in a population from Sub-Saharan Africa. Given the impact of geography and cultural traditions on microbiome composition, it is important to investigate the microbiome globally and not draw broad conclusions from homogenous populations.

Results

We used stool samples in a Ugandan biobank collected from COVID-19 cases during 2020–2022. We profiled the gut microbiomes of 83 symptomatic individuals who tested positive for SARS-CoV-2 along with 43 household contacts who did not present any symptoms of COVID-19. The inclusion of healthy controls enables us to generate hypotheses about bacterial strains potentially related to susceptibility to COVID-19 disease, which is highly heterogeneous. Comparison of the COVID-19 patients and their household contacts revealed decreased alpha diversity and blooms of Enterococcus and Eggerthella in COVID-19 cases.

Conclusions

Our study finds that the microbiome of COVID-19 individuals is more likely to be disrupted, as indicated by decreased diversity and increased pathobiont levels. This is either a consequence of the disease or may indicate that certain microbiome states increase susceptibility to COVID-19 disease. Our findings enable comparison with cohorts previously published in the Global North, as well as support new hypotheses about the interaction between the gut microbiome and SARS-CoV-2 infection.
A plant endophytic bacterium Burkholderia seminalis strain 869T2 increases plant growth under salt stress by affecting several phytohormone response pathways
Authors: Hwang Hau-Hsuan , Huang Yu-Ting , Chien Pei-Ru , Huang Fan-Chen , Wu Chih-Lin , Chen Liang-Yu , Hung Shih-Hsun Walter , Pan I-Chun , Huang Chieh-Chen
Published: February 2025

Background

Due to global warming and gradual climate change, plants are subjected to a wide range of environmental stresses, adversely affecting plant growth and production worldwide. Plants have developed various mechanisms to overpower these abiotic stresses, including salt stress, drought, and high light intensity. Apart from their own defense strategies, plants can get help from the beneficial endophytic bacteria inside host plants and assist them in enduring severe growth conditions. A previously isolated plant endophytic bacteria, Burkholderia seminalis 869T2, from vetiver grass can produce auxin, synthesize siderophore, and solubilize phosphate. The B. seminalis 869T2 can colonize inside host plants and increase the growth of bananas, Arabidopsis, and several leafy vegetables.

Results

We further demonstrated that different growth parameters of Arabidopsis and pak choi plants were significantly increased after inoculating the B. seminalis 869T2 under normal, salt, and drought stress conditions compared to the mock-inoculated plants. Both transcriptome analysis and quantitative real-time PCR results showed that expression levels of genes related to phytohormone signal transduction pathways, including auxin, gibberellin, cytokinin, and abscisic acid were altered in Arabidopsis plants after inoculated with the strain 869T2 under salt stress, in comparison to the mock-inoculated control with salt treatments. Furthermore, the accumulation levels of hydrogen peroxide (H2O2), electrolyte leakage (EL), and malondialdehyde (MDA) were lower in the 869T2-inoculated Arabidopsis and pak choi plants than in control plants under salt and drought stresses.

Conclusions

The plant endophytic bacterium strain B. seminalis 869T2 may affect various phytohormone responses and reduce oxidative stress damage to increase salt and drought stress tolerances of host plants.
The utility of Glaucoma Information Cards for grasping glaucoma subtypes: a single-center pilot study
Authors: Yamada Yukinori , Murase Tetsuya , Mashida Emiko , Kakeda Yuki , Shibata Yuuka , Matsuo Hiroaki
Published: February 2025

Background

In Japan, anticholinergic drugs were contraindicated for glaucoma, regardless of subtype. The contraindication in patients with open-angle glaucoma (OAG) led to excessive medication restrictions because anticholinergic drugs are associated with a low risk of acute glaucoma attacks in OAG. To eliminate this problem, the contraindications of anticholinergic drugs were reduced for types from all glaucoma to angle closure glaucoma (ACG) in 2019. This change requires differentiation of OAG from ACG for the proper use of drugs. The Japan Ophthalmologists Association created Glaucoma Information Cards to share glaucoma subtypes and restricted the medication list. However, only a few studies have investigated the efficacy of Glaucoma Information Cards. In this study, we evaluated the benefits of identifying glaucoma subtypes prior to admission by distributing Glaucoma Information Cards to patients through pharmacists.

Methods

Pharmacists distributed Glaucoma Information Cards to patients whose glaucoma subtype was unclear at the time of the preadmission pharmacist interview and asked them to have the treating ophthalmologist fill out the glaucoma subtype data. We collected patient data, hospitalized clinical department, status of realization of glaucoma subtypes, methods of realization of glaucoma subtypes, and usage of anticholinergic drugs from medical records.

Results

First, we investigated how hospital pharmacists identify the type of glaucoma. Pharmacists were able to determine the glaucoma type of most patients through medical records, patient interviews, and the Glaucoma Information Card. We analyzed the records of patients who were scheduled for ophthalmology visits prior to admission and had been given Glaucoma Information Cards. Eleven of the 13 patients brought the Glaucoma Information Card to the hospital, which was analyzed by an ophthalmologist. Two patients were administered anticholinergic drugs without restriction because of proven OAG according to the Glaucoma Information Card. One patient was administered cibenzoline for atrial fibrillation. Another patient received isosorbide dinitrate for coronary angiography. These cases indicate that the distribution of Glaucoma Information Cards can help avoid unnecessary medication restrictions in patients with OAG.

Conclusions

Our results suggest that the distribution of the Glaucoma Information Cards is useful for proper drug use in patients with glaucoma.
Seismic full-waveform inversion regularized with a migration image
Authors: Lu Ke , Wang Yanghua
Published: February 2025

Seismic full-waveform inversion (FWI) aims to reconstruct high-resolution velocity models of the subsurface from seismic data. However, it is known to face the problem of ill-posedness and has difficulties in reconstructing deep, low-illumination regions. To overcome these challenges, we use a migration image to regularize the FWI problem. In contrast to conventional approaches where the model regularization is added to the data misfit term, our method uses a U-net to introduce this prior information. We show that the prior information about the structure contained in a migrated image can be naturally and effectively incorporated into the generated output, and therefore use the migration image as input to the U-net. We reparametrize the velocity model as a combination of the U-net output and a background velocity model. The learnable parameters of the U-net are optimized against the FWI data misfit by using the gradient calculated from automatic differentiation. Our method requires no network pre-training and is time efficient due to the use of automatic differentiation accelerated by Graphic Processing Units (GPUs). We implement this method on the synthetic Marmousi and Sigsbee2a models, as well as on field data from the Gulf of Mexico. The results show a regularization effect for mitigating local minima issues, improving convergence speed, and preserving geological structures. Such a regularization effect is well suited to improve velocity reconstruction under poor illumination conditions, such as subsalt structures.