bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Treatment of Basilar Invagination
Authors: Botelho Ricardo Vieira , Alves Oscar L. , de Sá Carneiro Geraldo , Chen Zan , Yaman Onur , Parthiban Jutty , Visocchi Massimiliano , Klekamp Jörg , Goel Atul , Zileli Mehmet
Published: February 2025

Study Design.

A systematic literature review and consensus using Delphi method.

Objective.

This review aims to outline the therapeutic criteria and clarify the best surgical options for the different types of basilar invagination (BI).

Summary of Background.

BI is a complex developmental malformation for which many surgical remedies have been proposed without clear consensus.

Material and Methods.

Using PubMed, the authors reviewed the literature on the surgical treatment of BI published from 2011 to 2022 looking at different surgical options. A panel of spine surgeons and members of the WFNS Spine Committee used the Delphi technique to assess the strength of literature, elaborate, and vote on statements regarding the surgical management of BI.

Results.

Thirteen recommendations were issued covering the most relevant topics related to the surgical treatment of BI. Posterior fossa decompression alone is an option to treat BI without instability. Most cases of BI and AAI can be treated by C1-C2 fixation. In selected cases, distraction of the atlantoaxial joint may be required. Current evidence is lacking which technique is better to correct irreducible BI. OCF can be used in case of atlas assimilation, dysgenesis of C1 lateral mass, in irreducible cases, odontoidectomy and revision of failed C1-C2 fixation. Complications of the OCF may reach up to 50%. The role for anterior fusion for treatment of BI need to be better assessed by further studies. In the setting of irreducible anterior compression caused by BI, the anterior odontoidectomy can be indicated supplemented by C1-C2/occipital-cervical fusion.

Conclusions.

There are multiple surgical options for basilar invagination depending on the existence of compression, AAD or irreducibility. The WFNS spine committee proposed consensus recommendations based on relevant literature published after 2011 to help surgeons standardize the level of care and improve outcomes following treatment across the globe.
The Maastricht Intensive Care COVID Cohort: A Critical Appraisal of the Predefined Research Questions
Authors: Wintjens Marieke S.J.N. , Aydeniz Eda , van Rosmalen Frank , Driessen Rob G.H. , Hulshof Anne-Marije , Bergmans Dennis C.J.J. , van Kuijk Sander M.J. , van der Horst Iwan C.C. , van Bussel Bas C.T. ,   Maastricht Intensive Care COVID (MaastrICCht) collaborators
Published: February 2025

IMPORTANCE:

A review of the study processes and protocols afterward by the researchers themselves is scarce.

OBJECTIVES:

The present study aimed to evaluate the study design and the process of data collection of the Maastricht Intensive Care COVID (MaastrICCht) cohort during the COVID-19 pandemic. This evaluation provides information about the quality of the predefined questions and contributes to transparency in science.

DESIGN, SETTING, AND PARTICIPANTS:

Critical appraisal of studies using data from the MaastrICCht cohort.

MAIN OUTCOMES AND MEASURES:

Evaluation of the process of study design and data collection during the COVID-19 pandemic, focusing on the research process and results.

RESULTS:

From March 2020 to April 2023, all patients diagnosed with COVID-19 admitted to the ICU at Maastricht University Medical Center + (n = 544) were included in the MaastrICCht cohort. In total, 37 studies were carried out until April 2024. Fifteen studies addressed 11 of the 13 predetermined research questions, whereas 22 additional studies were performed based on the initial research questions described in the design. Furthermore, 10 studies were conducted with other researchers in national and international collaboration as a response to new arising questions based on evidence that appeared relevant during the pandemic.

CONCLUSIONS AND RELEVANCE:

Our critical appraisal indicated that using a study protocol enabled many publications and (inter)national collaborations, although formulating pertinent research questions in the context of a novel disease appeared daunting. Despite this, most questions were successfully addressed, whereas few were resolved by other researchers or lost importance due to the expanding body of knowledge.
Association of Omega-3 Status With Long-Term Risk of Hospitalization for Sepsis
Authors: Narayan Deo , Vlasschaert Caitlyn , Day Andrew G. , Norman Patrick , Rauh Michael J. , Maslove David M.
Published: February 2025

Objectives:

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection. Despite decades of clinical trials, there are no specific treatments; care of the nearly 50 million annual cases worldwide is limited to antimicrobials and supportive measures. A primary prevention strategy may therefore be of value. We hypothesized that higher premorbid omega-3 fatty acid levels would be associated with a reduced incidence of sepsis.

Design:

Population-based cohort study.

SETTING:

Retrospective data from the United Kingdom (U.K. Biobank).

Patients:

Two hundred seventy-three thousand three hundred twenty-five participants from the U.K. Biobank.

Interventions:

None.

Measurements and Main Results:

Our exposure was baseline estimated omega-3 index (eO3I), modeled both categorically in quartiles, and continuously with restricted cubic splines. Our outcome measure was hospital admission with an International Classification of Diseases, 10th Edition code consistent with sepsis. The median (interquartile range) baseline eO3I was 6.0% (4.8–7.3%). Over a mean follow-up period of 13 years, 9241 participants experienced hospitalization with sepsis. In our adjusted model, compared with the lowest eO3I quartile, participants had lower risks of sepsis incidence in the second quartile (hazard ratio [HR], 0.88; 95% CI, 0.86–0.91; p < 0.001), third quartile (HR, 0.80; 95% CI, 0.78–0.83; p < 0.001), and fourth quartile (HR, 0.75; 95% CI, 0.73–0.77; p < 0.001). When analyzed as a continuous variable, increasing eO3I was associated with a decreasing risk of sepsis (p < 0.001).

Conclusions:

In this population-based cohort study, baseline eO3I was inversely associated with subsequent sepsis incidence. Given that omega-3 levels can be increased with dietary supplementation, primary prevention should be explored to mitigate the burden of sepsis.
A Comparative Study of End-of-Life Care Before and During the COVID-19 Pandemic Using Electronic Nursing Records
Authors: Park Seul Ki , Sung Sumi , Min Yul Ha
Published: February 2025

This study aimed to identify the end-of-life care provided to patients admitted to a ward using electronic nursing records standardized with SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to analyze changes in end-of-life care before and during the COVID-19 pandemic. The study setting was oncology or hematology-oncology wards in a tertiary care hospital. A total of 161 069 nursing statements for 600 patients before COVID-19, admitted from January 2018 to December 2019, and 110 333 nursing statements for 454 patients during COVID-19, admitted from January 2020 to December 2021, were extracted from the clinical data warehouse of the study hospital. We mapped 427 unique nursing statements to SNOMED CT. The differences in the number of SNOMED CT concepts among the three groups—patients before COVID-19, patients without COVID-19 during COVID-19, and patients with COVID-19 during COVID-19—were analyzed using analysis of variance. “Acute pain,” “Patient on oxygen,” “Notification of physician,” “Oxygenation monitoring,” and “Pain assessment” were recorded most frequently. The frequency of nursing statements related to oxygenation was significantly lower in patients without COVID-19 during the COVID-19 pandemic compared with patients before COVID-19. Nursing statements pertaining to emotional or spiritual care appeared to be underrepresented in both the nursing assessment/outcome and nursing intervention domains. Our study showed that the standardized nursing records can be used as a source of information to explore changes in end-of-life care before and during the COVID-19 pandemic.
Cognitive Frailty for Young Breast Cancer Survivors After Chemotherapy: Implication for the Design of Health Education Materials
Authors: Jiang Lulu , Liu Yanyan , Wiley Joshua , Zhang Chengrui , Wang Xiyi , Hu Yun
Published: February 2025

Background:

As the most common cancer among women globally, breast cancer often leads to accelerated frailty in younger survivors, particularly during chemotherapy, causing cognitive impairments. This highlights the urgent need for tailored health education materials to address these challenges.

Objective:

To analyze cognitive load in young breast cancer survivors (YBCSs) after chemotherapy and contribute to the development of more tailored and effective health education materials for this population.

Methods:

Cognitive load theory informed a semistructured interview guide to investigate the challenges YBCSs face when engaging with health education materials.

Results:

Eleven participants aged 18–45 years were interviewed. Based on cognitive load theory, 4 themes were identified as follows: symptom burden, impairment of working memory, decrease the intrinsic cognitive load, and decrease the extraneous cognitive load.

Conclusions:

YBCSs frequently experience cognitive burden due to chemotherapy and perimenopause, which can trigger adverse personal states that lead to working memory overload and depletion. They prefer health education materials that offer credible, relevant information presented in modern formats, particularly short videos lasting around 10 seconds. However, excessive transient information and interactive elements may create unnecessary cognitive load.

Implications for Practice:

Developing health education materials should focus on conciseness, visual appeal, and small, digestible segments to ease cognitive load. Incorporating storytelling and relatable scenarios can significantly boost engagement and comprehension.

What is Foundational:

This model, informed by cognitive load theory, could be used as the basis of educational materials of greater care usefulness for these younger survivors of breast cancer.
Updated Review of Cellular Dermatofibroma: Benign or Not?
Authors: Le Nicholas T. , Fung Maxwell A. , Eisen Daniel B.
Published: February 2025

BACKGROUND

Cellular dermatofibromas (CDFs) are uncommon benign fibrous histiocytomas with histologic patterns resembling malignancies. Despite their benign nature, CDFs can recur and metastasize. Physicians are uncertain about the management of CDF, given its resemblance to dermatofibrosarcoma protuberans.

OBJECTIVE

This review aims to review CDF's clinical and histologic features, differentiate it from similar presenting malignancies, and discuss treatments and outcomes for better clinical management.

MATERIALS AND METHODS

In April 2024, a PubMed and Google Scholar search was completed using “cellular dermatofibroma” through the University of California Davis Medical School's library databases. The search included meta-analyses, randomized controlled trials, observational studies, reviews, and case studies published within the past 70 years. References from retrieved articles were utilized as additional resources.

RESULTS

Clinical signs of CDF include firm, skin-colored to hyperpigmented lesions usually larger than 2 cm, typically on extremities. Currently, there are no definitive indicators for CDF recurrence or metastasis. Diagnosis requires microscopic and histopathologic examination, with surgical excision as the preferred treatment. Recurrence is not uncommon, while metastasis is rare.

CONCLUSION

CDFs often develop in young/middle-aged adults with a tendency to recur and in rare cases can metastasize. Future studies could explore lesion characteristics that are associated with potential for recurrence and metastasis.
Fibrinolytic activity in infants undergoing cardiac surgery on cardiopulmonary bypass with routine tranexamic acid
Authors: Siemens Kristina , Parmar Kiran , Harris Julia , Hunt Beverley J. , Tibby Shane M.
Published: February 2025

BACKGROUND

Fibrinolytic activity contributes to bleeding after cardiopulmonary bypass (CPB).

OBJECTIVE

Our objectives were, in a group of infants undergoing cardiac surgery with CPB: to document the extent of peri-operative fibrinolysis using rotational thromboelastometry (ROTEM) and standard biomarkers; to compare the agreement between these fibrinolytic measures; to assess whether fibrinolytic activity is associated with early postoperative mediastinal bleeding and assess whether supplementation with fibrinogen concentrate affected fibrinolysis.

DESIGN

Prospective cohort, mechanistic substudy, nested within the FIBrinogen CONcentrate (FIBCON) randomised controlled trial.

SETTING

Single centre, tertiary paediatric cardiac surgery and paediatric intensive care units.

PATIENTS

Ninety infants (median age 6.3 months) undergoing cardiac surgery, who all received routine intra-operative tranexamic acid. The infants were randomised to receive either an individualised dose of fibrinogen concentrate (n = 60) or placebo (n = 30) during CPB.

MAIN OUTCOME MEASURES

We measured the ROTEM variable maximum clot lysis (ML), and fibrinolytic biomarkers including plasmin-antiplasmin (PAP) and tissue plasminogen activator antigen (tPA-Ag). Blood was sampled pre-CPB, on-CPB and post-CPB, and 4 h after PICU admission.

RESULTS

tPA-Ag, PAP and ROTEM ML increased significantly after CPB despite the use of tranexamic acid. The two fibrinolytic biomarkers t-PA and PAP, correlated (P = 0.001) but neither correlated with ROTEM ML. Early postoperative blood loss was inversely associated with PAP levels. Each 100 μg l−1 rise in PAP was associated with a 7.9% reduction in mean blood loss. Fibrinogen concentrate supplementation as expected did not affect tPA-Ag but was temporally associated with an increase in PAP levels and a decrease in ROTEM fibrinolytic activity.

CONCLUSION

Fibrinolysis is activated after paediatric cardiac CPB surgery as indicated by increased tPA-Ag and ROTEM ML. The substantial increase in tPA-Ag post-PICU admission is probably accompanied by a similar rise of plasminogen activator inhibitor 1 (PAI-1) as part of the acute phase response to surgery, thereby limiting clinical fibrinolysis. Supplementation of fibrinogen concentrate was associated with increased PAP activity and less clinical bleeding, consistent with the known role for fibrinogen in being a substrate for plasmin.

TRIAL REGISTRATION

ISCTRN:50553029, Eudract:2013-003532-68.
Adverse drug reactions in pulmonology
Authors: Horwitz Henrik , Jørgensen Theis Guldager , Heerfordt Ida Marie , Olsen Rasmus Huan
Published: February 2025

This study investigates the adverse reactions observed in pulmonary medicine. We used data from the Adverse Drug Event Manager (ADEM) of the Capital Region of Denmark from 2013 to 2024. Antibiotic drugs were the most common causes of adverse reactions reported but with very different side effect profiles. We observed a wide range of signals related to angioedema and Angiotensin Converting Enzyme (ACE) inhibitors as well as interstitial lung disease and nitrofurantoin and methotrexate. These findings were aligned with existing literature. Although the system captured well known adverse drug reactions, it struggled to detect new safety signals.
Risk Factors for Ectropion After Lower Eyelid and Cheek Reconstruction Following Mohs Micrographic Surgery
Authors: Rames Jess D. , Rames Melissa M. , Yu Caroline Y. , Sanchez Figueroa Nicole , Akpala Christeebela O. , Hussein Sara , Demer Addison M. , Sharaf Basel A. , Wagner Lilly H.
Published: February 2025

Background:

Development of ectropion is a frequently reported complication after reconstruction of infraorbital Mohs defects. This study aimed to characterize preoperative and surgical factors contributing to ectropion development in patients undergoing reconstruction after Mohs micrographic surgery.

Methods:

We conducted a retrospective single-center case-control study on patients undergoing reconstruction of Mohs micrographic surgery defects involving the nonmarginal lower eyelid and upper cheek from 2011 to 2023. Pre- and postoperative photographs were reviewed to confirm defect location and postreconstructive eyelid malposition. Ectropion risk factors were determined with uni- and multivariate odds ratio analyses.

Results:

A total of 202 patients were included, 45 cases in the ectropion group and 157 in the control group. Negative orbital vector (P = 0.02), recurrent disease (P = 0.01), and greater defects size (P = 0.007) were associated with postreconstructive ectropion. Ectropion was more likely after multidisciplinary reconstruction (13.3% versus 1.4%, P < 0.001) and reconstruction with cervicofacial flaps (28.9% versus 4.2%, P < 0.0005); and less likely after primary closure (8.9% versus 28.5%, P < 0.001). Multivariate assessment (odds ratio [95% confidence interval], P value) revealed that combined cheek and eyelid defect involvement (4.32 [1.36–13.6], P = 0.01), larger size (1.07 [1.03–1.13], P < 0.001), and negative orbital vector (12.11 [2.65–65.42], P = 0.002) were independent risk factors for ectropion development.

Conclusions:

Combined cheek/lower eyelid defects and negative orbital vector increase the risk of postreconstructive ectropion. These findings can be used to optimize surgical technique and counsel patients on increased likelihood of this complication with possible need for revision surgery.
Implant-based Cryopreserved Autologous Free Nipple Grafting for Breast Reconstruction: The ICEBERG Technique
Authors: Patel Sonia S. , Lu Nathan E. , Xia Thomas , Mailey Brian A.
Published: February 2025

Nipple creation is generally the final step of breast reconstruction. However, patients many times forego this procedure due to reconstructive fatigue. Herein, we describe a technique of harvesting the nipple–areola complex as a full-thickness skin graft during the initial mastectomy with direct-to-implant reconstruction, storing the harvested nipple tissue at −80°C, and then placing the nipple as a skin graft 2 weeks after the initial mastectomy. This method, termed the implant-based cryopreserved autologous free nipple grafting for breast reconstruction technique, serves as a feasible and shorter alternative to traditional procedures. The implant-based cryopreserved autologous free nipple grafting for breast reconstruction technique can, therefore, reduce the longevity of the reconstructive journey for patients.
In Vivo Bone Mineral Density Assessment With Spectral Localizer Radiographs From Photon-Counting Detector CT
Authors: Moser Lukas Jakob , Klambauer Konstantin , Diaz Machicado Maria Carolina , Frey Diana , Mergen Victor , Eberhard Matthias , Nowak Tristan , Schmidt Bernhard , Flohr Thomas , Distler Oliver , Alkadhi Hatem
Published: February 2025

Purpose

The aim of this study was to determine in a prospective patient study the accuracy of areal bone mineral density (aBMD) measurements with spectral localizer radiographs obtained with a clinical photon-counting detector computed tomography (PCD-CT) scanner in comparison with dual-energy x-ray absorptiometry (DXA).

Methods

In this institutional review board–approved, prospective study, 41 patients (15 females, 26 males; mean age 61.3 years, age range 35–78 years) underwent PCD-CT of the abdomen with a spectral localizer radiograph (tube voltage 140 kVp, tube current 30 mA) and DXA within a median of 45 days. aBMD values were derived for lumbar vertebrae L1–L4 from both methods and were compared with linear regression, Pearson correlation, intraclass correlation coefficients (ICCs), and Bland-Altman plots. T-scores were calculated on a patient level and were compared between methods.

Results

DXA and spectral localizer radiographs showed strong correlation in aBMD measurements (R = 0.97, P < 0.001) and patient level T-scores (R = 0.99, P < 0.001). There was a strong agreement between aBMD from both methods (ICC, 0.96; 95% CI, 0.94–0.97). Bland-Altman analysis revealed a very small mean difference in aBMD between methods (mean absolute error 0.019 g/cm2) with narrow limits of agreement (−0.083 g/cm2 to 0.121 g/cm2). Similarly, there were small differences in regard to the T-score (mean absolute error 0.156) with narrow limits of agreement (−0.422 to 0.734) between methods. ICCs indicated an excellent agreement between T-scores from DXA and spectral localizer radiographs (ICC, 0.98; 95% confidence interval, 0.95–0.99).

Conclusions

Our prospective patient study indicates that spectral localizer radiographs obtained with a clinical PCD-CT system enable accurate quantification of the lumbar bone areal mineral density. This opens up the opportunity for opportunistic screening of osteoporosis in patients who undergo CT for other indications.
A Case of McCune Albright Syndrome With Rare Extensive Polyostotic Fibrous Dysplasia
Authors: Ganesan Harinee , Madivanane Vasanth , Dhayalane Kabilash , Sainath Ragire , Goyal Harish
Published: February 2025

McCune-Albright syndrome is characterized by a triad of café au lait macules, polyostotic fibrous dysplasia (FD), and endocrine abnormalities. Bilateral and extensive presentation of FD is rarely reported. We report an interesting case of 24-year-old woman presenting with multiple episodes of slip and fall, sustaining multiple fractures with history of precocious puberty and skin complaints. On evaluation with 99mTc-MDP bone scan, all the long bones, ribs, pelvic bones, frontal bone, and maxilla showed deformities and increased osteoblastic activity, suggesting extensive polyostotic FD. Thus emphasizing the crucial role of 99mTc-MDP bone scan in the diagnosis of extensive FD and guides in understanding of the polyostotic involvement.
Surgical Complications After Fronto-orbital Advancement for Craniosynostosis: Analysis of a National Database
Authors: Lee Anna D. , Gomez Diego A. , Le Elliot L. H. , Palmer Skyler K. , French Brooke , Nguyen Phuong D. , Mathes David W. , Khechoyan David Y.
Published: February 2025

Background:

Fronto-orbital advancement (FOA) is the standard surgical intervention for patients with craniosynostosis and associated fronto-orbital dysmorphology. Although previous studies have provided insights into center-specific complications, comprehensive, large-scale analyses remain limited. This study utilizes a national database to address these gaps, offering a large-scale perspective on FOA outcomes.

Methods:

Patients aged 0 to 16 years who underwent FOA from 2007 to 2015 were identified using the PearlDiver database. Patients were divided into early (0–5 y) and late (6–16 y) groups. Complications were identified using a combination of ICD and CPT codes. Intraoperative complications, including hematoma/hemorrhage, cerebrovascular infarction, and cardiac arrest, were defined as those occurring within 48 hours of the procedure. Postoperative complications analyzed at intervals of 0, 30, 90, 180, and 365 days post-operation included cerebrospinal fluid leak, hardware-related complications, hemorrhage, seizure, surgical site infection, wound dehiscence, and death. Summary statistics were conducted utilizing Bellwether software in PearlDiver.

Results:

A total of 2026 patients underwent FOA, with a mean of 1.5 years in the younger cohort (n=1905) and 9.0 years in the older cohort (n=121). Although rare, hemorrhage was the most common intraoperative complication. One-year postoperative complications were predominantly related to wound dehiscence and surgical site infection in the younger (5.10%) and older (14.1%) cohorts. The 1-year reoperation rate was 7.2% for the younger cohort and 19.0% for the older cohort.

Conclusions:

FOA is a safe operation with an overall low complication rate. However, older patients demonstrate a higher rate of reoperations, emphasizing the need to identify the optimal timing for FOA in patients with craniosynostosis.
Novel Robotic Valvuloplastic Esophagogastrostomy Technique After Proximal Gastrectomy: A Safety and Feasibility Study
Authors: Amini Neda , Kinoshita Takahiro , Arrieta Manuel , Yoshida Mitsumasa , Nagata Hiromi , Habu Takumi , Komatsu Masaru , Yura Masahiro
Published: February 2025

Background:

Esophagogastrostomy is one of the reconstruction techniques after proximal gastrectomy, but reflux and esophagitis are significant concerns. We introduced a new robotic valvuloplasty technique (single-flap), taking advantage of robotic surgery to address these issues and simplify the technique, especially for tumors with esophageal invasion.

Methods:

Between March 2022 and March 2024, patients who underwent robotic proximal gastrectomy with the single-flap technique were included. Based on the difficulty of the surgery, patients were divided into 2 groups: one with esophageal invasion requiring anastomosis in the mediastinum and the second group with tumors in the upper third of the stomach requiring anastomosis in the abdomen.

Results:

A total of 22 patients were included: 13 in the esophageal invasion group and 9 in the upper stomach group. The median size of esophageal invasion was 2 cm (1 to 3 cm). The median operative time was 320 minutes (esophageal invasion 326 vs. upper stomach 280 min, P=0.51), with a median blood loss of 35 g (31 vs. 38 g, P=0.19). No postoperative mortality, anastomotic leaks, reflux symptoms, or pancreatic fistulas were observed. Eighteen patients underwent endoscopic evaluation, and no sign of esophagitis was detected. Five patients (22.7%) developed grade III strictures requiring endoscopic balloon dilation (esophageal invasion 32.1% vs. upper stomach 22.2%; P=0.96).

Conclusions:

Robotic proximal gastrectomy with single-flap valvuloplastic esophagogastrostomy is a safe and feasible option for gastroesophageal junction tumors with up to 3 cm of esophageal invasion.
Thermodynamics of free bosons and fermions in the hyperball
Authors: Batle Josep , Malomed Boris A.
Published: February 2025

Many-particle systems pose commonly known computational challenges in quantum theory. The obstacles arise from the difficulty in finding sets of eigenvalues and eigenvectors of the underlying Hamiltonian while enforcing fermion or boson statistics, not to mention the prohibitive increase in the computational cost with the system’s size. The first obvious step in this direction is to elaborate the theory for Fermi or Bose gases without inter-particle interactions. The traditional approach to the work is with the ideal gases confined in a cubic container with impenetrable walls (in arbitrary dimensions). This approach allows one to find the particle’s spectra and compute all thermodynamic quantities of the confined gas. In the present work, we consider the gas confined in a spherical container (in other words, an infinitely deep spherical potential well in D dimensions), solving the corresponding Schrödinger equation using zero boundary conditions. We address the case of a finite number of particles N, either bosons or fermions, in the spherical potential box, as well as the thermodynamic limit, corresponding to

N

→ ∞. Owing to Weyl’s relations, in the latter limit, the results do not depend on the shape of the box and thus approach the commonly known ones valid in the infinite space. Owing to the underlying SO(D) symmetry, we are dealing with particles carrying a well-defined angular momentum that, together with sorted energy eigenvalues, imparts a shell structure to the system.
Exploring the genomic landscape of Chlamydiifrater species: novel features include multiple truncated major outer membrane proteins, unique genes and chlamydial plasticity zone orthologs
Authors: Hölzer Martin , Reuschel Charlotte , Vorimore Fabien , Laroucau Karine , Sachse Konrad
Published: February 2025

Recently discovered obligate intracellular bacteria belonging to the genus Chlamydiifrater with the species of Chlamydiifrater phoenicopteri and Chlamydiifrater volucris were studied to explore the composition of their genomes and their relatedness to Chlamydia, the other genus of the family Chlamydiaceae. We investigated 4 isolates of Cf. volucris, 2 of them newly sequenced, and one of Cf. phoenicopteri alongside 12 representatives of the Chlamydia species. Our study uncovers previously unrecognized genomic structures within Chlamydiifrater using a hybrid sequencing approach and advanced annotation pipelines, providing insights into species-specific adaptations and evolutionary dynamics. The integration of long-read sequencing data, comprehensive re-annotation strategies and pan-genomics enabled the localization of the unique plasticity zone and the identification of novel gene clusters in Chlamydiifrater strains, which improves our understanding of chlamydial genome architecture and plasticity in the family Chlamydiaceae. Our analysis revealed that 761 CDS (~80%) are shared among members of both genera. We further identified 158 unique genes of Chlamydiifrater species, but their annotation remains challenging because of the absence of functionally annotated orthologs in public databases. A full-length ompA gene encoding the major outer membrane porin was seen in all Chlamydiifrater strains. We also describe the localization and structure of multiple truncated CDS of ompA family members, representing one of this study’s most interesting findings. While genome analysis of Chlamydiifrater spp. confirmed numerous common features shared with representatives of the genus Chlamydia, many unique genomic elements were identified that underpin the distinct phenotype and separate genetic position of these new microorganisms.
Use of Medroxyprogesterone Acetate and Risk of Meningiomas: A Comparative Safety Study
Authors: Frey Connor , Sodhi Mohit , Fatehi Mostafa , Kezouh Abbas , Etminan Mahyar
Published: February 2025

Medroxyprogesterone acetate (MPA), a popular contraceptive agent has recently been associated with meningiomas. However, this risk compared to other available contraceptive agents has not been elucidated.

We sought to quantify the risk of meningiomas in women on MPA compared to those using oral contraceptives containing ethinylestradiol-levonorgestrel (EE-LNG) by undertaking a nested case-controls study using the PharMetrics Plus database (IQVIA, USA). After creating a cohort of new users of MPA and EE-LNG from 2006 to 2020 new cases of meningioma were identified. Cases were and matched to controls by age and calendar time. Conditional logistic regression was used to adjust for previous exposure to radiotherapy, previous use of hormonal contraceptives, and obesity The adjusted incident rate ratio (IRR) for meningioma for greater than one year of use was 3.55 (95%ICI: 1.85-6.55). Women using MPA have an increased risk of developing meningioma compared to users of EE-LNG.
Cutaneous leishmaniasis in Casablanca-Settat region (Morocco): spatio-temporal analysis of disease dynamic and machine learning based case prediction
Authors: El Idrissi Saik Imane , Talimi Hasnaa , Badri Bouchaib , Bouhout Souad , Fissoune Rachida , Riyad Myriam , Lemrani Meryem
Published: February 2025

Cutaneous leishmaniasis (CL) caused byLeishmaniaprotozoa and transmitted through infected sandfly bites, poses a significant public health burden in Morocco. Our research aims to retrospectively assess spatio-temporal patterns of CL in the most densely populated region of the country, Casablanca-Settat, during a period of 14 years (2009–2022). We investigate epidemiological trends, seasonal fluctuations and climatic factors influence on CL prevalence and predict cases in the region’s most important CL focus. Using Geographic Information Systems (GIS) and statistical methods, we analyzed CL data obtained from the Moroccan Ministry of Health and Social Protection with demographic information and climate-related parameters. Four machine learning prediction models for CL cases in the El Brouj focus were compared and their performance was evaluated. Our results revealed a steady increase in CL cases until 2019, followed by a significant surge, withLeishmania tropicaidentified as the causative agent for all documented cases. The incidence rates varied among demographic groups, with higher rates observed in females and children aged 5-14. Seasonal analysis indicated a notable increase in cases during spring. Spatial distribution analysis identified El Brouj as the sole endemic CL focus_and the highest hotspot in the area, underscoring the necessity of targeted interventions in this location. Furthermore, Spearman correlation analysis revealed a significant association between CL cases and low temperature and precipitation, emphasizing climate variables role in disease incidence. Prediction modeling for future CL cases in El Brouj focus was assessed with six different models and Linear Regression was the most suitable. This retrospective study provides crucial insights into CL epidemiology in the Casablanca-Settat region, highlighting the need for implementing a coordinated approach tailored to the region that could help curb the spread of CL in Settat province, given the predictive model’s outlook on future CL trends in this area.
Improving Efficiency in the Inpatient Echocardiography Laboratory: A Quality Improvement Project
Authors: Samples Stefani , Roytman Zhanna , McCaw Carrie , Jone Pei-Ni
Published: February 2025

Background

Pediatric echocardiograms are performed daily on inpatient hospital units, predominantly in the Cardiac Intensive Care Unit. Understanding the precise study indication from the ordering providers is critical for completing imaging. Given the volume of echocardiograms ordered daily and staffing shortages, timely completion of echocardiograms is important for maintaining efficiency and productivity. The aim of this study was to identify areas to improve efficiency using quality improvement methodologies.

Methods

The SMART aim was to decrease the total echo completion time by 10% within 6 months. Using a fishbone diagram, limitations in the ordering system and inadequate ordering provider knowledge were identified as areas for improvement. Primary process and outcome metrics included total echo completion time, pre-echocardiogram buffer time, and order documentation of pertinent clinical history. PDSA 1 implemented order updates to provide increased specificity in orders with a picklist of common reasons for inpatient echocardiograms. PDSA 2 implemented a physician alert for STAT studies to reduce the number of inappropriate orders. PDSA 3 implemented additional order updates and staff education.

Results

Total echo completion time decreased with each cycle for total 25% reduction. This correlated with a decrease in the pre-echocardiogram buffer time of 56% without any significant changes in the number of images obtained per study or the daily inpatient volume. The documentation of pertinent clinical history increased by 18% and maintained at 99% appropriate documentation for the final two PDSA cycles. Pre and post intervention surveys indicated an overall improvement in the ordering process for both the inpatient ordering providers and echocardiography laboratory staff.

Conclusions

Echocardiography laboratory efficiency significantly improved throughout the course of this project without negative effects on the ordering providers or echocardiography laboratory staff. Our project demonstrates the ability to affect clinically relevant improvements utilizing simple workflow process changes in the pediatric echocardiography laboratory.
sciLaMA: A Single-Cell Representation Learning Framework to Leverage Prior Knowledge from Large Language Models
Authors: Hu Hongru , Zhang Shuwen , Choi Yongin , Malladi Venkat S. , Quon Gerald
Published: February 2025

Abstract

Single-cell RNA sequencing (scRNA-seq) enables high-resolution exploration of cellular diversity and gene regulation, yet analyzing such data remains challenging due to technical and methodological limitations. Existing task-specific deep generative models like Variational Auto-Encoder (VAE) and its variants struggle to incorporate external biological knowledge, while transformer-based foundational large Language Models (LLMs or large LaMs) face limitations in computational cost and applicability to tabular gene expression data. Here, we introduce sciLaMA (single-cell interpretable Language Model Adapter), a novel representation learning framework that bridges these gaps by integrating static gene embeddings from multimodal LaMs with scRNA-seq tabular data through a paired-VAE architecture. Our approach generates context-aware representations for both cells and genes and outperforms state-of-the-art methods in key single-cell downstream tasks, including batch effect correction, cell clustering, and cell-state-specific gene marker and module identification, while maintaining computational efficiency. sciLaMA offers a computationally efficient, unified framework for comprehensive single-cell data analysis and biologically interpretable gene module discovery.
Association of human gut microbiota with Alzheimer’s disease pathogenesis: An exploratory clinical study
Authors: Ohara Tadashi , Taki Yasuyuki , Yamamoto Shinya
Published: February 2025

The relationship between Alzheimer’s disease (AD) onset and the brain–gut axis has garnered increasing attention. This study aimed to investigate the potential role of the brain–gut axis in AD pathogenesis, with a specific focus on microbiota composition. This exploratory study enrolled 10 patients with AD and 13 healthy adults, grouped by age (≤30 years, 31–40 years, and ≥41 years). Fecal samples were collected, and 16S rRNA gene sequencing was employed to analyze differences in fecal microbiota composition at the bacterial species level. Certain bacterial species appeared more abundant in the AD group (e.g.,Ruminococcus inulinivoransandRuminococcus torques), while others were relatively more abundant in healthy adults (e.g.,Prevotella vulgatus 1,Bacteroides wexlerae,Clostridium butyricum, andAlistipes rectalis). However, these differences were not statistically significant, likely because of the limited sample size. These findings suggest that fecal microbiota composition may differ between patients with AD and healthy individuals, with a potential intermediate group at risk of AD development. Larger-scale clinical studies are necessary to further elucidate the bacterial species associated with AD pathogenesis, potentially enabling the use of microbiota composition as a screening tool to distinguish between healthy individuals, patients with AD, and those with preclinical AD.
Targeting Mycobacterial Transpeptidases: Evaluating the Roles of Ldt and PBP Inhibition in SuppressingMycobacterium smegmatis
Authors: de Munnik Mariska , Calvopiña Karina , Rabe Patrick , Schofield Christopher J.
Published: February 2025

β-Lactams demonstrate promising in vitro activity againstMycobacteriumspecies and are being explored for tuberculosis treatment; however, evidence of their in vivo efficacy versusMycobacterium tuberculosisremains limited. To achieve broad clinically relevant potency, optimisation of the classical β-lactam scaffolds or development of new or non-β-lactam inhibitors for mycobacterial transpeptidases is likely required. In mycobacteria, potential targets of β-lactams include L,D-transpeptidases (Ldts) and penicillin-binding proteins (PBPs). Reports suggest that dual inhibition of Ldts and PBPs may be necessary to achieve effective anti-mycobacterial activity, yet the specific contributions of Ldt and PBP inhibition to the β-lactam antibacterial mechanisms are not understood. We used fluorogenic substrate mimics to investigate the effects of β-lactams and reported LdtMt2inhibitors onMycobacterium smegmatis(Msm), assessing their impacts on the transpeptidase activities of Ldts and PBPs in living cells. The results reveal a statistically significant correlation between both Ldt and PBP inhibition andMsmgrowth suppression; though under the tested conditions a stronger correlation between Ldt inhibition andMsmgrowth suppression was observed. Notably, inhibition of both PBPs and Ldts was observed in all active inhibitors, though β-lactams manifest increased potency of PBP inhibition. The combination of the β-lactams meropenem and faropenem with selected LdtMt2inhibitors manifested an additive inhibitory effect againstMsm. Our results highlight the importance of further optimising PBPs and Ldt transpeptidase inhibition, particularly of Ldts, to improve β-lactam efficacy versus mycobacteria.
Outcomes of low-risk non-gynecological abdominal surgery in pregnant and nonpregnant women: a comparative study
Authors: Alotaibi Abdulrahman Muaod
Published: February 2025

Women typically undergo an appendectomy and cholecystectomy, which are the most commonly performed non-gynecological abdominal surgeries. Despite advancements, research on the safety and efficacy of laparoscopic surgery for low-risk, non-gynecological abdominal conditions in later-stage pregnant women remains limited. This study aimed to assess the efficacy and postoperative outcomes of low-risk non-gynecological abdominal surgery in female patients, including pregnant women. Female patients diagnosed with appendicitis and biliary disease were included. Based on the pregnancy status, the participants were divided into pregnant and nonpregnant groups. The study identified 11 (1%) cases of pregnancy among the 1029 female patients enrolled. Patients in the pregnant group were younger (30 ± 4.7 years vs. 39 ± 13.5 years, p = 0.002), more likely to undergo emergency surgery (90 vs. 21%, p = 0.001), had a higher rate of undergoing the open-entry approach (18.2 vs. 2.1%, p = 0.002), and more frequently required a postoperative drain (36.4 vs. 10.4%, p = 0.023) than did those in the nonpregnant group. The comorbidities, American Society of Anesthesiologists score, length of hospital stay, operative time, blood loss, postoperative complications, 30-day readmission rate, and mortality rate remained statistically consistent across both groups. Surgery was performed primarily for acute appendicitis in 72% of pregnant women and for biliary disease in 83% of nonpregnant women. None of the pregnant patients experienced preterm labor or fetal mortality after surgery. One patient had an abortion 8 weeks after laparoscopic appendectomy. In conclusion, the overall complication rate of non-gynecological abdominal surgery for appendicitis and biliary disease is 2%. Biliary disease is the most common indication of non-gynecological abdominal surgery among nonpregnant women, whereas appendicitis is the most common indication among pregnant women. Emergency surgery is a significant predictor of complications in pregnant women.
The Influence of NIHSS and Onset-to-Angiography Time on Neurological Outcomes Among Patients with Acute Ischemic Stroke Receiving Endovascular Thrombectomy-A Retrospective Observation Study
Authors: Lin Kuei-Ming , Lu Shuang-Yu , Shih Hong-Mo , Hsu Tai-Yi , Huang Fen-Wei , Wu Shih-Hao , Tsai Sheng-Ta , Liu Chien-Yu , Lin Chin-Han
Published: February 2025

Background

Acute ischemic stroke is a life-threatening condition requiring urgent intervention. For patients with large vessel occlusion (LVO), timely endovascular thrombectomy (EVT) is critical. This retrospective observational study investigates the impact of the National Institute of Health Stroke Scale (NIHSS) and onset-to-angiography time (OAT) on one-month neurological outcomes in acute ischemic stroke patients.

Methods

A total of 300 acute ischemic stroke patients with LVO who underwent EVT at a tertiary medical center in Taiwan from Jan. 2015 to Dec. 2018 were included. The NIHSS-time score was calculated by multiplying the pre-EVT NIHSS score by OAT. Favorable outcomes were defined as a modified Rankin Scale (mRS) ≤ 2 at one month. Multivariate logistic regression was used to identify the association between NIHSS-time scores and outcomes, adjusting for confounders.

Results

Patients with a NIHSS-time score < 4093 had significantly higher odds of achieving favorable outcomes (adjusted OR = 2.94, 95% CI = 1.56–5.56, p < 0.001). This highlights the importance of early EVT and initial stroke severity assessment in predicting recovery.

Conclusion

This study demonstrates that lower NIHSS-time scores are strongly associated with favorable neurological outcomes. Patients with a NIHSS-time score less than 4093 had a significantly higher ratio of favorable neurological function after one month. The NIHSS-time score offers a practical tool for prognostic evaluation, emphasizing the urgency of EVT in acute ischemic stroke patients. However, further studies are needed to validate these findings and explore their generalizability.
Neoadjuvant anti-4-1BB confers protection against spontaneous metastasis through low-affinity intratumor CD8+T cells in triple-negative breast cancer
Authors: Lim Bryan Jian Wei , Liu Mingyong , Wang Liuyang , Kong Sharleen Li Ying , Yin Tao , Yan Chengsong , Xiang Kun , Cao Chengjie , Wu Haiyang , Mihai Ariana , Tay Felicia Pei-Ling , Wang Ergang , Jiang Qizhou , Ma Zhehao , Tan Lianmei , Chia Rui Ning , Qin Diyuan , Pan Christopher C. , Wang Xiao-Fan , Li Qi-Jing
Published: February 2025

Neoadjuvant immunotherapy seeks to harness the primary tumor as a source of relevant tumor antigens to enhance systemic anti-tumor immunity through improved immunological surveillance. Despite having revolutionized the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC), a significant portion of patients remain unresponsive and succumb to metastatic recurrence post-treatment. Here, we found that optimally scheduled neoadjuvant administration of anti-4-1BB monotherapy was able to counteract metastases and prolong survival following surgical resection. Phenotypic and transcriptional profiling revealed enhanced 4-1BB expression on tumor-infiltrating intermediate (Tint), relative to progenitor (Tprog) and terminally exhausted (Tterm) T cells. Furthermore, Tintwas enriched in low-affinity T cells. Treatment with anti-4-1BB drove clonal expansion of Tint, with reduced expression of tissue-retention marker CD103 in Tprog. This was accompanied by increased TCR clonotype sharing between paired tumors and pre-metastatic lungs. Further interrogation of sorted intratumor T cells confirmed enhanced T cell egress into circulation following anti-4-1BB treatment. In addition, gene signature extracted from anti-4-1BB treated Tintwas consistently associated with improved clinical outcomes in BRCA patients. Combinatorial neoadjuvant anti-4-1BB and ablation of tumor-derived CXCL16 resulted in enhanced therapeutic effect. These findings illustrate the intratumor changes underpinning the efficacy of neoadjuvant anti-4-1BB, highlighting the reciprocity between local tissue-retention and distant immunologic fortification, suggesting treatment can reverse the siphoning of intratumor T cells to primary tumor, enabling redistribution to distant tissues and subsequent protection against metastases.