bluuebunny/crossref_metadata_2025_split huggingface dataset:
Illuminating the Challenges and Diagnostic Utility of Plasma Microbial Cell-Free DNA Sequencing in Suspected Infective Endocarditis: A Retrospective Observational Cohort Study
Authors: Kim Myeongji , Damronglerd Pansachee , Molina Garcia Sofia , Yetmar Zachary A , Razi Samrah , Ranganath Nischal , Mahmood Maryam , Abu Saleh Omar M 
Published: February 2025

Abstract

Background
Infective endocarditis (IE) is a life-threatening infection often challenging to diagnose, particularly in culture-negative cases. Plasma microbial cell-free DNA (mcfDNA) sequencing has shown potential for detecting pathogens in IE. However, the clinical utility, diagnostic impact, and limitations of mcfDNA sequencing remain debated. This study evaluates its use in diagnosing and managing IE in a tertiary care setting.

Methods
This single-center retrospective cohort study included adult patients (≥18 years) who underwent mcfDNA sequencing via the Karius test for suspected IE at Mayo Clinic Rochester between December 2019 and February 2024. Diagnostic classification followed the 2023 Duke - International Society of Cardiovascular Infectious Diseases (ISCVID) criteria. Data on demographics, clinical features, routine microbiological work-up, and mcfDNA sequencing results were collected. Statistical analysis was conducted to evaluate the diagnostic utility and treatment impact.

Results
Among 141 patients, 66 had a diagnosis of IE, with mcfDNA sequencing identifying pathogens in 60.6% of cases compared to 39.4% with routine work-up. mcfDNA sequencing was the sole positive microbiologic test in 33.3% of cases, leading to antimicrobial adjustments in 50.0% of these patients. Clinically insignificant mcfDNA sequence detection occurred in 28.6% of cases without a diagnosis of IE.

Conclusions
mcfDNA sequencing is a valuable adjunctive tool for diagnosing culture-negative IE and guiding antimicrobial therapy when clinical suspicion is high. However, its utility depends on appropriate clinical context, highlighting the need for careful test interpretation and further prospective studies to assess patient-centered outcomes and cost-effectiveness.
Enhancing the Thermostability and solubility of a single-domain catalytic antibody
Authors: Cui Yunhang , Zhou Xuchen , Li Sainan , Chen Jingfei , Qin Mingming , An Liaoyuan , Wang Yefei , Yao Lishan 
Published: February 2025

Abstract
Catalytic antibodies have the ability to bind to and degrade antigens, offering a significant potential for therapeutic use. The light chain of an antibody, UA15-L, can cleave the peptide bond of Helicobacter pylori urease, thus inhibiting the spread of the bacteria. However, the variable domain of UA15-L has a poor thermostability and solubility. In this study, we employed a combined computational and experimental approach to enhance the protein’s stability and solubility properties. The protein unfolding hotspots were initially identified using molecular dynamics simulations. Following this, a disulfide bond was designed in an unfolding hotspot to stabilize the protein. Subsequently, protein solubility was enhanced with the assistance of computational methods by introducing polar or charged residues on the protein surface. The combination of multiple mutations resulted in UA15-L variable domain variants with improved thermostability, solubility, expression, and enhanced activity at elevated temperatures. These variants represent promising candidates for further engineering of catalytic activity and specificity.
Early acupuncture intervention for pain relief in emergency department patients with suspected acute renal colic caused by urinary calculi: A randomized clinical trial
Authors: Cao Ying , Qu Zhicheng , Zhang Shuwen , Liu Yunhua , Jia Liancheng , Pei Xiaolu , Wang Xiao , Zhang Dantong , Li Binyan , Lu Haitian , Ding Maoyu , Bai Yinglu , Wang Shuang , Yang Yufei , Hu Jing , Peng Wei , Guo Wei , Xu Xiaolong , Liu Qingquan 
Published: February 2025

Abstract

Background
Renal colic is one of the worst types of pain in acute renal colic caused by urinary calculi (ARCUC). We previously proved that acupuncture can alleviate the pain in ARCUC patients, but its effect on suspected ARCUC remains unclear.

Objective
The objective was to evaluate the effectiveness and safety of acupuncture in patients with suspected ARCUC.

Design
This prospective, double-blind, sham acupuncture-controlled, randomized clinical trial was conducted from July 2021 to June 2024 in an emergency department in China.

Methods
The patients immediately received acupuncture treatment or sham acupuncture treatment after randomization.The primary outcome was the response rate at 10 minutes (pain relief rate) after needle manipulation.The secondary outcomes included the response rates at 0, 5, 15, 20, and 30 minutes, trends in the NRS score over time, patient satisfaction, the analgesic injection rate at 30 minutes, the surgical intervention rate, the revisit rate, and the occurrence of adverse events.

Results
This trial enrolled 84 participants with suspected ARCUC patients, who immediately received acupuncture treatment or sham treatment after randomization. The pain response rates at 10 minutes were 64.3% and 16.7% in the acupuncture group and sham group, respectively, and the difference between the groups was 47.6% (95% CI, 29.3% to 66%; P &lt; 0.01). The response rates of acupuncture were also significantly higher than those of sham acupuncture at 0, 5, 15, 20, and 30 minutes.

Conclusions
These results suggest that acupuncture could alleviate the pain in patients with suspected ARCUC safely.

Trial Registration
Chinese Clinical Trial Registry: ChiCTR2100049069.
Harnessing the diversity and potential of endogenous skeletal stem cells for musculoskeletal tissue regeneration
Authors: Weldon Kelly C , Longaker Michael T , Ambrosi Thomas H 
Published: February 2025

Abstract
In our aging society, the degeneration of the musculoskeletal system and adjacent tissues is a growing orthopedic concern. As bones age, they become more fragile, increasing the risk of fractures and injuries. Furthermore, tissues like cartilage accumulate damage, leading to widespread joint issues. Compounding this, the regenerative capacity of these tissues declines with age, exacerbating the consequences of fractures and cartilage deterioration. With rising demand for fracture and cartilage repair, bone-derived stem cells have attracted significant research interest. However, the therapeutic use of stem cells has produced inconsistent results, largely due to ongoing debates and uncertainties regarding the precise identity of the stem cells responsible for musculoskeletal growth, maintenance and repair. This review focuses on the potential to leverage endogenous skeletal stem cells (SSCs)—a well-defined population of stem cells with specific markers, reliable isolation techniques, and functional properties—in bone repair and cartilage regeneration. Understanding SSC behavior in response to injury, including their activation to a functional state, could provide insights into improving treatment outcomes. Techniques like microfracture surgery, which aim to stimulate SSC activity for cartilage repair, are of particular interest. Here, we explore the latest advances in how such interventions may modulate SSC function to enhance bone healing and cartilage regeneration.
Towards optimization in the use of hemostatic agents and blood products in the early treatment of patients with traumatic brain injury (TBI)
Authors: Maegele Marc 
Published: February 2025

Purpose of the review
The treatment of patients with traumatic brain injury (TBI) with subsequently evolving hemostatic failure and hemorrhagic lesion progression remains challenging. New studies highlight windows of opportunity for treatment optimization.

Recent findings
Results from recent randomized studies suggest an earlier treatment with antifibrinolytic tranexamic acid at a higher initial bolus dose. There seems to be a new window of opportunity for the early prehospital use of thawed plasma. Viscoelastic-based goal-directed treatment strategies are still not delivered timely in most patients although a recent meta-analysis has confirmed a survival benefit with this approach.

Summary
Mortality in TBI with subsequent evolving hemostatic failure can be reduced through treatment optimization delivering early prehospital high-dose tranexamic acid and in-hospital goal-directed treatment algorithms to timely correct coagulopathy and restore hemostasis.
Pregnancy-Related Mortality in California Due to Obstetric Hemorrhage
Authors: Krakowiak Paula , Morton Christine H. , McCain Christy , Sun Dan , Mathur Deepika , Butwick Alexander J. , Gupta Neeru , Nijagal Malini A. , Williams Amanda , Seacrist Marla , Shields Laurence E. , Reyes Carolina , Klassen Miranda , Yznaga Elizabeth , Main Elliott K. 
Published: February 2025

OBJECTIVE:
To identify underlying causes, contributing factors, and quality-improvement opportunities of pregnancy-related hemorrhage deaths.

METHODS:
The California Pregnancy-Associated Mortality Review examined pregnancy-related hemorrhage deaths in California that occurred in 2014–2018. Data were abstracted from multiple sources (vital records, hospital encounter data, medical records, and coroner or autopsy reports). A multidisciplinary expert panel reviewed all case summaries. Data from reviews were aggregated to determine underlying causes of death, preventability, contributing factors, and quality-improvement opportunities at the patient, clinician, facility, and system levels.

RESULTS:
During the study period, there were 2,409,732 live births and 49 pregnancy-related hemorrhage deaths. Placenta accreta spectrum accounted for 16 (32.7%) of deaths; intra-abdominal bleeding and uterine atony each accounted for 10 deaths (20.4%). Compared with the California birth population, a significantly higher proportion of women who died were born in China (14.3% vs 3.9%); were 35 years of age or older (49.0% vs 21.9%); had two or more prior births (57.4% vs 29.1%); had cesarean deliveries (74.4% vs 31.8%); or delivered at hospitals with fewer than 1,200 births per year (33.3% vs 12.2%) (all P<.05). The committee determined that 63.3% of all hemorrhage deaths were highly preventable with substantial variation by cause. Clinician-, facility-, and system-level contributing factors were noted in 88.9% of cases and included delayed response or escalation (77.8%), delayed recognition (72.2%), and insufficient quantities of blood products used (52.8%). Corresponding quality-improvement opportunities included timely hemorrhage risk assessment; increased vigilance for identifying signs and symptoms of hemorrhage; escalation of care and aggressive management; preparation for hemorrhage complications and ongoing training for all hospitals, particularly low-resource facilities; and adherence to severe hemorrhage protocols.

CONCLUSION:
Obstetric hemorrhage remains a leading cause of pregnancy-related mortality and has multiple causes with various levels of preventability. Optimizing system-based approaches for hemorrhage preparedness, detection, and clinical management is critical to reduce preventable deaths from hemorrhage, especially among patients who do not respond to first-line treatment.
Nocturnal hypertension represents an uncontrolled burden in patients with metabolic dysfunction-associated steatotic liver disease
Authors: Martin Anna , Lang Sonja , Schifferdecker Felix , Allo Gabriel , Chon Seung-Hun , Neumann-Haefelin Christoph , Demir Münevver , Steffen Hans-Michael , Kasper Philipp 
Published: February 2025

Background&Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular morbidity and mortality. Another critical risk factor in these patients is arterial hypertension (AH). Although it is estimated that 50% of MASLD patients are suffering from AH, 24-h ambulatory blood pressure monitoring (24-h-ABPM), the gold standard for diagnosing hypertension, is often neglected. However, only 24-h-ABPM can identify hypertension subtypes, particularly nocturnal hypertension (NH), which is a stronger predictor of cardiovascular mortality than daytime or 24-h blood pressure. The aim of this study was to investigate the prevalence of NH in MASLD patients and to identify associated risk factors.

Methods:
To this end, 226 MASLD patients with or without known AH were prospectively recruited in an outpatient liver department and underwent 24-h-ABPM together with repeated office-blood-pressure measurements.

Results:
24-h-ABPM datasets from 218 patients were included in the final analysis. NH was observed in 112 patients (51.3%), of whom 54 (48.2%) were receiving antihypertensive treatment (uncontrolled hypertension). Univariable regression analysis showed that age, increased waist-to-hip ratio, a waist-to-height ratio ≥0.5, type 2 diabetes mellitus (T2DM), dyslipidemia, a lower estimated glomerular filtration rate and increased liver stiffness were significantly associated with a higher risk of NH. In multivariable regression analysis, T2DM [odds ratio (OR) 2.56; 95% confidence interval (CI) 1.09–6.23; P = 0.033], dyslipidemia (OR 3.30; 95% CI, 1.67–6.73; P = 0.001) and liver stiffness (OR 1.09; 95% CI, 1.02–1.18; P = 0.021) were identified as independent risk factors.

Conclusions:
In conclusion, particularly MASLD patients with accompanying T2DM, dyslipidemia, and increased liver stiffness should undergo 24-h-ABPM to detect and treat NH, as they are at the highest risk of adverse cardiovascular events.

Clinical trial:
NCT-04543721
Tension band tendon-approximating cerclage for surgical fixation of patellar fractures: a novel surgical technique
Authors: Revelt Nicolas , Beason Austin , Sleiman Anthony , Gardner Matthew 
Published: February 2025

Abstract
Patellar fractures are potentially debilitating injuries due to loss of extensor mechanism function, resulting in an inability to extend the leg. Traditionally, these fractures have been surgically managed with open reduction and internal fixation using a tension band construct. This can be performed with K-wires or cannulated screws with suture or cable as the tension band. Plate osteosynthesis is another option that is increasing in popularity. Incorporating the tension band construct converts tensile force into a healing-compatible compressive force. However, these techniques often fail when used for comminuted patellar fractures. There is also a high reoperation rate due to metal implant discomfort. Reoperation rates have been reported as high as 41% for K-wires and 23% for cannulated screws. A more optimal technique would provide adequate reduction and strong fixation without the risk of implant irritation that can apply to all/most fracture types. We report a new technique that implements a multistrand, long-chain, ultra–high-molecular weight, polyethylene core suture material with a braided jacket of polyester (FiberWire) without the need for any associated plates, K-wires, or cannulated screws. The suture is woven to create a tension band tendon-approximating cerclage construct that incorporates the proximal and distal bone fragments as well as the patellar and quadriceps tendons. This technique can be used for both simple and comminuted fractures and provides optimal fixation strength while minimizing the complications associated with metal implants. The efficacy of this technique may lend to future studies including biomechanical and retrospective analyses.
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Authors: Nwinyi Obinna C. , Balogun Daniel Oluwatobiloba , Isibor Patrick O. 
Published: February 2025

The increasing resistance to pyrethroids poses a significant challenge to effective vector control in Africa. This study assessed mosquito species composition and resistance level to pyrethroids in selected towns in Ado Odo Ota Local Govt, Ogun; a 6-month longitudinal entomological survey was carried out using light trap and larval sampling. Mosquitoes were collected, and Anopheles species were identified through morphological examination using Coetzee’s taxonomic keys and molecular analyses. Sporozoite detection using ELISA was conducted. The susceptibility status of Anopheles gambiae sensu lato to permethrin (0.75%) and deltamethrin (0.05%) was assessed using the World Health Organization insecticide susceptibility test. The identified species were also screened for knockdown (kdr) target site resistance alleles. Five hundred seventy-nine (579) adult mosquitoes were collected and morphologically identified. Two-thirds (376/579) of the mosquitoes were identified as Culex spp., constituting the most abundant species in the selected towns. Molecular identification using intentional mismatch primers confirmed Anopheles coluzzii's presence as the communities' main species. Thirty per cent 30% (22.5 – 37.5) of the Anopheles gambiae mosquitoes were susceptible to permethrin after 24 hours, while 98% (95.7 -100) of the vectors were susceptible to deltamethrin. Sporozoite detection showed none (0/40) of the tested blood-fed female Anopheles gambiae were positive for sporozoites, and the West African and East African knockdown resistance genes were detected in very high frequencies among the sampled population (L1014F – 64% [0.36 – 0.83], L1014S – 60% [0.30 – 0.77]). This study revealed that Anopheles coluzzii (99%) is the predominant species in the study area, and Deltamethrin is still effective in the tested communities; however, the high knockdown resistance of both the east and west alleles calls for urgent implementation of integrated vector control.
Computational Mechanisms of Approach-Avoidance Conflict Predictively Differentiate Between Affective and Substance Use Disorders
Authors: Mehta Marishka M. , Hakimi Navid , Pena Orestes , Torres Taylor , Goldman Carter M. , Lavalley Claire A. , Stewart Jennifer L. , Berg Hannah , Ironside Maria , Paulus Martin P. , Aupperle Robin , Smith Ryan 
Published: February 2025

AbstractPsychiatric disorders are highly heterogeneous and often co-morbid, posing specific challenges for effective treatment. Recently, computational modeling has emerged as a promising approach for characterizing sources of this heterogeneity, which could potentially aid in clinical differentiation. In this study, we tested whether computational mechanisms of decision-making under approach-avoidance conflict (AAC) – where behavior is expected to have both positive and negative outcomes – may have utility in this regard. We first carried out a set of pre-registered modeling analyses in a sample of 480 individuals who completed an established AAC task. These analyses aimed to replicate cross-sectional and longitudinal results from a prior dataset (N=478) – suggesting that mechanisms of decision uncertainty (DU) and emotion conflict (EC) differentiate individuals with depression, anxiety, substance use disorders, and healthy comparisons. We then combined the prior and current datasets and employed a stacked machine learning approach to assess whether these computational measures could successfully perform out-of-sample classification between diagnostic groups. This revealed above-chance differentiation between affective and substance use disorders (balanced accuracy > 0.688), both in the presence and absence of co-morbidities. These results demonstrate the predictive utility of computational measures in characterizing distinct mechanisms of psychopathology and may point to novel treatment targets.
IMPROVING THE MANAGEMENT OF LEPROSY ULCERS THROUGH A COMMUNITY SELF-CARE INTERVENTION USING A STEPPED WEDGE CLUSTER RANDOMISED TRIAL IN SOUTH-EAST NIGERIA
Authors: Meka Anthony , Ugwu Linda , Wang Yixin , Watson Samuel I. , Ilozumba Onaedo , Akunna Uchechukwu , Choudhury Sopna , Chukwu Joseph N , Gill Paramjit , Lindenmeyer Antje , Murphy-Okpala Ngozi , Ndubuizu Nchekwube , Sartori Jo , Griffiths Frances , Lilford Richard J. 
Published: February 2025

Background: People with sensory neuropathy caused by leprosy suffer from recurrent ulcers. Self-care is used to promote ulcer healing and reduce recurrence. The challenge is to maximise use of self-care and to optimise the way it is practised. RedAid Nigeria in South-East Nigeria adapted and implemented a recently developed international guideline for self-care of ulcers in an area with a high prevalence of leprosy. We report a prospective evaluation of the effectiveness of this intervention in reducing the prevalence and severity of ulcers and in improving wellbeing. Methods: A mixed methods partial stepped wedge cluster randomized trial across 15 clinics serving patients affected by neuropathy and recurrent ulcers. Outcomes were number and area of ulcers, self-rated health and wellbeing. We used a Bayesian analysis to estimate treatment effects and a process analysis based on descriptive statistics and thematic analysis of qualitative data. Results: The ulcers at baseline were long-standing – mean (sd) of ulcer duration at baseline was 58.55 (94.49) months and total disability rate was high (65.99%). There was no evidence of an intervention effect on the persistence of ulcers (OR: 1.00 (95% credible interval (CrI) 0.29 – 3.56) or relative area of ulcers (cm2) 1.12 (0.53 – 2.27). There was evidence of an increase in self-reported health and wellbeing associated with the intervention (EQ-5D VAS mean difference 10.93 (8.60, 13.23) out of 100; life satisfaction 1.18 (0.65, 1.72) out of 10). Process data indicate the intervention was delivered as planned. Qualitative data triangulated with quantitative data findings suggest enthusiasm among participants for and adherence to the intervention. Improved wellbeing was described in terms of improved confidence in administering self-care and better integration in local communities. Discussion: The intervention improved perceptions of health and wellbeing, despite having small and uncertain effects on ulcer-related outcomes. Effecting an improvement in ulcer size and number through a community intervention may be difficult to achieve in poor, rural contexts, even if patients respond positively to the intervention.
Build heatmaps of cell frequencies and marker intensities for correct interpretations
Authors: Lohmann Eugénie , Gorvel Laurent , Granjeaud Samuel 
Published: February 2025

AbstractHigh-content cytometry is an important technique in clinical research, producing data that is rich and complex to analyze. The resulting clusters of cells must be profiled to determine their role and function, and analyzed to identify changes in cell frequency or marker intensity. The heat map is the most suitable tool for presenting this information in a synthetic way. However, its construction must be adapted to the information and the objective. Here we describe the step-by-step construction of heat maps of marker intensity and cell frequency using Excel, Phantasus or R, including the conversion of numbers to colors and the organization of rows and columns. Researchers who master these steps will be able to correctly interpret heat maps and derive the most benefit from high-content cytometry.