bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination Dornase and Alteplase for Intra-abdominal Drain, Abscess, and Hematoma Clearance: A Retrospective Case Series
Authors: Schultz Michelle , Patel Jasmine , Olsen Megumi , Nordbeck Sarah 
Published: October 2024

Background: Since the advent of the MIST2 trial, the combined instillation of dornase and alteplase has become an effective nonsurgical treatment option for empyema and pleural fluid collection. Percutaneous drainage of abdominal abscesses and fluid collections, rather than open surgical treatment, also has become commonplace. The are several case reports and studies on the use of fibrinolytics to drain abdominal fluid collections but no literature reporting use of both alteplase and dornase for abdominal administration. Objective: We present a case series from an academic medical center where dornase therapy was added to fibrinolytic therapy to treat intra-abdominal fluid collections, hematoma, and abdominal drainage catheters with low output. Methods: This is an institutional review board-approved retrospective case series of 13 patients who underwent combination use of alteplase and dornase via intra-abdominal route. The primary objective was to assess for increased drain output, reduction in size of the fluid collection, and adverse events. Results: Many patients had improved drain output after dornase-alteplase therapy. One patient had significant bleeding complications. Conclusions: All patients were discharged alive from the hospital. Clinical success was difficult to define due to variable goals of therapy. Further data are needed to establish the safety and efficacy of this practice, especially compared with intra-abdominal alteplase alone. Patients in our series generally received larger doses of alteplase than in prior studies due to use of dosing modeled on the MIST2 trial. Based on the limited experience of our study, we recommend holding therapeutic anticoagulation during the administration of intra-abdominal dornase-alteplase.
IGF1R signaling in perinatal mesenchymal stem cells determines definitive hematopoiesis in bone marrow
Authors: Lou Qi , Jiang Kaizheng , Wang Xiaoqi , Pan Yuan , Qiu Guo , Wu Binghuo , Yuan Lisha , Xie Siyu , Chen Jian , Xu Quanhui , Zhao Meng , Jiang Linjia 
Published: October 2024

Abtract
During the transition from embryonic to adult life, the sites of hematopoiesis undergo dynamic shifts across various tissues. In adults, although bone marrow (BM) becomes the primary site for definitive hematopoiesis, the establishment of the BM niche for accommodating hematopoietic stem cells (HSCs) remains incompletely understood. Here, we reveal that perinatal BM mesenchymal stem cells (BMSCs) exhibit highly activated insulin-like growth factor 1 receptor (IGF1R) signaling compared with adult BMSCs (aBMSCs). Deletion of Igf1r in perinatal BMSCs (pBMSCs) hinders the transition of HSCs from the fetal liver to the BM in perinatal mice and disrupts hematopoiesis in adult individuals. Conversely, the deletion of Igf1r in aBMSCs, adipocytes, osteoblasts, or endothelial cells does not affect HSCs in the BM. Mechanistically, IGF1R signaling activates the transcription factor nuclear factor of activated T cells c1 in pBMSCs, which upregulates CXCL12 and other niche factors for HSC retention. Overall, IGF1R signaling in pBMSCs regulates the development of the BM niche for hematopoiesis.
A phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed or refractory acute myeloid leukemia
Authors: Liu Yuchen , Bollino Dominique R. , Bah Osman M. , Strovel Erin T. , Le Tien V. , Zarrabi Jinoos , Philip Sunita , Lapidus Rena G. , Baer Maria R. , Niyongere Sandrine , Duong Vu H. , Dougherty Christine C. , Beumer Jan H. , Caprinolo Katherine D. , Kamangar Farin , Emadi Ashkan 
Published: October 2024

Abstract
Glutamine dependency has been shown to be a metabolic vulnerability in acute myeloid leukemia (AML). Prior studies using several in vivo AML models showed that depletion of plasma glutamine, induced by long-acting crisantaspase (pegcrisantaspase [PegC]) was synergistic with the B-cell lymphoma-2 (BCL-2) inhibitor venetoclax (Ven), resulting in significantly reduced leukemia burden and enhanced survival. Here, we report a phase 1 study of the combination of Ven and PegC (VenPegC) for treating adult patients with relapsed or refractory AML, including patients who had previously received Ven. The primary end points were the incidence of regimen-limiting toxicities (RLTs) and the maximum tolerated dose (MTD). Twenty-five patients received at least 1 PegC dose with Ven, and 18 efficacy-evaluable patients completed at least 1 VenPegC cycle; 12 (67%) had previously received Ven. Hyperbilirubinemia was the RLT and occurred in 60% of patients treated with VenPegC; 20% had grade ≥3 bilirubin elevations. MTD was determined to be Ven 400 mg daily with biweekly PegC 750 IU/m2. The most common treatment-related adverse events of any grade in 25 patients who received VenPegC included antithrombin III decrease (52%), elevated transaminases (36%-48%), fatigue (28%), and hypofibrinogenemia (24%). No thromboembolic or hemorrhagic adverse events or clinical pancreatitis were observed. The overall complete remission rate in efficacy-evaluable patients was 33%. Response correlated with alterations in proteins involved in messenger RNA translation. In patients with RUNX1 mutations, the composite complete remission rate was 100%. This study was registered at www.ClinicalTrials.gov as #NCT04666649.
Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection
Authors: Visram Alissa , Larson Dirk , Norman Aaron , Dispenzieri Angela , Murray David , Kyle Robert , Rajkumar S. Vincent , Slager Susan , Kumar Shaji , Vachon Celine 
Published: October 2024

Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant disorder. The current standard of care is not to screen for MGUS, so it is often incidentally diagnosed in the clinic. It is unknown whether the outcomes of screened vs clinically detected MGUS differ. We compared the progression risk between screened vs clinical MGUS cohorts and assessed whether the MGUS detection method affected risk prediction of established clinical factors (score). We included 379 screened MGUS cases from the Olmsted County population-based study and 1384 patients with MGUS diagnosed during routine clinical evaluation at Mayo Clinic. Median follow-up time for the screened vs clinical cohort was 26.6 and 40.1 years, respectively. Accounting for death as a competing risk, the cumulative incidence of progression at 25 years was similar in the screened (11.1% [95% confidence interval [CI], 8.3-14.8]) vs clinical (10.1% [95% CI, 8.6-11.8]) MGUS cohorts, even when stratified by sex, age, or the baseline MGUS risk score. Overall, 0.9 (95% CI, 0.6-1.2) of patients with screened MGUS vs 1.0 (95% CI, 0.9-1.2) of those with clinically detected MGUS experienced disease progression for every 100 person-years of follow-up. MGUS detection method did not modify the association between MGUS risk score and progression risk (pinteraction = 0.217) and did not add to known risk factors for progression (likelihood ratio test; P = .839). Here, we show that progression risk among patients with screened vs clinically detected heavy-chain MGUS was similar. Future studies are needed to assess whether tailored follow-up of patients with screened MGUS affects clinical outcomes.
Deformation Evolution and Perceptual Prediction for Additive Manufacturing of Lightweight Composite Driven by Hybrid Digital Twins
Authors: Xu Jinghua , Wang Linxuan , Gao Mingyu , Jia Chen , Chen Qianyong , Wang Kang , Zhang Shuyou , Tan Jianrong , Fei Shaomei 
Published: October 2024

AbstractThis paper proposes a deformation evolution and perceptual prediction methodology for additive manufacturing of lightweight composite driven by hybrid digital twins (HDT). In order to improve manufacturing quality of irregular lightweight composite through boosting conceptual design in aeronautic and aerospace engineering, the HDT meaning hybridization of physical and digital domains, including deformation and energy efficiency can be built, where the essential parameters can be perceptually predicted in advance, by virtue of the fusion of physical sensors and digital information. The long short term memory (LSTM) can be employed to void vanishing gradient problem and improve predicting precision via Recurrent Neural Networks, thereby laying a foundation for the HDT. The diverse manufacturing requirements of different regions are integrated into the parameters designing phase by attaching region weights confirmed via empiricism and in-service simulation. The effects of slicing strategy and external support structures on manufacturing quality are considered from the perspective of improving dimensional accuracy. The manufacturing efficiency and comprehensive costs are accounted as consideration factors, which are perceptually predicted via LSTM. The designed manufacturing parameters through HDT were virtually examined by evaluating the deformation and equivalent stress distributions of fabricated lightweight component with composite material through AM process simulation. The physical experiments were conducted to verify the HDT-based pre-designing and optimization method of manufacturing parameters via fused deposition modeling (FDM). The energy consumption of actual manufacturing process was measured via digital power meter and applied to evaluate accuracy of perceptual prediction outcomes. The dimensional accuracy and distortion distribution of the manufactured lightweight prototype made with composite material were measured through the coordinate measuring machine (CMM) and 3D optical scanner. The proposed method demonstrates effectiveness in improving manufacturing quality and accurately predicting energy consumption, which have been verified with a three-way solenoid valve element, in which the maximum deformation was reduced by 39.78% and the mean absolute percentage error for perceptual prediction was 3.76%.
Translation regulation by RNA stem-loops can reduce gene expression noise
Authors: Çelik Candan , Bokes Pavol , Singh Abhyudai 
Published: October 2024

Abstract
Background
Stochastic modelling plays a crucial role in comprehending the dynamics of intracellular events in various biochemical systems, including gene-expression models. Cell-to-cell variability arises from the stochasticity or noise in the levels of gene products such as messenger RNA (mRNA) and protein. The sources of noise can stem from different factors, including structural elements. Recent studies have revealed that the mRNA structure can be more intricate than previously assumed.

Results
Here, we focus on the formation of stem-loops and present a reinterpretation of previous data, offering new insights. Our analysis demonstrates that stem-loops that restrict translation have the potential to reduce noise.

Conclusions
In conclusion, we investigate a structured/generalised version of a stochastic gene-expression model, wherein mRNA molecules can be found in one of their finite number of different states and transition between them. By characterising and deriving non-trivial analytical expressions for the steady-state protein distribution, we provide two specific examples which can be readily obtained from the structured/generalised model, showcasing the model’s practical applicability.
Genomic dynamics of high-risk carbapenem-resistant Klebsiella pneumoniae clones carrying hypervirulence determinants in Egyptian clinical settings
Authors: Abdelsalam Nehal Adel , ElBanna Shahira A. , Mouftah Shaimaa F. , Cobo-Díaz José F. , Shata Ahmed H. , Shawky Sherine M. , Atteya Reham , Elhadidy Mohamed 
Published: October 2024

Abstract
Background
Ongoing studies have revealed the global prevalence of severe infections caused by the hypervirulent strains of Klebsiella pneumoniae (K. pneumoniae). Meanwhile, the World Health Organization and the Centers for Disease Control declared carbapenem-resistant K. pneumoniae as an urgent public health threat, requiring swift and effective action to mitigate its spread. Low- and middle-income countries are severely impacted by such devastating infectious diseases owing to the ill implementation of antimicrobial practices and infection control policies. Having both hypervirulence and carbapenemase gene determinants, the emergence of convergent hypervirulent carbapenem-resistant K. pneumoniae is now being reported worldwide.

Methods
In this study, we sequenced 19 carbapenemase-producing K. pneumoniae strains recovered from various clinical specimens. Additionally, we evaluated the phenotypic antimicrobial susceptibility to multiple antimicrobial classes using the VITEK2 automated system. Utilizing the sequencing data, we characterized the sequence types, serotypes, pangenome, resistance profiles, virulence profiles, and mobile genetic elements of the examined isolates. We highlighted the emergence of high-risk clones carrying hypervirulence genetic determinants among the screened isolates.

Results
Our findings revealed that all carbapenem-resistant isolates exhibited either extensive- or pan-drug resistance and harbored multiple variants of resistance genes spanning nearly all the antimicrobial classes. The most prevalent carbapenemase genes detected within the isolates were blaNDM−5 and blaOXA−48. We identified high-risk clones, such as ST383-K30, ST147-K64, ST11-K15, and ST14-K2, which may have evolved into putative convergent strains by acquiring the full set of hypervirulence-associated genetic determinants (iucABCD, rmpA and/ or rmpA2, putative transporter peg-344). Additionally, this study identified ST709-K9 as a high-risk clone for the first time and uncovered that capsule types K15 and K9 carried hypervirulence genetic determinants. The most frequent Inc types found in these isolates were Col440I, IncHI1B, and Inc FII(K).

Conclusion
This study highlights the emergence of high-risk, extensively carbapenem-resistant K. pneumoniae strains co-carrying hypervirulence determinants in Egyptian clinical settings. This poses an imminent threat not only to Egypt but also to the global community, underscoring the urgent need for enhanced surveillance and control strategies to combat this pathogen.
The nexus between maternal antenatal care attendance, newborn postnatal care and neonatal mortality in India: a matched case-control study
Authors: Meitei Wahengbam Bigyananda , Singh Abhishek 
Published: October 2024

Abstract
Introduction
Our study examines the relationship between newborn postnatal care and neonatal mortality stratified by maternal antenatal care attendance under a matched case-control framework.

Methods
Data from the fifth round of the National Family Health Survey was used. A total of 172,079 recent births to eligible women (15–49 years) in five years preceding the survey were included in the study. We used the conditional logistic regression model, a commonly used regression model to fit matched case-control data to examine the effects of newborn postnatal care on neonatal mortality. The mother’s age at birth of the newborn, previous birth intervals, birth order of the newborn, and birthsize of the newborn were included as the matching variables.

Results
Newborns receiving postnatal care within two days or more than two days of birth are less likely to die during the neonatal period. Preferences for newborn postnatal care were also observed to increase with more maternal antenatal care visits. Our study also found a lower risk of neonatal mortality among those newborns whose umbilical cord was examined within two days of birth, regardless of the number of maternal antenatal care visits. Similarly, the risk of newborn deaths was lower among babies whose body temperature was measured within two days of birth. The tendency to breastfeed their newborns within an hour after delivery was considerably higher among those births that occurred to mothers who had a higher number of maternal antenatal care visits. The risk of newborn deaths was also observed to be lower among those born in public or private healthcare facilities.

Conclusion
Considering the cohesive nature of the relationship between neonatal mortality and maternal and child healthcare utilisation, strategic planning and management of the existing policies and programmes related to accessibility, availability, and affordability of maternal and child healthcare services is needed to achieve goal 3.2 of the Sustainable Development Goals. Promoting cost-effective measures such as continuous monitoring of the baby’s body temperature and umbilical cord care could also effectively help reduce neonatal mortality.
Social inequalities in child mental health trajectories: a longitudinal study using birth cohort data 12 countries
Authors: Cadman Tim , Avraam Demetris , Carson Jennie , Elhakeem Ahmed , Grote Veit , Guerlich Kathrin , Guxens Mònica , Howe Laura D. , Huang Rae-Chi , Harris Jennifer R. , Houweling Tanja A. J. , Hyde Eleanor , Jaddoe Vincent , Jansen Pauline W. , Julvez Jordi , Koletzko Berthold , Lin Ashleigh , Margetaki Katerina , Melchior Maria , Nader Johanna Thorbjornsrud , Pedersen Marie , Pizzi Costanza , Roumeliotaki Theano , Swertz Morris , Tafflet Muriel , Taylor-Robinson David , Wootton Robyn E. , Strandberg-Larsen Katrine 
Published: October 2024

Abstract
Background
Social inequalities in child mental health are an important public health concern. Whilst previous studies have examined inequalities at a single time point, very few have used repeated measures outcome data to describe how these inequalities emerge. Our aims were to describe social inequalities in child internalising and externalising problems across multiple countries and to explore how these inequalities change as children age.

Methods
We used longitudinal data from eight birth cohorts containing participants from twelve countries (Australia, Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Norway, Spain and the United Kingdom). The number of included children in each cohort ranged from N = 584 (Greece) to N = 73,042 (Norway), with a total sample of N = 149,604. Child socio‐economic circumstances (SEC) were measured using self‐reported maternal education at birth. Child mental health outcomes were internalising and externalising problems measured using either the Strengths and Difficulties Questionnaire or the Child Behavior Checklist. The number of data collection waves in each cohort ranged from two to seven, with the mean child age ranging from two to eighteen years old. We modelled the slope index of inequality (SII) using sex‐stratified multi‐level models.

Results
For almost all cohorts, at the earliest age of measurement children born into more deprived SECs had higher internalising and externalising scores than children born to less deprived SECs. For example, in Norway at age 2 years, boys born to mothers of lower education had an estimated 0.3 (95% CI 0.3, 0.4) standard deviation higher levels of internalising problems (SII) compared to children born to mothers with high education. The exceptions were for boys in Australia (age 2) and both sexes in Greece (age 6), where we observed minimal social inequalities. In UK, Denmark and Netherlands inequalities decreased as children aged, however for other countries (France, Norway, Australia and Crete) inequalities were heterogeneous depending on child sex and outcome. For all countries except France inequalities remained at the oldest point of measurement.

Conclusions
Social inequalities in internalising and externalising problems were evident across a range of EU countries, with inequalities emerging early and generally persisting throughout childhood.
High-cost users still came to hospitals during the COVID-19 pandemic during first wave data in Thailand: secondary data analysis
Authors: Karunayawong Picharee , Gaewkhiew Piyada , Sarajan Myka Harun , Boonma Chulathip , Butchon Rukmanee , Sukmanee Jarawee , Saeraneesopon Thanayut , Teerawattananon Yot , Isaranuwatchai Wanrudee 
Published: October 2024

Abstract
Background
The phenomenon of high-cost users (HCUs) in health care occurs when a small proportion of patients account for a large proportion of health care expenditures. By understanding this phenomenon during the COVID-19 pandemic, tailored interventions can be provided to ensure that patients receive the care they need and reduce the burden on the health system.

Objectives
This study aimed to determine (1) whether the HCUs phenomenon occurred during the pandemic in Thailand by exploring the pattern of inpatient health expenditures over time from 2016 to 2021; (2) the patient characteristics of HCUs; (3) the top 5 primary diagnoses of HCUs; and (4) the potential predictors associated with being an HCU.

Methods
The secondary data analysis was conducted via inpatient department (IPD) e-Claim data from the National Health Security Office for the Universal Coverage Scheme, which provides health care to ~ 80% of the Thai population. Health care expenditure over time was calculated, and the characteristics of the population were examined via descriptive analysis. Multinomial logistic regression was applied to explore the potential predictors associated with being an HCU.

Results
The characteristics of HCUs remained relatively the same from 2016 to 2021. In terms of the proportion of male (55%) to female patients (45%), the age ranged from 55 to 57 years, with an estimated 8-day length of hospital stay and 7 admissions per year, and the average health care cost per patient was ≥ USD 2,860 (100,000 THB). The low-cost users (LCUs) group (the bottom 50% of the population), had more female patients (55%), a younger age ranging from 27 to 33 years, a 3-day length of stay, 1‒2 admissions per year, and a lower average health care cost per patient, which was less than USD 315 (≤ 11,000 THB).

Conclusion
The HCUs phenomenon still existed even with limited health care accessibility or lockdown measures implemented during the COVID-19 pandemic. This finding could indicate the uniqueness of the need for health services by HCUs, which differ from those of other population groups. By understanding the trends of health care utilization and expenditure, along with potential predictors associated with being an HCU, policies can be introduced to ensure the appropriate allocation of health resources to the right people in need of the right care during future pandemics.