bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cost-Benefit Analysis of Osseointegrated Prostheses for Lower Limb Amputees in the US Health Care System
Authors: Black Grant G. , Jung Wooram , Wu Xian , Rozbruch S. Robert , Otterburn David M. 
Published: May 2022

Background
Patients with transfemoral and transtibial amputations generally rely on socket-suspended (SS) prostheses for ambulation. The use of these aids can be complicated by poor fit, leading to tissue damage, pain at the socket-limb interface, and inability to ambulate. Osseointegrated implants (OIs) directly anchor a prosthesis to the patient’s residual limb, eliminating these issues. However, they require customized components and additional surgeries. The purpose of this study was to conduct the first cost–benefit analysis of OI prostheses compared to SS prostheses for lower limb amputees in the United States.

Methods
A retrospective chart review was performed on all patients who received unilateral lower limb OI prostheses at our institution. Costs were calculated in a bottom-up approach using Current Procedural Terminology codes. Utilities and SS prosthesis costs were derived from previous studies. A Monte Carlo model was used to project costs and lifetime quality-adjusted life years for OI and SS prostheses, and the incremental cost-effectiveness ratio (ICER) of OI compared SS prostheses was determined.

Results
Twenty-five patients (12 female) were included in the study. The mean follow-up was 17 months postimplantation. The average cost of OI surgery was $54,463. Twenty percent of patients required preimplantation soft tissue revision surgery ($49,191). Complication rates per year and average costs were as follows: soft tissue infection (29%, $435), bone/implant infection (11%, $11,721), neuroma development (14%, $14,659), and mechanical failure (17%, $46,513). The ICER was $44,660. A cost-effectiveness acceptability curve demonstrated that OI was favored over SS in 78% of cases at a willingness-to-pay of $100,000 per quality-adjusted life year. In a 1-way sensitivity analysis, the ICER was most sensitive to the mechanical failure rate, mechanical failure cost, and prior SS prosthesis costs.

Conclusions
The model shows that OI prostheses provide a higher quality of life at affordable costs when compared to poorly tolerated SS prostheses in patients with lower limb amputations in the United States. The cost-effectiveness is largely determined by the patient's previous SS prosthesis costs and is limited by the frequency and costs of OI mechanical failure. More research must be done to understand the long-term benefits and risks of OI prostheses.
Committee on Surgical Combat Casualty Care position statement on the use of single surgeon teams and invited commentaries
Authors: Gurney Jennifer M. , Jensen Shane D. , Gavitt Brian J. , Edson Theodore D. , Brown Shaun R. , Cunningham Cord W. , Drew Brendon G. , Eckert Matthew J. , Hall Andrew B. , Holcomb John B. , Knipp Brian S. , Lesperance Richard N. , Polk Travis M. , Schreiber Martin A. , Tadlock Matthew D. , Shackelford Stacy A. 
Published: May 2022

BACKGROUND
Over the last 20 years of war, there has been an operational need for far forward surgical teams near the point of injury. Over time, the medical footprint of these teams has decreased and the utilization of mobile single surgeon teams (SSTs) by the Services has increased. The increased use of SSTs is because of a tactical mobility requirement and not because of proven noninferiority of clinical outcomes. Through an iterative process, the Committee on Surgical Combat Casualty Care (CoSCCC) reviewed the utilization of SSTs and developed an expert-opinion consensus statement addressing the risks of SST utilization and proposed mitigation strategies.

METHODS
A small triservice working group of surgeons with deployment experience, to include SST deployments, developed a statement regarding the risks and benefits of SST utilization. The draft statement was reviewed by a working group at the CoSCCC meeting November 2021 and further refined. This was followed by an extensive iterative review process, which was conducted to ensure that the intended messaging was clear to senior medical leaders and operational commanders. The final draft was voted on by the entire CoSCCC membership. To inform the civilian trauma community, commentaries were solicited from civilian trauma leaders to help put this practice into context and to further the discussion in both military and civilian trauma communities.

RESULTS
After multiple revisions, the SST statement was finalized in January 2022 and distributed to the CoSCCC membership for a vote. Of 42 voting members, there were three nonconcur votes. The SST statement underwent further revisions to address CoSCCC voting membership comments. Statement commentaries from the President of the American Association for the Surgery for Trauma, the chair of the Committee on Trauma, the Medical Director of the Military Health System Strategic Partnership with the American College of Surgeons and a recently retired military surgeon we included to put this military relevant statement into a civilian context and further delineate the risks and benefits of including the trauma care paradigm in the Department of Defense (DoD) deployed trauma system.

CONCLUSION
The use of SSTs has a role in the operational environment; however, operational commanders must understand the tradeoff between tactical mobility and clinical capabilities. As SST tactical mobility increases, the ability of teams to care for multiple casualty incidents or provide sustained clinical operations decreases. The SST position statement is a communication tool to inform operational commanders and military medical leaders on the use of these teams on current and future battlefields.
Lentilactobacillus rapi subsp. dabitei subsp. nov., a lactic acid bacterium isolated from naturally fermented dairy product
Authors: Li Yu , Li Weicheng , Luo Rui , Sakandar Hafiz Arbab , Zhang Heping , Liu Wenjun 
Published: May 2022

Two lactic acid bacterial strains (IMAU80584T and IMAU92037) were isolated from naturally fermented dairy products (kurut and yoghurt) in China and Russia. Based on sequence analysis of the 16S rRNA gene it was revealed that these strains belonged to

Lentilactobacillus rapi

. However, phylogenetic tree analyses of two housekeeping genes, rpoA (encoding RNA polymerase alpha subunit) and pheS (encoding phenylalanyl-tRNA synthase alpha subunit), and 88 core genes, indicated the two strains were separated into an independent monophyletic branch from

L. rapi

DSM 19907T, forming an infra-specific subgroup. The average nucleotide identity and digital DNA–DNA hybridization values between IMAU80584T and

L. rapi

DSM 19907T were 93.1 and 52.8 %, respectively. Strains IMAU80584T and IMAU92037 are distinguished from

L. rapi

DSM 19907T because they have different polar lipids and fatty acids. The novel subgroup strains could not ferment gluconate potassium. The DNA G+C content of strain IMAU80584T was 42.3 mol%. The major cellular fatty acids were C16 : 0, C18 : 1
ω9t and summed feature 5 (C18 : 0 ante and/or C18 : 2
ω6c and/or C18 : 2
ω9c). Therefore, based on the results of polyphasic taxonomic analysis, IMAU80584T and IMAU92037 could be considered as a novel subspecies in the species

L. rapi

with the proposed name

Lentilactobacillus rapi

subsp. dabitei subsp. nov. The type strain is IMAU80584T (=GDMCC 1.2566T=JCM 34647T).
Predicting Oncogene Mutations of Lung Cancer Using Deep Learning and Histopathologic Features on Whole-Slide Images
Authors: Tomita Naofumi , Tafe Laura J. , Suriawinata Arief A. , Tsongalis Gregory J. , Nasir-Moin Mustafa , Dragnev Konstantin , Hassanpour Saeed 
Published: May 2022

AbstractLung cancer is a leading cause of death in both men and women globally. The recent development of tumor molecular profiling has opened opportunities for targeted therapies for lung adenocarcinoma (LUAD) patients. However, the lack of access to molecular profiling or cost and turnaround time associated with it could hinder oncologists’ willingness to order frequent molecular tests, limiting potential benefits from precision medicine. In this study, we developed a weakly supervised deep learning model for predicting somatic mutations of LUAD patients based on formalin-fixed paraffin-embedded (FFPE) whole-slide images (WSIs) using LUAD subtypes-related histological features and recent advances in computer vision. Our study was performed on a total of 747 hematoxylin and eosin (H&E) stained FFPE LUAD WSIs and the genetic mutation data of 232 patients who were treated at Dartmouth-Hitchcock Medical Center (DHMC). We developed our convolutional neural network-based models on 172 training cases and tested on 60 independent cases to analyze whole slides and predict five major genetic mutations, i.e., BRAF, EGFR, KRAS, STK11, and TP53. We additionally used 111 cases from the LUAD dataset of the CPTAC-3 study for external validation. Our model achieved an AUROC of 0.799 (95% CI: 0.686-0.904) and 0.686 (95% CI: 0.620-0.752) for predicting EGFR genetic mutations on the DHMC and CPTAC-3 test sets, respectively. Predicting TP53 genetic mutations also showed promising outcomes. Our results demonstrated that H&E stained FFPE LUAD whole slides could be utilized to predict oncogene mutations, such as EGFR, indicating that somatic mutations could present subtle morphological characteristics in histology slides, where deep learning-based feature extractors can learn such latent information.
Development and Validation of Audio-based Guided Imagery and Progressive Muscle Relaxation Tools for Functional Bloating
Authors: Tee Vincent , Kuan Garry , Kueh Yee Cheng , Abdullah Nurzulaikha , Sabran Kamal , Tagiling Nashrulhaq , Sahran Nur-Fazimah , Alang Tengku Ahmad Iskandar Tengku , Lee Yeong Yeh 
Published: May 2022

AbstractMind-body techniques, including Guided Imagery (GI) or Progressive Muscle Relaxation (PMR), may effectively manage bloating. The current study aimed to develop and validate (psychometric and psychological responses) audio-based GI and PMR techniques for bloating. Audio scripts were first developed from literature reviews and in-depth interviews of participants with bloating diagnosed based on the Rome IV criteria. Scripts were validated using psychometric (content & face validity index) and physiological approaches (brain event-related potentials & heart rate variability). 45/63 participants completed the in-depth interview, and ‘balloon’ emerged as the synonymous imagery description for bloating, of which inflation correlated with a painful sensation. The final tools consisted of narrated audio scripts in the background of a validated choice of music. Overall, content and face validity index for PMR and GI ranged from 0.92 - 1.00. For ERP and HRV, 17/20 participants were analysed. For ERP, there was significant difference between GI and PMR for alpha waves (p=0.029), delta waves (p=0.029) and between PMR and control for delta waves (p=0.014). For HRV, both GI and PMR exhibited similar autonomic responses over controls (overall p<0.05). The newly developed GI and PMR audio-based tools have been validated using psychometric and physiological approaches.
Pregnant women’s knowledge of obstetrical danger signs: A cross-sectional survey in Kigali, Rwanda
Authors: Uwiringiyimana Emmanuel , Manirambona Emery , Byiringiro Samuel , Nsanzimana Albert , Uhawenayo Neophyte , Ufitinema Pacifique , bayizere Janviere , Moreland Patricia J. , Meharry Pamela , Ntasumbumuyange Diomede 
Published: May 2022

ABSTRACTBACKGROUNDMaternal mortality remains critically high worldwide, particularly in sub-Saharan Africa. The leading causes of maternal death in Rwanda include postpartum hemorrhage and obstructed labor. Maternal recognition of obstetrical danger signs is critical for timely access to emergency care, in order to reduce maternal mortality.OBJECTIVETo assess the knowledge of obstetrical danger signs among pregnant women attending antenatal care in Kigali, Rwanda.METHODSA cross-sectional study was conducted between September and December 2018 at five health centers and one district hospital in Kigali, Rwanda. Pregnant women attending antenatal care (ANC) services completed a structured questionnaire. Data were analyzed using descriptive statistics.RESULTSA total of 382 pregnant women were included in the study. The majority of women (67.8%) were aged 23-35 years, and 44.5% had completed secondary education. Almost half (43.2%) reported traveling more than 30 minutes to reach the health facility; only 23.3% were within 15 minutes of the health facility. Over half (57%) reported attending three or more ANC visits during pregnancy. The majority (85.6%) knew at least one obstetrical danger sign, with nearly half (46.1%) obtaining knowledge of danger signs from midwives and nurses.CONCLUSIONKnowledgeability was significantly associated with the parity and number of ANC visits, though CHW was also a good source of information for pregnant women. We encourage a systematically designed curriculum to teach mothers during their follow-up visits for ANC.
Generating variability from motor primitives during infant locomotor development
Authors: Hinnekens Elodie , Barbu-Roth Marianne , Do Manh-Cuong , Berret Bastien , Teulier Caroline 
Published: May 2022

AbstractMotor variability is a fundamental feature of developing systems allowing motor exploration and learning. In human infants, leg movements involve a small number of basic coordination patterns called locomotor primitives, but whether and when motor variability could emerge from these primitives remains unknown. Here we longitudinally followed 10 neonates (∼4 days old) until walking onset (∼14 months old) and recorded the activity of their leg muscles during locomotor or rhythmic movements. Using unsupervised machine learning, we show that the structure of trial-to-trial variability changes during early development. In the neonatal period, infants own a minimal number of motor primitives but generate a maximal motor variability across trials thanks to variable activations of these primitives. A few months later, toddlers generate significantly less variability despite the existence of more primitives, due to more regularity within their activation. These results suggest that human neonates initiate motor exploration as soon as birth by variably activating a few basic locomotor primitives that later fraction and become more consistently activated by the motor system.
Soil microbe-induced plant resistance alters aphid inter-genotypic competition leading to rapid evolution with consequences for plant growth and aphid abundance
Authors: Xi Xinqiang , Zytynska Sharon E. 
Published: May 2022

AbstractPlants and insect herbivores are two of the most diverse multicellular groups in the world, and both are strongly influenced by interactions with the belowground soil microbiome. Effects of reciprocal rapid evolution on ecological interactions between herbivores and plants have been repeatedly demonstrated, but it is unknown if (and how) the soil microbiome could mediate these eco-evolutionary processes.We tested the role of a plant-beneficial soil bacterium (Acidovorax radicis) in altering eco-evolutionary interactions between sap-feeding aphid herbivores (Sitobion avenae) feeding on barley (Hordeum vulgare). We reared two aphid genotypes separately or together on three barley varieties that were inoculated with or without A. radicis bacteria. In the first experiment we counted the aphid number and plant biomass after 7, 14 and 21 days of aphid growth, while in a second experiment we counted and removed offspring every 1-2 days to assess aphid longevity and fecundity.Results showed that A. radicis increased plant growth and suppressed aphids of both genotypes. The strength of effect was dependent on aphid genotype and barley variety, while the direction of effect was altered by aphid population mixture. Fescue aphids experienced increased growth when they were sharing the plant with Sickte aphids on inoculated plants; this increase was not seen in the control plants without A. radicis and was only apparent after 14 days of aphid population growth.Plant inoculation with A. radicis reduced aphid survival (reduced number of reproductive days) and fecundity (reduced daily reproductive output for surviving aphids). In the second experiment, when density was controlled, Fescue aphids did not experience increased reproduction in mixed populations, suggesting this is a density-dependent effect. Using Lotka-Volterra modelling, we demonstrated that A. radicis inoculation decreased aphid population stability as it increased inter-genotype competition but decreased the intra-genotype competition (likely through reduced population density).Our work demonstrates the important role that plant-associated microbiomes can have in mediating eco-evolutionary interactions between herbivores and host plants.
Identification of viral dose and administration time in simulated phage therapy occurrences
Authors: Plunder Steffen , Lauer Ulrich M. , Helling Thomas , Venturelli Sascha , Marongiu Luigi 
Published: May 2022

AbstractThe rise in multidrug-resistant bacteria has sprung a renewed interest in applying phages as antibacterial, a procedure Western practitioners eventually abandoned due to several downfalls, including poor understanding of the dynamics between phages and bacteria. A successful phage therapy needs to account for the loss of infective virions and the multiplication of the hosts. The parameters critical inoculation size (VF) and failure threshold time (TF) have been introduced to assure that the viral dose (vϕ) and administration time (tϕ) would lead to an effective treatment. The problem with the definition of VF and TF is that they are non-linear equations with two unknowns; thus, their solution is cumbersome and not unique. The current study used machine learning in the form of a decision tree algorithm to determine ranges for the viral dose and administration times required to achieve an effective phage therapy. Within these ranges, a Pareto optimal solution of a multi-criterial optimization problem (MCOP) provides values leading to effective treatment. The algorithm was tested on a series of microbial consortia that described allochthonous invasions (the outgrowing of a species at high cell density by another species initially present at low concentration) to inhibit the growth of the invading species. The present study also introduced the concept of ‘mediated phage therapy’, where targeting a booster bacteria might decrease the virulence of a pathogen immune to phagial infection. The results demonstrated that the MCOP could provide pairs of vϕ and tϕ that could effectively wipe out the bacterial target from the considered micro-environment. In summary, the present work introduced a novel method for investigating the phage/bacteria interaction that could help increase the effectiveness of phage therapy.Author summaryPhage therapy is a treatment that can help fight infections with bacteria resistant to antibiotics. However, several phage therapy application have failed, possibly because phages were administered at the wrong time or in insufficient amounts. The present study implemented a machine learning protocol to correctly calculate the administration time and viral load to obtain effective phage therapy. Four simulated microbial consortia, including one case where the pathogen was not directly a phage’s host, were employed to prove the procedure’s concept. The results demonstrated that the procedure is suitable to help the microbiologists to instantiate an effective phage therapy and clear infections.
Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism
Authors: Khanh Le-Trilling Vu Thuy , Banchenko Sofia , Paydar Darius , Leipe Pia Madeleine , Binting Lukas , Lauer Simon , Graziadei Andrea , Gotthold Christine , Bürger Jörg , Bracht Thilo , Sitek Barbara , Lebbink Robert Jan , Malyshkina Anna , Mielke Thorsten , Rappsilber Juri , Spahn Christian M. T. , Voigt Sebastian , Trilling Mirko , Schwefel David 
Published: May 2022

AbstractHuman cytomegalovirus (CMV) is a highly relevant and ubiquitously distributed human pathogen. Its rodent counterparts such as mouse and rat CMV serve as common infection models. Here, we conducted the first global proteome profiling of rat CMV-infected cells and uncovered a pronounced loss of the transcription factor STAT2, which is crucial for interferon signalling. Deletion mutagenesis documented that STAT2 is targeted by the viral protein E27. Cellular and in vitro analyses showed that E27 exploits host-derived Cullin4-RING ubiquitin ligases (CRL4) to induce poly-ubiquitylation and proteasomal degradation of STAT2. A cryo-electron microscopic structure determination revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors called DDB1- and Cullin4-associated factors (DCAFs) to displace them from the catalytic core of CRL4. Moreover, structural analyses elucidated the mechanism of STAT2 recruitment and indicate that E27-binding additionally disturbs STAT2-dependent interferon signalling by occupying its IRF9 binding interface. For the first time, these data provide structural insights into cytomegalovirus-encoded interferon antagonism and establish an atomic model for STAT2 counteraction by CRL4 misappropriation with important implications for viral immune evasion.
The modulation of acute stress on Model-Free and Model-Based reinforcement learning in Gambling Disorder
Authors: Wyckmans Florent , Banerjee Nilosmita , Saeremans Mélanie , Ross Otto , Kornreich Charles , Vanderijst Laetitia , Gruson Damien , Carbone Vincenzo , Bechara Antoine , Buchanan Tony , Noël Xavier 
Published: May 2022

ABSTRACTBackground and aimsExperiencing acute stress is common in behavioral addictions such as gambling disorder. Additionally, like most substance-induced addictions, aberrant decision-making wherein a reactive habit-induced response (conceptualized as a Model-free [MF] in reinforcement learning) suppresses a flexible goal-directed response (conceptualized as a Model-based [MB]) is also common in gambling disorder. In the current study we investigated the influence of acute stress on the balance between habitual response and the goal-directed system.MethodsA sample of N = 116 pathological gamblers (PG) and healthy controls (HC) performed an acute stress task – the Socially Evaluated Cold pressure task (SECPT) – or a control task. Self-reported stress and salivary cortisol were collected as measures of acute stress. Following the SECPT, participants performed the Two-Step Markov Task to account for the relative contribution of MB and MF strategies. Additionally, verbal working-memory and IQ measures were collected to account for their mediating effects on the orchestration between MB/MF and the impact of stress.ResultsBoth groups had comparable baseline and stress-induced cortisol response to the SECPT. Non-stressed PG displayed lower MB learning than HC. MANOVA and regression analyses showed a deleterious effect of stress-induced cortisol response on the orchestration between MB and MF learning in HC but not in PG. Neither working memory nor IQ mediated these effects.Discussion and ConclusionsDespite normal cortisol response to stress, we found an abnormal pattern of modulation of stress on the orchestration between MB and MF learning among PG.