bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxycycline for the Treatment of Lyme Disease in Young Children
Authors: Brown Katie , Corin Sarah , Handel Andrew S. 
Published: October 2023

Background:
Doxycycline is considered the first-line treatment of Lyme disease in adolescents and adults, but largely disproven concerns of permanent tooth staining prevented its use and evaluation in children <8 years old. We sought to describe short-term adverse effects and treatment failures among young children receiving oral doxycycline for Lyme disease.

Methods:
We completed a 2-pronged evaluation of children with Lyme disease treated with doxycycline. We performed a retrospective case series of patients <8 years old who were diagnosed with Lyme disease and treated with doxycycline. We then performed a telephone follow-up survey study of the patients’ parents to gather additional details regarding clinical outcomes and adverse reactions to doxycycline. Descriptive statistics were calculated.

Results:
A total of 32 patients were identified through the retrospective case series and 18 participated in the follow-up survey. The most common clinical diagnosis (22/32; 69%) was single erythema migrans. Seven (22%) had neurological Lyme disease. Three patients (9%) stopped doxycycline treatment prematurely due to adverse effects. During telephone follow-up, 2 children were reported to have dental staining. No patients were identified with treatment failure during the retrospective case series. On telephone follow-up, 3 patients had residual symptoms after treatment, though none were convincing of treatment failure.

Conclusions:
Our study suggests that doxycycline is generally well-tolerated and an effective treatment of Lyme disease in young children. Prospective, observational studies with long-term assessment of dental staining and clinical outcomes are needed. Alternative antibiotics, principally amoxicillin, remain the preferred treatment of non-neurological Lyme disease manifestations in young children, but doxycycline is likely a safe and effective alternative when needed.
Ten-year Single Center Experience With Colistin Therapy in NICU
Authors: Kaya Tuğba Barsan , Sürmeli Onay Özge , Aydemir Özge , Tekin Ayşe Neslihan 
Published: October 2023

Background:
Colistin, a cationic polypeptide antibiotic of the polymyxin class has come back into use due to its potent antimicrobial activity against multidrug-resistant Gram-negative bacteria and the lack of new antibiotics. The purpose of this study was to assess the critically ill infants treated with colistin in our neonatal intensive care unit and to identify predisposing factors for the emergence of acute kidney injury (AKI) following colistin treatment.

Methods:
This was a retrospective case-control study that included infants with proven or suspected nosocomial infections in the neonatal intensive care unit of a University Hospital between January 2012 and March 2022. Over the same time period, the clinical and laboratory characteristics and outcomes of patients who received antibiotic combination with colistin were compared to patients who received antibiotic combination without colistin.

Results:
A total of 77 patients were in the colistin group (ColG) and 77 patients were in the control group. The demographic and clinical characteristics of the study groups were similar. In the ColG compared to the control group, hyponatremia, hypokalemia, hypophosphatemia, hypomagnesia and AKI were all more prevalent (P < 0.05). The most important finding in our study was the higher incidence of AKI and mortality in ColG, as well as the increasing nephrotoxic effect of other medications when used in conjunction with colistin.

Conclusion:
During colistin therapy, newborn infants must be closely monitored for AKI. Clinicians should be aware of an increased incidence of hyponatremia, hypokalemia, hypophosphatemia, hypomagnesia, AKI and its consequences in infants given colistin. As awareness increases, harmful effects will decrease.
Prescribing Pattern and Efficacy of Oral Antibiotics for Pediatric Urinary Tract Infections in Japan: A Descriptive Study Using a Nationwide Claims Database
Authors: Muramatsu Daichi , Yanai Takanori , Yoshida Satomi , Kawakami Koji 
Published: October 2023

Background:
Pediatric urinary tract infections are often treated with third-generation cephalosporins; however, the increasing prevalence of Escherichia coli resistant to cephalosporins has reduced their effectiveness. Although resistance is prevalent in Asia, the prescribing patterns and clinical effectiveness of antibiotics have mostly been reported in the United States. This study aimed to describe the prescription patterns and effectiveness of oral antibiotics for treating pediatric urinary tract infections in Japan.

Methods:
This descriptive study used data from a nationwide Japanese claims database. We identified patients <6 years old with urinary tract infections who received oral antibiotics between January 2016 and December 2020. Descriptive analyses were performed to assess prescription patterns. Moreover, logistic regression analyses were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for treatment failure among the commonly prescribed antibiotics and patient characteristics. Treatment failure was defined as the prescription of different antibiotics within 7 days of the primary prescription.

Results:
Of the 4,127 patients, 2,766 (67.0%) were prescribed third-generation cephalosporins, and 347 (8.4%) were prescribed amoxicillin. Trimethoprim-sulfamethoxazole and amoxicillin-clavulanate were prescribed to 63 (1.5%) and 50 (1.2%) patients, respectively. Treatment failure was observed in 118 (2.9%) patients and more often in amoxicillin-treated patients than in cefcapene pivoxil-treated patients [OR, 2.18 (95% CI: 1.04–4.58)].

Conclusions:
Third-generation cephalosporins are the most commonly prescribed antibiotics for the initial therapy of pediatric urinary tract infections in Japan. Third-generation cephalosporins are still effective in Japan, despite the high prevalence of resistance against cephalosporins.
Identifying Obstructive Sleep Apnea Risk Using the STOP-BANG Questionnaire in a Cardiology Clinic
Authors: Rogel Megan , Iverson Lindsay , Hall Alex 
Published: October 2023

ABSTRACT
Untreated obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality, warranting enhanced awareness, screening, and action among healthcare providers to optimize patient outcomes. Attempting to address the potential under detection of OSA, this quality improvement project implemented the STOP-Bang Sleep Apnea Questionnaire at a cardiology clinic, with the goals to stratify risk for OSA in 100% of patients and increase provider referral of high risk patients for sleep studies. The setting was an outpatient cardiology clinic in Pensacola, Florida. The sample included new and existing patients 18 years or older who had one or more of the following diagnoses: hypertension, heart failure, coronary artery disease, atrial fibrillation, or arrhythmia. Methods involved collecting and comparing preintervention sleep study referral rate data with 6-week STOP-Bang questionnaire implementation data. Results demonstrated a 65% (279 of 428 patients seen) screening implementation rate and a modest but statistically significant increase in the overall referral rate from 2.6% preintervention to 5.1% postintervention (p = .040). Overall, standard use of the STOP-Bang questionnaire may enable higher detection and referral of OSA.
Improving Utilization of a Nursing-Initiated Supportive Medication Order Panel in the Inpatient Setting
Authors: Tatara Alexandra W. , Lipten Samuel D. 
Published: October 2023

ABSTRACT

Background:
Many medications are low-risk but must undergo the same ordering process as high-risk medications in the inpatient setting. Nurses identify the need for supportive medications and notify providers. An order panel and policy were developed to allow nurses to order low-risk, supportive medications.

Purpose:
The aim of this study was to increase order panel utilization from a 6% to a goal of 15%.

Methods:
This was a quality improvement study at a 1000-bed academic medical center. Five plan-do-study-act (PDSA) cycles were implemented. The primary end point was order panel utilization, and secondary end points were individual nursing unit utilization and the number of orders for each medication on the panel.

Results:
After each PDSA cycle, order panel utilization improved to 7.8%, 13.2%, 7.5%, 10.2%, and 10.6%, respectively. The units using the order panel most often were general medicine (n = 95, 28%), medical intensive care (n = 71, 21%), and inpatient oncology (n = 40, 12%). The medication most frequently ordered was lanolin alcohols–mineral oil with petrolatum (Eucerin) cream (n = 220, 28%).

Conclusions:
Order panel utilization improved from a baseline of 6% to an average of 9.9%. Increasing awareness of the order panel and adding medications will contribute to improvement in order panel utilization in the long-term.
Burnout Among Family Physicians in the United States: A Review of the Literature
Authors: Hoff Timothy , Trovato Kathryn , Kitsakos Aliya 
Published: October 2023

Background and Objectives:
Burnout among physicians who work in primary care is an important problem that impacts health care quality, local communities, and the public's health. It can degrade the quality of primary care services in an area and exacerbate workforce shortages. This study conducted a review of the published research on burnout among family physicians working in the United States.

Methods:
We used a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided approach and several article databases to identify, filter, and analyze published research on US family physician burnout that uses data collected from 2015 onward.

Results:
Thirty-three empirical studies were identified with findings that included US family physician burnout prevalence and/or associations between burnout and specific personal and contextual drivers. Mean family physician burnout prevalence across studies that measured it was 35%. Almost half of the studies classified one-third or more of their family physician samples as burned out. Physician gender (being female), age (being younger), and job/work-related factors (workload, time pressures) were the most commonly identified correlates of family physician burnout. The vast majority of studies were cross-sectional and used secondary data.

Conclusions:
The extant research literature on family physician burnout in the United States shows that burnout is currently a meaningful problem. Several important correlates of the problem can be identified, some of which managers and health care organizations can proactively address. Other correlates require managers and health care organizations also viewing family physicians in differentiated ways. The collective literature can be improved through a more consistent focus on similar burnout correlates across studies; inclusion of interventions aimed at lessening the effects of key burnout correlates; employment of more robust longitudinal and quasi-experimental research designs; and additional pandemic-era data collection on burnout.
Distinct information conveyed to the olfactory bulb by feedforward input from the nose and feedback from the cortex
Authors: Zak Joseph D. , Reddy Gautam , Konanur Vaibhav , Murthy Venkatesh N. 
Published: October 2023

AbstractSensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Odorant mixtures of increasing complexity evoked progressively denser OSN activity, yet cortical feedback activity was of similar sparsity for all stimuli. Representations of complex mixtures were similar in OSNs but were decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibited a sigmoidal relationship, cortical axonal responses were complex and non-monotonic, which could be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to both local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.
Stromal localization of inactive CD8+T cells in metastatic mismatch repair deficient colorectal cancer
Authors: Küçükköse Emre , Baars Matthijs J.D. , Amini Mojtaba , Schraa Suzanna J. , Floor Evelien , Bol Guus M. , Rinkes Inne H.M. Borel , Roodhart Jeanine M.L. , Koopman Miriam , Laoukili Jamila , Kranenburg Onno , Vercoulen Yvonne 
Published: October 2023

AbstractBackgroundThe determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC.MethodsWe profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of stromal and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry.ResultsHigh-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8+T cells, which expressed significantly lower levels of markers reflecting proliferation (Ki67) and antigen-experience (CD45RO) compared to CD8+T cells in non-metastatic tumors. CD8+T cells showed intra-epithelial localization in non-metastatic tumors, but stromal localization in metastatic tumors, which was validated in a second cohort.ConclusionWe conclude that localization of phenotypically distinct CD8+T cells within stroma may predict metastasis formation in MSI-H CRC.
Changes in electrophysiological aperiodic activity during cognitive control in Parkinson’s disease
Authors: Monchy Noémie , Modolo Julien , Houvenaghel Jean-François , Voytek Bradley , Duprez Joan 
Published: October 2023

AbstractCognitive symptoms in Parkinson’s disease (PD) are common and can significantly affect patients’ quality of life. Therefore, there is an urgent clinical need to identify a signature derived from behavioral and/or neuroimaging indicators that could predict which patients are at increased risk for early and rapid cognitive decline. Recently, converging evidence identified electroencephalogram (EEG) aperiodic activity as meaningful physiological information associated with age, development, cognitive and perceptual states or pathologies. In this study, we aimed to investigate aperiodic activity in PD during cognitive control and characterize its possible association with behavior.Here, we recorded high-density EEG (HD-EEG) in 30 healthy controls and 30 PD patients during a Simon task. We analyzed task-related behavioral data in the context of the activation-suppression model and extracted aperiodic parameters (offset, exponent) at both scalp and source levels.Our results showed behavioral alterations of cognitive control as well as higher offsets in patients in the parieto-occipital areas, suggesting increased excitability in PD. A small congruence effect on aperiodic parameters in pre- and post-central brain areas was also found, possibly associated with task execution. Significant differences in aperiodic parameters between the resting state, pre- and post-stimulus phases all across the scalp and cortex confirmed that the observed changes in aperiodic activity are linked to task execution. No correlation was found between aperiodic activity and behavior or clinical features.Our findings provide evidence that EEG aperiodic activity in PD is characterized by greater offsets, and that aperiodic parameters differ depending on arousal state. However, our results do not support the hypothesis that the behavior-related differences observed in PD are related to aperiodic changes. Overall, this study highlights the importance of considering aperiodic activity contributions in brain disorders and further investigating the relationship between aperiodic activity and behavior.
Multidimensional Analysis of the Adult Human Heart in Health and Disease using Hierarchical Phase-Contrast Tomography (HiP-CT)
Authors: Brunet J. , Cook A. C. , Walsh C. L. , Cranley J. , Tafforeau P. , Engel K. , Berruyer C. , Burke O’Leary E. , Bellier A. , Torii R. , Werlein C. , Jonigk D. D. , Ackermann M. , Dollman K. , Lee P. D. 
Published: October 2023

AbstractCardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP-CT), using new (4th) generation synchrotron sources, potentially overcomes this limitation, allowing micron resolution imaging of intact adult organs with unprecedented detail. In this proof of principle study (n=2), we show the utility of HiP-CT to image whole adult human hearts ex-vivo: one ‘control’ without known cardiac disease and one with multiple known cardiopulmonary pathologies. The resulting multiscale imaging was able to demonstrate exemplars of anatomy in each cardiac segment along with novel findings in the cardiac conduction system, from gross (20 um/voxel) to cellular scale (2.2 um/voxel), non-destructively, thereby bridging the gap between macroscopic and microscopic investigations. We propose that the technique represents a significant step in virtual autopsy methods for studying structural heart disease, facilitating research into abnormalities across scales and age-groups. It opens up possibilities for understanding and treating disease; and provides a cardiac ‘blueprint’ with potential for in-silico simulation, device design, virtual surgical training, and bioengineered heart in the future.
Do calcium channel blockers applied to cardiomyocytes cause increased channel expression resulting in reduced efficacy?
Authors: Jæger Karoline Horgmo , Charwat Verena , Wall Samuel , Healy Kevin E. , Tveito Aslak 
Published: October 2023

AbstractIn the initial hours following the application of the calcium channel blocker (CCB) nifedipine to microtissues consisting of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we observe notable variations in the drug’s efficacy. Here, we investigate the possibility that these temporal changes in CCB effects are associated with adaptations in the expression of calcium ion channels in cardiomyocyte membranes. To explore this, we employ a recently developed mathematical model that delineates the regulation of calcium ion channel expression by intracellular calcium concentrations. According to the model, a decline in intracellular calcium levels below a certain target level triggers an upregulation of calcium ion channels. Such an upregulation, if instigated by a CCB, would then counteract the drug’s inhibitory effect on calcium currents. We assess this hypothesis using time-dependent measurements of hiPSC-CMs dynamics and by refining an existing mathematical model of myocyte action potentials incorporating the dynamic nature of the number of calcium ion channels. The revised model forecasts that the CCB-induced reduction in intracellular calcium concentrations leads to a subsequent increase in calcium ion channel expression, thereby attenuating the drug’s overall efficacy. The data and fit models suggests that dynamic changes in cardiac cells in the presence of CCBs may be explainable by induced changes in protein expression, and that this may lead to challenges in understanding calcium based drug effects on the heart unless timings of applications are carefully considered.
A target-free approach to estimate thermal camera pose in LiDAR scenes of feature-deficient environments
Authors: Jandeleit Julian , Beleyur Thejasvi , Goldlüecke Bastian 
Published: October 2023

AbstractModern animal behaviourists are able to collect vast amounts of data from multiple sensors. Sensor fusion however still remains a challenge given the unique sensor types biologists use. Here we study thermal camera-LiDAR alignment. While LiDAR-RGB scene alignment is well-established in feature-rich scenes with reliable inter-camera correspondences, thermal scenes are often captured with low-resolution devices and suffer from halo and history effects, and thus require sensor-specific algorithms. To deal with this, we present the depth-map correspondence (DMCP) algorithm. DMCP is a semi-automatic algorithm to fuse Li-DAR with feature-deficient thermal scenes without explicit calibration objects. The user annotates at least 4 corresponding points on the thermal image and a depth map of the LiDAR scene, which allows us to compute the position and orientation of the thermal camera within the scene. We quantify the accuracy of alignment using 2D reprojection error and 3D nearest-neighbour distances of known world points across experimental trials. A median reprojection error of 7.7 (95%ile: 3.7-23.5) pixels was achieved. Known objects lying on the LiDAR mesh showed a median nearest-neighbour mesh distance of 0.12 m (95%ile: 0.007-5.61 m). We present the first such alignment of feature-deficient thermal scenes and LiDAR data. DMCP has two advantages 1) it is computationally straightforward to implement and 2) requires minimal user annotation to work. DMCP could be broadly applied to any type of mesh-image alignment problem. Finally we provide DMCP and the Ushichka dataset as a baseline for further research on the challenging problem of subterranean thermal-LiDAR alignment.
Systemic Metabolic Depletion of Intestine Microbiome Undermines Melanoma Immunotherapy Effectiveness
Authors: Zakharevich Natalia V. , Morozov Maxim D. , Kanaeva Vera A. , Ivanov Artem B. , Ulyantsev Vladimir I. , Klimina Ksenia M. , Olekhnovich Evgenii I. 
Published: October 2023

AbstractImmunotherapy has proven to be a boon for patients grappling with metastatic melanoma, significantly enhancing their clinical condition and overall quality of life. A compelling connection was discovered between the composition of the intestinal microbiome and the effectiveness of immunotherapy substantiated in both animal models and human patients. Nonetheless, the precise biological mechanisms through which gut microbes influence melanoma treatment outcomes remain poorly understood. This study conducted a high-resolution metagenomic meta-analysis, employing cutting-edge bioinformatics techniques including genome-resolved metagenomics, strain profiling, comparative genomics, and metabolic reconstruction. According to the obtained results, the systemic metabolic depletion of the gut microbiome causes a lack of response to immunotherapy. Specifically, the presence of bacteria adept at utilizing polysaccharides, as well as those responsible for cobalamin, amino acids, and fatty acids production, decreased in patients who experienced unfavorable treatment outcomes. In contrast, patients who had successful outcomes after immunotherapy exhibited a prevalence of amino acids and cobalamin prototrophs, while autotrophy in these substances characterized the microbiomes of patients with unsuccessful outcomes. The metabolic reconstruction of short-chain fatty acid biosynthesis pathways did not differentiate bacteria linked to treatment outcomes based on their ability to produce acetate, butyrate, or propionate. However, the cobalamin-dependent Wood-Ljungdahl pathway of acetate synthesis was directly associated with immunotherapy effectiveness.