bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 viral liver aggregates and scarce parenchymal infection implicate systemic disease as a driver of abnormal liver function
Authors: Pepe-Mooney Brian J. , Smith Colton J. , Sherman Marc S. , North Trista E. , Padera Robert F. , Goessling Wolfram
Published: October 2023

Background:

Liver function tests (LFTs) are elevated in >50% of hospitalized individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with increased enzyme levels correlating with a more severe COVID-19 course. Despite these observations, evaluations of viral presence within liver parenchyma and viral impact on liver function remain controversial.

Methods and Results:

Our work is a comprehensive immunopathological evaluation of liver tissue from 33 patients with severe, and ultimately fatal, cases of SARS-CoV-2 infection. Coupled with clinical data, we reveal the absence of SARS-CoV-2 infection in cholangiocytes and hepatocytes despite dramatic systemic viral presence. Critically, we identify significant focal viral sinusoidal aggregates in 2/33 patients and single viral RNA molecules circulating in the hepatic sinusoids of 15/33 patients. Utilizing co-immunofluorescence, focal viral liver aggregates in patients with COVID-19 were colocalized to platelet and fibrin clots, indicating the presence of virus-containing sinusoidal microthrombi. Furthermore, this patient cohort, from the initial months of the COVID-19 pandemic, demonstrates a general downtrend of LFTs over the course of the study timeline and serves as a remarkable historical time point of unattenuated viral replication within patients.

Conclusions:

Together, our findings indicate that elevated LFTs found in our patient cohort are not due to direct viral parenchymal infection with SARS-CoV-2 but rather likely a consequence of systemic complications of COVID-19. This work aids in the clinical treatment considerations of patients with SARS-CoV-2 as therapies for these patients may be considered in terms of their direct drug hepatotoxity rather than worsening hepatic function due to direct infection.
Predictors of treatment intensification in uncontrolled hypertension
Authors: Kasanagottu Koushik , Mukamal Kenneth J. , Landon Bruce E.
Published: October 2023

Purpose:

Prior studies have shown that treatment intensification for patients presenting with uncontrolled hypertension (HTN) rarely occurs, even during visits to the patient's own primary care physicians (PCPs). In this article, we identified predictors of treatment intensification for uncontrolled HTN.

Methods:

We conducted a cross-sectional study using nationally representative survey data on visits by patients aged 18 or above with uncontrolled HTN, defined as a recorded SBP at least 140 and/or a DBP at least 90 using data from the National Ambulatory Medical Care Survey (NAMCS) 2008–2018. Our outcome is treatment intensification defined as the addition of a new blood pressure medication.

Results:

We analyzed 22 559 visits to PCPs where uncontrolled HTN was noted, representing 801 023 786 visits nationally. Among these encounters, 2138 (10.3%) of the visits resulted in treatment intensification. Visits with the patient's own PCP had higher rates of treatment intensification than visits to another PCP (10.8 vs. 5.9%, P < 0.0001). Visits for patients previously on antihypertensive medications had lower rates of treatment intensification (11% for no medications, 10.4% for one medication, 6.6% for ≥2 medications, P < 0.0001), but there were no statistically significant differences in rates of intensification for those with relevant comorbidities (9.4% for no chronic conditions, 10.8% for one to two chronic conditions, 8.9% for at least three chronic conditions, P = 0.12). Multivariable adjusted results were similar to the unadjusted findings.

Conclusion:

Visits for patients with uncontrolled HTN rarely result in treatment intensification. Substantial opportunity exists to improve management of HTN, particularly for patients on fewer medications or seen by a covering provider.
Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension
Authors: Ma Hongkun , Wang Chongjian , Jiang Mengdi , Jin Kexin , Xu Tingting , Wang Zhiyu , Xu Jing , Ni Liyan , Shi Hao , Shen Pingyan , Chen Yongxi , Feng Xiaobei , Zhang Wen
Published: October 2023

Background and objectives:

Malignant hypertension (MHT) characterized by acute hypertension with retinopathy or multiorgan damage, is a severe form of hypertensive emergency and associated with target organ involvement and poor kidney outcome. However, the underlying mechanisms are unclear.

Methods:

Eighty-four patients with acute severe hypertension from the Nephrology Department and Emergency Department in a single center during January 2016 and December 2017 were prospectively enrolled and divided into MHT (n = 48) and non-MHT (n = 36) subgroups according to target organ evaluation. Forty healthy controls were recruited. Serum soluble Fms-like tyrosine kinase-1 (sFlt-1) levels and plasma ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity were examined at baseline and 12-month follow-up. Renal endpoints were defined as a significant decrease in the estimated glomerular filtration rate (eGFR) of more than 40% or the occurrence of end-stage renal disease.

Results:

Serum sFlt-1 levels were persistently elevated in MHT. Baseline serum sFLT-1 levels were correlated with plasma ADAMTS13 activity and markers of target organ damage. Plasma ADAMTS13 activity was reduced in both MHT and non-MHT patients and recovered to the normal range at 12-month follow-up. During an average follow-up time of 53 ± 13 months, the restoration of reduced ADAMTS13 activity was correlated with the improvement of kidney function and independently reduced the risk of renal endpoints.

Conclusions:

Abnormal angiogenesis and endothelial damage are involved in the pathophysiology of hypertensive emergency. Evaluation of ADAMTS13 and sFlt-1 may help in the diagnosis and assessment of MHT. Recovery of ADAMTS13 predicts better renal outcome in patients with hypertensive emergencies.
The relationship between cardiorespiratory fitness and blood pressure among airline pilots: a mediation analysis of body composition
Authors: Wilson Daniel , Driller Matthew , Johnston Ben , Gill Nicholas
Published: October 2023

Objective:

Blood pressure (BP), cardiorespiratory fitness (CRF), and body composition are independently associated with health outcomes, yet the relationship between these variables has not been explored among airline pilots. The aim of this study was to evaluate the relationship between CRF and BP, and further examine whether the relationship is mediated by body composition.

Methods:

A cross-sectional study was conducted among 356 airline pilots in New Zealand. We measured height, body mass, BP, waist circumference, skinfolds, and CRF (via a WattBike cycle ergometer submaximal VO2max test). Partial correlation coefficients were estimated to examine the relationships between all variables while controlling for age and sex. Haye's PROCESS macro and the Sobel test were utilized for the mediation analysis.

Results:

All body composition variables (body mass index, waist circumference and body fat percentage) were positively correlated with all BP variables (systolic pressure, diastolic pressure and mean arterial pressure) (P < 0.001). CRF was negatively correlated with all body composition and BP variables (P < 0.001). The Sobel test and indirect effect were significant (P < 0.001), confirming that all body composition variables partially mediate the relationship between CRF and all blood pressure variables.

Conclusion:

Lower CRF is associated with higher blood pressure, and body composition partially mediates the relationship between these health risk factors. These findings highlight the importance of physical fitness and healthy body composition in the management of blood pressure among this occupational group.
Momelotinib in Myelofibrosis Patients With Thrombocytopenia: Post Hoc Analysis From Three Randomized Phase 3 Trials
Authors: Kiladjian Jean-Jacques , Vannucchi Alessandro M. , Gerds Aaron T. , Gupta Vikas , Verstovsek Srdan , Egyed Miklos , Platzbecker Uwe , Mayer Jiří , Grosicki Sebastian , Illés Árpád , Woźny Tomasz , Oh Stephen T. , McLornan Donal , Kirgner Ilya , Yoon Sung-Soo , Harrison Claire N. , Klencke Barbara , Huang Mei , Kawashima Jun , Mesa Ruben
Published: October 2023

The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts <100 × 109/L) from randomized phase 3 studies: MOMENTUM (momelotinib versus danazol; JAK inhibitor experienced); SIMPLIFY-1 (momelotinib versus ruxolitinib; JAK inhibitor naïve); and SIMPLIFY-2 (momelotinib versus best available therapy; JAK inhibitor experienced); these studies were not statistically powered to assess differences in thrombocytopenic subgroups, and these analyses are descriptive. The treatment effect of momelotinib versus ruxolitinib on week 24 response rates (spleen volume reduction ≥35%/Total Symptom Score reduction ≥50%/transfusion independence) was numerically comparable or better in thrombocytopenic patients versus the overall JAK inhibitor naive population; rates were preserved with momelotinib in thrombocytopenic patients but attenuated with ruxolitinib (momelotinib: 27%/28%/67% overall versus 39%/35%/61% in thrombocytopenic group; ruxolitinib: 29%/42%/49% overall versus 0%/22%/39% in thrombocytopenic group, respectively). In contrast to ruxolitinib, momelotinib maintained high dose intensity throughout the treatment. In the JAK inhibitor experienced population, thrombocytopenic patients had the following: (1) numerically higher symptom and transfusion independence response rates with momelotinib than in control arms; and (2) preserved spleen, symptom, and transfusion independence response rates with momelotinib relative to the overall study populations. The safety profile of momelotinib in thrombocytopenic patients was also consistent with the overall study population. In summary, momelotinib represents a safe and effective treatment option for patients with MF and moderate-to-severe thrombocytopenia.
Effects of mind-body exercise on body constitution and circadian rhythm in people with suboptimal health status
Authors: Kung Yen-Ying , Shen Yuh-Chiang , Li Jia-Yi , Kao Yao-Kai , Kuo Terry B. J. , Yang Cheryl C. H.
Published: October 2023

Background:

Suboptimal health status (SHS) is a dynamic state in which people have not been diagnosed with a disease but tend to develop diseases. People with SHS are more prone to conditions such as cardiovascular disease and metabolic syndrome. Suitable interventions in people with SHS can prevent disease development. SHS is correlated with traditional Chinese medicine (TCM)-based constitutions, including Yang-Xu (yang deficiency), Yin-Xu (yin deficiency), and stasis types. The circadian rhythm is a potential biomarker of health and metabolism. Baduanjin exercise, a kind of mind-body exercise, has been regarded to adjust body constitution and metabolism, but few studies have evaluated the effects of Baduanjin exercise on body constitution and circadian rhythms. Therefore, this randomized controlled trial investigated the effects of Baduanjin exercise on body constitution and circadian rhythms in people with SHS.

Methods:

Seventy-six participants with SHS were divided into the Baduanjin exercise and control groups (watching a Baduanjin video), with the interventions lasting 12 weeks. The Body Constitution Questionnaire (BCQ), SHS Questionnaire-25 (SHSQ-25), and actigraphy for circadian rhythm measurement were conducted.

Results:

The scores of SHSQ-25, Yang-Xu, Yin-Xu, and BCQ stasis decreased significantly after 12 weeks in the Baduanjin exercise group, but not in the control group. Interdaily stability of the circadian rhythm increased significantly in the Baduanjin exercise group but not in the control group.

Conclusion:

This is the first report of improved health status, modulated body constitution, and increased interdaily stability of the circadian rhythm in participants with SHS who practiced Baduanjin exercise.
Chinese Expert Consensus on the Diagnosis and Treatment of Adult Dermatomyositis (2022)#
Authors: Cao Hua , Chen Ai-Jun , Cui Yong , Deng Dan-Qi , Gao Xing-Hua , He Yan-Ling , Kang Xiao-Jing , Jin Hong-Zhong , Li Cheng-Xin , Li Feng , Li Heng-Jin , Liao Wen-Jun , Liu Xiao-Ming , Lu Qian-Jin , Lu Yan , Pan Meng , Pan Wei-Hua , Shu Xiao-Ming , Sun Qing , Tang Ke-Yun , Tao Juan , Wang Yu , Xiao Ting , Zhang Fu-Ren , Zhang Han-Lin ,   Dermatology Branch of the China International Exchange and Promotion Association for Medical and Health Care; National Clinical Research Center for Dermatologic and Immunologic Diseases
Published: October 2023

Dermatomyositis, an idiopathic inflammatory myopathy, is characterized by distinctive skin manifestations, proximal muscle weakness, and multiple organ involvement and can be accompanied by malignancies. To provide a reference for dermatologists and clinicians in other relevant fields of clinical practice, experts from the Dermatology Branch of the China International Exchange and Promotion Association for Medical and Health Care and the National Clinical Research Center for Dermatologic and Immunologic Diseases developed this consensus on the diagnosis and treatment of adult dermatomyositis using Chinese and international literature and expert advice.
Metabolic Syndrome Accelerates the Age-Related Increase of Intraductal Papillary Mucinous Neoplasm of the Pancreas
Authors: Tanaka Shunta , Tsujimae Masahiro , Masuda Atsuhiro , Inoue Jun , Inomata Noriko , Uemura Hisahiro , Kohashi Shinya , Nagao Kae , Masuda Shigeto , Abe Shohei , Gonda Masanori , Yamakawa Kohei , Ashina Shigeto , Nakano Ryota , Tanaka Takeshi , Yamada Yasutaka , Sakai Arata , Kobayashi Takashi , Shiomi Hideyuki , Fujita Koichi , Anami Takahiro , Fujita Tsuyoshi , Watanabe Akihiko , Kodama Yuzo
Published: October 2023

Objectives

Aging is associated with a high prevalence of pancreatic cysts and intraductal papillary mucinous neoplasms (IPMNs). Metabolic syndrome (MS) may increase the risk of neoplasms, including those that develop in the pancreas. However, the influence of factors associated with MS on the development of IPMN remains unclear.

Methods

A total of 9363 patients who underwent abdominal ultrasound examinations between April 2012 and May 2013 were included in this study. Multivariate logistic regression analysis was performed to identify factors associated with the presence of IPMN by age.

Results

Pancreatic cysts were detected in 198 of 9363 patients, of whom 129 were found to have IPMNs. The presence of IPMN significantly correlated with age (10-year increments; odds ratio, 2.73; 95% CI, 2.28–3.29; P < 0.001). High body mass index, history of smoking, hyperlipidemia, hypertension, and MS were associated with a higher prevalence of IPMN with advancing age. In multivariate analysis, the presence of IPMN was more frequent in elderly patients with MS (odds ratio, 3.14; 95% CI, 3.14–6.72; P = 0.003).

Conclusions

The present study suggests that the incidence of IPMN increases with age and is accelerated in the presence of MS.
Deep Learning for Detection of Pneumothorax and Pleural Effusion on Chest Radiographs
Authors: Tejani Ali , Dowling Thomas , Sanampudi Sreeja , Yazdani Rana , Canan Arzu , Malja Elona , Xi Yin , Abbara Suhny , Peshock Ron M. , Kay Fernando U.
Published: October 2023

Purpose:

To study the performance of artificial intelligence (AI) for detecting pleural pathology on chest radiographs (CXRs) using computed tomography as ground truth.

Patients and Methods:

Retrospective study of subjects undergoing CXR in various clinical settings. Computed tomography obtained within 24 hours of the CXR was used to volumetrically quantify pleural effusions (PEfs) and pneumothoraxes (Ptxs). CXR was evaluated by AI software (INSIGHT CXR; Lunit) and by 3 second-year radiology residents, followed by AI-assisted reassessment after a 3-month washout period. We used the area under the receiver operating characteristics curve (AUROC) to assess AI versus residents’ performance and mixed-model analyses to investigate differences in reading time and interreader concordance.

Results:

There were 96 control subjects, 165 with PEf, and 101 with Ptx. AI-AUROC was noninferior to aggregate resident-AUROC for PEf (0.82 vs 0.86, P < 0.001) and Ptx (0.80 vs 0.84, P = 0.001) detection. AI-assisted resident-AUROC was higher but not significantly different from the baseline. AI-assisted reading time was reduced by 49% (157 vs 80 s per case, P = 0.009), and Fleiss kappa for Ptx detection increased from 0.70 to 0.78 (P = 0.003). AI decreased detection error for PEf (odds ratio = 0.74, P = 0.024) and Ptx (odds ratio = 0.39, P < 0.001).

Conclusion:

Current AI technology for the detection of PEf and Ptx on CXR was noninferior to second-year resident performance and could help decrease reading time and detection error.
Functional Impairment in Small Airways Associated With the Breathlessness Symptoms in Long–Coronavirus Disease
Authors: Kim Minsuok , Hwang Jeongeun , Grist James T. , Abueid Gabriele , Yoon Soon Ho , Grau Vicente , Fraser Emily , Gleeson Fergus V.
Published: October 2023

Purpose:

This study aimed to determine the association between functional impairment in small airways and symptoms of dyspnea in patients with Long-coronavirus disease (COVID), using imaging and computational modeling analysis.

Patients and Methods:

Thirty-four patients with Long-COVID underwent thoracic computed tomography and hyperpolarized Xenon-129 magnetic resonance imaging (HP Xe MRI) scans. Twenty-two answered dyspnea-12 questionnaires. We used a computed tomography–based full-scale airway network (FAN) flow model to simulate pulmonary ventilation. The ventilation distribution projected on a coronal plane and the percentage lobar ventilation modeled in the FAN model were compared with the HP Xe MRI data. To assess the ventilation heterogeneity in small airways, we calculated the fractal dimensions of the impaired ventilation regions in the HP Xe MRI and FAN models.

Results:

The ventilation distribution projected on a coronal plane showed an excellent resemblance between HP Xe MRI scans and FAN models (structure similarity index: 0.87 ± 0.04). In both the image and the model, the existence of large clustered ventilation defects was not identifiable regardless of dyspnea severity. The percentage lobar ventilation of the HP Xe MRI and FAN model showed a strong correlation (ρ = 0.63, P < 0.001). The difference in the fractal dimension of impaired ventilation zones between the low and high dyspnea-12 score groups was significant (HP Xe MRI: 1.97 [1.89 to 2.04] and 2.08 [2.06 to 2.14], P = 0.005; FAN: 2.60 [2.59 to 2.64] and 2.64 [2.63 to 2.65], P = 0.056).

Conclusions:

This study has identified a potential association of small airway functional impairment with breathlessness in Long-COVID, using fractal analysis of HP Xe MRI scans and FAN models.
New Imaging Protocol to Assess Endotracheal Tube Placement
Authors: Liubaskas Rokas , Eisenberg Ronald L. , Chakrala Nihara L. , Liubauske Aurelija , Liberman Yuval , Oren-Grinberg Achikam , Tridente Daniela M. , Litmanovich Diana E.
Published: October 2023

Purpose:

After intubation, a frontal chest radiograph (CXR) is obtained to assess the endotracheal tube (ETT) position by measuring the ETT tip-to-carina distance. ETT tip location changes with neck position and can be determined by assessing the position of the mandible. As the mandible is typically not visualized on standard CXRs, we developed a new protocol where the mandible is seen on the CXR, hypothesizing that it will improve the accuracy of the ETT position assessment.

Patients and Methods:

Two groups of intubated patients studied (February 9, 2021 to May 4, 2021): CXR taken in either standard or new protocol (visible mandible required). Two observers independently assessed the images for the neck position (neutral, flexed, and extended) based on the mandible position relative to the vertebral bodies. With the mandible absent (ie, neck position unknown), we established terms: “gray zone” (difficult to assess the ETT position adequately) and “clear zone” (confident recommendation to retract, advance, or maintain ETT position). We compared the rate of confident assessment of the ETT in the standard versus the new protocol.

Results:

Of 308 patients, 155 had standard CXRs and 153 had the new protocol. Interrater agreements for the distance between the ETT and the carina and mandible height based on vertebral bodies were 0.986 (P < 0.001) and 0.955 (P < 0.001), respectively. The mandible was visualized significantly more often (P < 0.001) with the new protocol (92%; 141/153) than with the standard protocol (21%; 32/155). By visualizing the mandible or the presence of the ETT within the clear zone, a reader could confidently assess the ETT position more often using the new protocol (96.7% vs 51.6%, P < 0.001).

Conclusions:

Mandible visibility on postintubation CXR is helpful for assessing the ETT position. The new protocol resulted in a significant increase in both visualizing the mandible and accurately determining ETT position on postintubation CXR.
Infectious Granuloma With Mycobacterium abscessus After Facial Injection of Botulinum Toxin: A Case Report
Authors: Li Congying , Shen Chen , Zhang Wei
Published: October 2023

Botulinum toxin injections have garnered increasing employment in facial rhytidectomy due to their demonstrable efficacy and safety profile. In this study, the authors present the case of a 39-year-old woman who manifested painful crimson nodules and multiple abscesses on her face, which manifested 1 week postinjection. Subsequent histopathological scrutiny unveiled the development of histiocytic granulomas accompanied by infiltrates of inflammatory cells, and microbiological investigation and polymerase chain reaction assays identified the causative agent as Mycobacterium abscessus.
Is Ketamine an Effective Treatment of Acute Agitation in the Emergency Department? Implications for APRN Practice
Authors: Brown Andrea C. , Evans Dian Dowling , Tucker Paula
Published: October 2023

This article reviews the results of a randomized controlled trial, “Rapid Agitation Control with Ketamine in the Emergency Department: A Blinded, Randomized Controlled Trial” by D. Barbic et al. (2021), comparing time to sedation, level of sedation, and adverse outcomes between intramuscular ketamine versus intramuscular midazolam and haloperidol among acutely agitated patients presenting to the emergency department (ED). The findings are discussed in the context of practice change for patient stabilization within the ED. Emergency department nurse practitioners must employ continuing education and remain current with clinical practices and treatment options to ensure that patients receive optimal safe care. Although the use of midazolam and haloperidol has historically been the first-line treatment for the acutely agitated patient, use of ketamine shows promise in providing a safe alternative for expedited patient stabilization for acutely agitated patients presenting to the ED.
Cast Removal: Pearls and Methods
Authors: Miller Brianne N. , Purnell Marcy C.
Published: October 2023

Cast removal is a common procedure that can involve risks to the patient and should be done by a qualified and experienced provider. Indications for removal, assessment parameters, and careful procedural steps should be understood by all technicians, practitioners, and physicians who will participate in the removal of casting materials. Because this procedure can also produce anxiety for the patient and their family members, it is good practice to thoroughly inform the patient and answer any questions in advance to help reduce anxiety and promote cooperation from all during the process. This article describes common techniques for cast removal and provides tips to facilitate safe and efficient outcomes during this procedure.
Low-Dose Electrocution and Atrial Fibrillation
Authors: Obeso-Martinez Ida
Published: October 2023

Emergency electrocution incidents present with various injuries, which can range from minor to severe injuries including death. Cardiac-related complications have a higher mortality incidence among patients with low-voltage injuries (M. R. Zemaitis et al., 2023). When managing electrical injury patients, the literature recommends managing them as both trauma and cardiac cases. However, the diagnostic approach is based on each individual case and patient presentation. Electrical injury complications include arrhythmias, myocardial tissue damage, and conduction disturbances (Pilecky et al., 2019). The purpose of this case study is to discuss a postelectrocution atrial fibrillation case and common related arrhythmias associated with electrical injuries.
Content Validation of an Emergency Department Skin Risk Assessment Instrument
Authors: Flarity Kathleen , Haylett Wendy J. , Childers Melissa
Published: October 2023

Pressure injuries (PIs) are an important quality and patient safety metric for health care organizations. PI monitoring and treatment are often overlooked in the emergency department (ED). Emergency care professionals must be proactive about PI early identification and prevention strategies. A team at a Level 1 trauma center recognized the need for ED-friendly documentation and a validated ED skin risk assessment instrument. The Bjorklund 25-item ED Skin/Risk Assessment Tool was selected. However, because the tool was not fully validated, permission to validate/use was obtained from the author. The purpose of this research study was to determine the content validity of the Bjorklund Tool. Using a prospective survey design, content experts were recruited from wound, quality, and ED and participated in two rounds of content validation. The experts reviewed the Tool for relevance, clarity, and appropriateness for the ED population. Item-level content validity index (I-CVI) and scale-level CVI (S-CVI) were calculated, with 0.78 and 0.90 as the lower limits of acceptability for individual items and the overall scale, respectively. Of the first round I-CVI ratings, 24 of 75 were below 0.78, including 14 for relevance, four for clarity, and six for appropriateness. S-CVI was 0.7574 for relevance, 0.8809 for clarity, 0.8592 for appropriateness, and 0.8325 overall. The Bjorklund Tool was determined to be invalid in its current form. A novel tool was thus created in the second round per content experts' recommendations. After redesign and simplifying items and images, all I-CVIs rated above 0.78. S-CVI was 0.923 for relevance, 0.9743 for clarity, 0.9615 for appropriateness, and 0.9529 overall. These CVIs indicate excellent content validity of the new UCHealth ED Skin Risk Assessment Instrument. This research contributes to establishment of content validity of a skin risk assessment instrument which can be used in the unique ED setting.
Recognition of Cutaneous Symptoms of Common Tick-Borne Illness in the Emergency Department
Authors: May Erica
Published: October 2023

Tick-borne diseases occur throughout the United States, with a disease burden that ranges from mild to severe. As temperatures rise with climate change, the active season for ticks increases, and more tick-borne illness is seen (Centers for Disease Control and Prevention, 2022a). Many patients present to the ED for suspected tick bites, rashes, and generalized medical complaints that may be related to a tick-borne disease, so it is important for the emergency nurse practitioner (ENP) to accurately diagnose these conditions. Because of this increasing disease burden, it has become vital for these illnesses to be recognized early, as early diagnosis can reduce possible complications of chronic illness. Familiarity with the cutaneous rashes present in several tick-borne diseases can aid the ENP to effectively diagnose and treat these conditions.
Use of multiplex PCR in pleural effusion: Is it necessary to change the paradigm of culture-based methods?
Authors: Londono-Ruiz Juan Pablo , Vargas-Garcia Andrea , Cardenas-Muller Adriana , Bejarano-Quintero Ana Maria , Mantilla Maria Ximena , Gutierrez-Tobar Ivan Felipe
Published: October 2023

The microbiological diagnosis of pleural effusion is largely based on classical microbiology methods, but these methods have a high rate of false negative results. Some previous studies have shown improved diagnostic performance for pathogens such as S. pneumoniae using molecular biology methods. We present the use of a Multiplex-PCR platform (BIOFIRE® FILMARRAY® Pneumonia Panel) for the etiological diagnosis of pleural effusion in pediatric pneumonia. We present a case series of 17 pleural fluid samples that were processed by culture-based microbiology and molecular biology methods. Microbiological isolation was successful in 4 cases (25%) through traditional culture methods. In contrast, the molecular biology panels allowed for detection in 16 out of 17 cases (94%). The results from these panels led to a change in management for 9 out of the 17 cases (52%). This study found an increase in etiological diagnosis in complicated pneumonia in children using molecular biology methods, which led to a significant change in patient management.
Streptomyces chengmaiensis sp. nov., isolated from the stem of a mangrove plant in Hainan
Authors: Lin Yongrui , Chu Xiaoxiao , Xie Yuhui , Xie Xinqiang , Huang Xiaolong , Zhou Shuangqing
Published: October 2023

A novel

Streptomyces

strain, designated as HNM0663T, was isolated from the stem of a mangrove plant (Avicennia marina) collected from the coast of Chengmai city, Hainan Island, PR China. On the basis of the alignment of 16S rRNA gene sequences, strain HNM0663T was closely related to

Streptomyces lichenis

LCR6-01T (98.67 %),

Streptomyces nanningensis

YIM 33098T (98.12 %) and

Streptomyces palmae

CMU-AB204T (97.93 %). Genome-based comparisons showed that strain HNM0663T was distinguished from its closest related species with 80.3 % average nucleotide identity and 20.2 % digital DNA–DNA hybridization values. The main cellular fatty acids were iso-C16 : 0, iso-C15 : 0 and anteiso-C15 : 0. The main menaquinones were MK-9 (H6), MK-9 (H4) and MK-8 (H4). The predominant phospholipids contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylcholine. Based on these polyphasic taxonomy results, strain HNM0663T should represent a novel

Streptomyces

species, for which the name Streptomyces chengmaiensis sp. nov. is proposed. The type strain is HNM 0663T (=CCTCC AA 2019075T=LMG 31909T).
Pseudomonas hormoni sp. nov., a plant hormone producing bacterium isolated from Arctic grass, Ellesmere Island, Canada
Authors: Sorty Ajay Madhusudan , Zervas Athanasios , García de Salamone Inés Eugenia , Nelson Louise M. , Stougaard Peter
Published: October 2023

Bacterial strain G20-18T was previously isolated from the rhizosphere of an Arctic grass on Ellesmere Island, Canada and was characterized and described as

Pseudomonas fluorescens

. However, new polyphasic analyses coupled with phenotypic, phylogenetic and genomic analyses reported here demonstrate that the affiliation to the species

P. fluorescens

was incorrect. The strain is Gram-stain-negative, rod-shaped, aerobic and displays growth at 5–25 °C (optimum, 20–25 °C), at pH 5–9 (optimum, pH 6–7) and with 0–4 % NaCl (optimum, 2 % NaCl). The major fatty acids are C16 : 0 (35.6 %), C17 : 0 cyclo ω7c (26.3 %) and summed feature C18 : 1/C18 : 1 ω7c (13.6 %). The respiratory quinones were determined to be Q9 (93.5 %) and Q8 (6.5 %) and the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Strain G20-18T was shown to synthesize cytokinin and auxin plant hormones and to produce 1-aminocyclopropane-1-carboxylate deaminase. The DNA G+C content was determined to be 59.1 mol%. Phylogenetic analysis based on the 16S rRNA gene and multilocus sequence analysis (concatenated 16S rRNA, gyrB, rpoB and rpoD sequences) showed that G20-18T was affiliated with the

Pseudomonas mandelii

subgroup within the genus

Pseudomonas

. Comparisons of the G20-18T genome sequence and related

Pseudomonas

type strain sequences showed an average nucleotide identity value of ≤93.6 % and a digital DNA–DNA hybridization value of less than 54.4 % relatedness. The phenotypic, phylogenetic and genomic data support the hypothesis that strain G20-18T represents a novel species of the genus

Pseudomonas

. As strain G20-18T produces or modifies hormones, the name Pseudomonas hormoni sp. nov. is proposed. The type strain is G20-18T (=LMG 33086T=NCIMB 15469T).
Corynebacterium suedekumii sp. nov and Corynebacterium breve sp. nov., isolated from raw cow’s milk
Authors: Baer Mareike Katharina , Marke Gina , Mehl Lena , Hellmuth Ronja , Bartholomäus Alexander , Lipski André
Published: October 2023

Four Gram-positive, rod-shaped, none-sporeforming, non-motile isolates were obtained from various raw milk samples taken from the cooling tank on a research farm in Königswinter, Germany. Based on phylogenetic analysis of the 16S rRNA genes and whole genome sequences, all isolates were assigned to the genus

Corynebacterium

, but were divided in two different groups. All isolates contained C18 : 1
cis 9 and C16 : 0 as predominant fatty acids, as well as traces of C18 : 0. They all contained menaquinones MK-8 (H2) and MK-9 (H2) and produced mycolic acids characteristic for the majority of species belonging to the genus

Corynebacterium

. 16S rRNA gene sequence similarity values to the closest related type strains

Corynebacterium humireducens

DSM 45392T and

Corynebacterium pilosum

DSM 20521T were below 98.7 %, average nucleotide identity values were below 86 % and digital DNA–DNA-hybridization values were below 25 %, indicating that the isolates represent two novel species. The names Corynebacterium suedekumii sp. nov. and Corynebacterium breve sp. nov. are proposed, represented by the type strains LM112T (=DSM 116216T=HAMBI 3782T) and R4T (=DSM 116183T=HAMBI 3785T), respectively.
Ambient Temperature Bacterial Large Ribosomal Subunit Structure Enabled by Serial Femtosecond X-ray Crystallography
Authors: Tosun Bilge , Rao Yashas , Destan Ebru , Dao E. Han , Ertem Fatma Betul , Yilmaz Merve , Yapici Ilkin , Gul Mehmet , Ayan Esra , Johnson Jerome , Shafiei Alaleh , Kulakman Cahine , Hayes Brandon , Liang Mengning , Yoon Chun Hong , Su Zhen , Hunter Mark S. , Kupitz Christopher , Poitevin Frederic , Ciftci Halil Ibrahim , Sierra Raymond G. , Gregory Steven T. , Milon Pohl , Kurkcuoglu Ozge , DeMirci Hasan
Published: October 2023

Ribosomes are the supramolecular complexes responsible for protein synthesis. The large 50S ribosomal subunit catalyzes the peptidyl transferase reaction and peptide bond formation between amino acids. The 50S is targeted by many known clinically effective antibiotics. Available structures, obtained at cryogenic temperatures (CT), are used for drug discovery despite that active or important target sites may display a structural configuration that is CT-induced. The introduction of ultrafast and ultrabright X-ray free electron laser (XFEL) pulses has enabled the structural observation of biological macro- and supramolecules at previously unattainable, near-physiological temperatures. In this study, we use ultrafast and ultrabright XFEL pulses to solve the apo form of 50S ribosomal subunit isolated from the extremely thermophilic bacteriumThermus thermophilusat ambient temperature (AT). The dimeric structure of the 50S subunit presented in this work is among the largest (∼3 megadalton) structures determined using an XFEL source to date. This study demonstrates the ability to obtain new information about ribosome structural dynamics at AT through serial femtosecond X-ray crystallography (SFX). This allowed us to capture previously unobserved dynamics of ribosomal protein uL23 and coordination by hexahydrated magnesium cations at ahithertounseen resolution at near-physiological temperature. Also, residue A2602, at the core of the peptidyl transferase center (PTC), shows a rather different orientation of the sugar moiety if compared to CT structures. In addition, our structure highlights the importance of flexible residues at both the PTC and in the binding sites for antibiotics erythromycin and chloramphenicol. The method implemented here may also serve as a starting point for future structural research involving the 50S subunit complexes by employing time-resolved mix-inject and probe kineto-crystallography experiments at XFELs. Unveiling ligand-dependent 50S dynamics at physiological temperatures shall guide further development of next-generation antibiotics that target the translation machinery.
Neural-circuit basis of song preference learning in fruit flies
Authors: Imoto Keisuke , Ishikawa Yuki , Aso Yoshinori , Funke Jan , Tanaka Ryoya , Kamikouchi Azusa
Published: October 2023

As observed in human language learning and song learning in birds, the fruit flyDrosophila melanogasterchanges its’ auditory behaviors according to prior sound experiences. Female flies that have heard male courtship songs of the same species are less responsive to courtship songs of different species. This phenomenon, known as song preference learning in flies, requires GABAergic input to pC1 neurons in the central brain, with these neurons playing a key role in mating behavior by integrating multimodal sensory and internal information. The neural circuit basis of this GABAergic input, however, has not yet been identified.

Here, we find that pCd-2 neurons, totaling four cells per hemibrain and expressing the sex-determination genedoublesex, provide the GABAergic input to pC1 neurons for song preference learning. First, RNAi-mediated knockdown of GABA production in pCd-2 neurons abolished song preference learning. Second, pCd-2 neurons directly, and in many cases mutually, connect with pC1 neurons, suggesting the existence of reciprocal circuits between pC1 and pCd-2 neurons. Finally, GABAergic and dopaminergic inputs to pCd-2 neurons are necessary for song preference learning. Together, this study suggests that reciprocal circuits between pC1 and pCd-2 neurons serve as a sensory and internal state-integrated hub, allowing flexible control over female copulation. Consequently, this provides a neural circuit model that underlies experience-dependent auditory plasticity.

Significance

To find a suitable mate, an organism must adapt its behavior based on past experiences. In the case ofDrosophila, female assessments of male song signals, which contain information about the status and species of the sender, are experience dependent. Here, we show that reciprocal circuits in the central brain modulate the female’s song response depending on her previous auditory experiences. These circuits exhibit feedback and lateral inhibition motifs, and are regulated by dopaminergic and GABAergic inputs. While the effects of prior auditory experiences on sound responsiveness have been extensively studied in other species, our research advances the use ofDrosophilaas a model for dissecting the circuitry underlying experience-dependent auditory plasticity at single-cell resolution.
Where to stop Ψ-BLAST iterations so that the found sequences remain related to the query sequence?
Authors: Bogatyreva Natalya S. , Finkelstein Alexei V. , Ivankov Dmitry N.
Published: October 2023

The BLAST program [Altschul et al., 1990, J. Mol. Biol., 215:403-410] stands as a widely used tool for the search of the most similar sequences, while the iterative Ψ-BLAST program [Altschul et al., 1997, Nucl. Acids Res., 25:3389-3402] offers a high sensitivity for detecting remote homologs of the query sequence through an iterative usage of the BLAST search. However, the number of iterations that have to be used by the Ψ-BLAST is rather poorly justified in the literature. Our study shows that, as the number of iterations increases, Ψ-BLAST rapidly loses the ability to be guided by the query sequence in the search for homologs. When working with the non-redundant (nr) sequence database of 2021, Ψ-BLAST, already after the second iteration, retains the query sequence at the top of the list of the found homologs to this sequence in only 18% of cases. Moreover, a query sequence is still listed among homologs found by Ψ-BLAST after the recommended 10 iterations [Altschul et al., 1997, Nucl. Acids Res., 25:3389-3402] in only 42% of cases. Using a considerably smaller nr database-2011 as a reference, we reveal that these effects intensify over time. Our findings underscore the necessity for circumspection when interpreting Ψ-BLAST outcomes; the degree of vigilance must increase with the database size. A vigilant monitoring of the position of the query sequence in the array of detected homologs is needed. We recommend using the disappearance of the query sequence from the list of homologs produced by Ψ-BLAST as a criterion to conclude the Ψ-BLAST iterations.
Alpha-Asarone Attenuates Alcohol-Induced Hepatotoxicity in a Murine Model by Ameliorating Oxidative Stress, Inflammation, and Modulating Apoptotic-Autophagic Cell Death
Authors: Abdelhamid Amir Mohamed , Ali Nada A.M. , El Sayed Norhan M. , Radwan Asmaa
Published: October 2023

Alcoholic liver disease (ALD) is a major cause of chronic liver injury characterized by steatosis, inflammation, and fibrosis. This study explored the hepatoprotective mechanisms of alpha-asarone in a mouse model of chronic-binge alcohol feeding. Adult male mice were randomized into control, alcohol, and alcohol plus alpha-asarone groups. Serum aminotransferases and histopathology assessed liver injury. Oxidative stress was evaluated via malondialdehyde content, glutathione, superoxide dismutase, and catalase activities. Pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified by ELISA. P53-mediated apoptosis was determined by immunohistochemistry. Key autophagy markers AMPK, Beclin-1, and LC3 were examined by immunoblotting. Alcohol administration increased serum ALT, AST and ALP, indicating hepatocellular damage. This liver dysfunction was associated with increased oxidative stress, inflammation, p53 expression and altered autophagy. Alpha-asarone treatment significantly decreased ALT, AST and ALP levels and improved histological architecture versus alcohol alone. Alpha-asarone also mitigated oxidative stress, reduced TNF-α, IL-1β and IL-6 levels, ameliorated p53 overexpression and favorably modulated autophagy markers. Our findings demonstrate that alpha-asarone confers protective effects against ALD by enhancing antioxidant defenses, suppressing hepatic inflammation, regulating apoptotic signaling, and restoring autophagic flux. This preclinical study provides compelling evidence for the therapeutic potential of alpha-asarone in attenuating alcohol-induced liver injury and warrants further evaluation as a pharmacotherapy for ALD.
Signal Peptide of Human Serum Albumin (residues 1-18) Forms Amyloid-like Aggregates
Authors: Thakur D. C. , Saumya Kumar Udit , Singh Vipendra Kumar , Giri Rajanish
Published: October 2023

Signal peptides (SPs) are essential tools in sorting or translocating the synthesized proteins. However, except few examples, their studies in isolation are quite limited. Here we asked a question of the aggregation propensity of signal peptide (residues 1-18) of Human Serum Albumin (HSA). Molecular dynamic simulations were used to acquire observations into the mechanism through which signal peptides of HSA self-aggregated in physiological conditions. Further, we confirmed our results by combining dye-based assays, atomic force microscopy, and transmission electron microscopy techniques. It was noted that the signal peptide of HSA (region 1-18) forms typical amyloid-like fibrils.

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The force-sensing GPCR LPHN2 is indispensable for normal auditory function
Authors: Yang Zhao , Wang Ming-Wei , Zhou Shu-Hua , Song Zhi-Chen , Zhu Kong-Kai , Wen Xin , Zhang Qi-Yue , Guan Ying , Gao Jia-Rui , Wang Xiao-Hui , Wang Ya-Qi , Liu Wen-Wen , Xu Lei , Xiong Wei , Chai Ren-Jie , Wang Chuan , Xu Zhi-Gang , Yu Xiao , Sun Jin-Peng
Published: October 2023

The conversion of force sensation into electrical signals via mechanoelectrical transduction (MET) is considered the key step in auditory perception. Here, we found that G protein-coupled receptor (GPCR) LPHN2/ADGRL2 was expressed at the tips of stereocilia in cochlear hair cells and was associated with MET channel components. Hair cell-specific LPHN2 deficiency caused hearing loss and impaired MET responses. A specific inhibitor of LPHN2, developed by in silico screening and pharmacological characterization, reversibly blocked the MET response. Mechanistically, administration of force to LPHN2 activated TMC1 through direct interaction and caused conformational changes in TMC1 in vitro. Furthermore, the sensing of force by LPHN2 stimulated Ca2+responses and neurotransmitter release in hair cells. Finally, hearing loss in LPHN2-deficient mice was reversed by the re-expression of LPHN2-GAIN in cochlear hair cells. The important roles of LPHN2 in auditory perception and a TMC-coupled force sensor indicated that GPCRs could be candidate auditory receptors.
A force-sensitive adhesion GPCR is indispensable in normal equilibrioception
Authors: Yang Zhao , Zhou Shu-Hua , Zhang Qi-Yue , Song Zhi-Chen , Liu Wen-Wen , Sun Yu , Wang Ming-Wei , Fu Xiao-Long , Zhu Kong-Kai , Guan Ying , Qi Jie-Yu , Wang Xiao-Hui , Sun Yu-Nan , Lu Yan , Ping Yu-Qi , Xi Yue-Tong , Xu Zhi-Gang , Xiong Wei , Qin Wei , Yang Wei , Yi Fan , Yu Xiao , Chai Ren-Jie , Sun Jin-Peng
Published: October 2023

Abstract

Equilibrioception is essential for the perception and navigation of mammals in the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells plays a critical role in positional and motional perception. Here, we identified that the G protein-coupled receptor LPHN2/ADGRL2, which is expressed in the apical membrane of utricular hair cells, is required for maintenance of normal balance. Hair cell-specific Lphn2 deficiency in mice impaired both balance behaviors and MET responses. Functional analyses usingPou4f3-CreER+/-;Lphn2fl/flmice and LPHN2-specific inhibitors revealed that LPHN2 regulated the tip link-independent MET current at the apical surface of the utricular hair cell by converting force stimuli into transmembrane channel-like protein 1 (TMC1) activity. Force sensation by LPHN2 also induced glutamate release and calcium signaling in utricular hair cells. Reintroduction of LPHN2 into the hair cells of Lphn2-deficient mice restored the vestibular functions and MET responses. Our data suggest an indispensable role for a mechanosensitive GPCR in equilibrioception.