bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oomycete Metabolism Is Highly Dynamic and Reflects Lifestyle Adaptations
Authors: Rodenburg Sander Y. A. , de Ridder Dick , Govers Francine , Seidl Michael F. 
Published: April 2024

The selective pressure of pathogen-host symbiosis drives adaptations. How these interactions shape the metabolism of pathogens is largely unknown. Here, we use comparative genomics to systematically analyze the metabolic networks of oomycetes, a diverse group of eukaryotes that includes saprotrophs as well as animal and plant pathogens, with the latter causing devastating diseases with significant economic and/or ecological impacts. In our analyses of 44 oomycete species, we uncover considerable variation in metabolism that can be linked to lifestyle differences. Comparisons of metabolic gene content reveal that plant pathogenic oomycetes have a bipartite metabolism consisting of a conserved core and an accessory set. The accessory set can be associated with the degradation of defense compounds produced by plants when challenged by pathogens. Obligate biotrophic oomycetes have smaller metabolic networks, and taxonomically distantly related biotrophic lineages display convergent evolution by repeated gene losses in both the conserved as well as the accessory set of metabolisms. When investigating to what extent the metabolic networks in obligate biotrophs differ from those in hemibiotrophic plant pathogens, we observe that the losses of metabolic enzymes in obligate biotrophs are not random and that gene losses predominantly influence the terminal branches of the metabolic networks. Our analyses represent the first metabolism-focused comparison of oomycetes at this scale and will contribute to a better understanding of the evolution of oomycete metabolism in relation to lifestyle adaptation. Numerous oomycete species are devastating plant pathogens that cause major damage in crops and natural ecosystems. Their interactions with hosts are shaped by strong selection, but how selection affects adaptation of the primary metabolism to a pathogenic lifestyle is not yet well established. By pan-genome and metabolic network analyses of distantly related oomycete pathogens and their nonpathogenic relatives, we reveal considerable lifestyle- and lineage-specific adaptations. This study contributes to a better understanding of metabolic adaptations in pathogenic oomycetes in relation to lifestyle, host, and environment, and the findings will help in pinpointing potential targets for disease control. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The role of morphine‐ and fentanyl‐induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota‐gut‐brain axis
Authors: Muchhala Karan H. , Kallurkar Prajkta S. , Kang Minho , Koseli Eda , Poklis Justin L. , Xu Qingguo , Dewey William L. , Fettweis Jennifer M. , Jimenez Nicole R. , Akbarali Hamid I. 
Published: April 2024

AbstractRecent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid‐induced antinociception, suggesting an important role of the gut‐brain axis in mediating opioid effects. The mechanism underlying opioid‐induced dysbiosis, however, remains unclear. Host‐produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine‐treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine‐naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine‐dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin‐degrading A. muciniphila in morphine‐dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota‐gut‐brain axis.
Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis
Authors: Du Xinyan , Zhang Xuena , Liu Junxia , Wang Zhendi 
Published: April 2024

ABSTRACT

Objective
To synthesize the effects of oxygen-based therapy on patients with a chronic wound.

Data Sources
The authors searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials from database inception. Investigators measured risk of bias using the Cochrane Collaboration’s Risk of Bias tool.

Study Selection
The included randomized controlled trials focused on the effects (short- or long-term wound healing, amputation rate, percentage of reduction in ulcer size, and poststudy transcutaneous oxygen measurement [TcPO2]) of oxygen-based therapy (including hyperbaric oxygen therapy, topical oxygen therapy, and continuous diffusion of oxygen) on patients with a chronic wound.

Data Extraction
Researchers extracted information regarding participant characteristics and primary and secondary outcomes from the included studies.

Data Synthesis
Pooled effects of 31 included studies showed that patients treated with oxygen had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987), a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599), lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862), shorter wound healing time (SMD, −0.705; 95% CI, −0.908 to −0.501), and higher poststudy TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group. For long-term wound healing, there was no statistically significant difference (RR, 1.227; 95% CI, 0.976 to 1.542).

Conclusions
Oxygen-based therapy improves short-term parameters of wound healing in patients with chronic wounds.
Lower Extremity Angiosarcoma: A Life-Threatening Complication of Lymphedema
Authors: Garimella Vishal , Anand Nimay , Campbell Elliott H. , Baum Christian L. , Alavi Afsaneh 
Published: April 2024

ABSTRACTWhen angiosarcoma, a rare and aggressive tumor of the soft tissue, develops in the setting of chronic lymphedema, it is referred to as Stewart-Treves syndrome. It is usually seen in chronic lymphedema of the upper limbs postmastectomy. Angiosarcoma developing in the lower limb in the setting of chronic lymphedema is rare and has a poor outcome. The presentation of angiosarcoma can vary, ranging from a bleeding papule to a plaque or a subcutaneous mass, which can later progress to ulceration or necrosis. Treatment for Stewart-Treves syndrome is aggressive because of its poor prognosis and usually requires a multidisciplinary approach of surgery, radiation, and chemotherapy. Several theories have been put forth to explain the mechanism of Stewart-Treves syndrome, but it remains ambiguous. The current literature regarding angiosarcoma developing in the setting of chronic lymphedema in the lower limb is limited to single case reports. Herein, the authors report a series of six cases of biopsy-proven angiosarcoma in the setting of lower extremity lymphedema. Providers should include angiosarcoma in the differential diagnosis of ulcerative or vascular tumors arising in the context of lower extremity lymphedema.
Standardized In-harness Ultrasound Protocol Improves Success Rate of Brace Treatment for Dislocated Hips
Authors: Pargas-Colina Carlos D. , Allred Caleb M. , Gupta Apeksha , Blumberg Todd J. 
Published: April 2024

Objective:
Infant hip dislocations benefit from early detection and treatment for optimal outcomes. Prior studies have identified that there remains wide variability in the success rate of bracing between institutions. Although there are standardized methods to screen infants for hip dysplasia, there are no clear guidelines regarding how to image a child being treated for a hip dislocation with a Pavlik harness. As a result, there is substantial variability in how treatment success or failure is monitored between and within institutions. The goal of our study is to determine whether a standardized in-harness imaging protocol improves outcomes and the likelihood of successful treatment for dislocated hips being treated with the Pavlik harness.

Methods:
All patients with hip dislocations and pretreatment ultrasound (US) were included from July 2018 to July 2022. A new institutional US protocol was implemented in July 2020, during which standardized in-harness imaging was obtained for patients with hip dislocations. Patients treated before the implementation of standardized in-harness imaging were categorized as nonstandardized and after implementation as a standardized group. Outcomes were compared between standardized and nonstandardized groups. P <0.05 determined the statistical significance.

Results:
One hundred twenty-eight hips met the inclusion criteria (n = 97 patients). The mean age at diagnosis was 41.6 ± 23.4 days and was predominantly female (85.6%). There was no significant difference between the patients' demographics and baseline clinical characteristics between the standardized and nonstandardized groups. Pavlik harness success rate was significantly higher in the standardized group (85% vs 60%, P = 0.0024). Twenty-eight hips in the nonstandardized group remained dislocated and were indicated for surgical treatment, whereas only 8 hips remained dislocated in the standardized group and necessitated closed or open reduction.

Conclusions:
Standardization of in-harness imaging for patients undergoing treatment for developmental hip dislocations can significantly improve the Pavlik harness success rate. These findings emphasize the importance of obtaining images with the hip in flexion and abduction to prevent inadvertent stress during US evaluation for hips that have not yet stabilized, which may lead to premature cessation of the Pavlik harness.

Level of Evidence:
Level III.
Science of Learning Strategy Series: Article 5, Incentivizing Sleep in Continuing Professional Development
Authors: Van Hoof Thomas J. , Madan Christopher R. , Sumeracki Megan A. , Meehan Thomas P. 
Published: April 2024

Abstract
The science of learning (learning science) is an interprofessional field that concerns itself with how the brain learns and remembers important information. Learning science has compiled a set of evidence-based strategies, such as distributed practice, retrieval practice, and interleaving, which are quite relevant to continuing professional development (CPD). Spreading out study and practice separated by cognitive breaks (distributed practice), testing oneself to check mastery and memory of previously learned information (retrieval practice), and mixing the learning of distinct but related material (interleaving) represent strategies that are underutilized in CPD. Participants and planners alike can benefit from learning science recommendations to inform their decisions. Sleep, the subject of this article and critical to distributed practice, is the ideal circumstance for the brain to process priority information. The authors make the case for sleep as a legitimate part of a learning activity and worthy of consideration in the award of CPD credits.
Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach
Authors: Chang Anne Lynn S. , Brown Ryanne , Li Shufeng , Betancourt Nicolas , Teng Joyce 
Published: April 2024

Abstract:
Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 (P
adjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: P
adjusted < 0.0001; cytoplasmic: P
adjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.
Clinical analysis of patients with deep sternal wound infection-induced sepsis: a retrospective cohort study
Authors: Song Bin , Cui Zhentian , Ju Hongyan , Sun Yue , Liu Dandan , Li Guanggang 
Published: April 2024

AbstractBackgroundThis study aimed to summarize the clinical characteristics of patients with deep sternal wound infection-induced sepsis after median sternotomy and improve the treatment outcomes of infection-related sepsis.MethodsA retrospective cohort study was conducted on 21 patients with deep sternal wound infection-induced sepsis after median sternotomy who were admitted to the Department of Critical Care. The clinical manifestations, laboratory test results, infection control, and organ and nutritional support of the patients were summarized, and the follow-up data were obtained.ResultsThe primary symptoms of deep sternal wound infection-induced sepsis included dyspnea, high fever, chills, and altered state of consciousness. Laboratory test results revealed increased inflammatory markers and decreased oxygenation index. Renal and liver function injury were observed in 8 and 4 patients, respectively; 18 and 12 patients demonstrated elevated D-dimer and N-terminal Pro B type natriuretic peptide levels, respectively. Of the 8 patients whose wound secretions tested positive for bacteria,Acinetobacter baumanniiandStaphylococcus aureusinfections were present in 6 and 2 patients, respectively. One of the 6 patients whose blood cultures tested positive for bacteria demonstratedCandida albicansinfection. Fifteen patients received ventilator-assisted ventilation and 2 patients received renal replacement therapy. Of all the 21 patients, 17 were cured, 2 died, and 2 were discharged.ConclusionPostmedian sternotomy sepsis attributed to a deep sternal wound infection usually results from a preexisting condition. The most prominent clinical manifestation is dyspnea, which is sometimes accompanied by the impairment of organ function. Infection prevention, proper nutrition support, and maintenance of healthy organ function are the cornerstones for successful treatment outcomes.
Evaluation of the Homogenous Mobility Shift Assay for Infliximab and Adalimumab Anti-drug Antibody Detection in the Clinical Laboratory
Authors: Keating Paula Elizabeth , Hock Barry D. , Chin Paul K. L. , O'Donnell John Liston , Barclay Murray Lindsay 
Published: April 2024

Background:
Detecting antidrug antibodies (ADAs) against infliximab or adalimumab is useful for therapeutic drug monitoring. Various ADA detection methods exist, and antibody titer is an output in some algorithms. Homogenous mobility shift assay (HMSA) measures relative ADA concentration and determines drug-ADA complex size in vitro. However, the relevance of complex size determination in drug monitoring remains unclear. Hence, the association between complex size, ADA concentration, and sample detectable neutralizing activity was evaluated.

Methods:
Sera from infliximab-treated and adalimumab-treated patients who tested positive for ADA in the National Screening Service were analyzed using 3 ADA assays. HMSA determined the relative ADA concentrations and complex sizes, competitive ligand-binding assay evaluated the sample neutralizing capacity, and enzyme-linked immunosorbent assay detected immunoglobulin (Ig)G4 ADA.

Results:
Most ADA-positive samples (>80%) formed drug-ADA dimer complexes, whereas 17% had dimer and multimer complexes, and 3% had multimeric complexes. Multimer presence had 100% positive predictive value for detectable neutralizing activity. ADA concentration and detectable neutralizing activity were moderately correlated (r = 0.65) in adalimumab-treated patients and strongly correlated (r = 0.81) in infliximab-treated patients. In adalimumab-treated patients, multimer presence was a stronger predictor of neutralizing activity than ADA concentration was, but not in infliximab-treated patients. However, in infliximab-treated patient samples, multimer presence revealed a distinct subset with high ADA concentrations, neutralizing activity, and IgG4 ADA.

Conclusions:
Multimers detected using HMSA had a strong positive predictive value for competitive ligand-binding assay detectable neutralizing activity. Multimeric IgG4-containing ADA-drug complexes revealed a distinct subset of infliximab-treated patient samples, whose clinical relevance merits further investigation.
Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method
Authors: Parant François , Delignette Marie-Charlotte , Charpiat Bruno , Lacaille Louis , Lebosse Fanny , Monneret Guillaume , Mohkam Kayvan , Mabrut Jean-Yves , Aubrun Frederic , Heyer Laurent , Antonini Teresa 
Published: April 2024

Background:
Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients.

Methods:
This single-center study included 265 patients who underwent orthotopic liver transplantation. In total, 942 blood samples were collected. TAC trough concentrations were measured using LC-MS/MS and 2 immunoassays in parallel. The plasma concentrations of conjugated bilirubin were measured in all samples. The results were analyzed using Bland–Altman plots and Passing–Bablok regressions.

Results:
The Bland–Altman plot analysis showed that the TAC QMS immunoassay has a significant bias (+37%) compared with LC-MS/MS, and this bias was higher in patients with cholestasis with hyperbilirubinemia (≤+70% in patients with conjugated bilirubin >150 µmol/L). In comparison, the chemiluminescence microparticle immunoassay showed acceptable analytical performance in patients with hyperbilirubinemia (bias <10%).

Conclusions:
In agreement with previous findings, the TAC QMS immunoassay showed a positive bias compared with LC-MS/MS. This bias is remarkably high in patients with cholestasis and hyperbilirubinemia, suggesting the cross-reactivity of TAC metabolites with the monoclonal antibody used in the QMS immunoassay.
Analyzing the trend of mortality due to traffic and nontraffic accidents: a study in the north of Iran
Authors: Nikbakht Hossein-Ali , Farajpour Fatemeh , Farhadi Zeynab , Hashemi Seyedeh N. , Jahani Mohammad-Ali 
Published: April 2024

Background:
Examining the raw and standardized mortality rates is the primary strategy for improving life expectancy and human health in society through identifying risk factors and dealing with the factors that cause them.

Objectives:
This study examined the trend of mortalities due to traffic and nontraffic accidents.

Methods:
This cross-sectional study examines the registered mortalities during the years 2016–2022 in the form of a census in the health department’s death registration and classification system. Mortality was analyzed as raw and standardized mortality in each 100 000 population.

Results:
Out of 18 265 deaths during 2016–2022, 1305 (7.15%) were related to accidents and incidents. The age-standardized total mortality rate in the first year was 32.9, and in the final year of the study, it was 33.3 per 100 000 people; although there are fluctuations, this trend is upward (P.trend=0.021). Also, the age-standardized traffic death rate in the first year is 19, and in the final year is 12 per 100 000 people; this decreasing trend was not statistically significant (P.trend=0.061). The incidence of age-standardized intentional nontraffic deaths was 1.7 in the first year of the study interval and 9.8 in the last year in 100 000 people, which showed an upward trend (P.trend<0.001).

Conclusion:
In light of the generally increasing trend of accidents, especially nontraffic accidents, universal and well-rounded measures are necessary for safety matters and reducing mortality.
Association of detrusor wall thickness (DWT) with lower urinary tract symptom severity in benign prostatic hyperplasia: a cross-sectional study
Authors: Bhattarai Kishor , Khadka Hensan , Thapa Bikash Raj , Katwal Shailendra 
Published: April 2024

Background and objective:
Benign prostatic hyperplasia manifests as lower urinary tract symptoms (LUTS) and prostate gland enlargement, leading to bladder outlet obstruction with consequent structural and functional impacts on the bladder. Urodynamic studies are resource-intensive and invasive. Detrusor wall thickness (DWT) assessment offers a cost-effective, reproducible alternative for evaluating LUTS severity in males with bladder outlet obstruction, utilizing ultrasonographic examination.

Methods:
This prospective cross-sectional study, conducted at a tertiary care center from May 2023 to January 2024, included 171 patients with LUTS who underwent transabdominal ultrasound for DWT measurements. LUTS severity, assessed using International Prostate Symptom Scores (IPSS) classified participants into mild and moderate-to-severe symptom groups. Pearson’s correlation coefficient assessed the association between DWT and IPSS, and an independent sample t-test compared means, using a significance level of 5% (P-value ≤0.05).

Results:
This study involved participants aged 65.01±11.55 years with an IPSS score ranging from 1 to 35, with a mean for mild and moderate-to-severe symptom groups were 4±2.12 and 15.93±6.74, respectively. DWT mean of 1.64±0.38 mm for mild, and 2.4±0.43 mm for moderate to severe symptoms. Pearson’s correlation (r=0.697, n=171, P<0.001) indicated a strong DWT-LUTS correlation and a significant DWT mean difference between mild and moderate-to-severe symptom groups was found via an independent t-test (P<0.001, 95% CI: −0.8970 to −0.6414).

Conclusion:
The study establishes the value of transabdominal ultrasound-detected DWT as a cost-effective, noninvasive, and reproducible tool for assessing LUTS severity in males with benign prostatic hyperplasia.