bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Preoperative Exposure to Benzodiazepines on Opioid Consumption After One and Two-level Anterior Cervical Discectomy and Fusion
Authors: Meade Matthew H. , Schultz Matthew J. , Radack Tyler , Michael Mark , Hilibrand Alan S. , Kurd Mark F. , Hsu Victor , Kaye Ian David , Schroeder Gregory D. , Kepler Christopher , Vaccaro Alexander R. , Woods Barrett I.
Published: June 2023

Study Design:

Retrospective cohort.

Objective:

Investigate the relationship between preoperative benzodiazepine exposure and postoperative opioid use in patients undergoing primary 1 or 2-level anterior cervical discectomy and fusion (ACDF).

Background:

Little is known about the effect of preoperative benzodiazepine exposure on postoperative opioid use in spine surgery.

Patients and Methods:

Patients undergoing primary 1 or 2-level ACDF at a single institution from February 2020 to November 2021 were identified through electronic medical records. The prescription drug monitoring program was utilized to record the name, dosage, and quantity of preoperative benzodiazepines/opioids filled within 60 days before surgery and postoperative opioids 6 months after surgery. Patients were classified as benzodiazepine naïve or exposed according to preoperative usage, and postoperative opioid dose and duration were compared between groups. Regression analysis was performed for outcomes that demonstrated statistical significance, adjusting for preoperative opioid use, age, sex, and body mass index.

Results:

Sixty-seven patients comprised the benzodiazepine-exposed group whereas 90 comprised the benzodiazepine-naïve group. There was no significant difference in average daily morphine milligram equivalents between groups (median: 96.0 vs 65.0, P = 0.11). The benzodiazepine-exposed group received postoperative opioids for a longer duration (median: 32.0 d vs 12.0 d, P = 0.004) with more prescriptions (median: 2.0 vs 1.0, P = 0.004) and a greater number of pills (median: 110.0 vs 59.0, P = 0.007). On regression analysis, preoperative benzodiazepine use was not significantly associated with postoperative opioid duration [incidence rate ratio (IRR): 0.93, P = 0.74], number of prescriptions (IRR: 1.21, P = 0.16), or number of pills (IRR: 0.89, P = 0.58).

Conclusions:

While preoperative benzodiazepine users undergoing primary 1 or 2-level ACDF received postoperative opioids for a longer duration compared with a benzodiazepine naïve cohort, preoperative benzodiazepine use did not independently contribute to this observation. These findings provide insight into the relationship between preoperative benzodiazepine use and postoperative opioid consumption.

Level of Evidence:

Level III.
Cancer treatment-related cardiotoxicity: a focus on sacubitril/valsartan
Authors: Hu Feng , Yu Huajiong , Chen Zhaoyang , Chen Lianglong
Published: June 2023

Cardiotoxicity is the most dramatic complication of cancer therapies, and it results in the cessation of potentially life-saving antitumor treatment regimens and a poor survival prognosis in a nonnegligible proportion of patients. Angiotensin converting enzyme inhibitors (ACEIs) and β-blockers are effective in the treatment of cancer therapy-related cardiac dysfunction (CTRCD), whereas their roles in the prevention of cardiotoxicity are unclear. Sacubitril/valsartan, which is an angiotensin receptor-neprilysin inhibitor, has been shown to be advantageous over ACEIs in heart failure patients with reduced ejection fraction for further the reduction of cardiovascular death or rehospitalization. However, patients with CTRCD were excluded from pivotal trials involving sacubitril/valsartan. Although several small observational studies have observed excellent performance in improving cardiac structure and function in patients with CTRCD, large-scale prospective clinical studies are required to confirm these results. In this review, we described the contemporary literature concerning the potential benefit of sacubitril/valsartan in the cardio-oncology setting.
Can Ursodeoxycholic Acid Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection or Reduce the Coronavirus Disease 2019 Severity? Current Knowledge and Unresolved Issues
Authors: Pan Shida , Zhang Yang , Meng Fanping , Wang Fu-Sheng
Published: June 2023

A recent study revealed that the inhibition of the farnesoid X receptor using ursodeoxycholic acid (UDCA) significantly reduces angiotensin-converting enzyme 2 (ACE2) expression. Therefore, considerable attention has been paid to the use of UDCA to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reduce the severity of the disease. This review comprehensively summarizes the role of ACE2 in SARS-CoV-2 infection and the potential role and mechanisms of UDCA in the prevention of SARS-CoV-2 infection or reinfection. It also discusses unresolved issues and the potential use of UDCA in the treatment of patients with coronavirus disease.
Etiology of Bacterial Sepsis and Isolate Resistance Patterns in Hospitalized Neonates in Zambia
Authors: Egbe Franklyn N. , Cowden Carter , Mwananyanda Lawrence , Pierre Cassandra , Mwansa James , Lukwesa Musyani Chileshe , Lyondo Angela , Kapasa Monica L. , Machona Sylvia , Chilufya Moses M. , Munanjala Gertrude , Coffin Susan E. , Hamer Davidson H. , Bates Matthew A.
Published: June 2023

Background:

The Sepsis Prevention in Neonates in Zambia study is a prospective cohort study that evaluated an infection prevention and control (IPC) bundle in the University Teaching Hospital neonatal intensive care unit (NICU) in Lusaka, Zambia. We present here the etiologies, antimicrobial resistance profiles, and associated mortality of bloodstream infections (BSI) in this cohort.

Methods:

Venous blood was collected from neonates with clinically suspected sepsis and cultured with an automated blood culture system. Organism identification and susceptibility testing were done using the Vitek II system. We used the CDC National Health Safety Network criteria to define pathogens and commensals.

Results:

There were 1120 blood cultures performed for 1060 neonates with suspected sepsis. Overall, 38% (424/1120) of cultures were positive of which 72% (306/424) grew pathogens. Blood cultures obtained after, as compared to before, 2 days of hospitalization were more likely to yield a pathogen (77% vs. 65%; P < 0.001). Klebsiella pneumoniae was the most prevalent organism, accounting for 74% (225/306) of all pathogens. K. pneumoniae isolates were highly resistant: 98% (221/225) were extended-spectrum beta-lactamase (ESBL)-positive, while 81% were resistant to gentamicin (182/225) and fluoroquinolones (177/219). Only one isolate was carbapenem resistant. Observed mortality rate was 32% (122/380); 61% (75/122) of the deaths was related to Klebsiella BSI.

Conclusions:

Multidrug-resistant ESBL-producing Klebsiella species were the main organisms responsible for BSI and were associated with increased mortality. BSI risk increased with prolonged hospitalization, underscoring the importance of IPC measures in the NICU.
Sleep Quality and Related Factors Among Liver Transplant Recipients in Korea: A Cross-Sectional Study
Authors: LIM Serah , CHOI Mona , KIM Heejung , KIM Jong Man
Published: June 2023

Background

Poor sleep quality is common after liver transplantation, which lowers health-related quality of life. However, the detection and management of sleeping difficulties in liver transplant recipients have been limited.

Purpose

This study was designed to assess sleep quality in liver transplant recipients in Korea and associated factors, including symptom experience, depression, and family support, using the theory of unpleasant symptoms as a theoretical framework.

Methods

This cross-sectional study of 149 liver transplant recipients in a Korean tertiary hospital was conducted in 2019. Data were obtained using several structured self-report questionnaires, including the Pittsburgh Sleep Quality Index, Modified Transplant Symptom Occurrence and Symptom Distress Scale, Center for Epidemiologic Studies Depression Scale-Revised, and Family Support Scale. Multiple linear regression was used to determine the factors associated with sleep quality.

Results

The prevalence of sleep disturbance was 55% in the sample. Low sleep quality was associated with being female and with having a higher symptom experience, higher depressive symptoms, and lower family support. In the multiple linear regression analysis, depression and symptom experience was shown to significantly affect sleep quality.

Conclusions/Implications for Practice

The liver transplant recipients in this study reported poor sleep quality. The factors associated with the sleep quality included depression and symptom experience. To enhance sleep quality, interventions designed to reduce depression and symptoms related to liver transplantation should be provided. The results of this study may be used to develop nursing strategies to improve sleep quality in liver transplant recipients.
A National Survey of the Training and Practice Patterns of Practicing Pediatric Advanced Endoscopists in the United States
Authors: Chu Christopher , Tran Paul , Moreau Christopher , Mark Jacob A. , Kramer Robert E. , Piester Travis L.
Published: June 2023

Background and Aims:

Pediatric advanced endoscopy consists primarily of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) and is becoming more common in pediatrics. This study aims to characterize the current landscape of pediatric advanced endoscopy training and practice by directly surveying independently practicing pediatric advanced endoscopists (PAEs). We also aim to ascertain expert opinion on competency in pediatric ERCP and EUS.

Methods:

A 66-question REDCap survey and a 73-question Qualtrics survey were distributed to members of the ERCP Special Interest Group of North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Respondents currently performing ERCP or EUS independently in children were included. Statistical analysis was performed using Mann-Whitney U test.

Results:

Of 41 PAEs surveyed, 38 (92.7%) responded and 27 independent practitioners were included. Thirteen respondents performed EUS. PAEs who completed an advanced endoscopy fellowship (AEF) were more comfortable performing American Society for Gastrointestinal Endoscopy grade 3 or grade 4 ERCPs (P < 0.0008) and felt more prepared to practice EUS independently than other trainees. Expert opinion of PAEs felt a threshold of 200 procedures was needed to attain competency in either ERCP or EUS. Pediatric duodenoscope exposure improved comfort in performing ERCP in children <10 kg (P = 0.009).

Conclusions:

Training of pediatric gastroenterologists in ERCP and EUS are highly variable, though the skills attained are similar. AEF-trained specialists reported greater training volumes and felt more prepared to practice independently than those who did not. Competency thresholds determined by expert PAEs for ERCP and EUS agree with American Society for Gastrointestinal Endoscopy guidelines for adult advanced endoscopy trainees.
Decisional Conflict, Patient Involvement, and the Associated Psychological Factors Relating to Mastectomy Decisions Among Women With Breast Cancer
Authors: Liu Jing , Chan Sally Wai-Chi , Guo Dongmei , Lin Qin , Hunter Sharyn , Zhu Jiemin , Lee Regina Lai Tong
Published: June 2023

Background

Most women with breast cancer in China have received a mastectomy despite emerging breast-conserving alternatives. Their decision-making relating to mastectomy is unclear.

Objective

To investigate decisional conflict, women’s involvement, and psychological factors relating to mastectomy decisions.

Methods

Women with breast cancer 18 years and older who had a mastectomy were recruited from 2 hospitals in China. A conceptual framework adapted from the Ottawa Decisional Support Framework was used to guide this study. Data were collected using the 16-item Decisional Conflict Scale, the 9-item Shared Decision-Making Questionnaire, and a 19-item psychological factor list.

Results

A total of 304 women participated. Overall, they reported a low-level conflict and high-level involvement. “Cancer not return” was rated as the most important psychological factor influencing mastectomy decisions. Lower decisional conflict was predicted by higher involvement. Higher involvement was predicted by younger age and increased family income.

Conclusions

This study is the first to demonstrate decisional conflict, involvement, and the associated factors specifically in Chinese women undergoing mastectomy. Results determined the importance of several psychological factors influencing mastectomy decisions. Future qualitative studies are required to deepen understanding of women’s decision-making experiences regarding this surgery.

Implications for Practice

Nurses need to provide support to Chinese women in making treatment decisions, especially for older women, and those who are economically disadvantaged. Measures are needed to promote their involvement and improve their understanding of breast cancer and its treatments, which may help reduce decisional conflict, and potentially improve their satisfaction with treatment and quality of life.
Humerus fractures: selecting fixation for a successful outcome
Authors: Kandemir Utku , Naclerio Emily H. , McKee Michael D. , Weatherby David J. , Cole Peter A. , Tetsworth Kevin
Published: June 2023

Current evidence suggests at least one-third of humeral shaft fractures initially managed nonoperatively will fail closed treatment, and this review highlights surgical considerations in those circumstances. Although operative indications are well-defined, certain fracture patterns and patient cohorts are at greater risk of failure. When operative intervention is necessary, internal fixation through an anterolateral approach is a safe and sensible alternative. Determining which patients will benefit most involves shared decision-making and careful patient selection. The fracture characteristics, bone quality, and adequacy of the reduction need to be carefully evaluated for the specific operative risks for individuals with certain comorbid conditions, inevitably balancing the patient's expectations and demands against the probability of infection, nerve injury, or nonunion. As our understanding of the etiology and risk of nonunion and symptomatic malunion of the humeral diaphysis matures, adhering to the principles of diagnosis and treatment becomes increasingly important. In the event of nonunion, respect for the various contributing biological and mechanical factors enhances the likelihood that all aspects will be addressed successfully through a comprehensive solution. This review further explores specific strategies to definitively restore function of the upper extremity with the ultimate objective of an uninfected, stable union.
Comparison of PD-L1 IHC 22C3 PharmDx Combined Positive Score (CPS) in Primary Versus Metastatic Nodal Squamous Cell Carcinomas of the Head and Neck: Is There a Significant Difference?
Authors: Surucu Ahmet , Hou Tieying , Kuhar Matthew , Durm Greg , Mesa Hector
Published: June 2023

PD-L1 IHC 22C3 pharmDx is an FDA-approved companion test to select patients for anti-PD-L1 immunotherapy. In head and neck squamous cell carcinoma PD-L1 expression is determined using a Combined Positive Score (CPS), which evaluates expression in tumor cells and tumor-associated leukocytes. We hypothesized that in nodal metastasis, the CPS should be higher given their inherent higher proportion of leukocytes. A significant difference in CPS between sites would mean that the tissue chosen for PD-L1 testing would impact patient eligibility for therapy. Currently, guidelines about which tissue should be tested do not exist. PD-L1 22C3 IHC was performed in the primary and nodal metastases of 35 head and neck squamous cell carcinoma, and a CPS was generated by 3 pathologists. Mean CPS was higher at the primary than the nodal metastasis: 47.2 versus 42.2; however, the difference was not statistically significant: P=0.259. By therapeutic groups: negative (CPS <1), low (CPS 1–19) and high (CPS≥20), low-expression was more common in the primary: 40 vs. 26%, and high-expression in the nodal metastasis: 74 vs. 60% but this difference was not statistically significant: P=0.180. Stratified by positive versus negative (CPS <1 vs. ≥1), there were no differences between sites. Interobserver agreement for CPS among the 3 raters was slight for both sites: ƙ=0.117 and 0.025, fair if stratified by therapeutic group: ƙ=0.371 and 0.318, and near perfect if stratified as negative versus positive: ƙ=0.652 and 1. There were no statistically significant differences in CPS between primary and nodal metastases independent of how the CPS was stratified.
Acute and chronic stress associations with blood pressure: An ecological momentary assessment study on an app-based platform
Authors: Mak Hio Wa , Gordon Amie M. , Prather Aric A. , Epel Elissa S. , Mendes Wendy Berry
Published: June 2023

Objective

This study examines the within- and between-person associations of acute and chronic stress with blood pressure (BP) and heart rate (HR) using an app-based research platform.

Methods

We examined data from 31,964 adults (aged 18–90) in an app-based ecological momentary assessment study that used a research-validated optic sensor to measure BP.

Results

Within-person associations revealed that moments with (vs. without) acute stress exposure were associated with higher systolic (SBP: b = 1.54) and diastolic BP (DBP: b = 0.79) and HR (b = 1.53; ps < .001). During moments with acute stress exposure, higher acute stress severity than usual was associated with higher SBP (b = 0.26), DBP (b = 0.09), and HR (b = 0.40; ps < .05). During moments without acute stress, higher background stress severity than usual was associated with higher BP and HR (SBP: b = 0.87; DBP: b = 0.51; HR: b = 0.69; ps < .001). Between-person associations showed that individuals with more frequent reports of acute stress exposure or higher chronic stress severity had higher SBP, DBP, and HR (ps < .05). Between-person chronic stress severity moderated within-person physiological responses to stress such that individuals with higher chronic stress severity had higher average BP and HR levels but showed smaller responses to momentary stress.

Conclusion

Technological advancements with optic sensors allow for large-scale physiological data collection, which provides a better understanding of how stressors of different timescales and severity contribute to momentary BP and HR in daily life.
Improving Reporting Culture Through Daily Safety Huddles
Authors: MacKay Margaret Malague , Jordan Kathleen S. , Powers Kelly , Munn Lindsay Thompson
Published: June 2023

Background and Objectives:

A major obstacle to safer care is lack of error reporting, preventing the opportunity to learn from those events. On an acute care unit in a children's hospital in southeastern United States, error reporting and Survey for Patient Safety Culture (SOPS 1.0) scores fell short of agency benchmarks. The purpose of this quality improvement project was to implement a Safety Huddle Intervention to improve error reporting and SOPS 1.0 scores related to reporting.

Methods:

Marshall Ganz's Change through Public Narrative Framework guided creation of the project's intervention: A story of self, a story of us, a story of now. A scripted Safety Huddle was conducted on the project unit daily for 6 weeks, and nurses on the project unit and a comparison unit completed the SOPS 1.0 before and after the intervention. Monthly error reporting was tracked on those same units.

Results:

Error reporting by nurses significantly increased during and after the intervention on the project unit (P = .012) but not on the comparison unit. SOPS 1.0 items purported to measure reporting culture showed no significant differences after the intervention or between project and comparison units. Only 1 composite score increased after the intervention: communication openness improved on the project unit but not on the comparison unit.

Conclusion:

Using a Safety Huddle Intervention to promote conversation about error events has potential to increase reporting of errors and foster a sense of communication openness. Both achievements have the capacity to improve patient safety.
Photon-Counting Detector CT Angiography for Endoleak Detection After Endovascular Aortic Repair
Authors: Turrion Gomollon Ana Maria , Mergen Victor , Sartoretti Thomas , Polacin Malgorzata , Nakhostin Dominik , Puippe Gilbert , Alkadhi Hatem , Euler André
Published: June 2023

Objectives

The aim of this study was to compare image quality and endoleak detection after endovascular abdominal aortic aneurysm repair between a triphasic computed tomography (CT) with true noncontrast (TNC) and a biphasic CT with virtual noniodine (VNI) images on photon-counting detector CT (PCD-CT).

Materials and Methods

Adult patients after endovascular abdominal aortic aneurysm repair who received a triphasic examination (TNC, arterial, venous phase) on a PCD-CT between August 2021 and July 2022 were retrospectively included. Endoleak detection was evaluated by 2 blinded radiologists on 2 different readout sets (triphasic CT with TNC-arterial-venous vs biphasic CT with VNI-arterial-venous). Virtual noniodine images were reconstructed from the venous phase. The radiologic report with additional confirmation by an expert reader served as reference standard for endoleak presence. Sensitivity, specificity, and interreader agreement (Krippendorf α) were calculated. Image noise was assessed subjectively in patients using a 5-point scale and objectively calculating the noise power spectrum in a phantom.

Results

One hundred ten patients (7 women; age, 76 ± 8 years) with 41 endoleaks were included. Endoleak detection was comparable between both readout sets with a sensitivity and specificity of 0.95/0.84 (TNC) versus 0.95/0.86 (VNI) for reader 1 and 0.88/0.98 (TNC) versus 0.88/0.94 (VNI) for reader 2. Interreader agreement for endoleak detection was substantial (TNC: 0.716, VNI: 0.756). Subjective image noise was comparable between TNC and VNI (4; IQR [4, 5] vs 4; IQR [4, 5], P = 0.44). In the phantom, noise power spectrum peak spatial frequency was similar between TNC and VNI (both fpeak = 0.16 mm−1). Objective image noise was higher in TNC (12.7 HU) as compared with VNI (11.5 HU).

Conclusions

Endoleak detection and image quality were comparable using VNI images in biphasic CT as compared with TNC images in triphasic CT offering the possibility to reduce scan phases and radiation exposure.
Contrast-Enhanced Ultrasonography as a Diagnostic Strategy for Severe Endometrial Injury
Authors: Liu Tao , Zhou Miao , Yang Huihui , Liang Weixiang , Cai Ruiming , Cai Mingjin
Published: June 2023

Endometrial injury is associated with poorer pregnancy outcomes. The purpose of this study was to evaluate the diagnostic efficacy of contrast-enhanced ultrasonography (CEUS) in the detection of endometrial injury. This study included women who underwent CEUS of the uterus at the author's hospital between April 2020 and January 2021. The diagnostic performances of the CEUS-derived parameters in the detection of severe endometrial injury were evaluated by receiver operating characteristic curve analyses. The study included 67 participants (healthy control, n = 14; mild endometrial injury, n = 24; severe endometrial injury, n = 29). Enhancement intensity (EI) and area under the time-intensity curve (AUCTIC) were significantly lower in the severe endometrial injury patients than healthy and mild endometrial injury subjects for both endometrial and subendometrial regions (P < 0.05). Correlations analysis showed that EI and AUCTIC were positively correlated with endometrial thickness (r = 0.460, P = 0.01, and r = 0.555, P < 0.01, respectively) and subendometrial thickness (r = 0.501, P < 0.01, and r = 0.438, P = 0.01, respectively). The area under the receiver operating characteristic curve, sensitivity, and specificity were 0.720 (P = 0.002), 79.31%, and 66.67% for endometrial EI; 0.818 (P < 0.001), 75.86%, and 79.17% for subendometrial EI; 0.917 (P < 0.001), 72.41%, and 95.83% for endometrial AUCTIC; and 0.810 (P < 0.001), 89.66%, and 70.83% for subendometrial AUCTIC, respectively. Contrast-enhanced ultrasonography may have clinical utility in the prediction of endometrial injury in women of childbearing age.
Concurrent Killian-Jamieson and Zenker’s Diverticula
Authors: Alotaibi Fahad Zarraq , Lee Geun-Dong , Lee Yoon Se
Published: June 2023

Pharyngoesophageal diverticula are rare causes of dysphagia. Zenker’s diverticulum is the most common type, followed by Killian–Jamieson diverticulum. A 44-year-old male presented to our clinic with a longstanding history of dysphagia and globus sensation. Bilateral pharyngoesophageal diverticula were confirmed by imaging CT and esophagogastroscopy. He underwent transcervical resection, and a right Killian–Jamieson diverticulum was observed during surgery. The left diverticulum was found to originate above the cricopharyngeus muscle and was labeled as Zenker’s diverticulum. Bilateral pharyngoesophageal diverticula are rare, and physicians should be aware of the variable clinical presentations and management options for pharyngoesophageal diverticula.
Functional trait trade-offs define plant population stability across different biomes
Authors: Conti Luisa , Valencia Enrique , Galland Thomas , Götzenberger Lars , Lepš Jan , E-Vojtkó Anna , Carmona Carlos P. , Májeková Maria , Danihelka Jiří , Dengler Jürgen , Eldridge David J. , Estiarte Marc , García-González Ricardo , Garnier Eric , Gómez Daniel , Hadincová Věra , Harrison Susan P. , Herben Tomáš , Ibáñez Ricardo , Jentsch Anke , Juergens Norbert , Kertész Miklós , Klumpp Katja , Krahulec František , Louault Frédérique , Marrs Rob H. , Ónodi Gábor , Pakeman Robin J. , Pärtel Meelis , Peco Begoña , Peñuelas Josep , Rueda Marta , Schmidt Wolfgang , Schmiedel Ute , Schuetz Martin , Skalova Hana , Šmilauer Petr , Šmilauerová Marie , Smit Christian , Song MingHua , Stock Martin , Val James , Vandvik Vigdis , Ward David , Wesche Karsten , Wiser Susan K. , Woodcock Ben A. , Young Truman P. , Yu Fei-Hai , Zobel Martin , de Bello Francesco
Published: June 2023

Ecological theory posits that temporal stability patterns in plant populations are associated with differences in species' ecological strategies. However, empirical evidence is lacking about which traits, or trade-offs, underlie species stability, especially across different biomes. We compiled a worldwide collection of long-term permanent vegetation records (greater than 7000 plots from 78 datasets) from a large range of habitats which we combined with existing trait databases. We tested whether the observed inter-annual variability in species abundance (coefficient of variation) was related to multiple individual traits. We found that populations with greater leaf dry matter content and seed mass were more stable over time. Despite the variability explained by these traits being low, their effect was consistent across different datasets. Other traits played a significant, albeit weaker, role in species stability, and the inclusion of multi-variate axes or phylogeny did not substantially modify nor improve predictions. These results provide empirical evidence and highlight the relevance of specific ecological trade-offs, i.e. in different resource-use and dispersal strategies, for plant populations stability across multiple biomes. Further research is, however, necessary to integrate and evaluate the role of other specific traits, often not available in databases, and intraspecific trait variability in modulating species stability.
The novel expression of clonality following whole-genome multiplication compensates for reduced fertility in natural autopolyploids
Authors: Šingliarová Barbora , Hojsgaard Diego , Müller-Schärer Heinz , Mráz Patrik
Published: June 2023

Exploring the fitness consequences of whole-genome multiplication (WGM) is essential for understanding the establishment of autopolyploids in diploid parental populations, but suitable model systems are rare. We examined the impact of WGM on reproductive traits in three major cytotypes (2x, 3x, 4x) ofPilosella rhodopea, a species with recurrent formation of neo-autopolyploids in mixed-ploidy populations. We found that diploids had normal female sporogenesis and gametogenesis, high fertility, and produced predominantly euploid seed progeny. By contrast, autopolyploids had highly disturbed developmental programs that resulted in significantly lower seed set and a high frequency of aneuploid progeny. All cytotypes, but particularly triploids, produced gametes of varying ploidy, including unreduced ones, that participated in frequent intercytotype mating. Noteworthy, the reduced investment in sexual reproduction in autopolyploids was compensated by increased production of axillary rosettes and the novel expression of two clonal traits: adventitious rosettes on roots (root-sprouting), and aposporous initial cells in ovules which, however, do not result in functional apomixis. The combination of increased vegetative clonal growth in autopolyploids and frequent intercytotype mating are key mechanisms involved in the formation and maintenance of the largest diploid-autopolyploid primary contact zone ever recorded in angiosperms.
Ecological interactions driving population dynamics of two tick-borne pathogens,Borrelia burgdorferiandBabesia microti
Authors: Tufts Danielle M. , Adams Ben , Diuk-Wasser Maria A.
Published: June 2023

Borrelia burgdorferi(Bb) andBabesia microti(Bm) are vector-borne zoonotic pathogens commonly found co-circulating inIxodes scapularisandPeromyscus leucopuspopulations. The restricted distribution and lower prevalence ofBmhas been historically attributed to lower host-to-tick transmission efficiency and limited host ranges. We hypothesized that prevalence patterns are driven by coinfection dynamics and vertical transmission. We use a multi-year, multiple location, longitudinal dataset with mathematical modelling to elucidate coinfection dynamics betweenBbandBmin natural populations ofP. leucopus, the most competent reservoir host for both pathogens in the eastern USA. Our analyses indicate that, in the absence of vertical transmission,Bbis viable at lower tick numbers thanBm.However, with vertical transmission,Bmis viable at lower tick numbers thanBb. Vertical transmission has a particularly strong effect onBmprevalence early in the active season while coinfection has an increasing role during the nymphal peak. Our analyses indicate that coinfection processes, such as facilitation ofBminfection byBb, have relatively little influence on the persistence of either parasite. We suggest future work examines the sensitivity ofBmvertical transmission and other key processes to local environmental conditions to inform surveillance and control of tick-borne pathogens.
A model of cue integration as vector summation in the insect brain
Authors: Mitchell Robert , Shaverdian Shahrzad , Dacke Marie , Webb Barbara
Published: June 2023

Ball-rolling dung beetles are known to integrate multiple cues in order to facilitate their straight-line orientation behaviour. Recent work has suggested that orientation cues are integrated according to a vector sum, that is, compass cues are represented by vectors and summed to give a combined orientation estimate. Further, cue weight (vector magnitude) appears to be set according to cue reliability. This is consistent with the popular Bayesian view of cue integration: cues are integrated to reduce or minimize an agent's uncertainty about the external world. Integration of orientation cues is believed to occur at the input to the insect central complex. Here, we demonstrate that a model of the head direction circuit of the central complex, including plasticity in input synapses, can act as a substrate for cue integration as vector summation. Further, we show that cue influence is not necessarily driven by cue reliability. Finally, we present a dung beetle behavioural experiment which, in combination with simulation, strongly suggests that these beetles do not weight cues according to reliability. We suggest an alternative strategy whereby cues are weighted according to relative contrast, which can also explain previous results.
Ranging behaviours across ecological and anthropogenic disturbance gradients: a pan-African perspective of giraffe (
Giraffa
spp
.
) space use
Authors: Brown Michael Butler , Fennessy Julian T. , Crego Ramiro D. , Fleming Christen H. , Alves Joel , Brandlová Karolina , Fennessy Stephanie , Ferguson Sara , Hauptfleisch Morgan , Hejcmanova Pavla , Hoffman Rigardt , Leimgruber Peter , Masiaine Symon , McQualter Kylie , Mueller Thomas , Muller Ben , Muneza Arthur , O'Connor David , Olivier Adriaan Jacobus , Rabeil Thomas , Seager Steven , Stacy-Dawes Jenna , van Schalkwyk Louis , Stabach Jared
Published: June 2023

Animal movement behaviours are shaped by diverse factors, including resource availability and human impacts on the landscape. We generated home range estimates and daily movement rate estimates for 148 giraffe (
Giraffa
spp
.
) from all four species across Africa to evaluate the effects of environmental productivity and anthropogenic disturbance on space use. Using the continuous time movement modelling framework and a novel application of mixed effects meta-regression, we summarized overall giraffe space use and tested for the effects of resource availability and human impact on 95% autocorrelated kernel density estimate (AKDE) size and daily movement. The mean 95% AKDE was 356.4 km
2
and the mean daily movement was 14.1 km, both with marginally significant differences across species. We found significant negative effects of resource availability, and significant positive effects of resource heterogeneity and protected area overlap on 95% AKDE size. There were significant negative effects of overall anthropogenic disturbance and positive effects of the heterogeneity of anthropogenic disturbance on daily movements and 95% AKDE size. Our results provide unique insights into the interactive effects of resource availability and anthropogenic development on the movements of a large-bodied browser and highlight the potential impacts of rapidly changing landscapes on animal space-use patterns.
Honeybees (Apis mellifera) decrease the fitness of plants they pollinate
Authors: Travis Dillon J. , Kohn Joshua R.
Published: June 2023

Most flowering plants require animal pollination and are visited by multiple pollinator species. Historically, the effects of pollinators on plant fitness have been compared using the number of pollen grains they deposit, and the number of seeds or fruits produced following a visit to a virgin flower. While useful, these methods fail to consider differences in pollen quality and the fitness of zygotes resulting from pollination by different floral visitors. Here we show that, for three common native self-compatible plants in Southern California, super-abundant, non-native honeybees (Apis melliferaL.) visit more flowers on an individual before moving to the next plant compared with the suite of native insect visitors. This probably increases the transfer of self-pollen. Offspring produced after honeybee pollination have similar fitness to those resulting from hand self-pollination and both are far less fit than those produced after pollination by native insects or by cross-pollination. Because honeybees often forage methodically, visiting many flowers on each plant, low offspring fitness may commonly result from honeybee pollination of self-compatible plants. To our knowledge, this is the first study to directly compare the fitness of offspring resulting from honeybee pollination to that of other floral visitors.
Actinomyces israelii and Fusobacterium nucleatum brain abscess in an immunocompetent patient: case report
Authors: Lamtri Laarif Mouhsine , Schils Raphael , Lifrange Fréderic , Valkenborgh Christophe , Pitti Pauline , Brouwers Pauline , Bianchi Elettra , Meex Cécile , Hayette Marie-Pierre
Published: June 2023

Introduction. Brain abscess is the most common focal infectious neurological injury. Until the nineteenth century this condition was fatal, however the development of neuroimaging for early diagnosis, neurosurgery and antibiotic therapy in the twentieth century has led to new therapeutic strategies decreasing mortality from 50 % in the 1970s to less than 10 % nowadays. In this context we report a case of brain abscess with a dental origin.

Case report. A immunocompetent man without any addiction presented to the emergency department with dysarthria and frontal headache at home. The clinical examination was normal. Further investigations revealed a polymicrobial brain abscess as a consequence of an ear, nose or throat (ENT) infection with locoregional extension with a dental starting point involving

Actinomyces israelii

and

Fusobacterium nucleatum

. In spite of a rapid diagnosis and a neurosurgical management associated with an optimal treatment by a dual therapy made of ceftriaxone and metronidazole the patient unfortunately died.

Conclusion. This case report shows that despite a low incidence and a good prognosis following the diagnosis, brain abscesses can lead to patient’s death. Thereby, when the patient’s condition and urgency allow, a thorough dental examination of patients with neurological signs following the recommendations would improve the diagnosis made by the clinician. The use of microbiological documentation, the respect of pre-analytical conditions, the interaction between the laboratory and the clinicians are indispensable for an optimal management of these pathologies.
An initial genomic blueprint of the healthy human oesophageal microbiome
Authors: Gilroy Rachel , Adam Mina E. , Kumar Bhaskar , Pallen Mark J.
Published: June 2023

Background. The oesophageal microbiome is thought to contribute to the pathogenesis of oesophageal cancer. However, investigations using culture and molecular barcodes have provided only a low-resolution view of this important microbial community. We therefore explored the potential of culturomics and metagenomic binning to generate a catalogue of reference genomes from the healthy human oesophageal microbiome, alongside a comparison set from saliva.

Results. Twenty-two distinct colonial morphotypes from healthy oesophageal samples were genome-sequenced. These fell into twelve species clusters, eleven of which represented previously defined species. Two isolates belonged to a novel species, which we have named Rothia gullae. We performed metagenomic binning of reads generated from UK samples from this study alongside reads generated from Australian samples in a recent study. Metagenomic binning generated 136 medium or high-quality metagenome-assembled genomes (MAGs). MAGs were assigned to 56 species clusters, eight representing novel Candidatus species, which we have named Ca. Granulicatella gullae, Ca. Streptococcus gullae, Ca. Nanosynbacter quadramensis, Ca. Nanosynbacter gullae, Ca. Nanosynbacter colneyensis, Ca. Nanosynbacter norwichensis, Ca. Nanosynococcus oralis and Ca. Haemophilus gullae. Five of these novel species belong to the recently described phylum

Patescibacteria

. Although members of the

Patescibacteria

are known to inhabit the oral cavity, this is the first report of their presence in the oesophagus. Eighteen of the metagenomic species were, until recently, identified only by hard-to-remember alphanumeric placeholder designations. Here we illustrate the utility of a set of recently published arbitrary Latinate species names in providing user-friendly taxonomic labels for microbiome analyses.

Our non-redundant species catalogue contained 63 species derived from cultured isolates or MAGs. Mapping revealed that these species account for around half of the sequences in the oesophageal and saliva metagenomes. Although no species was present in all oesophageal samples, 60 species occurred in at least one oesophageal metagenome from either study, with 50 identified in both cohorts.

Conclusions. Recovery of genomes and discovery of new species represents an important step forward in our understanding of the oesophageal microbiome. The genes and genomes that we have released into the public domain will provide a base line for future comparative, mechanistic and intervention studies.
Epidemiology and characterization of KPC-2-producing Providencia stuartii isolated from hospitalized patients in southern Brazil: A possible emerging pathogen
Authors: Guidone Gustavo Henrique Migliorini , Cardozo Jennifer Germiniani , Silva Luana Carvalho , Sanches Matheus Silva , Galhardi Ligia Carla Faccin , Kobayashi Renata Katsuko Takayama , Vespero Eliana Carolina , Rocha Sergio Paulo Dejato
Published: June 2023

The study aimed to characterize the virulence factors and antimicrobial resistance of Providencia stuartii, an opportunistic pathogen that causes infections in humans. Were examined the 45 isolates of P. stuartii genotypically and phenotypically by studying their adherence to HeLa cells, biofilm formation, cytotoxicity, and antimicrobial resistance, and analyzing their genomes for putative virulence and resistance genes. The study found that most isolates possessed multiple virulence genes, including fimA, mrkA, fptA, iutA, ireA and hlyA and were cytotoxic to Vero cells. All isolates were resistant to amoxicillin/clavulanic acid, levofloxacin, and sulfamethoxazole/trimethoprim, and most were resistant to ceftriaxone and cefepime. All isolates harbored CTM-M-2 genes and 51.11% also had CTM-M-9 genes. The gene KPC-2 were found in 17.77% of isolates. The study also found clonality among the isolates, indicating the possible spread of the pathogen among patients at the hospital. The results have significant clinical and epidemiological implications and emphasize the importance of continued understanding of the virulence and antimicrobial resistance of this pathogen for the prevention and treatment of future infections.
Grimontia kaedaensis sp. nov., isolated from the estuary of Kaeda river in Miyazaki, Japan
Authors: Sakaguchi Masahiro , Urbanczyk Yoshiko , Kikuchi Taisei , Urbanczyk Henryk
Published: June 2023

Strain 020920NTwas isolated from the estuary of the Kaeda river in the Miyazaki prefecture in Japan. Phylogenetic analysis based on the 16S rRNA gene showed the strain’s close evolutionary relationship with bacteria from the genusGrimontia, in the familyVibrionaceae. Phenotypic and chemotaxonomic features of the strain were investigated. Whole genome sequencing revealed that the strain 020920NTgenome consists of two chromosomes and a plasmid, for a total of 5.52 Mbp. Calculations of whole genome average nucleotide identity and phylogenetic analysis based on the whole genome sequence showed that the strain represents a new species in the genusGrimontia, for which we propose the nameGrimontia kaedaensissp. nov. with the type strain 020920NT(=LMG 32507T=JCM 34978T).
Circulating tumor DNA analysis in advanced urothelial carcinoma: insights from biological analysis and extended clinical follow-up
Authors: Lindskrog Sia Viborg , Birkenkamp-Demtröder Karin , Nordentoft Iver , Laliotis George , Lamy Philippe , Christensen Emil , Renner Derrick , Andreasen Tine Ginnerup , Lange Naja , Sharma Shruti , ElNaggar Adam , Liu Minetta C. , Sethi Himanshi , Aleshin Alexey , Agerbæk Mads , Jensen Jørgen Bjerggaard , Dyrskjøt Lars
Published: June 2023

Purpose

To investigate whether circulating-tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease.

Experimental Design

We present full follow-up results (median follow-up: 68 months) from a previously described cohort of 68 neoadjuvant chemotherapy (NAC)-treated patients who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed ctDNA evaluation of 153 plasma samples collected before and after radical cystectomy (RC) in a separate cohort of 102 NAC-naïve patients (median follow-up: 72 months). Total RNA-sequencing of tumors was performed to investigate biological characteristics of ctDNA shedding tumors.

Results

Assessment of ctDNA after RC identified metastatic relapse with a sensitivity of 94% and specificity of 98% using the expanded follow-up data for the NAC-treated patients. ctDNA dynamics during NAC was independently associated with patient outcomes when adjusted for pathological downstaging (HR=4.7,p=0.029). For the NAC-naïve patients, ctDNA was a prognostic predictor before (HR=3.4,p=0.0005) and after RC (HR=17.8,p=0.0002). No statistically significant difference in recurrence-free survival for patients without detectable ctDNA at diagnosis was observed between the cohorts. Baseline ctDNA positivity was associated with the Ba/Sq subtype and enrichment of epithelial-to-mesenchymal transition and cell-cycle associated gene sets.

Conclusions

ctDNA is prognostic in NAC-treated and NAC-naïve patients with more than five years follow-up and outperforms pathological downstaging in predicting treatment efficacy. Patients without detectable ctDNA at diagnosis may benefit significantly less from NAC, but additional studies are needed.
Serum amyloid A-dependent inflammasome activation and acute injury in a mouse model of experimental stroke
Authors: Yu Jin , Zhu Hong , Taheri Saeid , Lee June-Yong , Diamond David M. , Kirstein Cheryl , Kindy Mark S.
Published: June 2023

BACKGROUND

Serum amyloid A (SAA) proteins increase dramatically in the blood following inflammation. Recently, SAAs are increased in humans following stroke and in ischemic animal models. However, the impact of SAAs on whether this signal is critical in the ischemic brain remains unknown. Therefore, we investigated the role of SAA and SAA signaling in the ischemic brain.

METHODS

Wildtype and SAA deficient mice were exposed to middle cerebral artery occlusion and reperfusion, examined for the impact of infarct volumes, behavioral changes, inflammatory markers, TUNEL staining, and BBB changes. The underlying mechanisms were investigated using SAA deficient mice, transgenic mice and viral vectors.

RESULTS

SAA levels were significantly increase following MCAo and mice deficient in SAAs showed reduced infarct volumes and improved behavioral outcomes. SAA deficient mice showed a reduction in TUNEL staining, inflammation and decreased glial activation. Mice lacking acute phase SAAs demonstrated a reduction in expression of the NLRP3 inflammasome and SAA/NLRP3 KO mice showed improvement. Restoration of SAA expression via SAA tg mice or adenoviral expression reestablished the detrimental effects of SAA. A reduction in BBB permeability was seen in the SAA KO mice and anti-SAA antibody treatment reduced the effects on ischemic injury.

CONCLUSIONS

SAA signaling plays a critical role in regulating NLRP3-induced inflammation and glial activation in the ischemic brain. Blocking this signal will be a promising approach for treating ischemic stroke.

GRAPHIC ABSTRACT

A graphic abstract is available for this article.