bluuebunny/crossref_metadata_2025 huggingface dataset:
Core circadian clock and light signaling genes brought into genetic linkage across the green lineage
Authors: Michael Todd P
Published: June 2022

The circadian clock is conserved at both the level of transcriptional networks as well as core genes in plants, ensuring that biological processes are phased to the correct time of day. In the model plant Arabidopsis (Arabidopsis thaliana), the core circadian SHAQKYF-type-MYB (sMYB) genes CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and REVEILLE (RVE4) show genetic linkage with PSEUDO-RESPONSE REGULATOR 9 (PRR9) and PRR7, respectively. Leveraging chromosome-resolved plant genomes and syntenic ortholog analysis enabled tracing this genetic linkage back to Amborella trichopoda, a sister lineage to the angiosperm, and identifying an additional evolutionarily conserved genetic linkage in light signaling genes. The LHY/CCA1–PRR5/9, RVE4/8–PRR3/7, and PIF3–PHYA genetic linkages emerged in the bryophyte lineage and progressively moved within several genes of each other across an array of angiosperm families representing distinct whole-genome duplication and fractionation events. Soybean (Glycine max) maintained all but two genetic linkages, and expression analysis revealed the PIF3–PHYA linkage overlapping with the E4 maturity group locus was the only pair to robustly cycle with an evening phase, in contrast to the sMYB–PRR morning and midday phase. While most monocots maintain the genetic linkages, they have been lost in the economically important grasses (Poaceae), such as maize (Zea mays), where the genes have been fractionated to separate chromosomes and presence/absence variation results in the segregation of PRR7 paralogs across heterotic groups. The environmental robustness model is put forward, suggesting that evolutionarily conserved genetic linkages ensure superior microhabitat pollinator synchrony, while wide-hybrids or unlinking the genes, as seen in the grasses, result in heterosis, adaptation, and colonization of new ecological niches.
CYSTEINE-RICH RECEPTOR-LIKE KINASE5 (CRK5) and CRK22 regulate the response to Verticillium dahliae toxins
Authors: Zhao Jun , Sun Yuhui , Li Xinyue , Li Yingzhang
Published: June 2022

Cysteine-rich receptor-like kinases (CRKs) play critical roles in responses to biotic and abiotic stresses. However, the molecular mechanisms of CRKs in plant defense responses remain unknown. Here, we demonstrated that two CRKs, CRK5 and CRK22, are involved in regulating defense responses to Verticillium dahliae toxins (Vd-toxins) in Arabidopsis (Arabidopsis thaliana). Biochemical and genetic analyses showed that CRK5 and CRK22 may act upstream of MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6 to regulate the salicylic acid (SA)-signaling pathway in response to Vd-toxins. In addition, MPK3 and MPK6 interact with the transcription factor WRKY70 to modulate defense responses to Vd-toxins. WRKY70 directly binds the promoter domains of the SA-signaling-related transcription factor genes TGACG SEQUENCE-SPECIFIC BINDING PROTEIN (TGA2) and TGA6 to regulate their expression in response to Vd-toxins. Thus, our study reveals a mechanism by which CRK5 and CRK22 regulate SA signaling through the MPK3/6–WRKY70–TGA2/6 pathway in response to Vd-toxins.
Certainty about uncertainty in sleep staging: a theoretical framework
Authors: van Gorp Hans , Huijben Iris A M , Fonseca Pedro , van Sloun Ruud J G , Overeem Sebastiaan , van Gilst Merel M
Published: June 2022

Sleep stage classification is an important tool for the diagnosis of sleep disorders. Because sleep staging has such a high impact on clinical outcome, it is important that it is done reliably. However, it is known that uncertainty exists in both expert scorers and automated models. On average, the agreement between human scorers is only 82.6%. In this study, we provide a theoretical framework to facilitate discussion and further analyses of uncertainty in sleep staging. To this end, we introduce two variants of uncertainty, known from statistics and the machine learning community: aleatoric and epistemic uncertainty. We discuss what these types of uncertainties are, why the distinction is useful, where they arise from in sleep staging, and provide recommendations on how this framework can improve sleep staging in the future.
PAs and NPs improve patient care and productivity in a radiology consult practice
Authors: Virarkar Mayur , Coleman Joseph A. , Siddiqui Zeeshan A. , Leal Viola B. , McClinton Angel E. , Steele Joseph R. , Yang Wei , Bhosale Priya , Klekers Albert R.
Published: June 2022

Objective:

To evaluate the effects on efficiency and patient care of the addition of physician assistants (PAs) and NPs to the abdominal radiology consult service.

Methods:

We obtained radiologist productivity and patient care metrics for 3 months before and 3 months after the integration of PAs and NPs into our consult service.

Results:

Integrating PAs and NPs into the workflow led to a significant increase in mean RVUs/shift (15.2 ± 0.9 versus 6.2 ± 1.8; P = .02), number of studies read per shift (10.1 ± 0.5 versus 4.4 ± 1.5; P = .003), revenue per shift hour ($756.20 ± $55.40 versus $335.40 ± $132.60; P = .007), protocol prescription to patient appointment lead time (39.3 ± 6.7 versus 16.3 ± 2.9 days; P = .005), and significant decreases in mean CT (19.3% ± 0.6 versus 3.3% ± 0.6; P = .001) and MRI (11.7% ± 0.6 versus 8.3% ± 0.12; P = .011) same-day protocol changes as patient appointments.

Conclusions:

PAs and NPs can be effectively integrated into abdominal radiology consult service, increasing the productivity of radiologists, and enhancing clinical care.
Managing a patient with acute colonic diverticulitis
Authors: Donovan Elizabeth , Rizzolo Denise
Published: June 2022

Acute diverticulitis is a common condition in Western society with the potential for substantial patient morbidity. Depending on the severity, the patient's clinical presentation and treatment options vary considerably, leaving uncertainty about optimal management. Traditionally, surgery was recommended to prevent complications, persistent symptoms, and recurrent episodes. Improvements in the understanding of the disease's natural history, diagnostic imaging, and long-term outcomes have prompted changes to diagnosis and treatment guidelines.
Advancing Salary Equity in Schools of Medicine in the United States
Authors: Travis Elizabeth L. , Ellinas Elizabeth H. , Maurana Cheryl A. , Kerschner Joseph E.
Published: June 2022

Equity, in broad terms, is a critical issue and has been identified as an area that needs particular attention in academic medicine. Gender equity, as a subset of overall equity, has equally been shown to be lacking in academic medicine, and most medical schools and academic health systems are involved in substantive journeys to improve all dimensions of equity, diversity, and inclusion. This Invited Commentary calls for including gender-based salary equity as a foundational accomplishment for institutions seeking to achieve overall equity. In addition, the authors provide evidence and recommendations to guide institutions toward best practices in achieving salary equity. They propose 4 areas of consideration: (1) prioritization by leadership; (2) prioritization of resources to ensure success; (3) development of corrective action plans which are “automatic” and based on clear guidelines; and (4) transparency of methodology, data, and results.
Escalation of Opioid Withdrawal Frequency and Subsequent AMA Rates in Hospitalized Patients From 2017 to 2020
Authors: Horton Terry , Subedi Keshab , Sharma Ram A. , Wilson Beverly , Gbadebo Bayo M. , Jurkovitz Claudine
Published: June 2022

Objective

To measure trends for the emergence of opioid withdrawal (OW) and leaving against medical advice (AMA) among hospitalized patients.

Method

Retrospective time-series of hospitalized patients with OW, defined by a Clinical Opioid Withdrawal score >8, using electronic health record data at a tertiary health system and of patients with a discharge status of AMA from January 1, 2017 to December 31, 2020.

Results

The average number of monthly hospitalizations with OW showed a year-to-year increment of 15% in 2018, 21% in 2019, and 34% from 2019 to 2020, whereas the total monthly hospitalizations remained stable. The segmented regression analysis showed that the upward trend in hospitalizations with OW became significant after January 2019 (slope: 1.14, 95% confidence interval [CI]: 0.70, 1.57). After August 2019, Fentanyl was added to the hospital urine drug testing panel and was identified in most OW patients. The monthly proportion of patients who left AMA was significantly higher among the OW patients than among all other admitted patients. There was a significant increase of 0.39 (95% CI: 0.29–0.49, P < 0.001) per month in %AMA among patients with OW. The estimated difference in %AMA among OW patients versus all other patients was 7.25 (95% CI: 5.12–9.38) in January 2017, and 16.92 (95% CI: 14.60–19.24) in December 2020.

Conclusions

The number of hospitalized patients either presenting with or developing OW increased between 2017 and 2020 with a significant rise occurring after January 2019. The percentage of patients who left AMA among those who developed OW steadily worsened during the entire study period.
Inconsistent Benefits From Mobile Information Communication Technology in Adults With Peripheral Arterial Disease
Authors: Aronow Wilbert S. , Avanesova Anna A. , Frishman William H. , Shamliyan Tatyana A.
Published: June 2022

Introduction:

Quality of evidence regarding telemedicine in adults with peripheral arterial disease has not been systematically appraised.

Objectives:

To explore benefits and harms from mobile information communication technology devices and applications in peripheral arterial disease.

Methods:

Systematic rapid evidence review and appraisal with the grading of recommendations assessment, development, and evaluation working group approach.

Results:

Sixteen randomized controlled clinical trials (RCT) examined various self-monitoring devices, telemedicine platforms, and individualized telephone counseling. Low-quality evidence suggested that the odds of treatment failure (pooled Peto odds ratio 0.8; 95% CI, 0.4–1.7; 5 RCTs), adverse effects (pooled Peto odds ratio 0.9; 95% CI, 0.5–1.5; 2 RCTs), and physical performance (standardized mean difference in 6-minute walking test 0.2; 95% CI, –0.3–0.7; 4 RCTs) did not differ between mobile interventions and usual care. Single RCTs suggested large but inconsistent improvement in the quality of life: EuroQol5D standardized mean difference = 5.0 (95% CI, 4.4–5.7; 1 RCT) after telehealth program for promoting patient self-management and standardized mean difference = 1.4 (95% CI, 0.4–2.3; 1 RCT) after structured rehabilitation with mobile self-monitoring. Inconsistent reporting of patient-centered outcomes and small sample sizes hampered the quality of evidence.

Conclusions:

Improved quality of life after specific mobile applications should be confirmed in powered RCTs and large postmarketing studies.
Correlation among four questionnaires that evaluate menopausal symptoms
Authors: Souza Laura A. Cota e , Araujo Amanda T. , Lima Angelica A.
Published: June 2022

Objective:

The number of specific scales to measure menopausal symptoms has increased significantly in the last decades. However, the lack of standardization as well as prioritization of which scale should be used in exploring menopausal symptoms poses problems in most populations. Thus, we aimed at demonstrating the correlation among four questionnaires evaluating menopausal symptoms: the Menopause Rating Scale (MRS), Greene Climacteric Scale (GCS), Kupperman Menopausal Index, and Women's Health Questionnaire (WHQ).

Methods:

We recruited 336 women between 40 and 65 years of age who responded to all four questionnaires. For each questionnaire, we calculated the overall score and the subscale scores. We then compared variables using the Spearman rank correlation coefficient (Rho).

Results:

We found a very strong correlation (Rho > 0.80; P 
< 0.001) between all the questionnaires. The strongest correlations were those observed in the comparisons involving the GCS (Rho 0.92-0.95; P 
< 0.001), whereas the weakest ones were observed using the WHQ scale (Rho –0.86 to –0.89; P 
< 0.001). Like in the overall score analyses, vasomotor, somatic, and psychological symptoms demonstrated the strongest correlations in the GCS comparisons and the weakest correlations between the WHQ and MRS.

Conclusions:

The MRS, GCS, Kupperman Menopausal Index, and WHQ assessed menopausal symptoms in a very similar way. We recommend further studies to adjust and improve the existing questionnaires, test their robustness in different settings, and ensure their applicability in research and clinical practice.
Physical Characteristics of SurgiMend Meshed Biological ADM in Immediate Prepectoral Implant Breast Reconstruction
Authors: Gui Gerald , Gui Marcus , Gui Adrian , Tasoulis Marios Konstantinos
Published: June 2022

With increasing acceptance of prepectoral implant breast reconstruction, there has been a requirement for biological acellular dermal matrices with conformational properties, high tensile strength, and rapid integration. SurgiMendPRS Meshed is a biological acellular dermal matrix derived from fetal calf with these specific characteristics for prepectoral implant breast reconstruction. The aim of this study was to test the performance of this mesh by recreating its surgical use ex-vivo using a variety of implants in an effort to define its physical properties. The mesh is usually attached with a number of interrupted sutures to the implant periphery, the variable being at the inferior border, where it can be attached as a snug fit at the level of the inframammary crease (“tent” technique) or sewn behind the implant, cradling the lower pole (“hammock” technique). The results show mesh elasticity to stretch with increasing implant weight. When used as a “hammock,” greater stretch was demonstrated compared with the “tent” technique, allowing greater degrees of ptosis to be achieved. The suture points demonstrated lines of tension that progress evenly over the anterior implant surface. The mesh performed better when used at maximum stretch, but should not be forcibly stretched over an implant as the lines of stress show uneven distribution of lines of tension. These data provide a structural basis on optimum clinical use of this acellular dermal matrix in prepectoral implant breast reconstruction.
Spondylodiscitis in Pediatric Age: A Retrospective Cohort Study
Authors: Cavalieri Stefano , Pessina Benedetta , Indolfi Giuseppe , Galli Luisa , Trapani Sandra
Published: June 2022

Background:

Pediatric spondylodiscitis is rare, hardly diagnosed and treated due to the nonspecificity of clinical presentation and laboratory investigations, difficulty of etiologic identification and lack of management guidelines.

Methods:

A retrospective study was conducted on 29 children with spondylodiscitis. Clinical, hematic and radiologic data were collected and compared between 2 age-subgroups (below and from 4 years old on) to investigate age-related differences. Epidemiologic, management and follow-up data were also described.

Results:

Slight male predominance and a peak of incidence <2 years were observed. Symptoms were significantly differently distributed in the 2 age-subgroups: children <4 years showed mainly refusal/inability to sit or bear weight, irritability, limping and poor general conditions; children ≥4 years most frequently had back pain and fever, and pain upon palpation of the spine. The lumbar spine and more than 1 vertebra were most frequently involved. Median diagnostic delay of 12 days was observed, without significant difference between age-subgroups, and delay >2 months was always associated with multivertebral involvement and complications. All children were treated with broad-spectrum antibiotics for a median of 12 weeks. Only in 1 complicated case, surgical treatment was also required.

Conclusions:

The clinical presentation of spondylodiscitis may be age-specific, with younger children often exhibiting subtle signs and symptoms. Broad-spectrum antibiotics covering for Staphylococcus aureus should be initiated as soon as possible and performed many weeks, being effective in treating the infection without clinical sequelae, even in patients with comorbidities. Surgical treatment should be reserved for complicated cases with neurologic involvement.
Multimodal imaging findings in Purtscher-like retinopathy after retrobulbar anesthesia
Authors: Gliagias Vasiliki , Pandey Avi , Cheela Isha
Published: June 2022

Introduction:

This is a case of Purtscher-like retinopathy with an unusual etiology of retrobulbar anesthesia, evidenced by optical coherence tomography-angiography (OCT-A) images.

Patient and Clinical Findings:

After cataract surgery with a retrobulbar block, a 65-year-old woman experienced sudden dramatic visual reduction with superficial white retinal patches on fundus examination and corresponding capillary bed infarcts on fluorescein angiography and OCT-A.

Diagnosis, Intervention, and Outcomes:

Using advanced OCT-A, fluorescein angiography imaging, and fundus photography, the patient was diagnosed with Purtscher-like retinopathy. The patient was treated with topical steroids, nonsteroidal anti-inflammatory drops, and antibiotic drops, with gradual and nearly complete resolution of visual acuity.

Conclusions:

This case represents a rare but possible complication of retrobulbar anesthesia associated with cataract surgery. Despite dramatic changes on OCT-A, and in contrast to other reports with similar characteristic findings, our patient regained significant vision.
Elevated 18:0 lysophosphatidylcholine contributes to the development of pain in tissue injury
Authors: Friston Dominic Anthony , Cuddihy Joshua , Souza Luiz Jessica , Truong An Hoai , Ho Laptin , Basra Meirvaan , Santha Peter , Oszlacs Orsolya , de Sousa Valente Joao , Marczylo Tim , Junttila Sini , Laycock Helen , Collins Declan , Vizcaychipi Marcela , Gyenesei Attila , Takats Zoltan , Jancso Gabor , Want Elizabeth , Nagy Istvan
Published: June 2022

Tissue injuries, including burns, are major causes of death and morbidity worldwide. These injuries result in the release of intracellular molecules and subsequent inflammatory reactions, changing the tissues' chemical milieu and leading to the development of persistent pain through activating pain-sensing primary sensory neurons. However, the majority of pain-inducing agents in injured tissues are unknown. Here, we report that, amongst other important metabolite changes, lysophosphatidylcholines (LPCs) including 18:0 LPC exhibit significant and consistent local burn injury-induced changes in concentration. 18:0 LPC induces immediate pain and the development of hypersensitivities to mechanical and heat stimuli through molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1, and member 2 at least partly via increasing lateral pressure in the membrane. As levels of LPCs including 18:0 LPC increase in other tissue injuries, our data reveal a novel role for these lipids in injury-associated pain. These findings have high potential to improve patient care.
Hospital-Based Case Management Model for Child Protection Teams in Taiwan: An Action Research Approach
Authors: CHEN Chia-Jung , CHEN Yi-Wen , CHANG Hsin-Yi , FENG Jui-Ying
Published: June 2022

Background

Hospital-based child protection teams play an important role in the multidisciplinary assessment, treatment, care, and rehabilitation of abused children and their families. However, the process by which these teams are built and promoted has not been explored adequately in the literature.

Purpose

This study was developed to examine the process used to promote child protection team case management and to evaluate the related results.

Methods

An action research model was adopted in this study. The participants and the investigator were members of a child protection team at a medical center in southern Taiwan. Qualitative and quantitative assessments were used to identify problems related to organizational structure, intervention procedures, and evaluation effectiveness. Thereafter, the study program was implemented, and the results were evaluated. Content analysis of the qualitative data, including transcribed interviews with external benchmark members and members of the hospital's team and text entries from the investigator's reflective journal, was conducted. Quantitative data, including monitoring indicators for team case management, were analyzed using descriptive statistics.

Results

Three important concepts emerged related to changes in the promotion of case management by hospital child protection teams. These included formulation of a team operation model through visits to benchmark hospitals, establishment of the case management and monitoring mechanism based on team consensus, and expansion of collaboration with external agencies through the establishment of a child and adolescent protection medical regional integration center. The results of the promotion process were affected by factors that included member willingness, teamwork, hospital support, and national policy.

Conclusions/Implications for Practice

Use of the hospital child protection team case management model developed in this study was shown to facilitate the provision of consultation services, integrate the opinions and resources of experts from various fields, and allow the timely provision of acute care, follow-up family environment support, and social resources required by children and their family members. These measures help prevent the reoccurrence of child abuse and enable children to grow up healthily and free from violence.
Burn Pit Exposure Is Associated With Increased Sinonasal Disease
Authors: Hill Christopher J. , Meyer Charles D. , McLean James E. , Anderson Danielle C. , Hao Yajing , Lin Feng-Chang , Kimple Adam J. , Capra Gregory G.
Published: June 2022

Objective

The aim of this study was to determine whether self-reported burn pit exposure is associated with increased subjective and objective sinus disease.

Design

A cross-sectional study was performed evaluating consecutive adult patients presenting to a US Military rhinology clinic. Demographics, medical histories, sinonasal quality-of-life scores, and nasal endoscopy examinations were obtained. Participants were divided into three cohorts based on self-reported exposure histories and outcomes compared.

Results

One hundred eighty-six patients met the inclusion criteria, the majority of whom were male. Patients with burn pit exposure had worse Sinonasal Outcome Test-22 scores (49.9) compared with those deployed without burn pit exposure (31.8) or never deployed (31.5). Endoscopic findings demonstrated worse disease within those exposed (Lund-Kennedy score, 3.3) compared with the other cohorts (1.8 and 1.7, respectively).

Conclusions

These novel findings suggest that deployment-related burn pit exposure is associated with increased subjective and objective sinus disease.
Disparity in Occupational Health Risk During the Pandemic
Authors: Yuan Bocong , Lan Junbang , Li Jiannan
Published: June 2022

Objective

This study clarifies potential misestimation of occupational risk caused by the dichotomy of frontline essential and nonessential occupations in prior studies.

Methods

The linear regression is used to investigate the occupational risk in terms of incidence rate, hospitalization, and mortality on community level during the pandemic.

Results

Overall, frontline essential occupations were positively associated with incidence rate, hospitalization, and mortality (156.06, 18.47, and 3.49; P < 0.01). Among essential occupations, however, education, training, and library occupations were negatively associated with them, whereas transportation, protective service, food preparation, and serving occupations were insignificantly associated with them. Moreover, among nonessential occupations, building and grounds cleaning, construction, and extraction occupations were positively associated with them.

Conclusion

The dichotomy of frontline essential and nonessential occupations can bring overestimation and underestimation of occupational risk during the COVID-19 pandemic.
Migraine Headache in an Employed Population
Authors: Burton Wayne N. , Schultz Alyssa B. , Shepherd Martha E. , Hines David
Published: June 2022

Objective

Demographics, health risks, pharmaceutical utilization, and other characteristics of adults with and without migraine who were employed by a school district in the southern United States were compared.

Methods

A total of 4528 employees completed a health risk appraisal. A diagnosis of migraine was reported by 11%. Employees with and without migraine were compared on several measures.

Results

Demographic and health risk differences were observed among the comparison groups. One-fifth of migraineurs had a prescription for an opioid, which was associated with very high average annual health care costs ($17,791) compared with migraineurs without opioid ($3907).

Conclusions

Migraine is common in the workforce. Employers may want to educate employees with migraine about evidence-based treatments. Benefit plan design should be consistent with current accepted treatment guidelines for opioid use.
Development of the National Institute for Occupational Safety and Health Worker Well-Being Questionnaire
Authors: Chari Ramya , Sauter Steven L. , Petrun Sayers Elizabeth L. , Huang Wenjing , Fisher Gwenith G. , Chang Chia-Chia
Published: June 2022

Objective

This article describes development of the National Institute for Occupational Safety and Health (NIOSH) Worker Well-Being Questionnaire (WellBQ).

Methods

The NIOSH WellBQ was developed through literature reviews and expert panel recommendations. We drew from a representative sample of the civilian, noninstitutionalized, US working population to pilot the questionnaire. Psychometric analyses were performed on data from 975 respondents to finalize items and optimize the NIOSH WellBQ's psychometric properties.

Results

The final questionnaire consists of 16 scales, 5 indices, and 31 single items across 5 domains: (1) work evaluation and experience; (2) workplace policies and culture; (3) workplace physical environment and safety climate; (4) health status; and (5) home, community, and society (experiences and activities outside of work). The instrument demonstrated adequate reliability and validity.

Conclusions

The NIOSH WellBQ is a reliable and valid instrument that comprehensively measures worker well-being.
Lasers for benign prostatic hyperplasia (hybrid, blue diode, TFL, Moses). Which one to choose?
Authors: Doizi Steeve
Published: June 2022

Purpose of review

To present the evidence of latest developments of lasers for the surgical treatment of benign prostatic hyperplasia (BPH). We focused on recent advancements in Ho:YAG laser such as Moses technology, the Thulium Fiber Laser (TFL), the blue diode laser, and hybrid laser.

Recent findings

Laser enucleation of prostate techniques using either Ho:YAG laser with the Moses technology and Moses 2.0, or TFL seem efficient and safe compared with the standard enucleation using Ho:YAG laser. Only in vitro studies evaluated the blue diode laser and hybrid laser (combination of a continuous wave TFL and blue diode laser). Blue diode laser showed intermediate incision depth and minimal coagulation depth compared with Ho:YAG laser and Super Pulse TFL. Hybrid laser showed deep incision depth and small coagulation area compared with Ho:YAG laser and continuous wave TFL.

Surgical treatment of BPH using Moses technology, Moses 2.0, and TFL shows encouraging results comparable to the standard enucleation using Ho:YAG laser. Only in vitro data are currently available for blue diode laser and hybrid laser. Future well-designed studies comparing these technologies and evaluating them on specific risk groups of patients as well as the long-term durability of outcomes are needed.
Systematic Review and Meta-Analysis to Estimate the Treatment Effect and Inform a Noninferiority Margin for a Phase 3 Noninferiority Trial in Uncomplicated Urogenital Gonorrhea
Authors: Mitrani-Gold Fanny S. , Fix Jonathan , Donald Alison
Published: June 2022

Background

Active-controlled noninferiority studies are used to investigate novel agents for uncomplicated urogenital gonorrhea (uUGC) as placebo-controlled trials are unethical. A systematic literature review and meta-analysis were conducted to estimate the ceftriaxone and proxy-for-placebo microbiological treatment effect and determine an appropriate noninferiority margin for phase 3 trials.

Methods

Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. To account for interstudy variability, a weighted, noniterative random-effects model was fitted using “R” software to estimate the microbiological response rate and 95% confidence intervals (CIs) for ceftriaxone and proxy-for-placebo (treatment with an antibiotic the isolate was subsequently confirmed resistant to, or spontaneous resolution without treatment). I
2, τ
2, and P values were computed and included in the meta-analysis forest plot.

Results

Seventeen studies were included in the meta-analysis; 14 reported ceftriaxone response in micro-intent-to-treat and microbiologically evaluable populations, and 3 reported proxy-for-placebo treatment response in uUGC (microbiologically evaluable population only). Microbiological treatment effect was estimated by subtracting the upper end of the CI for placebo from the lower end of the CI for ceftriaxone. Overall microbiological response was 98% (95% CI, 97–99) for ceftriaxone and 44% (95% CI, 34–54) for proxy-for-placebo, resulting in a microbiological treatment effect of 43%. A noninferiority margin of 15% preserved 65% of the ceftriaxone treatment effect, exceeding the 50% recommended per US Food and Drug Administration guidance for noninferiority studies.

Conclusions

Results of this systematic literature review and meta-analysis could help inform the design, conduct, and analysis of future clinical studies in uUGC.
Progressive-Tension Sutures in Reconstruction of Posterior Trunk Defects in Pediatric Patients: A Prospective Series
Authors: Crowe Christopher S. , Hauptman Jason S. , Lee Amy , Ellenbogen Richard G. , Ettinger Russell E. , Susarla Srinivas M.
Published: June 2022

Following neurosurgical repair of spinal dysraphism defects, soft-tissue reconstruction is often required to obtain robust coverage of the dura. Layered closure utilizing local muscle and muscle fascia has proven reliable for this purpose, but it often results in significant dead space necessitating closed suction drainage. Progressive-tension sutures have been reported as an alternative to drains for prevention of fluid collection in several other procedures. In this study, the use of progressive-tension sutures for eliminating subcutaneous dead space and obtaining tension-free skin closure was prospectively evaluated in pediatric patients undergoing soft-tissue reconstruction for congenital spinal anomalies. Primary outcomes of interest included wound breakdown, seroma, hematoma, and cerebrospinal fluid leak. Patients were excluded if a lumbar, submuscular, or subcutaneous drain was placed during the index procedure. Over a 3-year period, 45 patients underwent muscle flap reconstruction for coverage of dural defects. The primary diagnoses were myelomeningocele (10 patients), lipomyelomeningocele (eight patients), myelocystocele (three patients), tethered cord release (15 patients), meningocele (three patients), spinal tumor (two patients), and hardware exposure following spinal instrumentation (three patients). During the follow-up period, three patients (6.7 percent) had postoperative wound complications. One patient had superficial dehiscence, one had cerebrospinal fluid leak requiring operative revision, and one had a surgical site infection necessitating operative drainage. No patients developed hematomas, seromas, cerebrospinal fluid fistulae, or wound breakdown requiring operative revision. The use of progressive-tension sutures is an effective method for eliminating subcutaneous dead space in pediatric soft-tissue reconstruction and eliminates the need for drain placement.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Factors Causing Variation in World Health Organization Surgical Safety Checklist Effectiveness—A Rapid Scoping Review
Authors: Wani Mudassir M. , Gilbert John H.V. , Mohammed Ciraj Ali , Madaan Sanjeev
Published: June 2022

Introduction

This review was conducted to determine what factors might be responsible for prejudicing the outcomes after the implementation of a World Health Organization Surgical Safety Checklist (WHO SSC), grouping them appropriately and proposing strategies that enable the SSC a more helpful and productive tool in the operating room.

Methods

It was a rapid scoping review conducted as per Preferred Reporting Items for Systematic Review and Meta-analyses extension guidelines for scoping reviews (PRISMA-Scr). Comprehensive search on MEDLINE and Embase was carried out, to include all relevant studies published during last 5 years. Twenty-seven studies were included in analysis. The barriers to SSC implementation were classified into 5 main groups, with further subdivisions in each.

Results

The results of review revealed that there are 5 major barriers to SSC at the following levels: organizational, checklist, individual, technical, and implementation. Each of these major barriers, on further evaluation, was found to have more than one contributing factors. All these factors were analyzed individually.

Conclusions

This rapid scoping review has consolidated data, which may pave the way for experts to further examine steps that might be taken locally or globally in order that the WHO SSC to successfully achieve all its desired goals.
Use of Machine Learning Algorithms to Predict the Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke Patients With an Extended Therapeutic Time Window
Authors: Lu Shanshan , Zhang Jiulou , Wu Rongrong , Cao Yuezhou , Xu Xiaoquan , Li Ge , Liu Sheng , Shi Haibin , Wu Feiyun
Published: June 2022

Objective

The aim of this study was to evaluate the performance of machine learning (ML) algorithms in predicting the functional outcome of mechanical thrombectomy (MT) outside the 6-hour therapeutic time window in patients with acute ischemic stroke (AIS).

Methods

One hundred seventy-seven consecutive AIS patients with large-vessel occlusion in the anterior circulation who underwent MT in the extended time window were enrolled. Clinical, neuroimaging, and treatment variables that could be obtained quickly in the real-world emergency settings were collected. Four machine learning algorithms (random forests, regularized logistic regression, support vector machine, and naive Bayes) were used to predict good outcomes (modified Rankin Scale scores of 0–2) at 90 days by using (1) only variables at admission and (2) both baseline and treatment variables. The performance of each model was evaluated using receiver operating characteristic (ROC) curve analysis. Feature importance was ranked using random forest algorithms.

Results

Eighty patients (45.2%) had a favorable 90-day outcome. Machine learning models including baseline clinical and neuroimaging characteristics predicted 90-day modified Rankin Scale with an area under the ROC curve of 0.80–0.81, sensitivity of 0.60–0.71 and specificity of 0.71–0.76. Further inclusion the treatment variables significantly improved the predictive performance (mean area under the ROC curve, 0.89–0.90; sensitivity, 0.77–0.85; specificity, 0.75–0.87). The most important characteristics for predicting 90-day outcomes were age, hypoperfusion intensity ratio at admission, and National Institutes of Health Stroke Scale score at 24 hours after MT.

Conclusions

Machine learning algorithms may facilitate prediction of 90-day functional outcomes in AIS patients with an extended therapeutic time window.
Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge
Authors: Avery Robin Kimiko
Published: June 2022

Major changes have occurred in therapeutics for coronavirus-19 (COVID-19) infection over the past 12–18 mo, most notably in early outpatient therapy. In most cases, solid organ transplant recipients were not included in the original clinical trials of these agents, so studies of real-world outcomes have been important in building our understanding of their utility. This review examines what is known about clinical outcomes in solid organ transplant recipients with newer therapies. SARS-CoV-2 monoclonal antibodies for early treatment or prophylaxis have likely prevented many hospitalizations and deaths. In addition, convalescent plasma, the oral drugs nirmatrelvir/ritonavir and molnupiravir, remdesivir for early outpatient treatment, anti-inflammatory therapy, and investigational virus-specific T-cell therapy will be discussed. Finally, the later consequences of COVID-19, such as secondary infections, long COVID symptoms, and persistent active infection, are identified as areas for future research.
Immunotherapy in autoimmune encephalitis
Authors: Trewin Benjamin P. , Freeman Isaak , Ramanathan Sudarshini , Irani Sarosh R.
Published: June 2022

Purpose of review

Autoimmune encephalitis (AE) refers to immune-mediated neurological syndromes often characterised by the detection of pathogenic autoantibodies in serum and/or cerebrospinal fluid which target extracellular epitopes of neuroglial antigens. There is increasing evidence these autoantibodies directly modulate function of their antigens in vivo. Early treatment with immunotherapy improves outcomes. Yet, these patients commonly exhibit chronic disability. Importantly, optimal therapeutic strategies at onset and during escalation remain poorly understood. In this review of a rapidly emerging field, we evaluate recent studies on larger cohorts, registries, and meta-analyses to highlight existing evidence for contemporary therapeutic approaches in AE.

Recent findings

We highlight acute and long-term treatments used in specific AE syndromes, exemplify how understanding disease pathogenesis can inform precision therapy and outline challenges of defining disability outcomes in AE.

Early first-line immunotherapies, including corticosteroids and plasma exchange, improve outcomes, with emerging evidence showing second-line immunotherapies (especially rituximab) reduce relapse rates. Optimal timing of immunotherapy escalation remains unclear. Routine reporting of outcome measures which incorporate cognitive impairment, fatigue, pain, and mental health will permit more accurate quantification of residual disability and comprehensive comparisons between international multicentre cohorts, and enable future meta-analyses with the aim of developing evidence-based therapeutic guidelines.
Emulator-based decomposition for structural sensitivity of core-level spectra
Authors: Niskanen J. , Vladyka A. , Niemi J. , Sahle C.J.
Published: June 2022

We explore the sensitivity of several core-level spectroscopic methods to the underlying atomistic structure by using the water molecule as our test system. We first define a metric that measures the magnitude of spectral change as a function of the structure, which allows for identifying structural regions with high spectral sensitivity. We then apply machine-learning-emulator-based decomposition of the structural parameter space for maximal explained spectral variance, first on overall spectral profile and then on chosen integrated regions of interest therein. The presented method recovers more spectral variance than partial least-squares fitting and the observed behaviour is well in line with the aforementioned metric for spectral sensitivity. The analysis method is able to independently identify spectroscopically dominant degrees of freedom, and to quantify their effect and significance.
First definitive record of Abelisauridae (Theropoda: Ceratosauria) from the Cretaceous Bahariya Formation, Bahariya Oasis, Western Desert of Egypt
Authors: Salem Belal S. , Lamanna Matthew C. , O'Connor Patrick M. , El-Qot Gamal M. , Shaker Fatma , Thabet Wael A. , El-Sayed Sanaa , Sallam Hesham M.
Published: June 2022

Numerous non-avian theropod dinosaur fossils have been reported from the Upper Cretaceous (Cenomanian) Bahariya Formation, Bahariya Oasis, Western Desert of Egypt, but unambiguous materials of Abelisauridae have yet to be documented. Here we report Mansoura University Vertebrate Paleontology Center (MUVP) specimen 477, an isolated, well-preserved tenth cervical vertebra of a medium-sized abelisaurid from the Bahariya Formation. The new vertebra shows affinities with those of other Upper Cretaceous abelisaurids from Madagascar and South America, such as
Majungasaurus crenatissimus
,
Carnotaurus sastrei
,
Viavenator exxoni
and a generically indeterminate Patagonian specimen (Museo Padre Molina specimen 99). Phylogenetic analysis recovers the Bahariya form within Abelisauridae, either in a polytomy of all included abelisaurids (strict consensus tree) or as an early branching member of the otherwise South American clade Brachyrostra (50% majority rule consensus tree). MUVP 477, therefore, represents the first confirmed abelisaurid fossil from the Bahariya Formation and the oldest definitive record of the clade from Egypt and northeastern Africa more generally. The new vertebra demonstrates the wide geographical distribution of Abelisauridae across North Africa during the middle Cretaceous and augments the already extraordinarily diverse large-bodied theropod assemblage of the Bahariya Formation, a record that also includes representatives of Spinosauridae, Carcharodontosauridae and Bahariasauridae.
Stability of two-dimensional potential flows using bicomplex numbers
Authors: Kleine V. G. , Hanifi A. , Henningson D. S.
Published: June 2022

The use of the complex velocity potential and the complex velocity is widely disseminated in the study of two-dimensional incompressible potential flows. The advantages of working with complex analytical functions made this representation of the flow ubiquitous in the field of theoretical aerodynamics. However, this representation is not usually employed in linear stability studies, where the representation of the velocity as real vectors is preferred by most authors, in order to allow the representation of the perturbation as the complex exponential function. Some of the classical attempts to use the complex velocity potential in stability studies suffer from formal errors. In this work, we present a framework that reconciles these two complex representations using bicomplex numbers. This framework is applied to the stability of the von Kármán vortex street and a generalized formula is found. It is shown that the classical results of the symmetric and staggered von Kármán vortex streets are just particular cases of the generalized dynamical system in bicomplex formulation.
Loss-of-heterozygosity facilitates a fitness valley crossing in experimentally evolved multicellular yeast
Authors: Baselga-Cervera Beatriz , Gettle Noah , Travisano Michael
Published: June 2022

Determining how adaptive possibilities do or do not become evolutionary realities is central to understanding the tempo and mode of evolutionary change. Some of the simplest evolutionary landscapes arise from underdominance at a single locus where the fitness valley consists of only one less-fit genotype. Despite their potential for rapid evolutionary change, few such examples have been investigated. We capitalized on an experimental system in which a significant evolutionary shift, the transition from uni-to-multicellularity, was observed in asexual diploid populations ofSaccharomyces cerevisiaeexperimentally selected for increased settling rates. The multicellular phenotype results from recessive single-locus mutations that undergo loss-of-heterozygosity (LOH) events. By reconstructing the necessary heterozygous intermediate steps, we found that the evolution of multicellularity involves a decrease in size during the first steps. Heterozygous genotypes are 20% smaller in size than genotypes with functional alleles. Nevertheless, populations of heterozygotes give rise to multicellular genotypes more readily than unicellular genotypes with two functional alleles, by rapid LOH events. LOH drives adaptation that may enable rapid evolution in diploid yeast. Together these results show discordance between the phenotypic and genotypic multicellular transition. The evolutionary path to multicellularity, and the adaptive benefits of increased size, requires initial size reductions.
The ontogeny of selection on genetic diversity in harvester ants
Authors: Wiernasz Diane C. , Cole Blaine J.
Published: June 2022

Selection may favour traits throughout an individual's lifetime or at a particular life stage. In many species of social insects, established colonies that are more genetically diverse outperform less diverse colonies with respect to a variety of traits that contribute to fitness, but whether selection favours high diversity in small colonies is unknown. We tested the hypothesis that selection favours genetically diverse colonies during the juvenile period using a multi-year field experiment with the harvester ant,Pogonomyrmex occidentalis. We used controlled matings to generate colonies that varied in genetic diversity and transplanted them into the field. We monitored their survival for seven (the 2015 cohort,n= 149) and six (the 2016 cohort,n= 157) years. Genetically more diverse colonies had greater survival, resulting in significant viability selection. However, in both cohorts survival was not influenced by genetic diversity until colonies were three years old. We suggest that changes in their internal organization enabled colonies to use the benefits of multiple genotypes, and discuss possible mechanisms that can generate this pattern.
Influence of visual background on discrimination of signal-relevant colours in zebra finches (Taeniopygia guttata)
Authors: Davis Alexander , Zipple Matthew N. , Diaz Danae , Peters Susan , Nowicki Stephen , Johnsen Sönke
Published: June 2022

Colour signals of many animals are surrounded by a high-contrast achromatic background, but little is known about the possible function of this arrangement. For both humans and non-human animals, the background colour surrounding a colour stimulus affects the perception of that stimulus, an effect that can influence detection and discrimination of colour signals. Specifically, high colour contrast between the background and two given colour stimuli makes discrimination more difficult. However, it remains unclear how achromatic background contrast affects signal discrimination in non-human animals. Here, we test whether achromatic contrast between signal-relevant colours and an achromatic background affects the ability of zebra finches to discriminate between those colours. Using an odd-one-out paradigm and generalized linear mixed models, we found that higher achromatic contrast with the background, whether positive or negative, decreases the ability of zebra finches to discriminate between target and non-target stimuli. This effect is particularly strong when colour distances are small (less than 4 ΔS) and Michelson achromatic contrast with the background is high (greater than 0.5). We suggest that researchers should consider focal colour patches and their backgrounds as collectively comprising a signal, rather than focusing on solely the focal colour patch itself.